Walking exercise through smartphone application plus branched-chain amino acid supplementation benefits skeletal muscle mass and strength in liver cirrhosis: A prospective control trial.

INTRODUCTION AND OBJECTIVES: Whether a combination of exercise and branched-chain amino acid (BCAA) supplementation was more beneficial than those given alone in sarcopenia related to liver cirrhosis (LC) is unknown. Widely used smartphone applications provide continuous and easily expandable management of chronic liver disease (CLD). This study is to investigate the effects of unsupervised walking exercise using WeChat combined with BCAA supplementation on skeletal muscle mass and strength in LC. MATERIALS AND METHODS: The 127 LC patients of Child-Pugh A/B were assigned to group A (BCAA supplements, n=42), group B (walking exercise, n=43) and group C (walking exercise plus BCAA supplements, n=42). Laboratory data, average daily steps, serum BCAA, skeletal muscle mass index (SMI) and grip strength were analyzed pre- and 3 months after interventions. RESULTS: Of the 124 patients who completed interventions, albumin and daily steps were significantly increased in all groups (p=0.0001). Post-intervention BCAA were significantly elevated in group A (A vs B, p=0.001) and C (C vs B, p=0.012;). While post-intervention daily steps in group B (B vs A, p=0.0001) and C (C vs A, p=0.0001) were higher. Grip strength (C vs A, p=0.020; C vs B, p=0.036) and SMI (C vs A, p=0.035; C vs B, p=0.012) were increased in group C. Prevalence of sarcopenia was significantly decreased in group C (p=0.015). CONCLUSIONS: A combination of unsupervised walking exercise using smartphone applications and BCAA supplementation might be an effective and safe treatment for cirrhosis patients with Child-Pugh A/B to improve skeletal muscle mass and strength or to prevent progress of sarcopenia.

Efficacy and Safety of Endoscopic Submucosal Dissection for Dysplasia in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer. Current guidelines recommend endoscopic resection if the lesion is visible with distinct margins and a complete resection can be achieved. However, submucosal fibrosis due to chronic inflammation may increase the procedural risk and reduce the complete resection rate. The aim of this study is to assess the efficacy and safety of endoscopic submucosal dissection (ESD) for dysplasia in UC patients. MATERIALS AND METHODS: A systematic search of databases was performed until May 30, 2021. Studies that reported the resection rates and complication rates of ESD for dysplasia in UC patients were included. A random-effects model was used to generate conservative estimates of the prevalence of the outcome variables. All data analyses were performed using software Stata (version 15). RESULTS: 8 studies were enrolled in the meta-analysis, with a total of 203 dysplastic lesions in 192 UC patients. The mean lesion size was 26.7 mm. About 83% of the lesions were located in the left-side colon, and 90% of the lesions were nonpolypoid, and about 71% of the lesions had submucosal fibrosis. The mean procedural time of ESD was 83 minutes. The en bloc resection rate, complete resection rate, and curative resection rate were 94%, 84%, and 81%, respectively, with a local recurrence rate of 5%. The pooled prevalence of bleeding and perforation were 8% and 6%, respectively. The rates of metachronous tumors and additional surgery after ESD were 6% and 10%, respectively. CONCLUSION: Despite some limitations, our study suggests that ESD is an effective and safe treatment for dysplasia in UC patients. However, randomized controlled multicenter studies with less heterogeneity and longer follow-up are needed to better assess the clinical outcomes of ESD in UC patients.

Examine the Correlation between Heat Shock Protein IbpA and Heat Tolerance in Cronobacter sakazakii.

We used a proteomic approach to identify IbpA in Cronobacter sakazakii (C. sakazaki), which is related to heat tolerance in this strain. The abundance of IbpA in C. sakazakii strains strongly increased after heat shock. C. sakazakii CMCC 45402 ibpA deletion mutants were successfully constructed. The C. sakazakii CMCC 45402 ΔibpA and wild-type strains could not be distinguished based on colony morphology on LB agar plates or biochemical assays. The growth of the C. sakazakii CMCC 45402 ΔibpA mutant in heat shock conditions was indistinguishable from that of the isogenic wild-type, but showed greater heat resistance than E. coli O157:H7 strain CMCC 44828. This study suggests that the absence of a single ibpA gene has no obvious effect on the phenotype or heat resistance of the strain C. sakazakii CMCC 45402.

Comparative observation of vitrectomy with macular epiretinal membranes peeling with or without air tamponade for idiopathic macular epiretinal membranes / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To compare the treatment efficacy of vitrectomy with macular epiretinal membrane ( MEM ) peeling combined with or without air tamponade for idiopathic macular epiretinal membranes( IMEM) .·METHODS: Forty-two cases of IMEM patients ( 46 eyes ) associated with cataract were randomly divided into two groups. Twenty-five eyes of 23 cases in Group A were performed with vitrectomy with macular epiretinal membrane peeling combined with air tamponade. The other 21 eyes of 19 cases in Group B only underwent vitrectomy and macular epiretinal membrane peeling ( without air tamponade ) . The visual acuity and central macular thickness ( CMT ) were compared between the two groups before and after the surgery. The intraoperative and postoperative complications were also observed in both groups in the mean time.· RESULTS: There was no statistical significant difference between two groups in age, visual acuity and CMT before operation (P>0. 05). By 1wk, 3 and 6mo follow-up after operation, mean visual acuity improved significantly; mean CMT decreased obviously in both groups after the operation and the difference was statistically significant (P<0. 05). But for mean visual acuity and CMT, there were not statistically significant difference between two groups postoperatively at the same time(P>0. 05),there was no correlation between postoperative mean visual acuity and CMT in the two groups. No serious complications occurred during and after operation.· CONCLUSION: Vitrectomy with macular epiretinal membrane peeling can be a safe and effective treatment for IMEM, meanwhile air tamponade in vitreous cavity does not reveal more advantages in the treatment.

Berberine improves mesenteric artery insulin sensitivity through up-regulating insulin receptor-mediated signalling in diabetic rats.

BACKGROUND AND PURPOSE: Berberine, a small molecule derived from Coptidis rhizome, has been found to be potent at lowering blood glucose and regulating lipid metabolism. Recent clinical studies have shown that berberine reduces blood pressure and increases systemic insulin sensitivity in patients with metabolic syndrome; however, the underlying mechanism is still unclear. Here, we investigated the mechanism by which berberine improves vascular insulin sensitivity in diabetic rats. EXPERIMENTAL APPROACH: Diabetes was induced in male Sprague­Dawley rats by feeding a high-fat diet and administration of a low dose of streptozotocin. These diabetic rats were treated with berberine (200 mg·kg(−1)·day(−1), gavage) for 4 weeks. Vascular dilation was determined in isolated mesenteric artery rings. Effects of berberine on insulin signalling were also studied in human artery endothelial cells cultured in high glucose (25 mmol·L(−1)) and palmitate (500 µmol·L(−1)). KEY RESULTS: Berberine treatment for 4 weeks significantly restored the impaired ACh- and insulin-induced vasodilatation of mesenteric arteries from diabetic rats. In isolated mesenteric artery rings, berberine (2.5­10 µmol·L(−1)) elicited dose-dependent vasodilatation and significantly enhanced insulin-induced vasodilatation. Mechanistically, berberine up-regulated phosphorylation of the insulin receptor and its downstream signalling molecules AMPK, Akt and eNOS, and increased cell viability and autophagy in cultured endothelial cells. Moreover, down-regulating insulin receptors with specific siRNA significantly attenuated berberine-induced phosphorylation of AMPK. CONCLUSIONS AND IMPLICATIONS: Berberine improves diabetic vascular insulin sensitivity and mesenteric vasodilatation by up-regulating insulin receptor-mediated signalling in diabetic rats. These findings suggest berberine has potential as a preventive or adjunctive treatment of diabetic vascular complications. LINKED ARTICLES: This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23.

Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Helicobacter pylori is one of the most common gastric pathogens, affecting at least half the world's population, and is strongly associated with gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma. We aimed to assess the efficacy, safety, and immunogenicity of a three-dose oral recombinant H pylori vaccine in children in China. METHODS: We did this randomised, double-blind, placebo-controlled, phase 3 trial at one centre in Ganyu County, Jiangsu Province, China. Healthy children aged 6-15 years without past or present H pylori infection were randomly assigned (1:1), via computer-generated randomisation codes in blocks of ten, to receive the H pylori vaccine or placebo. Participants, their guardians, and study investigators were masked to treatment allocation. The primary efficacy endpoint was the occurrence of H pylori infection within 1 year after vaccination. We did analysis in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT02302170. FINDINGS: Between Dec 2, 2004, and March 19, 2005, we randomly assigned 4464 participants to either the vaccine group (n=2232) or the placebo group (n=2232), of whom 4403 (99%) participants completed the three-dose vaccination schedule and were included in the per-protocol efficacy analysis. We extended follow-up to 3 years. We recorded 64 events of H pylori infection within the first year (14 events in 2074·3 person-years at risk in the vaccine group vs 50 events in 2089·6 person-years at risk in the placebo group), resulting in a vaccine efficacy of 71·8% (95% CI 48·2-85·6). 157 (7%) participants in the vaccine group and 161 (7%) participants in the placebo group reported at least one adverse reaction. Serious adverse events were reported in five (<1%) participants in the vaccine group and seven (<1%) participants in the placebo group, but none was considered to be vaccination related. INTERPRETATION: The oral recombinant H pylori vaccine was effective, safe, and immunogenic in H pylori-naive children. This vaccine could substantially reduce the incidence of H pylori infection; however, follow up over a longer period is needed to confirm the protection of the vaccine against H pylori-associated diseases. FUNDING: Chongqing Kangwei Biological Technology.

Parthenolide, an inhibitor of the nuclear factor-κB pathway, ameliorates dextran sulfate sodium-induced colitis in mice.

BACKGROUND: Activation of nuclear factor-kappa B (NF-κB), which controls transcription of various pro-inflammatory cytokine genes, has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). Parthenolide, a sesquiterpene lactone compound isolated from extracts of the herb Feverfew (Tanacetum parthenium), has been demonstrated to be a potent inhibitor of NF-κB activation. This study was designed to investigate the effects of parthenolide on an experimental murine colitis model. MATERIALS AND METHODS: Experimental colitis was induced by dextran sulfate sodium (DSS), and mice were divided into 3 groups: normal control, DSS+saline, and DSS+parthenolide. The disease activity index (DAI) and histological score were observed. The tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels were measured by enzyme-linked immunosorbent assay. Phospho-IκBα, IκBα and phospho-NF-κB p65 expression were assessed by western blot analysis. Myeloperoxidase (MPO) activity was determined by using MPO assay kit. RESULTS: Administration of parthenolide significantly reduced the severity of DSS-induced colitis as assessed by DAI and histological score, and resulted in downregulation of MPO activity and phospho-NF-κB p65 expression by the blockade of phosphorylation and subsequent degradation of IκB protein, strikingly reduced the production of TNF-α and IL-1ß. CONCLUSION: Parthenolide exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.

Akt-centered amplification loop plays a critical role in vascular endothelial growth factor/stromal cell-derived factor 1-α cross-talk and cardioprotection.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of major mediators of angiogenesis and survival factor in some tissue, however, its direct effects on cardiomyocytes remain poorly understood. METHODS: Rat neonatal ventricular myocytes were cultured in vitro. Akt phosphorylation was measured by Western blotting; the expression of stromal cell-derived factor α (SDF-1α)/CXCR4 axis was evaluated by real-time PCR and Western blotting. LY294002 and AMD3100 were used to interfere with the signaling of VEGF and SDF-1α/CXCR4 axis. Cardiac myocytes viability and injury were evaluated by trypan blue staining and lactate dehydrogenase (LDH) release. RESULTS: Treatment of neonatal rat ventricular myocytes with VEGF induced phosphorylation of Akt in a dose and Flk-1 dependent manner. VEGF attenuated H2O2 induced cardiac myocyte death. The phosphoinositol-3-kinase (PI3K) inhibitor, LY294002 and Flk-1 antibody abolished the beneficial effects of VEGF on H2O2 induced cell death. In the mean time SDF-1α-CXCR4 axis was up-regulated by VEGF through PI3K-Akt signaling and contributed to the protective effects of VEGF on H2O2 induced cell death. Interestingly, SDF-1α also promoted production of VEGF in cultured cardiac myocytes and LY294002 reversed the up-regulation of VEGF induced by SDF-1α. CONCLUSION: VEGF has direct protective effects on cardiomyocytes; a crosstalk between VEGF and SDF-1α through PI3K-Akt serves a survival role in cardiomyocytes in vitro.

Nitric oxide induces heat shock protein 72 production and delayed protection against myocardial ischemia in rabbits via activating protein kinase C.

BACKGROUND: Nitric oxide (NO) is a biologically active molecule which has been reported to protect the heart against ischemia and reperfusion injury in different species. This study aimed to test the hypothesis that nitric oxide may induce the expression of heat shock protein 72 (HSP72) which may protect the heart against ischemia. METHODS: Rabbits were given intravenous saline or S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, or Zaprinast, an inhibitor of cyclic guanosine monophosphate (GMP)-phosphodiesterase, which may increase myocardial cyclic GMP content. Twenty-four hours later, the rabbits were either sampled to measure HSP72, or induced with a 30-minute coronary occlusion followed by a 120-minute reperfusion, and then the infarct size was measured. Meanwhile, chelerythrine (CHE, an inhibitor of protein kinase C) was given intravenously 5 minutes before SNAP injection and the effect on HSP72 expression and infarct size was determined. RESULTS: Twenty-four hours after pretreatment, immunoblotting showed HSP72 expression increased in the SNAP group compared with control groups, and this was blocked by CHE. Myocardial infarct size in the SNAP group was smaller than that of the control group ((32.4 +/- 5.8)% vs (51.1 +/- 4.7)%, P < 0.05). Pretreated with CHE abolished the infarct size-limiting effect of SNAP ((46.0 +/- 5.1)%). Pretreatment with Zaprinast neither induced HSP72 expression nor reduced infarct size ((55.4 +/- 5.4)%). CONCLUSION: NO induced HSP72 expression and a delayed protection to the heart via the activities of protein kinase C by a cyclic GMP-independent pathway.

Preparation of monoclonal antibody and development of enzyme-linked immunosorbent assay specific for Escherichia coli O157 in foods.

OBJECTIVE: To prepare monoclonal antibodies (MAb) and antisera specific for Escherichia coli (E. coli) O157, and to develop a sandwich enzyme-linked immunosorbent assay (ELISA) to detect E. coli O157 in foods. METHODS: Spleen cells from BALB/c mice immunized with the somatic antigen of E. coli O157:H7 were fused with murine Sp2/0 myeloma cells. The hybridoma cell line specific for E. coli O157 was established after having been subcloned. Antisera specific for E. coli O157 was prepared by intravenous injection into New Zealand rabbits with a stain of E. coli O157:H7. The sandwich ELISA was developed with the polyclonal antibody as the capture antibody and the MAb 3A5 as the detection antibody. The inoculated ground poultry meat and pasteurized milk were tested to confirm efficiency of the method. RESULTS: MAb 3A5 specific for E. coli O157 and O113:H21 belonged to subtype IgM. The ascetic titers of the antibody was 1:1x10(6). No cross-reactivity of the MAb was observed with strains of Salmonella spp, Yersinia enterocolitica, Shigella dysenteriae, etc. The purified polyclonal antibody had a titer of 1:1x10(5) with E. coli O157. The detection limit of this sandwich ELISA was 10(3)-10(4) cfu E. coli O157/mL in pure culture with a high specificity, which was characterized by every non-O157 strain with negative response. With 10h enrichment procedure, E. coli O157:H7 recovered well from inoculated ground poultry meat and pasteurized milk at levels of 0.1 cfu/g and 0.1 cfu/mL. CONCLUSION: MAb 3A5 specific for E. coli O157 and O113:H21 can be produced by immunizing BALB/c mice with a strain of E. coli O157:H7. Then a sandwich ELISA can be developed with the polyclonal antibody as the capture antibody and the MAb 3A5 as the detection antibody. The method is proved to be a sensitive and specific technique to detect low number of E. coli O157 in food.

[Application of green fluorescence protein in the detection of E. coli O157:H7 in food].

OBJECTIVE: To introduce green fluorescence protein (GFP) into E. coli O157:H7 and improve the detection methods for this bacteria, and to study the kinetics of E. coli O157:H7. METHODS: The plasmid pGFP was transferred into E. coli O157:H7. The characteristic of the new built O157:H7-pGFP strain was evaluated. Some food samples were inoculated with the recombinant strain under certain temperature to imitate different storage circumstances. The contaminated E. coli O157:H7 were counted after certain time. RESULTS: The pGFP was stable in E. coli O157:H7. The E. coli O157:H7-pGFP inoculated in ground poultry meat and pasteurized milk were enriched to 35 000 approximately 200 000 times in 12 h under higher storage temperature (37 degrees C), whereas the quantity decreased slowly under lower temperature (4 degrees C). CONCLUSION: The recombinant strain with the characters of ampicillin resistance and green fluorescence under UV 365 nm was a useful tool in detection methods improvement and bacteria survival studies.