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.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
3.Distribution of respiratory pathogens in patients with pneumonia in Yinzhou,Ning-bo,2015-2024
Ziming YANG ; Shuya LI ; Xiaotong LI ; Peng SHEN ; Yexiang SUN ; Hongbo LIN ; Zhiqin JIANG ; Siyan ZHAN ; Zhike LIU
Journal of Peking University(Health Sciences) 2025;57(3):496-506
Objective:To describe the epidemiological characteristics of 22 common respiratory patho-gens in patients with pneumonia in Yinzhou,Ningbo,from January 1,2015 to December 21,2024.Methods:The test data of 22 common respiratory pathogens in patients diagnosed with pneumonia or lung infection in the Yinzhou Regional Health Information Platform from January 1,2015 to December 21,2024 were collected.The positive cases,positive rates,and positive proportions were calculated.The epidemiological characteristics were described by the year,sex,age group,season,and coronavirus disease 2019(COVID-19)pandemic period.Results:A total of 77 531 pneumonia patients were included,with 492 696 respiratory pathogen tests performed.The number of respiratory pathogen tests and positive cases of pneumonia patients in Yinzhou showed an upward trend.In the study,34.63%of the pneumo-nia patients tested positive for at least one pathogen,and the pathogen non-detection rate decreased from 79.44%in 2015 to 58.38%in 2024.The overall pathogen positive rate was 9.12%,which decreased during the COVID-19 pandemic and had not returned to the historical level after the COVID-19 pande-mic.The positive rate was highest in children aged 6-17 years(13.99%),and lowest in the elderly over 60 years(4.16%).The top 3 highest number of positive cases was Mycoplasma pneumoniae,influenza A virus,and influenza B virus;the top 3 highest positive rates of pathogen tests were Mycoplasma pneu-moniae(25.26%),rhinovirus(12.02%),and Bordetella pertussis(11.66%).The pathogen spectrum proportion in men was similar to that in women,only showing a higher ratio of Mycobacterium tuberculosis and a slightly lower ratio of Mycoplasma pneumoniae(P<0.001).Mycoplasma pneumoniae,respiratory syncytial virus,and rhinovirus infections were more common in children,while influenza virus,Mycobac-terium tuberculosis,and Streptococcus pyogenes infections were more common in adults and the elderly(P<0.001).Influenza virus and human metapneumovirus infections were more common in winter,rhi-novirus and Bordetella pertussis infections were more common in spring,and Mycoplasma pneumoniae in-fections were relatively more common in fall(P<0.001).After the COVID-19 pandemic,the propor-tions of rhinovirus,respiratory syncytial virus,and human metapneumovirus infections in the pneumonia patients increased signi-ficantly,reaching 7.53%,4.26%,and 2.25%,respectively,while the propor-tions of influenza B virus and Mycobacterium tuberculosis infections decreased to 4.14%and 2.80%,re-spectively(P<0.001).Conclusion:In the past decade,the scale of respiratory pathogen infection in the pneumonia population in Yinzhou had expanded significantly,and there were differences in distribu-tion by the year,gender,age group,and season.The respiratory pathogen spectrum in pneumonia pa-tients after the COVID-19 pandemic had a trend of diversification.
4.Effect of Kaiqiao Xingshen acupuncture combined with Buyang Huanwu decoction on IL-2,MMP-9,BDNF,and cerebral blood flow in patients with cerebral hemorrhage during recovery period(Qi defi-ciency and blood stasis syndrome)
Tianzhong PENG ; Xuedi HUANG ; Xingzhen LIN ; Juan YUAN ; Feng ZHOU ; Langhui LIU ; Qi'nan ZHAN ; Manhua ZHU
The Journal of Practical Medicine 2025;41(3):428-433
Objective To explore the application value of Kaiqiao Xingshen acupuncture combined with Buyang Huanwu decoction in the treatment of patients with cerebral hemorrhage in the recovery period(Qi defi-ciency and blood stasis syndrome),and to observe its impact on inflammatory indicators and neurokines.Method A total of 166 patients with cerebral hemorrhage in the recovery period(Qi deficiency and blood stasis syndrome)treated in Hongdu Traditional Chinese Medicine Hospital from September 2021 to October 2023,were randomly divided into control group(83 cases treated with conventional western medicine),and observation group(83 cases treated with a combination of Kaiqiao Xingshen acupuncture and Buyang Huanwu decoction).The therapeutic effect in the two groups was compared after 8 weeks of treatment.Results After treatment,the serum levels of matrix metalloproteinase-9(MMP-9),endothelin-1(ET-1),interleukin-2(IL-2),homocysteine(Hcy),and Bcl-2-associated X protein(bax)decreased in both groups,while brain-derived neurotrophic factor(BDNF)increased,and the improvement was more significant in the observation group,showing statistical significance(P<0.05);the average cerebral vascular flow and flow velocity in the observation group increased,while peripheral vascular resistance decreased,and the improvement in the observation group was more significant(P<0.05);the total symptom score of traditional Chinese medicine in the observation group decreased,while the Fuel Meyer functional score(FMA score)increased,and the improvement in the observation group was more significant(P<0.05);The total effective rate of the observation group was 93.98%(78/83),which was higher than that of the control group(80.72%,67/83)(P<0.05).Conclusion For patients with cerebral hemorrhage in the recovery period(Qi deficiency and blood stasis syndrome),Kaiqiao Xingshen acupuncture and Buyang Huanwu decoction help alleviate inflammatory reactions,promote the recovery of the blood-brain barrier,improve cerebral blood flow,promote neurological function recovery,and enhance clinical efficacy.
5.Study of application of Common Data Model of Observational Medical Outcomes Partnership in China
Meng ZHANG ; Peng SHEN ; Zhike LIU ; Van Zandt MUI ; Jing LI ; Chao LI ; Yexiang SUN ; Junqing XIE ; Hripcsak GEORGE ; Yong CHEN ; Hongbo LIN ; Siyan ZHAN ; Feng SUN
Chinese Journal of Epidemiology 2025;46(5):907-913
Objective:To comprehensively evaluate the application of Common Data Model (CDM) of Observational Medical Outcomes Partnership (OMOP) in China, and provide reference for the implementation of data standardization and evidence sharing in China.Methods:PubMed, Embase, Web of Science, CNKI, VIP, WanFang and SinoMed databases were used for literature retrieval to collect the research papers of OMOP CDM application for data standardization in China until March 15, 2023. The information about institutions, types and numbers of patients were extracted.Results:A total of 14 research papers, including 9 in English and 5 in Chinese, were selected. The research papers published since 2018 were collected, which focused on patients with hypertension, diabetes, and depression. A total of 12 institutions or platforms transformed data into OMOP CDM. Jiangsu Provincial People's Hospital was the first one to apply the CDM and demonstrated its feasibility in China. Additionally, the regional information system in Yinzhou District of Ningbo, Zhejiang Province, standardized the multi-dimensional data of patients with diabetes and hypertension. Based on this platform, a series of prediction models for complications in patients with diabetes were constructed. Another major database in Beijing Anding Hospital applied OMOP CDM to analyze the characteristics of patients with late-life depression and dementia.Conclusions:This study analyzed the application of OMOP CDM in China. Through in-depth analysis of specific cases, the study provided guidance for the future cross-regional evidence sharing and collaboration.
6.Study of application of Common Data Model of Observational Medical Outcomes Partnership in China
Meng ZHANG ; Peng SHEN ; Zhike LIU ; Van Zandt MUI ; Jing LI ; Chao LI ; Yexiang SUN ; Junqing XIE ; Hripcsak GEORGE ; Yong CHEN ; Hongbo LIN ; Siyan ZHAN ; Feng SUN
Chinese Journal of Epidemiology 2025;46(5):907-913
Objective:To comprehensively evaluate the application of Common Data Model (CDM) of Observational Medical Outcomes Partnership (OMOP) in China, and provide reference for the implementation of data standardization and evidence sharing in China.Methods:PubMed, Embase, Web of Science, CNKI, VIP, WanFang and SinoMed databases were used for literature retrieval to collect the research papers of OMOP CDM application for data standardization in China until March 15, 2023. The information about institutions, types and numbers of patients were extracted.Results:A total of 14 research papers, including 9 in English and 5 in Chinese, were selected. The research papers published since 2018 were collected, which focused on patients with hypertension, diabetes, and depression. A total of 12 institutions or platforms transformed data into OMOP CDM. Jiangsu Provincial People's Hospital was the first one to apply the CDM and demonstrated its feasibility in China. Additionally, the regional information system in Yinzhou District of Ningbo, Zhejiang Province, standardized the multi-dimensional data of patients with diabetes and hypertension. Based on this platform, a series of prediction models for complications in patients with diabetes were constructed. Another major database in Beijing Anding Hospital applied OMOP CDM to analyze the characteristics of patients with late-life depression and dementia.Conclusions:This study analyzed the application of OMOP CDM in China. Through in-depth analysis of specific cases, the study provided guidance for the future cross-regional evidence sharing and collaboration.
7.Distribution of respiratory pathogens in patients with pneumonia in Yinzhou,Ning-bo,2015-2024
Ziming YANG ; Shuya LI ; Xiaotong LI ; Peng SHEN ; Yexiang SUN ; Hongbo LIN ; Zhiqin JIANG ; Siyan ZHAN ; Zhike LIU
Journal of Peking University(Health Sciences) 2025;57(3):496-506
Objective:To describe the epidemiological characteristics of 22 common respiratory patho-gens in patients with pneumonia in Yinzhou,Ningbo,from January 1,2015 to December 21,2024.Methods:The test data of 22 common respiratory pathogens in patients diagnosed with pneumonia or lung infection in the Yinzhou Regional Health Information Platform from January 1,2015 to December 21,2024 were collected.The positive cases,positive rates,and positive proportions were calculated.The epidemiological characteristics were described by the year,sex,age group,season,and coronavirus disease 2019(COVID-19)pandemic period.Results:A total of 77 531 pneumonia patients were included,with 492 696 respiratory pathogen tests performed.The number of respiratory pathogen tests and positive cases of pneumonia patients in Yinzhou showed an upward trend.In the study,34.63%of the pneumo-nia patients tested positive for at least one pathogen,and the pathogen non-detection rate decreased from 79.44%in 2015 to 58.38%in 2024.The overall pathogen positive rate was 9.12%,which decreased during the COVID-19 pandemic and had not returned to the historical level after the COVID-19 pande-mic.The positive rate was highest in children aged 6-17 years(13.99%),and lowest in the elderly over 60 years(4.16%).The top 3 highest number of positive cases was Mycoplasma pneumoniae,influenza A virus,and influenza B virus;the top 3 highest positive rates of pathogen tests were Mycoplasma pneu-moniae(25.26%),rhinovirus(12.02%),and Bordetella pertussis(11.66%).The pathogen spectrum proportion in men was similar to that in women,only showing a higher ratio of Mycobacterium tuberculosis and a slightly lower ratio of Mycoplasma pneumoniae(P<0.001).Mycoplasma pneumoniae,respiratory syncytial virus,and rhinovirus infections were more common in children,while influenza virus,Mycobac-terium tuberculosis,and Streptococcus pyogenes infections were more common in adults and the elderly(P<0.001).Influenza virus and human metapneumovirus infections were more common in winter,rhi-novirus and Bordetella pertussis infections were more common in spring,and Mycoplasma pneumoniae in-fections were relatively more common in fall(P<0.001).After the COVID-19 pandemic,the propor-tions of rhinovirus,respiratory syncytial virus,and human metapneumovirus infections in the pneumonia patients increased signi-ficantly,reaching 7.53%,4.26%,and 2.25%,respectively,while the propor-tions of influenza B virus and Mycobacterium tuberculosis infections decreased to 4.14%and 2.80%,re-spectively(P<0.001).Conclusion:In the past decade,the scale of respiratory pathogen infection in the pneumonia population in Yinzhou had expanded significantly,and there were differences in distribu-tion by the year,gender,age group,and season.The respiratory pathogen spectrum in pneumonia pa-tients after the COVID-19 pandemic had a trend of diversification.
8.Effect of Kaiqiao Xingshen acupuncture combined with Buyang Huanwu decoction on IL-2,MMP-9,BDNF,and cerebral blood flow in patients with cerebral hemorrhage during recovery period(Qi defi-ciency and blood stasis syndrome)
Tianzhong PENG ; Xuedi HUANG ; Xingzhen LIN ; Juan YUAN ; Feng ZHOU ; Langhui LIU ; Qi'nan ZHAN ; Manhua ZHU
The Journal of Practical Medicine 2025;41(3):428-433
Objective To explore the application value of Kaiqiao Xingshen acupuncture combined with Buyang Huanwu decoction in the treatment of patients with cerebral hemorrhage in the recovery period(Qi defi-ciency and blood stasis syndrome),and to observe its impact on inflammatory indicators and neurokines.Method A total of 166 patients with cerebral hemorrhage in the recovery period(Qi deficiency and blood stasis syndrome)treated in Hongdu Traditional Chinese Medicine Hospital from September 2021 to October 2023,were randomly divided into control group(83 cases treated with conventional western medicine),and observation group(83 cases treated with a combination of Kaiqiao Xingshen acupuncture and Buyang Huanwu decoction).The therapeutic effect in the two groups was compared after 8 weeks of treatment.Results After treatment,the serum levels of matrix metalloproteinase-9(MMP-9),endothelin-1(ET-1),interleukin-2(IL-2),homocysteine(Hcy),and Bcl-2-associated X protein(bax)decreased in both groups,while brain-derived neurotrophic factor(BDNF)increased,and the improvement was more significant in the observation group,showing statistical significance(P<0.05);the average cerebral vascular flow and flow velocity in the observation group increased,while peripheral vascular resistance decreased,and the improvement in the observation group was more significant(P<0.05);the total symptom score of traditional Chinese medicine in the observation group decreased,while the Fuel Meyer functional score(FMA score)increased,and the improvement in the observation group was more significant(P<0.05);The total effective rate of the observation group was 93.98%(78/83),which was higher than that of the control group(80.72%,67/83)(P<0.05).Conclusion For patients with cerebral hemorrhage in the recovery period(Qi deficiency and blood stasis syndrome),Kaiqiao Xingshen acupuncture and Buyang Huanwu decoction help alleviate inflammatory reactions,promote the recovery of the blood-brain barrier,improve cerebral blood flow,promote neurological function recovery,and enhance clinical efficacy.
9.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
10.Usage and Dosage Analysis and Countermeasures for Development of Compound Preparations of Han Dynasty Famous Classical Formulas
Yan JIN ; Bing LI ; Wei ZHANG ; Huasheng PENG ; Huamin ZHANG ; Huihui LIU ; Lin ZHANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):1-10
In order to provide a reference basis for the development of relevant compound preparations, this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives, and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics, decoction methods, administration and dosage, and combining conversion methods of weights and measures by ancient medical practitioners, along with the dosage and administration of the listed Han dynasty famous classical formulas, it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents[13.8 g per Liang(两)], ensuring the safe and effective medication of these formulas. After combing, it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty, the administration is flexible. The crude drug amount per administration serves as the foundational dose, with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study, it is recommended that when developing compound formulations of famous classical formulas in Han dynasty, the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose, with the frequency of administration described within a range(1 to N times per day, where N is the maximum number of administrations as per the original text). The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies, where the dosage per administration serves as the basis for toxicity research, and the toxicity profile at the maximum administration frequency should be observed, providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.

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