Macrolide analog F806 suppresses esophageal squamous cell carcinoma (ESCC) by blocking β1 integrin activation

The paucity of new drugs for the treatment of esophageal squamous cell carcinoma (ESCC) limits the treatment options. This study characterized the therapeutic efficacy and action mechanism of a novel natural macrolide compound F806 in human ESCC xenograft models and cell lines. F806 inhibited growth of ESCC, most importantly, it displayed fewer undesirable side effects on normal tissues in two human ESCC xenograft models. F806 inhibited proliferation of six ESCC cells lines, with the half maximal inhibitory concentration (IC₅₀) ranging from 9.31 to 16.43 μM. Furthermore, F806 induced apoptosis of ESCC cells, contributing to its growth-inhibitory effect. Also, F806 inhibited cell adhesion resulting in anoikis. Mechanistic studies revealed that F806 inhibited the activation of β1 integrin in part by binding to a novel site Arg610 of β1 integrin, suppressed focal adhesion formation, decreased cell adhesion to extracellular matrix and eventually triggered apoptosis. We concluded that F806 would potentially be a well-tolerated anticancer drug by targeting β1 integrin, resulting in anoikis in ESCC cells.     

Methylated arsenic metabolites bind to PML protein but do not induce cellular differentiation and PML-RARα protein degradation

Arsenic trioxide (As₂O₃) is one of the most effective therapeutic agents used for patients with acute promyelocytic leukemia (APL). The probable explanation for As₂O₃-induced cell differentiation is the direct targeting of PML-RARα oncoprotein by As₂O₃, which results in initiation of PML-RARa degradation. However, after injection, As₂O₃ is rapidly methylated in body to different intermediate metabolites such as trivalent monomethylarsonous acid (MMA^III) and dimethylarsinous acid (DMA^III), therefore, it remains unknown that which arsenic specie is actually responsible for the therapeutic effects against APL. Here we have shown the role of As₂O₃ (as iAs^III) and its intermediate metabolites (i.e., MMA^III/DMA^III) in NB4 cells. Inorganic iAs^III predominantly showed induction of cell differentiation, while MMA^III and DMA^III specifically showed to induce mitochondria and endoplasmic reticulum-mediated apoptosis, respectively. On the other hand, in contrast to iAs^III, MMA^III showed stronger binding affinity for ring domain of PML recombinant protein, however, could not induce PML protein SUMOylation and ubiquitin/proteasome degradation. In summary, our results suggest that the binding of arsenicals to the ring domain of PML proteins is not associated with the degradation of PML-RARa fusion protein. Moreover, methylated arsenicals can efficiently lead to cellular apoptosis, however, they are incapable of inducing NB4 cell differentiation.     

人性化护理在产科病房的应用

随着护理学科的发展与人们物质水平的不断提高,人们对本以及与之密切相关的医疗服务特别是护理服务水平的需求越来越高,同时,伴随中外护理理念的不断交融,"人性照护"的护理模式被引入国内临床护理实践中[1].人性化护理是一种创造性的、个性化的、整体的、有效的护理模式,其目的是使病人在心理、社会、精神上处于满足而舒适的状态,减少或降低不适的程度,人性化护理更注意给予服务对象人性化的关怀和照顾,具体到临床工作中,要求护理人员更注重"以人为本"的整体护理[2],现将2005年以来我科实施人性化护理报告如下.     

Risk factors for heat related death during the August 2003 heat wave in Paris, France, in patients evaluated at the emergency department of the Hôpital Européen Georges Pompidou

Objectives

This study sought to determine the risk factors for short term mortality in the victims of the heat wave of August 2003 in France from among patients evaluated in our emergency department (ED). It was hypothesised that age, temperature, and some long term therapies and pre‐existing pathologies were factors associated with short term mortality.

Methods

A retrospective analysis of a seven day period. Four experts decided blindly, in pairs, whether a patient had presented with a heat related problem. Inclusion criteria were: core temperature ⩾38 °C and/or clinical signs of dehydration. Comparisons were made between the survivors and one month non‐survivors for 57 different items. Short term mortality was defined as death in the ED or within the first month of the ED visit.

Results

Of 841 patients attending the ED in the study period, 165 were included in the study, of which most were elderly women. Thirty one (18.8%) died within one month. Factors associated with short term mortality were: a greater degree of dependent living; more severe clinical condition on admission (higher temperature and heart rate, lower blood pressure, hypoxia, and altered mental status); higher values of blood glucose, troponin, and white blood cell count; lower values of serum protein and prothrombin levels; pre‐existing ischaemic cardiomyopathy; pneumonia as associated infection; and previous psychotropic treatment. The total number of survivors at one year was 91.

Conclusions

Although this study is limited because of the small sample size, the results have helped determine factors useful for future identification of patients at greatest risk of death in order to implement a more efficient patient care protocol.     

Intratumoral IL-18 gene transfer improves therapeutic efficacy of antibody-targeted superantigen in established murine melanoma

Antibody-targeted superantigen C215Fab-SEA is a fusion protein of staphylococcal enterotoxin A (SEA) and the Fab region of the tumor-reactive C215 mAb. It can trigger CTL against C215 antigen-positive tumor cells and induce tumor-suppressive cytokines. However, the antitumor effect of C215Fab-SEA is not satisfactory because of suboptimal production of Th1 cytokines after repeated administration. Interleukin 18 (IL-18) is a novel cytokine with profound effects on Th1 cellular response. In this study, we showed that adenovirus-mediated intratumoral IL-18 gene transfer strongly improved the therapeutic efficacy of C215Fab-SEA in the pre-established C215 antigen-expressing B16 melanoma murine model. More significant tumor inhibition and prolonged survival time were observed in tumor-bearing mice received combined therapy of C215Fab-SEA and Ad IL-18 than those of mice treated with C215Fab-SEA or AdIL-18 alone. Combination therapy augmented NK and CTL activities of tumor-bearing mice more markedly. The production of IL-2 and IFN-gamma also increased more significantly. More potent antitumor effect of combined therapy was observed in IL-10 KO mice with enhanced Th1 response. Our data demonstrated that the antitumor effect of C215Fab-SEA immunotherapy could be potentiated significantly by combination with intratumoral IL-18 gene transfer through more efficient activation of Th1 immune responses.     

老年人哮喘的辨证论治初探

老年人哮喘多伴有慢性支气管炎、阻塞性肺气肿、冠心病以及左心衰竭等疾病,症状复杂,而从中医中药辨证论治,如扶正祛邪,顾护脾胃,润养肺肾,对改善临床症状有其独特疗效.     

Hepatic Arterioportal Fistulas: A Retrospective Analysis of 97 Cases

Background and AimsHepatic arterioportal fistulas (HAPFs) are abnormal shunts or aberrant functional connections between the portal venous and the hepatic arterial systems. Detection of HAPFs has increased with the advances in diagnostic techniques. Presence of HAPFs over a prolonged period can aggravate liver cirrhosis and further deteriorate liver function. However, the underlying causes of HAPFs and the treatment outcomes are now well characterized. This study aimed to summarize the clinical characteristics of patients with HAPFs, and to compare the outcomes of different treatment modalities.MethodsData of 97 patients with HAPFs who were admitted to the Second Xiangya Hospital between January 2010 and January 2020 were retrospectively reviewed. Demographic information, clinical manifestations, underlying causes, treatment options, and short-term outcomes were analyzed.ResultsThe main cause of HAPF in our cohort was hepatocellular carcinoma (78/97, 80.41%), followed by cirrhosis (10/97, 10.31%). The main clinical manifestations were abdominal distention and abdominal pain. Treatment methods included transcatheter arterial embolization (n=63, 64.9%), surgery (n=13, 13.4%), and liver transplantation (n=2, 2.1%); nineteen (19.6%) patients received conservative treatment. Among patients who underwent transcatheter arterial embolization, polyvinyl alcohol, lipiodol combined with gelatin sponge, and spring steel ring showed comparable efficacy.ConclusionsHepatocellular carcinoma and cirrhosis are common causes of HAPFs. Transcatheter arterial embolization is a safe and effective method for the treatment of HAPFs, and polyvinyl alcohol, lipiodol combined with gelatin sponge, and spring steel ring showed comparable efficacy in our cohort.     

FilmArray脑炎/脑膜炎多重病原体核酸联检试剂盒在中枢神经系统感染病原学诊断中的价值

目的:探讨FilmArray脑炎/脑膜炎多重病原体核酸联检试剂盒(FilmArray ME Panel)在中国儿童中枢神经系统感染病原学诊断方面的应用价值。方法:收集2019年3月至11月上海交通大学医学院附属上海儿童医学中心收治的145例疑诊中枢神经系统感染患儿的经腰椎穿刺获得的脑脊液标本,对所有患儿的脑脊液标本行培...