Effect of enhanced patient instructions on Helicobacter pylori eradication: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: To improve Helicobacter pylori (H. pylori) eradication rate, enhanced patient instructions (EPI) such as telephone-based re-education, short-message service, and Wechat have been proposed with conflicting results. The aim of this meta-analysis was to evaluate the effect of EPI on H. pylori eradication. METHODS: The PROSPERO registered number of this study is CRD42021278536. PubMed, Embase, and CENTRAL database were searched to identify relevant randomized controlled trials (RCTs) from inception to September 2021. Meta-analysis was performed to estimate the pooled relative risk (RR) with 95% confidence intervals (CI) using a random-effects model. Trial sequential analysis (TSA) was conducted to determine the robustness of the H. pylori eradication rate. RESULTS: Nine RCTs were included. Compared with patients receiving only regular instructions, patients received EPI showed significantly higher H. pylori eradication rate (n = 8 RCTs, ITT analysis: RR = 1.20, 95% CI: 1.06-1.35; PP analysis: RR = 1.12, 95% CI:1.02-1.23) and better patient compliance (n = 8 RCTs, RR = 1.23, 95% CI: 1.09-1.39), as well as higher patient satisfaction (n = 3 RCTs, RR = 1.42, 95% CI: 1.14-1.76). However, there were no significant difference between groups in the incidence of total adverse events (n = 6 RCTs, RR = 0.66, 95%CI: 0.40-1.08) and symptom relief rates (n = 2 RCTs, RR = 1.17, 95% CI: 0.89-1.54). The TSA result indicated that the effect was robust. CONCLUSIONS: Evidence from our meta-analysis shows that EPI intervention may be a promising strategy to improve H. pylori eradication rate, patient compliance, and patient satisfaction.

Saccharomyces boulardii as an adjuvant therapy for Helicobacter pylori eradication: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND AND AIMS: Whether Saccharomyces boulardii (S boulardii) as an adjuvant therapy are beneficial to H pylori eradication remains controversial. The aim of the study was to update and determine the effects of S boulardii as an adjuvant therapy on H pylori eradication rates and adverse effects. METHODS: We searched PubMed, Embase, CENTRAL, and Web of Science to collect all randomized controlled trials assessing the effects of S boulardii as an adjuvant therapy for H pylori eradication from inception to February 2019. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis was performed to control the risk of type I and type II errors. RESULTS: Eighteen trials with 3592 patients were eligible for meta-analysis. Compared with standard eradication regimen, the S boulardii supplementation could significantly improve eradication rates [risk ratio (RR) = 1.09, 95% confidence interval (CI):1.05-1.13; moderate quality evidence] and reduce the incidence of total side effects (RR = 0.47, 95%CI:0.36-0.61; low quality evidence), as well as some gastrointestinal adverse effects, especially diarrhea (RR = 0.33, 95%CI:0.23-0.47; low quality evidence) and constipation (RR = 0.37, 95%CI:0.23-0.57; moderate quality evidence). In addition, the need for discontinuation rate in S boulardii supplementation group was significantly lower than in the control group (RR = 0.33, 95%CI:0.16-0.69, P = .003; moderate quality evidence). The TSA results for overall eradication rates and total side effects indicated that the effects were conclusive. CONCLUSIONS: Our meta-analysis shows that S boulardii supplementation on standard eradication therapy significantly increased H pylori eradication rates and reduced the incidence of total side effects and some gastrointestinal adverse effects during eradication therapy.

Association between Helicobacter pylori infection and nonalcoholic fatty liver disease: A systematic review and meta-analysis of observational studies.

BACKGROUND: The association between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) has been shown in many observational studies, but these conclusions remain controversial. Hence, we performed a meta-analysis to elucidate the association. METHODS: A comprehensive search was conducted on relevant studies published from inception to December 31, 2018, in PubMed, EMBASE, and Web of Science databases. Odds ratio (OR) with 95% confidence interval (95% CI) were pooled by random-effect model, generic inverse variance method. Subgroup and sensitivity analyses were also done. Publication bias was estimated by the funnel plot, Begg's test, and Egger's test. RESULTS: Fifteen studies (eleven cross-sectional, two case-control, and two cohort studies) were included in this meta-analysis. The pooled OR of NAFLD in patients with H. pylori infection was 1.19 (95% CI: 1.11-1.29, P < 0.00001) when compared with the patients without H. pylori infection. Similar results were observed when the subgroup analyses were stratified by different geographical locations, study designs, and confounders adjustment. In subgroup analysis stratified by different H. pylori testing methods, the correlation still exists when using UBT, serology, RUT, or SAT, but there was no statistically significant difference when using multiple detection methods (OR = 2.96, 95% CI: 0.37-23.94, P = 0.31). Sensitivity analyses showed that our results were robust. No evidence of substantial publication bias was detected. CONCLUSIONS: Current evidence indicated that a positive association between H. pylori infection and the risk of NAFLD. Further prospective studies are warranted to strengthen the association and to clarify whether there is a causative link between them.

Association Between Non-alcoholic Fatty Liver Disease and Risk of Stroke: A Systematic Review and Meta-Analysis.

Background/Objectives: Recent observational studies have explored the association between non-alcoholic fatty liver disease (NAFLD) and stroke with controversial results. We therefore performed a meta-analysis to investigate this possible association. Methods: PubMed, EMBASE and Web of Science database were searched from inception until December 2019, and updated on May 2021. Random-effects meta-analyses were performed by generic inverse variance method. Subgroup and sensitivity analyses were also conducted. The PROSPERO registered number of this study is CRD42020167330. Results: Twenty observational (15 cohort, 4 cross-sectional, and 1 case-control) studies with 17,060,388 participants were included in the meta-analysis. Meta-analysis of data from 18 studies with 17,031,672 participants has shown that NAFLD was associated with mildly increased risk of stroke (OR = 1.18, 95% CI: 1.08-1.30, P = 0.0005). Similar results were observed in most of the subgroup analyses we performed. Sensitivity analyses did not alter these findings. Meta-analysis of data from 3 studies with 29,614 participants has shown that insufficient evidence to support the proposed association between NAFLD-fibrosis and an increased risk of stroke. Conclusions: We found that NAFLD was associated with increased risk of stroke. However, there was insufficient evidence to support the proposed association between NAFLD-fibrosis and an increased risk of stroke. To better understand any association, future well-designed prospective studies that take fully account of specific population, type of stroke, and confounding factors are warranted. Systematic Review Registration: Unique Identifier: CRD42020167330.

An exploration of aptamer internalization mechanisms and their applications in drug delivery.

INTRODUCTION: As 'chemical antibodies', aptamers have some advantages, such as lack of immunogenicity, rapid tissue penetration, cell internalization and so on. Consequently, more and more aptamers have been screened out by the systematic evolution of ligands through exponential enrichment for the desired cells or membrane receptors. On the basis of the result, researchers use aptamers to guide drug targeting to the desired cells and internalization in vivo. AREAS COVERED: In this review, we explore the mechanisms of cargo- or aptamer-mediated internalization, and then briefly summarize five strategies for exploring the mechanism of aptamer internalization. Finally, we focus on four types of applications involving aptamer internalization: aptamers as drugs, aptamers as chemical drug-delivery systems, aptamer-based chimeras and aptamer-conjugated nanoparticles or block copolymer micelles. EXPERT OPINION: Two aptamer-internalization mechanisms are known, namely receptor-mediated endocytosis and macropinocytosis. The latter mechanism, which is has only been verified in the internalization of nucleolin aptamer shuttles between the nucleus and cytoplasm, may be important for nuclear internalization and cargo molecule escape from the endosomal compartment. Thus, it is feasible to use some strategies to further explore the macropinocytosis internalization mechanism and then to screen for aptamers similar to the nucleolin aptamer for use with the desired cell types as a targeted delivery tool.

Post-marketing Re-evaluation of Tongxiening Granules () in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Multi-center, Randomized, Double-Blind, Double-Dummy and Positive Control Trial.

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death.

The major obstacle to successful treatment of gastric cancer is chemotherapy resistance. Our study was designed to investigate the role of phosphoinositide 3-kinase (PI3K)/Akt pathway in the development of chemoresistance in gastric cancer. In the present study, elevated Akt expression and Akt phosphorylation (Ser 473), as well as decreased PTEN expression were observed in 28 cases of gastric cancer tissues. Etoposide and doxorubicin stimulated Akt and PI3K activities in 2 gastric cancer cell lines (BGC-823 and SGC-7901), and the activities were concentration and time-dependent. Up-regulation of PTEN expression in BGC-823 cells by PEAK8-PTEN transient transfection obviously decreased the basal and anticancer drugs induced Akt activities, then sensitized BGC-823 cells to etoposide and doxorubicin. Pretreatment of BGC-823 and SGC-7901 cells with wortmannin, a PI3K inhibitor, attenuated cells's resistance to etoposide and doxorubicin. In addition, pretreatment of wortmannin blocked etoposide and doxorubicin induced IkappaB-alpha degradation, NFkappaB activation, phosphorylation of Akt, MDM-2 and forkhead transcription factors. Wortmannin pretreatment also promoted the accumulation of p27/Kip, but inhibited the Mcl-1 expression. Furthermore, wortmannin promoted etoposide and doxorubicin induced caspase-3, caspase-9 activation and poly ADP-ribose polymerase cleavage. Taken together, the observations indicate the PI3K/Akt pathway plays an important role in the chemoresistance of gastric cancer cells. A new strategy for combined chemotherapy of gastric cancer should be designed to more specifically block PI3K/Akt pathway and then decrease the amount of resistant cells.

[Impact of PI3K /Akt /mdm2 signaling pathway on the sensitivity of gastric cancer cell line SGC7901 to doxorubicin].

OBJECTIVE: To explore whether PI3K/Akt/mdm2 signalling pathway affect the sensitivity of gastric cancer cell line SGC7901 cells to doxorubicin. METHODS: Gastric cancer cell line SGC7901 cells were exposed to doxorubicin and specific PI3K inhibitor wortmannin. Cell apoptosis was detected using flow cytometry. PI3K activity was detected by radioactive immunoprecipitation-kinase assay. Western blotting was employed to evaluate the expressions of PI3K-p85, pAkt-S473, Akt, pmdm2-S166 and p53. RESULTS: The level of apoptosis in gastric cancer SGC7901 cells treated with doxorubicin was gradually increasing. wortmannin enhanced its effects significantly. PI3K activity and the expression of pAkt-S473 increased in a time-dependent manner, pmdm2-S166, p53 were also increased wortmannin inhibited phosphorylation of mdm2 and improved the p53 expression. CONCLUSION: PI3K/Akt/mdm2 signalling pathway can be activated by doxorubicin and suppress apoptosis by promoting phosphorylation of mdm2. PI3K inhibitor wortmannin can enhance sensitivity of gastric cancer cells to chemotherapy.

Aberrant expression of Eag1 potassium channels in gastric cancer patients and cell lines.

Recently, an interesting relationship between potassium channels and cancer has evolved. The aim of this study is to investigate expression of Eag1 potassium channel in gastric cancer and its role in cancer cells growth. The expression of Eag1 for gasric cancer patients and cell lines as well as gastric adenoma was investigated by immunohistochemistry and reverse transcription polymerase chain reaction. In addition, imipramine was used to identify the involvement of Eag1 in the growth of SGC-7901 and BGC-823 cells. Frequency of positive expression of Eag1 protein was 70.5% (67/95) and Eag1 mRNA was 68.2% (15/22) in gastric cancer primary tissues. Eag1 mRNA was positively expressed in two gastric cell lines. Eag1 protein and mRNA were negatively expressed in paired non-cancerous matched tissues and 5 cases of adenoma tissues. The expression level of Eag1 protein was associated with lymph node metastasis (P = 0.049) and stage (P = 0.039), but had no correlation with sex, age, differentiation grades, and other organs metastases. Imipramine significantly inhibited the proliferation of SGC-7901 and BGC-823 cells at 12 h and 24 h detected by cells number counting and MTT assay (P < 0.01). The study indicates Eag1 is aberrantly expressed in gastric cancer tissues and cell lines and associated with cancer lymph node metastasis and stage and play an important role in the proliferation of gastric cancer cells.