Gypenosides Prevent H2O2-Induced Retinal Ganglion Cell Apoptosis by Concurrently Suppressing the Neuronal Oxidative Stress and Inflammatory Response

Journal of Molecular Neuroscience - Our previous study demonstrated that gypenosides (Gp) exert protective effects on retinal nerve fibers and axons in a mouse model of experimental autoimmune...     

研析奥氮平治疗老年晚期癌症患者抑郁状态的血药浓度与临床疗效关系

目的：研析奥氮平治疗老年晚期癌症患者抑郁状态的血药浓度与临床疗效的关系，促进合理用药。方法：80例这类患者服用2.5 ~ 10 mg·d-1奥氮平，应用全自动二维液相色谱法（2D-LC/UV）检测患者用药后4周内每周奥氮平血药浓度（C奥氮平）；采用汉密尔顿抑郁量表（HAMD-24）于治疗前、治疗后4周内每周评估疗效，应用线性回归方程分析奥氮平剂量与血药浓度相关性，运用Logistic回归和受试者工作曲线（ROC）分析奥氮平血药浓度与临床疗效相关性；采用副反应量表（TESS）评估药物不良反应。结果：奥氮平日剂量（D日）和C奥氮平线性方程呈正相关（r=0.634，P<0.001）。治疗的第1、2、3、4周末，有效组与无效组患者D日、C奥氮平、HAMD-24量表减分率存在显著性差异（P<0.05）。经Logistic回归分析得出年龄大、奥氮平血药浓度低是导致奥氮平治疗效果不理想的影响因素。以C奥氮平作为疗效预测因子绘制治疗第1、2、3、4周末ROC曲线，得出约登指数最大时对应的最佳临界值切点分别11.18、13.89、11.55、12.44 ng·mL-1；未发现C奥氮平与TESS量表评分相关（P>0.05）。结论：奥氮平血药浓度与日剂量、临床疗效密切相关，治疗老年晚期癌症患者抑郁状态最低有效血药浓度范围为11~14 ng·mL-1。     

无创产前检测联合孕妇血清可溶性转铁蛋白受体、生长分化因子-15、红细胞体积分布宽度变异系数检测对胎儿β-地中海贫血的诊断价值研究

目的探讨无创产前检测(NIPT)联合孕妇血清可溶性转铁蛋白受体(sTfR)、生长分化因子(GDF)-15、红细胞体积分布宽度变异系数(RDW-CV)检测，对胎儿β-地中海贫血的诊断价值。 方法选择2017年1月至2018年6月，于自贡市妇幼保健院接受羊膜腔穿刺术确诊胎儿为β-地中海贫血的120例孕妇为研究对象。根据其妊娠胎儿的β-地中海贫血轻、中、重型，将其分别纳入轻型组(n＝48)、中型组(n＝40)与重型组(n＝32)。选取同期于本院建卡进行常规产前检查，并且妊娠胎儿发育正常的100例健康孕妇作为对照，纳入对照组。采集4组孕妇空腹肘静脉血，提取孕妇外周血浆中胎儿细胞外游离DNA(cfDNA)，采用2次PCR方法扩增后，采用反向斑点杂交方法检测胎儿β-地中海贫血基因。采用酶联免疫吸附测定法，测定4组孕妇血清sTfR、GDF-15、RDW-CV水平。对4组孕妇血清sTfR、GDF-15与RDW-CV水平分别总体比较，采用单因素方差分析，进一步两两比较，采用最小显著性差异(LSD)-t检验。与胎儿β-地中海贫血诊断"金标准"比较，计算NIPT联合孕妇血清sTfR、GDF-15、RDW-CV水平及这4项指标单独检测，对于胎儿β-地中海贫血诊断的敏感度、特异度、粗符合率、阳性预测值、阴性预测值。本研究严格按照2013年修订的《世界医学协会赫尔辛基宣言》要求进行。4组孕妇年龄及其妊娠胎儿的胎龄等一般临床资料比较，差异均无统计学意义(P>0.05)。 结果①夫妻双方β-地中海贫血基因型相同的40例孕妇中，NIPT与羊膜腔穿刺术对于胎儿β-地中海贫血诊断的符合率为90.0%(36/40)；夫妻双方β-地中海贫血基因型不同的80例孕妇中，上述2种方法对于胎儿β-地中海贫血诊断的符合率亦为90. 0%(72/80)。②4组孕妇血清sTfR、GDF-15、RDW-CV水平分别总体比较，差异均有统计学意义(F＝2 283.445、323.181、45.900，P均<0.001)，进一步两两比较，任意2组孕妇血清sTfR、GDF-15、RDW-CV水平比较，差异均有统计学意义(P<0.05)，并且孕妇血清sTfR、GDF-15、RDW-CV水平随着β-地中海贫血胎儿严重程度增加而逐渐升高。③NIPT联合孕妇血清sTfR、GDF-15、RDW-CV水平检测，对于胎儿β-地中海贫血诊断的敏感度、特异度、粗符合率、阳性预测值与阴性预测值，分别为86.7%、88.0%、87.3%、86.7%与84.6%，其特异度与阳性预测值，均显著高于单独检测孕妇血清sTfR、GDF-15、RDW-CV水平，并且差异均有统计学意义(与孕妇血清sTfR水平比较：χ²＝8.866、5.301，P＝0.003、0.021；与孕妇血清GDF-15水平比较：χ²＝9.765、5.929，P＝0.002、0.015；与孕妇血清RDW-CV水平比较：χ²＝7.167、4.327，P＝0.007、0.038)。 结论孕妇血清sTfR、GDF-15、RDW-CV可能成为诊断胎儿β-地中海贫血的生物标志物，NIPT联合这3项指标检测，可提高诊断胎儿β-地中海贫血的特异度与阳性预测值。由于本研究纳入样本量相对较小，NIPT联合孕妇血清sTfR、GDF-15、RDW-CV水平，对胎儿β-地中海贫血的诊断价值，仍然有待进一步研究、证实。     

Teaching and practice of pharmaceutical comprehensive study in China

Pharmaceutical comprehensive study (PCS) is a new system of experimental teaching in China, which integrates multidisciplinary pharmaceutical knowledge and covers the basic process of new drug discovery. To explore the feasibility of this experiment teaching system and mode, we developed PCS as an elective course. The PCS is designed with two sections: pharmaceutical comprehensive design (PCD) and pharmaceutical comprehensive experiment (PCE). The PCD section includes literature review, comprehensive project design and oral examination. PCE can be divided into four parts: synthesis, quantitative determination, pharmacodynamic evaluation, and formulation and quality determination. Course grade was determined by experimental performance, written report, literature review, new project design and oral examination. The learning interest,experimental ability, theoretical level and literature retrieval ability, team spirit and interpersonal skills have been all significantly improved among students taking this course. A survey was administered at the end of the semester to the enrolled students. The responses were reported as percentages, and the feedback was positive. The course was highly recommended by the teaching inspection committee. This new course plays an important role in developing students’ creativity and comprehensive ability. It could help students understand the focus and features of every secondary discipline, as well as establish scientific and reasonable knowledge system. Most students can better understand the processof drug research after this course.     

集中带量,还是挂网议价采购——生物类似物采购模式研究

生物制品疗效显著、价格高昂,采购是价格调控的重要措施。我国目前已有4个生物类似物获批上市。生物类似物应如何开展采购,在确保临床用药安全与供应的同时,有效控制价格,成为各方关注的问题。本文重点探讨生物类似物采购模式,并就生物类似物的采购方案给出政策建议。     

Partitioning heritability analyses unveil the genetic architecture of human brain multidimensional functional connectivity patterns

Resting‐state functional connectivity profiles have been increasingly shown to be important endophenotypes that are tightly linked to human cognitive functions and psychiatric diseases, yet the genetic architecture of this multidimensional trait is barely understood. Using a unique sample of 1,704 unrelated, young and healthy Chinese Han individuals, we revealed a significant heritability of functional connectivity patterns in the whole brain and several subnetworks. We further proposed a partitioned heritability analysis for multidimensional functional connectivity patterns, which revealed the common and unique enrichment patterns of the genetic contributions to brain connectivity patterns for several gene sets linked to brain functions, including the genes expressed preferentially in the central nervous system and those associated with intelligence, educational attainment, attention‐deficit/hyperactivity disorder, and schizophrenia. These results for the first time reveal the genetic architecture of multidimensional brain connectivity patterns across different networks and advance our understanding of the complex relationship between gene sets, neural networks, and behaviors.     

EEG source estimation in a rare patient with cold‐induced reflex epilepsy

Temperature‐related reflex epilepsy most often takes the form of hot water epilepsy, but very rarely, reflex epilepsy is related to cold temperature. We report a 70‐year‐old male who had seizures triggered by cold sensations in the body. Four antiepileptic drugs were taken during the drug treatment, and oxcarbazepine was the most effective at stopping the seizures. We implemented clinical seizure induction and obtained EEG data from an interictal period and two complete ictal periods. Source estimation was performed to identify and map the primary sources involved in the seizures on the cortical level. We found that β rhythm appeared on the prefrontal lobes during the whole ictal period. The low‐frequency slow δ and θ rhythms, especially the δ rhythm, appeared in the occipital lobe in the early ictal stage and propagated to the right temporal lobe in the mid‐late ictal stage. The prefrontal lobe and right temporal lobe were mainly involved in the generation and propagation of the epileptic activities. This study provides a valuable reference for clinical drug therapy and provides insights into the characteristics of the brain activities involved in cold‐induced reflex epilepsy. [Published with video sequences].     

肩关节镜术后糖皮质激素注射时间和剂量与术后感染的相关性

目的探讨肩关节镜术后糖皮质激素注射时间与剂量对术后感染的影响，为防治肩关节镜术后并发症提供新思路。 方法选取2014年2月至2018年3月普宁市人民医院收治的行肩关节镜手术94例患者为研究对象，根据术后是否发生感染将患者分为感染组（21例）和未感染组（73例）。分析两组术后感染发病率和病原菌分布。探讨患者的年龄、性别、住院时间、手术时间、糖皮质激素使用等与术后感染发生率的相关性。通过ROC曲线预测糖皮质激素注射时间与剂量对肩关节镜术后感染的影响。 结果肩关节镜术后感染者共21例，感染率为22.3%，其中革兰阴性菌8株（38.0%），革兰阳性菌12株（57.2%），真菌1株（4.8%）。与未感染组相比，感染组患者年龄、住院时间、手术时间、合并糖尿病、抗菌药物使用时间、糖皮质激素治疗日均剂量和使用时间差异均有统计学意义（P均< 0.05）；多因素Logistic回归分析显示，手术时间（OR = 1.238、P = 0.026）、糖皮质激素治疗日均剂量（OR = 1.485、P = 0.019）和使用时间（OR = 0.968、P = 0.018）均为肩关节镜术后感染的独立危险因素。ROC曲线分析显示，肩关节镜术后糖皮质激素的累计治疗时间ROC曲线下面积为0.805，95%CI：0.685～0.924，临界值为5.16；肩关节镜术后糖皮质激素日均剂量ROC曲线下面积为0.909，95%CI：0.830～0.988，临界值为12.67，差异均有统计学意义（P均< 0.001）。 结论肩关节镜术后感染以革兰阳性菌为主，长时间与高剂量糖皮质激素注射可能会导致术后感染的风险增高。肩关节镜术后合理应用糖皮质激素是避免感染发生的重要措施。