超声引导下关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普)治疗血友病性关节病

目的 观察超声引导下关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（益赛普）治疗血友病性关节病（HA）的价值。方法 回顾性分析32例接受超声引导下穿刺关节腔注射益赛普的HA患者，对比观察治疗前及治疗后1个月血友病关节健康评分（HJHS）、视觉模拟评分（VAS），以及超声所示目标关节增生滑膜厚度、血流信号、Melchiorre及中国早期血友病性关节病超声检测（HEAD-US-C）评分，评估其治疗价值。结果 对32例均成功完成超声引导下穿刺关节腔及腔内注射益赛普，共对18例膝关节、7例肘关节及7例踝关节进行治疗。术后未出现感染、出血等并发症。治疗后1个月，目标关节HJHS、VAS、Melchiorre评分、HEAD-US-C评分及增生滑膜最大厚度、平均厚度、血流信号均低于治疗前（P均<0.01）。结论 超声引导下关节腔内注射益赛普治疗HA安全、有效。     

Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.     

Administration of testosterone improves the prothrombotic and antifibrinolytic parameters associated with its deficiency in an orchidectiomized rat model

This study investigated the effect of testosterone deficiency and replacement on platelets function and aggregation, coagulation, and fibrinolysis in young adult healthy male rats. Rats were classified into three groups (n = 6/group) of either “a sham-operated+ vehicle,” “an orchidectomized (ORX)+ vehicle,” and “an ORX+testosterone propionate (0.5 mg/kg, 3X/week, S.C).” All treatments were carried out for 12 weeks. Our results showed that ORX rats had induced platelets aggregation and coagulation and inhibited fibrinolysis. ORX-induced rats had increased ratios of adenosine diphosphate-induced aggregation, shorter bleeding time, clotting time, prothrombin time, and activated partial thromboplastin time and their sera showed increased levels of thromboxane B2 and fibrinogen levels. Concomitantly, their plasma showed increased TPA-1 and decreased tissue plasminogen activator (tPA) levels. At molecular levels, the aorta of ORX-induced rats showed increased aortic mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), protein levels of von Willebrand Factor (vWF) and decreased mRNA and protein levels of tPA, and their liver showed increased protein levels of prothrombin and factor VII. Testosterone post-therapy to ORX-induced rats significantly reversed all these hematological and molecular changes. In conclusion, independent of any other risk factors, testosterone deficiency induces platelets aggregation and hypercoagulation and inhibits fibrinolysis, effects that can be reversed by testosterone therapy.     

氯吡格雷联合前列地尔对急性脑梗死患者疗效、血流动力学及凝血功能水平的影响

目的：探讨氯吡格雷联合前列地尔对急性脑梗死患者的疗效及对患者血流动力学、凝血功能水平的影响。方法：选取2015年6月-2017年6月某院收治的急性脑梗死患者90例，按照随机数字表法分为对照组与观察组，每组各45例。对照组患者在常规治疗基础上给予氯吡格雷治疗，观察组患者在对照组治疗基础上给予前列地尔治疗。比较2组患者临床治疗效果；检测治疗前、后2组患者血浆黏度（PV）、血浆纤维蛋白原（FIB）、血小板聚集率（PAR）、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、D-二聚体（D-D）水平。结果：对照组患者治疗后临床总有效率为64.44%；观察组患者治疗后临床总有效率为86.67%。两者比较差异有显著性（P<0.05）。治疗前，2组患者血流动力学指标PV、FIB、PAR及凝血功能指标PT、APTT、D-D水平比较，差异无显著性（P>0.05）。治疗后，对照组及观察组患者PV、FIB、PAR及D-D水平均明显低于本组治疗前，PT、APTT水平均明显高于本组治疗前；观察组患者治疗后PV、FIB、PAR及D-D水平均明显低于对照组治疗后，PT、APTT水平均明显高于对照组治疗后，差异均有显著性（P<0.05）。结论：氯吡格雷联合前列地尔对急性脑梗死患者具有较好的临床疗效，可通过抑制血小板活性及降低血液黏度，起到改善患者血流动力学水平，调节患者凝血功能的作用。     

Debate: Bipolar disorder: extremely rare before puberty and antipsychotics cause serious harms – a commentary on Van Meter et al. (2019)

‘Paediatric bipolar disorder’ (PBD) remains controversial; because it is based on the hypothesis that bipolar disorder (BD) often begins in childhood with atypical forms of mania. A meta-analysis of 12 epidemiological surveys found a high prevalence of PBD among children and adolescents worldwide (1.8%), however, our study of the measurement issues (Child and Adolescent Mental Health, 23, 2018, 14) found that PBD rates were lower than claimed. Our findings are consistent with the developmental trajectory of BD, as described by most longitudinal studies of high-risk offspring. BD is extremely rare in childhood with nearly all index manic/hypomanic episodes being in midadolescence or later. Treatment for BD should not commence until the first well-defined manic/hypomanic episode, because children and younger adolescents are extremely sensitive to the side effects of second-generation antipsychotics including weight gain, metabolic syndrome, extrapyramidal side effects and the risk of cerebral atrophy, as observed in studies of juvenile animals.     

Crystalloids,colloids, blood products and blood substitutes

Understanding the physiology of fluid distribution in the human body is fundamental to good clinical practice in anaesthesia and intensive care. Intravenous fluid therapies have a range of clinical and metabolic consequences, and they should be context and patient specific. Inadequate or excessive fluid treatment is harmful to patients. There are numerous trials, both historical and current, investigating best practice in fluid therapy. New paradigms and guidelines are being published, and it is important for clinicians to keep up to date with current practice. There is also a continued drive to improve the safety of donor blood products and prevent transfusion errors. Knowledge of how blood products are collected, separated, stored and administered is essential to prevent harm to patients through transfusions. The development of blood substitutes is progressing, and multinational trials are ongoing.