基于调控肠道菌群探讨中药防治脑卒中

肠道菌群是一个独特的生态系统,被称为人体"被遗忘的器官",被誉为人类的"第二基因组"。肠道菌群失调与许多中枢神经系统疾病相关,例如帕金森病、阿尔茨海默症、精神分裂症及多发性硬化等。脑卒中具有高的发病率、复发率、死亡率和致残率的特点。肠道菌群在脑卒中的发生、发展中起着关键的作用,可通过影响机体的吸收、代谢、血压、血糖、血脂及动脉粥样斑块等因素,进一步影响脑卒中的发病。中医认为脾胃气血流注失度、阴阳盛衰失衡,机体生理功能失调,化生"风、火、痰、虚、瘀"等病理产物,可致中风的发生。脾胃主腐熟运化水谷,肠道菌群影响饮食的消化吸收,现代研究的肠道菌群功能与中医之脾胃功能失调相关。因此,调整肠道菌群的稳态,可作为一个潜在的干预靶点预防和治疗缺血性脑卒中。中药干预脑卒中已经取得了很好的疗效,是否与调节肠道菌群有关,值得未来做进一步的研究。同时对中药有效成分(小檗碱、黄芩苷、白藜芦醇等),中药单方(丹参、红景天等)和中药组方(补阳还五汤、脑心通胶囊、补中益气汤等)防治脑缺血的研究进展进行综述,为缺血性脑卒中的预防和开发提供新的途径和思路。     

Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT-I and COMFORT-II studies

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

• Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
• Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
• Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
• Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.

     

电针复合TCI靶控输注在单肺通气食管癌开胸手术麻醉中的应用与安全性＊

目的 探讨电针复合靶控输注（Target Controlled Infusion， TCI）在单肺通气食管癌开胸手术麻醉中的应用价值。方法 选取于我院拟行单肺通气食管癌开胸切除手术患者60例作为研究对象。随机将其分为试验组与对照组，对照组30例采取气管插管全麻及TCI靶控输注维持麻醉深度，试验组30例则在对照组方案基础上辅助电针麻醉，记录两组患者手术麻醉时间、药物用量、苏醒时间、并发症；以及术前（T_Ⅰ）、插管前即刻（T_Ⅱ）、插管后1 min（T_Ⅲ）、切皮即刻（T_Ⅳ）、去骨时（T_Ⅴ）、拔管即刻（T_Ⅵ）时平均动脉压（MAP）、平均心率（HR）、BIS值；术前、术后1天、术后3天简易智能精神状态检查量表（MMSE）；并于麻醉诱导前（T₀）、手术开始2 h（T₁）、术后1天（T₂）、术后3天（T₃）时抽取患者外周静脉血检测IL-1β、IL-6、IL-10、TNF-α浓度。结果 试验组手术用时、麻醉时间略低于对照组，但差异无统计学意义（P>0.05），试验组异丙酚、舒芬太尼用量以及苏醒时间均明显低于对照组（P<0.05）；T_Ⅱ时两组平均动脉压（Mean Arterial Pressure， MAP）、心率（Heartrate， HR）较术前明显降低，且试验组MAP明显低于对照组（P<0.05），但两组T_Ⅱ时HR比较无显著差异（P>0.05）；T_Ⅲ、T_Ⅵ时对照组MAP、HR明显高于T_Ⅰ时，而试验组MAP、HR与T_Ⅰ比较无显著差异（P>0.05）。术后1天、3天试验组简易智能精神状态检查量表（Mini-Mental State Examination， MMSE）评分低于对照组，有显著性差异（P<0.05）。T₁、T₂、T₃时试验组白介素-1β（IL-1β）、白介素-6（IL-6）、肿瘤坏死因子（Tumor Necrosis Factor-α， TNF-α）水平明显低于对照组（P<0.05），白介素-10（IL-10）水平明显高于对照组（P<0.05）。结论 采用电针复合TCI靶控输注麻醉方案可有效提升单肺通气食管癌开胸手术麻醉效果，能够降低患者术后认知功能障碍发生风险。     

Gray platelet syndrome: Management of perioperative bleeding in redo cardiac surgery

Gray platelet syndrome (GPS) is a rare (<1/1 000 000) and inherited platelet function disorder characterized by macrothrombocytopenia, α-granule deficiency, and hemorrhages. Bleeding intensity does not correlate with platelet count nor with functional test results. We hereby describe the perioperative bleeding prevention and management of a patient with GPS requiring multiple redo cardiac surgeries.