1.Effect of m6A demethylase ALKBH5 on proliferation and migration of cardiac fibroblasts induced by high glucose
Zhi-yan LIU ; Li-chan LIN ; Zhen-yu LIU ; Ji-ming SHA ; Peng LIU ; Sui MAO ; Yun-sen ZHANG ; Rui LI ; Ye ZHANG ; Hui TAO
Chinese Pharmacological Bulletin 2025;41(2):235-241
Aim To investigate the effect of N6-methy-ladenosine(m6A)demethylase ALKBH5 on the prolif-eration and migration of cardiac fibroblasts(CFs)in-duced by high glucose.Methods Primary CFs were isolated from neonatal mouse hearts and identified u-sing optical and confocal microscopy.Cell activation was induced using a high-glucose medium(33 mmol·L-1 glucose).An ALKBH5 overexpression model was established by transfecting CFs with an ALKBH5 ex-pression vector in a high-glucose medium.The expres-sion of ALKBH5 in CFs was assessed through immuno-fluorescence staining,Western blot and RT-qPCR.Changes in m6A levels were evaluated using Dot blot a-nalysis.Additionally,Alterations in the expression of proliferating cell nuclear antigen(PCNA)and collagenⅠ,a pivotal fibrosis indicator,were measured using Western blot.The proliferation and migration ability of CFs were assessed through EdU staining and Transwell migration assay,respectively.Results Following treatment with high glucose,the expression of ALKBH5 in CFs notably decreased,while m6A level increased.This was accompanied by a significant increase in the expression of the proliferation marker PCNA and the fi-brosis marker collagen Ⅰ.Additionally,there was a sig-nificant improvement in the ability of proliferation and migration.Overexpression of ALKBH5 resulted in a significant decrease in the expressions of PCNA and collagen Ⅰ,leading to the inhibition of both proliferation and migration in CFs.Conclusion Overexpression of ALKBH5 suppresses the expression of PCNA and colla-gen Ⅰ,consequently reducing the proliferation and mi-gration of CFs,potentially through m6A methylation modification.
2.Quantitative analysis of motion of cardiac substructures in deep inspiratory breath holding radiotherapy for left breast cancer
Zhao-hui TANG ; Zhe ZHANG ; Wei-bin MAO ; Bo HUANG ; Jun-feng AI ; Chao-fan ZHU ; Zhi-chao XIE ; Ya-jie LIU
Chinese Medical Equipment Journal 2025;46(3):54-58
Objective To quantify the volume and movement of cardiac substructures by using coronary computed tomography angiography(CCTA)to provide guidance for the design of deep inspiratory breath-holding radiation therapy for left breast cancer and the protection of organs at risk.Methods Totally 18 female patients who received conventional chest plain scan and CCTA were selected to simulate the design process of radiotherapy plan for left breast cancer patients with internal mammary lymph nodes.Retrospective reconstruction of CCTA data was performed for each patient,with 10 phase images(with an interval of 10%)within a R-R cardiac cycle(10%-100%)to simulate the true range of motion of the heart.The heart,left atrium(LA),left ventricle(LV),right atrium(RA),right ventricle(RV),left anterior descending artery(LAD),left circumflex coronary artery(LCX)and right coronary artery(RCA)were contoured at each phase.The distances from the centroid position to the average position of LAD,LCX and RCA were measured at each phase in the superior-inferior(SI),anterior-posterior(AP)and left-right(LR).The average volume and range of volume changes of LA,LV,RA,RV and heart were analyzed within a cardiac cycle.The expansion margins of planning organs at risk volume(PRV)were calculated.SPSS 19.0 software was used for statistical analysis.Results The following average absolute displacements were found in SI,AP and LR coordinates:(1.8±0.7)mm,(1.2±0.5)mm and(1.5±0.5)mm for LAD,respectively;(2.1±0.7)mm,(1.5±0.6)mm and(1.9±0.7)mm for LCX,respectively;(1.6±0.5)mm,(2.2±0.9)mm and(2.2±0.8)mm for RCA,respectively.The volume changes of LA,LV,RA,RV and heart within a cardiac cycle ranged from 34.3 to 63.9 cm3,122.1 to 154.3 cm3,29.3 to 53.6 cm3,57.2 to 94.3 cm3 and 480.1 to 515.4 cm3,respectively.The theoretical expansion margins of LAD,LCX and RCA in all the three directions were within 2 mm.Conclusion The ranges of movement and volume changes of cardiac substructure are quantitati-vely displayed,and references are provided for the planning of deep inspiratory breath-holding radiation therapy for left breast cancer and the protection of organs at risk.[Chinese Medical Equipment Journal,2025,46(3):54-58]
3.Clinical Efficacy of Tianma Xiongling Zhixuan Tablets in Treating Patients with Hypertension of the Type of Hyperactivity of Liver Yang or Combined with Phlegm and Blood Stasis,and Analysis of Plasma Metabolomics
Zhi-xiang CHEN ; Jun-liu HU ; Man WANG ; Fei-ying WANG ; Yao-wu CHEN ; Mao-wen WANG ; Meng-li JI ; Hui-hui LIU ; Jian-min FAN ; Wen ZHANG
Progress in Modern Biomedicine 2025;25(13):2138-2153
Objective:To evaluate the clinical efficacy of Tianma Xionglin Zhixuan Tablets in treating hypertension patients with liver yang hyperactivity or comorbid phlegm-stasis syndrome and explore its therapeutic mechanisms through plasma metabolomics.Methods:Thirty-six hypertension patients(4 dropouts)diagnosed with liver yang hyperactivity or phlegm-stasis syndrome were enrolled as the treatment group from June 2022 to September 2023 at the First Affiliated Hospital of Hunan University of Chinese Medicine,while 30 healthy volunteers with balanced constitutions were recruited as the blank group.Plasma samples were collected from patients pre-and post-treatment and from healthy volunteers.Clinical outcomes,including syndrome scores,office blood pressure(BP),and 24-hour ambulatory BP,were recorded.Plasma metabolomic profiling was performed using liquid chromatography-mass spectrometry(LC-MS).Results:Compared with baseline,Tianma Xionglin Zhixuan Tablets significantly reduced traditional Chinese medicine syndrome scores(P<0.01),office systolic/diastolic BP(P<0.01),and 24-hour ambulatory BP parameters(24-hour mean BP,daytime/nighttime mean BP;all P<0.01).Metabolomic analysis identified 45 differential metabolites between the blank group and pretreatment patients,and 64 metabolites altered post-treatment(VIP>1,P<0.05).Enrichment analysis of 16 overlapping endogenous metabolites revealed that Tianma Xionglin Zhixuan Tablets primarily modulated arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion:Tianma Xionglin Zhixuan Tablets demonstrates significant clinical efficacy in hypertension patients with liver yang hyperactivity or phlegm-stasis syndrome,potentially mediated through regulation of arachidonic acid and sphingolipid metabolism.
4.Quantitative analysis of motion of cardiac substructures in deep inspiratory breath holding radiotherapy for left breast cancer
Zhao-hui TANG ; Zhe ZHANG ; Wei-bin MAO ; Bo HUANG ; Jun-feng AI ; Chao-fan ZHU ; Zhi-chao XIE ; Ya-jie LIU
Chinese Medical Equipment Journal 2025;46(3):54-58
Objective To quantify the volume and movement of cardiac substructures by using coronary computed tomography angiography(CCTA)to provide guidance for the design of deep inspiratory breath-holding radiation therapy for left breast cancer and the protection of organs at risk.Methods Totally 18 female patients who received conventional chest plain scan and CCTA were selected to simulate the design process of radiotherapy plan for left breast cancer patients with internal mammary lymph nodes.Retrospective reconstruction of CCTA data was performed for each patient,with 10 phase images(with an interval of 10%)within a R-R cardiac cycle(10%-100%)to simulate the true range of motion of the heart.The heart,left atrium(LA),left ventricle(LV),right atrium(RA),right ventricle(RV),left anterior descending artery(LAD),left circumflex coronary artery(LCX)and right coronary artery(RCA)were contoured at each phase.The distances from the centroid position to the average position of LAD,LCX and RCA were measured at each phase in the superior-inferior(SI),anterior-posterior(AP)and left-right(LR).The average volume and range of volume changes of LA,LV,RA,RV and heart were analyzed within a cardiac cycle.The expansion margins of planning organs at risk volume(PRV)were calculated.SPSS 19.0 software was used for statistical analysis.Results The following average absolute displacements were found in SI,AP and LR coordinates:(1.8±0.7)mm,(1.2±0.5)mm and(1.5±0.5)mm for LAD,respectively;(2.1±0.7)mm,(1.5±0.6)mm and(1.9±0.7)mm for LCX,respectively;(1.6±0.5)mm,(2.2±0.9)mm and(2.2±0.8)mm for RCA,respectively.The volume changes of LA,LV,RA,RV and heart within a cardiac cycle ranged from 34.3 to 63.9 cm3,122.1 to 154.3 cm3,29.3 to 53.6 cm3,57.2 to 94.3 cm3 and 480.1 to 515.4 cm3,respectively.The theoretical expansion margins of LAD,LCX and RCA in all the three directions were within 2 mm.Conclusion The ranges of movement and volume changes of cardiac substructure are quantitati-vely displayed,and references are provided for the planning of deep inspiratory breath-holding radiation therapy for left breast cancer and the protection of organs at risk.[Chinese Medical Equipment Journal,2025,46(3):54-58]
5.Effect of m6A demethylase ALKBH5 on proliferation and migration of cardiac fibroblasts induced by high glucose
Zhi-yan LIU ; Li-chan LIN ; Zhen-yu LIU ; Ji-ming SHA ; Peng LIU ; Sui MAO ; Yun-sen ZHANG ; Rui LI ; Ye ZHANG ; Hui TAO
Chinese Pharmacological Bulletin 2025;41(2):235-241
Aim To investigate the effect of N6-methy-ladenosine(m6A)demethylase ALKBH5 on the prolif-eration and migration of cardiac fibroblasts(CFs)in-duced by high glucose.Methods Primary CFs were isolated from neonatal mouse hearts and identified u-sing optical and confocal microscopy.Cell activation was induced using a high-glucose medium(33 mmol·L-1 glucose).An ALKBH5 overexpression model was established by transfecting CFs with an ALKBH5 ex-pression vector in a high-glucose medium.The expres-sion of ALKBH5 in CFs was assessed through immuno-fluorescence staining,Western blot and RT-qPCR.Changes in m6A levels were evaluated using Dot blot a-nalysis.Additionally,Alterations in the expression of proliferating cell nuclear antigen(PCNA)and collagenⅠ,a pivotal fibrosis indicator,were measured using Western blot.The proliferation and migration ability of CFs were assessed through EdU staining and Transwell migration assay,respectively.Results Following treatment with high glucose,the expression of ALKBH5 in CFs notably decreased,while m6A level increased.This was accompanied by a significant increase in the expression of the proliferation marker PCNA and the fi-brosis marker collagen Ⅰ.Additionally,there was a sig-nificant improvement in the ability of proliferation and migration.Overexpression of ALKBH5 resulted in a significant decrease in the expressions of PCNA and collagen Ⅰ,leading to the inhibition of both proliferation and migration in CFs.Conclusion Overexpression of ALKBH5 suppresses the expression of PCNA and colla-gen Ⅰ,consequently reducing the proliferation and mi-gration of CFs,potentially through m6A methylation modification.
6.Clinical Efficacy of Tianma Xiongling Zhixuan Tablets in Treating Patients with Hypertension of the Type of Hyperactivity of Liver Yang or Combined with Phlegm and Blood Stasis,and Analysis of Plasma Metabolomics
Zhi-xiang CHEN ; Jun-liu HU ; Man WANG ; Fei-ying WANG ; Yao-wu CHEN ; Mao-wen WANG ; Meng-li JI ; Hui-hui LIU ; Jian-min FAN ; Wen ZHANG
Progress in Modern Biomedicine 2025;25(13):2138-2153
Objective:To evaluate the clinical efficacy of Tianma Xionglin Zhixuan Tablets in treating hypertension patients with liver yang hyperactivity or comorbid phlegm-stasis syndrome and explore its therapeutic mechanisms through plasma metabolomics.Methods:Thirty-six hypertension patients(4 dropouts)diagnosed with liver yang hyperactivity or phlegm-stasis syndrome were enrolled as the treatment group from June 2022 to September 2023 at the First Affiliated Hospital of Hunan University of Chinese Medicine,while 30 healthy volunteers with balanced constitutions were recruited as the blank group.Plasma samples were collected from patients pre-and post-treatment and from healthy volunteers.Clinical outcomes,including syndrome scores,office blood pressure(BP),and 24-hour ambulatory BP,were recorded.Plasma metabolomic profiling was performed using liquid chromatography-mass spectrometry(LC-MS).Results:Compared with baseline,Tianma Xionglin Zhixuan Tablets significantly reduced traditional Chinese medicine syndrome scores(P<0.01),office systolic/diastolic BP(P<0.01),and 24-hour ambulatory BP parameters(24-hour mean BP,daytime/nighttime mean BP;all P<0.01).Metabolomic analysis identified 45 differential metabolites between the blank group and pretreatment patients,and 64 metabolites altered post-treatment(VIP>1,P<0.05).Enrichment analysis of 16 overlapping endogenous metabolites revealed that Tianma Xionglin Zhixuan Tablets primarily modulated arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion:Tianma Xionglin Zhixuan Tablets demonstrates significant clinical efficacy in hypertension patients with liver yang hyperactivity or phlegm-stasis syndrome,potentially mediated through regulation of arachidonic acid and sphingolipid metabolism.
7.Application of droplet digital PCR in etiological diagnosis of severe acute pancreatitis patients with suspected bloodstream infection
Xin-Yu WANG ; Gang LI ; Wen-Jian MAO ; Jie YANG ; Jing-Zhu ZHANG ; Lu KE ; Wei-Qin LI ; Zhi-Hui TONG
Chinese Journal of Infection Control 2024;23(1):9-15
Objective To explore the value of droplet digital polymerase chain reaction(ddPCR)in the etiological diagnosis of severe acute pancreatitis(SAP)patients with suspected bloodstream infection(BSI).Methods SAP patients admitted to the department of critical care medicine in a hospital July to September 2022 were enrolled.When BSI was suspected,venous blood was collected for both ddPCR detection and blood culture(BC)with antimi-crobial susceptibility testing(AST)simultaneously.The time required for two detection methods was recorded,and the detection results of ddPCR and BC were compared.The etiological diagnostic efficacy of ddPCR was calculated,and the correlation between the value of pathogen load detected by ddPCR and the level of infection parameters was explored.Results A total of 22 patients were included in the analysis,and 52 venous blood specimens were collec-ted for detection.BC revealed 17 positive specimens(32.7%)and 29 pathogenic strains,while ddPCR showed 41 positive specimens(78.8%)and 73 pathogenic strains.Detection time required for ddPCR was significantly lower than that of BC([0.16±0.03]days vs[5.92±1.20]days,P<0.001).Within the detection range of ddPCR and taking BC results as the gold standard,the sensitivity and specificity of ddPCR were 80.0%and 28.6%,respective-ly.With the combined assessment of BSI based on non-blood specimen microbial evidence within a week,the sensi-tivity and specificity of ddPCR detection increased to 91.9%and 76.9%,respectively.ddPCR detected resistance genes of blaKPC,blaNDM/IMP,VanA/VanM,and mecA from 19,9,6,and 5 specimens,respectively.Correlation analysis showed a positive correlation between pathogen load and levels of C-reactive protein as well as procalcitonin(r=0.347,0.414,P<0.05).Conclusion As a supplementary detection method for BC in BSI diagnosis,ddPCR has the advantages of higher sensitivity and shorter detection time,and is worthy of further exploration in clinical application.
8.Advances in clinical research of CAR-T immunotherapy for systemic rheumatic diseases
Zhi LI ; Mengying ZHANG ; Chuanmiao ZHU ; Li MAO ; Hui PENG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(8):937-946
Systemic rheumatic disease is a kind of autoimmune disease which is caused by the dys-function of autoimmune cells and the damage of multiple systems and organs.Traditional immuno-suppressants play an important role in the treat-ment of systemic rheumatic diseases,but there are still a considerable number of refractory systemic rheumatic diseases that do not respond well to tra-ditional immunosuppressant therapy,and new ther-apeutic methods need to be explored.Chimeric an-tigen receptor T cell therapy(CAR-T)immunothera-py was initially used for the treatment of malig-nant hematological diseases and has shown good efficacy.Recently,CAR-T immunotherapy has also achieved remarkable efficacy in refractory systemic lupus erythematosus.It brings new hope for the treatment of systemic rheumatic diseases.This arti-cle summarizes the progress of clinical application of CAR-T immunotherapy in systemic rheumatic dis-eases in recent years,aiming to enhance clinicians'cognition of CAR-T immunotherapy and promote the further development of CAR-T immunotherapy in systemic rheumatic diseases.
9.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
10.Application status and analysis of Fu's subcutaneous needling in the treatment of peripheral facial paralysis.
Zhi-Hong XIE ; Jing LI ; Kang LI ; Mao-Hui ZHU
Chinese Acupuncture & Moxibustion 2023;43(5):607-610
This paper summarizes the status of application and research of Fu's subcutaneous needling for peripheral facial paralysis, and the characteristics of different stages of peripheral facial paralysis treated with Fu's subcutaneous needling are analyzed from the aspects of intervention timing, protocol design, needle insertion point, sweeping and reperfusion activity, tube retaining time and acupuncture frequency. It is found that there are no norms and standards in sweeping and reperfusion, tube retention and acupuncture frequency in clinical application,and the exploration of staged treatment is insufficient in the research. In the future, it is necessary to form standardized operation to promote clinical promotion, and improve the research on treatment rules and mechanism according to the characteristics of disease stage.
Humans
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Facial Paralysis/therapy*
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Vascular Surgical Procedures
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Acupuncture Therapy
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Needles

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