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.

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 effects and underlying mechanisms of Yiqi Huoxue Decoction(YQHX)on mitochon-drial midzone division and peripheral fission in myocardial tissue after myocardial infarction(MI).METHODS A total of 48 male SPF-grade C57BL/6N mice were randomly divided into a sham-operated group(Sham,n=12)and a left anterior descending coronary ar-tery ligation MI model(n=36).After MI surgery,mice deemed to have successfully developed the model were randomly divided into a model group(MI,n=12),a YQHX group(n=12),and an empagliflozin group(EMPA,n=12)based on echocardiographic results.Four weeks after infarction,cardiac function and structural changes were comprehensively evaluated using echocardiography imaging,serum myocardial injury biomarkers,and hematoxylin-eosin(HE)staining.Transmission electron microscopy(TEM)was employed to observe mitochondrial ultrastructural,morphological,and quantitative changes at the peri-infarct zone.Myocardial mitochondria and cytoplas-mic fractions were isolated from myocardial tissue using a mitochondrial extraction kit,and the spatial expression changes of mitochon-drial fission-related proteins in both mitochondria and cytoplasm of the peri-infarct myocardium were analyzed by Western blot.These proteins included dynamin-related protein 1(Drp1),its phosphorylated form at serine 616(P-Drp1-Ser616),mitochondrial fission fac-tor(MFF),and mitochondrial fission protein 1(Fis1).RESULTS Compared with the MI group,mice in the YQHX group exhibited sig-nificantly increased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.000 1),as well as decreased left ventricular internal dimension-diastole(LVIDd)and left ventricular end-systolic diameter(LVIDs)(P<0.05,P<0.01),suggesting improved cardiac function.Additionally,serum levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)were significantly reduced in the YQHX group(P<0.05,P<0.001),indicating cardio-protective effects of YQHX against ischemic in-jury.HE staining showed that YQHX improved cellular morphology,suggesting structural improvement.TEM showed that YQHX sig-nificantly improved mitochondrial swelling and reduced mitochondrial fragmentation in the marginal zone of myocardial infarction,thereby preserving mitochondrial ultrastructure.Furthermore,Western blot showed that YQHX treatment significantly downregulated P-Drp1-Ser616 expression(P<0.05)in the cytoplasm.Interestingly,YQHX treatment significantly downregulated mitochondrial Fis1 expression(P<0.05),thereby inhibiting peripheral mitochondrial fission.Meanwhile,YQHX treatment significantly increased MFF ex-pression in mitochondria(P<0.01),which may promote mitochondrial midzone fission.CONCLUSION YQHX improves cardiac structure and function after MI,potentially by promoting myocardial mitochondrial midzone fission and inhibiting mitochondrial periph-eral fission in ischemic cardiomyocytes.

Objective:To investigate the clinical efficacy of botulinum toxin type A（BTX-A）bladder injection in the treatment of neurogenic detrusor overactivity（NDO）with autonomic dysreflexia（AD）.Methods:The patients with spinal cord injury at or above T6，who were treated at Guangdong Provincial Work Injury Rehabilitation Hospital from January 2018 to December 2022，were included in this study prospectively. Inclusion criteria：①chronic spinal cord injury patients over 18 years old（with no progression of neurological symptoms within 3 months）；② presence of NDO and AD；③ inadequate response or intolerance to oral antimuscarinic agent（M-receptor antagonists or β 3-receptor agonists）④ perform clean intermittent catheterization to empty the bladder. Exclusion criteria：① primary disease in the acute or progressive phase；② previous surgeries that would affect lower urinary tract function，such as transurethral sphincterotomy，bladder neck resection，prostatectomy，or bladder surgery；③ allergy to BTX-A or its adjuvants，or those with allergic predisposition ④ patients who were pregnant，breastfeeding，or planning for pregnancy in the near future；⑤ patients did not accept or were unable to perform intermittent catheterization. Before treatment，all patients were required to maintain 3-5 day urine diary，along with urodynamic studies（UDS），incontinence specific quality of life instrument（I-QOL）and AD symptom severity assessment，and blood pressure monitored. Key UDS parameters recorded included maximum bladder capacity，maximum detrusor pressure during filling phase，changes in maximum systolic blood pressure（SBP）relative to baseline（ΔSBP）during UDS examination，and the frequency of 24-hour blood pressure exceeding baseline by 20 mmHg. After general anesthesia or epidural anesthesia，BTX-A（200 U）was injected into the bladder at 30 points（including the triangle）under the cystoscope using a special injection needle，6.7 U per injection，and then the catheter was kept for 3-5 days after treatment. Three months later，relevant indicators were collected and compared with pre-treatment data. Results:A total of 43 patients were included in this study，including 34 males and 9 females. The age was（39.23±13.17）years old and the disease course was（2.69±3.27）years old. There were 33 cervical and 10 thoracic cases. The American Spinal Injury Association Injury Scale score distribution was as follows：26（60%）A，4（9%）B，9（21%）C，and 4（9%）D. The presence of AD was confirmed in all patients during urodynamic examination（UDS），that was the systolic blood pressure（SBP）suddenly increased and exceeded 20 mmHg（1 mmHg = 0.133 kPa）. Before treatment，The AD symptoms severity score（consist of headache，sweating，goose bumps，anxiety and palpitation）were（14.53±2.51），Bladder-related AD frequency was 10.67 episodes/day. Baseline SBP was（103.51±9.64）mmHg，the maximum SBP was（150.40±22.75）mmHg，and the change in SBP（ΔSBP）from maximum to baseline SBP during UDS examination was（43.83±21.01）mmHg. The UDS indicated that the maximum detrusor pressure during storage phase was（54.95±24.68）cmH 2O，and the bladder capacity was（131.70±75.29）ml. Bladder diary showed the volume of catheterization each time from was（181.16±49.86）ml，and The I-QOL score was（44.07±8.60）. Three months after treatment，the AD symptoms severity score（consist of headache，sweating，goose bumps，anxiety and palpitation）were（11.37±2.39）. The frequency of bladder-related AD episodes was（7.51±2.37）episodes/day，showing statistically significant differences compared to pre-treatment（ P<0.05）.The SBP before UDS examination was（102.12±10.28）mmHg，with no statistically significant difference from baseline（ P = 0.518）. The maximum SBP in perfusion phase and the ΔSBP were（132.84±16.30）mmHg and（28.72 ± 14.02）mmHg，respectively，both demonstrating statistically significant differences（ P < 0.05）. The UDS examination revealed that the maximum detrusor pressure during the storage phase was（29.77±13.72）cmH 2O，showed a significant decrease，and the bladder capacity was（272.63±79.75）ml，which were both statistically different before and after surgery. Bladder diary showed the volume of catheterization each time was（326.74±63.71）ml；I-QOL score was（71.86±11.45），both were significant different after treatment（ P < 0.01）. Conclusion:BTX-A intravesical injection in the treatment of NDO can also alleviate the severity and frequency of bladder related AD.

Objective Under the theory guidance of the Fuxingjue and the Tang-Ye-Jing-Fa map,this study aims to explore the common patterns and unique characteristics of five-flavor combinations in formulas for treating different syndromes of cough.Methods Chinese herbal formulas for cough treatment were collected from traditional Chinese medicine(TCM)clinical practice guidelines,consensuses,and textbooks,and their flavor combinations and distribution were clarified.Based on the theory of the Tang-Ye-Jing-Fa map regarding the five flavors for lung diseases(sour for tonifying,salty for purging,and pungent for transforming),the dominant flavors in each formula were statistically analyzed.Further classification was conducted according to the cold-heat properties and the amount of phlegm,and the characteristics and five-flavor combination patterns of formulas for different syndromes were analyzed.Results A total of 21 formulas for treating different syndromes of cough were statistically analyzed,among which 85.7%of the formulas had dominant flavors of"sour,salty,and pungent".For hot cough(9 formulas),sour was mainly used to tonify the lung and bitter to purge the heart(e.g.,Sangxing Tang and Qingjin Huatan Tang);for cold cough(4 formulas),pungent was mainly used to tonify the liver and warm yang(e.g.,San'ao Tang combined with Zhike San and Xiaoqinglong Tang);for cough with abundant phlegm(7 formulas),the focus was on using pungent to purge the spleen and eliminate dampness(e.g.,Erchen Tang combined with Sanzi Yangqin Tang);for cough with little or no phlegm(6 formulas),sour was used as the core to tonify the lung and nourish yin(e.g.,Sha Shen Mai Dong Tang).Conclusion From the perspective of the Tang-Ye-Jing-Fa map,the flavors of"sour,salty,and pungent"play an important role in the composition of formulas for treating cough.Although the five-flavor combinations of formulas for different syndromes of cough vary,they share common characteristics when classified according to cold-heat properties and phlegm amount.These findings provide a theoretical basis for optimizing the combination of Chinese herbal formulas for cough treatment by adjusting the proportion of the five flavors in clinical practice.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To investigate the clinical manifestation, therapy, and prognosis of Susac syndrome and enhance the understanding of this disease.Methods:A case summary was made.The clinical data of two siblings with Susac syndrome treated at Children′s Medical Center, Peking University First Hospital in January 2024 were summarized.Reported cases of pediatric Susac syndrome were reviewed.Results:The onset of the disease in the two siblings was at the age of 3.00 and 6.75 years, with recurrent headaches, tinnitus, hearing loss and encephalopathy symptoms.Cranial magnetic resonance imaging showed multiple cerebral microbleeding and microinfarction lesions, " snowball like" in the corpus callosum and diffuse white matter edema in the brain.Audiometry revealed sensorineural hearing loss.In one case, ophthalmic fluorescein angiography revealed ischemic changes due to branch retinal artery occlusions.No pathogenic variants were detected in gene testing.This child was diagnosed with Susac syndrome, and the symptoms were improved after treatment with Corticosteroids and Rituximab.No relapse was observed during the 9-month follow-up.A total of 20 pediatric cases of Susac syndrome were retrieved, including 18 reported previously and 2 cases from this study.There were 2 boys and 18 girls, with the age of onset ranging from 2.5 to 17.0 years.The common initial symptoms included headache (19 cases), vertigo and tinnitus or hearing loss (9 cases), and vision impairment or visual field defect (4 cases). The symptoms were improved after immunotherapy.Conclusions:With a low incidence, Susac syndrome is rare in children and difficult to diagnose.There may be a genetic predisposition in such disease.Early diagnosis and immunotherapy can low the relapse and improve the prognosis.