自动化技术在现代医药工业上的应用

介绍了和自控相关的制药工艺当前的改进.重点叙述了pH值控制已成为先进过程控制的重点参数;循环、多效制药系统中过程优化已成为有实效的控制系统;为确保药品生产符合GMP,必须采用批量控制和管理系统;并推荐节能的控制方案及环境检测的实用仪表.     

糖耐量正常的冠心病患者胰岛素抵抗与冠脉病变程度的关系

目的观察正常糖耐量的冠心病患者中冠脉病变与胰岛素抵抗的关系。方法回顾性分析本院行冠脉造影的129例冠心病患者的临床资料,根据Gensini积分评估冠脉病变的严重程度,采用HOMA-IR来评估机体的胰岛素抵抗,最后探讨两者的关系。结果单因素相关分析表明胰岛素抵抗组的冠脉病变程度明显高于胰岛素敏感组,且随着胰岛素抵抗的加重,冠脉病变程度和支数随之加重;多因素相关分析表明,胰岛素抵抗与Gensini积分、冠脉有无病变显著相关。结论在糖耐量正常的冠心病患者中,血糖、糖化血红蛋白可能不是冠脉病变的危险因素,而胰岛素抵抗可能是冠脉病变发生发展最强的危险因素,在冠心病的防治时有必要对正常糖耐量患者的胰岛素抵抗进行有效的干预。     

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??OBJECTIVE To establish dose-related lung inflammatory injury in rats model with intratracheal atomization of lipopolysaccharide (lipopolysaccharides, LPS). METHODS Four groups of 4 rats were subjected to solvent or a single dose of LPS by intratracheal route using a IA-1B-2 inches-microsprayer. The male rats received 200 ??L solvent (control), LPS solutions (15, 5, 0.5 mg??kg^-1). All rats were sacrificed 24 h after dose administration, biochemical analysis and cell counts on bronchoalveolar lavage fluid (BALF) were performed on each rat. Lung, trachea and kidney were examined histologically. Serum chemistry profiles of creatinine, ALB, Na, K, Cl^- were detected. RESULTS Cell counts in BALF showed LPS groups had different degrees of inflammatory reaction. The alkaline phosphatase and total protein concentration were higher in LPS high dose group compared with other groups. In addition, the concentration of TNF-?? increased consistently with LPS dose and has statistical significance compared with the control group. Histopathology findings demonstrated that LPS produced an accumulation of foamy macrophages in the lungs and high degree of inflammation. CONCLUSION The results recommends intratracheally atomizing doses of LPS in rats model produced ranks of lung inflammatory injury.     

DIRBoost–An algorithm for boosting deformable image registration: Application to lung CT intra-subject registration

We introduce a boosting algorithm to improve on existing methods for deformable image registration (DIR). The proposed DIRBoost algorithm is inspired by the theory on hypothesis boosting, well known in the field of machine learning. DIRBoost utilizes a method for automatic registration error detection to obtain estimates of local registration quality. All areas detected as erroneously registered are subjected to boosting, i.e. undergo iterative registrations by employing boosting masks on both the fixed and moving image. We validated the DIRBoost algorithm on three different DIR methods (ANTS gSyn, NiftyReg, and DROP) on three independent reference datasets of pulmonary image scan pairs. DIRBoost reduced registration errors significantly and consistently on all reference datasets for each DIR algorithm, yielding an improvement of the registration accuracy by 5–34% depending on the dataset and the registration algorithm employed.     

NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder

IntroductionMajor depressive disorder (MDD) is a very prevalent disease which pathogenic mechanism remains elusive. There are some hypotheses and pilot studies suggesting that cytokines may play an important role in MDD. In this respect, we have investigated the role of NLRP3 inflammasome complex in the maturation of caspase-1 and the processing of its substrates, IL-1β and IL-18, in blood cells from MDD patients.MethodsForty MDD patients were selected for this study, twenty without treatments and twenty treated with amitriptyline, a common tricyclic antidepressant. Blood samples from twenty healthy volunteers were included in the study. The inflammasome activation was studied by Western blot and real-time PCR of NLRP3 and caspase 1 and serum levels of IL-1β and 18.ResultsWe observed increased gene expression of NLRP3 and caspase-1 in blood cells, and increased serum levels of IL-1β and IL-18 in non-treated patients. IL-1β and IL-18 correlated with Beck Depression Inventory (BDI) scores of MDD patients. Interestingly, amitriptyline treatment reduced NLRP3 and caspase-1 gene expression, and IL-1β and IL-18 serum levels. As it is well established that oxidative stress is associated with NLRP3 inflammasome activation, we next studied mitochondrial ROS and lipid peroxidation (LPO) levels in MDD patients. Increased levels of mitochondrial ROS and LPO were observed in MDD patients, however oxidative damage was higher in MDD patients treated with amitriptyline.ConclusionsThese findings provide new insight into the pathogenesis of MDD and the effects of amitriptyline treatment on NLRP3 inflammasome activation and IL-1β and IL-18 serum levels.     

肥胖的2型糖尿病患者体质成分变化及对骨密度的影响

目的分析肥胖的2型糖尿病患者体质成分及骨密度变化,以阐明机体脂肪含量和肌肉含量在维持骨量中的作用。方法采用双能X线分析仪(DEXA)测定76例2型糖尿病患者全身各部位的骨密度和肌肉、脂肪含量,并根据体重指数将病人分为肥胖组24例与正常体重组52例。结果两组间骨密度和肌肉含量无显著差异(P>0.05),肥胖组全身及局部脂肪含量明显增高(P<0.01)。两组糖尿病患者骨密度与全身及局部肌肉含量呈显著正相关(P<0.05～0.01)。肥胖组全身骨密度与手臂脂肪含量呈显著负相关(P<0.05),且各部位脂肪含量与肌肉含量呈显著负相关(P<0.05)。结论肥胖的2型糖尿病患者以脂肪含量升高为主,肌肉组织含量和脂肪异常分布对骨密度有显著的影响作用。     

高血糖促进T细胞激活加重糖尿病小鼠心肌功能障碍的作用

目的 研究CD4+T细胞在糖尿病性心肌病(diabetes cardiomyopathy, DCM)中的作用。方法 SPF级C57BL/6小鼠,雄性,4周龄,饲喂高脂饲料(high fat diet, HFD)6周,腹腔注射链脲菌素(streptozotocin, STZ),普通饲料喂养的C57BL/6小鼠作为对照,饲喂6周后腹腔注射柠檬酸缓冲液。注射1周后两组小鼠做心脏超声检测,后处死小鼠,心肌组织进行H-E染色,观察心肌病理改变情况,Q-PCR检测两组小鼠心肌组织中相关炎症因子的表达水平。流式细胞检测小鼠体内CD4+T细胞的表型。结果 与普通饮食喂养小鼠相比,2型糖尿病模型小鼠出现了明显的心功能损害和心肌病理学改变。糖尿病模型小鼠心肌组织中Th1细胞转录因子T-bet及炎症因子TNF-α和IFN-γmRNA均较对照组明显升高。糖尿病模型小鼠纵隔淋巴结中CD4+CD44+T细胞比例较对照组明显升高。结论 2型糖尿病模型小鼠出现了明显的心功能损害,纵隔淋巴结CD4+CD44+T细胞比例明显增加,心肌组织中Th1细胞转录因子T-bet升高,提示激活的CD4+Th1细胞可能在DCM中扮演着重要角色,TNF-α可能也参与了这一过程。     

ROCK2在前列腺癌中的表达及意义

目的 探究ROCK2蛋白在临床局限性前列腺癌患者肿瘤组织内部不同区域的表达水平及其意义。方法选取2005年1月至2010年12月行前列腺癌根治术的32例临床局限性前列腺癌患者,其中17例生化复发,15例至末次随访无生化复发。收集记录患者的前列腺特异抗原(prostate specific antigen, PSA)水平、Gleason评分、肿瘤分期及是否复发等资料。对这些前列腺根治标本进行免疫组化检测,评估肿瘤中心区、肿瘤前缘区及癌旁前列腺组织中ROCK2的表达水平,分析其与患者血PSA、肿瘤分期、分级及复发的关系。结果 ROCK2在前列腺癌组织肿瘤前缘区表达显著高于肿瘤中心区,且肿瘤前缘区ROCK2高表达与前列腺癌病理分级及生化复发相关,而肿瘤中心区ROCK2表达与前列腺癌病理分级及生化复发无相关。ROCK2表达与患者PSA水平及病理分期均无相关。结论ROCK2在前列腺癌前缘组织中高表达与肿瘤恶性程度及复发相关,该蛋白可能是前列腺癌的预后因子。     

线粒体通透性转换孔在慢性心力衰竭中的作用及n-3PUFA的保护机制

目的 观察线粒体通透性转换孔(mitochondrial permeablity transition pore, MPTP)在慢性心力衰竭模型中的作用,并初步探讨n-3PUFA的干预作用及其可能机制。方法 采用阿霉素腹腔注射Wistar大鼠建立心力衰竭模型。正常对照组10只,青年和老年心力衰竭组各20只(安慰剂组和n-3PUFA组各10只)。进行超声心动图心功能检测和心肌病理组织学检查;ELISA法检测各组大鼠血清中BNP的表达;提取心肌线粒体,检测膜电位和MPTP孔活性;TUNEL法检测心肌细胞凋亡指数;免疫组化法检测各组大鼠左心室心肌细胞Cleaved-Caspase3的表达。结果 n-3PUFA治疗组与安慰剂组相比,各项心功能指标均明显改善,LVEDD和LVESD明显降低,LVEF及LVFS明显升高(P<0.05),而且心肌损害明显减轻,血清BNP明显降低(P<0.05)。心力衰竭组与对照组相比,心肌线粒体膜电位降低,MPTP孔活性增加,通透性增强,心肌细胞凋亡指数增加,心肌Cleaved-Caspase3蛋白表达升高(P<0.05)。n-3PUFA治疗组与安慰剂组相比,心肌线粒体膜电位增加,MPTP孔活性降低,通透性降低,心肌细胞凋亡指数降低,心肌Cleaved-Caspase3表达下调(P<0.05)。结论 n-3PUFA可能通过抑制心肌线粒体MPTP孔活性,抑制心肌细胞凋亡,有效改善年心力衰竭模型的心功能。     

Relationship between T-helper cell 17/regulatory T cell imbalance and atherosclerosis cardiovascular disease in maintenance hemodialysis patients

Objective To investigate whether the T-helper cell 17 (Th17)/regulatory T cell (Treg) of patients on maintenance hemodialysis (MHD) present imbalance in terms of proportion and function, and if so, the relationship between such imbalance and atherosclerosis cardiovascular disease (ASCVD). Methods Fifty-seven MHD patients, included 25 with ASCVD and 32 without ASCVD, and 24 healthy volunteers were enrolled. The common carotid artery intima media thickness (CCA-IMT), carotid plaque and plaque area were determined with high-resolution B-mode ultrasonography. Treg (CD4+CD25+Foxp3+) and Th17 (CD4+IL-17+) were measured by flow cytometry. The Foxp3 and RAR-related orphan receptor γt (RORγt) mRNA expressions were measured by real-time PCR. TGF-β1, IL-10, IL-17 and IL-6 in serum were detected by ELISA. Results There were decreased Treg proportion, Foxp3 mRNA, TGF-β1 and IL-10, and increased Th17 proportion, RORγt mRNA, IL-17, IL-6 and Th17/Treg in the ASCVD group compared with that in the non-ASCVD group and healthy group (all P＜0.01). No correlation was observed between Treg and CCA-IMT, but IL-10 were negatively correlated with CCA-IMT (P＜0.05). Th17, IL-17 and ratio of Th17/Treg were positively correlated with CCA-IMT (all P＜0.05). MHD patients with carotid plaques had lower Treg, TGF-β1 and IL-10, higher Th17, IL-17 and ratio of Th17/Treg than those without carotid plaques (all P＜0.05). Moreover, Treg proportion was negatively correlated with carotid plaque area in MHD patients with carotid plaques (P＜0.01). Conclusions The Th17/Treg numerical and functional imbalance exists in MHD patients, especially in patients with ASCVD. This might act synergistically with micro-inflammation on immune-mediated atherosclerosis and contribute to the high incidence of ASCVD.