1.Underlying target of bullatine A in treating rheumatoid arthritis based on LiP-SMap drug target proteomics
Hao-hong ZHANG ; Nan-ting ZOU ; Chun-fei ZHANG ; Qing-yan MO ; Ming-qian JU ; Xiao-hong LI ; Shuai LIU ; Mao-kui HUANG ; Hong-yun WANG ; Chun-ping WAN
Chinese Pharmacological Bulletin 2025;41(6):1072-1078
Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P<0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P<0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P<0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.
2.Research Progressin Application of Ultrasound in the Diagnosis and Treatment of Greater Trochanteric Pain Syndrome.
Fan WU ; Yi MAO ; Chun-Bao LI ; Long-Tao YAN ; Ming-Bo ZHANG
Acta Academiae Medicinae Sinicae 2025;47(2):289-294
Greater trochanteric pain syndrome(GTPS)is a disease caused by structural lesions of the muscles,fascia,ligaments,and bursae near the greater trochanter of the femur.GTPS causes lateral hip joint pain,severely affecting patients' quality of life.Ultrasound has many advantages,such as real-time diagnosis,portable operation,non-radiation,and high resolution,demonstrating a high application value in the diagnosis and interventional therapy of GTPS.This article reviews the current status of ultrasound in the diagnosis and interventional therapy of GTPS and prospects its application.
Humans
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Ultrasonography
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Femur/diagnostic imaging*
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Hip Joint/diagnostic imaging*
;
Arthralgia/therapy*
3.Application of OpenSim musculoskeletal model in biomechanics research of orthopedics and traumatology.
Rui LI ; Yang LIU ; Zhao-Jie ZHANG ; Xin-Wei ZHANG ; Yan-Zhen ZHANG ; Yan-Qi HU ; Can YANG ; Shu-Shi MAO ; Jia-Ming QIU
China Journal of Orthopaedics and Traumatology 2025;38(3):319-324
OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans
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Biomechanical Phenomena
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Orthopedics
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Traumatology
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Software
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Medicine, Chinese Traditional
;
Musculoskeletal System
;
Models, Biological
4.Development and application of pilot hypoxia endurance testing system
Lin-xia LI ; Guo-yun MAO ; Ming-rui HU ; Jia-ling XU ; Yao-xuan JI ; Na ZHI ; Yan-qing BAI ; Yun-ying WANG
Chinese Medical Equipment Journal 2025;46(10):23-28
Objective To develop a hypoxia endurance testing system for aviation physiological training of pilots.Methods The hypoxia endurance testing system comprised a low-oxygen mixed gas generator,a pressurization system for low-oxygen mixed gas and a personal breathing apparatus.The low-oxygen mixed gas generator consisted of a main unit composed of an air compressor,a filter,a buffer tank,polymer membrane,a control module,sensors and regulators,wire cables,supporting hoses,etc.;the pressurization system for low-oxygen mixed gas was made up of a protective box,a cooling fan,a motor and a driver,a control module,a solenoid valve,a convergence block,a pressure gauge,etc.;the personal breating apparatus was composed of a gas cylinder,a pressure reducer,an oxygen supply regulator,etc.Forty-eight subjects were selected for hypoxia exposure tests to verify the effectiveness of the system.Results The system developed had the functions of low-oxygen gas preparation,pressurized filling and hypoxia experiment,and the experimental results indicated the acute hypoxia exposure by the system significantly caused signs and symptoms of hypoxia and weakened physiological functions.Conclusion The system developed gains advantages in high accuracy of gas volume fraction control,safety and remarkable effect of simulated hypoxia,and can be an effective tool for acute high-altitude hypoxia testing and training of pilots.[Chinese Medical Equipment Journal,2025,46(10):23-28]
5.Correlations of serum transforming growth factor-β1 and insulin-like growth factor-1 with pathological features and postoperative recurrence in patients with adenomyosis
Tingting MAO ; Qiong JIANG ; Yan WANG ; Xia MING ; Yinghua LOU
Journal of Clinical Medicine in Practice 2025;29(4):103-107
Objective To investigate the correlations of expression levels of serum transforming growth factor-β1(TGF-β1)and insulin-like growth factor-1(IGF-1)with clinicopathological features of patients with adenomyosis,and the clinical value of their prediction of postoperative recurrence.Methods Eighty-two patients with adenomyosis were selected as study subjects(study group).Patients were followed up for two years after surgery and divided into recurrence group(n=15)and non-recur-rence group(n=67)based on their postoperative status.An additional 85 healthy individuals who un-derwent physical examinations during the same period were selected as control group.Serum TGF-β1 and IGF-1 levels were compared between the study group and the control group.The correlations of se-rum TGF-β1 and IGF-1 levels with the clinicopathological characteristics of adenomyosis patients was analyzed.Serum TGF-β1 and IGF-1 levels were compared between the recurrence and non-recurrence groups.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic efficacy of serum TGF-β1 and IGF-1 levels in predicting postoperative recurrence in adenomyosis pa-tients.Results Serum TGF-β1 and IGF-1 levels in the study group were significantly higher than those in the control group(P<0.05).Serum TGF-β1 levels were correlated with menstrual vol-ume,history of curettage,uterine volume,pathological type,lesion volume,endometrial status and ectopic gland cycle(P<0.05).Serum IGF-1 levels were correlated with menstrual volume,history of curettage,uterine volume,pathological type,endometrial status and ectopic gland cycle(P<0.05).Postoperative serum TGF-β1 and IGF-1 levels in the recurrence group were significantly higher than those in the non-recurrence group(P<0.05).ROC curve analysis showed that the area under the curve(AUC)for predicting postoperative recurrence using serum TGF-β1,IGF-1 and their combination were 0.823,0.803 and 0.940,respectively.The clinical efficacy of TGF-β1 and IGF-1 in combination in predicting postoperative recurrence was superior to that of TGF-β1 alone(ZcombinedwithTGF-β1=2.001,ZcombinedwithIGF-1=2.318,P=0.045,0.021).Conclusion The serum levels of TGF-β1 and IGF-1 in patients with adenomyosis are significantly increased,which are closely related to the clinicopathological features of the patients.The combination of serum TGF-β1 and IGF-1 levels has high clinical efficacy in predicting postoperative recurrence.
6.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.
7.Characteristics of pain-anxiety-depression-fatigue symptom clusters in adolescents with acute lymphoblastic leukemia during early chemotherapy
Lei CHENG ; Yan-qing WANG ; Hai-ying HUANG ; Ling YU ; Ming-xia DUAN ; Xiao-rong MAO
Fudan University Journal of Medical Sciences 2025;52(6):803-810
Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.
8.Development and application of pilot hypoxia endurance testing system
Lin-xia LI ; Guo-yun MAO ; Ming-rui HU ; Jia-ling XU ; Yao-xuan JI ; Na ZHI ; Yan-qing BAI ; Yun-ying WANG
Chinese Medical Equipment Journal 2025;46(10):23-28
Objective To develop a hypoxia endurance testing system for aviation physiological training of pilots.Methods The hypoxia endurance testing system comprised a low-oxygen mixed gas generator,a pressurization system for low-oxygen mixed gas and a personal breathing apparatus.The low-oxygen mixed gas generator consisted of a main unit composed of an air compressor,a filter,a buffer tank,polymer membrane,a control module,sensors and regulators,wire cables,supporting hoses,etc.;the pressurization system for low-oxygen mixed gas was made up of a protective box,a cooling fan,a motor and a driver,a control module,a solenoid valve,a convergence block,a pressure gauge,etc.;the personal breating apparatus was composed of a gas cylinder,a pressure reducer,an oxygen supply regulator,etc.Forty-eight subjects were selected for hypoxia exposure tests to verify the effectiveness of the system.Results The system developed had the functions of low-oxygen gas preparation,pressurized filling and hypoxia experiment,and the experimental results indicated the acute hypoxia exposure by the system significantly caused signs and symptoms of hypoxia and weakened physiological functions.Conclusion The system developed gains advantages in high accuracy of gas volume fraction control,safety and remarkable effect of simulated hypoxia,and can be an effective tool for acute high-altitude hypoxia testing and training of pilots.[Chinese Medical Equipment Journal,2025,46(10):23-28]
9.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.
10.Underlying target of bullatine A in treating rheumatoid arthritis based on LiP-SMap drug target proteomics
Hao-hong ZHANG ; Nan-ting ZOU ; Chun-fei ZHANG ; Qing-yan MO ; Ming-qian JU ; Xiao-hong LI ; Shuai LIU ; Mao-kui HUANG ; Hong-yun WANG ; Chun-ping WAN
Chinese Pharmacological Bulletin 2025;41(6):1072-1078
Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P<0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P<0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P<0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

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