Re‐structuring the negotiated order of the hospital

Researchers continue to lament the lack of organisational focus in the sociology of health and illness. Although studies have increasingly focused on boundaries between organizations, little such research has focused on the formal boundaries within the hospital itself. Given its dramatic compartmentalisation, and continuing prevalence in health systems, the lack of organisational perspective in hospital research limits insights into the effects (as well as the construction) of the order of health work and care. With a greater emphasis on ‘ordering’ in the concept of negotiated order, the aim of this study is to examine the manifestation and consequences of the formal boundaries of hospital departments. Fieldwork featured 12 months of ethnography, including formal and informal observations, 80 audio‐recorded, semi‐structured interviews, and 56 field interviews, in the Emergency Departments (EDs) of two tertiary referral hospitals. Compared with in‐patient hospital departments, the ED has limited legitimacy claims of organ‐specific knowledge to transfer patients out of the ED. The manifestation of specialised knowledge hierarchies in organisational structures disadvantages patients who are older and who have chronic conditions, underpinning the argument that effects as well as the negotiation of stable organisational orders deserve increased attention in the sociology of health and illness.     

In Vitro and In Vivo Evaluation of Core–Shell Mesoporous Silica as a Promising Water-Insoluble Drug Delivery System: Improving the Dissolution Rate and Bioavailability of Celecoxib With Needle-Like Crystallinity

The objective of our study was to prepare mesoporous silica nanoparticles with a core–shell structure (CSMSNs) and improve the dissolution and bioavailability of celecoxib (Cxb), a water-insoluble drug, by changing its needle-like crystal form. CSMSNs are prepared by a core-shell segmentation self-assembly method. The S_BET and V_t of CSMSNs were 890.65 m²/g and 1.23 cm³/g, respectively. Cxb was incorporated into CSMSNs by the solvent evaporation method. The gastrointestinal irritancy of the CSMSNs was evaluated by a gastric mucosa irritation test. In vitro dissolution and in vivo pharmacokinetic tests were carried out to study the improvement in the dissolution behavior and oral bioavailability of Cxb. In conclusion, gastric mucosa irritation study indicated the good biocompatibility of CSMSNs. The cumulative dissolution of CSMSNs-Cxb is 86.2% within 60 min in SIF solution, which may be ascribed to the crystal form change caused by control of the nanochannel for CSMSNs. Moreover, CSMSNs could enhance the 9.9-fold AUC of Cxb. The cumulative dissolution and bioavailability of Cxb were both significantly enhanced by CSMSNs. CSMSNs with a core–shell structure are suitable as a carrier for a poorly water-soluble drug (Cxb).     

Comparison of Acoustic Structure Quantification,Transient Elastography (FibroScan) and Histology in Patients with Chronic Hepatitis B and without Moderate to Severe Hepatic Steatosis

The purpose of this study was to compare acoustic structure quantification (ASQ) with transient elastography for staging liver fibrosis. One hundred eighty-two patients with chronic hepatitis B and without moderate to severe hepatic steatosis scheduled for liver biopsy underwent ASQ and transient elastography examinations. All ASQ parameters, including total mode, total average, red mode, red average, red standard deviation, blue mode, blue average, blue standard deviation and focal disturbance (FD) ratio and liver stiffness obtained via transient elastography were found to correlate with fibrosis stage (Spearman's r?=?0.783, 0.791, 0.750, 0.771, 0.544, 0.718, 0.691, 0.439, 0.815 and 0.814, respectively; all p values < 0.001). Among the ASQ parameters, the FD ratio had the highest correlation with the stage of fibrosis. The areas under the receiver operating characteristic curves (AUCs) of FD ratio and liver stiffness were 0.911 and 0.906 for F ≥ F1, 0.918 and 0.882 for F ≥ F2, 0.911 and 0.914 for F ≥ F3 and 0.926 and 0.978 for F?=?F4, respectively. There was no significant difference in AUCs between FD ratio and liver stiffness in predicting different stages of fibrosis (p?=?0.062–0.912). ASQ is a promising technique for assessing liver fibrosis in the absence of moderate to severe hepatic steatosis.     

Annexin A13 predicts poor prognosis for lung adenocarcinoma patients and accelerates the proliferation and migration of lung adenocarcinoma cells by modulating epithelial–mesenchymal transition

This study aimed to investigate the role of ANXA13 in lung adenocarcinoma (LUAD) growth, migration, and the underlying mechanisms. Firstly, in the TCGA dataset for LUAD, ANXA13 is found to be highly expressed in patients with LUAD and high expression of ANXA13 predicted poor outcomes in LUAD patients. Consistently, the data of qRT-PCR showed that the expression of ANXA13 was higher in LUAD cell lines (Calu-3, LTEP-a-2, and NCI-H1395) than that in normal lung cell line BEAS2B. Then, we performed gain- and loss of function of ANXA13 in NCI-H1395 and Calu-3 cells, respectively. The results displayed that deficiency of ANXA13 suppresses cell proliferation, invasion, and migration in Calu-3 cells and overexpression of ANXA13 augments cell proliferation, invasion, and migration in NCI-H1395 cells. Finally, it was found that silencing of ANXA13 obviously raised the protein expression levels of E-cadherin and reduced the protein levels of N-cadherin, Vimentin, and Snail in Calu-3 cells whereas overexpression of ANXA13 obviously receded the protein expression levels of E-cadherin and enhanced the protein levels of N-cadherin, Vimentin, and Snail in NCI-H1395 cells. This study analyzed the biological effects of ANXA13 in LUAD cells, indicating that ANXA13 could regard as a therapeutic target for LUAD.     

Geometric architecture of viruses

In the current SARS-CoV-2 disease (COVID-19) pandemic, the structural understanding of new emerging viruses in relation to developing effective treatment and interventions are very necessary. Viruses present remarkable differences in geometric shapes, sizes, molecular compositions and organizations. A detailed structural knowledge of a virion is essential for understanding the mechanisms of capsid assembly/disassembly, antigenicity, cell-receptor interaction, and designing therapeutic strategies. X-ray crystallography, cryo-electron microscopy and molecular simulations have elucidated atomic-level structure of several viruses. In view of this, a recently determined crystal structure of SARS-CoV-2 nucleocapsid has revealed its architecture and self-assembly very similar to that of the SARS-CoV-1 and the Middle-East respiratory syndrome virus (MERS-CoV). In structure determination, capsid symmetry is an important factor greatly contributing to its stability and balance between the packaged genome and envelope. Since the capsid protein subunits are asymmetrical, the maximum number of inter-subunit interactions can be established only when they are arranged symmetrically. Therefore, a stable capsid must be in a perfect symmetry and lowest possible free-energy. Isometric virions are spherical but geometrically icosahedrons as compared to complex virions that are both isometric and helical. Enveloped icosahedral or helical viruses are very common in animals but rare in plants and bacteria. Icosahedral capsids are defined by triangulation number (T = 1, 3, 4, 13, etc.), i.e., the identical equilateral-triangles formed of subunits. Biologically significant defective capsids with or without nucleic acids are common in enveloped alpha-, flavi- and hepadnaviruses. The self-assembling, stable and non-infectious virus-like particles have been widely exploited as vaccine candidates and therapeutic molecules delivery vehicles.     

筛窦基板层次气化分析及其在鼻内镜鼻窦手术中的应用

目的探讨应用筛窦基板层次性分析方法,指导内镜下筛窦层次性开放的可行性。方法通过鼻窦CT扫描的薄层DICOM数据,层厚层距均为0.65 mm,ImageViewer软件三维重建分析筛窦的基板（III V）层次及其气化情况。结果获得100例（200侧）患者鼻窦CT原始薄层数据,通过三维重建分析发现筛骨结构包含5个基板（I V）：①基板V的出现率为60.0%,相邻基板间存在潜在的层次间隙;②Haller气房出现率为28.0%,与中鼻甲、上鼻甲基板结构气化相关者分别占19.5%、8.5%;③上鼻甲及基板气化发生率为91.5%,其中19.1%气化为Onodi气房。最上鼻甲及基板出现率60.0%,气化发生率为76.7%,其中15.8%气化为Onodi气房。Onodi气房出现率为33.0%,来源于上鼻甲基板、最上鼻甲基板的分别占17.5%,9.5%,来源于二者共同气化的占6.0%。各基板及其气化结构组成相对独立的通气引流系统,可单独出现引流障碍。手术中筛窦的开放（III V基板）过程,以上鼻甲、最上鼻甲为标志结构,结合CT提示的气化变异,可在其前方分别充分地开放III基板、IV基板气化结构构成的筛窦迷路（包括变异气房,如Haller气房）,而根据CT提示V基板的气化状况和方向,可进一步实现V基板及其气化结构（包括Onodi气房）的开放。结论通过分析筛窦基板的层次性结构,对指引内镜下筛窦开放过程实现层次性、标准化有重要指导价值。     

Epigenetic regulation of insulin action and secretion – role in the pathogenesis of type 2 diabetes

The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide. Obesity, physical inactivity and ageing increase the risk of T2D. Epigenetic modifications can change due to environmental exposures and may thereby predispose to disease. This review aims at summarizing recent advances in epigenetics related to T2D, with a special focus on impaired insulin action and secretion in humans. There will be an emphasis on analyses in human tissues; both from T2D case‐control cohorts and intervention studies. Current data support an important role for epigenetics in the pathogenesis of T2D. Numerous studies have found differential DNA methylation and gene expression in skeletal muscle, adipose tissue, the liver and pancreatic islets from subjects with T2D compared with nondiabetic controls. For example, PDX1 has increased DNA methylation and decreased expression in pancreatic islets from patients with T2D compared with nondiabetic controls. Nongenetic risk factors for T2D such as ageing, unhealthy diets and physical activity do also impact the epigenome in human tissues. Interestingly, physical activity altered DNA methylation of candidate genes for T2D such as THADA in muscle and FTO, KCNQ1 and TCF7L2 in adipose tissue. There is also a strong interaction between genetic and epigenetic factors that together seem to affect T2D. mQTL studies in human adipose tissue and pancreatic islets showed that SNPs associated with DNA methylation levels in numerous sites. Several of these SNPs are also associated with T2D. Recent data also support that DNA methylation of some sites in blood may be developed into biomarkers that predict T2D since methylation of, for example TXNIP, ABCG1 and SREBF1 associated with future T2D. Future studies should use this information for development of new therapies and biomarkers and thereby improve prediction, prevention and treatment of T2D and its complications.