Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Background:Acute severe gastrointestinal bleeding is one of the severe complications of Crohn's disease (CD),and clinical data conceming its mechanism,characteristics and treatment are rare.Aims:To analyze the clinical characteristics and prognosis of acute severe gastrointestinal bleeding in CD.Methods:Clinical data of CD patients with acute severe gastrointestinal bleeding from January 2009 to April 2017 at Jinling Hospital were retrospectively analyzed,and the effect of various factors on rebleeding rate was analyzed.Results:Altogether 44 cases had acute severe gastrointestinal bleeding.Small intestine,ileocecum and anastomosis were the main bleeding sites,and 17 cases occurred with obscure bleeding site.History of enterectomy was found in 20 cases.Surgery was performed in 22 cases.Rebleeding occurred in 13 cases,including 11 cases within 1-year.No significant differences in rebleeding rate and 1-year rebleeding rate were found between patients received surgery and non-surgery treatment,patients with emergency surgery and selective surgery (P ＞0.05).Rebleeding rate was significantly lower in patients with bleeding site resected than in paitents with obscure bleeding stie (P ＜ 0.05),however,no significant difference in 1-year rebleeding rate was found betwwen the two groups (P =0.083).Conclusions:The incidence of acute severe gastrointestinal bleeding in CD is rather low,and the major bleeding sites are small intestine (among patients without enterectomy history) and anastomosis (among patients with enterectomy history).Surgery with bleeding site resected can decrease the recurrence of bleeding,which might be a protective factor for preventing rebleeding in CD patients.

OBJECTIVETo compare short-term outcomes of laparoscopic vs. open intestinal resection in patients with Crohn's disease (CD) under enhanced recovery after surgery(ERAS) program.

METHODSClinical data of 51 CD patients receiving laparoscopic surgery under ERAS program at our IBD center between January 2013 and March 2014 were retrospectively analyzed. Laparoscopic cases were matched to those undergoing open surgery from June 2011 to December 2012 with age, gender, location and behavior of disease. Intraoperative and postoperative data were collected.

RESULTSFifty-one laparoscopic cases were matched with 51 open cases. Laparoscopic group had a shorter median length of postoperative hospital stay (7 d vs. 9 d, P=0.034), shorter median time to first passage of gas(45 h vs. 59 h, P=0.024), shorter time to bowel movement(58 h vs. 76 h, P=0.018), less intraoperative estimated blood loss (35 ml vs. 75 ml, P=0.034) and longer median operative time (145 min vs. 105 min, P=0.003). Postoperative complications, reoperation and 30-day re-admission rates were similar and there was no mortality in the two groups.

CONCLUSIONLaparoscopic surgery is a safe and acceptable option for CD patients, and it promotes recovery of gastrointestinal movement and shortens postoperative hospital stay.

Case-Control Studies ; Crohn Disease ; Humans ; Laparoscopy ; Length of Stay ; Operative Time ; Postoperative Complications ; Reoperation ; Retrospective Studies ; Treatment Outcome

Objective To compare short-term outcomes of laparoscopic vs. open intestinal resection in patients with Crohn′s disease (CD) under enhanced recovery after surgery(ERAS) program. Methods Clinical data of 51 CD patients receiving laparoscopic surgery under ERAS program at our IBD center between January 2013 and March 2014 were retrospectively analyzed. Laparoscopic cases were matched to those undergoing open surgery from June 2011 to December 2012 with age , gender, location and behavior of disease. Intraoperative and postoperative data were collected. Results Fifty-one laparoscopic cases were matched with 51 open cases. Laparoscopic group had a shorter median length of postoperative hospital stay (7 d vs. 9 d, P=0.034), shorter median time to first passage of gas(45 h vs. 59 h, P=0.024), shorter time to bowel movement (58 h vs. 76 h, P=0.018), less intraoperative estimated blood loss (35 ml vs. 75 ml, P=0.034) and longer median operative time (145 min vs. 105 min, P=0.003). Postoperative complications, reoperation and 30-day re-admission rates were similar and there was no mortality in the two groups. Conclusion Laparoscopic surgery is a safe and acceptable option for CD patients, and it promotes recovery of gastrointestinal movement and shortens postoperative hospital stay.

Objective To compare short-term outcomes of laparoscopic vs. open intestinal resection in patients with Crohn′s disease (CD) under enhanced recovery after surgery(ERAS) program. Methods Clinical data of 51 CD patients receiving laparoscopic surgery under ERAS program at our IBD center between January 2013 and March 2014 were retrospectively analyzed. Laparoscopic cases were matched to those undergoing open surgery from June 2011 to December 2012 with age , gender, location and behavior of disease. Intraoperative and postoperative data were collected. Results Fifty-one laparoscopic cases were matched with 51 open cases. Laparoscopic group had a shorter median length of postoperative hospital stay (7 d vs. 9 d, P=0.034), shorter median time to first passage of gas(45 h vs. 59 h, P=0.024), shorter time to bowel movement (58 h vs. 76 h, P=0.018), less intraoperative estimated blood loss (35 ml vs. 75 ml, P=0.034) and longer median operative time (145 min vs. 105 min, P=0.003). Postoperative complications, reoperation and 30-day re-admission rates were similar and there was no mortality in the two groups. Conclusion Laparoscopic surgery is a safe and acceptable option for CD patients, and it promotes recovery of gastrointestinal movement and shortens postoperative hospital stay.

OBJECTIVETo study the relationship between the TCM Syndrome Differentiation-types of congestive heart failure (CHF) and thyroid hormones, including triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH), and atrial natriuretic peptide (ANP), as well as cardiac function parameters, including left ventricular ejection fraction (LVEF), mean velocity of circumferentid fiber shortening (mVcf) and A peak/E peak (A/E).

METHODSOne hundred patients with CHF were divided into 4 Syndrome Differentiation-type groups, their cardiac function parameters, ANP and thyroid hormones were determined and compared with those in the 23 subjects in the control group.

RESULTSIn CHF patients with edema and blood stasis Syndrome type, the level of plasma ANP was significantly higher than that in the control group (P < 0.05); level of T3 was significantly lower than that in the control group and in CHF patients of other three (Xin-qi deficiency, Yin-deficiency and blood stasis) Syndrome groups (P < 0.01, P < 0.01, P < 0.05 and P < 0.01); levels of LVEF and mVcf were significantly lower than those in the other three Syndrome groups (all P < 0.01). Level of T4 in other three Syndrome groups significantly increased than that in the edema and blood stasis Syndrome type. A/E value showed a higher level in patients of all TCM type than that in the control (P < 0.01). Correlation analysis showed that T3 was positively correlated with LVEF and T4 (r = 0.200, P < 0.05, and r = 0.293, P < 0.01), and negatively correlated with ANP (r = -0.263, P < 0.01); T4 was negatively correlated with A/E (r = -0.226, P < 0.05).

CONCLUSIONThe lowering of T3 and T4 and increasing of ANP may be one of the important reasons for lowering of LVEF in CHF patients with edema and blood stasis Syndrome-type. The decrease of T4 may be one of the important reasons for elevation of A/E and aggravation of left ventricular diastolic dysfunction in CHF patients of all the 4 TCM Syndrome-types.

Adult ; Aged ; Atrial Natriuretic Factor ; metabolism ; Diagnosis, Differential ; Female ; Heart Failure ; blood ; physiopathology ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Myocardial Contraction ; Stroke Volume ; physiology ; Thyroid Hormones ; blood ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood ; Ventricular Dysfunction, Left ; physiopathology ; Ventricular Function, Left