基于网络药理学和实验验证研究柴胡疏肝散治疗慢性萎缩性胃炎的作用机制＊

目的 通过网络药理学的方法进行预测，再深一步进行动物实验验证来研究柴胡疏肝散治疗CAG的作用机制。方法 首先在TCMSP数据库中检索柴胡疏肝散的所有活性成分与药物靶点；通过收集PharmGkb、OMIM、GeneCards和DrugBank数据库中收录的慢性萎缩性胃炎的相关靶点。将药物靶点与疾病靶点进行映射筛选出交集靶点，将得到的交集靶点构建PPI网络与活性成分-共同靶点网络，并对其进行GO和KEGG富集分析。最后利用Vina软件进行分子对接实验验证，并通过免疫印迹法验证柴胡疏肝散对两种受体蛋白EGFR和STAT1的影响。结果 最终筛选得到柴胡疏肝散活性成分104个，潜在靶点238个，与慢性萎缩性胃炎的交集靶点52个；GO与KEGG富集分析分别得到2166条目和148条目，主要涉及到JAK-STAT信号通路、TNF信号通路、HIF-1信号通路等；分子对接结果显示EGFR、STAT1两个靶点能够与核心活性成分能够自发结合成较为稳定的构像；免疫印迹法实验证明柴胡疏肝散能够降低大鼠胃黏膜组织EGFR和STAT1蛋白表达。结论 通过网络药理学和实验验证，发现柴胡疏肝散可能通过调节EGFR和STAT1蛋白表达来共同调控胃黏膜细胞增殖与凋亡，进而发挥着治疗慢性萎缩性胃炎的效果，为深入进行柴胡疏肝散治疗慢性萎缩性胃炎的作用机制研究提供新思路和新方法。     

玳玳果黄酮降脂提取物体内组织分布规律及特征研究

目的：建立UPLC-MS/MS分析方法同时测定玳玳果黄酮降脂提取物效应组分新橙皮苷和柚皮苷在大鼠10种脏器组织中含量，分布规律及特征。方法：采用UPLC-MS/MS技术建立提取物效应组分新橙皮苷及柚皮苷在大鼠心、肝、脾、肺、肾、脑、胃、小肠、脂质、肌肉组织中的定量分析方法；大鼠给药后分别于0.33，0.67，1，4，8 h的5个时间点，分别摘取以上10种脏器组织，测定脏器组织及血液中效应组分的质量浓度，采用DAS（V 2.0）药动学软件对各样本的药物浓度-时间数据进行房室拟合，并计算不同组织效应组分的药-时曲线下面积（AUC）及平均滞留时间（MRT）。结果：所建立的UPLC-MS/MS定量分析方法具备良好的专属性、标准曲线及线性范围良好、方法准确度与精密度、定量下限均符合有关规定；玳玳果黄酮降脂提取物效应组分在血液中的分布符合一室模型，除肾脏及脑组织外，其余脏器中提取物效应组分的房室特征多为静脉注射的二室模型，柚皮苷在肾脏中的拟合结果为非静脉注射的二室模型，新橙皮苷在脑组织拟合结果为静脉注射的三室模型，给药后8 h各组织中效应组分新橙皮苷及柚皮苷AUC值大小顺序均为小肠 > 胃 > 肾 > 脂质 ≈ 脾脏 > 肺 > 肌肉 > 肝 > 心 > 脑，效应组分在各脏器中均无明显蓄积；效应组分在血液、肾脏、肝脏中的滞留时间较长，MRT均大于2 h，脂质最短，MRT不足1 h；各脏器中新橙皮苷的药-时曲线下面积约是柚皮苷的3倍，而心、肝、肾中则是3.5，2.1和3.4倍。结论：玳玳果黄酮降脂提取物效应组分在大鼠组织中分布迅速，达峰时间早于血液；效应组分在肠道内消除缓慢，给药8 h后在各脏器中的含量均显著下降且无特异的蓄积部位。研究结果揭示玳玳果黄酮降脂提取物效应组分在大鼠体内的分布特征及规律，为进一步理解玳玳果黄酮降脂提取物在体内的作用靶点及机制奠定了基础。     

Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.     

消风散合凉血五根汤联合西药治疗成人过敏性紫癜性肾炎临床疗效及对患者血表皮生长因子、血小板活化因子乙酰水解酶的影响

目的观察消风散合凉血五根汤联合西药治疗成人过敏性紫癜性肾炎(HSPN)的临床疗效及对患者血表皮生长因子(EGF)、血小板活化因子乙酰水解酶(PAF-AH)的影响。方法将90例成人HSPN患者按照随机数字表法分为2组。对照组45例予常规西医治疗;治疗组45例在对照组基础上加服消风散合凉血五根汤治疗。2组均治疗8周。比较2组治疗前后中医证候评分、血肌酐(Cr)、尿素氮(BUN)、24 h尿蛋白定量、尿红细胞计数(U-RBC)、尿微量白蛋白尿肌酐比值(UACR)、估算肾小球滤过率(e GFR)、血EGF、PAF-AH水平,并统计2组临床疗效及不良反应情况。结果治疗组总有效率88.89%,对照组总有效率68.89%,治疗组疗效优于对照组(P<0.05)。治疗后2组各项中医证候评分及总分均降低(P<0.05),治疗组治疗后各项中医证候评分及总分均低于对照组(P<0.05)。治疗后2组Cr、BUN、24 h尿蛋白定量、U-RBC、UACR均降低(P<0.05),e GFR升高(P<0.05);治疗组治疗后Cr、BUN、24 h尿蛋白定量、U-RBC、UACR均低于对照组(P<0.05),e GFR高于对照组(P<0.05)。治疗后2组血EGF、PAF-AH水平均降低(P<0.05),治疗组治疗后血EGF、PAF-AH水平均低于对照组(P<0.05)。治疗组不良反应率(11.11%)低于对照组(26.67%,P<0.05)。结论成人HSPN在西医治疗基础上,加用消风散合凉血五根汤可提高临床疗效,不仅可改善临床症状,还能改善肾功能,降低糖皮质激素不良反应,其机制之一可能与其下调血EGF、PAF-AH水平有关。     

针刺配合肠炎散保留灌肠治疗肛窦炎临床研究

目的观察肛窦炎应用针刺配合肠炎散保留灌肠治疗的效果。方法选取2017年10月-2018年10月就诊的72例肛窦炎患者,采用随机数字表法分为观察组(n=36)与对照组(n=36)。对照组给予肠炎散保留灌肠治疗,观察组为针刺配合肠炎散保留灌肠治疗,比较2组症状、疗效及安全性。结果观察组症状(放射痛、指诊症状及镜检症状)少于对照组,总有效率高于对照组,差异有统计学意义(P<0.05);2组安全性相比,差异无统计学意义(P>0.05)。结论针对肛窦炎患者,予以针刺配合肠炎散保留灌肠治疗效果确切,可减少临床症状,加快疾病转归,且治疗安全性较好。     

Revisiting the Hydrogen Storage Behavior of the Na-O-H System

Solid-state reactions between sodium hydride and sodium hydroxide are unusual among hydride-hydroxide systems since hydrogen can be stored reversibly. In order to understand the relationship between hydrogen uptake/release properties and phase/structure evolution, the dehydrogenation and hydrogenation behavior of the Na-O-H system has been investigated in detail both ex- and in-situ. Simultaneous thermogravimetric-differential thermal analysis coupled to mass spectrometry (TG-DTA-MS) experiments of NaH-NaOH composites reveal two principal features: Firstly, an H₂ desorption event occurring between 240 and 380 °C and secondly an additional endothermic process at around 170 °C with no associated weight change. In-situ high-resolution synchrotron powder X-ray diffraction showed that NaOH appears to form a solid solution with NaH yielding a new cubic complex hydride phase below 200 °C. The Na-H-OH phase persists up to the maximum temperature of the in-situ diffraction experiment shortly before dehydrogenation occurs. The present work suggests that not only is the inter-phase synergic interaction of protic hydrogen (in NaOH) and hydridic hydrogen (in NaH) important in the dehydrogenation mechanism, but that also an intra-phase H^δ+… H^δ– interaction may be a crucial step in the desorption process.     

红参发酵产物联合长春瑞滨及顺铂化疗方案治疗晚期非小细胞肺癌患者的疗效

目的探讨红参发酵产物联合长春瑞滨及顺铂化疗方案治疗晚期非小细胞肺癌患者的疗效。方法将104例晚期非小细胞肺癌患者随机分为治疗组及对照组,每组52例。对照组患者给予单纯长春瑞滨^+顺铂化疗方案,治疗组患者在对照组基础上联合应用红参发酵产物。分别在治疗前后采用疲劳症状量表(FSI)、肺癌治疗功能评价量表(FACT-L)评价两组患者疲劳症状及生活质量,并比较治疗前后两组患者血清肿瘤标志物水平、免疫功能指标水平、药物不良反应及生存情况。结果治疗前,两组患者FSI各维度评分及总分,FACT-L各维度评分及总分,细胞角质蛋白19片段抗原21-1(CYFRA21-1)、神经元特异性烯醇化酶(NSE)、癌胚抗原(CEA)、自然杀伤(NK)细胞、CD3^+、CD4^+、CD8^+、CD4^+/CD8^+水平比较,差异均无统计学意义(P﹥0.05)。治疗后,对照组患者FSI各维度评分及总分均高于治疗前及治疗组;治疗组患者生理状态、情绪状态、对疾病关注度评分及总分均高于治疗前,且生理状态、社会家庭状态、情绪状态、功能状态、对疾病关注度评分及总分均高于对照组;两组患者CEA、CYFRA21-1及NSE水平均较治疗前下降,且治疗组患者均低于对照组患者;治疗组患者NK细胞、CD3^+、CD4^+及CD4^+/CD8^+水平均较治疗前上升,且均高于对照组患者,差异均有统计学意义(P﹤0.05)。治疗组患者血液学不良反应发生例数少于对照组,差异有统计学意义(P﹤0.05)。结论红参发酵产物联合长春瑞滨及顺铂化疗方案能够有效提高晚期非小细胞肺癌患者的免疫功能及生活质量,降低血清肿瘤标志物水平,并减轻血液学不良反应。     

Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo melanostictus, Schneider) skin extract on U937 and K562 cells.

The antiproliferative, cytotoxic and apoptogenic activities of Bufo melanostictus (Indian common toad) skin extract (TSE) on U937 and K562 leukemic cell line has been investigated. TSE significantly (P<0.001) reduced the time-dependent cell proliferation and decreased MTT values in U937 and K562 cells. TSE (IC50 doses) suppressed the proliferating cell nuclear antigen expression in both the cells. It was demonstrated that, TSE (IC50 doses) primarily arrested the U937 and K562 cells at G1 phase of the cell cycle. Confocal microscopy showed the altered fragmented nuclei and apoptotic bodies formation in TSE (IC50 doses) treated U937 and K562 cells. Membrane blebbing, cell surface shrinkage and perforation were observed through scanning electron microscope. TSE-induced DNA fragmentation in U937 and K562 cells was reflected in single-cell gel electrophoresis. TSE significantly (P<0.001) increase the length-width ratio of DNA mass as compared to control in comet assay. The flow cytometric analysis of annexin-V binding to the cancer cells further supported the apoptotogenic activity of TSE. The effect of TSE on normal human peripheral blood mononuclear cells viability and cytotoxicity was studied in culture and found to be less cytotoxic than on the U937 and K562 cells. The findings from the present study suggested that TSE might possess potent antineoplastic agent having antiproliferative, cytotoxic and apoptogenic activity against U937 and K562 myeloid leukemic cells.     

银杏叶提取物联合脑蛋白水解物治疗脑梗塞68例

目的观察银杏叶提取物与脑蛋白联用治疗脑梗塞的疗效及对血液流变学指标的影响。方法132例脑梗塞患者随机分为治疗组及对照组。治疗组给舒血宁20 mL,脑蛋白注射液60 mg,1次/d静滴,连用14 d观察治疗前后疗效及血流变指标变化。结果与对照组比较治疗前后疗效及血流变指标均有显著改善。结论银杏叶提取物(舒血宁)合用脑蛋白注射液治疗脑梗塞,可降低血粘度,促进神经功能改善。