Antimicrobial resistance(AMR)is a growing public health crisis that requires innovative solutions.Emerging multidrug resistant(MDR)Salmonella typhimurium has raised concern for its effect on pathogenic infection and m...Antimicrobial resistance(AMR)is a growing public health crisis that requires innovative solutions.Emerging multidrug resistant(MDR)Salmonella typhimurium has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases.To combat these MDR Salmonella typhimurium pathogens,highly effective and broad-spectrum antibiotics such as flufenicol(FFC)need to be evaluated for their potent antibacterial activity against Salmonella typhimurium.However,the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR.In this work,we develop a novel nano-formulation,flufenicol nano-micelles(FTPPM),which are based on d-α-tocopherol polyethylene glycol 1,000 succinate(TPGS)/poloxamer 188(P188),for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine.Herein,FTPPM were prepared via a thin film hydration method.The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems,which can further decrease production costs.The optimized FTPPM demonstrated outstanding stability and sustained release.An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy(68.17%)than did florfenicol-loaded TPGS polymer micelles(FTPM),flufenicol active pharmaceutical ingredients(FFC-API),and flufenicol commercially available medicine(FFC-CAM),and also exhibited outstanding biocompatibility.Notably,FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms.More importantly,FTPPM effectively restored intestinal flora disorders induced by drug-resistant Salmonella typhimurium in mice.In summary,FTPPM significantly improved the solubility and oral bioavailability of florfenicol,enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo.FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.展开更多
AIM:To validate the usefulness of screening endoscopy findings for predictingHelicobacter pylori (H. pylori) infection status. METHODS:H. pylori infection status was determined by histology, serology, and the urea bre...AIM:To validate the usefulness of screening endoscopy findings for predictingHelicobacter pylori (H. pylori) infection status. METHODS:H. pylori infection status was determined by histology, serology, and the urea breast test in 77 consecutive patients who underwent upper endoscopy. Based on the findings, patients were categorized as H. pylori -uninfected, -infected, or -eradicated cases. Using six photos of certain sites in the stomach per case, we determined the presence or absence of the following endoscopic findings:regular arrangement of collecting venules (RAC), linear erythema, hemorrhage, fundic gland polyp (FGP), atrophic change, rugal hyperplasia, edema, spotty erythema, exudate, xanthoma, and mottled patchy erythema (MPE). The diagnostic odds ratio (DOR) and inter-observer agreement (Kappa value) for these 11 endoscopic findings used in the determination of H. pylori infection status were calculated. RESULTS:Of the 77 patients [32 men and 45 women; mean age (SD), 39.7 (13.4) years] assessed, 28 were H. pylori uninfected, 28 were infected, and 21 were eradicated. DOR values were significantly high (< 0.05) for the following H. pylori cases:uninfected cases with RAC (11.5), linear erythema (24.5), hemorrhage (4.1), and FGP (34.5); for infected cases with atrophic change (8.67), rugal hyperplasia (15.8), edema (14.2), spotty erythema (11.5), and exudate (3.52); and for eradicated cases with atrophic change (32.4) and MPE (103.0). Kappa values were excellent for FGP (0.93), good for RAC (0.63), hemorrhage (0.79), atrophic change (0.74), and MPE (0.75), moderate for linear erythema (0.51), rugal hyperplasia (0.49), edema (0.58), spotty erythema (0.47), and exudate (0.46), and poor for xanthoma (0.19). CONCLUSION:The endoscopic findings of RAC, hemorrhage, FGP, atrophic change, and MPE will be useful for predicting H. pylori infection status.展开更多
Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.Howeve...Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.However,H.pylori can also be regarded as a commensal symbiont.Unlike other pathogenic/opportunistic bacteria,H.pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance.Fucosylated gastric mucin glycans,which are an important part of the innate and adaptive immune system,mediate the adhesion of H.pylori to the surface of the gastric epithelium,contributing to successful colonization.H.pylori may have beneficial effects on the host by regulating gastrointestinal(GI)microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease.The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H.pylori.The inverse association between H.pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota.Eradication of H.pylori can cause various adverse effects and alter the GI microbiota,leading to short-term or long-term dysbiosis.Overall,studies have shown that gastric Actinobacteria decrease after H.pylori eradication,Proteobacteria increase during short-term follow-up and then return to baseline levels,and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up.Various gastric mucosal bacteria(Actinomyces,Granulicatella,Parvimonas,Peptostreptococcus,Prevotella,Rothia,Streptococcus,Rhodococcus,and Lactobacillus)may contribute to precancerous gastric lesions and cancer itself after H.pylori eradication.H.pylori eradication can also lead to dysbiosis of the gut microbiota,with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria.The increase in gut Proteobacteria may contribute to adverse effects during and after eradication.The decrease in Actinobacteria,which are pivotal in the maintenance of gut homeostasis,can persist for>6 mo after H.pylori eradication.Furthermore,H.pylori eradication can alter the metabolism of gastric and intestinal bacteria.Given the available data,eradication cannot be an unconditional recommendation in every case of H.pylori infection,and the decision to eradicate H.pylori should be based on an assessment of the benefit-risk ratio for the individual patient.Thus,the current guidelines based on the unconditional"test-and-treat"strategy should be revised.The most cautious and careful approach should be taken in elderly patients with multiple eradication failures since repeated eradication can cause antibiotic-associated diarrhea,including severe Clostridioides difficile-associated diarrhea and colitis and antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca.Furthermore,since eradication therapy with antibiotics and proton pump inhibitors can lead to serious adverse effects and/or dysbiosis of the GI microbiota,supplementation of probiotics,prebiotics,and microbial metabolites(e.g.,butyrate+inulin)should be considered to decrease the negative effects of eradication.展开更多
Objective:The aim of our study was to perform a systematic review and meta-analysis of the efficacy of short-term protocols for Helicobacter pylori eradication and to review the safety and adverse profiles of these er...Objective:The aim of our study was to perform a systematic review and meta-analysis of the efficacy of short-term protocols for Helicobacter pylori eradication and to review the safety and adverse profiles of these eradication protocols.Methods:Literatures were located through electronic searches by PubMed,Medline,ISI Web of Knowledge,and Cochrane Library using the relevant terms.Abstracts of important meetings were searched manually in some journal supplements.Additional bibliographies were identified from the reference lists of identified studies.Three independent reviewers systemically identified randomized controlled trials(RCTs) comparing short-duration protocols vs.7-d proton pump inhibitor(PPI)-based triple protocols,as well as studies reporting eradication rates of short-duration protocols for H.pylori.Summary effect size was calculated as relative risk(RR) and 95% confidence intervals(CI) using Review Manager 4.2,and P<0.05 was defined as statistically significant in all analyses.Results:Among 90 abstracts retrieved,15 studies were analyzed,including a total of 30 treatment regimens with 1856 subjects.Mean intention-to-treat(ITT) cure rates of 63.2% and 81.3% were achieved with short-term protocols and 7-d PPI-containing protocols,respectively.Per-protocol(PP)-based overall cure rates were 66.6% and 86.1%,respectively.Short-term therapy was inferior to 7-d triple regimen(P<0.00001).After sub-analysis,however,comparing the effects of ≥3-d protocols and 7-d triple protocols,the cumulative ITT RR was 0.95(P=0.26),and PP RR was 0.95(P=0.10),without significant heterogeneity.Moreover,slightly fewer adverse-effects were found in short-term protocols.Conclusions:Although more economical,short-duration protocols are inferior to 7-d PPI-based triple protocols with regarding to eradication rate of H.pylori.Protocols of more than 3 d,however,may be equivalent to 7-d protocols.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach,damaging the gastric mucosa through various mechanisms and leading to various digestive di...BACKGROUND Helicobacter pylori(H.pylori)is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach,damaging the gastric mucosa through various mechanisms and leading to various digestive disorders.Accurate assessment and precise treatment are essential in initial intensive therapy.AIM To investigate the efficacy and safety of a vonoprazan(VPZ)-based triple regimen for first-line eradication of H.pylori in China.METHODS This multicenter noninferior randomized controlled trial(June 2022 to November 2023)involved 524 H.pyloripositive patients across 19 centers in Shandong,China.Participants were randomized to 14-day esomeprazole/bismuth/amoxicillin/clarithromycin(EBAC),14-day VPZ/amoxicillin/clarithromycin(VACa),or 10-day VPZ/amoxicillin/clarithromycin(VACb)-all administered twice daily.Primary outcomes(eradication rates)were assessed via intention-to-treat(ITT)and per-protocol(PP)analyses.Secondary endpoints included adverse events and adherence.Noninferiority testing andχ^(2)tests were used for statistical comparisons.RESULTS A total of 524 patients participated in this study.In ITT analysis,the eradication rates of the EBAC,VACa,and VACb groups were 72.6%(127/175),88.0%(154/175),and 83.3%(145/174),respectively(P=0.001).The difference in the eradication rate between the EBAC and VPCa groups was 15.4%[95%confidence interval(CI):7.3-23.6,P<0.001],and that between the EBAC and VACb groups was 10.8%(95%CI:2.1-19.4,P=0.018).In PP analysis,the eradication rates of the EBAC,VACa,and VACb groups were 81.4%(127/156),93.9%(154/164),and 90.6%(145/160),respectively(P=0.001).There was no significant difference in the incidence of adverse reactions among the three groups,which were 36.6%,33.8%and 29.6%,respectively(P=0.50).CONCLUSION VPZ-based triple therapies demonstrate noninferiority to 14-day bismuth-containing regimens,with the 10-day regimen showing comparable efficacy and similar adverse event rates.展开更多
Multidrug-resistant Klebsiella pneumoniae(MDR-KP)is characterized by high mortality and risk of nosocomial transmission,and biofilm constitutes the primary challenge in the treatment of its implant-associated and refr...Multidrug-resistant Klebsiella pneumoniae(MDR-KP)is characterized by high mortality and risk of nosocomial transmission,and biofilm constitutes the primary challenge in the treatment of its implant-associated and refractory pulmonary infections.Notably,the hypoxic microenvironment and the physical barrier of biofilm leading to the increased tolerance of the bacteria to antibiotics.Herein,a hypoxia-responsive hybrid nanoparticle(CHLip@FLD/COL)loaded separately with anti-biofilm candidate fingolimod(FLD)and antibiotic colistin(COL)is achieved targeting antibacterial efficacy against MDR-KP in vitro and in vivo.CHLip@FLD/COL is composed of hybridizing hypoxia-responsive lipids(HLipid)and lipid A targeting materials DSPE-mPEG-COL.HLipid is synthesized by hexadecanedioic acid esterified with nitroimidazole,while DSPE-mPEG is coupling with vector COL via amide reaction.The relative level of extracellular polymeric substances and the NIR-IIb sO2 images of the infection site are used as indicators to establish mature biofilm models.CHLip@FLD/COL readily releases FLD and COL in hypoxic conditions,and its MIC against MDR-KP is only one-sixteenth of that when COL is used alone in vitro.The nanoparticle exhibits bacterial targeting ability and antibacterial effect in the pulmonary infection and biofilm infection mice models.Bacterial loads eliminated by 4 Log10 CFU and 2 Log10 CFU,respectively.The strategy provides a valuable reference for the treatment of refractory infections caused by MDR-KP.展开更多
Pinewood nematode is a devastating forest pathogen and is considered a quarantine organism worldwide.First identified in China 40 years ago,the disease has been spreading since.In response,Chinese authorities have int...Pinewood nematode is a devastating forest pathogen and is considered a quarantine organism worldwide.First identified in China 40 years ago,the disease has been spreading since.In response,Chinese authorities have introduced new requirements for preventing and controlling the disease.This paper proposes a new and highly effective preventive drug,a trunk injection agent usable at normal temperatures.Its use is suggested for localized epidemic areas to reduce diseased and dead trees and as a preventive measure in adjacent non-epidemic areas to prevent the infection from spreading,particularly protecting important and ancient pine trees.展开更多
Antibiotic resistance in Helicobacter pylori is reshaping eradication strategies worldwide.Analysis of 1408 treatment-naive isolates collected across Taiwan China between 2019 and 2024 reveals a striking shift in resi...Antibiotic resistance in Helicobacter pylori is reshaping eradication strategies worldwide.Analysis of 1408 treatment-naive isolates collected across Taiwan China between 2019 and 2024 reveals a striking shift in resistance patterns.Tetracycline resistance,once negligible,rose to 3.5%,threatening the durability of bismuthbased quadruple therapy.Conversely,metronidazole resistance declined markedly,while clarithromycin and levofloxacin resistance remained stable at moderate levels,with levofloxacin showing significant regional variation.Emerging dual resistance involving tetracycline underscores the fragility of empiric regimens and highlights the need for culture-guided or molecular approaches.These findings reflect the dual influence of stewardship successes and environmental antibiotic pressures,while also signaling the limits of empiricism in eradication therapy.Potassium-competitive acid blockers provide a promising pharmacologic pivot,capable of enhancing antibiotic efficacy and sustaining eradication outcomes.Taiwan’s China resistance profile thus offers both cautionary lessons and actionable insights for future regional and global treatment strategies.展开更多
BACKGROUND Effective acid suppression significantly enhances the eradication rate of Helicobacter pylori(H.pylori).AIM To assess the efficacy and safety of high-dose dual therapy(HDDT)utilizing various highly potent a...BACKGROUND Effective acid suppression significantly enhances the eradication rate of Helicobacter pylori(H.pylori).AIM To assess the efficacy and safety of high-dose dual therapy(HDDT)utilizing various highly potent antisecretory medications,thereby providing additional clinical guidance for H.pylori eradication.METHODS The study population comprised untreated H.pylori patients from three medical centers in central China.From February 10,2024 to March 31,2024,439 subjects were randomly allocated to either the esomeprazole-amoxicillin(EA)or esomeprazole-amoxicillin-clarithromycin-bismuth(B-quadruple)group.Subsequently,from April 1,2024 to May 10,2024,367 subjects were randomly assigned to either the vonoprazan-amoxicillin(VA)or vonoprazan-amoxicillin-clarithromycin(VAC)group.The study recorded treatment efficacy,adverse events,compliance,symptom alleviation,and associated costs.RESULTS EA-dual demonstrated non-inferiority to B-quadruple regimen in modified intention-to-treat(mITT)and perprotocol(PP)analyses(P<0.025).However,the eradication rate of EA was lower than that of the B-quadruple group[70.59%vs 83.49%,92.86%vs 98.38%,93.94%vs 98.38%,intention-to-treat(ITT),mITT,PP respectively,P<0.05].In ITT,mITT,and PP analyses,VA-dual was non-inferior to VAC treatment(84.15%vs 83.15%,96.25%vs 92.73%,96.75%vs 93.75%,P<0.025).No significant differences were observed in adverse events,compliance,and symptom relief between groups.VA exhibited the lowest cost.Antibiotic use within 2 years,poor compliance,and suburban residence were associated with reduced eradication efficacy(P<0.05).CONCLUSION The HDDT based on vonoprazan demonstrated non-inferiority to the VAC triple regimen,suggesting its potential as a recommended first-line treatment for H.pylori eradication.While B-quadruple therapy showed better eradication rate than EA therapy,the latter proved non-inferior in mITT and PP analyses.Notably,antibiotic use within the preceding two years,adherence to treatment protocols,and patient residence emerged as critical factors influencing eradication success.展开更多
Nujiang’s success in eliminating poverty sets a good example for the developing countries to follow.Poverty continues to be a major problem in many parts of the world.China’s poverty eradication experience demonstra...Nujiang’s success in eliminating poverty sets a good example for the developing countries to follow.Poverty continues to be a major problem in many parts of the world.China’s poverty eradication experience demonstrates that developing countries can end poverty through perseverance and sustained efforts,noted Irina Bokova,former director general of UNESCO.展开更多
OBJECTIVE:To evaluate the efficacy and safety of 14-day Qingwei Zhitong pellets(清胃止痛微丸,QZ)-containing quadruple therapy(QZQT)compared to bismuth-containing quadruple therapy(BQT)in treatment-naive patients with ...OBJECTIVE:To evaluate the efficacy and safety of 14-day Qingwei Zhitong pellets(清胃止痛微丸,QZ)-containing quadruple therapy(QZQT)compared to bismuth-containing quadruple therapy(BQT)in treatment-naive patients with Helicobacter pylori(H.pylori)infection.METHODS:This single-center,randomized controlled clinical trial enrolled 333 patients,who were divided into either the QZQT group(QZ pellets,3.2 g,three times daily;rabeprazole,10 mg,twice daily;amoxicillin 1000 mg,twice daily;clarithromycin,500 mg,twice daily)or the BQT group(bismuth potassium citrate,1000 mg,three times daily;rabeprazole,10 mg,twice daily;amoxicillin,1000 mg,twice daily;clarithromycin,500 mg,twice daily)for 14 d.The 13C-urea breath test assessed eradication success at least four weeks after treatment.The primary outcome focused on the eradication rate,with secondary outcomes including safety and patient compliance.RESULTS:From August 2022 to June 2023,342 subjects were screened,and 333 were randomized.The QZQT and BQT groups showed eradication rates of 68.9%and 67.8%(P=0.838)by intention-to-treat(ITT)analysis,respectively,and 71.1%and 68.3%(P=0.612)by perprotocol(PP)analysis,respectively.QZQT was non-inferior to BQT in both ITT and PP analyses.QZQT was associated with fewer side effects(57.8%of patients)than BQT(90.4%)(P<0.001).CONCLUSION:The 14 d QZQT treatment demonstrates equal efficacy in eradicating H.pylori infection and improved patient compliance and safety compared to BQT.These results provide evidence supporting 14-day QZQT as an acceptable treatment for H.pylori infection.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is a Gram-negative bacillus classified as a Group I carcinogen by the World Health Organization.However,the efficacy of eradi-cation therapies has declined in recent years,prima...BACKGROUND Helicobacter pylori(H.pylori)is a Gram-negative bacillus classified as a Group I carcinogen by the World Health Organization.However,the efficacy of eradi-cation therapies has declined in recent years,primarily due to the increasing prevalence of antibiotic resistance.The Maastricht VI/Florence Consensus Report highlights the importance of tailoring treatment strategies to local epidemiological data and individual antimicrobial susceptibility patterns.AIM To investigate the efficacy of precision-guided first-line therapy for H.pylori in-fection using genotypic antibiotic susceptibility testing(G-AST).METHODS This single-center randomized controlled trial enrolled 194 H.pylori-positive patients at a tertiary hospital in Qingdao,China(October 2022-August 2024).Participants were randomized to receive either a 14-day bismuth quadruple therapy(BQT:Amoxicillin,clarithromycin,esomeprazole,and bismuth)or a 14-day G-AST-guided regimen with tailored antibiotics(clarithromycin,levofloxacin,or tetracycline).Treatment efficacy and adverse events were compared between groups using intention-to-treat(ITT)and per-protocol(PP)analyses.Primary and secondary outcomes were analyzed with χ^(2) tests.RESULTS Of 194 patients enrolled,180(92.8%)completed the study as planned.In the ITT analysis,the eradication rate was higher in the G-AST group than in the BQT group[92.8%(95%CI:85.8-96.5)vs 79.4%(95%CI:70.3-86.2),P=0.007],with a risk difference of 13.4%(95%CI:3.7-23.2).In the PP analysis,eradication rates were 97.8%(95%CI:92.4-99.4)in the G-AST group and 84.1%(95%CI:75.1-90.3)in the BQT group(P=0.001),with a risk difference of 13.7%(95%CI:5.5-23.0).Adverse event incidence did not differ significantly between groups(30.9%vs 28.9%,P=0.754).CONCLUSION G-AST-guided therapy yielded higher eradication rates than empirical BQT in first-line H.pylori treatment without increasing adverse events,supporting the clinical utility of individualized,resistance-based therapy.展开更多
Objective: To compare the eradication rates of Helicobacter pylori (HP) and the incidence of adverse reactions among three treatment methods. Methods: A total of 139 patients with Helicobacter pylori infection diagnos...Objective: To compare the eradication rates of Helicobacter pylori (HP) and the incidence of adverse reactions among three treatment methods. Methods: A total of 139 patients with Helicobacter pylori infection diagnosed at the outpatient clinic or during hospitalization in the Department of Gastroenterology of West Electric Group Hospital from January 2022 to April 2023 were enrolled. Patients were divided into three groups: dual therapy group (46 cases), triple therapy group (62 cases), and quadruple therapy group (31 cases). The dual therapy group received omeprazole and amoxicillin;the triple therapy group received omeprazole, amoxicillin, and probiotics;the quadruple therapy group received omeprazole, colloidal bismuth pectin capsules, amoxicillin, and furazolidone. All treatments lasted for two weeks. The eradication rates and incidence of adverse reactions were compared among the three groups. Results: The eradication rates for the dual, triple, and quadruple therapy groups were 84.8%, 85.5%, and 85%, respectively (P > 0.05). The primary adverse reactions included gastrointestinal symptoms such as bloating, abdominal pain, loss of appetite, and abdominal discomfort, with incidence rates of 1, 2, and 6 cases in the dual, triple, and quadruple therapy groups, respectively (P = 0.574). However, a significant difference was found between the dual and quadruple therapy groups (P = 0.03) and between the triple and quadruple therapy groups (P = 0.026). Neurological side effects, such as dizziness and headache, were rare, with incidences of 0, 1, and 1 cases in the dual, triple, and quadruple therapy groups, respectively (P = 0.611). Conclusion: The efficacy of dual, triple, and quadruple therapy for eradicating Helicobacter pylori showed no significant difference. However, the dual and triple therapy groups had lower adverse reaction rates, making them suitable alternatives to traditional quadruple therapy for reducing patient discomfort. The probiotic group also contributed to the restoration of normal gastrointestinal microbiota.展开更多
There has been a rise in the incidence of esophageal adenocarcinoma(EAC)over the past five decades in the United States,and it remains a highly lethal ma-lignancy due to frequent late-stage diagnosis.Barrett’s esopha...There has been a rise in the incidence of esophageal adenocarcinoma(EAC)over the past five decades in the United States,and it remains a highly lethal ma-lignancy due to frequent late-stage diagnosis.Barrett’s esophagus(BE),a well-established precursor to EAC,presents a critical window for early intervention through screening,surveillance,and endoscopic eradication therapy.Despite gastrointestinal society guideline recommendations for screening,the majority of patients with BE or early EAC remain undiagnosed until symptoms of late-stage cancer emerge.This review outlines current challenges and evolving strategies in the United States in BE detection and management,including risk stratification models,non-endoscopic screening tools,high-quality endoscopic techniques,tissue-based biomarkers,and artificial intelligence-enhanced imaging.We high-light best practices for surveillance,emphasizing the importance of thorough inspection of high-risk anatomic zones and the integration of advanced imaging.Endoscopic eradication therapy,including endoscopic mucosal resection and ablation,achieves high rates of complete eradication when performed with meti-culous technique,especially with comprehensive treatment of the gastroeso-phageal junction and gastric cardia.Long-term surveillance remains essential due to the risk of recurrence.As new technologies continue to emerge,integrating precision tools into routine practice will be key to improving outcomes and reducing EAC mortality.展开更多
稻瘟病菌(Magnaporthe oryzae)作为主要的农业病原微生物,其引起的稻瘟病严重威胁着水稻等谷类作物的生产安全。内质网相关蛋白质降解途径(Endoplasmic reticulum-associated protein degradation,ERAD)是生物体应答内质网压力的主要方...稻瘟病菌(Magnaporthe oryzae)作为主要的农业病原微生物,其引起的稻瘟病严重威胁着水稻等谷类作物的生产安全。内质网相关蛋白质降解途径(Endoplasmic reticulum-associated protein degradation,ERAD)是生物体应答内质网压力的主要方式之一,其在机体生长发育过程中具有重要作用。而HRD(HMG-CoA reductase degradation)复合物作为ERAD的关键组分,主要由Hrd1、Hrd3、以及凝集素Yos9等蛋白组成,负责内质网中错误折叠蛋白的识别、转运以及泛素化过程,最终由蛋白酶体降解,从而有效缓解内质网压力,保证细胞的正常生理活动。有研究表明,Hrd3属于单次跨膜蛋白,在内质网腔中与Hrd1、Yos9相结合,负责底物的识别并起着稳定Hrd1的作用。目前Hrd3在稻瘟病菌中的生物学功能尚不清楚。本研究通过基因敲除及互补试验获得了稻瘟病菌的ΔMohrd3突变体和ΔMohrd3-C回补菌株,并以野生型为对照,对突变体的生物学表型进行了分析。结果显示,ΔMohrd3突变体的生长速率、产孢量明显下降;对大麦和水稻的致病力显著减弱。进一步胁迫试验表明,MoHRD3的缺失导致稻瘟病菌对外界盐胁迫、渗透压胁迫的耐受性增强,对内质网胁迫耐受性减弱,而对细胞壁胁迫无明显变化。同时,MoHRD3基因的缺失激活了未折叠蛋白响应途径(Unfolded protein response,UPR)。上述结果表明,MoHRD3参与调控稻瘟病菌的营养生长、无性繁殖、致病及对不同环境胁迫的响应过程。展开更多
基金supported by the grants from the National Key Research and Development Program of China(Grant No.:2024YFE0106300)the Key Projects of Natural Science Foundation of Anhui Provincial Department of Education,China(Grant No.:2023AH051017)+2 种基金the Outstanding Youth Scientific Research Foundation of the Anhui Education Department,China(Grant No.:2024AH030019)the National Natural Science Foundation of China(Grant No.:32302923)Natural Science Foundation of Anhui Province,China(Grant No.:2208085MC79).
文摘Antimicrobial resistance(AMR)is a growing public health crisis that requires innovative solutions.Emerging multidrug resistant(MDR)Salmonella typhimurium has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases.To combat these MDR Salmonella typhimurium pathogens,highly effective and broad-spectrum antibiotics such as flufenicol(FFC)need to be evaluated for their potent antibacterial activity against Salmonella typhimurium.However,the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR.In this work,we develop a novel nano-formulation,flufenicol nano-micelles(FTPPM),which are based on d-α-tocopherol polyethylene glycol 1,000 succinate(TPGS)/poloxamer 188(P188),for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine.Herein,FTPPM were prepared via a thin film hydration method.The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems,which can further decrease production costs.The optimized FTPPM demonstrated outstanding stability and sustained release.An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy(68.17%)than did florfenicol-loaded TPGS polymer micelles(FTPM),flufenicol active pharmaceutical ingredients(FFC-API),and flufenicol commercially available medicine(FFC-CAM),and also exhibited outstanding biocompatibility.Notably,FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms.More importantly,FTPPM effectively restored intestinal flora disorders induced by drug-resistant Salmonella typhimurium in mice.In summary,FTPPM significantly improved the solubility and oral bioavailability of florfenicol,enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo.FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.
基金Supported by A Grant from the National Center for Global Health and Medicine
文摘AIM:To validate the usefulness of screening endoscopy findings for predictingHelicobacter pylori (H. pylori) infection status. METHODS:H. pylori infection status was determined by histology, serology, and the urea breast test in 77 consecutive patients who underwent upper endoscopy. Based on the findings, patients were categorized as H. pylori -uninfected, -infected, or -eradicated cases. Using six photos of certain sites in the stomach per case, we determined the presence or absence of the following endoscopic findings:regular arrangement of collecting venules (RAC), linear erythema, hemorrhage, fundic gland polyp (FGP), atrophic change, rugal hyperplasia, edema, spotty erythema, exudate, xanthoma, and mottled patchy erythema (MPE). The diagnostic odds ratio (DOR) and inter-observer agreement (Kappa value) for these 11 endoscopic findings used in the determination of H. pylori infection status were calculated. RESULTS:Of the 77 patients [32 men and 45 women; mean age (SD), 39.7 (13.4) years] assessed, 28 were H. pylori uninfected, 28 were infected, and 21 were eradicated. DOR values were significantly high (< 0.05) for the following H. pylori cases:uninfected cases with RAC (11.5), linear erythema (24.5), hemorrhage (4.1), and FGP (34.5); for infected cases with atrophic change (8.67), rugal hyperplasia (15.8), edema (14.2), spotty erythema (11.5), and exudate (3.52); and for eradicated cases with atrophic change (32.4) and MPE (103.0). Kappa values were excellent for FGP (0.93), good for RAC (0.63), hemorrhage (0.79), atrophic change (0.74), and MPE (0.75), moderate for linear erythema (0.51), rugal hyperplasia (0.49), edema (0.58), spotty erythema (0.47), and exudate (0.46), and poor for xanthoma (0.19). CONCLUSION:The endoscopic findings of RAC, hemorrhage, FGP, atrophic change, and MPE will be useful for predicting H. pylori infection status.
基金Supported by the Russian Science Foundation,No.20-65-47026。
文摘Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.However,H.pylori can also be regarded as a commensal symbiont.Unlike other pathogenic/opportunistic bacteria,H.pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance.Fucosylated gastric mucin glycans,which are an important part of the innate and adaptive immune system,mediate the adhesion of H.pylori to the surface of the gastric epithelium,contributing to successful colonization.H.pylori may have beneficial effects on the host by regulating gastrointestinal(GI)microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease.The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H.pylori.The inverse association between H.pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota.Eradication of H.pylori can cause various adverse effects and alter the GI microbiota,leading to short-term or long-term dysbiosis.Overall,studies have shown that gastric Actinobacteria decrease after H.pylori eradication,Proteobacteria increase during short-term follow-up and then return to baseline levels,and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up.Various gastric mucosal bacteria(Actinomyces,Granulicatella,Parvimonas,Peptostreptococcus,Prevotella,Rothia,Streptococcus,Rhodococcus,and Lactobacillus)may contribute to precancerous gastric lesions and cancer itself after H.pylori eradication.H.pylori eradication can also lead to dysbiosis of the gut microbiota,with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria.The increase in gut Proteobacteria may contribute to adverse effects during and after eradication.The decrease in Actinobacteria,which are pivotal in the maintenance of gut homeostasis,can persist for>6 mo after H.pylori eradication.Furthermore,H.pylori eradication can alter the metabolism of gastric and intestinal bacteria.Given the available data,eradication cannot be an unconditional recommendation in every case of H.pylori infection,and the decision to eradicate H.pylori should be based on an assessment of the benefit-risk ratio for the individual patient.Thus,the current guidelines based on the unconditional"test-and-treat"strategy should be revised.The most cautious and careful approach should be taken in elderly patients with multiple eradication failures since repeated eradication can cause antibiotic-associated diarrhea,including severe Clostridioides difficile-associated diarrhea and colitis and antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca.Furthermore,since eradication therapy with antibiotics and proton pump inhibitors can lead to serious adverse effects and/or dysbiosis of the GI microbiota,supplementation of probiotics,prebiotics,and microbial metabolites(e.g.,butyrate+inulin)should be considered to decrease the negative effects of eradication.
基金(No. 2008C33053) supported by the Science and Technology Program of Zhejiang Province,China
文摘Objective:The aim of our study was to perform a systematic review and meta-analysis of the efficacy of short-term protocols for Helicobacter pylori eradication and to review the safety and adverse profiles of these eradication protocols.Methods:Literatures were located through electronic searches by PubMed,Medline,ISI Web of Knowledge,and Cochrane Library using the relevant terms.Abstracts of important meetings were searched manually in some journal supplements.Additional bibliographies were identified from the reference lists of identified studies.Three independent reviewers systemically identified randomized controlled trials(RCTs) comparing short-duration protocols vs.7-d proton pump inhibitor(PPI)-based triple protocols,as well as studies reporting eradication rates of short-duration protocols for H.pylori.Summary effect size was calculated as relative risk(RR) and 95% confidence intervals(CI) using Review Manager 4.2,and P<0.05 was defined as statistically significant in all analyses.Results:Among 90 abstracts retrieved,15 studies were analyzed,including a total of 30 treatment regimens with 1856 subjects.Mean intention-to-treat(ITT) cure rates of 63.2% and 81.3% were achieved with short-term protocols and 7-d PPI-containing protocols,respectively.Per-protocol(PP)-based overall cure rates were 66.6% and 86.1%,respectively.Short-term therapy was inferior to 7-d triple regimen(P<0.00001).After sub-analysis,however,comparing the effects of ≥3-d protocols and 7-d triple protocols,the cumulative ITT RR was 0.95(P=0.26),and PP RR was 0.95(P=0.10),without significant heterogeneity.Moreover,slightly fewer adverse-effects were found in short-term protocols.Conclusions:Although more economical,short-duration protocols are inferior to 7-d PPI-based triple protocols with regarding to eradication rate of H.pylori.Protocols of more than 3 d,however,may be equivalent to 7-d protocols.
基金Supported by Qilu Health Outstanding Young Talent Cultivation Project,No.QDFY-3839。
文摘BACKGROUND Helicobacter pylori(H.pylori)is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach,damaging the gastric mucosa through various mechanisms and leading to various digestive disorders.Accurate assessment and precise treatment are essential in initial intensive therapy.AIM To investigate the efficacy and safety of a vonoprazan(VPZ)-based triple regimen for first-line eradication of H.pylori in China.METHODS This multicenter noninferior randomized controlled trial(June 2022 to November 2023)involved 524 H.pyloripositive patients across 19 centers in Shandong,China.Participants were randomized to 14-day esomeprazole/bismuth/amoxicillin/clarithromycin(EBAC),14-day VPZ/amoxicillin/clarithromycin(VACa),or 10-day VPZ/amoxicillin/clarithromycin(VACb)-all administered twice daily.Primary outcomes(eradication rates)were assessed via intention-to-treat(ITT)and per-protocol(PP)analyses.Secondary endpoints included adverse events and adherence.Noninferiority testing andχ^(2)tests were used for statistical comparisons.RESULTS A total of 524 patients participated in this study.In ITT analysis,the eradication rates of the EBAC,VACa,and VACb groups were 72.6%(127/175),88.0%(154/175),and 83.3%(145/174),respectively(P=0.001).The difference in the eradication rate between the EBAC and VPCa groups was 15.4%[95%confidence interval(CI):7.3-23.6,P<0.001],and that between the EBAC and VACb groups was 10.8%(95%CI:2.1-19.4,P=0.018).In PP analysis,the eradication rates of the EBAC,VACa,and VACb groups were 81.4%(127/156),93.9%(154/164),and 90.6%(145/160),respectively(P=0.001).There was no significant difference in the incidence of adverse reactions among the three groups,which were 36.6%,33.8%and 29.6%,respectively(P=0.50).CONCLUSION VPZ-based triple therapies demonstrate noninferiority to 14-day bismuth-containing regimens,with the 10-day regimen showing comparable efficacy and similar adverse event rates.
基金granted by National Key Research and Development Program of China(2021YFD1800900)Science and Technology Innovation Key R&D Program of Chongqing(CSTB2024TIAD-STX0038)+3 种基金National Natural Science Foundation of China(82574334,32501226)Chongqing Science and Technology Commission(CSTB2023NSCQ-JQX0002)Special Fund for Youth Team of Southwest University(SWU-XJLJ202306)Chongqing Natural Science Foundation(CSTB2024NSCQ-MSX0547).
文摘Multidrug-resistant Klebsiella pneumoniae(MDR-KP)is characterized by high mortality and risk of nosocomial transmission,and biofilm constitutes the primary challenge in the treatment of its implant-associated and refractory pulmonary infections.Notably,the hypoxic microenvironment and the physical barrier of biofilm leading to the increased tolerance of the bacteria to antibiotics.Herein,a hypoxia-responsive hybrid nanoparticle(CHLip@FLD/COL)loaded separately with anti-biofilm candidate fingolimod(FLD)and antibiotic colistin(COL)is achieved targeting antibacterial efficacy against MDR-KP in vitro and in vivo.CHLip@FLD/COL is composed of hybridizing hypoxia-responsive lipids(HLipid)and lipid A targeting materials DSPE-mPEG-COL.HLipid is synthesized by hexadecanedioic acid esterified with nitroimidazole,while DSPE-mPEG is coupling with vector COL via amide reaction.The relative level of extracellular polymeric substances and the NIR-IIb sO2 images of the infection site are used as indicators to establish mature biofilm models.CHLip@FLD/COL readily releases FLD and COL in hypoxic conditions,and its MIC against MDR-KP is only one-sixteenth of that when COL is used alone in vitro.The nanoparticle exhibits bacterial targeting ability and antibacterial effect in the pulmonary infection and biofilm infection mice models.Bacterial loads eliminated by 4 Log10 CFU and 2 Log10 CFU,respectively.The strategy provides a valuable reference for the treatment of refractory infections caused by MDR-KP.
基金supported by the National Key Research and Development Program of China(Grant Number:2021YFD1400903).
文摘Pinewood nematode is a devastating forest pathogen and is considered a quarantine organism worldwide.First identified in China 40 years ago,the disease has been spreading since.In response,Chinese authorities have introduced new requirements for preventing and controlling the disease.This paper proposes a new and highly effective preventive drug,a trunk injection agent usable at normal temperatures.Its use is suggested for localized epidemic areas to reduce diseased and dead trees and as a preventive measure in adjacent non-epidemic areas to prevent the infection from spreading,particularly protecting important and ancient pine trees.
文摘Antibiotic resistance in Helicobacter pylori is reshaping eradication strategies worldwide.Analysis of 1408 treatment-naive isolates collected across Taiwan China between 2019 and 2024 reveals a striking shift in resistance patterns.Tetracycline resistance,once negligible,rose to 3.5%,threatening the durability of bismuthbased quadruple therapy.Conversely,metronidazole resistance declined markedly,while clarithromycin and levofloxacin resistance remained stable at moderate levels,with levofloxacin showing significant regional variation.Emerging dual resistance involving tetracycline underscores the fragility of empiric regimens and highlights the need for culture-guided or molecular approaches.These findings reflect the dual influence of stewardship successes and environmental antibiotic pressures,while also signaling the limits of empiricism in eradication therapy.Potassium-competitive acid blockers provide a promising pharmacologic pivot,capable of enhancing antibiotic efficacy and sustaining eradication outcomes.Taiwan’s China resistance profile thus offers both cautionary lessons and actionable insights for future regional and global treatment strategies.
基金Supported by the National Natural Science Foundation of China,No.82270594the National Natural Science Foundation for Youths of China,No.82103151+1 种基金the Outstanding Youth Foundation of Hunan Province,No.2022JJ20092the Wisdom Accumulation and Talent Cultivation Project of Third Xiangya Hospital of Central South University,No.YX202103.
文摘BACKGROUND Effective acid suppression significantly enhances the eradication rate of Helicobacter pylori(H.pylori).AIM To assess the efficacy and safety of high-dose dual therapy(HDDT)utilizing various highly potent antisecretory medications,thereby providing additional clinical guidance for H.pylori eradication.METHODS The study population comprised untreated H.pylori patients from three medical centers in central China.From February 10,2024 to March 31,2024,439 subjects were randomly allocated to either the esomeprazole-amoxicillin(EA)or esomeprazole-amoxicillin-clarithromycin-bismuth(B-quadruple)group.Subsequently,from April 1,2024 to May 10,2024,367 subjects were randomly assigned to either the vonoprazan-amoxicillin(VA)or vonoprazan-amoxicillin-clarithromycin(VAC)group.The study recorded treatment efficacy,adverse events,compliance,symptom alleviation,and associated costs.RESULTS EA-dual demonstrated non-inferiority to B-quadruple regimen in modified intention-to-treat(mITT)and perprotocol(PP)analyses(P<0.025).However,the eradication rate of EA was lower than that of the B-quadruple group[70.59%vs 83.49%,92.86%vs 98.38%,93.94%vs 98.38%,intention-to-treat(ITT),mITT,PP respectively,P<0.05].In ITT,mITT,and PP analyses,VA-dual was non-inferior to VAC treatment(84.15%vs 83.15%,96.25%vs 92.73%,96.75%vs 93.75%,P<0.025).No significant differences were observed in adverse events,compliance,and symptom relief between groups.VA exhibited the lowest cost.Antibiotic use within 2 years,poor compliance,and suburban residence were associated with reduced eradication efficacy(P<0.05).CONCLUSION The HDDT based on vonoprazan demonstrated non-inferiority to the VAC triple regimen,suggesting its potential as a recommended first-line treatment for H.pylori eradication.While B-quadruple therapy showed better eradication rate than EA therapy,the latter proved non-inferior in mITT and PP analyses.Notably,antibiotic use within the preceding two years,adherence to treatment protocols,and patient residence emerged as critical factors influencing eradication success.
文摘Nujiang’s success in eliminating poverty sets a good example for the developing countries to follow.Poverty continues to be a major problem in many parts of the world.China’s poverty eradication experience demonstrates that developing countries can end poverty through perseverance and sustained efforts,noted Irina Bokova,former director general of UNESCO.
基金the China Zhongguancun Precision Medicine Science and Technology Foundation:Study on the Evaluation of Eradication Rate and Safety of Helicobacter Pylori in a Quadruple Therapy using Qingwei Zhitong Pellets as a Substitute for Bismuth Agent(320.6799.2022.09.24)。
文摘OBJECTIVE:To evaluate the efficacy and safety of 14-day Qingwei Zhitong pellets(清胃止痛微丸,QZ)-containing quadruple therapy(QZQT)compared to bismuth-containing quadruple therapy(BQT)in treatment-naive patients with Helicobacter pylori(H.pylori)infection.METHODS:This single-center,randomized controlled clinical trial enrolled 333 patients,who were divided into either the QZQT group(QZ pellets,3.2 g,three times daily;rabeprazole,10 mg,twice daily;amoxicillin 1000 mg,twice daily;clarithromycin,500 mg,twice daily)or the BQT group(bismuth potassium citrate,1000 mg,three times daily;rabeprazole,10 mg,twice daily;amoxicillin,1000 mg,twice daily;clarithromycin,500 mg,twice daily)for 14 d.The 13C-urea breath test assessed eradication success at least four weeks after treatment.The primary outcome focused on the eradication rate,with secondary outcomes including safety and patient compliance.RESULTS:From August 2022 to June 2023,342 subjects were screened,and 333 were randomized.The QZQT and BQT groups showed eradication rates of 68.9%and 67.8%(P=0.838)by intention-to-treat(ITT)analysis,respectively,and 71.1%and 68.3%(P=0.612)by perprotocol(PP)analysis,respectively.QZQT was non-inferior to BQT in both ITT and PP analyses.QZQT was associated with fewer side effects(57.8%of patients)than BQT(90.4%)(P<0.001).CONCLUSION:The 14 d QZQT treatment demonstrates equal efficacy in eradicating H.pylori infection and improved patient compliance and safety compared to BQT.These results provide evidence supporting 14-day QZQT as an acceptable treatment for H.pylori infection.
基金Supported by Qilu Health Outstanding Young Talent Cultivation Project,No.QDFY-3839.
文摘BACKGROUND Helicobacter pylori(H.pylori)is a Gram-negative bacillus classified as a Group I carcinogen by the World Health Organization.However,the efficacy of eradi-cation therapies has declined in recent years,primarily due to the increasing prevalence of antibiotic resistance.The Maastricht VI/Florence Consensus Report highlights the importance of tailoring treatment strategies to local epidemiological data and individual antimicrobial susceptibility patterns.AIM To investigate the efficacy of precision-guided first-line therapy for H.pylori in-fection using genotypic antibiotic susceptibility testing(G-AST).METHODS This single-center randomized controlled trial enrolled 194 H.pylori-positive patients at a tertiary hospital in Qingdao,China(October 2022-August 2024).Participants were randomized to receive either a 14-day bismuth quadruple therapy(BQT:Amoxicillin,clarithromycin,esomeprazole,and bismuth)or a 14-day G-AST-guided regimen with tailored antibiotics(clarithromycin,levofloxacin,or tetracycline).Treatment efficacy and adverse events were compared between groups using intention-to-treat(ITT)and per-protocol(PP)analyses.Primary and secondary outcomes were analyzed with χ^(2) tests.RESULTS Of 194 patients enrolled,180(92.8%)completed the study as planned.In the ITT analysis,the eradication rate was higher in the G-AST group than in the BQT group[92.8%(95%CI:85.8-96.5)vs 79.4%(95%CI:70.3-86.2),P=0.007],with a risk difference of 13.4%(95%CI:3.7-23.2).In the PP analysis,eradication rates were 97.8%(95%CI:92.4-99.4)in the G-AST group and 84.1%(95%CI:75.1-90.3)in the BQT group(P=0.001),with a risk difference of 13.7%(95%CI:5.5-23.0).Adverse event incidence did not differ significantly between groups(30.9%vs 28.9%,P=0.754).CONCLUSION G-AST-guided therapy yielded higher eradication rates than empirical BQT in first-line H.pylori treatment without increasing adverse events,supporting the clinical utility of individualized,resistance-based therapy.
文摘Objective: To compare the eradication rates of Helicobacter pylori (HP) and the incidence of adverse reactions among three treatment methods. Methods: A total of 139 patients with Helicobacter pylori infection diagnosed at the outpatient clinic or during hospitalization in the Department of Gastroenterology of West Electric Group Hospital from January 2022 to April 2023 were enrolled. Patients were divided into three groups: dual therapy group (46 cases), triple therapy group (62 cases), and quadruple therapy group (31 cases). The dual therapy group received omeprazole and amoxicillin;the triple therapy group received omeprazole, amoxicillin, and probiotics;the quadruple therapy group received omeprazole, colloidal bismuth pectin capsules, amoxicillin, and furazolidone. All treatments lasted for two weeks. The eradication rates and incidence of adverse reactions were compared among the three groups. Results: The eradication rates for the dual, triple, and quadruple therapy groups were 84.8%, 85.5%, and 85%, respectively (P > 0.05). The primary adverse reactions included gastrointestinal symptoms such as bloating, abdominal pain, loss of appetite, and abdominal discomfort, with incidence rates of 1, 2, and 6 cases in the dual, triple, and quadruple therapy groups, respectively (P = 0.574). However, a significant difference was found between the dual and quadruple therapy groups (P = 0.03) and between the triple and quadruple therapy groups (P = 0.026). Neurological side effects, such as dizziness and headache, were rare, with incidences of 0, 1, and 1 cases in the dual, triple, and quadruple therapy groups, respectively (P = 0.611). Conclusion: The efficacy of dual, triple, and quadruple therapy for eradicating Helicobacter pylori showed no significant difference. However, the dual and triple therapy groups had lower adverse reaction rates, making them suitable alternatives to traditional quadruple therapy for reducing patient discomfort. The probiotic group also contributed to the restoration of normal gastrointestinal microbiota.
文摘There has been a rise in the incidence of esophageal adenocarcinoma(EAC)over the past five decades in the United States,and it remains a highly lethal ma-lignancy due to frequent late-stage diagnosis.Barrett’s esophagus(BE),a well-established precursor to EAC,presents a critical window for early intervention through screening,surveillance,and endoscopic eradication therapy.Despite gastrointestinal society guideline recommendations for screening,the majority of patients with BE or early EAC remain undiagnosed until symptoms of late-stage cancer emerge.This review outlines current challenges and evolving strategies in the United States in BE detection and management,including risk stratification models,non-endoscopic screening tools,high-quality endoscopic techniques,tissue-based biomarkers,and artificial intelligence-enhanced imaging.We high-light best practices for surveillance,emphasizing the importance of thorough inspection of high-risk anatomic zones and the integration of advanced imaging.Endoscopic eradication therapy,including endoscopic mucosal resection and ablation,achieves high rates of complete eradication when performed with meti-culous technique,especially with comprehensive treatment of the gastroeso-phageal junction and gastric cardia.Long-term surveillance remains essential due to the risk of recurrence.As new technologies continue to emerge,integrating precision tools into routine practice will be key to improving outcomes and reducing EAC mortality.
文摘稻瘟病菌(Magnaporthe oryzae)作为主要的农业病原微生物,其引起的稻瘟病严重威胁着水稻等谷类作物的生产安全。内质网相关蛋白质降解途径(Endoplasmic reticulum-associated protein degradation,ERAD)是生物体应答内质网压力的主要方式之一,其在机体生长发育过程中具有重要作用。而HRD(HMG-CoA reductase degradation)复合物作为ERAD的关键组分,主要由Hrd1、Hrd3、以及凝集素Yos9等蛋白组成,负责内质网中错误折叠蛋白的识别、转运以及泛素化过程,最终由蛋白酶体降解,从而有效缓解内质网压力,保证细胞的正常生理活动。有研究表明,Hrd3属于单次跨膜蛋白,在内质网腔中与Hrd1、Yos9相结合,负责底物的识别并起着稳定Hrd1的作用。目前Hrd3在稻瘟病菌中的生物学功能尚不清楚。本研究通过基因敲除及互补试验获得了稻瘟病菌的ΔMohrd3突变体和ΔMohrd3-C回补菌株,并以野生型为对照,对突变体的生物学表型进行了分析。结果显示,ΔMohrd3突变体的生长速率、产孢量明显下降;对大麦和水稻的致病力显著减弱。进一步胁迫试验表明,MoHRD3的缺失导致稻瘟病菌对外界盐胁迫、渗透压胁迫的耐受性增强,对内质网胁迫耐受性减弱,而对细胞壁胁迫无明显变化。同时,MoHRD3基因的缺失激活了未折叠蛋白响应途径(Unfolded protein response,UPR)。上述结果表明,MoHRD3参与调控稻瘟病菌的营养生长、无性繁殖、致病及对不同环境胁迫的响应过程。
