This study highlighted the role of nine significant risk factors in the development of VTE after THA or TKA. Among all risk factors, history of VTE seems the one main indication for more potent anticoagulation. All other risk factors need to be considered and discussed with patients individually and balanced against the risk of bleeding and infection. Individual patient risk assessment, rather than a "blanket policy", is considered the best management strategy before deciding on the type of chemical prophylaxis.

USP18 associates with and deubiquitinates TAK1 to protect against hepatic steatosis, insulin resistance, and the inflammatory response. (Hepatology 2017;66:1866-1884).

Hepatocyte DUSP14 is required for maintaining hepatic metabolic homeostasis and for suppressing inflammation, a novel function that relies on constraining TAK1 hyperactivation. (Hepatology 2018;67:1320-1338).

BackgroundNonalcoholic fatty liver disease (NAFLD) refers to fatty infiltration of liver in the absence of excessive alcohol abuse. However, the problem that whether NAFLD is correlated with subclinical atherosclerosis assessed by carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) remains a source of controversy. This can be attributed to the differences in diagnosis methods, population ethnicity, sampling size and bias. This study aimed to further investigate the association of NAFLD with subclinical atherosclerosis.MethodsA cross-sectional study was carried out in the current study on population aged over 40 years derived from Kailuan community-based prospective study among Chinese adults from June 2010 to June 2011. NAFLD was evaluated through ultrasonography and histories of alcohol consumption. Clinical parameters and medical histories of patients were collected in the manner of interview performed by trained investigators using the standardized questionnaires. The biochemical parameters were analyzed at the central laboratory. CIMT and ba-PWV of each patient were measured. Multivariate logistic regression was used to analyze the associations of NAFLD with subclinical atherosclerosis assessed by CIMT or ba-PWV.ResultsA total of 4112 participants aged over 40 years were enrolled from Kailuan cohort, including 2229 men and 1883 women. The overall prevalence of NAFLD was 38.2% in the total population. Statistically significant differences were found in CIMT (P < 0.0001) and ba-PWV (P = 0.0007) according to the presence of NAFLD. It is notably that the multivariate logistic regression revealed NAFLD was independently associated with elevated CIMT after adjusting the conventional cardiovascular and metabolic risk factors (OR = 1.663, 95% CI = 1.391–1.989, P < 0.0001). In addition, NAFLD was also found to be positively associated with elevated ba-PWV after adjusting age, gender, BMI, current smoking and regular exercising (OR = 1.319, 95% CI = 1.072–1.624, P = 0.0089).ConclusionsOur findings suggest that NAFLD is remarkably correlated with subclinical atherosclerosis, which should be strongly advised to engage in the preventive strategies for cardiovascular diseases (CVDs).

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Sterile inflammation is an essential factor causing hepatic ischemia/reperfusion (I/R) injury. As a critical regulator of inflammation, the role of monocyte chemoattractant protein-induced protein 1 (MCPIP1) in hepatic I/R injury remains undetermined. In this study, we discovered that MCPIP1 downregulation was associated with hepatic I/R injury in liver transplant patients and a mouse model. Hepatocyte-specific Mcpip1 gene knockout and transgenic mice demonstrated that MCPIP1 functions to ameliorate liver damage, reduce inflammation, prevent cell death, and promote regeneration. A mechanistic study revealed that MCPIP1 interacted with and maintained hypoxia-inducible factor 1α (HIF-1α) expression by deubiquitinating HIF-1α. Notably, the HIF-1α inhibitor reversed the protective effect of MCPIP1, whereas the HIF-1α activator compensated for the detrimental effect of MCPIP1 deficiency. Thus, we identified the MCPIP1-HIF-1α axis as a critical pathway that may be a good target for intervention in hepatic I/R injury. (Hepatology 2018; 00:000-000).

The rapidly increasing prevalence of metabolic disorders associated with nonalcoholic fatty liver disease (NAFLD) warrants further study of the underlying mechanisms to identify key regulators as targets for the development of therapeutic interventions. Caspase recruitment domain protein 6 (Card6), as a member of the CARD family that regulates cell death and immunity, may potentially control this process. Indeed, Card6 down-regulation was found to be closely associated with the fatty livers observed in NAFLD patients, obese mice, and a palmitate-treated hepatocyte model. Gain-of-function and loss-of-function Card6 mouse models demonstrated that Card6 protected mice from insulin resistance, hepatic steatosis, and inflammatory responses upon high-fat diet administration. Mechanistically, Card6 interacted with and inhibited apoptosis signal-regulating kinase 1 (Ask1) and its subsequent downstream c-Jun N-terminal kinase/p38 signaling. Furthermore, Ask1 was sufficient to mediate Card6 function, and the interaction between Ask1 and Card6 was absolutely required for Card6 function in vivo. Adenovirus-mediated Card6 overexpression in the liver effectively ameliorated insulin resistance and hepatic steatosis in ob/ob mice. Therefore, we identified Card6 as an important negative regulator in NAFLD. Conclusion: Targeting Ask1 by Card6 may be a good strategy to develop a therapeutic method against NAFLD.

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