As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To investigate the potential effectiveness of a computer-based gastrointestinal (GI) endoscopy simulator in assessing the competence of GI endoscopy trainees.Methods Fifty trainees working in the endoscopy center of General Hospital of Chinese PLA between February 2009 and October 2011 were enrolled.These participants were divided into four groups based on their prior endoscopic experience:novices (no endoscopy experience),intermediate experienced (≤200 colonoscopies or ≤ 500 gastroscopies),experienced (201-1000 colonoscopies or 501-2000 gastroscopies),and experts (＞ 1000 colonoscopies or ＞ 2000 gastroscopies).Assessment of endoscopic skills was performed during a hand-eye coordination task (Endo Bubble level 1) and was based on parameters measured by the computer system including time to finish,average time between two bubbles,number of times wall touched.Results When GI trainees were categorized by their prior gastroscopy number,the time to finish of each group were (302.43 ± 108.96)s,(188.00 ± 59.88) s,135.00 (40.00) s,150.00 (69.00) s,and the average time between two bubbles were (14.29 ± 5.47) s,(8.82 ± 3.28) s,6.00 (2.00) s,7.00 (4.00) s,respectively.Pairwise comparison showed that except experienced and experts groups (P ＞ 0.05),there were significantly differences between remaining groups (P ＜0.01).However,based on the colonoscopic experiences,the time to finish of each group were 220.00(91.00)s,127.00(28.25)s,155.50(81.00)s,150.00(58.50)s,respectively,which were significantly different between each two groups (P ＜ 0.01).Average time between two bubbles of each group were 10.00 (4.00) s,5.50 (1.50) s,7.00 (3.75) s,7.00 (3.50) s,respectively,which were found significantly different among whole groups (P ＜ 0.05 or P ＜ 0.01),but there were no differences between novice and experienced trainees and between intermediate experienced and experts groups.In contrast,the number of wall-touch was insufficient for assessment.Except the significant difference between novice and experienced group (P ＜ 0.05) as categorized by gastroscopy experience,there were no values to differentiate the trainees of different practical competence on gastroscopy or colonoscopy.Conclusion The parameter,time to finish,during a hand-eye coordination task using a virtual reality simulator might be able to differentiate the competence of operators,which was used prior to training in real-life endoscopy,but lack of accurate discriminatory function between experienced and experts.

Objective To summarize and analyze the clinical characteristic of blue rubber bleb nevus syndrome (BRBNS).Methods The clinical data of four cases treated since 2001 and 30 BRBNS cases reported by domestic literature were retrospectively analyzed.The clinical manifestation,family history,endoscopy and imageology examination,site of lesions,treatment and follow up were analyzed.Results The male to female ratio was 1.8∶1 and median age was 19.5 years.A total of 33 cases (97.1％) presented with gastrointestinal bleeding,median age of gastrointestinal bleeding detected was 9.0 years.Among the 33 cases,anemiawas found as the primary symptom in nine cases (27.3％),and one case complicated with intussusception and intestinal necrosis accompanied with abdominal pain.Two cases have family history.Gastroscopy (85.3 ％) and colonoscopy(73.5 ％) were mainly examinations for detection.Lesions mainly involved skin (100.0％) and digestive tract (97.1％),and the locations of the lesion in digestive tract was stomach (64.7％),small intestine (64.7％),colon (58.8％),esophagus (29.4％).Treatment methods included symptomatic treatment,endoscopic therapy and surgery.Banding ligation and polypectomy resection were common endoscopic therapies.Gastrointestinal bleeding did not recur in six cases with endoscopic therapy and four cases receiving surgery during short-term follow up.Conclusions BRBNS lesions mainly involve skin and digestive tract,mostly complicated with gastrointestinal bleeding.For gastrointestinal bleeding,so far endoscopic therapy and surgery are the effective therapies.