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Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl‐CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle‐type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6‐HMGCS1‐YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non‐alcoholic fatty liver diseases‐ associated HCC. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. The results identify a CSN6‐HMGCS1‐YAP1 axis mediating tumor outgrowth in hepatocellular carcinoma (HCC) and propose a therapeutic strategy of targeting non‐alcoholic fatty liver diseases‐associated HCC.

R541.78; 陆战伤引起的心脏骤停(CA)是创伤性心搏骤停的一种,与战术战伤救治(TCCC)密不可分,故其诊断及后期治疗策略须根据TCCC的不同阶段(即火线救护阶段、战术战区救护阶段及战术后送救护阶段)而因时、因地制宜.对于胸部外伤导致肺、胸膜及心脏损伤的患者,可考虑实施腹部提压心肺复苏术.此外,还应重视便携式超声在CA可逆病因筛查中的作用.

R826.63