Time-dependent Effects of Klebsiella pneumoniae Endotoxin on Hepatic Drug-metabolizing Enzyme Activity in Rats

The time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic cytochrome P450-dependent drug-metabolizing capacity (cytochrome P450 and b₅ content, activity of aminopyrine N-demethylase, p-nitroanisole O-demethylase, aniline hydroxylase and benzphetamine N-demethylase) and on the pharmacokinetics of antipyrine have been determined in rats. Measurement of enzyme activity and antipyrine (after intravenous injection of 20 mgkg^?1) were performed 2, 24 and 96 h after a single intraperitoneal injection of endotoxin (1 mgkg^?1) and after repeated doses (once daily for 4 days). The contribution of tumour necrosis factor α (TNFα) to the endotoxin-induced changes was also examined in rats pretreated with granulocyte colony-stimulating factor (G-CSF). The systemic clearance of antipyrine and the activity of hepatic cytochrome P450-dependent drug-metabolizing enzymes were dramatically reduced 24 h after a single injection of endotoxin, but had returned to control levels by 96 h. The magnitudes of these decreases in these measurements after repeated doses of endotoxin were similar to those seen 24 h after the single dose. The systemic clearance of antipyrine correlated significantly with cytochrome P450 content and aminopyrine N-demethylase activity. In histopathological experiments, moderate hypertrophy of Kupffer cells was observed, with no evidence of severe liver-tissue damage. G-CSF pretreatment suppressed the increased plasma concentrations of TNFα produced 2 h after single endotoxin injection, but did not eliminate the endotoxin-induced decrease in the systemic clearance of antipyrine, suggesting that TNFα is not the sole component responsible for the reduction of cytochrome P450-mediated drug-metabolizing enzyme activity. These results provide evidence that a single intraperitoneal injection of 1·0 mgkg^?1 K. pneumoniae endotoxin in rats reduces hepatic P450 and b₅ levels, and reduces the activity of various cytochrome P450-mediated drug-metabolizing enzymes without causing severe liver-tissue damage. This suggests that the effect of endotoxin on hepatic cytochrome P450-mediated drug-metabolizing isozymes is non-selective.     

Long-Term Protection against HIV-1 Infection Conferred by tat or rev Antisense RNA Was Affected by the Design of the Retroviral Vector

We have constructed a series of retroviral vectors in which the expression of antisense RNA targeted at the full length coding sequence of HIV-1 tat or rev was driven by three different promoters and in the context of double-copy or single-copy vectors. Jurkat cells transduced by these vectors were shown to express the expected tat or rev antisense RNA without alteration in cell proliferation or surface CD4 expression. After challenge with HIV, four patterns of protection were identified, with the degree of protection being determined primarily by the design of the expression system. In those patterns showing long-term complete protection, we could detect no HIV p24 in the culture supernatants or in the cells, and no HIV RNA or HIV proviral DNA (by PCR), during a 23-week follow-up. Experiments designed to rescue any live virus still formed in the culture after 20 weeks’ challenge demonstrated that, with some constructs, infectious virus could no longer be isolated, while with other constructs, only a low level of infectious virus was still being formed and providing a continuing virus challenge, although all other markers of infection remained undetectable. Our results demonstrated that antisense RNA expression driven by tRNA promoter in the context of a double-copy vector conferred better long-term protection against HIV infection compared to that driven by HIV LTR or MLV LTR promoters, and that the optimized vectors may be useful in developing a gene therapy against HIV-1 infection and AIDS.     

DWI、IVIM参数与脑胶质瘤患儿肿瘤标志物水平相关性

目的 探究扩散加权成像(diffusion weighted imaging, DWI)、体素不相干运动扩散加权成像(diffusion-weighted imaging of voxel incoherent motion, IVIM)参数与脑胶质瘤患儿肿瘤标志物水平相关性及诊断价值。方法 选取于我院进行诊断的疑似脑胶质瘤患儿89例,以病理检查为金标准,最终确诊脑胶质瘤患儿62例为观察组,其余27例为对照组。所有研究对象均进行DWI技术、IVIM技术检查,酶联免疫吸附实验法检测糖链抗原125(carbohydrate antigen 125,CA125)、表皮生长因子(epidermal growth factor, EGF)、癌胚抗原(carcinoembryonic antigen, CEA)水平,对比不同病情患儿表观弥散系数(apparent dispersion coefficient, ADC)、相对脑血容量(relative cerebral blood volume, rCBV)、真实水分子弥散系数(true water molecular dispersion coe...     

sCD14、Ang2、CRP与急诊创伤骨折伴多发伤患者病情转归关系探究

目的 探讨可溶性白细胞分化抗原14（soluble cluster of differentiation antigen 14,sCD14）、血管生成素2（angiopoietin 2,Ang2）、C反应蛋白（C-reactive protein,CRP）与急诊创伤骨折伴多发伤患者病情转归的关系及意义。 方法 选取创伤骨折伴多发伤患者324例,根据患者出院时病情转归情况分为良好组（275例）、不良组（49例）,比较2组一般资料、sCD14、Ang2、CRP水平,应用Pearson分析sCD14、Ang2、CRP与损伤严重程度评分（injury severity score,ISS）关系,采用Cox回归分析急诊创伤骨折伴多发伤患者病情转归的相关影响因素,采用受试者工作特征曲线（receiver operating characteristic,ROC）分析sCD14、Ang2、CRP对病情转归预测价值。 结果 不良组ISS评分高于良好组（P＜0.05）;不良组sCD14、Ang2、CRP高于良好组（P＜0.05）;sCD14（r=0.785）、Ang2（r=0.778）、CRP（r=0.842）与ISS评分呈正相关（P＜0.05）;sCD14、Ang2、CRP均是预后相关独立危险因素（P＜0.05）;sCD14、Ang2、CRP预测病情转归的ROC下面积（area under the curve,AUC）依次为0.813、0.757、0.749;挑选出预测敏感度最高（sCD14）、特异度最高（Ang2）的两个指标进行sCD14+Ang2的联合ROC分析显示,两者联合预测病情转归的AUC为0.935,大于任一单一指标（P＜0.05）。 结论 sCD14、Ang2、CRP与急诊创伤骨折伴多发伤患者病情严重程度及病情转归有关,均可作为预测病情转归的标志物,但联合检测sCD14、Ang2能提高预测可靠性,为临床诊疗及护理提供更准确的参考信息。     

自主神经功能与功能性便秘患者临床症状的相关性分析

目的：根据功能性便秘（functional constipation,FC）患者临床资料分析内脏自主神经功能与便秘症状特征、心理状态及生活质量的相关性。方法：评估102例FC患者和42例健康对照者的一般资料、精神心理状态和心率变异性（heart rate variability,HRV）检测结果,再根据HRV检测结果将FC患者分为自主神经张力偏向正常组、严重偏向交感神经张力组和严重偏向副交感神经张力组;比较各组间Zung’s焦虑自评量表（self-rating anxiety scale,SAS）和抑郁自评量表（self-rating depression scale,SDS）、便秘评分系统（constipation scoring system,CSS）和便秘患者症状自评量表（patient assessment of constipation symptoms, PAC-SYM）、便秘患者生活质量自评问卷（patient assessment of constipation quality of life,PAC-QOL）分值差异,同时比较不同 HRV分组间肛直肠测压参数、肠电图参数差异,分析便秘患者生活质量与自主神经功能、精神心理状态、便秘症状之间的相关性。结果：与健康对照组相比,FC患者焦虑抑郁水平显著升高,HRV检测结果显示自主神经功能异常率高。不同HRV分组的 FC患者间肛直肠测压参数、肠电图参数差异无统计学意义;与交感-副交感神经张力偏向正常组相比,严重偏向交感神经张力组患者明显存在明显的焦虑抑郁情绪、PAC-SYM较高、生活质量降低（主要是躯体不适和担心焦虑两个维度）。严重偏向副交感神经张力组患者CSS评分最高,可能与抑郁情绪为主导有关。多重线性回归显示,患者的焦虑抑郁情绪、自主神经功能显著影响便秘患者生活质量。结论：自主神经功能紊乱的便秘患者存在明显的焦虑抑郁情绪,与便秘严重程度相比,自主神经功能紊乱、焦虑抑郁情绪对便秘患者的生活质量具有更明显的负面影响。调节自主神经功能、心理干预或中枢神经药物等治疗可能具有重要临床意义。     

莱菔硫烷对ox-LDL诱导血小板活化的抑制作用

目的：探讨莱菔硫烷（sulforaphane,SFN）对氧化低密度脂蛋白（oxidized low-density lipoprotein,ox-LDL）诱导血小板活化的影响及其可能的分子机制。方法：在体外实验中,将健康人纯化血小板与不同浓度的SFN(1.0、2.5、5.0μmol/L)共同孵育40 min,然后用ox-LDL激活血小板20 min,并检测血小板活化的指标,包括CD62P的表达、胞内血小板因子4(platelet factor4,PF4)和趋化因子配体5(chemokine ligand 5,CCL5)的释放水平。机制上,用Western blot蛋白免疫印迹法检测血小板肉瘤酪氨酸激酶（sarcoma tyrosine kinase,Src）及其下游的脾酪氨酸激酶（spleen tyrosine kinase,Syk）磷酸化水平;用活性氧（reactive oxygen species,ROS）检测试剂盒测定胞内总ROS水平。结果：ox-LDL诱导的血小板CD62P的表达以及PF4和CCL5的释放水平均可被SFN显著抑制（P <0.05）;SFN显著下调ox-LD...     

Ache、P-selectin、CDK5在病毒性脑炎中的表达及相关性研究

目的 探究乙酰胆碱酯酶(acetylcholinesterase, Ache)、P-选择素(P-selectin)、细胞周期素依赖蛋白激酶5(cyclin-dependent kinase 5,CDK5)在病毒性脑炎(viral encephalitis, VE)中的表达及相关性。方法 本研究选取在本院健康体检及神经内科就诊治疗、住院治疗的病毒性脑炎患者130例作为研究对象,并纳入研究组,根据患者的病情时间将其分为急性期和恢复期,其中急性期组85例,恢复期组45例。根据患者的临床表现,将其分为轻度组和重度组,其中轻度组76例,重度组54例,选择同期在我院接受体检的健康患者60例作为对照组。应用丁酰硫代胆碱底物法检测Ache水平;酶联免疫吸附法检测血清P-selectin水平;CDK5分离试剂盒检测CDK5水平。观察研究组和对照组、急性期和恢复期及重度组和轻度组患者Ache、P-selectin、CDK5水平,分析病毒性脑炎患者Ache、P-selectin和CDK5之间相关性,利用ROC曲线比较Ache、P-selectin、CDK5单独检测及联合检测在VE中的诊断价值。结果 研究组A...     

脑卒中患者发生骨质疏松症的时间及其影响因素分析

目的：探究脑卒中患者发生骨质疏松症的时间及其影响因素。方法：采用回顾性队列研究方法,筛查2010年1月—2017年1月在溧阳市人民医院康复科诊断为脑卒中的685例患者的病历资料。将其中符合标准的105例患者纳入本研究。根据在5年内是否发生骨质疏松症,分为骨质疏松症组46例和非骨质疏松症组59例。以5年内是否发生骨质疏松症为结局,应用logistic回归分析影响脑卒中患者发生骨质疏松症的因素。应用Kaplan-Meier法计算骨质疏松症组发生骨质疏松的中位时间和95%可信区间。应用多因素Cox回归分析影响脑卒中患者脑卒中后发生骨质疏松症速度的因素。结果：性别（女性）（OR=8.145,95%CI:1.361～48.735,P=0.022）和年龄（OR=1.263,95%CI:1.135～1.406,P <0.001）对脑卒中后骨质疏松症的发生具有影响;脑卒中发生骨质疏松症的中位时间为3.42年（95%CI:3.14～3.69年）;年龄对卒中后骨质疏松症的发生时间具有影响（HR=1.162,95%CI:1.029～1.313,P=0.016）;相对于体力劳动,脑力劳动对卒中后骨质疏松...     

病房康复延伸护理对脑卒中迟缓性偏瘫患者三维步态时空参数的影响

目的:观察病房康复延伸护理对脑卒中迟缓性偏瘫患者三维步态时空参数的影响。方法:将60例脑卒中迟缓性偏瘫患者随机分为常规护理组(A组,n=30)、病房康复延伸护理组(B组,n=30)两组,予以相应的方法治疗8周,评估治疗前后两组患者三维步态时空参数。结果:与治疗前相比,治疗后两组患者的步长、步幅、步速、步频、支撑相、双支撑相等参数及B组摆动相均有不同程度的改善(P<0.05); A组摆动相和步宽及B组步宽的变化差异无统计学意义(P>0.05)。与治疗后A组比较,治疗后B组的步长、步幅、步速、步频、支撑相、双支撑相等参数改善较为明显(P<0.05),步宽和摆动相的改善差异无统计学意义(P>0.05)。结论:病房康复延伸护理能改善脑卒中迟缓性偏瘫患者三维步态时空参数,具有临床意义。     

小鼠原始卵泡形成过程中可变剪切的动态变化

目的：通过对新生小鼠卵巢单个生殖细胞转录组数据进行挖掘,探究可变剪切事件是否参与调控小鼠卵泡组装过程的阶段转换。方法：基于小鼠单个生殖细胞转录组数据,用生物信息学方法分析卵泡组装过程3个细胞发育阶段的可变剪切事件及阶段转换之间的差异可变剪切事件,并用PCR验证差异可变剪切相关同源异构体的变化。结果：在小鼠卵泡组装3个发育阶段转换之间均检测到差异可变剪切事件,其中卵泡生成阶段可变剪切事件以及包囊破裂到卵泡生成时期的差异可变剪切事件富集最多,PCR验证了减数分裂相关同源异构体的变化。结论：可变剪切和小鼠卵泡组装细胞发育阶段转换相关,调控生殖细胞到卵母细胞转变过程。