Enhancing effect of natural borneol on the absorption of geniposide in rat via intranasal administration

Both geniposide (Ge) and natural borneol (NB) are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography (HPLC) after intranasal administration of Ge (4 mg/kg) alone and combined with different doses (0.08, 0.8, and 8 mg/kg) of NB. The intravenous administration was given as a reference (4 mg/kg of Ge and 8 mg/kg of NB). Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter (3–5 min vs. 40 min); the peak concentration became higher (1.32–4.25 μg/ml vs. 0.67 μg/ml); and, the relative bioavailability of Ge combined with NB was 90.3%–237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.     

冰片在中风及假手术大鼠体内的药代动力学研究(英文)简

Objective： This study was designed to investigate the pharmacokinetics of borneol in the pathological conditions of stroke and evaluate the pharmacokinetic differences of borneol caused by stroke after oral administration of borneol and Xingnaojing （XNJ）. Methods： The rats were divided into two groups, ischemia-reperfusion （IR） and sham-operated （SO） rats. Each group contained two subgroups： pure borneol and XNJ subgroups. After administration with the same dosages of borneol 162.0 mg/kg, plasma samples were collected. The cerebral ischemia-reperfusion model was created by reversible middle cerebral artery occlusion （MCAO）. The blood samples were collected punc- tually after oral administration and a specific gas chromatographic system-flame ionization detector （GC-FID） method was developed and employed to determine the level of borneol in the plasma. The pharmacokinetic parameters were analyzed using non-compartmental methods with Kinetica. Results： After administration of borneol, the maximum plasma concentration （Cmax） and area under the curve （AUC） values in stroke rats significantly increased by 302% and 275%, respectively, compared with the SO rats, and the same phenomenon appeared after administration of XNJ. In the rats with the same physiological conditions, the Cmax and AUC had higher values in the borneol subgroup （P〈0.05）. Conclusions： These results suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of borneol and that there are some components in XNJ inhibiting the absorption of borneol.     

顺铂联合热处理对术中回收血红细胞及其中混杂的肝肿瘤细胞株(HepG2)的影响（英文）

目的:研究离体热处理和顺铂联合热处理对术中回收血红细胞功能的影响及其中混杂的肝肿瘤细胞株(HepG2)的杀灭作用。创新点:(1)采用多种评价指标研究了不同时间离体热处理对术中回收血中混杂的HepG2的杀灭作用及对红细胞的影响,并确定了对红细胞安全且能有效杀灭HepG2的离体热处理时间。(2)从多个角度评价了离体顺铂联合热处理对术中回收血红细胞的影响及对其中混杂的HepG2的杀灭作用,确定了该方案中对红细胞安全且能有效去除HepG2的顺铂浓度。方法:采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)、5-乙炔基-2’脱氧尿嘧啶核苷(EdU)和平板克隆形成评估HepG2的细胞存活率、DNA复制率和克隆形成能力(图1和3);从红细胞渗透脆性、携氧能力(2,3-二磷酸甘油酸(2,3-DPG)、半饱和氧分压(P50))、能量代谢(Na+-K+-ATPase、pH)、膜完整性(游离血红蛋白(Hb)、血清K+和Na+浓度、细胞膜磷脂酰丝氨酸外翻比例)等角度评估红细胞功能(图2和4;表3)。结论:肝肿瘤术中回收血经离体顺铂联合热处理(42°C,50μg/ml)60min后,能有效清除其中混杂的HepG2,但对红细胞无显著影响,值得体内进一步研究顺铂热处理有效应用于肿瘤手术自体血液回输的安全方案。     

Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine

Objective: To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and on cell migration of cultured rat vascular smooth muscle cells (VSMCs). Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods: Rat VSMCs were incubated with different concentrations of homocysteine (50–5 000 μmol/L). Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin (10⁻⁹–10⁻⁵ mol/L) were added when VSMCs were induced with 1 000 μmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results: Homocysteine (50–1 000 μmol/L) increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5 000 μmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and activation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine (50–5 000 μmol/L) stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions: Homocysteine (50–1 000 μmol/L) significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and activation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.     

瞬时受体电位通道TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性和神经病理性疼痛模型中的镇痛作用(英文)

目的:评价瞬时受体电位通道(TRP通道)TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性、持续性和神经病理性疼痛模型中的作用。方法:通过辣椒素实验、异硫氰酸烯丙酯(AITC)实验和福尔马林实验,评估TRP通道拮抗剂在小鼠神经源性疼痛模型中的镇痛作用;通过建立紫杉醇诱导的小鼠神经病理性疼痛模型,对TRP通道拮抗剂的抗痛觉(冷、热、触觉)过敏效应进行评估;通过旋转法实验对小鼠的运动协调性进行评估。结论:TRP通道家族包含了不同的小鼠疼痛模型。TRP通道拮抗剂能减轻神经源性、持续性和神经病理性疼痛,但是其镇痛效果与疼痛模型有关。     

冰片对血脑屏障P-糖蛋白功能的影响

观察冰片对血脑屏障(BBB)P-糖蛋白功能的影响。取NIH小鼠,随机分为冰片高、中、低剂量组,维拉帕米组和溶剂对照组。灌胃给药,每日2次,共7次。末次给药后,分别从尾静脉和脑室注射罗丹明123(Rho-123)。注射Rho-123后取血浆和脑组织,荧光分光光度法测定血浆及脑组织中Rho-123含量。结果表明:尾静脉注射Rho-123后,冰片对小鼠血浆Rho-123含量无明显影响;5,10,20和30min冰片高、中剂量组小鼠脑组织Rho-123浓度均显著高于溶剂对照组(P0.01)。脑室注射Rho-123后5,10,20和30 min,冰片高剂量组小鼠血浆Rho-123浓度均显著低于溶剂对照组(P0.05);20,30min冰片中剂量组小鼠血浆Rho-123浓度亦显著低于溶剂对照组(P0.05);1,5,10和20 min冰片高剂量组小鼠脑组织Rho-123浓度显著高于溶剂对照组(P0.01或P0.05);5,10 min冰片中剂量组小鼠脑组织Rho-123浓度亦显著高于溶剂对照组(P0.05)。说明冰片能抑制BBB P-gp功能。     

川芎挥发油鼻腔喷雾剂脑靶向性研究

目的：研究川芎挥发油经大鼠鼻腔给药后在体内和脑组织中的药动学特性,并评价其脑靶向性。方法：大鼠尾静脉注射或经鼻腔给予川芎挥发油溶液,采用RP—HPLC法分别测定血浆及脑组织中藁本内酯的浓度。结果：川芎挥发油溶液鼻腔给药后,可快速进入血液和脑组织,其T_max为0．18h,脑靶向性指数为1．16。结论：川芎挥发油溶液鼻腔给药具有一定的脑靶向性,是一种值得推荐及研究的给药途径。     

Hydroxychavicol,a polyphenol from Piper betle leaf extract,induces cell cycle arrest and apoptosis in TP53-resistant HT-29 colon cancer cells

This study aims to elucidate the antiproliferative mechanism of hydroxychavicol(HC).Its effects on cell cycle,apoptosis,and the expression of c-Jun N-terminal kinase(JNK)and P38 mitogen-activated protein kinase(MAPK)in HT-29 colon cancer cells were investigated.HC was isolated from Piper betle leaf(PBL)and verified by high-performance liquid chromatography(HPLC),nuclear magnetic resonance(NMR),and gas chromatography-mass spectrometry(GC-MS).The cytotoxic effects of the standard drug 5-fluorouracil(5-FU),PBL water extract,and HC on HT-29 cells were measured after 24,48,and 72 h of treatment.Cell cycle and apoptosis modulation by 5-FU and HC treatments were investigated up to 30 h.Changes in phosphorylated JNK(pJNK)and P38(pP38)MAPK expression were observed up to 18 h.The half maximal inhibitory concentration(IC₅₀)values of HC(30μg/mL)and PBL water extract(380μg/mL)were achieved at 24 h,whereas the IC₅₀of 5-FU(50μmol/L)was obtained at 72 h.Cell cycle arrest at the G0/G1 phase in HC-treated cells was observed from12 h onwards.Higher apoptotic cell death in HC-treated cells compared to 5-FU-treated cells(P<0.05)was observed.High expression of pJNK and pP38 MAPK was observed at 12 h in HC-treated cells,but not in 5-FU-treated HT-29 cells(P<0.05).It is concluded that HC induces cell cycle arrest and apoptosis of HT-29 cells,with these actions possibly mediated by JNK and P38 MAPK.     

Effect of lipopolysaccharide on the hemocyte apoptosis of Eriocheir sinensis

In the present study, we investigated the possible toxicity mechanism of lipopolysaccharide (LPS) extracted from Gram-negative bacteria in Eriocheir sinensis hemocytes. Apoptotic hemocytes and reactive oxygen species (ROS) production induced by the LPS were monitored by the combination of flow cytometry and microscope observation. It was shown that LPS induced serious damage on the DNA and morphological changes in hemocytes, including cell shrinkage, fracture of nucleus membrane, margination, condensation and fragmentation of chromatin, and formation of apoptotic bodies indicating obvious hemocyte apoptosis. As compared with the control group, the apoptotic cell ratio increased to 30.61% and 39.01% after 1-h exposure and 57.72% and 75.01% after 2-h exposure to 1 and 10 μg/ml LPS, respectively (P<0.05). Significant outburst of ROS production was observed in LPS-treated hemocytes with approximately 176.6% of relative dichlorofluorescein mean fluorescence at 1-h exposure, followed by a drastic decline (P<0.05). These results indicated that LPS would induce oxidative stress on hemocytes from E. sinensis and cause ROS burst, DNA damage, and subsequently apoptosis. The process of ROS-mediated apoptosis might be one of the potential toxicity mechanisms of LPS on crustacean hemocytes.     

Immunological effects of a 10-μg dose of domestic hepatitis B vaccine in adults

Objective: To evaluate the immunological effects of three types of domestic 10-μg/dose hepatitis B vaccines in adults compared with a foreign vaccine, and to provide scientific evidence in support of adult hepatitis B vaccination. Methods: Adults from five counties (Deqing, Changxing, Nanxun, Wuxing, Anji) in Huzhou City, Shaoxing County and Tongxiang County, Zhejiang Province, China were selected. Blood samples were taken to assess serum HBsAg, anti-HBs, and anti-HBc using a chemiluminescence immunoassay. Adults, aged 16 to 49 years and who were anti-HBs negative at baseline, received hepatitis B immunizations at 0, 1, and 6 months. Anti-HBs levels were assessed one month after the third and final vaccination. Results: A total of 1 872 adults were immunized and the average positive rate was 89.5%. Four types of hepatitis B vaccine were used, including three from Chinese companies (Shenzhen Kangtai, Dalian High-Tech, and North China Pharmaceutical) and one from a UK company (GlaxoSmithKline). Their seroconversion rates were 81.67%, 95.05%, 89.64%, and 86.81%, respectively. There was a significant difference between the anti-HBs positive conversion rates of the four types (P<0.005) but the seroconversion rates among the different vaccines were not significantly different (χ ²=2.123, P=0.145). The average anti-HBs geometric mean titers (GMTs) of non-immune adults immunized with each of the four vaccines were 177.28, 473.23, 246.13, and 332.20 mIU/ml, respectively. There were no statistically significant differences in the GMTs between the three types of domestic vaccine and the foreign vaccine (t=−1.575, P=0.116). Conclusions: Domestic recombinant hepatitis B vaccines can achieve immunization effects comparable to those of a foreign vaccine.     

Effect of compatible herbs on the pharmacokinetics of effective components of <Emphasis Type="Italic">Panax notoginseng</Emphasis> in Fufang Xueshuantong Capsule

Fufang Xueshuantong (FXT) is a well-known Chinese herbal formula which has been used to treat cardiovascular and ophthalmic diseases, especially diabetic retinopathy. Panax notoginseng (Burkill) F.H. Chen (PN) is the main herb of FXT, whose major bioactive constituents are ginsenosides. However, the scientific basis of the compatibility of FXT is still ambiguous. The present study investigated the scientific basis of the compatibility of FXT by comparing the pharmacokinetics of marker compounds after oral administrations of PN and FXT. A high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for simultaneous detection of notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1), and ginsenoside Rb1 (GRb1) in rat plasma. The pharmacokinetic studies of FXT and PN were performed using the established method with the pharmacokinetic parameters being determined by non-compartmental analysis. The results showed that the pharmacokinetic parameters (maximum concentration, area under the curve (AUC_0–t ), clearance, and mean residence time) of NR1, GRg1, and GRb1 were significantly different after oral administration of FXT (P<0.05) compared with PN. The AUC_0–t values of GRg1 and GRb1 were 1.7- and 3.4-fold greater, respectively, in FXT than in PN. The compatible herbs of FXT could prolong the retention time and increase the systemic exposure of NR1, GRg1, and GRb1 compared with PN in vivo, providing some scientific basis for the compatibility and clinical use of FXT.     

植物修复的应用:毛竹苗对铅的积累与耐性研究(英文)

目的:探索毛竹在修复铅污染土壤的植物修复潜力。创新点:使用了毛竹作为一种全新的植物修复材料进行研究。得到了毛竹幼苗在铅胁迫下的生长与生理反应情况,不同植物组织对铅的吸收与积累情况,铅胁迫下毛竹幼苗表层与细胞超微结构的特征。方法:根系形态分析(图3)、植物重金属含量分析(表1)、扫描电镜分析(图4)和透射电镜分析(图5)。结论:各组织部位铅浓度的值揭示了,毛竹是一个很好的固定铅污染土壤的植物材料;但是由于毛竹茎的高生物量,也可以作为铅污染土壤的植物修复材料。在0~200μmol/L铅处理下,毛竹的生物量与根系形态没有显著性差异,生长正常未出现中毒症状。通过扫描电镜观察铅胁迫导致叶片的气孔减少,根与茎内含物增多。通过透射电镜观察高浓度的铅胁迫导致部分细胞内部叶绿体变形、内质网消失、细胞核与核仁缩小和类囊体膜消失。尽管超微结构观察到细胞内部的损害,但是未出现视觉的毒性症状。毛竹铅的高耐性与茎的高生物量,提供了毛竹作为材料修复土壤重金属铅更大的可能性。     

恒速静脉点滴、口服药或肌注等几种给药途径的药动学模型

快速静脉注射、恒速静脉点滴、口服药或肌注是几种不同的给药途径。在这几种给药途径下,体内血药浓度的变化曲线是不同的。快速静脉注射能使血药浓度立即达到峰值,常用于急救等紧急情况;恒速静脉点滴与口服药或肌注也有一定的差异,主要表现在血药浓度的峰值出现在不同的时刻,血药的有效浓度保持时间也不尽相同。事实上,这几种给药途径的药动学模型是不同的。     

Analysis of Student Performance in Large-Enrollment Life Science Courses

This study examined the historical performance of students at Michigan State University in 12 life sciences courses over 13 yr to find variables impacting student success. Hierarchical linear modeling predicted 25.0–62.8% of the variance in students’ grades in the courses analyzed. The primary predictor of a student''s course grade was his or her entering grade point average; except for the second course in a series (i.e., Biochemistry II), in which the grade for the first course in the series (i.e., Biochemistry I) was often the best predictor, as judged by β values. Student gender and major were also statistically significant for a majority of the courses studied. Female students averaged grades 0.067–0.303 lower than their equivalent male counterparts, and majors averaged grades were 0.088–0.397 higher than nonmajors. Grades earned in prerequisite courses provided minimal predictive ability. Ethnicity and involvements in honors college or science residential college were generally insignificant.     

加强廉政建设规范教务管理 保障人才培养模式改革进行——以成都大学为例

教务管理是高校廉政建设的一个重要领域,成都大学教务处大力推进党风廉政建设,规范教务管理,保障人才培养模式改革的顺利进行。加强思想观念建设,把廉政思想教育摆在首位,认真做好与廉政思想教育相关的各项工作。加强规章制度建设,制定、修订和完善有关廉政建设和规范教务管理的各项规章制度。加强监督体系建设,对教务处领导班子和处内的各项工作进行监督,对重点事件、重点环节、重点科室、重点人员进行监督。加强工作作风建设,建立起学习的长效机制,全面提高管理人员的综合素质,坚持以学生和教师为中心,服务教师,服务学生。     

加强廉政建设规范教务管理 保障人才培养模式改革进行——以成都大学为例

教务管理是高校廉政建设的一个重要领域,成都大学教务处大力推进党风廉政建设,规范教务管理,保障人才培养模式改革的顺利进行。加强思想观念建设,把廉政思想教育摆在首位,认真做好与廉政思想教育相关的各项工作。加强规章制度建设,制定、修订和完善有关廉政建设和规范教务管理的各项规章制度。加强监督体系建设,对教务处领导班子和处内的各项工作进行监督,对重点事件、重点环节、重点科室、重点人员进行监督。加强工作作风建设,建立起学习的长效机制,全面提高管理人员的综合素质,坚持以学生和教师为中心,服务教师,服务学生。     

试析我国行政成本过高的原因及应对策略

现今我国行政成本增长的速度已大大超过西方发达国家,并出现了结构不合理、浪费严重的问题。其主要原因是正确行政观念的缺失、公务员队伍庞大且整体素质偏低、行政绩效评估操作困难、现行财务预算制度的弊端以及监督机制不健全等。应通过强化成本意识,树立效益观念;精简机构,提高素质;重建政府绩效考核体制;完善现行财务预算制度;健全审计制度等方面加以解决,使行政成本合理。     

Early effects of oral administration of omeprazole and roxatidine on intragastric pH

Objective

The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress-related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset of action to promote hemostasis and relieve the symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor, omeprazole 20 mg, and an H₂-receptor antagonist, roxatidine 75 mg.

Methods

Ten Helicobacter pylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 h after single oral administration of omeprazole 20 mg and roxatidine 75 mg. Each administration was separated by a 7-d washout period.

Results

During the 6-h study period, the average pH after administration of roxatidine was higher than that after administration of omeprazole (median: 4.45 vs. 2.65; P=0.0367). Also during the 6-h study period, a longer duration of maintenance at pH above 2, 5, and 6 was observed after administration of roxatidine 75 mg than after administration of omeprazole 20 mg (median: 90.6% vs. 55.2%, P=0.0284; 43.7% vs. 10.6%, P=0.0125; 40.3% vs. 3.3%, P=0.0125; respectively).

Conclusions

In Helicobacter pylori-negative healthy male subjects, oral administration of roxatidine 75 mg increased the intragastric pH more rapidly than that of omeprazole 20 mg.     

XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer: a meta-analysis in 17 studies

Objective: XRCC1 polymorphism is a research hotpot in individual treatment for non-small cell lung cancer (NSCLC). To obtain the association between XRCC1 polymorphism and clinical outcome of platinum-based treatment for NSCLC, a meta-analysis was conducted. Methods: Databases including PubMed, Embase, Cochrane, and Chinese National Knowledge Infrastructure (CNKI) were searched for publications that met the inclusion criteria. A fixed effect model was used to estimate pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC. A chi-squared-based Q-test was used to test the heterogeneity hypothesis. Egger’s test was used to check publication bias. Results: Seventeen published case-control studies that focus on the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC in 2 256 subjects were included in this meta-analysis, of whom 522 were AA genotypes (23.2% frequency), 916 AG genotypes (40.6% frequency), and 818 GG genotypes (36.2% frequency). The overall response rate (ORR) was 45.2% (110/243) for AA genotype patients, 29.9% for AG genotype (73/244), and 30.7% for GG genotype (124/403). The heterogeneity test did not show any heterogeneity and the Egger’s test did not reveal an obvious publication bias among the included studies. The meta-analysis indicated that AA genotype patients presented higher response rates toward platinum drug treatment compared with G model (GG+GA) patients (GG vs. AA model: OR=0.489, 95% CI 0.266–0.900, P=0.021; AG vs. AA model: OR=0.608, 95% CI 0.392–0.941, P=0.026; GA+AA vs. GG model: OR=1.259, 95% CI 0.931–1.701, P=0.135; GG+GA vs. AA model: OR=0.455, 95% CI 0.313–0.663, P=0.0001). However, no evidence validates XRCC1 associates with the survival following platinum drug therapy. Conclusions: Our meta-analysis suggested that XRCC1 Arg399Gln is related with the sensitivity of NSCLC patients to platinum-based treatment. AA genotype patients present more desirable curative effectiveness compared with other patients.