Background: Considering the high likelihood of chronicity, it is imperative to understand the risk factors and outcomes associated with severe anorexia nervosa (AN), for which Danish registers provide a unique opportunity. We developed a measure of AN severity adapted from clinical literature for use in register-based research. Methods: The study population included all Danish individuals born between 1963 and 2007 who were diagnosed with AN from 1969 to 2013. Using register data, we constructed the Anorexia Nervosa Register-based Severity Index (AN-RSI), incorporating early or late illness onset, number of inpatient admissions and outpatient treatments, cumulative treatment length, and illness duration, each weighted based on clinical importance. Associations between AN-RSI scores, evaluated five years after first AN diagnosis, and mortality were estimated using survival analysis. Results: Among 9,167 individuals diagnosed with AN, 132 died during follow-up: 17 from AN; 30 from suicide; and 85 from other causes. Higher AN-RSI scores were associated with increased rates of mortality from AN, somatic anorexia diagnosis, suicide, alcohol-related causes, and any cause. AN cases who scored in the top 20% of AN-RSI had especially high mortality rates. Furthermore, severe AN cases were also more likely to be in treatment in the next five years after severity was established. Conclusions: AN-RSI effectively captures mortality and long-term treatment in the absence of detailed patient records and is associated with later mortality in AN patients. AN-RSI could serve as a tool to examine epidemiological and genetic risk factors associated with AN course and outcomes.
Abstract: Melanoma is one of the deadliest skin cancers and accounts for most skin-related deaths due to strong resistance to chemotherapy drugs. In the present study, we investigated the mechanisms of dabrafenib-induced drug resistance in human melanoma cell lines A375 and MEL624. Our studies support that both endoplasmic reticulum (ER) stress and autophagy were induced in the melanoma cells after the treatment with dabrafenib. In addition, ER stress-induced autophagy protects melanoma cells from the toxicity of dabrafenib. Moreover, inhibition of both ER stress and autophagy promote the sensitivity of melanoma cells to dabrafenib. Taken together, the data suggest that ER stress-induced autophagy determines the sensitivity of melanoma cells to dabrafenib. These results provide us with promising evidence that the inhibition of autophagy and ER stress could serve a therapeutic effect for the conventional dabrafenib chemotherapy. Keywords: melanoma, dabrafenib, ER stress, autophagy, apoptosis
XML(eXtensible Markup Language)has been recognized as a standard for data exchange over the Internet. The SOAP(simple object access protocol) is a platform-independent protocol for the exchange of information in the distributed and heterogeneous environment. In this paper, a cross-platform web collaborative environment is constructed to deal with the problems of collaborative work among inhomogeneous platforms. And the collaborative workflows of processes are explained in detail simultaneously. Finally, the implementation of this collaborative environment is also illuminated based on Java language, SOAP, basic transmission protocol (HTTP) and component technology.
Objective:To take collagen as main ingredients plus herbal medicine Kushen(Radix Sophorae Flavescentis) and Banlangen(Radix Isatidis) ,a new suppository was prepared for anti-inflammation and elevating healing of uterine neck's wound. Methods:Add Kushen and Banlangen to the high purity collagen and base material to prepare the suppository. To evaluate the suppository's hemostatic effects and diminish inflammation by determination of physicochemical property and quality,toxicology and pharmacodynamics. Results:The quality of suppository was stable,pH was 5.5,the result of toxicology test was feminine. Pharmacodynamics test showed that the healing rate in preparation one was 90%. The average of healing time was five or six days. Compared with control group,the effects was more obvious(P0.01) .Conclusion:Shen-Lan-collagen suppository has excellent clinic curative value which possesses hemostatic effect and anti-inflammation effect hence it would be advance in the treatment of uterine neck's wound healing.
Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor in klfs family, is known for its crucial role in regulating cell growth, proliferation, and differentiation. This research aimed to explore the prognostic significance of KLF4 in hepatocellular carcinoma's (HCC) patients after curative resection and the role of KLF4 in HCC progression. There were 185 HCC patients who had hepatectomy from July 2010 to July 2011 included in this study. KLF4 expression was detected by microarray immunohistochemical technique, western blot, and qRT-PCR. Then, the correlation between the prognosis of patients and KLF4 expression was evaluated based on patients' follow-up data. The research found KLF4 expression was significantly downregulated in HCC tissues compared to para-tumorous tissues. More importantly, the overall survival rate (OS) and recurrence-free survival rate (RFS) of HCC patients with low KLF4 expression were both significantly decreased compared to those with a high level of KLF4. Further function and mechanism analysis showed that KLF4 could inhibit the proliferation, migration, invasion and epithelial-mesenchymal transition of HCC cells. The study revealed that KLF4 was not only a tumor suppressor in HCC but also can be regarded as a valuable prognostic factor and potential biological target for diagnosis and treatment in HCC patients.
The present study investigated the mechanism(s) of non‑alcoholic steatohepatitis‑related hepatocellular carcinoma (NASH‑HCC) developed from diabetes. Streptozotocin and a high‑fat diet (STZ‑HFD) were used to induce NASH‑HCC in ApoE‑/‑ mice. Mouse liver functions were evaluated by H&E staining, liver/body weight and serum biochemical analysis. The expression levels of inflammation‑associated factors were determined by RT‑qPCR. Gene expression profiles related to molecular functions and pathways of NASH‑HCC were examined by principal component analysis, heatmap, gene ontology and KEGG pathway enrichment analysis. Differentially expressed genes (DEGs) in tumor tissues were confirmed by RT‑qPCR. The expression of Asxl2 in human NASH‑HCC, other HCC tissues and HCC cells was measured by western blot (WB analysis) and RT‑qPCR. For SNU‑182 cells transfected with siAsxl2 or Hep3B cells with Asxl2 overexpression, cell proliferation, cell cycle, migration and invasion were respectively determined by CCK‑8 assays, flow cytometry, wounding healing and Transwell assays. The expression levels of cell metastasis‑ and cycle‑related proteins were determined by WB analysis and RT‑qPCR. NASH‑HCC model mice exhibited tumor protrusion with severe steatosis. The blood glucose concentration, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and low‑density lipoprotein (LDL), total bile acid (TBA) and the levels of interleukin (IL)‑6, tumor necrosis factor (TNF)‑α, glypican 3 (GPC3) and transforming growth factor (TGF)‑β were all increased in NASH‑HCC model mice. DEGs were mainly related to chromosome organization, the cell cycle and the mitogen‑activated kinase (MAPK) pathway. Asxl2 was significantly downregulated in HCC tissues and cells, and this regulated cell growth, migration and invasion. The gene expression pattern, related molecular functions and signaling pathways of NASH‑HCC differed from those of normal liver tissues. Additionally, the downregulation of Asxl2 may play a potential role in development of NASH‑HCC in patients with diabetes.
Compared to younger people, older people have a higher risk and poorer prognosis of acute pancreatitis, but the effect of gut microbiota on acute pancreatitis is still unknown. We aim to investigate the effect of aging gut microbiota on acute pancreatitis and explore the potential mechanism of this phenomenon.Eighteen fecal samples from healthy adult participants, including nine older and nine younger adults were collected. C57BL/6 mice were treated with antibiotics for fecal microbiota transplantation from older and younger participants. Acute pancreatitis was induced by cerulein and lipopolysaccharide in these mice. The effect of the aged gut microbiota was further tested via antibiotic treatment before or after acute pancreatitis induction.The gut microbiota of older and younger adults differed greatly. Aged gut microbiota exacerbated acute pancreatitis during both the early and recovery stages. At the same time, the mRNA expression of multiple antimicrobial peptides in the pancreas and ileum declined in the older group. Antibiotic treatment before acute pancreatitis could remove the effect of aging gut microbiota, but antibiotic treatment after acute pancreatitis could not.Aging can affect acute pancreatitis through gut microbiota which characterizes the deletion of multiple types of non-dominant species. This change in gut microbiota may potentially regulate antimicrobial peptides in the early and recovery stages. The level of antimicrobial peptides has negative correlations with a more severe phenotype.
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