医学科研设计是医学研究生重要的专业基础课程.文章围绕医学科研设计的教学内容凝炼出敬畏生命的人文精神、学术诚信的底线意识、勇攀科学高峰的使命担当三条课程思政主线,并以中国科学家首次人工合成胰岛素的创新过程为例介绍如何深度挖掘思政元素,通过将蕴含思政元素的科学研究案例融入课堂讲授、慕课和微信推送、在线讨论及考试试题中,构建线上线下相结合的、将课程思政覆盖医学科研设计教学全过程的有效路径.

"医学科研设计"作为方法类课程是医学研究生重要的专业基础课.文章在简述医学科研设计教学目标的基础上,围绕医学科研设计慕课教学团队的建设、教学短视频资源和非视频资源建设、教学活动的组织与成绩评定分享"医学科研设计"的课程建设经验,并进一步结合"医学科研设计"慕课的应用从有利于满足不同学习者个性化学习需求、有利于促进研究生教育的课堂教学改革及有利于构建"互联网+"课程思政模式提出思考和建议.

目的:miR-24、miR-132在类风湿关节炎(RA)患者外周血单个核细胞(PBMC)中的表达及临床意义.方法:收集160例RA患者、65例骨关节炎(OA)患者和65名健康对照者作为研究对象.RA患者按照DAS28评分分为低活动组(n=64)和中高活动组(n=96),Sharp评分分为非骨侵蚀组(n=73)和骨侵蚀组(n=87).采用实时定量PCR(RT-PCR)法检测各组PBMC中miR-24、miR-132表达水平.应用ROC曲线分析miR-24、miR-132对RA的诊断价值,Pearson相关分析RA患者miR-24、miR-132与DAS28评分、Sharp评分的相关性.结果:RA组PBMC中miR-24(3.62±0.75 vs 0.91±0.18,0.86±0.13)及miR-132(2.48±0.23 vs 1.07±0.14,0.96±0.11)表达水平均明显高于OA组和对照组(P<0.01).中高活动组PBMC中miR-24(5.86±1.15 vs 1.20±0.41)及miR-132(3.25±0.42 vs 1.14±0.19)表达水平明显高于低活动组(P<0.01).骨侵蚀组PBMC中miR-24(6.12±1.24 vs 1.14±0.39)及miR-132(3.48±0.46 vs 1.06±0.17)表达水平均明显高于非骨侵蚀组(P<0.01).ROC曲线分析显示miR-24、miR-132诊断RA的临界值分别为1.93、1.65,两项联合诊断RA的AUC(0.925,95％CI:0.863～0.972)最大,其敏感度和特异度为90.2％和85.8％.相关分析显示,RA患者miR-24、miR-132与Sharp评分、DAS28评分均呈正相关(P<0.05).结论:RA患者PBMC中miR-24、miR-132高表达,与疾病活动度和骨侵蚀程度相关,两项联合检测有助于提高RA诊断的价值.

Objective To study the effect of fucoidan on immune activity of macrophage cell line RAW264.7 and to explore its mechanism preliminarily.Methods RAW264.7 cells were cultured in vitro,colorimetric analysis was used to assay the phagocytosis of RAW264.7 cells exposed to fucoidan(0、100、200、300、400、500μg/mL).MTT method was used to assay the proliferation of RAW264.7 cells exposed to fucoidan(0、50、250、500μg/mL).The level of phosphorylation of MAPK/ERK1/2 was determined by Western Blotting.Results Fucoidan promoted the phagocytosis and proliferation of RAW264.7 cells in dose dependent.Western Blotting showed that ERK1/2 was phosphorylated at 10 minutes after exposed to 200μg/mL fucoidan and reached to maximum at 30 minutes.Conclusion Fucoidan could promote the phagocytosis and proliferation of RAW264.7 cells,the mechanism possibly involved that fucoidan directly activated MAPK/ERK1/2 signal transduction pathways in RAW264.7.

Objective To investigate the expression of miR-326 and miR-223 in peripheral blood mononuclear cells (PBMC) and plasma in patients with rheumatoid arthritis (RA) and their clinical significances.Methods One hundred and fifty-two patients with RA,65 patients with Osteoarthritis (OA) and 65 healthy controls in Xiangya Hospital and People's Hospital of Danzhou from January 2015 to June 2017 were enrolled in this study.PBMC and plasma miR-326 and miR-223 expression levels were detected by RT-PCR.The diagnostic value of PBMC and plasma miR-326,miR-223 and rheumatoid factor (RF) in RA were evaluated by ROC curve.Pearson correlation analysis was used to explore the correlation between PBMC and plasma miR-326,miR-223,RF,C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in RA patients.Results The expression of PBMC/plasma miR-326 and miR-223 in the RA group were significantly higher than those in the OA group and the control group [PBMC/plasma miR-326 (2-△△Ct):(0.12 ± 0.05) vs (0.05 ± 0.03) and (0.04 ± 0.03),(3.56 ± 1.04) vs (1.24 ± 0.36) and (1.13 ± 0.32);PBMC/plasma miR-223 (2-△ △Ct):(0.42 ± 0.13) vs (0.21 ± 0.08) and (0.18 ± 0.06),(6.95 ± 2.16) vs (5.13 ± 1.42) and (4.86 ± 1.25),all P ＜ 0.05].The expression of PBMC/plasma miR-326 and miR-223 in the high activity group were significantly higher than those in the low active group [PBMC/plasma miR-326(2△ △Ct):(0.18 ± 0.09) vs (0.05 ± 0.04),(5.62 ± 1.58) vs (1.43 ± 0.52);PBMC/plasma miR-223 (2-△ △Ct):(0.67 ± 0.24) vs (0.23 ± 0.12),(8.28 ± 2.63) vs (5.47 ± 1.48),all P ＜ 0.01].The AUC of miR-326,miR-223,RF and the combination of three markers in diagnosis of RA were 0.805(0.745-0.867),0.824(0.761-0.893),0.762(0.697-0.828),0.893(0.825-0.961) for PBMC,and 0.882(0.817-0.953),0.837(0.775-0.906),0.852(0.786-0.918),0.936(0.868-0.996) for plasma,respectively.Correlation analysis showed that in RA group,PBMC/plasma miR-326 was positively correlated with RF,miR-223 and CRP (All P ＜ 0.05),plasma miR-326 and miR-223 were positively correlated with ESR (P ＜ 0.05),plasma/PBMC miR-326 was positively correlated with miR-223 (P ＜ 0.01).Conclusion miR-326 and miR-223 are abnormally high in PBMC and plasma in patients with RA,and they are related to the activity of RA,which can be used as a biological marker for RA diagnosis.

目的：探讨解剖条件复杂的肾下型腹主动脉瘤实施主动脉腔内覆膜支架修复技术治疗的安全性和有效性。<br>　　方法：从2003年1月至2011年3月，我科采用主动脉腔内覆膜支架修复技术治疗了427例腹主动脉瘤患者，对其中48例解剖条件复杂的患者的临床资料进行回顾性研究。本组男性37例，女性11例，年龄50~81岁，平均年龄71.4岁。14例患者腹主动脉瘤近端瘤颈长度<15毫米，13例患者近端瘤颈成角严重（>60°），15例患者同时伴有严重扭曲的髂动脉，6例患者髂动脉狭窄（<8 mm）。所有患者均采用了分叉型腹主动脉覆膜支架治疗。

Objective: In order to detect two Signal Nucleotide Polymorphisms(SNPs),rs12422499 and rs2066807 gene of Signal Transducer and Activator of Transcription Factor 2(STAT2),a simple and reliable method,named polymerase chain reaction-primer introduced restriction analysis(PCR-PIRA) was established.Methods: DNA from peripheral blood was extracted using the trace salting-out method.Design PCR primers to amplify the gene fragment containing STAT2 SNP,rs2066807 or rs12422499,respectively.Digest the corresponding PCR product by PsyI or BseDII.Separate the digested products by electrophoresis.And then,the PCR products were sequenced.Results: The length of PCR product of the gene fragment containing rs2066807 was 469 bp.This product was digested by PsyI following by electrophoresis.According to the electrophretic maps,three genotypes of rs2066807 which were C/C(469 bp),G/G(262 bp and 207 bp) and C/G(469 bp,262 bp and 207 bp) were decided.The length of PCR product of the gene fragment containing rs12422499 was 189 bp.This product was digested by BseDI following by electrophoresis.According to the electrophretic maps,three genotypes of rs12422499 which were C/C(189 bp),G/G(134 bp and 55 bp),and C/G(189 bp,134 bp and 55 bp) were decided,The PCR products were sequenced.The sequencing results of the two SNPs were in good agreement with that detected by PCR-PIRA.Conclusion: The PCR-PIRA method for detection of SNPs of STAT2 was established.The procedure of PCR-PIRA is very simple and convenient,only including a PCR amplification followed by digestion by an enzyme.The sequencing results of the two SNPs were consistent with that detected by PCR-PIRA,demonstrating that PCR-RIPA is reliable.The strategy of PCR-PIRA does not only offer an experimental method for detection of polymorphism of STAT2,but also a mean of gene point mutation.

【Objective】To construct the(signal transducer and activator of transcription 4,STAT4) eukaryotic expression plasmid and express it in HEK293 cells.【Methods】STAT4 cDNA was amplified from human peripherial blood mononuclear cells(PBMC) by reverse-transcription polymerase chain reaction(RT-PCR) and inserted into the pEGFP-C1 vector digested by SalI/BamHI for construction of pEGFP-STAT4 plasmid.This plasmid was identified by sequencing as well as double enzymes digestion.pEGFP-STAT4 was transfected into HEK293 cells.The fusion protein EGFP-STAT4 was detected by fluorescence microscope and Western Blot.【Results】2 247 bp fragment of STAT4 cDNA full-length sequence was cloned by RT-PCR,and it was consistent with the known STAT4 sequence in GenBank.After the plasmid pEGFP-STAT4 was transfected into HEK293 cells,the fusion protein GFPSTAT4 was instantaneously expressed in some of cells.【Conclusion】The recombined pEGFP-STAT4 eukaryotic expression plasmid is successfully constructed and instantaneously expressed in HEK293 cells.

目的：探讨胸主动脉覆膜支架修复技术（Thoracic Endovascular Aortic Repair，TEVAR）联合相关的辅助技术治疗累及主动脉弓部的Stanford B型主动脉夹层的方法。<br>　　方法：回顾性研究我院自2002年7月至2013年2月采用主动脉覆膜支架腔内修复技术治疗的109例第一破口邻近或累及左锁骨下动脉起始端的Stanford B型主动脉夹层患者的临床资料。其中27例合并Marfan综合症，47例为夹层逆撕累及升主动脉和主动脉弓部的Stanford B型夹层，78例合并内脏动脉或周围动脉缺血，41例合并严重的胸腔积液。治疗中，106例患者采用腔内技术封堵了左锁骨下动脉起始端，其中28例采用了PDA封堵器；26例采用了颈部动脉搭桥手术；1例采用联合升主动脉至主动脉弓部分支动脉搭桥手术和主动脉腔内修复技术的杂交手术；43例采用了“烟囱”技术，3例采用“双烟囱”技术；1例采用主动脉覆膜支架开窗技术。

教育部明确提出"科研素质和能力训练要贯穿在各个教学阶段,在基础教学阶段着重培养学生掌握医学科学研究的基本方法和技术;在临床教学阶段,着重培养学生的临床思维方法和能力"[1].医学免疫学是基础医学重要课程,因此针对医学免疫学的特点,对医学生进行早期学科科研训练,不仅能培养学生的学习能力,也为八年制学生后期开展学位论文研究奠定功底,为培养合格的高级临床医学人才打下坚实基础.

Stress during pregnancy impacts on the offspring a lot,this impact is complex.Studies have shown that prenatal stress experience can lead to long-term immune dysfunction after birth of the offspring.The root causes of these changes with recovery of bone marrow lymphoid stem cells related to the change.This paper reviews how the experience of stress during pregnancy affects the bone marrow stem cells of offspring and explains the changes in the immune system.This review based on existing researches,and proposed hypotheses for further study of the mechanism that how stress during pregnancy causes changes in the immune system of offspring.

Recently it was reported that signal transducer and activator of transcription 2(STAT2) involves in carcinogenesis. Previous study showed that several kinds of tumor tissues as well as tumor cell lines highly expressed STAT2. Therefore,in order to further explore the effects of STAT2 on carcinogenesis,STAT2 expression level in cervical cancer cell line HeLa was decreased by using RNA silencing assay.Assayed by XTT,colony formation in soft agar and tumor formation in nude mice.It was demonstrated that STAT2 gene silencing inhibits tumor cell growth in vitro and in vivo, suggesting that STAT2 promotes cell proliferation.

目前人们认为肿瘤既是遗传性疾病,也可能是免疫学疾病。因此深入探讨肿瘤发生发展与免疫系统的相互关系,才有可能产生更多新策略对肿瘤进行免疫治疗。文章简述肿瘤与免疫系统相互关系,介绍肿瘤逃避免疫应答机制的最新研究进展,并就新近肿瘤免疫治疗策略进行综述。

现代教学理念以教师讲授为主的单一课堂教学模式向个性学习、自主式学习方向转变,这种开放条件下新教学模式的确立为免疫学教学改革明确了方向。根据专业免疫教学特点和网络教学实践经验,对硕士研究生高级免疫学教学模式创新尝试结果表明:我们所采用的教学模式不仅激发了学生主动学习积极性,训练和提高了诸如获得科研材料、制作多媒体及现场答辩等方面的能力,还激发和增强了教师责任心。教学改革中发现了一些问题并就此提出了建议。

互联网已深入社会的每个角落,成为当今人们工作和生活不可或缺的一种工具。互联网的优势和长处有目共睹,但其负面影响也是众人皆知,尤其是对广大在校的学生。如何加强互联网络的德育建设,如何保护涉世不深的大中小学生,如何充分发挥互联网的优势而又使学生健康地在网上学习和生活,值得全社会关注和重视,尤其是学校要担负起教育好学生的重任,开展网络德育工作,开辟学校德育工作新天地。

SOCS是一类新型的免疫抑制分子,可抑制多种细胞因子、激素和生长因子的生物学作用.生理情况下,SOCS在组织中低水平表达.此外,它也受到转录水平、蛋白合成水平及降解水平的严密调控.SOCS分子主要通过抑制JAK/STAT通路抑制信号转导,从而对细胞因子、激素、生长因子作用的强度和持续时间进行调控.

考试违纪和舞弊这种不正之风已成为各高校学风建设棘手的问题.本文结合实际,分析了当前高校考风不正的各种原因,提出了考风建设的基本思路.

细胞因子信号转导抑制因子(SOCS)是一类存在于细胞中,对细胞因子具有负反馈调节作用的蛋白质因子,它能抑制胞内多种信号的转导.脂多糖(LPS)是革兰氏阴性细菌胞膜外层的主要成分,它可促进单核细胞、巨噬细胞及上皮细胞等靶细胞合成和分泌细胞因子和炎性介质,使机体产生多种病变甚至败血性休克.SOCS可抑制STAT1丝氨酸和酪氨酸的磷酸化及NF-κB活性,从而阻断LPS的信号转导,并能降低机体对LPS的敏感性和增加机体对LPS的耐受性.