基于网络药理学和分子对接技术研究黄芪-赤芍治疗COPD的作用机制＊

目的 基于网络药理学和分子对接技术探究黄芪-赤芍配伍对治疗慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）的作用机制。方法 利用TCMSP，Pharmmaper数据库，筛选黄芪-赤芍治疗COPD的活性成分和潜在靶点；结合Genecards数据库挖掘的COPD相关靶点，对黄芪-赤芍药对与COPD靶点进行PPI网络构建，交互处理得到黄芪-赤芍药对治疗COPD的关键靶点，并进行GO分析和KEGG通路富集分析；并采用分子对接技术将主要活性成分与TNF-α（肿瘤坏死因子），IL-6（白细胞介素6）等进行分子对接；最后利用A549炎症细胞与人脐静脉内皮细胞缺氧损伤模型进行体外细胞实验对结果加以验证。结果 黄芪-赤芍药对中44个有效成分作用于COPD，核心成分为：槲皮素、山奈酚、丁子香萜、芍药苷、（2R，3R）-4-methoxyl-distylin、二氢异黄酮；黄芪-赤芍药对通过IL6、PTGS2、TNF等113个靶蛋白，调控Ras、PI3KAkt、IL-17等多条信号通路治疗COPD，且分子对接结果显示槲皮素、山奈酚、丁子香萜、芍药苷与IL-6、PTGS2、TNF大分子蛋白有良好的结合性，体外细胞试验证实，槲皮素与山奈酚均能减少IL-8，MMP-9炎症因子的分泌，具有不同程度的抗炎效果；芍药苷有明显的扩血管、抗血栓之效。结论 黄芪-赤芍药对治疗COPD具有多成分、多靶点、多通路、整体调节的作用特点。初步揭示了黄芪-赤芍药对通过抑制炎症反应、调节上皮细胞生长增强保护屏障等预测出黄芪-赤芍药对治疗COPD的潜在作用机制，以期为其活性成分的药效物质基础提供理论研究和思路。     

“保胆”理念正误

胆囊切除术是公认的胆囊良性疾病的治愈手段，国内外学术界对于手术适应证和手术时机已有明确共识。近年来，“保胆手术”治疗胆囊良性疾病颇受热议，一些医生将“保护胆囊”的学术观点等同于“保留胆囊”的手术技术，这种误解可能导致病人出现差异性的预后。因此，临床医师应明晰“保护胆囊”理念与“保胆手术”的差别，对胆囊良性疾病的诊疗原则有正确的理解和应用。     

Thyroid Embolization for Nonsurgical Treatment of Nodular Goiter: A Single-Center Experience in 56 Consecutive Patients

PurposeTo investigate the safety and efficacy of thyroid artery embolization (TAE) in the treatment of nodular goiter (NG).MethodsDuring a 5.5-year period, 56 consecutive patients with a NG underwent TAE. In Group A, there were 20 patients with a solitary/dominant 5–11-cm nodule, and in Group B, there were 36 patients with numerous nodules. Of the 56 patients, 47 (84%) had a retrosternal goiter and 25 had hyperthyroidism. In all patients, clinical and radiological evaluations were made at baseline and 6 months after TAE, and these parameters were statistically compared.ResultsIn 56 patients, 145 of the 146 thyroid arteries were successfully embolized. The 30-day mortality rate was 1.8%. Minor and major complications occurred in 25 and 2 patients, respectively. Six months after the TAE, the mean nodule volume was reduced from 80.2 mL to 25.0 mL, the mean thyroid volume was reduced from 147.0 mL to 62.6 mL, and the mean intrathoracic extension was reduced from 31.7 mm to 15.9 mm (P < .001). Of the 22 patients with non–Graves hyperthyroidism, 19 (86%) became euthyroid. The mean thyroid-related patient-reported outcome scores improved from 155.4 to 70.4 (P < .001). Of the 51 patients, 50 (98%) declared that they would recommend TAE to other patients with NG.ConclusionsTAE is safe and effective for the treatment of NG, with a significant volume reduction of the nodule(s) and thyroid gland.     

La consultation psychiatrique d’Yves Pélicier ou l’art de la biographie

The teaching and clinical practice of professor Yves Pélicier contributed to the international development of a psychiatry centered on the whole of the person in a humanist approach. The theoretical developments were marked by the authenticity of the practice of the therapist and its deep sense of the human being thus truly founding a School.     

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

Emerging therapeutic options in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease that requires chronic treatment throughout the evolution of the disease, with a complex physiopathology that entails great challenges for the development of new and specific treatments for ulcerative colitis and Crohn´s disease. The anti-tumor necrosis factor alpha therapy has impacted the clinical course of IBD in those patients who do not respond to conventional treatment, so there is a need to develop new therapies and markers of treatment response. Various pathways involved in the development of the disease are known and the new therapies have focused on blocking the inflammatory process at the gastrointestinal level by oral, intravenous, subcutaneous, and topical route. All these new therapies can lead to more personalized treatments with higher success rates and fewer relapses. These treatments have not only focused on clinical remission, but also on achieving macroscopic changes at the endoscopic level and microscopic changes by achieving mucosal healing. These treatments are mainly based on modifying signaling pathways, by blocking receptors or ligands, reducing cell migration and maintaining the integrity of the epithelial barrier. Therefore, this review presents the efficacy and safety of the new treatments that are currently under study and the advances that have been made in this area in recent years.