Sequential Therapy or Standard Triple Therapy for Helicobacter pylori Infection: An Updated Systematic Review.

The effectiveness of standard triple therapy (STT) for the eradication of Helicobacter pylori has decreased recently. Sequential therapy (SQT) is a new regimen proposed to address this problem. The aim of this study was to compare the efficacy of SQT versus STT for H. pylori eradication. We searched The Cochrane Library, MEDLINE, Web of Science, and EMBASE databases up to July 2014. The risk ratios (RRs) of eradication rate were pooled, with a 95% confidence interval (CI). Thirty-six randomized clinical trials including a total of 10,316 patients met the inclusion criteria. The RR for eradication of H. pylori with SQT compared with STT was 1.14 (95% CI: 1.09-1.17), the eradication rates were 84.1% and 75.1%, respectively. There was significant heterogeneity between trial results (I = 73%; P < 0.00001). Subgroup analyses showed that SQT was superior to both 7- and 10-day STT, but not significantly better than 14-day STT. This superiority existed when patients were treated with either metronidazole or tinidazole. Patients with single clarithromycin-resistant strain showed a greater benefit of SQT over STT (eradication rates 80.9% vs. 40.7%), RR = 1.98 (95% CI: 1.33-2.94). There was no significant difference between groups in terms of the risk of adverse effects. In conclusion, SQT is more efficacious than STT (7 days and 10 days) in the eradication of HP, but the pooled rate seemed suboptimal. Further research is needed to develop more effective therapeutic approaches. Surveillance of resistance rates should be performed to guide treatment.

[Effect of hypoxia on the activation and visfatin expression in rat hepatic stellate cells].

OBJECTIVE: To investigate the effect of hypoxia on the visfatin and the expression of smooth muscle-actin (alpha-SMA) and hypoxia-inducible factor-1alpha (HIF-1alpha) in rat hepatic stellate cells (HSCs). METHODS: Rat primary HSCs were isolated from SD rats by in situ perfusion of collagenase and pronase and single-step Nycodenz density gradient centrifugation, and then cultured and activated. Completely activated primary HSCs were exposed to hypoxic conditions (37 degrees C, 5% CO2, 1% O2, 94% N2), or normoxic conditions (37 degrees C, 5% CO2, 21% O2, 74% N2), for 3, 6, 12 or 24 h respectively. The expression of alpha-SMA, the marker of HSC activation, and visfatin were assessed by Real time-PCR and Western blot. The Expression of HIF-1alpha was detected by Real time-PCR. RESULTS: HIF-1alpha mRNA in rat HSCs was induced after exposed to hypoxia for 3 h, and maintained elevated status up to 24 h. HSCs exposed to 1% O2 hypoxic conditions for 6 h increased alpha-SMA mRNA and protein expression. Visfatin mRNA expression was up-regulated after subjected to hypoxia for 12 h, and protein level was elevated after 6 h hypoxia. A positive linear correlation existed between alpha-SMA and visfatin expression in responsible to hypoxia (r = 0.991 (genes) and r = 0.968 (proteins), P < 0.05). CONCLUSION: Microcirculation impairment could significantly induce alpha-SMA and visfatin expression in rat HSCs, which might potentate the activation process of HSCs.

[Construction of shRNA expressing plasmid targeted rat NogoB and observation of the effection about NogoB on hepatic stellate cells].

OBJECTIVE: To construct shRNA expressing plasmid inhibiting rat NogoB and to observe its possible effect on rat primary hepatic stellate cells (HSCs) contraction. METHODS: Three pairs of shRNAs targeting different sequence of rat NogoB were designed and constructed into pSuper plasmid by DNA recombination technique. Culture-activated HSCs were transfected with NogoB-shRNA plasmids to scan the effective plasmid which could inhibit NogoB gene expression by Real-time PCR. And this depressant effect was also confirmed with Western blot. After NogoB was knocked-down effectively, ETA and ETB mRNA expression were assessed by Real-time PCR. RESULTS: Among the three pairs of recombinant plasmids, NogoB-shRNA2 plasmid could inhibit NogoB expression specifically. In HSCs, NogoB knockdown decreased the ratio of ETA and ETB. CONCLUSION: We constructed specific NogoB-shRNA expression plasmid successfully which might be involved in contraction of HSCs.

[Comparison of clinical features between gastroesophageal reflux diseases with atypical and typical symptoms].

OBJECTIVE: To study the differences between gastroesophageal reflux disease (GERD) with atypical symptoms (a-GERD) and typical symptoms (t-GERD). METHODS: 30 patients of suspected a-GERD were recruited and examined with upper gastrointestinal endoscopy, high-resolution manometry (HRM), 24 h esophageal multichannel intra-luminal impedance monitoring with pH sensor (MII-pH) and proton pump inhibitor (PPI) trials. The results were compared with those of 33 cases of GERD with typical symptoms. RESULTS: Among the 30 patients of suspected GERD, 24 were confirmed with a-GERD. One third of those patients were over sixty-years old, significantly higher than those with typical GERD (P < 0.05). No significant differences in prevalence of esophageal mucosa breakage and esophageal manometry readings were found between the two groups (P > 0.05). The a-GERD patients had higher data readings in 24 h esophageal MCII-pH monitoring than the t-GERD patients (P < 0.05). Supine type of GER and mixed reflux were predominately seen in the a-GERD patients, while upright type of GER was predominate seen in the t-GERD patients. The response rate of PPI in the a-GERD patients was significantly lower than that in the t-GERD patients when a course of standard dosage of PPI was given (45.8% vs. 78.8%, P < 0.01). But there was no significant difference in PPI response between these two groups when a second course with double standard dosage of PPI combined with pro-motility agents were given (72.7% vs. 88.0%, P < 0.05). CONCLUSION: Compared with patients of t-GERD, older onset age, more severe degree of acid reflux are presented in patients of a-GERD. a-GERD should be considered when it is hard to explain the symptoms of upper part of the chest in clinical practice. 24 h esophageal MII-pH monitoring and/or diagnostic therapy with double standard dosage of PPI helps make a correct diagnosis.

[Role of macrophage migration inhibitory factor in hepatic stellate cells activation].

OBJECTIVE: To investigate the role of macrophage migration inhibitory factor (MIF) in activation of primary hepatic stellate cells (HSC), and to explore the blocking effect of specific antisense oligonucleotides (ASONs) targeting MIF on the activation of primary HSCs. METHODS: Rat primary HSC were isolated from SD rats by in situ perfusion of collagenase and pronase and single-step Nycodenz density gradient centrifugation, and then cultured and activated. The expression of alpha-smooth muscle actin (alpha-SMA), the marker of HSC activation, was assessed by RT-PCR and immunocytochemistry (ICC). The expression of MIF was detected by RT-PCR, enzyme-linked immuno sorbent assay (ELISA), immunofluorescence (IF) or ICC. Completely activated primary HSC were transfected with MIF-specific antisense oligonucleotide (MIF-ASONs), mis-sense oligonucleotides of MIF, or blank liposome (negative-control). RESULTS: Quiescent HSC expressed very low level of MIF, while MIF gene and protein expression increased significantly during the process of HSC activation. Positive correlation was found between the expression of alpha-SMA and MIF (r = 0.944, P < 0.01). Compared with the control, activated primary Gen HSC transfected with MIF-ASONs showed lower MIF and alpha-SMA expressions at gene and protein profiles (P < 0.05). CONCLUSION: The expression of MIF was up-regulated in the process of HSC activation. Activation in culture of primarily isolated rat HSC could be inhibited by MIF-ASONs, suggesting at least in part that, MIF might be a novel and important factor involved in HSC activation and hepatic fibrosis.