培养创新型临床医学人才的思考

文章从创新及创新型人才的概念入手，通过调研指出，目前临床医学人才培养存在的主要问题，提出在新时期要转变教育教学观念、强化创新意识教育、增强创新思维训练、着力创新人格塑造，以培养创新型临床医学人才。     

YD383、YD439对JAK-STAT6信号传导通路作用的特异性研究

目的:探讨化合物YD383和YD439对STAT6信号传导通路的作用是否具有特异性.方法:通过瞬时转染的方法将分别依赖于STAT1和STAT6活性的带有荧光素酶报告基因的质粒转染至HeLa细胞株,两种细胞株在各自相应的细胞因子(IFN-γ或IL-4)刺激下激活JAK-STAT1或JAK-STAT6信号传导通路.通过测定荧光素酶的活性来评价细胞株在化合物存在的情况下报告基因的表达.结果:YD383和YD439均能降低相应细胞因子刺激引起的报告基因的表达,并且具有剂量依赖性.随着化合物剂量的增加,报告基因的表达降低(P＜0.05).但化合物引起的两种转染细胞报告基因表达降低的差异比较无统计学意义(P＞0.05).结论:两种化合物对JAK-STAT1和JAK-STAT6信号传导通路均有抑制作用,对JAK-STAT6通路的抑制不具有特异性.     

1958例系统性红斑狼疮住院患者临床特征分析

目的回顾性分析系统性红斑狼疮(SLE)住院患者的临床特征,分析其发病形式及患者就诊时的情况。方法采用流行病学调查的方法,随机抽取江苏省10年来1 958例SLE住院患者的病历,分析其临床特征,采用SPSS 13.0软件包进行统计学分析。结果①在1 958份病例中,临床特征以关节痛(炎)最多(53.8%),其次为面部红斑(48.3%)、发热(36.1%)、肾损害症状(24.5%)。②男女发病比例为1.0︰15.0,男性以皮疹最多见,占59.0%,高于女性47.6%,其次为发热(47.5%),高于女性(35.3%),关节痛(炎)(45.9%低于女性(54.3%),男性肾损害(36.9%),高于女性(23.7%)。③不同年龄患病率:≤20岁(19.2%),>40岁(18.8%),20～40岁(62.0%)。④从出现症状到住院:发热13.8个月,肾损害症状19.5个月,关节痛(炎)36.9个月,面部红斑37.2个月。结论关节痛(炎)、面部红斑、发热是SLE最常见的临床表现,是就诊的主因。中青年女性发病率高,男性皮疹、发热、肾损害发生率高,而女性关节痛(炎)发生率高于男性。     

microRNA调控NK细胞KIR3DL1表达初探

目的初步探寻人外周血自然杀伤细胞（Nature Killer,NK）杀伤细胞免疫球蛋白样受体（Killer Cell Immnoglobulin-Like Receptor,KIR3DL1）表达可能存在的microRNA（miR）调控机制。方法利用生物信息学方法,从miR信息库中筛选出可能与KIR3DL1相关的miRs,构建含KIR3DL1 3’非翻译区（UTR）的PGL3质粒,分别将含相应miR的PcDNA3.0质粒与前者共转染293T细胞,通过荧光素酶报告实验及之后的突变实验筛选出可能调控KIR3DL1的miR。结果通过TARGET SCAN信息库筛选了miR-146b等10个miR;转染miR-146b后,荧光素酶活性下降最多（61.3%）,突变其KIR3DL1 3’UTR靶位点后荧光素酶活性恢复（91.4%）。结论 miR-146b可与KIR3DL1’UTR在靶位点特异结合,很可能参与KIR3DL1表达的调控。     

抗血小板膜糖蛋白Ibα胞内段多肽多克隆抗体的制备及初步应用

目的 制备兔抗人血小板膜糖蛋白(GP)Ibα C端557～561氨基酸序列多肽的多克隆抗体,并初步用于人血小板GPIbα C端559位丝氨酸磷酸化状态的检测.方法 应用化学方法合成C-R-G-S-L-P(559位丝氨酸非磷酸化,Ser559)和C-R-G-s(p)-L-P(559位丝氨酸磷酸化,pSer559)多肽.将2种多肽分别与钥孔蜮血蓝蛋白交联后,以皮下注射法分别免疫新西兰大白兔,分离获得2种抗血清(抗Ser559多抗和抗pSer559多抗).应用斑点印迹和酶联免疫吸附试验(ELISA)方法 对抗血清进行鉴定并检测效价.从人血小板裂解液中分离纯化血小板GPIbα,利用抗Ser559多抗和抗pSer559多抗、采用ELISA方法检测人血小板GPIbαC端559位丝氨酸磷酸化状况.结果 所制备的2种多抗分别特异性识别各自抗原,效价分别为1:32 000和1:64 000.2种多抗均可与纯化的人血小板GPIbα特异结合,表明人血小板GPIbα 559位点丝氨酸存在磷酸化与非磷酸化两种状态.结论 应用人工合成多肽成功制备出2种可特异性识别丝氨酸磷酸化状态的兔抗人血小板GPIbα胞内段多肽多抗,并证明人血小板GPIbαC端559位丝氨酸存在磷酸化状态.     

New indicators for delay in initiation of antiretroviral treatment: estimates for Cameroon

Objective

To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon.

Methods

We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d’Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010.

Findings

In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/μl (interquartile range, IQR: 66 to 210) in 2007–2009 to 163 cells/μl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2).

Conclusion

The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful.     

Effects of insulin resistance and insulin secretion on the efficacy of interventions to retard development of type 2 diabetes mellitus: the DA Qing IGT and Diabetes Study

OBJECTIVE: To investigate the effects of insulin resistance (IR) and insulin secretion (IS) on the development of diabetes mellitus in individuals with impaired glucose tolerance (IGT) who underwent lifestyle interventions. METHODS: 284 out of 577 individuals with IGT identified by population-based screening in Da Qing, China, who were randomized to undergo diet change and/or increased physical activity had baseline fasting and 2 h post-load insulin determinations. They were followed for 6 years for the development of diabetes. IR and IS were assessed using calculated indices based on fasting plasma insulin and glucose. The interactions of IR, IS, obesity and plasma glucose and the effects of the lifestyle interventions were evaluated using Cox Proportional Hazards analysis. RESULTS: Both IR and IS were significantly associated with the development of diabetes. Lifestyle interventions were more effective in those with lower IT and higher IS at baseline. Diet plus exercise interventions resulted in significantly lower incidence of diabetes, even after controlling for IR, IS, BMI and 2hrPG. CONCLUSION: Both IR and beta-cell function were predictors of diabetes in Chinese with IGT. Lifestyle intervention reduced the incidence of DM and these interventions were more effective in those with less IR.     

Interleukin-11 stimulates multilineage progenitors, but not stem cells, in murine and human long-term marrow cultures

Interleukin-11 (IL-11) is a bone marrow microenvironment-derived growth factor with pleiotropic effects on a variety of hematopoietic cells. To more accurately assess the effects of IL-11 on stem and progenitor compartments within the hematopoietic microenvironment (HM), we added recombinant human (rh) IL-11 to human and murine long-term bone marrow cultures (LTMC) and analyzed primitive (high proliferative potential- colony forming cells [HPP-CFC], long-term culture-initiating cells [LTC- IC], and long-term reconstituting stem cells) and progenitor (day 12 colony forming unit-spleen [CFU-S12], colony forming unit-megakaryocyte [CFU-Mk] and colony forming unit-granulocyte/macrophage [CFU-GM]) compartments throughout the duration of the cultures. rhIL-11 (100 ng/mL) added twice weekly resulted in significantly increased nonadherent (NA) cellularity, CFU-GM, and CFU-Mk production in human LTMC. Addition of rhIL-11 to murine LTMC was associated with a 5- to 40- fold increase in CFU-GM and a four- to 20-fold increase in day 12 CFU-S in NA cells. However, IL-11 had no significant effect on total HPP-CFC concentration and decreased the size of the more primitive stem/progenitor compartment as evidenced by both decreased LTC-IC frequency in human LTMC and decreased frequency of long-term reconstituting stem cells in murine LTMC. These data suggest that IL-11 may increase commitment of stem cells into a multipotential progenitor compartment.     

Comparative outcomes of open versus laparoscopic sacrocolpopexy among medicare beneficiaries

Introduction and hypothesis

Since the first reported laparoscopic sacrocolpopexy in 1991, a limited number of single-center studies have attempted to assess the procedure’s effectiveness and safety. Therefore, we analyzed a national Medicare database to compare real-world short-term outcomes of open and laparoscopically assisted (including robotic) sacrocolpopexy in a United States sample of patients.

Methods

Public Use File data for a 5 % random national sample of all Medicare beneficiaries aged 65 and older were obtained from the Centers for Medicare and Medicaid Services for the years 2004–2008. Women with pelvic organ prolapse were identified using ICD-9 diagnosis codes. CPT-4 procedure codes were used to identify women who underwent open (code 57280) or laparoscopic (code 57425) sacrocolpopexy. Individual subjects were followed for 1 year post-operatively. Outcomes measured, using ICD-9 and CPT-4 codes, included medical and surgical complications and re-operation rates.

Results

Seven hundred and ninety-four women underwent open and 176 underwent laparoscopic (including robotic) sacrocolpopexy. Laparoscopic sacrocolpopexy was associated with a significantly increased rate of re-operation for anterior vaginal wall prolapse (3.4 % vs 1.0 %, p?=?0.018). However, more medical (primarily cardiopulmonary) complications occurred post-operatively in the open group (31.5 % vs 22.7 %, p?=?0.023). When sacrocolpopexy was performed with concomitant hysterectomy, mesh-related complications were significantly higher in the laparoscopic group (5.4 % vs 0 %, p?=?0.026).

Conclusion

Laparoscopic sacrocolpopexy resulted in an increased rate of reoperation for prolapse in the anterior compartment. When hysterectomy was performed at the time of sacrocolpopexy, the laparoscopic approach was associated with an increased risk of mesh-related complications.