Association of vitamin D receptor gene polymorphism with type 1 diabetes mellitus risk in children: A protocol for systematic review and meta-analysis

Background:Recent genetic association studies showed that there are contradictory results on the relationship between vitamin D receptor (VDR) gene polymorphisms and type 1 diabetes mellitus (T1DM) risk in children. The purpose of this systematic review is to collect the currently available evidence to evaluate the relationship between VDR gene polymorphisms and the risk of T1DM in children.Methods:Such medical databases as Wanfang Data, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science were extensively searched for relevant literatures published before June 2021 with the focus on the relationship between VDR gene polymorphisms and the risk of T1DM in children. The risk of bias was evaluated as per the Newcastle-Ottawa Scale by 2 independent researchers. Meta-analysis was performed to quantify the relationship between VDR gene polymorphisms and T1DM risk in children.Results:The results of this meta-analysis would be submitted to a peer-reviewed journal for publication.Conclusion:The relationship between VDR gene polymorphisms and T1DM risk in children is explored via this meta-analysis.Ethics and dissemination:Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.Osf Registration Number:DOI 10.17605/OSF.IO/Q8XA5.     

Effectiveness and safety of Liuhedan for treating acute pancreatitis: A protocol for systematic review and meta analysis

Background:Liuhedan is a famous traditional Chinese medicine (TCM) formula used to treat acute pancreatitis (AP) in China. However, there is no systematic reviews for the evidence and the therapeutic effectiveness and safety of Liuhedan for treating AP. The aim of this study is to summarize previous evidence, assessing the efficacy and safety of Liuhedan in the treatment of AP.Methods:We will search the EMBASE, WANFANG DATA, Web of Knowledge, CNKI, PubMed, ClinicalTrials.gov and Cochrane Library from inception to June 30, 2021 to retrieve relevant studies using the search strategy: (“Liuhedan” OR “Liuhe Pill” OR “Liu-He-Dan”) AND (“pancreatitis” OR “pancreatitides”). Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I² statistic.Results:This study assessed the efficiency and safety of Liuhedan for treating acute pancreatitis.Conclusions:This study will provide reliable evidence-based evidence for the clinical application of Liuhedan for treating AP.Ethics and dissemination:Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.     

Effectiveness and safety of proton pump inhibitors for treating acute pancreatitis: A protocol for systematic review and meta analysis

Background:Previous studies have showed that anti-acid therapy with proton pump inhibitors (PPIs) can inhibit pancreatic secretion and it may be used in treating acute pancreatitis (AP). But at present, there is no systematic reviews for the evidence and the therapeutic effectiveness and safety of anti-acid therapy with PPIs in AP were not unclear. Therefore, we will undertake a systematic review of the literature to summarize previous evidence regarding this topic, in order to clarify the effectiveness and safety of anti-acid therapy with PPIs in AP.Methods:We will search the EMBASE, WANFANG DATA, Web of Knowledge, China National Knowledge Infrastructure, PubMed, ClinicalTrials.gov and Cochrane Library from inception to June 30,2021 to retrieve relevant studies using the search strategy: (“Proton pump inhibitors” OR “PPI” OR “PPIs” OR “Omeprazole” OR “Tenatoprazole” OR “Pantoprazole” OR “acid suppression therapy” OR “acid suppression drugs”) AND (“pancreatitis” OR “pancreatitides”). Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I² statistic.Results:This study assessed the efficiency and safety of proton pump inhibitors for treating acute pancreatitis.Conclusions:This study will provide reliable evidence-based evidence for the clinical application of PPIs for treating AP.Ethics and dissemination:Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.     

Risk factors of enteral feeding intolerance in severe acute pancreatitis patients: A protocol for systematic review and meta-analysis

Background:Patients with severe acute pancreatitis (SAP) have gastrointestinal dysfunction, and enteral nutrition intolerance is easy to occur during the implementation of enteral nutrition, which leads to the suspension or termination of enteral nutrition. Enteral nutrition cannot tolerate the influence of many factors. At present, there is a lack of analysis on the influencing factors of enteral nutrition intolerance in patients with SAP. Therefore, this study analyzed the factors of enteral nutrition intolerance in patients with SAP by meta-analysis, to provide a basis for the protection of enteral nutrition in patients with SAP.Methods:Databases (PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang) were searched using index words to find relevant studies published before March 2021. Meta-analyses of relative risk were performed for the identification of risk factors.Results:We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.Conclusion:This study systematically reviewed the existing evidence and determined the incidence and predictors of enteral nutrition intolerance in patients with SAP.     

Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease

Background and Aims: The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran. Methods: In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two‐year period (2004–2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction—restriction fragment length polymorphism (PCR‐RFLP) method. The genotype–phenotype association for these polymorphisms was analyzed. Results: Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 and P < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype–phenotype association was observed with any mutations. Conclusions: This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.     

Evaluation of the efficiency of calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis: A protocol for systematic review and meta-analysis

Background:Administering corticosteroid is an effective therapeutic strategy for treating most inflammatory conditions. However, there is a chance for corticosteroid treatment to adversely affect bones, resulting in corticosteroid-induced osteoporosis, which is a highly prevalent type of secondary osteoporosis. Elevated bone resorption and reduced formation of bone are pathogenesis indicators of corticosteroid-induced osteoporosis. Preventative therapy is recommended for patients initiating steroids. This study aims to evaluate the efficiency of calcium and vitamin D in treating adults diagnosed with osteoporosis caused by corticosteroid therapy.Methods:Electronic databases will be searched systematically to source studies that have evaluated the efficiency of calcium and vitamin D as a treatment method for adult patients with osteoporosis from corticosteroid therapy. The databases include, PubMed, EMBASE, the Cochrane Library, Scopus, and Web of Science. The timeline of the search will be limited from inception to November 2020. This study will utilize the Cochrane risk of bias tool to assess the quality of the studies reviewed. Moreover, appropriate methods will be chosen to analyze the data. The RevMan 5.3 software is utilized to perform statistical analysis.Results:This study will provide additional practical and targeted results of evaluating the efficiency of calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis.Conclusion:The results of this study will provide further evidence about calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis, clinicians and policymakers can make practical use of the results.Ethics and dissemination:Since this systematic review does not involve any human or animal participants, an ethics approval is not required.Systematic review registration:Aug 19, 2021. osf.io/zvb38. (https://osf.io/zvb38/).     

The association between interleukin-8 gene-251 A/T polymorphism and sepsis: A protocol for systematic review and meta analysis

Background:Emerging evidence has indicated that interleukin-8 (IL-8) gene-251A/T polymorphism may affect individual susceptibility to sepsis. However, the results of published studies are inconclusive. The aim of this meta-analysis was to elucidate the association between this polymorphism and the risk and mortality of sepsis.Methods:Relevant publications were searched from PubMed, EmBase, and Web of Science databases up to January 31, 2021, with studies only in English. The reference lists of the retrieved studies were investigated as well. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to figure out the relationship between IL-8-251 A/T polymorphisms and the risk and mortality of sepsis. All of the data were analyzed with Stata 16.0.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This meta-analysis will summarize the relationship between IL-8-251 A/T polymorphism and the risk and mortality of sepsis.     

Oral high dose vitamin D for the treatment of diabetic patients with COVID-19: A protocol for systematic review and meta-analysis

Background:Type 2 diabetes mellitus patients complicated with infections experience severe vitamin D deficiency. High-dose vitamin D is applied to the treatment of corona virus disease 2019 (COVID-19) by some researchers, and good results have been achieved. However, the efficacy of vitamin D in the treatment of infections in COVID-19 patients with diabetes remains unclarified. This study aims to explore the effect of oral high-dose vitamin D in the treatment of diabetic patients with COVID-19.Methods:Randomized controlled trials about the application of high-dose vitamin D in the treatment of diabetic patients with COVID-19 will be retrieved from such electronic databases as Embase, PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure database, Chinese Wanfang database and Chinese Biomedical Literature database. The retrieval time is from their inception to December 2020. According to the pre-designed inclusion/exclusion criteria, the data will be extracted independently by two researchers. The risk of bias of the included studies will be assessed by the Cochrane collaboration''s tool. Meta-analysis will be conducted by using Revman 5.3 software.Results:A high-quality and comprehensive evaluation of oral high-dose vitamin D for the treatment of diabetic patients with COVID-19 will be made.Conclusion:The article will provide more convincing evidence and evidence-based guidance for clinical practice.Ethics and dissemination:The private information of individuals will not be made public, and this systematic evaluation will also not infringe on the rights of participants. Ethical approval is not required. Research results may be published in a peer-reviewed journal or disseminated in relevant conferences.PROSPERO Registration Number:CRD42020214284.     

Association between MMP-2 gene polymorphism and cataract susceptibility: A protocol for systematic review and meta-analysis

Background:Matrix metalloproteinase-2 (MMP-2) polymorphisms have been considered as risk factors of cataracts, but the results still remain controversial. In this study, we have performed a systematic meta-analysis to evaluate the association between MMP-2 polymorphisms and cataract risks.Methods:Published literature was retrieved from Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases. The case–control studies that explored the association between MMP-2 polymorphisms and cataract risks were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model.Results:This study could provide high-quality and evidence-based medical evidence for the correlation between MMP-2 polymorphisms and cataract risksConclusion:The study could provide updated evidence for the evaluation of the relationship between MMP-2 polymorphism and cataract risk.Ethics and dissemination:The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF Registration Number:DOI 10.17605/OSF.IO/KU9NE.     

Effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus: A protocol for systematic review and meta analysis

Background:There is limited study that has conducted a review investigating the clinical effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus (GDM). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with GDM.Methods:This protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We will conduct systematic reviews and meta-analyses to identify relevant randomized controlled trials (RCTs) involving vitamin and omega-3 fatty acid co-supplementation on GDM in electronic databases including PubMed, Web of Science, Embase, and the Cochrane Library up to June 2021. Exclusion criteria include observational studies, non-RCTs, review articles, studies with a sample size <50, and studies with insufficient outcome data. The primary outcomes include fasting glucose and insulin. Secondary outcomes are evaluated in a homeostasis model of insulin resistance, total antioxidant capacity, triglycerides, total cholesterol, low-density lipoprotein cholesterol, preterm birth and macrosomia over 4 kg.Results:The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.Registration number:10.17605/OSF.IO/NSW54.     

Maxingshigan decoction for treating COVID-19: A protocol for systematic review and meta analysis

Background:Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has been in a public health emergency of international concern since its outbreak in 2020. Due to the complex pathogenesis and susceptibility of COVID-19, many commonly used drugs for the treatment of COVID-19 have not shown excellent clinical effects. Traditional Chinese medicine has a long clinical history of preventing and treating this respiratory infectious disease. Maxingshigan Decoction (MXSG) is widely used in China to treat COVID-19. However, there is no comprehensive and systematic evidence on the effectiveness and safety of Maxingshigan Decoction.Methods:PubMed, EMBASE, Clinical Trials, the Cochrane Library, Sino Med, and China National Knowledge Infrastructure up to September 2020. This study only screens clinical randomized controlled trials on MXSG for COVID-19 to evaluate its efficacy and safety. Data were extracted by 1 investigator and checked by an independent investigator. Review Manager 5.3 software was used for the data analysis. The dichotomous data is represented by relative risk, and the continuous is expressed by mean difference or standard mean difference, eventually the data is synthesized using a fixed effect model or a random effect model depending on whether or not heterogeneity exists.Results:The time from a positive diagnosis to a negative result of 2 consecutive nucleic acid tests (not on the same day), cure rate. The results of our research will be published in a peer-reviewed journal.Conclusion:The purpose of this systematic review is to provide new evidence for the effectiveness and safety of Maxingshigan decoction in the treatment of COVID-19.PROSPERO registration number:CRD42020211962.     

Association between vitamin D receptor gene polymorphisms and tubular citrate handling in calcium nephrolithiasis

OBJECTIVES: Hypocitraturia is a risk factor for calcium nephrolithiasis. 1,25(OH)2D3 influences renal citrate handling and enhances citraturia. The aim of this study was to evaluate the relationship between vitamin D receptor (VDR) allelic variant and urinary citrate excretion in recurrent stone formers (SF) patients. DESIGN: Case-control study. SUBJECTS: A total of 220 recurrent calcium oxalate SF patients and 114 healthy control (C) subjects were enrolled for this study. Subjects with urinary tract infections, hyperparathyroidism, cystinuria >70 micromol/24 h, gouty diathesis, renal tubular acidosis, renal failure, chronic diarrhoeal states, intake of thiazide diuretics, angiotensin-converting enzyme (ACE)-inhibitors, glucocorticoids or oestrogens were excluded. A standard constant diet was given for 7 days. The 24-h urinary citrate excretion and the active tubular reabsorption of filtered citrate (Rcit) were evaluated. Hypocitraturia was defined as a urinary citrate excretion lower than 1.7 mmol day-1. Stone formers patients and C were genotyped for BsmI and TaqI VDR alleles. Contingency table chi-square tests were used to compare genotype frequencies in hypocitraturic SF patients, normocitraturic SF and C. RESULTS: The prevalence of hypocitraturia in SF patients was 32.7% (72 of 200). Hypocitraturia in these patients resulted from excessive Rcit of a normal load of citrate. We found a different distribution (P < 0.05) of BsmI and TaqI VDR genotypes in hypocitraturic SF patients compared with normocitraturic SF and C. In particular, the prevalence of bb and TT VDR genotypes in hypocitraturic SF was significantly higher than in normocitraturic SF and C. CONCLUSIONS: These results point to a genetic association between BsmI and TaqI VDR polymorphisms and idiopathic hypocitraturia in calcium-oxalate recurrent SF patients.     

Clinical Yi-guan decoction for liver cirrhosis: A protocol for systematic review and meta analysis

Background:At present, Liver Cirrhosis (LC) is common in most later liver and gallbladder diseases that its morbidity and mortality seriously affect human health. The limitation and effectiveness of western medicine on LC have become a huge clinical challenge. However, a large number of clinical studies have shown that Yi-guan decoction has become a complementary treatment for LC. Therefore, this systematic review will aim to explore the safety and feasibility of Yi-guan decoction in the treatment of LC.Methods:We will conduct a comprehensive literature search in Medline, PubMed, Cochrane Database of Systematic Reviews, Embase, Chinese Biomedical Literatures Database, China National Knowledge Infrastructure, Wang Fang Database, Chinese Scientific Journal Database from inception to December 2020 without any language restriction, In addition, relevant literature will be searched manually. The main subject terms searched: “Yi-guan decoction” “cirrhosis” “LC”. Data entry will be performed by 2 researchers separately. Primary outcomes will be concluded: Liver function indicators: Total bilirubin, Alanine transaminase, Aspartate aminotransferase, etc. Secondary outcome indicators: Total effective rate, Nutrition index, Survival analysis, Adverse events; All randomized controlled trials collected in this study will be evaluated and rated using the Cochrane risk-of-biasassessment tool. Meta-analysis will be performed using RevMan 5.4.0 software. The heterogeneity test will be conducted between the studies, P < .1 and I² > 50% are the thresholds for the tests. Using solid effect model or random effect model will be based on its heterogeneity value.Results:This systematic review provides a theoretical basis for Yi-guan decoction to treat LC, we will report this result soon.Conclusion:This study will explore Yi-guan decoction can will be used as one of the non drug therapies to prevent or treat LC.Trial registration number:INPLASY2020120114.     

Association between Toll-like receptor gene polymorphisms and risk of Helicobacter pylori infection: A protocol for systematic review and meta-analysis

Background:There were many case-control studies performed the association between TLRs gene polymorphisms and the correlation of Helicobactor pylori infection, these results were inconformity. Therefore, a comprehensive meta-analysis was performed to evaluate the TLRs gene polymorphism and susceptibility to H. pylori infection.Methods:Eligible studies were searched from PubMed, EMBASE, Web of science, Cochrane library, CNKI, CBM, Wan Fang Database and VIP Database, all the databases were searched from inception to December 2020. OR with the corresponding 95% CI were presented as associations between certain TLR gene polymorphism and the risk of H. pylori infection, all the included data will be analyzed with the software of Review Manager 5.2 and STATA 14.2.Results:This study will provide a high-quality evidence to find the TLR gene polymorphisms with H. pylori infection susceptibility.Conclusion:This study will explore which TLR genotype increase the risk of H. pylori infection.     

Association of cytochrome P450 2C19 polymorphisms with coronary heart disease risk: A protocol for systematic review and meta analysis

Background:Polymorphisms in the cytochrome P450 2C19 (CYP2C19) gene have been reported to be associated with coronary heart disease (CHD), but the results were not consistently analyzed among different patient groups. To derive a more precise estimation of these associations, we will conduct a meta-analysis to investigate the polymorphisms of CYP2C19 in all published studies.Methods:Electronic databases (Google Scholar, ISI Web of Science, Pubmed, Embase, China National Knowledge Infrastructure, Wanfang, and China Biological Medicine) will be used to search clinical case-control or cohort studies about CYP2C19 polymorphism and CHD published until November 2020. Two reviewers will independently select the study, extract the data, and evaluate the quality of the study. Odds ratios with 95% confidence interval will be used to evaluate the strength of the association between the CYP2C19 polymorphism and CHD susceptibility under 4 genetic models. Subgroup analysis will be conducted by different ethnicity and genotyping method. Sensitivity analysis will be performed via sequentially omitting each of the included studies 1 at a time. Begg funnel plots and Egger test will be used to examine the potential publication bias. All the statistical analyses will be performed using Review Manager 5.3 and Stata 12.0.Results:This study will provide a better understanding of the association between CYP2C19 polymorphisms and coronary heart disease risk.Conclusion:The publication of this protocol will minimize the possibility of bias due to post hoc changes to the analysis protocol, thus helping to obtain reliable evidence.OSF registration number:DOI 10.17605/OSF.IO/R7U93     

Association between CYP2A13 polymorphisms and lung cancer: A protocol for systematic review and meta-analysis

Background:Recently, lung cancer has become the most common cause of cancer-related death, several studies indicate that the cytochrome P450 2A13 (CYP2A13) polymorphisms may be correlated with lung cancer susceptibility, but the results have been inconsistent and inconclusive. Therefore, the aim of this meta-analysis is to provide a precise conclusion on the potential association between CYP2A13 polymorphisms and the risk of lung cancer based on case-control studies.Methods:The PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) databases will be searched for case-control studies published up to September 2020. Odds ratio (OR) and 95% confidence interval (95% CI) were used to determine the effects of the CYP2A13 polymorphism on lung cancer risk, respectively.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This meta-analysis will summarize the association between CYP2A13 polymorphisms and the risk of lung cancer.INPLASY registration number:INPLASY202090102