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.

Aim To explore the MST1 knockdown at-tenuates the inhibitory effect of salvianolic acid B(Sal B)on pERK anti-renal fibrosis.Methods In vitro experiments stimulated human renal cortical proximal tubular epithelial cells(HK-2)with XMU-XP-1(10μmol·L-1)inhibitor;in vivo experiments induced wild-type(WT)and MST1 systemic knockout mouse(MST1-/-)renal fibrosis models with DEN/CCl4/C2H5OH(DCC)and interfered with Sal B(15 mg·kg-1·d-1,ig)intervention.Renal histopathology was observed by HE and Masson staining;α-SMA and pERK protein expression was detected by Western blot;and pERK protein expression was detected by im-munofluorescence.Results In vitro results showed that Sal B could inhibit pERK protein expression.In vivo results showed that Sal B could improve DCC-in-duced renal tissue pathological injury and inhibit α-SMA and pERK protein expression;MST1-/-aggrava-ted pathological injury and significantly up-regulated α-SMA and pERK protein expression.Conclusion Sal B reduces the stimulatory effect of XMU-MP-1 on HK-2 cells by inhibiting the phosphorylation of ERK protein;Sal B exerts its anti-renal fibrosis effect by inhibiting the phosphorylation of α-SMA protein and ERK pro-tein;and MST1-/-,aggravating the pathological inju-ry of renal tissue,significantly up-regulated the expres-sion of α-SMA and pERK protein,which in turn atten-uated the antirenal fibrosis effect of Sal B.

Objective:To investigate the association between serum thyroid-stimulating hormone(TSH) level and the 10-year risk of atherosclerotic cardiovascular disease(ASCVD) in men over 50 years old with type 2 diabetes mellitus(T2DM).Methods:This study included male T2DM patients aged≥50 years, diagnosed at the First Hospital of Lanzhou University between July 2021 and March 2022. Patients were categorized into three groups based on serum TSH level: elevated TSH group(T3, TSH>5.91 mIU/L) and normal TSH group, which was further divided into T1(0.56 mIU/L≤TSH<3.24 mIU/L) and T2(3.24 mIU/L≤TSH≤5.91 mIU/L) group. The 10-year ASCVD risk index was compared across groups. Spearman correlation and multiple linear regression analyses were used to assess the independent association between TSH level and 10-year ASCVD risk index. Results:A total of 490 male T2DM patients aged≥50 years were included(T1: 310, T2: 131, T3: 49). The 10-year ASCVD risk index was significantly higher in T3 group than that in T1 group(18.40% vs 13.90%, χ2=9.47, P<0.05). Serum TSH level showed a positive correlation with the 10-year ASCVD risk( r=0.144, P<0.05). After adjusting for confounders such as age, hypertension, lipid profile, diabetes duration, aspartate aminotransferase, albumin, lactate dehydrogenase, estimated glomerular filtration rate, creatinine, and phosphorus, multiple linear regression confirmed that TSH level was independently associated with the 10-year ASCVD risk index( β=0.23, 95% CI 0.02-0.45). Conclusions:Higher serum TSH level is independently associated with an increased 10-year ASCVD risk in men over 50 years old with T2DM. Regular TSH monitoring may aid in cardiovascular risk stratification in this population.

Aim To explore the MST1 knockdown at-tenuates the inhibitory effect of salvianolic acid B(Sal B)on pERK anti-renal fibrosis.Methods In vitro experiments stimulated human renal cortical proximal tubular epithelial cells(HK-2)with XMU-XP-1(10μmol·L-1)inhibitor;in vivo experiments induced wild-type(WT)and MST1 systemic knockout mouse(MST1-/-)renal fibrosis models with DEN/CCl4/C2H5OH(DCC)and interfered with Sal B(15 mg·kg-1·d-1,ig)intervention.Renal histopathology was observed by HE and Masson staining;α-SMA and pERK protein expression was detected by Western blot;and pERK protein expression was detected by im-munofluorescence.Results In vitro results showed that Sal B could inhibit pERK protein expression.In vivo results showed that Sal B could improve DCC-in-duced renal tissue pathological injury and inhibit α-SMA and pERK protein expression;MST1-/-aggrava-ted pathological injury and significantly up-regulated α-SMA and pERK protein expression.Conclusion Sal B reduces the stimulatory effect of XMU-MP-1 on HK-2 cells by inhibiting the phosphorylation of ERK protein;Sal B exerts its anti-renal fibrosis effect by inhibiting the phosphorylation of α-SMA protein and ERK pro-tein;and MST1-/-,aggravating the pathological inju-ry of renal tissue,significantly up-regulated the expres-sion of α-SMA and pERK protein,which in turn atten-uated the antirenal fibrosis effect of Sal B.

Diabetic nephropathy(DN)ranks as a frequent and serious complication in diabetes mellitus,and it's a key factor in chronic kidney disease and end-stage renal disease(ESRD),greatly diminishing the life quality of patients.Presently,the conventional treatment approaches for DN mainly involve strict regulation of blood sugar and pressure,in conjunction with the application of renin-angiotensin-aldosterone system inhibitors.While these therapies can slow down the advancement of DN,they are ineffective in stopping its final development into ESRD.Lately,the involvement of the gut-kidney axis in the development and advancement of DN has attracted growing interest.Individuals suffering from DN show changes in the variety of gut microbiota,which are crucial in the development and management of DN due to metabolic interactions with the host.The goal of this analysis is to explore the fundamental processes of gut microbiota's role in DN and explore treatment approaches focusing on gut microbiota,aiming to offer new perspectives for the clinical handling of DN.

Diabetic kidney disease(DKD)is one of the common microvascular complications of diabetes mellitus,and it has become the main cause of chronic kidney disease and end stage renal disease.Traditional Chinese medicine can delay the progress of DKD by inhibiting oxidative stress,improving renal tissue damage,restoring renal function.This paper will summarize the relationship between oxidative stress and DKD and the prevention and treatment of DKD by traditional Chinese medicine,so as to provide reference for clinical drug application,basic research and new drug research and development of DKD.

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.

AIM To investigate the protective effects of Shuangyi Qushi Tongluo Capsules(Shuangyi Capsules)on Dexamethasone(Dex)induced osteoporosis in mice.METHODS The C57BL/6J mice were randomly divided into the control group,the model group,the Xianling Gubao Capsules group(1.5 g/kg),and the low-dose,moderate-dose,and high-dose Shuangyi Capsules groups(0.6,1.2,and 2.4 g/kg).The mouse model of osteoporosis was induced by 8-week intraperitoneal injection of Dex sodium phosphate injection(5 mg/kg).The mice had their femur osteogenesis observed with hematoxylin and eosin(HE)staining and tartrate-resistant acid phosphatase(TRAP)staining;their serum alkaline phosphatase(ALP)and osteocalcin(BGP)activities detected by ELISA;their femoral mRNA expressions of Col-Ⅰ,OCN,and OPN detected by RT-qPCR;and their femoral protein expressions of OPG and RANKL detected by Western blot.Upon the MC3T3-E1 cells exposed to Dex and Shuangyi Capsules,their viability was evaluated by CCK-8 assay;their mineralization determined by alkaline phosphatase staining and alizarin red staining(ARS);and their intracellular ROS level detected using DCFH-DA probe.RESULTS Compared with the model group,Shuangyi Capsules groups demonstrated improved fracture of femoral trabeculae and reduced number of osteoclasts;increased serum ALP and BGP activities(P＜0.05,P＜0.01);increased femoral expressions of Col-Ⅰ mRNA and OPG protein(P＜0.05,P＜0.01);and decreased RANKL protein expression(P＜0.05).Compared with the MC3T3-E1 cells stimulated by Dex,those underwent further treatment of Shuangyi Capsules demonstrated increased cell viability and ALP activity(P＜0.05,P＜0.01);increased mineralization and calcium nodule formation;increased expressions of Col-Ⅰ,OCN,OPN mRNA and OPG protein(P＜0.05,P＜0.01);decreased RANKL protein expression(P＜0.05,P＜0.01);and reduced ROS levels.CONCLUSION Shuangyi Capsules ameliorate Dex-induced osteoporosis in mice by suppressing osteoclast overactivation,enhancing osteoblast activity,and stimulating bone formation through modulation of Col-Ⅰ,OCN,OPN mRNA and OPG/RANKL protein levels.

Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P＜0.05,P＜0.01).The levels of WBC and NE in the model-A increased significantly(P＜0.01).The level of LY in model-B decreased significantly(P＜0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P＜0.01).The levels of IL-6 in model-A and model-B were significantly increased(P＜0.05,P＜0.01).The collagen volume fraction of model-A and model-B were significantly increased(P＜0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P＜0.01),and the expression levels of IκBα/β-actin were significantly decreased(P＜0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P＜0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.

Suppressor of cytokine signaling 3(SOCS3),a member of SOCS family,plays a major role in cell signaling trans-duction.SOCS3 is important in regulation of immune homeostasis and also involved in the control of energy metabolism,mainly through regulating JAK/STAT pathway.Recent studies have shown that SOCS3 was closely associated with glycolipid metabolic diseases like diabetes and obesity,and can be used as a new target for treatment of these glycolipid metabolic diseases.This review focuses on the latest research progress of the role and mechanism of SOCS3 in glycolipid metabolic diseases,and discusses the possibility of SOCS3 as a therapeutic target for glycolipid metabolic diseases.