“双导”理念与“1+2”模式在专业学位硕士研究生科研创新能力培养中的作用探讨——以浙江中医药大学为例

医学专业学位研究生招生规模逐年扩大,医学院校重临床、轻科研的培养理念暴露出对专业学位研究生教育中的不足。研究生对待科研意识薄弱,积极性不高。本文基于问卷调查,提出以研究生科研创新需求为导向的带教模式和激励策略,旨在提高专业学位研究生参与科研的主动性和创新能力,提高研究生教育质量,培养能力综合的高端人才。     

热牙胶充填技术联合不同封闭剂在根管充填治疗中的疗效评价

目的: 评价热牙胶充填技术联合不同封闭剂在根管充填治疗中的临床疗效。方法: 选取2015年6月—2017年6月在我院接受根管充填的牙髓炎患者95例,按随机数表法分为A组（n=30）、B组（n=33）和C组（n=32）。A组采用热牙胶充填技术+iRoot SP,B组采用热牙胶充填技术+AH plus,C组采用热牙胶充填技术+Vitapex。比较3组术后7 d的根管充填质量,评估患者疼痛程度。采用SPSS19.0软件包对数据进行统计学分析。结果: 3组适充率比较差异无统计学意义（P>0.05）。A、B组1级疼痛率分别为6.7%、6.1%,显著低于C组的28.1%（P<0.05）。结论: 热牙胶充填技术联合iRoot SP、AH plus或Vitapex,均具有较好的根管封闭效果;但iRoot SP、AH plus相较于Vitapex,可以更有效减轻根管治疗术后疼痛症状,推荐作为根管充填治疗中的首选封闭剂。     

大剂量分割照射人肝癌细胞系移植瘤的实验研究

目的:研究不同大剂量分割照射模式对BALB/c-nu裸鼠移植瘤(人原发性肝细胞癌细胞系HepG2)抑制肿瘤作用的差异.方法:将原发性肝细胞癌移植瘤种鼠的肿瘤组织制备成1 mm3大小的肿瘤组织块,选择实验裸鼠右后肢外侧小腿腓肠肌处接种,建立原发性肝细胞癌细胞系移植瘤裸鼠照射模型.待肿瘤直径达1.0 cm时将40只实验裸鼠分成4个组:未照射空白对照组、5 Gy×6次分割组(5 Gy组)、10 Gy×3次分割组(10 Gy组)、15 Gy * 2次分割组(15 Gy组).各照射组均在2周内完成照射,照射完成后继续观察裸鼠肿瘤体积的变化.结果:实验过程中无出现裸鼠死亡,亦未观察到明显的裸鼠进食、活动减少,皮疹、腹泻、脱皮等不良反应.三种大剂量分割方案均对裸鼠的移植瘤有明显抑制作用.5 Gy组、10 Gy 组和15 Gy组肿瘤抑制率分别为30.2％,68.4％,73.1％.相对于5Gy和10 Gy照射组,15 Gy组对移植瘤的抑制作用更显著.结论:BALB/c-nu裸鼠移植瘤(人肝细胞癌细胞系HepG2)对大剂量分割照射模式能较好耐受.在相同总剂量情况下,剂量越高,移植瘤的生长抑制作用越强.15 Gy×2次较10 Gy×3次和5Gy×6次有更强的肿瘤生长抑制作用.     

安全文化在手术室护理管理中的应用体会

目的：探讨安全文化在手术室护理管理中的作用。方法：深圳市龙岗中心医院2005年起建立并逐步健全手术室护理安全文化建设,分析其具体实施措施和取得的临床护理效果。结果：自开展此项活动以来,手术室护理质量得到了极大的提高。无一例相关手术室护理的医疗事故发生,日常护理差错事故发生率也明显降低,患者手术前后的护理满意率得到了极大的提高。结论：在日常护理工作中严格按照护理安全制度执行,重视患者的护理安全,将安全文化融入到整体的护理工作当中,以提升医院的整体质量水平,营造良好的医疗诊治环境。     

老年糖尿病患者血尿酸水平检测的临床分析

目的探讨老年2型糖尿病(T2DM )患者血尿酸(UA)水平检测结果的临床意义.方法选择2007年2月至2010年2月160例老年2型糖尿病患者及同期健康体检老年人群160例作为对照,比较两组空腹静脉血UA 水平;将 T2DM 组按 UA 水平分为:高 UA 组和 UA 正常组,比较两组肌酐(Cr)、总胆固醇(TC)、三酰甘油(TG)、空腹血糖(FBG)、糖化血红蛋白水平(HbA1c)水平,及合并冠状动脉粥样硬化心脏病、高血压疾病、脑血管疾病及随访期间死亡情况等方面的差异.结果老年2型糖尿病患者 UA 水平(481.52±76.29)μ mol/L 明显高于健康体检人群(336.72±56.73)μmol/L ,差异有统计学意义(P <0.05);T2DM 组中70例高 UA 血症患者与90例UA 正常患者比较 HbA1c 和 FBG 差异无统计学意义(P >0.05),高 UA 血症组 TC 、TG 和 Cr 水平高于 UA 正常组,差异有统计学意义(P<0.05);高 UA 血症组中冠心病、高血压疾病、脑血管疾病及随访期间病死率均高于 UA正常组(P<0.05).结论老年2型糖尿病患者 UA 水平较高,对于老年2型糖尿病患者的高尿酸血症应予以高度重视,积极降糖调脂的同时也要控制血尿酸水平.     

君力达盐酸二甲双胍肠溶胶囊联合阿卡波糖对糖尿病患者空腹及餐后2h血糖、糖化血红蛋白以及甘油三酯水平的影响

目的探讨君力达盐酸二甲双胍肠溶胶囊联合阿卡波糖对糖尿病患者空腹及餐后2h血糖、糖化血红蛋白以及甘油三酯水平的影响。方法选取在该科住院治疗的糖尿病患者52例,按照数字随机方式将患者分为对照组和观察组,各组为26例,分别对两组患者进行严格饮食控制及加强锻炼,对照组在此基础上实施君力达盐酸二甲双胍肠溶胶囊予以口服治疗,0.5 g/次,3次/d;观察组患者在上述药物基础上给予联合阿卡波糖50 mg予以治疗,嚼碎吞服,3次/d,持续12周。结果两组患者治疗前,就空腹血糖(FPG)及餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)以及甘油三酯(TG)水平组间比较无明显差异(P0.05)。两组患者治疗12周后,其空腹血糖(FPG)及餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)以及甘油三酯(TG)水平均呈现出明显降低状况,观察组患者治疗后与对照组相比,降低幅度明显高于后者且差异显著(P0.05);观察组后总有效率(96.15%)与对照组(76.92%)相比,明显高于后者且差异明显(P0.05);观察组治疗12周后,其血糖控制的疗效与对照组相比,明显高于后者(P0.05)。结论针对糖尿病患者,在对其进行严格的控制饮食及加强锻炼的基础上,采取君力达盐酸二甲双胍肠溶胶囊联合阿卡波糖进行治疗,其疗效更为确切,能够对患者的血糖水平具有很好的改善效果,有效降低低血糖相应发生率,在临床当中具有很好的应用和推广价值。     

Endolysosomal trafficking of viral G protein-coupled receptor functions in innate immunity and control of viral oncogenesis

The ubiquitin-proteasome system degrades viral oncoproteins and other microbial virulence factors; however, the role of endolysosomal degradation pathways in these processes is unclear. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, and a constitutively active viral G protein-coupled receptor (vGPCR) contributes to the pathogenesis of KSHV-induced tumors. We report that a recently discovered autophagy-related protein, Beclin 2, interacts with KSHV GPCR, facilitates its endolysosomal degradation, and inhibits vGPCR-driven oncogenic signaling. Furthermore, monoallelic loss of Becn2 in mice accelerates the progression of vGPCR-induced lesions that resemble human Kaposi’s sarcoma. Taken together, these findings indicate that Beclin 2 is a host antiviral molecule that protects against the pathogenic effects of KSHV GPCR by facilitating its endolysosomal degradation. More broadly, our data suggest a role for host endolysosomal trafficking pathways in regulating viral pathogenesis and oncogenic signaling.Phagocytosis and autophagy are two processes that deliver microbes and their constituent proteins to the lysosome for degradation, thereby contributing to the clearance of pathogens and to the presentation of peptide antigens to T cells (1, 2). However, it is not known whether endocytic internalization and lysosomal targeting of virus-encoded cell-surface receptors contributes to the control of viral infection and disease.Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of AIDS-related and other forms of Kaposi’s sarcoma (KS), primary effusion lymphoma, and multicentric Castleman’s disease (3–5). KS is a multifocal tumor characterized by proliferating spindle cells (possibly of endothelial origin), angiogenesis, vascular slits, erythrocyte extravasation, and inflammatory cells. Proinflammatory signaling by the dominant KS cell, the spindle cell, is considered the driving force in KS lesions (6). The risk of KSHV-associated malignancies increases with increased lytic viral replication (7–9), suggesting that KSHV-induced oncogenesis may be related to the levels of expression of viral oncoproteins.The oncogenic KSHV G protein-coupled receptor (vGPCR), encoded by the KSHV ORF74 lytic gene, is a constitutively active chemokine receptor expressed in patients with KSHV-associated tumors (10). At least in animal studies, there are strong data that vGPCR substantially contributes to the onset and progression of KSHV-associated neoplasia in vivo (11–19). Although only a small proportion of tumor cells express vGPCR (10), they are both sufficient and necessary for KSHV-induced sarcomagenesis. The endothelial-specific expression of vGPCR (but of neither KSHV latent genes, such as vCyclin, vFlip, and Kaposin, nor other KSHV lytic genes, such as vBcl-2 or vIRF1) or injection of murine endothelial cells stably expressing vGPCR (but not other KSHV genes, such as vCyclin, vFlip, Kaposin, LANA, vIL-6, vBcl-2, and K1) causes multifocal KS-like tumors in mice (15, 18). Furthermore, injection of a small number of endothelial cells expressing vGPCR increases the tumorigenic potential, in a paracrine fashion, of endothelial cells expressing other KSHV latent genes (vCyclin and vFlip), whereas eradication of the small number of vGPCR-expressing cells in established mix-cell tumors induces tumor regression (15, 18). Moreover, in a nude mouse model of KS driven by transfection of a KSHV bacterial artificial chromosome into bone marrow endothelial-lineage cells, siRNA interference (RNAi)-mediated suppression of vGPCR expression dramatically reduces angiogenesis and tumor formation (19). In addition, immunocompetent mice that transgenically express doxycycline (DOX)-inducible KSHV GPCR in endothelial cells (hereafter referred to as ikGPCR⁺) manifest lesions that strongly resemble human Kaposi’s sarcoma (16, 17). Importantly, the progression of lesions in ikGPCR⁺ mice is reversible because DOX withdrawal leads to significant regression of vGPCR-induced lesions (17), suggesting that vGPCR-driven oncogenesis is highly dependent on sustained vGPCR expression and signaling.Based on these previous observations in animal models regarding KSHV GPCR and oncogenesis, we developed the hypothesis that cell-intrinsic mechanisms that decrease vGPCR protein levels may function as an important host defense mechanism for controlling viral oncogenesis. Recently, we showed that the autophagy protein, Beclin 2 (but not the related autophagy protein Beclin 1) is essential for the endolysosomal degradation of certain cellular GPCRs that are regulated by GASP1 rather than by ubiquitination and the endosomal sorting complexes required for the transport pathway (20). This function of Beclin 2, but not Beclin 1, regulates mouse brain cannabinoid receptor levels and metabolism in vivo (20). Therefore, we investigated whether Beclin 2 may play a role in the endolysosomal degradation of viral GPCRs and thereby represent an important host defense mechanism against KSHV GPCR-induced oncogenic effects. Our results demonstrate a crucial role for Beclin 2 in KSHV GPCR trafficking, proinflammatory signaling, and in vivo tumorigenicity, and thus represent a previously undescribed role for endolysosomal trafficking in innate immunity and the control of viral GPCR-driven oncogenesis.     

中哈边境口岸臀突客蚤检出立克次氏体核酸

目的了解中哈边境地区臀突客蚤(Xenopsylla minax)中立克次氏体携带情况。方法收集阿拉山口口岸臀突客蚤样本,PCR扩增立克次体17 kDa基因片段,PCR产物测序并BLAST比对,利用Mega 6.0构建分子遗传进化树。结果42.86%(3/7)的臀突客蚤携带立克次体,17 kDa基因遗传进化树显示与Candidatus Rickettsia senegalensis和Rickettsia bellii同源性最高。结论中哈边境口岸地区臀突客蚤携带立克次体核酸。     

乙型肝炎病毒基因变异、p16蛋白失活与肝癌的相关性研究

目的探讨乙型肝炎病毒（HBV）基因变异及肿瘤抑制基因p16蛋白失活与肝癌发生的关系。方法用基因芯片和核苷酸序列分析技术对114例HBV感染者（观察组）血清和43份肝组织标本中HBV DNA（前C区1814、1896、BCP区1762、1764位）进行分析,用流式细胞荧光染色法检测观察组和20例正常献血者（正常对照组）外周血白细胞中p16蛋白表达。结果观察组慢性重症乙型肝炎、肝硬化、肝癌患者血清HBV基因总突变率显著高于慢性乙型肝炎患者（P〈0．01）,肝硬化、肝癌肝组织HBV基因总突变率显著高于正常组织;正常对照组外周血自细胞中p16蛋白阳性率显著低于慢性乙型肝炎、肝硬化、肝癌患者,肝硬化、肝癌患者阳性率显著高于慢性乙型肝炎患者。结论HBV变异可能是肝癌发生的始动因子,而p16蛋白失活是肝癌发生的重要因素。     

川芎嗪-丹参-当归配伍剂与尼莫地平对大鼠脑缺血-再灌注损伤影响的比较

目的探讨川芎嗪-丹参-当归配伍剂（TSA）对大鼠脑缺血-再灌注损伤的神经保护作用。方法取21只成年雄性Wistar大鼠,应用线栓法制作大鼠右侧大脑中动脉阻塞（MCAO）3h模型。剔除模型制作过程中死亡的3只大鼠,随机分成3组,TSA组、尼莫地平组和对照组,每组6只。通过尾静脉给药,对大鼠脑缺血-再灌注模型进行干预。分别给予3组大鼠以下药物：川芎嗪（0．35mg／100g）＋丹参（200mg／100g）＋当归（165mg／100g）、尼莫地平（0．1mg／100g）和等渗盐水1．5ml。给药时间为再灌注前20min、再灌注后12h和36h。在MCAO期间和再灌注后48h,应用脑血流监测仪记录大鼠脑血流量;在再灌注前20rain和再灌注后48h,测评大鼠神经功能缺损评分并计算评分恢复值;再灌注后48h,Trc染色检测大鼠脑梗死体积。结果TSA组、尼莫地平组和对照组：①脑血流量变化相对值为（138±44）、（86±18）和（69±8）％;②神经功能评分恢复值为1．3±0．4,1．2±1．0和0．6±0．7;③大鼠脑梗死体积为（144±38）、（344±92）和（382±93）mm^3。TSA组与尼莫地平组比较,所有观测指标差异均具有统计学意义（P〈0．01或P〈0．05）。结论TSA提高大鼠脑血流量和减少梗死体积的疗效更佳,对大鼠脑缺血-再灌注损伤的保护作用优于尼奠地平。