Aim To investigate the protective effects of curcumin(CUR)on crystal-induced renal injury and its underlying mechanism in the mouse model of neph-rolithiasis.Methods The mouse model of stone for-mation was established via successive intraperitoneal injection of glyoxylate.Proximal tubular epithelial cell line HK-2 treated with calcium oxalate monohydrate(COM)was used as an in vitro model.The protective role of CUR on nephrolithiasis was tested by determina-tion of tubular injury,crystal deposition and adhesion,levels of inflammatory cytokines.In vitro,the effects of CUR on the cell viability and inflammatory factors of HK-2 cells were measured.The proteins in the Toll-like receptor 4(TLR4)/nuclear factor κB(NF-κB)and nuclear factor erythroid 2-related factor 2(NRF2)/hemeoxygenase-1(HO-1)signaling path-ways were measured by Western blot for confirming the relationship between CUR and these pathways.Final-ly,NRF2 inhibitor ML385 and TLR4 activator CCL-34 were respectively used on COM-induced HK-2 cells ex-posed to CUR for the conduction of gain-of-function and loss-of-function assays.Results CUR improves the damage in the mouse model of kidney stone forma-tion,inhibits inflammation and antioxidative effects;promotes the viability of HK-2 cells induced by COM,and inhibits the expression of inflammatory factors.CUR suppresses the expression of proteins in the TLR4/NF-κB pathway,promotes the transfer of NRF2 from the cytoplasm to the nucleus,and enhances the ex-pression of HO-1.ML385 and CCL-34 respectively counteract the anti-inflammatory effects of CUR on COM-induced HK-2 cells.Conclusions Taken togeth-er,our study demonstrates the protective effect of CUR on the deposition of kidney stone and consequent tubu-lar injury.CUR through regulation of the TLR4/NF-κB and NRF2/HO-1 pathways improves renal injury.

Objective:Different methods were used to determine the dissolution of piroxicam patch,and the disso-lution results were evaluated,in order to select a determination method that could more accurately reflect the drug release process of piroxicam patch,so as to provide a reference for the scientific and accurate evaluation of drug quality.Methods:The liquid chromatography method for the detection of piroxicam was established,and the 24 hour dissolution curves of piroxicam patch were investigated by paddle over disk method,rotating cylinder method and vertical diffusion cell method,and the dissolution curves were compared by f1 difference factor method,f2 simi-larity factor method and Weibull model fitting,and the in vitro dissolution behavior of different methods was evalua-ted.Results:Piroxicam had a good linear relationship in the range of 1-150 μg·mL-1(r=1.000),the accura-cy was 100.9％(n=9),the precision was 1.7％(n=9),and the sample solution was stable within 72 hours.The results of the comparison of dissolution curves showed that the dissolution of piroxicam patch was more in line with the Weibull model.Under the same conditions of dissolution medium and temperature,there was little differ-ence between the paddle over disk method and rotating cylinder method,and there was a possibility of substitution for each other,and there were significant differences between the vertical diffusion cell method and the other two methods.Conclusion:The vertical diffusion cell method is more in line with the dissolution process of drugs in actual use,and provides more references for quality evaluation.

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.

Objective To understand the changing distribution and antimicrobial resistance profiles of Klebsiella strains in 52 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Antimicrobial susceptibility testing was carried out according to the unified CHINET protocol.The susceptibility results were interpreted according to the breakpoints in the Clinical & Laboratory Standards Institute(CLSI)M100 document.Results A total of 241,549 nonduplicate Klebsiella strains were isolated from 2015 to 2021,including Klebsiella pneumoniae(88.0％),Klebsiella aerogenes(5.8％),Klebsiella oxytoca(5.7％),and other Klebsiella species(0.6％).Klebsiella strains were mainly isolated from respiratory tract(48.49±5.32)％.Internal medicine(22.79±3.28)％,surgery(17.98±3.10)％,and ICU(14.03±1.39)％were the top 3 departments where Klebsiella strains were most frequently isolated.K.pneumoniae isolates showed higher resistance rate to most antimicrobial agents compared to other Klebsiella species.Klebsiella isolates maintained low resistance rates to tigecycline and polymyxin B.ESBLs-producing K.pneumoniae and K.oxytoca strains showed higher resistance rates to all the antimicrobial agents tested compared to the corresponding ESBLs-nonproducing strains.The K.pneumoniae and carbapenem-resistant K.pneumoniae(CRKP)strains isolated from ICU patients demonstrated higher resistance rates to majority of the antimicrobial agents tested than the strains isolated from non-ICU patients.The CRKP strains isolated from adult patients had higher resistance rates to most of the antimicrobial agents tested than the corresponding CRKP strains isolated from paediatric patients.Conclusions The prevalence of carbapenem-resistant strains in Klebsiella isolates increased greatly from 2015 to 2021.However,the Klebsiella isolates remained highly susceptible to tigecycline and polymyxin B.Antimicrobial resistance surveillance should still be strengthened for Klebsiella strains.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

The polycomb repressive deubiquitinase complex(PR-DUB)is a member of the polycomb group protein involved in the epigenetic modification of chromosomes by regulating histone modifications.The polycomb repressive complex 1(PRC1)and PR-DUB complex protect active genes from aberrant si-lencing through a balance of ubiquitination and deubiquitination modifications of H2AK119Ub.The deu-biquitination function of the PR-DUB complex is associated with the promotion of gene activation and the establishment of transcriptionally permissive chromatin states,in addition to the activation of enhancers and the facilitation of DNA damage repair at double-strand breaks.Additional sex combs-like 1(ASXL1)serves as an epigenetic scaffold for the assembly of chromatin-modifying complexes and tran-scription factors involved in epigenetic regulation.BRCA1-associated protein 1(BAP1)acts as a deubiq-uitinating enzyme to remove ubiquitination modification of substrates.The PR-DUB complex consists of a core dimer and other cofactors.BAP 1 forms a core dimer with ASXL1,and other subunits interact to reg-ulate the targeting and functioning of the PR-DUB complex.ASXL1 and BAP1 are the two subunits most relevant to the deubiquitination function of the PR-DUB complex,and the DEUBAD domain of ASXL1 activates BAP1 to exert its deubiquitination function to hydrolyze H2AK119Ub1.Understanding the struc-ture and interaction mechanism of ASXL1 and BAP1 is essential to study the mechanism of deubiquitina-tion specific to the PR-DUB complex.In humans,mutations in the components of the PR-DUB complex frequently cause a variety of hematologic neoplasms.Mutations in the ASSXL1 gene often result in prema-ture termination of protein translation,mostly due to the absence of the C-terminal PHD domain.The in-teraction of mutated ASXL1 or BAP1,epigenetic factors,and targets or signaling pathways such as Akt/mTOR in PR-DUB is now considered as a possible mechanism to promote the development of hematologi-cal tumors.This is crucial for the research and development of new specific targeted therapeutic agents a-gainst potential therapeutic targets.In this paper,focusing on ASXL1 and BAP1,we will introduce the structure and function of the PR-DUB complex,and its mechanism in the occurrence of hematological tumor diseases,and systematically summarize the potential targeted therapeutic drugs,with a view to pro-viding scientific references for the research of the PR-DUB complex in the prevention and treatment of he-matological diseases.

AIM To establish the HPLC fingerprints for Tanacetum tatsienense(Bureau & Franchet)K.Bremer & Humphries and to determine the contents of chlorogenic acid,quercetin-3-O-glucoside,luteolin-7-O-glucoside,luteolin-7-O-glucuronide,apigenin-7-O-glucuronide,luteolin and apigenin.METHODS The analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX Extend C18 column(4.6 mm×250 mm,0.5 μm),with the mobile phase comprising of 0.5％phosphoric acid-acetonitrile flowing at 1.0 mL/min,and the detection wavelength was set at 350 nm.Subsequently,principal component analysis,partial least squares discriminant analysis and cluster analysis were carried out.RESULTS There were twelve common peaks in the fingerprints for fourteen batches of samples with the similarities of 0.761-0.975.Seven constituents showed good linear relationships within their own ranges(R2≥0.999 1),whose average recoveries were 84.00％-105.11％with the RSDs of 1.28％-2.86％.Various batches of samples were clustered into three types,and seven differential constituents were observable,containing peaks 4(luteolin-7-O-glucoside),12(apigenin),9(apigenin-7-O-glucuronide),8,11(luteolin),5(luteolin-7-O-glucuronide)and 2.CONCLUSION This precise,stable,specific and reproducible method can be used for the quality control of T.tatsienense.