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.

OBJECT IVE To deeply unders tand the utilization of monoclonal antibody drugs in different levels of medical institutions in China ，so as to provide an empirical basis for further promoting tiered healthcare delivery system. METHODS The basic informations of listed monoclonal antibody drugs in China as of May 2021 were collected through the official websites of government agencies such as National Medical Products Administration and National Healthcare Security Administration ，so as to understand the overall development status of monoclonal antibody drugs in China. The clinical utilization data of monoclonal antibody drugs in all categories of antitumor drugs and immune modulators were collected through “chemical drug terminal of Chinese public medical institutions ”database of Metnet ；the clinical application of monoclonal antibody drugs in medical institutions at different levels was analyzed. RESULTS As of May 2021，there were 53 monoclonal antibody drugs had been approved for listing in China ，including 31 imported monoclonal antibody drugs and 22 domestic monoclonal antibody drugs. From 2015 to 2019，the amount and quantity of monoclonal antibody drugs used in urban medical institutions were the highest among the three levels of medical institutions （both accounted for more than 95％ for five consecutive years ），but the growth rate of drug use in county-level medical institutions was the fastest. In 2019，the cumulative proportion of DDDs and drug amount of the top 10 monoclonal antibody drugs ranked in DDDs were the highest among county-level medical institutions ，being 97.09％ and 94.16％ respectively. From the change trend of DDDc of monoclonal antibody drugs from 2015 to 2019，DDDc of cetuximab decreased the most （70.32％），followed by trastuzumab （67.29％） and bevacizumab（62.89％）. From 2015 to 2019，the number of monoclonal antibody drugs with B/A value of no less than 1 ranked the top 10 of the annual cost were 6，6，6，7 and 5， respectively. CONCLUSIONS In China ，the overall approval and listing speed of monoclonal antibody drugs has accelerated，their quantity has increased rapidly ，and the accessibility is also improved. Among them ，the quantity of monoclonal antibody drugs has increased the fastest in county-level medical institutions ，and they are mainly medical insurance drugs ，and the effect of tiered healthcare delivery system has gradually appeared.

Objective:To analyze the correlation of phthalate metabolites in neonatal umbilical cord blood with birth indicators in Beijing, 2015.Method:From February to July in 2015, 161 pregnant women and their newborns who met the criteria were recruited from the Maternal and Child Health Hospital in Haidian District, Beijing. Questionnaires were used to collect the demographic information of pregnant women such as age, smoking, drinking, and cord blood after delivery. An ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of phthalate metabolites in umbilical cord blood. The multiple linear regression model was used to analyze the correlation of phthalate metabolites in umbilical cord blood with the neonatal weight, length, and ponderal index.Result:The age of 161 pregnant women was (30.3±3.0) years. The weight, length and ponderal index of 161 newborns were (3 447.2±413.0) kg, (50.2±1.1) cm, and (26.7±2.2) kg/m 3; 51.6% of newborns (83 cases) were boys. The concentrations of seven phthalate metabolites detected in umbilical cord blood, i.e., mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP),mono-(2-isobutyl) phthalate (MiBP), mono-n-butyl phthalate (MBP), mono-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), was (3.50±0.28), (2.65±0.47), (4.31±0.55), (6.26±0.57), (1.71±0.13), (1.10±0.09) and (0.47±0.06) ng/ml, respectively. The result of multiple linear regression model analysis showed that the concentrations of seven phthalate metabolites were not related to the neonatal weight, length, and ponderal index (all P values> 0.05). Conclusion:The concentrations of phthalate metabolites in neonatal umbilical cord blood are low, and they are not related to the neonatal weight, length, and ponderal index.

Objective:To analyze the correlation of phthalate metabolites in neonatal umbilical cord blood with birth indicators in Beijing, 2015.Method:From February to July in 2015, 161 pregnant women and their newborns who met the criteria were recruited from the Maternal and Child Health Hospital in Haidian District, Beijing. Questionnaires were used to collect the demographic information of pregnant women such as age, smoking, drinking, and cord blood after delivery. An ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of phthalate metabolites in umbilical cord blood. The multiple linear regression model was used to analyze the correlation of phthalate metabolites in umbilical cord blood with the neonatal weight, length, and ponderal index.Result:The age of 161 pregnant women was (30.3±3.0) years. The weight, length and ponderal index of 161 newborns were (3 447.2±413.0) kg, (50.2±1.1) cm, and (26.7±2.2) kg/m 3; 51.6% of newborns (83 cases) were boys. The concentrations of seven phthalate metabolites detected in umbilical cord blood, i.e., mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP),mono-(2-isobutyl) phthalate (MiBP), mono-n-butyl phthalate (MBP), mono-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), was (3.50±0.28), (2.65±0.47), (4.31±0.55), (6.26±0.57), (1.71±0.13), (1.10±0.09) and (0.47±0.06) ng/ml, respectively. The result of multiple linear regression model analysis showed that the concentrations of seven phthalate metabolites were not related to the neonatal weight, length, and ponderal index (all P values> 0.05). Conclusion:The concentrations of phthalate metabolites in neonatal umbilical cord blood are low, and they are not related to the neonatal weight, length, and ponderal index.

Objective To discuss the value of ABCD2 score in predicting medium and long-term prognosis in patients with ischemic stroke.Methods 184 patients with ischemic stroke admitted to department of neurology from March 2014 to December 2014 were selected as the research object.According to the ABCD2 score points prior to admission, the patients were divided into 3 groups: 40 cases in the low risk group, 76 in the moderate group and 68 in the high risk group based on whether or to what extent he was able to do self care.The phone call reviews were made for the clinical symptoms of patients discharged from the hospital after six months..According to the modified Rankin scale classification standard, the patients discharged from the hospital after six months were divided into 2 groups: 126 cases in the self-care group and 56 cases in care-needing group.The groups were compared in terms of conditions.Results The self-care rate in the low risk group was 90.00%, the moderate group 77.63% and the high-risk group 45.59%.The care needing rates in the three groups was 5%, 19.74% and 48.53%, respectively.The care needing rate in the low risk group was obviously lower than that in the moderate-risk group and the high risk group (P<0.05).The care needing rate in the moderate risk group was obviously lower than that in the high risk group (P< 0.05).The self-care rates in the low risk group and the moderate group were higher than that in the high risk group (P<0.05).Conclusion The ABCD2 score has a higher predictive value for medium and long-term prognosis in patients with ischemic stroke.

Objective To investigate the effect of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on hypoxia/reoxygenation (H/R)-induced cardiomyocytes death under high glucose condition and the potential mechanisms.Methods H9C2 cardiomyocytes were divided into 4 groups:normal glucose (N,5 mmol/L),high glucose (G,20 mmol/L),high glucose in combination with liraglutide (L,100 nmol/L),high glucose in combination with liraglutide and wortmannin (W,25 nmol/L).The apoptosis of H9C2 was detected by TUNEL assay.Nitric oxide synthetase(eNOS),nitric oxide (NO) and reactive oxygen(ROS) in supernatants were measured by enzymatic analysis,p-PI3K,PI3K,p-Akt,Akt,Bcl-2,caspase-3 were examined by western blotting.Results Compared with cells in N group,the apoptosis of H9C2 cells induced by H/R was markedly increased [(15.79 ± 3.92) ％ vs (9.74 ± 1.14) ％,P =0.028] in G group.The same was true for ROS [(489.63 ±21.01) U/ml vs (338.50 ±43.60) U/ml,P ＜0.001] and caspase-3 levels (1.87 ±0.03 vs 1.15 ±0.04,P ＜0.001),but not for Bcl-2 protein expression (1.79 ± 0.06 vs 1.89 ±0.03,P =0.047).Pretreatment of cells with liraglutide (100 nmol/L) prevented the cell death induced by high glucose and H/R together with decrease of ROS and caspase-3 levels and increase of Bcl-1 expression.Moreover,treatment of cells with liraglutide also significantly increased phosphorylation of PI3K and Akt (p-PI3K/PI3K:0.87 ± 0.07 vs 0.59 ± 0.09,P =0.002;p-Akt/Akt:0.34 ± 0.01 vs 0.08 ± 0.01,P＜0.001),eNOS[(41.29 ±0.56) μmpl/L vs (37.20 ±0.52)μxmpl/L,P ＜0.001]and NO [(31.24 ±0.40) μmpl/L vs (26.66 ±0.53) μmpl/L,P ＜0.001] levels.Furthermore,addition of PI3K/Akt inhibitor wortmanin markedly inhibited the expression of p-PI3K/PI3K,p-Akt/Akt,reversed the changes of eNOS,NO,caspase-3 and Bcl-2 by liraglutide,and abolished the protective effect of liraglutide on cell apoptosis.Conclusions GLP-1 receptor agonist liraglutide treatment could alleviate cardiomyoeytes apoptosis induced by high glucose and H/R through the activation of PI3K-Akt-eNOS-NO signaling pathway and inhibition of oxidative stress.

The article introduces the concept of stigma and the measurement tools of stigma in abortion women as well as research progress of sociological factors, quality of life and interventions of abortion women. This article points out that china is still lack of related research. Strengthening the care for artificial abortion women from people of all walks of life is called on.

Abstrac:Aim To study the effect of hydroxysafflor yellow A ( HYSA ) on the proliferation of vascular smooth muscle cells ( VSMCs) and the related molecu-lar mechanism. Methods The inhibitory effects of hydroxysafflor yellow A on VSMC proliferation was de-tected using cell culture, MTT assay, Western blot and immunohistochemical staining. Results The results showed that HYSA inhibited cell proliferation induced by PDGF in a dose-dependent (5,10,20,40 μmol· L-1 ) manner, reduced proliferating cell nuclear anti-gen ( PCNA ) expression and blocked PDGFR-MEK-ERK1/2 signaling pathway activated by PDGF in VSMCs. Conclusion HYSA inhibits VSMCs prolifer-ation via reducing the expression of PCNA and blocking signal transduction of MEK-ERK1/2 in VSMCs.

BACKGROUNDAs an X-linked recessive way, arginine vasopressin receptor 2 (AVPR2) gene mutation resulted in a hereditary disease - congenital nephrogenic diabetes insipidus (CNDI). We found a suspect clinical CNDI pedigree. In order to identify the genetic etiology, we performed the genetic analysis.

METHODSThe clinical features of the proband and his family members were recorded. The laboratory tests and imaging inspections were analyzed. The water deprivation and pituitrin loading test were performed in the proband and his brother. The genomic DNA of all the members of the pedigree was extracted and then PCR amplification on AVPR2 gene was carried out. Sequencing in both directions was performed to identify mutation on AVPR2 gene.

RESULTSBoth the proband and his brother were diagnosed as CNDI, meanwhile the other members of this pedigree were normal. No severe biochemical abnormality was found in the two CNDI patients. Both the patients had moderate urinary retention, severe megaloureter and hydronephrosis, and mild renal insufficiency. Two mutations of AVPR2 gene were discovered in the 3rd exon in the patients, a silent mutation L309L and a nonsense mutation R337X. The AVPR2 gene R337X mutation was co-segregated with CNDI. R337X mutation was not a reported mutation in the mainland of China.

CONCLUSIONThe AVPR2 gene R337X mutation was also a genetic etiology of CNDI patients in the mainland of China.

Adult ; Diabetes Insipidus, Nephrogenic ; genetics ; Female ; Humans ; Male ; Mutation ; Pedigree ; Receptors, Vasopressin ; genetics ; Vasopressins ; genetics

Objective To observe the effect of fluvastatin on urinary albumin excretion rate(UAER)of microalbuminuria in type 2 diabetes patients.Methods Type 2 diabetes patients with mieroalbuminuria were randomly divided into fluvastatin goup(n=126)and control group(n=129).Fluvastatin group was given fluvastatin 40 mg each night.Follow up was conducted for 1.5 years.The UAER and glomerular filtration rate(GFR)as well as blood lipid level before and after therapy were compared.Results UAER in fluvastatin group was significantly lower than that in control group[(59.6±10.5)vs(87.5±12.3)mg/min,P＜0.05]before therapy[(104.4±25.2)vs(110.6±19.7)mg/min,P＜0.05],which was independent of its lowering-lipid effect.But GFR had no signifimicroalbuminuria which is independent of lowering-lipid effect in type 2 diabetic nephropathy patients and delay the progress of diabetic nephropathy.