Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.     

Recent advances in lipid nanoparticles for delivery of nucleic acid,mRNA, and gene editing-based therapeutics

Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed.     

四川省三州地区卫生人力资源配置与公平性评价分析

目的:了解2011-2017年四川省三州地区卫生人力资源配置现状,为三州地区卫生人力资源的合理配置提供参考。方法:利用千人卫生人力资源拥有量指标、基尼系数和卫生人力资源密度指数(HRDI)分析卫生人力资源配置现状及其公平性。结果:三州地区千人卫生人力资源拥有量呈增长趋势;基尼系数大多超过0.4,仅护士按人口分布的基尼系数较小;卫生人力资源密度指数较小,需要量、缺乏量及缺乏比例均较大。结论:三州地区卫生人力得到一定程度改善;但配置公平性较差,尤其按地理、经济分布很不均衡;医护人员短缺,需要重点投入。     

胃癌患者根治术后腹腔灌洗液中CEA mRNA表达的临床意义

目的：探讨胃癌患者根治术后腹腔冲洗液中CEA mRNA表达情况及其临床意义。方法: 回顾性分析了2013 年1 月至2017 年12 月在南京大学医学院附属鼓楼医院接受胃癌根治切除术后进行腹腔灌洗液CEA mRNA检测的139 名患者的病历资料，并进行术后常规随访。用RT-PCR检测139 胃癌患者根治术后腹腔灌洗液中CEA mRNA表达情况。卡方检验分析腹腔灌洗液中CEA mRNA表达与临床基本特征、组织病理学资料、血液学指标及复发方式之间的关系。采用Logistic 单因素及多因素回归分析筛查影响CEA mRNA表达水平的因素。结果：139 名患者中44 名（31.7%）患者腹腔灌洗液CEA mRNA阳性。分析显示，胃癌患者腹腔灌洗液CEA mRNA阳性表达与性别、年龄、病理分级、Lauren 分型和HER2、EGFR、VEGFR等标记物间均没有明显的关联（均P>0.05），与病理类型、脉管是否侵犯、局部浸润深度、淋巴结转移程度和临床AJCC 分期有明显的关联（均P<0.05）。CEA mRNA阳性患者腹膜复发率明显高于阴性患者（P=0.012）。Logistic 单因素回归分析显示，印戒细胞癌（P=0.04，HR=2.810，95% CI: 1.050~7.520）、T 分期（P=0.016，HR=6.329，95% CI: 1.417~28.264）、N 分期（P=0.022，HR=3.068，95% CI: 1.172~8.027）、AJCC分期（P=0.016 ，HR=3.971 ，95% CI: 1.295~12.173 ）、神经侵犯（P=0.002 ，HR=6.738，95% CI: 1.995~22.757）、脉管侵犯（P<0.001，HR=16.36，95% CI: 3.85~69.512）为胃癌患者腹腔灌洗液CEA mRNA阳性表达的危险因素。Logistic 多因素回归分析显示，经过对其他因素的校正，脉管侵犯（P<0.001，HR=21.314，95% CI: 4.21~107.907）为胃癌患者腹腔灌洗液CEA mRNA阳性表达的独立危险因素。结论：胃癌腹腔灌洗CEA mRNA阳性的患者腹膜复发转移风险高且预后不良，应考虑包括腹腔局部治疗在内的更加积极的抗肿瘤治疗。     

Prevalence of HER2 Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population

Objective: Human epidermal growth factor receptor 2 (erbb2/HER2) overexpression, has now been implicatedin advanced gastric and gastroesophageal junction cancers. The study was conducted to determine the rate of HER2positivity in patients with locally advanced or metastatic gastric and gastroesophageal adenocarcinoma in North-EastIndia and to assess the impact of various demographic and clinical parameters on HER2 positivity. Methods: A total of68 patients of age >18 years of gastric and gastroesophageal adenocarcinoma diagnosed on histopathological examinationfrom September 2016 to February 2018 at Dr B Borooah Cancer Institute, Assam were enrolled for the observational(epidemiological) study. All patients were subjected to the HER2 immunohistochemistry test using a FDA-approved,standardized test kit. HER2 expression was correlated with various demographic and clinicopathological parameters.Results: The overall rate of HER2 positivity in the population studied was 56% (n=38). The rate was non-significantlyhigher in male, older age group (>60 years) and Hindu population. Similarly, HER2 positivity rate was higher in patientswith well differentiated histology and was more common in patients with stage II and III diseases, but neither of theassociations is statistically significant. HER2 positivity rate was significantly higher in proximal and in GEJ tumours(56% versus 44%, P=0.002). Conclusion: HER2 overexpression was evident in 56% of the North-East Indian patientswith locally advanced and metastatic gastric and gastroesophageal adenocarcinoma. The overexpression correlatedsignificantly with primary tumour site. Routine testing of gastric and gastroesophageal tumours for HER2 expressionis recommended to provide a therapeutic advantage in Indian patients.     

AuNP flares-capped mesoporous silica nanoplatform for MTH1 detection and inhibition

The human mutT homologue MTH1, a nucleotide pool sanitizing enzyme, represents a vulnerability factor and an attractive target for anticancer therapy. However, there is currently a lack of selective and effective platforms for the detection and inhibition of MTH1 in cells. Here, we demonstrate for the first time a gold nanoparticle (AuNP) flares-capped mesoporous silica nanoparticle (MSN) nanoplatform that is capable of detecting MTH1 mRNA and simultaneously suppressing MTH1 activity. The AuNP flares are made from AuNPs that are functionalized with a dense shell of MTH1 recognition sequences hybridized to short cyanine (Cy5)-labeled reporter sequences and employed to seal the pores of MSN to prevent the premature MTH1 inhibitors (S-crizotinib) release. Just like the pyrotechnic flares that produce brilliant light when activated, the resulting AuNP flares@MSN (S-crizotinib) undergo a significant burst of red fluorescence enhancement upon MTH1 mRNA binding. This hybridization event subsequently induces the opening of the pores and the release of S-crizotinib in an mRNA-dependent manner, leading to significant cytotoxicity in cancer cells and improved therapeutic response in mouse xenograft models. We anticipate that this nanoplatform may be an important step toward the development of MTH1-targeting theranostics and also be a useful tool for cancer phenotypic lethal anticancer therapy.     

Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.