There is growing evidence of a relationship between anti-seizure medication (ASM) use and the risk of dementia. This study examined this association using a meta-analysis approach.PubMed, EMBASE, and Cochrane Library were systematically searched for peer-reviewed observational studies published up to February 2023. Study quality was evaluated using the Newcastle-Ottawa Scale, and an overall odds ratio (OR) was pooled using fixed or random-effects models.P = 0.003] in general population. However, this association disappeared  when the study data adjusted for drug indications were pooled. Subgroup analysis based on individual drugs found only a positive association among those exposed to valproate, carbamazepine, and clonazepam. Furthermore, an increased risk was found in patients with bipolar disorder exposed to ASMs .The analysis included 9 publications with 10 studies. The results showed that overall ASM exposure was associated with an increased risk of dementia [OR: 1.09, 95% confidence interval (CI): 1.03–1.15; The statistically significant association between ASM and dementia in general population may be driven by unmeasured confounding or several individual first-generation ASMs. However, a higher risk of dementia was observed among bipolar disorder patients treated with ASMs. Given the few included studies and evidence of high heterogeneity, further larger, prospective studies that control for important confounders are needed to verify our findings. Dementia is a progressive neurodegenerative disease characterized by progressive cognitive and functional decline constituting one of the leading causes of disability worldwide . It mainAnti-seizure medication (ASM) are widely used to treat epilepsy and bipolar disorder . While ePreferred Reporting Items for Systematic Reviews and Meta-analysis framework guidelines (PRISMA) were followed for this meta-analysis.A comprehensive literature search of the PubMed, EMBASE, and Cochrane Library databases was conducted on February 2, 2023, according to the PRISMA statement, with no year restrictions. The search incorporated index terms (Mesh) and free text words for the search concepts:  AND  AND (risk OR ratio OR prospective studies OR epidemiologic studies OR case-control studies OR cohort studies). An additional search was conducted in the bibliographies of relevant articles and relevant reviews.The studies were assessed by two independent reviewers who determined whether the studies met the inclusion criteria. Observational studies were included if they were: (1) a peer-reviewed study with a case–control or cohort design published in English, (2) included ASM exposure preceding a diagnosis of dementia, (3) included participants 18 years or older, (4) explored the association between ASM exposure and the risk of dementia, and (5) provided sufficient data to allow the calculation of risk estimates if adjusted data were not provided. Case reports, case series, animal studies, editorials, reviews, and meta-analyses were excluded. Studies that considered dementia as comorbidity and not as an outcome were also excluded.Two authors extracted information from all selected studies using piloted data extraction sheets. Any discrepancies in the extracted data were resolved by a third author. The following information was collected from each study: author, publication year, study location, sample demographics, information on ASM exposure, diagnostic criteria for dementia, number of subjects in each group, statistical adjustments, and study quality.The quality of the included observational studies was assessed using the Newcastle-Ottawa Scale (NOS) , which iI2 statistic was used to assess between-study heterogeneity; The I2 values were classified into four groups: of 0–29%, 30–49%, 50–74%, and 75–100%, representing very low, low, medium, and high inconsistency, respectively  to perform meta-analysis. A random-effects model was used to pool the odds ratios (ORs) and 95% confidence intervals (CI) of individual studies; such models are optimal in terms of allowing the results to be generalized because they can deal with potential heterogeneity . ORs werectively . Funnel ectively , 23. AllAfter using the keywords, 4,687 records were identified in the initial search. Of these, 1,124 were duplicates, and 3,511 records were not relevant to the Research Topic after title and abstract screening, leaving 52 potentially eligible studies for which the full text was reviewed. Based on the inclusion and exclusion criteria, 9 publications with 10 studies were eligible for inclusion; all nine  were obsP = 0.003) (I2 = 85.6%). As shown in P = 0.3).The results of all analyses are listed in = 0.003) . High heP = 0.02; I2 = 73.3%), but a non-significant trend toward an increased risk of dementia in case–control studies .A subgroup analysis by study design found a significant association in cohort studies , but no significant association in those adjusting for more than five .Considering the number of adjustment variables revealed a significantly increased dementia risk in those studies adjusting for fewer than five variables , carbamazepine , or clonazepam , but no significant association was observed for those using levetiracetam , topiramate , lamotrigine , gabapentin , pregabalin , primidone , or phenytoin .When we grouped studies by ASM type, significant associations were observed for those using valproate  .Three studies compared the risk of dementia in bipolar disorder patients who were and were not exposed to ASMs; the combined OR of dementia was 1.43  . When ouThis meta-analysis of current observational evidence suggests that the statistically significant association between ASM use and dementia in general population can be partially explained by unmeasured confounding. However, subgroup analyses based on individual ASMs found that only valproate, carbamazepine, and clonazepam were associated with an increased risk of dementia. Furthermore, we found that bipolar disorder patients who were prescribed ASM showed an increased risk of dementia.in vitro and in vivo (The impact of ASM use on cognitive function is controversial. Theoretically, ASMs can adversely affect cognitive functions by suppressing neuronal excitability or enhancing inhibitory neurotransmission , 24; how in vivo . Consist in vivo , 24 haveAlthough these modifying effects of ASMs on dementia are biologically plausible, the results of the included studies were discordant, as reflected in the high heterogeneity in the overall meta-analysis. This heterogeneity could not be accounted for in the subgroup analyses based on study design, location, or quality; number of adjustments; drug indications; and individual drugs. The existence of clinical heterogeneity should lead to a degree of statistical heterogeneity in the results.Most of the studies in our overall analysis drew conclusions based on general-population data and did not consider the drug indications. However, epilepsy was shown to be associated with an increased risk of dementia . It is rThe high heterogeneity of the overall analysis may also arise from the types of ASM. In our subgroup analysis of individual ASMs, only valproate, carbamazepine, and clonazepam, which are first-generation ASMs, were found to increase the risk of dementia. Previous studies demonstrated that the main cognitive effects of ASM use were impaired attention, vigilance, and psychomotor speed. One double-blind, placebo-controlled study  reportedTo our knowledge, this meta-analysis is the first to explore the association between ASM use and dementia risk. The strengths of this work are the comprehensive search and the rigorous systematic review and meta-analysis of all relevant reports to date. We also performed several additional analyses to test the robustness of the results. Nonetheless, there are several limitations to this meta-analysis. First, residual confounders are always a concern in epidemiological observational studies. Second, all of the included studies considered Western populations and not subjects from Asia or Africa, which may have affected the generalizability of our results. Third, information on the dose of ASM used in the included studies could not be extracted; therefore, any exposure parameter possibly associated with dementia could not be defined.In summary, this systematic review and meta-analysis only observed a greater risk of dementia with the use of valproate, carbamazepine, or clonazepam in general population. We also found that ASMs are associated with an increased risk of dementia in bipolar disorder. However, large, well-designed, prospective cohort studies that consider a greater number of confounding factors are warranted to verify our findings.The original contributions presented in the study are included in the article/LZ and H-yJ searched the library, wrote the manuscript text, extracted data, and reviewed all articles. W-jL designed the manuscript. All authors reviewed the manuscript. All authors contributed to the article and approved the submitted version.


Considering the high reoperation rate in degenerative lumbar spondylolisthesis (DLS) patients undergoing lumbar surgeries and controversial results on the risk factors for the reoperation, we performed a systematic review and meta-analysis to explore the reoperation rate and risk factors for the reoperation in DLS patients undergoing lumbar surgeries.Literature search was conducted from inception to October 28, 2022 in Pubmed, Embase, Cochrane Library, and Web of Science. Odds ratio (OR) was used as the effect index for the categorical data, and effect size was expressed as 95% confidence interval (CI). Heterogeneity test was performed for each outcome effect size, and subgroup analysis was performed based on study design, patients, surgery types, follow-up time, and quality of studies to explore the source of heterogeneity. Results of all outcomes were examined by sensitivity analysis. Publication bias was assessed using Begg test, and adjusted using trim-and-fill analysis.A total of 39 cohort studies (27 retrospective cohort studies and 12 prospective cohort studies) were finally included in this systematic review and meta-analysis. The overall results showed a 10% (95%CI: 8%-12%) of reoperation rate in DLS patients undergoing lumbar surgeries. In surgery types subgroup, the reoperation rate was 11% (95%CI: 9%-13%) for decompression, 10% (95%CI: 7%-12%) for fusion, and 9% (95%CI: 5%-13%) for decompression and fusion. An increased risk of reoperation was found in patients with obesity , diabetes , and smoking .We found a 10% of reoperation rate in DLS patients after lumbar surgeries. Obesity, diabetes, and smoking were risk factors for the reoperation.The online version contains supplementary material available at 10.1186/s12893-023-02082-8. Degenerative lumbar spondylolisthesis (DLS) refers to anterolisthesis of one vertebral body over another vertebral body secondary to osteoarthritic degeneration, leading to spinal canal stenosis . DLS is Surgeries have been regarded as the standard treatment modality for intractable cases . The proConsidering the controversial results, we aimed to perform a systematic review and meta-analysis to evaluate the incidence and risk factors of reoperation in DLS patients for the purpose of improving surgical outcomes and prognosis.This study was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . Two resStudies meeting the following inclusion criteria were selected: (1) population: DLS patients; (2) patients undergoing lumbar surgeries, including decompression surgeries and fusion surgeries; (3) outcome: reoperation rate and risk factors; and (4) studies: cohort studies. The population included DLS patients and DLS patients with lumbar spinal stenosis (LSS). Fusion surgeries included posterolateral lumbar fusion (PLF) and lumbar interbody fusion (LIF). Reoperation was defined as the secondary lumbar surgeries due to progression of lumbar degenerative changes or postoperative instability . Risk faStudies were excluded by meeting one of the following criteria: (1) animal studies; (2) other degenerative spinal diseases including lumbar spine stenosis, degenerative disc disease, and degenerative cervical spondylosis; (3) not English articles; (4) unable to extract data; (5) case reports, conference abstracts, letters, reviews, and meta-analysis.The following data were extracted: the first author, year of publication, country, study design, patients, definition of spondylolisthesis, sample size, age, sex, BMI, disease duration, surgery types, follow-up time, number of reoperations, reasons for reoperation, reoperation methods, and risk factors of reoperation. The Newcastle–Ottawa Scale (NOS) was applied to evaluate the quality of cohort studies . This sc2). Random-effect model was used for analysis if I2 ≥ 50%, and fixed-effect model was used if I2 < 50%. For the high heterogeneity (I2 ≥ 50%), subgroup analysis was conducted based on study design, patients, surgery types, follow-up time, and quality of studies to explore the source of heterogeneity. Sensitivity analysis was carried out for all outcomes. Begg test was used to assess publication bias for the outcome included more than 10 articles. Trim-and-fill analysis was used to adjust the publication bias. P < 0.05 was considered statistically significant.All statistical analyses were performed using Stata15.1 software . Rate was used as the effect index in the analysis of reoperation rate. Odds ratio (OR) was used as the effect index for categorical data, and effect size was represented as 95% confidence interval (CI). Heterogeneity test was performed for each outcome effect size, and results were quantified as I-squared (In = 1026), Embase (n = 1349), Web of Science (n = 4441), and Cochrane Library (n = 846). After removing the duplicates, 5,251 articles remained. Further, 5,150 articles were excluded due to publishing as reviews or meta-analyses (n = 929), conference abstracts (n = 310), animal trials (n = 22), case reports (n = 226), and letters (n = 9), not English articles (n = 112), and topic not meeting the requirements (n = 3542). In the remaining 101 articles, we further excluded 3 articles unable to extract data, 29 articles reporting other degenerative spinal diseases, and 30 articles with topic not meeting the requirements. Finally, 39 cohort studies were retained in this meta-analysis [A total of 7,662 articles were searched from Pubmed . To explore the source of heterogeneity, subgroup analyses were performed. In study design subgroup, 10% of reoperation rate was found in both prospective cohort study (95%CI: 7%-13%) and retrospective cohort study (95%CI: 8%-13%). In patients subgroup, DLS patients showed 11% of reoperation rate (95%CI: 8%-13%) and DLS patients with LSS showed 10% of reoperation rate (95%CI: 6%-13%). In surgery types subgroup, the reoperation rate was 11% (95%CI: 9%-13%) in patients undergoing decompression, 10% (95%CI: 7%-12%) in patients undergoing fusion, 9% (95%CI: 5%-13%) in patients undergoing decompression and fusion, and 7% (95%CI: 3%-11%) in patients undergoing other surgeries. In follow-up time subgroup, the reoperation rate was 9% (95%CI: 6%-12%), 12% (95%CI: 9%-14%), and 10% (95%CI: 6%-15%) at follow-up time < 5 years, between 5 to 10 years, and ≥ 10 years, respectively. In study quality subgroup, there was 11% (95%CI: 9%-13%) of reoperation rate in studies with fair quality and 7% (95%CI: 5%-10%) of reoperation rate in studies with high quality. The overall and subgroup analysis results were shown in Table This meta-analysis showed a 10% (95%CI: 8%-12%) of reoperation rate in DLS patients , diabetes , and smoking  were associated with an increased risk of reoperation. Age , sex , and more bleeding  were not associated with the reoperation. The overall results were demonstrated in Table The meta-analysis showed that obesity   Table A. TherefThe reoperation rate of DLS patients undergoing lumbar surgeries remains high in spite of improved surgical skills and techniques; therefore, exploring risk factors of reoperation is important , 8. ConsSeveral previous studies have reported the reoperation rate after lumbar surgeries in DLS patients , 49–52. Identifying risk factors of reoperation for patients after lumbar surgeries is of clinical interest. In this study, obesity, diabetes, and smoking were found to be associated with higher risk of reoperation. Rabah et al. and Chan et al. have confirmed that smoking status was associated with greater risk of reoperation , 23. AlsAnimal studies have long recognized the close association between diabetes and lumbar spine disorders –57. DiabThis meta-analysis explores the reoperation rate and risk factors for the reoperation. Results show that there is 10% of reoperation after lumbar surgeries, and obesity, diabetes, and smoking are found to increase the risk of reoperation. Our findings suggest that DLS patients should control glycemic level and weight, and reduce smoking to decrease the risk of reoperation. There are some limitations in this study. First, all fusion techniques (PLF and LIF) were put together. Due to the limitations of the included studies, it is unable to further analyze the reoperation rate in DLS patients undergoing the single fusion technique. Second, the number of studies reporting the risk factors of reoperation is relatively small, and some outcomes can only be qualitatively described, which may affect the stability of the results. Third, the risk of reoperation may be different according to the severity of lumbar spondylolisthesis and the first surgical methods; however, data provided in the currently available studies are insufficient to further analyze. Future meta-analysis including more relevant studies are needed to verify our findings and to explore the effect of lumbar spondylolisthesis severity and the first surgical methods on the risk of reoperation.Our meta-analysis found 10% of reoperation rate in DLS patients undergoing lumbar surgeries, and identified obesity, diabetes, and smoking as risk factors for the reoperation. Our findings suggested that patients should improve glycemic level and weight, and quit smoking to reduce the reoperation after lumbar surgery.Additional file 1: Supplementary figure 1. Funnel plot for publication bias before and after trim-and-fillanalysis.


The relationship between platelet-associated parameters and psoriasis has been controversial. The purpose of our meta-analysis was to assess whether platelet count, platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW) are associated with psoriasis.We performed a thorough documentation retrieval via PubMed, EMBASE, and Web of Science until June 2021. Pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model.P = .210), while PLR , MPV , and PDW  were remarkably greater in the psoriatic patients than in the healthy individuals, and similar results were found in subgroup analyses. The analytical results of susceptibility revealed that the outcomes were robust, and no evidence of substantial publication bias was identified.Overall, 22 studies involving 1749 patients with psoriasis and 1538 healthy controls were selected for the meta-analysis. The outcomes showed that platelet count presented non-significant differences between psoriatic patients and normal individuals (SMD = 0.12, 95% CI =  −0.07 to 0.32, Patients with psoriasis present significantly higher PLR, MPV, and PDW than healthy individuals, suggesting that psoriasis is accompanied by low-grade systemic inflammation and platelet activation. Although the etiology and pathogenesis of psoriasis remain unclear, inflammation and immunity are involved in its development and progression.,4Psoriasis is a chronic inflammatory disease of the skin characterized by erythema, papules, and scales, which affects approximately 2% to 3% of the general population.–7 Platelets are activated and bind to leukocytes in immune-mediated inflammatory responses, and platelet-leukocyte interactions release a high concentration of cytokines, chemokines, and growth factors.,9 Psoriasis is characterized by leukocyte infiltration into the skin, which may arise from platelet activation and subsequent excessive cytokines and chemokines.,11 Platelet activation can be assessed by changes in platelet count and volume, and mean platelet volume (MPV) and platelet distribution width (PDW) are good indicators of platelet size. Platelet-to-lymphocyte ratio (PLR) has recently been introduced as a superior marker to monitor systemic inflammation, which has been shown to be higher in a multitude of inflammatory disorders. An increased PLR may stem from an elevated platelet count (PLT) , decreased lymphocyte number, or both.Recently, increasing evidence has suggested that platelets play a role in regulating immune and inflammatory responses beyond their traditional role as regulators of hemostasis and wound repair.Over the past few years, the comparisons of different platelet-associated parameters between psoriatic patients and healthy individuals have been significantly inconsistent in different studies. Moreover, most studies evaluating the relationship between them have been limited by the small sample size. Therefore, in order to better understand the role played by different platelet-associated parameters in the development of psoriasis, we conducted a systematic review and meta-analysis of published studies that compared PLT, PLR, MPV, and PDW between psoriatic patients and healthy individuals.2 Since this study is a systematic review and meta-analysis, no ethical approval was required.The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.2.1A thorough documentation retrieval was carried out using electronic databases including PubMed, EMBASE, and Web of Science until June 18, 2021. The retrieval keywords are presented below: (psoriasis OR psoria∗) AND (“platelet count” OR “platelet number” OR “platelet-to-lymphocyte ratio” OR “platelet-lymphocyte ratio” OR PLR OR “mean platelet volume” OR MPV OR “platelet distribution width” OR PDW). We searched the bibliography of the relevant literature for more related information.2.2A research would be taken as appropriate if it reached the pre-determined selection standards below: studies in patients ≥18 years old; studies contrasting platelet-associated parameters  between psoriatic patients and normal controls; and studies written in English. Studies were deemed unsuitable if no necessary data or comparative groups; sample repetition with other studies; or reviews, case presentations, mails, or conference summaries.2.3Data were obtained by 2 researchers separately (Li Li and Jianxiu Yu), and conflicts were resolved by another researcher (Zhongwei Zhou). The following data were extracted from each appropriate research: the name of the first author, publishing time, research regions, and research design; relevant demographic information and clinical status of psoriatic cases, including age, sex, disease duration, and the Psoriasis Area and Severity Index (PASI) score; specimen scale, PLT, or PLR, MPV, or PDW in psoriatic cases and healthy controls.2.4 As the maximum score stood at 9, the quality of the included articles was considered inferior, medium, or superior according to a score of 0 to 3, 4 to 6, or 7 to 9, separately.Two investigators (Li Li and Jianxiu Yu) assessed the quality of the included studies according to the Newcastle-Ottawa Quality Assessment Scale (NOS) for observational studies modified by van Dijk et al.2.5 The heterogeneous results of statistics among studies were evaluated using the chi-square test, and significant levels were P < .10. The qualification of heterogeneous levels was determined by I2, and I2 > 50% indicated significant heterogeneity. To unveil the reasons for the heterogeneous results, our team carried out subgroup studies and meta-regression analysis. The former was classified by the research region and research design. For meta-regression analysis, SMD was the dependent variable, and age, the percentage of males, sample size, disease duration, PASI score of psoriatic patients, and publishing time of included studies were chosen as independent variables. Sensitivity studies were carried out by sequentially reducing 1 study in each turn to evaluate the stability of the results. Publication bias was first evaluated by visually inspecting funnel plots and statistically assessed using Egger test.Our team adopted Stata15.0  to carry out the entire study statistically. For each study, we calculated standardized mean differences (SMDs) and 95% confidence intervals (CIs) to estimate the diversity in platelet-associated parameters between psoriatic patients and healthy controls. A random-effects model (REM) was adopted for the estimate, which was more conserved than the fixed-effect model.P score below .05 had significance on statistics, unless otherwise pointed out.The 33.1–38 and the process of the selected and discarded studies is displayed in Figure We initially identified 266 records; after the elimination of 159 duplicate publications, 107 records remained, of which 74 publications were excluded according to the title and abstract. Of the remaining 33 publications selected for full-text studies, 11 were discarded due to missing outcome data, non-English language, or repetitive information with other studies. Eventually, 22 articles were eligible for the meta-analysis,3.2The primary characteristics of the selected studies are summarized in Table The outcomes of the evaluation of qualities are also presented in Table 3.33/μL in the sufferers and 197.0 to 276.0 × 103/μL in the healthy individuals. Seven studies reported PLR ranging from 101.3 to 159.2 in the patient group and 101.0 to 220.0 in the control group. Seventeen studies demonstrated that the MPV ranged from 8.0 to 13.49 FL in the patients and 7.0 to 10.46 FL in the healthy individuals. Five researches displayed that the PDW ranged from 11.48 to 16.8 FL in the sufferers and 10.98 to 16.77 FL in the healthy individuals.The outcomes of platelet-associated parameters of psoriatic patients and healthy individuals are summarized in Table 3.4P = .210, Fig. P = .031, Fig. P < .001, Fig. P = .027, Fig. I2 scores between 70.2% and 86.9%.To compare platelet-associated parameters between psoriatic patients and healthy controls, a REM meta-analysis using SMD with 95% CI was conducted. Specifically, PLT presented non-significant differences between psoriatic patients and normal individuals , but not with age, sample size, the PASI score of patients, and the publishing time of selected studies (P > .05). MPV was significantly associated with publication year of the included studies (P = .034), but not with age, male proportion, sample size, disease duration, and the PASI score of patients (P > .05). The results are presented in more detail in Table To identify whether the potential moderating variables had impacts on the gathered effect size, a REM meta-regression study was performed with pre-defined independent variables reported in greater than or equal to 10 studies. We found that PLT was significantly associated with male proportion .We did not observe any evidence of publication bias in the combined survey of PLT Fig. A and MPV4The present study is the first meta-analysis of the association between platelet-associated parameters and psoriasis. The results of this study indicated that higher PLR, MPV, and PDW, but not PLT, are associated with psoriasis. Subgroup analysis showed that the pooled results were not affected by the study design and location. No obvious publication bias was observed among the included studies. Sensitivity analysis revealed that the pooled results were not influenced by any individual study. Therefore, the results of the present meta-analysis were stable and robust.; therefore higher PLR in psoriatic patients suggests that psoriasis is accompanied by systemic inflammation. As already mentioned, an increased PLR may be due to an elevated platelet number, decreased lymphocyte number, or both. In this meta-analysis, there was a trend toward higher PLT in psoriatic patients than in healthy controls, although the difference was not statistically significant. Therefore, a higher PLR in psoriatic patients, in part, may result from the increased PLT. Recently, a meta-analysis carried out by Paliogiannis et al evaluated the relationship between PLR and psoriasis, which was consistent with our findings that psoriatic patients presented a significantly higher PLR than healthy individuals; the current meta-analysis included 7 studies on PLR in the comparison between psoriatic patients and normal individuals, while Paliogiannis et al involved only 4 studies. Therefore, this study provides updated evidence of a significant association between PLR and psoriasis.Platelet-associated parameters are easily available in routine laboratories with considerably low cost, high efficiency, and high reproducibility; therefore, they have long been considered a powerful tool for efficient diagnosis and therapeutic monitoring of multiple medical conditions. PLR is usually used as an indicator of chronic low-grade inflammation In this meta-analysis of 22 included studies, 17 examined MPV in psoriatic patients, which provided us with an adequate number of studies to conclude that patients with psoriasis are accompanied by increased MPV. Several previous meta-analyses also demonstrated that MPV was significantly higher in patients with metabolic diseases, such as diabetes, non-alcoholic fatty liver disease, and cardiovascular diseases.–43 Currently, there is a growing consensus that psoriasis is a systemic disease that is intimately related to comorbid diseases such as diabetes, obesity, and cardiovascular diseases, although it is mostly present with local inflammatory lesions in the skin. Two recent meta-analyses consistently showed that lipid metabolism was abnormal in psoriatic patients, and there were significant associations between psoriasis and obesity and cardiovascular disease.,46 Therefore, platelet activation may serve as a bridge between psoriasis and related metabolic diseases. Moreover, several studies included in this meta-analysis showed that plasma levels of platelet-derived microparticles, soluble P-selectin, and CD62, which closely reflect platelet activation, were also significantly elevated in patients with psoriasis.MPV is the most frequently used platelet parameter that reflects platelet activation in inflammatory and immune-related diseases. PDW has usually been used to evaluate the volume heterogeneity of platelets, and an increased PDW indicates that the volume of platelets is not homogeneous. There is evidence indicating that PDW can more sensitively reflect the changes in platelet volume related to the formation of pseudopodia and shape changes during platelet activation than MPV. Therefore, a higher PDW is considered a sensitive indicator of platelet activation. Similar to MPV, recent studies have also suggested that PDW is positively associated with a higher risk of diabetes and cardiovascular diseases.,51 However, among the 22 studies included in the present meta-analysis, only 5 reported the results of PDW. Therefore, more research is needed to substantiate the observation that there are significant associations between psoriasis and PDW.Recently, increasing attention has been given to the relationship between PDW and a variety of diseases.,53 were examined in the studies included in this meta-analysis. Therefore, we failed to identify the relationship between platelet-associated parameters and inflammatory markers in patients with psoriasis. Fourth, although the findings of our analyses are based on the merged results from multiple previously reported studies that can increase sample size to a certain extent, the overall sample size is still not large enough, especially for the analysis of PLR and PDW. Fifth, as nearly half of the studies did not provide information on blood analyzers for measuring platelet-associated parameters, we failed to carry out subgroup analysis according to different analyzers. Imperfect detection from earlier hematology analyzers may misidentify small red cells as platelets, resulting in falsely elevated PLT and MPV to varying degrees, which may be one of the main reasons for the significant negative correlation between MPV and publication year. Sixth, since over half of the studies included in this meta-analysis were conducted in Turkey (14 out of 22), the results of these meta-analyses may not be representative of the overall population. However, our subgroup analyses based on research regions showed that the pooled outcomes of both Turkish and non-Turkish cases were consistent with the overall results. Finally, selective bias was probably inevitable, as only articles published in English were selected for this meta-analysis.This meta-analysis had several potential limitations. First, considerable heterogeneity was observed in all pooled outcomes. Although subgroup analysis suggested that the pooled results of PLT and MPV were not moderated by study design and study location, the sources of heterogeneity still cannot be reasonably explained. In the following univariate meta-regression analysis, significant negative correlations between PLT and the proportion of male patients and between MPV and publication year suggest that these 2 variables, in part, contribute to the heterogeneity in the pooled results of PLT and MPV. Meta-regression analysis can not only explore potential sources of heterogeneity, but also identify the relationships between the independent and dependent variables. In this study, we failed to find significant relationships between PASI score and PLT and MPV by meta-regression analysis, suggesting that both PLT and MPV cannot reflect the severity of psoriasis. Second, since the number of included studies on PLR and PDW was relatively small, we did not conduct subgroup and meta-regression analyses to explore the sources of heterogeneity, and we failed to evaluate whether PLR and PDW can reflect the severity of psoriasis. Moreover, some potential confounders such as the levels of inflammation and the use of drugs in patients are limited in the eligible studies, which prevented us from analyzing whether these factors contributed to the heterogeneity between studies. Third, psoriasis is a chronic inflammatory dermatosis, and platelet activation is involved in inflammatory processes. However, other than PLR, almost no other inflammatory parameters such as C-reactive protein and certain inflammatory cytokines, especially IL-1 and TGF-β, which have been demonstrated to be most strongly associated with platelet activation,5In conclusion, this meta-analysis indicated that psoriatic patients had higher PLR, MPV, and PDW, rather than PLT, than healthy individuals. However, this study failed to find a relationship between platelet-associated parameters and psoriasis severity. Further studies are needed to confirm the current outcomes, especially the relationship between PLR, PDW, and psoriasis.Conceptualization: Zhongwei Zhou.Data curation: Li Li, Jianxiu Yu.Writing – original draft: Li Li, Jianxiu Yu.Writing – review & editing: Zhongwei Zhou.


The current meta-analysis offers a general perspective on the echocardiographic measurements of heart dimensions in sound Thoroughbred and Standardbred horses. The study was performed according to the guidelines of PRISMA. The echocardiographic findings varied from one study to the next due to the fact that there were multiple investigations. The meta-analysis indicates variations in results among different studies. This result should be considered when evaluating a horse for heart disease and each case should be evaluated independently.p < 0.001) and 8.5 (p < 0.001). However, the Q statistic was 886.6 (p < 0.001). Moreover, the I-squared was 98.08, and the tau-squared was 6.6. By contrast, the effects of LVID fell on the negative side of zero, (2.8–83.9). The present meta-analysis provides an overview of the echocardiographic measurements of cardiac diameters in healthy Thoroughbred and Standardbred horses. The meta-analysis indicates variations in results among different studies. This result should be considered when evaluating a horse for heart disease and each case should be evaluated independently.The purpose of this study was to provide a systematic meta-analysis on echocardiographic measurements in normal Thoroughbred and Standardbred horses. The current systematic meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). All the available published papers on the reference values of echocardiographic assessment via M-mode echocardiography were searched, and fifteen studies were finally selected for analysis. In both fixed and random effect, the confidence interval (CI) for the interventricular septum (IVS) was 2.8–3.1 and 4.7–7.5; for the left ventricular free-wall (LVFW) thickness, it was 2.9–3.2 and 4.2–6.7; and for the left ventricular internal diameter (LVID), it was −5.0–4.6 and −10.0–−6.7, respectively. For IVS, the Q statistic, I-squared, and tau-squared were 925.3, 98.1, and 7.9, respectively. Similarly, for LVFW, all the effects were on the positive side of zero, with a range of 1.3–68.1. The CI indicated a significant variation among the studies . The z-values of LVFW for fixed and random effects were, respectively, 41.1 ( Echocardiography is a non-invasive procedure that permits the thorough visualization of cardiac chambers as well as their valves and is helpful in the diagnosis and monitoring of animals with suspected or known heart diseases . EchocarM-mode echocardiography is used to obtain high-resolution real-time images of cardiac structures ,6. It waEchocardiography’s ability to measure cardiac diameters is widely regarded as a pivotal technique for assessing the severity and prognosis of cardiac disease and the heart’s reaction to physical exertion . Indeed,Meta-analysis is defined as a quantitative, epidemiological study design used to systematically assess previous research studies to reach conclusions about that body of research . Meta-anMeta-analysis assists to overcome the lack of the statistical capacity to reach concrete conclusions in independent studies, as well as the failure to appropriately analyze the differences in the risk of extremely uncommon adverse events in large-scale studies . When thIn fact, extensive meta-analysis studies on echocardiographic measurements in humans have been carried out . HoweverThe reference values for the echocardiographic evaluation of heart diameters in Thoroughbred and Standardbred horses were generated in this meta-analysis.None of the horses investigated had any cardiac abnormalities or pathological conditions that might affect cardiac function or size. Any level of sample size was acceptable.-For papers written in a foreign language, the availability of the English version of the reports;-Measurements were obtained via M-mode echocardiography;-Measurements were obtained via the right parasternal short-axis view (RPSAX);-Measurements were obtained at end-systole and end-diastole.-Measurements taken from other different breeds;-Methods of examination other than RPSAXs;-Incomplete parameters of cardiac diameters;-Non-English published papers.The goal was to find all published publications dating back to the early days of regular echocardiography. The authors searched the PubMed, Ovid, Sage, BESCO, CAB, Scopus, and ISI web of knowledge databases from the beginning of time until July 2018 using the search phrases ECHOCARDIOGRAPHY (title/abstract) AND (“NORMAL VALUES”) (title/abstract) OR (“REFERENCE VALUES”) (title/abstract). This method was supplemented by citation evaluation, Google Scholar searches, expert suggestions, and hand-searching. Using EndNote, a reference application, we integrated the database results . The articles included in this study are shown in The following information was extracted using a data extraction form: the study’s year, sample size, and provided summary statistics , types of breed, and the measurements and methods of cardiac diameters during the cardiac cycle .The current systematic meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . All thep-value [p < 0.05, and the I2 statistic was used to define the % of true heterogeneity among the analyses. The I2 statistic was used to estimate the degree of heterogeneity, which refers to the total variation depending on the Q statistic and the number of trials (K). In fact, a negative value of I2 was considered equal to zero, and consequently, the I2 statistic ranged between 0% and 100%, and a value equal to or more than 50% was considered heterogeneous [p-value < 0.05 was considered significant.For statistical analyses, a commercial software program for meta-analysis was used . Descriptive statistics were applied to present the mean values of echocardiographic parameters in the finally selected papers. The variables meta-analysis used were fixed and random-effect models, 95% confidence intervals, effect size, heterogeneity, and weight. The effect size was determined using a standardized Z statistic and p-value . Heterogogeneous . With vaogeneous . Study wThe final model of meta-analysis for the measurement of IVS, LVID, and LVFW in healthy Standardbred and Thoroughbred horses is presented in p < 0.001) and 8.7 (p < 0.001), respectively. For heterogenicity, the Q statistic was 925.3, compared with the expected value of 17 (p < 0.001); the I-squared was 98.1, and the tau-squared was 7.9.The results revealed that all the effects of IVS were on the positive side of zero, in the range of 1.36–66.08. The 95% confidence interval (CI) supported this finding in both fixed and random effects, indicating significant variations among the studies  and 9.7 (p < 0.001), respectively. For heterogenicity, the Q statistic was 844.949 (p < 0.001), and the I-squared and tau-squared values were 97.988 and 11.977, respectively.On the other side, all the effects of LVID fell on the negative side of zero, in the range of 2.8–83.9. The 95% CI indicated a significant variation among the studies  . Under ap < 0.001) and 8.545 (p < 0.001), respectively. However, for heterogenicity, the Q statistic of LVFW was 886.648, compared with the expected value of 17 (p < 0.001), while the I-squared was 98.083, and the tau-squared was 6.680.Similarly, for LVFW, all the effects were on the positive side of zero, in the range of 1.350 to 68.176. The 95% CI indicated a significant variation among studies . Under aIn the present study, we conducted a systematic meta-analysis on the echocardiographic measurements of IVS, LVID, and LVFW, in Thoroughbred and Standardbred horses. For IVS, LVID, and LVFW, considering both types of effects (fixed and random), there was a variation among the results of the measurements. It is speculated that the controversy about the reliability of studies is due to the precision of the technique used. This finding is consistent with that previously reported . In the For IVS, the confidence interval (CI) of 95% in the study of Al-Haidar et al.  was abouFor LVID, the 95% CI reported by Pipers and Hamlin  was abouFor LVFW, the 95% CI stated by Slater and Herrtage  was abouThe confidence interval (CI) of 95% for IVS supported these findings in both fixed and random effects, indicating a significant variation among the studies  and for LVID  and for LVFW . The measurements of the three variables varied among the studies, which may be due to the wide range of horse breeds and ages in most of the studies.The relative weight is the average of weights as a proportion of total weights, with all relative weights added up to 100% . For IVSFor LVID, the study of Leadon et al. (1991)  was assip < 0.001) and 8.793 (p < 0.001), and for LVID, they were 48.090 (p < 0.001) and 9.719 (p < 0.001). For LVFW, the z-values were 41.114 (p < 0.001) and 8.545 (p < 0.001), respectively.Regarding heterogeneity, under both fixed (common) and random (true) effects, the null hypothesis was that the effect would be zero. The null hypothesis was tested using the z-value, which was computed as Hedges’s g/standard error (G/SE) for the corresponding model . In our p < 0.001). The Q statistic implied the observed dispersion, whereas the null hypothesis for heterogeneity argued that the studies assigned a common effect size. Therefore, the degrees of freedom were assumed to be equal to the Q statistic [In the present study, the Q statistic for IVS was 925.307, while for LVID, it was 844.949, and for LVFW, it was 886.648, compared with the expected value of 17 . To give weights, however, the tau-squared is really set to zero . UnfortuThe limitations of the present investigation should be acknowledged. First, like other meta-analyses reporting reference values, remarkable heterogeneity was an innate limitation, although we attempted to explore the source of heterogeneity and define reference values with detailed information. Second, not all variables were comparable, as only IVS, LVID, and LVFW were presented via M-mode echocardiography. These variables were selected for investigation in all the studies. However, in other meta-analytical studies in humans and animals, a wide range of cardiac diameters was included ,50,51. MThis is the first meta-analysis that summarizes the results of the currently available studies looking at the identification of normative values for IVS, LVID, and LVFW, as assessed via M-mode echocardiography in horses. All the variables of this meta-analysis indicated variations in the results among the different studies. This result should be considered when evaluating a horse for heart disease, and each case should be evaluated independently.


MTHFR ) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI , CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism , while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism , which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.Recent studies have shown that two common methylenetetrahydrofolate reductase (  MTHFR ) polymorphisms and thyroid dysfunction , such as Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). AITDs can affect people at any age, but women of reproductive age (30~50 years old) are more likely to suffer from these diseases   , 2 . Thunction   . One ofntified   .MTHFR gene has been mapped to chromosomal region 1p36.22 and consists of 12 exons, encoding the 656-amino-acid protein.Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism that catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. MTHFR plays a crucial role in the regulation of DNA synthesis, the methylation cycle, and homocysteine concentrations in the blood  and A1298C (rs1801131) are the two most common single nucleotide polymorphisms (SNPs) in the 01133 andld-type   . A largld-type   . Moreovld-type   , which MTHFR gene polymorphisms and thyroid diseases , but the results remain controversial. Here, we conducted a meta-analysis of all case-control and cohort studies to shed some light on the association between the MTHFR C677T and A1298C polymorphisms and thyroid dysfunction.To date, several studies   - 32  haPubMed (1950-2021), EMBASE (1974-2021) and Chinese databases, including the China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBMdisc), WeiPu and Wanfang databases, were searched up to September 2021. Two authors independently performed a comprehensive literature search for relevant studies using the following terms: (“Methylenetetrahydrofolate reductase” OR “MTHFR”) AND (“thyroid” OR “thyroid diseases” OR “thyroid dysfunction” OR “hyperthyroidism” OR “hypothyroidism” OR “autoimmune thyroid disease” OR “Graves’ disease” OR “Hashimoto’s thyroiditis”). All references cited in the included studies or relevant reviews were also hand searched to identify any additional articles.MTHFR C677T and/or A1298C polymorphism and thyroid dysfunction  or autoimmune thyroid diseases (Graves’ disease and/or Hashimoto’s thyroiditis); ;    provideThe quality of the included studies was evaluated according to the Newcastle-Ottawa Scale (NOS), and only studies with a quality score of 6 or better were included for further analyses. Two authors independently extracted data from all eligible studies. Disagreement was settled by discussions. For each of the included studies, the following data were collected: the first author’s last name, publication year, country, ethnicity, thyroid function and sample size of cases and controls. Hardy-Weinberg equilibrium (HWE) in the controls was also performed as another reference to determine the quality of eligible studies.MTHFR C677T and/or A1298C polymorphism and thyroid diseases were assessed by calculating the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). The statistical significance of the summary OR was determined with the Z-test. Five models, including the allele model , dominant model , recessive model , homozygote model  and heterozygote model , were compared. The heterogeneity across the studies was estimated by the chi-square-based Q statistic test and the I2 test. The fixed-effect model (using the Mantel-Haenszel method) was used if I2 ≤ 50%; otherwise, the random-effect model (using the DerSimonian-Laird method) was applied. Subgroup analyses were performed by ethnicity and thyroid function. The Revman 5.3  was used for all statistical analyses. Stata software  was used to analyze publication bias and for sensitivity analysis. Publication bias was investigated with Begg’s funnel plot, and funnel plot asymmetry was further assessed by Egger’s linear regression test ( The associations between the on test   . The siTSA 0.9.5.10 software (http://www.ctu.dk/tsa/) was used for trial sequential analysis to minimize the type-I error and random error   . The reRelevant citations were retrieved and preliminarily screened. Seventy studies were identified after discarding duplicates, and fifty-eight were excluded because they were thematically irrelevant based on the title and abstract. Thus, the full text of thirteen studies was searched and assessed. One conference abstract    was excMTHFR C677T polymorphism meta-analysis, and seven studies were eligible for MTHFR A1298C polymorphism meta-analysis. All the included studies were divided into “hyperthyroidism”, “hypothyroidism” or “not applicable (NA)” groups according to the thyroid function of the cases. The distributions of the MTHFR C677T and A1298C genotypes and the HWE of the included studies are shown in In the present meta-analysis, eight studies met our criteria for MTHFR C677T polymorphism and thyroid diseases in any of the five comparison models. However, subgroup analyses stratified by thyroid function showed a significant association of the MTHFR C677T polymorphism with hypothyroidism     . No relhnicity   .MTHFR A1298C polymorphism, only the recessive model comparison of a total of five publications reached a significant difference . Subgroup analysis stratified by ethnicity showed a significant difference in Caucasians      . There = 0.02)   , but noroidism   .vs. C). Then, Egger’s test was adopted to provide statistical evidence of the funnel plot symmetry. The results still showed no publication bias (P = 0.152). The results of sensitivity analysis demonstrated no significant effect of an individual study on the overall pooled OR, indicating the reliability of the results  increased in hypothyroidism  with the C677T polymorphism, and Abu-Hassan and cols. suggested that the interaction of the SNPs within haplotypes might act as a major determinant of disease susceptibility in comparison with the single polymorphisms in the MTHFR gene among hypothyroidism cases. They believed that carriers of the CC (677C-1298C) and TA (677T-1298A) haplotypes had significantly lower risks of hypothyroidism, whereas those with TC (677T-1298C) haplotypes had a higher likelihood of having hypothyroidism  — another mutation occurs at position 1,793 and results in alteration of the translation of an arginine to a glutamine. They observed that individuals with the variant genotypes (GA+AA) appeared to have a slightly higher risk of GD, but it was not statistically significant  is necessary to elucidate the true relationship with MTHFR gene polymorphisms.There are a few limitations in our meta-analysis. First, the numbers of included studies for our meta-analysis were relatively small, especially in the subgroup analyses. Second, our results were based on unadjusted estimates, and some other covariants, including age, sex, environmental factors, and other lifestyle factors, were not controlled in our analysis. Moreover, several included studies were inconsistent with HWE in the controls. The studies of Abu-Hassan and cols. in 2019 and Kvaratskhelia and cols. in 2020 included females only, which would result in nonconformity with HWE. Mao and cols. stated that conformity to HWE among each population was performed in their article, but the present data suggested a departure from HWE of the MTHFR gene increases the risk of hypothyroidism, while the MTHFR A1298C variation may protect patients against hypothyroidism. However, further well-designed, large-sample-size studies are warranted to confirm the association between the MTHFR C677T polymorphism and hypothyroidism.In conclusion, the present meta-analysis suggests that the C677T variant of the


Q test and inconsistency I2 statistics. The methodologic quality of the selected studies was assessed using the Newcastle-Ottawa Scale for observational studies. Our analysis, including 11 publications involving 1,200,885 participants, showed that AD use increased lung cancer risk by 11%  but was not associated with overall survival . One study examined cancer-specific survival. Subgroup analysis showed that serotonin and norepinephrine reuptake inhibitors (SNRIs) were associated with an increased lung cancer risk by 38% . The quality of selected studies was good (n = 5) to fair (n = 6). Our data analysis suggests that SNRIs were associated with an elevated risk of lung cancer, raising concerns regarding the use of AD treatment in patients vulnerable to lung cancer. The effects of ADs—particularly SNRIs—and their interplay with cigarette use and lung cancer risk in vulnerable patients merits further study.Recent preclinical studies have linked antidepressants (AD) to their potential anticancer effects in multiple cancers, but the impact on lung cancer remains unclear. This meta-analysis examined the associations between ADs and lung cancer incidence and survival. The Web of Science, Medline, CINAHL, and PsycINFO databases were searched to identify eligible studies published by June 2022. We conducted a meta-analysis using a random-effects model to compare the pooled risk ratio (RR) and 95% confidence interval (CI) in those treated with or without ADs. Heterogeneity was examined using Cochran In this meta-analysis of 11 observational studies, we found evidence of a statistically significant association between the use of certain ADs and lung cancer risk. This effect merits further study, particularly as it relates to known environmental and behavioral drivers of lung cancer risk, such as air pollution and cigarette smoke. Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide, accounting for approximately 11% of newly diagnosed cancers and 18% of cancer deaths in 2020 . As the in vitro and preclinical studies have suggested that ADs may have anticarcinogenic or tumor-suppressive effects. Cordero and colleagues showed that amitriptyline, a tricyclic antidepressant (TCA), had antitumor effects on human tumor cell lines, including lung cancer, cervical cancer, and hepatoma (Antidepressants (AD), which were used by 13.2% of U.S. adults in the past 30 days during 2015–2018  and was registered in the International Prospective Register of Systematic Reviews  platform with the registration number CRD42022350719. As this study is a summary of previously published studies, no ethical review is required.A comprehensive search was conducted using key terms to maximize the identification of the studies examining the association between AD use and lung cancer incidence and survival. Online search platforms, EBSCOhost  and Web of Science, were searched from inception to June 2022. The search terms included: lung cancer or lung neoplasms or lung tumor or lung adenocarcinoma or NSCLC or non–small cell lung cancer or SCLC or small cell lung cancer AND antidepressant(s) or anti-depressant(s) or AD medication or SSRI or selective serotonin reuptake inhibitor(s) or SNRI or serotonin-norepinephrine reuptake inhibitor(s) or TCA or tricyclic AND mortality or mortality rate or death or death rate or survival rate or survival outcomes or clinical outcomes or incidence or risk. Filters included human studies and articles published in peer-reviewed journals. We also reviewed the reference lists of the included studies and prior meta-analyses and reviews to identify additional publications that could be eligible. The full search strategies are shown in The search results from four databases were first uploaded to Covidence software .Population characteristics: eligibility criteria, age (mean or distribution), gender, smoking, depression, lung cancer histology, and treatments received.Exposure: types , timing (prediagnosis or postdiagnosis), ascertainment methods , and comparison  of AD use.Endpoints included incidence or survival, the total number of outcomes , and ascertainment methods .Covariates included in the multivariable model.Overall findings from the study, including odds ratio (OR), risk ratio (RR), or hazard ratio (HR) and a 95% confidence interval (CI) comparing two treatment groups or by dose increment (if available).Outcome:The meta-analysis was performed by combining the multivariable-adjusted OR/RR/HR of the association between AD use and lung cancer from each study using the Bayesian random-effects pooling model. A Bayesian approach reflects uncertainty in the estimation of between-study heterogeneity and is a better approach when the number of studies in the meta-analysis is small compared with a classic approach using the DerSimonian–Laird method . When thQ test and inconsistency 2I test. Egger test and the funnel plot were used to determine the potential existence of publication bias in meta-analysis. Statistical analyses were performed using the Comprehensive Meta-Analysis software  and Stata – Release 17 (StataCorp). A two-tailed P < 0.05 was considered statistically significant.Subgroup analysis was conducted to investigate potential sources of heterogeneity. First, the extent to which AD type was associated with lung cancer risk or survival was assessed. Second, study characteristics  were evaluated to examine whether the associations were consistent for different study conditions. Third, AD use with respect to lung cancer diagnosis was evaluated to assess whether prediagnosis and postdiagnosis AD use had a differential association with survival. Heterogeneity between studies was quantitatively assessed using the Cochran The data generated in this study for the meta-analyses are available upon request from the corresponding author. The data generated in this study, apart from the data used for the meta-analyses, are available within the article.We screened 545 abstracts, 12 of which were reviewed in full for eligibility. We excluded one full-text publication due to no results being reported separately for AD use , leavingThe characteristics of included studies are summarized in n = 2; refs. n = 9; refs. Regarding the types of ADs used, two studies  did not n = 2; refs. n = 4; refs. n = 1; refs. n = 3; refs. n = 2; refs. Six studies  evaluaten = 5; refs. n = 6; refs. The result of the quality assessment of selected studies was reported in I2 = 65.03%; n = 6). Further subgroup analysis by the type of ADs displayed in n = 2); however, SSRIs  and TCAs  were not associated with an increased lung cancer risk.As shown in the forest plot , the metI2 = 83.40%; n = 4), as shown in n = 2) nor TCAs  were associated with survival. None of the studies examined SNRIs. Furthermore, the results varied by the definition of exposure and the reference group. For example, Shoval and colleagues (n = 3). Studies conducted in Hungary  and TCAs  from the meta-analysis, health professionals need to be aware of the potential toxicity with long-term use of ADs.First, AD use increased the risk of lung cancer, which is somewhat contrasting with the results from previous meta-analyses in other cancers. Meta-analyses for breast cancer , colon cIn our analysis, only SNRIs showed an increased risk for lung cancer. SNRIs are commonly prescribed for depressive disorders, anxiety, and chronic pain for their ability to inhibit the reuptake of serotonin and norepinephrine, increasing the concentration of these neurotransmitters in the brain . BecauseAlthough many preclinical studies have reported tumor suppressive effects of AD use , our metn ≤ 5; ref. There are several limitations of the current analysis that should be considered. First, there was substantial heterogeneity in key study features among the published reports, including study setting, study populations, the definition of exposure, and study designs, which probably contributed to the summary measures of the meta-analysis. Second, the number of studies included in the current meta-analysis is relatively small, so the meta-analysis effect estimates are estimated with low precision. Therefore, the results of our study should be interpreted cautiously because the estimation of heterogeneity can be challenging in meta-analyses where the number of studies included in the analysis is small  are evaluated on cancer outcomes in individuals with lung cancer and with or without a diagnosis of depression.Supplementary Table S1Full Search StrategiesClick here for additional data file.Supplementary Table S2Criteria for inclusion and exclusion of studiesClick here for additional data file.Supplementary Figure S1Supplementary Figure 1: A funnel plot for the meta-analysis between antidepressant use and lung cancer risk and mortality.Click here for additional data file.


Some studies have shown that a pro-inflammatory diet may be associated with cognitive function, but their conclusions have varied considerably. We here present a meta-analysis of the current published literature on DII score and its association with cognitive health.In this meta-analysis, the PubMed, Embase, Web of Science, and Cochrane databases were searched in September 2022. The reported indexes, specifically OR, RR, and β, were extracted and analyzed using R version 3.1.0.A total of 636 studies in databases were identified, and 12 were included in the meta-analysis. Higher DII was associated with an increased risk of AD and MCI . Meanwhile, it may also cause global function impairment  and verbal fluency impairment . But there was no significant association between DII and executive function  or episodic memory .A pro-inflammatory diet is related to AD, MCI, and the functions of some cognitive domains . However, the current evidence on the role of diet-induced inflammation in different cognitive domains should be supported by further studies in the future. The aging of today’s population has become a critical challenge worldwide. The proportion of the elderly population has been gradually increasing. By 2030, the proportion of people aged 60 and over may increase from 1 billion to 1.4 billion. By 2050, the world’s population aged 60 and older may double (2.1 billion)  in recent studies , 6. WhetIn order to determine the inflammatory potential of a given diet, Shivappa et al. proposed a dietary inflammatory index (DII), which includes 36 anti-inflammatory parameters for fiber, alcohol, monounsaturated fatty acids, polyunsaturated fatty acids, omega 3, omega 6, niacin, thiamin, riboflavin, vitamin B6, B12, zinc, magnesium, selenium, vitamin A, vitamin C, vitamin D, vitamin E, folic acid, β carotene, anthocyanidins, flavan-3-ols, flavonols, flavanones, flavones, isoflavones, garlic, ginger, onions, thyme, oregano, saffron, turmeric, rosemary, eugenol, caffeine and tea, and 9 pro-inflammatory parameters for energy, carbohydrates, proteins, total fat, trans fat, cholesterol, vitamin B12, saturated fatty acids, and iron, for a total of 45 parameters. Individuals’ diets were classified along the DII according to inflammatory potential on a continuum from maximum pro-inflammatory to maximum anti-inflammatory. The higher the DII score, the greater the inflammatory potential of the given diet .Existing epidemiological studies have explored the association between DII and cognitive impairment  and cognitive function , or other common cognitive function tests such as the digit span-backward test or MoCA-score). All studies on the relationship between DII and the incidence of MCI or AD showed a positive relationship . Some stThis meta-analysis was performed in accordance with the PRISMA statement to ensure comprehensive and transparent reporting of methods and results.The literature databases PubMed, EMBASE, Web of Science, and Cochrane were searched in September 2022 and the search terms used were “mild cognitive impairment” OR dementia OR “Alzheimer disease” OR “cognitive function” OR “cognitive decline” AND “dietary inflammatory index” OR “anti-inflammatory diet” OR “inflammatory diet.” Two authors independently screened each title and abstract and then read the full text to assess the article for compliance with the inclusion and exclusion criteria which will be mentioned later. Disagreements were resolved through consensus.in vitro studies, animal studies or duplicate studies.Studies included in this meta-analysis met all the following inclusion criteria: (1) studies that focused on humans and were published in English; (2) investigated the association between the DII/E-DII and cognitive function  or the risk of cognitive disorders ; (3) the study design was case–control, cohort or cross-sectional study. (4) If multiple studies were published using the same cohort, only the most recent study was selected. If more than one article based on the same cohort was from a different population or reported different results, both were included. Studies were excluded if they were systematic reviews or narrative reviews, reports, letters, Two authors (TD and MA) screened the papers and abstracted the data independently, and conflicts were resolved by a third reviewer (DB) who was blinded to the authors and institutions of the studies undergoing review. The following information was extracted from each study: name of the first author, year of publication, country, study design, sample size, study period, dietary assessment method, number of food parameters, cognitive assessment methods, cognitive domains, results, and covariates used for adjustment.Q test and the I2statistic. Significance was defined as p < 0.05. The I2 statistic represents the amount of total variation that could be attributed to heterogeneity. I2 values ≤25%, ≤50%, ≤75%, and >75% indicated no, little, moderate, and high heterogeneity, respectively. For lower heterogeneity (I2 ≤ 50%), the fixed effect models were used, and random effect models were used for higher heterogeneity (I2 > 50%). A sensitivity analysis had been conducted by excluding one study at a time to identify potential sources of heterogeneity when the result had a high heterogeneity (I2 > 50%). The meta-analysis was performed using the “meta” package in R. Statistical analyses were performed using R version 3.1.0 .In this meta-analysis, all the reported effects, odds ratios (ORs), hazard ratios (HRs), risk ratios (RRs) and β with 95% confidence intervals and effect size were extracted. The heterogeneity test was assessed using Cochrane’s A total of 636 studies were identified in the PubMed, Embase, Web of Science, and Cochrane databases. Of these, 605 studies were excluded after reviewing their titles and abstracts to assess relevance and eligibility. Then 16 articles were excluded because they were duplicates. After careful perusal of the full texts of these articles, 3 were excluded because of unavailable or unclear outcomes and inappropriate design. Finally, 12 studies were included in the meta-analysis .The characteristics of the included studies are summarized in I2 = 0%, p = 0.39). After taking the article . The sensitivity analysis (p = 0.39) with substantially unchanged effect size . However, when it comes to the other three studies which used continuous variables, the relationship between DII and global cognition is not significant  and heterogeneity is high . The sensitivity analysis . Both heterogeneities were not high .Only three studies  evaluateI2 = 25%, p = 0.26).In terms of the association between DII and executive function, two articles , 20 usedI2 = 47%, p = 0.15).The association between DII and verbal fluency is shown in This meta-analysis summarizes the evidence underlying associations between DII and cognitive function. High DII was associated with an increased risk of overall cognitive decline, including the morbidity rate of AD and MCI, decline of both global cognition and verbal fluency. However, there was hardly any association detected between DII and either executive function or episodic memory.The dietary inflammation index (DII)  is a quaI2 = 87%, p < 0.01). And the source of heterogeneity could not be found by sensitivity analysis  in analysis . This coanalysis  used sucanalysis  only useanalysis  used theI2 = 54%, p = 0.07). After excluding the paper written by Skoczek-Rubińska, the heterogeneity was reduced to 0% (p = 0.39) with a substantially unchanged effect size . Although the small sample size and the single assessment method may be one of the reasons for the larger contribution to heterogeneity, we believe that the greatest feature of this article is the study of postmenopausal women as a specific population. Depletion of estrogen due to menopausal transition is also associated with a decline in cognitive health in women. This happens since estrogen benefits hippocampal and prefrontal cortical function, potentially enhancing verbal memory and executive function  in function , 39. TheI2 = 63%, p = 0.10). However, because only two articles were included in the meta-analysis, we were unable to perform a sensitivity analysis to identify the source of heterogeneity. We can only speculate that the possible reasons for the high heterogeneity are different study populations (one was American while another was French) and different episodic memory assessment methods (one used CERAD while another used RI-48). Although few papers took these three cognitive domains into account, we did find one paper published in 2020 that did so , because fewer than three studies were included, we were unable to conduct sensitivity analysis to further identify the source of heterogeneity. Meanwhile, although current evidence suggests that inflammation has influences on cognitive function to some extent, the mechanism is still not clear. We look forward to further studies to address this issue in the future.In conclusion, data from this study support an association between DII and increased risk of AD and MCI. A negative association was observed between DII and global cognition and verbal fluency. However, there was no significant association observed between DII and executive function or episodic memory. This study indicates that an anti-inflammatory diet can help prevent cognitive decline. However, current evidence on the role of diet-induced inflammation in different cognitive domains should be supplemented with further work in the future.DB: conceptualization, formal analysis, resources, writing – review and editing, and funding acquisition. DB, LW, SC, TD, and MA: methodology and investigation. TD and MA: writing – original draft preparation. JS: visualization. All authors contributed to the article and approved the submitted version.This research was funded by Medicine and Engineering Interdisciplinary Research Fund of Shanghai Jiao Tong University, grant number (YG2022QN011), Shanghai Municipal Health Commission, grant number (2020YJZX0139), Shanghai Municipal Science and Technology (22692191800) and National Key Research and Development Program of China (2021YFE0111800).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This meta-analysis presents strong evidence of the relationship between the two variables. Limitations and practical implications are discussed.Problematic Internet use has become a major problem worldwide due to its numerous negative correlates in the field of health, both mental and physical, and its increasing prevalence, making it necessary to study both its risk and protective factors. Several studies have found a negative relationship between resilience and problematic Internet use, although the results are inconsistent. This meta-analysis assesses the relationship between problematic Internet use and resilience, and analyses its possible moderating variables. A systematic search was conducted in PsycInfo, Web of Science and Scopus. A total of 93,859 subjects from 19 studies were included in the analyses. The results show that there is a statistically-significant negative relationship ( Internet use has grown substantially over the last few decades, with the number of users increasing by 1331.9% between 2000 and 2021 . AlthougPIU has been associated with numerous negative variables related to both mental and physical health, such as anxiety and depression , low selHow to conceptualize resilience is a widely debated topic in the field of psychology . Resiliehttp://www.covidence.org accessed on 14 November 2022) was used to manage the study selection process.This meta-analysis (registered in PROSPERO database #CRD42022382337) was conducted according to the criteria of the PRISMA statement  Appendi. A systeThe retrieved studies were selected based on the following inclusion criteria: (1) original empirical and quantitative cross-sectional or longitudinal studies; (2) published in peer-reviewed scientific journals; (3) published in English or Spanish; (4) include assessments of PIU and resilience; (5) present Pearson’s correlation coefficient between PIU and resilience or the statistical data necessary to calculate it: (6) present the sample size; and (7) the full text was available. In case of studies with partially duplicated samples, the study with the largest sample size was selected.Conducting a meta-analysis without taking into consideration the methodological quality of the included studies may lead to biased results. Therefore, an assessment of the methodological quality of the studies analyzed in a meta-analysis is essential to be able to draw reliable conclusions. The risk of individual bias of the studies included in the meta-analysis was assessed using the short version of the Newcastle-Ottawa scale developed by Deng et al. . The scaA recording sheet was prepared to code the following information for the studies included: author(s), year of publication, country in which the study was conducted, continent, sample size, mean age of participants, gender , test used to assess PIU, test used to assess resilience, risk of individual bias and Pearson’s correlation between PIU and resilience. Data coding was performed by two reviewers working independently. The reviewers matched their data after extraction and revisited papers in case of disagreements. In the event of missing data, we contacted the authors of the study to request the necessary information; where we received no response or the authors refused to provide it, the information is listed as missing. To meet the independence assumption, in the case of longitudinal studies only the first correlation between PIU and resilience was coded.χ2, this result was converted to Pearson correlations using the formula r = √(χ2/n). Subsequently, to normalize their distributions, all Pearson correlations were converted to Fisher’s Z-scores using the formula Z = 0.5 × ln[(1 + r)/(1 − r)]. All analyses were performed with Z-scores, although the overall effect size and its confidence interval were transformed back to Pearson correlations for better interpretation following the recommendation of Borenstein et al. [Most of the studies had Pearson correlations. For those studies with n et al. .Q test, while the degree of true heterogeneity not explained by random sampling error was assessed using the I2 statistic. I2 values of 25%, 50% and 75% are interpreted respectively as low, moderate and high heterogeneity [Due to the variability observed in the selected studies in terms of the countries in which they were conducted, the number of subjects and tests used, a random-effects meta-analysis with the restricted maximum likelihood method was chosen. Random-effects models generally produce more precise estimates and allow for greater generalizability of results ,40,41. Togeneity .The validity of a meta-analysis may be challenged by the presence of publication bias, a phenomenon whereby studies with statistically significant results or high effect sizes are more likely to be published . PublicaA jacknife sensitivity analysis was performed, estimating the pooled effect size while eliminating each study alternatively, to assess the individual influence on the overall effect size of each of the studies included in the meta-analysis.2 index.We examined the possible moderating role of the following variables: sex and age of participants, measures for assessing PIU and resilience, the continent in which the studies were conducts, individual risk of bias and year of publication. For continuous variables, meta-regression analyses were conducted, while for categorical variables, subgroup analyses were conducted. For subgroup analysis, and as recommended by Fu et al. , each suAnalyses were performed in R Studio using the metafor statistical package .As can be seen in rZ = −0.28 , which transformed back to Pearson’s correlation gives a result of r = −0.27 , and which, following the interpretation criteria proposed by Cohen [rZ = −0.12 to rZ = −0.55. The Cochran’s Q test result was 281.4128, p < 0.0001, hence the homogeneity hypothesis is rejected, while the I2 value reached a value of 97.46%, which is considered high according to Higgins and Thompson’s criteria [The estimated overall effect size for the correlation between PIU and resilience was by Cohen , can be criteria .z = 0.2996, p = 0.76) and the Begg and Mazumdar rank correlation test  show non-significant results, thus ruling out the presence of publication bias. Likewise, the calculation of the number of safety according to Rosenthal’s method yielded a value of n = 18,877 (p < 0.001), making 18,877 unpublished studies with an effect size equal to zero necessary to make the p-value non-significant, exceeding the critical value which, for this meta-analysis, is set at 105 studies, according to the formula (5 × k) + 10, and k being the number of studies included in the meta-analysis [Although the funnel plot is not fully symmetrical see , both thanalysis .rZ = −0.26 to rZ = −0.29 when alternately omitting each of the studies.The sensitivity analysis, performed using the jackknife method, did not show excessive individual influence of any of the studies on the estimated overall effect size, with the effect size ranging from b = −0.0028, p = 0.72) and percentage of males among participants  did not show up as moderating variables, while year of publication  does moderate the relationship between the two variables, with a total explained variability of 16.55%, with more recent studies showing lower correlations.Meta-regression analyses were conducted to examine the possible moderating effect of year of publication, mean age of participants and percentage of males in the sample on the correlation between PIU and resilience. Both mean age  between the two variables, whereby those who showed higher levels of resilience had lower levels of PIU. Sensitivity analysis reveals that this result is consistent, with none of the studies having an excessive influence on the overall effect size. Furthermore, the various tests performed to assess the risk of publication bias ruled out the presence of bias. Despite the high degree of heterogeneity found, only the year of publication proved to be a moderating variable in the correlation between PIU and resilience, explaining 16.55% of the observed heterogeneity.The systematic search identified a total of studies that met the inclusion criteria with a total sample of 93,859 subjects. The results of the meta-analyses showed a statistically significant negative correlation of moderate intensity (The result found has important implications for the prevention of PIU, a phenomenon with significant negative repercussions on mental and physical health, as well as significant associated economic costs . ResilieAmong the possible moderating variables of the relationship between PIU and resilience examined, the only statistically significant moderator was the studies’ year of publication, with more recent articles showing a smaller effect size among the variables studied. One possible explanation for this is that the more recent studies, conducted during the pandemic when many countries were in lockdown, show a lower relationship between PIU and resilience since individuals during this period suffered greater stress that could not be compensated for by their resilience levels, leading to excessive internet use to reduce this stress. By contrast, participants’ gender and age, as well as the geographical area in which the studies were conducted, are not statistically significant moderators of the relationship between PIU and resilience. The fact that there is little heterogeneity regarding these variables, especially age and geographic area, in the included studies could be influencing this result.The results of this meta-analysis should be interpreted with caution due to certain limitations. Firstly, the number of studies that met the inclusion criteria is limited, so it would be advisable for future systematic reviews or meta-analyses to extend the search to other databases. Secondly, only studies published in Spanish or English were included, which could be considered a selection bias, despite English being the most widely used language in the scientific literature. Thirdly, only one of the possible moderating variables was found to have a significant effect and it could not explain a significant percentage of the heterogeneity found. It would therefore be important for future meta-analyses to examine the role of new potential moderators of the correlation between PIU and resilience, such as the population in which the studies were carried out or the scores obtained. Fourth, given the cross-sectional design of most of the included studies, it is not possible to establish causal relationships between the variables analyzed or to examine their evolution over time, hence it would be desirable to conduct further longitudinal or experimental design research in the future to examine these matters. Finally, most of the studies were conducted in Asian countries and with adolescent and young participants, with very limited research in other geographical areas and with subjects in other age groups.PIU has become a growing problem in recent years, especially among adolescents and young people, being associated with many harmful variables, mainly psychological, hence studying its risk and protective factors to help to prevent and treat it should be a priority, bearing in mind both its negative effects and the number of people who suffer from this problem. This meta-analysis has synthesized the results on PIU and resilience. The results of this review, despite its limitations, indicate the existence of a significant negative relationship of moderate intensity between both variables that does not appear to depend on age, gender, geographical area or the tests used. This result has implications that go beyond the theoretical field by supporting the fact that working on people’s resilience can reduce the risk of PIU. Moreover, increasing resilience levels through appropriate training programs would have beneficial effects beyond reducing the risk of IPU, since resilience has also been shown to be a protective factor against other addictive behaviors such as alcohol consumption , gamblin


Subgroup analysis also revealed potential factors that may affect the outcomes, for example, the physiological condition of participants, duration, gender, and type of breakfast. In conclusion, skipping breakfast may reduce body weight while increasing the level of serum LDL-C at the same time. In view of the limited trials, further studies are needed to expound the role of breakfast omission in cardiovascular diseases.Skipping breakfast is one of the most prevalent irregular eating habits. Several pieces of evidence have reported the association between breakfast omission and a higher risk of cardiovascular diseases. Numerous publications have focused on the impact of skipping breakfast on various cardiovascular risk factors. Therefore, the current systematic review and meta-analysis aimed to assess this impact, especially with regard to anthropometric measurements, serum lipid profiles, blood pressure, and glycemic control indicators. A comprehensive search was performed in PubMed, Web of Science, Embase, Scopus, and the Cochrane Central Register of Controlled Trials up to 1 April 2023. A total of 11 eligible trials were identified to evaluate the combined effects of skipping breakfast. Final integrated results demonstrated that breakfast omission significantly decreased the body weight (mean difference = −0.66, 95% CI: −1.09 to −0.24,  Skipping breakfast is defined as the omission of any food except water . For a lAccording to the data from the American Heart Association (AHA), more than 26 million adults in the United States suffer from cardiovascular diseases (CVDs), excluding hypertension . In 201822.1A comprehensive systematic search was conducted in PubMed, Web of Science, Embase, Scopus, and the Cochrane Central Register of Controlled Trials from database inception to 1 April 2023. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Guideline was followed to evaluate the effect of skipping breakfast on cardiovascular risk factors . The met2.2Two authors (J.Y. and Y.L.) collected the characteristics of 11 included trials independently including (a) name of the first author, year of publication, and study region; (b) sample size, number of male and female participants, mean age of participants, study design, and duration; and (c) health status of participants, intervention details, and outcomes of interest. A third reviewer (D.X. or Y.W.) checked the extracted data in case of any errors. Cochrane Risk of Bias 2.0 tool (RoB2) was conducted to assess the risk of bias in RCTs including four domains: bias due to the randomization process, deviations from intended interventions, missing outcome data, and selection of the reported results . Meanwhi2.3The data of interest were presented in the form of mean and standard error or 95% confidence intervals (CIs). For data only in graphs or figures, we contacted the original authors if possible. For parallel-controlled trials, mean difference (MD) was calculated by the change from baseline in both control and intervention groups. Moreover, the value of the last endpoint was selected to analyze if there was more than one endpoint while the final level of cardiovascular risk factors was extracted to compute the MD in crossover trials. The following formula was used if the net change of SD is not provided:R = 0.5  had an intervention duration of more than 4 weeks. The detailed summary is shown in The 11 studies evaluating the effect of skipping breakfast on cardiovascular risk factors were included in this systematic review, namely, 9 RCTs, 1 randomized crossover trial, and 1 cohort study –35. The 3.3Full details of the risk of bias and grading of the evidence are shown in 3.43.4.1p = 0.002, I2 = 0.0). No significant changes were observed in other indicators: BMI: mean difference = −0.13, 95% CI: −0.30 to 0.04, p = 0.144, I2 = 0.0; Waist circumference: mean difference = −0.37, 95% CI: −1.15 to 0.40, p = 0.344, I2 = 59.4; waist-to-hip ratio: mean difference = 0.00, 95% CI: −0.01 to 0.01, p = 0.344, I2 = 59.4.Ten trials investigated the effect of skipping breakfast on anthropometrics . No statistical significance was observed in the remaining indicators: serum TC: mean difference = 7.42, 95% CI: −2.74 to 17.58, p = 0.152, I2 = 41.0; serum TG: mean difference = 3.17, 95% CI: −3.55 to 9.89, p = 0.355, I2 = 0.0; serum HDL-C: mean difference = 0.35, 95% CI: −0.53 to 1.24, p = 0.435, I2 = 0.0.Six trials probed the effect of skipping breakfast on serum lipid profiles  or DBP .Four studies focused on the effect of skipping breakfast on blood pressure , HbA1c , and HOMA-IR .Seven trials reported the effect of skipping breakfast on glycemic control indicators  tend to lose more weight compared with healthy individuals . Moreover, the level of serum LDL-C among healthy people  was higher than that of other participants . Outcome measures, especially weight, waist circumference, serum LDL-C, and TC, were affected by the treatment duration . Gender and type of breakfast also had their role in subgroup analysis. More details of subgroup analysis are presented in Subgroup analysis was performed based on the physiological condition of the participants, duration of the trials, gender, intervention of the control groups, and the design of the studies. Very little literatures focusing on DBP and HbA1c led to the failure of their subgroup analysis. A series of subgroup analyses elucidated that participants with overweight/obesity or metabolic syndrome  with this meta-analysis, although the results were not statistically different. From an eating time perspective, breakfast skipping is similar to the strategy of delayed time-restricted feeding (dTRE). Compared to simply skipping breakfast, dTRE restricts feeding to at least after 10 a.m. until 8 a.m. the next day without energy restriction; in other words, this strategy skips breakfast . The latIn general, the contemporary dietary pattern is becoming increasingly diverse, emphasizing the need for vigilance regarding unhealthy eating behaviors or habits, such as skipping breakfast. Recent research has revealed a multitude of health outcomes and effects associated with breakfast consumption or omission. Furthermore, scholarly attention has been drawn to determining the healthier and more balanced breakfast options, highlighting the significance of considering aspects like the proportion of carbohydrates and proteins, as well as their respective sources , 87–92.This current systematic review has several strengths and limitations. This is a comprehensive meta-analysis focusing on the effect of skipping breakfast on cardiovascular risk factors. For the first time, we noticed that gender differences, health status, and duration may affect the pooled results. Possible causes and mechanisms of pooled results were presented. Subject to the number of relevant literature and low to moderate level of evidence, more high-quality and large-sample studies are needed to verify or expand our findings.5Skipping breakfast may lead to weight loss and elevated levels of serum LDL-C. While it might be an alternative way to lose weight, it is a bad idea because of its negative effects on some cardiovascular risk factors.GS: Funding acquisition, Supervision, Validation, Writing – review & editing. JY: Conceptualization, Data curation, Formal Analysis, Methodology, Writing – original draft. JX: Conceptualization, Data curation, Writing – review & editing. DX: Investigation, Methodology, Software, Supervision, Writing – review & editing. YW: Formal Analysis, Project administration, Writing – review & editing. SY: Data curation, Formal Analysis, Resources, Investigation, Software, Writing – review & editing. YL: Project administration, Supervision, Validation, Conceptualization, Investigation, Writing – review & editing. HX: Visualization, Writing – review & editing. SW: Methodology, Project administration, Resources, Visualization, Writing – review & editing.