螺旋CT泌尿系统成像技术和临床应用

目的 :探讨螺旋 CT泌尿系统成像的检查技术及临床应用价值。方法 :采用 6 5 %安其格纳芬 80～ 10 0 ml静脉缓慢注射 ,延迟 8～ 10 min后行螺旋 CT容积扫描 ,将轴位原始图像传至工作站进行编辑及重建 ,可以显示包括肾盏、肾盂、输尿管及膀胱在内的整个泌尿系立体影像。结果 :检查 35例 ,发现肾癌 1例 ,肾盂癌 1例 ,肾转移瘤 1例 ,输尿管良性狭窄 4例 ,输尿管结石 2例 ,膀胱癌 4例 ,正常 2 2例。提供了良好的肾脏形态和尿路解剖结构 ,诊断敏感性达 10 0 %。与轴位图像结合 ,在揭示病变和尿路梗阻之间的关系方面有独特之处。能显示尿路梗阻部位和程度 ,清晰地诊断尿路梗阻的病因。结论 :螺旋 CT泌尿系成像是一种安全可靠、方便快捷的技术 ,可提供高分辨尿路图像。将成为诊断泌尿系疾病的一种新型无创伤影像学手段。     

低成本两孔胸腔镜手术治疗原发性气胸

目的探讨一种简单、微创、经济的腔镜方法治疗自发性气胸。 方法收集2011年10月至2016年2月胸腔镜手术治疗自发性气胸84例,其中两孔胸腔镜肺大疱结扎54例(试验组),三孔胸腔镜肺大疱切割缝合器楔形切除30例(对照组)。试验组,根据胸壁不同厚度把肺大疱拉近操作孔或拉至操作孔或拉出操作孔用手直接结扎/缝扎后做机械摩擦的胸膜固定术;对照组按常规进行,用切割缝合器行肺楔形切后做机械摩擦的胸膜固定术。 结果两组患者的临床效果差异无统计学意义(P>0.05),试验组的住院费用低于对照组[(16 747.30±2 586.41) 元 vs (21 088.54±6 005.68)元,P<0.05]。 结论两孔胸腔镜下肺大疱用手缝扎/结扎技术治疗自发性气胸简单、微创、经济。     

反义AKT2 RNA逆转C6胶质瘤的细胞恶性表型

目的研究反义AKT2RNA逆转C6鼠脑胶质瘤细胞恶性表型。方法将逆转录病毒LXSN为载体的反义AKT2构建体脂质体复合物直接转染人脑胶质瘤细胞系TJ905和鼠脑胶质瘤细胞系C6,LXSN载体转染组为空载对照。随机筛选阳性克隆并应用蛋白印记和原位杂交鉴定转染。MTT法和TUNEL法评价细胞的增殖活性和凋亡,Transwell法分析侵袭能力,划痕实验研究细胞迁移能力,流式细胞法分析细胞周期,并进行GFAP的表达分析。结果转染ASAKT2cDNA后C6细胞AKT2表达显著抑制。与C6对照组和LXSN空载组比较,转染反义AKT2后C6细胞存活率均明显下降(P<0.01),凋亡指数增加(0.33vs13.67,P<0.01),侵袭能力和细胞迁移能力抑制,诱导细胞出现G0/G1细胞周期阻滞,上调GFAP的表达。结论反义AKT2RNA基因治疗通过抑制肿瘤细胞增殖、诱导凋亡、抑制肿瘤细胞侵袭与迁移并使G0/G1细胞周期阻滞逆转其恶性表型,AKT2可作为基因治疗胶质瘤的重要优选靶的。     

Glucagon-Like Peptide 1/Glucagon Receptor Dual Agonism Reverses Obesity in Mice

OBJECTIVE

Oxyntomodulin (OXM) is a glucagon-like peptide 1 (GLP-1) receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide that reduces body weight in obese subjects through increased energy expenditure and decreased energy intake. The metabolic effects of OXM have been attributed primarily to GLP1R agonism. We examined whether a long acting GLP1R/GCGR dual agonist peptide exerts metabolic effects in diet-induced obese mice that are distinct from those obtained with a GLP1R-selective agonist.

RESEARCH DESIGN AND METHODS

We developed a protease-resistant dual GLP1R/GCGR agonist, DualAG, and a corresponding GLP1R-selective agonist, GLPAG, matched for GLP1R agonist potency and pharmacokinetics. The metabolic effects of these two peptides with respect to weight loss, caloric reduction, glucose control, and lipid lowering, were compared upon chronic dosing in diet-induced obese (DIO) mice. Acute studies in DIO mice revealed metabolic pathways that were modulated independent of weight loss. Studies in Glp1r^−/− and Gcgr^−/− mice enabled delineation of the contribution of GLP1R versus GCGR activation to the pharmacology of DualAG.

RESULTS

Peptide DualAG exhibits superior weight loss, lipid-lowering activity, and antihyperglycemic efficacy comparable to GLPAG. Improvements in plasma metabolic parameters including insulin, leptin, and adiponectin were more pronounced upon chronic treatment with DualAG than with GLPAG. Dual receptor agonism also increased fatty acid oxidation and reduced hepatic steatosis in DIO mice. The antiobesity effects of DualAG require activation of both GLP1R and GCGR.

CONCLUSIONS

Sustained GLP1R/GCGR dual agonism reverses obesity in DIO mice and is a novel therapeutic approach to the treatment of obesity.Obesity is an important risk factor for type 2 diabetes, and ∼90% of patients with type 2 diabetes are overweight or obese (1). Among new therapies for type 2 diabetes, peptidyl mimetics of the gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) stimulate insulin biosynthesis and secretion in a glucose-dependent manner (2,3) and cause modest weight loss in type 2 diabetic patients. The glucose-lowering and antiobesity effects of incretin-based therapies for type 2 diabetes have prompted evaluation of the therapeutic potential of other glucagon-family peptides, in particular oxyntomodulin (OXM). The OXM peptide is generated by post-translational processing of preproglucagon in the gut and is secreted postprandially from l-cells of the jejuno-ileum together with other preproglucagon-derived peptides including GLP-1 (4,5). In rodents, OXM reduces food intake and body weight, increases energy expenditure, and improves glucose metabolism (6–8). A 4-week clinical study in obese subjects demonstrated that repeated subcutaneous administration of OXM was well tolerated and caused significant weight loss with a concomitant reduction in food intake (9). An increase in activity-related energy expenditure was also noted in a separate study involving short-term treatment with the peptide (10).OXM activates both, the GLP-1 receptor (GLP1R) and glucagon receptor (GCGR) in vitro, albeit with 10- to 100-fold reduced potency compared with the cognate ligands GLP-1 and glucagon, respectively (11–13). It has been proposed that OXM modulates glucose and energy homeostasis solely by GLP1R agonism, because its acute metabolic effects in rodents are abolished by coadministration of the GLP1R antagonist exendin(9–39) and are not observed in Glp1r^−/− mice (7,8,14,15). Other aspects of OXM pharmacology, however, such as protective effects on murine islets and inhibition of gastric acid secretion appear to be independent of GLP1R signaling (14). In addition, pharmacological activation of GCGR by glucagon, a master regulator of fasting metabolism (16), decreases food intake in rodents and humans (17–19), suggesting a potential role for GCGR signaling in the pharmacology of OXM. Because both OXM and GLP-1 are labile in vivo (T_1/2 ∼12 min and 2–3 min, respectively) (20,21) and are substrates for the cell surface protease dipeptidyl peptidase 4 (DPP-4) (22), we developed two long-acting DPP-4–resistant OXM analogs as pharmacological agents to better investigate the differential pharmacology and therapeutic potential of dual GLP1R/GCGR agonism versus GLP1R-selective agonism. Peptide DualAG exhibits in vitro GLP1R and GCGR agonist potency comparable to that of native OXM and is conjugated to cholesterol via a Cys sidechain at the C-terminus for improved pharmacokinetics. Peptide GLPAG differs from DualAG by only one residue (Gln³→Glu) and is an equipotent GLP1R agonist, but has no significant GCGR agonist or antagonist activity in vitro. The objective of this study was to leverage the matched GLP1R agonist potencies and pharmacokinetics of peptides DualAG and GLPAG in comparing the metabolic effects and therapeutic potential of a dual GLP1R/GCGR agonist with a GLP1R-selective agonist in a mouse model of obesity.     

老年心血管病合并焦虑抑郁症患者心律失常的动态心电图分析

目的 探讨动态心电图监测下,老年心血管病患者伴焦虑抑郁症与心律失常的关系.方法 选取2011-01至2012-08期间我院收治的伴焦虑抑郁症的老年心血管病患者80例作为观察组,以不伴有焦虑抑郁症的老年心血管病患者70例作为对照组,观察动态心电图监测下的心律失常发生情况,阐明焦虑抑郁症与心律失常之间的关系.结果 观察组患者心律失常检出率明显高于对照组,数据分析发现其差异具有统计学意义（P〈0.05）.结论 通过动态心电图对伴焦虑抑郁症老年心血管病患者进行监测,可明显发现心血管病患者其焦虑抑郁症患者与心律失常的发生密切相关,具有广泛的应用前景,值得在临床上推广使用.     

正常前列腺外周带的MR测量研究

目的测量正常前列腺外周带宽径及T2信号强度并探讨其与年龄、体重及身高的变化关系。资料与方法选取217例无泌尿系统症状(临床表现为无尿路刺激、无排尿困难、无并发症之一)的成年男性为研究对象。按年龄段分为7组:第1组(20～29岁,n=22),第2组(30～39岁,n=29),第3组(40～49岁,n=47),第4组(50～59岁,n=45),第5组(60～69岁,n=37),第6组(70～79岁,n=22),第7组(80岁及以上,n=15)。MRI测量轴位外周带的五点及七点处宽径;测量闭孔内肌、臀肌、外周带的T2信号强度,并计算外周带的相对信号强度,即外周带分别与闭孔内肌、臀肌的比值。比较分析不同年龄段上述MR测量值的变化特点。结果正常组前列腺的外周带宽径左侧为(1.15±0.25)cm,右侧为(1.16±0.23)cm。不同年龄段前列腺的外周带左右宽径有统计学意义(P<0.000)。外周带分别与闭孔内肌及臀肌的T2信号强度比分别为4.97±1.33、2.80±0.68。结论外周带宽径随年龄的变化有先变大后减小趋势,T2信号强度随年龄增大有先增高后减低趋势,可出现局灶性信号减低。外周带左右宽径、体积及相对T2信号强度与身高、体重无明显相关关系。     

血浆灌流治疗腹部开放伤海水浸泡犬肝功能损伤的研究

目的 探讨血浆灌流对腹部开放伤后海水浸泡实验犬肝功能损伤的治疗作用.方法24只腹部开放伤实验犬分为对照组(海水浸泡1.5 h后打捞出水,单纯观察),普通治疗组(海水浸泡后打捞出水,给予一般的急救及补液处理)和血浆灌流组(经海水浸泡后打捞出水,给予一般的急救补液处理,30 h后给予血浆灌注治疗),每组8只.于致伤前及致伤后定时取血测定总胆红素(TB)、血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)、凝血酶原时间(PT)、内毒素、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6),同时对肝组织进行病理检查.结果 对照组和普通治疗组血清TB、ALT、AST和LDH明显升高,血浆灌流组灌流后ALT、AST、LDH、TB、内毒素、TNF-α比灌流前明显下降(P<0.05),血细胞、血小板数量与普通治疗组比较明显下降.结论 血浆灌流对外伤后海水浸泡导致的实验犬肝功能损伤的治疗效果良好,此法可应用于该类肝损害的治疗.     

MEDPOR材料片薄筋膜覆盖的实验研究

目的　试以极薄的颞深筋膜替代较厚的颞浅筋膜覆盖MEDPOR耳廓支架 ,以求能更清晰地显露支架的仿真外观。但颞深筋膜不包含轴型血管 ,成岛状瓣后其血运不足以支持移植皮片成活。该实验观察能否通过MEDPOR相互交通的细密孔隙 ,以毛细血管长入的方式 ,与支架背面的颞浅筋膜建立血运联系 ,以支持移植皮片成活。方法　在兔背部深、浅两层筋膜之间插入 30mm× 15mm× 2mm的MEDPOR片。对照组即时于深筋膜深面掀起 ,上植皮片 ;实验组原位缝回 ,3周后再于深筋膜深面掀起 ,切断深筋膜蒂部后 ,于深筋膜深面植皮 ,观察两组植皮成活情况。结果　对照组兔 6只 ,4只皮片全部坏死 ,2只植皮 80 %以上坏死 ;实验组兔 6只 ,皮片全部成活。结论　不含轴型血管的深筋膜成瓣后 ,其血运不足以支持皮片成活 ;深、浅两层筋膜之间 3周内可通过一定厚度的MEDPOR材料的孔隙建立血运联系 ,且仅依靠此新建立的跨MEDPOR的血运联系 ,即能支持深筋膜上所植皮片的成活。     

85例髓母细胞瘤临床病理学分析

目的探讨髓母细胞瘤临床病理学特征及其影响患者预后的主要危险因素。方法收集85例髓母细胞瘤患者的临床病理学资料,观察其组织病理学及免疫学表型特征,分析其临床特点及影响患者预后的相关危险因素。结果 85例髓母细胞瘤患者中男性49例,女性36例,平均发病年龄(9.35±1.18)岁。75例患者病变位于小脑(其中59例位于小脑半球,16例位于小脑蚓部),10例分别位于脊髓(5例)、第四脑室(1例)、大脑颞叶(1例)、大脑额叶(1例)、大脑枕叶(1例)、中脑(1例)。临床表现主要为颅内压增高、共济失调及患侧肢体运动障碍等,部分病人表现为言语不清、记忆力下降及肢体感觉麻木等。免疫组织化学检查:突触素(Syn)阳性表达率为64%,β连环蛋白(β-catenin)阳性表达率为45%,胶质纤维酸性蛋白(GFAP)阳性表达率为50%;NF、CD99肿瘤细胞散在或弱阳性表达;Vimentin、CK、Neu-N、EMA肿瘤细胞呈阴性表达;肿瘤细胞Ki-67增殖指数较高,约为60%。结论髓母细胞瘤儿童多发,预后不良,β-catenin和Ki-67免疫组化染色对其诊断与鉴别诊断有一定参考价值,可能成为髓母细胞瘤判断预后的重要指标。     

无创正压通气联合纳洛酮治疗慢性阻塞性肺疾病急性加重期并发呼吸衰竭的耐受性及安全性分析

目的 评价无创正压机械通气(NPPV)联合纳洛酮(NLX)治疗慢性阻塞性肺疾病急性加重期(AECOPD)并发Ⅱ型呼吸衰竭的耐受性及安全性。方法 将85例因AECOPD伴有Ⅱ型呼吸衰竭进行NPPV治疗的住院患者采用数字表法随机分为观察组42例和对照组43例,对照组给予临床常规治疗和NPPV治疗,观察组在对照组的基础上应用NLX治疗;监测两组治疗前后动脉血气分析、呼吸频率、心率的变化以及气管插管率、辅助呼吸肌评分及NPPV不耐受放弃的例数。结果 与治疗前比较,两组治疗后PaCO₂下降、PaO₂上升、pH值上升,同时患者呼吸频率、心率减慢,差异有统计学意义(P<0.05)。与对照组比较,观察组NPPV治疗后24h各项指标改善较明显(P<0.05)。观察组气管插管率、辅助呼吸肌评分及NPPV不耐受放弃的例数均明显低于对照组,差异有统计学意义(P<0.05)。结论 NPPV联合NLX治疗AECOPD并发Ⅱ型呼吸衰竭可显著改善患者血气分析指标,降低其呼吸频率及心率,提高患者对NPPV的耐受性,并且安全性良好。