2021年 · 第101卷第48期

Non-alcoholic steatohepatitis (NASH) is characterized by hepatic cellular steatosis, inflammation, and fibrosis that can lead to end-stage liver disease and ultimately hepatocellular carcinoma. TNF-α-induce protein 8-like 1 (TIPE1), a new member of the TNF-α-induce protein 8 family, has been explored to some extent in immunology and oncology research, but its role in metabolic diseases is poorly known. In this study, C57BL/6J mice were fed with high fat and high cholesterol diet for 16 weeks to establish an animal model of NASH. It was found that the expression level of TIPE1 in the liver of NASH mice was significantly reduced compared with that of normal diet mice. In mice that specifically knocked out hepatocyte TIPE1, the degree of hepatocyte steatosis, inflammation, fibrosis, and systemic metabolic disorders induced by diet were exacerbated; In contrast, hepatocyte-specific overexpression of TIPE1 significantly prevented the progression of these abnormal pathologies, suggesting that TIPE1 has a protective effect on the liver during the pathological progression of NASH induced by high-fat and high-cholesterol diet. Under metabolic stress, TIPE1 directly interacts with apoptosis signal-regulated kinase 1 (ASK1) to inhibit its TNF receptor-associated factor 6 (TRAF6) -catalyzed polyubiquitination activation, thereby inhibiting downstream c-Jun N-terminal kinase and p38 signaling pathway, protecting hepatocytes, and alleviating the degree of hepatic steatosis, inflammation, and fibrosis. Therefore, targeting the TIPE1 or TIPE1-ASK1 axis may be a novel clinical therapeutic strategy for nonalcoholic fatty liver disease and related metabolic dysfunction diseases.

Instant detection of novel coronavirus (POCT) can effectively alleviate the crowd gathering and the number of high-frequency tests for large-scale nucleic acid screening, and the rapid results of POCT can help to quickly start tracking and isolating infected people. Especially during the outbreak of SARS-CoV-2 pneumonia, the implementation of SARS-CoV-2 POCT has great urgency and practical significance, which can quickly initiate infected person tracking, isolation and quarantine, so it is necessary to balance the need for rapid test results, quality assurance and resource availability. During periods of high epidemic incidence, the detection rate of positive cases is high, and if the detection method is highly specific, even with low sensitivity, it can provide useful information. In order to better play the detection role of POCT, equipment must be distributed quickly, which means having a supportive quality infrastructure, being ready for rapid training, and implementing testing and monitoring performance in a manner that optimizes work performance to improve possible situations. The traditional POCT quality framework is not feasible in this context and does not meet the need for rapid setup and implementation. Therefore, we need to pay attention to the standardization of sampling requirements, biosafety, POCT methods, detection performance and limitations, detection selection, detection utility, development and implementation of quality management systems, quality improvement, and medical and scientific supervision.