人脐带间充质干细胞重复静脉注射动物毒性试验

摘要 目的：评价多次尾静脉注射脐带间充质干细胞（hUC-MSCs）对小鼠的体内毒性作用。方法：48只健康ICR小鼠,按性别和体重随机分为4组（即对照组、低剂量组、中剂量组和高剂量组）。小鼠通过微静脉注射不同剂量hUC-MSCs悬浮液,间隔3天给药1次,共给药4次。记录小鼠摄食量、体重、体温,给药结束后恢复两周后牺牲动物作大体解剖,检查各个器官器质性病变;利用流式细胞仪分别检测CD3、CD4、CD8阳性细胞亚群数量;ELISA试剂盒检测血清IgM、IgG、C3、C4指标;对肺脏、脾脏、肾脏行组织病理学检查。结果：实验组与对照组相比较,注射不同剂量干细胞后一般观察、体重、体温、摄食量、IgM以及C3在给药期和恢复期均未发生显著变化。在恢复期,注射中、高剂量hUC-MSCs组血清IgG和C4水平略有降低,但未达到显著水平P<0.05;CD4阳性T细胞集群数量以及CD4/CD8系数在hUC-MSCs中、高剂量组显著上升（P<0.05）。大体剖检,除脾脏相比溶媒对照组略显增大外其它各器官均未发现肉眼可见明显异常;称重后发现hUC-MSCs高剂量组脾重量与溶媒对照组相比显著升高（P<0.05）。脾脏、肺脏、肾脏病理学检测未见明显异常。结论：健康ICR小鼠尾静脉注射临床剂量hUC-MSCs（1×10⁶ cells/kg）可能调动动物免疫反应,此外,未观察到hUC-MSCs对小鼠有明显毒副作用。     

非阿片类镇痛复合静脉全麻在鼾症手术患者中的疗效

目的:观察三重措施预防为基础,联合非阿片镇痛药复合静脉全麻在行鼾症手术患者术后恶心呕吐的应用效果。方法:选择择期行鼾症手术男性病人80例,随机分为两组:吸入麻醉组(inhalation group, IHLA组)和静脉麻醉组(intravenous group, TIVA组),每组40例,两组均采用三重措施预防恶心呕吐,IHLA组采用以舒芬太尼为基础复合七氟烷吸入麻醉,TIVA组以氯胺酮和右美托咪定镇痛基础上丙泊酚全凭静脉麻醉。评估两组病人恶心呕吐危险系数,采用李克特量表(Likert scale),记录并分析两组患者术后6~8 h在麻醉后监测治疗室(post anesthesia care unit, PACU)及病房24 h恶心呕吐发生情况及补救用药用量。结果:两组患者一般临床资料、恶心呕吐风险评分、手术时间、术后恢复期补救用药量人数无显著差异(P>0.05);IHLA组在PACU恶心呕吐发生率为39.5%,TIVA组发生率为18.9%,两者相比有显著性差异(P<0.05);IHLA组病房24 h恶心呕吐严重程度高于TIVA组,两组术后需要补救应用抗呕吐药物用量无显著差异(P>0.05)。结论:以三重措施预防为基础,与吸入麻醉相比,非阿片类镇痛药复合静脉麻醉可以减少肥胖病人鼾症手术术后恶心呕吐发生率和严重程度,降低围术期风险,有利于患者早期恢复。     

A Model of Chronic Nutrient Infusion in the Rat

Chronic exposure to excessive levels of nutrients is postulated to affect the function of several organs and tissues and to contribute to the development of the many complications associated with obesity and the metabolic syndrome, including type 2 diabetes. To study the mechanisms by which excessive levels of glucose and fatty acids affect the pancreatic beta-cell and the secretion of insulin, we have established a chronic nutrient infusion model in the rat. The procedure consists of catheterizing the right jugular vein and left carotid artery under general anesthesia; allowing a 7-day recuperation period; connecting the catheters to the pumps using a swivel and counterweight system that enables the animal to move freely in the cage; and infusing glucose and/or Intralipid (a soybean oil emulsion which generates a mixture of approximately 80% unsaturated/20% saturated fatty acids when infused with heparin) for 72 hr. This model offers several advantages, including the possibility to finely modulate the target levels of circulating glucose and fatty acids; the option to co-infuse pharmacological compounds; and the relatively short time frame as opposed to dietary models. It can be used to examine the mechanisms of nutrient-induced dysfunction in a variety of organs and to test the effectiveness of drugs in this context.     

局部进展期胃癌术前动静脉结合化疗的疗效观察

目的:局部进展期胃癌,即使没有出现远处转移或腹膜种植,预后也极不理想.我们对局部进展期胃癌患者进行术前mECF方案的动静脉结合化疗,以评价其治疗疗效.方法:选取自2009年1月至2011年6月间我院局部进展期胃癌Ⅱ-ⅢC期患者38例,均由影像学确定淋巴结高度可疑转移或浸润、包绕主要血管结构,且没有发现远处转移或腹膜种植,进行2个周期的术前动静脉结合化疗后,行手术治疗.记录化疗毒性反应、临床、病理缓解率、手术并发症发生率和病死率以及1年无病生存率.结果:化疗毒性反应低,3级反应不超过10％,仅有1例出现4级反应,表现为腹泻、恶心和呕吐.38例患者中临床CR有6例,占15.8％,PR17例,占44.7％,NC13例(34.2％),PD2例(5.3％),RR为60.5％(23/38).全部患者均施行了手术,37例患者进行了根治性手术,R0切除率为97％.病理缓解率为5例完全缓解(13.2％),21例部分缓解(55.3％),8例轻微缓解(21.1％),4例未缓解(10.5％).手术并发症发生率为7.9％,无治疗相关死亡发生.1年无病生存率为81.6％.结论:局部进展期胃癌患者术前进行mECF方案的动静脉化疗毒性反应低,疗效理想,之后行手术完整切除后临床效果突出,是理想的治疗方法.     

A CD4 mimic as an HIV entry inhibitor: Pharmacokinetics

To date, several small molecules of CD4 mimics, which can suppress competitively the interaction between an HIV-1 envelope glycoprotein gp120 and a cellular surface protein CD4, have been reported as viral entry inhibitors. A lead compound 2 (YYA-021) with relatively high potency and low cytotoxicity has been identified previously by SAR studies. In the present study, the pharmacokinetics of the intravenous administration of compound 2 in rats and rhesus macaques is reported. The half-lives of compound 2 in blood in rats and rhesus macaques suggest that compound 2 shows wide tissue distribution and relatively high distribution volumes. A few hours after the injection, both plasma concentrations of compound 2 maintained micromolar levels, indicating it might have promise for intravenous administration when used combinatorially with anti-gp120 monoclonal antibodies.     

rh-BNP联合阿托伐他汀治疗急性心梗后心衰的临床疗效及对患者血清cTn-I、Myo、CK-MB水平的影响

目的:研究重组人脑利钠肽(rh-BNP)联合阿托伐他汀治疗急性心梗后心衰的临床效果及对患者血清心肌肌钙蛋白(cardiac troponin,cTn-I)、肌红蛋白(Myoglobin,Myo)、肌酸激酶同工酶(CK-MB)水平的影响。方法:选择我院2017年2月～2019年1月收治的72例急性心梗后心衰患者,按随机数字表法分为观察组38例,对照组34例。对照组给予阿托伐他汀治疗,观察组在对照组基础上另加rh-BNP,观察和比较两组的临床疗效,治疗前后血清cTn-I、Myo、CK-MB水平的变化及治疗后不良反应的发生情况。结果:治疗后,观察组总有效率明显高于对照组(P0.05),血清cTn-I、Myo、CK-MB水平均显著低于对照组[(0.23±0.10) vs.(0.16±0.08)、(27.54±3.86) vs.(21.62±2.54)、(70.82±9.25) vs.(61.28±8.33)](P0.05)。观察组治疗后不良反情况总发生率为7.89%,明显低于对照组(26.47%,P0.05)。结论:与单用阿托伐他汀治疗相比,静脉注射rh-BNP联合阿托伐他汀治疗急性心梗后心衰可显著提高临床疗效和安全性,有效减低血清cTn-I、Myo、CK-MB水平。     

七氟醚复合瑞芬太尼静吸麻醉对急性胆囊炎腹腔镜手术患者麻醉效果、血流动力学及炎性因子的影响

摘要 目的：探讨七氟醚复合瑞芬太尼静吸麻醉对急性胆囊炎腹腔镜手术患者麻醉效果、血流动力学及炎性因子的影响。方法：选取2018年1月到2019年12月期间我院收治的120例急性胆囊炎腹腔镜手术患者,根据信封抽签法分为对照组60例（丙泊酚复合瑞芬太尼）和观察组60例（七氟醚复合瑞芬太尼）,对比两组麻醉效果、血流动力学、炎性因子及不良反应。结果：观察组术毕（T5）时间点心率（HR）、平均动脉压（MAP）与麻醉前（T1）比较未见显著性差异（P>0.05）,观察组插管后1 min（T2）~T5时间点HR、MAP高于对照组（P<0.05）。两组术后1 d、术后3 d 肿瘤坏死因子-α（TNF-α）、C反应蛋白水平（CRP）、白介素-6（IL-6）均高于术前,观察组术后1 d、术后3 d CRP、IL-6、TNF-α低于对照组（P<0.05）。观察组自主呼吸恢复时间、定向力恢复时间、睁眼时间、言语应答时间均短于对照组（P<0.05）。两组不良反应发生率组间比较无显著性差异（P>0.05）。结论：急性胆囊炎腹腔镜手术患者采用七氟醚复合瑞芬太尼静吸麻醉,麻醉效果较好,可平稳患者血流动力学,减轻炎症应激且安全性较好。     

基于控制模型的药物动力学静注问题的研究

在新药临床的研究中,以静脉注射方式给药时,药物进入全身循环快速分布到体内的各个组织,通过将机体作为单室模型对血药浓度进行控制,可以从血药浓度的变化得到组织药物水平的状态、本文针对药物动力学的特点,利用控制模型,给出了对其稳定性分析的方法．     

Dose-dependent effects of peptide YY(3-36) on conditioned taste aversion in rats

We used a conditioned taste aversion test to assess whether PYY(3-36) reduces food intake by producing malaise. Two-hour IV infusion of PYY(3-36) (8, 15, and 30 pmol/kg/min) at dark onset in non-food-deprived rats produced a dose-dependent inhibition of feeding and a conditioned aversion to the flavored chow paired with PYY(3-36) infusion. In food-deprived rats, PYY(3-36) at 2 and 4 pmol/kg/min inhibited intake of a flavored saccharin solution without producing conditioned taste aversion, whereas higher doses (8 and 15 pmol/kg/min) inhibited saccharin intake and produced taste aversion. These results suggest that anorexic doses of PYY(3-36) may produce a dose-dependent malaise in rats, which is similar to that reported for PYY(3-36) infusion in humans. Previous studies have shown that PYY(3-36) potently inhibits gastric emptying, and that gut distention can produce a conditioned taste aversion. Thus, PYY(3-36) may produce conditioned taste aversion in part by slowing gastric emptying.     

肾移植术后人微小病毒B19 感染导致纯红细胞增生障碍性贫血

目的:探讨肾移植术后人微小病毒B19感染所致纯红细胞再生障碍性贫血的诊断及其治疗。方法:回顾性分析4例肾移植术后纯红细胞再生障碍性贫血患者的临床特点,诊断方法,治疗过程及预后。结果:两周内在本中心接受肾移植手术的6例患者中,有4例在术后60天内均出现发热、血红蛋白进行性下降等相似症状;综合骨髓穿刺、ELISA方法检测血清特异性IgG、IgM等方法诊断为人微小病毒B19感染;经静脉注射免疫球蛋白、调整免疫抑制方案等综合治疗后,4例患者病情均明显缓解。结论:(1)贫血是肾移植术后患者感染人微小病毒B19的典型临床症状;(2)PCR检测和/或ELISA方法,结合骨髓穿刺及其他实验室指标可诊断人微小病毒感染;(3)静脉注射免疫球蛋白是肾移植术后人微小病毒B19感染导致PRCA的首选治疗方法,病情反复时,再次应用仍然有效。同时予以调整免疫抑制剂方案等综合治疗,可获得理想疗效。