药物分析实验中翻转课堂与传统课堂的动态结合教学实践

介绍了药物分析实验课程中翻转课堂与传统课堂动态结合的初步设计和实践。研究者采用“低-高-低”型教学结构序列，学生课前利用校内网络教学平台资源、公共在线资源和传统教学资源自主进行低结构化认知和探索，课中以“讲解-讨论-实验操作-再讨论”模块进行高结构化的教师协助学习，课后学生利用各种资源自主进行低结构化总结和拓展。之后，教师综合评价学生成绩并设计后续课程的教学方案。结果表明，与传统课堂相比，翻转课堂与传统课堂的动态结合，对学生认知、探索、实践、创新等方面能力提高更明显，也让教师加速转变为课程教学的主动研究者和创新者。     

Laparoendoscopic Single-site Surgery for Comprehensive Staging of Early Ovarian Cancer

Study ObjectiveTo demonstrate the procedure and suspension skills of laparoendoscopic single-site (LESS) staging surgery with infrarenal para-aortic lymphadenectomy for early-stage ovarian cancer.DesignA presentation of the surgery through this technical video.SettingA hospital.Patient and InterventionsA 45-year-old woman presented with a pelvic mass on gynecologic examination and a serum cancer antigen 125 level of 5910 U/mL (normal = <35 U/mL). A computed tomographic scan revealed a mixture of solid and cystic components (70 × 77 × 71 mm) arising from the right ovary and characterized by the “ovarian vascular pelvic” sign. Clinically early-stage ovarian cancer was suspected. Subsequently, LESS staging surgery was performed by an experienced surgeon in our department.ResultsThe surgery lasted 280 minutes, and the volume of blood loss was 50 mL; there were no intra- or postoperative complications. We “hid” the incision perfectly for cosmetic purposes. The histopathologic findings supported high-grade serous ovarian cancer of the right ovary with the left fallopian tube involved as well. In addition, a total of 34 negative pelvic and 18 negative para-aortic lymph nodes were identified, and a stage of IIA was diagnosed as a result.ConclusionWe performed an LESS staging surgery for early-stage ovarian cancer successfully. Our video shows that the LESS approach provided feasible, cosmetic, and safe access among the selected malignant gynecologic surgery. Therefore, we have experienced that the effective suspension was an auxiliary measure for LESS lymphadenectomy. In addition, compared with multiport laparoscopy, the LESS approach could provide easier access to infrarenal para-aortic regions; furthermore, it was safe and quick to extract an unknown sample.     

Identification of UGTs and BCRP as potential pharmacokinetic determinants of the natural flavonoid alpinetin

1. Alpinetin is a natural flavonoid showing a variety of pharmacological effects such as anti-inflammatory, anti-tumor and hypolipidemic activities. Here, we aim to determine the roles of UDP-glucuronosyltransferases (UGTs) and breast cancer resistance protein (BCRP) in disposition of alpinetin.

2. Glucuronidation potential of alpinetin was evaluated using pooled human liver microsomes (pHLM), pooled human intestine microsomes (pHIM) and expressed UGT enzymes supplemented with the cofactor UDPGA. Activity correlation analyses with a bank of individual HLMs were performed to identify the main contributing UGT isozymes in hepatic glucuronidation of alpinetin. The effect of BCRP on alpinetin disposition was assessed using HeLa cells overexpressing UGT1A1 (HeLa1A1) cells.

3. Alpinetin underwent extensive glucuronidation in pHLM and pHIM, generating one glucuronide metabolite. Of 12 test UGT enzymes, UGT1A3 was the most active one toward alpinetin with an intrinsic clearance (CL_int?=?V_max/K_m) value of 66.5?μl/min/nmol, followed by UGT1A1 (CL_int?=?48.6?μl/min/nmol), UGT1A9 (CL_int?=?21.0?μl/min/nmol), UGT2B15 (CL_int?=?16.7?μl/min/nmol) and UGT1A10 (CL_int?=?1.60?μl/min/nmol). Glucuronidation of alpinetin was significantly correlated with glucuronidation of estradiol (an activity marker of UGT1A1), chenodeoxycholic acid (an activity marker of UGT1A3), propofol (an activity marker of UGT1A9) and 5-hydroxyrofecoxib (an activity marker of UGT2B15), confirming the important roles of UGT1A1, UGT1A3, UGT1A9 and UGT2B15 in alpinetin glucuronidation. Inhibition of BCRP by its specific inhibitor Ko143 significantly reduced excretion of alpinetin glucuronide, leading to a significant decrease in cellular glucuronidation of alpinetin.

4. Our data suggest UGTs and BCRP as two important determinants of alpinetin pharmacokinetics.

     

Benefits and Safety of Tripterygium Glycosides and Total Glucosides of Paeony for Rheumatoid Arthritis: An Overview of Systematic Reviews

Objective: To summarize the evidence from systematic reviews (SRs) on the benefits and safety of Tripterygium glycosides (TG) and total glucosides of paeony (TGP), commonly used to treat rheumatoid arthritis (RA) in China, for patients with RA. Methods: SRs of randomized controlled trials (RCTs) on TG or TGP in treating RA were included, by searching 8 databases from their inception until December 2017. Two authors extracted data independently. We assessed the quality of SRs using AMSTAR and graded the quality of evidence according to the GRADE approach. Results: Eleven SRs containing an average of 7.6 RCTs, involving a total of 7,012 participants were included in this overview. On the basis of included SRs, TG and TGP could improve the following indexes for RA patients: American College of Rheumatology (ACR) 20 response rate, ACR50 response rate and ACR70 response rate, swollen joint count, tender joint count, erythrocyte sedimentation rate and C-reactive protein. Moreover, TGP could reduce incidence of hepatotoxicity. The most common adverse effects of TG were gastrointestinal discomfort and gonad toxicity, while for TGP was mild to moderate diarrhea. The overall quality of evidence for these findings ranged from "low" to "moderate". Conclusions: TG and TGP might be 2 potentially effective complementary and alternative drugs for patients with RA. Nevertheless, due to gonad toxicity, TG should only be considered in elderly patients or patients without reproductive needs. More evidence from high quality RCTs and SRs is warranted to support the use of TG and TGP for RA patients.     

中医健康状态辨识模式的研究现状与展望

健康状态的辨识是把握健康的前提。当前学界已存在专家辨识模式、标准辨识模式、数字辨识模式、智能辨识模式以及微观辨识模式等。联合多种辨识方法,构建健康状态辨识体系,形成常态与动态结合、主观与客观结合、人机互参的中医健康状态个体化辨识方法是研究的趋势所在。文章对未来的研究方向进行展望,探讨了多元辨识模式、远程辨识模式、终身辨识模式、自动辨识模式的思路方法,以期促进全民健康事业,助力"健康中国"战略。     

当归补血汤对糖尿病合并抑郁症模型大鼠血清炎症因子的干预作用

目的:探讨当归补血汤治疗糖尿病并发抑郁症的可能作用机制。方法:40只大鼠其中8只Wistar大鼠为空白对照组,其余32只GK大鼠随机分为模型组、氟西汀组及中药高、低剂量组,每组8只。除空白对照组外,其余各组通过慢性温和不可预知性刺激(chronic mild unpredictable stimulation,CUMS)建立糖尿病并发抑郁症模型。应激造模的同时中药高、低剂量组分别按照4 g·kg~(-1)·d~(-1)和8 g·kg~(-1)·d~(-1)剂量给予当归补血汤,氟西汀组按照2.2 mg·kg~(-1)·d~(-1)剂量给予氟西汀,空白对照组和模型组给予等体积的生理盐水溶液,同时检测大鼠体质量及随机血糖。灌胃28 d后,Elisa法检测大鼠血清中炎症因子白细胞介素-6(interleukin-6,IL-6)、白细胞介素-8(interleukin-8,IL-8)、白细胞介素-10(interleukin-10,IL-10)、超敏C反应蛋白(C-reactionprotein protein,CRP)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的含量。结果:模型组大鼠血糖一直高于空白对照组,而与模型组比较,给药后大鼠血糖明显下降,差异有统计学意义(P0.05)。与空白对照组比较,模型组大鼠血清中IL-10表达显著降低,TNF-α、CRP、IL-6和IL-8的表达均显著升高,差异有统计学意义(P0.001);与模型组比较,氟西汀组、中药低剂量组和中药高剂量组大鼠血清中IL-10的表达均显著提高,但TNF-α、CRP、IL-6和IL-8的表达均显著降低,差异有统计学意义(P0.05或P0.01)。结论:当归补血汤可降低糖尿病并发抑郁症大鼠随机血糖水平,抑制大鼠全身炎症反应,是该方治疗糖尿病并发抑郁症的可能机制之一。     

2015 - 2018年四川省542例流行性乙型脑炎病例流行病学特征分析

目的 分析2015 - 2018年四川省流行性乙型脑炎病例流行病学特征，为乙脑预防控制提供科学依据。方法 收集四川省报告发生542例流行性乙型脑炎病例疫情资料、个案调查表及实验室检测结果，描述性分析其流行病学特征。结果 2015 - 2018年四川省乙脑年平均发病率0.1647/10万，主要发病人群为10岁以下的小年龄组儿童（334例，61.62%），职业分布以散居儿童（185例，34.13%）和学生（184例，33.95%）居多，发病高峰为每年的7 - 9月；165例（30.44%）无疫苗接种史，146例（26.94%）有乙脑疫苗接种史，231例（42.62%）免疫史不详；临床分型以重型和普通型为主， 95例（17.50%）出现并发症，32例（10.96%）患者存在不同程度的后遗症，21例（3.87%）患者死亡。结论 四川省乙脑分布具有明显的季节性和地区性，病情重、预后差，且存在较大免疫空白，加强健康教育及预防接种工作是防控乙脑的关键措施。