Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

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祛寒逐风合剂联合西医常规疗法治疗膝骨关节炎风寒痹阻证临床研究

目的观察祛寒逐风合剂联合西医常规疗法对膝骨关节炎风寒痹阻证的临床疗效,以及对关节症状及相关实验室指标的影响。方法采用随机数字表法将94例膝骨关节炎风寒痹阻证患者分为观察组和对照组各47例。对照组采用常规药物疗法+康复训练,观察组在对照组基础上予祛寒逐风合剂,每次50m L,每日3次,口服。2组均连续治疗2周。比较2组临床疗效,观察2组治疗前后美国西大略湖和麦克马斯特大学骨关节炎指数(WOMAC)评分、视觉模拟评分法(VAS)评分、压痛指数、中医症状评分,白细胞介素(IL)-1β、IL-6、血管内皮生长因子(VEGF)、肿瘤坏死因子(TNF)-α、骨钙素、抗酒石酸盐酸性磷酸酶异构体(TRACP)-5b、骨特异性碱性磷酸酶(BALP)、纤维蛋白原、红细胞沉降率和红细胞聚集指数,对2组进行安全性评价。结果观察组总有效率为89.36%(42/47),对照组为74.47%(35/47),观察组明显优于对照组(P<0.05)。与本组治疗前比较,2组治疗后WOMAC评分、VAS评分、压痛指数、中医症状评分明显下降(P<0.05);2组治疗后比较,观察组WOMAC评分、VAS评分、压痛指数、中医症状评分明显低于对照组(P<0.05)。与本组治疗前比较,2组治疗后IL-1β、IL-6、TNF-α、VEGF、TRACP-5b水平明显下降,骨钙素、BALP水平明显升高(P<0.05);2组治疗后比较,观察组IL-1β、IL-6、TNF-α、VEGF、TRACP-5b水平明显低于对照组,骨钙素、BALP水平明显高于对照组(P<0.05)。与本组治疗前比较,观察组治疗后纤维蛋白原、红细胞沉降率、红细胞聚集指数明显下降(P<0.05);2组治疗后比较,观察组血液流变学各项指标明显低于对照组(P<0.05)。2组均未发生不良反应。结论祛寒逐风合剂联合西医常规疗法治疗膝骨关节炎风寒痹阻证患者疗效较好,可明显改善关节症状及相关实验室指标。     

Acute Immobilization Stress and Intraventricular Injection of CRF Suppress Naloxone-Induced LH Release in Ovariectomized Estrogen-Primed Rats

The present study was undertaken to evaluate the role and possible interaction of the endogenous opioid peptide (EOP) and corticotropin-releasing factor (CRF) in the acute stress-induced suppression of gonadotropin secretion in ovariectomized estrogen-primed rats. An intravenous (i.v.) injection of naloxone (10 or 20  mg/kg), an EOP antagonist, significantly elevated serum luteinizing hormone (LH) levels within 10  min in non-stressed animals. The naloxone-induced LH release was completely eliminated when tested 30  min after the onset of acute immobilization. In a subsequent study, it was found that suppression of the naloxone-induced LH release occurred as early as 5  min after the stress onset, and was still evident 60  min after the end of a 30-min period of immobilization. The effect of naloxone was restored 3  h after liberation of the animal from the 30-min immobilization. An intraventricular (i.c.v.) injection of CRF (1 or 5  μg) also significantly suppressed, in a dose-related manner, the effect of a subsequent i.v. injection of naloxone. However, an i.c.v. injection of α -helical CRF(9-41) (25 or 50  μg), a CRF antagonist, prior to immobilization, could not interfere with the suppressive effect of stress on naloxone-induced LH release. These results suggest that both acute immobilization stress and CRF can inhibit the LH secretory activity without mediation by EOP neurons. However, the stress-related suppression may involve non-CRF mechanism(s).     

东北地区风寒指数气候特征与冷习服锻炼日期的确定

应用中国东北４８个站１０年的逐日气象资料，分析了风寒指数（Ｖｔ）的候、月、旬、日平均值，据此，提出了各地可供冷习服锻炼的天数及可开始锻炼的日期等。研究结果在生物气候区划和指导部队耐寒锻炼等方面有重要作用，也有助于较精确的估算冷应激强度及寒冷环境对作业能力影响的预测。     

头风痛胶囊治疗头风病(偏头痛)风瘀证临床观察附:62例病例报告

目的　观察中药四类新药头风痛胶囊治疗头风病 (偏头痛 )风瘀证的临床疗效及安全性。方法　采用随机对照试验 ,将 6 2例病人随机分为治疗组和对照组 ,每组 31例 ,分别服用头风痛胶囊和头风痛丸 ,疗程 1月 ,观察其疗效和副作用。结果　治疗组的头痛疗效为显效率 6 4 5 2 %、有效率 87 10 % ;中医证候疗效为显效率 6 1 2 9%、有效率 90 32 %。两组疗效之差异无统计学意义 (P >0 0 5 )。临床试验期间未发现头风痛胶囊所致的不良反应。结论　头风痛胶囊有较好的祛风止痛作用 ,服用安全 ,与头风痛丸具有相同的疗效 ,是头风痛丸的理想新剂型     

Coexisting Endogenous and Exogenous Llpold Pneumonia and Pulmonary Alveolar Proteinosis in a Patient with Neurodevelopmental Disease

We report a unique case of coexistingexogenous lipoid pneumonia, endogenous lipoid pneumonia (EU), and pulmonary alveolar proteinosis (PAP) in a 5-year-old patient with severe neurodevelop mental disease. The patient presented with gastroesophageal reflux and presumed chronic lung disease resulting from recurrent aspiration pneumonias and succumbed to respiratory failure. The autopsy showed lipid-laden macrophages and periodic acid-SchiJf9ositive granular matm'al i n alveolar spaces and multilamellated structures within both alveolar macrophages and extracellular debris.

These findings were similar to those in previous reports of coexisting E I P and PAP in the setting of gastroesophageal refux [I] . However, the present case diJfered by the presence of scattered large osmiophilic extracellular lipid vacuob. Besides strengthening the association between EIP and PAP and their relationship to gastroesophageal refux, this case suggests that t h q may arise together with exogenous lipoid pneumonia, through related mechanisms, in the setting of neurodevelopmental disease.     

加味半夏白术天麻汤治疗风痰阻络型脑梗塞的临床研究

目的：观察加味半夏白术天麻汤治疗风痰阻络型脑梗塞的临床疗效及对血液流变学、血清超敏C反应蛋白（he—CRP）的影响。方法：对照组给予阿斯匹林片0．1g，日1次；胞二磷胆碱0．5g加入生理盐水100ml中静脉点滴，日1次；脑水肿明显者应用甘露醇脱水治疗。治疗组在对照组基础上加用半夏白术天麻汤加味。连续治疗一个月后进行临床疗效及神经功能的评定，治疗前后检查血液流变学及he—CRP。结果：治疗组总有效率95％，对照组81．67％，治疗组优于对照组，有显著差异（P〈0．05）；在改善神经功能评分、血液流变学及he—CRP方面，治疗组均优于对照组，有显著性差异（P〈0．05，或P〈0．01）。结论：加味半夏白术天麻汤治疗风痰阻络型脑梗塞临床疗效较好，并能减少神经功能缺损程度评分，改善血液流变学及降低he—CRP。     

Construction of a risk model of steroid-induced necrosis of the femoral head and prediction of potential Chinese medicine treatments北大核心

背景:随着疾病治疗模式的改变,人们已经意识到中医药在激素性股骨头坏死治疗过程中的重要性,因此利用生物信息学从分子水平分析激素性股骨头坏死的发病机制,构建疾病风险模型,并预测具有潜在治疗作用的中药,为后期中医药治疗激素性股骨头坏死提供一定的理论依据。目的:基于生物信息学挖掘激素性股骨头坏死的竞争性内源RNA(ceRNA)调控网络,分析其在激素性股骨头坏死中的分子调控机制,预测相关疾病靶点并构建疾病风险模型,同时预测具有潜在治疗作用的中药。方法:检索GEO数据库,下载激素性股骨头坏死的矩阵文件GSE123568和基因注释文件GPL15207。借助R语言等软件分析得到差异表达的长链非编码RNA与mRNA,并通过公共数据库预测与差异表达长链非编码RNA关联的miRNA-mRNA,再将预测到的mRNA与差异表达mRNA取交集,整合得到ceRNA网络。随后采用STRING数据库和Cytoscape软件筛选关键基因,利用R语言分析关键基因的功能与相关通路,并挖掘关键ceRNA网络。最后根据关键基因构建激素性股骨头坏死的风险模型,并进行中药预测。结果与结论:(1)与健康对照相比,激素性股骨头坏死患者共有7个长链非编码RNA和1763个mRNAs存在差异表达;(2)筛选出STAT3、KAT2B、AGO4、JAK2、JAK1、PTGS2共6个关键基因;(3)关键基因所富集的功能包括对肽激素的反应、白细胞介素6介导的信号通路、细胞对白细胞介素6的反应等生物学过程,涉及JAK-STAT、脂肪细胞因子、催乳素等信号通路;(4)4种mi RNAs(mi R-135a-5p、mi R-137、mi R-17-5p、miR-20b-5p)和2种长链非编码RNA(SNHG11、C20orf197)可能在导致激素性股骨头坏死发生发展过程中发挥关键作用;(5)KAT2B最有可能是激素性股骨头坏死发生发展的风险因子;(6)郁金、淫羊藿、黄芪具备治疗激素性股骨头坏死疾病靶点的可能。通过对激素性股骨头坏死相关长链非编码RNA介导的ceRNA网络进行分析,识别出潜在的疾病靶点、信号通路及潜在治疗中药,为进一步阐明其发病机制,并为后续的实验研究提供参考依据。