Current knowledge of risk factors for testicular germ cell tumors

The development of the human gonads is tightly regulated by the correct sequential expression of many genes and hormonal activity. Disturbance of this regulation does not only prevent proper development of the gonads, but it also contributes to the development of testicular germ cell tumors. Recent genetic studies, especially genome‐wide association studies, have made great progress in understanding genetic susceptibility. Although there is strong evidence of inherited risks, many environmental factors also contribute to the development of testicular germ cell tumors. Histopathological studies have shown that most testicular germ cell tumors arise from germ cell neoplasia in situ, which is thought to be arrested and transformed primordial germ cells. Seminoma has features identical to germ cell neoplasia in situ or primordial germ cells, whereas non‐seminoma shows varied differentiation. Seminomas and embryonic cell carcinomas have the feature of pluripotency, which is thought to be the cause of histological heterogeneity and mixed pathology in testicular germ cell tumors. Testicular germ cell tumors show high sensitivity to chemotherapies, but 20–30% of patients show resistance to standard chemotherapy. In the present review, the current knowledge of the epidemiological and genomic factors for the development of testicular germ cell tumors is reviewed, and the mechanisms of resistance to chemotherapies are briefly mentioned.     

当归注射液对葡萄糖致血管内皮细胞损伤的保护作用

目的：探讨当归对高浓度葡萄糖所致血管内皮细胞损伤保护作用的机制。方法：以不同浓度的葡萄糖（葡萄糖组，7．5—60mmol／L）、不同浓度当归（当归组，12．5—200mg／L）及联合组，当归联合24h半数致死量（24hIC50）葡萄糖，30mmol／L作用于人体脐静脉内皮细胞（VEC-304）24h，观察细胞生长状态、MTT法检测细胞增长率、RT—PCR检测细胞内皮生长因子（VEGF）mRNA表达及Westernblot检测VEGF蛋白水平。结果：与对照组比较，不同浓度作用VEC一30424h，葡萄糖组A值明显降低；当归组则明显升高（P〈0．05或P〈0．01）；联合组于低浓度当归（12．5—100mg／L）联合葡萄糖对细胞起抑制作用，高浓度（100—200mg／L）当归联合葡萄糖则有增殖作用。RT-PCR和West—ernblot显示，葡萄糖组VEGFmRNA和蛋白表达下调；联合组则表达正常。结论：高浓度葡萄糖可损伤血管内皮细胞，当归可保护高浓度葡萄糖下血管内皮细胞，这可能是当归治疗糖尿病并发组织缺血性疾病的机制之一。     

Angiotensin receptors in Dupuytren’s disease: a target for pharmacological treatment?

Background: Attempts at the pharmacological treatment of Dupuytren’s disease have so far been unsuccessful, and the disease is not yet fully understood on a cellular level. The Renin-Angiotensin System has long been understood to play a circulating hormonal role. However, there is much evidence showing Angiotensin II to play a local role in wound healing and fibrosis, with ACE inhibitors being widely used as an anti-fibrotic agent in renal and cardiac disease.

Methods: This study was designed to investigate the presence of Angiotensin II receptors 1 (AT1) and 2 (AT2) in Dupuytren’s tissue to form a basis for further study into the pharmacological treatment of this condition. Tissue was harvested from 11 patients undergoing surgery for Dupuytren’s disease. Each specimen was processed into frozen sections and immunostaining was employed to identify AT1 and AT2 receptors.

Results: Immunostaining for AT1 receptors was mildly positive in one patient and negative in all the remaining patients. However, all specimens stained extensively for AT2 receptors. This suggests that the expression of AT2 receptors is more prominent than AT1 receptors in Dupuytren’s disease.

Conclusion: These findings have opened a new avenue for future research involving ACE inhibitors, AT2 agonists, and AT2 antagonists in Dupuytren’s disease.     

Observations From Intraatrial Recordings on the Termination of Electrically Induced Atrial Fibrillation in Humans

Background: The circulating wavelet hypothesis suggests that atrial fibrillation could terminate by either progressive fusion or simultaneous block of all wavelets. Methods: Intraatrial recordings from the right atrial free wall were made during procainamide induced (n = 8) or spontaneous (n = 7) termination of electrically induced atrial fibrillation in 14 patients. Atrial rate, mean magnitude squared coherence, and direction of activation during sequential electrograms were measured. Rate and coherence were calculated from the earliest point within 5 minutes prior to termination as well as from the 4-second interval just prior to termination. Results: Termination was directly to sinus rhythm (13 episodes) or to atrial flutter (2 episodes). For the eight procainamide induced terminations, rate decreased between the first measurement and the measurement just prior to termination, from 443 ±127 beats/ min to 322 ± 119 beats/min. For the seven spontaneous terminations, rate also decreased from 373 ± 119 beats/min to 323 ± 88 beats/min; however, a slight increase in atrial rate prior to termination was observed in three episodes. No specific patterns of atrial cycle lengths were seen during the final few seconds of fibrillation. No increase in coherence was observed. In seven episodes, recordings were made using orthogonal bipoles in the x, y, and z directions, allowing direction of activation of wavefronts to be measured. Three episodes showed multiple instances where direction of activation remained similar over several electrograms as we have previously reported for chronic fibrillation. However, no such instances precipitated termination in any of the seven episodes. Conclusions: Atrial fibrillation usually terminates directly to sinus rhythm and does so abruptly and without forewarning. While we and others have previously reported that the rate of atrial fibrillation decreases with procainamide infusion, a decrease in the rate of atrial fibrillation is not required for the rhythm to terminate and consequently may not be a part of the termination process at all. Coherence does not demonstrate a progressive increase in the organization of atrial fibrillation prior to termination. Lack of stabilization in the direction of activation of wavefronts in the final few seconds also fails to support fusion of wavefronts as the mechanism of termination of atrial fibrillation. Simultaneous block of all wavelets is consistent with, but not proven by our observations.     

滞针术临床研究进展

滞针术是指毫针刺入腧穴后,将针柄向同一个方向进行捻转,使针身与肌纤维相缠绕的一种使针感保持持续且强烈的行针手法。滞针术临床多用于痛症、急症、顽症的治疗,相比于常规针刺治疗,其具有操作简便、取穴少、针感强烈等优势。对滞针术的起源、机制及临床应用进行综述,分析现存问题并提出展望,以期可以更好地指导临床应用。     

水蛭在糖尿病心血管疾病中的作用机制与应用

糖尿病的发病率不断升高,其中心血管事件成为糖尿病致死的主要原因。积极的防治糖尿病心血管疾病是减低糖尿病致死率的关键。水蛭在糖尿病心血管疾病的治疗当中,发挥着调节代谢、改善血液流变、保护血管内皮、调节细胞因子、抗纤维化、改善心功能等综合作用。临床上可用于治疗糖尿病合并高脂血症、动脉粥样硬化、冠心病、不稳定型心绞痛、陈旧性心肌梗死、心肌缺血等。用药安全,疗效确切,为糖尿病心血管疾病的全面防治提供了参考。     

基于网络药理学探讨抗感方抗病毒作用机制

目的基于网络药理学方法研究抗感方治疗冠状病毒、呼吸道合胞病毒(RSV)的作用机制。方法借助TCMSP数据库筛选出抗感方活性成分及作用靶点,通过Gene Cards数据库筛选出冠状病毒、RSV的疾病靶点。利用Cytoscape软件、STRING数据库分别构建“药物-成分-靶点-疾病”的相互作用和潜在靶点PPI网络图,并进行GO和KEGG富集分析,最后进行分子对接验证。结果抗感方中174种潜在活性成分,涉及51个抗病毒关键靶点,可能通过IL-17、AGE-RAGE、TNF、Toll样受体、NOD样受体等炎症、免疫信号通路发挥抗病毒作用。16种主要活性成分对冠状病毒和RSV关键靶蛋白(Mpro与RSV-F)均有较好地结合力。结论抗感方中多种活性成分通过多靶点、多通路协同作用发挥对冠状病毒与RSV的干预作用,为临床应用于多种病毒的防治提供理论依据。     

基于实体语法系统的泽漆治疗肺癌的作用机制研究

目的:利用数据融合及分析手段研究泽漆治疗肺癌的分子机制。方法:通过实体语法系统将泽漆化学成分数据、泽漆“成分-靶点”关系数据、人类蛋白-蛋白相互作用(PPI)数据等进行融合,得到有向网络;利用实体语法系统进行定性推理,得到泽漆化学成分作用于肺癌的靶点;利用基因本体(GO)富集分析、通路富集分析等解析泽漆治疗肺癌的作用机制。结果:通过实体语法系统推理,获得泽漆7个化学成分及55个肺癌治疗靶点;经过实体语法推理和富集分析,泽漆成分中的木犀草素可抑制生长因子(GF)、没食子酸甲酯和槲皮素可抑制上皮生长因子(EGFR)、槲皮素可抑制周期蛋白依赖性激酶1(CDK1),共同发挥抑制肺癌细胞增殖的作用;没食子酸和木犀草素可直接激活半胱氨酸天冬氨酸蛋白酶-3(CASP3)发挥促进肺癌细胞凋亡的作用;泽漆内酯B和泽漆内酯C通过抑制三磷酸腺苷结合盒转运蛋白G2(ABCG2)发挥逆转肺癌肿瘤多药耐药的作用。结论:泽漆主要通过调节丝裂原活化蛋白激酶(MAPK)信号通路和磷脂酰肌醇3-激酶(PI3K)-蛋白激酶B(Akt)信号通路等发挥抑制肺癌细胞增殖和促进肺癌细胞凋亡的综合作用,为泽漆的应用和肺癌的治疗提供参考。     

基于网络药理学对枸杞子-五味子治疗注意缺陷多动障碍的机制探究

目的:基于网络药理学探讨枸杞子-五味子药对治疗注意缺陷多动障碍的药效物质基础和作用机制。方法:检索ETCM数据库,筛选枸杞子-五味子活性成分及靶基因;检索Drugbank、Genecards、DisGeNET和TTD数据库,筛选ADHD相关靶基因;利用Cytoscape构建药对活性成分-靶点网络并进行拓扑结构分析;对疾病靶点与药对靶点绘制维恩图筛选关键靶点,利用David进行GO分析和KEGG分析。结果:筛选出枸杞子-五味子有36个活性成分,207个靶基因,活性成分-靶点拓扑结构分析得到Inosine和其他基因互相关联程度最高;筛选出ADHD相关靶基因1 861个,维恩图提取关键靶点73个,GO分析得到11条生物过程,12条细胞组分表达过程,14个分子功能相关过程;KEGG分析显示21条信号通路,包括类固醇激素的合成、细胞色素P450代谢、GABA能突触及胆碱能突触调节、色氨酸代谢等。结论:枸杞子-五味子药对活性成分通过多成分、多靶点、多通路调控机体类固醇激素代谢、神经递质代谢、中枢神经系统调节、免疫调节对ADHD发挥治疗作用。