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 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.

Purpose To investigate the correlation between tumor budding in penile squamous cell carcinoma(SCC)and its clinicopathological features.Methods Clinical data and pathological slides from 69 cases of penile SCC were collected.Tumor budding was examined microscopically,and statistical analyses were performed to assess the relationship between tumor budding and various clinicopathological features.Results Among the 69 cases of pe-nile SCC,41 cases exhibited low-grade tumor budding and 28 cases displayed high-grade tumor budding.Tumor bud-ding was significantly correlated with tumor size,urethral invasion,invasion of the urethral corpus spongiosum,inva-sion of the penile corpus cavernosum,tumor necrosis,nerve invasion,vascular tumor thrombus,and pathological T stage(all P＜0.05).In contrast,no significant association was found between tumor budding and HPV-related versus non-HPV-related penile SCC(P＞0.05).Log-rank survival analysis indicated that patients with high-grade tumor bud-ding had a significantly lower survival rate compared to those with low-grade tumor budding(P＜0.05).Conclusion Tumor budding is a distinct pathological feature of penile SCC,and high-grade tumor budding is associated with a more aggressive biological behavior.

Objective:To explore the prognostic influencing factors of patients with pulmonary large cell neuroendocrine carcinoma (LCNEC), to develop a nomogram-based predictive model for the overall survival (OS) of LCNEC patients and to make validation.Methods:The clinical data of 2 947 patients with LCNEC in the Surveillance, Epidemiology, and End Results (SEER) database (the modeling group) and 147 patients with LCNEC in Beijing Chest Hospital Affiliated to Capital Medical University from 2010 to 2023 (the validation group). The data of patients in the both groups were compared. Cox proportional hazards model was used to screen out the factors influencing the OS of patients with LCNEC. A nomogram model was constructed to predict the OS based on the multivariate analysis result. Internal validation of the predictive model's performance was conducted through 500 repeated samplings based on the Bootstrap method. The predictive performance of the nomogram model was evaluated by using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The consistency index (CI) was used to analyze the discrimination of the nomogram model in predicting the survival of LCNEC patients; calibration curves were used to analyze the consistency between the survival predicted by the nomogram model and the actual survival outcomes; and the decision curve analysis (DCA) was used to assess the net benefit of the model for actual clinical decision-making.Results:The differences in the proportions of patients with different age, gender, race, tumor staging, N stage, M stage, hepatic metastasis or not, pulmonary metastasis or not, chemotherapy and radiotherapy or not between the modeling group and the validation group were statistically significant (all P < 0.05). The median OS time of LCNEC patients in the modeling group was 14.0 months, with the 1-year OS rate of 53.3% and the 5-year OS rate of 21.2%; the median OS time of LCNEC patients in the validation group was 17.5 months, with the 1-year OS rate of 58.7%; there was no statistically significant difference in OS between the 2 groups ( P = 0.280). In the modeling group, the median OS time of female and male LCNEC patients was 18.0 and 12.0 months, respectively, and the difference in OS between the 2 groups was statistically significant ( P < 0.05); for patients with stage Ⅰ-Ⅱ, Ⅲ, and Ⅳ LCNEC, the median OS time was 48.0, 16.0, and 6.0 months, respectively, and the difference in OS among the 3 groups was statistically significant ( P < 0.05); the median OS time of patients receiving surgery and not receiving surgery was 28.0 and 8.0 months, respectively, and the difference in OS between the 2 groups was statistically significant ( P < 0.05). The differences in OS among female and male, patients in stages Ⅰ-Ⅱ, Ⅲ and Ⅳ, patients who underwent surgery or not were statistically significant (all P < 0.05). The results of multivariate Cox regression analysis in the modeling group showed that patients aged >60 years old (>60 years old vs. ≤60 years old: HR = 1.234, 95% CI: 1.114-1.367, P < 0.01), M 1 stage (M 1 stage vs. M 0 stage, HR = 2.646,95% CI: 2.385-2.935, P < 0.001), T 2-4 stage (T 2-4 stage vs. T 1 stage: HR = 1.199, 95% CI: 1.147-1.252, P < 0.001), N 1-3 stage (N 1-3 stage vs. N 0 stage: HR = 1.281, 95% CI: 1.225-1.340, P < 0.001) were independent risk factors of the OS in patients with LCNEC; female (female vs. male: HR = 0.877, 95% CI: 0.805-0.956, P = 0.003), surgery (yes vs. no: HR = 0.612, 95% CI: 0.554-0.676, P < 0.001), chemotherapy (yes vs. no: HR = 0.520, 95% CI: 0.470-0.575, P < 0.001) were independent protective factors of the OS in patients with LCNEC. A nomogram model for predicting 1, 3, and 5-year OS rates of LCNEC patients was constructed based on age, gender, T stage, N stage, M stage, surgery and chemotherapy. The result of ROC curve analysis indicated that the AUC of the nomogram model for predicting 1, 3, and 5-year OS rates in the modeling group was 0.822, 0.821 and 0.821, respectively, while the AUC of 1-year OS rate predicted by the validation group was 0.660. The CI of the modeling group and the validation group was 0.756 and 0.660, respectively. The calibration curve showed that 1, 3, and 5-year OS rates predicted by the modeling group were highly consistent with the actual OS rates. The DCA showed that the nomogram model for predicting OS in the modeling group and the validation group both had good clinical net benefits. Conclusions:The constructed nomogram model for predicting the prognosis of LCNEC patients is proved to be reliable and has good clinical values.

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.

Purpose To investigate correlation of ADP ribosylation-like factor 6 interacting protein 4(ARL6IP4)expression with the pathological characteristics and clinical prognosis in primary colon cancer.Methods The ARL6IP4 mRNA expression in tumor and adjacent normal tissues of 133 colon cancer patients was analyzed by RT-qPCR,and its relationship with tumor location,pathological TNM stage,and 3-year survival prognosis was assessed.Additionally,ARL6IP4 protein expression was analyzed by immunohistochemistry in 30 cases,of which 16 cases were analyzed by immunofluorescence.Results The colon cancer presented significantly higher mRNA and protein levels of ARL6IP4 than adjacent normal tissues(t=4.221,P=5.200 × 10-5;t=7.421,P=3.537 × 10-8).The relative ex-pression level of ARL6IP4 mRNA in colon cancer was positively correlated with pathological TNM stage,N stage and M stage(P＜0.05),and negatively correlated with 3-year cumulative survival probability(P＜0.01).Additionally,sig-moid colon cancer presented significantly higher ARL6IP4 expression than other colon cancers,and at the cellular lev-el,ARL6IP4 was predominantly expressed in the cell nucleus.Conclusion The ARL6IP4 expression in colon cancer is higher than that in adjacent normal tissues,which is closely related to tumor metastasis and clinical prognosis.

AIM To evaluate the quality of Croci Stigma from different producing areas.METHODS The analysis was performed on a 25 ℃ thermostatic Waters Acquity UPLC HSS T3 column(2.1 mm× 100 mm,1.8μm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 0.35 mL/min in a gradient elution manner,and the detection wavelengths were set at 254,440 nm.The UPLC fingerprints were established,after which orthogonal partial least squares discriminant analysis was performed,picrocrocin,crocin-Ⅰ,crocin-Ⅱ,crocin-Ⅲ,crocin-Ⅳ contents and chromaticity values(L*,a*,b*,E*ab)were determined,Pearson correlation analysis was adopted in the investigation of correlations between chromaticity values and internal constituent contents.RESULTS There were 14 common peaks in the fingerprints for 22 batches of medicinal materials with the similarities of more than 0.98.Various batches of medicinal materials were clustered into 2 types,7 quality difference components were screened.crocin-Ⅰ content in medicinal materials from different producing areas demonstrated significant differences(P＜0.05);the redder the color of medicinal material,the higher the contents of crocins.Picrocrocin,crocin-Ⅰ,crocin-Ⅱ,crocin-Ⅳ contents displayed highly significant correlations with colorimetric values(P＜0.01),while crocin-Ⅲ content exhibited no significant correlation with the latter(P＞0.05).CONCLUSION This accurate and reliable method can provide references for the quality control and color-quality relationship elucidation of Croci Stigma.

Objective:To analyze the echocardiographic and genetic characteristics of fetuses with common arterial trunk（CAT）.Methods:A retrospective analysis was conducted on 77 480 fetal echocardiograms examined at the Maternal-Fetal Medicine center in Fetal Heart Disease of Beijing Anzhen Hospital from November 2010 to November 2024.Among them，106 fetuses were initially diagnosed with CAT，and 95 cases were ultimately confirmed（0.1%，95/77 480）. The echocardiographic and genetic features of CAT fetuses were analyzed. According to the modified Van Praagh classification，CAT was divided into types A1-A4［with ventricular septal defect（VSD）］and B1-B4（without VSD）based on the origin of the pulmonary artery branches and the presence or absence of a VSD. Additionally，CAT was categorized into isolated and complex types based on the presence of associated intracardiac or extracardiac anomalies.Results:① Among the 95 confirmed CAT fetuses，type A accounted for 90.5%（86/95），and type B accounted for 9.5%（9/95）. All 9 type B CAT fetuses exhibited no overriding of the arterial trunk ， with 8 cases showing left ventricular hypoplasia accompanied by mitral atresia or absence.② Of the 95 CAT fetuses，14 were isolated（14.7%，14/95） ， and 81 were complex（85.3%，81/95）.The main associated intracardiac anomalies included：single ventricle（22 cases），complete atrioventricular septal defect（12 cases），anomalous pulmonary venous drainage（10 cases），right aortic arch with mirror-image branching（16 cases），and persistent left superior vena cava（14 cases）. ③ Genetic testing was performed in 31 fetuses，with 18 showing positive results，primarily 22q11.21 deletion syndrome（29.0%，9/31）. Conclusions:Apart from VSD，the most common intracardiac anomaly associated with CAT fetuses is single ventricle. Type B CAT without trunk overriding is often associated with left ventricular hypoplasia and mitral atresia or absence. The most frequent genetic abnormality in CAT fetuses is 22q11.21 deletion syndrome. Prenatal echocardiography should clarify the CAT subtype and associated anomalies，and genetic testing is strongly recommended for perinatal counseling and prognostic evaluation.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics