一株L－亮氨酸产生菌的研究

以天津短杆菌（ＢｒｅｖｉｂａｃｔｅｒｉｕｍＴｉａｎｊｉｎｅｓｅ）Ｔ６～１３为出发菌株，采用紫外线进行诱变处理，筛选α－氨基－β－羟基戊酸和利福平抗性突变株，获得一株Ｌ－亮氨酸产生菌Ｎｏ。１４５，Ｌ－亮氨酸摇瓶产量可以达３２．１ｍｇ／ｍＬ。在１６Ｌ发酵罐中培养６０ｈ，Ｌ－亮氨酸产量可以达２１．８ｍｇ／ｍＬ葡萄糖转化率可以达２０％。发酵液经７３２强酸性阳离子树脂提取，再以等电点一有机溶媒法结晶。产品经生物鉴定，红外吸收光谱，纸层析和比旋光度等项测定，证明产品为Ｌ－亮氨酸。     

三种利福霉素类抗痨药物耐药状况对比分析

目的探讨三种利福霉素类抗痨药物的耐药状况。方法采用鸡蛋固体培养基对168例肺结核患者进行痰结核菌培养,对培养阳性菌株采用绝对浓度间接法对国产利福平、进口利福平及利福喷丁进行耐药检测,以50μg/ml为耐药界限。结果共获得结核分支杆菌54株,其中耐国产利福平者31株,耐进口利福平者36株,耐利喷丁者10株,耐药率分别为57.4%,66.7%和18.5%。利福喷丁耐药率明显低于国产利福平(χ2=17.3382,P<0.0001)和进口利福平(χ2=25.5989,P<0.0001),而国产利福平和进口利福平耐药率无差别(χ2=0.9829,P>0.05)。结论国产利福平和进口利福平耐药状况均非常严重,因此,在临床用药过程中,对国产利福平耐药者不宜以进口利福平代替,而应以利福喷丁替代以保证疗效。     

异福胶囊溶出度测定方法的建立

目的建立异福胶囊溶出度测定方法。方法采用转篮法,以0.1moL·L^-1盐酸溶液为溶剂,转速为100r·min^-1,45min时取样。以紫外可见-分光光度法测定利福平的溶出度,检测波长为474nm;以HPLC法,采用Water公司生产的十八烷基硅烷键合硅胶色谱柱,测定异烟肼的溶出度,以水-磷酸盐缓冲液-甲醇（850∶100∶50）为流动相,检测波长为254nm,流速为1.5mL·min^-1。结果利福平在12.61～51.91μg·mL^-1的浓度范围内,线性关系良好。利福平平均回收率为99.8%（RSD=0.14%,n=12）;异烟肼的进样量在0.3245～1.3335μg的范围内,线性关系良好。异烟肼平均回收率为99.6%（RSD=0.51%,n=12）。结论本方法操作简便,结果正确,为完善异福胶囊的质量标准提供有效手段。     

Antibiotic resistance determinants of multidrug-resistant Acinetobacter baumannii clinical isolates in Algeria

Antibiotic susceptibility testing was performed on 71 Acinetobacter baumannii clinical isolates, and presence of antibiotic resistance genes was screened for by PCR amplification and sequencing. Resistance rates were very high for aminoglycosides (22–80%), fluoroquinolones (>90%), and cephalosporins (>90%) but remained low for rifampin (2.8%) or null for colistin. Antibiotic resistance encoding genes detected were as follows: bla_TEM-128 gene (74.6%), aph(3′)-VI (50.7 %), aadA (63.4%), ant(2″)-I (14.1%), aac(3)-Ia (91.1%), aac(6′)-Ib (4.2%), mutation Ser83Leu in gyrA (94.4%), double mutations Ser83Leu and Ser80Leu (or Ser84Leu) in gyrA and parC (69.0%), and mutation I581N in RRDR of the rpoB gene.     

不同剂型利福平投药后血药浓度的监测结果分析

目的 分析两种不同剂型利福平投药后血药浓度的监测结果,以指导临床合理用药。方法 选择2016年5月至2017年6月昆明市第三人民医院结核二科收治的活动性肺结核患者130例,按照数字表法随机分为注射组(65例;利褔平采用静脉滴注的方式,0.6g/次,1次/d,用500ml 5%葡萄糖注射液配制)和口服组(65例;利褔平采用口服的方式,0.6g/次,1次/d);利福平最低抑菌浓度(MIC)为0.39~1.56μg/ml,本研究统计达到MIC为0.39μg/ml的患者例数。口服组最终有2例患者因不同时间点血药浓度监测数据存在遗漏,故剔除,本研究最终纳入128例患者,其中注射组65例,口服组63例。两组患者用药第7天后,采集不同时间点的血浆标本,通过超高效液相色谱-串联质谱法(UPLC-MS/MS)检测两组利福平的血药浓度值。结果 注射组利福平最高血药浓度出现在输注后1.5h,中位数(四分位数)[M(Q₁,Q₃)]为0.954(0.210,3.420)μg/ml;口服组最高血药浓度出现在服药后2h,M(Q₁,Q₃)为1.253(0.249,2.501)μg/ml。注射组峰值血药浓度为1.786(0.704,3.591)μg/ml,均值血药浓度为0.688(0.269,1.087)μg/ml,均高于口服组[分别为1.468(0.423,3.748)μg/ml和0.571(0.149,1.894)μg/ml],但差异均无统计学意义(Z值分别为-0.90和-0.02,P值分别为0.366和0.980);注射组谷值血药浓度为0.004(0.001,0.038)μg/ml,低于口服组[0.007(0.001,0.070)μg/ml],差异有统计学意义(Z=-8.74,P=0.000)。注射组总体达到MIC的比率为47.7%(248/520),口服组为49.4%(218/441),差异无统计学意义(χ²=0.29,P=0.591)。结论 患者采用注射和口服利福平的治疗方案,血药浓度值均较低,有超过50%的患者总体时间内并未达到MIC,无法满足利福平推荐的参考范围,可能存在剂量上的不足;应继续加强对利福平血药浓度的监测,规范使用利福平注射液。     

食管结核误诊为食管癌临床分析

目的分析食管结核的临床特点、误诊原因及防范措施。方法回顾性分析误诊为食管癌的食管结核2例的临床资料。结果1例因吞咽困难2个月,进行性加重伴持续性胸骨后疼痛1月余就诊,院外多次行胃镜及病理检查均提示食管癌可能性大,入院后经胃镜、病理检查及实验室检查结果确诊食管结核,给予三联抗结核治疗,症状明显好转。1例因进行性吞咽困难伴乏力、消瘦5个月就诊,两次胃镜及活检均考虑食管癌,择期行手术治疗,术后病理检查提示食管结核,给予三联抗结核治疗,病情明显好转。结论食管结核临床少见,部分患者无结核中毒症状,且临床表现无特异性,极易误诊为食管癌,提示临床应加强对本病的认识,多次多部位行病理检查,必要时行诊断性抗结核治疗,可一定程度避免误诊的发生。     

反相高效液相色谱法同时测定复方利福平胶囊中异烟肼、利福平的含量

应用反相高效液相色谱法,采用５μｍＨｙｐｅｂｓｉｌＯＤＳ色谱柱,以０．１ｍｏｌ／Ｌ磷酸二氢钠溶液：甲醇（４０：６０）为流动相,检测波长２６８ｎｍ,建立了同时测定复方利福平胶囊中异烟肼、利福平的含量测定法。采用外标对照法测定,方法平均回收率在９９．００％,以上,相对标准差小于１．０％,结果令人满意。     

Treatment and Evaluation Advances in Leprosy Neuropathy

Neuropathy and related disabilities are the major medical consequences of leprosy, which remains a global medical concern. Despite major advances in understanding the mechanisms of M. leprae entry into peripheral nerves, most aspects of the pathogenesis of leprosy neuropathy remain poorly understood. Sensory loss is characteristic of leprosy, but neuropathic pain is sometimes observed. Effective anti-microbial therapy is available, but neuropathy remains a problem especially if diagnosis and treatment are delayed. Currently there is intense interest in post-exposure prophylaxis with single-dose rifampin in endemic areas, as well as with enhanced prophylactic regimens in some situations. Some degree of nerve involvement is seen in all cases and neuritis may occur in the absence of leprosy reactions, but acute neuritis commonly accompanies both Type 1 and Type 2 leprosy reactions and may be difficult to manage. A variety of established as well as new methods for the early diagnosis and assessment of leprosy neuropathy are reviewed. Corticosteroids offer the primary treatment for neuritis and for subclinical neuropathy in leprosy, but success is limited if nerve function impairment is present at the time of diagnosis. A candidate vaccine has shown apparent benefit in preventing nerve injury in the armadillo model. The development of new therapeutics for leprosy neuropathy is greatly needed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01153-z.     

荧光定量PCR技术检测肺外结核患者样本临床应用

目的评估赛沛分子检测技术（结核分枝杆菌和利福平耐药基因）（GeneXpert MTB/RIF）检测心包和胸腔积液样本中结核分枝杆菌的有效性。 方法收集2015年1月至2017年6月天门市第一人民人民医院和汉川市人民医院收治的286例结核病疑似患者的临床资料,分别收集158例胸腔积液和128例心包积液样品。每个样品均经过抗酸染色涂片镜检、罗氏培养基结核分枝杆菌培养（LJ培养）和GeneXpert MTB/RIF测定。使用结核分枝杆菌罗氏培养作为金标准,评估GeneXpert MTB/RIF技术检测MTB的有效性。 结果在286例积液样本中,MTB通过LJ培养阳性者51例（17.8%）,GeneXpert MTB/RIF测定阳性者43例（15%）,抗酸染色镜检阳性者11例（3.8%）。GeneXpert技术灵敏度、特异性、阳性预测值和阴性预测值分别为84.3%、100%、100%和96.7%,抗酸染色方法的灵敏度、特异性、阳性预测值和阴性预测值分别为18.3%、99.1%、81.8%和85.4%。GeneXpert技术检查心包积液中MTB的灵敏度可达90%。GeneXpert MTB/RIF和抗酸染色镜检鉴定两种样本中结核分枝杆菌有效性的差异具有统计学意义（χ² = 233.199、33.715、P均< 0.001）。 结论GeneXpert MTB/RIF技术对于检测胸腔和心包积液中的MTB具有高灵敏度和高特异性。     

Effect of rifampicin on the risk of steroid‐induced osteonecrosis of the femoral head

Objective: To investigate the effects and possible mechanism of rifampicin on steroid‐induced osteonecrosis of the femoral head (ONFH). Methods: Bone marrow stromal cells (BMSC) separated from male rats were cultured in vitro without any treatment (Group mA), exposed to dexamethasone (Group mB), treated with rifampicin (Group mC), and exposed to dexamethasone and rifampicin simultaneously (Group mD) respectively (n = 5 in each group). After 7 days, P‐glycoprotein (P‐gp) activity and adipogenesis of the BMSC were evaluated. In an in vivo experiment, 80 rats were randomly divided into 4 groups (n= 20 in each group). Group A received intragastric saline for 5 weeks. Group B received intragastric saline for one week, followed by subcutaneous methylprednisolone and saline for 4 weeks. Group C received intragastric rifampicin for 5 weeks. Group D received intragastric rifampicin for one week, followed by subcutaneous methylprednisolone and rifampicin for 4 weeks. At the end of the experiment, all rats underwent analysis of P‐gp activity of BMSC, P‐gp expression in the femoral heads, MRI and histomorphometry of the femoral heads. Results: In vitro, the P‐gp activity of BMSC increased and lipid accumulation decreased significantly in Group mD, compared to Group mB. In vivo, P‐gp activity and P‐gp expression in Group D increased compared to Group B. The mean area of MRI abnormal signal, adipocytic variables and apoptotic cells in Group D decreased, mean percentage of the whole epiphysis made up by the epiphyseal ossification center and trabecular structure variables improved compared to those in Group B. The incidence of ONFH was lower in Group D (50%) than in Group B (80%). Conclusion: Rifampicin may decrease the risk of steroid‐induced ONFH by enhancing P‐gp activity, thus preventing steroid‐induced BMSC adipogenesis.