1.PARylation promotes acute kidney injury via RACK1 dimerization-mediated HIF-1α degradation.
Xiangyu LI ; Xiaoyu SHEN ; Xinfei MAO ; Yuqing WANG ; Yuhang DONG ; Shuai SUN ; Mengmeng ZHANG ; Jie WEI ; Jianan WANG ; Chao LI ; Minglu JI ; Xiaowei HU ; Xinyu CHEN ; Juan JIN ; Jiagen WEN ; Yujie LIU ; Mingfei WU ; Jutao YU ; Xiaoming MENG
Acta Pharmaceutica Sinica B 2025;15(9):4673-4691
Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.
2.Trends in prevalence of overweight and obesity among adult residents in Zhejiang Province from 2015 to 2023
CHEN Xiangyu ; WANG Meng ; HU Ruying ; GUAN Yunqi ; LIANG Mingbin ; HE Qingfang ; YAO Weiyuan ; ZHONG Jieming
Journal of Preventive Medicine 2025;37(11):1093-1098
Objective:
To investigate the prevalence levels and trends of overweight and obesity among adult residents in Zhejiang Province from 2015 to 2023, so as to provide a basis for developing regional weight management strategies.
Methods:
Permanent residents aged ≥18 years from Zhejiang Province who participated in the China Chronic Disease and Risk Factor Surveillance Project in 2015, 2018, and 2023 were selected as survey subjects. Data on sociodemographic information, height, weight and waist circumference were collected through questionnaire surveys and physical examinations. The prevalence of overweight, obesity, and central obesity were calculated and standardized using data from the Seventh National Population Census of Zhejiang Province in 2020. The Cochran-Armitage trend test was employed to analyze the trends in prevalence of overweight, obesity, and central obesity across different genders, ages and regions.
Results:
A total of 23 902 individuals were surveyed, comprising 10 985 males (45.96%) and 12 917 females (54.04%). Participants were aged ≥60 years, with 13 088 individuals accounting for 54.76%. There were 9 388 urban residents (39.28%) and 14 514 rural residents (60.72%). The standardized prevalence of overweight among residents increased from 30.05% in 2015 to 33.98% in 2023, the standardized prevalence of obesity increased from 7.67% to 15.22%, and the standardized prevalence of central obesity increased from 22.81% to 33.82%, all showed upward trends (all P<0.05). In 2015, 2018, and 2023, the standardized prevalence of overweight was higher in males than in females. In 2018 and 2023, the standardized prevalence of obesity and central obesity were higher in males than in females (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both males and females showed upward trends (all P<0.05). In 2015, 2018 and 2023, the prevalence of central obesity showed an increasing trend with age (all P<0.05). From 2015 to 2023, upward trends were observed in the prevalence of overweight, obesity, and central obesity among residents aged 18-<45 years and aged ≥60 years, as well as in the prevalence of obesity and central obesity among residents aged 45-<60 years (all P<0.05). In 2015, 2018 and 2023, the standardized prevalence of overweight obesity were higher in urban areas than in rural areas, while the standardized prevalence of central obesity was lower in urban areas (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both urban and rural areas showed upward trends (all P<0.05).
Conclusion
From 2015 to 2023, the prevalence of overweight, obesity, and central obesity among adult residents in Zhejiang Province showed increasing trends, with variations in prevalence levels and trends observed across genders, ages, and urban / rural areas.
3.Long-term efficacy of CMV/EBV bivirus-specific T cells for viral co-reactivation after stem cell transplantation.
Xuying PEI ; Meng LV ; Xiaodong MO ; Yuqian SUN ; Yuhong CHEN ; Chenhua YAN ; Yuanyuan ZHANG ; Lanping XU ; Yu WANG ; Xiaohui ZHANG ; Xiaojun HUANG ; Xiangyu ZHAO
Chinese Medical Journal 2025;138(5):607-609
4.Identification of novel pathogenic variants in genes related to pancreatic β cell function: A multi-center study in Chinese with young-onset diabetes.
Fan YU ; Yinfang TU ; Yanfang ZHANG ; Tianwei GU ; Haoyong YU ; Xiangyu MENG ; Si CHEN ; Fengjing LIU ; Ke HUANG ; Tianhao BA ; Siqian GONG ; Danfeng PENG ; Dandan YAN ; Xiangnan FANG ; Tongyu WANG ; Yang HUA ; Xianghui CHEN ; Hongli CHEN ; Jie XU ; Rong ZHANG ; Linong JI ; Yan BI ; Xueyao HAN ; Hong ZHANG ; Cheng HU
Chinese Medical Journal 2025;138(9):1129-1131
5.Establishment and evaluation of HPLC-MS/MS method in determining serum H2S
Xiangyu MENG ; Ao ZHANG ; Chunyan LI
China Medical Equipment 2024;21(2):42-47
Objective:To establish a determination method of high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)for serum hydrogen sulfide(H2S),so as to determine serum H2S.Methods:This study collected serum samples of 30 patients who admitted to Beijing Jishuitan Hospital affiliated to Capital Medical University from April 2023 to May 2023,and they were divided into osteoporosis group and control group according to whether existed osteoporosis,with 15 cases in each group.HPLC-MS/MS and enzyme-linked immunosorbent assay were used respectively to determine serum H2S.And then,the precision,accuracy and correlation between the two methods were evaluated.Results:HPLC-MS/MS can fast detect the content of serum H2S through detecting methylene blue in the serum,which analysis time was only 1.5 minutes,and its specificity was higher.The relative standard deviation(RSD)value of quality control plasma was 8.77%,and that of quality control plasma with the standard and pure water with standard were respectively 4.58% and 8.23%.The precisions of them met the requirement of detection(less than 20%).The recovery was 103.5% through used the above data,and the accuracy accorded with the requirements of quantitative detection(recovery was 103.5%).Conclusion:HPLC-MS/MS method is rapid and accurate in detecting H2S,which can accurately detect the content of serum H2S.This method has a series of advantages include fast,high throughput,high sensitivity and favorable stability,which contributes to conduct basic research of the content of serum H2S in the cellular pathways of human.
6.Analysis of the characteristics of platelet changes and influencing factors after transcatheter aortic valve implantation
Xiangyu LI ; Haibo ZHANG ; Fangyu YANG ; Shuai ZHENG ; Fei MENG ; Shengxun WANG ; Yuqing JIAO ; Yuehuan LI ; Kaisheng WU ; Jinglun SHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(06):832-837
Objective To analyze the characteristics of platelet changes and their influencing factors during postoperative hospitalization in patients who underwent transcatheter aortic valve implantation (TAVI). Methods The patients who underwent TAVI at Beijing Anzhen Hospital Valve Surgery Center between March 2017 and October 2021 were retrospectively selected. The patients were divided into a self-limiting group and a non-self-limiting group according to the characteristics of postoperative platelet decline. In addition, the general preoperative data, preoperative and postoperative ultrasound data, intraoperative data, and the use of anticoagulant drugs during the postoperative stay in the hospital were compared between the two groups. Results A total of 249 patients were enrolled in this study. There were 175 (70.3%) patients in the self-limiting group, including 100 males and 75 females, and there were 74 (29.7%) patients in the non-self-limiting group, including 43 males and 31 females, with no statistical difference between the two groups (P=0.863). The mean age of patients was 73.11±8.88 years in the self-limiting group and 71.54±10.39 years in the non-self-limiting group (P=0.231). The decline of platelets in the self-limiting group generally occurred on the postoperative day 2 and reached the lowest count on the postoperative day 4, and returned to the baseline level on the postoperative day 5-7, while the platelets in the non-self-limiting group changed by simple rise, fall or irregular fluctuation. Patients in the self-limiting group had severer preoperative aortic stenosis (P<0.001) and used more extracorporeal circulation assistance during surgery (P<0.001). Postoperatively, patients in the self-limiting group were more likely to have periaortic valve leakage than those in the non-self-limiting group (P=0.013). Conclusion Platelet changes in most patients after TAVI show a self-limiting decline, which may be related to the severity of patients’ preoperative aortic stenosis, intraoperative extracorporeal circulation device use, and postoperative perivalvular leakage.
7.Excess mortality risk associated with atmospheric PM2.5 exposure
ZHANG Kaiyue ; LI Xiaoqin ; XIA Junpeng ; DAI Xiangyu ; WU Jingjing ; JIANG Meng ; WANG Fang ; LU Shenghua
Journal of Preventive Medicine 2024;36(11):950-952,957
Objective:
To evaluate the risk of fine particulate matter (PM2.5) on excess mortality among residents.
Methods:
The data of residential mortality in Yangzhou City, Jiangsu Province from 2015 to 2021 were collected from the Chinese Disease Prevention and Control Information System. The average daily mass concentration of PM2.5 and meteorology data were collected from the Yangzhou Environmental Monitoring Station and Yangzhou Meteorological Bureau, respectively. The effects of PM2.5 on non-accidental mortality, morality of respiratory diseases and mortality of circulatory diseases were evaluated using a generalized additive model. The risk of excess mortality was evaluated using excess risk (ER) and the number of excess mortality.
Results:
The median average annual mass concentration of PM2.5 was 38.00 (interquartile range, 31.95) µg/m3 in Yangzhou City from 2015 to 2021, decreasing from 51.75 (interquartile range, 32.82) µg/m3 in 2015 to 28.00 (interquartile range, 23.42) µg/m3 in 2021. The median average annual number of non-accidental mortality, mortality of respiratory diseases and mortality of circulatory diseases were 96 (interquartile range, 22), 9 (interquartile range, 5) and 38 (interquartile range, 13) cases, respectively. The greatest effects of per 10 μg/m3 increase in PM2.5 mass concentration on non-accidental mortality, mortality of respiratory diseases, and mortality of circulatory diseases were seen at a cumulative lag of 1 day (ER=0.528%, 95%CI: 0.293%-0.763%), a cumulative lag of 2 days (ER=0.917%, 95%CI: 0.125%-1.714%) and a cumulative lag of 1 day (ER=0.595%, 95%CI: 0.232%-0.961%), respectively. The number of excess mortality caused by PM2.5 on non-accidental mortality, mortality of respiratory diseases, and mortality of circulatory diseases in Yangzhou City from 2015 to 2021 were 2 125, 412 and 977 cases, respectively; compared with 2015, the number of excess mortality in 2021 decreased by 66.95%, 75.53% and 64.42%, respectively.
Conclusions
An increase in the mass concentration of atmospheric PM2.5 may elevate the risk of excess mortality among residents. Compared to 2015, the number of excess deaths attributed to exposure to atmospheric PM2.5 declined in 2021.
8.Discussion on Application of Knowledge Graph in the Field of Traditional Chinese Medicine Theory
Journal of Zhejiang Chinese Medical University 2024;48(6):756-760
[Objective]To discuss the current situation and prospect of the application of knowledge graph in the field of traditional Chinese medicine theory.[Methods]Through the literature research method,the literature about the application of knowledge graph in the field of traditional Chinese medicine theory was collected and sorted out,and its application status,research value and practical significance were explored,with the development direction also discussed.[Results]Knowledge graph can realize semi-automatic and standardized collation of literature in the field of traditional Chinese medicine theory,reveal latent theoretical connotation,clarify the relationship among theories,deduce space-time matrix,and help the intelligent storage and popularization of traditional Chinese medicine theory.The complete automatic construction,interconnection,re-standardization and deep application development of knowledge graph related to traditional Chinese medicine theory field need to be deeply explored and comprehensively applied by the builder,and the builder should also strengthen the traditional Chinese medicine thinking behind the design of knowledge graph.[Conclusion]Knowledge graph can three-dimensional deconstruct and manifest the true context of traditional Chinese medicine theory.The continuous expansion and improvement of knowledge graph can help the inheritance,innovation and vigorous development of the system of traditional Chinese medicine theory in the new era.
9.Research on the construction of evaluation index system of internal control of medical equipment in public hospitals based on Delphi method and analytic hierarchy process
Qibo MA ; Mingzhuo DENG ; Shan LU ; Ni KANG ; Xiaochen SI ; Yu BAI ; Ming LI ; Xiangyu MENG ; Jianjun CHEN
China Medical Equipment 2024;21(5):133-137
Objective:To construct an evaluation index system of internal control medical equipment based on the internal control theory of The Committee of Sponsoring Organizations of the Treadway Commission(COSO)and combined with the current situation of medical equipment internal management in public hospitals,so as to provide reference and suggestions for the evaluation of internal control of medical equipment in public hospitals.Methods:Through literature research and expert consultation,the evaluation index system of internal control of medical equipment was preliminarily determined.Using the Delphi method,15 experts from 1 medical college and 3 tertiary hospitals in Beijing who were engaged in the use and management of medical equipment were selected to conduct two rounds of consultation on the evaluation index system of internal control of medical equipment,and the evaluation indicators were scored and screened.The analytic hierarchy process(AHP)was used to determine the index weights,and the internal control evaluation index system of medical equipment in public hospitals based on COSO was constructed.Results:The coefficient of the two rounds of expert consultation was 100%.The authority degree of consulting experts was 0.867.Finally,the evaluation index system of internal control of medical equipment in tertiary public hospitals was formed,which included 5 first-level indicators,17 second-level indicators and 50 third-level indicators.Conclusion:The evaluation index of internal control of medical equipment in public hospitals based on COSO has high expert enthusiasm,authority and coordination.The evaluation index system includes the unit level and the business level of internal control,with a wide coverage,which makes up for the limitations of traditional internal evaluation of medical equipment,which can make up for the limitations of the internal evaluation of traditional medical equipment,improve the internal control system of medical equipment in public hospitals,and optimize the medical equipment management system.
10.Clinical efficacy of patient-specific instrumentation assisted unicompartmental knee arthroplasty
Xiangyu MENG ; Zhixue WANG ; Peng WU ; Huanming FANG ; Peng ZHAO ; Xu WANG ; Yong DING
Chinese Journal of Orthopaedics 2024;44(22):1441-1449
Objective:To investigate the postoperative prosthesis position and early clinical efficacy of 3D printing patient-specific instrumentation (PSI)-assisted unicompartmental knee arthroplasty (UKA).Methods:The clinical data of 15 patients (17 knees, PSI group) with medial compartment knee osteoarthritis who underwent PSI-assisted UKA in the Second Affiliated Hospital, the Air Force Medical University from May to August 2023 were retrospectively analyzed, matched with fifteen patients (17 knees, non-PSI group) with medial compartment knee osteoarthritis undergoing conventional UKA. The differences in the prosthesis placement positions in the postoperative X-ray films between the two groups were compared, including the coronal varus-valgus angles of the tibial and femoral prostheses, the sagittal posterior inclination angle of the tibial prosthesis, the flexion-extension angle of the femoral prosthesis, and the height of the reconstructed joint line. The indicators related to the lower limb alignment (including the femoral valgus angle, the lateral femoral angle, the hip-knee-ankle angle, and the femur-tibia angle) and the range of motion of the knee joint before and after the operation were compared. The Oxford knee score (OKS), American Knee Society (AKS) knee score and function score, and the visual analogue scale (VAS) were used to evaluate the clinical effects of the two groups.Results:In the PSI group, the coronal varus-valgus angle of the tibial prosthesis was 1.6°±0.3° after the operation, and the sagittal posterior inclination angle was 5.7°±0.8°. The coronal varus-valgus angle of the femoral prosthesis was -0.5°±1.5°, and the sagittal flexion-extension angle was 4.0°±1.9°. In the non-PSI group, the corresponding angles were 2.3°±0.6°, 4.5°±1.0°, 1.4°±1.5°, and 7.3°±2.2° respectively with significant differences between the two groups ( P<0.05). The OKS of the PSI group before and after the operation were 26.5±1.8 and 38.6±4.1 points respectively. The AKS knee score were 56.9±8.6 and 89.2±7.2 points. The AKS function score were 70.1±4.2 and 77.5±9.4 points. The VAS were 4.5±3.7 and 2.3±0.3 points, and the range of motion of the knee joint were 115.2°±4.8° and 125.9°±4.6° with significant differences ( P<0.05). The OKS of the non-PSI group before and after the operation were 25.3±6.2 and 38.2±3.5 points respectively. The AKS knee score were 50.6±9.3 and 84.5±6.6 points. The AKS function score were 73.4±3.9 and 77.2±4.8 points. The VAS were 5.8±2.4 and 2.5±1.6 points, and the range of motion of the knee joint were 113.6°±6.7° and 122.3°±5.0° with significant differences ( P<0.05). There were inter-group differences in the AKS knee score and the range of motion of the knee joint after the operation between the two groups with significant differences ( P<0.05). Conclusion:PSI guides-assisted UKA can effectively correct the lower limb alignment of patients and improve knee joint function with good short-term efficacy. Compared with conventional UKA, PSI guides-assisted UKA is less time-consuming with higher precision in prosthesis installation position and fewer post-operative complications.


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