P = .000), and Asians , but not in non‐Asians . However, marked heterogeneity was existed  and subgroup analyses failed to investigate the sources of heterogeneity. Then, meta‐regression was performed and found that ethnicity could explain the observed between‐study heterogeneity (P = .002). Meanwhile, significant associations were found between paraoxonase 1 activity and diabetic macroangiopathy  and diabetic microangiopathy . In conclusion, paraoxonase 1 activity plays important roles in the risk of DM, diabetic macroangiopathy and microangiopathy with ethnicity differences. Further studies with large sample and well design are needed to confirm these results.We carried out this meta‐analysis to explore the influence of paraoxonase 1 activity on the susceptibility of diabetes mellitus (DM), diabetic macroangiopathy and diabetic microangiopathy. Relevant studies were identified from PubMed, Web of Science and CNKI without language limitation, following the inclusion and exclusion criteria. Statistical analyses were implemented with the STATA 12.0 statistical software. Thirty‐six case‐control studies were included in the meta‐analyses, in which 35 for the association between paraoxonase 1 activity and DM risk, 8 for diabetic macroangiopathy and 7 for diabetic microangiopathy. Paraoxonase 1 activity was significantly associated with the susceptibility of DM in pooled population (SMD = −1.37, 95% CI = −1.79 ∼ −0.96,  It was estimated that approximately 90% DM were type 2 diabetes mellitus (T2DM), which occurs due to cells developing a resistance to insulin. DM prevalence is rapidly increasing in developing countries with the development of economics. When DM was not properly managed, it can lead to life‐threatening complications,Paraoxonase 1, a member of hydrolases with a glycoprotein structure, is a 354 aa glycoprotein of about 45 kD that is synthesized in the liver, released to the blood and binds to the high‐density lipoprotein in calcium‐dependent manner.It has been reported that paraoxonase 1 activity was decreased in heart disease,2We carried out literature searches in PubMed, Web of Science and China National Knowledge Internet (CNKI) without language limitation, using the following key words: “PON1” or “paraoxonase 1,” “diabetes” or “diabetes mellitus” or “DM” or “T2DM” or “T1DM,” and “activity.” On the other hand, relevant articles were hand searched to identify additional reports.2.1The following criteria were used to select articles included in this meta‐analysis: (1) published as original case‐control studies; (2) paraoxonase 1 activity was detected in serum using paraoxon as the substrate; (3) reported an association between paraoxonase 1 activity and the susceptibilities of DM, diabetic macroangiopathy and/or diabetic microangiopathy. When the same series of patients were used in more than one article, we used the latest and most complete one.2.2WDL and WCF screened all searched articles and extracted data from all eligible publications independently. For each study, we carefully extracted the following information: name of the first author, published year, country, ethnicity, type of DM, type of control and paraoxonase 1 activity (mean ± SD) in each group. If there were any discrepancies, an agreement was reached after discussion; otherwise, another author was consulted to resolve the dispute.2.3Q test. The fixed effect model was used to calculated pooled SMD, when I2 < 50% and P > .05. Otherwise, the random effect model was applied. Meta‐regression analyses on published year, ethnicity, sample size, type of control and type of DM, and subgroup analyses on type of control, ethnicity and type of DM were conducted to assess heterogeneity sources across the study. Publication bias was investigated using Egger's test and funnel plot. STATA 12.0 software  was used in this meta‐analysis. P < .05 means statistical significance.Paraoxonase 1 activity in each group was described as mean ± SD. Standard mean differences (SMD) were used to evaluate the association between paraoxonase 1 activity and the susceptibilities of DM, diabetic macroangiopathy and/or diabetic microangiopathy. Heterogeneity was measured using a Chi‐square‐based 33.1Relevant publications were searched and preliminarily reviewed. As shown in Figure 3.2I2 = 98.10%, P = .000, Figure P = .002, Table As shown in Table P = .000, Figure P = .000), T1DM subgroup  and other types of DM  .Meta‐analysis showed significant relationship between paraoxonase 1 activity and susceptibility of DM .As shown in Table 3.4I2 = 92.0%, P = .000, Figure P = .018, Figure P = .533, data not shown).As shown in Table 4Our meta‐analysis firstly demonstrated the associations between paraoxonase 1 activity and DM, diabetic macroangiopathy and diabetic microangiopathy by polling the individual data set. In the overall meta‐analysis of paraoxonase 1 activity, susceptibility of DM significantly increased with low levels of paraoxonase 1 activity, but strong between‐study heterogeneity was found. Therefore, to address the substantial heterogeneity, subgroup analyses on ethnicity, type of control and type of DM were conducted. But significant heterogeneity was still existed. Then, meta‐regression was performed using the following covariates: published year, sample size, ethnicity, type of control and type of DM and the results showed that ethnicity could explain the observed between‐study heterogeneity. In addition, subgroup analysis showed significant associations between paraoxonase 1 activity and DM in Asian group, but not in non‐Asian group. Paraoxonase 1 activity was different from ethnicity, and significantly higher in Malays and Chinese than Indians.Diabetic macroangiopathy is one of the most common complications of DM, which reduced the mortality and life quality of DM patients. It is a specific type of accelerated atherosclerosis. In this meta‐analysis, paraoxonase 1 activity was significantly associated with the susceptibility of diabetic macroangiopathy. Diabetic microangiopathy including diabetic nephropathy and diabetic retinopathy is also one of the most common complications. Diabetic nephropathy is the leading global cause of end‐stage renal disease. In this meta‐analysis, paraoxonase 1 activity was significantly associated with the susceptibility of diabetic microangiopathy.Paraoxonase 1 can cleave oxidized lipids from low‐density lipoproteins. High‐density lipoproteins diminish the accumulation of lipid peroxides in low‐density lipoproteins mainly due to paraoxonase 1 activity. Paraoxonase 1 activity in human beings is very low at birth and increases with time.In this meta‐analysis, there existed some limitations. First, only articles with English and Chinese language were included in this study, some publication bias may exist. Second, significant heterogeneity was found in our analysis about the association between paraoxonase 1 activity and susceptibility of DM and diabetic complications, and for DM, ethnicity might explain some of the sources of between‐study heterogeneity. But there were only 8 and 7 articles included for analysis of the association between paraoxonase 1 activity and diabetic macroangiopathy and microangiopathy, respectively, so we failed to find the sources of heterogeneity. Thus, large sample and well‐designed studies needed to demonstrate the result in the further.In conclusion, paraoxonase 1 activity plays important roles in the risk of DM, diabetic macroangiopathy and microangiopathy with ethnicity differences. Further studies with large sample and well design are needed to confirm these results.All authors declared that there were no potential conflict of interests. Click here for additional data file.


The purpose of this comprehensive meta-analysis was to assess the association of aldehyde dehydrogenase (ALDH) expression with overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) in ovarian cancer patients.Systematic searches of Pubmed databases was performed to identify relevant literature published before February 28, 2018. A total of 14 studies (13 articles) with 2210 ovarian cancer patients were pooled. All included studies were performed by using Immunohistochemistry (IHC) for detection of ALDH expression. Hazard ratio (HR) and 95% confidence interval (CI) were extracted from included studies to evaluate the correlation of ALDH expression with OS and DFS/PFS.P = 0.113; Egger’s test, P = 0.355) and DFS/PFS  in ovarian cancer patients. The subgroup of studies with cut-off value of low expression showed that high expression of ALDH was correlated with poor OS  and DFS/PFS  in ovarian cancer patients, with no observed heterogeneity .High expression of ALDH was associated with worse OS  and poor DFS/PFS . No evidence of publication bias was observed in OS (Begg’s test, In conclusion, high expression of ALDH is correlated with worse survival profiles in ovarian cancer patients, indicating that ALDH might act as a potential molecular biomarker for prognosis of ovarian cancer. Ovarian cancer is one of the common gynecological malignancies featured by several symptoms  –4. It haCancer stem cells (CSCs) are considered as a small class of tumor cells mass with self-renewing capacity, heterogeneity as well as resistance to chemotherapy/ radiotherapy, which play critical roles in tumor initiation, progression and maintenance , 6. As oBased on the standard meta-analysis guidelines, we performed systematic searches of the National Center for Biotechnology Information (NCBI) Pubmed databases to identify relevant literature published before February 28, 2018 . The stuThe criteria for inclusion were as follows: (1) All patients were diagnosed as ovarian cancer by pathological findings. (2) The association of ALDH expression with OS, DFS or PFS was investigated. (3) ALDH expression was detected by Immunohistochemistry (IHC). The criteria for exclusion were as follows: (1) The studies about animals or cell lines. (2) Articles were reviews, letters, case reports, editorials as well as expert opinions. (3) The studies were lack of essential information related to survival. All articles from the NCBI Pubmed databases are English, and there was no geographic location restriction. This meta-analysis was designed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement . This waThe studies were selected, and the data were extracted independently by two authors. The following information was recorded: author’s name, publish year, country, patients size, histology and disease stage, survival data, cut-off value (There were 3 studies set cut-off class as high expression (> 20%), 6 studies defined cut-off class as low expression (≤20%) and 5 studies installed cut-off class as IRS), Hazard ratio (HR), 95% confidence interval (CI), and so on. Survival data included OS, DFS as well as PFS, and there were 13 studies for OS, 6 studies for DFS and 4 studies for PFS. Considering the number of studies related to DFS or PFS was relatively small, which might poor statistical power in this meta-analysis, thus, the survival data was classified as OS and DFS/PFS for final analysis, this classified method was similar with the method from previous study conducted by Feng et al. . Any dishttp://sourceforge.net). In addition, we selected the multivariate analysis if there were univariate analysis and multivariate analysis. Chi-squared test was used for the evaluation of heterogeneity that was assessed by I2 value, and I2 value < 50% was considered as no or moderate heterogeneity, while I2 value > 50% was considered as statistically significant heterogeneity. The significant heterogeneity was detected by using a random-effects model. Otherwise, the fixed effects model was used [p-values were two-sided, and p < 0.05 was considered statistically significant.All statistical analyses were performed with “meta” package in R. The major outcomes for this meta-analysis were the correlation of ALDH expression with OS and DFS/PFS in ovarian cancer patients. Some studies directly provided HR and 95% CI, while as to some other studies which did not give these data clearly, we used Engauge Digitizer version 4.1 and the relevant methods for calculation from available data or Kaplan-Meier survive cure   included in the final meta-analysis  included in this meta-analysis were summarized in Table 2 = 35%, P = 0.10).High expression of ALDH was associated with worse OS  Fig. . No sign2 = 0%, P = 0.45; IRS expression of ANRIL: I2 = 41%, P = 0.17). However, the subgroup of studies with cut off value of high expression revealed that there was no association of ALDH expression with OS in ovarian cancer patients , and significant heterogeneity existed using the random effects model .The results of subgroup meta-analysis of studies were shown in Fig. P = 0.113; Egger’s test, P = 0.355)  Fig. .Fig. 4FuSensitivity analysis was performed for the stability of the crude results, which showed that poor HR was not changed, and omitting Chang 2009 had a numerically great impact on OS compared to omitting other studies. Therefore, these results suggested that the conclusion was stable Fig. .Fig. 5Se2 = 72%, P < 0.01), the random effects model was performed for the calculation of the pooled HR with corresponding 95% CI.As presented in Fig. 2 = 0%, P = 0.55). Whereas the subgroups meta-analysis of studies with cut off value of high expression  as well as IRS expression  illustrated no correlation of ALDH expression with DFS/PFS in ovarian cancer patients, and heterogeneity was observed using the random effects model .As shown in Fig. P = 0.655; Egger’s test, P = 0.189) CD44(+)CD24(−) and ALDH (hi)CD44(+)CD133(+) cells present with enhanced tumorigenicity and metastasis compared to ALDH(low)CD44(low/−) cells, indicating that high ALDH severs as an important role in the enhanced malignant and metastatic ability of breast cancer cells . AnotherAlthough some interesting results were found in this meta-analysis, some limitations still existed. At first, there were 14 studies included in this comprehensive meta-analysis, and the numbers of studies were relatively small. Meanwhile, all ovarian cancer patients from this meta-analysis were just from five countries . In addition, significant heterogeneity still existed partly due to different characteristics of subjects, different cut off value of ALDH expression or other factors, which might lead to confounding bias. Furthermore, subgroup analyses of studies with other characteristics such as histological type, study region or follow-up duration were not carried out. Further meta-analysis included larger-scale studies is necessary.In conclusion, high expression of ALDH is correlated with worse survival profiles in ovarian cancer patients, indicating that ALDH might act as a potential molecular biomarker for prognosis of ovarian cancer.


Evidence of increased type 2 diabetes (T2D) risk associated with potatoes consumption is equivocal. We aimed to perform a meta-analyses on the association between potatoes consumption and T2D risk in prospective cohort studies.Studies published prior to 31 Aug 2016 were identified in PubMed, EMBASE, and Web of Science. Pooled relative risks (RR) and 95% confidence intervals (95%CI) based upon the highest vs. lowest category of potatoes consumption in each study were calculated in meta-analysis using random-effects models. Dose-response meta-analysis was fitted using generalized least squares regression in order to quantify the association between potatoes consumption and T2D risk.The pooled RR comparing the highest vs. lowest category of potato consumption was 1.077 . Dose-response meta-analysis revealed T2D risk increased 3.5%  for additional three serving per week serving of potato. The pooled RR comparing the highest vs. lowest category of French fries consumption was 1.362 . Dose-response meta-analysis indicated T2D risk increased 18.7%  for additional three serving per week of French fries.This meta-analysis support a significant positive association between high potatoes consumption and risk of T2D, especially the consumption of French fries. Type 2 diabetes (T2D) is a global health concern. The number of people worldwide with T2D is expected to rise to 642 million by 2040 . Health Prevention of T2D is a major public health challenge . AlthougTo provide clarification on this issue, we performed a dose-response meta-analyses of prospective cohort studies to quantify the association between potatoes consumption and T2D risk.This meta-analysis was conducted according to the guidelines of the meta-analysis of observational studies in epidemiology . We condOne author (YMZ) screened titles and abstracts, and two investigators (YMZ and NJL) reviewed full texts of potentially relevant articles and assessed study eligibility independently. Studies were included in this meta-analysis if they met the following inclusion criteria: 1) the study design was a prospective cohort study; 2) the exposure of interest was potatoes; 3) the endpoint of interest was T2D; 4) the relative risk (RR) or odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (95%CI) for at least three categories of potato consumption were reported.Data extraction was completed by two independent authors (NJL and DHD), and the discrepancies in the extraction were resolved by a third party (DYY). The following data was extracted by using a template: last name of the first author; study name; year of publication; study location; length of follow-up; number of cases and participants; demographic characteristics ; exposure (highest vs. lowest); the confounders adjusted in a multivariate analysis; and the adjusted RR, OR, or HR and 95%CIs in the corresponding exposure categories. In cases where the median or mean consumption for each category of potatoes consumption was not available, the midpoint of the upper and lower boundaries in each category was assigned as the average intake. If the lower or upper boundary for the lowest and highest category were not reported, the boundary had the same amplitude as the closest category . PotatoeP<0.10). The 2I statistic was calculated to measure the variation across studies. We considered low, moderate, and high heterogeneity equivalent to 2I values of 25%, 50%, and 75%, respectively . After exclusion of duplicates and studies that did not fulfill the inclusion criteria, we identified 143 potentially relevant studies. Two kinds of literature used the same cohort and we included only the most recently published . FinallyThe characteristics of the included studies were listed in The participants were followed over a range of 4–26 yr. Of the 6 prospective cohort studies, the Nurses’ Health Study II had the largest number of participants (n=87739) , while t2I=6.4%; P=0.375) (P=0.50)  in the random-effects model, with no heterogeneity among studies (P=0.375) . The Beg(P=0.50) .2I=70.9%; P=0.03) (P=0.74). P=0.03) . The Beg P=0.03) . Egger’sWhen we calculated potato consumption, the sensitivity analyses suggested the pooled RRs were not substantially modified by any single study, with a range from 1.050  to 1.103 . Moreover, when we calculated French fries, the sensitivity analyses suggested our results were not substantially modified by any single study, with a range from 1.189  to 1.610 .P=0.026 for linearity). The dose-response analysis revealed that the risk of T2D was increased by 3.5% for additional three serving per week of potato, the difference was statistically significant (P=0.026)  . When weP=0.0016 for linearity). The dose-response analysis revealed that the risk of T2D was increased by 18.7%  for additional three serving per week of French fries (P=0.002).Similarly, a two-stage random-effects dose-response model was performed to fit the linear dose-response relationship through generalized least squares regression, and a linear dose-response relationship was observed between French fries consumption and the risk of T2D  have been completely observed by the authors.


PD) might result from a single nucleotide polymorphism (SNP) in the glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) gene. We thus performed a meta‐analysis exploring the relationship between the rs4998386 SNP of the GRIN2A gene and PD susceptibility.Dopaminergic neuronal degeneration seen in Parkinson's disease  and 95% confidence intervals (CIs).We searched PubMed, GRIN2A gene and PD susceptibility when assuming an allelic model , a dominant model , or a recessive model .Meta‐analysis results did not show a significant association between the rs4998386 polymorphism of the GRIN2A gene is not associated with risk of PD in either Europeans or white Americans. However, large sample studies with different ethnicities should be conducted to establish the role of the rs4998386 polymorphism in PD pathophysiology.Our meta‐analysis found that the rs4998386 polymorphism of the  PD was historically considered sporadic in nature, without genetic origin. In the past decade, however, genetic studies performed in various geographical regions worldwide have strengthened the hypothesis that PD has a substantial genetic component. Numerous genes have unequivocally been tied to familial PD, including Current evidence suggests an association between glutamate‐mediated excitatory neurotoxicity and neurodegenerative diseases.The substantia nigra pars compacta (SNPC), the location of the primary pathological lesion, is predisposed to oxidative stress as well as toxic and metabolic insults.GRIN2A) gene encodes for an epsilon subunit of NMDAR . No studies have focused on an association between the SNP of the GRIN2A gene and PD susceptibility. However, four studies to date have established an interaction between rs4998386 polymorphisms of the GRIN2A gene and caffeine on PD risk. Though these studies were not performed to establish association between GRIN2A rs4998386 SNP and PD, we extracted relevant data from these studies to perform a meta‐analysis exploring the relationship between the rs4998386 SNP of the GRIN2A gene and PD susceptibility.With this supporting data, we hypothesized that dopaminergic neuronal degeneration seen in PD could result from a single nucleotide polymorphism (SNP) in the NMDAR. The glutamate ionotropic receptor NMDA type subunit 2A  statement.2.1GRIN2A gene polymorphism,” “glutamate ionotropic receptor NMDA type subunit 2A gene polymorphism,” “NMDAR2A gene polymorphism,” or “rs4998386 polymorphism” in combination with “Parkinson's disease,” “idiopathic disease,” or “neurodegenerative disease.” Titles and abstracts were screened and full text was acquired for all papers. Those that met inclusion criteria were manually reviewed for confirmation of their eligibility. Screening, report retrieval, and inclusion/exclusion of studies were conducted by two authors (G. N. and R. O.). Any uncertainty about study eligibility was resolved through discussion with the third author.We searched PubMed, EMBASE, Web of Science, Google Scholar, and China National Knowledge Infrastructure for studies published between January 2005 and January 2019. Searches were conducted using the following keywords and phrases: “2.2Studies conducted on human subjects were included, without limitation of study language. In this meta‐analysis, all included studies met the following criteria: (a) studies focused on the association between rs4998386 polymorphism and PD susceptibility, (b) patients with PD were diagnosed using standard diagnostic criteria by a neurologist, and (c) there were sufficient data of the genotypes in the case‐control groups to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs). The exclusion criteria were: (a) publications with overlapping cases and controls from a similar study, (b) no genotypic data available, and (c) publications with patients with other forms of parkinsonism.2.3Relevant data from each study, along with their supplementary files, were independently extracted by two reviewers (G. N. and R. O.) using a standardized, structured methodology that included the following: first author, type of design, site of study, patient ethnicity, year of publication, sample size of cases and controls, control design, Hardy‐Weinberg equilibrium, source of DNA, genotyping method, and data of the genotypes in the case‐control groups. The methodological quality of each study was assessed independently by two reviewers (G. N. and R. O.) using the parameters previously used by Kumar et al.2.4Q test and the I2 test. The presence of P values above .1 or I2 more than 50% was considered an indicator of significant heterogeneity. When significant heterogeneity was present, we selected the random‐effects model to calculate the effects size. Three genetic models were examined: the allelic model , the dominant model (TT + TC vs CC), and the recessive model (TT vs CC + TC). Subgroup analyses were conducted according to geographic location. Sensitivity analysis was performed to examine the stability of analysis. Egger's linear regression test and Begg's test were used to identify publication biases. Statistical analysis was performed using Comprehensive Meta‐Analysis software .The association between the rs4998386 polymorphism and PD susceptibility was evaluated by calculating the pooled ORs and 95% CIs. Heterogeneity between the included studies was determined with Cochran's 33.1The results of the systematic literature search and selection are summarized in Figure 3.2Our research included four studies with data from 12 different cohorts. All studies used a case‐control design. There were 5783 cases and 8788 controls in our study. Hamza et al used four different cohorts from the United States in their study: (i) NeuroGenetics Research Consortium (NGRC); (ii) Parkinson, Environment and Gene (PEG); (iii) Parkinson's, Genes, and Environment (PAGE) from the prospective NIH‐AARP Diet and Health Study cohort; and (iv) Hussman Institute for Human Genomics (HIHG).Of the 12 different cohorts included in our study, nine were from the United States, with all included participants of Caucasian race. Methods of PD case and control ascertainment are given in Table 3.3GRIN2A gene and PD susceptibility when assuming an allelic model , a dominant model , or a recessive model . Forest plots of the results for the allelic, recessive, and dominant models are demonstrated in Figures Due to significant heterogeneity within studies in the allelic and dominant models, we used a random‐effects model to estimate pooled ORs and 95% CIs. The recessive model was without heterogeneity, so we used a fixed‐effects model to estimate pooled ORs and 95% CIs. Meta‐analysis results did not show a significant association between the rs4998386 polymorphism of the P = .36; Begg's test: P = .71), recessive model , or dominant model . In addition, on inspection of the funnel plot, publication bias was not obvious. Funnel plots for the detection of publication bias in the allelic, recessive, and dominant models are demonstrated in Figures There was no evidence of publication bias on the allelic model (Egger's test: P = .12) or white Americans . In the dominant model, the rs4998386 polymorphism was not associated with PD in either Europeans  or white Americans . Similarly, in the recessive model, the rs4998386 polymorphism was not associated with PD in either Europeans  or white Americans .For all three genetic models, we sequentially excluded a single study from the pooled analysis and recalculated the summary ORs to check whether the summary ORs were significantly changed. The recalculated ORs also indicated stability of analysis. We performed a subgroup analysis based on the geographical location of the study (Europe vs America). In the allelic model, the rs4998386 polymorphism was not associated with PD in either Europeans (OR, 0.73; 95% CI, 0.49‐1.09; 4While the NMDAR is involved in synaptic plasticity and learning, its excessive activation results in excitotoxic neuronal damage, which is hypothesized to be a mechanism underlying several neurologic and neurodegenerative disorders. Increased glutamatergic transmission through the NMDAR is believed to play a role in the degeneration of the nigrostriatal dopaminergic pathway seen in PD pathophysiology. This deterioration leads to significant changes in striatal circuit structure and function, including modifications of the corticostriatal glutamatergic synaptic architecture and, consequently, loss of striatal synaptic plasticity and dopaminergic neurons.GRIN2A to be a PD modifier gene via interaction with coffee.The neuronal NMDAR signaling has been found to be an important pathway in the development and progression of schizophrenia,GRIN2A, genetic alteration in other subunits of NMDARs are also associated with PD. A study by Wu et al found that polymorphisms in the GRIN1 and GRIN2B genes may serve as potential biomarkers for a reduced risk of PD among the Chinese population in Taiwan.GRIN2B gene were associated with an increased risk of developing impulse‐control behaviors among PD patients.GRIN2A gene of NMDAR and PD risk. Therefore, we conducted a meta‐analysis to examine the association between the rs4998386 polymorphism of the GRIN2A gene and PD risk.Apart from GRIN2A polymorphism alone is uncommon and small in effect, our power to detect genetic effects may have been reduced. PD is a multigenic disorder, with combined effects of multiple genotype polymorphisms predisposing carriers to increased PD risk. In two of the three genetic models, statistically significant heterogeneity was evident. Several aspects may contribute to this heterogeneity, including the diagnostic criteria used, early/late‐onset PD ratio, sex ratio, mean allele frequency, methods of genotyping, and source of DNA. Moreover, heterogeneity may also be due to the variations in age and environmental factors.Our meta‐analysis found that the rs4998386 polymorphism is not associated with PD in Europeans or white Americans in any of the three genetic models, though our results may have been influenced by several factors. Given assumptions that PD is multi‐determined and that the In addition, the following study limitations should be acknowledged. First, only people of European ancestry were included in our study. Therefore, results should be cautiously interpreted. Second, some useful information, such as diagnostic criteria, clinical stage of PD, onset age of PD patients, and other environmental factors, was not available. Third, significant heterogeneity was evident in our meta‐analysis. Lastly, gene‐gene interaction and gene‐environment interaction could not be analyzed due to lack of sufficient data.5GRIN2A gene is not associated with risk of PD in either Europeans or white Americans. However, considering the study limitations, large sample studies with different ethnicities should be conducted to establish the role of the rs4998386 polymorphism in PD pathophysiology. Furthermore, age of onset, sex, and environmental factors that interact with rs4998386 polymorphisms should be investigated.Our meta‐analysis found that the rs4998386 polymorphism of the G. N. and J. R. designed the study. G. N. and R. O. carried out the literature search, review, and selection. G. N. and J. R. carried out the statistical analysis and drafted the manuscript. All authors were involved in revising the manuscript critically for important intellectual content. All authors read and approved the final manuscript.The authors declare no conflicts of interest.


Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS.The association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI).All relevant studies reporting the association between the A total of 30 case–control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model . Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations.This meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene–environment and gene–gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS. Multiple sclerosis (MS) is a chronic and demyelinating disorder of the brain and spinal cord that mainly develops in young individuals , 2. TissVDR gene is located on the chromosome 12q12–14 and series of restriction fragment length polymorphisms (RFLP) in the human VDR gene have been reported, containing BsmI (rs1544410), ApaI (rs7975232), FokI (rs2228570), and TaqI (rs731236) restriction sites [VDR gene in the intron between exons 8 and 9, and shown to be in strong linkage disequilibrium (LD) with each other [VDR gene is involved in the regulation of gene expression by regulating the mRNA stability and expression level [The human on sites . ApaI, Bg BsmI rs44410, Apon level .VDR gene single nucleotide polymorphisms (SNPs) has been investigated in several studies. Particularly, studies have evaluated associations between the most common SNPs of the VDR gene  and MS. While studies in Australia [VDR gene polymorphism and MS risk. Nevertheless, the other meta-analysis by Zhang et al. [VDR gene polymorphisms and susceptibility to MS.The association between MS and ustralia , Kuwait ustralia , and souustralia  reportedustralia , Slovakiustralia , and Greustralia  have faiustralia ., and Gaustralia . have ing et al. ., and Tig et al. . demonstThe current systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement .VDR gene FokI (rs2228570) or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. The following search terms were applied: (VDR” or “vitamin D receptor”) AND (“multiple sclerosis” OR “MS”) AND (“polymorphisms” OR “single nucleotide” OR “polymorphism” OR “SNP” OR “variation” OR “mutation”). As a complementary approach, in order to detect additional potentially relevant studies, manual evaluation of the reference list of the included eligible studies was performed. In this meta-analysis, the strategy of search was restricted solely to the English-language publications and human population.All relevant studies reporting the association between the Two reviewers independently assessed titles and abstract of all studies retrieved in the initial search. Articles not following the eligibility criteria were excluded by applying a hierarchical approach based on study design. Full-text examination was applied if we could not decide include or exclude based on titles and abstract. In particular conditions, if an author has published more than one study by the same case series, the most recently published study was included. Any disagreements were discussed and resolved by consensus.VDR gene single nucleotide polymorphisms and the risk of MS as the main outcome; 2) Sufficient data are available to extract or calculate odds ratios (ORs) and 95% confidence intervals (CI); 3) Contained genotypic or allelic distributions of case and healthy individuals for VDR gene polymorphism in the studies. The exclusion criteria were as follows: 1) Studies which genotype or allelic frequency could not be extracted; 2) Letters, case reports, reviews, comments, book chapter, and abstracts; 3) Duplicated reports and studies with repetitive subjects. The application of these criteria yielded 30 case–control studies eligible for the meta-analysis.Studies considered eligible if meet the following criteria: 1) All eligible case–control studies that evaluate the relationship between the Two reviewers independently extracted all data according to standardized extraction form for the following data: The author’s name, journal and year of publication, country of origin, ethnicity, number of cases and controls for every gender separately, mean or range of age, genotyping method, total sample size of cases and controls, and the number of cases and controls for each genotype. For quality assessment of the included publications, the Newcastle-Ottawa Scale (NOS) was applied . StudiesVDR gene FokI, TaqI, BsmI, and ApaI polymorphisms and susceptibility to MS was evaluated by OR and 95% CI. Defined model for FokI, TaqI, BsmI, ApaI were as follow, respectively: FokI; dominant model (ff + Ff vs. FF), recessive model (ff vs. Ff + FF), allelic model (f vs. F), homozygote model (ff vs. FF), and heterozygote model (Ff vs. FF); TaqI; dominant model (tt + Tt vs. TT), recessive model (tt vs. Tt + TT), allelic model (t vs. T), homozygote model (tt vs. TT), and heterozygote model (Tt vs. TT); BsmI; dominant model (bb + Bb vs. BB), recessive model (bb vs. Bb + BB), allelic model (b vs. B), homozygote model (bb vs. BB), and heterozygote model (Bb vs. BB); ApaI; dominant model (aa+Aa vs. AA), recessive model (aa vs. Aa+AA), allelic model (a vs. A), homozygote model (aa vs. AA), and heterozygote model (Aa vs. AA). For each genetic model, subgroup analysis was applied to evaluate ethnicity effects. In consideration of the possibility of heterogeneity (between study variability) across included studies, chi-square based Q-test was used [I2) was calculated as the percentage of heterogeneity. There was significant heterogeneity if an I2 values exceeded 50% or the Q statistic had a P value less than 0.1. In the presence of significant heterogeneity, the random effects model (DerSimonian–Laird approach) was performed. Otherwise, the fixed effects model (Mantel–Haenszel approach) was performed for combination of data [P value< 0.05 was considered statistically significant) [Deviation from Hardy–Weinberg equilibrium (HWE) for distribution of the allele frequencies was analyzed using Chi-Square test in control group. Sensitivity analysis was conducted to estimate the stability of the results by removing the studies not in HWE. The strength of association between the was used . Additio of data , 31. Visificant) , 33. TheThe primary search in web of science, Scopus, and PubMed databases yielded a total of 636 publications. After removal of duplicates and evaluation of title/abstract, only 76 studies remained for full-text examination. Eventually, 30 studies met the inclusion criteria and included for quantitative synthesis. The search workflow is shown in Fig. I2 < 50%, fixed-effects models; I2 > 50%, random-effects models) ascertained the application of Fixed-effects or random-effects models.The distributions of FokI, TaqI, BsmI and ApaI genotypes of the included studies are shown in Table  in European populations. And finally, Wang et al. [VDR gene polymorphisms act as a potential risk factor in development or progression of autoimmune disorders.g et al. . describo et al. . represeo et al.  showed tg et al.  reportedVDR gene polymorphisms and MS, these findings were inconclusive due to the variations of the literature and selected databases. Hence, for resolving these inconsistencies, and to decrease the heterogeneity and the probability of random errors, we set out an updated meta-analysis. In this study, 30 studies met the inclusion criteria and were included for quantitative synthesis. No evidence of publication bias was observed for all four SNP in subgroup analysis and overall populations under five genetic models. Regarding the essential role of genetic factors in the pathogenesis of MS, we categorized our results according to ethnicity. Our meta-analysis revealed that BsmI, ApaI, and TaqI polymorphisms may play a significant role in the pathogenesis of MS in overall and Asian population. The results of this study indicated that TaqI polymorphism was associated with MS susceptibility under heterozygote contrast in overall population.Although four meta-analyses have been conducted in the past 10 years to evaluate the relationship between the VDR gene polymorphisms and the MS risk in European population. However, a significant association between BsmI and ApaI polymorphisms and MS susceptibility was detected in Asian population. BsmI polymorphism was associated with 64% increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with 37.5 and 34.5% decreased risk of MS under recessive model and aa vs. AA model in Asian populations, respectively. The possible reason of the conflicting results among Asian, European, and overall population could be related to environmental factors the individuals exposed to and different genetic backgrounds, which may have disproportionate effects on MS risk.Subgroup analysis based on continent rejected any association between VDR gene polymorphisms and the MS susceptibility, but no significant association was found. Another study by Garcia-Martin et al. that analyzed ten studies with 2944 MS patients and 3166 healthy subjects, reported that TaqI and FokI polymorphisms were not associated with the MS risk. In accordance with our study, the study of Zhang et al. [VDR gene polymorphisms and the MS susceptibility. However, there are some obvious differences in the findings of these studies in comparison with our study. Meta-analysis of Tizaoui et al.. reported an association of the FokI FF and ApaI AA genotypes with an elevated susceptibility of MS in a total of 3300 MS patients and 3194 healthy subjects from 13 case-control studies. In contrast, our analysis, consisting of 20 case-control studies, showed that ApaI polymorphism was associated with decreased risk of MS in Asian populations. In addition, the study of Zhang et al. reported that the A allele was related with the onset of disease in Asian populations. Nevertheless, the sensitivity analysis, by removing the studies not in HWE, rejected any association between the A allele and risk of MS, which was dissimilar to the results of the non-sensitivity analysis. Moreover, they failed to find any association between TaqI, BsmI, and ApaI polymorphisms and MS susceptibility in overall populations, Asians, and Caucasians. The main reasons that VDR gene polymorphism plays a diverse function across different studies or in different ethnic populations may be due to the following hints. Firstly, in many cases, controls in included studies deviated from HWE. Secondly, the differences in the ethnic contextual characteristics of the patients may be an important factor for these variations. Thirdly, VDR SNPs were suggested to be related with the basal levels of 1,25(OH)2D3 and vitamin D structure and function [These findings are inconsistent with the results of the Huang et al.  and Garcg et al. . and Tizg et al. . showed function , which iSeveral epidemiological studies have strongly proposed that vitamin D insufficiency and sunshine contributes to MS risk in temperate countries. Vitamin D sufficiency and insufficiency could be a protective and risk factor, respectively, among many other factors, and may be constantly regulating the global MS susceptibility from the mother’s pregnancy to adulthood. The main role of vitamin D in MS seems to be immunomodulatory, affecting the different groups of T and B cells in the general immune system, however, neurotrophic and neuroprotectant mechanisms could also be applied at the central nervous system (CNS) , 63. IntPermutations and combinations of common variants account as a predisposition factors in the etiology of several complex diseases. Variations of DNA sequence like SNPs exert modest biological impacts . Three pSome limitations of this meta-analysis should be considered. First, inaccessibility to the original data of the included studies restricted our further assessment of potential interactions, since the interactions between and even various polymorphic region of the same gene may affect the risk. Moreover, this study was solely focused on the articles published in the English language. We detected significant heterogeneity in all of the genetic models, which could be derived by various factors, such as variations in ethnicities. In the current study, ethnicities were Caucasians from Asians, Caucasians from Europe and Australia. Also, heterogeneity may be created by publication year of included studies, which extended between 1999 and 2018. There are several other possible reasons which may be regarded as a source of heterogeneity. Firstly, the criteria of MS diagnosis are inconsistent between studies. While some of them employed Poser’s criteria, other studies used McDonald’s criteria for MS diagnosis. Secondly, gender may act as a potential source for heterogeneity. Although both male and female subjects were enrolled in most studies, two studies were not sex-matched and one study only included women subjects , 43, 45.MHC genes with VDR gene have been demonstrated to be important in MS [The results from the studies examined in this met-analysis should be interpreted with cautious for some reasons. Our findings suggest that, to afford accurate estimates of the relation between VDR polymorphisms and MS risk, several factors should be regarded. Although there are many functional VDR polymorphisms in the promoter region of the VDR gene, only four SNPs in the VDR gene have been evaluated. The interaction of the nt in MS , 75. RemTaken all together, the current meta-analysis affords a comprehensive investigation of the available information for the association between the VDR polymorphisms and MS susceptibility. This meta-analysis of 30 case-control studies reveled a significant association between TaqI polymorphism and MS susceptibility. In subgroup analysis, BsmI polymorphism was associated with increased risk of MS in Asian populations. In addition, ApaI polymorphism was associated with decreased risk of MS in Asian populations. However, neither in overall population nor in subgroup analysis significant association between Fok1 (rs2228570) polymorphism and MS susceptibility was found. Future large-scale studies on gene–environment and gene–gene interactions are required to estimate related risk factors and assist early diagnosis of patients at high risk for MS.Additional file 1: Figure 1. Forest plot of association between Fok1 gene Polymorphism and MS risk; Dominant model, Recessive model allelic model, ff VS. FF model, Ff vs FF model. Figure 2. Forest plot of pooled odds ratio (OR)) and 95% confidence interval of individual studies and pooled data for the association between Fok1 polymorphism and MS risk in different ethnicity subgroups and overall populations for Dominant model, Recessive model, allelic model, ff VS. FF model, Ff vs FF model. Figure 3. Forest plot of association between Taq1 gene Polymorphism and MS risk; Dominant model, Recessive model, allelic model, tt VS. TT model, Tt vs TT model. Figure 4. Forest plot of pooled odds ratio (OR)) and 95% confidence interval of individual studies and pooled data for the association between Taq1 polymorphism and MS risk in different ethnicity subgroups and overall populations for Dominant model, Recessive model, allelic model, tt vs TT model, Tt vs TT model. Figure 5. Forest plot of association between Bsm1 gene Polymorphism and MS risk; Dominant model, Recessive model, allelic model, bb VS. BB model, Bb vs BB model. Figure 6. Forest plot of pooled odds ratio (OR)) and 95% confidence interval of individual studies and pooled data for the association between Bsm1polymorphism and MS risk in different ethnicity subgroups and overall populations for Dominant model, Recessive model allelic model, bb VS. BB model, Bb vs BB model. Figure 7. Forest plot of association between Apa1 gene Polymorphism and MS risk; Dominant model, Recessive model, allelic model, aa VS. AA model, Aa vs AA model. Figure 8. Forest plot of pooled odds ratio (OR)) and 95% confidence interval of individual studies and pooled data for the association between Apa1 polymorphism and MS risk in different ethnicity subgroups and overall populations for Dominant model, Recessive model, allelic model, aa VS. AA model, Aa vs AA model.


MMP-8 rs11225395 promoter polymorphism. Relevant studies published by 12 June 2019 were identified by systematically searching PubMed, Web of Science, Cochrane Library, CNKI and Wanfang databases. R programs and STATA software were used to calculate odds ratio (OR) and 95% confidence interval (CI). In total, 7375 cancer samples and 8117 controls were included by integrating 15 case-control data sets. Pooled estimates from the statistical analysis revealed no statistical significance for the association between this polymorphism and cancer risk. All pooled estimates resulting from subgroup analyses by cancer type and sample size were not materially altered and did not draw significantly different conclusions. The stratified analyses according to geographic region showed the statistical significance for increased cancer risk of the MMP-8 rs11225395 polymorphism in non-Asian populations under the allele model , homozygote model , heterozygote model , and dominant model . However, no statistical significance was detected in Asian populations. In conclusion, these findings suggested that the MMP-8 rs11225395 polymorphism is associated with elevated susceptibility to cancer in non-Asian populations.This meta-analysis aimed to systematically review the evidence on cancer risk of the  Cancer is still one of the most devastating diseases, leading to millions of deaths worldwide each year. As a multifactorial disease, this life-threatening malignancy could result from lifestyle factors, dietary habits, environmental impact, and genetic predispositions. Its relevance to genome variations, including single-nucleotide polymorphism (SNP), has been backed up with more and more scientific evidence ,2,3,4.Matrix Metallopeptidase 8 (MMP-8) gene, located on chromosome 11q22.2, encodes a collagenase participating in the process of extracellular matrix degradation and remodeling, whose deregulation could promote tumorigenesis and progression. Although several previous studies have reported the inhibitory effect of the MMP-8 gene on carcinogenesis and metastasis, conflicting evidence for its function as an oncogene also exists. In oral tongue squamous cell carcinoma, high MMP-8 expression could reduce tumor invasion and migration  and leadMMP-8 rs11225395 (C-799T) polymorphism could lead to a C to T single-nucleotide variation in the promoter region. Scattered evidence illustrated that the T allele of this polymorphism could lead to significantly higher promoter activity and protein expression than its C allele [The C allele ,14. ProgC allele , but theC allele . Based oMMP-8 rs11225395 polymorphism and cancer risk have been reported. The limited sample size of all these studies may also markedly reduce the statistical power of their conclusions. To better elucidate the genetic impact of the MMP-8 rs11225395 polymorphism, these scattered case-control studies should be pooled into a meta-analysis.Discrepant results for the association between the https://www.ncbi. nlm.nih.gov/pubmed), Clarivate Web of Science (https://www.webofknowledge.com/), Cochrane Library (https://www.cochranelibrary.com/advanced-search), CNKI (http://www.cnki.net/), and Wanfang Data (http://www.wanfangdata.com.cn/). The retrieval type consists keywords for polymorphism ID, gene name and symbol , aliases for cancer , and terms representing single-nucleotide polymorphism . Articles citing the studies involved in this meta-analysis were also retrieved by Google Scholar (https://scholar. google.com/). The references of the eligible articles and reviews were manually examined to identify additional relevant studies. Results retrieved from the inception of these databases up to 12 June 2019 were considered for this meta-analysis.Potentially eligible studies were queried in five literature databases: PubMed  not for cancer risk; (c) no genotype data for cancer and control samples. Inclusion criteria were as follows: (a) enough data for pooled estimates in at least one genetic model; (b) no benign tumor samples were included in the case group; (c) in Chinese or English.To evaluate the eligibility of each study, four authors independently screened the list of identified literature by sticking to the same inclusion and exclusion criteria. For a study to be excluded from further analysis, the full-text context should be accessible, and the study had to meet at least one of the following prespecified exclusion criteria: (a) not for the p < 0.05 indicates statistical significance) and then qualitatively labeled as a study characteristic. The Newcastle–Ottawa Scale (NOS) system was applied to evaluate the quality of the studies involved . A study scoring greater than or equal to seven out of nine will be labeled with ‘high quality’, four to six as ‘medium quality’ and less than four as ‘poor quality’.Four authors independently performed the data extraction. The following information regarding study design features and patient characteristics were recorded: (a) name of the first author, (b) year of publication, (c) cumulated genotype number in cancer and control groups, (d) geographic region of involved samples, (e) sample size, (f) genotyping method, (g) cancer type. Additionally, appropriateness of the Hardy–Weinberg equilibrium (HWE) in the control group was statistically measured  programmers were delegated to develop statistical analysis scripts for statistics analysis. Moreover, two STATA software  operators were also appointed to validate the results. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated to quantitatively assess the cancer risk in the allele model (T vs. C), homozygote model (TT vs. CC), heterozygote model (CT vs. CC), dominant model (CT+TT vs. CC), and recessive model (TT vs. CC+CT). A chi-squared Q-test was performed to detect the heterogeneity among studies . If significant between-study heterogeneity was identified, data were pooled using the DerSimonian–Laird algorithm (random effects model) [p was less than 0.05, publication bias was considered to be of statistical significance). A leave-one-out sensitivity analysis was conducted to evaluate the statistical stableness.Two R  . Otherwis model)  was appls model) . Publicas model)  and Beggs model)  were useAll processes in this meta-analysis strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines .https://www.ncbi.nlm.nih.gov/snp/rs11225395#frequency_tab), such as the Population Architecture using Genomics and Epidemiology study , the 1000 genome project (1000 G) [https://gnomad.broadinstitute.org/).The workflow for the literature screen and data selection fully revealed our rigid adherence to the PRISMA guidelines . A syste(1000 G) , and theA random effects model was applied in the allele model, homozygote model, dominant model, and recessive model because significant between-study heterogeneity was identified. The observed overlaps between the vertical line showing the null hypothesis (OR = 1) and the 95% CIs for pooled estimates indicated no statistical significance for altered cancer risk  and Begg’s test  revealed no significance. These results ruled out the possibility of publication bias.Publication bias in all genetic models was graphically measured using the Begg’s funnel plots . No obviTo verify whether the significance of the results was driven by any single data set, a sensitivity analysis was executed. The pooled estimates showed no statistical significance, which indicated no material change . These dp = 0.16; homozygote model: p = 0.25; dominant model: p = 0.22; recessive model: p = 0.63). Re-calculated pooled estimates under these genetic models remained stable .To explore the source of between-study heterogeneity, we analyzed the statistics for heterogeneity in Galbraith plot analysis. Two data sets in the allele model ,26, two MMP-8 rs11225395 polymorphism on cancer risk. Based on the enlarged sample size and accumulated evidence, statistical power in the meta-analysis could be markedly enhanced, which consequently derives a more accurate and credible estimation. In this study, insignificant results were obtained for the impact of the MMP-8 rs11225395 polymorphism on cancer susceptibility for the overall population. Similarly, no evidence of differential cancer risk in subgroups of cancer type was found. Neither the subgroups with large sample size nor those with small sample size revealed increased cancer risk. However, to our surprise, when stratified according to region, the non-Asian populations showed a significant association between elevated cancer risk and the T allele. The regional difference may be interpreted by the ethnic variance of genetic backgrounds, which could result in a synergistic interaction with other genetic factors. Haplotype risk estimation should be implemented when detailed genotype data for more loci are available. Environmental and lifestyle differences between regions should also be considered. Further adjustment for confounding factors, including cigarette smoking, alcohol consumption, environmental pollution, occupational exposure to hazardous chemicals, sanitary condition, and diet habits for the pooled estimates should be performed to evaluate their combined effect with this polymorphism when clinical information is ready.Meta-analysis is a requirement before the evidence for a pathogenesis association can be regarded as reliable. The current epidemiologic literature was systematically summarized to quantitatively assess the genetic impact of the This meta-analysis is useful to clearly realize the magnitude of the effect of rs11225395 on cancer risk. An important note of caution should be sounded, as the limited number of involved studies and relatively small sample size in both Asian and non-Asian subgroups may consequently lead to insufficient statistical power to determine the significance and potentially restrict the interpretation of the pooled estimates for cancer risk, in particular, concerning the influence of the risk variant on a specific type of cancer. The effect of rs11225395 on cancer susceptibility needs to be confirmed further. In addition, specific meta-analysis per tumor site should be performed individually to derive a more precise estimation of its genetic effects.Significant between-study heterogeneity was identified in four genetic models. After removing the identified sources of heterogeneity from the Galbraith plot analyses, the statistic for heterogeneity showed no statistical significance, and the pooled estimates remained stable. These results illustrated the robustness of our conclusions.A principal limitation is that our data sets search strategy was only used for databases in which the literature is in Chinese and English. Foreign languages, including French, German, and Japanese, were not taken into account due to our language limitation. Although the use of the five particular cyber databases in our systematic review provides significant data coverage security, additional data sets might have been retrieved if more databases had been queried. Furthermore, another primary limitation of this review is the statistically substantial heterogeneity for the results of pooled estimates, limiting the capability to precisely assess the size of the effects. Last but not least, analyzing rare events represents an inherent limitation because small variances in data could lead to material change for statistical significance. The use of relative measures of effect  in meta-analysis could further exaggerate the instability of the results . These lThe main superiority of this systematic review is the methodology, including the literature search, study selection, information extraction, statistical analysis, and data interpretation, was rigorous. Most involved studies were identified to be of a good or moderate quality. Moreover, the advantage in sample size over a single case-control study led to the increased statistical power. Finally, the robustness and veracity of the pooled estimates were statistically ensured by our publication bias and sensitivity analyses. All these preponderances guaranteed the reliability of this meta-analysis.MMP-8 rs11225395 polymorphism and cancer risk are reassuring, and suggest that this polymorphism is associated with elevated susceptibility to cancer in non-Asian populations. However, more large-scale case-control and prospective studies are needed to validate this population-specific correlation.Our results of this meta-analysis evaluating the relationship between the


To determine the association of lymphatic vessel density (LVD) with the prognosis of Asian non-small cell lung cancer (NSCLC) patients via a meta-analysis.Eligible studies were selected by searching PubMed and EMBASE from inception to July 25, 2017. The reference lists of the retrieved articles were also consulted. The information was independently screened by two authors. When heterogeneity was significant, a random-effects model was used to determine overall pooled risk estimates.p = 0.000, I2 = 73.2%). Subgroup analyses were performed on 5 VEGFR-3 groups , 3 LYVE-1 groups , 5 D2–40 groups , and 2 podoplanin groups . Sensitivity analysis indicated robust results. There was no publication bias.A total of 15 studies with 1075 patients were finally included in the meta-analysis. LVD was positively associated with the prognosis of NSCLC in the overall analysis (hazard ratio (HR) 1.14, 95% confidence interval (95% CI): 1.02–1.27, LVD is an indicator of poor prognosis in Asian NSCLC patients. Lung cancer is a malignant disease associated with the highest mortality rate 18.2%) among all types of cancer worldwide 8.2% amon. ApproxiCancer relapse and metastasis lead to poor prognosis. The most common mode of metastasis is lymph node metastasis. During the early stages of tumor dissemination, malignant cells spread from primary sites to regional lymph nodes. Therefore, the lymphatic system plays an important role in cancer biology . The fordrosophila homeobox gene product that is involved in the regulation of early lymphatic development [Previous studies have identified novel molecular markers of the lymphatic endothelium that have been used to study tumor-associated lymphangiogenesis via immunochemistry. These markers include VEGFR-3, Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), D2–40, podoplanin, Prox-1 and desmoplakin, among others –16. VEGFelopment . Desmoplelopment –24, but elopment –27. TherPubMed and EMBASE were searched from inception to July 25, 2017, to find related studies. The search terms used were 1) “Non-small cell lung cancer”, “Non-small cell lung carcinoma”, “NSCLC”, “lung adenocarcinoma”, “adenocarcinoma of lung”, “lung squamous cell cancer”, “squamous cell cancer of the lung”, “lung squamous cell carcinoma”, “squamous cell carcinoma of the lung”, “lung large cell cancer”, “large cell cancer of the lung”, “lung large cell carcinoma”, and “lung large cell carcinoma”; 2) “Lymphangiogenesis”, “Lymphangiogeneses”, “Lymphatic microvessel density”, “Lymphatic vessel density”, “Lymphatic microvessel”, and “Lymphatic vessel”; and 3) “prognostic”, “prognosis”, and “survival”.The inclusion criteria were as follows: 1) a cohort study; 2) an Asian study population; 3) diagnosis of NSCLC based on lung histology, with the most important histological types being ADC, SCC and large cell cancer (LCC); 4) evaluation of the association between LVD and the prognosis of NSCLC patients; 5) analysis of lymph microvessel markers by immunohistochemistry; and 6) the presence of sufficient data to calculate the adjusted hazard ratio (HR) or risk ratio (RR) and the corresponding 95% confidence intervals (CIs). Studies were excluded if they had non-human study subjects. If the data were duplicated or the same population was used in more than one study, we chose the most recent or complete study.The eligible studies selected for our meta-analysis were independently evaluated by two reviewers (XXQ and XSL) based on the aforementioned selection criteria. The following information was extracted from the eligible studies: the name of the first author, publication year, study period, country, sample number, sex of patients, median follow-up period, mean age or age range of patients, histology, histological type, TNM stage, and lymphatic endothelium markers in Table . In addi2 test were used to assess heterogeneity among the studies [P values for the Q-test, which represented heterogeneity; heterogeneity was present if the P value was less than 0.10. The random-effects model was applied when I2 > 50% [To compute a pooled HR with a 95% CI, the Q-test and the I studies . We alsoI2 > 50% ; otherwiI2 > 50% . SubgrouI2 > 50% . FinallyI2 > 50% . The datUsing the predefined search strategy and inclusion criteria, 15 studies , 33–41 iThe characteristics of the 15 eligible studies are shown in Table 2 = 73.2%; P = 0.000).LVD was positively associated with the prognosis of NSCLC in the overall analysis  . No statistically significant heterogeneity was observed in the 5 VEGFR-3 group ; however, there was considerable heterogeneity in the 3 LYVE-1 groups , the 5 D2–40 groups  and the 2 podoplanin groups   or Egger’s linear regression test (p > |z| = 0.133)  Figs.  and 6.FiNSCLC is the most common subtype of lung cancer, with a high incidence, high mortality, low survival rate, low diagnosis rate and treatment rate. It has been challenging to improve survival rates due to the lack of precise prognostic markers. To overcome this problem, a comprehensive understanding of lymphatic endothelium markers is needed. It is important to examine whether LVD can be an indicator of the prognosis in Asian NSCLC patients.In our present meta-analysis, LVD was positively associated with the prognosis of NSCLC , indicating that high LVD indeed predicts poor survival in Asian NSCLC populations. To date, only Wang and colleagues  have desThe role of LVD as a prognostic predictor in NSCLC remains controversial. Kajita and colleagues were the first to report VEGFR-3 expression in lung cancer cells, but they did not evaluate its impact on the prognosis or the correlation of VEGFR-3 expression with clinicopathologic features in patients with NSCLC . Later, VEGFR-3, D2–40, LYVE-1 and podoplanin are widely used and extremely valuable markers of lymphatic vessels. However, one study has reported that lymphatic endothelium markers are not only expressed on lymphatic vessels but also expressed on blood vessels, tumor cells or in normal tissues . One of Irrespective of its strengths, the meta-analysis also has certain limitations. First, although we searched all retrospective studies for the association between LVD and the prognosis of NSCLC, the eligible studies were restricted to those published in English or Chinese. Because of linguistic barrier, some non-English or non-Chinese studies were excluded. In addition, we also missed some studies that may have been published in books or journals that were not available in the online databases. Additionally, studies with negative data may not have been submitted by investigators, or studies with nonsignificant results may have been rejected by journals. Nevertheless, there was no significant publication bias in our study, although we could not completely rule out publication bias. Second, few studies did not present clear or complete data, making data analysis difficult. When we could not obtain original data from the authors via email or other means, we had to exclude those studies. Third, because of the small number of eligible articles, our study was not the most comprehensive. Fourth, our results cannot be generalized to populations worldwide, especially non-Asian populations. Thus, more comprehensive and higher quality analyses are still required in the future.In summary, this meta-analysis indicated that LVD is an indicator of the prognosis of Asian NSCLC patients. However, higher quality and more comprehensive analyses are still needed as more data are published in the future.


Neuroblastoma (NB), a neuroendocrine tumour, is one of the most prevalent cancers in children. The link between LMO1 polymorphisms and NB has been investigated by several groups, rendering inconclusive results. Here, with this comprehensive systematic review and up‐to‐date meta‐analysis, we aim to distinctively elucidate the possible correlation between LMO1 polymorphisms and NB susceptibility. Eligible studies were systematically researched and identified using PubMed, Web of Science and Scopus databases up to 10 February 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the associations. Our findings revealed that rs110419 and rs2168101 polymorphisms were significantly associated with a decreased risk of NB in all genetic models. In addition, the rs4758051 variant appeared protective against NB in homozygous, dominant and allele genetic models, whereas the rs10840002 variant markedly decreased the risk of NB in the allele model. In contrast, the rs204938 polymorphism showed a positive association with NB susceptibility in allele genetic models. In summary, our meta‐analysis is the first to provide clear evidence of an association between specific polymorphisms of LMO1 and susceptibility to NB. Of note, additional larger well‐designed studies would be helpful to further evaluate and confirm this association. The search keywords were ‘neuroblastoma’ and ‘LIM domain only 1 or LMO1’ and ‘polymorphism or mutation or variation’. Studies were included in our meta‐analysis if they met the following inclusion criteria: (a) original case‐control studies; and (b) studies comprising necessary genotyping data of LMO1 polymorphisms in both disease cases and controls. The exclusion criteria were as follows: (a) case reports, conference abstracts, meta‐analyses and duplication data; and (b) studies lacking genotype information.2.2Two investigators independently searched literature and extracted the appropriate data from eligible studies. Data collected from each study included: the first author, publication date, country, ethnicity of study participants, control‐population source, genotyping methods of LOM1 polymorphisms, genotype distributions in cases and controls, and the result of the HWE test (Table 2.3χ2 test. The strength of the association between LMO1 polymorphisms and NB risk was assessed by pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The Z‐test was implemented to establish the statistical significance of the pooled ORs. We estimated the between‐study heterogeneity by the Q‐test and I2‐test, with P < .10 indicating the presence of heterogeneity. In case of heterogeneity, a random‐effect model was used; otherwise, a fixed‐effect model was employed.All analyses were performed using STATA 14.1 (Stata Corporation). Departure from Hardy‐Weinberg equilibrium (HWE) in controls was examined by the We determined publication bias using funnel plots for visual inspection and by conducting quantitative estimations using the Egger's test. Sensitivity analyses were carried out by sequentially ignoring a single study at a time to assess the impact of individual data sets on the pooled ORs.33.1Figure 3.1.1P < .00001, AG vs AA), homozygous , dominant, , recessive  and allele  genetic models , dominant  and allele  genetic models , homozygous , dominant , recessive  and allele  genetic models  is needed to conclusively confirm the impact of specific LMOI polymorphisms on NB susceptibility and development. Unfortunately, at present we lack sufficient number of studies (studied populations) to reliably perform such analyses. Nevertheless, the presented analysis offers interesting insight into the analysed polymorphisms, as outlined above.The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript or in the decision to publish the results.M. Hashemi, S. Sarabandi, S. Karami, A. Moazeni‐Roodi, J. Śmieja: involved in conceptualization, data collection, validation, statistical analysis and manuscript writing (first draft); S. Ghavami and MJ Łos: formally analysed and finalized the manuscript.


Hormone replacement therapy (HRT) use has shown to be associated with a reduced risk of colorectal cancer, however, its impact on survival among women with colorectal cancer remains uncertain. This meta-analysis aimed to systematically assess the survival benefit of HRT use in patients with colorectal cancer.PRISMA guidelines for the reporting of meta-analyses were followed. We systematically searched PubMed, Embase, Cochrane library, Scopus, and PsycINFO from inception to 12 January 2019, with no language restrictions, for randomized controlled trials and cohort studies reporting the association between hormone replacement therapy and risk of colorectal cancer mortality or all-cause mortality in colorectal cancer survivors. We used the Newcastle-Ottawa Scale to assess the risk of bias of the included studies. We summarized the association as hazard ratio  using random-effects meta-analysis. The study protocol was registered in PROSPERO (CRD42017071914).I2 = 0%) and overall mortality . Low between-study variance was also suggested by the narrow prediction interval for colorectal cancer-specific mortality (0.58–0.86) and overall mortality (0.63–0.87), which indicated that a future study will show survival benefits in women with current HRT use compared with those with no HRT exposure. Inverse associations with colorectal cancer-specific  and overall mortality  were not observed for former users of HRT. Sensitivity analyses revealed no differences in the risk estimates between two groups.Of 1648 articles identified, five cohorts including 10,013 colorectal cancer survivors were included in this meta-analysis. Compared with women with no prior use of HRT, those reporting current use of HRT had lower risks of colorectal cancer-specific mortality (HR, 0.71 , The findings suggest that the current use of HRT is associated with lower risks of colorectal cancer-specific and overall mortality in patients with colorectal cancer. Further investigations to elucidate the underlying mechanism are warranted. Colorectal cancer is the third most common cause of cancer mortality in women, with 0.8 million new cases in 2018 worldwide . DespiteIdentification of factors associated with better prognosis among colorectal cancer survivors has important implications to inform provision of survivorship care. Extensive evidence from observational studies and clinical trials suggests that hormone replacement therapy (HRT) might have protective effect against colorectal cancer incidence. A meta-analysis of four randomized control trials and 16 observational studies showed a 26% reduction in colorectal cancer risk associated with any use of combined estrogen and progestin . SimilarIn this systematic review and meta-analysis, we aimed to summarize the available evidence and to quantify the association of HRT with colorectal-specific and all-cause mortality in women with diagnosis of colorectal cancer.The review protocol was registered in PROSPERO CRD42017071914). In this study, we followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the reporting of meta-analyses  Published original articles of randomized controlled trials or cohort studies with a minimum sample sizes larger than 50 participants; (2) Studies that enrolled colorectal cancer survivors aged 40 to 75 years, or studies that evaluated peri- or post-menopausal women; and (3) The exposure of interest was HRT. In the meta-analysis, study must either provide hazard ratio (HR), relative risk (RR), or odds ratio (OR) with 95% confidence intervals (CIs); or provide sufficient data that would allow the risk estimate to be calculated. The primary outcome was colorectal cancer-specific mortality. Secondary outcome was all-cause mortality in survivor with colorectal cancer. We excluded case-control studies, reviews, editorials, letters, and animal studies. For publications assessing duplicate population, only studies with larger sample size were included. For non-English articles, we consulted native speakers for translation. Two reviewers (YCJ and HLH) independently screened the title and abstract of potentially eligible articles for inclusion. Disagreement on eligibility was resolved by discussion between the reviewers.Two independent reviewers (YCJ and HLH) extracted the data from identified articles, and a third reviewer (CYL) crosschecked the abstracted data for accuracy. We extracted data using a standardized observation form, items of the form included name of first author, publication year, age, study design, study period, country; number of participants; cancer stage and grade at diagnosis; HRT type and recency; mortality ; and follow-up time. We extracted the most finely adjusted risk estimates from the included studies. The Newcastle-Ottawa scale (NOS) proposed by Well and colleagues was used to assess the methodological quality for cohort studies .I2 statistic, which quantifies the percentage of total variation across study results that could be explained by between-study heterogeneity rather than chance [I2 statistic of 25, 50, and 75%, respectively [p < 0.0001, exact p values are provided. We used STATA version 15.1  to analyse data.In the analysis, random-effects meta-analysis was used to pool the association between hormone replacement therapy and risk of colorectal cancer mortality and the risk of all-cause mortality in patients with colorectal cancer diagnosed. We assessed methodological and clinical heterogeneity by n chance . In thisectively . As a seectively . Potentiectively . Also, wectively . In addiFigure Overall, four prospective cohort studies –16 and oI2 = 0%) and all-cause mortality  in survivors with colorectal cancer  and all-cause mortality  . Similarly, no significant difference was observed between questionnaire assessment  and objective document  for all-cause mortality (p = 0.486).We examined the included studies for potential information bias. Among current users, the result showed no significant difference in pooled HRs of CRC-specific mortality for studies where HRT exposure was assessed by either questionnaire  or objective document   and (0.63–0.87) for colorectal cancer-specific and all-cause mortality among current HRT users, respectively. Accordingly, it is likely that a future study will show a reduced mortality risk in colorectal cancer survivors with hormone replacement therapy compared with non-hormone users.There are several limitations that merit further discussion. First, owing to the study-level nature of the data and small numbers of studies, subgroup analyses and the assessment of publication bias were limited. Second, although we extensively searched for the best available evidence, studies identified in this analysis were from the United States and Sweden, which has limited the generalizability of the findings. However, we have provided prediction interval to provide the potential ranges of future studies. Third, meta-analyses of observational studies are susceptible to information bias. However, four of the five studies included were prospective design, which could minimize information bias. Also, in our meta-regression, no significant difference was observed between questionnaire assessment group or objective document group. Fourth, the mean follow-up period of included studies were relatively short, ranging from 4.0 to 7.7 years, which may be inadequate to reflect optimal long-term outcomes. Lastly, the ability to stratify the analyses by dose, duration, and types of hormone used was limited by the paucity of data, therefore, the pooled estimates represent a combined effect of estrogen and estrogen plus progesterone. Future research is needed to understand how these factors might influence survival of perimenopausal and postmenopausal women with a history of colorectal cancer.In this systematic review and meta-analysis, the current use of hormone replacement therapy was associated with a lower risk of colorectal cancer-specific mortality and all-cause mortality in colorectal cancer survivors. Further investigation is needed on the underlying mechanism to facilitate a personalized healthcare to inform cancer survivors.Additional file 1: Table S1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the reporting of meta-analyses. Table S2. Search strategies on the PubMed. Table S3. Search strategies on the Ovid Embase. Table S4. Search strategies on the Cochrane library. Table S5. Search strategies on the Scopus. Table S6. Search strategies on the PsycINFO. Table S7. List of references with final exclusion reasons. Table S8. Newcastle-Ottawa Quality Assessment Scale for cohort studies. Figure S1. Prediction interval of colorectal cancer mortality for current users of hormone replacement therapy, using random-effects model. Figure S2. Prediction interval of all-cause mortality for current users of hormone replacement therapy, using random-effects model. Figure S3. Funnel plot of colorectal cancer mortality. Figure S4. Funnel plot of all-cause mortality. Figure S5. Forest plot of risk estimates of colorectal cancer mortality using the fixed-effect model. Figure S6. Forest plot of risk estimates of all-cause mortality using the fixed-effect model.


Background/Objective: China is now faced with a serious population aging challenge, and the health of the Chinese elderly is becoming an imminent concern. Consequently, it is critical to establish a lifestyle evaluation system for promoting the health of the Chinese elderly. Methods: Interviews with experts and questionnaire surveys were conducted. Factor analysis, analytic hierarchy process, and statistical analyses were also adopted in this study. Results: Besides evaluation metrics and standards, a two-level category system including 50 indices and associated weights from three level 1 categories  and thirteen level 2 categories were obtained. Discussion and Conclusions: Based on the confirmatory factor analysis and Cronbach’s test, such an evaluation system excels in effectiveness and reliability, and is ready to be popularized in Chinese society. We expect that the Chinese elderly will benefit from our system and that it will lead to a healthy lifestyle accordingly. According to a demographics study, China is faced with an aging challenge, and the elderly population will be doubled in upcoming decades . In ordeAs defined by the WHO, healthy aging is “the process of developing and maintaining the functional ability that enables wellbeing in older age” . Such a Healthy aging can be influenced by numerous factors. Some of these factors can be controlled by individuals, such as lifestyle factors ,8. In 20The health of the Chinese elderly can be evaluated based on indices from a two-level category system: three level 1 categories  and thirteen level 2 categories.Such an evaluation system excels in effectiveness and reliability and is ready to be popularized in Chinese society.Two hypotheses are formed in this study, as shown below:The main objective of this work was to establish a lifestyle evaluation system for promoting the health of the Chinese elderly. The secondary objective was to validate the effectiveness and reliability of the proposed lifestyle evaluation system.In 2016, a questionnaire survey was conducted among 500 subjects from 15 community centers in the metropolitan area of Xi’an city through a combination of stratified and random samplings. The respondents are representative of the entire population, and the sample size and power of the study have been calculated. The questionnaire titled “Questionnaire on health-promoting lifestyles of the elderly from Xi’an” see  was desi2 test failed to show significant differences (p > 0.05) across different age groups  method to evaluate the effectiveness of such a system.We used the analytic hierarchy process (AHP) to determine the weights of selected indices obtained in Step 2.4.3. The AHP provides a comprehensive framework based on mathematics and psychology and is particularly effective in complex decision making.In order to obtain both the level 1 (by category) and level 2  weights of indices, the analytic hierarchy process (AHP) was employed. All calculations were conducted in the MATLAB environment.(1) Determining Level 1 Weights(a) Build a Pairwise Comparison MatrixWe first built the following pairwise comparison matrix for the three criteria:(b) Compute the Weight Vector and the Largest EigenvalueWe found the largest eigenvalue and associated eigenvector satisfying:The results are shown below:(c) Calculate the Consistency IndexTo measure the consistency of matrix A, we calculated its consistency index C.I.:(2) Determining Level 2 WeightsSimilarly, we obtained the largest eigenvalues, C.I., R.C.I., and C.R., which are summarized in From In Step 3, the effectiveness test of the lifestyle evaluation system was conducted in AMOS 7.0 . In Step 4, calculations involved in AHP were conducted in the MATLAB 7.0  environment. The remaining statistical calculation results in this study were obtained by SPSS 16.0 .As defined by the World Health Organization (WHO), health is a “state of complete physical, mental, and social wellbeing, and not merely the absence of disease or infirmity” . Such a From the WHO framework where indices for evaluating each aspect of human health have been proposed and validated, we have summarized all available results and added more indices based on our interview results with experts (professors and doctors) who have rich knowledge and experience in the health of the Chinese elderly. Finally, we concluded our preliminary research with seventy-two indices in total from three aspects of health: physical, mental, and social wellbeing.We designed a questionnaire on the level of importance of each index based on the Likert Scale from 1  to 5 (very important). We asked the same experts to complete the questionnaires, and then we collected the answers and conducted the statistical analysis. We calculated the mean p-value of the Bartlett’s test was less than 0.05, we could assume that both tests demonstrated statistical significance, i.e., the data would be suitable for factor analysis. First, to find out whether the data were suitable for factor analysis, we conducted the Kaiser–Meyer–Olkin (KMO) test and Bartlett’s test. If the KMO test gave a value larger than 0.6 and the Then, we further screened the indices based on factor analysis and removed the index if (a) its communality was low; (b) it showed in only one factor; and (c) it gave high factor loadings in more than one factor. We iteratively conducted principal component analysis and varimax rotation and removed indices until no such criteria were met. Results are summarized below.(1) Factor Analysis on Indices Impacting Physical Healthp-value of Bartlett’s test was less than 0.05. As a result, both tests demonstrated statistical significance, i.e., the factor analysis on the data is statistically valid. While the KMO test gave 0.81, the Six factors with eigenvalues above 1 were selected after the analysis, and twenty-six indices were included in total and explained 60.26% of total variance contained in the dataset. Such factors were composed of 3, 5, 4, 4, 6, and 4 indices reflecting the physical condition, eating routine, exercise habits, quality of sleep, use of drugs or alcohol, and living environment, respectively.(2) Factor Analysis on Indices Impacting Mental Healthp < 0.05, respectively, showing that the data were suitable for factor analysis. Four factors with eigenvalues above 1 were selected, thirteen indices were included in total, and they explained 56.85% of total variance. The factors contained 4, 3, 3, and 3 indices related to the mental status, emotion control, stress handling, and self-regulation, respectively.The KMO test and Bartlett’s test gave 0.76 and (3) Factor Analysis on Indices Impacting Social Well Beingp < 0.05. In this case, we chose three factors with eigenvalues above 1, eleven indices were included, and they explained 52.66% of total variance. The three factors were composed of 5, 3, and 3 indices regarding prosocial behaviors, interpersonal relationships, and social recognition, respectively.Similarly, the factor analysis on indices data impacting social wellbeing was also proven to be statistically justifiable, as demonstrated by the KMO and Bartlett’s tests giving 0.88 and As shown in p < 0.01). Such a result suggests that our lifestyle evaluation system has decent generalizability, i.e., external validity.In addition, to study the generalizability of the established lifestyle evaluation system, we tested its external validity. It is universally acknowledged that lifestyle plays a fundamental role in promoting individual health. As a result, we correlated the individual performance of our lifestyle evaluation system with that of the health self-evaluation system published by WHO  and obtaAfter finalizing the indices used for evaluating the lifestyle of the Chinese elderly, we established assessment criteria based on (1) current standards, state policies, and regulations, including “Chinese Resident Health Literacy”, “Chinese Dietary Guidelines”, and “National Fitness Program and Regulations”; (2) established scientific theories and state-of-the-art research regarding human health and promoting healthy lifestyles. For example, our assessment criteria for the eating routine is “with a regular and balanced diversity of sources of protein, fiber, carbohydrate, lipid, vitamins, and minerals”. We expected the respondents to assess their individual performance based on the Likert Scale from 1 (nonconformity) to 5 (conformity).The results from both the validity and reliability tests show that our lifestyle evaluation system excels in structure validity, generalizability, stability, and consistency. In our study, a new system was established to evaluate from different aspects the lifestyles of the Chinese elderly. This survey is more comprehensive than the one established by the WHO. Although the subjects in this paper were from Xi’an city only, we are confident that subjects from other cities will generate similar results. In the future, we will test such a system on subjects from other cities such as Beijing and Shanghai.However, there are a few limitations in this study. First, the data used in our study were collected through filling out questionnaires, and currently there is a lack of objective measuring tools that are shielded from subjective views. In the future, we will incorporate indices obtained from physiological experiments in the evaluation system. Second, our current cross-sectional study has not validated the effects of intervention. As a result, in the future, we will design intervention strategies for lifestyle improvements of the elderly and conduct associated tests. In the current study, we established a novel lifestyle evaluation system for the Chinese elderly and obtained associated indices and relevant weights from reviewing the relevant WHO framework, interviews with experts, questionnaire surveys, factory analysis, and an analytic hierarchy process. The proposed two-level category system includes 50 indices from three level 1 categories  and thirteen level 2 categories. The validity and reliability of such a lifestyle evaluation system have been verified through confirmatory factor analysis (CFA) and Cronbach’s test. As a result, the system is ready to be tested in more cities and is expected to be promoted in Chinese society during the next stage. Furthermore, it can contribute to the Chinese senior care system in the future.