OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To investigate the relationship between serum annexin A1 (ANXA1), macrophage inflammatory protein 1-α (MIP-1α), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and pulmonary infection in elderly patients with coronary heart disease complicated with heart failure and their predictive value.Methods:A total of 197 elderly patients with coronary heart disease combined with heart failure admitted to the Second Hospital of Qinhuangdao from January 2021 to January 2023 were retrospectively selected, and divided into pulmonary infection group (36 cases) and non pulmonary infection group (161 cases) according to whether the patients had pulmonary infection during hospitalization. Serum ANXA1, MIP-1α and sTREM-1 levels were detected in two groups. Multivariate logistic regression model was used to analyze the influencing factors of lung infection in elderly patients with coronary heart disease combined with heart failure. The predictive value of serum ANXA1, MIP-1α and sTREM-1 levels on lung infection in elderly patients with coronary heart disease combined with heart failure was analyzed by receiver operating characteristic (ROC) curve.Results:The incidence of pulmonary infection in 197 elderly patients with coronary heart disease combined with heart failure was 18.27%(36/197). Compared with the non pulmonary infection group, the pulmonary infection group had higher levels of serum ANXA1, MIP-1 α, sTREM-1, C-reactive protein, procalcitonin, and higher proportion of New York Heart Association (NYHA) heart function grade Ⅳ and diabetes, and lower left ventricular ejection fraction (all P<0.05). Multivariate logistic regression analysis showed that NYHA cardiac function grade Ⅳ, diabetes mellitus and elevated levels of procalcitonin, ANXA1, MIP-1α and sTREM-1 were independent risk factors for pulmonary infection in elderly patients with coronary heart disease combined with heart failure (all P<0.05). ROC curve analysis showed that the area under the curve predicted by serum ANXA1, MIP-1α and sTREM-1 combined was 0.909, which was larger than that predicted by serum ANXA1, MIP-1α and sTREM-1 alone. Conclusions:Elevated levels of serum ANXA1, MIP-1α and sTREM-1 are independent risk factors for pulmonary infection in elderly patients with coronary heart disease combined with heart failure, and can be used as auxiliary predictors of pulmonary infection in elderly patients with coronary heart disease combined with heart failure.

Objective:To investigate the prospective association between lifestyle and the risk for all-cause mortality in middle-aged and elderly residents in China.Methods:The data from China Health and Retirement Longitudinal Study were used. Baseline information about the lifestyle were collected through questionnaire survey and physical measurements, and the mortality data were obtained through surveys conducted at 2-3 year intervals. A total of 5 436 study participants were included. A comprehensive lifestyle including smoking, alcohol consumption, sleep, BMI and physical activity was constructed, and a multivariate-adjusted Cox proportional hazards regression model was used to estimate the association between lifestyle and the risk for all-cause mortality.Results:During the follow-up of average 8.2 years, 695 deaths were recorded. The comprehensive lifestyle score was linearly associated with the risk for all-cause mortality. Compared with the study participants with comprehensive lifestyle score of 0-1, those with score of 2-5 all had lower risk for all-cause mortality, with HRs of 0.78 (95% CI: 0.62-0.98), 0.56 (95% CI: 0.44-0.72), 0.36 (95% CI:0.27-0.48), and 0.33 (95% CI: 0.21-0.52), respectively. The results of Cox proportional hazards regression model analysis of single lifestyle showed that compared with those with unhealthy lifestyles, the HRs of all-cause mortality for study participants who never smoked, had moderate alcohol consumption, had appropriate night sleep, maintained healthy body weight and kept active physical activity were 0.70 (95% CI: 0.57-0.84), 0.76 (95% CI: 0.64-0.90), 0.79 (95% CI: 0.67-0.94), 0.73 (95% CI: 0.62-0.87), and 0.68 (95% CI: 0.58-0.80), respectively. Conclusions:Keeping healthy lifestyles can significantly reduce the risk for all-cause mortality in middle-aged and elderly residents China. The higher the healthy lifestyle level, the lower the risk for all-cause mortality.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective To study the correlation between the serum ferritin level and the pathological classification,tumor stage,PD-L1 expression,disease control rate(DCR),and survival period of patients with lung cancer.Methods A total of 85 patients with lung cancer admitted to our hospital from February 2020 to February 2021 were selected as the research subjects.All patients received immunotherapy,and the serum ferritin levels of patients before and after immunotherapy were detected.Meanwhile,according to the difference in serum ferritin levels before and after immunotherapy,the patients were divided into the increased group(31 cases)and the decreased group(54 cases).The correlation between the serum ferritin level and the pathological classification,tumor stage and PD-L1 expression level of patients was analyzed,and the DCRs and survival periods of patients with serum ferritin level≥300 ng/mL and<300 ng/mL before treatment were compared,as well as the increased group and the decreased group.The survival curve of patients in each group was analyzed by the Kaplan-Meier.Results Patients with tumor stage Ⅰ to Ⅲ showed significantly lower serum ferritin levels than patients with tumor stage Ⅳ(P<0.05).The DCR,3-year survival rate and progression-free survival(PFS)of patients with serum ferritin level≥300 ng/mL were significantly lower/shorter than those of patients with serum ferritin level<300 ng/mL(P<0.05).The DCR,3-year survival rate and PFS of patients in the increased group were significantly lower/shorter than those in the decreased group(P<0.05).Conclusion The increased serum ferritin level in lung cancer patients before treatment and the further increase after treatment are significantly associated with the reduced efficacy of immunotherapy and the shortened survival period.The combination of baseline serum ferritin levels before treatment and dynamic changes after treatment may serve as a clinical biomarker panel for predicting immunotherapy outcomes.

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 : To investigate the effect and mechanism of sex-determining region Y-box transcription factor 4(SOX4) on autophagy in small cell lung cancer(SCLC) cells. Methods : Human SCLC cell line NCI-H446 was transfected with small interfering RNA(siRNA) to knockdown SOX4. RT-qPCR and Western blot were used to verify the transfection efficiency. NCI-H446 cells were divided into control group, si-SOX4 group, si-SOX4+oe-Beclin1 group and oe-Beclin1 group. Western blot analysis was performed to detect the ratio of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ expression and the expression of Beclin1 and p62 in different groups of cells. The transcriptional regulation of Beclin1 by SOX4 was detected by dual luciferase reporter assay and chromatin immunoprecipitation PCR(ChIP-PCR) assay. CCK-8 assay was used to detect the proliferation ability of NCI-H446 cells in different groups. Flow cytometry was used to detect the apoptosis rate of NCI-H446 cells in different groups. Transwell assay was performed to determine the cell migration and invasion ability in different groups. Results: Compared with the control group or the si-NC group, the relative mRNA and protein expression level of SOX4 in si-SOX4 group were down-regulated(P<0.05), and the ratio of LC3-Ⅱ/LC3-Ⅰ protein expression and the relative protein expression level of Beclin1 in si-SOX4 group decreased(P<0.05), the relative protein expression of p62 increased(P<0.05). The relative luciferase activity of Beclin1 WT in the si-SOX4 group was lower than that in the si-NC group(P<0.05); the relative enrichment of Beclin1 promoter in the Anti-SOX4 group was higher than that in the Anti-Ig G group( P<0. 05). Compared with control group,cell proliferation activity decreased,cell apoptosis rate increased,migration number and invasion number decreased in si-SOX4 group( P<0. 05). Compared with the si-SOX4 group,the ratio of LC3-Ⅱ/LC3-Ⅰ protein expression and the relative protein expression of Beclin1 increased in si-SOX4 + oe-Beclin1 group,while the relative protein expression of p62 decreased,cell proliferation activity increased,apoptosis rate decreased,migration number and invasion number increased( P<0. 05). Conclusion Down-regulation of SOX4 can inhibit autophagy,decrease proliferation activity of NCI-H446 cells,and inhibit cell migration and invasion by inhibiting Beclin1 expression.