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.

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.

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.

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.

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.

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.

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.

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.

Examination of Ureaplasma urealyticum and Mycoplasma hominis in 4082 Chinese patients

The objective of this study was to analyze the infection rate and drug resistance of Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) in the genitourinary tract of Chinese patients. From December 2018 to June 2019, vaginal secretion or urinary secretion of outpatients in our hospital were selected for culture and drug sensitivity analysis of Ureaplasma urealyticum and Mycoplasma hominis. In 4082 Chinese samples, 1567 Mycoplasma were detected, a detection rate of 38.39%, among which 1366 cases were UU single positive, accounting for 33.47%, 15 cases were MH single positive, accounting for 0.36%, 186 cases were UU and MH mixed positive, accounting for 4.56%. The most affected age groups were 21-30 years and 31-40 years, accounting for 19.09 and 15.05%, respectively. The results of drug sensitivity showed that doxycycline, minocycline, josamycin, clarithromycin, and roxithromycin were more sensitive to mycoplasma infection. The distribution of Ureaplasma urealyticum and Mycoplasma hominis in the human genitourinary system and their sensitivity to antibiotics is different for sex and age groups.

Prediction of drug-induced cell viability by SAE-XGBoost algorithm based on LINCS-L1000 perturbation signal / 生物工程学报

Different cell lines have different perturbation signals in response to specific compounds, and it is important to predict cell viability based on these perturbation signals and to uncover the drug sensitivity hidden underneath the phenotype. We developed an SAE-XGBoost cell viability prediction algorithm based on the LINCS-L1000 perturbation signal. By matching and screening three major dataset, LINCS-L1000, CTRP and Achilles, a stacked autoencoder deep neural network was used to extract the gene information. These information were combined with the RW-XGBoost algorithm to predict the cell viability under drug induction, and then to complete drug sensitivity inference on the NCI60 and CCLE datasets. The model achieved good results compared to other methods with a Pearson correlation coefficient of 0.85. It was further validated on an independent dataset, corresponding to a Pearson correlation coefficient of 0.68. The results indicate that the proposed method can help discover novel and effective anti-cancer drugs for precision medicine.

Analysis of Mycobacterium tuberculosis drug susceptibility test results and its spatial distribution characteristics in Dali Bai Autonomous Prefecture from 2017 to 2019 / 中华检验医学杂志

Objective:Analyze the drug resistance of Mycobacterium tuberculosis (MTB) to commonly used anti-tuberculosis drugs and its spatial distribution in Dali Bai Autonomous Prefecture from 2017 to 2019, which would provid a reference for the treatment of tuberculosis and the prevention and control of drug-resistant tuberculosis. Methods:A total of 1 013 Mycobacterial strains were isolated from sputum samples in the tuberculosis laboratories of the designated People′s hospital of 12 counties (cities) of Dali Bai Autonomous Prefecture from January 2017 to December 2019. Proportional method was used to conduct drug susceptibility tests and strain identification of 6 anti-tuberculosis drugs. Further used ArcMap10.2 and GeoDa1.14 software to visualize the map display and spatial autocorrelation analysis of the drug resistance of MTB.Results:From 2017 to 2019, the drug resistance rates of MTB in Dali Prefecture were 10.33%(28/271), 10.35%(55/531) and 30.00%(51/170), respectively, showing an rising trend ( χ2=26.62, P<0.05). Among 1 030 samples, 972 strains (95.95%) was MTB and 41 strains (4.05%) was non-tuberculous Mycobacterium (NTM). The total resistance rate of 972 strains of MTB was 13.79% (134/972), of which the single resistance rate was 6.59% (64/972), the multi-drug resistance rate was 4.84% (47/972), and the poly-drug resistance rate was 2.06% (20/972), the rate of extensive drug resistance is 0.31% (3/972). There are 25 combinations of drug resistance patterns. The detection rate of NTM was 4% (41/1 013), among which Midu County had the highest detection rate (0.89%, 9/1 013). The spatial distribution showed that the number of MTB resistant strains among counties and cities had a negative spatial correlation (Moran′s I value was -0.367, P<0.05). It shows that there is no clustering of drug resistance among counties and cities, and the resistance is serious in individual counties and cities. Yongping County and Nanjian Yi Autonomous County had low and high aggregation, and Yunlong County had high and low aggregation. Conclusions:The drug resistance of MTB showed an rising trend in Dali Bai Autonomous Prefecture from 2017 to 2019. The number of drug-resistant strains among regions was not randomly distributed, the regional difference was large, and spatial autocorrelation analysis provided theoretical clues and basis for the formulation of drug resistance prevention and control measures for tuberculosis in the whole state.

Identification and analysis of two Mycobacterium abscess with different morphology / 中华检验医学杂志

Two types of Mycobacterium abscesses (Mab) were found in sputum from a patient with severe pneumonia in May 2020. One was Mycobacteriumabscessus with smooth morphology (Mab S), the other was Mycobacteriumabscessus with rough morphology (Mab R). Both of them were compared and drug susceptibility testing were performed to provide clinical scientific diagnosis and treatment. Morphology, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA were used to analyze Mab S and Mab R, phylogenetic evolution tree was constructed by gene sequence alignment for homology, proportion and broth drug test were used for in vitro drug sensitivity test. There were morphological differences between Mab S and Mab R. MALDI-TOF MS analysis showed that there were 223 protein peaks in Mab R and 147 protein peaks in Mab S. Mab S contained 1 397 bp and Mab R contained 1 402 bp as 16s rRNA gene sequencing revealed. Drug susceptibility testing showed that both of them were almost resistant to all antituberculosis drugs, but sensitive to most of antibiotics. Mab S and Mab R were not only different in manifestations, but also in protein and gene comparison. Both of them were generally resistant to antituberculosis drugs. Antibiotic combined therapy has been confirmed to be an effective treatment in clinic.

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.

Development of molecular markers of Mycobacterium tuberculosis rifampicin resistance gene rpoB by PARMS technology / 生物工程学报

The purpose of this study is to provide a simple and reliable genetic typing approach for molecular drug susceptibility test of Mycobacterium tuberculosis, through the developing of fluorescence molecular marker of rifampicin resistance gene rpoB. Eleven fluorescent molecular markers of the rpoB gene were established by using the sequence difference between the amino acid positions 531, 526, 516, 511 and 513 of rpoB gene of rifampicin-resistant strains and the alleles of rifampicin-sensitive strains, combined with the PARMS technique (Penta-primer amplification refractory mutation system). We used 104 clinical isolates of Mycobacterium tuberculosis to validate this marker and it was verified by sequencing as 100% correct. These samples were also tested with proportional drug sensitivity test. The coincidence rate was 94.23%. The molecular markers had high reliability for genotyping of rpoB gene. It can also detect low-concentration drug-resistant samples (511/533 unit point mutations) whose phenotypic susceptibility cannot be detected. The eleven sets of fluorescent molecular markers could cover 92%-96% of rpoB gene mutation types of rifampicin-resistant strains, and provide new idea for rapid detection of rifampin-resistant Mycobacterium tuberculosis.

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.

Sensitization of hepatocellular carcinoma cells towards doxorubicin and sorafenib is facilitated by glucosedependent alterations in reactive oxygen species, P-glycoprotein and DKK4

Altered glucose uptake and metabolism is the key characteristic of cancer cells including hepatocellularcarcinoma (HCC). However, role of glucose availability in chemotherapeutic outcome of HCC is unclear. Thepresent study investigates the effect of glucose facilitated sensitization of HCC cells towards doxorubicin(DOX) and sorafenib (SORA). In HCC cells, we observed that hyperglycemic culture condition (HG) isassociated with increased sensitivity towards DOX and SORA. P-glycoprotein (P-gp), a transporter involved indrug efflux, was elevated in HCC cells in NG, rendering them less susceptible to DOX and SORA. Further, thisstudy demonstrated that knockdown of dickkopf protein 4 (DKK4), a Wnt antagonist protein, causes enhancedglucose uptake and reduction in P-gp level rendering HCC cells in NG sensitive to DOX and SORA.Moreover, HG elevates the level of intracellular reactive oxygen species (ROS), which regulates P-gp.Alteration in intracellular ROS did not directly affect regulation of DKK4 in HCC cells. Functional assayssuggest that alterations in DKK4 and P-gp level in HCC cells are dependent on glucose availability andchanges in ROS level because of enhanced glucose utilization, respectively. Collectively, the present studyhighlights direct involvement of glucose-induced ROS, DKK4 and P-gp in altering the sensitivity of HCC cellstowards DOX and SORA.

A study on risk factors of intestinal bacteria colonization and antibiotic resistance in NICU neonates / 中国新生儿科杂志

Objective To study the risk factors of intestinal bacteria colonization and antibiotic resistance among newborns in neonatal intensive care unit (NICU).Method From May 2014 to May 2015,newborns admitted to NICU in our hospital were enrolled and their feces were prospectively collected and cultured from day 5 to day 7 after birth.VITEK-2 system was used to identify the bacteria and determine their antibiotic susceptibility.Newborns were assigned into 8 groups according to their gestational age,mode of delivery and use of antibiotics,and the colonization rates of Escherichia coli (E.coli),Enterococcus and Klebsiella pneumoniae were compared.Result A total of 572 feces of newborns were collected,328 strains of E.coli,243 strains of Enterococcus and 70 strains of Klebsiella pneumoniae were isolated.The multi-drug resistance rates of E.coli and Enterococcus were 68.3％ (136/199) and 76.1％ (185/243),respectively.The colonization rates of E.coli,Enterococcus and Klebsiella pneumoniae of the full-term delivery without antibiotics group (77 cases),full-term Cesarean section (C-section) without antibiotics group (30 cases),premature C-section without antibiotics group (28 cases),premature delivery without antibiotics group (16 cases),premature delivery with antibiotics group (53 cases),full-term delivery with antibiotics group (155 cases),full-term C-section with antibiotics group (99 cases),premature C-section with antibiotics group (114 cases) were different.The antibiotics groups showed significantly less E.coli colonization rates and higher Enterococcus colonization rates than the non-antibiotics groups of the same gestational age and delivery mode (P ＜ 0.05).The result between the full-term C-section newborns and naturally delivered newborns without antibiotics indicated the similar trend (P ＜ 0.05).The colonization rates of Klebsiella pneumoniae showed no significant differences among the groups (P ＞ 0.05).Conclusion The multi-drug resistance of E.coli and Enterococcus in neonatal intestinal colonization is common and worrisome.Bacterial colonization is affected by antibiotics and the mode of delivery and prudent use of antibiotics is advised.

Standardizing Diagnosis of Helicobacter pylori Infection to Improve Diagnostic Accuracy / 胃肠病学

Eradication of Helicobacter pylori (Hp) is important for the prevention and treatment of chronic gastritis, peptic ulcer and gastric cancer. The Chinese consensus on the management of Hp infection has taken "confirmed Hp infection" as an indication for eradication. The World Gastroenterology Organisation global guideline states the "test-and-treat strategy" for Hp infection. Accurate diagnosis of Hp infection is a prerequisite for standardized eradication. There are many methods to diagnose Hp infection. Each has its advantages and disadvantages. Different methods are suitable for different diseases and patients, and each method has strict requirements for reagents, equipment, testers and patients. Therefore, increasing the awareness of physicians and testers about the standardized diagnosis of Hp infection is essential to improve the diagnostic accuracy.