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 provide technical met hods for marketing authorization holder （MAH）to effectively use the data of adverse drug reaction （ADR），actively monitor and control the production quality risk ，and carry out drug production risk management. METHODS ：Through establishing three-dimensional risk matrix and risk trend model ，the risk early warning system of MAH production line based on ADR report data is designed and developed ；the main functions of the system were applied and analyzed according to the actual ADR report data of a certain company. RESULTS ：MAH production line risk warning system was established preliminarily. The main framework included data source and and processing module ，model construction module （three-dimensional matrix model included possibility index ，severity index and sensitivity index ，risk trend model was set according to the principle of product production batch number preparation ），and result output & analysis module. Five major functional modules included system configuratio ，production line signal detection ，visual statistical early warning ，ADR report management and standard data management. The application and analysis of ADR report data of a certain company showed that the system could realize detection and warning of the company ’s production line risk ，which intuitively reflected its high-risk production lines ，varieties and batch numbers. It was consistent wit h the actual safety sit uation of the company ’s varieties. CONCLUSIONS：The system can help MAH make use of ADR report data to actively monitor drug production quality risks in a timely manner ，investigate risk factors for high-risk production lines ， high-risk varieties and high-risk batch numbers，and assist in decision-making on the direction of risk investigation.

Objective:To investigate the effects of different concentrations of hydrogen peroxide (H 2O 2) on the expression of histone deacetylase-2(HDAC-2) and mitogen activated protein kinases phosphatases-1(MKP-1) in A549 cells. Methods:The experimental models of A549 cells were established by intervening of different concentrations of H 2O 2(0, 100, 200, 400, 600, 800 μmol/L)for 2 h, 4 h, 8 h, 12 h and 24 h, respectively.The survival rate of A549 cells was detected by thiazolyl blue(MTT) assay, and the apoptosis of A549 cells was tested by lactic dehydrogenase(LDH) assay.The expression of HDAC-2 and MKP-1 protein was detected by Western blot. Results:(1)MTT results showed that compared with the control group (H 2O 2 was 0 μmol/L), the survival rate of A549 cells was decreased with the increase of H 2O 2 concentration at 2 h, 4 h, 8 h, 12 h, 24 h and 48 h. (2)LDH results showed that, compared with the control group, the inhibition rate of A549 cells increased with the increase of H 2O 2 concentration at 2 h, 4 h, 8 h, 12 h, 24 h and 48 h. (3)The expression of HDAC-2 protein decreased ( F=14.588, P<0.01), and the expression of MKP-1 protein increased ( F=64.297, P<0.01) in a concentration-dependent manner with the increase of H 2O 2 concentration at 12 h after H 2O 2 treatment. Conclusions:H 2O 2 participates in oxidative stress injury of lung cells by regulating the expression of HDAC-2 and MKP-1.

Bronchopulmonary dysplasia (BPD) is a common chronic respiratory complication in preterm infants without fully understand the mechanism or effective treatment, which could significantly affect the survival rate and prognosis of these infants. Studies have confirmed that epigenetic mechanisms, including histone modification, non-coding RNA and DNA methylation may play an essential role in the onset and development of BPD. And most related epigenetic changes are reversible, which might serve as a potential target for BPD treatment. Therefore, further studies on epigenetics will shed light on a better understanding of the pathogenesis, prevention, and treatment of BPD.

Objective To investigate the clinical effect ofYishen-Lishi formula combined with conventional treatment for gouty nephropathy.MethodsA total of 118 patients with gout nephropathy were included and divided randomly into a conventional treatment group (n=60) and a combined treatment group (n=58) according to the random number table method. The patients in the conventional treatment group were treated with allopurinol and those in the combined treatment group were treated with allopurinol and Yishen-Lishi formula, both for 3 months. Serum uric acid, blood urea nitrogen (BUN), serum creatinine (SCr), 24 h endogenous creatinine clearance (CCr), 24 h urine protein, urineb2 microglobulin, serum triacylglycerol (TG), serum total cholesterol (TC), serum apolipoprotein A1, 24 h urine volume and urine pH were determined. The therapeutic effect was evaluated.ResultsThe urine pH (6.43 ± 0.6vs.6.21 ± 0.4;t=2.351,P=0.020), 24 h urine volume (3.3 ± 0.4vs.2.8 ± 0.6 L;t=5.308,P<0.001), 24 h CCr (1.61 ± 0.11 ml/svs. 1.33 ± 0.10 ml/s;t=14.477,P<0.001) and serum apolipoprotein A1 (1.90 ± 0.40 g/Lvs. 1.01 ± 0.33 g/L;t=13.203,P<0.01) in the combined treatment groupwere significantly higher than those in the standard treatment group. The serum uric acid (312.01 ± 33.56mmol/Lvs.350.12 ± 35.21 mol/L;t=6.015,P<0.001), BUN (6.22 ± 0.91 mmol/Lvs.11.50 ± 4.01 mmol/L;t=9.586,P<0.001), SCr (87.32 ± 13.90mmol/Lvs.122.54 ± 18.37mmol/L;t=11.743,P<0.001), 24 h urine protein (0.7 ± 0.2 gvs.1.2 ± 0.5 g;t=7.087,P<0.001), urineb2 microglobulin (220.3 ± 90.3mg/Lvs.330.1 ± 90.1mg/L;t=6.611,P<0.01), serum TG (5.11 ± 0.50 mmol/Lvs.6.30 ± 0.50 mmol/L;t=12.923,P<0.001), serum TC (1.50 ± 0.50 mmol/Lvs.2.30 ± 0.52 mmol/L;t=8.689,P<0.001) in the combined treatment group were significantly higher than those in the standard treatment group. The total effective rate inthe standard treatment group was significantly higher than those in the standard treatment group (89.7%vs.70.0%;χ2=5.871,P=0.015). ConclusionYishen-Lishi formula combined with conventional treatmentmay protect renal function, and reduce the blood lipids, its therapeutic effect is superior to conventional treatment alone in patients with gouty nephropathy.

Strokes due to atrial fibrillation (AF) are common and frequently devastating.While oral anticoagulant agents are the mainstay in the prevention of embolic events,they have several limitations and not all patients can tolerate them long term.The left atrial appendage (LAA) has been identified as the source of thrombus formation in nonvalvular AF.Several LAA closure devices have been developed,they have been successful in stroke prevention in patients with nonvalvular AF and fewer periprocedural complications.This article reviews the application of percutaneous left atrial appendage closure for stroke prevention in patients with nonvalvular AF.

Objective To observe and explore clinical efficacy ofTianma-Gouteng decoction combined valsartan in the treatment of patients with renal hypertension and its effects on renal function. Methods A total of 130 patients with renal hypertension were enrolled and randomly divided into a study group (68 patients) and a control group (62 patients). Both groups were given prescription of lower sodium diet, exercising and enalaprilscheme. On this basis, the control group plus valsartan, and the study group was further added withTianma-Gouteng decoction. After 2 courses treatment, renal function, and blood pressure of both groups were compared, and clinical efficacy on blood pressure were evaluated.Results After treatment, the SBP (126.8 ± 9.1 mmHg vs. 134.1 ± 8.8 mmHg,t=4.648), DBP (82.4± 5.0 mmHgvs. 85.3 ± 5.4 mmHg, t=3.167), Scr (148.5 ± 46.3μmol/Lvs. 172.1 ± 52.0μmol/L, t=2.723), BUN (8.3 ± 2.7 mmol/Lvs. 9.7 ± 3.1 mmol/L,t=2.734) and 24hAlb (1.7 ± 0.6 gvs. 1.9 ± 0.7 g,t=2.209) in the study group were significantly lower than control group (P<0.05 orP<0.01). The total effective rate in the study group was significantly increased than that in the control group (91.2%vs. 79.0%;χ2=0.383,P=0.050).Conclusion Valsartan combined with Tianma-Gouteng decocntion can reduce blood pressure, and alleviate the kidney damage effectively.

Objective To evaluate the relationship of biological status of HPV 16 and expression of L1 protein with the degree of cervical tumorigenesis.Methods Sixty-one patients with cervical lessions were enrolled and divided into five groups according to pathology of cervical lesions,including chronic cervicitis(n = 27),cervical intraepithelial neoplasia(CIN) Ⅰ-Ⅱ(n = 10),carcinoma in situ(n = 8),early-stage(n =7)and mid/late-stage(n = 9)of cervical carcinoma.HPV type and its biological status were detected by PCR amplification,and L1 protein in HPV 16 positive tissues was detected by Western blot.Kruskal-Wallis was used to compare between the groups,and Pearson correlation analysis was used to evaluate the relationship of HPV biological status and L1 protain expression with cervical lesions.ResultsFifty-three out of 61 patients with cervical lesions were detected with HPV positive(86.9%).All 25 patients with chronic cervicitis were in HPV free mode; in CIN Ⅰ-Ⅱ group,6 patients were in free and 2 in integral mode; in carcinoma in situ group,1 patient in free,3 in mixed and 3 in integral mode; in the early-stage cervical cancer group,2 patients in mixed and 4 in integral mode; in mid/late-stage cancer group,1 patient in mixed and 6 in integral mode.A strong positive correlation was found between the HPV in integral mode and the severity of cervical lesions(r = 0.705,P ＜0.01).The expression of L1 protein was negatively correlated with the aggravation of cervical lesions in HPV 16-positive patients(r = -0.755,P ＜0.01).Conclusion The integral mode of HPV16 and low expression of L1 protein may have predictive value for the severity of cervical lesions.

Zinc-fingers and homeoboxes 2 (ZHX2) is a novel transcriptional repression factor participating in regulating the expression of alpha fetal protein (AFP). ZHX2 has been confirmed to be largely correlated with development and metastasis of hepatocellular carcinoma (HCC) and invasion of multiple myeloma.

Objective To observe the effects of misoprostol on the reduction of postpartum bleeding in cesarean section.Methods With oxytocin as control,the amount of bleeding during and two hours after cesarean section was observed.Results The mean amount of bleeding was (232.0±46.6) ml in misoprostol group and (385.0±74.7) ml in oxytocin group respectively.The difference between the two groups was significant (P＜0.01).Conclusion Misoprostol is more effective to improve uterin contraction than oxytocin and is better in the reduction of postpartum bleeding with safety and convenience.