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.Wendan Decoction ameliorates metabolic phenotypes in rats with metabolic syndrome and phlegm syndrome by modulating the gut microbiota-bile acid axis.
Kaiyue HUANG ; Jingxin QI ; Wenqian LUO ; Yixuan LIN ; Meimei CHEN ; Huijuan GAN
Journal of Southern Medical University 2025;45(6):1174-1184
OBJECTIVES:
To investigate the therapeutic mechanism of Wendan Decoction for phlegm syndrome in rats with metabolic syndrome (MS).
METHODS:
Forty Wistar rats were randomly divided into normal control group (n=8) and 3 phlegm syndrome model groups (induced by high-fat, high-sugar, and high-salt feeding and a single-dose intraperitoneal STZ injection; n=24) treated with daily gavage of saline, Wendan Decoction (3.6 g/kg), or metformin (0.1 g/kg) for 4 weeks. General conditions and glucose and lipid metabolism parameters of the rats were monitored, and serum LPS, liver histopathology, hepatic expressions of FXR, CYP7A1 and FGFR4 and ileal expressions of FXR and FGF15 were examined. Gut microbiota structure was analyzed using 16S rDNA sequencing, and serum bile acids were quantified with UHPLC-MS/MS.
RESULTS:
The rat models of phlegm syndrome exhibited severe hepatic steatosis and necrosis, increased body weight, abdominal circumference, Lee's index, FBG, FINS, HOMA-IR, TG, TC, LDL and LPS, and decreased HDL level. The abundance of Bacteroidetes, Megamonas, and Bacteroides in gut microbiota increased while Firmicutes, Lachnospiraceae_NK4A136_group, isohyodeoxycholic acid, and glycohyodeoxycholic acid decreased significantly; hepatic FXR and FGFR4 expressions and ileal FXR and FGF15 expressions decreased while hepatic CYP7A1 expression increased significantly in the rat models. Treatment with Wendan Decoction effectively alleviated hepatic pathology, reduced body weight and abdominal circumference, improved glucose and lipid metabolic profiles and gut microbiota structure, and reversed the changes in hepatic and ileal protein expressions. Correlation analysis revealed that Firmicutes and Lachnospiraceae_NK4A136_group were positively correlated while Bacteroidetes, Megamonas and Bacteroides were negative correlated with the levels of isohyodeoxycholic acid and hyodeoxycholic acid.
CONCLUSIONS
Wendan Decoction can significantly improve metabolic profiles in rats with phlegm syndrome of MS possibly by regulating the intestinal flora-bile acid axis to modulate the intestinal flora structure and maintain bile acid homeostasis via the FXR signaling pathway.
Animals
;
Gastrointestinal Microbiome/drug effects*
;
Metabolic Syndrome/microbiology*
;
Bile Acids and Salts/metabolism*
;
Rats, Wistar
;
Drugs, Chinese Herbal/therapeutic use*
;
Rats
;
Male
;
Fibroblast Growth Factors/metabolism*
;
Liver/metabolism*
;
Cholesterol 7-alpha-Hydroxylase/metabolism*
;
Receptors, Cytoplasmic and Nuclear/metabolism*
3.Effect of modified Zhuyu Decoction combined with oxytocin on uterine involvment and residual of placenta in postpartum patients
Wenjing LIN ; Yuting HU ; Meimei WANG ; Jun WANG ; Yajie YAN
Journal of Chinese Physician 2024;26(11):1642-1646
Objective:To investigate the effect of Jiawei Zhuyu Decoction combined with oxytocin on uterine involvement and residual of placenta in postpartum patients.Methods:A total of 91 patients with postpartum placenta residue admitted to Baoji Central Hospital from January 2023 to January 2024 were selected as the study objects. According to random number table method, the patients were divided into observation group (45 cases) and control group (46 cases). The control group was treated with oxytocin, and the observation group was treated with Jiawei Zhuyu decoction. Treatment effect, Traditional Chinese Medicine (TCM) symptom score, Visual Analogue Scale (VAS) score, SF-36 score, uterine reversion, uterine residual area, levels of beta human chorionic gonadotropin (β-HCG), progesterone (P), estradiol (E 2), duration of vaginal bleeding, length of hospital stay and adverse reactions were compared between the two groups. Results:The total effective rate of the observation group was higher than that of the control group [95.6%(43/45) vs 78.3%(36/46), χ 2=5.943, P=0.015]. After treatment, TCM syndrome scores, VAS scores and SF-36 scores of 2 groups were significantly improved (all P<0.05), and TCM syndrome scores and VAS scores of observation group were lower than those of control group, and SF-36 scores were higher than those of control group (all P<0.05). After treatment, the sum of three diameters of uterus, endometrial thickness and area of uterine residue in both groups decreased (all P<0.05), and the sum of three diameters of uterus, endometrial thickness, rate of uterine decline and area of uterine residue in the observation group were smaller than those in the control group (all P<0.05). After treatment, the levels of β-HCG, P, E 2 in 2 groups were improved compared with before (all P<0.05), and the levels of β-HCG and P in observation group were lower than those in the control group, and E 2 levels were higher than those in the control group (all P<0.05). The duration of vaginal bleeding and hospitalization in the observation group were shorter than those in the control group (all P<0.05). The incidence of adverse reactions in the observation group was lower than that in the control group [6.67%(3/45) vs 21.7%(10/46), χ 2=4.220, P=0.040]. Conclusions:Jiawei Zhuyu Decoction combined with oxytocin has a good effect on postpartum placenta residue, can effectively reduce the intrauterine placenta residue, promote uterine involution, and accelerate the recovery of patients.
4.Application effect of theory of inventive problem solving in the management of loaner instruments in central sterile supply department
Qian LU ; Fang YAO ; Lin JIA ; Yali WANG ; Zhezhe HE ; Meimei YU ; Lili WANG ; Xiaomei XU ; Na YANG ; Rui LIU
China Medical Equipment 2024;21(9):150-154
Objective:To explore the application effect of theory of inventive problem solving(TRIZ)in the management of loaner instruments in central sterile supply department(CSSD).Methods:TRIZ management team was set up to analyze problems in cleaning,disinfection and sterilization of loaner instruments.The invention principles of TRIZ were compared to determine targeted solutions to the corresponding problems.A total of 1,000 pieces of loaner instruments received by The Third Affiliated Hospital of Air Force Medical University were selected from January and December 2023 were selected,the 500 pieces received from January to June were managed by routine standard management mode,and the 500 pieces received from July to December were managed by the TRIZ management mode.The qualification rates of instruments cleaning,disinfection,packaging and sterilization,the incidence of adverse events,the satisfaction scores of clinical departments and assessment results of newly hired nurses of CSSD were compared between the two management modes.Results:The qualification rates of instruments cleaning,disinfection,packaging and sterilization of TRIZ management mode were 98.00%(490/500),97.20%(486/500),96.40%(482/500)and 96.00%(480/500),respectively,which were higher than those of routine standard management mode,the difference was statistically significant(x2=12.029,11.685,8.859,8.322,P<0.05).The incidence of adverse events of TRIZ management mode was 0%,the routine standard management mode was 1.20%,the difference was statistically significant(x2=6.036,P<0.05).The average scores of CSSD newly hired nurses in of theoretical knowledge,treatment process,cleaning,disinfection and sterilization and packaging of TRIZ management mode were(89.20±6.69)points,(88.47±3.48)points,(92.47±5.37)points and(92.00±5.83)points,respectively,which were higher than those of routine standard management mode,the difference was statistically significant(t=3.993,4.402,3.926,3.332,P<0.05).The satisfaction scores of clinical department personnel with instruments quality,distribution,handover,information traceability,service attitude and overall satisfaction of TRIZ management mode were(18.65±0.81)points,(18.85±1.04)points,(18.95±1.05)points,(18.40±0.75)points,(18.35±0.93)points and(93.20±1.91)points,respectively,which were higher than those of the routine standard management mode,the difference was statistically significant(t=3.599,5.889,4.851,4.865,2.075,8.723,P<0.05).Conclusion:The application of TRIZ in the management of loaner instruments in CSSD can significantly improve theoretical knowledge and practical skills of newly hired nurses in CSSD,thereby improving the qualification rates of instruments cleaning,disinfection,packaging and sterilization of loaner instruments,reducing the occurrence of instrument-related adverse events and improving satisfaction of department personnel with instruments use.
5.Establishment and application of drug use evaluation criteria for aspirin enteric-coated tablets
Meimei LIN ; Jing ZHANG ; Caiyun ZHENG ; Yan CHEN ; Yanling GAO ; Shicai CHEN ; Jinhua ZHANG
Chinese Journal of Pharmacoepidemiology 2024;33(5):489-499
Objective To establish the drug use evaluation(DUE)criteria for aspirin enteric-coated tablets and provide a reference for the rationally clinical application of aspirin enteric-coated tablets.Methods DUE criteria for aspirin enteric-coated tablets were established from three aspects of indications,medications and medication results with reference to drug instructions of aspirin enteric-coated tablets,related guidelines,expert consensus and literature,and through Delphi method.A retrospective analysis was conducted to evaluate the medical records of patients who took aspirin enteric-coated tablets from January 2021 to June 2022 in Fuqing Hospital affiliated to Fujian Medical University.Results A total of 1 071 medical records were included.683 cases fully met the DUE criteria,with a rational rate of 63.77%.Irrational drug use mainly included inappropriate indications(6.26%),off-label drug use without approval(28.48%),contraindications(1.03%),inappropriate usage and dosage(1.68%),drug interactions with potential clinical significance(0.65%)and other inappropriate drug use(2.71%).Conclusion The established DUE standard for aspirin enteric-coated tablets has strong scientific practicability and feasibility.The irrational rate of aspirin enteric-coated tablets in this hospital is high.Corresponding intervention measures should be formulated to ensure the safety of clinical medication.
6.Research progress on health literacy of cancer caregivers
Huan LIN ; Meimei SHANG ; Qian WANG ; Tingting SHEN ; Wenchong LIU ; Hongxia GE
Chinese Journal of Practical Nursing 2023;39(5):390-395
This paper was reviewed the research status of health literacy of cancer caregivers, including an overview of health literacy, assessment tools for health literacy of cancer caregivers, factors affecting health literacy of cancer caregivers and measures to improve health literacy of cancer caregivers. To provide theoretical basis for the localized development of health literacy assessment tools for cancer caregivers and further research.
7.User persona application in the field of cancer basing on online health community: a scoping review
Yuting LIN ; Zhumei SHAO ; Meimei SHANG ; Qian WANG ; Rong YAN ; Min DING ; Xiangmin MENG
Chinese Journal of Practical Nursing 2023;39(11):871-876
Objective:To summarize the research on the application of online health community-based user personain the field of cancer at home and abroad, so as to provide reference for the related research and application in this field in the future.Methods:Computer search of CNKI, China biomedical literature database, VIP, Wanfang, Web of Science, Embase, MEDLINE, PubMed, CINAHL, Cochrane Library, a total of 10 Chinese and English databases, focused on the relevant research on building user personas based on online health communities in the field of cancer, and the search time limit was from the establishment of the database to April 20, 2022. Literature was screened, data extracted and summarized.Results:Totally 11 literatures were included. The construction process of user persona based on online health community included data collection, tag extraction and persona presentation. The functional diversity and implementation feasibility were showed in the application content in the field of cancer. It can quickly identify the differences in health information needs of cancer patients, provide personalized decision support and nursing services, strengthen health information education, and improve patients′ self-management ability.Conclusions:The integration of user persona and cancer field based on online health community was in the initial exploration stage, and the feasibility and effectiveness of promoting patients′ health behavior were confirmed by existing studies. In the future, it is still necessary to be promoted in the empirical research on its application in clinical practice, so as to lay a foundation for providing targeted patient health management programs in the future.
8.Basic skills level of health literacy and its influencing factors in permanent residents in Fujian province in 2020
Zhu LIN ; Meimei XIE ; Jinhui CHEN
Chinese Journal of Health Management 2023;17(2):124-129
Objective:To investigate and analyze on the basic skills level of health literacy and its influencing factors in permanent residents in Fujian province in 2020.Methods:In this cross-sectional study, from April to November in 2020, 3 304 urban and rural permanent residents aged 15-69 years in 13 counties (cities or districts) in Fujian province were selected by stratified multistage cluster sampling and random sampling for household questionnaire survey. Based on “Health literacy of Chinese citizens—basic knowledge and skills”, the questionnaire included three aspects: basic knowledge and concept, healthy lifestyle and behavior and basic skills. There were 50 questions in total, including 12 questions about basic skills with a total score of 16 points. A score of 13 points and above was considered as having basic skills. A total of 3 304 questionnaires were issued and reclaimed, and among which 3 250 questionnaires were valid. According to the data of the Sixth National Census in 2010 in Fujian province and the basic data collected in the monitoring process, the basic weight, no response and post-stratification adjustment of the samples were made to obtain the representative data of the province. The χ2 test and multivariate logistic regression were applied to analyze the influencing factors of basic skill level of health literacy in permanent residents in Fujian province in 2020. Results:According to the weighted data, the basic skill level of health literacy in permanent residents in Fujian province in 2020 was 26.02%, and it was higher in urban area than that in rural area (35.00% vs 20.15%). It was higher in people aged 25-34 years (35.36%), people with high education level (college/undergraduate and above 47.20%), civil servants (47.49%), medical personnel (44.00%), people with chronic diseases (27.04%) and people with good health condition (31.31%), respectively (all P<0.05). Among the 12 questions on basic skills, the correct rate in 6 questions was ≥50%. The question with the highest correct rate was “The correct practices after the occurrence of severe infectious diseases in the local area” (88.2%), and the question with the lowest correct rate was “Correctly identify drugs with‘OTC’ printed on the label”(28.7%). Education level (illiterate/less literate, OR=0.036, 95% CI: 0.018-0.073; primary school, OR=0.091, 95% CI: 0.053-0.155; junior high school, OR=0.230, 95% CI: 0.148-0.357; senior high school/vocational high school/technical secondary school, OR=0.351, 95% CI: 0.232-0.532; college/undergraduate and above, OR=1.000) was positively correlated with the basic skill level of residents′ health literacy ( P<0.001). Conclusions:The overall level of basic health skills in permanent residents in Fujian province in 2020 is relatively high, educational level is a positive correlation factor.
9.A Meta-synthesis of qualitative studies of treatment experiences in cancer patients receiving immune checkpoint inhibitors therapy
Xiangmin MENG ; Meimei SHANG ; Qian WANG ; Rong YAN ; Kai JIANG ; Wenhui LIU ; Junai XIANG ; Yuting LIN ; Min DING
Chinese Journal of Practical Nursing 2023;39(32):2553-2561
Objective:To synthesize the findings of qualitative research on the treatment experience of cancer patients receiving immune checkpoint inhibitors therapy to provide a basis for developing relevant health education strategies and other supportive care interventions.Methods:Qualitative research on the treatment experience of cancer patients receiving immune checkpoint inhibitors therapy, published by May 2022, were searched in English and Chinese databases, including Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, Web of Science, CNKI, Wanfang, VIP, and CBM. The quality of the included studies was evaluated by Joanna Briggs Institute Critical Appraisal Tool for qualitative studies. The research results were summarized and Meta-synthesis using the pooled integration method.Results:A total of 13 articles were included and 62 findings were grouped into 12 new categories according to their similarities. These 12 categories resulted in 4 synthesized findings: life was affected, facing multiple decision scenarios, presence of some unmet needs and gaining positive experiences and personal growth.Conclusions:Although patients experience some positive experiences, a large proportion of them experience significant health distress. Healthcare professionals should develop targeted health education with supportive care strategies on the basis of a comprehensive assessment.
10.Predictive value of serum ferritin in early gestation,pre-pregnancy body mass index and gestational age for gestational diabetes mellitus
Meimei LIN ; Hongping ZHANG ; Xiaoyuan HUANG ; Ye WANG ; Yanjun HU
China Modern Doctor 2023;61(36):18-20,24
Objective To investigate the predictive value of serum ferritin(SF)in early gestation,pre-pregnancy body mass index(BMI)and gestational age for gestational diabetes mellitus(GDM).Methods A total of 260 pregnant women who had a routine prenatal examination in Wenzhou People's Hospital were collected from January 2021 to December 2022.Fasting venous blood was collected at the first prenatal examination(within 14 weeks'gestation)for SF.According to the results of 75 grams oral glucose tolerance test(OGTT)between 24 weeks and 28 weeks,they were divided into GDM group(n=62)and normal glucose tolerance(NGT)group(n=198).The general clinical data of the two groups were compared;Multivariate Logistic regression analysis was conducted to determine the independent risk factors of GDM.Receiver operating characteristic(ROC)curve was used to further analyze the predictive value of SF in early gestation,pre-pregnancy BMI and gestational age for GDM.Results Pregnant women in GDM group had higher SF,BMI and gestational age in early pregnancy than those of NGT group(P<0.05).Pre-pregnancy BMI,gestational age and SF increased in early pregnancy were independent risk factors for GDM(P<0.05).The area under the curve(AUC)of SF in early pregnancy as well as pre-pregnancy BMI and gestational age for predicting GDM were 0.612,0.691 and 0.664.The best tangent point values were 94.045ng/ml,21.125kg/m2 and 28.500 years old,respectively.The total AUC of ROC predicted GDM by SF in early gestation,pre-pregnancy BMI and gestational age was 0.750,the sensitivity and specificity were 66.1%and 79.3%,respectively.Conclusion SF in early gestation,pre-pregnancy BMI and gestational age are important factors in the development of GDM,the combined detection of SF in early pregnancy,pre-pregnancy BMI and gestational age has a certain predictive value for GDM.

Result Analysis
Print
Save
E-mail