1.Nanoengineered cargo with targeted in vivo Foxo3 gene editing modulated mitophagy of chondrocytes to alleviate osteoarthritis.
Manyu CHEN ; Yuan LIU ; Quanying LIU ; Siyan DENG ; Yuhan LIU ; Jiehao CHEN ; Yaojia ZHOU ; Xiaolin CUI ; Jie LIANG ; Xingdong ZHANG ; Yujiang FAN ; Qiguang WANG ; Bin SHEN
Acta Pharmaceutica Sinica B 2025;15(1):571-591
Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.
2.Study of characteristics of faculty of high-level public health schools in China based on internet information
Huiwen DENG ; Shengfeng WANG ; Yajun XU ; Huakang TU ; Xueyan JING ; Hongmei WANG ; Xifeng WU ; Ying LI ; Siyan ZHAN
Chinese Journal of Epidemiology 2025;46(3):476-483
Objective:To understand the characteristics of faculty in high-level public health schools in China, and analyze the differences in age, area and school level.Methods:Based on the internet information, the faculty information of 18 high-level public health schools was collected for a descriptive analysis on faculty characteristics.Results:There were 1 642 faculty members in the schools of public health in China, in whom 51.8% were women, 92.8% had doctorate, 32.4% had postdoctoral experience and 56.8% were former students staying to teach. The average age of the faculty members was (45.6±9.8) years. Meanwhile the top three study subjects were epidemiology and health statistics (31.0%), occupational health and environmental sanitation (16.5%), and health toxicology (16.3%). In the faculty members aged >40 years, 90.2% had doctorate, 62.6% were former students staying to teach, and 24.7% had no educational background of public health. The proportions of faculty members aged ≤40 years in the three groups mentioned above were 98.2%, 45.8% and 39.1% respectively. In terms of study subject, big data study were mainly conducted in the schools with top subject ranking and the schools in developed areas.Conclusions:The public health faculty was characterized by cross education background and high capability. The study subjects and sub-disciplines varied with schools and areas.
3.Analysis of virtual labor medication rules and clinical experience based on data mining
Ting WANG ; Yahui CHANG ; Zujie QIN ; Chenglong WANG ; Meng ZHANG ; Yangmeng CAO ; Siyan DENG
China Modern Doctor 2025;63(29):43-46,55
Objective To analyze the medication rules and clinical experience of Qin Zujie in treating virtual labor based on data mining.Methods Outpatient medical records of Qin Zujie,diagnosed with deficiency syndrome at Ethnic Medicine Characteristic Diagnosis and Treatment Center,Guangxi International Zhuang Medical Hospital from January to December 2024 were selected.A standardized database was established and processed,yielding 148 clinical prescriptions containing 171 herbal ingredients.Frequency analysis,association rule analysis,and cluster analysis were employed to examine medication rules and clinical experience.Results The 20 Chinese herbal ingredients used more than 30 times each,with the first three being Zhigancao,Baizhu,Danggui.These herbs are primarily warm in nature,neutral in temperature,and slightly cold in effect,characterized by sweet,pungent,and bitter flavors.They mainly affect the spleen meridian and function to tonify deficiency,with Qi-tonifying herbs being the most common.Through association rule analysis,the most frequently combined pairs were Baizhu-Dangshen.Cluster analysis identified three core prescription clusters.Conclusion Qin Zujie's academic thought of treating virtual labor is to supplement deficiency as the main,detoxification as the auxiliary,and treat both the symptoms and the causes.
4.Epidemiological characteristics of febrile seizure among children under 6 years old in Ningbo City from 2015 to 2021
Guangxu LIU ; Liang ZHANG ; Houyu ZHAO ; Siwei DENG ; Junting YANG ; Ning LI ; Rui MA ; Yan HE ; Guozhang XU ; Zhike LIU ; Siyan ZHAN
Journal of Peking University(Health Sciences) 2025;57(3):584-591
Objective:To describe the epidemiological characteristics and changes of febrile seizure(FS)among children under 6 years old in Ningbo City,Zhejiang Province from 2015 to 2021.Methods:Based on the Ningbo Regional Health Information Platform,a dynamic cohort was established using vacci-nation registration information,and the cases of FS were identified by the diagnostic results of Chinese terms or International Classification of Diseases 10th revision(ICD-10)R56.0 code in the electronic medical records.The first visit of FS during the observation period was defined as a new case,and a re-currence case was defined as the case with a visit interval of more than 7 days.The 95%confidence in-terval(CI)of FS incidence density was calculated by the Poisson distribution.Results:From January 2015 to June 2020,there were 1.3 million children under 6 years old in Ningbo,with male accounting for 52.87%.The median follow-up time was 2.83(1.55-4.00)years.During the follow-up period,12 776 new onset cases had FS,with more males than females,with an overall incidence density of 4.34(95%CI:4.27-4.40)/1 000 person-years and a recurrence rate of 21.63%.There was a higher inci-dence density in children who were male,born in Ningbo and of non-mobility.The incidence density of FS was higher in urban areas than in rural and rural-urban fringe areas,and the incidence density was different among districts and counties.The peak density was found in children aged 18-23 months[8.42(95%CI:8.11-8.74)/1 000 person-years].From 2015 to 2019,the incidence density in-creased with calendar year(Ptrend<0.001),and the highest was 5.62(95%CI:5.43-5.81)/1 000 person-years.The incidence density of FS decreased significantly during the period between 2020 and 2021.The incidence density was higher in winter.Conclusion:From 2015 to 2019,the overall inci-dence density of FS in children under 6 years old in Ningbo City presented an increasing trend.More at-tention should be paid to the health education,the improvement of the health maintenance model,the en-hancement of the cognition of FS,the identification and treatment of FS among high-risk population and regions so as to prevent its recurrence and reduce the disease burden during the corona virus disease 2019(COVID-19)epide-mic.
5.Study of characteristics of faculty of high-level public health schools in China based on internet information
Huiwen DENG ; Shengfeng WANG ; Yajun XU ; Huakang TU ; Xueyan JING ; Hongmei WANG ; Xifeng WU ; Ying LI ; Siyan ZHAN
Chinese Journal of Epidemiology 2025;46(3):476-483
Objective:To understand the characteristics of faculty in high-level public health schools in China, and analyze the differences in age, area and school level.Methods:Based on the internet information, the faculty information of 18 high-level public health schools was collected for a descriptive analysis on faculty characteristics.Results:There were 1 642 faculty members in the schools of public health in China, in whom 51.8% were women, 92.8% had doctorate, 32.4% had postdoctoral experience and 56.8% were former students staying to teach. The average age of the faculty members was (45.6±9.8) years. Meanwhile the top three study subjects were epidemiology and health statistics (31.0%), occupational health and environmental sanitation (16.5%), and health toxicology (16.3%). In the faculty members aged >40 years, 90.2% had doctorate, 62.6% were former students staying to teach, and 24.7% had no educational background of public health. The proportions of faculty members aged ≤40 years in the three groups mentioned above were 98.2%, 45.8% and 39.1% respectively. In terms of study subject, big data study were mainly conducted in the schools with top subject ranking and the schools in developed areas.Conclusions:The public health faculty was characterized by cross education background and high capability. The study subjects and sub-disciplines varied with schools and areas.
6.Analysis of virtual labor medication rules and clinical experience based on data mining
Ting WANG ; Yahui CHANG ; Zujie QIN ; Chenglong WANG ; Meng ZHANG ; Yangmeng CAO ; Siyan DENG
China Modern Doctor 2025;63(29):43-46,55
Objective To analyze the medication rules and clinical experience of Qin Zujie in treating virtual labor based on data mining.Methods Outpatient medical records of Qin Zujie,diagnosed with deficiency syndrome at Ethnic Medicine Characteristic Diagnosis and Treatment Center,Guangxi International Zhuang Medical Hospital from January to December 2024 were selected.A standardized database was established and processed,yielding 148 clinical prescriptions containing 171 herbal ingredients.Frequency analysis,association rule analysis,and cluster analysis were employed to examine medication rules and clinical experience.Results The 20 Chinese herbal ingredients used more than 30 times each,with the first three being Zhigancao,Baizhu,Danggui.These herbs are primarily warm in nature,neutral in temperature,and slightly cold in effect,characterized by sweet,pungent,and bitter flavors.They mainly affect the spleen meridian and function to tonify deficiency,with Qi-tonifying herbs being the most common.Through association rule analysis,the most frequently combined pairs were Baizhu-Dangshen.Cluster analysis identified three core prescription clusters.Conclusion Qin Zujie's academic thought of treating virtual labor is to supplement deficiency as the main,detoxification as the auxiliary,and treat both the symptoms and the causes.
7.Epidemiological characteristics of febrile seizure among children under 6 years old in Ningbo City from 2015 to 2021
Guangxu LIU ; Liang ZHANG ; Houyu ZHAO ; Siwei DENG ; Junting YANG ; Ning LI ; Rui MA ; Yan HE ; Guozhang XU ; Zhike LIU ; Siyan ZHAN
Journal of Peking University(Health Sciences) 2025;57(3):584-591
Objective:To describe the epidemiological characteristics and changes of febrile seizure(FS)among children under 6 years old in Ningbo City,Zhejiang Province from 2015 to 2021.Methods:Based on the Ningbo Regional Health Information Platform,a dynamic cohort was established using vacci-nation registration information,and the cases of FS were identified by the diagnostic results of Chinese terms or International Classification of Diseases 10th revision(ICD-10)R56.0 code in the electronic medical records.The first visit of FS during the observation period was defined as a new case,and a re-currence case was defined as the case with a visit interval of more than 7 days.The 95%confidence in-terval(CI)of FS incidence density was calculated by the Poisson distribution.Results:From January 2015 to June 2020,there were 1.3 million children under 6 years old in Ningbo,with male accounting for 52.87%.The median follow-up time was 2.83(1.55-4.00)years.During the follow-up period,12 776 new onset cases had FS,with more males than females,with an overall incidence density of 4.34(95%CI:4.27-4.40)/1 000 person-years and a recurrence rate of 21.63%.There was a higher inci-dence density in children who were male,born in Ningbo and of non-mobility.The incidence density of FS was higher in urban areas than in rural and rural-urban fringe areas,and the incidence density was different among districts and counties.The peak density was found in children aged 18-23 months[8.42(95%CI:8.11-8.74)/1 000 person-years].From 2015 to 2019,the incidence density in-creased with calendar year(Ptrend<0.001),and the highest was 5.62(95%CI:5.43-5.81)/1 000 person-years.The incidence density of FS decreased significantly during the period between 2020 and 2021.The incidence density was higher in winter.Conclusion:From 2015 to 2019,the overall inci-dence density of FS in children under 6 years old in Ningbo City presented an increasing trend.More at-tention should be paid to the health education,the improvement of the health maintenance model,the en-hancement of the cognition of FS,the identification and treatment of FS among high-risk population and regions so as to prevent its recurrence and reduce the disease burden during the corona virus disease 2019(COVID-19)epide-mic.
8.Meta analysis of interventional effect of aerobic combined resistance exercise on hemodialysis patients
Yixiu LIU ; Siyan DENG ; Xiju LUO ; Huagang HU ; Jinhua LIU
Chongqing Medicine 2024;53(12):1856-1863
Objective To systematically assess the interventional effects of aerobic combined resistance exercise on walking ability,cardiorespiratory endurance,dialysis adequacy and quality of life in the patients with hemodialysis(HD).Methods The published randomized controlled trials on the interventional effects of aerobic combined resistance exercise in HD patients were retrieved from the databases of PubMed,Cochrane Library,Embase,Ovid,Web of Science,CNKI,VIP,Wanfang and China Biomedical Literature Service System(SinoMed).The retrieval time was from the database establishment to May 28,2021;the included literatures were analyzed by using RevMan 5.4 software.Results A total of 24 studies with 1 086 research subjects were included.The results showed that compared with the control group(adopting the usual care or conducting no-resistance limb movement),the walking ability,cardiopulmonary endurance and the dimensions of partial quality of life in the HD patients of the intervention group(aerobic combined resistance exercise)were signifi-cantly improved.The dialysis adequacy during dialysis in the intervention group was significantly improved compared with that in the control group.Conclusion Aerobic combined resistance exercise could improve the physical function,quality of life and dialysis adequacy in HD patients,and it is recommended that the patients are encouraged to conduct the aerobic combined resistance exercise by combining with the specific situation.
9.Role of peripheral clock genes in the progression, prevention, and treatment of nonalcoholic steatohepatitis
Siyan LIU ; Jingyi TIAN ; Yuyang HUANG ; Tianqi GU ; Mingyue DENG ; Pan YANG
Journal of Clinical Hepatology 2024;40(12):2505-2512
As a severe clinical manifestation of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH) is characterized by lipid deposition and inflammatory damage in the liver. At present, clinical medications for NASH are still in the exploratory phase, and it is urgent to make progress. Recent studies have shown that the pathogenesis of NASH is associated with circadian rhythm disorders in the liver, with the specific manifestation of dysregulated expression of liver clock genes such as BMAL1, which increases hepatic lipogenesis, reduces fatty acid oxidation, and activates pro-inflammatory factors. Therefore, improving circadian rhythm of the liver and regulating the expression of liver clock genes are feasible strategies for the prevention and treatment of NASH. Currently, some medications for NASH via activating the proteins encoded by clock genes have been applied in animal experiments, for example, the REVERB full-agonist SR9009 can inhibit the development of liver inflammation, which confirms the possibility of NASH treatment by targeting the proteins encoded by clock genes. This article summarizes the role of hepatic clock genes in regulating lipid metabolism and the development and progression of inflammation in the liver and elaborates on the recent advances in medications targeting clock genes and the proteins encoded by clock genes, in order to provide new targets for the treatment of NASH.
10.Identification process of time-related bias in pharmacoepidemiologic research based on a scoping review
Siwei DENG ; Houyu ZHAO ; Siyan ZHAN
Chinese Journal of Epidemiology 2024;45(9):1273-1282
Objective:To summarize the characteristics of pharmacoepidemiologic research involving diabetes patients, which were published in recent years, in terms of study design and analysis, and develop an identification process for time-related biases in pharmacoepidemiologic research.Methods:PubMed, Embase, CNKI and Wanfang were used for a systematical literature retrieval of relevant study papers published between January 1,2012 and September 26, 2022. Literature screening and data extraction were performed independently by two reviewers. Based on the mechanisms of different time-related biases and the characteristics of included study papers in terms of study design and analysis methods, an identification process for all types of time-related biases was developed.Results:A total of 281 study papers were included, of which 58 (20.64%) specifically mentioned certain time-related biases considered in the study. Based on the scoping review results, key points to identify time-related biases were summarized, involving data source, study design, control selection, comparator drugs, matching the duration of diabetes, identification of the washout period, identification of the induction/latency period, identification of the initiation of follow-up, identification of time window, statistical analysis methods, sensitivity analysis, and other design and analytical elements, in the identification process for time-related biases in pharmacoepidemiologic research.Conclusions:Time-related biases are common in pharmacoepidemiologic research and might significantly impact the study results. Based on scoping review results, this study further developed an identification process for time-related biases in pharmacoepidemiologic research, which will help researchers identify and avoid time-related biases and improve the reliability of related evidence in pharmacoepidemiologic research.

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