Bang-li Hu

Association of ADIPOQ polymorphisms with obesity risk: a meta-analysis

BACKGROUND The association between ADIPOQ polymorphisms and the risk of obesity remains controversial. We perform a comprehensive meta-analysis to clarify the current understanding of this association. METHODS We searched for relevant studies in PubMed, Embase and Cochrane library before February 2014. The strengths of the association between ADIPOQ polymorphisms and obesity risk were estimated by odds ratios (OR) with 95% confidence intervals (CI). RESULTS Eighteen case-control studies analyzing four SNPs (rs17300539, rs266729, rs1501299 and rs2241766) of ADIPOQ gene were eligible for the present meta-analysis. The pooling results showed that rs17300539 (2GG+GA vs. 2AA+GA: OR=0.78, 95%CI=0.69-0.89) and rs1501299 (2GG+GA vs. 2AA+GA: OR=0.89, 95%CI=0.80-0.98) were associated with obesity risk in Caucasian ethnicity. The rs266729 were associated with obesity risk in Asian ethnicity (2CC+CG vs. 2GG+GCG: OR=0.77, 95%CI=0.65-0.92). However, there were no associations between rs2241766 and the obesity risk (P>0.05). No publication bias was found among these studies (all P>0.05). CONCLUSIONS This study suggests that ADIPOQ rs17300539 and rs1501299 are associated with risk of obesity in Caucasian ethnicity, and the rs266729 is associated with obesity risk in Asian ethnicity. However, there is no association between rs2241766 and obesity risk.

The Association of Diabetes Mellitus with Clinical Outcomes after Coronary Stenting: A Meta-Analysis

Background Previous studies have shown inconsistent results on the association between diabetes mellitus (DM) and some clinical outcomes. We conducted a meta-analysis of observational studies to assess effect of DM on clinical outcomes after coronary stenting. Methods We searched for studies without language restriction in PubMed, Embase and Cochrane library prior to 2012. The clinical outcomes including in-stent restenosis (ISR), major adverse cardiac events (MACE), stent thrombosis (ST), target lesion revascularization (TLR) and target vessel revascularization (TVR). Adjusted odds ratio (OR), and the corresponding 95% confidence interval (95% CI) was summarized. Results 55 studies involving 128,084 total patients (38,416 DM patients and 89,668 controls) were eligible for our analysis. Overall, there were significant associations between DM and ISR (OR = 1.70, 95% CI: 1.53–1.89, I2 = 0.0%), MACE (OR = 1.54, 95% CI: 1.36–1.73, I2 = 29.0%), ST (OR = 2.01, 95% CI: 1.36–2.97, I2 = 47.7%), TLR (OR = 1.46, 95% CI: 1.26–1.68, I2 = 43.3%) as well as TVR (OR = 1.33, 95% CI: 1.17–1.51, I2 = 48.3). Subgroup analysis showed that the associations were similar between BMS and DES implantation. Moreover, there was no significant association in the ST subgroup after 1–3 years follow-up. Conclusions Our meta-analysis suggests that after coronary stent implantation, DM is associated with ISR, MACE, ST, TLR and TVR. DM appears to be a vital risk factor of these clinical outcomes.

Association between baseline lipoprotein (a) levels and restenosis after coronary stenting: Meta-analysis of 9 cohort studies

BACKGROUND Previous studies have shown inconsistent results on the association between baseline plasma Lipoprotein (a) [Lp(a)] levels and in-stent restenosis (ISR) after coronary stenting. OBJECTIVE We conducted a meta-analysis of observational studies to assess the association between baseline Lp(a) levels and the restenosis after successful coronary stenting. METHODS We searched for studies without language restriction in PubMed, Embase, Cochrane library, Ovid library database prior to October 2012. Random-effects method was applied to estimate the pooled standard mean difference (SMD). Heterogeneity, sensitivity and subgroup analysis were used to evaluate the results. Meta-regression analysis was employed to investigate sources of heterogeneity. RESULTS 9 cohort studies including 1834 patients (600 ISR and 1234 no-ISR patients) were eligible for our analysis. Overall, we found significantly elevated baseline Lp(a) levels in ISR (in-stent restenosis) patients (SMD = 0.42, 95% CI: 0.14-0.71, P = 0.003). High heterogeneity existed between the individual studies (P < 0.001, I(2) = 86.9%). The association was stronger in the Asian population than the overall association found. Further, similar observations were made in the subgroup with drug-eluting stent and the group in which Lp(a) was assayed by immunoturbidimetry. Multivariable regression analysis suggested that ethnicity was the major source of heterogeneity in the data (P = 0.036). CONCLUSIONS Our meta-analysis suggests that significantly elevated baseline plasma Lp(a) level is associated with ISR. The Lp(a) level appears to be a good predictor of ISR, especially in the Asian population or patients who received drug-eluting stent implantation. Further research is warranted to evaluate the association by taking the ethnicity and type of stent into account.

Interleukin-22 ameliorates liver fibrosis through miR-200a/beta-catenin.

IL-22 ameliorates liver fibrosis by inhibiting hepatic stellate cells (HSC), and loss of miR-200a is associated with the development of liver fibrosis. The study aimed to investigate the interplay between IL-22 and miR-200a in regulating liver fibrosis in vivo and in vitro. We observed that IL-22 significantly reduced the proliferation of HSC and increased the expression of p-STAT3. β-catenin was identified as a target gene of miR-200a by luciferase reporter assay, and upregulation of miR-200a significantly attenuated the proliferation of HSC and reduced β-catenin expression. IL-22 treatment increased expression of miR-200a and decreased expression of β-catenin in HSC. The expression of p-STAT3 and miR-200a was elevated while β-catenin was decreased in fibrotic rat liver after IL-22 treatment. Expression levels of β-catenin and p-STAT3 were inversely correlated in fibrotic rat liver and HSC. Upregulation of β-catenin suppressed expression of p-STAT3 in HSC. We concluded that IL-22 inhibits HSC activation and ameliorates liver fibrosis through enhancing expression of miR-200a and reducing expression of β-catenin, suggesting there may be a crosstalk between IL-22/STAT3 and β-catenin pathway.

Diagnostic Value of Magnetic Resonance Cholangiopancreatography for Biliary Complications in Orthotopic Liver Transplantation: A Meta-analysis

BACKGROUND AND OBJECTIVE Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive procedure to diagnose biliary complications. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of MRCP to diagnose biliary complications post-orthotopic liver transplantation (OLT). METHODS A systematic review was performed by searching electronic bibliographic databases prior to May 2012. Sensitivity, specificity, and other measures of the accuracy of MRCP for diagnosis of post-OLT were summarized using a random-effects or a fixed-effects model. Receiver operating characteristic curves were used to summarize overall test performance. RESULTS Fourteen studies, which involved 892 subjects were eligible for the analysis. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under cure of MRCP for diagnosis of biliary complications were as follows: 0.95, 0.92, 10.23, 0.08, 206.59, and 0.979, respectively. The results for biliary strictures in four studies involving 177 subjects were 0.94, 0.95, 0.96, 0.09, 178.33, and 0.973 respectively. CONCLUSIONS MRCP is a sensitive and specific technique to diagnose biliary complications.

A deleterious role for Th9/IL-9 in hepatic fibrogenesis

T helper 9 (Th9) cells, a recently recognized Th cell subset, are involved in autoimmune diseases. We aimed to investigate the role of Th9/interleukin-9 (IL-9) in the pathogenesis of hepatic fibrosis. Th9 and Th17 cells were quantified in chronic hepatitis B (CHB) patients with hepatic fibrosis, HBV-associated liver cirrhosis (LC) patients and healthy controls (HC). The percentages of Th9 and Th17 cells, concentrations of IL-9 and IL-17, as well as expression of IL-17, TNF-α, IL-6, IL-4, IL-21, TGF-β1 and IFN-γ were significantly increased in plasma of CHB and LC patients compared with those in HC. Splenic Th9 and Th17 cells, plasma concentrations and liver expression of IL-9 and IL-17A were significantly elevated in mice with hepatic fibrosis compared with controls. Neutralization of IL-9 in mice ameliorated hepatic fibrosis, attenuated the activation of hepatic stellate cells, reduced frequencies of Th9, Th17 and Th1 cells in spleen, and suppressed expression of IL-9, IL-17A, IFN-γ, TGF-β1, IL-6, IL-4 and TNF-α in plasma and liver respectively. Our data suggest a deleterious role of Th9/IL-9 in increasing hepatic fibrosis and exacerbating disease endpoints, indicating that Th9/IL9 based immunotherapy may be a promising approach for treating hepatic fibrosis.

Association of Helicobacter pylori with Elevated Blood Ammonia Levels in Cirrhotic Patients: A Meta-Analysis

Purpose The association between Helicobacter pylori (H. pylori) and blood ammonia levels in cirrhotic patients is controversial. We aimed to clarify this controvercy by performing a meta-analysis of published studies. Materials and Methods We searched PubMed, EMBASE and Cochrane library for studies which explored the association between H. pylori and blood ammonia levels in cirrhotic patients before May 2012. Six cohort studies involved in 632 H. pylori positive and 396 H. pylori negative cirrhotic patients were eligible for our analysis. The summary estimates were presented as standard means differences (SMD) and 95% confidence intervals (CI) from individual studies. Results Overall, there was significant association between H. pylori infection and the elevated blood ammonia levels in cirrhotic patients (SMD=0.34, 95% CI=0.21-0.47, I2=42.1%). Sensitivity analysis further confirmed this association. Subgroup analysis showed that the association was found only in Asian ethnicity, but not in Caucasian ethnicity. Conclusion H. pylori infection is associated with elevated blood ammonia levels in cirrhotic patients, and more large scale studies and stratify analysis are warranted in order to further evaluate this association.

Meta-analysis of prognostic and clinical significance of CD44v6 in esophageal cancer

Abstract CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis. We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects. Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR = 9.19, 95% CI = 6.30–13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR = 6.91, 95% CI = 4.81–9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56–3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P > 0.05). Moreover, no publication bias was found among the studies (all P > 0.05). This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages.

Identification of novel therapeutic target genes and pathway in pancreatic cancer by integrative analysis

Background: Gene alterations are crucial to the molecular pathogenesis of pancreatic cancer. The present study was designed to identify the potential candidate genes in the pancreatic carcinogenesis. Methods: Gene Expression Omnibus database (GEO) datasets of pancreatic cancer tissue were retrieval and the differentially expressed genes (DEGs) from individual microarray data were merged. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein–protein interaction (PPI) networks, and gene coexpression analysis were performed. Results: Three GEO datasets, including 74 pancreatic cancer samples and 55 controls samples were selected. A total of 2325 DEGs were identified, including 1383 upregulated and 942 downregulated genes. The GO terms for molecular functions, biological processes, and cellular component were protein binding, small molecule metabolic process, and integral to membrane, respectively. The most significant pathway in KEGG analysis was metabolic pathways. PPI network analysis indicated that the significant hub genes including cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1), mitogen-activated protein kinase 3 (MAPK3), and phospholipase C, gamma 1 (PLCG1). Gene coexpression network analysis identified 4 major modules, and the potassium channel tetramerization domain containing 10 (KCTD10), kin of IRRE like (KIRREL), dipeptidyl-peptidase 10 (DPP10), and unc-80 homolog (UNC80) were the hub gene of each modules, respectively. Conclusion: Our integrative analysis provides a comprehensive view of gene expression patterns associated with the pancreatic carcinogenesis.

Interleukin-9 Promotes Pancreatic Cancer Cells Proliferation and Migration via the miR-200a/Beta-Catenin Axis

Background. Both IL-9 and miR-200a are involved in the pathogenesis of cancers; however, the role of IL-9 in pancreatic cancer and the possible underlying mechanisms remain unknown. The aim of this study was to investigate the effect of IL-9 on pancreatic cancer cells and its interaction with miR-200a. Methods. Pancreatic cancer cells (PANC-1 and AsPC-1) were treated with IL-9 and the expression of miR-200a and β-catenin in pancreatic cancer cells was measured. β-Catenin was examined as a target gene of miR-200a in pancreatic cancer cells. The interaction between IL-9 and miR-200a in pancreatic cancer cells was determined by infecting miR-200a mimics prior to IL-9 treatment and then measuring miR-200a and β-catenin expression. Results. IL-9 significantly promoted the proliferation, invasion, and migration of pancreatic cancer cells; however, the effect on pancreatic cancer cell apoptosis was insignificant. β-Catenin was verified as a target gene of miR-200a in pancreatic cancer cells. Overexpression of miR-200a in pancreatic cancer cells significantly attenuated proliferation and metastasis and reduced β-catenin expression. IL-9 treatment of pancreatic cancer cells decreased miR-200a expression and increased β-catenin expression. The effect of miR-200a on pancreatic cancer cells decreased following IL-9 treatment. Conclusions. IL-9 promotes proliferation and metastasis in pancreatic cancer cells; this effect may partly involve regulation of the miR-200a/β-catenin axis.