Construction and validation of a scoring model for pathogen characteristics and short-term prognosis risk prediction of candidemia / 解放军医学杂志

Objective To analyze the pathogenic characteristics and drug sensitivity of candidaemia,and construct a short-term mortality risk prediction scoring model.Methods The clinical data of patients with candidaemia admitted to the 909 Hospital of Joint Logistics Support Force from January 2011 to December 2020 were retrospectively analyzed,and the composition of pathogen composition,drug sensitivity test results and incidence of hospitalized patients were analyzed.324 cases of candidaemia were randomly divided into modeling group(190 cases)and validation group(134 cases),and the risk factors were screened by binary logistic regression.According to the odds ratio(OR)score,the 30 day mortality risk prediction scoring model was constructed,and the predictive performance of the model was verified both in modeling and validation groups.Results 356 strains of Candida including 126 strains of C.albicans(35.39%),79 strains of C.tropicalis(22.19%),74 strains of C.parapsilosis(20.79%),48 strains of C.glabrata(13.48%),14 strains of C.guilliermondii(3.93%),8 strains of C.krusei(2.25%),and 7 strains of other Candida(1.97%)were detected in 336 patients with candidemia.The incidence of candidaemia among hospitalized patients increased from 0.20 ‰ in 2011 to 0.48 ‰ in 2020.The resistance rate of candida to amphotericin B was significantly lower than that of fluconazole,voriconazole and itraconazole(P＜0.05).Among the 324 cases included in the model,95 patients died in 30 days after diagnosis,and the mortality rate was 29.32%.The proportion of males,fever,and parenteral nutrition in modeling group was significantly higher than that in validation group(P＜0.05),while the proportion of chronic lung disease and surgical history within one month were lower than those in validation group(P＜0.05).Logistic regression analysis showed that chronic renal failure,mechanical ventilation,severe neutropenia,failure to receive anti-fungal treatment within 72 hours,and APACHE Ⅱ≥20 were risk factors for short-term death of candidaemia,the OR values were 3.179,1.970,2.979,2.080,and 2.399,and the risk scores were 6,4,6,4,and 5,respectively.The area under the curve(AUC)of the risk scoring model for modeling group was 0.792(95%CI 0.721-0.862),and the result of Hosmer-Lemeshow(H-L)test was P=0.305;The AUC of validation group was 0.796(95%CI 0.735-0.898),and the H-L test result was P=0.329.A risk score≤8 indicated a low risk group for short-term mortality,a score of 9-15 indicated a medium risk group,and a score≥16 indicated a high risk group.Conclusions The incidence of candidemia in hospitalized patients is increasing and the mortality is high.The risk prediction score model can effectively predict the short-term prognosis and facilitate the early identification of the prognosis.

Distribution of urinary tract pathogens and susceptibility to nenofloxacin and levofolxacin in patients with community-acquired urinary tract infection / 中华泌尿外科杂志

Objective:To investigate the distribution characteristics of urinary tract pathogens in patients with community-acquired urinary tract infection and their sensitivity to nenoxacin and levofloxacin.Methods:This prospective, multicenter clinical trial included patients with community-acquired urinary tract infection who were admitted to urological clinics at 9 clinical research centers from November 2021 to August 2022.Inclusion criteria: Patients aged 18-70 years with community-acquired acute uncomplicated cystitis(AUC), recurrent acute episodes of urinary tract infection(rUTI), and non-febrile complicated urinary tract infection(cUTI) with signs of urinary tract irritation and abnormal elevation of routine white blood cells in urine. Exclusion criteria: ①Patients who received effective antimicrobial therapy within 72 h before enrollment and lasted for more than 24 h. ②Fever (>37.3℃) or symptoms of upper urinary tract infection such as low back pain, tapping pain in the kidney area, etc. ③Indwelling urinary catheter. At the first visit, clean midstream urine samples were taken for bacterial culture, and the distribution characteristics of urinary pathogens of different types of urinary tract infections were analyzed. Extended spectrum β-lactamases (ESBLs) were measured for Gram-negative bacteria. The susceptibility of nenoxacin and levofloxacin to urinary tract pathogens was determined by disk diffusion method. Drug resistance rate, sensitivity rate were analyzed between different disease groups.Results:There were 404 enrolled patients from 9 hospitals, including 364 (90.1%) females and 40 (9.9%) males. A total of 177 strains of pathogenic bacteria were isolated, among which the highest proportion of Escherichia coli was 66.1% (117/177).Klebsiella pneumoniae was followed by 6.8% (12/177) and Streptococcus agalactis 5.1% (9/177). The bacterial spectrum distribution of AUC and rUTI were similar, and the proportions of Escherichia coli were 70.6% (85/119) and 65.9% (29/44), respectively. However, the proportions of Escherichia coli isolated from cUTI patients were only 28.6% (4/14) and Enterococcus faecalis 7.1%(1/14). The overall detection rate of ESBLs in Gram-negative bacteria was 30.9%(43/139). The sensitivity rate of nenoxacin was 74.6%(91/122), and the resistance rate was 25.4%(31/122). The overall sensitivity rate of levofloxacin was 44.9%(70/156) and the resistance rate was 36.5%(57/156). The rate of resistance of urinary tract pathogens to levofloxacin was 48.2% (27/56) in patients with previous urinary tract infection history, and 30.0% (30/100) in patients with no previous urinary tract infection history, the difference was statistically significant( P=0.023).The sensitivity rate of Gram-negative bacteria to nenofloxacin was 70.7% (65/92) and that to levofloxacin was 50.0% (46/92, P<0.001). The sensitivity of Gram-positive bacteria to nenofloxacin was 80.0% (16/20), and that to levofloxacin was 70.0% (14/20, P=0.009). Conclusions:The bacterial profile of out-patient community acquired urinary tract infection varies greatly according to different diseases. The proportion of Escherichia coli in AUC and rUTI patients is higher than that in cUTI. The detection rate of ESBLs in Gram-negative bacteria was lower than the domestic average.Patients with a history of urinary tract infection had a high risk of treatment failure with levofloxacin. The sensitivity of common urinary tract pathogens to nenofloxacin was higher than levofloxacin.

Construction of a prognostic model and drug prediction for clear cell renal cell carcinoma based on endoplasmic reticulum stress-related lncRNA / 现代泌尿外科杂志

【Objective】 To construct a prognostic model of clear cell renal cell carcinoma (ccRCC) based on endoplasmic reticulum stress (ERS)-related long non-coding ribonucleotides (lncRNA),so as to explore the correlation between immune cell infiltration and prognosis of ccRCC patients,and to search for new drugs for the treatment of ccRCC. 【Methods】 The transcriptome and clinical data of cancerous and paracancerous tissues of ccRCC were obtained from the TCGA database.The ERS-associated gene set was obtained from the MSigDB database.ERS co-expressed lncRNAs were screened with Pearson correlation analysis.ERS-related lncRNA (ERSRL) with prognostic significance were screened with Lasso regression,univariate and multivariate Cox regression analyses,and a prognostic model was constructed.The risk value of each sample was calculated according to the prognostic model formula.The patients were divided into high- risk and low- risk groups for survival difference analysis.The predictive performance of the prognostic model was evaluated with survival curve,receiver operating characteristic (ROC) curve and calibration curve.The infiltration of immune cells in high-and low-risk groups was analyzed with CIBERSORT database.The relationship between ERSRL and drug sensitivity was analyzed with GDSC database to identify drugs with potential efficacy against ccRCC. 【Results】 A total of 9 lncRNAs with independent prognostic significance were screened to construct the prognostic model.Kaplan-Meier analysis showed significant survival differences between the high- and low-risk groups.Univariate and multivariate Cox regression analyses showed that age,grade,stage and risk score could be used as independent prognostic factors.The area under the ROC curve (AUC) of the 1-,3-,and 5-year survival rates of the training set were 0.754 (95%CI:0.659-0.848),0.744 (95%CI:0.667-0.815),and 0.759 (95%CI:0.662-0.820),respectively,and the C-index was 0.777 (95%CI:0.759-0.796).Immune infiltration results showed that plasma cells,activated memory CD4+T cells,regulatory T cells,M0 macrophages,and activated mast cell infiltration levels were higher in the high-risk group than those in the low-risk group.Drug susceptibility analysis identified 12 drugs with potential curative effects on ccRCC,including AZD8055. 【Conclusion】 Based on 9 ERSRLs,a prognostic model for ccRCC patients was constructed,and 12 drugs with potential therapeutic effects were screened,including AZD8055.

Changes in the isolation and drug resistance rate of Escherichia coli in a hospital over the past 10 years / 中国医科大学学报

Objective To summarize the isolation and drug resistance rate of Escherichia coliin The First Hospital of China Medical University over the past 10 years,in order to provide evidence for the efficacies of clinical anti-infection treatments.Methods The data was collected from Escherichia coli isolated from patients treated at The First Hospital of China Medical University between 2013 and 2022.VITEK 2 and VITEK MS were used for bacterial identification,VITEK2 and KB method were used for drug sensi-tivity testing,and WHONET 5.6 software was used for analysis.Results From 2013 to 2022,6 845 strains were isolated,including 80.5%from inpatients and 19.5%from emergency and outpatients.The specimens were most commonly found in the urine(57.8%),blood(15.0%),secretions(9.2%),and drainage fluid(8.1%).The isolation rate of extended-spectrumβ-lactamase(ESBL)producing Escherichia coli was 57.2%(54.3%to 61.5%).The drug resistance rate of Escherichia coli to carbapenems was low,at only 1.2%(0.2%to 2.6%).Conclusion Escherichia coli remains an important pathogen in clinical infections,with varying degrees of resist-ance to multiple antibiotics,and the resistance rate is increasing.Clinical physicians should pay sufficient attention to this issue.

Research progress of organoid models in bladder cancer / 中国肿瘤临床

Organoids are novel in vitro models that can effectively simulate the complexities of tumor microenvironments.Compared to tra-ditional preclinical models,organoids retain most of the histological and molecular properties of the primary tumor;therefore,they are more useful for studying tumor heterogeneity,underlying functional pathways,and immune microenvironments as well as for research on biomarker discovery,drug screening,and individual chemotherapy.Furthermore,current limitations,challenges such as low modeling suc-cess rates,high costs,and lack of standardization are expected to be overcome by continued innovations in bioengineering technologies and interdisciplinary integration.This article reviews the advantages,establishment processes,and prospects and challenges associated with the clinical application of organoids in bladder cancer.

Analysis of immune microenvironment and potential sensitive drugs in esophageal squamous cell carcinoma based on GEO database and bioinformatics method / 中国胸心血管外科临床杂志

@#Objective    To construct a prognostic model of esophageal squamous cell carcinoma (ESCC) based on immune checkpoint-related genes and explore the potential relationship between these genes and the tumor microenvironment (TME). Methods     The transcriptome sequencing data and clinical information of immune checkpoint genes of samples from GSE53625 in GEO database were collected. The difference of gene expression between ESCC and normal paracancerous tissues was evaluated, and the drug sensitivity of differentially expressed genes in ESCC was analyzed. We then constructed a risk model based on survival-related genes and explored the prognostic characteristics, enriched pathway, immune checkpoints, immune score, immune cell infiltration, and potentially sensitive drugs of different risk groups. Results    A total of 358 samples from 179 patients were enrolled, including 179 ESCC samples and 179 corresponding paracancerous tissues. There were 33 males and 146 females, including 80 patients≤60 years and 99 patients>60 years. 39 immune checkpoint genes were differentially expressed in ESCC, including 14 low expression genes and 25 high expression genes. Drug sensitivity analysis of 8 highly expressed genes (TNFRSF8, CTLA4, TNFRSF4, CD276, TNFSF4, IDO1, CD80, TNFRSF18) showed that many compounds were sensitive to these immunotherapy targets. A risk model based on three prognostic genes (NRP1, ICOSLG, HHLA2) was constructed by the least absolute shrinkage and selection operator analysis. It was found that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P<0.001). Similar results were obtained in different ESCC subtypes. The risk score based on the immune checkpoint gene was identified as an independent prognostic factor for ESCC. Different risk groups had unique enriched pathways, immune cell infiltration, TME, and sensitive drugs. Conclusion     A prognostic model based on immune checkpoint gene is established, which can accurately stratify ESCC and provide potential sensitive drugs for ESCC with different risks, thus providing a possibility for personalized treatment of ESCC.

Analysis of drug susceptibility test results of 697 cases of drug-resistant Mycobacterium tuberculosis in Hainan Province / 中国热带医学

@#Abstract: Objective To investigate the type and distribution of drug resistance of Mycobacterium tuberculosis (MTB) in Hainan tuberculosis hospital from 2019 to 2021, and to provide reference for the development of drug resistant tuberculosis prevention and control strategy. Methods From 2019 to 2021, a total of 1 687 strains of sputum were isolated and cultured and identified as MTB. Drug sensitivity testing was performed on eight anti-tuberculosis drugs: isoniazid (INH), rifampicin (RFP, R), ethambutol (EMB), streptomycin (SM), kanamycin (KM), capreomycin (CPM), ofloxacin (OFX), and propylthioisoniacamide (PTO). The drug resistance analysis was conducted. Results Among the 1 687 MTB strains, the overall drug resistance rate was 41.32% (697), with a single drug resistance rate of 11.62% (196), a multi-drug resistance rate of 4.10% (69), a extensive drug resistance rate of 23.71% (400), a pan-drug resistance rate of 1.90% (32), and a rifampicin resistance rate of 28.10% (474), and the main drug resistance types were extensive drug resistance and rifampicin resistance. The order of resistance to the eight drugs was OFX (64) > SM (62) > INH (48) > RFP (19) > CPM (2) > KM (1) > EMB (0) and PTO (0). The rate of resistance to INH and RFP of first-line drugs in newly treated patients was lower than that in retreated patients (χ2=0.110, 0.765; P>0.05); the rate of resistance to second-line drugs OFX, CPM and KM in initially treated patients was lower than that in retreated patients (χ2=1.037, 1.212, 1.653; P>0.05). The total drug resistance rate in 2019 was 51.16%, which was higher than that in 2020 (35.08%) and 2021 (38.89%). The difference between groups was significant (χ2=29.25,16.60; P=0.000), but there was no significant difference in overall drug resistance rate between 2020 and 2021 (χ2=1.823, P=0.177). Among the occupational types of tuberculosis patients, farmers were the main ones, accounting for 56.25% (949). The patients with drug-resistant tuberculosis were mainly distributed in Haikou City (165) > Wanning City (72) > Chengmai County(64) > Wenchang City (51) = Dongfang City (51) > Danzhou City (48), and patients in these six areas accounting for 64.71%(451/697). Conclusions The drug resistance rate of tuberculosis in Hainan Province is relatively high, with OFX and SM resistance being the main types of drug resistance. The extensive drug resistance rate is higher than the national average level. Therefore, surveillance and treatment should be strengthened and optimized to reduce the prevalence of drug-resistant tuberculosis.

The role of long-chain non-coding RNA LINC-PINT in drug sensitivity of hypoxia induced in head and neck squamous cell carcinoma through the Hippo/YAP signaling pathway / 实用肿瘤学杂志

Objective The aim of this study was to investigate the role of long chain non-coding RNA LINC-PINT in drug sensitivity of hypoxia induced in head and neck squamous cell carcinoma(HNSCC)through the Hippo/Yes-associated protein(YAP)signaling pathway.Methods The proliferative changes of HNSCC cell lines(AGZY-973 cells,HN4 cells,and HN30 cells)and nor-mal human oral keratinocytes(NHOKs)in hypoxic environment were detected by CCK-8 assay;HN30 cells in good condition were taken and set them as the normal group,hypoxia group,hypoxia+LINC-PINT overexpression group,and hypoxia+overexpression negative control group.The expression of LINC-PINT in HN30 cells was detected by qRT-PCR;CCK-8 assay was applied to de-tect the drug sensitivity of HN30 cells,and the effect of cisplatin on proliferation in HN30 cells;cell apoptosis was detected by flow cy-tometry;and Western blot was applied to detect the expression of hypoxia inducible factor-1α(HIF-1α),p-YAP,and YAP protein in HN30 cells.Results Under hypoxia conditions,the proliferative rates of AGZY-973 cells,HN4 cells and HN30 cells were obvi-ously higher than that of NHOKs cells(P＜0.05).Compared with the normal group,the IC50 value,the expression of HIF-1 α and p-YAP/YAP in the hypoxic group were obviously increased in HN30 cells,the rate of apoptosis,the rates of cell growth inhibition at 24 h and 48 h,and the expression of LINC-PINT protein were obviously decreased(P＜0.05);Compared with the hypoxia+overex-pression negative control group,the IC50 values,the expression of HIF-1α and p-YAP/YAP cells in the hypoxia overexpression of LINC-PINT group was obviously reduced in HN30,the rates of apoptosis,the rates of cell growth inhibition at 24 h and 48 h,and the expression of LINC-PINT protein were significantly increased(P＜0.05).Conclusion Overexpression of LINC-PINT can en-hance the hypoxia-induced cisplatin sensitivity in HNSCC,which may be related to the inhibition of the activation of Hippo/YAP sig-naling pathway.

A novel cuproptosis-related gene signature for prediction of prognosis, drug sensitivity and immunotherapy response in patients with hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To construct a novel cuproptosis-related gene signature (CRGS) for prediction of prognosis, immunotherapy response and drug sensitivity in patients with hepatocellular carcinoma (HCC).Methods:Data materials for this study were obtained from the international cancer genome consortium (ICGC), the cancer genome atlas (TCGA) database and Migort210 database, and protein expression profiles were obtained from the human protein atlas image classification database. Based on the TCGA cohort, the least absolute shrinkage and selection operator algorithm was applied to construct the CRGS and calculate the risk score for each HCC patient. HCC patients were grouped according to the median risk score: HCC patients in the TCGA cohort were divided into a high-risk group TCGA and a low-risk group TCGA with 184 cases in each group; HCC patients in the ICGC cohort were divided into a high-risk group ICGC and a low-risk group ICGC with 116 cases in each group. Patients in the Migort210 cohort were divided into a responder group ( n=68) and a non-responder group ( n=230) based on their response to immunotherapy. We assessed the value of CRGS in predicting the prognosis of HCC patients in the TCGA cohort and validated whether CRGS could be used to predict the prognosis of HCC patients in the ICGC dataset. To explore the role of CRGS in predicting immunotherapy response and drug sensitivity in HCC patients based on data from the TCGA cohort, and to apply the Migort210 immunotherapy cohort to validate the clinical value of CRGS in predicting immunotherapy in malignant tumors. Results:CRGS consists of four copper death-related genes: GLS, CDKN2A, LIPT1, and DLAT. Patients in the high-risk group TCGA had lower overall survival (OS), disease-specifical survival, and progression-free interval than those in the low-risk group TCGA (all P<0.01). OS of patients in the high-risk group ICGC was lower than that in the low-risk group ICGC ( P=0.022). Multivariate Cox regression analysis showed that CRGS was an independent risk factor for poor prognosis in HCC patients (TCGA: HR=2.991, 95% CI: 1.781-5.049, P<0.001; ICGC: HR=4.621, 95% CI: 1.685-12.674, P=0.033). Risk scores were positively correlated with the expression levels of CTLA4, PDCD1, CD80 and HLLA2 (all P<0.001). Patients in the high-risk group TCGA had lower tumor immune dysfunction and rejection scores than those in the low-risk group TCGA [-0.04(-0.07, -0.02) vs. -0.02(-0.04, 0) points], and the difference was statistically significant ( P<0.001). Patients in the responder group had a higher risk score than the non-responder group [1.70 (1.56, 1.90) vs. 1.63 (1.52, 1.80)], with a statistically significant difference ( P<0.05). The half-inhibitory concentrations (IC 50) for sunitinib, rapamycin and etanercept were higher in the high-risk group TCGA than that in the low-risk group TCGA, while the IC 50 for erlotinib was lower than that in the low-risk group TCGA, and the differences were all statistically significant (all P<0.001). Conclusion:The CRGS might be served as a potential biomarker to predict the prognoses, immunotherapy response, and drug sensitivity of patients with HCC.

Effect of MXRA7 on the Biological Functions of Acute B Lymphoblastic Leukemia Cell Line REH / 中国实验血液学杂志

OBJECTIVE@#To discover the relationship between matrix remodeling associated 7 (MXRA7) and acute B lymphoblastic leukemia (B-ALL), and explore the effect of MXRA7 on the biological functions of B-ALL cell line REH.@*METHODS@#The expression of MXRA7 in blood diseases was searched and analyzed through BloodSpot database. Real-time qPCR was used to detect the expression level of MXRA7 in B-ALL cell line 697 and REH cells. Lentivirus-mediated shRNA interference technology was utilized to knock down the expression of MXRA7 in REH cells. The effects of MXRA7 on the biological functions of REH cells were studied by in vitro experiments. Cell proliferation was detected by CCK-8 assay, cell cycle was detected by PI staining, cell apoptosis was detected by Annexin V and 7-AAD staining, and the expression of apoptosis pathway related proteins was detected by Western blot.@*RESULTS@#Database analysis showed that MXRA7 was highly expressed in B-ALL patients, and real-time qPCR results showed that MXRA7 was also highly expressed in cell lines 697 and REH cells. Knockdown of MXRA7 in REH cells inhibited the cell proliferation and increased the percentage of G0/G1 phase cells. After treatment with cytarabine, the apoptotic ratio was increased in MXRA7-impaired REH cells, and the activation of caspase-3 and caspase-9 were also increased.@*CONCLUSION@#Knockdown of MXRA7 can reduce the malignancy of REH cells by inhibiting the cell proliferation and increasing the sensitivity of REH cells to cytarabine. These results indicate MXRA7 may be as a novel target for the treatment of B-ALL, and the potential usefulness of MXRA7 in B-ALL deserves further investigation.

Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma / 中国医学科学杂志(英文版)

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

Deubiquitinating enzyme JOSD2 affects susceptibility of non-small cell lung carcinoma cells to anti-cancer drugs through DNA damage repair / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and mechanisms of deubiquitinating enzyme Josephin domain containing 2 (JOSD2) on susceptibility of non-small cell lung carcinoma (NSCLC) cells to anti-cancer drugs.@*METHODS@#The transcriptome expression and clinical data of NSCLC were downloaded from the Gene Expression Omnibus. Principal component analysis and limma analysis were used to investigate the deubiquitinating enzymes up-regulated in NSCLC tissues. Kaplan-Meier analysis was used to investigate the relationship between the expression of deubiquitinating enzymes and overall survival of NSCLC patients. Gene ontology enrichment and gene set enrichment analysis (GSEA) were used to analyze the activation of signaling pathways in NSCLC patients with high expression of JOSD2. Gene set variation analysis and Pearson correlation were used to investigate the correlation between JOSD2 expression levels and DNA damage response (DDR) pathway. Western blotting was performed to examine the expression levels of JOSD2 and proteins associated with the DDR pathway. Immunofluorescence was used to detect the localization of JOSD2. Sulforhodamine B staining was used to examine the sensitivity of JOSD2-knock-down NSCLC cells to DNA damaging drugs.@*RESULTS@#Compared with adjacent tissues, the expression level of JOSD2 was significantly up-regulated in NSCLC tissues (P<0.05), and was significantly correlated with the prognosis in NSCLC patients (P<0.05). Compared with the tissues with low expression of JOSD2, the DDR-related pathways were significantly upregulated in NSCLC tissues with high expression of JOSD2 (all P<0.05). In addition, the expression of JOSD2 was positively correlated with the activation of DDR-related pathways (all P<0.01). Compared with the control group, overexpression of JOSD2 significantly promoted the DDR in NSCLC cells. In addition, DNA damaging agents significantly increase the nuclear localization of JOSD2, whereas depletion of JOSD2 significantly enhanced the sensitivity of NSCLC cells to DNA damaging agents (all P<0.05).@*CONCLUSIONS@#Deubiquitinating enzyme JOSD2 may regulate the malignant progression of NSCLC by promoting DNA damage repair pathway, and depletion of JOSD2 significantly enhances the sensitivity of NSCLC cells to DNA damaging agents.

Antimicrobial Sensitivity Pattern of Bacterial Isolates Associated with Urinary Tract Infection in a Tertiary Care Hospita

Introduction : Urinary Tract Infection (UTI) is a common infection and a major health problem. Considering the bacterial resistance developed globally, knowledge regarding sensitivity and resistance pattern of isolated uropathogens in a defined area becomes critically important for choosing appropriate antimicrobial agents for treatment. Objectives : We conducted this study to detect the common UTI causing microorganisms and to evaluate their culture sensitivity pattern in a Tertiary Care Hospital. Methods : This retrospective record based observational study was conducted over a period of two months (January and February, 2021). Patients in the General Ward in the Department of General Medicine, Medical College, Kolkata whose urine samples were collected within 48 hours of admission were included. Identification of bacteria was done by standard microbiologic methods and using Kirby disc diffusion test their antimicrobial susceptibility test was performed. The causative organisms for UTI along with its antibiotic sensitivity pattern were retrospectively reviewed and analysed. Results : Among 150 culture positive samples 34.67% were from male and 65.33% were from female with highest prevalence in the age group of 21-30 years (22.67%). Most prevalent uropathogens isolated was Escherichia coli (E coli) (60.66%) followed by Enterobactor (21.33%) and Klebsiella (9.33%). E coli showed most sensitivity against ceftazidime, clarithromycin, piperacillin-tazobactam and clindamycin (100% in all cases). Resistance (>70%) of E coli was found against levofloxacin and cefotaxime. Conclusion : The present study reveals microbiological profile regarding UTI in patients attending our hospital. As resistant to first line antibiotic is increasing, antibiotic stewardship programme should be strengthened. Antibiotic policies agreed among Clinicians, Microbiologists and Pharmacologists will guide good prescribing, provide maximum coverage for treating infections and ensure antibiotic cycling.

Analysis of pathogens and drug sensitivity in bronchoalveolar lavage fluid of children with severe community acquired pneumonia in Qingdao area / 中国小儿急救医学

Objective:To analyze the distribution and drug sensitivity of pathogens in bronchoalveolar lavage fluid(BALF)of children with severe community acquired pneumonia(CAP)in Qingdao from 2018 to 2020.Methods:The clinical data of 482 children with severe CAP in Qingdao admitted to Women and Children′s Hospital of Qingdao University were collected.BALF was collected by bronchoscopy for detection of bacteria and mycoplasma.Results:(1)Bacterial infection was detected in 139 cases(27.84%), mycoplasma infection in 119 cases(24.69%), and virus infection in 141 cases(29.25%). (2)The detection rates of bacteria and virus infection in the 1-12 months old group were higher.The detection rate of mycoplasma pneumoniae was the highest in the group over 5 years old.(3)A total of 139 strains were positive in bacterial culture of lavage fluid under bronchoscope: 55 strains(39.57%) of gram-negative bacilli and 84 strains(60.43%) of gram-positive cocci.Streptococcus pneumoniae was the most common gram-positive bacteria.Haemophilus influenzae was the most common gram-negative strain.(4)Streptococcus pneumoniae and Staphylococcus aureus were highly sensitive to amoxicillin clavulanate potassium, vancomycin and linezolid.The resistance rate to erythromycin was high(100%). (5)Haemophilus influenzae, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were highly sensitive to meropenem and cefoperazone sulbactam.They were highly resistant to amoxicillin, ampicillin and cefuroxime(>80%).Conclusion:Severe CAP in Qingdao area is mainly caused by virus and bacteria within 1 year old.Mycoplasma pneumoniae infection is the main cause of children over 5 years old.Respiratory syncytial virus, adenovirus and parainfluenza virus are main causes of virus infection.Streptococcus pneumoniae and haemophilus influenzae are the main pathogens, which are more sensitive to vancomycin, linezolid, meropenem and cefoperazone sulbactam, but resistant to erythromycin and amoxicillin.

Etiology and drug sensitivity of bacterial keratitis in recent 40 years in China: a Meta-analysis / 中华实验眼科杂志

Objective:To evaluate the distribution and drug sensitivity of pathogenic bacteria in patients with bacterial keratitis in recent 40 years in China.Methods:A Meta-analysis was conducted.Five databases including PubMed, ScienceDirect, Embase, CNKI and Wanfang Data Knowledge Service Platform were searched.The research was limited to the hospital-based cross-sectional studies published in Chinese and English between 1980 and 2020, without limitations of subject.Two researchers followed the inclusion and exclusion criteria to complete literature retrieval, data extraction and methodological quality evaluation.The literature quality was assessed with reference to a methodological scoring system for rates. Q test and I2 test were used to quantify the degree of heterogeneity of the included literature.According to the heterogeneity, the fixed effects model or random-effects model was used to calculate the combined rates indicators to perform the Meta-analysis. Results:Twenty-seven original studies were incorporated, including 50 046 cases of bacterial keratitis.A random-effects model for the Meta-analysis showed that the positive rate of bacterial culture in bacterial keratitis was 28% (95% CI: 0.24-0.32). Among the culture-positive bacteria, the percentages of gram-positive cocci and gram-negative bacilli were 57% (95% CI: 0.52-0.62) and 32% (95% CI: 0.28-0.37), respectively.The percentages of gram-positive bacilli and gram-negative cocci were 8% (95% CI: 0.06-0.10) and 1% (95% CI: 0.01-0.02), respectively.In the recent 40 years, the proportion of gram-positive cocci isolated from corneas in China was on the rise, and the proportion of gram-negative bacilli was on the decline.Among them, coagulase-negative Staphylococcus accounted for 23% (95% CI: 0.17-0.30), followed by Pseudomonas aeruginosa 18% (95% CI: 0.14-0.23), Streptococcus pneumoniae 8% (95% CI: 0.06-0.12), Staphylococcus aureus 6% (95% CI: 0.04-0.08), Corynebacterium 4% (95% CI: 0.03-0.07), and Escherichia coli 4% (95% CI: 0.02-0.06). The results of the drug sensitivity test showed that gram-positive cocci were highly sensitive to vancomycin, moxifloxacin, levofloxacin and ofloxacin. Pseudomonas aeruginosa was most sensitive to tobramycin, and Escherichia coli was most sensitive to ofloxacin. Conclusions:This Meta-analysis indicates that the proportion of gram-positive cocci isolated from corneas in China has been on the rise, while the proportion of gram-negative bacilli was on the decline during the recent 40 years.Coagulase-negative Staphylococcus and Pseudomonas aeruginosa have become the most common pathogens of bacterial keratitis in China.The sensitivity of various bacteria to commonly used antibiotics shows a downward trend.The sensitive antibiotics should be selected correctly according to the drug sensitivity results.

The role of SDH2 gene in the environmental adaptability of Candida albicans / 药学实践杂志

Objective To investigate the role of SDH2 gene in the environmental adaptability of Candida albicans. Methods Wild-type C. albicans strain SC5314, SDH2 gene knockout mutant sdh2Δ/Δ and reintegrated strain sdh2Δ/SDH2 were used as experimental objects. Spot assay was conducted to assess the sensitivity of the WT C. albicans strain SC5314, SDH2 gene knockout mutant sdh2Δ/Δ and reintegrated strain sdh2Δ/SDH2 to external stress stimulants and antifungal drugs. The effect of SDH2 gene deletion on drug efflux ability of C. albicans was determined by rhodamine 6G efflux assay. Results After SDH2 gene deletion, C. albicans showed slight tolerance to cell wall stress stimulants caffeine, oxidative stress stimulators diamide and menadione. Notably, the sensitivity of SDH2 gene knockout mutant sdh2Δ/Δ to azole antifungal drugs was significantly increased. The drug efflux capacity of C. albicans was decreased due to the deletion of SDH2 gene. Conclusion SDH2 gene deletion lead to changes in environmental adaptability of C. albicans, including changes in response to external environmental stress and increased sensitivity to azole antifungal drugs. The development of fungal-specific inhibitor targeting SDH2 gene may lead to the discovery of new antifungal drugs which have synergistic effect with azole drugs.

Pathogen and clinical characteristics of bacterial enteritis in a third class children′s hospital in Shanghai city from 2016 to 2020 / 中国小儿急救医学

Objective:To investigate the pathogens and drug resistance of bacterial enteritis in children, analyze the clinical characteristics of bacterial enteritis in children, and provide basis for clinical diagnosis and treatment.Methods:The fecal culture strain and drug sensitivity of patients with bacterial enteritis admitted to our hospital from January 2016 to December 2020 were analyzed and summarized, and the clinical characteristics of patients who were infected by Salmonella and Escherichia coli were compared.Results:There were a total of 173 patients, aged from 21 days to 15 years, with a median age of 2.00(1.10, 3.54)years.Bacterial enteritis was most likely to occur in summer and autumn, and the incidence rate was 40.5% and 29.5%, respectively.One hundreds and seventy-three strains of bacteria were cultured in feces, including 148 strains of Salmonella(85.5%), 18 strains of Escherichia coli(10.4%), five strains of Staphylococcus aureus and two strains of Shigella.One hundreds and one of 141 patients who were infected with Salmonella were detected for leukocytes of in feces(71.6%), and four of 16 patients with Escherichia coli were detected for leukocytes(25.0%). The difference was significant( χ2=14.1, P<0.001). Eighty-eight of 113 patients(77.9%) who were infected by Salmonella with increased CRP(CRP>8 mg/L)and the proportion in Escherichia coli infection cases was 6/13(46.2%). There was significant difference( χ2=4.63, P=0.03). The drug sensitivity of Salmonella and Escherichia coli was summarized.There was no carbapenem resistant strain cultured; The sensitivity to piperacillin/tazobactam and cefoperazone/sulbactam was higher than 85%; The sensitivity to cefepime, ceftazidimeand ceftriaxone was higher than 75%; The sensitivity to ampicillin was lower than 30%, and the sensitivity to quinolones was between 20%-40%. Conclusion:Children aged 1-3 years are prone to bacterial enteritis in summer and autumn.The most common pathogens causing bacterial enteritis are Salmonella and Escherichia coli.White blood cells are more easily detected in feces of patients with Salmonella infection, and the increase rate of C-reactive protein in peripheral blood is higher.Patients with bacterial enteritis are recommended to use the third-generation cephalosporins and aforementioned antibiotics and piperacillin/tazobactam for empirical treatment.The sensitivity to quinolones is reduced, and may not be suitable for clinical application.

In vitro activity of Schinus terebinthifolius extract and fractions against Sporothrix brasiliensis

BACKGROUND Sporothrix brasiliensis is the causative agent of zoonotic cases of sporotrichosis in Brazil and is associated with atypical and severe presentations in cats, dogs, and humans. Sporotrichosis treatment is usually time- and cost-consuming, sometimes with poor response and host toxicity. Schinus terebinthifolius has proven efficacy against bacteria and fungi of clinical interest. OBJECTIVE To determine the in vitro activity of S. terebinthifolius against S. brasiliensis. METHODS Five S. brasiliensis isolates and three reference strains were subjected to a hydroethanol extract derived from the leaves of S. terebinthifolius and its fractions. The minimal inhibitory concentration (MIC) was determined using the broth microdilution method according to the M38-A2 CLSI guidelines. Also, the fungicidal/fungistatic activity of the extract and fractions was studied. FINDINGS The crude extract of S. terebinthifolius inhibited the growth of S. brasiliensis (MIC: 0.5-1.0 µg/mL), while the partitioned extracts dichloromethane, ethyl acetate, and butanol demonstrated growth inhibition at 8 µg/mL due to a fungistatic activity. MAIN CONCLUSIONS Due to its in vitro efficacy against S. brasiliensis and its known pharmacological safety, S. terebinthifolius is a candidate to be tested using in vivo models of sporotrichosis.

In vitro antibacterial effects of imipenem combined with conventional antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae / 中国基层医药

Objective:To investigate the in vitro antibacterial effects of imipenem combined with common antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae (CRKP) targeting bla KPC-2 gene. Methods:Six strains of unrepeated bla KPC-2 type confirmed by polymerase chain reaction and DNA sequence were isolated in Yueqing People's Hospital, China between January 2018 and January 2019 were included in this study. The susceptibility rate of imipenem against nine conventionally used antibiotics was determined. The sensitivity test of imipenem combined with eight antibiotics was performed with the checkerboard method. Fractional inhibitory concentration was calculated to assess the efficacy of imipenem combined with common antibiotics. The in vitro treatment time-antibacterial effect curve was drawn to evaluate the antibacterial effects. Results:The resistance rate of six strains of bla KPC-2 type was 100.00% (6/6) for imipenem, meropenem, ceftazidime, ciprofloxacin, rifampicin and cefotaxime, and it was 66.67% (4/6) for minocycline and clavulanic acid and 33.33% (2/6) for tigecycline. Imipenem combined with tigecycline had a better antibacterial effect and exhibited a synergistic effect on four strains of bla KPC-2 type CRKP and an additive effect on two strains of Bla KPC-2 type CRKP. The curve of time for in vitro treatment of KPN2 with imipenem combined with tigecycline against bactericidal effect revealed that the antibacterial rate of imipenem at the 1/2 minimum inhibitory concentration combined with tigecycline at the 1/4 minimum inhibitory concentration was > 95% at (t+2) and the antibacterial effect could maintain (t+10) hours to (t+12) hours. The antibacterial rate of imipenem combined with tigecycline against strain 002 was gradually decreased with time, and the growth curve of strain 002 rised gradually. Conclusion:In vitro drug sensitivity test revealed that imipenem combined with tigecycline exhibits a good synergistic effect on bla KPC-2 type CRKP. Findings from this study provide a reference for clinical treatment of bla KPC-2 type CRKP.

Analysis of main clinical features and pathogenic bacteria of lacrimal tracheitis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the main clinical features, pathogen distribution and drug sensitivity of lacrimal angiitis, and to provide evidence for clinical diagnosis and treatment.<p>METHODS:Retrospective study. A total of 45 patients(45 eyes)diagnosed with lacrimal angiitis in Hebei Eye Hospital from December 2016 to October 2020 were selected to analyze the general information, clinical manifestations and previous treatment history, bacterial culture results, and drug sensitivity test results.<p>RESULTS:All 45 patients had monocular disease, including 21 eyes with tears, increased secretion, conjunctival congestion in inner canthus, 14 eyes with red and swollen inner canthus, 6 eyes similar to eyelid cyst, and 4 eyes were found and diagnosed during routine preoperative examination. 27 eyes were previously diagnosed with other eye diseases, and the misdiagnosis rate was 60.0%. The positive rate of bacterial culture was 80.0%(36/45), Staphylococcus epidermidis was the most common, followed by Streptococcus; 52.8%(19/36)of the patients were infected with multidrug-resistant bacteria. The sensitivity rate of bacteria to fluoroquinolones(82.9%, 97/117)was higher than that of aminoglycosides(70.1%, 68/97)and cephalosporins(68.1%, 111/163). Except vancomycin, rifampicin, levofloxacin and chloramphenicol were highly sensitive to Gram-positive bacteria.<p>CONCLUSION: Staphylococcus epidermidis is the most common pathogen of dacryocystitis, followed by Streptococcus. Levofloxacin and rifampicin can be the first choice antibiotics for local anti-infection. Rational drug use can reduce the formation of multidrug-resistant bacteria. The cure rate can be improved by complete removal of stones by incision and plasty of lacrimal canaliculus.