血清IL-6和胃蛋白酶原Ⅰ/Ⅱ比值对老年胃癌患者预后评估的价值

目的探究老年胃癌患者术前血清白细胞介素6 (IL-6)、胃蛋白酶原(PG)Ⅰ、Ⅱ及PG-Ⅰ/Ⅱ比值在患者预后评估中的意义。方法选择2016年1月—2017年1月南通大学附属海安医院收治的101例外科手术治疗的老年胃癌患者为研究对象。收集患者的临床病理资料,检测血清IL-6和PG-Ⅰ/Ⅱ水平。以全因死亡为随访终点,使用Kaplan-Meier曲线明确患者预后与各指标间的关系。结果受试者工作特征曲线提示,IL-6、PG-Ⅰ和PG-Ⅰ/Ⅱ比值在最佳切割值为10.23pg/mL、30.65μg/L和2.44时,可评估患者的预后,而PG-Ⅱ则无法评估患者的预后。与IL-6≤10.23pg/mL组相比,IL-6> 10.23pg/mL组的肿瘤细胞分化更差、TNM分期Ⅲ期比例明显升高。Kaplan-Meier曲线结果表明,IL-6> 10.23pg/mL组的中位生存期显著短于IL-6≤10.23pg/mL组(28个月vs47个月,P<0.001);PG-Ⅰ≤30.65μg/L组的中位生存期显著短于PG-Ⅰ>30.65μg/L组(34个月vs49个月,P=0.008);PG-Ⅰ/Ⅱ≤2.44组的中位生存期显著短于PG-Ⅰ/Ⅱ> 2.44组(29个月vs56个月,P=0.02)。多因素Cox回归分析表明,肿瘤分化程度、TNM分期、IL-6及PG-Ⅰ/Ⅱ比值是影响患者生存率的独立危险因素。结论术前检测IL-6及PG-Ⅰ/Ⅱ比值有助于评估老年胃癌患者的预后。     

Priorities for content for a short-course on postoperative care relevant for low- and middle-income countries: an e-Delphi process with training facilitators

Most surgical and anaesthetic mortality and morbidity occurs postoperatively, disproportionately affecting low- and middle-income countries. Various short courses have been developed to improve patient outcomes in low- and middle-income countries, but none specifically to address postoperative care and complications. We aimed to identify key features of a proposed short-course addressing this topic using a Delphi process with low- and middle-income country anaesthesia providers trained as short-course facilitators. An initial questionnaire was co-developed from literature review and exploratory workshops to include 108 potential course features. Features included content; teaching method; appropriate participants; and appropriate faculty. Over three Delphi rounds (panellists numbered 86, 64 and 35 in successive cycles), panellists indicated which features they considered most important. Responses were analysed by geographical regions: Africa, the Americas, south-east Asia and Western Pacific. Ultimately, panellists identified 60, 40 and 54 core features for the proposed course in each region, respectively. There were high levels of consensus within regions on what constituted core course content, but not between regions. All panellists preferred the small group workshop teaching method irrespective of region. All regions considered anaesthetists to be key facilitators, while all agreed that both anaesthetists and operating theatre nurses were key participants. The African and Americas regional panels recommended more multidisciplinary healthcare professionals for participant roles. Faculty from high-income countries were not considered high priority. Our study highlights variability between geographical regions as to which course features were perceived as most locally relevant, supporting regional adaptation of short-course design rather than a one-size-fits-all model.     

王琦教授新冠肺炎预防方预防新型冠状病毒肺炎机制的网络药理学探讨＊

目的 借助网络药理学的方法，探究两组王琦教授新冠肺炎预防方（简称预防方）预防新型冠状病毒肺炎（COVID-19）的分子靶点和机制。方法 通过TCMSP数据库检索并筛选其活性成分及其作用靶点，通过Uniprot数据库进行蛋白标准化处理。从Genecards数据库中以“Novel coronavirus pneumonia”为关键词搜索获取COVID-19的靶标，构建相交靶点韦恩图。通过cytoscape3.7.2构建PPI蛋白互作网络，寻找富集数目最多的靶点。通过R语言对预防方治疗COVID-19的靶点进行GO和KEGG富集分析，并绘制气泡图。结果 预防方与新冠肺炎相关靶点涉IL-6、TNF、CXCL8、VEGFA、MMP9；GO功能富集分析分别获得53、57条通路；27、29条KEGG相关信号通路。结论 王琦教授新冠肺炎预防方中的主要活性成分为槲皮素、山奈酚、木犀草素、β-谷甾醇、植物甾醇等，可能通过作用于IL-6、TNF、CXCL8、VEGFA、MMP9、CXCL8、IL10、CCL2、IL1B等靶点和介导TNF信号通路、T细胞受体信号通路、Toll样受体信号通路等发挥作用，从而促进免疫反应、炎症反应及细菌防御反应，预防COVID-19。     

我国家庭医生签约服务政策执行的制约因素与优化路径：基于史密斯政策执行过程模型

深化家庭医生签约服务是深化医药卫生体制改革、强化基层医疗卫生服务、实现"健康中国"战略目标的重要选择，也是当前更好维护人民群众健康的重要途径。为有效推进签约服务工作，国家陆续推出各项政策，全国各地也在积极进行实践探索，成效明显。但是，签约服务仍面临诸多问题，其中"执行难"是签约服务深度推进的一大困境。通过史密斯政策执行过程模型，结合签约服务政策执行过程，发现签约服务仍存在法治性不足、政策执行人员水平不高、激励不足、政策环境影响等诸多制约因素。因此，需要从法律和制度方面进行顶层设计、提升执行人员素质和职业认同、建立医患互信、优化政策执行环境等角度进行政策创新，探索家庭医生签约服务可持续发展的路径。     

Process of forgiveness in the recovery of Chinese women survivors of intimate partner violence: Empowerment,transformation, and integration

Forgiveness has been found one substantial element in the recovery for women survivors from intimate partner violence following the termination of the abusive relationship. To further investigate the details of forgiveness in this specific context, the present study explored the process of forgiveness using grounded theory. In-depth and semi-structured interviews were conducted with 25 Chinese women survivors of IPV. The findings suggest that forgiveness is a strength-based process including empowerment, transformation, and integration phases. In the empowerment phase, survivors obtain strength at the intrapersonal, behavioural, and interpersonal levels. In the transformation phase, survivors complete cognitive transformation for their IPV experiences and emotional transformation towards former partners. In the integration phase, survivors—now freed from the past—reflect upon and apply the changes they have undergone. Two trajectories in the process were found. One trajectory is going through stages sequentially and the other trajectory is experiencing back and forth between empowerment and transformation stages before moving into the integration stage. The study's findings broaden our knowledge of the strength-based forgiveness process that women survivors of IPV undergo during recovery. Practitioners and policymakers could develop programmes and policies that support forgiveness by holistically facilitating their recovery and empowerment like assistance in dealing with life difficulties and promoting their reconnection with social networks. To improve the transferability and validity of the findings, the forgiveness of survivors of IPV could be explored in a diverse sample (e.g., survivors with low educational background or live in the rural area).     

Future directions in managing aniridia-associated keratopathy

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.     

A novel PAX6 mutation causes congenital aniridia with or without retinal detachment

Background: Aniridia is a rare developmental eye disorder characterized by complete or partial iris hypoplasia often accompanied with other ocular changes that affect the cornea, anterior chamber, lens, retina, and optic nerve. Most cases of aniridia are inherited with an autosomal dominant mode of inheritance caused by PAX6 mutations or deletions. To reveal the underlying genetic defect in a four-generation Iranian family with aniridia, we carried out a genetic screening of PAX6.

Methods: Complete ophthalmic examinations were performed for available affected family members. All PAX6 exons and their flanking regions were sequenced for affected individuals. Candidate variation was screened for segregation in the pedigree by Sanger sequencing. Bioinformatics prediction was done to evaluate the deleterious effects of the mutation on protein product. Real-time PCR was used to investigate the impact of the variant on PAX6 mRNA expression.

Results: All patients were diagnosed with isolated aniridia associated with variable phenotypic features including retinal detachment. A novel heterozygous deletion c.320_348delTGTCCGAGGGGGTCTGTACCAACGATAAC (p.Leu107HisfsX16) on PAX6 gene was detected. Decreased mRNA level of PAX6 in the affected individuals indicated that the mutation caused nonsense-mediated mRNA decay (NMD).

Conclusions: To the best of our knowledge, it is the first report on the genetics of aniridia in Iran. Segregation analysis, bioinformatics prediction and confirmation of NMD, all support the proposition that the novel observed PAX6 mutation is the cause of aniridia in the pedigree. Retinal detachment in some of the affected members, which is a rare reported phenotypic feature of aniridia patients, may be associated with this mutation.     

Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

股骨转子间骨折的稳定性重建概念演化与研究进展

目的总结近年来股骨转子间骨折在稳定性重建方面的概念演化与研究进展。方法查阅国内外相关文献并结合自身经验，从股骨转子间骨折的解剖特点、稳定型骨折与不稳定型骨折分类、稳定性复位与不稳定性复位、术中加压初始稳定与术后滑动二次稳定、内固定术后稳定性评估、早期下地站立负重等方面进行总结分析。结果股骨转子间骨折发生于股骨颈干骺端转换区，具有天然的内翻不稳定倾向。骨折复位质量是影响后续内固定物安放的最重要前提因素。判断骨折复位质量有对线和对位两方面，对线采用 Garden 指数；在对位方面，随着皮质对位理念（正性、中性、负性）的提出，特别强调前内侧皮质的相互砥住支撑（解剖、正性），是获得骨折稳定性复位的关键，而不再强调后内侧小转子骨块的作用。术后影像学的稳定性评分为早期下地站立负重提供了量化指标。但术中的前内侧皮质支撑复位，在术后头颈骨块滑动获得二次稳定的过程中，仍有皮质对位丢失现象，需研究其危险因素和防范措施。结论股骨转子间骨折在取得良好对线的基础上，只要获得了前内侧皮质的相互砥住和支撑，并用内固定器械维持住，就获得了术后稳定性。术后稳定性评分优良者，可以安全地早期下地负重、站立行走活动。