住院双相障碍与精神分裂症患者自知力水平的保护性因素

目的 探讨住院双相障碍与精神分裂症患者自知力水平及其保护性因素。方法 在广州市4家精神科住院部连续入组符合《国际疾病分类（第10版）》（ICD-10）双相障碍或精神分裂症诊断标准的患者465例。采用自编人口学及临床特征问卷、自知力与治疗态度问卷（ITAQ）进行调查，比较不同自知力水平患者的人口学和临床特征，采用两分类Logistic回归分析探讨自知力的保护因素。结果 年龄小（OR=0.977）、男性（OR=1.705）、曾经结婚或同居（OR=1.677）、诊断为双相障碍（OR=2.185）、最近一个月有悲观厌世（OR=2.663）、每天睡眠时间≥7小时（OR=1.620）、每周运动1~2次（OR=1.770）是住院双相障碍和精神分裂症患者自知力的保护因素。结论 住院双相障碍和精神分裂症患者自知力水平与多种人口学特征及临床特征相关。     

北京市怀柔区社区严重精神障碍患者免费服药依从性相关因素分析

目的 探索了解北京市怀柔区社区居家严重精神障碍患者免费服药依从性的相关因素。 方法 采用简单随机抽样的方法，对 2018 年 3 月至 2019 年 3 月期间，登记在“北京市怀柔区精神卫生管 理系统”的社区免费服药的严重精神障碍患者 600 例进行 Morisky 自我报告服药依从性问卷（MAQ-8）调 查，依据调查情况分为依从性差（MAQ-8 得分＜ 6 分）组与依从性好（MAQ-8 得分 6～8 分）组。收集所有 对象的一般特征（性别、年龄、工作情况、居住环境、婚姻状态、居住方式、躯体疾病、家族史、药敏史、疾 病类型、家庭收入、受教育年限、住院次数等）以及影响服药依从性的因素。采用访谈法对 15 例严重精 神障碍患者进行个案访谈，通过现象学分析法对资料进行分析，得到影响服药依从性的 9 个主题；采用 t检验和χ2 检验分析依从性差组与依从性好组患者一般特征的差异，采用多因素 Logistic 回归分析方法 分析影响患者依从性的因素。结果 本次研究共筛查 600 例，采集有效信息 435 例，其中 325 例（74.7%） 服药依从性好，110 例（25.3%）服药依从性差；未按医嘱服药的原因中，选择率最高者为忘记服用（60.0%， 66/110），其次为无监护人管理督促（43.6%，48/110）和自知力缺乏（35.5%，39/110）。多因素 Logistic 回归 分析结果显示，居住环境在平原区的患者服药依从性劣于山区的患者（OR=2.41，95%CI：1.14～5.10，P＜ 0.05）；家庭月收入＜ 3 000 元的患者服药依从性优于家庭月收入≥ 5 000 元的患者（OR=0.36，95%CI： 0.19～0.70，P＜ 0.01）；受教育程度低是服药依从性的危险因素（OR=13.81，95%CI：2.82～67.7，P＜ 0.01）。 结论 北京市怀柔区的居家免费服药的严重精神障碍患者中，居住环境、家庭月收入、受教育年限是影 响依从性的主要影响因素。未按医嘱服药的原因主要为各种原因忘记服用，其次为无监护人管理督促 而未服药和自知力缺乏。     

Interrelationships Between BDNF,Superoxide Dismutase,and Cognitive Impairment in Drug-Naive First-Episode Patients With Schizophrenia

The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ.     

针刺配合康复训练治疗脑卒中上肢功能障碍的队列研究

目的:探讨针刺配合康复训练对脑卒中上肢功能障碍患者神经功能特异性烯醇化酶(NSE)、硫化氢(H_2S)、神经营养因子(NGF)与脑血管动力学的影响。方法:选取2016年5月至2017年10月空军军医大学唐都医院收治的脑卒中上肢功能障碍患者198例进行回顾性分析。将患者分为针刺配合康复训练治疗观察组100例,单纯依靠康复训练治疗对照组98例。比较与分析2组治疗前后的NSE、H_2S、NGF与脑血管动力学等。结果:观察组治疗后NSE(12. 36±6. 35)μg/L,H_2S(52. 19±3. 77)μmol/L,NGF(152. 94±32. 67) pg/m L。对照组治疗后NSE (16. 28±7. 45)μg/L,H_2S (36. 67±6. 95)μmol/L,NGF(129. 81±33. 02) pg/m L。观察组治疗后颈动脉血流速度平均值(V_(mean))(26. 45±3. 79) cm/s,血流量(Q_(mean))(18. 52±3. 32) cm~3/s,外周阻力(RV)(82. 37±22. 39) k Pa·s/m,舒张压与临界压差值(DP)(0. 45±0. 08) k Pa. s/m,动态阻力(DR)(32. 36±10. 08) k Pa。对照组治疗后V_(mean)(19. 86±3. 73) cm/s,Q_(mean)(14. 79±2. 72) cm3/s,RV(95. 31±30. 45)k Pa·s/m,DP(0. 63±0. 14) k Pa·s/m,DR(42. 37±9. 67) k Pa。观察组治疗前FMA评分为(38. 41±7. 52)分,治疗后FMA评分为(54. 61±5. 34)分,改善值(16. 22±6. 46)分。MBI指数治疗前为(36. 75±6. 87),治疗后为(60. 33±12. 73),改善值为(23. 58±9. 34)。观察组中医证候积分治疗前(16. 52±0. 68)和治疗后(4. 60±0. 22)。对照组中医证候积分治疗前(16. 95±0. 83)分和治疗后(8. 72±0. 27)分。结论:针刺配合康复训练能够有效的帮助脑卒中上肢功能障碍患者的恢复神经功能,加速脑血管血流速度,减少压强阻力,从而达到治疗患者上肢及手功能,恢复日常生活活动能力的效果。     

Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Research question

Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone–oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone–oestradiol ratio?

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors

This study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition. This was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD. Adverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses). Continuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested.