PBK/TOPK通过改变糖酵解关键酶表达水平增加结直肠癌细胞放射敏感性

目的:探讨在结直肠癌细胞中PDZ结合激酶(PDZ binding kinase,PBK)/T-淋巴因子激活的杀伤细胞来源的蛋白激酶(T-cell-originated protein kinase,TOPK)能否通过影响糖酵解关键酶表达改变放射敏感性.方法:通过慢病毒转染敲低LS174T细胞中的PBK/TOPK表达水平...     

左乙拉西坦pH敏感鼻用凝胶在大鼠体内的药代动力学研究

目的 研究左乙拉西坦(LEV)pH敏感鼻用凝胶在大鼠体内的药代动力学.方法 用高效液相色谱法测定大鼠血中LEV的浓度.色谱柱为Wondasil C18柱(250.0 mm×4.6 mm,5.0μm),流动相为乙腈-水(11:89),检测波长为205 nm,内标为甲硝唑.按照体质量将大鼠随机分为实验组和对照组,每组6只....     

Tuberculin skin testing and the health care worker: Lessons of the prophit survey

Setting: Concern about occupationally-acquired tuberculosis continues to grow, even as control of tuberculosis in the USA has improved. Many health care workers have developed occupationally-acquired tuberculosis in recently described outbreaks and several have died. Regulatory agencies are struggling to develop a rational policy that promises both worker safety as well as cost-effectiveness. Future infection control efforts will be evaluated by results of tuberculin skin tests of employees. However, unlike many modern diagnostic tests, the tuberculin skin test is poorly understood, may be unreliable, and requires individual physician interpretation.Design: Review of the British Prophit Survey, conducted from 1933–1944, which involved tuberculin testing of 10 000 young adults, with the goal of defining ‘the relationship between tuberculin sensitivity and tuberculous immunity’.Results: Four findings are particularly pertinent to the current debate: 1. job-specific rates of tuberculin conversion and subsequent development of disease; 2. risk of exogenous re-infection among already-tuberculin positive health care workers; 3. rates of tuberculin skin test reversion; and 4. implications of induration size.Conclusion: The British Prophit Survey produced a great deal of meaningful information regarding the meaning of a positive tuberculin skin test, a negative test, and a change in tuberculin status. Proper interpretation of this test requires full appreciation of its many idiosyncrasies.     

Home blood pressure telemonitoring for improving blood pressure control in middle‐aged and elderly patients with hypertension

The blood pressure (BP) control rate among treated hypertensives in China remains low at 37.5%. The relationship between home blood pressure telemonitoring (HBPT) and BP control is controversial. The authors aimed to investigate the relationship between HBPT and BP control in middle‐aged and elderly hypertensives. In total, 252 hypertension patients aged between 60 and 79 years were enrolled. The patients were given either HBPT through interactive platforms between physicians and patients (telemonitoring group, n = 126) or conventional management (routine management group, n = 126). All patients were followed‐up for 15 months. BP control was defined as home systolic blood pressure < 135 mm Hg and home diastolic blood pressure < 85 mm Hg. At baseline, there were no significant differences in the baseline BP control rate (p = .083). However, after 15 months, the BP control rate improved in both groups, and the telemonitoring group (71.3%) had a significantly higher BP control than the routine management group (49.8%) (p < .001). The change of BP control rate from baseline in the routine management group increased by 26.1%, and that of the telemonitoring group increased by 35.4%. The results of the fully adjusted binary logistic regression showed that HBPT was positively associated with BP control after adjusting for confounders (OR = 4.15, 95% CI 2.05–8.39). Similar results were observed after 3, 9, and 12 months. The association of HBPT with BP control was similar in subgroups. In conclusions, HBPT is recommended for BP control in middle‐aged and elderly hypertensives in the community setting.     

214例老年缓慢性心律失常植入心脏起搏器治疗的临床观察

目的 观察不同年龄段的老年患者在治疗缓慢性心律失常时植入心脏起搏器的临床特征。方法 选取2019年1月—2021年12月在内蒙古医科大学附属医院接受心脏永久起搏器植入治疗的214例缓慢性心律失常老年患者为研究对象,根据年龄不同分为60～69岁组（60例）、70～80岁组（82例）、> 80岁组（72例）。对比３组患者首发症状、起搏器植入病因、起搏器类型及随访电极参数。结果 所有入选者首发症状以黑蒙、晕厥为主（33.64%）。不同年龄组首发症状比较,差异无统计学意义（P >0.05）;老年女性乏力比例高于男性（P <0.05）。植入起搏器的病因依次为：病态窦房结综合征（以下简称病窦）79例（36.92%）、房室传导阻滞（AVB）78例（36.44%）、心房颤动（以下简称房颤）合并长间歇34例（15.89%）、双结病变23例（10.75%）。60～69岁组、70～80岁组病窦的占比均高于>80岁组（P <0.05）,而>80岁组房颤合并长间歇占比高于其他两组（P <0.05）。老年女性病窦的占比高于男性,而男性Ⅱ度Ⅱ型AVB的占比高于女性（P <0.05）。起搏器植入类型以双腔为主体（185例,86.45%）,>80岁组单腔起搏器植入数量高于70～80岁组（P <0.05）;术后7、90 d各组患者电极阈值和阻抗较术中均下降（P <0.05）,术后7 d与术后90 d比较,差异无统计学意义（P >0.05）。各组患者相同时间点各个电极参数比较,差异无统计学意义（P >0.05）。结论 接受心脏永久起搏器治疗的缓慢性心律失常老年患者的临床特征具有年龄和性别差异。通过短期随访,不同年龄的老年患者右心室中低位间隔固定电极均安全有效。     

人脐带间充质干细胞对糖尿病肾病大鼠肾脏HIF-1α表达的影响

目的 观察人脐带间充质干细胞（HUMSC）对糖尿病肾病大鼠肾脏缺氧诱导因子（HIF-1α）表达的影响。方法 50只健康清洁级8周龄雄性SD大鼠,随机选取20只为健康对照组,其余30只采用链脲菌素复制糖尿病肾病大鼠模型（模型组）,两组大鼠饲养12周。第12周,随机选取两组大鼠各3只分别尾静脉注射DiR-HUMSCs,代谢12～16 h后在小动物活体光学3D成像系统下观察DiR-HUMSCs在大鼠体内的分布。随机选取9只模型组大鼠进行HUMSCs移植（HUMSCs移植组）。HUMSCs移植采用尾静脉注射方式移植浓度为1×10⁶个/mL HUMSCs 500 μL至大鼠体内,每周1次,连续4周,共28 d。检测3组大鼠的24 h尿蛋白定量（24 h UPro）、血清肌酐（Scr）、血尿素氮（BUN）、尿肌酐（Ucr）、尿白蛋白与肌酐比值（UACR）水平;酶联免疫吸附试验（ELISA）检测3组大鼠血清HIF-1α水平;采用PAS和Masson染色进行肾脏组织病理检测;免疫荧光法检测3组大鼠肾组织HIF-1α、Slc12A3和Aquaporin1蛋白的表达。结果 移植HUMSCs治疗4周后,与健康对照组比较,模型组和HUMSCs移植组大鼠Ucr水平降低（P <0.05）,Scr、24 h UPro、BUN、UCAR均升高（P <0.05）;与模型组比较,HUMSCs移植组大鼠Ucr水平差异无统计学意义（P >0.05）,Scr、24 h UPro、BUN、UCAR均降低（P <0.05）。糖尿病肾病大鼠病理损伤缓解,系膜增生和基底膜增厚改善,小管空泡变性减少,间质纤维化减轻。模型组大鼠血清HIF-1α水平较健康对照组升高（P <0.05）,HUMSCs移植组血清HIF-1α水平较模型组下降（P <0.05）。与健康对照组比较,模型组大鼠肾脏远端小管中HIF-1α蛋白水平增加（P <0.05）;HUMSCs移植组的HIF-1α蛋白水平较模型组降低（P <0.05）。模型组远端小管标记蛋白Slc12A3水平低于健康对照组（P <0.05）,HUMSCs移植组Slc12A3水平较模型组升高（P <0.05）。HUMSCs移植组的Aquaporin1蛋白水平较模型组和健康对照组均降低（P <0.05）。糖尿病肾病大鼠近端小管中无HIF-1α表达。结论 HIF-1α主要在糖尿病肾病大鼠肾脏远端小管表达,且HUMSCs可通过抑制HIF-1α的表达修复肾小管的损伤。     

Determination of α2-antiplasmin-plasmin complex in human plasma with an enzyme-linked immunosorbent assay

A novel enzyme-linked immunosorbent assay (ELISA) for quantification of α₂-antiplasmin-plasmin complex (APP) in undiluted plasma was developed. The assay follows the sandwich principle and uses two different antibodies directed against plasmin-modified α₂-antiplasmin and plasminogen, respectively. The antibodies bind selectively to the corresponding antigen moieties of APP. The assay was calibrated with definite concentrations of preformed purified APP added to APP-poor plasma. The lower limit of sensitivity of the assay was 10ng/ml. Mean coefficients of variation of 5.8% (intraassay) and 7.2% (interassay) were found for APP concentrations between 50 and 5000 ng/ml. A reference range from 80–470 ng/ml was calculated from APP concentration in plasma samples from 178 healthy donors (mean value±SD: 210±88). In plasma samples from patients during thrombolytic therapy, APP was found up to 20000 ng/ml. From our data we conclude that quantification of APP can be a sensitive tool for specific detection of an activation of the fibrinolytic system.     

The effects of acute stress on ethanol absorption in LS and SS mice

Previously, our laboratory demonstrated that naive long-sleep (LS) mice absorb ethanol faster than short-sleep (SS) mice when administered 6.0 g/kg ethanol intragastrically (IG). We also demonstrated that the removal of the adrenal glands results in decreased absorption in both lines of mouse. The present study was designed to assess whether acute short-term elevations of corticosterone produced by exposure to a mild stressor could also alter ethanol absorption in LS and SS mice. Because a difference in ethanol absorption rates was observed in LS mice as a function of time of day, all stress experiments were performed in the morning. CCS elevation was induced by exposure to an elevated plus-maze for 45 min. LS mice demonstrated greater CCS release in response to this stressor than SS mice. This exposure to a mild stressor produced an increase in ethanol absorption in both lines of mice receiving a 6.0 g/kg intragastric dose of ethanol. Although this effect of stress on ethanol absorption could be prevented by adrenalectomy in SS mice, adrenalectomy alone did not completely block these effects of stress on ethanol absorption in LS mice. Dexamethasome treatment at the time of adrenalectomy was required to block the effects of stress on ethanol absorption in LS mice. These results suggest that exposure to mild stressors may alter ethanol pharmacokinetic parameters but that genetic factors may play a role in this response via regulation of the hypothalamic-pituitary-adrenal axis.     

Ifosfamide plus doxorubicin in previously untreated patients with advanced soft tissue sarcoma

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft tissue sarcoma. Treatment was doxorubicin 50 mg/m² followed by a 24 h infusion of ifosfamide 5 g/m² plus mesna 2.5 g/m² repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of 203 patients entered, 175 were evaluable for response. The response rate was 35% (95% CI 28–42%), with 9% of the patients achieving a complete remission and 26% a partial remission. The median time to progression was 29 weeks for all evaluable patients, and 67, 40 and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (WHO grade 3 and 4) in 73% of evaluable treatment courses. Other side-effects were rare and usually well manageable.