BACKGROUND: Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China. METHODS: This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%. RESULTS: The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P  = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P  = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles. CONCLUSION: Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China. TRIAL REGISTRATION ClinicalTrials.gov , NCT04198363.
Humans ; Esomeprazole/therapeutic use* ; Double-Blind Method ; Helicobacter Infections/drug therapy* ; Male ; Female ; Middle Aged ; Helicobacter pylori/pathogenicity* ; Pyrroles/therapeutic use* ; Sulfonamides/therapeutic use* ; Adult ; Clarithromycin/therapeutic use* ; Amoxicillin/therapeutic use* ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Pyrrolidines/therapeutic use* ; Drug Therapy, Combination ; Proton Pump Inhibitors/therapeutic use*

Helicobacter pylori ( H. pylori ) infects approximately half of the population worldwide and causes chronic gastritis, peptic ulcers, and gastric cancer. Test-and-treat strategies have been recommended for the prevention of H. pylori -associated diseases. Advancements in high-throughput sequencing technologies have broadened our understanding of the complex gastrointestinal (GI) microbiota and its role in maintaining host homeostasis. Recently, an increasing number of studies have indicated that the colonization of H. pylori induces dramatic alterations in the gastric microbiota, with a predominance of H. pylori and a reduction in microbial diversity. Dysbiosis of the gut microbiome has also been observed after H. pylori infection, which may play a role in the development of colorectal cancer. However, there is concern regarding the impact of antibiotics on the gut microbiota during H. pylori eradication. In this review, we summarize the current literature concerning how H. pylori infection reshapes the GI microbiota and the underlying mechanisms, including changes in the gastric environment, immune responses, and persistent inflammation. Additionally, the impacts of H. pylori eradication on GI microbial homeostasis and the use of probiotics as adjuvant therapy are also discussed. The shifts in the GI microbiota and their crosstalk with H. pylori  may provide potential targets for H. pylori -related gastric diseases and extragastric manifestations.
Helicobacter Infections/microbiology* ; Humans ; Helicobacter pylori/pathogenicity* ; Gastrointestinal Microbiome/drug effects* ; Probiotics/therapeutic use* ; Anti-Bacterial Agents/therapeutic use*

Objective To observe the efficacy and safety of endoscopic variceal ligation (EVL) and esophageal variceal sclerotherapy (EVS) with different hardeners for esophageal variceal bleeding (EVB).Methods Clinical data of 314 patients with EVB were retrospectively reviewed.The patients were divided into 5 groups according to the endoscopic treatments they have received,i.e.,endoscopic variceal ligation (EVL) group (n =112),sodium morrhuate sclerotherapy (EVS1) group (n =48),lauromacrogol sclerotherapy (EVS2) group (n =40),EVL plus sodium morrhuate sclerotherapy (EVLS1) group (n =26) and EVL plus lauromacrogol sclerotherapy (EVLS2) group (n =88).The efficacy,variceal recurrence rate and complication rate were evaluated.Results There was no significant difference in efficacy of stop bleeding among 5 groups,which was 85.7％ (96/112) in EVL group,83.3％ (40/48) in EVS1 group,92.5％(37/40) in EVS2 group,92.3％ (24/26) in EVLS1 group and 94.3％ (83/88) in EVLS2 group (P ＞0.05).The complete cure rates in EVLS1 group (88.5％,23/26) and EVLS2 group (87.5％,77/88)were significantly higher than those in 3 other groups (P ＜ 0.05).Rebleeding rates in EVS1 group (18.8％,9/48) and EVL group (11.6％,13/112) were significantly higher than those in other 3 groups (P ＜0.05).The patients were followed up for 6-18 months,and the varices recurrence rate was highest in group EVL (23.2％,26/112) and lowest in EVLS2 (10.2％,9/88,P ＜0.05).The complication rate in group EVS1 (32.2％,49/152) was significantly higher than that in other 4 groups (P ＜0.05).Conclusion EVL plus EVS,either with sodium morrhuate or lauromacrogol EVS is safe and effective for EVB,especially EVL plus Lauromacrogol EVS,may become an optimal therapy to control esophageal variceal bleeding and rebleeding.

The present investigation was to construct lentiviral vector carrying the human gene NK4 and transfect the human bone mesenchymal stem cells (hBMSCs) and to determine the expression of NK4 gene in hBMSCs after transfection. The NK4 gene was obtained from HGF cDNA by polymerase chain reaction(PCR), and the pGC-FU-NK4 plasmid was constructed by double restriction enzyme digestion and gene recombinant. The titer of virus was tested by real-time quantitative PCR. After transfected by lentivirus, the green fluorescent protein (GFP) in hBMSCs was observed using fluorescence microscope, and the expression of NK4 in culture supernatant was detected by enzymelinked immunosorbent assay (ELISA). The sequence of the PCR product was consistent with the data of GeneBank by DNA sequencing. The virus titer was 2 X 10(8)TU/ml. Strong green fluorescence was observed in the cell membrane and cytoplasm of hBMSCs with fluorescent microscopy. The expression of NK4 in culture supernatant was increased with time extension. The hBMSCs can be transfected by NK4 gene expressing lentiviral vector safely and effectively, and the expressin and secretion of NK4 was persistent and stable.
Bone Marrow Cells ; metabolism ; Genetic Vectors ; genetics ; Hepatocyte Growth Factor ; biosynthesis ; genetics ; Humans ; Lentivirus ; genetics ; metabolism ; Mesenchymal Stromal Cells ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; Transfection

Objective To study the therapeutic effect of cholinergie receptor,an nicotinic acetylcholine receptor(nAChR)α7 agonist,on trinitrobeazene sulfonic acid(TNBS)-induced colitis in mice.Methods BALB/C mice were randomly divided into control group,TNBS group,anabaseine(AN)as the agonist of nAChRα7(AN group),and chlorisondamine diiodide(CHD)as the antagonist of nAChRα7(CHD group).TNBS-induced colitis was produced at day 1,either 10 μg anabaseine or 1.5 μg chlorisondamine diiodide was administrated after the induction of colitis,and repeated on interval day till the mice were sacrificed at day 8.The myeloperoxidase(MPO)activity and level of tumor necrosis factors(TNF)-α in colonic tissue were examined by histological method and enzyme-linked immunosorbent assay (ELISA),respectively.Lamina propria mononuclear cells(LPMCs)were isolated,and NF-κB activation was further detected by Western blot.Results Compared with TNBS group,the tissue damage,MPO activity and concentration of TNF-α in mice treated with anabaseine were decreased[MPO activity:(7.6±2.1)U/mg vs(12.2±2.6)U/mg,TNF-α level:(396±98)pg/g vs(627±112)Pg/g],and NF-κB activation in LPMCs was inhibited.Whereas the MPO activity[(14.1±1.8) U/mg)]and concentration of TNF-α[(692±79)pg/g)]in mice treated with chlorisondamine diiodide were increased and NF-κB activation in LPMCs were amplified. Conclusion nAChRa7 agonist can inhibit colonic inflammatory response by down-regulating the consentration of TNF-α and inhibiting NF-κB activation.

Objectives To investigate the clinical characteristics and the regularity of seasonal changes that influence peptic ulcer (PU) in Nanehang area and to provide a theoretical basis for the treatment and prevention of PU.Methods Data collected from patients with PU diagnosed by clinic and gastroendoseopy between October 2003 to May 2008 were retrospectively analyzed.The PU was further divided into gastric ulcer,duodenal ulcer and complex ulcer.The lesion of gastric ulcer was calculated by five locations that were antral,angular,corporal,pyloric canal,fundic and cardia.The lesion of duodenal ulcer was calculated by five locations that were anterior wall of bulb,posterior wall,lesser curvature, greater curvature and postbulbar.The climate changes that influnced the incidence of PU disease were also observed.The detective rates of different types of PU were analyzed and its association with gender,age, lesion locations,seasons,Helicobacter pylori (Hp) infection and complications were also investigated. Results Among 83 888 patients who underwent endoscopy,PU was found in 21 308 patients (25.4%) including 66.33% duodenal ulcer,24.88% gastric ulcer and 8.79% complex ulcer.The male and femal ratio was 2.44 : 1 in PU,2.53 : 1 in duodenal ulcer,2.26 : 1 in gastric ulcer,and 2.33 : 1 in complex ulcer.The average age of patients with gastric ulcer was 48.0 years that was about 6.7 years higher than that of patients with duodenal ulcer.The prevalence of duodenal ulcer and gastric ulcer peaked in the 30- 39 years and 50-59 years,respectively.PU was more common from December to February (30.17%) and less common from June to August (22.54%) (P＜0.01) .The 57.43% of duodenal ulcer was found on anterior wall of bulb,18.26% on greater curvature,13.21% on lesser curvature,7.34% on posterior wall and 3.76% on postbulbar.The 45.69% of gastric ulcer was found on antral,20.54% on angular, 15.54% on corporal,9.36% on pyloric canal,and 8.87% on fundic and cardia.The 91.83% (12 318/ 13 414) of patients were positive for Hp infection.There was no significant difference of Hp infection among patients with different types of PU.The complications in patients with PU were bleeding (4.94%),pyloric obstruction (3.51%) and chronic perforation(0.04%).Conclusions The detective rate of PU in Nanchang area is 25.4%,which is higher than that in northern area of China.The incidence of PU is highly associated with sex,age,seasons and ulcer locations,with high Hp infections and a low incidence of complications.

Objective To research the mechanism of High Volume Hemofiltration (HVHF) on acute lung injury (ALI) induced by LPS in dogs. Methods After injection of LPS (650 ?g/kg) via central vein within 30 min, Sixteen healthy hybrid male dogs were divided into control group and treatment group randomly (n=8). PaO2、PaCO2 in artery blood were recorded. Contents of TNF-?、IL-6 and IL-10 in plasm were measured by radioimmunity. The activity of NF-?B in lung homogenate was measured by flow cytometer. The content of surfactant protein B (SP-B) in lung homogenate was measured by Western-blotting.Changes of lung histopathology was observed via electron microscopy. Results After injection of LPS, PaO2 and PaO2/FiO2 began to decrease. PaO2 and PaO2/FiO2 in treatment group kept higher than that in control group (P

PTEN(Phosphatase and Tensin Homology deleted from Chromosome ten),a putative antioncogene,encodes a PTEN protein that has a dual specificity phosphatase activity with both protein phosphatase and lipid phosphatase,which regulates a variety of molecules through inhibiting the PI3K/Akt signaling pathway.Recently,some scholars dedicate to the modulation of PTEN,which demonstrates that PTEN can be regulated by multiple factors at the level of gene and protein.This review briefly summarizes up-to-date information about the modulation of PTEN and its mechanisms.

Objective To observe the influence of heat shock preconditioning on the expressions of heat shock protein(HSP)60,70 and induced nitric oxidase synthase(iNOS)in gastric mucosa of severely burned rats and investigate the protective mechanism of burn-induced acute gastric mucosal lesion.Methods Ninety-six Wistar rats were divided into two groups:burn(B)and heat shock preconditioning before burn(HB).The extent of gastric mucosal lesions(UI)was evaluated grossly and histologically.HSP70 mRNA expression was determined by RT-PCR.Immunohistochemical method was used to analyze the protein expressions of iNOS,HSP60 and HSP70.Results Rats in B group were induced conspicuous gastric mucosal lesions,while UI in HB group was significantly lower.The expressions of HSP70 and HSP60 were significantly increased and the expression of iNOS was obviously decreased in HB group as compared with B group.Conclusion Heat shock preconditioning protects against acute gastric mucosal lesion caused by burn through enhancing the expressions of induced HSPs and reducing the iNOS expression.

Objective To investigate the expression of telomerase-associated genes and c-myc protein before and after eradication of Helicobacter pylori(H.pylori) and to elucidate the possible correlation between human telemerase catalytic subunit(hTERT) and human telomerase RNA(hTR) and c-myc protein. Methods Thirty nine H.pylori positive and 21 negative patients were enrolled. The expression of hTR,hTERT and c-myc protein before and after H.pylori eradication were compared. The expression of hTR was determined by in situ RNA hybridization whereas hTERT and c-myc protein were detected by immunohistochemical staining. Results Before treatment,the positive expression of hTR,hTERT and c-myc protein in H.pylori -positive group were significantly higher than those in H.pylori -negative group(51.3% vs. 19.0%,53.8% vs. 23.8% ,53.8% vs. 28.6%,P 0.05). Conclusions H.pylori infection may upregulate the expression of hTERT by inducing the overexpression of c-myc protein,which can cause telomerase activation and gastric carcinogenesis. The expression of telomerase-associated genes and c-myc protein may decrease or disappear after H.pylori eradication,which can lower the risk of gastric carcinogenesis.