Meta-analysis of the Use of ACEI for Inhibiting Albuminuria in Diabetic Patients

Aim To examine whether AER(albumin excretion rate) in normotensive diabeticpatients can be effectively inhibited by ACEI. Methods Literature on randomized controlled trials ofACEI for inhibiting AER in normotensive diabetic patients was searched. The electronic databasesretrieved were Medline (1980 ― 2003), Embase database (1980 ― 2000), Cochrane Library, CL( 1980 ―2004), CBMdisc( 1980 ― 2002), and IPA( 1980 ― 2002). Seven studies were chosen. Data werecombined by Revman 4.2. Results: The pooled effect of change in AER is - 56.31 μg·min^(-1)) [ -81.96, -30.66] (P<0.0001). According to the analysis of subgroups, the pooled effects of 1 - 5 yearsare - 11.97 μg·min^(-1)[-22.04, -1.89] (P = 0.02), -28.01 μg·min^(-1)[-34.50, -21.52](P<0.00001), -43.24 μg·min^(-1) [ -57.15, -29.32] (P< 0.00001), -61.65 μg·min^(-1)[77.77,-45.54] (P< 0.00001), and -98.41 μg·min^(-1)[-162.02,-34.79] (P = 0.002). Regarding progression toclinincal proteinuria as end-point, the pooled Peto OR =0.27 [0.18,0.40] (95% CI), P < 0.00001.According to the analysis of subgroups, the pooled effects of 2 and 5 years are Peto OR = 0.30[0.18,0.51] (P<0.00001) and Peto OR=0.25 [0.13, 0.50](P<0.0001). Publication bias is small.Conclusion In normotensive diabetic patients, ACEI inhibits AER effectively and reduces theprobability of progression of microalbuminuria to clinical proteinuria.

Effect of preoperative biliary drainage on malignant obstructive jaundice:A meta-analysis

AIM: To evaluate the effect of preoperative biliary drainage (PBD) on obstructive jaundice resulting from malignant tumors. METHODS: According to the requirements of Cochrane systematic review, studies in the English language were retrieved from MEDLINE and Embase databases from 1995 to 2009 with the key word "preoperative biliary drainage". Two reviewers independently screened the eligible studies, evaluated their academic level and extracted the data from the eligible studies confirmed by cross-checking. Data about patients with and without PBD after resection of malignant tumors were processed for meta-analysis using the Stata 9.2 software, including postoperative mortality, incidence of postoperative pancreatic and bile leakage, abdominal abscess, delayed gastric emptying and incision infection.RESULTS: Fourteen retrospective cohort studies involving 1826 patients with malignant obstructive jaundice accorded with our inclusion criteria, and were included in meta-analysis. Their baseline characteristics were comparable in all the studies. No significant difference was found in combined risk ratio (RR) of postoperative mortality and incidence of pancreatic and bile leakage, abdominal abscess, delayed gastric emptying between patients with and without PBD. However, the combined RR for the incidence of postoperative incision infection was improved better in patients with PBD than in those without PBD (P < 0.05). CONCLUSION: PBD cannot significantly reduce the post-operative mortality and complications of malignant obstructive jaundice, and therefore should not be used as a preoperative routine procedure for malignant obstructive jaundice.

Effi cacy of tricyclic antidepressants in irritable bowel syndrome:A meta-analysis

We aimed to evaluate the efficacy of tricyclic antidepressants(TCAs) as a therapeutic option for irritable bowel syndrome(IBS) through meta-analysis of randomized controlled trials.For the years 1966 until September 2008,PubMed,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were searched for double-blind,placebo-controlled trials investigating the effi cacy of TCAs in the management of IBS.Seven randomized,placebo-controlled clinical trials met our criteria and were included in the metaanalysis.TCAs used in the treatment arm of these trials included amitriptyline,imipramine,desipramine,doxepin and trimipramine.The pooled relative risk for clinical improvement with TCA therapy was 1.93(95% CI:1.44 to 2.6,P<0.0001).Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15(95% CI:-53.27 to -35.04,P<0.0001).It is concluded that low dose TCAs exhibit clinically and statistically signifi cant control of IBS symptoms.

Relationship between hepatitis C virus infection and type 2 diabetes mellitus:Meta-analysis

AIM:To investigate the association between hepatitis C infection and type 2 diabetes mellitus.METHODS:Observational studies assessing the relationship between hepatitis C infection and type 2 diabetes mellitus were identified via electronic and hand searches.Studies published between 1988 to March 2011 were screened,according to the inclusion criteria set for the present analysis.Authors performed separate analyses for the comparisons between hepatitis C virus(HCV) infected and not infected,and HCV infected and hepatitis B virus infected.The included studies were further subgrouped according to the study design.Heterogenity was assessed using I2 statistics.The summary odds ratios with their corresponding 95% CIs were calculated based on a random-effects model.The included studies were subgrouped according to the study design.To assess any factor that could potentially affect the outcome,results were further stratified by age group(proportion of ≥ 40 years),gender(proportion of male gender),body mass index(BMI)(pro-portion of BMI ≥ 27),and family history of diabetes(i.e.,self reported).For stability of results,a sensitivity analysis was conducted including only prospective studies.RESULTS:Combining the electronic database and hand searches,a total of 35 observational studies(in 31 articles) were identified for the final analysis.Based on random-effects model,17 studies(n = 286 084) compared hepatitis C-infected patients with those who were uninfected [summary odds ratio(OR):1.68,95% CI:1.15-2.45].Of these 17 studies,7 were both a cross-sectional design(41.2%) and cohort design(41.2%),while 3 were case-control studies(17.6%).Nineteen studies(n = 51 156) compared hepatitis C-infected participants with hepatitis B-infected(summary OR:1.92,95% CI:1.41-2.62).Of these 19 studies,4(21.1%),6(31.6%) and 9(47.4%) were cross-sectional,cohort and case-control studies,respectively.A sensitivity analysis with 3 prospective studies indicated that hepatitis C-infected patients had a higher risk of developing type 2 diabetes compared with uninfected controls(summary odds ratio:1.41,95% CI:1.17-1.7;I2 = 0%).Among hepatitis C-infected patients,male patients(OR:1.26,95% CI:1.03-1.54) with age over 40 years(summary OR:7.39,95% CI:3.82-9.38) had an increased frequency of type 2 diabetes.Some caution must be taken in the interpretation of these results because there may be unmeasured confounding factors which may introduce bias.CONCLUSION:The findings support the association between hepatitis C infection and type 2 diabetes mellitus.The direction of association remains to be determined,however.Prospective studies with adequate sample sizes are recommended.

Meta-analysis of laparoscopic vs open liver resection for hepatocellular carcinoma

AIM:To conduct a meta-analysis to determine the safety and efficacy of laparoscopic liver resection(LLR) and open liver resection(OLR) for hepatocellular carcinoma(HCC).METHODS:PubMed(Medline),EMBASE and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials in the Cochrane Library were searched systematically to identify relevant comparative studies reporting outcomes for both LLR and OLR for HCC between January 1992 and February 2012.Two authors independently assessed the trials for inclusion and extracted the data.Meta-analysis was performed using Review Manager Version 5.0 software(The Cochrane Collaboration,Oxford,United Kingdom).Pooled odds ratios(OR) or weighted mean differences(WMD) with 95%CI were calculated using either fixed effects(Mantel-Haenszel method) or random effects models(DerSimonian and Laird method).Evaluated endpoints were operative outcomes(operation time,intraoperative blood loss,blood transfusion requirement),postoperative outcomes(liver failure,cirrhotic decompensation/ascites,bile leakage,postoperative bleeding,pulmonary complications,intraabdominal abscess,mortality,hospital stay and oncologic outcomes(positive resection margins and tumor recurrence).RESULTS:Fifteen eligible non-randomized studies were identified,out of which,9 high-quality studies involving 550 patients were included,with 234 patients in the LLR group and 316 patients in the OLR group.LLR was associated with significantly lower intraoperative blood loss,based on six studies with 333 patients [WMD:-129.48 mL;95%CI:-224.76-(-34.21) mL;P = 0.008].Seven studies involving 416 patients were included to assess blood transfusion requirement between the two groups.The LLR group had lower blood transfusion requirement(OR:0.49;95%CI:0.26-0.91;P = 0.02).While analyzing hospital stay,six studies with 333 patients were included.Patients in the LLR group were found to have shorter hospital stay [WMD:-3.19 d;95%CI:-4.09-(-2.28) d;P < 0.00001] than their OLR counterpart.Seven studies including 416 patients were pooled together to estimate the odds of developing postoperative ascites in the patient groups.The LLR group appeared to have a lower incidence of postoperative ascites(OR:0.32;95%CI:0.16-0.61;P = 0.0006) as compared with OLR patients.Similarly,fewer patients had liver failure in the LLR group than in the OLR group(OR:0.15;95%CI:0.02-0.95;P =0.04).However,no significant differences were found between the two approaches with regards to operation time [WMD:4.69 min;95%CI:-22.62-32 min;P = 0.74],bile leakage(OR:0.55;95%CI:0.10-3.12;P = 0.50),postoperative bleeding(OR:0.54;95%CI:0.20-1.45;P = 0.22),pulmonary complications(OR:0.43;95%CI:0.18-1.04;P = 0.06),intra-abdominal abscesses(OR:0.21;95%CI:0.01-4.53;P = 0.32),mortality(OR:0.46;95%CI:0.14-1.51;P = 0.20),presence of positive resection margins(OR:0.59;95%CI:0.21-1.62;P = 0.31) and tumor recurrence(OR:0.95;95%CI:0.62-1.46;P = 0.81).CONCLUSION:LLR appears to be a safe and feasible option for resection of HCC in selected patients based on current evidence.However,further appropriately designed randomized controlled trials should be undertaken to ascertain these findings.

Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis

AIM: To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBVGN) patients. METHODS: A computerized literature search was carried out in the PubMed database, Embase, the Cochrane Library, Chinese BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were remission of proteinuria, clearanceof HBV e-antigen, and elevation of serum albumin. The secondary outcomes were blood levels of alanine aminotransferase, serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review Manager 5.1. Fixed or random effect models were employed to combine the results after a heterogeneity test. The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN. RESULTS: Twelve clinical trials with 317 patients were included. A significantly higher incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI: 1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI: -12.97-10.93) without significant alterations of liver function (mean difference: 4.62, 95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14-20.45). No signif icant activation of HBV-DNA replication occurred (mean difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria remission (P = 0.76) and between different pathological types of HBV-GN [membranous glomerulonephritis (MN) vs mesangial proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative glomerulonephritis, P = 0.27]. CONCLUSION: Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBVGN patients without altering HBV replication or damaging liver and renal functions.

Laparoscopic distal pancreatectomy is as safe and feasible as open procedure:A meta-analysis

AIM:To evaluate the feasibility and safety of laparoscopic distal pancreatectomy(LDP) compared with open distal pancreatectomy(ODP).METHODS:Meta-analysis was performed using the databases,including PubMed,the Cochrane Central Register of Controlled Trials,Web of Science and BIOSIS Previews.Articles should contain quantitative data of the comparison of LDP and ODP.Each article was reviewed by two authors.Indices of operative time,spleen-preserving rate,time to fluid intake,ratio of malignant tumors,postoperative hospital stay,incidence rate of pancreatic fistula and overall morbidity rate were analyzed.RESULTS:Nine articles with 1341 patients who underwent pancreatectomy met the inclusion criteria.LDP was performed in 501(37.4%) patients,while ODP was performed in 840(62.6%) patients.There were significant differences in the operative time,time to fluid intake,postoperative hospital stay and spleen-preserving rate between LDP and ODP.There was no difference between the two groups in pancreatic fistula rate [random effects model,risk ratio(RR) 0.996(0.663,1.494),P = 0.983,I2 = 28.4%] and overall morbidity rate [random effects model,RR 0.81(0.596,1.101),P = 0.178,I2 = 55.6%].CONCLUSION:LDP has the advantages of shorter hospital stay and operative time,more rapid recovery and higher spleen-preserving rate as compared with ODP.

Salvage liver transplantation in the treatment of hepatocellular carcinoma:A Meta-analysis

AIM:To evaluate survival and recurrence after salvage liver transplantation(SLT) for the treatment of hepatocellular carcinoma(HCC) compared with primary liver transplantation(PLT) using a meta-analysis.METHODS:Literature on SLT versus PLT for the treatment of HCC published between 1966 and July 2011 was retrieved.A meta-analysis was conducted to estimate pooled survival and disease-free rates.A fixed or random-effect model was established to collect the data.RESULTS:The differences in overall survival and disease-free survival rates at 1-year,3-year and 5-year survival rates were not statistically significant between SLT group and PLT group(P > 0.05).After stratifying the various studies by donor source and Milan criteria,we found that:(1) Living donor liver transplantation recipients had significantly higher 1-year survival rate,lower 3-year and 5-year survival rates compared with deceased-donor liver transplantation(DDLT) recipients.And in DDLT recipients they had better 1-year and 5-year disease-free survival rate in SLT group;and(2) No difference was seen in 1-year,3-year and 5-year survival rates between two groups who beyond Milan criteria at the time of liver transplantation.CONCLUSION:SLT can be effectively performed for patients with recurrence or deterioration of liver function after hepatectomy for HCC.It does not increase the perioperative mortality and has a similar long-term survival rates compared to PLT.

Hemihepatic versus total hepatic inflow occlusion during hepatectomy:A systematic review and meta-analysis

AIM： To evaluate the clinical outcomes of patients undergoing hepatectomy with hemihepatic vascular occlusion （HHO） compared with total hepatic inflow occlusion （THO）. METHODS： Randomized controlled trials （RCTs） co- mparing hemihepatic vascular occlusion and total he- patic inflow occlusion were included by a systematic literature search. Two authors independently assessed the trials for inclusion and extracted the data. A meta- analysis was conducted to estimate blood loss, transfu- sion requirement, and liver injury based on the levels of aspartate aminotransferase （AST） and alanine arni- notransferase （ALT）. Either the fixed effects model or random effects model was used. RESULTS- Four RCTs including 338 patients met the predefined inclusion criteria. A total of 167 patients were treated with THO and 171 with HHO. Metaanalysis of AST levels on postoperative day 1 indicated higher levels in the THO group with weighted mean dif- ference （WMD） 342.27; 95% confidence intervals （CI） 217.28-467.26; P = 0.00001; I2 = 16%. Meta-analysis showed no significant difference between THO group and HHO group on blood loss, transfusion requirement, mortality, morbidity, operating time, ischemic duration, hospital stay, ALT levels on postoperative day 1, 3 and 7 and AST levels on postoperative day 3 and 7. CONCLUSION： Hemihepatic vascular occlusion does not offer satisfying benefit to the patients undergoing hepatic resection. However, they have less liver injury after liver resections.

Meta-analysis and systematic review of colorectal endoscopic mucosal resection

AIM:To evaluate the proportion of successful complete cure en-bloc resections of large colorectal polyps achieved by endoscopic mucosal resection(EMR). METHODS:Studies using the EMR technique to resect large colorectal polyps were selected.Successful complete cure en-bloc resection was defined as one piece margin-free polyp resection.Articles were searched for in Medline,Pubmed,and the Cochrane Control Trial Registry,among other sources. RESULTS:An initial search identified 2620 reference articles,from which 429 relevant articles were selected and reviewed.Data was extracted from 25 studies(n =5221)which met the inclusion criteria.All the studies used snares to perform EMR.Pooled proportion of en-bloc resections using a random effect model was 62.85%(95%CI:51.50-73.52).The pooled proportion for complete cure en-bloc resections using a random effect model was 58.66%(95%CI:47.14-69.71).With higher patient load(>200 patients),this complete cure en-bloc resection rate improves from 44.19%(95%CI: 24.31-65.09)to 69.17%(95%CI:51.11-84.61). CONCLUSION:EMR is an effective technique for the resection of large colorectal polyps and offers an alternative to surgery.

Effect of Timing of Tracheotomy on Clinical Outcomes: an Update Meta-analysis Including 11 Trials

Objective To estimate the relative effect of early vs. late tracheotomy on clinical end-points in unselected intensive care unit （ICU） patients undergoing mechanical ventilation. Methods We searched electronic databases （up to February 27, 2013） for both randomized control trials and observational studies satisfying the predefined inclusion criteria.

Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensinaldosterone system

Background Obstructive sleep apnea （OSA） is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin-angiotensin-aldosterone system （RAAS）. We meta-analyzed the effects of OSA on plasma levels of RAAS components. Methods Full-text studies published on MEDL1NE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea-hypopnea index or respiratory disturbance index 〉 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the 12 statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed. Results The meta-analysis included 13 studies, of which 10 reported results on renin （n = 470 cases and controls）, 7 on angiotensin II （AnglI, n = 384）, and 9 on aldosterone （n = 439）. AnglI levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI： 2.00-4.79, P 〈 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension （mean differences = 1.32 ng/dL, 95% CI： 0.58-2.07, P = 0.0005）. Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL （95% CI： 0.88-1.82, P 〈 0.00001） emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies. Conelusions OSA is associated with higher AnglI and aldosterone levels, espe- cially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity.

Meta-analysis of capsule endoscopy in patients diagnosed or suspected with esophageal varices

AIM:To review the literature on capsule endoscopy(CE) for detecting esophageal varices using conventional esophagogas troduodenoscopy(EGD)as the standard. METHODS:A strict literature search of studies comparing the yield of CE and EGD in patients diagnosed or suspected as having esophageal varices was conducted by both computer search and manual search.Data were extracted to estimate the pooled diagnostic sensitivity and specificity. RESULTS:There were seven studies appropriate for meta-analysis in our study,involving 446 patients. The pooled sensitivity and specificity of CE for detecting esophageal varices were 85.8%and 80.5%, respectively.In subgroup analysis,the pooled sensitivity and specificity were 82.7%and 54.8%in screened patients,and 87.3%and 84.7%in the screened/ patients under surveillance,respectively. CONCLUSION:CE appears to have acceptable sensitivity and specificity in detecting esophageal varices.However,data are insufficient to determine the accurate diagnostic value of CE in the screen/ surveillance of patients alone.

Effects of Different Extract of Pseudostellaria Heterophylla on Immunological Function in Mice based on Meta-analysis and Network Meta-analysis

To evaluate the effects of different extract of Pseudostellaria heterophylla on immunological function in mice based on Meta-analysis and Network meta-analysis,the article retrieved domestic and foreign databases according to the"PICO"retrieval strategy,and used Stata and ADDIS software for Meta analysis.A total of 6 reports,10 randomised controlled trials(RCTs)were eventually involved.Meta analysis results showed that:compared with the control group,the experimental group of polysaccharide,saponin and crude extract were better than that of the control(P<0.05),which significantly improved the immunological function in mice.Network meta-analysis results showed that the saponin had the best effect on the increase of phagocytic index and the differences were statistically significant[MD=1.50,95%CI(0.71,2.28),P<0.05];The polysaccharide and saponin had better effect on the increase of spleen index than the control and crude extract,and the differences were statistically significant[MD=0.77,95%CI(0.27,1.31),P<0.05],[MD=0.71,95%CI(0.01,1.50),P<0.05];the polysaccharide had the best effect on the increase of thymus index and the differences were statistically significant[MD=0.70,95%CI(0.11,1.34),P<0.05].The rank probability showed that the saponin of Pseudostellaria heterophylla had the maximum probability to increase phagocytic index of mice;the probability for the components of Pseudostellaria heterophylla increasing spleen index of mice was in the order of crude extract>polysaccharide>saponin;the probability for the components of Pseudostellaria heterophylla increasing thymus index of mice was in the order of saponin>polysaccharide>crude extract.Based on the available evidence,the extract of Pseudostellaria heterophylla could improve the immunity of mice,and the clinical effect of polysaccharide and saponin was the best,which provided a more valuable scientific reference for evidencing that the polysaccharide and saponin of Pseudostellaria heterophylla was the effective components for improving immunological function,and also was conducive to the proper further development of Pseudostellaria heterophylla resources.

Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced non-small cell lung cancer： a meta-analysis

Objective： To evaluate the clinical efficacy of Shenqi Fuzheng injection combined with gemcitabine plus cisplatin（GP） in the treatment of advanced non-small cell lung cancer （NSCLC）. Methods： we performed a systematicsearch in the electronic databases such as Cochrane Library, Pubmed, Embase, Chinese Journal Full-text Database,Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Full-text Database andWanfang Database up to 30 January 2017. Randomized controlled trials （RCT） of Shenqi Fuzheng Injectioncombined with GP chemotherapy in the treatment of advanced NSCLC were searched, and all the RCTs wereconducted on methodological quality assessment. Data extraction and data analysis were according to standards ofCochrane systematic review. Results： Eight trials were included including a total of 701 patients. Meta-analysisresults： Shenqi Fuzheng injection combined with GP chemotherapy could significantly improve the functionalstatus of patients with NSCLC （OR = 3.44, 95% CI [2.26, 5.25], P 〈 0.0001） and clinical treatment efficacy （OR =（OR = 0.31, 95%CI [0.20, 0.47], P 〈 0.0001. The rate of leukopenia （OR = .31, 95%CI [0.20,0.47], P 〈 0.0001）,thrombocytopenia （OR = 0.58, 95%CI [0.37, 0.91], P = 0.020）, hemoglobin decline （（OR = 0.31, 95%CI [0.16,0.59], P = 0.0004） and incidence of gastrointestinal reactions （OR = 0.58,P 〈 0.05） could be reduced. Conclusion：Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced NSCLC obtainedsignificantly clinical efficacy. The quality of the literature incorporated is low, the conclusion requires high-qualityresearch to further prove.

Meta-Analysis of the Association between Mir-196a-2 Polymorphism and Cancer Susceptibility

Objective MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis. The miR- 196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility. This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. Methods A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism. Results A significant association was found between rs11614913 polymorphism and cancer risk in four genetic models （CT vs. TT, OR-1.15, 95%CI=1.05-1.27; CC vs. TT, OR=1.23, 95%CI=1.08-1.39; Dominant model, OR=1.17, 95%CI=1.06-1.30; Additive model, OR-1.08, 95%CI=1.01-1.14）. In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectat cancer, but not with liver, gastric, or esophageal cancer. In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup. Conclusions The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations.

Bisphosphonate use and gastrointestinal tract cancer risk:Meta-analysis of observational studies

AIM:To perform a meta-analysis of observational studies to further elucidate the relationship between oral bisphosphonate use and gastrointestinal cancer risk.METHODS:Systematic literature search was conducted in MEDLINE,EMBASE,and the Cochrane Library to identify studies through January 2011.Search terms were "bisphosphonates" or trade names of the drugs,and "observational studies" or "cohort studies" or "case-control studies".Two evaluators reviewed and selected articles on the basis of predetermined selection criteria as followed:(1) observational studies(casecontrol or cohort studies) on bisphosphonate use;(2) with at least 2 years of follow-up;and(3) reported data on the incidence of cancer diagnosis.The DerSimonian and Laird random effects model were used to calculate the pooled relative risk(RR) with 95% confidence interval(CI).Two-by-two contingency table was used to calculate the outcomes not suitable for meta-analysis.Subgroup meta-analyses were conducted for the type of cancer(esophageal,gastric and colorectal cancers).Sensitivity analyses were performed to examine the effect sizes when only studies with long-term follow-up(mean 5 years;subgroup 3 years) were included.RESULTS:Of 740 screened articles,3 cohort studies and 3 case-control studies were included in the analyses.At first,4 cohort studies and 3 case-control studies were selected for the analyses but one cohort study was excluded because the cancer outcomes were not categorized by type of gastrointestinal cancer.More than 124 686 subjects participated in the 3 cohort studies.The mean follow-up time in all of the cohort studies combined was approximately 3.88 years.The 3 casecontrol studies reported 3070 esophageal cancer cases and 15 417 controls,2018 gastric cancer cases and 10 007 controls,and 11 574 colorectal cancer cases and 53 955 controls.The percentage of study participants who used bisphosphonate was 2.8% among the cases and 2.9% among the controls.The meta-analysis of all the studies found no significant association between bisphosphonate use and gastrointestinal cancer.Also no statistically significant association was found in a meta-analysis of long-term follow-up studies.There was no negative association between bisphosphonate use and the incidence of esophageal cancer in the overall analysis(RR 0.96,95% CI:0.65-1.42,I 2 = 52.8%,P = 0.076) and no statistically significant association with long-term follow-up(RR 1.74,95% CI:0.97-3.10,I 2 = 58.8%,P = 0.119).No negative association was found in the studies reporting the risk of gastric cancer(RR 0.89,95% CI:0.71-1.13,I 2 = 0.0%,P = 0.472).In case of colorectal cancer,there was no association between colorectal cancer and bisphosphonate use(RR 0.62,95% CI:0.30-1.29,I 2 = 88.0%,P = 0.004) and also in the analysis with long-term follow-up(RR 0.61,95% CI:0.28-1.35,I 2 = 84.6%,P = 0.011).CONCLUSION:Oral bisphosphonate use had no significant effect on gastrointestinal cancer risk.However,this finding should be validated in randomized controlled trials with long-term follow-up.

Effect of dietary fiber on constipation:A meta analysis

AIM:To investigate the effect of dietary fiber intake on constipation by a meta-analysis of randomized controlled trials(RCTs).METHODS:We searched Ovid MEDLINE(from 1946 to October 2011),Cochrane Library(2011),PubMed for articles on dietary fiber intake and constipation using the terms:constipation,fiber,cellulose,plant extracts,cereals,bran,psyllium,or plantago.References of important articles were searched manually for relevant studies.Articles were eligible for the meta-analysis if they were high-quality RCTs and reported data on stool frequency,stool consistency,treatment success,laxative use and gastrointestinal symptoms.The data were extracted independently by two researchers(Yang J and Wang HP) according to the described selection criteria.Review manager version 5 software was used for analysis and test.Weighted mean difference with 95%CI was used for quantitative data,odds ratio(OR)with 95%CI was used for dichotomous data.Both I2 statistic with a cut-off of ≥ 50% and the χ2 test with a P value < 0.10 were used to define a significant degree of heterogeneity.RESULTS:We searched 1322 potential relevant articles,19 of which were retrieved for further assessment,14 studies were excluded for various reasons,five studies were included in the analysis.Dietary fiber showed significant advantage over placebo in stool frequency(OR = 1.19;95%CI:0.58-1.80,P < 0.05).There was no significant difference in stool consistency,treatment success,laxative use and painful defecation between the two groups.Stool frequency were reported by five RCTs,all results showed either a trend or a significant difference in favor of the treatment group,number of stools per week increased in treatment group than in placebo group(OR = 1.19;95%CI:0.58-1.80,P < 0.05),with no significant heterogeneity among studies(I2= 0,P = 0.77).Four studies evaluated stool consistency,one of them presented outcome in terms of percentage of hard stool,which was different from others,so we included the other three studies for analysis.Two studies reported treatment success.There was significant heterogeneity between the studies(P < 0.1,I2 > 50%).Three studies reported laxative use,quantitative data was shown in one study,and the pooled analysis of the other two studies showed no significant difference between treatment and placebo groups in laxative use(OR = 1.07;95%CI 0.51-2.25),and no heterogeneity was found(P = 0.84,I2= 0).Three studies evaluated painful defecation:one study presented both quantitative and dichotomous data,the other two studies reported quantitative and dichotomous data separately.We used dichotomous data for analysis.CONCLUSION:Dietary fiber intake can obviously increase stool frequency in patients with constipation.It does not obviously improve stool consistency,treatment success,laxative use and painful defecation.

X-ray repair cross-complementing group 1 polymorphisms and hepatocellular carcinoma:A meta-analysis

AIM： To perform a systematic meta-analysis to in- vestigate the association between X-ray repair crosscomplementing group 1 （XRCC1） polymorphisms and hepatocellular carcinoma （HCC） risk. METHODS： Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios （ORs） and 95% confidence interval （CI） of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. RESULTS： Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria （four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln）. The meta-analysis revealed no associations between the Arg194Trp and Arg399GIn polymorphisms of the XRCC1 gene and HCC risk under all contrast models （codominant, dominant and recessive models） in the overall analysis and sensitivity analysis （the studies with controls not in the Hardy-Weinberg equilibrium were excluded）. For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant associa- tion between the His/His genotype and the increased risk of HCC （His/His vs Arg/Arg model, OR： 1.96, 95% CI： 1.03-3.75, P = 0.04）. However, sensitivity analysis showed an altered pattern of result and non-significant association （OR： 2.06, 95% CI： 0.67-6.25, P = 0.20）. The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg＇s and Egger＇s tests did not find any obvious publication bias. CONCLUSION： The XRCC1 Arg194Trp and Arg399GIn polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement ofXRCC1 Arg280His polymorphism in HCC susceptibility.

Faecal pyruvate kinase isoenzyme type M2 for colorectal cancer screening:A meta-analysis

AIM:To present a critical discussion of the efficacy of the faecal pyruvate kinase isoenzyme type M2(faecal M2-PK) test for colorectal cancer(CRC) screening based on the currently available studies.METHODS:A literature search in PubMed and Embase was conducted using the following search terms:fecal Tumor M2-PK,faecal Tumour M2-PK,fecal M2-PK,faecal M2-PK,fecal pyruvate kinase,faecal pyruvate kinase,pyruvate kinase stool and M2-PK stool.RESULTS:Stool samples from 704 patients with CRC and from 11 412 healthy subjects have been investigated for faecal M2-PK concentrations in seventeen independent studies.The mean faecal M2-PK sensitivity was 80.3%;the specificity was 95.2%.Four studies compared faecal M2-PK head-to-head with guaiacbased faecal occult blood test(gFOBT).Faecal M2PK demonstrated a sensitivity of 81.1%,whereas the gFOBT detected only 36.9% of the CRCs.Eight independent studies investigated the sensitivity of faecal M2-PK for adenoma(n = 554),with the following sensitivities:adenoma < 1 cm in diameter:25%;adenoma > 1 cm:44%;adenoma of unspecified diameter:51%.In a direct comparison with gFOBT of adenoma > 1 cm in diameter,47% tested positive with the faecal M2-PK test,whereas the gFOBT detected only 27%.CONCLUSION:We recommend faecal M2-PK as a routine test for CRC screening.Faecal M2-PK closes a gap in clinical practice because it detects bleeding and nonbleeding tumors and adenoma with high sensitivity and specificity.