To investigate the risk factors for acute kidney injury (AKI) following the use of amphotericin B deoxycholate and to develop a predictive model to guide clinical monitoring and intervention.

Renal fibrosis (RF) is a prevalent clinical symptom of numerous chronic kidney illnesses and a significant pathological alteration in end-stage renal disease resulting from various mechanisms, such as abnormally activated signaling pathways, microRNAs, aging, autophagy disorders, and fibrotic ecological niches, all of which contribute to RF development. Inhibiting, blocking, or delaying the aforementioned mechanisms may yield novel approaches for treating RF. This article explores advancements in the comprehension of the mechanisms and therapeutic approaches for RF.

Intestinal permeability plays a pivotal role in the gut-liver axis and has emerged as a critical target for the prevention and treatment of liver diseases. Based on recent studies in China and globally， this article reviews the definitions and interrelationship of intestinal barrier function and intestinal permeability， the methods for assessing intestinal permeability， and the mechanism of action and clinical significance of intestinal permeability in the development and progression of various liver diseases. Studies have shown that increased intestinal permeability is a significant hallmark and an important driving factor for multiple liver diseases， and this state leads to the translocation of bacteria and harmful substances， trigger a systemic inflammatory response， and thus exacerbates liver injury， fibrosis， and metabolic dysregulation. Therefore， it is closely associated with the development and progression of metabolic associated fatty liver disease， alcoholic liver disease， autoimmune liver diseases， and their end-stage events， including liver cirrhosis， liver failure， and hepatocellular carcinoma. Future research should focus on the standardization of assessment methods， the exploration of underlying mechanisms， and the clinical translation of these findings.

Objective:To explore and compare the effect and prognosis of small bone window surgery at different timings in the treatment of hypertensive intracerebral hemorrhage (HICH).Methods:Using a retrospective analysis, HICH patients admitted to department of neurosurgery of Guihang Guiyang Hospital were selected from May 2021 to May 2023. According to the different surgical timings, the patients were divided into ultra-early group (time from onset to surgery <6 h) and early group (onset to surgery time ≥6~<24 h). Propensity score was used to match 51 cases in each group. The perioperative indicators (surgical time, intraoperative blood loss, hospital stay, hematoma clearance rate), incidence rates of complications, neurological function (National Institute of Health Stroke Scale (NIHSS), Barthel index), endothelin and arginine vasopressin (AVP) before surgery and after 7 days of surgery, clinical efficacy (Glasgow Outcome Scale (GOS)) at 1 month after surgery, rebleeding rate and mortality rate within 1 year after surgery were compared between both groups. Chi-square test was used for between-group comparison of enumeration data, t test was adopted for between-group comparison of measurement data with normal distribution, and non-parametric rank sum test was adopted for comparison of ranked data between groups.Results:The intraoperative blood loss and hospital stay in ultra-early group with (186.54±20.15) mL and (14.45±2.04) d were significantly less or shorter than (220.10±24.61) mL and (16.79±2.52) d in early group, the difference was statistically significant ( t values were 7.54 and 5.15; both P<0.001). At 7 days after surgery, the NIHSS ((14.55±1.57) and (16.14±2.13) points), endothelin ((69.14±6.37) and (73.48±6.83) mg/L) and AVP ((12.81±2.02) and (14.35±2.23) μg/L) in ultra-early group and early group were significantly lower than before ((32.67±3.81) and (32.38±3.53) points, (89.67±7.25) and (88.24±6.38) mg/L, (18.47±2.41) and (18.04±2.37) μg/L) while the Barthel index ((72.35±10.14) and (67.45±9.78) points) was significantly higher than before ((49.45±7.41) and (47.87±7.37) points),and the difference was statistically significant ( t values were 31.40, 28.13, 15.19, 11.28, 12.85, 8.10, 13.02, and 11.42, respectively; all P<0.001) and the NIHSS, endothelin and AVP in ultra-early group were significantly lower than in early group, while the Barthel index was significantly higher than early group, the difference was statistically significant ( t values were 4.29, 3.32, 3.66, and 2.48 respectively; P values were <0.001, 0.001, <0.001, and 0.015, respectively ). GOS grading (grade I-grade V: 1, 3, 9, 22, 16 cases) in ultra-early group at 1 month after surgery was significantly better than that in early group (grade I-V: 3, 5, 10, 26, 7 cases) ( Z=1.97, P=0.049). Conclusion:Both ultra-early and early small bone window surgery have good results in the treatment of HICH, but ultra-early surgery is more beneficial to the recovery of patients' neurological function and has better prognosis, which can be used as a reference.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective We proposed a new method that combines autoencoder in deep learning with optimally tuned robust improper maximum likelihood estimator(OTRIMLE)for multi－omics data robust clustering,and further applied it to lower－grade gliomas(LGG)patients clustering.Methods The dimension of LGG's miRNA,mRNA and methylation data was reduced nonlinearly by autoencoder,and then OTRIMLE method was used for robust clustering.Cox proportional hazard model was conducted to evaluate the prognostic risk of different clusters,and differentially expressed miRNAs(DEmiRNAs),differentially expressed mRNAs(DEmRNAs)and differentially methylated genes(DMGs)among different clusters were screened out by differential expression analysis.GO enrichment analysis was performed on the overlapping genes of target genes of DEmiRNAs,DEmRNAs,and DMGs.Finally,we compared the level of infiltrating immune cells and pathway activity in different clusters.Results LGG patients were classified into four clusters,in which the risk of death of patients in cluster 4 was 5.903 times higher than that in cluster 3.8 DEmiRNAs,2890 DEmRNAs and 46 DMGs were identified,and 658 overlapping genes obtained by joint analysis were enriched in 423 GO items.13 pathways with different activity and 4 immune cells with different level of immune infiltration were screened out.Conclusion The OTRIMLE method based on deep learning can effectively handle noise,sparsity and outliers in multi－omics data,achieving robust clustering for LGG patients.The identified immune cells and pathways provide theoretical bases for the subsequent targeted treatment of LGG.