1.RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ-AMPKα axis.
Lijun CAI ; Meimei YIN ; Shuangzhou PENG ; Fen LIN ; Liangliang LAI ; Xindao ZHANG ; Lei XIE ; Chuanying WANG ; Huiying ZHOU ; Yunfeng ZHAN ; Gulimiran ALITONGBIEKE ; Baohuan LIAN ; Zhibin SU ; Tenghui LIU ; Yuqi ZHOU ; Zongxi LI ; Xiaohui CHEN ; Qi ZHAO ; Ting DENG ; Lulu CHEN ; Jingwei SU ; Luoyan SHENG ; Ying SU ; Ling-Juan ZHANG ; Fu-Quan JIANG ; Xiao-Kun ZHANG
Acta Pharmaceutica Sinica B 2025;15(7):3611-3631
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.
2.Determination of chloride,sulfate and bicarbonate ions in Compound polyethylene glycol electrolyte powder (Ⅲ) by ion chromatography
Xianhua ZHANG ; Yuxin ZHAO ; Haiyan ZHOU ; Xiaolu ZHU ; Dengyan LAI ; Jiao ZHU ; Tao PENG ; Shichun YE
China Pharmacy 2024;35(22):2769-2772
OBJECTIVE To establish an ion chromatography method for the simultaneous determination of chloride, sulfate and bicarbonate ions in Polyethylene glycol electrolyte powder (Ⅲ). METHODS The chromatographic column was a Dionex IonpacTM AS11-HC anion analysis column, with a Dionex IonPacTM AG11-HC guard column. The mobile phase was 10 mmol/L potassium hydroxide at an isocratic elution flow rate of 1.2 mL/min. The detector was a conductivity detector, and the suppressor was a Dionex AERS with a suppressor current of 30 mA. The column temperature was maintained at 30 ° C, and the injection volume was 10 μL. Chloride and sulfate contents were calculated by external standard method, while bicarbonate content was determined by double logarithmic fitting standard curve method. RESULTS Under these chromatographic conditions, chloride, sulfate and bicarbonate ions were effectively separated with linear ranges of 0.055 to 0.219 mg/mL (r=0.999 9), 0.155 to 0.618 mg/mL (r=1.000 0), and 0.065 to 0.121 mg/mL (r=0.999 9), respectively. The recoveries were 98.06% to 101.34%, 97.37% to 101.25%, and 97.16% to 99.81%, respectively, with RSDs of 1.1%, 1.3% and 1.0% (n=9). The RSDs for the evaluation of precision, accuracy, stability and ruggedness were all less than 2%. CONCLUSIONS The established ion chromatography is simple, rapid, accurate, precise and durable, can simultaneously determine the contents of chloride, sulfate and bicarbonate ions in Polyethylene glycol electrolyte powder (Ⅲ), which is suitable for its quality control.
3.The Genetic Polymorphism and Structural Analysis of 47 Microhaplotypes in a Jiangsu Changshu Chinese Han Population
Kun-Peng PAN ; Yao-Sen FENG ; Wen-Shuai YU ; Zong-Wei LIU ; Yi-Ren YAO ; Jie ZHAO ; Ke-Lai KANG ; Chi ZHANG ; Le WANG ; Jian WU
Progress in Biochemistry and Biophysics 2024;51(2):423-434
ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (Ae) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.
4.Intervention of best possible self for mental health in new recruits during intensive training
Zihao JIN ; Han LAI ; Gongjin CHEN ; Wen HAO ; Aijun ZHAO ; Xuanyun YAN ; Bo LIU ; Li PENG ; Min LI
Journal of Army Medical University 2024;46(8):912-918,封3
Objective To investigate the intervention efficacy of best possible self (BPS)on the mental health of new recruits (including state optimism and pessimism,perceived stress and subjective well-being).Methods A non-randomized controlled trial was conducted on 212 new recruits subjected with cluster sampling from an army unit in a training base for new recruits in September 2023.Based on their organizational structure,they were divided into a study group (n=100,receiving BPS intervention 15 min/d,for 2 consecutive weeks)and a control group[n=112,typical day (TD)intervention,15 min/d,same period].Future Expectancy Scale (FEX),Chinese Perceived Stress Scale (CPSS),Positive and Negative Affect Scale (PANAS ) and Satisfaction with Life Scale (SWLS ) were used to measure the 2 groups of participants at T0 (baseline),T1 (end of the first week of intervention),T2 (end of the second week of intervention)and T3 (1 week after the end of intervention)in order to evaluate the intervention efficacy on above mentioned mental health indicators.Results There were no significant differences in demographic and baseline psychological variables listed above between the 2 groups.However,as the training progressed,obvious differences were observed in the training effects on state pessimism,perceived stress and subjective well-being (including affective and cognitive well-being)between them.When compared with the baseline data (T0),the study group had notably reduced state pessimism (P<0.01)and elevated affective (P<0.001) and cognitive well-being (P<0.001)during T1 and T3,and decreased perceived stress at T1 (P<0.05)and T3 (P<0.001).However,no such changes of above indicators were observed in the control group before and after training.Conclusion A 2-week BPS intervention can effectively reduce state pessimism and perceived stress,promote subjective well-being,and improve mental health in new recruits during new recruit training.
5.Screening and bioinformatics analysis of SNP in PPARGC1B gene of Sichuan Yak
Xuanxu CHEN ; Xinyi JIANG ; Jinghao PENG ; Jing LI ; Fengshuai MIAO ; Zhihui ZHAO ; Haibin YU ; Weizhong LAI ; Ping JIANG ; Ziwei LIN
Chinese Journal of Veterinary Science 2024;44(10):2179-2189
The peroxisome proliferator-activated receptor gamma(peroxisome proliferator-activated receptor gamma,coactivator 1 beta,PPARGC1B)gene is an intranuclear receptor transcription fac-tor responsible for regulating the expression of target genes.To comprehend the characteristics and mutations of the PPARGC1B gene within the Sichuan yak population,the SNP loci of the PPARGC1B gene were identified through direct sequencing of PCR products.Additionally,the cod-ing region of the PPARGC1B gene was obtained via PCR amplification and sequencing.Bioinforma-tics analyses were conducted to predict protein-coding and mRNA secondary structure.This study identified four exon SNP mutation sites(E9-189A→C,E9-387G→A,E9-542C→T,and E9-554T→C)based on the single nucleotide polymorphism analysis of the PPARGC1B gene in Sichuan yaks.Notably,the E9-387G→A and E9-554T→C loci exhibited significant correlations with shear force and backfat thickness in Sichuan yaks.Subsequently,bioinformatics analysis of the four mutation sites revealed that the PPARGC1B protein is an acidic,unstable,non-transmembrane,and non-secretory hydrophilic protein with a coiled helix structure.It lacks a signal peptide and transmembrane region,predominantly functions in the nucleus,and features 106 phosphorylation sites,one glycosylation site,and one conserved RRM structure.The secondary structure comprises mainly α-helix and random coils.Although the protein structure of the PPARGC1B gene remained unchanged post-mutation,there were significant differences in mRNA secondary structure.These findings suggest that the polymorphic loci of the PPARGC1B gene in Sichuan yaks could serve as a theoretical basis for enhancing meat quality traits through molecular biological methods,presen-ting practical applications in breeding.
6.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
7.Chemical constituents from the methanol fraction of Premna fulva leaves and their anti-inflammatory activities
Fei-Fan HE ; Ning-Tao ZHAO ; Xiao-Jie YAN ; Feng-Lai LU ; Xiao-Hua JIANG ; He-Ping LI ; Dian-Peng LI ; Yue-Yuan CHEN
Chinese Traditional Patent Medicine 2024;46(6):1894-1899
AIM To study the chemical constituents from the methanol fraction of Premna fulva Craib leaves and their anti-inflammatory activities.METHODS The methanol fraction from P.fluva were isolated and purified by TLC,column chromatography,and HSCCC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Twelve compounds were isolated and identified as vitexin(1),balanophonin(2),inotodisaccharide(3),4-allyl-2,6-dimethoxyphenol-β-D-glucopyranoside(4),dehydrovomifoliol(5),loliolide(6),(E)-4-((1S,3R,4R)-1-hydroxy-4,5,5-trimethyl-7-oxabicyclo[4.1.0]heptan-1-yl)but-1-en-3-o-ne(7),(E)-4-hydroxyphenylprop-7-ene 4-O-β-D-glucopyranoside(8),4-O-β-D-glucopyranosylbenzoic acid(9),vicenin(10),oleanicacid(11),sesamin(12),respectively.Compounds 1,2,5,7,10,and 12 showed good inhibitory activities against NO,and the IC50 values were(26.42±2.5)、(21.24±2.2)、(25.88±1.9)、(29.72±2.1)、(8.90±1.1)、(9.73±0.7)μmol/L,respectively.CONCLUSION Compounds 2,4-8 are isolated from Premna genus plants for the first time.Compounds 1,2,5,7,10,12 have anti-inflammatory activities.
8.Investigation on total radioactivity in drinking water following operation of the second phase expansion project at Qinshan Nuclear Power Plant
Lei ZHOU ; Yiyao CAO ; Hong REN ; Peng WANG ; Hua ZOU ; Shunfei YU ; Yaoxian ZHAO ; Zhiqiang XUAN ; Zhongjun LAI ; Dongxia ZHANG
Chinese Journal of Radiological Medicine and Protection 2023;43(12):1003-1009
Objective:To investigate and analyze the level of the gross radioactivity, and its variation trend, in surrounding drinking water since the second phase expansion project at Qinshan Nuclear Power Plant was officially put into operation.Methods:From 2010 to 2022, the source water, factory water and tap water within 30 km of Qinshan Nuclear Power Plant were collected in the flood season (May) and dry period (October) every year. The total α and total β radioactivity concentrations in drinking water was measured and analyzed. The levels of total radioactivity in drinking water around different nuclear power plants in China and around non-nuclear power plant areas was compared.Results:The mean radioactivity concentrations of total α and total β were (0.021±0.019) and (0.204±0.058) Bq/L in source water, (0.010±0.005) and (0.185±0.056) Bq/L in factory water , and (0.012±0.007) and (0.170±0.058) Bq/L in tap water, respectively, all lower than the limits stipulated in the Sanitary Standards for Drinking Water. There were no significant differences in the monitoring result of betweem the three types of water samples both in the flood and dry periods ( P> 0.05). The total radioactivity level in drinking water around Qinshan Nuclear Power Plant site was close to that in drinking water around different nuclear power plants in China and around areas without nuclear power plants. Conclusions:Following the second phase of the expansion project officially being put into operation, the total α and β radioactivity level in drinking water around the Qinshan Nuclear Power Plant has been in a stable trend and lower than the guidance level given in national standard.
9. Effects of methionine restriction on oral cancer cell proliferation, migration and invasion
Yue-Rong PENG ; Ke-Xin ZHENG ; Han-Si CHEN ; Xue-Peng WANG ; Yun-Hao LAI ; Su-Jin ZHOU ; Zi-Jian ZHAO ; Zheng-Gang ZHAO ; Fang-Hong LI
Chinese Pharmacological Bulletin 2023;39(8):1444-1450
Aim To investigate the effect of methionine restriction on the proliferation, migration and invasion of human oral squamous carcinoma CAL-27 cells. Methods Cell proliferation and colony formation ability were detected by cell counting and colony forming assay. The changes in cell cycle and apoptosis were detected by propidium iodide (PI) staining flow cytometry and Annexin V/7-amino-actinomycin staining flow cytometry. The migration and invasion ability of CAL-27 was detected by scratch and Transwell assay. The expression levels of apoptosis proteins Bax and Bcl-2, cyclins CDK2 and CDK4 and migration and invasion proteins N-cadherin and E-cadherin were examined by Western blot. Results Methionine restriction significantly inhibited the proliferation and clone formation of oral squamous cancer cell CAL-27 (P < 0. 01), induced cell cycle arrest at G
10. Prevention and inhibition of nasopharyngeal carcinoma growth by attenuated salmonella SGN1
Yun-Hao LAI ; Ting-Qi HUANG ; Shi LIU ; Yue-Rong PENG ; Fang-Hong LI ; Zheng-Gang ZHAO ; Su-Jin ZHOU ; Zi-Jian ZHAO ; Qi-Ting TAN ; Jia-Luo MAI
Chinese Pharmacological Bulletin 2023;39(10):1867-1873
Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

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