石家庄市部分学校肺结核密切接触者的患病率和结核病防治知识知晓情况

目的了解学生肺结核密切接触者的患病情况和结核病防治知识的知晓情况,为制定学校结核病控制措施提供依据。方法以学生或教师肺结核患者为线索,对其进行流行病学调查。对密切接触者进行结核病筛查,并以其他学生为对照,采用筛选的方法,首先做结核菌素试验,强阳性者再做胸部X线检查,对有症状者做痰结核菌检查和胸部X线检查,同时进行结核病防治5条核心知识知晓率调查。结果肺结核密切接触者2年内筛查出的结核患者患病率为9.95%,高于其他学生的0.46%;学生的5条核心知识知晓率比线索病人低。结论学生对结核病防治知识和政策的知晓率偏低是结核病在学校流行的主要原因,先做PPD试验、阳性者再进行胸部X线检查是控制学校结核病流行的必要措施。     

社会交往和自我效能感对老年人生存质量的影响

目的探讨社会交往和自我效能感对老年人生存质量的影响。方法采用WHOQOL-BREF生活质量测定量表和一般自我效能感量表(GSES)等工具对251名老年人进行评价。结果生理、心理、社会和环境领域的回归方程分别能够解释34.8%、26.00%、18.10%和23.10%的总变异。自我效能感高的老年人在各领域均具有较高的生存质量,年龄、性别和婚姻状况对生理领域的生存质量有明显影响,参加锻炼的老年人在生理和社会关系领域的生存质量高于不锻炼的老年人。社会交往越活跃,心理和社会关系领域的生存质量也越高。环境领域的生存质量随着平均月收入的增加而提高。结论增加老年人的自我效能感与社会交往有助于改善生存质量。     

磨牙症患者（牙合）接触特征的研究

目的 :研究磨牙症患者牙合接触的特征 ,探索牙合因素与磨牙症的关系。方法 :用T -scanII型咬合分析仪对 2 3名磨牙症患者与 13名对照者分别进行正中牙合位、前伸及侧方运动的咬合检查 ,测量闭合接触时间、前伸与侧方牙合分离时间 ,观察平衡侧牙合干扰出现的情况。结果 :磨牙症患者的闭合时间小于对照组 ;侧方牙合分离时间比对照组长 ;与对照组相比多数磨牙症患者出现平衡侧牙合干扰。结论 :平衡侧牙合干扰可能是与磨牙症有密切关系的重要的牙合因素     

Dynamical network of residue–residue contacts reveals coupled allosteric effects in recognition,catalysis, and mutation

Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis remains ambiguous. Here, we simulate CypA using multiple-microsecond-long atomistic molecular dynamics in explicit solvent and carry out NMR experiments. We analyze a large amount of time-dependent multidimensional data with a coarse-grained approach and map key dynamical features within individual macrostates by defining dynamics in terms of residue–residue contacts. The effects of substrate binding are observed to be largely sensed at a location over 15 Å from the active site, implying its importance in allostery. Using NMR experiments, we confirm that a dynamic cluster of residues in this distal region is directly coupled to the active site. Furthermore, the dynamical network of interresidue contacts is found to be coupled and temporally dispersed, ranging over 4 to 5 orders of magnitude. Finally, using network centrality measures we demonstrate the changes in the communication network, connectivity, and influence of CypA residues upon substrate binding, mutation, and during catalysis. We identify key residues that potentially act as a bottleneck in the communication flow through the distinct regions in CypA and, therefore, as targets for future mutational studies. Mapping these dynamical features and the coupling of dynamics to function has crucial ramifications in understanding allosteric regulation in enzymes and proteins, in general.As a biomolecule samples various conformations governed by its free energy landscape, it undergoes a wide spectrum of motions that range over a broad timescale and length scale (1). Except for certain cases in which large-scale displacements are observed upon ligand binding (2), these motions, in general, account for modest fluctuations around an average native structure (3). Despite extensive studies, detailed understanding of how conformational dynamics lead to or facilitate function remains formidable (4–6). It has been frequently observed that enzymes in their free unliganded state sample 3D conformations that consist of those visited in the presence of the ligand (7). Differences in intrinsic conformational dynamics in the wild type and the mutant maltose-binding proteins have been shown to be related to association and dissociation of ligand and thereby to affect dissociation constants (8). Enzyme dynamics in Cyclophilin A (CypA), a peptidyl prolyl cis–trans isomerase, have been demonstrated to occur on the same millisecond timescale as the catalytic turnover (9). Mutants of dihydrofolate reductase that lead to suppressed conformational dynamics in the active site have exhibited concomitant loss in enzymatic activity (10).These exemplary studies are suggestive of a key role for conformational dynamics in recognition and catalysis. This notion has been controversial (10–13) due to limited or, in some cases, a complete lack of microscopic analysis of experimental observations. The suppressed catalytic activity in mutants may be a result of an increase in activation energy and not decreased dynamics (14, 15). Although enzyme dynamics may not be responsible for catalytic speed up relative to the uncatalyzed reaction, CypA dynamics has been shown to be coupled to catalytic function (16). Allosteric regulation, i.e., modification of binding or catalysis at the active site due to binding of a ligand at a distal nonoverlapping site, is widespread in biochemical signaling (17, 18). It is natural that allosteric regulation depends on modulation of protein motions, because substrate binding and catalysis are linked to conformational dynamics (19, 20). Unlike static X-ray structures, solution NMR relaxation dispersion techniques have been instrumental in providing high-resolution conformational exchange information using site-specific isotope labeling (21). In NMR studies of CypA, a dynamic continuum has been identified such that the relaxation profiles cannot be globally fit to one or two exchange phenomena and are instead indicative of more localized motions (22). Exchange rates coalesce somewhat during turnover, perhaps suggesting an increase in coordination throughout the protein, but appear to still consist of localized motions that are not fully coherent (23). However, dynamical signals during catalytic turnover could be affected by substrate binding and unbinding, especially if the substrate binding affinity is low, thereby leading to ambiguity in the interpretation of NMR analysis (23).Complementary to experiments, long-timescale molecular dynamics (MD) simulations can be greatly instrumental in providing a microscopic picture of biomolecular dynamics and establishing its exact linkage to function. However, the challenge at hand is to elucidate the key dynamical features and correlations between different parts of the protein from a vast amount of multidimensional time-dependent data from MD. Principal component analysis (PCA) is often used to reduce the dimensionality of conformational space and map the differences in conformational ensembles. PCA, which is usually performed on Cartesian coordinates, may sometimes mask certain important long-range dynamical relations and complex features of biomolecular conformational dynamics. Comparing residue–residue contacts in various isoforms from difference contact maps built from simulation trajectories has aided in determining certain similar structural properties and some unique to a particular isoform (24). Another analysis that involves monitoring the time evolution of residue–residue contact formation and breaking has been proven useful in identifying certain characteristic events during conformational transitions (25). Correlated motions between different biomolecular segments have been identified using cross-correlation analysis and building dynamical networks (25–29). However, interpretation of the results of such analysis in case of CypA, which exhibit subtle changes upon substrate binding and catalysis, has been ambiguous.Here, we characterize the conformational dynamics of CypA using very long atomistic standard MD simulations in explicit solvent, and the results are validated using NMR experiments. CypA is an archetypal and extensively studied enzyme belonging to the family of peptidyl prolyl isomerases (PPIases), speeding the cis–trans isomerization of peptidyl prolyl ω-bond in its protein substrates by more than 10⁵ times (30–34). In five independent microsecond-long simulations, we monitored the dynamics in wild-type CypA, V29L variant of CypA, CypA bound to a substrate analogue in the trans, transition state, and cis configurations. When we apply our method of analyzing the trajectories at a coarse-grained level, i.e., interresidue contact interactions, and use PCA in contact space, the specific differences in CypA dynamics upon association to its substrate, during the catalytic process and upon alteration of a single residue distant from the active site are revealed.     

短刺法针刺治疗颈源性头痛的疗效观察

[目的]观察短刺法针刺对颈源性头痛的治疗效果。[方法]将80例患者随机分为2组,每组40例,观察组采用短刺法针刺,对照组采用常规针刺。治疗前后观察头痛视觉模拟评分值变化。[结果]两组疼痛视觉模拟评分(VAS)评分与疗前差异均有统计学意义(P0.05);两组治疗后比较,组间差异有统计学意义(P0.05),观察组优于对照组。观察组临床治愈25例,显效11例,有效4例,无效0例,愈显率为90.0%;对照组临床治愈18例,显效11例,有效9例,无效2例,愈显率为72.5%,两组愈显率差异有统计学意义(P0.05)。[结论]短刺法针刺治疗颈源性头痛的疗效较常规针刺显著。     

南昌市一起新型冠状病毒肺炎聚集性疫情传播链分析

目的 通过对南昌市一起新型冠状病毒肺炎（COVID-19）聚集性疫情调查,分析传播过程及病例发病前和无症状感染者的传染性,了解不同接触方式的传播风险。方法 通过传统流行病学调查,结合大数据轨迹开展病例调查,用传播链示意图展示传播关系。结果 传播关联病例27例,其中确诊病例25例,疑似病例1例（指征病例）,无症状感染者1例。搜索到密切接触者347人,密切接触者的感染率为7.2%（25/347）,其中,一代、二代、三代和四代病例的密切接触者感染率分别为52.6%（10/19）、6.1%（13/213）、2.3%（2/88）和0.0%（0/27）。无症状感染者能引起家庭内传播,与病例同餐、同住/同屋、工作接触、邻居间接触、诊疗护理/同病房和同一交通工具的密切接触者的感染率分别为10.6%（17/160）、10.0%（20/201）、5.3%（5/94）、0.0%（0/30）、0.0%（0/18）和0.0%（0/17）。结论 此次疫情传染源为来自武汉市的疑似病例D某,轨迹大数据分析可以帮助精准搜索病例和密切接触者,此次调查的基础上,提出的针对疫情防控措施有效。     

2013-2014年浙江省奉化市手足口病患者及其密切接触者监测结果分析

目的 了解浙江省奉化市手足口病患者及其密切接触者病原分布情况,分析2013-2014年手足口病疫情和病原学监测结果,为手足口病防控提供科学依据。方法 每月采集手足口病患者5例及其15名密切接触者粪便标本检测肠道病毒,同时开展住院病例病原学监测,对2013-2014年病原学监测结果和手足口病疫情进行描述性流行病学分析。结果 2013-2014年奉化市手足口病发病率分别为225.99/10万和365.07/10万;街道发病率高于乡镇;发病率最高为1岁组。病例肠道病毒A组71型（EV71）、柯萨奇病毒A组16型（Cox A16）和其他肠道病毒阳性率分别为20.94%、20.42%和38.74%;2013年优势病毒为其他肠道病毒（占61.00%）,2014年为Cox A16和EV71;EV71发病年龄大于其他肠道病毒（Z=-3.70,P=0.00）;肠道病毒阳性病例和阴性病例的密切接触者阳性率分别为48.44%和18.75%,差异有统计学意义;不同病毒阳性病例的密切接触者其他肠道病毒阳性率在44.96%～48.15%之间,差异无统计学意义;病例与密切接触者肠道病毒以同型为主（Kappa值0.53）;1～8岁密切接触者阳性率42.08%,12～66岁密切接触者阳性率31.73%,差异无统计学意义。结论 奉化市手足口病处于高流行态势,流动人口密集地区高发。多种病毒流行,优势病毒处于变化中,流行特征与病原体有关,病原监测有助于采取适当的防控措施,必要时应对其他肠道病毒开展进一步分型。密切接触者带病毒率高,应关注密切接触者管理。     

Predictors of change in social networks,support and satisfaction following a first episode psychosis: A cohort study

BackgroundDiminished social networks are common in psychosis but few studies have measured these comprehensively and prospectively to determine how networks and support evolve during the early phase. There is little information regarding perceived support in the early phase of illness. The aim of this study was to describe social support, networks and perceived satisfaction, explore the clinical correlates of these outcomes and examine whether phases of untreated psychosis are linked with social network variables to determine potential opportunities for intervention.MethodsDuring the study period, we assessed 222 people with first-episode psychosis at entry into treatment using valid and reliable measures of diagnosis, positive and negative symptoms, periods of untreated psychosis and prodrome and premorbid adjustment. For follow-up we contacted participants to conduct a second assessment (n = 158). There were 97 people who participated which represented 61% of those eligible. Social network and support information obtained at both time points included the number of friends, self-reported satisfaction with support and social network size and clinician’s evaluation of the degree of support received through networks. Mixed effects modelling determined the contribution of potential explanatory variables to social support measured.ResultsA number of clinical variables were linked with social networks, support and perceived support and satisfaction. The size of networks did not change over time but those with no friends and duration of untreated psychosis was significantly longer for those with no friends at entry into treatment (n = 129, Median = 24.5 mths, IQR = 7.25–69.25; Mann-Whitney U = 11.78, p = 0.008). Social support at baseline and at one year was predicted by homelessness (t = −2.98, p = 0.001, CI −4.74 to −1.21), duration of untreated psychosis (t = −0.86, p = 0.031, CI −1.65 to −0.08) and premorbid adjustment (t = −2.26, p = 0.017, CI −4.11 to −0.42). Social support improved over time but the duration of untreated psychosis was not linked with the rate of improvement in this outcome.ConclusionsImproved social support could indicate greater reliance on social support or becoming more adept at mobilising resources to meet social needs. Particularly vulnerable groups with very long duration of untreated psychosis confirm the need for earlier intervention or targeted social network interventions to preserve social connectedness.     

闭合复位与经皮桡侧交叉克氏针固定治疗儿童肱骨髁上骨折

目的：评价闭合复位、经皮桡侧交叉克氏针固定治疗儿童肱骨髁上骨折的临床效果。方法2007年2月至2015年2月笔者收治肱骨髁上骨折患儿467例,其中 GartlandⅡ型87例,Ⅲ型380例;伸直型445例,屈曲型22例。患儿年龄1岁1个月至11岁7个月（平均5.6岁）。均采用闭合复位、经皮桡侧交叉克氏针固定治疗,在静脉麻醉下和“C”型臂透视下,先行闭合整复骨折,然后经皮桡侧交叉穿入2～3枚克氏针固定。结果467中,434例获随访,随访时间6～60个月（平均为25.9个月）。根据功能标准评价：优402例,良22例,可10例,差0例,优良率97.7％;根据美观标准评价：优396例,良24例,可13例,差1例,优良率为96.8％。随访时无一例发生 Volkmann 挛缩、肘内翻畸形及尺神经损伤。结论儿童肱骨髁上骨折采用闭合复位、经皮桡侧交叉克氏针固定治疗,能减少尺神经损伤、肘内翻畸形及 Volkmann 挛缩等并发症,无切口,美观,创伤小,住院时间短,肘关节功能恢复良好,临床效果良好,是一种较好的治疗Ⅱ型、Ⅲ型儿童肱骨髁上骨折的方法,值得推广。     

Theta-phase closed-loop stimulation induces motor paradoxical responses in the rat model of Parkinson disease

Background

High-frequency deep brain stimulation (DBS) has become a widespread therapy used in the treatment of Parkinson's Disease (PD) and other diseases. Although it has proved beneficial, much recent attention has been centered around the potential of new closed-loop DBS implementations.