1.Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.
Qihui ZHOU ; Panpan CEN ; Zhi CHEN ; Jie JIN
Journal of Zhejiang University. Science. B 2025;26(10):972-994
Nuclear factor erythroid 2-related factor 2 (Nrf2) is an intracellular transcription factor that helps protect against oxidative stress in different types of cells under pathological conditions. Mitochondria are vital organelles that function in diverse metabolic processes in the body, including redox reactions, lipid metabolism, and cell death. Mitophagy, a specific form of autophagy for damaged mitochondria, plays a critical role in the pathophysiology of liver diseases. In this review, we explain in detail the roles of the Nrf2 signaling pathway and mitophagy, and the relationship between them, in various hepatic diseases (nonalcoholic fatty liver disease, viral hepatitis, alcoholic liver disease, drug-induced liver injury, autoimmune hepatitis, hepatic ischemia‒reperfusion injury, and liver cancer). We also offer some potential insights and treatments relevant to clinical applications.
Humans
;
NF-E2-Related Factor 2/metabolism*
;
Mitophagy/physiology*
;
Kelch-Like ECH-Associated Protein 1/metabolism*
;
Signal Transduction
;
Liver Diseases/etiology*
;
Animals
;
Oxidative Stress
;
Mitochondria/metabolism*
;
Non-alcoholic Fatty Liver Disease
;
Liver Neoplasms
2.Effects of ACBT Technique Combined with Resistance Breathing Training on Patients with AECOPD
Mei CEN ; Ming JIN ; Rui ZHANG ; Yi YANG ; Zhixiang ZHANG
Journal of Kunming Medical University 2025;46(3):171-176
Objective To investigate the effects of active respiratory circulation technique(ACBT)combined with resistance breathing training on pulmonary function and exercise capacity in patients with acute exacerbations of chronic obstructive pulmonary disease(AECOPD).Methods A total of 60 hospitalized AECOPD patients from the Geriatrics Department of a tertiary hospital in Kunming were selected as research subjects from January to May 2024.Patients were randomly divided into two groups,with 30 patients in each group.The control group received conventional pulmonary rehabilitation nursing,and the observation group received ACBT combined with resistance breathing training.Pulmonary function indicators,modified British Medical Council(mMRC)dyspnea scores,6-minute walk test(6MWT)distances,and the COPD Assessment Test(CAT)scores were collected 4 weeks after discharge to evaluate the intervention's effectiveness.Results After the intervention,the observation group showed significant improvements in lung function,mMRC scores,6M WT distances,and CAT scores compared to pre-intervention levels,and all were superior to the control group(P<0.05).Conclusion ACBT combined with resistance breathing training can more effectively promote sputum clearance,reduce respiratory muscle fatigue,increase exercise endurance,and improve dyspnea severity and lung function in AECOPD patients.
3.Trajectories of executive function development and its neural mechanisms in patients with attention deficit hyperactivity disorder
Ruilin JIN ; Jiaqi ZHOU ; Teng ZHU ; Jiayun YU ; Wanying ZHENG ; Hanlin LI ; Mengjie ZHANG ; Xiaolei CEN ; Chuang YANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(3):277-282
Executive function(EF) is an advanced cognitive function of the central nervous system, and is closely related to an individual's capacity for daily living and adaptation. Patients with attention deficit hyperactivity disorder (ADHD) typically exhibit significant executive dysfunction. While most existing studies on the executive function of individuals with ADHD are cross-sectional, and little is known about the longitudinal maturation process of related brain structures and functional connectivity patterns. The findings indicate that ADHD patients exhibit differential developmental trajectories in brain structural and functional connectivity compared with typically developing group.Furthermore, there is a lifespan association between abnormal brain network development and ADHD symptoms. This article aims to elucidate the characteristics of executive function deficits in ADHD patients across different developmental stages, examining their relationship with the nervous system’s development from a development perspective.
4.Trajectories of executive function development and its neural mechanisms in patients with attention deficit hyperactivity disorder
Ruilin JIN ; Jiaqi ZHOU ; Teng ZHU ; Jiayun YU ; Wanying ZHENG ; Hanlin LI ; Mengjie ZHANG ; Xiaolei CEN ; Chuang YANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(3):277-282
Executive function(EF) is an advanced cognitive function of the central nervous system, and is closely related to an individual's capacity for daily living and adaptation. Patients with attention deficit hyperactivity disorder (ADHD) typically exhibit significant executive dysfunction. While most existing studies on the executive function of individuals with ADHD are cross-sectional, and little is known about the longitudinal maturation process of related brain structures and functional connectivity patterns. The findings indicate that ADHD patients exhibit differential developmental trajectories in brain structural and functional connectivity compared with typically developing group.Furthermore, there is a lifespan association between abnormal brain network development and ADHD symptoms. This article aims to elucidate the characteristics of executive function deficits in ADHD patients across different developmental stages, examining their relationship with the nervous system’s development from a development perspective.
5.5-HT Promotes Proliferation and Inhibits Apoptosis of Megakarycytes through 5-HT2BR
Hui-Min KONG ; Yu-Rong CEN ; Mo YANG ; Qiang PENG ; Jin-Qi HUANG
Journal of Experimental Hematology 2025;33(1):75-81
Objective:To investigate the effect of 5-hydroxytryptamine(5-HT)on the proliferation,apoptosis and colony-forming unit-megakaryocyte(CFU-MK)of Meg-01 cells and its possible mechanisms.Methods:The uptake and metabolism of 5-HT in Meg-01 cells were analysed by reverse-phase high-performance liquid chromatography(RP-HPLC)with electrochemical detection.The expression of 5-HT2B receptor(5-HT2BR)in megakaryocytes was detected by immunofluorescence staining.The cell proliferation and viability were measured by MTT and Trypan blue staining after Meg-01 cells were single-cultured or co-cultured with different concentrations of 5-HT/5-HT2BR inhibitor Ketanserin for 48 h.Meg-01 cells were incubated with 5-HT/Ketanserin for 72 h,then the flow cytometry was used to detect early apoptosis of the cells and the activity of caspase-3.Using CFU-MK assay to investigate the effect of 5-HT on the differentiation of megakaryocytes.Results:5-HT could be uptaken by Meg-01 cells,and metabolized into 5-hydroxyindoleacetic acid(5-HIAA).The expression of 5-HT2BR on megakaryocytes could be detected after immunofluorescence staining.5-HT could promote the proliferation of Meg-01 cells at a dose-dependent manner(r=0.82),with the most significant effect observed at a concentration of 200 nmol/L(P<0.001).Trypan blue staining also indicated that 200 nmol/L 5-HT had the most significant effect on the viability of Meg-01 cells(P<0.05).The proliferation of Meg-01 cells treated with 5-HT was increased compared with the untreated control(P<0.001),while the combination of 5-HT with ketanserin downregulated this effect.5-HT significantly reduced the early apoptosis rate(P<0.001)and caspase-3 activity(P<0.05)of Meg-01 cells,while addition of ketanserin significantly increased the early apoptosis rate of Meg-01 cells(P<0.001)and caspase-3 activity also increased to some extent.5-HT promoted the formation of CFU-MK in bone marrow cells in a dose-dependent manner(r=0.89).The addition of ketanserin reduced the promoting effect of 5-HT on CFU-MK formation(P<0.01).Conclusion:There may be monoamine oxidase present in megakaryocytes,which can metabolize and decompose 5-HT into 5-HIAA.5-HT may promote the proliferation and differentiation of megakaryocytes through 5-HT2BR.Besides,5-HT can also reduce the apoptosis of megakaryocytes,and its anti-apoptotic effect may be mediated by 5-HT2BR and caspase-3 pathways.
6.Study on the characteristics of lymphocyte-specfic protein-tyrosine kinase methylation in the peripheral blood circulation of patients with rheumatoid arthritis
Lingxia XU ; Cen CHANG ; Ping JIANG ; Kai WEI ; Jia′nan ZHAO ; Yixin ZHENG ; Yu SHAN ; Yiming SHI ; Hua Ye JIN ; Yi SHEN ; Shicheng GUO ; Dongyi HE ; Jia LIU
Chinese Journal of Rheumatology 2024;28(3):155-161
Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.
7.Research progress on drug resistance mechanism of sorafenib in radioiodine refractory differentiated thyroid cancer
En-Tao ZHANG ; Hao-Nan ZHU ; Zheng-Ze WEN ; Cen-Hui ZHANG ; Yi-Huan ZHAO ; Ying-Jie MAO ; Jun-Pu WU ; Yu-Cheng JIN ; Xin JIN
The Chinese Journal of Clinical Pharmacology 2024;40(13):1986-1990
Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.
8.Latent class analysis of therapeutic effects of Huoxiang Zhengqi Oral Liquid on patients with cold due to wind-cold and dampness stagnation.
Miao WU ; Shi-Sui LUO ; Jin YIN ; Si-Cen JIN ; Lin SUN ; Hao-Qi ZHOU ; Xin-Ting HUANG ; Xiao-Hua ZHOU
China Journal of Chinese Materia Medica 2024;49(21):5944-5950
The demographic characteristics, drug use, clinical symptoms and other data of the patients treated with Huoxiang Zhengqi Oral Liquid were collected. The latent class analysis(LCA) was performed to reveal the distribution of primary symptoms, and then the doubly robust estimation was employed to analyze the efficacy of different doses of Huoxiang Zhengqi Oral Liquid in different populations. A total of 11 273 patients were enrolled in this study, including 4 347 males and 6 926 females. A total of 15 primary symptoms were included, with the top 3 being dizziness(53.9%), head heaviness(39.6%), and nausea(39.4%). According to the LCA, the population was divided into 3 groups of spleen deficiency and dampness exuberance(5 604 cases, 49.71%), upward harassing of wind-phlegm(4 955 cases, 43.96%), and spleen Qi deficiency(714 cases, 6.33%). Double robust estimation showed that the time to recovery of the patients with spleen Qi deficiency had no significant difference regarding the daily dose. Compared with the daily dose of 20 mL, the daily doses of 40, and 60 mL shortened the time to recovery by 16.67(95%CI[5.23, 28.12]) and 15.94 h(95%C1[7.45, 24.43]) in the patients with upward harassingof wind-phlegm, the daily doses of 30, 40, and 60 mL shortened the time to recovery by 4.42(95%CI[1.06, 7.77]), 13.07(95%CI[1.61, 24.54]), 13.92 h(95%CI[5.14, 22.70]) in the patients with spleen deficiency and dampness exuberance, respectively. The patients with cold due to wind-cold and dampness stagnation had more primary syndromes, and the disease locations were mainly in the head, stomach, and spleen. In clinical practice, the daily dose of Huoxiang Zhengqi Oral Liquid can be increased according to the symptoms of patients, which can shorten the time to recovery.
Humans
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Male
;
Female
;
Drugs, Chinese Herbal/therapeutic use*
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Middle Aged
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Adult
;
Young Adult
;
Aged
;
Adolescent
;
Administration, Oral
;
Wind
;
Child
;
Spleen/drug effects*
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Cold Temperature
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Aged, 80 and over
9.Development of Vital Signal Monitoring System Based on Accelerometer.
Jian CEN ; Xingliang JIN ; Sanchao LIU ; Huacheng LUO ; Nong YAN ; Xianliang HE ; Yumei MA ; Hanyuan LUO ; Jie QIN ; Yinbing YANG
Chinese Journal of Medical Instrumentation 2023;47(6):602-607
OBJECTIVE:
Reduce the number of false alarms and measurement time caused by movement interference by the sync waveform of the movement.
METHODS:
Vital signal monitoring system based on motion sensor was developed, which collected and processed the vital signals continuously, optimized the features and results of vital signals and transmitted the vital signal results and alarms to the interface.
RESULTS:
The system was tested in many departments, such as digestive department, cardiology department, internal medicine department, hepatobiliary surgery department and emergency department, and the total collection time was 1 940 h. The number of false electrocardiograph (ECG) alarms decreased by 82.8%, and the proportion of correct alarms increased by 28%. The average measurement time of non-invasive blood pressure (NIBP) decreased by 16.1 s. The total number of false respiratory rate measurement decreased by 71.9%.
CONCLUSIONS
False alarms and measurement failures can be avoided by the vital signal monitoring system based on accelerometer to reduce the alarm fatigue in clinic.
Humans
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Monitoring, Physiologic
;
Electrocardiography
;
Arrhythmias, Cardiac
;
Blood Pressure
;
Accelerometry
;
Clinical Alarms
10.Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with inv(16)/t(16;16)(p13.1;q22) and/or CBFβ-MYH11.
Ye-Min WANG ; Ping CAI ; Mei-Jia ZHOU ; Ying-Ying GONG ; Jin-Lan PAN ; Jian-Nong CEN ; Xiao-Fei YANG ; Su-Ning CHEN
Journal of Experimental Hematology 2022;30(2):367-372
OBJECTIVE:
To summarize the clinical and laboratory characteristics of patients with acute myeloid leukemia (AML) with inv(16)/t(16;16) (p13.1;q22), and to analyze the risk factors affecting the prognosis of the patients.
METHODS:
AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFβ-MYH11+ admitted to the Department of Hematology, The First Affiliated Hospital of Soochow University from January 1, 2008 to October 30, 2019 were retrospective analyzed, the clinical and laboratory indicators, as well as treatment plans and efficacy evaluations of the patients were all recorded. Furthermore, related factors affecting the overall survival (OS) and event-free survival (EFS) of the patients were analyzed.
RESULTS:
Among 151 AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFβ-MYH11+, the percentage of additional chromosomal abnormalities was about 27.8%, and the most common additional chromosomal abnormality was +22 (33/151, 21.8%), followed by +8 (11/151, 7.3%). There were 112 patients with perfect NGS examination, and the result showed the most common accompanying gene mutations were KIT mutation (34/112, 30.4%) and FLT3 mutation (23/112, 20.5%). Univariate analysis showed that factors affecting EFS included: NE≤0.5×109/L (P=0.006) and combined K-RAS mutation (P=0.002); Factors affecting OS included: Age≥50 years old (P<0.001) and NE≤0.5×109/L (P=0.016). Multivariate analysis showed that NE≤0.5×109/L (P=0.019) was the risk factors affecting OS. The proportion of bone marrow eosinophilia (BME)≥10.00% (P=0.029) was the risk factors affecting EFS.
CONCLUSION
The prognosis for those newly diagnosed AML patients who were of advanced age, the high proportion of bone marrow eosinophils, K-RAS mutations, and agranulocytosis is poor. The treatment plans can be adjusted in the early stage to improve the prognosis of such patients.
Chromosome Inversion
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Humans
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Leukemia, Myeloid, Acute/genetics*
;
Middle Aged
;
Myosin Heavy Chains/genetics*
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Oncogene Proteins, Fusion
;
Prognosis
;
Retrospective Studies

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