1.PDGF-C: an Emerging Target in The Treatment of Organ Fibrosis
Chao YANG ; Zi-Yi SONG ; Chang-Xin WANG ; Yuan-Yuan KUANG ; Yi-Jing CHENG ; Ke-Xin REN ; Xue LI ; Yan LIN
Progress in Biochemistry and Biophysics 2025;52(5):1059-1069
Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.
2.Investigation and Trend Prediction of Disease Burden of Hypertensionin the Elderly Population Globally and in China from 1990 to 2021
Xiaoxiao ZHAO ; Xiaohui LU ; Lixin KE ; Wulin GAO ; Xiangran MENG ; Lili REN ; Yunhan DING ; Qiang ZHANG ; Yangqin XUN ; Jibiao WU ; Cuncun LU
Medical Journal of Peking Union Medical College Hospital 2025;16(3):647-658
To analyze the disease burden of hypertension in the elderly population from 1990 to 2021 and to predict future trends in China and globally, thereby providing insights for public health decision-making regarding older adults with hypertension in China. Data on hypertension-related deaths and disability adjusted life years (DALYs) for individuals aged ≥60 years was extracted from the Global Burden of Disease (GBD)2021 database for the world, China, and five sociodemographic index (SDI) regions. Age-standardized mortality and DALYs rates for hypertension in the elderly population were calculated, and Joinpoint regression was used to assess trend changes of disease burden, with results reported as average annual percentage change (AAPC). Additionally, subgroup analyses were conducted based on age and sex. The relative impact of aging, population growth, and epidemiological changes on disease burden was analyzed using a three-factor decomposition method. Future projections for the disease burden from 2022 to 2040 were performed using a Bayesian model. From 1990 to 2021, both age-standardized mortality and DALYs rates for hypertension in the elderly population demonstrated a significant downward trend globally and in China (both AAPC values were negative, all Although age-standardized mortality and DALYs rates for hypertension among the elderly in China have shown a downward trend over the past three decades, the absolute burden remains substantial. There is an urgent need for the formulation and implementation of more effective public health policies and clinical interventions to address this critical public health challenge.
3.The application dilemmas and solutions of medical generative artificial intelligence from the perspective of law: focusing on ChatGPT
Jianhua KE ; Fuzhuan REN ; Yuanlei YUE ; Huizhe QI
Chinese Medical Ethics 2025;38(9):1141-1148
Generative artificial intelligence (AI), particularly the ChatGPT series, has great application potential in the medical field. Several products have been introduced into the market, triggering widespread attention across society. Although medical ChatGPT has numerous advantages, its internal technical flaws based on algorithms, data, and platforms may bring about representative external application dilemmas, such as the allocation of legal liability, medical ethical disputes, medical dispute handling, and intellectual property protection. However, China’s current legal norms may not be able to address these issues effectively. To effectively address these contradictions, it is necessary to govern its internal technical flaws through the concept of good governance and to regulate its external application challenges based on the principles of fairness, accountability, remedy, and phased implementation.
4.Effects of mindful attention awareness on sleep quality of soldiers stationed in plateau areas: Chain-mediated effect of burnout and occupational stress
Lei SHI ; Fei REN ; Shen XIN ; Yuan WANG ; Danni LI ; Qin SUN ; Ke LI
Journal of Environmental and Occupational Medicine 2024;41(2):146-152
Background Sleep quality is one of the important factors affecting soldiers’ task performance. Objective To explore the effects of mindful attention awareness, burnout, and occupational stress on sleep quality among soldiers in plateau areas. Methods A total of 1090 soldiers were selected from four units in plateau areas by cluster sampling method and were asked to participate a cross-sectional questionnaire survey using the Pittsburgh Sleep Quality Index (PQSI), Occupational Stress Inventory (OSI), Maslach Burnout Inventory-General Survey (MBI-GS), and Mindful Attention Awareness Scale (MAAS). Correlation analysis, regression analysis, and mediated effect test were conducted for the study. Results Of the 1090 soldiers recruited, 1082 soldiers returned valid questionnaires, and the valid recovery rate was 99.26%. The median (P25, P75) score of PSQI was 4.00 (2.00,7.00), the median score of OSI was 26.00 (17.00, 34.00), the median score of MBI-GS was 3.53 (3.13, 4.00), and the median score of MAAS was 71.00 (59.00, 82.00). The burnout and mindful attention awareness levels varied among military personnel of different age groups (P<0.05), so did the burnout and occupational stress levels among military personnel of different length of service groups (P<0.05), and the occupational stress, PSQI, burnout, and mindful attention awareness levels among military personnel with different educational backgrounds and genders (P<0.05). The results of mediated effect test showed that occupational stress and burnout had both a parallel mediated effect and a sequential mediating effect on the relationship between mindful attention awareness and sleep quality, with effect sizes of 15.3%, 21.5% and 31.8%, respectively. Conclusion There is a mediated effect on the relationship between mindful attention awareness and sleep quality by the occupational stress and burnout of military personnel in plateau areas, and sleep quality is also affected by mindful attention awareness through the chain-mediated effect of occupational stress and burnout.
5. Study on the mechanism of astragalus glycyrrhiza decoction regulating SIRT1 / FOXO1 pathway to prevent QT interval prolongation induced by arsenic trioxide based on metabolomics
Lan XU ; Ke REN ; Yarong ZHANG ; Haoshi CAO ; Dongling LIU ; Yang HAI
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(2):130-138
AIM: To explore the protective effect of astragalus glycyrrhiza decoction (AGD) on arsenic trioxide (ATO)-induced QT interval prolongation and its mechanism based on metabonomics. METHODS: The model of ATO-induced QT interval prolongation in rats was established, and ECG, blood routine, and metabonomics were detected, and the key targets were collected combined with network pharmacology. The possible candidate genes and pathways for the protective effect of AGD were screened by GO and KEGG enrichment analysis and then verified by experiments in vitro. RESULTS: AGD could significantly alleviate the ATO-induced QT interval of SD rats. GO enrichment analysis was mainly related to inflammatory response, reactive oxygen species, oxidative stress, inner cell vesicles, folds, inner cell vesicles, SMAD binding, R-SMAD binding, and signal receptor activator activity. KEGG analysis showed that it was mainly concentrated in the PI3K-Akt signal pathway, lipid and arteriosclerosis, FOXO signal pathway, TNF signal pathway, HIF-1, and other signal pathways. Through the H9c2 cell model in vitro, it was verified that AGD could reverse the expression of SIRT1 and FOXO1 proteins. CONCLUSION: AGD may improve the ATO-induced QT interval prolongation and reduce the cardiotoxicity of ATO by regulating the SIRT1 / FOXO1 signal pathway.
6.Toxicokinetics of MDMA and Its Metabolite MDA in Rats
Wei-Guang YU ; Qiang HE ; Zheng-Di WANG ; Cheng-Jun TIAN ; Jin-Kai WANG ; Qian ZHENG ; Fei REN ; Chao ZHANG ; You-Mei WANG ; Peng XU ; Zhi-Wen WEI ; Ke-Ming YUN
Journal of Forensic Medicine 2024;40(1):37-42
Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.
7.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.
8.Stroke incidence of the household population inShanghai's Qingpu District in 2017 - 2022
Yiwen HUANG ; Zhihua REN ; Zhouli WU ; Jie LU ; Ke ZHANG ; Ye LU ; Yue WANG ; Ya WU
Journal of Public Health and Preventive Medicine 2024;35(4):70-73
Objective To understand the characteristics and temporal trends of stroke incidence in the household population of Shanghai's Qingpu District and to provide a basis for the development of comprehensive prevention and control strategies. Methods The stroke case database for Qingpu District from 2017-2022 was obtained from the Shanghai Stroke and Acute Myocardial Infarction Registry and Reporting Information System. The average age of onset, incidence rate, standardised incidence rate, and constitutive ratio were calculated. Independent samples t-tests were used for comparisons between groups, 2-tests and 2-trend tests for comparisons of rates, and the Joinpoint regression model for calculating the annual percentage change (APC) to analyse the temporal trend of rates. Results Between 2017 and 2022, the average age of stroke onset in the household population of Shanghai's Qingpu District was 73.69±11.60 years. The average annual incidence rate was 556.62/100 000, with an average annual standardised incidence rate of 333.76/100000. There was an increasing trend in the incidence and standardised incidence of stroke in males (APC=7.06%, t=3.44, P=0.03, APC=5.32%, t=3.04, P=0.04). The incidence of stroke increases with age, with cases mainly concentrated in those aged 65 years and above, accounting for 79.47%. Ischemic stroke dominates the stroke typology, accounting for 91.08% of cases, while the incidence of hemorrhagic stroke shows an increasing trend (APC=4.64%, t=4.59, P=0.01). Conclusion The occurrence of stroke in the general population of Shanghai’s Qingpu District is concerning. The study indicates that males, individuals aged 65 years and above, and ischaemic stroke are significant factors that require attention for stroke prevention and control.
9.Efficacy and mechanism of static progressive stretch with different parameters in treatment of stiff knee in rats
Ke CHEN ; Xin ZHANG ; Kai REN ; Hui LIU ; Yingying LIAO ; Chenghong WEN ; Xiaoping SHUI
Chinese Journal of Orthopaedic Trauma 2024;26(3):255-261
Objective:To investigate the efficacy and mechanism of static progressive stretch (SPS) with different parameters in the treatment of stiff knee in rats.Methods:Fifty-six male 8-week SD rats were randomly divided into an operation group ( n=48) and a blank group ( n=8, normal feeding rats without any treatment). The knee joints of the rats in the operation group were fixed with Kirschner wire for 4 weeks to create models of right knee flexion stiffness. The 42 rats with successful modeling were randomly divided into 6 groups ( n=7): the model group was executed and sampled after successful modeling, the spontaneous recovery group was not given any treatment after successful modeling, group T1 was given SPS treatment for 20 min once per day, group T2 was given SPS treatment for 30 min once per day, group T3 was given SPS treatment for 20 min once every 2 days, and group T4 was given SPS treatment for 30 min once every 2 days. After 16 days, the range of knee motion, number of myofibroblasts, and positive proportion of transforming growth factor- β1 (TGF- β1) in the joint capsule were detected and compared between groups. Results:The ranges of knee motion in the spontaneous recovery group and the 4 SPS treatment groups were significantly greater than those before treatment ( P<0.05), and the improvements in the range of knee motion in the 4 SPS treatment groups were significantly greater than that in the spontaneous recovery group ( P<0.05). The range of knee motion in group T2 (112.29°±1.89°) was improved the most significantly. The number of myofibroblasts was (23.72±10.75)/HP, which was significantly smaller than that in T3 group [(55.72±33.56)/HP] or in T4 group [(50.72±33.34)/HP] ( P<0.05). The positive proportions of TGF- β1 in the joint capsule in the 4 SPS treatment groups were significantly lower than that in the model group, and the positive proportion of TGF- β1 in the joint capsule in group T2 (0.51%±0.38%) was significantly lower than those in group T3 and T4 ( P<0.05). Conclusions:As SPS treatment can reduce the expression of TGF- β1 in the joint and inhibit the excessive proliferation of myofibroblasts to alleviate the pathological changes in a stiff knee, it has a significant effect on the stiff knee in rats. The SPS treatment for 30 minutes and once per day may lead to the best efficacy.
10.Investigation and analysis of the current status of transjugular intrahepatic portosystemic shunt treatment for portal hypertension in China
Haozhuo GUO ; Meng NIU ; Haibo SHAO ; Xinwei HAN ; Jianbo ZHAO ; Junhui SUN ; Zhuting FANG ; Bin XIONG ; Xiaoli ZHU ; Weixin REN ; Min YUAN ; Shiping YU ; Weifu LYU ; Xueqiang ZHANG ; Chunqing ZHANG ; Lei LI ; Xuefeng LUO ; Yusheng SONG ; Yilong MA ; Tong DANG ; Hua XIANG ; Yun JIN ; Hui XUE ; Guiyun JIN ; Xiao LI ; Jiarui LI ; Shi ZHOU ; Changlu YU ; Song HE ; Lei YU ; Hongmei ZU ; Jun MA ; Yanming LEI ; Ke XU ; Xiaolong QI
Chinese Journal of Radiology 2024;58(4):437-443
Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.


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