目的 系统评价胰岛素联用α-葡萄糖苷酶抑制剂(AGIs)治疗成人1型糖尿病(T1DM)的疗效和安全性。方法 检索中英文数据库,纳入关于胰岛素联用AGIs治疗成人T1DM患者的随机或非随机对照试验。使用Review Manager 5.3软件进行Meta分析。结果 共纳入10项研究,616例患者。与安慰剂或空白对照相比,在有效性方面,胰岛素联合AGIs可改善成人T1DM患者的糖化血红蛋白;降低平均血糖、空腹血糖和餐后2小时血糖;改善血糖波动情况,包括平均血糖波动幅度和最大血糖波动幅度(均P<0.05)。在安全性方面,AGIs增加总不良反应发生的风险(P<0.05),其中主要是胃肠道不适,但未增加低血糖的发生率和发生次数(均P>0.05)。胰岛素联合AGIs减少了每日胰岛素总剂量(P<0.05),但对体重、甘油三酯和高密度脂蛋白胆固醇无显著影响(均P>0.05)。结论 胰岛素联合AGIs可降低成人T1DM患者的糖化血红蛋白,改善血糖水平和血糖波动情况。AGIs不会增加低血糖的风险,但需重视其不良反应,特别是胃肠道不良反应。

Objective To systematically evaluate the efficacy and safety of adding alpha-glucosidase inhibitors (AGIs) to insulin therapy in adult patients with type 1 diabetes (T1DM). Methods Articles about randomized or non-randomized controlled trials of insulin combined with AGIs in adult patients with T1DM were retrieved from Chinese and English database. Meta-analyses were performed by using Review Manager 5.3. Results A total of 616 patients were included from 10 clinical trials. Compared with adding placebo or nothing, in terms of efficacy, the addition of AGIs resulted in decreased HbA1c, mean blood glucose, fasting plasma blood glucose and 2-hour postprandial blood glucose levels (all P<0.05). And this scheme improved the glucose variability including mean amplitude of glycemic excursions and the largest amplitude of glycemic excursions (P<0.05, respectively). As to safety, AGIs increased the risk of total adverse reactions (P<0.05), most of them were gastrointestinal complaints, while the occurrence and the frequency of hypoglycemia were similar (P>0.05, respectively). This scheme could also lead to the reduced total daily insulin dose (P<0.05) but had no significant effect on body weight, triglyceride or cholesterol concentration (P>0.05, respectively). Conclusions The addition of AGIs to insulin therapy in adult patients with T1DM may reduce HbA1c and improve the glucose levels and glucose variability. But total adverse effects especially the gastrointestinal complaints should also be considered in the use of AGIs although it does not increase the risk of hypoglycemia.

目的 评价鞘内注射雷帕霉素对CCI神经病理性痛大鼠的痛阈及脊髓背角胶质细胞表达的影响。方法 健康雄性SD大鼠30只随机分为6组:①CCI组:CCI术后14天处死;②正常对照组:不做任何处理; ③前对照剂组:鞘内置管3天后行CCI术,术后4小时后鞘内给同体积生理盐水,连给3天; ④前给药组:鞘内置管3天后行CCI术,术后4小时鞘内给雷帕霉素溶液,连给3天; ⑤后对照剂组:鞘内置管3天后行CCI术,术后7天鞘内给同体积生理盐水,连给3天;⑥后给药组:鞘内置管3天后行CCI术,术后7天鞘内给雷帕霉素溶液,连给3天。各组于CCI术前1天和术后第2、4、6、8、10、12、14天测机械痛阈和热痛阈。术后14天测痛后用多聚甲醛灌注大鼠,取L4~5脊髓,免疫组化染色,星形胶质细胞标记蛋白(GFAP)检测星形胶质细胞表达变化,并定量分析。结果 与对照组相比,CCI手术组热痛阈和机械痛阈从CCI手术后第4天开始下降(P<0.05);前后给药对照剂组与CCI组相比,差别无统计学意义(P>0.05)。前给药组痛阈从CCI手术后第4天开始上升并持续至手术后第14天,与CCI组相比,差别有统计学意义 (P<0.05)。与CCI组相比,后给药组痛阈从CCI第8天开始上升并持续至手术后第14天,差别有统计学意义(P<0.05)。 与正常对照组比较,CCI组、前、后对照剂组手术侧脊髓背角GFAP染色阳性区平均光密度与阳性面积均有增加,差别有统计学意义(P<0.05)。前、后给药组手术侧GFAP染色阳性区平均光密度与阳性面积与CCI组比较,均有明显降低,差别有统计学意义(P<0.05)。结论 鞘内注射雷帕霉素可缓解大鼠神经病理性痛,并抑制脊髓背角胶质细胞的激活。

Objective To evaluate the effects of intrathecal injection of rapamycin on pain threshold and spinal cord gliacyte activation in rats of neuropathic pain. Methods Healthy 30 male SD rats were randomly divided into 6 groups(n=5 in each group): ① control group without operation or intrathecal injection. ②CCI group without intrathecal injection. ③ intrathecal injection of rapamycin 10 μg(10 μL) 4 hours after CCI operation and the next 2 days once a day. ④ intrathecal injection of NS10 μL 4 hours after CCI operation and the next 2 days once a day. ⑤ intrathecal injection of rapamycin 10 μg(10 μL) 7 days after CCI operation and the next 2 days once a day.⑥ intrathecal injection of NS10 μL 7 days after CCI operation and the next 2 days once a day. Mechanical and thermal threshold were tested 1 day before the CCI operation and 2^th、4^th、6^th、8^th、10^th、12^th、14^th days after the CCI operation for all the rats. Lumbar segment of spinal cords was removed for determination of glial fibrillary acidic protein(GEAP) in spinal cord by immuohistochemistry dyeing and assay in the 14th day after CCI operation for all the rats. Results Mechanical and thermal hyperalgesia emerged on 4th day and maintained till 14th day after CCI operation(P<0.05). After intrathecal injection of rapamycin 4 hours or 7days after CCI, mechanical and thermal threshold significantly increased compared to intrathecal injection of NS(P<0.05). And the sum area of GFAP positive and the mean density of GFAP positive area in the dorsal horn of operation side greatly increased in rapamycin treated groups compared NS treated groups(P<0.05). Conclusion Intrathecal injection of rapamycin may attenuate CCI induced hyperalgesia and inhibit the activation of astrocyte.

目的 探讨心肌细胞RyR2和L型钙通道的基因变异与室性心律失常和心源性猝死的相关性。方法 回顾分析2010年1月—2012年12月在我院就诊的慢性心力衰竭患者622例的临床资料,并选取同一时期体检中心体检的健康人群516例作为对照组,门诊或者电话随访记录慢性心力衰竭患者的死亡为终点,通过候选基因分析可能具有相关功能的4个基因变异,rs41315858(G1885E)、rs3766871(G1886S)、rs790896(G>A)和rs723672(T>C),采用Logestic、Cox回归分析对4个候选基因变异进行相关性研究。结果 入选622例慢性心力衰竭患者和516例对照组,基因分析结果显示RyR2上的基因变异rs376687lA等位基因携带可以增加慢性心力衰竭患者发生室性心律失常的风险性;校正可能与该疾病相关的危险因素后,rs376687lA等位基因携带会增加心源性死亡和心源性猝死的风险,RyR2上的基因变异rs790896A等位基因携带可以降低心源性猝死风险。结论 RyR2上的基因变异rs376687lA是室性心律失常和心源性猝死的遗传学预测因子,而rs790896A等位基因是慢性心力衰竭患者的保护因子,可降低室性心律失常和心源性猝死的风险。

Objective To investigate the myocardial cells RyR2 and L-type calcium channel gene variants with ventricular arrhythmias and sudden cardiac death correlation. Methods Retrospective analysis of patients with chronic heart failure from January 2010 to December 2012 in our hospital including 622 cases of clinical data, and to select 516 cases of healthy people in medical examination center during the same period as a control group.Clinic or telephone follow-up recorded chronic patients with heart failure and sudden death acting as end. We analyzed possible candidate genes, according to four gene variants related functions, rs41315858 (G1885E), rs3766871 (G1886S), rs790896 (G> A) and rs723672 (T> C), by using Logestic, Cox regression analysis of four candidate gene variants for related research. Results 622 cases of chronic heart failure patients were enrolled and 516 patients in the control group. Genetic analysis showed that the gene variant alleles carried rs376687lA RyR2 may increase in patients with chronic heart failure ventricular arrhythmia risk; correction may be associated with the disease after risk factors, rs376687lA allele carries an increased risk of cardiogenic death and sudden cardiac death, and gene mutation alleles carried on rs790896A RyR2 can reduce the risk of sudden cardiac death. Conclusion Gene mutation rs376687lA RyR2 on genetics is predictor of ventricular arrhythmias and sudden cardiac death, and rs790896A allele is protective factor in patients with chronic heart failure which can be reduced ventricular arrhythmias and sudden cardiac death in risk.