1.Identification and functional study of DNA damage-induced tsRNAs in HepG2 cells
Guanzi CHEN ; Fuyang HONG ; Yuanhao JIANG ; Yuzhen ZHANG ; Yusheng JIE
Chinese Journal of Pathophysiology 2025;41(4):688-695
AIM:To identify the expression characteristics of transfer RNA-derived small RNAs(tsRNAs)re-sponding to DNA damage in human hepatoblastoma HepG2 cells,and to investigate their potential functions.METHODS:Based on paired HepG2 cells and TP53 gene knockout HepG2 cells,we successfully constructed a DNA damage cellular model using adriamycin(ADR).Transcriptome analysis of small noncoding RNAs was performed to systematically identi-fy a set of tsRNAs responding to ADR and involved in p53 regulation.Functional enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Additionally,after silencing the expression of target tsRNA genes,the biological functions of these tsRNAs in HepG2 cells were initially confirmed through CCK-8 assay and plate colo-ny formation assay.RESULTS:DNA damage induced a set of tsRNAs involved in p53 regulation,among which tRF-5-1(tRF-5_tRNA-Gly-TCC-2-1)and tRF-i-1(tRF i_tRNA-Tyr-GTA-11-1)showed the most significant up-regulation in HepG2 cells(P<0.05).Silencing of either tRF-5-1 or tRF-i-1 gene inhibited the proliferative activity of HepG2 cells(P<0.05).CONCLUSION:A group of tsRNAs responding to DNA damage can be identified in HepG2 cell model,and tsRNAs can promote the proliferative activity of HepG2 cells,suggesting that tsRNAs may play an important role in the de-velopment and progression of liver malignancies.
3.Effect of electroacupuncture on learning and memory abilities in vascular dementia rats via the NCOA4/FTH1 signaling pathway-mediated ferritinophagy.
Wei SUN ; Yinghua CHEN ; Tong WU ; Hongxu ZHAO ; Haoyu WANG ; Ruiqi QIN ; Xiaoqing SU ; Junfeng LI ; Yuanyu SONG ; Yue MIAO ; Xinran LI ; Yusheng HAN
Chinese Acupuncture & Moxibustion 2025;45(9):1271-1280
OBJECTIVE:
To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD.
METHODS:
A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot.
RESULTS:
Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01).
CONCLUSION
Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals
;
Electroacupuncture
;
Dementia, Vascular/genetics*
;
Male
;
Rats
;
Signal Transduction
;
Humans
;
Memory
;
Rats, Sprague-Dawley
;
Nuclear Receptor Coactivators/genetics*
;
Ferritins/genetics*
;
Learning
;
Hippocampus/metabolism*
;
Acupuncture Points
4.Analysis of etiological composition and clinical characteristics in 960 cases of unexplained liver disease diagnosed by liver biopsy
Zhicong LONG ; Shuang LIU ; Guanzi CHEN ; Yusheng JIE
Journal of Clinical Hepatology 2025;41(8):1627-1631
Objective To investigate the composition ratios and trends of different etiologies after liver biopsy for patients with unexplained liver diseases.Methods A retrospective analysis was performed for the etiology of 960 patients with unexplained liver diseases who were hospitalized and underwent liver biopsy in The Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to December 2020,and the etiologies were categorized by year and age group.The chi-square test was used for comparison of categorical data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups.Results There was a tendency of increase in the overall composition ratio of unexplained liver diseases over the past decade.The leading diagnosis after liver biopsy was autoimmune liver disease(AILD)in 306 patients(31.9%),followed by nonalcoholic fatty liver disease(NAFLD)in 95 patients(9.9%)and drug-induced liver disease(DILI)in 82 patients(8.5%),and there were still 320 patients with undetermined causes(33.3%).There were significant differences in sex ratio and median age distribution between the patients with different etiologies(sex ratio:χ2=155.36,P<0.001;median age distribution:H=182.48,P<0.001).AILD had been the leading etiology in 2011-2020,and there was a tendency of reduction in the composition ratio of AILD(χ2=24.40,P<0.001).NAFLD accounted for the highest proportion of 17.6%in the adolescent stage,while AILD accounted for the highest proportion of 17.8%,47.3%,and 56.3%,respectively,in the young,middle-aged,and elderly stages.Conclusion There is a tendency of increase in the composition ratio of unexplained liver diseases in patients undergoing liver biopsy,with AILD being the main disease diagnosed after liver biopsy,followed by NAFLD and DILI,but one-third of the patients still have an unclear etiological diagnosis.
5.Epidemic characteristics of severe fever with thrombocytopenia syndrome in Tiantai County, Zhejiang Province
Haiyan HU ; Xikai CHEN ; Yingjun CHEN ; Shanshan CHU ; Tianlan PANG ; Luwei WANG ; Dingling CHEN ; Yusheng CHEN
Chinese Journal of Endemiology 2025;44(9):752-757
Objective:To investigate the epidemic characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Tiantai County Zhejiang Province, and provide a scientific basis for prevention and control of SFTS.Methods:The case data of SFTS in Tiantai County from 2014 to 2024 were collected through the Chinese Disease Control and Prevention Information System, and descriptive epidemic method was employed to analyze its epidemic and clinical characteristics.Results:From 2014 to 2024, a total of 114 SFTS cases were reported in Tiantai County, with an average annual incidence rate of 2.21/100 000. The peak incidence occurred in 2021 (3.40/100 000, 16 cases). Nine cases died, with a mortality rate of 7.89% (9/114). The male-to-female ratio was 1.00∶0.97 (58∶56). The high-risk population was middle-aged and elderly people aged over 50 years old, accounting for 91.23% (104/114). The occupation was mainly farmers, accounting for 92.98% (106/114). The incidence of SFTS had obvious seasonality, with a peak from April to September, accounting for 83.33% (95/114). The average onset date was calculated to be June 25th, and the peak period was from April 19th to August 31st. The distribution of cases was mainly in Tantou Town (34 cases), Shiliang Town (23 cases), Yongxi Township (17 cases), and Pingqiao Town (12 cases), accounting for 75.44% (86/114). From 2014 to 2024, the affected areas had gradually expanded from 1 township/subdistrict to 13 townships/subdistricts, showed a phenomenon of migration from east to west. Among the 114 patients with SFTS, the initial symptom was fever. The proportion of neuropsychiatric symptoms, atrial fibrillation and heart failure in the death group was significantly higher than those in the survival group (χ 2 = 19.24, 16.44, 23.90, P < 0.001). Conclusion:From 2014 to 2024, the incidence of SFTS in Tiantai County fluctuates with obvious seasonal and regional migration characteristics.
6.Analysis of etiological composition and clinical characteristics in 960 cases of unexplained liver disease diagnosed by liver biopsy
Zhicong LONG ; Shuang LIU ; Guanzi CHEN ; Yusheng JIE
Journal of Clinical Hepatology 2025;41(8):1627-1631
Objective To investigate the composition ratios and trends of different etiologies after liver biopsy for patients with unexplained liver diseases.Methods A retrospective analysis was performed for the etiology of 960 patients with unexplained liver diseases who were hospitalized and underwent liver biopsy in The Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to December 2020,and the etiologies were categorized by year and age group.The chi-square test was used for comparison of categorical data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups.Results There was a tendency of increase in the overall composition ratio of unexplained liver diseases over the past decade.The leading diagnosis after liver biopsy was autoimmune liver disease(AILD)in 306 patients(31.9%),followed by nonalcoholic fatty liver disease(NAFLD)in 95 patients(9.9%)and drug-induced liver disease(DILI)in 82 patients(8.5%),and there were still 320 patients with undetermined causes(33.3%).There were significant differences in sex ratio and median age distribution between the patients with different etiologies(sex ratio:χ2=155.36,P<0.001;median age distribution:H=182.48,P<0.001).AILD had been the leading etiology in 2011-2020,and there was a tendency of reduction in the composition ratio of AILD(χ2=24.40,P<0.001).NAFLD accounted for the highest proportion of 17.6%in the adolescent stage,while AILD accounted for the highest proportion of 17.8%,47.3%,and 56.3%,respectively,in the young,middle-aged,and elderly stages.Conclusion There is a tendency of increase in the composition ratio of unexplained liver diseases in patients undergoing liver biopsy,with AILD being the main disease diagnosed after liver biopsy,followed by NAFLD and DILI,but one-third of the patients still have an unclear etiological diagnosis.
7.Epidemic characteristics of severe fever with thrombocytopenia syndrome in Tiantai County, Zhejiang Province
Haiyan HU ; Xikai CHEN ; Yingjun CHEN ; Shanshan CHU ; Tianlan PANG ; Luwei WANG ; Dingling CHEN ; Yusheng CHEN
Chinese Journal of Endemiology 2025;44(9):752-757
Objective:To investigate the epidemic characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Tiantai County Zhejiang Province, and provide a scientific basis for prevention and control of SFTS.Methods:The case data of SFTS in Tiantai County from 2014 to 2024 were collected through the Chinese Disease Control and Prevention Information System, and descriptive epidemic method was employed to analyze its epidemic and clinical characteristics.Results:From 2014 to 2024, a total of 114 SFTS cases were reported in Tiantai County, with an average annual incidence rate of 2.21/100 000. The peak incidence occurred in 2021 (3.40/100 000, 16 cases). Nine cases died, with a mortality rate of 7.89% (9/114). The male-to-female ratio was 1.00∶0.97 (58∶56). The high-risk population was middle-aged and elderly people aged over 50 years old, accounting for 91.23% (104/114). The occupation was mainly farmers, accounting for 92.98% (106/114). The incidence of SFTS had obvious seasonality, with a peak from April to September, accounting for 83.33% (95/114). The average onset date was calculated to be June 25th, and the peak period was from April 19th to August 31st. The distribution of cases was mainly in Tantou Town (34 cases), Shiliang Town (23 cases), Yongxi Township (17 cases), and Pingqiao Town (12 cases), accounting for 75.44% (86/114). From 2014 to 2024, the affected areas had gradually expanded from 1 township/subdistrict to 13 townships/subdistricts, showed a phenomenon of migration from east to west. Among the 114 patients with SFTS, the initial symptom was fever. The proportion of neuropsychiatric symptoms, atrial fibrillation and heart failure in the death group was significantly higher than those in the survival group (χ 2 = 19.24, 16.44, 23.90, P < 0.001). Conclusion:From 2014 to 2024, the incidence of SFTS in Tiantai County fluctuates with obvious seasonal and regional migration characteristics.
8.Research progress on the pathogenesis of chronic obstructive pulmonary disease complicated with lung cancer
Anying LI ; Zhiwei LI ; Dianhan SUN ; Yong CHEN ; Jun WU ; Yusheng SHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(06):855-862
Chronic obstructive pulmonary disease (COPD), which predominantly affects middle-aged and elderly individuals, is associated with a significantly reduced quality of life and often triggers various other pulmonary conditions. Lung cancer, as one of the most prevalent and deadly pulmonary malignancies worldwide, poses a severe threat to global public health. The risk of developing lung cancer is markedly higher in COPD patients compared to the general population, indicating numerous associations between the two conditions that warrant in-depth investigation. Although a substantial body of research has explored the relationship between COPD and lung cancer, studies focusing on the molecular mechanisms underlying their connection remain limited. This article reviews the latest research progress on the mechanisms of COPD complicated by lung cancer from four perspectives: the role of chronic pulmonary inflammation, programmed cell death, genetic and molecular interactions, and dysbiosis of the pulmonary microbiome. The aim of this article is to provide new insights and references for the prevention and therapeutic strategies of COPD complicated with lung cancer.
9.Identification and functional study of DNA damage-induced tsRNAs in HepG2 cells
Guanzi CHEN ; Fuyang HONG ; Yuanhao JIANG ; Yuzhen ZHANG ; Yusheng JIE
Chinese Journal of Pathophysiology 2025;41(4):688-695
AIM:To identify the expression characteristics of transfer RNA-derived small RNAs(tsRNAs)re-sponding to DNA damage in human hepatoblastoma HepG2 cells,and to investigate their potential functions.METHODS:Based on paired HepG2 cells and TP53 gene knockout HepG2 cells,we successfully constructed a DNA damage cellular model using adriamycin(ADR).Transcriptome analysis of small noncoding RNAs was performed to systematically identi-fy a set of tsRNAs responding to ADR and involved in p53 regulation.Functional enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Additionally,after silencing the expression of target tsRNA genes,the biological functions of these tsRNAs in HepG2 cells were initially confirmed through CCK-8 assay and plate colo-ny formation assay.RESULTS:DNA damage induced a set of tsRNAs involved in p53 regulation,among which tRF-5-1(tRF-5_tRNA-Gly-TCC-2-1)and tRF-i-1(tRF i_tRNA-Tyr-GTA-11-1)showed the most significant up-regulation in HepG2 cells(P<0.05).Silencing of either tRF-5-1 or tRF-i-1 gene inhibited the proliferative activity of HepG2 cells(P<0.05).CONCLUSION:A group of tsRNAs responding to DNA damage can be identified in HepG2 cell model,and tsRNAs can promote the proliferative activity of HepG2 cells,suggesting that tsRNAs may play an important role in the de-velopment and progression of liver malignancies.

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