BACKGROUND:Triptolide,a bioactive component of the traditional Chinese medicine Tripterygium wilfordii,has a certain protective effect on neurons.OBJECTIVE:To investigate the effect of triptolide on cerebral ischemia/reperfusion injury.METHODS:(1)Cell experiment:Hippocampal neurons(HT22 cells)were randomly divided into control group,glucose oxygen deprivation/reoxygenation(OGD/R)group,OGD/R+triptolide group,OGD/R+triptolide+si-TIGAR group,OGD/R+si-TIGAR group,and OGD/R+triptolide+rapamycin group.HT22 cell viability was detected by cell counting kit 8.Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,7 members of the solsolic vector family 11,sphingosine kinase 1(SPHK1)and(mTOR)were detected by western blot assay.Glutathione,malondialdehyde and iron level were detected using the biochemical kit.(2)Animal experiment:Rats were randomly divided into sham surgery group,model group,and triptolide group.Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups.Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days.Twenty-four hours after administration,LONGA method was used to evaluate the neurological impairment of rats,TTC method was used to observe the conditions of cerebral infarction,TUNEL staining was used to detect cell apoptosis,and western blot was performed to detect the expression level of related proteins.RESULTS AND CONCLUSION:(1)At the cellular level,triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R.Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,and 7 members of the solsolic vector family 11,activated the SPHK1/mTOR pathway,increased glutathione content,inhibited malondialdehyde content and iron levels.Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells.(2)At the animal level,triptolide significantly reduced neurological deficits,infarct volume,and cell apoptosis,and inhibited neuronal ferroptosis in brain tissue of rats.To conclude,triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling,and thereby reduced cerebral ischemia/reperfusion injury.These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.

BACKGROUND:Triptolide,a bioactive component of the traditional Chinese medicine Tripterygium wilfordii,has a certain protective effect on neurons.OBJECTIVE:To investigate the effect of triptolide on cerebral ischemia/reperfusion injury.METHODS:(1)Cell experiment:Hippocampal neurons(HT22 cells)were randomly divided into control group,glucose oxygen deprivation/reoxygenation(OGD/R)group,OGD/R+triptolide group,OGD/R+triptolide+si-TIGAR group,OGD/R+si-TIGAR group,and OGD/R+triptolide+rapamycin group.HT22 cell viability was detected by cell counting kit 8.Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,7 members of the solsolic vector family 11,sphingosine kinase 1(SPHK1)and(mTOR)were detected by western blot assay.Glutathione,malondialdehyde and iron level were detected using the biochemical kit.(2)Animal experiment:Rats were randomly divided into sham surgery group,model group,and triptolide group.Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups.Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days.Twenty-four hours after administration,LONGA method was used to evaluate the neurological impairment of rats,TTC method was used to observe the conditions of cerebral infarction,TUNEL staining was used to detect cell apoptosis,and western blot was performed to detect the expression level of related proteins.RESULTS AND CONCLUSION:(1)At the cellular level,triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R.Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,and 7 members of the solsolic vector family 11,activated the SPHK1/mTOR pathway,increased glutathione content,inhibited malondialdehyde content and iron levels.Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells.(2)At the animal level,triptolide significantly reduced neurological deficits,infarct volume,and cell apoptosis,and inhibited neuronal ferroptosis in brain tissue of rats.To conclude,triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling,and thereby reduced cerebral ischemia/reperfusion injury.These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

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:This study aimed to examine the association between malnutrition diagnosed by the Global Leadership Initiative on Malnutrition(GLIM)criteria and clinical outcomes in surgical patients,as well as to assess its prognostic impact on postoperative adverse clinical outcomes.Methods:Electronic databases,including PubMed,Embase,Web of Science,CINAHL,Scopus,The Cochrane Library,Clinical Trials,CNKI,Wanfang Data Knowledge Service Platform,and the Chinese Biomedical Literature Database,were systematically searched.Relevant cohort studies utilizing GLIM criteria to preoperatively diagnose malnutrition in surgical inpatients were included.The exposed group comprised surgical patients diagnosed with preoperative malnutrition using GLIM criteria,while the control group consisted of surgically treated patients without malnutrition as per GLIM criteria.Literature quality was evaluated using the Newcastle-Ottawa Scale(NOS),and meta-analysis was performed using Review Manager 5.4 software.Results:Fourteen literatures were included,with a total sample size of 10,045 patients.Meta-analysis revealed that the malnourished group had a higher incidence of postoperative complications compared to the non-malnourished group[risk ratio(RR)=1.81,95%CI:1.66～1.98),P<0.00001].Additionally,the incidence of severe complications was significantly higher in GLIM-diagnosed malnourished patients.The malnourished group exhibited poorer overall survival[hazard ratio(HR)=1.90,95%CI:1.55～2.34,P<0.00001]and disease-free survival[HR=2.25,95%CI:1.02～4.93,P=0.04]compared to the non-malnourished group.Conclusion:GLIM-diagnosed malnutrition is significantly associated with adverse clinical outcomes in surgical patients,increasing postoperative complication rates and reducing overall and disease-free survival.The GLIM criteria demonstrate value in predicting adverse clinical outcomes in this population.Further high-quality studies are warranted to validate these findings.

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.

To identify factors associated with the recurrence of polymyalgia rheumatica(PMR) within one year.

Age-related macular degeneration (AMD) represents a predominant cause of blindness among older adults, with limited therapeutic options currently available. Oxidative stress, inflammation, and retinal pigment epithelium injury are recognized as key contributors to the pathogenesis of AMD. Regulated cell death plays a pivotal role in mediating cellular responses to stress, maintaining tissue homeostasis, and contributing to disease progression. Recent research has elucidated several regulated cell death pathways-such as apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy-that may contribute to the progression of AMD owing to cell death in the retinal pigment epithelium. These discoveries open new avenues for therapeutic interventions in patients with AMD. In this review, we provide a comprehensive summary and analysis of the latest advancements regarding the relationship between regulated cell death and AMD. Moreover, we examined the therapeutic potential of targeting regulated cell death pathways for the treatment and prevention of AMD, highlighting their roles as promising targets for future therapeutic strategies.