Calpain10 (CAPN10) gene was the first identified susceptibility gene for type 2 diabetes mellitus and closely related to insulin sensitivity. A lot of research attention has been attracted on the relationship between CAPN10 polymorphisms and PCOS risk, but they didn’t reach a consistent conclusion. We therefore performed this systematic review and meta-analysis to assess the association of CAPN10 common variants with PCOS susceptibility. A total of 21 studies were eligible for inclusion. Meta-analyses were done for 5 variants that had at least two data sources: UCSNP-19, -43, −44, −56 and −63. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under five genetic models. Subgroup analyses by ethnicity, PCOS diagnostic criteria, and source of controls were conducted. Moreover, false-positive report probability (FPRP) test and trial sequential analysis (TSA) were performed to assess the significant associations. The results showed a possible negative association between UCSNP-19 and PCOS risk . In subgroup analyses, FPRP test indicated that noteworthy associations were observed in mixed ethnicities for UCSNP-43  and in Asians for UCSNP-44 , but TSA plots showed that the accumulated sample sizes of these associations were insufficient to draw firm conclusions. In summary, our study suggested that UCSNP-19, UCSNP-43, and UCSNP-44 in CAPN10 gene may be involved in PCOS susceptibility. These findings warrant further studies.Insulin resistance plays an important role in the pathogenesis of polycystic ovarian syndrome (PCOS).  Polycystic ovarian syndrome (PCOS) is the most common reproductive endocrine disorder affecting 5%-20% of women at childbearing age worldwide, depending on the diagnostic criteria . The conCalpain10 (CAPN10) gene is located on the human chromosome 2q37.3 and consists of 15 exons and 14 introns spanning 31 kb. It is the first susceptibility gene for T2DM identified through a genome-wide scan followed by positional cloning , China National Knowledge Infrastructure (CNKI), and Wanfang Database. Keyword search was performed using the following terms: (PCOS OR “polycystic ovary syndrome” OR “polycystic ovarian syndrome”) AND . The full details of search strategy were listed in CAPN10 polymorphisms and PCOS susceptibility. The exclusion criteria included: (1) case-only studies; (2) family-based studies; (3) comments or review articles; (4) duplicate or overlapping data.Studies selected in our systematic review had to meet all the following criteria: (1) case-control studies based on unrelated subjects; (2) the diagnosis of PCOS was clear; (3) human studies; (4) the study assessed the association between All records obtained through the database search were collected in the EndNote software. After removal of duplicates, all the titles and abstracts were screened to exclude the irrelevant studies and then the full texts of the remaining records were reviewed for eligibility independently by two researchers (YML and TH). Reference lists of the eligible studies were also reviewed.The following items was extracted from each eligible study: the first author, year of publication, country, ethnicity, sample size, age of cases and controls, diagnostic criteria used for PCOS, source of control subjects, genotyping methods, and allele and genotype frequencies in cases and controls.The quality of included studies was assessed using the Newcastle–Ottawa Scale (NOS) . The NOSTwo researchers (YML and TH) independently performed study screening, data extraction and quality assessment based on the specified selection criteria. All disagreements were resolved by consensus after discussion with the other authors.Meta-analysis was performed for genetic variants with at least two available datasets using the STATA version 14.0 software . Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under five genetic models: allelic model , heterozygous model (MW vs. WW), homozygous model (MM vs. WW), recessive model (MM vs. WW + MW), and dominant model (MW + MM vs. WW) .I2 index were used to assess the heterogeneity across the eligible studies  was conducted in meta-analysis. Otherwise, the fixed effect model (Mantel–Haenszel method) was applied.The Cochrane’s Q test and  studies . p valueSubgroup analyses were performed by ethnicity, diagnostic criteria, and source of controls to determine the source of heterogeneity. Funnel plots and Egger’s linear regression test were used to assess potential publication bias of included studies . Sensitip value was <0.05. The false positive report probability (FPRP) values at different prior probability levels for all significant associations were calculated by the Excel spreadsheet which was offered on Wacholder’s website , and to assess if quantitative findings were robust . We estin = 7), not about CAPN10 polymorphisms (n = 6), reviews (n = 13), conference abstracts (n = 7), or family-based studies (n = 1), and the remaining 29 papers were included in the full-text review. Finally, 21 studies were eligible for the systematic review, and 19 of them had sufficient data for meta-analysis for 5 common variants: UCSNP-19, -43, -44, -56 and -63.n = 19), and the remaining 2 studies adopted the National Institutes of Health (NIH) criteria. All the included studies had good quality with the NOS score ranging from 7 to 9.CAPN10 gene were investigated, including UCSNP-19 (rs3842570 Del>Ins), UCSNP-22 (rs2953152 G>A), UCSNP-43 (rs3792267 G>A), UCSNP-44 (rs2975760 T>C), UCSNP-45 (rs2241766 A>C), UCSNP-56 (rs2975762 G>A), UCSNP-58 (rs2975766 A>G), UCSNP-63 (rs5030952 C>T) and UCSNP-110 (rs7607759 A>G). UCSNP-43 was the focus of most studies (n = 15), followed by UCSNP-19 (n = 13), UCSNP-63 (n = 12) and UCSNP-44 (n = 8). There were 3, 2 and 2 studies for UCSNP-56, UCSNP-58 and UCSNP-110, and one study for each of UCSNP-22 and UCSNP-45.Nine common variants in As shown in 12 studies consisting of 1299 PCOS patients and 1948 controls were included in the meta-analysis for UCSNP-19. The pooled estimate of recessive model revealed a significant association  . In the With regard to UCSNP-43, 13 studies involving 2124 cases and 2607 controls met the eligibility criteria for meta-analysis. No significant associations between UCSNP-43 and PCOS susceptibility were observed under all genetic models . In the Data from 6 studies (692 cases and 1613 controls) showed that UCSNP-44 was not significantly associated with PCOS risk in all genetic models . In the For UCSNP-56, 2 studies consisting of 582 cases and 602 controls were included in the meta-analysis. No significant associations were observed under all genetic models . The subFor UCSNP-63, 11 studies involving 1329 cases and 1926 controls were eligible for meta-analysis. No significant associations were observed under all genetic models in overall and subgroup analyses .The results of Egger’s test still did not suggest any evidence of publication bias in the analysis . BesidesSensitivity analyses were carried out by excluding studies not in HWE for UCSNP-43, UCSNP-44, and UCSNP-63, and all the results remained practically unchanged . SensitiThe TSA showed that cumulative Z curve reached the RIS and crossed the conventional boundary, but it did not cross the trial sequential monitoring boundary, suggesting that the correlation within UCSNP-19 polymorphism and PCOS susceptibility may be invalid and more studies are needed for stable conclusion . For UCSCAPN10 polymorphisms and susceptibility to PCOS. The results showed a possible negative association between UCSNP-19 and PCOS susceptibility. UCSNP-43 and UCSNP-44 may be associated with increased risk of PCOS among mixed ethnicities and Asians, respectively. However, no significant association was observed between UCSNP-22, -45, -56, -58, -63 and -110 polymorphisms and PCOS risk.The identification of genetic variants associated with PCOS and related traits has the potential to inform our understanding for pathogenesis of PCOS. The current study provided a systematic assessment of the association between CAPN10 gene, is a 2-allele polymorphism consisting of 2 or 3 copies of 32-bp sequence. The association may be attributed to the effect of UCSNP-19 polymorphism or the possible haplotypes of CAPN10 gene. Although UCSNP-19 did not alter the amino acid sequence, the variable number of tandem repeat polymorphism may be involved in the transcription modification and consequent protein expression (Our finding about the significant association of UCSNP-19 with PCOS was consistent with the previous meta-analyses by pression . The happression . Besidespression .CAPN10 gene (In subgroup analyses, ethnic-specific genetic associations of UCSNP-43 and -44 with PCOS were observed in our study. The role of these two SNPs in PCOS susceptibility have been attracted much attention due to the strong relevance between two SNPs and T2DM. The UCSNP-43 in intron 3 was the variant most strongly linked with T2DM among Mexican Americans . AfterwaN10 gene . EthniciN10 gene . These fN10 gene . But it However, the present study did not show significant association between UCSNP-63 and PCOS susceptibility overall or within any subgroup, which was somewhat different from the previous meta-analyses . The disCAPN10 gene is the first putative diabetes gene and encodes the cysteine protease calpain10 that involved in pro-insulin processing and insulin secretion and action (CAPN10 gene individually or in combination were demonstrated to regulate gene expression and be associated with insulin resistance and PCOS (CAPN10 may be an important susceptibility gene for PCOS.Although the mechanisms underlying PCOS remain elusive, recent studies have suggested that hyperandrogenism and insulin resistance were the core etiology and primary endocrine characteristics of this condition . Insulind action . Multipland PCOS . AccordiThis systematic review had several strengths. First, our study has been well-designed with explicit criteria and methods for study selection, data extraction and data analysis compared with the previous meta-analyses , which mCAPN10 gene polymorphisms and PCOS, they were not robust enough to withstand statistical interrogation. Further rigorous studies in various populations are needed to draw more definite conclusions.In conclusion, our study showed a possible negative association between UCSNP-19 and PCOS susceptibility, while UCSNP-43 and UCSNP-44 may be associated with increased risk of PCOS in specific ethnicities. Although the findings reflected the correlation between


Plant-based dietary patterns are gaining more attention due to their potential in reducing the risk of developing major chronic diseases, including type 2 diabetes (T2D), cardiovascular disease (CVD), cancer, and mortality, while an up-to-date comprehensive quantitative review is lacking. This study aimed to summarize the existing prospective observational evidence on associations between adherence to plant-based dietary patterns and chronic disease outcomes.We conducted a systematic review and meta-analysis of evidence across prospective observational studies. The data sources used were PubMed and MEDLINE, Embase, Web of Science, and screening of references. We included all prospective observational studies that evaluated the association between adherence to plant-based dietary patterns and incidence of T2D, CVD, cancer, and mortality among adults (≥ 18 years).I2 ranged: 30.2–95.4%). The inverse associations with T2D, CVD and cancer were strengthened when healthy plant-based foods, such as vegetables, fruits, whole grains, and legumes, were emphasized in the definition of plant-based dietary patterns . Association for mortality was largely similar when the analyses were restricted to healthy plant-based diets . In contrast, unhealthy plant-based diets were positively associated with these disease outcomes. Among four studies that examined changes in dietary patterns, increased adherence to plant-based dietary patterns was associated with a significantly reduced risk of T2D  and a marginally lower risk of mortality .A total of 76 publications were identified, including 2,230,443 participants with 60,718 cases of incident T2D, 157,335 CVD cases, 57,759 cancer cases, and 174,435 deaths. An inverse association was observed between higher adherence to a plant-based dietary pattern and risks of T2D , CVD (0.90 [0.85–0.94]), cancer (0.88 [0.84–0.92]), and all-cause mortality (0.84 [0.78–0.92]) with moderate to high heterogeneity across studies  with the registration number CRD42022290202.This review was registered at the PROSPERO International Prospective Register of Systematic Reviews (The online version contains supplementary material available at 10.1186/s12937-023-00877-2. According to the World Health Organization, type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer account for nearly one of every two deaths globally – close to 30 million people in 2020 –3. TheseAlthough a few systematic reviews and meta-analyses have examined associations between long-term vegetarian versus non-vegetarian dietary patterns and risks of CVD , 8 and cTo summarize the current evidence regarding plant-based diets in relation to human health, we conducted an updated systematic review and meta-analysis of prospective studies to assess the association of adherence to plant-based dietary patterns and changes in plant-based dietary patterns with risks of major chronic diseases, including T2D, CVD, and cancer, as well as mortality. We hypothesized that higher adherence to plant-based dietary patterns is associated with lower risks of T2D, CVD, cancer, and mortality.We systematically searched three databases, including PubMed and MEDLINE, Embase, and Web of Science through June 29, 2023. The search initially started in June 2021, and then updated in June 2023. Reference lists of prior systematic reviews were also checked to identify relevant original studies that were not found in three databases. Search terms included “plant-based diet”, “vegetarian”, “vegan”, “type 2 diabetes”, “cardiovascular disease”, “stroke”, “coronary artery disease”, “myocardial infarction”, “angina pectoris”, “cerebrovascular disorders”, “cancer”, and “mortality”. MESH and Emtree terms with explosion of narrower terms were used to broaden search results. The detailed search strategy for each database and the number of records retrieved was presented in Supplemental Table The current analysis considered prospective studies  that assessed associations between adherence to a priori-defined plant-based dietary patterns and the incidence of T2D, CVD, cancer, and mortality among adults (aged ≥ 18 years). Other types of studies , studies using a posteriori approach  to derive dietary patterns, or studies reported outcomes other than T2D , CVD, cancer, and mortality were excluded. The detailed inclusion and exclusion criteria were presented in Supplemental Table The primary exposure of interest was adherence to plant-based dietary patterns, defined as higher consumption of plant-based foods and lower consumption or exclusion of animal-based foods, or changes in plant-based dietary patterns. By this definition, vegetarian or vegan dietary patterns were also considered as plant-based dietary patterns. In studies that classified plant-based dietary patterns using overall, healthful or unhealthful plant-based dietary indices , the association for overall plant-based dietary index was included in the pooled risk estimate. We also summarized studies that explicitly examined healthful or unhealthful plant-based dietary patterns that further de-emphasize the intake of unhealthy plant-based foods, such as refined grains, starchy vegetables , or sugar .For studies that used dietary indices, we used the risk estimate that compared the highest with lowest quantiles, which represent the best (highest quantile) and poorest (lowest quantile) adherence to the plant-based dietary pattern. For studies that compared distinct dietary patterns , we considered the study estimates comparing diets that are most restrictive of animal-based foods (vegan or vegetarian) with the least restrictive, such as omnivorous diets.The primary outcomes were T2D, any CVD, any cancer, and all-cause mortality. In the secondary analysis, we also examined subtypes of CVD , cancer , and mortality .https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools). This tool assigns a maximum score of 14 to each study where 0 indicates that the study does not meet any of the criteria for quality assessments and 14 indicates that the study meets all 14 criteria based on potential areas of bias such as duration of follow-up, assessment of exposure and outcomes, and rates of loss to follow-up. Studies identified with high risk of bias  were excluded in a sensitivity analysis.Data from included studies were independently extracted by three authors . Any discrepancies were evaluated by another author (Q.S.) and discussed among four authors. The following information was extracted from each study: author, year, study name, region, disease outcome, number of participants and cases of incident T2D, CVD, cancer, or deaths, mean age, mean body mass index , sex (percentage of men), follow-up duration, dietary assessment method, method of scoring adherence to plant-based diet, outcome ascertainment, and covariates that were adjusted for in the statistical models. The study quality was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies available on the National Heart, Lung, and Blood Institute website (riskconv package from STATA) ), but not with risks of stroke  and heart failure  , digestive system cancer , pancreatic cancer , and prostate cancer , but not with risks of colorectal cancer , liver cancer , lung cancer , or stomach cancer   and cancer mortality        ; 14% for CVD ; 7% for cancer ; and 16% for mortality .The associations between plant-based dietary pattern and T2D, CVD, cancer, and mortality remained similar when using an inverse-variance fixed-effects model  and a marginally lower risk of mortality   Figs. –S10 [16,P-heterogeneity = 0.02). The association for T2D was stronger in studies that examined vegan or vegetarian diets compared to studies reporting on a priori defined plant-based diets (P-heterogeneity = 0.048). No other sources of heterogeneity were observed for CVD and cancer associations.The stratified analyses by study characteristics are shown in Table P = 0.0001 and P = 0.01, respectively) and CVD (P = 0.04 and P = 0.21); but tests did not detect significant publication bias for cancer (P = 0.12 and P = 0.96) and mortality (P = 0.83 and P = 0.52). After performing the trim-and-fill analysis to evaluate the robustness of associations after accounting for potential publication bias, our results remained largely unchanged. The random-effects pooled RR was 0.84 (95% CI: 0.80–0.90) for T2D, 0.91 (95% CI: 0.86–0.96) for CVD, 0.91 (95% CI: 0.87–0.95) for cancer and 0.83 (95% CI: 0.76–0.90) for mortality  biosynthesis and depleted pathways for processing animal-derived components [Several mechanisms for the favorable effect of plant-based dietary patterns on CVD, cancer, and T2D have been proposed previously. As obesity is the common risk factor for CVD, T2D, and certain types of cancer , a healtmponents . Both thIn addition, plant-based diets contain no or less consumption of red and processed meat, the intake of which has been associated with higher risks of CVD, T2D, and various cancer types such as breast, colorectal, and lung cancers , 68, 69.Our findings have important clinical and public health implications. First, our results suggest that plant-based dietary patterns, especially those based on healthy plant food sources, may be beneficial for the primary prevention of T2D, CVD, cancer, and mortality. A comparative analysis of the health and climate change benefits of global dietary changes projected that moving to diets with fewer animal-sourced foods would result in around 5–8 million avoidable deaths and ~ 200 million life years saved in 2050 . In addiThe main strength of the current study was the comprehensive assessment of all available prospective studies on various outcomes including CVD, cancer, T2D, and mortality. We evaluated adherence to and changes in plant-based dietary patterns and examined the effect of vegetarian diets and plant-based dietary indices. We estimated effects from both overall and healthy plant-based dietary patterns and evaluated overall disease outcomes and specific disease subtypes. We assessed the robustness of the results by using different statistical methods and observed consistent results across various subgroups.Nevertheless, some limitations merit consideration. First, since dietary intake was self-reported using food frequency questionnaire or 24-hour recall in included studies, and majority of the studies did not have repeated measurements of the dietary intake, measurement error and misclassification may exist. However, it is likely to be nondifferential among people who developed CVD, cancer, T2D, or mortality and those who did not, which may result in an underestimation of the true effect size of associations between plant-based patterns and chronic diseases. Second, all included studies were prospective cohort studies; therefore, unmeasured or residual confounding factors cannot be ruled out. In addition, included studies adjusted for different covariates in the multivariable models, had different socio-demographic and clinical characteristics, and thus may contribute to the observed moderate-to-high heterogeneity across studies. However, results from random-effects models were similar to those from fix-effects models, and subgroup results were largely similar. Third, study points on some diseases are limited , and therefore it is unknown whether the observed non-significant association is true or due to the lack of statistical power. Future studies with larger sample sizes are warranted to examine associations of these diseases and plant-based dietary patterns.In conclusion, higher adherence to plant-based dietary patterns, especially from healthy sources, may be universally beneficial for the primary prevention of T2D, CVD, cancer, and mortality. The current analysis provides further evidence in support of the current recommendations that emphasize consuming high-quality plant-based foods for achieving an optimal health. Future studies are needed to elucidate associations for certain individual health outcomes, as well as mechanistic pathways linking plant-based diets with multiple disease outcomes.Below is the link to the electronic supplementary material.Additional file 1Additional file 2


Non-alcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease worldwide. We estimated the prevalence and predefined associated factors for NAFLD among South-Asian adults.We searched PubMed and included descriptive, epidemiological studies with satisfactory methodology, reporting the prevalence of NAFLD with ultrasound. Two authors screened and extracted data independently. Gender, urban/rural settings, general population and individuals with metabolic diseases (MetD) stratified the analysis. In addition, a random-effects meta-analysis of the prevalence and effect sizes of associations of NAFLD was performed.Twenty-two publications were included after the quality assurance process. The difference in the NAFLD prevalence between the general population and people with MetD was found to be statistically significant . The pooled overall prevalence of NAFLD in the general population was 26.9% (95% CI: 18.9–35.8%) with high heterogeneity. The prevalence was similar among men and women . The NAFLD prevalence in the rural communities was 22.6% (95% CI: 13.6–33.1%), and the prevalence in urban communities was 32.9% (95% CI: 22.8–43.8%) and the difference was not statistically significant . The pooled overall prevalence of NAFLD in patients with MetD was 54.1% (95% CI: 44.1–63.9%) with high heterogeneity. The pooled overall prevalence of NAFLD in the non-obese population was 11.7% (95% CI: 7.0–17.3%). The pooled prevalence of non-obese NAFLD in the NAFLD population was 43.4% (95% CI: 28.1–59.4%). Meta-analysis of binary variables showed that NAFLD in the South Asian population was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity and metabolic syndrome. Gender was not associated with NAFLD.The overall prevalence of NAFLD among adults in South Asia is high, especially in those with MetD, and a considerable proportion is non-obese. In the South Asian population, NAFLD was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity, and metabolic syndrome.None. The prevalence of non-alcoholic fatty liver disease (NAFLD) in South Asian countries is high. There have been two previous systematic reviews on NAFLD from the South Asian region. These studies evaluated NAFLD’s prevalence, associations, and phenotype in South Asian countries, including Bangladesh, India, Nepal, Pakistan, and Sri Lanka. However, there has been no meta-analysis of epidemiological data on NAFLD from this region.The present study is the only meta-analysis on the prevalence of NAFLD in the South Asian region. The meta-analysis comprehensively assesses the available data over 17 years (2004–2021). The prevalence of NAFLD among adults in the South Asian region seems comparable to the global average. A considerable proportion of adults were found to be non-obese and NAFLD prevalence was notably higher among individuals with metabolic abnormalities. Diabetes mellitus, hypertension, dyslipidaemia, metabolic syndrome, and obesity  were associated with NAFLD in the South Asian region.The present study highlights the growing burden on NAFLD in the South Asian region, the most populous and densely populated geographical region in the world, with a population of 1.9 billion. Targeted health strategies should be implemented across the South-Asian region to address this growing public health problem of NAFLD and its long-term medical consequences.Non-alcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease worldwide.,Recent studies report the global pooled prevalence of NAFLD at 25.2%, with wide geographical variation worldwide.,The prevalence of NAFLD in South Asian countries is high,There have been two previous systematic reviews on NAFLD from the South Asian region. These studies evaluated NAFLD’s prevalence, associations, and phenotype in South Asian countries, including Bangladesh, India, Nepal, Pakistan, and Sri Lanka. However, there has yet to be a meta-analysis of epidemiological data on NAFLD from this region.In the present paper, studies on the prevalence of NAFLD and its associations in South Asian countries up to May 2021 were searched and included in a meta-analysis. The aim was to estimate the overall prevalence and effect sizes of the associated pre-defined co-factors for NAFLD among adults in the South Asian region.A comprehensive survey on PubMed was carried out for articles published up to May 2021 with information on the prevalences and associated factors for NAFLD in South Asia. The search terms included “Prevalence of NAFLD (Non-Alcoholic Fatty Liver Disease)” AND “South Asia” AND individual South Asian countries . For reporting, we followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines for the conduct of this study .Fig. 1PRThe following inclusion criteria were used to select eligible articles published before May 2021: (1) descriptive, epidemiological studies reporting NAFLD, (2) studies conducted in the South Asian region , (3) studies including adults 18 years of age and over, (4) studies that confirmed NAFLD with an ultrasound imaging and (5) studies published in the English language. In addition, we also included studies reporting NAFLD prevalence among participants with metabolic conditions, such as morbid obesity, diabetes mellitus, metabolic syndrome, and polycystic ovarian disease. The exclusion criteria were: (1) articles in a non-English language, (2) review articles and guidelines, and (3) clinical trials.All the selected studies fulfilled the diagnostic criteria for NAFLD. This included fatty liver detected by ultrasound imaging and exclusion of causes of secondary fatty liver, including unsafe alcohol intake.Two authors  independently screened the title and abstract of all the studies identified to select potentially eligible studies for the meta-analysis. Full texts of eligible articles were retrieved and studied in depth. The final decision on the inclusion of an article was in line with the agreed criteria, and a third author (DSE) resolved disagreements and disparities during the process.The meta-analysis was conducted in two main steps: (i) pooling the prevalence of NAFLD and (ii) pooling the effect sizes of pre-defined associations of NAFLD . In the The following data were extracted from the studies: author name, year of publication, study designs, sample size, age group of participants (>18 years), study setting, diagnostic criteria used for diagnosing NAFLD, characteristics of the study population, and risk category of the participants. Data from selected studies were extracted to estimate pooled rates for the NAFLD prevalence and associations. Two authors performed data extraction independently , and any discrepancies were resolved by discussion with a third author (DSE).Based on the available data, the selected studies were categorised as having a “general population” or “individuals having metabolic diseases”. The “general population” studies had chosen participants from the community with a presumed “average risk” of NAFLD. On the other hand, studies with “individuals having metabolic diseases” had participants with a metabolic derangement  with presumed “high risk” for NAFLD. The studies that were identified as “general population” were further divided into “rural” and “urban”.−2) were included in the general obese category. Similarly, participants directly categorised as having central obesity and participants with “high” waist circumference  were included in the category of central obesity.Factors associated with NAFLD were extracted from the selected articles, after which, frequently reported factors were considered for pooling in the second step of the study. The selected factors were: male gender, general obesity, central obesity, diabetes mellitus, dysglycaemia, hypertension, dyslipidaemia and metabolic syndrome. Since studies reported different forms of glycaemic abnormalities, the term “dysglycaemia” was also used to combine diabetes mellitus, hyperglycaemia, and insulin resistance. However, the cut-off values for dyslipidaemia varied across the selected articles. Therefore, the participants, (i) who were already categorised as having hypertriglyceridemia/dyslipidaemia/high triglyceride (TG) levels or low high-density lipoproteins (HDL) on treatment, (ii) TG levels above 150 mg/dL or (iii) HDL below 40 mg/dL were included in the category of dyslipidaemia. As varying definitions have been used for general obesity, the participants who were directly categorised as obese in the study and participants with a BMI above the Asia-Pacific cut-off value , gender  and study settings . Therefore, the overall NAFLD prevalence (pooled estimates) across the studies was determined by performing a random-effects meta-analysis of proportions using the Der Simoniane Laird model. The number of NAFLD patients amongst the total number sampled in each study was considered for the analysis, and inverse variance weighting was used to pool the studies.2 = 98.8%, Q = 1845.36, DF = 22, P < 0.001). The overall NAFLD prevalence was 40.4% (95% CI: 33.1–47.9%) when all the studies were considered together. There were 11 studies representing the “general population”  and 12 studies from “individuals with metabolic disease” (2943 participants and 1367 NADLF cases), including three studies with overweight or obese NAFLD populations and one with a morbidly obese population. Subgroup analysis showed a difference in the prevalence rates between the general population and people with metabolic diseases and the difference was found to be statistically significant . Therefore, a separate analysis was conducted for the general population and people with metabolic diseases  within general and urban populations. Subsequently, the reported associated factors  were evaluated to obtain pooled estimates for risk ratios using random-effects models. This was done by conducting a meta-analysis of binary variables where the number of NAFLD cases amongst people with and without the given risk factor was evaluated. Forest plots were developed to summarise the results of the meta-analysis, and the publication bias was assessed and visualised using a funnel plot. A P value of 0.05 was considered statistically significant. Data was analysed using R programming language 3.6.3 and a meta-analysis of proportions was carried out using the “meta” library. Outliers and influential cases were identified using “dmetar” library. Risk of bias plots and traffic light plots were obtained from “robvis” library.Not applicable.A total of 158 articles were identified during the initial literature search. We included descriptive epidemiological studies with satisfactory methodological quality, reporting the prevalence of NAFLD with a valid diagnostic method.Only 22 publications  were included in the subsequent meta-analysis after the quality assurance process , Table 2The quality assessment of the selected studies for the meta-analysis is presented in 2 = 99.1%).Eleven studies reported NAFLD prevalence rates in the general population from Bangladesh, India, Nepal, Pakistan, and Sri Lanka. There were 12,512 individuals, including 3374 NAFLD cases. The pooled overall prevalence of NAFLD in the general population was estimated as 26.9% (95% CI: 18.9–35.8%) . The preThe general population included 5939 males and 6000 females. The overall NAFLD prevalence among males was 23.9% (95% CI: 17.6–31.0%), and among females was 22.7% (95% CI: 15.3–31.3%). The subgroup analysis did not show gender differences in the NAFLD prevalence rates  . There w2 = 96.4%).Twelve studies reported NAFLD prevalence rates in people with metabolic disorders from Bangladesh, India, Pakistan, and Sri Lanka. There were 2943 individuals, including 1367 NAFLD cases. The pooled overall prevalence of NAFLD in patients with metabolic diseases was 54.1% (95% CI: 44.1–63.9%) . The pre,,From these studies, data were available for 1209 males and 1341 females. One study had only males,2 = 97.1%, 2 = 97.2%, Six studies provided data on non-obese NAFLD, which included 5612 non-obese participants and 651 non-obese NAFLD cases. The pooled overall estimate for prevalence of NAFLD in the non-obese population was 11.7% (95% CI: 7.0–17.3%)  for each associated factor from random effect models is shown in This meta-analysis involved 22 studies, with 15,455 participants and 4741 NAFLD cases from five South Asian countries . We estimated that the pooled prevalence of NAFLD among adults in the general population was 26.9%. Our estimated pooled prevalence of NAFLD in South Asia is comparable to the estimated global prevalence of 25.4%.Estimating the prevalence of NAFLD in the general population (with average risk) is challenging as the disease is mainly asymptomatic. However, the current study determined that the overall prevalence of NAFLD among the general population, excluding those with metabolic diseases, was 26.9%. This finding highlights the high proportion of apparently metabolically normal people in the community with NAFLD. Furthermore, there was no difference between prevalence estimates for NAFLD in the current study between males and females as well as residents of urban and rural communities.In the current meta-analysis, the pooled prevalence of NAFLD among individuals with metabolic diseases with high risk was 54.1%, significantly higher than the prevalence in the general population. The pooled prevalence of NAFLD among individuals with metabolic disorders is comparable with the estimated global prevalence of NAFLD among patients with Type 2 diabetes mellitus, 55.5%.,,,2) may still have central obesity, evidenced by increased WC, reflecting an increase in visceral fat. Studies have demonstrated that visceral fat, originally considered a passive depot for energy storage, is an active endocrine tissue that releases many mediators that regulate metabolism, inflammation, and immunity that is also involved in the pathogenesis of NAFLD. The increase in visceral fat is closely related to the presence of fatty liver, liver inflammation and fibrosis.,15,A major proportion of South Asian NAFLD patients are non-obese. This paradox,,Before the present study, only a limited number of studies evaluated the prevalence of NAFLD in South Asia. A review article on NAFLD in South Asia in 2016 estimated the epidemiology and determinants of NAFLD in different South Asian countries, including India, Sri Lanka, Bangladesh, Pakistan and Nepal.The most recent review article on NAFLD in South Asians, published in 2017, was based on a comprehensive search of available articles on NAFLD in South Asian countries from 1980 to 2016.At the time of the final analysis of our study, a systemic review and meta-analysis of the prevalence of NAFLD in India was published by Lee and colleagues.Another recent study by Kam and colleagues reported clinical profiles of Asians with NAFLD.Our study has several strengths and limitations. The present study is the only meta-analysis on the prevalence of NAFLD in the South Asian region and the meta-analysis comprehensively assessed the available data over 17 years (2004–2021). We have performed sub-analyses for the general population, rural and urban settings, non-obese populations, and those with metabolic abnormalities. For uniformity, we selected only studies that diagnosed NAFLD based on abdominal ultrasound for the meta-analysis. We conducted an extensive quality assessment of the studies included in the analysis. Only epidemiological studies with satisfactory methodological quality were included to minimise the heterogenicity and risk of bias.A major limitation of our study is the lack of data from three South Asian countries , which limits the generalisability of our findings beyond the countries included in the analysis. We avoided including further data from abstracted publications to expand the results across the region due to the potential lack of quality of those data. Also, the information on alcohol consumption was obtained by direct questioning of the participants in the studies included in the analysis. This may have led to under-reporting of alcohol use patterns with consequent overestimation of the prevalence of NAFLD. Furthermore, we could not evaluate age as a risk factor for NAFLD due to lack of individual data in most studies. All the studies considered for the meta-analysis did not include all the associated factors assessed for NAFLD. Therefore, we could only conduct univariable meta-analyses of associated factors as there were not sufficient data for a meta-regression analysis. Hence, the analysis of associated factors should be interpreted as exploratory analysis.Furthermore, the current study was limited to available data among adults, excluding the paediatric and adolescent populations. According to the reported pooled prevalence of NAFLD in the paediatric and teenage population,,Elastographic techniques are widely adopted and recommended by guidelines for assessing NAFLD. Transient elastography (TE) permits the simultaneous measure of steatosis by controlled attenuation parameter (CAP) and liver fibrosis by liver stiffness measurement. A few studies on NAFLD using TE were not included in the systematic review, as the researchers believed insufficient studies used TE and CAP specifically conducted in the South Asian population.The prevalence of NAFLD among adults in the South Asian region seems comparable to the global average and a considerable proportion of adults were non-obese. NAFLD prevalence was notably higher among individuals with metabolic abnormalities. Diabetes mellitus, hypertension, dyslipidaemia, metabolic syndrome, and obesity  were identified as associated factors of NAFLD in the South Asian region. Well-designed community-based studies are needed to assess NAFLD prevalence across the South Asian region to plan resource allocation to mitigate the disease burden. Targeted health strategies should be implemented across the South-Asian region to address this growing public health problem.MAN and DSE conceptualised the study. MAN, MYW, SD, DSE and HJdeS formulated the methodology. MAN, MYW, SD and STDeS extracted the data. DSE and SD analysed the data. MAN, SD and DSE drafted the manuscript. STDeS and HJdeS critically analysed and revised the manuscript. All authors read and approved the final manuscript.Data supporting this meta-analysis can be obtained through corresponding author on special request.None.


Gastric cancer has a complex aetiology including genetic factors. Individual case-control studies of toll like receptor (TLR) 9  polymorphisms in the gastric cancer risk were available, and they showed variation in the findings. Therefore, we performed a meta-analysis to synthesize the evidence on the association between polymorphisms of TLR 9  and the risk of gastric cancer using data from eligible studies.This study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed.I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38–4.09, I2 = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer . Under the heterozygous model, there was no significant association with the risk of gastric cancer overall or among any ethnic subgroup. Under the homozygous model in the absence of heterogeneity, only the Asian group had a significantly higher risk of gastric cancer . Under the allele model, a significantly increased risk of gastric cancer was observed only in the Asian group . Four studies investigated the association between TLR 9 (-1237 T/C) polymorphism and the risk of developing gastric cancer. Under any of the five genetic models, there was no association between TLR 9 (-1237 T/C) and the development of gastric cancer in overall or in any ethnic subgroup. Sensitivity analysis revealed that the effect was unstable. With a small number of studies with a small number of participants, we addressed the issue of insufficient power for drawing conclusions.Eight case-control studies with 3,644 participants  were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating . TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer  may play a role in the risk of gastric cancer specific to the Asian ethnic group. To substantiate the findings on the association between these two polymorphisms  and the risk of gastric cancer, future well-designed case-control studies with a sufficient number of participants in multi-ethnic groups are recommended.The online version contains supplementary material available at 10.1186/s12885-023-11509-7. Helicobacter pylori (H. pylori) colonization as risk factors for the development of gastric cancer, which modify the nature and extent of gastrointestinal disorders . Publication bias was not done due to the presence of eight studies only. Data analysis was done with RevMan 5.4 (Copenhagen), and Figure Eight studies (nine datasets), incorporating 3,644 participants  across nine countries that assessed the association of two TLR 9 polymorphisms  were eligible for the current analysis. The main characteristics of the eight included studies is provided in Table I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00–1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38–4.09, I2 = 89%)  . Under the homozygous model, a significantly increased the risk of gastric cancer was observed only in the Asian group    investigated the association between polymorphism of TLR 9 (-1486 T/C) and the gastric cancer risk , 29–31. I2= 85%; Asian: OR = 3.19, 95%CI = 0.96–10.56, I2 = 0%, non-Asian: OR = 1.23, 95%CI = 0.67–2.28, I2 = 87%)  assessed the association between this polymorphism and the gastric cancer risk , 28, 30.We conducted a leave-one-out sensitivity analysis by sequentially discarding one study at a time due to variations in sample size, genotyping techniques, and the presence of small studies. The results of the sensitivity analysis revealed that the effect estimates were unstable. For instance, TLR 9 (-1237 T/C) and the risk of gastric cancer among non-Asians and the overall group were significantly related under the allele model . None hThe estimates for all five genetic models were reanalysed after a study that departed from HWE in TL9 -1486T/C)  was remo86T/C  waGiven the association between inflammation and carcinogenesis, candidate gene approaches are becoming more and more attractive for identifying genes that may initiate and progress inflammation-associated carcinogenesis, particularly gastric cancer, in the gastrointestinal tract. In this meta-analysis, we evaluated the influence of two prominent SNPs (1237 C/T and − 1486 T/C) in the TLR9 gene on the risk of gastric cancer across six countries.H. Pylori infection [H. pylori infection, but it does not appear that they determine what happens subsequently in the development of cancer [A previous review that included two case-control studies on gastric cancer revealed a lack of statistical significance between TLR 9 -1237 T/C) and the risk of gastric cancer employing the selected inheritance model . This is37 T/C anf cancer . NotableH. pylori infection status. Due to the inconsistent manner of reporting, we were unable to do meta regression with common covariates. Moreover, in small studies identified by the current analysis, a statistically significant finding would actually be a false-positive report probability (FRPP). The FRPP, which is the probability of no association between a genetic variant and a disease  gives statistically significant results in terms of the observed p value, the prior probability that the association between the genetic variant and the disease  is real, and the statistical power of the test [There are several limitations that should be acknowledged. First, the sample sizes in the current study were small. For example, less than ten studies were identified, and only one study included the Asian-subgroup in TLR 9 (-1237 T/C). Hence, a type II error is a concern. We acknowledge the issue that there may be more specific ethnic differences that exist amongst populations in the same country. Also, there might be a common confounding factor such as age, gender, the test . We inclThe included studies used different genotyping methods, which might be associated with different genotyping success rates and data quality. However, genotyping errors are expected to be small, and thus the resulting biases are likely to be small . As the H. Pylori infection.Based on limited data presented in this review, we still do not confirm whether TL9 gene polymorphisms (-1237 T/C and − 1486 T/C) increase or reduce the risk of gastric cancer. Our analysis highlights the need for additional studies on the role of the TLR 9 gene polymorphisms in the risk of gastric cancer, and the findings should be used to inform healthcare providers considering screening for genetic risk factors. Such research could aid in identifying patients who have considerably higher risks of disease progression and may guide the development of customized prevention and management plans for The findings suggested that TLR9 (-1237 T/C and − 1486 T/C) have some roles in the associated risk of gastric cancer. The information size was inadequate to achieve confirmatory evidence. Future well-designed case-control studies with an adequate number of participants in multi-ethnic groups, stratified with common factors, are recommended to substantiate the evidence on the relationship between these two polymorphisms and gastric cancer risk.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Supplementary Material 3Supplementary Material 4Supplementary Material 5Supplementary Material 6


Based on subgroup analyses, it was observed that the impact of a low-ratio LA/ALA diet on elevated plasma insulin  and HOMA-IR  levels exhibited greater prominence in North America compared to Asian and European countries. Publication bias was not detected for FBS, insulin, HOMA-IR, and HbA1c levels according to the Begg and Egger tests. Furthermore, the conducted sensitivity analyses indicated stability, as the effects of the low-ratio LA/ALA diet on various glycemic and related metrics remained unchanged even after removing individual studies. Overall, based on the available studies, it can be concluded that the low-ratio LA/ALA diet has limited impact on blood glucose-related biomarker levels.The objective of this meta-analysis was to examine the impact of a low-ratio linoleic acid/α-linolenic acid (LA/ALA) diet on the glycemic profile of adults. A comprehensive search was performed across four databases  to evaluate the influence of the low-ratio LA/ALA. Relevant references were screened up until February 2023. Intervention effects were analyzed by calculating change values as weighted mean differences (WMD) and 95% confidence intervals (CI) using fixed-effects models. Additionally, subgroup analysis and meta-regression were employed to investigate potential sources of heterogeneity. Twenty-one randomized controlled trials (RCTs) were included, and the low-ratio LA/ALA diet had no significant effect on fasting blood sugar (FBS, WMD: 0.00 mmol/L, 95% CI: −0.06, 0.06,  Diabetes is a prevalent chronic disease characterized by abnormalities in glucose metabolism, and its global incidence is on the rise. According to the International Diabetes Federation (IDF), the global prevalence of diabetes was estimated to be 10.5%  in 2021, with projections indicating a rise to 12.2%  by 2045 ,7.Strategies such as dietary patterns, individual nutrients and lifestyle are effective in the prevention and management of diabetes . The quaAlthough LA and ALA are some of the most common forms of PUFA supplementation, the complete metadata on the relationship between LA/ALA ratio and glycemia are still lacking. Consequently, the objective of this study was to comprehensively assess and compare the impacts of the low-ratio LA/ALA diet on FBS, insulin, HbA1c, and HOMA-IR using randomized controlled trials (RCTs) as the basis.To ensure that the study was conducted and reported in a systematic manner, we adhered to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive search was performed on four electronic databases, namely Web of Science, Scopus, Embase, and PubMed, up until February 2023. The search strategy employed is elaborated upon in In order to be included in this review, studies had to meet specific criteria. These criteria included (1) focusing on the impact of LA/ALA ratio  on various biological markers related to blood glucose control, such as FBS, insulin, HOMA-IR, and HbA1c; (2) the study participants consisted of individuals aged 18 years or older; (3) the intervention duration lasted at least two weeks; (4) the primary outcomes of articles reported sufficient information on baseline and final study; (5) the LA/ALA ratio was explicitly reported in the article, or it could be obtained by proper calculation; (6) to isolate the specific impact of the LA/ALA ratio on glucose, the included studies differentiated it from the influence of other dietary sources or interventions, such as fish oil, and conjugated linoleic acid (CLA), and physical activity programs. This approach allowed for a more focused analysis of the independent effects of the LA/ALA ratio on blood glucose control, minimizing confounding factors that could potentially influence the results.Two researchers independently conducted the data extraction based on the predefined inclusion criteria. The Cochrane Risk of Bias tool was employed to assess the methodological quality of the included studies. In case of any disputes, the original literature was re-evaluated to ensure accuracy and consistency. If there were any disagreements or conflicts during the study selection, a third reviewer was consulted to establish a consensus and resolve any discrepancies. The following data were extracted from each eligible study: the first author’s name, publication year, country where the study was conducted, type and duration of the intervention, total number of participants, participants characteristics , protein, carbohydrates, and fat  as percentage of total energy, LA/ALA ratio, and the mean and standard deviation (SD) changes in blood-glucose-related biomarkers at pre-treatment and post-treatment. In cases where multiple articles reported the same outcomes, preference was given to the article with the largest number of participants and longest duration for inclusion in the review.change = square root [(SD pre-treatment)2 + (SD post-treatment)2 − (2R × SD pre-treatment × SD post-treatment)] (R = 0.5). Moreover, when data were solely presented graphically, the relevant information was digitally extracted and quantified using the GetData Graph Digitizer software (GetData 2.25). The statistical significance of net changes was assessed using the weighted mean difference (WMD) with a 95% confidence interval (CI). The level of heterogeneity was classified as low (I2 ≤ 50%) or high (50% < I2), accordingly. Sensitivity analysis was conducted to investigate potential sources of heterogeneity, where each study was individually excluded to assess the impact of any specific study on the overall validity of the effect size. We utilized Begg’s tests, Egger regression tests, and visual calculations using funnel plots to evaluate possible publication bias. Furthermore, predetermined subgroup analyses were conducted to examine association between different subgroups and glucose. A p value below 0.05 was used to assess the statistical significance.Endnote software (Endnote X9.1) was employed to process the article, eliminating any duplicate entries. Subsequently, the screening and full text review were conducted using Microsoft Excel software (Microsoft Excel 16.0). To conduct the primary analysis, sensitivity analyses, and assess publication bias, we utilized STATA software . Mean (SD) were extracted to perform a combined effect size analysis. Conversion formulas were utilized to calculate SD in situations where they were not directly provided . If the A total of 12,184 publications were initially searched from four databases, and 8769 articles were retained after eliminating duplicates. Subsequently, 217 articles were selected for full-text examination based on the titles and abstracts. Ultimately, 21 articles were included in this meta-analysis ,43,44,45A detailed summary of the characteristics of the eligible trials is provided in The Cochrane Collaboration Risk of Bias Tool was utilized for the quality assessment of the included studies . Ten artp = 0.989). The I2 test indicated no statistically significant heterogeneity among the included studies . p = 0.360). The included trials exhibited non-significant heterogeneity . p = 0.243). Heterogeneity was not significant, as indicated by the I2 value . The forest plot of HbA1c is shown in p = 0.836). Additionally, no substantial heterogeneity among the included trials was observed .The forest plot of FBS is shown in p = 0.058), insulin (p = 0.844), HOMA-IR (p = 0.815), and HbA1c (p = 0.371). Similarly, the Egger’s test showed no publication bias for FBS (p = 0.149), insulin (p = 0.669), HOMA-IR (p = 0.841), and HbA1c (p = 0.523).To assess the influence of individual studies on the overall effect size, we conducted sensitivity analyses by sequentially excluding each trial from the analysis. The pooled effect size for the remaining studies, excluding the current study, is indicated by the circles in p = 0.037, I2 = 32.0%). However, low-ratio LA/ALA supplementation had no significant effect on insulin level in Asia  and Europe . Studies stratified by health status showed a combined effect, showing significantly lower HbA1c level in subjects with polycystic ovary syndrome . When the trials were categorized by region, the comprehensive analysis revealed a significant increase on HOMA-IR among subjects in North America  and an increase, but not a significant one, among subjects in Europe  and Asia .Subsequently, we conducted subgroup analyses to stratify the studies based on LA/ALA ratio , region, health status, age , BMI (<12 and ≥12 weeks), smoking, and duration (<12 and ≥12 weeks), as indicated in p = 0.386; LA/ALA ratio: p = 0.781; age: p = 0.214; BMI: p = 0.732). Similar findings were observed in the meta-regressions analyzing insulin and its continuous confounders , as well as in the meta-regressions examining HOMA-IR and its continuous confounders . However, due to the limited number of included studies (less than 10), a meta-regression for HbA1c was not conducted.To evaluate possible linear associations between the combined effect and continuous confounding factors , we conducted meta-regressions. Our analysis revealed no significant linear relationships between FBS and intervention duration, LA/ALA ratio, age, and BMI in the included studies (intervention duration: Despite the compelling evidence indicating the association between ALA and reduced cardiovascular disease (CVD) risk , as wellSeveral studies have reported that after dietary intake of low-ratio LA/ALA, FBS decreases ,43,51,52In the subgroup with polycystic ovary syndrome (POS), the low-ratio LA/ALA supplementation had a significant effect on the reduction of HbA1c level. Kalgaonkar’s study showed that 31 patients with POS received a diet containing 31 g of total fat per day with walnuts or almonds for 6 weeks. The walnut group reduced the low-ratio LA/ALA in the ration and plasma phospholipids, increasing insulin by 36 pmol/l and reducing HbA1c by 0.2% . AnotherNo significant differences were observed in the outcomes across the subgroups when grouping was based on the LA/ALA ratio. In the subgroups with low-ratio LA/ALA greater than 5, results were worse for all markers of glycemic control. In the range of LA/ALA ratio less than 1, levels of FBS and Insulin were decreased but not significantly. In the subgroups with the low-ratio LA/ALA greater than 1 less than 5, levels of FBS and HbA1c were decreased but not significantly. This suggests that the high-ratio LA/ALA may have a negative impact on diabetes. These findings align with a prior systematic review, which also found that the subgroup with a n−6/n−3 PUFA ratio of less than 5 exhibited tendencies towards improvements in FBS, insulin levels, and insulin resistance .When the intervention duration extended beyond 12 weeks, there was a tendency for a decrease in FBS, albeit not statistically significant. Conversely, when the intervention duration <12 weeks, the results showed the opposite trend. Despite the lack of statistical significance, it appeared that the low-ratio LA/ALA diet had a tendency to improve FBS level as compared to the high-ratio LA/ALA. This suggests that long-term treatment may have a stronger positive effect. Dietary intake of 9.5 g ALA for 6 months improved glycemic and lipid-related markers . Data frMost of the existing meta-analyses are mostly limited to analyzing the effect of ALA on diabetes risk and blood glucose. The current study represents a novel contribution by systematically investigating the correlation between plant-derived LA/ALA ratio and various glucose-related biomarkers. Notably, this study included high-quality summary statistics derived from a substantial sample size of 1415 subjects enrolled in 21 independent RCTs across 13 different countries. Furthermore, the robustness of the findings was supported by sensitivity analyses, and the absence of significant publication bias was demonstrated by Begg’s test and Egger’s test. However, it is important to acknowledge the limitations and shortcomings of our meta-analysis. Firstly, all the trials included in our analysis were conducted for relatively short durations, generally not exceeding 6 months. Therefore, the long-term impacts of dietary fat of the low-ratio LA/ALA on blood glucose level remain a topic that warrants further exploration in future research. Additionally, it should be noted that energy expenditure and the proportions of different types of FA were not constant across all the intervention periods in the included trials. These factors could potentially introduce variability and influence the outcomes of our analysis. It is worth noting that the FA compositions and other bioactive components can vary among different sources of LA and ALA. Thus, it remains necessary to investigate whether these factors mentioned above have an influence on the impacts of the LA/ALA ratio. Additionally, a significant proportion of the studies considered in our analysis consisted of limited sample sizes, frequently comprising less than 100 participants. Furthermore, the use of crossover (CO) designs in certain trials to bolster the effective sample size may have introduced certain complexities that could have impacted the overall outcomes. Insufficient data and imprecise categorization in certain studies might have compromised the subgroup analyses.The types of FA in the diet are complex, and rarely are LA or ALA ingested singly. This systematic review and meta-analysis pooled 21 RCTs of low-ratio LA/ALA diet, encompassing 1415 subjects in 13 countries. The results found no effect of low-ratio LA/ALA diet on FBS, insulin, HOMA-IR, and HbA1c. Plasma insulin and HOMA-IR levels were significantly higher in North American patients on a low-ratio LA/ALA diet, compared to Asian and European regions. To comprehensively assess the prolonged impacts of low-ratio LA/ALA diet, it is imperative to incorporate additional RCTs encompassing diverse geographical regions and ethnicities.


The association between uterine artery Doppler (UtA) measurements and small for gestational age (SGA) has not been quantitatively analyzed throughout the whole pregnancy. This systematic review and meta-analysis aims to comprehensively explore the association between UtA measurements and SGA in the first, second, and third trimesters.2 statistics. Sensitivity analysis was conducted for all outcomes, and publication bias was evaluated using Begg’s test.Studies were searched from Pubmed, Embase, Cochrane Library, and Web of Science. Weighted mean difference (WMD), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were used as the effect size. Heterogeneity of all effect sizes was tested and quantified using IP < 0.05). In the third trimester, PI z-score  and PI MoM  showed a significant increase in the SGA group. The odds of SGA were higher in the women with mean PI > 95% .A total of 41 studies were finally included in our meta-analysis. In the first trimester, mean PI was significantly higher in the SGA group than the non-SGA group . In the second trimester, odds of notch presence , mean PI , and mean RI  were higher in the SGA group. Also, abnormal UtA measurements were associated with the increased odds of SGA (all Abnormal UtA measurements were associated with high odds of SGA, suggesting that UtA might be an adjunctive screening method for SGA in the whole pregnancy.The online version contains supplementary material available at 10.1186/s12884-023-05968-w. Small for gestational age (SGA) refers to the fetal birth weight ≤ 10th percentile according to local standards .Uterine artery Doppler (UtA) has been used to assess the risk of SGA in pregnant women . StudiesMeta-analysis is a powerful tool to combine results from two or more separate studies, which shows a good evidence strength and facilitates healthcare decision-making , 7. A syThis meta-analysis was performed based on the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guideline . Pubmed,Only studies meeting the following criteria were included: (1) patients: women with single pregnancy; (2) intervention and control: abnormal UtA group vs. normal UtA group or SGA group vs. non-SGA group; (3) outcome: SGA; (4) study design: case–control studies and cohort studies.The UtA parameters we observed in this study were mean UtA-PI, mean UtA-RI, multiple of median (MoM) values of UtA-PI (UtA-PI MoM), UtA-PI z-score, and notch presence. PI was calculated as (peak systolic velocity-end diastolic velocity)/average velocity, and RI was calculated as (peak systolic velocity-end diastolic velocity)/peak systolic velocity. Mean PI and RI were the average from the left and right uterine arteries . Notch pThe following exclusion criteria were adopted: (1) animal studies; (2) studies irrelevant to the topic ; (3) reviews, meta-analyses, case reports, protocols, conference abstracts, guidelines, and expert consensus; (4) not published in English.Two researchers (RJZ and XPT) independently evaluated the data suitable for this meta-analysis, and extracted the following information: the first author, publication year, country, study design, group, sample size, age, body mass index (BMI), birth weight, gestational age, complications, smoking, and Doppler time. If conflicts existed, a third researcher (HEL) provided the consultation.The quality of case–control studies and cohort studies was assessed using Newcastle–Ottawa Scale (NOS) . For cas2 statistics. If the heterogeneity statistic I2 ≥ 50%, random effect model was used for analysis; otherwise, fixed effect model was used for analysis. Sensitivity analysis was performed to assess the effect of a single study on the whole estimate by removing studies one by one. Publication bias was assessed using Begg’s test for the outcomes included in more than nine studies [ P < 0.05 was considered to be statistically significant.Weighted mean difference (WMD) with 95% confidence interval (CI) was used as the effect size for measurement data, and odds ratio (OR) with 95%CI was used as effect size for counting data. If relative risk (RR) was provided in the publications, RR was combined for analysis. Heterogeneity was tested for all effect sizes and quantified using the I studies . All stahttps://gdt.gradepro.org/).The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The GRADE system categorized the certainty of the pooled estimate of effect as high, moderate, low, or very low according to the following criteria: study design, risk of bias, inconsistency, indirectness, imprecision, and other considerations. An evidence profile was produced to summarize the results using the GRADEpro GDT (n = 258), studies irrelevant to the topic , and reviews, meta-analyses, case reports, protocols, conference abstracts, guidelines and expert consensus (n = 856) were eliminated. After screening the full texts, 179 studies were removed due to irrelevant to the topic (n = 153) or not published in English (n = 24). Finally, 41 studies were included in our meta-analysis   or RI > 95% . Dugoff et al. reported that the risk of SGA incidence was higher in RI > 90% group compared to RI ≤ 90% group . In the P = 0.974).Sensitivity analysis showed that no study displayed an important effect on the final pooled UtA measurements and SGA incidence Tables  and 2. TWe used GRADE to assess the level of evidence. The results showed very low level of evidence for all outcomes , maternal smoking, and history of SGA may be the sources of heterogeneity. However, we were unable to perform the subgroup analysis to explore the sources of heterogeneity because the above factors could not be analyzed based on the included studies. Third, SGA is defined as fetal birth weight ≤ 10th percentile of the standard weight of the fetus at the same gestational age. In included studies, standard weight varies from region to region, which may cause some bias on the results. Fourth, the method of conception of the included pregnancies is likely heterogeneous. UtA-PI values are significantly different in pregnancies after different conception method . Fifth, In conclusion, our meta-analysis found a significant association between abnormal UtA measurements and increased odds of SGA in the whole pregnancy, indicating that UtA might be an adjunctive screening method for SGA in the whole pregnancy.Additional file 1:Supplementary table S1. Newcastle-Ottawa Scale assessment for cohort studies. Supplementary table S2. Newcastle-Ottawa Scale assessment for case-control studies. Supplementary table S3. Certainty of evidence for the included studies.


To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China.® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity.A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette–Guérin (BCG) vaccination history was a protective factor.A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access.A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4Registered on PROSPERO, Identifier: CRD42022297754.The online version contains supplementary material available at 10.1186/s12879-023-08575-4. Human immunodeficiency virus (HIV) infection is a major global public health issue, with 650 000 deaths from HIV-related causes reported in 2021 . TB can China has a large number of PLHIV and is one of the high-burden countries for TB. Epidemiological research has shown the presence of 1.14 million PLHIV , 58 53403 [HIV infection results in immune homeostasis perturbations, which is characterized by CD4 + T-cell depletion and immune activation . High in3 . The cas3 , 13, Ind3 . In addi3 . Prevale3 . An inst3 . A study3 . BCG is 3 .The lack of updated data on HIV/TB co-infection in China makes assessing the current prevalence and burden of the disease inadequate and results in ineffective policy making. Study period, sample source, place of study, and zone were significantly associated with the co-infection rate , 21. WHOThis systematic review and meta-analysis were designed, conducted, and reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines . This st®, EMBASE, Web of Science, and The Cochrane Library, were searched for HIV/TB co-infection-related publications from inception up to October 2022. Keywords and MeSH terms synonymous with “HIV”, “acquired immunodeficiency syndrome”, “tuberculosis”, “coinfection”, “comorbidity”, “prevalence”, and “risk factors” were used to identify suitable articles in the initial search. References were imported into EndNote™  for the initial screening, and duplicates were removed. In addition, reference lists from previous related reviews were screened to ensure a comprehensive search , Weipu database (VIP), WanFang Data, China Biology Medicine disc (CBM), PubMedThe inclusion criteria were as follows: (i) articles that reported Chinese studies with an observational method, which included cross-sectional, case–control, and cohort studies; (ii) study population comprising both adults and children with HIV/AIDS; (iii) studies reporting prevalence and risk factors; (iv) multiple studies from the same sample source included in the study with detailed data; (v) articles written in Chinese or English; (vi) research results related to risk factors expressed as relative risk or odds ratio (OR), provision of a 95% confidence interval (CI). The exclusion criteria were as follows: (i) articles that are periodic reports of a study, with complete results of the study reported in other articles; (ii) special samples that do not represent the general population, such as individuals with drug addiction and prisoners; (iii) studies with incomplete data, unclear data, or obvious errors; (iv) literature reviews, case reports, animal studies, and conference abstracts; (v) studies with a sample size < 100.A data extraction table was created using Microsoft Excel . The following data were extracted from the literature: first author, title, publication year, study period, disease diagnostic criteria, study area, study design, number of PLHIV, number of cases of HIV/TB co-infection, sex, age, sample source , and risk factors. Two evaluators (M.L. and Y.Z.) independently screened the literature, extracted data, evaluated the quality and cross-checked the data. Discrepancies were resolved through a centralized discussion or via consultation with a third-party expert (L. X.).The methodological quality of any included cross-sectional studies was assessed according to 11 criteria recommended by the American Agency for Healthcare Research and Quality . Statistical heterogeneity was assessed using the I2 test. Sources of heterogeneity were studied by subgroup analysis. This was performed using the sample size, publication time, research area, detection rate, and sample source. Furthermore, to investigate whether the prevalence of HIV/TB co-infection had changed over time, meta-regression analysis was performed to assess whether publication time was a factor for the source of heterogeneity. A funnel plot and Egger’s test were used to analyze the publication bias in the studies included. A P-value < 0.05 was considered statistically significant. The trim-and-fill method was used to identify and correct potential publication bias. In addition, sensitivity analyses were conducted to determine whether the inclusion/exclusion of studies led to conceptual differences that affected the final conclusions.The combined prevalence and OR of 95% CI were calculated by meta-analysis using STATAA total of 5241 studies were retrieved by the database searches. After removing duplicates and screening titles, abstracts and full-text, 44 studies (38 Chinese and six English studies) were included . The random-effects model was used to pool the data. Meta-analysis showed that the prevalence of TB among PLHIV in China was 6.0%  . Sensitivity analysis was performed by excluding studies individually. The results did not change significantly  and Egger’s test  suggested the absence of publication bias , smoking , intravenous drug use , unemployment , male sex , senior citizen status , advanced WHO stage , low education level , presence of other opportunistic infections , history of TB , engagement in commercial sex , age 30–45 years , and a long history of HIV . The protective factor was a history of Bacillus Calmette–Guérin (BCG) vaccination . No significant association was observed between low-income families (P > 0.05) among PLHIV.Fourteen risk factors with more than one occurrence and one protective factor were selected from 19 studies for the meta-analysis Table  30, 35,, 56–69. Forty-four studies were included in the current meta-analysis, and data from 30 studies were used to analyze the prevalence of HIV/TB co-infection, which was 6.0%. An earlier pooled study published data collected from 1999 to 2010  . The curThe results of statistical analysis are related to the sample size. A sample size less than 50 is considered very poor, a sample size less than 100 is considered poor, a sample size of approximately 200 is considered normal, a sample size of approximately 300 is considered good, a sample size of approximately 500 is considered very good, and a sample size of approximately 1000 is considered ideal; hence, the division by 1000 . Per theIn recent years, the prevalence rate of HIV/TB co-infection has decreased significantly from 6.6 to 5.5%, which indicates that local governments have paid more attention to this issue. However, the prevalence in the western region was higher than that in the central region, and that in the central region was higher than that in the eastern region. This may be related to the economic conditions of the country. More economically deprived regions have a higher incidence of HIV and a greater risk of concurrent TB . Of the + T cell count ≤ 200/µL, smoking, intravenous drug use, unemployment, male sex, senior citizen status, advanced WHO stage, low level of education, and presence of other opportunistic infections increased the risk of TB among PLHIV. CD4+ T cells are major immune cells in the human immune system and are the primary target of HIV. A decrease in the CD4+ T cell count weakens the immunity; this can lead to various infections. Smoking reduces lung function and destroys the mucous membranes and immune barriers of the respiratory tract. A previous study showed that smoking is associated with disease recurrence and death in patients with TB [Nineteen studies were used to analyze the risk factors of HIV/TB co-infection in the current study. The results showed that CD4 with TB . Drugs d with TB . Individ with TB . Unemplo with TB .Mycobacterium tuberculosis [M. tuberculosis granulomas [M. tuberculosis and effectively enhance immunity after vaccination to decrease the incidence of TB [The findings of this current meta-analysis demonstrated that patients with advanced WHO stage and a long history of HIV and other opportunistic infections had a higher risk of TB co-infection, which is associated with lower immunity in the later disease stages. People aged 30–45 years are considered young adults; because of work, life circumstances, and other reasons, such patients have considerable population mobility and high sexual activity. Therefore, they are more likely to be infected with rculosis . Based oanulomas . The preanulomas , 85. Theanulomas . Thus, wce of TB . BCG vacTo the best of our knowledge, this current meta-analysis is unique in investigating the prevalence and risk factors of TB among PLHIV/AIDS in China. The findings of this meta-analysis contribute to an understanding of the characteristics of HIV/TB co-infection in various regions of China, which can help formulate corresponding treatment measures. The literature included in this current meta-analysis varied in terms of the study time, study area, sample size, detection rate, and other factors. We performed a meta-regression analysis to assess whether publication time is a source of heterogeneity. The wide economic disparities in different regions of China, which result in a wide variation in the prevalence of HIV/TB co-infection, are also a source of heterogeneity. The included studies had varying samples sizes. Studies with a small sample size may have had sampling error and instability, which may have led to publication bias. Detection rates of less than 100% are also a common problem and do not reflect accurate prevalence rates. All studies included were observational, which may have led to high heterogeneity in the combined literature analysis. Most of the studies selected involved registered cases of HIV/AIDS and the method of TB testing in unregistered patients or patients in the window period remains a problem.+ T cell count ≤ 200/µL, smoking, intravenous drug use, unemployment, male sex, senior citizen status, advanced WHO stage, low level of education, and presence of other opportunistic infections. The current meta-analysis showed that the co-infection rate and infection characteristics were distinct in different regions of the country. Therefore, corresponding two-way prevention and control measures should be formulated for different regions in China. For example, for the economically backward Guangxi and Xinjiang areas, dissemination of information on HIV infection and TB should be improved. For transmission via blood transfusion in the Henan area, blood system supervision should be strengthened. In the Yunnan and Hunan regions, which have a high prevalence of drug abuse, AIDS prevention and anti-drug activities should be actively promoted. In the Sichuan and Chongqing areas, which record greater sexual transmission, the understanding of AIDS prevention should be improved, and people should be encouraged to use condoms and reduce risky sexual behavior. Paying more attention to high-risk populations, improving multi-departmental cooperation, using the advantages of multi-disciplinary studies, collectively controlling dual infection, improving the quality of life of patients, and reducing mortality should be the common goals of governments, researchers, and individuals alike.In conclusion, the pooled prevalence of TB among PLHIV was 6.0% in the current meta-analysis. Risk factors for HIV/TB co-infection included CD4Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Supplementary Material 3


The heterogeneous, complex condition known as ischemic stroke (IS) is brought on by the interaction of a number of risk factors and genetic variables. The association between C‐reactive protein (CRP) gene polymorphisms and IS has, however, been the subject of inconsistent findings. Therefore, we conducted a meta‐analysis to comprehensively address possible associations of CRP genes with the risk of IS.A comprehensive literature search for all the published articles was performed in electronic databases including PubMed, EMBASE, Cochrane Library, and Google Scholar from January 1, 1950 to June 30, 2022. Odds ratio (OR) with 95% Confidence interval (CIs) along with fixed/random effect models were used to calculate summary estimates.Twelve case‐control studies totalling 3880 IS cases and 5233 controls were included for the association of CRP gene polymorphisms . Across all genotyping models, we discovered that rs1130864, rs3093059, rs2794521, and rs1205SNPs were not substantially related to IS risk. A trend for significant association for rs1800947 under dominant , recessive  and allelic model  was observed. However, protective association for rs1130864 under dominant  and rs3093059 under allelic model  was found.Our thorough study revealed that the CRP gene variants rs1800947, rs1130864, rs3093059, rs2794521, and rs1205 could not be related to the risk of ischemic stroke. However, additional research must focus on the rs1800947 polymorphisms in a particular group.  AND (“CRP” OR “C Reactive Protein”) AND  AND (“Gene” OR "Genotype). The literature search covered all English‐language articles. Additionally, the reference list of retrieved studies, review articles and previous meta‐analyses, were manually searched for collecting more relevant studies, which were not found while performing the electronic search. Studies involving human subjects were considered in our meta‐analysis. When there were duplicates, the source with the most detailed information was utilised.The systematic literature review was performed using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) statement.  Case‐control studies investigating for the association of CRP gene polymorphisms rs1800947 and/or rs1130864 and/or rs3093059 and/or rs2794521 and/or rs1205 with risk of IS.; (b) The number of controls and cases in each group were reported; and (c) The odds ratio (OR) and 95% confidence interval (CI) or the data that might be used to calculate the OR and CI were used to describe the genotype and allele distribution.Exclusion criteria:(a) Letters, editorials, case studies, reviews, meta‐analyses, commentary, studies involving animals or the environment, and (b) non‐English studies.2.3The risk of bias was assessed by New‐castle Ottawa Scale (NOS) for quality assessment of all the included studies in the meta‐analysis. Stang,  NOS Scal2.4We gathered following information: the first author's name, the publication year, the nation, the method for measuring genotype, the sample size, the proportion of male and female participants, the mean age, and the genotype frequencies of the case and control groups. Separately reviewing the publications and gathering data, the two authors settled any disagreements by consensus or with the help of a third author.2.5I2 statistics. Fixed effect model was used if I2 of less than 50% was observed while I2 more than 50% is viewed as moderate to considerable heterogeneity and random effect model was used. A sensitivity analysis was performed by sequentially omitting a single study in each turn, to validate the pooled observed effect. All statistical analyses were done by STATA version 13.1 software.To determine the strength of the association between CRP gene polymorphisms and risk of IS, Odds Ratio (OR) with 95% confidence interval (CI) was calculated under the dominant model, recessive model, and allele model. Heterogeneity was calculated with the 2.6Trial sequential analysis (TSA) was conducted by following the guidelines mentioned by Meng et al. , recessive  was observed  was observed. No significant association was found under recessive  and allelic model . The forest plot for all the genetic models is illustrated in Figure Five studies  was found. However, non‐significant association was observed under dominant  and recessive model . Due to a high degree of heterogeneity, a random‐effect model was applied , recessive model  and allelic model  for all the four included studies , recessive model  and allelic model  conducted a genome‐wide association study in Han Chinese patients with IS found that the SNP rs3093059 in the CRP gene influences the 3‐month functional outcome of the first‐ever large artery atherosclerotic stroke. , González‐Giraldo et al. , Liu et According to the best of our knowledge, this is the first thorough meta‐analysis and systematic review analyzing the association of five SNPs in the CRP gene with IS. Although conducted comprehensively, following limitations were present in our meta‐analysis: (i) certain case‐control studies did not pass the Hardy–Weinberg equilibrium test, suggesting that there was a bias in the selection of the control group; (ii) the studies included in our systematic review and meta‐analysis varied in terms of ethnicity, age and environmental factors and sources of control subjects; (iii) we did not check for the false discovery rate which might arise from the multiple comparisons made in the meta‐analysis; (iv) due to the fact that among matched groups, the other covariates corrected were not the same, whereas within unmatched groups, some studies may have had other covariates adjusted for them while others may have had none at all and lastly; and (v) significant heterogeneity was present in some of the comparisons made in our meta‐analysis. However, we used a random‐effect model throughout to account for the between study heterogeneity and also assessed the quality of each included study.5Our thorough study revealed that the CRP gene variants rs1800947, rs1130864, rs3093059, rs2794521, and rs1205 could not be related to the risk of ischemic stroke. However, additional research must focus on the rs1800947 polymorphisms in a particular group.All authors contributed to the study conception and design. W.C., X.Z., L.J., and L.W. independently assessed the quality of included studies. Y.H., H.H., L.K., N.L., and J.Z. performed material preparation, data collection, and analysis. W.C., X.Z., L.J., and L.W. did the analysis of results. All authors read and approved the final draft.The authors report no relevant conflict of interest.https://publons.com/publon/10.1002/brb3.2976.The peer review history for this article is available at Figure‐S1(a‐e): Sensitivity Plot for the association between CRP gene polymorphisms (a) rs1800947; (b) rs1130864; (c) rs3093059; (d) rs2794521 and (e)rs1205 with risk of IS.Figure‐S2(a‐e): Funnel Plot for the association between CRP gene polymorphisms (a) rs1800947; (b) rs1130864; (c) rs3093059; (d) rs2794521 and (e) rs1205 with risk of IS.Click here for additional data file.Table S1: PRISMA checklist 2020Click here for additional data file.


Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This meta-analysis aimed to investigate the correlation between aspirin consumption and HCC.A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science databases. The search period was from the establishment of the database to July 1, 2022 with no language restrictions.I2 = 84.7%, P < 0.001). Subgroup analysis showed that aspirin significantly reduced the risk of HCC by 19% in Asia  and by 33%  in Europe and the U.S with no significant difference. Moreover, in patients with HBV or HCV infection, aspirin reduced 19% and 24% of the risk of HCC, respectively. However, aspirin administration might increase risks of gastrointestinal bleeding in patients with chronic liver disease . Sensitivity analysis showed no significant difference of results after excluding individual studies, suggesting that the results were robust.A total of 19 studies including three prospective studies and 16 retrospective ones with 2,217,712 patients were included. Compared with those who did not take aspirin, those who took aspirin had a 30% lower risk of HCC (hazard ratio [HR] = 0.70, 95% confidence interval [CI] 0.63–0.76, Aspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease.The online version contains supplementary material available at 10.1186/s40001-023-01204-5. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy that accounts for 75–85% of liver cancers. Patients with HCC have poor prognoses and the onset of HCC is insidious. Risk factors of HCC include chronic liver inflammation and liver fibrosis or cirrhosis. In recent years, the global incidence of HCC has increased and it is estimated that more than 1 million patients will die from HCC in 2030.Most HCC patients don’t have the opportunity for surgery because of advanced stages. Only a small number of patients that are diagnosed at an early stage can receive radical resection . Other tAspirin is a classical non-steroidal anti-inflammatory drug (NSAIDs) that exerts antiplatelet effects by acetylating platelet cyclooxygenase (COX), thereby reducing the risk of myocardial infarction and stroke . TherefoHowever, a randomized controlled trial showed that long-term administration of low-dose aspirin did not reduce the risk of overall cancer, breast cancer, colorectal cancer, or other site-specific cancers . TherefoA systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE and Web of Science databases from the establishment of the database to July 1, 2022, with no language restrictions. A combination of subject terms and free words were used for literature search using Boolean logic operator grouping  retrospective or prospective cohort studies that explored the relationship between aspirin and the risk of HCC (from 2015 to 2022); (2) reporting the hazard ratio (HR) and 95% confidence interval (CI) of HCC based on different administration of aspirin; (3) the diagnosis of HCC was made based on the diagnostic criteria. Exclusion criteria were as follows: (1) reviews, case reports, meta-analyses, conference abstracts, redundant publications, ecological studies, animal studies, and case–control studies; (2) studies on patients who have been diagnosed with HCC before aspirin use; (3) studies that did not explicitly report any HR or 95% CI.The Newcastle–Ottawa scale (NOS) was used to evaluate literature quality in terms of study population selection, comparability between groups, and outcome measures, with a maximum score of 9. We included high-quality literature with scores greater than or equal to 7 in this study.Two investigators independently screened the literature and extracted data according to the criteria. In case of disagreements, they discussed or consulted a third party to reach the consensus. During literature screening, the title was first read to exclude irrelevant literature, then the abstract and full text were read to include relevant studies. Corresponding authors were contacted by email to obtain necessary information if needed. The extracted information included (1) first author, year of publication, study region, and study type; (2) study population and whether they had liver disease; (3) the number of participants and cases; (4) reported outcomes, including HR and 95% CI and (5) study-adjusted confounding factors, etc.I2 value were used to evaluate the heterogeneity of the included studies. P ≥ 0.05, 0 ≤ I2 ≤ 50% indicated low heterogeneity, and a fixed effect model was used for analysis; P < 0.05 and I2 > 50% indicated significant heterogeneity, so that a random effect model was used to identify the source of heterogeneity and perform subgroup and sensitivity analyses. Publication bias was evaluated using a funnel plot, Beggs test, and Eggers. P < 0.05 indicated that the difference was statistically significant.Stata 14.2 software was used for meta-analysis, and the statistics were presented by HR and 95% CI, with a preference for the corrected values if they were provided in the literature. The Cochran q test (P heterogeneity) and the We retrieved 35, 221, 103, 419, and 19 papers from Pubmed, Scopus, Web of Science, EMBASE, and Cochrane Library, respectively. 240 duplicate papers were excluded. After reading the titles and abstracts and excluding irrelevant literature such as reviews, case reports, meta-analyses, conference abstracts, animal experimental studies, 49 articles were selected for full-text reading. Finally, 18 articles with a total of 2,217,712 participants were enrolled based on the criteria. The literature screening process is shown in Fig. This article included 18 articles containing 19 studies published from 2015 to 2022, in which 13 studies focused on patients with liver disease, 4 studies focused on general population, and the remaining 2 studies focused on specific patients with type 2 diabetes or head and neck squamous cell carcinoma (HNSCC); 3 were prospective studies and 16 were retrospective studies   and by 33% in Europe and the U.S.   and retrospective (n = 16) studies. The results showed that aspirin reduced the risk of HCC in the retrospective studies   and by 21% in male   or not ; however, there was no no significant difference between the two groups (P = 0.257)  and general population (n = 4). The remaining two studies were excluded. The results showed that aspirin reduced the risk of HCC in patients with chronic liver disease   and HCV (n = 4) groups based on different hepatitis viruses. The results showed that the risk of HCC was reduced by 19% in HBV-infected patients  and by 24% in HCV-infected patients . There was no significant difference between the two groups (P = 0.201)  and non-cirrhosis  groups  and 0.81  respectively. There was a significant difference between groups (P = 0.027)  Figs. .Fig. 11SI2 = 0.0%, P = 0.712)   Fig. .Fig. 13FIn recent years, many studies have demonstrated the anti-HCC effect of aspirin, which is believed to reduce the incidence of HCC . HoweverThis meta-analysis including 2,217,714 participants provides a systematic evaluation of the relationship between aspirin and the risk of HCC. Our results indicated that aspirin reduced the risk of HCC by 30% compared with that in patients who did not use aspirin. Since considerable heterogeneity was detected in the included study, we performed subgroup analyses according to study region, study type, sex, adjusted medication, and study population. Results indicated that use was associated with a reduced risk of HCC independent of these factors. As for patients with liver disease, we concluded consistent results regardless of the presence or absence of cirrhosis and adjustment for administration of antiviral drugs. In addition, the adjusted results showed a diminished effect of aspirin in reducing the risk of HCC compared with that in aspirin users who were not adjusted for both statins and metformin, suggesting that the combination of aspirin and these drugs may have a synergistic anti-HCC effect. Our results also suggest that aspirin is associated with an increased risk of gastrointestinal bleeding in patients with chronic liver disease.Compared with previous studies, our study has a large sample size with a long follow-up period. However, there are several limitations. First, the heterogeneity of included studies was obvious, which may be due to different study designs, different and highly variable sample sizes across studies, different inclusion and exclusion criteria, the presence of more confounding factors, inconsistent control of confounding factors across studies, and varied lengths of follow-up. In addition, the presence of confounding factors in this study should be considered. For example, aspirin is often concomitantly administered with statins, lipid-lowering agents, and clopidogrel. Studies suggested that statin and clopidogrel may reduce the risk of HCC , 40. TheAspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease.Additional file 1. : A combination of subject terms and free words were used for literature search using Boolean logic operator grouping.