Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role ...Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role in PD.Mesenchymal stem cells(MSCs)have emerged as a promising therapeutic approach for various nerve injuries,but there are limited reports on their use in PD and the underlying mechanisms remain unclear.Methods:We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa(hOM)-MSCs on neural functional recovery in both PD models and patients,as well as the preventive effects on mouse models of PD.To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure,we employed single-cell RNA sequencing(scRNA-seq),assay for transposase accessible chromatin with high-throughput sequencing(ATAC-seq)combined with full-length transcriptome isoform-sequencing(ISO-seq),and functional assay.Furthermore,we present the findings from an initial cohort of patients enrolled in a phaseⅠfirstinhuman clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients.Results:A functional assay identified that transforming growth factor-β1(TGF-β1),secreted from hOM-MSCs,played a critical role in modulating mitochondrial function recovery in dopaminergic neurons.This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN,which are closely associated with neuroinflammatory responses.Mechanistically,exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B(ALK/PI3K/Akt)signaling pathway in microglia located in the SN of PD patients.Furthermore,intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD.Conclusions:These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD.Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD.Additionally,TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.展开更多
Medical University,Shenyang 110122,China.The mechanical microenvironment of cells is recently reported to associate with the progression of renal fibrosis.However,the mechanism has not been fully elucidated.In the pre...Medical University,Shenyang 110122,China.The mechanical microenvironment of cells is recently reported to associate with the progression of renal fibrosis.However,the mechanism has not been fully elucidated.In the present study,based on the precision measurement of atom force microscope(AFM),hydrogel substrates of various stiffness were prepared to simulate the hardness of extracellular matrix(ECM)in normal and fibrotic kidney tissue.Renal mesangial cells were then cultured on the hydrogel matrix with different hardness.展开更多
OBJECTIVE:To establish a standardized framework encompassing the precise locations,manipulations,functions and indications of specific acupoints in the field of paediatric Tuina.METHODS:The development of consensus in...OBJECTIVE:To establish a standardized framework encompassing the precise locations,manipulations,functions and indications of specific acupoints in the field of paediatric Tuina.METHODS:The development of consensus involved three distinct stages.Initially,a list of paediatric Tuina specific acupoints was compiled based on an extensive literature review,which was subsequently supplemented through expert interviews.In the second stage,the Delphi method was employed to assess the significance of acupoint locations,manipulations,functions,and indications.In situations where the questionnaire survey failed to yield agreement or when the experts held reservations,the nominal group approach was utilized during the expert consensus meeting.The final version of the technical standardized material was ultimately determined during an expert consensus conference.After undergoing external peer review and evaluation,the completed draft was prepared for public dissemination RESULTS:The comprehensive list identified a total of 66 specific acupoints.The location and manipulation questionnaire consisted of 156 items based on the literature database,while the function and indication questionnaire contained 116 items.Two rounds of Delphi surveys were conducted for the location and manipulation category,and another two rounds of Delphi surveys were conducted for the function and indication category.During the experts consensus meeting The panel of experts conducted in-depth discussions on 61 questions,resulting in the formulation of technical guidelines for the locations,manipulations,functions,and indications of 64 paediatric Tuina acupoints.Subsequently,the research team compiled and edited the draft of the technical guidelines for acupoints of paediatric Tuina,which was finalized after external review and feedback.CONCLUSION:This study successfully established the recognized technical standards for practitioners of paediatric Tuina,thereby standardizing clinical practices and providing a foundation setting the framework for future research.The guidelines offer theoretical insights and recommendations for conducting clinical studies comparing different acupoint sites,as well as modifying or enhancing treatment regimens.展开更多
Uterine fibroids are the most common benign tumors in gynecology.Traditional Chinese medicine treats uterine fibroids according to syndrome differentiation and treatment.The treatment of uterine fibroids has the chara...Uterine fibroids are the most common benign tumors in gynecology.Traditional Chinese medicine treats uterine fibroids according to syndrome differentiation and treatment.The treatment of uterine fibroids has the characteristics of definitive curative effects and minor side-effects,but there are also many shortcomings,which require more in-depth research and exploration.展开更多
基金supported by the Key Research and Development Program of Hunan Province of China(2020SK2102)the Hunan Provincial Natural Science Foundation of China(2023JJ40420)+5 种基金the Changsha Municipal Natural Science Foundation(kq2208154)the Scientific Research Project of Hunan Provincial Health Commission(B202304088074)the Scientific Research Project of Hunan Provincial Health Commission(202203105045)the National Natural Science Foundation of China(82301435,82201484)the Hunan Provincial Natural Science Foundation of China(2024JJ4083)the Graduate Research and Innovation Project of Hunan Education Department(CX20220528).
文摘Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role in PD.Mesenchymal stem cells(MSCs)have emerged as a promising therapeutic approach for various nerve injuries,but there are limited reports on their use in PD and the underlying mechanisms remain unclear.Methods:We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa(hOM)-MSCs on neural functional recovery in both PD models and patients,as well as the preventive effects on mouse models of PD.To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure,we employed single-cell RNA sequencing(scRNA-seq),assay for transposase accessible chromatin with high-throughput sequencing(ATAC-seq)combined with full-length transcriptome isoform-sequencing(ISO-seq),and functional assay.Furthermore,we present the findings from an initial cohort of patients enrolled in a phaseⅠfirstinhuman clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients.Results:A functional assay identified that transforming growth factor-β1(TGF-β1),secreted from hOM-MSCs,played a critical role in modulating mitochondrial function recovery in dopaminergic neurons.This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN,which are closely associated with neuroinflammatory responses.Mechanistically,exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B(ALK/PI3K/Akt)signaling pathway in microglia located in the SN of PD patients.Furthermore,intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD.Conclusions:These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD.Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD.Additionally,TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.
文摘Medical University,Shenyang 110122,China.The mechanical microenvironment of cells is recently reported to associate with the progression of renal fibrosis.However,the mechanism has not been fully elucidated.In the present study,based on the precision measurement of atom force microscope(AFM),hydrogel substrates of various stiffness were prepared to simulate the hardness of extracellular matrix(ECM)in normal and fibrotic kidney tissue.Renal mesangial cells were then cultured on the hydrogel matrix with different hardness.
基金Grants from Key Research and Development Projects of the Ministry of Science and Technology Funding Support:Standards for Traditional Chinese Medicine Technology(No.2019YFC1712003)2023 First-class Discipline Construction Project of Beijing University of Chinese Medicine:Tuina。
文摘OBJECTIVE:To establish a standardized framework encompassing the precise locations,manipulations,functions and indications of specific acupoints in the field of paediatric Tuina.METHODS:The development of consensus involved three distinct stages.Initially,a list of paediatric Tuina specific acupoints was compiled based on an extensive literature review,which was subsequently supplemented through expert interviews.In the second stage,the Delphi method was employed to assess the significance of acupoint locations,manipulations,functions,and indications.In situations where the questionnaire survey failed to yield agreement or when the experts held reservations,the nominal group approach was utilized during the expert consensus meeting.The final version of the technical standardized material was ultimately determined during an expert consensus conference.After undergoing external peer review and evaluation,the completed draft was prepared for public dissemination RESULTS:The comprehensive list identified a total of 66 specific acupoints.The location and manipulation questionnaire consisted of 156 items based on the literature database,while the function and indication questionnaire contained 116 items.Two rounds of Delphi surveys were conducted for the location and manipulation category,and another two rounds of Delphi surveys were conducted for the function and indication category.During the experts consensus meeting The panel of experts conducted in-depth discussions on 61 questions,resulting in the formulation of technical guidelines for the locations,manipulations,functions,and indications of 64 paediatric Tuina acupoints.Subsequently,the research team compiled and edited the draft of the technical guidelines for acupoints of paediatric Tuina,which was finalized after external review and feedback.CONCLUSION:This study successfully established the recognized technical standards for practitioners of paediatric Tuina,thereby standardizing clinical practices and providing a foundation setting the framework for future research.The guidelines offer theoretical insights and recommendations for conducting clinical studies comparing different acupoint sites,as well as modifying or enhancing treatment regimens.
基金supported by a grant for a‘Study for effective TB controlincluding a cost-benefitanalysis of periodic health examination and BCG’from the Japanese Ministry of HealthLabour and Welfare(grant no17210601)
文摘Uterine fibroids are the most common benign tumors in gynecology.Traditional Chinese medicine treats uterine fibroids according to syndrome differentiation and treatment.The treatment of uterine fibroids has the characteristics of definitive curative effects and minor side-effects,but there are also many shortcomings,which require more in-depth research and exploration.
基金National Natural Science Foundation of China（31300695） Natural Science Foundation of Tianjin（13JCYBJC23500, 13JCQNJC11600） Special Foundation of the Ministry of Health （201002009）
