Low dose naltrexone (LDN) enhances maturation of bone marrow dendritic cells (BMDCs)

It has been demonstrated previously that immune cell activation and proliferation were sensitive to the effects of naltrexone, a non-peptidic δ-opioid receptor selective antagonist and opioid receptors on BMDCs have been detected [1]. However, there is little prior data published on naltrexone and DCs. Therefore, we hypothesized that LDN could exert modulating effect on BMDCs. In present study, we studied influence of LDN on both phenotypic and functional maturation of BMDCs. Changes of BMDC post-treatment with LDN were evaluated using conventional light microscope and transmission electron microscopy (TEM); flow cytometry(FCM); cytochemistry; acid phosphatase activity(ACP) test; FITC-dextran bio-assay; mixed lymphocytes and enzyme-linked immunosorbent assay (ELISA). We have found that LDN enhances maturation of BMDCs as evidenced by 1) up-regulating the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs; 2) down-regulating the rates of pinocytosis and phagocytosis accompanied by the results of decreased ACP, and FITC-dextran bio-assay; 3) mounting potential of BMDCs to drive T cell; and 4) inducing secretion of higher levels of IL-12 and TNF-α. It is therefore concluded that LDN can efficiently promote the maturation of BMDCs via precise modulation inside and outside BMDCs. Our study has provided meaningful mode of action on the role of LDN in immunoregulation, and rationale on future application of LDN for enhancing host immunity in cancer therapy and potent use in the design of DC-based vaccines for a number of diseases.     

Anesthetic gases and occupationally exposed workers

The aim of this study is to estimate whether the occupational exposure to low dose anesthetic gases could cause alterations of blood parameters in health care workers. 119 exposed subjects and 184 not exposed controls were included in the study. Each worker underwent the complete blood count test (CBC), proteinaemia, leukocyte count, serum lipids, liver and kidney blood markers.The liver blood markers show statistically significant differences in health care workers compared with controls (p < 0.05), a statistically significant decrease in neutrophils and an increase of lymphocytes in health care workers compared with controls (p < 0.05). The prevalence of values outside the range for GPT, GGT, total bilirubin, lymphocytes and neutrophils was statistically significant in health care workers compared with controls (p < 0.05). The results suggest that occupational exposure to low dose anesthetic gases could influence some haematochemical hepatic and hematopoietic parameters in exposed health care workers.     

瘘管切除合并内口结扎治疗肛瘘临床疗效分析(附74例报告)

目的观察瘘管切除合并内口结扎治疗肛瘘的临床疗效。方法选择74例内口在肛管齿线附近的肛瘘患者,采用将瘘管完全剥离切除,内口盲端结扎的方法手术的临床资料作回顾性分析。结果 74例患者全部一次性治愈,住院时间为12~23d,完全愈合时间为22~47d。痊愈后肛门外观无缺损、移位等改变,生理功能正常。3例患者早期有少许黏液泄漏,8~10周后症状消失,肛门无失禁。结论采用瘘管切除合并内口结扎的手术方法治疗肛瘘彻底,治愈率高,疗效确切,无肛瘘再次复发。     

Delayed acute kidney injury recognition is not associated with poor short?term outcomes: a propensity score matched study

Objective Acute kidney injury (AKI) is common but usually under?diagnosed in hospitalized patients, of the impact of which on patients is still unclear. The paper was aimed to investigate the impact of delayed recognition of AKI on short?time prognosis of patients through a propensity score matched study． Methods From Oct 2013 to Sep 2014，1401 adult hospitalized patients with AKI in the First Affiliated Hospital of Nanjing Medical University were divided into delayed recognition group and timely?diagnosed group according to propensity score matching (1∶1) without replacement method. Primary endpoint was 30?day all?cause mortality, and secondary endpoints included recovery of kidney at discharge, length of hospitalization, length of intensive care unit stay and hospital costs．Results There were significant differences in age, department distribution, complications, stage of AKI, Charlson index, APACHEⅡ score, SOFA score between the two groups before matching. After matching, there were no significant difference in demographic data, department distribution, complications, stage of AKI, Charlson index, APACHE II score, SOFA score between the two groups except in blood urea nitrogen (P=0.039) and use of diuretics (P=0.018). Delayed recognition of acute kidney injury was not associated with 30?day all?cause mortality in univariate (P=0.711) and multivariate Logistic regression analyses. The secondary endpoints did not differ in two groups. Conclusion Delayed acute kidney injury recognition did not associate with poor short?term outcomes in adult hospitalized patients．     

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world,multi-center,cohort study

BackgroundThere is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia.ObjectiveTo define the characteristics of phenotypic and genetic HoFH probands from mainland China.MethodsWe collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test.ResultsA total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH.ConclusionsThis report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.     

Differential miRNA profile on photoaged primary human fibroblasts irradiated with ultraviolet A

Photoaging is cell aging caused by long-wave ultraviolet (UVA) radiation which is the main cause of human skin aging produced by exogenous environment. As an endogenous noncoding small RNA, microRNAs (miRNAs) are sensitive to environmental changes, and the expression change of miRNAs is an important manner to adjust to environment. However, the miRNA profile on photoaged human skin irradiated with UVA remains unknown and whether UVA responsive miRNAs participate in the UVA-caused stress reaction of skin cells is also unclear. In this study, we established an in vitro photoaging model with UVA-radiated human primary cultured fibroblasts, which could mimic UVA-induced photoaging of skin. Differentially expressed miRNAs during photoaging, including five up- and seven downregulated miRNAs, were found by microarray analysis and were verified by quantitative real-time PCR. With bioinformatics methods, the predicted miRNA targets were suggested to be associated with pathways in cancers. Among the significantly UVA-downregulated miRNAs, miR-146a overexpression antagonized the UVA-induced proliferation inhibition and suppressed the upregulation of aging-related genes in photoaging of our model. Western blot and luciferase assay showed that Smad4 might be a target of miR-146a to exert miR-146a functions during photoaging. Therefore, UVA radiation-induced photoaging results in specific patterns of miRNA response and miR-146a are able to antagonize UVA-caused photoaging partially through targeting Smad4.     

Hepatic ischemia-reperfusion increases circulating bone marrow-derived progenitor cells and tumor growth in a mouse model of colorectal liver metastases

BackgroundHepatic pedicle clamping is often required to reduce blood loss and transfusion during liver resection. However, the question remains whether use of hepatic pedicle clamping promotes tumor growth. Endothelial progenitor cells (EPCs) are mobilized from bone marrow in response to tissue ischemia, which allows neovascularization of ischemic tissue. It has been suggested that EPCs are involved in tumor progression. We hypothesized that hepatic ischemia reperfusion (I/R)-induced mobilization of EPCs could enhance growth of microscopic tumor, therefore promoting liver metastasis in a mouse model of colorectal cancer.Materials and methodsWe used mouse models of hepatic I/R and hind limb ischemia. For comparison, we studied mice that underwent limb ischemia as positive controls of EPC mobilization. At day 0, we divided 40 mice into four groups: hepatic I/R, hind limb ischemia, combined hepatic I/R and hind limb ischemia, and control (sham midline incision laparotomy). At day 2, we induced liver metastasis in all mice by injecting CT-26 cells into the spleen. Time-dependent circulating EPCs were determined by flow cytometry. We evaluated liver metastasis and microvascular density on day 21.ResultsThe number of circulating progenitor cells increased rapidly in the ischemic groups compared with the control group. Hepatic I/R significantly increased tumor outgrowth compared with the control group. Increased tumor growth was associated with enhanced CD31-positive microvascular density in liver tissue.ConclusionsHepatic I/R leads to mobilization of bone marrow–derived EPCs and enhanced intra-hepatic angiogenesis, which is associated with increased tumor burden in an animal model of colorectal liver metastasis.