目的:探讨肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)对糖尿病大鼠钠潴留的影响及作用机制.方法:成功制备糖尿病大鼠模型后,采用蛋白免疫印迹及膜片钳等技术观察TNF-α对糖尿病大鼠钠平衡指数及髓袢升支粗段(thick ascending limb,TAL)管周膜氯通道(CLCNK)的影响.结果:1)与NC组相比,DM组空腹血糖明显升高(n=8,P＜0.01).2)与NC组相比,DM组TAL组织中TNF-α的蛋白表达明显升高(n=3,P＜0.01).3)与NC组相比,DM组24h钠平衡指数明显升高(n=8,P＜0.01);与DM组相比,DM+TNFR:Fc组24h钠平衡指数下降(n=8,P＜0.05).4)与NC组相比,DM组CLCNK蛋白表达明显升高(n=3,P＜0.01);与DM组相比,DM+TNFR:Fc组CLCNK蛋白表达下降(n=3,P＜0.05).5)与NC组相比,给予TNF-α后氯通道开放率明显升高(n=5,P＜0.01).结论:TNF-α通过增加糖尿病大鼠TAL管周膜氯通道活性而促进钠潴留的发生.

目的:探讨肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)对糖尿病大鼠肾脏肥大的影响.方法:成功制备糖尿病肾病大鼠模型后,采用蛋白免疫印迹等技术观察TNF-α对糖尿病大鼠肾脏肥大的影响.结果:1)与NC组相比,DM组空腹血糖及24h尿白蛋白排泄量明显升高(n=8,P＜0.01);2)与NC组相比,DM组肾组织中TNF-α的蛋白表达明显升高(n=3,P＜0.01);3)与NC组相比,DM组肾指数明显升高(n=8,P＜0.01);与DM组相比,DM+TNFR:Fc组肾指数下降(n=8,P＜0.05).结论:糖尿病肾病时TNF-α水平增高,并促进糖尿病肾脏肥大的发生.

作为糖尿病的主要并发症,糖尿病肾病已成为慢性肾衰竭的主要原因,最终导致终末期肾病的发生.因此,早期诊断并进行有效干预对防止糖尿病肾病进一步恶化具有重要意义.近年来发现多种与糖尿病肾病发生发展密切相关的生化指标,本文对其作一简要概述,以期为临床早期诊断糖尿病肾病寻求新的靶点.

Diabetic nephropathy is a major contributor to the morbidity and mortality of patients with diabetes. TNF-α expression is elevated during diabetes and is implicated in the pathogenesis of diabetic nephropathy; however, its underlying molecular mechanisms remain unclear. The present study aimed to investigate the effect and molecular mechanism of TNF-α on the basolateral inwardly rectifying potassium (Kir)4.1/Kir5.1 channels in the thick ascending limb (TAL) of rat kidneys using western blotting and the patch clamp technique to provide a theoretical basis for the cause of the decrease in kidney concentrating capacity during diabetes. The results demonstrated that urinary TNF-α excretion and protein TNF-α expression in the TAL increased and basolateral Kir4.1/Kir5.1 channel activity decreased during diabetes; however, diabetic rats exhibited amelioration of Kir4.1/Kir5.1 activity with a soluble TNF-α antagonist, TNF receptor fusion protein (TNFR:Fc). These results suggested that TNF-α inhibited the activity of the basolateral Kir4.1/Kir5.1 channel in the TAL of rat kidneys during diabetes. In addition, the protein expression levels of phospholipase A2 (PLA2) and cyclooxygenase-2 (COX2) increased in diabetic rats, the effects of which deceased following treatment with TNFR:Fc compared with the diabetic group. Furthermore, an agonist of PLA2 (melittin) and COX2 production [prostaglandin E2 (PGE2)] inhibited the basolateral Kir4.1/Kir5.1 channels. Taken together, the results of the present study suggested that the inhibitory effect of TNF-α on the basolateral Kir4.1/Kir5.1 channels in the TAL during diabetes is mediated by the PLA2/COX2/PGE2 signaling pathway.

创新精神是大学生应当具备的核心素养,而实验课是培养学生创新精神的重要阵地.本文以生物化学实验教学为例,从不同角度关注创新精神的培养,旨在提高实验教学的质量,培养社会需要的离素质创新人才.

目的 黄芩苷在降血糖血脂、改善代谢综合征方面的作用受到广泛关注,文章观察黄芩苷对糖尿病肾病(DN)大鼠肾的保护作用,探讨其可能的调控机制.方法 45只雄性SD大鼠随机数字表法分为正常对照组、DN模型组、黄芩苷处理组,每组15只.正常组常规饲养,模型组与黄芩苷处理组建立DN模型,分别给予相应制剂灌胃治疗.固定时间点后检测大鼠体重、空腹血糖(FBG)、血清尿素氮(BUN)、血肌酐(Scr)水平,观察各组大鼠肾的病理组织学变化,Western blot检测转化生长因子-β1(TGF-β1)与α-SMA蛋白表达.结果 与正常对照组大鼠相比,模型组大鼠空腹血糖在造模后4、8周明显升高,而体重降低(P<0.05);与模型组相比,黄芩苷治疗组大鼠在造模后4、8周血糖明显下降(P<0.05).与正常对照组BUN、Scr、24 h尿量[(8.01±0.92)mmol/L、(24.15±3.24)μmol/L、(10.78±1.24)mL]相比,模型组[(16.97±3.63)mmol/L、(52.58± 2.33)μmol/L、(32.65±2.69)mL]明显升高(P<0.05);而黄芩苷处理组较模型组[(12.73±0.67)mmol/L、(43.77±1.73)μmol/L、(19.34±2.16)mL]明显降低(P<0.05).结论 黄芩苷可延缓DN的进展,改善肾纤维化,其作用机制可能与黄芩苷通过低调节TGF-β1从而降低α-SMA的表达密切相关.

糖尿病肾病(DN)是糖尿病患者最常见且最严重的并发症之一.在糖尿病患者中,约三分之一可发展为DN,进而发展为终末期肾病(ESRD),是导致糖尿病人群死亡率的主要原因[1].有关DN病因和发病机制的阐述涉及诸多因素,普遍认为是由遗传和环境因素共同引发的一系列复杂病理生理事件[2].通过在细胞和分子水平上对DN病因学的深入探究发现,炎症是其致病的一种重要病理生理机制,只是该炎症区别于传统意义上以红、肿、热、痛为主要特征的经典炎症,因其具有慢性、轻微等特征,通常被称为“微炎症”[3].

CXCL3 belongs to the CXC-type chemokine family and is known to play a multifaceted role in various human malignancies. While its clinical significance and mechanisms of action in uterine cervical cancer (UCC) remain unclear. This investigation demonstrated that the UCC cell line HeLa expressed CXCL3, and strong expression of CXCL3 was detected in UCC tissues relative to nontumor tissues. In addition, CXCL3 expression was strongly correlated with CXCL5 expression in UCC tissues. In vitro, HeLa cells overexpressing CXCL3, HeLa cells treated with exogenous CXCL3 or treated with conditioned medium from WPMY cells overexpressing CXCL3, exhibited enhanced proliferation and migration activities. In agreement with these findings, CXCL3 overexpression was also associated with the generation of HeLa cell tumor xenografts in athymic nude mice. Subsequent mechanistic studies demonstrated that CXCL3 overexpressing influenced the expression of extracellular signal-regulated kinase (ERK) signaling pathway associated genes, including ERK1/2, Bcl-2, and Bax, whereas the CXCL3-induced proliferation and migration effects were attenuated by exogenous administration of the ERK1/2 blocker PD98059. The data of the current investigation support that CXCL3 appears to hold promise as a potential tumor marker and interference target for UCC.

糖尿病肾病是糖尿病的常见并发症,也是糖尿病患者的主要死因之一,其发病机制十分复杂,由多种因素和多种机制共同参与所致.本文主要从糖尿病肾病的发病机制及其防治方法等方面进行简要综述.

This paper introduces the first successful refracturing example of horizontal well in a tight volcanic gas reservoir of Xushen gas field. The well was fractured and put into production in 2008, with the accumulated gas production of 0.64×108 m3. Due to the limited technical conditions of the horizontal well-stage fracturing process at that time, only four fracturing stages have been carried out. the horizontal section of the volcanic gas reservoirs with more than 600 meters of the well was not fractured, leaving a large potential for increasing production. In 2017, based on the fine research of gas reservoirs, the refracturing optimization design, multi-stage perforation, fracturing and commissioning integrated tubular completion and the diagnosis control of complex fractures in fracturing construction, the refracturing job of the well is implemented successfully with a good result.

目的 探讨糖尿病肾病大鼠动物模型建立及TNF-α干预机制.方法 选择SD大鼠60只作为对象,随机数字法分为对照组和观察组,各30只.对照组大鼠腹腔注射柠檬酸缓冲液,观察组在对照组基础上采用高糖高脂饲料联合5％葡萄糖饮水喂养,诱导胰岛素抵抗,2周后腹腔注射STZ,连续注射3 d,诱发持续高糖血症.采用酶联免疫吸附法在建模前、建模2周、建模4周检测观察组大鼠血糖、尿白蛋白、肌酐水平,同时检测两组大鼠TNF-α水平,分析糖尿病动物模型建立及TNF-α干预机制.结果 ①对照组大鼠全身状态良好,体质量增加,皮毛光滑亮泽,观察组大鼠建模成功后出现多食、多饮、多尿及生长迟缓现象,成模4周后体重低于对照组,差异有统计学意义(P<0.05);②观察组建模2周血糖水平(8.21±0.21)mmol/L,建模4周血糖水平(31.21±1.04)mmol/L,均高于对照组的(6.32±0.19)mmol/L、(6.74±0.24)mmol/L),差异有统计学意义(P<0.05);③观察组建模2周TNF-α 水平为(3.03±0.23)mmol/L,建模4周TNF-α 水平为(12.10±1.12)mmol/L,均高于对照组的(1.64±0.58)mmol/L、(1.69±0.62)mmol/L,差异有统计学意义(P<0.05).结论 高糖高脂饲料联合浓度为5％葡萄糖饮水配合小剂量STZ能建立理想的糖尿病肾病大鼠动物模型,可以明确糖尿病肾病发展伴有TNF-α炎症因子水平升高,进一步为TNF-α干预机制研究奠定了基础.

糖尿病肾病是糖尿病的常见并发症,也是导致终末期肾病的主要原因,其早期病理改变主要表现为肾脏肥大,本文即从糖尿病性肾脏肥大的分类、形成机制及调控等方面进行简要综述.

Laboratory teaching is an important step in the basic medical education.Higher medical colleges and universities should strengthen laboratory teaching quality to cultivate scientific thinking,innovative consciousness and comprehensive analytical capability of medical students.

The aim of the present study was to investigate the acute effect and mechanism of tumor necrosis factor (TNF) on basolateral 50 pS K channels in the thick ascending limb (TAL) of the rat kidney. The TAL tubules were isolated from the rat kidney, and the activity of the 50 pS K channels was recorded using the patch-clamp technique. The results indicated that the application of TNF (10 nM) significantly activated the 50 pS K channels and the TNF effect was concentration-dependent. Inhibition of protein kinase A, phospholipase A(2) and protein tyrosine kinase using pathway inhibitors (H89, AACOCF3 and Herbimycin A, respectively) did not abolish the stimulatory effect of TNF, indicating that none of these pathways mediated the TNF effect. By contrast, the phenylarsine oxide inhibitor against protein tyrosine phosphatase (PTP) decreased the activity of the 50 pS K channels and blocked the stimulatory effect of TNF on these channels. Furthermore, western blot analysis demonstrated that the application of TNF (10 nM) in the TAL increased the phosphorylation of PTP, an indication of PTP activity stimulation. Thus, it was concluded that the acute application of TNF may stimulate the basolateral 50 pS K channel in the TAL and the stimulatory effect of TNF may be mediated by the PTP-dependent pathway.

Physiology is an important basic medical course, which is abstract and theoretical. Teachers should fully stimulate students' interest in learning and improve classroom teaching efficiency by using scientific teaching methods. This paper discusses how to improve the teaching efficiency of physiology from four aspects.

目的 比较讨论式教学与传统教学在肾脏内科病理教学中的应用效果.方法 选择2017年1月～6月肾脏内科病理培训生100名,根据教学方法不同分为对照组和观察组,各50例.对照组采用传统教学方法,观察组采用讨论式教学,两组均教学3个月.采用医院自拟测评试卷对两组学生学习兴趣、自主学习能力、病理分析能力、知识理解能力、合作协作能力及课堂活跃程度对教学质量进行评估,比较两组教学效果.结果 教学后,观察组学生学习兴趣(18.32±0.96)分、自主学习能力(18.05±0.85)分、病理分析能力(18.77±0.94)分、知识理解能力(18.13±0.83)分、合作协作能力(19.00±0.75)分及课堂活跃程度(19.32±0.58)分,均高于对照组,差异有统计学意义(P<0.05);观察组教学满意度为94.00％,高于的对照组84.00％,差异有统计学意义(P<0.05).结论 讨论式教学在肾脏内科病理教学中有助于提高教学质量及教学满意度,值得应用.

The present study aimed to examine the effects and mechanisms of exogenous C-X-C motif chemokine 5 (CXCL5) and lentiviral CXCL5 overexpression on the regulation of malignant behaviors of prostate cancer cells in vitro and in a nude mouse xenograft model. The expression levels of CXCL5 and a number of tumor-related genes were assessed by using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, ELISA, or immunohistochemistry in normal and cancerous prostate cells and tissues. Cell proliferation, colony formation, and Transwell assays were performed to determine the effects of exogenous, autocrine, and paracrine CXCL5 on prostate cancer cell proliferative and migratory capacity. The results indicated that CXCL5 expression was upregulated in PC‑3 and DU145 prostate cancer cells, in WPMY‑1 normal prostate stromal cells, and in RWPE‑1 prostate epithelial cells, as well as in prostate cancer tissue specimens. Exogenous CXCL5 exposure resulted in increase in prostate cancer cell proliferation, colony formation, and migration. In cells transfected with a CXCL5 overexpression vector, in cells cultured in conditioned medium from CXCL5-overexpressing WPMY cells, and in cells co-cultured with CXCL5‑OE WPMY cells prostate cancer cell malignant phenotypes were induced in an autocrine/paracrine fashion in vitro; similar results were observed in nude mouse xenografts. CXCL5 overexpression also regulated expression of tumor-related genes, including BAX, N-Myc downstream-regulated gene 3, extracellular signal-regulated kinase 1/2, C-X-C chemokine receptor type 2, interleukin 18, Bcl‑2, and caspase‑3. These data demonstrated that CXCL5 expression was upregulated in prostate cancer tissues and that exogenous CXCL5 protein exposure or CXCL5 overexpression promoted malignant phenotypes of prostate cancer cells in vitro and in vivo.

To study the interest and participation degree of medical students in double gen education activities by using questionnaire and examination result analysis,and explore the role of double innovation education in improving practical ability of medical students.Results showed that medical students have stronger consciousness to participate in the activities of double innovation education,and double innovation education can improve the practical skills of medical students.The main contradiction that restricts promotion of double innovation education is there are few opportunities for students.

培养大学生创新创业能力是新时代、新目标对大学生提出的新要求.“三位一体”培养医学院校医学生创新创业能力的教育理念和模式在探索中收到了良好成效.本文着重分析医学院校“三位一体”教育模式的立脚点、特点以及应采取的对策.

Learner-centered cultivated paradigm is focused on the individualized and whole process development of learners, which is conducive to the cultivation of diversified and complex talents. This paper described the basic connotation, the advantage and the practice process about learner-centered cultivated paradigm, emphasized not only the students are learners, but also teachers are learners, summarized the key to the teaching mode is the practice.