Clamp loading,unloading and intrinsic stability of the PCNA, β and gp45 sliding clamps of human,E. coli and T4 replicases

Background: The high speed and processivity of replicative DNA polymerases reside in a processivity factor which has been shown to be a ring-shaped protein. This protein (‘sliding clamp’) encircles DNA and tethers the catalytic unit to the template. Although in eukaryotic, prokaryotic and bacteriophage-T4 systems, the processivity factors are ring-shaped, they assume different oligomeric states. The Escherichia coli clamp (the β subunit) is active as a dimer while the eukaryotic and T4 phage clamps (PCNA and gp45, respectively) are active as trimers. The clamp can not assemble itself on DNA. Instead, a protein complex known as a clamp loader utilizes ATP to assemble the ring around the primer-template. This study compares properties of the human PCNA clamp with those of E. coli and T4 phage. Results: The PCNA ring is a stable trimer down to a concentration below 100 nm (K_d ≈ 21 nm ). On DNA, the PCNA clamp slides freely and dissociates from DNA slowly (t_1/2 ≈ 24 min). β is more stable in solution (K_d < 60 pm ) and on DNA (t_1/2 ≈ 1 h) than PCNA which may be explained by its simpler oligomeric state. The T4 gp45 clamp is a much less stable trimer than PCNA (K_d ≈ 250 nm ) and requires association with the polymerase to stabilize it on DNA as observed previously. The consequence of this cooperation between clamp and polymerase is that upon finishing a template and dissociation of the polymerase from DNA, the gp45 clamp spontaneously dissociates from DNA without assistance. However, the greater stability of the PCNA and β clamps on DNA necessitates an active process for their removal. The clamp loaders (RF-C and γ complex) were also capable of unloading their respective clamps from DNA in the presence of ATP. Conclusions: The stability of the different clamps in solution correlates with their stability on DNA. Thus, the low stability of the T4 clamp explains the inability to isolate gp45 on DNA. The stability of the PCNA and β clamps predicts they will require an unloading factor to recycle them on and off DNA during replication. The clamp loaders of PCNA and β double as clamp unloaders presumably for the purpose of clamp recycling.     

Complementary and alternative medical therapy utilization by people with chronic fatiguing illnesses in the United States

Background  

Chronic fatiguing illnesses, including chronic fatigue syndrome (CFS), pose a diagnostic and therapeutic challenge. Previous clinical reports addressed the utilization of health care provided to patients with CFS by a variety of practitioners with other than allopathic training, but did not examine the spectrum of complementary and alternative medicine (CAM) therapies used. This study was designed to measure CAM therapy use by persons with fatiguing illnesses in the United States population.     

小发卡RNA抗呼吸道合胞病毒效应的研究

目的 为从基因水平抑制呼吸道合胞病毒（respiratory syncytial virus，RSV）的复制，针对RSV的M2-2基因构建小发卡结构状RNA（short hairpin RNA，shRNA）重组质粒，在细胞水平观察shRNA对RSV复制的影响。方法 将成功构建的针对RSV M2-2基因的重组质粒pshRNA8260转染HEp-2细胞，利用光镜观察pshRNA8260对RSV致HEp-2细胞病变效应（cytopathogenic effect，CPE）的影响并计算CPE抑制率，空斑形成实验检测RSV滴度变化。结果 成功构建了针对人RSV M2-2基因mRNA的pshRNA8260重组质粒，研究发现pshRNA8260能明显改善RSV所致的病变效应，降低RSV在细胞内复制的病毒滴度。结论 针对RSV M2-2基因的pshRNA82（g）重组质粒具有明显的特异性抗RSV效应的作用。     

Efficacy of misoprostol (twice daily dosage) in acute healing of duodenal ulcer

This study was undertaken to evaluate the efficacy of misoprostol taken twice daily for the healing of duodenal ulcer. Three hundred thirty patients with endoscopically proven duodenal ulcer participated in a multicenter, double-blind, controlled trial comparing placebo with misoprostol 200 μg and 400 μg twice daily for up to four weeks. Patient characteristics were similar in all three treatment groups. Ulcers were between 0.3 cm and 2.0 cm in length. Healing was determined by endoscopy at two weeks; if ulcers were not healed, endoscopy was repeated at four weeks. All patients were given Al(OH)₃ antacid (up to 54 meq a day) to be used as needed for pain. Healing rates at four weeks for a total of 280 evaluable patients in the three treatment groups were as follows: misoprostol 400 μg bid, 65.4%; misoprostol 200 μg bid, 52.9%; and placebo, 42.2%. Misoprostol 400 μg bid was superior to placebo (P=0.002) in healing ulcers. However, the healing rate for misoprostol 200 μg bid did not differ significantly from placebo. The percentage of nonsmokers who healed at four weeks was higher than that of smokers in both misoprostoltreatment groups, although the difference was not analyzed for statistical significance. There were no differences in antacid consumption or pain relief among the three experimental groups during the study. Diarrhea was the most common side effect but was mild and self-limiting, occurring in 8.9%, 5.9%, and 1.8% of the misoprostol 400 μg, 200 μg, and placebo groups, respectively. These results indicate that misoprostol 400 μg, 200 μg, and for four weeks is effective and safe for the treatment of duodenal ulcers.     

2015—2020年四川省手足口病流行病学特征分析

目的 分析2015—2020年四川省手足口病流行病学及病原学特征,为手足口病的防控提供科学依据。 方法 利用描述流行病学方法对2015—2020年四川省手足口病监测资料进行统计分析。 结果 2015—2020年四川省累计报告手足口病520 147例,重症1 759例,死亡38例,2015—2020年四川省手足口病发病率呈波动状,年均发病率为104.82/10万,2015—2017和2019年呈现明显的双峰(4—7月和10—12月),2018、2020年呈单峰,发病高峰分别在7—11月和10—12月;年龄以 5 岁及以下儿童为主,男女性别比为1.38∶1;发病率居前五位的地区是成都市(221.25/10万)、眉山市(145.51/10万)、德阳市(115.52/10万)、雅安市(108.02/10万)和遂宁市(100.56/10);共报告实验室确诊病例44 410例,其中其他肠道病毒、CoxA16、EV71分别占65.53%、22.35%、12.12% 。 结论 2015—2020年四川省手足口病发病水平呈上升趋势,防控压力逐渐加大。四川省手足口病发病以5岁以下儿童为主,成都及周边,川东北发病率较高,优势病原分型构成发生变化,其他肠道病毒比重逐渐提高,病原学监测工作需要调整。     

2015—2019年北京市食源性致泻大肠埃希氏菌感染病例流行特征分析

目的分析2015—2019年北京市食源性致泻大肠埃希氏菌(diarrheagenic Escherichia coli,DEC)感染病例的流行病学特征和发病规律,为制定相应的防控策略与措施提供科学依据。方法收集2015—2019年北京市36家食源性疾病主动监测医院腹泻病例的粪便或肛拭子标本及其个人信息,采用χ^(2)检验对率或构成比进行比较。结果共收集27619份病例标本,其中有2485份为DEC阳性病例,检出率为9.00%,不同分型中肠产毒性大肠埃希菌检出率最高,为3.10%,其次为肠聚集性大肠埃希菌,检出率为3.02%。不同年龄组DEC检出率差异有统计学意义(χ^(2)=32.923,P<0.001),20~39岁年龄组DEC检出率最高,为9.81%,40~59岁年龄组感染肠产毒性大肠埃希菌高于其他年龄组,0~5岁年龄组肠致病性大肠埃希菌的检出率最高。时间分布上,第三季度为高发期,不同季度间DEC检出率差异有统计学意义(χ^(2)=606.032,P<0.001)。空间分布上,远郊的DEC检出率最高,且城区、近郊和远郊的DEC检出率差异有统计学意义(χ^(2)=28.034,P<0.001),肠产毒性大肠埃希菌的检出主要分布在城区和近郊,肠聚集性大肠埃希菌主要分布在远郊。结论2015—2019年北京市食源性DEC的检出率呈逐年上升趋势,应在夏秋高发季节针对重点人群积极开展防控工作。     

我国移动医疗APP服务质量与用户满意度关系研究

目的探讨移动医疗APP服务质量各维度与用户满意度的关系,提出针对性建议,为提高移动医疗APP服务质量提供参考。方法根据更新的信息系统成功理论（UDMISS）,结合移动医疗服务质量模型,建立了移动医疗服务质量与用户满意度关系模型。通过问卷调查,使用PLS-SEM法对模型及假设进行验证。结果移动医疗APP系统质量中的可靠性、效率性、隐私性以及信息质量中的功利效益对用户使用满意度有积极影响,而交互质量对用户使用满意度影响不显著。结论重视应用便利性和患者隐私保护,提高移动医疗APP系统质量;提供个性化服务和心理咨询服务,提高移动医疗APP交互针对性;在确保移动医疗APP信息质量的同时提供适度信息数量,以改善患者使用体验。     

推行PDCA循环的做法与体会

医院推行PDCA循环并非一成不变,每年的推进都是一个新的循环。介绍了推行PDCA循环的做法与体会,包括成立推进组织,加强组织领导;培育核心团队,坚持长期主义;重视关键节点,加强过程管理;秉承PDCA循环理念,不断持续改进等。针对推进中的问题和难点,认为必须化解推进中的阻力,必须秉承PDCA循环的理念持续改进,必须坚持长期主义等。     

新政府会计制度下公立医院会计核算的难点及对策

2019年1月1日公立医院正式开始实施新政府会计制度,通过研究公立医院在新制度下会计核算的衔接问题以及适应问题,找出公立医院会计核算将面临的难点,如固定资产及其累计折旧核算方式、应付职工薪酬、科教项目核算等,并给出相应的解决对策,如利用信息化手段对应付职工薪酬进行资金分配、利用成本配比处理医院科教项目核算难点等,帮助公立医院能够在改革中进步,提升公立医院会计核算管理水平。     

贵州省2014—2019年学生肺结核流行特征分析

目的 了解贵州省 2014—2019年学生肺结核的流行特征,进一步推进学校结核病防控工作提供参考依据。方法 对贵州省 2014—2019年“结核病管理信息系统”的学生肺结核病案进行分析。结果 2014—2016年学生肺结核发病率（30.52/10 万）低于2017—2019年年均发病率（46.82/10 万）。贵州省2014—2016年与2017—2019年学生肺结核发病数的年龄分布一致,均主要集中在15～19 岁、20～24 岁和 10～14 岁。贵阳市、六盘水市、遵义市、安顺市、铜仁市、黔西南州、毕节市、黔东南州、黔南州均为2014—2016年学生肺结核发病率（分别为10.79/10万、24.91/10万 、19.39/10万、13.39/10万、18.88/10万、24.03/10万、39.61/10万、24.59/10万、16.49/10万）分别低于同地区2017—2019年的发病率（分别为15.01/10万、35.35/10万、47.56/10万、30.38/10万、42.86/10万、42.22/10万、89.71/10万、47.62/10万、31.54/10万）。2014—2016年少数民族和汉族学生肺结核发病率（26.02/10万,33.69/10万）均低于2017—2019年（分别为39.06/10万,52.73/10万）。2014—2016年（26.02/10万）、2017—2019年（39.06/10万）少数民族学生肺结核发病率分别同期低于汉族学生肺结核发病率（33.69/10万和52.73/10万）。2014—2016年学生肺结核主动发现率10.09%（829例）低于2017—2019年学生肺结核主动发现率19.14%（2 531例）。结论 贵州省学生肺结核疫情仍然较重,学生肺结核发病率上升,建议进一步加强学校结核病的防治结合。