Contributions of the NICHD neonatal research network's generic database to documenting and advancing the outcomes of extremely preterm infants

The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) maintains a database of extremely preterm infants known as the Generic Database (GDB). Begun in 1987, this database now includes more than 91,000 infants, most of whom are extremely preterm (<29 weeks gestation). The GDB has been the backbone of the NRN, providing high quality, prospectively collected data to study the changing epidemiology of extreme prematurity and its outcomes over time. In addition, GDB data have been used to generate hypotheses for prospective studies and to develop new clinical trials by providing information about the numbers and characteristics of available subjects and the expected event rates for conditions and complications to be studied. Since its inception, the GDB has been the basis of more than 200 publications in peer-reviewed journals, many of which have had a significant impact on the field of neonatology.     

日本居家安宁疗护服务体系构建经验及其对我国的启示

21世纪的日本"少子高龄化"特征明显，发展居家安宁疗护、构建完备的居家安宁疗护服务体系，是日本卫生服务提供体制改革的重要方向。本文介绍了日本居家安宁疗护的含义与理念，以及关于居家安宁疗护服务提供机构、提供人员、提供内容及费用保障的法律规定，提示我国在条件成熟时应尽快健全安宁疗护相关立法，在卫生服务提供体系框架下实现居家安宁疗护的稳定发展，建立并强化安宁疗护过程中的协作机制，并为居家安宁疗护提供必要的经费保障，通过完善的制度设计保障老年人"居家善终"的权益。     

基于网络药理学和实验验证探讨香菇多糖抑制三阴乳腺癌的作用机制

目的 基于网络药理学研究香菇多糖抑制三阴乳腺癌（TNBC）的作用机制并采用细胞和动物实验进行验证。方法 通过GeneCards数据库和DisGeNET数据库筛选与TNBC相关基因靶点，利用TCMID、PubChem、SwissTargetPrediction和GeneCards数据库查询香菇多糖相关基因靶点。使用Sangerbox软件进行基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）通路富集分析。结合STRING数据库与Cytoscape 3.7.0软件将共同靶点进行可视化处理，筛选核心靶点，构建"化合物-靶点-通路"网络。利用Metascape软件进行转录因子及相关调控基因特异富集。体外培养小鼠TNBC细胞4T1和人TNBC细胞MDA-MB-231，磺酰罗丹明B染色法观察香菇多糖（31.25、62.5、125、250、500、1 000μg·mL^-1）对细胞存活率的影响；健康雌性BABLC小鼠sc接种1×10⁶个4T1-Luc细胞构建TNBC模型，通过小动物活体成像系统观察香菇多糖（100、200 mg·kg^-1）对肿瘤生长的影响，实时荧光定量PCR （qRT-PCR）技术检测肿瘤组织信号转导和转录活化因子3（STAT3）和血管内皮生长因子A （VEGFA） mRNA表达。结果 数据库及软件分析得到香菇多糖治疗TNBC关键靶点52个，靶点主要涉及PI3K-Akt、AGE-RAGE、HIF-1、MAPK信号通路和肿瘤蛋白多糖相关通路，PPI分析得到VEGFA、STAT3、MAPK1、IL2、TNF、RELA、AKT1、MAPK3、BCL2L1和HSP90AA1 10个hub基因。与对照组比较，香菇多糖对4T1和MDA-MB-231细胞存活率均有显著抑制作用（P<0.05、0.01），且作用呈浓度相关性；在给药14、21d后，与模型组比较，香菇多糖能够剂量相关性地抑制小鼠TNBC肿瘤的生长，高剂量组差异显著（P<0.05、0.01），21 d抑制率达到（91.9±4.7）%；与对照组比较，香菇多糖给药后能够剂量相关性抑制STAT3和VEGFA的mRNA表达，高剂量组差异显著（P<0.05、0.01）。结论 香菇多糖可通过多靶点、多途径协同作用抑制TNBC的生长。     

Noscapine hydrochloride (benzyl-isoquinoline alkaloid) effectively prevents protein denaturation through reduction of IL-6, NF-kB,COX-2, Prostaglandin-E2 in rheumatic rats

Noscapine hydrochloride (benzyl-isoquinoline antitussive alkaloid) is an opium derivative and generally used as a cough suppressant. Numerous studies on noscapine hydrochloride have reported that it has potent anti-inflammatory activity. However, the mechanisms by which it exerts an anti-inflammatory function is not well understood. Protein denaturation is the primary step that leads to the organ destruction and permanent arthritic disability. The above-mentioned facts provided the ground to plan this study using different in-vitro and in-vivo approaches. RT-qPCR and ELISA assays were used to assess the inflammatory markers related to protein denaturation in complete adjuvant persuaded rheumatism in Sprague - Dawley rats. The results were collected as paw volume and body weight changes, arthritic scoring and serum antioxidant enzymes assays. These findings demonstrated that all doses of noscapine hydrochloride (10, 20 and 40 mg/kg) studied in this study, significantly (p < 0.001) decreased the protein denaturation by preventing the increase in levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-kB (NF-kB), cyclooxygenase-2 (COX-2) and prostaglandin E2. Noscapine hydrochloride significantly reduced the paw volume (p < 0.001), arthritic scoring and reversed the body mass as compared to arthritic control diseased rats.     

ECFS standards of care on CFTR-related disorders: Updated diagnostic criteria

This paper is the first in a series providing updated guidance on the definition, evaluation and management of people with a Cystic Fibrosis Transmembrane conductance Regulator (CFTR)-Related Disorder (CFTR-RD). The need for this update relates to more precise characterisation of CFTR gene variants and improved assessment of CFTR protein dysfunction. The exercise is co-ordinated by the European CF Society Standards of Care Committee and Diagnostic Network Working Group and involves stakeholder engagement. This first paper was produced by a core group using an extensive literature review and papers graded for their quality. Subsequent wider stakeholder agreement was achieved.The definition of a CFTR-RD remains “a clinical condition with evidence of CFTR protein dysfunction that does not fulfil the diagnostic criteria for CF”. Clearer guidance on CFTR dysfunction and relevant CFTR variants will be provided. Thresholds for clinical presentations are presented and the paradigm that pathobiological processes may be evident in more than one organ is agreed. In this paper we reflect on the early patient journey, highlighting that CF specialists as well as other relevant specialists should be involved in the care of people with a CFTR-RD.     

超声引导下辅助诊断和治疗冻结肩的研究进展

冻结肩是常见的肩部疾病,传统非可视化治疗冻结肩效果欠佳。近年来,超声引导具有动态实时定位、无辐射、便携性、低成本等优点在辅助诊断和治疗冻结肩患者中得到成功应用,不仅能提供精确的诊断,也提高了患者中长期的疗效。本文就超声引导辅助诊断和治疗冻结肩的研究进展进行综述。     

The EQ-HWB: Overview of the Development of a Measure of Health and Wellbeing and Key Results

ObjectivesExisting measures for estimating quality-adjusted life-years are mostly limited to health-related quality of life. This article presents an overview of the development the EQ-HWB (EQ Health and Wellbeing), which is a measure that encompasses health and wellbeing.MethodsStages: (1) Establishing domains through reviews of the qualitative literature informed by a conceptual framework. (2) Generation and selection of items to cover the domains. (3) Face validation of these items through qualitative interviews with 168 patients, social care users, general population, and carers across 6 countries (Argentina, Australia, China, Germany, United Kingdom, United States). (4) Extensive psychometric testing of candidate items (using classical, factor analysis, and item response theory methods) on > 4000 respondents in the 6 countries. Stakeholders were consulted throughout.ResultsA total of 32 subdomains grouped into 7 high-level domains were identified from the qualitative literature and 97 items generated to cover them. Face validation eliminated 36 items, modified 14, and added 3. Psychometric testing of 64 items found little difference in missing data or problems with response distribution, the conceptual model was confirmed except in China, and most items performed well in the item response theory in all countries. Evidence was presented to stakeholders in 2 rounds of consultation to inform the final selection of items for the EQ-HWB (25-item) and the short version of EQ-HWB (9-items).ConclusionsEQ-HWB measures have been developed internationally for evaluating interventions in health, public health, and social care including the impact on patients, social care users, and carers.     

High frequency of extended-spectrum beta-lactamase-producing Enterobacteriaceae carriers at a Japanese long-term care hospital

IntroductionLong-term care hospitals (LTCHs) are at a high risk for the inflow and spread of antimicrobial resistance (AMR) pathogens. However, owing to limited laboratory resources, little is known about the extent to which AMR organisms are endemic.MethodsWe performed active surveillance for carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in newly admitted patients at Marugame Medical Center, a nearly 200-bedded LTCH located in Kagawa, Japan. From August to December 2021, we tested stool samples from patients wearing diapers and confirmed the genetic variants using specific PCR assays. We also collected clinical variables and compared them between AMR carriers and non-carriers.ResultsStool samples were collected from 75 patients, with a median age of 84 years. CRE strain was not detected, but 37 strains of ESBL-E were isolated from 32 patients (42.7%). During the study period, 4.9% of in-hospital patients (37 per 756 patients) were identified to be ESBL-E carriers in the routine microbiological processing, suggesting that active surveillance detected approximately 9-fold more ESBL-E carriers. The bla_CTX-M-9 group was the most common (38.5%), followed by the bla_TEM (26.9%). The clinical backgrounds of the ESBL-E non-carriers and carriers were not significantly different.ConclusionOur active screening demonstrated that nearly half of the patients hospitalized or transferred to a Japanese LTCH were colonized with ESBL-E. We highlight the enforcement of universal basic infection prevention techniques at LTCHs where patients carrying AMR pathogens gather.