First Line Anti-Tuberculosis Drugs Resistance Patterns of <i>Mycobacterium tuberculosis</i>Isolates from Newly Diagnosed Cases of Tuberculosis

Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.

Use of Cost Effective Semi-Automated (Mannual/Micro) MGIT System over BACTEC 960 to Perform First Line Anti-Tuberculosis Drugs Sensitivity Testing

Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.

Pyrrolidine dithiocarbamate alleviates the anti-tuberculosis drug-induced liver injury through JAK2/STAT3 signaling pathway:An experimental study

Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.

Follow-up Study of Retreatment TB Patients with Sputum Smear and/or Culture Positive Two Years after They were Declared Cured with First-line Anti-TB Drugs in Shandong Province

This study aimed to learn the recurrence rate in the retreatment TB patients with sputum smear and/or culture positive （ss＋ and/or c＋） two years after they were declared cured, and to explore causes of recurrence in order to improve long-time treatment outcome. 5 cities were selected as research locations. Recurrence of TB was judged by chest X-ray examination together with sputum smear and culture examination.

Adverse Drug Reactions in Patients on Second Line Anti-Tubercular Drugs for Drug Resistant Tuberculosis in Rural Tertiary Care Hospital in North India

Introduction: The adverse drug events (ADEs) to second-line anti-TB drugs are one of the major reasons for the patients default on treatment. A general awareness of various adverse drug events (ADE) and their management is essential for the effective management of tuberculosis. Identification of adverse drug reaction profile of patients can be useful for the early detection, management and prevention of adverse drug events. Material and methods: It was a prospective observational study conducted after approved Institutional Ethics Committee. A total of 104 drug resistant tuberculosis patients registered from 1st November 2012 to 31st October 2013 started with second line anti-tubercular drugs under PMDT-RNCP after taking written informed consent. Adverse drug reaction during treatment recorded and assessed by Hart wig and WHO scale. Results: 87% patients experienced adverse drug reactions. Total 346 ADR were reported. Most common were gastritis (65%) and arthralgia (60.6%), others were nausea (35.6%), vomiting (32.7%), hyperuricemia (30.8%), giddiness (27%), anorexia (17.3), generalized weakness (15.4), insomnia (10.6%), psychosis (8.6%), hearing impairment (6.7%), hypersensitivity reaction (5.8%), peripheral neuropathy (4.8%), visual disturbance (3.8%), nephrotoxicity (2.9%), forgetfulness (2.9%), gynaecomastia (1.9%), hypothyroidism (1%), seizure (1%), and thrombocytopenia (1%). Conclusion: Majority of patients experienced wide range adverse drug reactions. Most of patients faced the problem within 2 - 3 months of initiation of treatment and managed by symptomatic. Early identification, prompt management and standardized reporting adverse drug reactions at all the level of healthcare are needed.

Online-SPE-UPLC-MS/MS检测生活污水中20种毒品

对生活污水的前处理进行优化,建立了一种在线固相萃取-超高效液相色谱-串联质谱法(Online-SPE-UPLC-MS/MS)同时测定污水中20种毒品及人口标记物的方法。用金属螯合剂Na_(2)EDTA·2H_(2)O处理污水后加入同位素内标,接着用滤膜过滤后,以双柱交替模式上样。用Waters Oasis HLB固相萃取柱(2.1 mm×30 mm,20μm)进行富集浓缩后,用流动相将固相萃取柱上吸附的目标物反冲洗到Waters ACQUITY UPLC HSS T3色谱柱(2.1 mm×100 mm,1.8μm)上。柱温40℃,以乙腈-0.1%(体积分数)甲酸水溶液为流动相,采用梯度程序洗脱。采用电喷雾离子源正离子、多反应监测(MRM)模式定量检测。可替宁的线性范围在20~5000 ng·L^(-1),其余20种物质的线性范围在1~250 ng·L^(-1)之间,相关系数R2均大于0.99,检出限在0.01~0.25 ng·L^(-1)之间,加标回收率在91.57%~113.94%,精密度均小于15%。基于Online-SPE-UPLC-MS/MS建立了同时测定污水中20种毒品及人口标记物方法,该方法操作简单、灵敏高,具有良好的准确度和精密度,已成功应用于城市污水中的毒品检测,用于监测毒品滥用情况。

Effect of Antisense Oligodeoxynucleotide Directed to NF-κB-RelA on Bcl-x_L mRNA in Extended Drug Resistance Leukemia Cell Line HL- 60/E6

To explore the effect of NF κB on bcl x gene transcription in extended drug resistance leukemia cell line HL 60/E6, drug resistant subline HL 60/E6 was derived by intermittently exposing HL 60 cells to 6 ng/ml epirubicin. Indirect immunofluorescence was used to demonstrate the location of NF κB RelA in HL 60/E6 cells. FCM analysis and RT PCR were used to detect the efficiency of liposome mediated ODN transfection and the change of bcl x L mRNA levels after 5 μmol/L phosphorothioate (PS) derivatized antisense (AS) oligodeoxynucleotide (ODN) directed to RelA was transferred into HL 60/E6 cells. The results showed that RelA remained persistently active and located at the nuclei of HL 60/E6 cells,but in the cytoplasm of HL 60 cells, the efficiency of liposome mediated ODN transfection was significantly higher than that of null ODN ( P <0.01 in 4 h, 6 h, 12 h, 24 h). Exposure of HL 60/E6 cells to 5 μmol/L AS PS ODN directed to RelA led to a maximal 40 % decline of bcl x L mRNA levels within 8 h. The inhibition rate of bcl x L mRNA was (15±1.79) %, (28±2.34) %, (40±3.47) %, (20±1.54) % in 4 h, 6 h, 8 h, 15 h, respectively, but it was less than 15 % in control group. It was concluded that NF κB was involved in regulating bcl x transcription. It was suggested that NF κB was an important factor for drug resistance in leukemia cells.

EXPRESSION AND REVERSION OF DRUG RESISTANCE-AND APOPTOSIS-RELATED GENES OF A DDP-RESISTANT LUNG ADENOCARCINOMA CELL LINE

Objective: To investigate the co-expression of drug resistance- and apoptosis-related genes of cisplatin (CDDP)-selected lung adenocarcinoma cell line A 549 DDP for compared to the parental cell line A549, and reverse of drug resistance by antisense s-oligodeoxynucleotides (S-ODNs) of differentially expressed genes. Methods: Sense and antisense S-ODN were transferred into A 549 DDP cells by lipofectin. The expression of drug resistance and apoptosis related genes was examined by RT-PCR, immunocytochemistry and flow cytometry, respectively. Apoptostic cells were identified by DNA electrophoresis and terminal deoxynucleotidyl transferase (TdT)-mediated biotin dUTP nick end-labeling(TUNEL). Drug resistance of tumor cells was detected by a cell viability (MTT) assay. Results: The expression of bcl-2 was positive and that of multidrug resistance-associated protein (MRP) at mRNA and protein level was increased in A 549 DDP compared to A549 cells. MDR1, c-myc and topoisomeras II (TOPO II) were similarly co-expressed in two cell lines. Both cell lines were negative for c-erbB-2 expression. In A 549 DDP cells, the expression of bcl-2 and MRP was significantly inhibited by their respective antisense S-ODNs. Antisense S-ODNs could also decrease significantly drug resistance of A 549 DDP cells to CDDP by promoting cell apoptosis. Conclusion: Both intrinsic and acquired drug resistance were involved in co-expression of multiple MDR-related genes in lung adenocarcinoma. Cooperation of bcl-2 and MRP genes appeared to play an important action to confer the resistance of A 549 DDP cells to CDDP. Their antisense S-ODNs are responsible for the decrease of drug resistance of this cell line by promoting apoptosis.

First report on establishment and characterization of the extrahepatic cholangiocarcinoma sarcoma cell line CBC2T-2

BACKGROUND Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice.These cells consist of both epithelial and mesenchymal cells.Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma.However,cholangiocarcinoma sarcoma cell lines are not available in cell banks.AIM To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line,namely CBC2T-2.METHODS We conducted a short tandem repeat(STR)test to confirm the identity of the CBC2T-2 cell line.Furthermore,we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies.The tumorigenic potential of CBC2T-2 cells was tested in vivo using nonobese diabetic/severe combined immunodeficient(NOD/SCID)mice.The cells were injected subcutaneously and tumor formation was observed.In addition,immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts.The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma.Lastly,whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line.RESULTS The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue.The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology.The cells exhibited a high proliferation ratio with a doubling time of 47.11 h.This cell line has migratory,invasive,and clonogenic abilities.The chromosomes in the CBC2T-2 cells were polyploidy,with numbers ranging from 69 to 79.The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice.CBC2T-2 cells and xenografts were positive for both the epithelial marker,CK19,and the mesenchymal marker,vimentin.These results suggest that CBC2T-2 cells may have both epithelial and mesenchymal characteristics.The cells were also used to screen clinical agents in patients with cholangiocarcinoma sarcoma,and a combination of paclitaxel and gemcitabine was found to be the most effective treatment option.CONCLUSION We established the first human cholangiocarcinoma sarcoma cell line,CBC2T-2,with stable biogenetic traits.This cell line,as a research model,has a high clinical value and would facilitate the understanding of the pathogenesis of cholangiocarcinoma sarcoma.

Establishment and characterization of a new human ampullary carcinoma cell line,DPC-X1

BACKGROUND An in-depth study of the pathogenesis and biological characteristics of ampullary carcinoma is necessary to identify appropriate treatment strategies. To date, only eight ampullary cancer cell lines have been reported, and a mixed-type ampullary carcinoma cell line has not yet been reported.AIM To establish a stable mixed-type ampullary carcinoma cell line originating from Chinese.METHODS Fresh ampullary cancer tissue samples were used for primary culture and subculture. The cell line was evaluated by cell proliferation assays, clonal formation assays, karyotype analysis, short tandem repeat(STR) analysis and transmission electron microscopy. Drug resistances against oxaliplatin, paclitaxel, gemcitabine and 5-FU were evaluated by cell counting kit-8 assay. Subcutaneous injection 1 × 106 cells to three BALB/c nude mice for xenograft studies. The hematoxylin-eosin staining was used to detect the pathological status of the cell line. The expression of biomarkers cytokeratin 7(CK7), cytokeratin 20(CK20), cytokeratin low molecular weight(CKL), Ki67 and carcinoembryonic antigen(CEA) were determined by immunocytochemistry assay.RESULTS DPC-X1 was continuously cultivated for over a year and stably passaged for more than 80 generations;its population doubling time was 48 h. STR analysis demonstrated that the characteristics of DPC-X1 were highly consistent with those of the patient’s primary tumor. Furthermore, karyotype analysis revealed its abnormal sub-tetraploid karyotype. DPC-X1 could efficiently form organoids in suspension culture. Under the transmission electron microscope, microvilli and pseudopods were observed on the cell surface, and desmosomes were visible between the cells. DPC-X1 cells inoculated into BALB/C nude mice quickly formed transplanted tumors, with a tumor formation rate of 100%. Their pathological characteristics were similar to those of the primary tumor. Moreover, DPC-X1 was sensitive to oxaliplatin and paclitaxel and resistant to gemcitabine and 5-FU. Immunohistochemistry showed that the DPC-X1 cells were strongly positive for CK7, CK20, and CKL;the Ki67 was 50%, and CEA was focally expressed.CONCLUSION Here, we have constructed a mixed-type ampullary carcinoma cell line that can be used as an effective model for studying the pathogenesis of ampullary carcinoma and drug development.

Research progress on the drug action and resistance mechanism in Mycobacterium tuberculosis

Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and extensive use of anti-tuberculosis drugs,multidrug-resistant(MDR)TB,drug-resistant(XDR)TB and totally drug-resistant(TDR)TB became obstacles to the tuberculosis eradication worldwide.According to the World Health Organization(WHO)statistics,China is not only a high burden tuberculosis country in the world,but also a country with a serious epidemic of MDR.Traditional drugs fail to meet the needs of tuberculosis control.Therefore,it is urgent to find new targets of anti-tuberculosis drugs and develop new anti-tuberculosis drugs.Hence,this paper systematically summarizes the mechanism of traditional and newly developed anti-tuberculosis drugs,in which stressing the research progress of drug resistance mechanisms.This work provides us with new insights of new anti-tuberculosis drug developments,and may contribute to a reduction in the harm that tuberculosis brings to society.

Expression of cyclooxygenase-2 mRNA in drug-sensitive cell and drug-resistant strains of ovarian cancer cell lines

Objective： To investigate the expression of cyclooxygenase-2 （COX-2） mRNA in drug-sensitive cell and drugresistant clones of ovarian cancer cell lines. Methods： RT-PCR and immunocytochemistry were used to investigate the expression of cyclooxygenase-2 in 3 clones drug-sensitive and 5 clones drug-resistant ovarian cancer cell. Results： Strong COX-2 mRNA expressions were detected in 3 clones of drug-sensitive cell and weak expressions were detected in 5 clones of drug-resistant cell. The protein expression of COX-2 in drug-sensitive cell was strongly positive reaction in immunocytochemistry stain and there was a weak positive reaction in 5 clones of drug-resistant cell. Conclusion： The expression of COX-2 mRNA in drug-sensitive cell strains is much higher than that in drugresistant strains of ovarian cancer cell lines, providing a basis of the chemoprevention for ovarian cancer.

Pharmacological Isolation of Experimental Models of Drug-resistant Hepatocellular Carcinoma Cell Line

Drug resistance is one of the major challenges facing the success of chemotherapy against human hepatocarcinoma (HCC) as well as other types of cancer. Studies with cell lines can serve as initial screening for agents that could modulate drug resistance. Development of a good experimental model of drug-resistant cells is a prerequisite for the success of such cellular studies;but could be laborious and generally time-consuming. Additionally, the high mortality rate associated with advanced HCC calls for a probe into the mechanism of resistance by developing experimental model that mimics clinical method of its treatment. Consequently, we have reported a simplified method of selection of drug-resistant hepatocarcinoma cells from human hepatocellular carcinoma (HEPG2) cell line using pharmacologic agents, cisplatin (CDDP) and 5-fluorouracil (5-FU). HEPG2 cell line was incubated for 24 hours with different concentrations of CDDP (0 - 20 μM) or 5-FU (0 - 100 μM). Cell viability was assayed by CCK-8 (Cell Counting Kit) analysis, and the inhibitory concentrations (IC50) for CDDP and 5-FU were established by dose-dependent cytotoxicity curves. The IC50(s) were confirmed by flow cytometric analysis of cell death due to CDDP or 5-FU. Clinical method of treatment was imitated by treating the parental HEPG2 cell line in pulse, at the optimal concentration of either CDDP or 5-FU for 4 to 6 hours. Induction was repeated 6 times, whilst allowing the cells to attain at least 70% confluence between intervals of induction. The resultant drug-resistant sublines, (HEPG2CR) and (HEPG2FR) were found to be stable after over 3 months of drug withdrawal and maintenance in drug-free medium. This was done with the views of establishing a simple, efficient and direct protocol for the development of good cellular models for the study of drug resistance in liver cancer, with possible application in other cancer types.

微肿瘤PTC药敏检测优化骨肉瘤二线化疗方案选择的作用研究

目的:探讨微肿瘤(PTC)药敏检测优化骨肉瘤二线化疗方案选择的作用研究。方法:收集医院内行二线化疗方案治疗的50例骨肉瘤患者,根据治疗方案不同分组,其中12例患者采用伊立替康+长春新碱(A组),15例患者采用白蛋白结合型紫杉醇(B组);13例患者采用吉西他滨+多西他赛治疗(C组),10例患者给予长春瑞滨(D组)。比较各组微肿瘤PTC药敏检测结果、临床疗效及不良反应。结果:B组患者微肿瘤PTC药敏有效率高于A组、B组、D组(P<0.05),A组、B组、D组患者微肿瘤PTC药敏有效率的差异无统计学意义(P>0.05);B组患者临床治疗总有效率高于A组、B组、D组(P<0.05),A组、B组、D组患者临床治疗总有效率的差异无统计学意义(P>0.05)。各组患者间不良反应的差异无统计学意义(P>0.05)。结论:微肿瘤PTC药敏检测与临床疗效结果相近,提示微肿瘤PTC药敏检测对骨肉瘤二线化疗方案选择具有指导价值。

免疫治疗药物主体间性“双线”教学探索

免疫治疗药物是一类通过调节人体免疫系统功能治疗疾病的药物,作为临床一线用药,其在缓解疾病症状,改善重度炎症带来的不良预后方面尤为重要。近年来,伴随互联网技术迅速发展,科技产业不断掀起创新浪潮,国家出台多项指导意见,要求学校加强线上教学,推进“互联网+教育”发展。线上教学不受时间、区域的影响,促进了资源共享,激发了学生兴趣。然而,经过实践性检验,单一线上教学或线下教学模式均存在诸多弊端。本文以重度炎症免疫用药为例,融合主体间性的教学理念,进行免疫治疗药物的线上线下“双线”教学探索。以学生作为学习的主体,强调个体学习的重要性,解决了单一教学模式的弊端。主体间性“双线”教学模式的探索与应用,对互联网时代下的教育改革具有重要指导意义。

BPN组分粒径对Slapper-BPN型EFDI发火感度的影响

为了研究硼/硝酸钾(BPN)组分粒径对Slapper-BPN型爆炸箔爆燃点火器(EFDI)发火感度的影响,设计并制备了由不同粒径的硼粉和硝酸钾组成的多个BPN配方,采用激光粒度仪表征了硼粉的粒径,讨论了硼粉粒径数量分布和体积分布的特点;通过扫描电镜(SEM)获得硝酸钾粒径对BPN药剂界面形貌的影响;根据差示扫描量热法(DSC)数据,计算了不同配方BPN的指前因子、表观活化能、最低热解温度和热爆炸临界温度,分析了BPN组分粒径对其动力学性能的影响;根据兰利法获得了不同配方BPN的临界发火电压及标准误差,讨论了BPN动力学性能和药剂界面形貌对其发火感度的影响。结果表明,BPN组分粒径主要从BPN的热分解性能和药柱界面形貌影响EFDI发火感度;BPN组分粒径变大,会使BPN药剂的最低热解温度变高,从而降低了EFDI发火感度;BPN组分粒径变小,改变了BPN药柱界面形貌,会使BPN药柱颗粒堆积更密实,减小药剂颗粒空隙,阻碍BPN的传火传热通道,在低密度装药条件下,会明显降低EFDI发火感度。因此,硼粉粒径一致性对低密度BPN发火感度的标准差具有一定影响。

二线抗结核药物对患者心电图QTc间期的影响

目的探讨二线抗结核药物对耐药结核病患者心电图QTc间期的影响。方法回顾性分析河南省胸科医院2012年3月至2021年6月150例耐多药结核病患者的临床资料,将使用含贝达喹啉抗结核方案治疗的81例患者作为观察组,使用不含贝达喹啉抗结核方案治疗的69例患者作为对照组。比较两组患者用药不良反应发生率,分析观察组患者治疗期间QTc间期变化情况,对观察组患者出现QTc间期延长进行单因素和多因素分析。结果观察组81例中37例(45.68%)出现了QTc间期>450 ms(男)、460 ms(女),其中5例(6.17%)QTc间期>500 ms,复测后降至500 ms以下。对照组69例患者中18例(26.09%)出现了QTc间期>450 ms(男)、460 ms(女),其中4例(5.80%)QTc间期>500 ms,停用莫西沙星后缓解,观察组QTc间期延长发生率高于对照组,差异具有统计学意义(P<0.05),两组血液系统损伤、神经系统损伤等发生率差异无统计学意义(P>0.05);与基线期相比,患者的QTc间期随着贝达喹啉使用时间的增加而延长,差异具有统计学意义(P<0.05),自第4周后的每个复查时间点的瞬时QTc间期值均高于基线期QTc间期值,差异均有统计学意义(P<0.05);单因素分析显示,QTc间期延长与使用其他导致QTc间期延长药物有关,差异具有统计学意义(P<0.05),与年龄、性别、是否合并糖尿病、耐药类型无关,差异均无统计学意义(P>0.05);多因素分析结果显示,合并使用其他致QTc延长药物是导致耐多药结核患者QTc延长的危险因素,差异具有统计学意义(P<0.05)。结论含贝达喹啉抗结核方案治疗耐多药结核病的安全性较高,QTc间期延长与使用其他导致QTc间期延长药物有关,使用其他致QTc延长药物是导致耐多药结核患者QTc延长的危险因素。

全自动在线固相萃取-液质联用方法测定污水中11种常见毒品

建立全自动的在线固相萃取方法开展污水中11种常见毒品的全自动监测。整个方法中自动向样品中添加内标,混匀,大体积进样,自动进行在线固相萃取,对样品进行富集净化。方法验证的结果表明,该方法稳定可靠,回收率范围在87.7%~113.8%,进行3个浓度点的重复性试验,所有化合物浓度的相对标准偏差RSD在1.49%~7.39%之间。该方法灵敏度高,具有良好的准确度和重复性,完全满足污水中毒品监测的需求。同时将该方法用于实际污水样品的测定,效果良好。

高血压合并心力衰竭一线降压药物治疗的研究进展

降压药物治疗是伴发心力衰竭的高血压患者重要干预手段,血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体拮抗剂、血管紧张素受体脑啡肽酶抑制剂、利尿剂、钙通道阻滞剂及β受体阻滞剂是临床目前常用一线降压药物。对于高血压合并心力衰竭这类高危患者,临床普遍采取多种药物联合治疗方案,且不同左心室射血分数分级患者降压药物疗效存在差异,因此,使用降压药物前对高血压患者心血管病变情况进行分层将有利于指导临床进行合理用药。本文就最新一线降压药物对于高血压合并心力衰竭的治疗效果及研究进展进行综述。

Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.