卵巢细胞线粒体动力学变化与多囊卵巢综合征

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是常见的女性内分泌疾病之一.PCOS患者颗粒细胞中调节线粒体动力学平衡关键因子表达水平的异常,提示PCOS患者卵巢细胞清除功能异常,线粒体的能力降低.卵巢细胞中异常线粒体的积聚不仅会影响细胞的胰岛素敏感性及甾体激素合成能力,还会直接降低卵泡细...     

BPH微创术后前列腺段尿道形态对排尿力学的影响

目前众多的经尿道微创术式治疗良性前列腺增生(BPH)均通过扩大或再造前列腺段尿道(PU)的腔内空间发挥作用,因此,探讨BPH微创术后PU形态对排尿的力学影响,具有重要的指导意义。本研究采用计算流体力学(CFD)技术探讨PU/膀胱颈横径比(RPU-1)对尿流的影响。结果表明,在RPU-1>0.79时,PU两侧出现涡流;且...     

云南省瑞丽市新型冠状病毒肺炎暴发疫情传播力和控制效果模型分析

目的 针对2021年3月末瑞丽市COVID-19疫情暴发,本研究应用更新方程模拟COVID-19在瑞丽市的传播过程,快速测算其传播的流行病学参数传播序列间隔(SI)、再生数(R)及其在加强防控措施干预下的变化,为边境地区疫情防控策略提供科学依据。方法 收集官方网站公布的2021年3月30日至4月16日瑞丽市的病例信息,用Excel 2019软件进行流行病学分析,使用R 4.0.5软件建立更新方程模型,用马尔可夫链蒙特卡罗算法(MCMC)采样计算各参数值的中位数与95%置信区间,对不同索引病例情况下疫情发展进行预测,研究疫情防控政策执行效果。结果 2021年3月30日至4月16日,瑞丽市累计报告确诊病例90例,无症状感染者43例,共133例,其中19例无症状感染者转为确诊病例,确诊病例和无症状感染者的年龄中位数分别为32、28岁。通过模型得到SI中位数约为5.00(95%CI: 4.22～7.31)天,标准差中位数约为24.67(95%CI: 12.05～27.91)天; 在疫情暴发较早阶段,再生数R约为1.42(95%CI: 1.31～1.80),加强防控措施后1周内,R下降至0.58(95%CI: 0.07～0.72),位于临界值1.0以下; 模型预测4月17日以后,每天新增感染者数量≤1例。结论 在合理推测索引病例的前提下,更新方程模型能较好地拟合疫情数据,其预测瑞丽市的疫情将在短时间内得到控制。瑞丽市的防控措施和经验可为类似边境地区的防疫工作提供有益借鉴。     

The Genomic Evolution and the Transmission Dynamics of H6N2 Avian Influenza A Viruses in Southern China

In China, the broad prevalence of H6 subtype influenza viruses, increasingly detected in aquatic birds, promotes their exchange materials with other highly pathogenic human-infecting H5N1, H5N6, and H7N9 influenza viruses. Strikingly, some H6 subtype viruses can infect pigs, dogs, and humans, posing risks to public health. In this study, 9 H6N2 viruses recovered from waterfowl species in the Guangdong province of China in 2018 were isolated and sequenced. Phylogenetic analysis revealed that the genome sequences of these H6N2 viruses belonged to Group I, except for the NP gene in Group III. Coalescent analyses demonstrated that the reassortment of NA and NS genes have occurred in two independent clusters, suggesting H6 subtype viruses had been undergoing a complex reassortant. To examine the evolutionary dynamics and the dissemination of the H6 subtype viruses, a Bayesian stochastic search variable selection was performed for results showing higher viral migration rates between closer provinces, including Guangdong, Jiangxi, Guangxi, and Fujian. Notably, the transmission routes of the H6 subtype viruses were concentrated in Jiangxi Province, the most frequent location for input and output transmission and a region containing Poyang Lake, a well-known wintering site for migration birds. We also found that the aquatic birds, especially ducks, were the most common input source of the viral transmission. In addition, we also found that eight positively selected amino acid sites were identified in HA protein. Given their continuous dissemination and the broad prevalence of the H6 subtype influenza viruses, continued surveillance is warranted in the future.     

根管超声冲洗的计算流体动力学分析

目的 应用计算机模型分析当超声工作尖位于根管内一定深度时冲洗液的计算流体动力学特点,以期为临床应用提供参考.方法 首先使用扫描激光振测系统扫描超声工作尖,分析其在一定功率下的振动特点.然后应用ICEM CFD 18.0软件建立根管超声冲洗模型,设置超声工作尖放置的位置为距根尖止点1 mm,通过FLUENT 18.0软件...     

中药配方颗粒研究现状及产业动态

中药配方颗粒是中药汤剂发展至今,顺应时代的产物,具有方便携带和服用、剂量准确、易于调配和储存、质量稳定可控等优点,受众人群越来越广泛,临床处方量逐年增加,市场规模不断扩大。随着国家政策的相继出台,吸引了众多企业抓住政策出台后的窗口期,积极布局配方颗粒。本研究建议完善质量保证措施,将销售下沉到基层社区及医院,扩大销售终端,积极开拓海外市场,借助中药配方颗粒在国际上的高知名度,助推中医药走出国门,在世界的舞台上大放异彩。     

Understanding the Driving Forces That Trigger Mutations in SARS-CoV-2: Mutational Energetics and the Role of Arginine Blockers in COVID-19 Therapy

SARS-CoV-2 is a global challenge due to its ability to mutate into variants that spread more rapidly than the wild-type virus. Because the molecular biology of this virus has been studied in such great detail, it represents an archetypal paradigm for research into new antiviral drug therapies. The rapid evolution of SARS-CoV-2 in the human population is driven, in part, by mutations in the receptor-binding domain (RBD) of the spike (S-) protein, some of which enable tighter binding to angiotensin-converting enzyme (ACE2). More stable RBD-ACE2 association is coupled with accelerated hydrolysis of furin and 3CLpro cleavage sites that augment infection. Non-RBD and non-interfacial mutations assist the S-protein in adopting thermodynamically favorable conformations for stronger binding. The driving forces of key mutations for Alpha, Beta, Gamma, Delta, Kappa, Lambda and Omicron variants, which stabilize the RBD-ACE2 complex, are investigated by free-energy computational approaches, as well as equilibrium and steered molecular dynamic simulations. Considered also are the structural hydropathy traits of the residues in the interface between SARS-CoV-2 RBD and ACE2 protein. Salt bridges and π-π interactions are critical forces that create stronger complexes between the RBD and ACE2. The trend of mutations is the replacement of non-polar hydrophobic interactions with polar hydrophilic interactions, which enhance binding of RBD with ACE2. However, this is not always the case, as conformational landscapes also contribute to a stronger binding. Arginine, the most polar and hydrophilic among the natural amino acids, is the most aggressive mutant amino acid for stronger binding. Arginine blockers, such as traditional sartans that bear anionic tetrazoles and carboxylates, may be ideal candidate drugs for retarding viral infection by weakening S-protein RBD binding to ACE2 and discouraging hydrolysis of cleavage sites. Based on our computational results it is suggested that a new generation of “supersartans”, called “bisartans”, bearing two anionic biphenyl-tetrazole pharmacophores, are superior to carboxylates in terms of their interactions with viral targets, suggesting their potential as drugs in the treatment of COVID-19. In Brief: This in silico study reviews our understanding of molecular driving forces that trigger mutations in the SARS-CoV-2 virus. It also reports further studies on a new class of “supersartans” referred to herein as “bisartans”, bearing two anionic biphenyltetrazole moieties that show potential in models for blocking critical amino acids of mutants, such as arginine, in the Delta variant. Bisartans may also act at other targets essential for viral infection and replication (i.e., ACE2, furin cleavage site and 3CLpro), rendering them potential new drugs for additional experimentation and translation to human clinical trials.     

单／双磷酸化酪氨酸底物与蛋白酪氨酸磷酸酯酶1B相互作用分子动力学研究

目的：探索双磷酸化酪氨酸底物与蛋白酪氨酸磷酸酯酶1B（PTP1B）亲和能力比单磷酸化酪氨酸底物高的原因。方法：利用分子动力学模拟的方法来研究上述两种底物与PTP1B相互作用的差异。结果：双磷酸化酪氨酸底物和单磷酸化酪氨酸底物对PTP1B骨架运动影响模式相近。但双磷酸化酪氨酸底物可以增强底物与PTP1B的Asp48之间的形成氢键的概率。能量分解分析表明双磷酸化酪氨酸底物两个双磷酸化酪氨酸与PTP1B之间的强静电作用是导致双磷酸化酪氨酸底物与PTP1B相互作用能的主要原因。结论：双磷酸化酪氨酸底物与PTP1B比单磷酸化酪氨酸底物亲和力高的主要原因是双磷酸化酪氨酸底物与PTP1B中Asp48强氢键作用以及双磷酸化酪氨酸底物的两个双磷酸化酪氨酸与PTP1B之间的强静电作用。     

分子模拟技术在释药技术中的应用

环糊精包合技术和缓控释技术是发展较快的释药技术,分子模拟技术在这两种释药技术中的应用也越来越多。简述环糊精包合技术和缓控释释药技术的优点、影响因素和释药原理,介绍几种重要的分子模拟技术在环糊精包合技术和缓控释释药技术中的应用,并给出了分子模拟技术在具体应用中的力场及模拟的条件,分析分子模拟技术的在环糊精包合技术和缓控释技术中应用的优点和难点,展望分子模拟在其应用中的前景,指出分子模拟技术有望成为研究释药技术的一种常规项的工具。