Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To construct an enhancer-based prognostic risk prediction model for non-small cell lung cancer (NSCLC) by integrating DNA methylome data and transcriptome data. Methods The weighted gene co-expression network analysis (WGCNA) was used to identify NSCLC related genes from the differentially methylated positions (DMPs) of enhancers. Based on the transcriptome data,the prognostic risk prediction model was constructed using LASSO-Cox regression algorithm. Results Through the analysis on DNA methylome data of NSCLC,19784 DMPs were obtained and their distribution patterns were characterized,including 6089 DMPs of enhancers. WGCNA analysis screened 79 highly correlated DMPs of enhancer with NSCLC from the 6089 DMPs. After analyzing the target genes of 79 DMPs with LASSO-Cox regression based on the transcriptome data,10 genes were used to construct a prognostic risk prediction model. The prognostic risk prediction model was evaluated by calculating the areas under the curve (AUC) of 3-,5-,and 10-year time-dependent receiver operating characteristic (ROC) curves in training set and validation set;and the results showed that the 3-,5-,and 10-year AUC in training set and validation set were all higher than 0.7. Finally,a nomogram was constructed to predict the 3-,5-,and 10-year survival probabilities of NSCLC. Conclusion This study provides new insights into the role of enhancers in NSCLC and has the potential to improve the prognosis by guiding personalized treatment decisions.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

The Chinese medicine Zha Gui,the senior manager of traditional Chinese medicine dispensing,plays an important role and key function in the"front store and back factory"Chinese medicine pharmacy.Inheriting the valuable experience and excellent culture of Chinese medicine Zha Gui is of great academic value and practical significance in clarifying the development of the discipline of traditional Chinese medicine,standardizing the technical operation of traditional Chinese medicine preparation,and promoting the"living inheritance"of the old pharmacist's skills.At the start of the new era and opening up to new thinking,this paper examined the rise of old Chinese medicine stores and Chinese medicine Zha Gui,analyzed the post responsibility,inheritance path and future development of Chinese medicine Zha Gui,and put forward the strategy of cultivating high-quality Chinese medicine Zha Gui talents,aiming at cultivating compound innovative talents in the traditional Chinese medicine industry in line with the needs of the contemporary society.

Objective:To establish a niraparib-resistant ovarian cancer cell line and preliminarily explore its biological characteristics and metabolic signatures.Methods:(1) Using ovarian adenocarcinoma cell line A2780 as parental cells, the niraparib-resistant cell line A2780-NiraR was established by the method of concentration gradient increased induction, and its morphological characteristics were observed using inverted phase-contrast microscope. The half-inhibitory concentration (IC 50) of niraparib was determined by cytotoxicity assay. (2) Cell proliferation was determined by cell count kit-8 (CCK-8) assay and direct cell counting assay, cell cycle distribution was analyzed by flow cytometry. (3) The differential metabolites between A2780 and A2780-NiraR cells were detected by non-target metabolomics based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC/HRMS). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted on the above differential metabolites to explore related metabolic pathways. Results:(1) Compared with the parental A2780 cells, A2780-NiraR cells exhibited predominantly short-spindle or oval morphology with reduced cellular projections and indistinct cell borders. The IC 50 values of niraparib were 3.17 and 26.19 μmol/L against A2780 cells and A2780-NiraR cells, respectively ( F=98.50, P<0.001). (2) A2780-NiraR cells had a slower proliferation rate compared with A2780 cells ( F=146.80, P<0.001). The doubling time of A2780-NiraR cells [(37.5±1.9) hours] was significantly longer than that of A2780 cells [(14.5±1.0) hours; t=10.50, P<0.001]. Compared with the parental A2780 cells, A2780-NiraR cells had a significantly lower S phase fraction [(44.5±0.7)% in A2780 cells, (30.2±2.9)% in A2780-NiraR cells; t=4.78, P<0.001] and higher G 0/G 1 phase fraction [(35.4±1.2)% in A2780 cells, (52.2±3.1)% in A2780-NiraR cells; t=5.10, P<0.001]. (3) The metabolites of A2780 and A2780-NiraR cells were analyzed by non-target metabolomics. Forty-four differential metabolites between A2780 and A2780-NiraR cells were screened using the orthogonal partial least squares-discriminant analysis (OPLS-DA) model, the majority of which were significantly increased, such as pyrrolidone carboxylic acid, L-lysine and 1-pyrroline-4-hydroxy-2-carboxylate. Pathway enrichment analysis indicated that the arginine metabolism, purine metabolism, and pyrimidine metabolism were the most significantly enriched pathways. Conclusion:A2780-NiraR cells have acquired a stable niraparib resistance phenotype, and metabolic pathways including arginine metabolism may serve as potential therapeutic targets for enhancing niraparib efficacy in ovarian cancer.

Objective:To establish a niraparib-resistant ovarian cancer cell line and preliminarily explore its biological characteristics and metabolic signatures.Methods:(1) Using ovarian adenocarcinoma cell line A2780 as parental cells, the niraparib-resistant cell line A2780-NiraR was established by the method of concentration gradient increased induction, and its morphological characteristics were observed using inverted phase-contrast microscope. The half-inhibitory concentration (IC 50) of niraparib was determined by cytotoxicity assay. (2) Cell proliferation was determined by cell count kit-8 (CCK-8) assay and direct cell counting assay, cell cycle distribution was analyzed by flow cytometry. (3) The differential metabolites between A2780 and A2780-NiraR cells were detected by non-target metabolomics based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC/HRMS). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted on the above differential metabolites to explore related metabolic pathways. Results:(1) Compared with the parental A2780 cells, A2780-NiraR cells exhibited predominantly short-spindle or oval morphology with reduced cellular projections and indistinct cell borders. The IC 50 values of niraparib were 3.17 and 26.19 μmol/L against A2780 cells and A2780-NiraR cells, respectively ( F=98.50, P<0.001). (2) A2780-NiraR cells had a slower proliferation rate compared with A2780 cells ( F=146.80, P<0.001). The doubling time of A2780-NiraR cells [(37.5±1.9) hours] was significantly longer than that of A2780 cells [(14.5±1.0) hours; t=10.50, P<0.001]. Compared with the parental A2780 cells, A2780-NiraR cells had a significantly lower S phase fraction [(44.5±0.7)% in A2780 cells, (30.2±2.9)% in A2780-NiraR cells; t=4.78, P<0.001] and higher G 0/G 1 phase fraction [(35.4±1.2)% in A2780 cells, (52.2±3.1)% in A2780-NiraR cells; t=5.10, P<0.001]. (3) The metabolites of A2780 and A2780-NiraR cells were analyzed by non-target metabolomics. Forty-four differential metabolites between A2780 and A2780-NiraR cells were screened using the orthogonal partial least squares-discriminant analysis (OPLS-DA) model, the majority of which were significantly increased, such as pyrrolidone carboxylic acid, L-lysine and 1-pyrroline-4-hydroxy-2-carboxylate. Pathway enrichment analysis indicated that the arginine metabolism, purine metabolism, and pyrimidine metabolism were the most significantly enriched pathways. Conclusion:A2780-NiraR cells have acquired a stable niraparib resistance phenotype, and metabolic pathways including arginine metabolism may serve as potential therapeutic targets for enhancing niraparib efficacy in ovarian cancer.

Objective To construct an enhancer-based prognostic risk prediction model for non-small cell lung cancer (NSCLC) by integrating DNA methylome data and transcriptome data. Methods The weighted gene co-expression network analysis (WGCNA) was used to identify NSCLC related genes from the differentially methylated positions (DMPs) of enhancers. Based on the transcriptome data,the prognostic risk prediction model was constructed using LASSO-Cox regression algorithm. Results Through the analysis on DNA methylome data of NSCLC,19784 DMPs were obtained and their distribution patterns were characterized,including 6089 DMPs of enhancers. WGCNA analysis screened 79 highly correlated DMPs of enhancer with NSCLC from the 6089 DMPs. After analyzing the target genes of 79 DMPs with LASSO-Cox regression based on the transcriptome data,10 genes were used to construct a prognostic risk prediction model. The prognostic risk prediction model was evaluated by calculating the areas under the curve (AUC) of 3-,5-,and 10-year time-dependent receiver operating characteristic (ROC) curves in training set and validation set;and the results showed that the 3-,5-,and 10-year AUC in training set and validation set were all higher than 0.7. Finally,a nomogram was constructed to predict the 3-,5-,and 10-year survival probabilities of NSCLC. Conclusion This study provides new insights into the role of enhancers in NSCLC and has the potential to improve the prognosis by guiding personalized treatment decisions.

The Chinese medicine Zha Gui,the senior manager of traditional Chinese medicine dispensing,plays an important role and key function in the"front store and back factory"Chinese medicine pharmacy.Inheriting the valuable experience and excellent culture of Chinese medicine Zha Gui is of great academic value and practical significance in clarifying the development of the discipline of traditional Chinese medicine,standardizing the technical operation of traditional Chinese medicine preparation,and promoting the"living inheritance"of the old pharmacist's skills.At the start of the new era and opening up to new thinking,this paper examined the rise of old Chinese medicine stores and Chinese medicine Zha Gui,analyzed the post responsibility,inheritance path and future development of Chinese medicine Zha Gui,and put forward the strategy of cultivating high-quality Chinese medicine Zha Gui talents,aiming at cultivating compound innovative talents in the traditional Chinese medicine industry in line with the needs of the contemporary society.

Objective To evaluate the safety of immediate breast reconstruction using deep inferior epigastric perforator (DIEP) flaps in the patients after neoadjuvant treatment. Methods From January 2019 to February 2021, the data of patients with breast cancer undergoing total mastectomy and immediate breast reconstruction using DIEP flap in Comprehensive Breast Health Center, Department of General Surgery, Ruijin Hospital were collected. Comparison of clinicopathological features was done between neoadjuvant treatment group and control group. Univariate analysis was used to compare the rate of surgical complications between two groups. Results A total of 110 patients were enrolled with 23 cases (20.9%) in neoadjuvant treatment group and 87 cases (79.1%) in control group. None of carcinoma in situ (0 vs. 19.5%, P=0.003) and higher pTNM stage (P<0.001) was present in neoadjuvant treatment group compared with those in control group. However, there were no significant differences in the number of flap perforator of DIEP (P=0.472), the proportion of bipedicled flaps (P=0.489), operative time (P=0.651) and hospital length of stay (P=0.275) between two groups. No significant difference was found in the incidence of postoperative complications between two groups. Breast seroma was the most common recipient complication (13.0%, 3 cases) without donor complication in neoadjuvant treatment group. The most common complication was fat necrosis (12.6%, 11 cases) in recipient site and abdominal seroma (3.4%, 3 cases) in donor site of control group. Reoperation was done in one case (4.3%) of neoadjuvant treatment group and 4 cases (4.6%) of control group. DIEP flap necrosis with total flap loss occurred in 2 cases (2.3%) in control group, but none in neoadjuvant treatment group. Conclusions The imme-diate breast reconstruction with epigastric free flap for breast cancer patients after neoadjuvant treatment would be a safe surgical scheme.

Objective To analyze the prognostic factors in the patients with HER2-positive breast cancer adjuvant treated with trastuzumab.Methods We conducted a retrospective analysis of clinical data of 1 246 patients diagnosed with HER2-positive breast cancer between January 2009 and December 2019 who received treatment with trastuzumab.We investigated the factors impacting their prognosis by the Log-rank test univariate analysis and multivariate COX regression analysis.Results HER2-positive patients treated with trastuzumab had a poor prognosis in pT2-3(HR=2.10,P=0.003),pN2-3(HR=2.81,P<0.001),and no endocrine therapy(HR=2.50,P<0.001),and that had a better prognosis combined with taxane or other chemotherapy regimens(HR=0.40,P=0.017).We divided the patients into two subgroups according to the status of lymph node metastasis,and we found that in the negative lymph nodes group the patients with pT2-3 stage had poor prognosis(P=0.020),while the patients combined with taxane or other chemotherapy had better prognosis(P=0.032).In the positive lymph nodes group the patients with pT2-3 stage and no endocrine therapy had poor prognosis(P=0.012,P=0.001).Conclusions The patients with HER2-positive breast cancer treated with trastuzumab can be managed in different categories,for individuals without lymph node involvement and small tumor sizes,combining therapy with non-anthracycline chemotherapy is preferable for achieving improved outcomes,for patients with lymph node metastasis and large tumor sizes,if chemotherapy options are available,it is more recommended to use an anthracycline-free regimen to ensure the same prognosis while reducing the harm caused by the toxic side effects of chemotherapy.