Background Under the background of global warming, research on association between ambient temperature and risk of injury is needed. Objective To examine the effect of temperature on injury in Bao'an district, Shenzhen and identify the sensitive population, thereby providing a scientific basis for formulating prevention and control strategies and measures of injury. Methods The injury reports from the Injury Surveillance System and the meteorological data of Bao'an District between 2018 to 2022 were collected. The meteorological data were sourced from the fifth generation of the European Centre for Medium-Range Weather Forecasts (ECMWF) land reanalysis data. Based on time-stratified case-crossover design, conditional logistic regression combined with distributed lag nonlinear model was used to evaluate the exposure-response association between ambient temperature and injury. The stratified analyses were further conducted by gender, age, and causes of injury. Results A total of 156205 injury cases were collected from the injury surveillance sentinel hospitals in Bao'an District of Shenzhen from 2018 to 2022, and the median of daily average temperature during the same period was 20.0 ℃. The exposure-response curve showed that the risk of injury was positively correlated with temperature. The linearized analysis revealed that each 1°C increase in temperature was associated with a 1.05% (95%CI: 0.68%, 1.42%) rise in injury risk (ER). Notably, the effect was greater in females (ER=1.31%, 95%CI: 0.67%, 1.94%) than males (ER=0.92%, 95%CI: 0.47%, 1.37%). Among age groups, adults ＞60 years faced the highest risk (ER=1.91%, 95%CI: −0.36%, 4.24%). The top three temperature-associated injury risks were sharp instrument injuries (ER=2.19%, 95%CI: 1.16%, 3.22%), animal injuries (ER=1.71%, 95%CI: 0.86%, 2.56%), and blunt injuries (ER=071%, 95%CI: −0.08%, 1.51%). The impact of temperature on unintentional injuries (ER=1.11%, 95%CI: 0.72%, 1.49%) was higher than that on intentional injuries (ER=0.43%, 95%CI: −0.85%, 1.72%). Severe injuries (ER=2.20%, 95%CI: −3.09%, 7.77%) were more affected by temperature than mild injuries (ER=1.00%, 95%CI: 0.58%, 1.43%) and moderate injuries (ER=1.15%, 95%CI: 0.42%, 1.89%). Conclusion The increase in ambient temperature associates with injury occurrence, and the impact of temperature exhibits obvious heterogeneity among different populations, indicating that targeted intervention measures should be taken for different populations and types of injuries.

Aim To investigate the protective poten-tial of paeoniflorin 6-oxy-benzenesulfonate(CP-25)in preserving knee cartilage integrity in osteoarthritis mice through inhibition of GRK2 activity.Methods The posttraumatic osteoarthritis model was established fol-lowing DMM surgery.The experiment consisted of a sham operation group,a model group,a CP-25 admin-istration group,and a paroxetine positive control group.Intragastric administration commenced after the surgery.After 12 weeks of administration,the animals were euthanized.Micro-CT imaging was used to ob-serve the knee cartilage degeneration and abnormal bone remodeling,and the joint histopathology of mice was observed by staining with ferrubens solid green.Immunohistochemistry and immunofluorescence were used to detect the expression level of related molecules in cartilage tissue.Furthermore,Western blot was em-ployed to determine GRK2 and EP4 membrane protein expression levels as well as total protein levels of GRK2 and MMP13 following CP-25 treatment.Results Compared with the sham operation group,the articular cartilage in the model group was significantly degrad-ed,with the cartilage surface calcifying and osteo-phytes forming.CP-25 could significantly reduce the number of osteophytes and the thickness of the sub-chondral plate of articular cartilage,promote the regen-eration of the cartilage matrix,reduce the expression of cartilage matrix degradation protein,and have a signifi-cant protective effect on knee cartilage.Immunohisto-chemical and immunofluorescence results showed that compared with the model group,CP-25 treatment sig-nificantly decreased the expressions of GRK2,AD-AMTS5 and MMP13 in knee tissue and increased the expressions of Col Ⅱ and Aggrecan in knee tissue.The results of in vitro experiments showed that CP-25 ad-ministration could significantly reduce the expression levels of GRK2 membrane protein and total protein,in-crease the level of EP4 membrane protein,and de-crease the level of MMP13.Conclusions The ad-ministration of CP-25 can significantly promote the re-generation of articular cartilage matrix in OA mice,re-duce the degradation of cartilage matrix,and exhibit therapeutic effects on OA.The mechanism behind this is related to the inhibition of GRK2-mediated cartilage matrix metabolism.

Aim To establish limited sampling strategy to esti-mate area under the drug concentration versus time curve(AUC0-t)of lymphoma patients treated with autologous stem cell transplantation(ASCT)who had busulfan intravenous infu-sion.Methods Twelve lymphoma patients treated with ASCT received a conditioning regimen containing busulfan 105 mg·m-2,Ⅳ infusion for 3 h.Blood samples were obtained 1 h after the start of the first dose of the busulfan infusion,at 5 min,1 h,2 h,4 h,6 h and 18 h after the end of the drug administration.LC-MS/MS was used to determine the busulfan serum concentra-tion.After obtaining the clinical pharmacokinetic parameters of busulfan by traditional pharmacokinetic method,multiple linear stepwise regression analysis was used to establish the AUC0-t es-timation model of busulfan based on limited sampling method.The model was further verified by Jackknife and Bootstrap meth-od.Bland-Altman plots were used to evaluate the consistency between the limited sampling method and the classical pharma-cokinetic method.Results The multiple linear regression equa-tion analysis of C60min,C180min and C300min was obtained by the limited sampling method.The regression equation was AUC0-t=295.003C60min+233.050C180min+273.163C300min-1202.713,r2=0.995,MPE=-0.87％,RMSE=2.40％.Conclusion The limited sampling model with three-point estimation can be used to estimate the AUC0-t of busulfan exposure in lymphoma patients with ASCT to provide reference for clinical application of busulfan.

Ecto-nucleotide pyrophosphatases/phosphodiesterases(ENPPs)are involved in the hydrolysis of different purine nu-cleotides in a range of physiological processes.In recent years,it has also been found to be involved in tumor progression,with ENPP1 often overexpressed in local recurrence and tumor metas-tasis,which is associated with poor prognosis and survival in a range of solid tumors.The role of ENPP1 in tumors is mainly fo-cused on tumor proliferation,metastasis,immunity,recurrence,etc.,and it is speculated that ENPP1 can be used as a prognos-tic indicator for a variety of tumors.ENPP1 promotes the immu-nosuppressive tumor microenvironment by being obliquely in-volved in the regulation of ATP/adenosine homeostasis by com-bining with other components,which crosses with interferon gene stimulators to impair its potent immune response through the hy-drolysis of the effector 2',3'-cyclic GMP-AMP.Therefore,EN-PP1 blockade has become an effective means to induce immune remodeling and inhibit tumorigenesis and development.The ex-isting ENPP1 inhibitors mainly include natural small molecule compounds,nucleotide ENPP1 inhibitors,non-nucleotide EN-PP1 inhibitors,and novel small molecule ENPP1 inhibitors.So far,a small number of ENPP1 inhibitors have been developed and are rarely suitable for in vivo experiments,and they are still in the stage of developing effective compounds or lead com-pounds,and the research on ENPP1 inhibitors needs to be fur-ther studied.This review summarizes and discusses the role of ENPP1 in tumors,and summarizes the current research progress of various ENPP1 agents and their current research progress,in order to provide a reference for further research on the prepara-tion of drug candidates.

Aim To explore the mechanism of modified Wuzi Yanzong pill to reduce testicular toxicity of Tripterygium wilfordii by means of network pharmacolo-gy.Methods The effective chemical composition and target of modified Wuzi Yanzong Pill to reduce testicu-lar toxicity of Tripterygium wilfordii were analyzed by using multiple databases to understand the mechanism of action.Results The first five compounds of modi-fied Wuzi Yanzong pill are quercetin,sucrose,kaempferol,galactose and ellagic acid,respectively.The first five targets were TP53,SRC,EP300,MAPK3,STAT3;KEGG pathway enrichment analysis mainly concentrated in cancer pathway,lipid and atherosclero-sis,hepatitis B,apoptosis,diabetes complications AGE-RAGE signaling pathway,PI3K-Akt signaling pathway and other signaling pathways.Conclusions The ac-tive components of modified Wuzi Yanzong pill can re-duce the testicular toxicity of Tripterygium wilfordii mainly by interfering with TP53,SRC,EP300,MAPK3,STAT3 and other targets,regulating apoptosis,PI3K-Akt signaling pathway,diabetes complications AGE-RAGE signaling pathway,lipid metabolism and other pathways.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

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 understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.