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.

Objective:To explore the long-term clinical efficacy and complications of modified spinous process splitting laminoplasty using coralline hydroxyapatite (SLAC).Methods:The patients who underwent SLAC surgery in this hospital from 2005.5 to 2011.7 were included retrospectively. The perioperative data were collected and followed up. A total of 165 cases were included. Among them, there were 115 males and 50 females; the average age was 56.5±11.4 years (range: 26-84 years), and the average follow-up period was 136.5±23.2 months (range: 108-182 months). The modified Japanese Orthopedic Association (mJOA) score, the neck disability index (NDI) score were used to evaluate the clinical symptoms of patients, and follow-up imaging to observe the changes in cervical spine curvature and mobility.Results:In terms of functional score: mJOA score increased from 11.4±2.9 before surgery to 15.0±1.8 in the early postoperative period but dropped to 14.0±2.5 at the last follow-up ( F=77.096, P<0.001), and NDI score decreased from 19.2%±14.4% before surgery to 13.0%±15.0% in the early postoperative period, but it rose to 14.0%±14.9% at the last follow-up ( F=6.915, P<0.001). The improvement rate of mJOA was 63.5% (early postoperatively) and 50.8% (last follow-up). Regarding the curvature of the cervical spine, the C 2-C 7 Cobb angle decreased from 14.8°±9.1° before surgery to 11.1°±10.5°, and it was maintained at the last follow-up (11.0°±10.1°) ( F=1.083, P=0.342). The cervical spine range of motion decreased significantly, mainly because the Cobb angle in the flexion position decreased from -19.8°±13.6° before the operation to -3.7°±10.6° at the last follow-up ( P<0.001). Seventy-two patients (44.0%) had complications after operation. Six patients (3.6%) developed neurological symptoms aggravated during follow-up, and their mJOA decreased by more than 3 points. 62 patients (37.6%) developed axial symptoms, of which 7 cases were relieved early (within 6 months post-op), 55 patients had persisted symptom and 17 cases (10.3%) remained painful. C 5 nerve root palsy occurred in 10 cases (6.1%) after the operation, 9 cases resolved within two years and the last patient did not resolve. Conclusion:SLAC surgery can effectively alleviate the patient's neurological symptoms and maintain long-term efficacy and cervical lordosis. The occurrence of persistent axial symptoms and the loss of cervical flexion range are long-term complications after SLAC surgery.

Radiation-induced bowel injury is a common complication of radiation therapy for pelvic malignancy. Given the huge number of patients diagnosed with pelvic malignancy, the number of patients diagnosed with radiation-induced bowel injury increased year by year, which put a great burden on the clinical diagnosis and treatment of radiation-induced bowel injury. In particular, chronic radiation-induced bowel injury, which is manifested in the process of prolonged, repeated and progressive aggravation, seriously affects the physical and mental health of patients and makes clinical diagnosis and treatment difficult. However, due to insufficient attention and understanding from doctors and patients, standardized diagnosis and treatment of radiation-induced bowel injury still have a long way to go. Radiation-induced bowel injury is self-limited but irreversible. During diagnosis, we should pay attention to overall evaluation of the stage of disease based on clinical symptoms, endoscopic examination, imaging examination, pathology and nutritional risk. The treatment methods include health education, drug therapy, enema therapy, formalin local treatment, endoscopic treatment and surgical treatment, etc. The treatment decision-making should be based on clinical symptoms, endoscopic or imaging findings to alleviate the clinical symptoms of patients as the primary goal and to improve the long-term quality of life of patients as the ultimate goal.

In this study, a neutral desorption-extractive electrospray ionization mass spectrometry ( ND-EESI-MS) method was developed for the direct and rapid detection of dichlorvos ( DDVP) in honey samples without any sample pretreatment procedure. Under the positive ionization mode, the main characteristic parent ion of DDVP was m/z 223 (MW:222) and daughter ions were m/z 109 and m/z127. Under the optimized working conditions, with the signal intensity of m/z 127 as quantitative index, the quantitative information of DDVP residues in honey was acquired effectively. The results showed that the linear range of DDVP for spiked honey was 5-1000 ng/mL (R2=0. 998) with the limit of detection (LOD) of 1. 0 ng/mL (n=3) and the recoveries for the DDVP spiked honey samples at the concentration levels of 10 , 30 and 400 ng/mL were 93 . 0%-103. 0%, with the relative standard deviations (RSDs, n=6) of less than 4. 4%. Meanwhile, for detection of spiked honey with gas chromatography-flame photometric detector ( GC-FPD ) , the linear range was 5-1000 ng/mL (R2=0. 999) with the LOD of 1. 6 ng/mL(n=3), and the recoveries of DDVP at the spiked honey concentration levels of 10 , 30 and 400 ng/mL were 94 . 9%-110 . 3%, with the RSDs of less than 7. 6%.