罗格列酮联用维甲酸抗胃癌裸鼠移植瘤血管生成的研究

目的研究过氧化物酶体增殖物激活受体γ(PPARγ)的激动剂罗格列酮(ROS)联用全反式维甲酸(ATRA)对人胃低分化黏液癌MGC-803细胞的裸鼠移植瘤血管生成的影响,并初步探讨其抗血管生成的可能机制。方法建立胃癌裸鼠移植瘤模型,荷瘤裸鼠随机分为荷瘤未用药组、ROS组(ROS 25 mg·kg~(-1)·2d~(-1))、ATRA联用ROS低剂量组(ROS 18 mg+ATRA 11 mg·kg~(-1)·2d~(-1))、中剂量组(ROS 30 mg+ATRA 11mg·kg~(-1)·2d~(-1))、高剂量组(ROS 50 mg+ATRA 11mg·kg~(-1)·2d~(-1))。用药40d后,观察各组裸鼠移植瘤体积变化及抑瘤率；利用免疫组化观察移植瘤中血管内皮生长因子(VEGF)的表达,对移植瘤中的微血管密度(MVD)进行计数,同时用RT-PCR技术观察VEGF及缺氧诱导因子-1α(HIF-1α)的表达。结果①ROS组能缩小瘤体体积,其与荷瘤未用药组比较差异有统计学意义(P＜0．01),ATRA联用ROS低剂量,与ROS组抑瘤率相当(P＞0．05),随着ROS剂量增加,抑瘤率增加,呈剂量依赖关系；②ROS组能抑制肿瘤新生血管生成,降低VEGF、HIF-1αmRNA的表达；ROS与ATRA联用,随着ROS剂量增加,抑制肿瘤新生血管生成、降低VEGF、HIF-1αmRNA的表达更明显(P＜0．05)。结论25mg·kg~(-1)·2d~(-1)ROS有一定抑瘤效果,ATRA与ROS联用可发挥协同抗肿瘤作用,其机制可能是通过蛋白酪氨酸磷酸酶基因(PTEN)途径抑制肿瘤血管生成,从而抑制肿瘤的生长。     

阿司匹林干预野百合碱诱导的大鼠肺动脉高压的研究

目的探讨阿司匹林对野百合碱(MCT)诱导的大鼠肺动脉高压的作用。方法雄性Sprague Dawley(SD)大鼠120只,随机分为6组,每组20只,分别为:正常对照组(Ctrl组)、肺动脉高压组(PAH组)和阿司匹林不同剂量治疗组(ASA 0.5组,ASA 1组,ASA 2组,ASA 4组)。PAH组、阿司匹林各剂量治疗组于第0天一次性腹腔注射MCT 50 mg/kg。从第l天开始,阿司匹林各剂量治疗组分别给予阿司匹林0.5、1.0、2.0 mg·kg~(-1)和4.0mg·kg~(-1)·d~(-1)灌胃,共30d。第31天,对各组大鼠进行以下检测:(1)统计大鼠的体质量和生存率;(2)右心导管法测定肺动脉收缩压(sPAP);(3)心脏大体标本测定右心室肥厚指数(RVHI);(4)肺组织染色切片,运用IPP 6.0图像分析软件测定肺小动脉增厚指数(PATI)。结果与PAH组比较,ASA 2组和ASA 4组体质最增加[(464.6±62.6)g和(473.2±77.2)g比(424.9±68.5)g,均为P<0.05];ASA各治疗组合计生存率较PAH组明显提高(83.75%比60.00%,P<0.05);与PAH组比较,ASA各治疗组sPAP明显下降(均为P<0.05),RVHI显著降低(均为P<0.05);除ASA 0.5组以外,其他阿同匹林治疗组的PATI较.PAH组明显降低(均为P<0.05)。结论阿司匹林1、2 mg·kg~(-1)·d~(-1)和4 mg·kg~(-1)·d~(-1)能有效降低野百合碱诱导的肺动脉高压大鼠的肺动脉压力,减轻右心室肥厚和肺小动脉增生。     

氯沙坦或卡托普利对自发性高血压大鼠心脏纤维化的干预研究

目的　探讨在不同水平阻断肾素 -血管紧张素系统 (RAS)对高血压心肌纤维化的影响。方法　 2 9只自发性高血压大鼠 (SHR)随机分成 (1)SHR对照组 (n =15 ) ;(2 )氯沙坦组 (n =7,30mg·kg-1·d-1) ;(3)卡托普利组 (n =7,10 0mg·kg-1·d-1) ;(4)WKY(n =12 )为非高血压组。治疗组每日灌胃给药 ,对照组蒸馏水灌胃 15周后 ,获取标本。结果　 1.SHR心肌血管紧张素Ⅱ (AngⅡ )和醛固酮 (Ald)浓度、羟脯氨酸和Ⅰ /Ⅲ型胶原比值较同龄WKY大鼠明显增高 (P <0 0 1) ,而心肌胶原单体 /二聚体 (α/ β)比值和基质金属蛋白酶 - 1(MMPs- 1)活力降低 (P <0 0 1) ,且随病程而进一步升高或降低。 2 .经氯沙坦或卡托普利干预后 ,心肌AngⅡ、Ald浓度、心肌羟脯氨酸和Ⅰ、Ⅲ型胶原比值有不同程度的降低 (P <0 0 1) ,而心肌胶原单体 /二聚体 (α/ β)比值和MMPs- 1活性升高 (P <0 0 1) ,逆转了心肌纤维化。3.氯沙坦在改善胶原表型、胶原可溶性及提高MMPs- 1活性优于卡托普利。结论　不同水平阻断肾素血管紧张素系统对纤维化逆转不仅减少胶原含量 ,还改善表型和交联的异常     

动脉粥样硬化中单硝酸异山梨酯对内皮功能的保护

两项研究表明,硝酸戊四醇酯(6mg·kg~(-1)·d~(-1))对高脂食物喂养家兔的内皮功能不良有保护效应。该研究在于明确单硝酸异山梨酯(ISMN,200mg·kg~(-1)·d~(-1))在硝酸酯耐药的背景下是否仍发挥血管保护效应。新西兰大白兔(每组10只)分为3组,以正常饮食(NORM组),高胆固醇饮食(0.75％,CHOL组)和高胆固醇并单硝酸异山梨酯(C-ISMN组)。每日喂养家兔2次。16周后制成动脉环评价血管的损害结构、血     

口服Ⅱ型胶原肽—霍乱毒素B亚单位复合物对胶原诱导性关节炎的影响

目的 关节炎急性期胶原诱导性关节炎(CIA)小鼠口服Ⅱ型胶原免疫活性肽段(250-270))[CⅡ（250-270）]和霍乱毒素B亚单位(CTB)的共价复合物,观察其是否能产生免疫耐受。方法 DBA/1小鼠分成Ⅰ、Ⅱ、Ⅲ、Ⅳ组,Ⅰ组为健康对照,Ⅱ、Ⅲ、Ⅳ组小鼠制成CIA。Ⅲ组小鼠于关节炎发病率达到100％后,灌胃CⅡ(250-270 )-CTB共价复合物,Ⅳ组小鼠于初次免疫后第14日灌胃CⅡ(250-270)与CTB的混合物。记录小鼠关节炎症评分及病理评分。关节炎发生率比较采用Fisher精确概率法,关节炎累计评分及组织病理累计评分采用方差分析。结果 Ⅰ、Ⅱ、Ⅲ、Ⅳ组的关节炎发生率分别为0、100％、100％和25％;关节炎累计评分均值分别为0、5.0±1.7、10.8±2.8和1.0±2.0;关节炎病理累计评分均值分别为0、16±8、32±13和7±6。结论 CIA小鼠于免疫后的关节炎临床前期口服CⅡ( 250-270)与CTB的混合物能抑制关节炎的发生及严重程度,关节炎急性炎症期口服CⅡ(250-270)-CTB共价复合物后可能使关节炎症加重。     

建立微小隐孢子虫感染小鼠模型方法的研究

目的探索微小隐孢子虫传代和扩增模型小鼠的最佳性别、日龄、免疫抑制时间和免疫抑制剂地塞米松磷酸钠(DEXp)的最佳剂量。方法25、50、75日龄雌性和雄性BALB/c小鼠各3组,免疫抑制3 d后接种卵囊;各剂量组小鼠1 L饮水中含DEXp分别为1 mg、5 mg、10 mg、15 mg、20 mg、25 mg;各免疫抑制时间组小鼠分别在免疫抑制前6 d、3 d和免疫抑制后0 d、3 d、6 d、9 d感染卵囊。以上各组小鼠经口感染保存时间和方法相同的微小隐孢子虫卵囊的剂量均为2.0×105个,感染后逐日收集鼠粪,用饱和蔗糖漂浮法分离纯化卵囊。结果雌性小鼠排卵囊强度均较同日龄雄性小鼠大,而不同日龄小鼠中又以50日龄(26 g-28g)小鼠排卵囊量最多;各剂量组小鼠中,15 mg/L组排卵囊强度较其他各组大;免疫抑制时间组中,免疫抑制3 d感染组排卵囊强度最大。结论适合于卵囊扩增和传代的最佳鼠模型是50日龄(26-28g)雌性小鼠;DEXp的最佳剂量是15 mg/L;最佳免疫抑制时间是感染前3 d。     

细粒棘球蚴囊经甲苯达唑、阿苯达唑或阿苯达唑亚砜作用后其生发层的形态学变化和药物含量

小鼠的继发性细粒棘球蚴囊在含甲苯达唑阿苯达唑或阿苯达唑亚枫1及10μg/ml的培养液中培养l～7d时,囊壁所含各药物的量相近,但生发层的受损以甲苯达唑组较重,次为阿苯达唑亚砜和阿苯达唑组。感染小鼠ig上述3种苯并咪唑类化合物的等效剂量1～14d后24h,囊壁的药物含量甚低,但生发层的损害仍以甲苯达唑组的较重,并认为阿苯达唑亚矾是阿苯达唑的有效代谢物。     

合欢皮总皂苷治疗旋毛虫感染小鼠的疗效观察

目的研究合欢皮总皂苷对感染旋毛虫小鼠的治疗效果。方法将36只感染旋毛虫的ICR小鼠随机分为6组(每只小鼠感染300条旋毛虫),每组6只。组Ⅰ-Ⅲ为成虫组:组Ⅰ为感染对照组,组Ⅱ为合欢皮总皂苷治疗组,组Ⅲ为阿苯达唑治疗组;组Ⅳ-Ⅵ为肌幼虫组:组Ⅳ为感染对照组,组Ⅴ为合欢皮总皂苷治疗组,组Ⅵ为阿苯达唑治疗组。Ⅰ、Ⅱ、Ⅲ组于感染后第2d开始给药,连续给药3d,于感染后第7d处死,计数小肠内成虫;Ⅳ、Ⅴ、Ⅵ组于感染后第7d开始给药,连续给药14d,于感染后第40d处死,计数肌幼虫并计算减虫率,HE染色计数肌幼虫,免疫组化检测膈肌中IL-1β,IL-6,TNF-α,COX-2因子的表达。结果合欢皮总皂苷和阿苯达唑治疗组成虫数和肌幼虫数均少于感染对照组(P<0.01),成虫减虫率分别为71.60%和81.24%,肌幼虫减虫率分别为65.70%和89.94%;HE染色结果表明两个治疗组囊包幼虫均减少,炎症细胞表达均明显减轻;免疫组化结果显示治疗组IL-1β,IL-6,TNF-α,COX-2的表达降低。结论合欢皮总皂苷对旋毛虫成虫和囊包幼虫均有较好的杀虫效果,虽然效果略次于阿苯达唑,但其作为中药提取物毒性较低。     

PLGA—Ⅰ型胶原-壳聚糖复合人工硬脊膜生物相容性的研究

目的 观察聚乳酸-聚乙醇酸共聚物(PLGA)-Ⅰ型胶原-壳聚糖复合人工硬脊膜的生物相容性.方法 制作PLGA膜(膜Ⅰ)、PLGA-Ⅰ型胶原复合膜(膜Ⅱ)、PLGA-Ⅰ型胶原-壳聚糖(9∶ 1)复合膜(膜ⅢA)、PLGA-Ⅰ型胶原-壳聚糖(5∶ 5)复合膜(膜ⅢB),对其行接触角、吸水率测定及细胞毒性实验.结果 吸水率:膜Ⅰ＜膜ⅢB＜膜ⅢA＜膜Ⅱ,P均＜0.01;接触角:膜Ⅱ＜膜ⅢA ＜膜ⅢB＜膜Ⅰ,P均＜0.01;细胞毒性实验:第1天,各膜间OD值比较,P＞0.05;第3、7天,膜Ⅰ与膜Ⅱ、膜ⅢA,膜ⅢA与膜ⅢB比较,P均＜0.05.结论 PLGA膜经Ⅰ型胶原和壳聚糖改性后,可以促进细胞在膜上的黏附、贴壁能力.膜ⅢA在生物相容性方面基本符合人工硬脊膜的要求.     

卡维地洛和美托洛尔对大鼠急性心肌梗死后胶原重构影响的对比研究

目的　对比研究非选择性 β受体阻滞剂卡维地洛及选择性 β1 受体阻滞剂美托洛尔对大鼠心肌梗死后胶原的影响 ,以了解卡维地洛改善心室重构及心功能的机制。方法　将梗死后 4 8h存活大鼠分为心肌梗死对照组、美托洛尔组 (15mg·kg- 1 ·d- 1 )、低剂量卡维地洛组 (1mg·kg- 1 ·d- 1 )和高剂量卡维地洛组 (10mg·kg- 1 ·d- 1 )。另设假手术组。给药 6周后 ,测量血流动力学参数及心功能。取血测量血浆内皮素及血管紧张素Ⅱ。测量心肌梗死区及非梗死区的总间质胶原容积分数 (ICVF)及Ⅰ、Ⅲ型胶原的ICVF。结果　美托洛尔及卡维地洛均可减低左心室舒张末压、增加左心室内压最大上升和下降速率 ,以高剂量卡维地洛组效果最好。与心肌梗死对照组比较 ,高剂量的卡维地洛可减轻心肌非梗死区尤其是右心室的ICVF及Ⅰ、Ⅲ型胶原的ICVF。低剂量卡维地洛及美托洛尔对间质胶原影响不明显。结论　卡维地洛可抑制非梗死区胶原增生 ,减少心肌纤维化 ,而美托洛尔无此作用。卡维地洛对心肌纤维化的抑制可能较美托洛尔能更好地改善心肌梗死后心室重构及心功能     

Satisfaction with ambulatory care of persons with AIDS

OBJECTIVE: To examine the relation of patient characteristics and site of care to the perception of ambulatory care quality by persons with AIDS (PWAs). DESIGN: Patient surveys and medical record review were used to determine PWAs’ perceptions of their ambulatory care, self-perceived health status, primary care relationships, sociodemographic characteristics, and severity of illness. SETTING: A public-hospital HIV clinic, an academic group practice, and a staff-model health maintenance organization (HMO) that together care for 20% of all Massachusetts PWAs. PATIENTS: All active patients as of February 12, 1990, and all new AIDS patients at each of the three sites during the subsequent 13 months. MEASUREMENTS AND MAIN BESULTS: The primary outcome measure was a six-item scale of patient-rated quality of care (PRQC), a newly developed measure that combined patients’ ratings of their physician care, nursing care, involvement in medical decisions, and overall quality of care. Multiple logistic regression was carried out with low PRQC (lowest quart He) as the dependent variable, to identify correlates of patient perceptions of poor quality. Patients who had a primary nurse were significantly less likely to have low PRQC scores (OR=0.50, 95% CI=0.26 to 0.97). Black patients and patients who used injection drugs were significantly more likely to rate their care in the lowest quartile (OR=2.22, 95% CI=1.04 to 4.78; and OR=2.43, 95% CI=1.13 to 5.23, respectively), as were those who had lower self-perceived health status, after controlling for confounders; no association was found by site or severity. CONCLUSIONS: These results show that primary nursing may be an important determinant of how PWAs rate the quality of their ambulatory care. Furthermore, PWAs who are black or who are injection drug users are less satisfied than are others with the quality of their ambulatory AIDS care. Presented in part at the annual meeting of the Society of General Internal Medicine, April 30, 1993, Arlington, Virginia. Supported by the Agency for Health Care Policy and Research, grant number HS06239.     

分析老年糖尿病患者应用甘精胰岛素联合阿卡波糖治疗的效果

目的探讨甘精胰岛素联合阿卡波糖在老年糖尿病患者中的临床疗效。方法选取该院2018年7月—2019年7月收治的113例老年糖尿病患者作为研究对象,经随机数字表法,划分A组(n=56,阿卡波糖)和B组(n=57,甘精胰岛素+阿卡波糖),比较两组临床疗效、血糖指标。结果B组患者临床治疗总有效率显著高于A组;经治疗,B组患者空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbAlc)水平明显低于A组。两组之间比较差异有统计学意义(P<0.05)。结论在老年糖尿病患者中应用甘精胰岛素+阿卡波糖,临床疗效显著,使患者的空腹血糖、餐后2 h血糖、糖化血红蛋白等指标得到了明显改善,安全性强。     

Treatment of patients with Eisenmenger's syndrome with Bosentan

We treated prospectively 14 patients with Eisenmenger's syndrome, with a mean age of 10 years, ranging from 3 to 18 years. Treatment continued for 12 months, and demonstrated a lasting symptomatic improvement, but no improvement in terms of mean saturation of oxygen over 24 hours. Exercise capacity, as judged by peak uptake of oxygen, worsened in the six patients able to perform a treadmill test. The symptomatic benefit from dual blockage of endothelin receptors in these patients may be due to mechanisms other than selective pulmonary vasodilatation alone.     

Evaluation of atrial vulnerability with transoesophageal stimulation in patients with atrioventricular junctional: Comparison with patients with ventricular pre-excitation and with normal subjects

The aim of our work was to evaluate the inducibility of atrialfibrillation in a group of patients with atrioventricular junctionalreentrant tachycardia and to compare it with that of patientswith a Kent-type ventricular pre-excitation (Wolff-Parkinson-Whitesyndrome) and a control group. One hundred and twenty-five subjects were separated into groups.Group 1 comprised 49 Wolff-Parkinson-White patients, with amean age of 26.4, range 10.66 years; group 2, 51 patients withatrioventricular junctional reentrant tachycardia inducibleby transoesophageal atrial stimulation andlor clinically documented,with a mean age of 43.4, range 16–78 years; group 3, 25control subjects with a mean age of2.64, range 13–76 years. Each subject underwent atrial transoesophageal stimulation withthe following protocol: programmed atrial stimulation with 1and 2 stimuli during atrial pacing of 100. min^–1 and 150.min^–1; atrial stimulation for 10 s at a rate of 200–300–400–500–600.min^–1 with intervals of 10 s between stimulations, fivesuccessive ‘ramp-up’ atrial stimulations for 9 swith the rate increasing from 100 to 800. min^–1 with intervalsof 10 s between stimulations. The end point was the completionof the protocol or induction of sustained atrial fibrillation(>1 min). The chi-square test was used for statistical analysis. Our resultsshowed that in group 1 atrial fibrillation was induced in 27149patients (55.1%); this was sustained in 13149 (26.5%) and non-sustainedin 14149 (28.5%); in group 2, atrial fibrillation was inducedin 22151 patients (43.0%); it was sustained in 7151 (13.7%)and non-sustained in 15151 (29.4%); in group 3, sustained atrialfibrillation was not induced in any subject and in only onesubject was a non-sustained atrial fibrillation (4 s) induced. The chi-square test showed that group 2 vs group 1 were non-significant,while group 2 vs group 3 and group 1 vs group 3 were significant(P<0.003 and P<0.0007, respectively). Therefore group 2 patients showed a greater atrial vulnerabilityin comparison to the control subjects and a similar vulnerabilityto group 1 patients. It is possible that the greater atrialvulnerability in the patients of group 2 was due to the doublenodal pathway.     

小剂量垂体后叶素合并硝酸甘油治疗咯血

目的评价小剂量垂体后叶素联合硝酸甘油治疗咯血的疗效及不良反应。方法将50例咯血患者随机分为两组,治疗组在常规治疗基础上（n=26）应用小剂量垂体后叶素联合硝酸甘油;对照组（n=24）在常规治疗基础上仅应用小剂量垂体后叶素。分析其疗效及不良反应。结果48小时后治疗组有效率96.15％（25／26）,对照组有效率58.33％（14／24）,差异有统计学意义（P=0.012）;治疗组对血压影响小,无统计学意义（P〉0.05）,对照组能引起血压升高的副作用（P〈0.05）;治疗组出现头晕头痛、胸闷、心悸、腹痛、腹泻、恶心呕吐、出汗、面色苍白等不良反应比对照组少,差异有统计学意义（P〈0.05）。结论小剂量垂体后叶素联合硝酸甘油治疗中量咯血比垂体后叶素单药治疗中量咯血疗效明显提高,且能减少垂体后叶素不良反应。