BACKGROUNDConsidering the existence of a large number of liver cell degeneration and necrosis in fibrotic liver, liver function was damaged severely and could not effectively regenerate after partial hepatectomy (PHx). The aim of this study was to investigate whether decorin (DCN) could promote the liver regeneration after PHx in fibrotic mice.

METHODSForty mice (5-week-old, Balb/c) were injected with CCl4 intraperitoneally and liver fibrosis model was established after 5 weeks. The survival mice were randomly divided into two groups: control group and DCN group. Then, we performed 70% PHx on all these mice and injected DCN or phosphate-buffered saline plus normal saline (NS) to each group, respectively, after surgery. Liver body weight ratio (LBR), quantitative real-time polymerase chain reaction, and immunohistochemistry were used to analyze liver regeneration and fibrosis degree in both groups, and to find out whether exogenous protein DCN could promote the regeneration of fibrosis liver after PHx.

RESULTSExpressions of a-smooth muscle actin (SMA) mRNA and LBR had significant increases in the DCN group at postoperative Day 3 (POD 3, P < 0.05). The protein expressions of CD31, a-SMA, and tumor necrosis factor (TNF)-a were higher in the DCN group than those in the control group by immunohistochemistry at POD 3 (P < 0.05).

CONCLUSIONExogenous protein DCN could promote liver regeneration after PHx in fibrotic mice.

Animals ; Decorin ; therapeutic use ; Hepatectomy ; Immunohistochemistry ; Liver Cirrhosis ; drug therapy ; metabolism ; surgery ; Liver Regeneration ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism

Objective To analyze the immune genome environment of colon adenocarcinoma (COAD), find the immune genes related to the prognosis of COAD patients, and construct a prognostic risk score model to provide a basis for prognosis evaluation and individual diagnosis and treatment of COAD patients. Methods The RNA-seq data and clinical data of COAD patients were downloaded from TCGA (The Cancer Genome Atlas) database. Samples were divided into Tumor group and Normal group according to the type of tissues, and the differentially expressed immune genes were screened by R language. The immune genes related to the prognosis of COAD patients were screened by Cox regression analysis, and the prognostic risk score model was constructed. The COAD patients were divided into high-risk group and low-risk group according to their median risk score. The predictive efficiency of the immune gene prognosis model was evaluated by Kaplan-Meier analysis and Receiver Operating Characteristic (ROC) curve, and the correlation between immune gene prognostic risk model and the immune cell infiltration was analyzed. Results A total of 220 differentially expressed immune genes existed in Tumor group and Normal group. By Cox univariate and multivariate regression analysis, seven prognosis-related immune genes were screened, i.e. CXCL5 (C-X-C motif Chemokine Ligand 5), IGHV5-51 (Immunoglobulin Heavy Variable 5-51), IGKV1-33 (Immunoglobulin Kappa Variable 1-33), CHGA (Chromogranin A), UCN (Urocortin), VIP (Vasoactive Intestinal Peptide) and NR3C2 (Nuclear Receptor subfamily 3 group C member 2). The overall survival rate of COAD patients was higher in low-risk group than in high-risk group (P<0.001). The overall 5-year survival rate in high-risk group and low-risk group were 49.4% and 75.8%, respectively. ROC curve showed that AUC was 0.741, suggesting that the immune gene prognosis model had a good predictive efficiency, and was associated with immune cell infiltration of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages and natural killer cells. Conclusions An immune gene risk score model has been constructed, The importance of such a prognostic model is systematically evaluated and verified in individualized treatment of patients with colon adenocarcinoma, so as to provide a direction for finding new immunotherapy targets.

Because of the tumor barrier and the microenvironment of tumor tissue, the treatment of tumor immunotherapy is limited and increased adverse reactions. In recent years, nano-preparation has made many new advances in the process of tumor immunotherapy for regulating immune deficiency, remodeling tumor tissue microenvironment, and enhancing the effect of immunotherapy. This article mainly describes the microenvironmental factors of affecting the efficacy of tumor immunotherapy, and reviews the strategies of nano-preparation for remodeling the tumor microenvironment.

OBJECTIVE: Medication errors (ME) more frequently affect pediatric patients than adults. Chemotherapeutic drug MEs seems more serious and less detected, among which, the most commonly involved chemotherapeutic agent was methotrexate (MTX). To engage multidisciplinary teams of childhood malignancy in a multisite study using proactive risk assessment methods to identify how MTX errors occur and propose risk reduction strategies. METHODS: We recruited doctors, nurses, pharmacists and parents from three children's hospitals in the northeast and southeast China to participate in failure mode and effects analyses (FMEA). An FMEA is a systematic team-based proactive risk assessment approach in understanding ways a process can fail and develop prevention strategies. Steps included diagram the process, collect failure modes /risks and prioritize failure modes, and propose risk reduction strategies. We focused on MTX-use process in and out of hospitals. RESULTS: A multidisciplinary medication safety team was formed of total 66 members. They developed a four-stage flow diagram with four main phases, based on which, 56 potential risks were recognized and 17 were classified as higher risks by the hazard-scoring matrix. The highest priority failure modes in hospital included wrong solvents, wrong frequency label and lake of monitoring; furthermore, errors involving excessive intake of oral MTX after discharge were worth extra attention. Meanwhile, remediation strategies were developed, consisting of constrained and recommended strategies. CONCLUSION: FMEA is a useful tool to identify the risk of MTX MEs and several years later, with the concerted efforts of all the healthcare staff and technicians, we wish to see a reduction in the potential for errors being made and an improvement of children safety.

OBJECTIVETo study the epidemiology of Acinetobacter baumannii infection in patients with ventilator-associated pneumonia (VAP).

METHODSProspective clinical study was carried out with 176 episodes of VAP with etiologic diagnosis being followed in two groups.

RESULTSTwenty-six episodes were caused by Acinetobacter baumannii and one hundred-fifty episodes were caused by "other" organisms. Using logistic regression analysis, the risk of VAP due to Acinetobacter baumannii was found to be high in patients with head trauma [odds ratio (OR) = 4.20, 95% confidence interva (CI): 2.72 to 6.48], surgery (OR = 2.88, 95% CI: 1.78 to 4.66), acute respiratory dispnea syndrome (OR = 2.81, 95% CI: 1.19 to 6.64), and large-volume pulmonary aspiration (OR = 6.71, 95% CI: 3.91 to 11.50).

CONCLUSIONSAcinetobacter baumannii pulmonary infection in incubated patients had an epidemiological pattern that different from "other" organisms. Patients with high risk identified in our study might mark the existence of cross-infection during airway manipulation.

Acinetobacter ; classification ; isolation & purification ; Acinetobacter Infections ; epidemiology ; etiology ; Aged ; Aged, 80 and over ; China ; epidemiology ; Cross Infection ; epidemiology ; etiology ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Male ; Middle Aged ; Pneumonia, Bacterial ; etiology ; microbiology ; Prospective Studies ; Respiration, Artificial ; adverse effects ; Respiratory Distress Syndrome, Adult ; complications ; Risk Factors ; Time Factors ; Ventilators, Mechanical ; adverse effects

The status of health inspection,the setting of courses,teaching reform,requirement of professional and the training pattern of innovative professional were deeply discussed and researched.The pros and cons of several patterns on professional training were summarized.The courses setting and reform emphasis of the innovative professional training were proposed,all of which provided useful view and ideas for training health inspection professionals.

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.
Animals ; Benzothiazoles ; pharmacology ; Brain Chemistry ; drug effects ; Epilepsy ; chemically induced ; complications ; Hippocampus ; chemistry ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Histidine ; pharmacology ; Hypothalamus ; chemistry ; Kindling, Neurologic ; physiology ; Memory Disorders ; drug therapy ; etiology ; Pentylenetetrazole ; Phenoxypropanolamines ; pharmacology ; Piperidines ; pharmacology ; Pyrilamine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H2 ; drug effects ; physiology ; Spatial Memory ; drug effects ; Spectrometry, Fluorescence ; Thalamus ; chemistry

Objective To explore a method of constructing engineered sweat gland organoids in vitro by transdifferentiation of epidermal keratinocytes into sweat gland-like cells after lineage re-programming to achieve functional repair of sweat glands. Methods CRISPR/dCas9 system was used to up-regulate the expression of endogenous ectodermal dysplasia ectodysplasin (EDA) genes in human immortalized cuticle keratin HaCaTs, the positive HaCaTs were then screened and cultured. The cells were cultured according to HaCaT group (HaCaT cells cultured in sweat gland medium), HaCaT+Dox group (HaCaT cells cultured in sweat gland medium with 5 μg/ml Dox), HaCaT-E group (HaCaT-E cells cultured in sweat gland medium) and HaCaT-E+Dox group (HaCaT-E cells cultured in sweat gland medium with 5 μg/ml Dox), respectively. RT-PCR and Western blotting were used to detect the expression level of EDA in each group to verify plasmid transfection. In addition, the cells were divided as HaCaT-E group (cultured in sweat gland medium) and HaCaT-E+Dox group (cultured in sweat gland medium with 5 μg/ml Dox) to identify the expression levels of sweat gland-related markers using immunofluorescence staining to verify whether HaCaT were reprogrammed to sweat gland like cells. Furthermore, the sweat gland development microenvironment was imitatively reconstructed using Matrigel as the main extracellular scaffold, which induced sweat gland-like cells to assemble into sweat gland organoids, and the expression of sweat gland surface markers was detected by immunofluorescence staining. After transplantation of sweat gland organoids to mouse scalded paw pads, iodine-starch sweating experiment and histomorphology were performed to detect the involvement of engineered sweat gland organoids in sweat gland regeneration and skin wound repair. Results After transfection with CRISPR/dCas9 lentiviral expression system, positive HaCaT-E cells were obtained. RT-PCR showed the expression level of EDA mRNA in HaCaTE+ Dox group was up-regulated about (4.62±0.19) times than that in HaCaT group (P<0.05), while compared with HaCaT group, EDA mRNA level wasn't increased significantly in HaCaT-E group and HaCaT+Dox group (P>0.05). Western blotting showed the same trend as did by RT-PCR. After 2-7 days of inducted incubation with sweat gland culture medium containing doxycycline, the cells showed fusiform shape, lumenized networks, as well as up-regulated expression of sweat gland-related markers. After mixedly cultured in a 3-D culture system containing Matrigel for 7 days, the cells proliferated and volume increased to form sweat glands organoids with cystic cavity, and the sweat gland surface markers and functional markers cytokeratin 18 (CK18), a-smooth muscle actin (a-SMA) and aquaporin 5 (AQP5) were positively expressed. In vivo experiments showed that the iodine-starch sweating test was positive in mice, and tissue immunofluorescence staining showed that green fluorescent protein (GFP) positive cells were mainly distributed in the basal layer and subunit basal layer of the epidermis, and the tubular glandular structure was found in the deep and subcutaneous tissues of the dermis, and the GFP and sweat gland cell markers CK18 and a-SMA were observed. Conclusions Up-regulation of endogenous EDA gene by CRISPR/dCas9 system may successfully reprogram HaCaT into sweat gland-like cells. A three-dimensional culture environment constructed with Matrigel as the main extracellular scaffold can induced engineered sweat gland-like cells to self-assembly and develop into sweat gland organoids in vitro. The engineered organoids not only possessed the phenotype and structural characteristics of the sweat gland primordia, but also promoted the regeneration of sweat glands in vivo, thus achieving functional wound repair.