GDNF-induced seminomatous tumours in mouse--an experimental model for human seminomas?

Glial-cell-line-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor superfamily. It binds to and activates a receptor complex consisting of GFR-alpha1 and Ret receptor tyrosine kinase. In testis, GDNF is expressed by Sertoli cells. We have shown by transgenic loss- and gain-of-function mouse models that GDNF regulates the cell fate decision of undifferentiated spermatogonia. In the GDNF +/- mice, the spermatogonia differentiate in excess leading to the depletion of germ cells. In the mice overexpressing GDNF in testes, undifferentiated spermatogonia accumulate in the tubules, no sperm is produced, and the mice are infertile. After a year, the GDNF overexpressing mice frequently (89%) develop testicular tumours, and most of them are bilateral (56%). All these tumours show the same histological pattern. They are composed of round spermatogonial/gonocytic cells with only a scant cytoplasm. The tumours are locally invasive but do not metastasise. They express germ line markers, are positive for alkaline phosphatase, and aneuploid with a triploid peak. Thus, by several histological, molecular, and histochemical characteristics, the GDNF-induced tumours mimic classical seminomas in men, but the precursor lesions are apparently different in mouse and man.     

中医药对糖尿病足溃疡相关细胞因子调控作用的研究进展

糖尿病足溃疡是糖尿病严重的破坏性并发症,致残率及致死率逐年增高,严重威胁人类身心健康。中医药治疗糖尿病足溃疡,注重辨证论治与整体观念相结合,不仅能改善中医证候,更能在加速创面愈合的同时减少创面的复发,一定程度上延缓了糖尿病足溃疡的进一步恶化,降低其致残率及致死率。现代研究发现,糖尿病足溃疡难以愈合与各种细胞因子如炎症因子、生长因子、趋化因子等分布异常密切相关;随着现代医学对中医药研究的不断深入,中药单体及复方调控细胞因子治疗糖尿病足溃疡已成为研究热点,该文通过对目前国内外研究现状进行归纳,得出以下总结：(1)芝麻酚、栀子苷、当归补血汤、紫朱软膏等调节肿瘤坏死因子-α(TNF-α)、白细胞介素（IL）-1、IL-6、IL-10等炎症因子,抑制创面炎症。(2)白芷、丹酚酸B、四效散、壮药拔毒生肌膏等调节血管内皮生长因子（VEGF）、血小板衍生生长因子（PDGF）、转化生长因子（TGF）、表皮生长因子（EGF）等生长因子,促进创面胶原沉积及血管新生。(3)芍药苷、隐丹参酮、蜂毒、回阳生肌汤等调节CXC趋化因子配体（CXCL）1、CXCL2、CC趋化因子配体（CCL）2、CCL3、基质细胞衍生...     

慢性肾功能衰竭患者血清IL-8和TNF-α的检测及意义

细胞因子在慢性肾功能衰竭(CRF)中的作用日益受到人们的重视,尤其是白细胞介素-8(IL-8)和肿瘤坏死因子(TNF-α)〔1〕。本文作者测定了19例CRF患者血清IL-8和TNF-α的含量,探讨其在CRF的发生、发展过程中所起的作用及意义。 　　1　材料与方法 　　1.1　病例选择　19例CRF患者均为我院住院病人,男11例,女8例,年龄21～68岁,平均41.5岁;原发病为慢性肾小球肾炎11例,慢性肾盂肾炎5例,高血压肾病2例,多囊肾1例。健康对照组20例为中心血站献血队员。两组在采血前两周内无感染史及应用免疫抑制剂或增强剂药物史。     

基于肠道菌群和代谢组学研究化滞柔肝颗粒治疗非酒精性脂肪肝的作用机制

目的 探讨化滞柔肝颗粒治疗非酒精性脂肪肝（nonalcoholic fatty liver disease,NAFLD）的作用机制。方法 高脂饮食饲养8周构建大鼠NAFLD模型,化滞柔肝颗粒ig给药4周。半自动生化分析仪测定大鼠血脂相关指标;油红O染色观察肝脏组织病理变化;Illumina Miseq测序平台对V3～V4可变区进行扩增和测序,超高效液相色谱串联质谱（UPLCMS/MS）开展血浆代谢组学研究,并结合Spearman进行肠道菌群与代谢组学之间的关联分析。结果 与模型组相比,化滞柔肝颗粒中、高剂量组可显著降低大鼠体质量（P<0.05、0.01）和血清总胆固醇（totalcholesterol,TC）、三酰甘油（triacylglycerol,TG）水平（P<0.01）,升高高密度脂蛋白（high-density lipoprotein cholesterol,HDL-C）水平（P<0.05、0.01）。此外,化滞柔肝颗粒高剂量组还可显著降低大鼠低密度脂蛋白（low-density lipoprotein cholesterol,LDL-C）水平（P<0...     

Clinicopathological characteristics,prognosis, and chemosensitivity in patients with metastatic upper tract urothelial carcinoma

PurposeTo investigate the clinical characteristics, chemosensitivity, and outcome of metastatic upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of patients with metastatic UTUC since January 2005 were retrieved from a database that included clinical and survival data. Statistical analyses including survival and multivariate analyses of factors were respectively performed by the Kaplan-Meier method and Cox proportional hazard model.ResultsA total of 250 consecutive UTUC cases were evaluated. There were 56 patients (22.4%) with initially diagnosed stage IV disease. The most common metastatic sites were lung (39.6%), distant lymph nodes (39.2%), bone (19.6%), liver (18.0%), and adrenal gland (7.2%), respectively, and the local recurrence rate was 10.4%. Two hundred thirteen patients received first-line chemotherapy. The overall response rate was only 28.7% and the median progression-free survival time was only 5.0 months. The overall survival time of the cohort was 18.0 months. Multivariate analyses showed that initially diagnosed stage IV disease, number of metastatic organs ≥3, no response to chemotherapy and cycles of chemotherapy ≤2 were adverse prognosticators for overall survival.ConclusionUTUC presented to be more prone to metastasize than locally recur and thought to have low chemosensitivity. Stage IV disease at initial diagnosis, number of metastatic organs, response and cycles of chemotherapy were independent prognosticators for metastatic UTUC.     

用非同位素原位杂交组化在光镜和电镜水平观察前阿黑皮素mRNA在垂体的分布

用地高辛标记反意前阿黑皮素(pro-opiomelanocortin,POMC)cRNA探针原位杂交组化在光镜和电镜水平观察了POMC mRNA在大鼠垂体的分布,并比较了碱性磷酸酶(AKP)显色系统和辣根过氧化酶(HRP)显色系统在光镜水平上的敏感性.结果:POMC mRNA广泛地分布于垂体的中间叶和前叶.中间叶全部细胞均为POMC mRNA阳性.前叶中除前叶的腹侧缘和前叶与中间叶交界处阳性细胞较少外,都有较多的POMC mRNA阳性细胞分布.AKP显色系统比HRP显色系统敏感.在电镜水平,POMC mRNA主要分布于粗面内质网,少数分泌颗粒可能呈阳性反应,胞核未见阳性反应沉淀.文内还就阳性分泌颗粒在调节细胞合成功能方面可能起的作用进行了讨论.     

不同机制大动脉粥样硬化型脑卒中基线特征和血管内治疗后结局比较

目的 本研究旨在比较颅内大血管伴/不伴同侧颈内动脉闭塞的大动脉粥样硬化型脑卒中患者基线特征以及行血管内治疗后结局的差异。方法 对DIRECT-MT亚组进行回顾性分析,以比较前循环大动脉粥样硬化（large-artery atherosclerosis,LAA）型卒中串联闭塞和颅内闭塞接受血管内治疗（endovascular treatment,EVT）的患者的基线特征和预后,分析不同机制学特征（动脉粥样硬化或动脉-动脉栓塞）对临床结局的影响。结果 LAA型卒中患者共108例,其中串联闭塞63例,颅内闭塞45例。颅内闭塞组患者高血压史率高于串联闭塞组（77.8% vs. 52.4%, P=0.007）。颅内闭塞组闭塞部位最常见于大脑中动脉M1段（88.6%）,而串联闭塞组颅内闭塞主要位于颈内动脉颅内段（49.2%）和大脑中动脉M1段（49.2%）（P＜0.001）。两组患者在年龄、性别、术前抗栓、他汀类药物的使用,卒中、房颤、吸烟史,基线mRS、NIHSS评分,是否静脉溶栓,侧枝循环,以及救治流程时间差异均无统计学意义（P均＞0.05）。90天mRS 0-2分的患者比例两组差异无统计学意义（53.3% vs. 41.9%, P=0.243）。颅内闭塞组术后成功再灌注率高于串联闭塞组（93.3% vs. 77.4%, P=0.026）,但术后24-72小时血管再通的比例前组低于后组（57.1% vs. 77.2%, P=0.034）。最终梗死体积,颅内闭塞组小于串联闭塞组（20.1 vs. 34.5, P=0.025）。术后NIHSS评分,90天EQ-5D-5L评分和BI指数等其他次要结局,两组间差异无统计学意义（P均＞0.05）。两组在90天内的死亡率,发生的无症状性和症状性颅内出血率,5-7天时在另外的血管区域新发脑梗死,以及新流域栓塞的患者百分比相似,差异无统计学意义（P均＞0.05）。结论 动脉粥样硬化导致的串联闭塞相较于孤立颅内闭塞,末次造影成功再灌注率较低,梗死体积更大,但术后24-72小时再通率更高,且神经功能良好预后率以及不良事件发生率均与颅内闭塞相仿。     

特瑞普利单抗联合舒尼替尼治疗晚期肾细胞癌的初步疗效分析

目的：评估特瑞普利单抗联合舒尼替尼治疗晚期肾细胞癌的疗效与安全性。方法：回顾性分析2020年1月—2022年3月海军军医大学第二附属医院接受特瑞普利单抗联合舒尼替尼治疗的25例晚期肾癌患者临床资料,其中男21例,女4例,中位年龄为59 (33~80)岁。25例患者病理类型均为透明细胞癌,其中2例为TFE3融合基因相关肾癌,1例部分肉瘤样变,25例患者均发生局部进展或远处转移。评价其生存获益和相关不良反应发生情况。结果：中位随访时间11.0(2.5～24)个月,25例患者均可评价疗效,总体人群ORR 36.0%,DCR 84.0%,9例患者部分缓解,12例患者病情稳定,4例患者疾病进展,中位PFS 12.7个月(95%置信区间：10.7～14.7),中位OS尚未达到。治疗总体不良反应发生率为88.0%,常见不良反应包括皮疹、腹泻、手足皮肤反应、高血压等,90%的不良反应为1~2级。