磁共振扩散张量成像及波谱分析在帕金森病早期诊断中的应用

目的:探讨磁共振弥散张量成像技术(DTI)及磁共振波谱(MRS)在帕金森病(PD)的早期诊断中的价值。方法:选取早期PD患者20例(早期PD组)、中晚期PD患者20例(中晚期PD组)和非PD志愿者20例(对照组),同时行DTI、MRS,观察3组在DTI中双侧基底核区、双侧额叶、双侧丘脑区的FA值和ADC值及MRS所显示的乙酰天门冬氨酸(NAA)/肌酸(Cr)、胆碱(Cho)/Cr值。结果:3组双侧基底核区的FA值从大到小依次为对照组、早期PD组、中晚期PD组,差异有统计学意义(P0.05);3组双侧丘脑区、双侧额叶区的FA值从大到小依次为对照组、中晚期PD组、早期PD组,差异有统计学意义(P0.05)。3组各兴趣区的ADC值之间差异无统计学意义(P0.05)。3组NAA/Cr值、Cho/Cr值从大到小依次为对照组、早期PD组、中晚期PD组,差异有统计学意义(P0.05)。结论:早期PD患者,DTI中FA值在双侧基底核区开始减小,在双侧丘脑区、双侧额叶区出现明显减小;MRS中NAA/Cr值、Cho/Cr值随着PD患者病情进展不断下降。     

外科辅助上颌骨快速扩弓对鼻气道和上颌复合体影响的系统评价

目的 评价外科辅助上颌骨快速扩弓对鼻气道和上颌复合体的影响.材料和方法 我们计算机检索和手动检索以下数据库:PubMed,ISI Web of Knowledge,Ovid,EBSCO Dentistry & Oral Science Source,Cochrane Library and Cochrane Central Register of Controlled Trials (CENTRAL),纳入采用外科辅助上颌骨快速扩弓治疗的研究,要求受试者人数＞10.依据方法学质量评价量表对纳入的文献进行质量评价.结果 初步检索后获得111篇相关的文献,最终对符合纳入标准且方法学质量评价得分较高的4篇文献的4个结果进行Meta分析.结果表明扩弓后,鼻腔后部容积、使用鼻粘膜减充血剂后鼻腔后部最小横截面积、牙弓前后部宽度均增加显著(P＜0.05).结论 从本研究Meta分析中得出结论:随着上颌基骨和牙槽骨的增宽,外科辅助上颌骨快速扩弓增加鼻腔后部最小横截面积并显著增加鼻腔容积,从而减小鼻气道阻力.     

野百合碱注射建立大鼠肺动脉高压模型的方法

目的探讨野百合碱注射建立大鼠肺动脉高压模型的方法和关键点。方法 SPF级雄性SD大鼠30只,随机分为实验组和对照组各15只。实验组大鼠颈背部皮下注射野百合碱50 mg/kg;对照组皮下注射0.9%氯化钠注射液1 ml。3周后大鼠行右心导管检查、病理检查和免疫组化检查。结果实验组大鼠表现为进行性右心功能衰竭,死亡2只,平均肺动脉压力、右心室收缩压均明显高于对照组[(40.05±1.78)mm Hg vs(18.63±1.80)mm Hg(1 mm Hg=0.133 k Pa),(62.99±2.03)mm Hg vs(28.04±2.26)mm Hg,P均<0.05]。病理切片HE染色,实验组大鼠肺血管中膜明显增生,管腔狭窄,中膜管壁厚度百分比、中膜管腔面积百分比、右心室肥厚指数[RV/(LV+IVS)]均明显大于对照组[(0.292±0.064)vs(0.106±0.026)、(0.0495±0.092)vs(0.200±0.045)、(0.473±0.041)vs(0.295±0.035),P均<0.05]。实验组大鼠肺血管增殖细胞核抗原免疫组化IA值明显高于对照组[(39.5±8.7)vs(18.5±5.3),P<0.05]。结论经颈背部皮下注射野百合碱建立大鼠肺动脉高压动物模型是一种操作简单、有效可靠的方法,把握几个关键点可以提高建模成功率。     

Effects of enteral nutrition support combined with enhanced recovery after surgery on the nutritional status,immune function,and prognosis of patients with esophageal cancer after Ivor-Lewis operation

BackgroundEsophageal cancer (EC) with a high incidence of malnutrition is a highly malignant digestive tract tumor. We investigated the effect of enteral nutrition (EN) support combined with enhanced recovery after surgery (ERAS) on the nutritional status, immune function, and prognosis of patients with EC after Ivor-Lewis operation.MethodsOne hundred patients were randomly divided into the observation group (n=42) and the control group (n=58). The patients in observation group were treated with EN combined with ERAS intervention after Ivor-Lewis operation, and the patients in control group were treated with conventional postoperative EN intervention. The situation of operation, nutritional status, immune function recovery and prognosis between the two groups were compared.ResultsThere was no statistically significant difference in operation time or intraoperative blood loss between the two groups (P>0.05). The chest tube removal time and oral feeding time of the observation group after operation were shorter than those of the control group (P<0.05). After intervention, serum albumin (ALB), transferrin (TF), pre-albumin (PA) and hemoglobin (Hb) levels in both groups were significantly decreased. These indexes were significantly higher in the observation group than in the control group (P<0.05). There were no significant changes in the levels of immunoglobulin (Ig) A, IgG, and IgM, or the numbers of CD3⁺, CD4⁺ and CD4⁺/CD8⁺ T cells in the observation group before and after intervention (P>0.05); however those indexes were significantly decreased in the control group after the intervention (P<0.05). Interestingly, the levels of IgA, IgM, IgG, CD3⁺ T cells, CD4⁺ T cells and CD4⁺/CD8⁺ T cells in the observation group were significantly higher than those in the control group after intervention (P<0.05). The incidence of pulmonary infection in the observation group was significantly lower than that in the control group. The postoperative exhaust time, postoperative defecation time and postoperative hospital stay were shorter in the observation group than in the control group (P<0.05). There was no significant difference in hospitalization cost between the two groups (P>0.05).ConclusionsEN combined with ERAS was more beneficial to the improvement of nutritional status and immune function recovery of patients with EC after Ivor-Lewis operation. It also shortened the length of hospital stay.     

新型口服抗凝药的药物基因组学研究进展

新型口服抗凝药（NOAC）在心脑血管血栓疾病的防治中发挥了重要作用。由于参与NOAC体内过程的转运体和代谢酶的基因多态性,不同个体口服相同剂量的NOAC后,其体内药代动力学参数存在差异。相对于药物转运体,药物代谢酶的基因多态性对NOAC的药代动力学性质影响较大,但目前相关研究较少。本文分析总结了基因多态性对NOAC药代动力学性质的影响。     

丙泊酚对未成年肥胖模型大鼠认知功能损害的机制

目的 研究丙泊酚对未成年肥胖大鼠认知功能的影响,并探讨其与海马组织中血红素加氧酶1（HO-1）、超氧化物歧化酶1（SOD1）蛋白及血浆中S100钙结合蛋白β（S100β）表达的关系。方法 取3周龄雄性SD大鼠140只,随机分为基础饲料组（n=40）和高脂饲料组（n=100）。基础饲料组予基础饲料喂养,高脂饲料组予高脂饲料喂养。喂养4周后,取高脂饲料组体质量≥基础饲料组平均体质量+1.4倍标准差的40只大鼠判定为肥胖建模成功。将基础饲料组大鼠随机分为正常脂肪乳组（NL组）、正常丙泊酚组（NP组）,将建模成功的肥胖大鼠随机分为肥胖脂肪乳组（OL组）、肥胖丙泊酚组（OP组）,每组均为20只。丙泊酚组腹腔注射丙泊酚100 mg/kg,脂肪乳组（对照）腹腔注射脂肪乳100 mg/kg,每天注射1次,连续7 d。停药后第1天,各组大鼠行Morris水迷宫实验评估大鼠空间学习记忆能力,ELISA检测大鼠血浆S100β含量,蛋白质印迹法检测海马组织中HO-1、SOD1蛋白表达,H-E染色观察海马CA1区神经元的变化。结果 与OL组比较,OP组第1～5天逃逸潜伏期均延长（P均<0.05）,第三象限停留时间缩短（P<0.05）,穿越平台次数减少（P<0.05）,血浆中S100β蛋白表达升高（P<0.05）,海马组织中HO-1和SOD1蛋白相对表达量均降低（P均<0.05）,海马CA1区神经元数量减少（P<0.01）。与NL组比较,NP组第1、2天逃逸潜伏期均延长（P均<0.05）,上述其余指标差异均无统计学意义（P均>0.05）。结论 丙泊酚通过下调未成年肥胖大鼠海马组织中抗氧化因子HO-1和SOD1的表达使大鼠S100β表达和氧化应激增加,从而导致其认知功能损害。     

间歇性低氧大鼠模型心肌氧化应激损伤变化及依达拉奉的干预作用

目的:通过建立间歇性低氧(IH)大鼠模型,探讨IH对大鼠心肌氧化应激损伤的影响及其可能作用机制,并进一步了解依达拉奉的干预作用,为临床阻塞性睡眠呼吸暂停低通气综合征及其相关心血管并发症的研究及防治提供新思路。方法:选取健康雄性Wistar大鼠80只,随机分为正常对照(NC)组、IH组、IH+依达拉奉组、IH+生理盐水(NS)组,每组20只。采用气体控制装置向密闭模拟舱中充入氮气、氧气及压缩空气的方法建立IH大鼠模型。造模4周后,检测大鼠血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)及心肌组织丙二醛(MDA)、超氧化物歧化酶(SOD)、羟自由基的含量;测定心肌细胞线粒体腺嘌呤核苷三磷酸(ATP)水平;光镜、透射电镜观察心肌形态学及超微结构改变;反转录-聚合酶链反应技术检测心肌组织Bcl-2、Bax、半胱氨酸蛋白酶3(Caspase-3) mRNA的表达情况。结果:(1)与NC组相比,IH组及IH+NS组LDH、CK、CK-MB、MDA、羟自由基含量明显增加,Bax、Caspase-3 mRNA表达明显升高( P值均<0.05);而SOD活力显著降低,ATP含量显著减少,Bcl-2 mRNA表达明显下降( P值均<0.05)。(2)光镜和透射电镜下,NC组心肌组织未见明显损伤,而IH组及IH+NS组心肌组织的形态学及超微结构均受损。(3)经依达拉奉干预后,血清LDH、CK、CK-MB及心肌组织MDA、羟自由基含量明显降低,Bax、Caspase-3 mRNA表达下降( P值均<0.05);SOD活力明显升高,ATP含量增加,Bcl-2 mRNA表达水平升高( P值均<0.05);且光镜及电镜下心肌组织损伤程度得到一定缓解。(4)心肌细胞Caspase-3 mRNA表达水平与CK( r=0.575)、CK-MB( r=0.460)、MDA( r=0.643)、羟自由基( r=0.454)、Bax mRNA( r=0.741)呈正相关,与ATP( r=-0.525)、Bcl-2 mRNA( r=-0.578)呈负相关。 结论:(1)IH可通过增加氧化物、降低抗氧化物及激活Bcl-2、Bax、Caspase-3引起大鼠心肌氧化应激损伤;(2)IH所致的心肌氧化应激损伤可能通过线粒体介导的细胞凋亡实现;(3)依达拉奉对IH所致的大鼠心肌损伤具有干预作用。     

Safety and efficacy of coblopasvir and sofosbuvir in patients with genotypes 1, 2, 3 and 6 HCV infections without or with compensated cirrhosis

A simple, pangenotypic and effective treatment regimen for patients with a broad range of chronic hepatitis C virus (HCV) infections remains an unmet medical need. We conducted a phase 2, randomized, open study involving untreated patients with chronic HCV genotypes 1, 2, 3, or 6 infections. Patients without cirrhosis were randomly assigned in a 1:2 ratio to receive capsules of the NS5A inhibitor coblopasvir at a dose of 30 or 60 mg plus tablets of the nucleotide polymerase inhibitor sofosbuvir (400 mg) once daily for 12 weeks. Patients with cirrhosis received 60 mg coblopasvir plus sofosbuvir for 12 weeks. The primary endpoint was the sustained virologic response at 12 weeks after the end of therapy (SVR12). Of the 110 patients who were enrolled in the study, 59 were male, 62.7% had HCV genotype 1, 24.5% had genotype 2, 6.4% had genotype 3, and 6.4% had genotype 6. The average age was 45.5 years. A total of 10.9% of patients had compensated cirrhosis. The rate of SVR12 was 98.2% in the intention‐to‐treat (ITT). One genotype 6 patient with cirrhosis experienced virologic relapse. One genotype 2 patient without cirrhosis failed to complete the follow‐up and quit the study. Serious adverse events (SAEs) were reported in 2 patients and were not related to coblopasvir and sofosbuvir. Most adverse events (AEs) did not require treatment. Coblopasvir plus sofosbuvir taken once daily for 12 weeks provided high rates of sustained virologic response (SVR) and had a good safety profile among patients with HCV genotypes 1, 2, 3, or 6 infections, including those with compensated cirrhosis.