Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challengin...Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.展开更多
Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promisin...Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.展开更多
The study was conducted to explore the effect of imatinib,nilotinib,and dasatinib in the treatment of chronic myeloid leukemia(CML)patients.Around 66 patients with CML in chronic phase were selected,subsequently the p...The study was conducted to explore the effect of imatinib,nilotinib,and dasatinib in the treatment of chronic myeloid leukemia(CML)patients.Around 66 patients with CML in chronic phase were selected,subsequently the patients were subdivided into 3 groups with 22 patients in each group:Group A were treated with imatinib;Group B were treated with nilotinib;and Group C were treated with dasatinib.The study showed that,at 18 months of treatment,compared with group A,the molecular biology remission rates of group B and group C were significantly higher,p<0.05;at 6 months and 18 months of treatment,compared with group A,the complete cytogenetic remission rates of group B and group C were significantly higher,p<0.05;and compared with group A,the incidences of vomiting,headache and edema in groups B and C were significantly lower,p<0.05.However,no significant different p>0.05 were observed in the complete hematologic remission rates,and the incidences of neutropenia and thrombocytopenia among the three groups.In summary,nilotinib and dasatinib are effective in the treatment of patients with CML in the chronic phase,which is significantly better than imatinib treatment.展开更多
Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previou...Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.展开更多
Objective To evaluate the pharmacokinetics and bioequivalence of generic dasatinib in patients with chronic myeloid leukemia in the choronie phase(CML-CP).Methods Using randomized,parallel,overlapping,self-
Objective To explore the impact of patient reported outcome of tyrosine kinase inhibitor(TKI)related side effects on daily life in Chinese patients with chronic myceloid leukemia(CML)in the chronic phase(CP).Methods F...Objective To explore the impact of patient reported outcome of tyrosine kinase inhibitor(TKI)related side effects on daily life in Chinese patients with chronic myceloid leukemia(CML)in the chronic phase(CP).Methods From May to November in 2014。展开更多
Objective To compare the efficacy and safety between Chinese generic imatinib(Xinwei~,Jiansu Hansoh Pharmaceutical Group Co.,Ltd.)and branded imatinib(Glivec~,Novartis)in patients with newly-diagnosed chronic myel...Objective To compare the efficacy and safety between Chinese generic imatinib(Xinwei~,Jiansu Hansoh Pharmaceutical Group Co.,Ltd.)and branded imatinib(Glivec~,Novartis)in patients with newly-diagnosed chronic myeloid leukemia in chronic phase(CML-CP).Methods Patients with newly diagnosed CML-CP展开更多
目的:研究双侧经颅直流电刺激(dual-hemispheric transcranial direct current stimulation,Dual-tDCS)对慢性期脑卒中患者上肢运动功能的影响,为治疗慢性期脑卒中上肢功能障碍提供基于神经机制的理论依据。方法:选取某院24例慢性期脑...目的:研究双侧经颅直流电刺激(dual-hemispheric transcranial direct current stimulation,Dual-tDCS)对慢性期脑卒中患者上肢运动功能的影响,为治疗慢性期脑卒中上肢功能障碍提供基于神经机制的理论依据。方法:选取某院24例慢性期脑卒中上肢运动功能障碍患者,按照随机数字表法将其分为研究组(n=13)和对照组(n=11)。对照组采用tDCS伪刺激联合常规康复治疗,研究组采用Dual-tDCS联合常规康复治疗。治疗前后,采用Fugl-Meyer运动功能评定量表上肢部分(Fugl-Meyer assessment upper limb scale,FMA-UL)及日常生活活动能力(activities of daily living,ADL)测评量表对患者活动能力进行评估。对比治疗前后初级运动皮层(M1区)与全脑功能连接(functional connectivity,FC)的变化。使用SPSS 24.0统计学软件进行数据分析。结果:治疗后,2组患者的FMA-UL、ADL评分比治疗前均显著提高,且研究组评分明显高于对照组,差异有统计学意义(P<0.05)。M1区与全脑FC分析显示,治疗后对照组健侧M1区到患侧枕中回、健侧舌回、健侧角回FC降低(P<0.01);患侧M1区未见FC变化脑区。治疗后研究组健侧M1区到健侧小脑、健侧小脑蚓部FC降低,到患侧中央前回FC增加(P<0.01);患侧M1区到患侧小脑、患侧颞中回FC增加,到健侧中央前回FC降低(P<0.01)。结论:Dual-tDCS对大脑的神经调控作用可改善慢性期卒中患者运动和非运动相关脑区的FC,可能是慢性期脑卒中上肢运动功能障碍的康复机制。展开更多
Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury（SCI）.By contrast,there are still only a few studies have focused on the treatment of the chronically in...Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury（SCI）.By contrast,there are still only a few studies have focused on the treatment of the chronically injured spinal cord,in which cell-based regenerative medicine seems less effective.Since the majority of SCI patients are in the chronic phase,representing a major challenge for the clinical application of cellbased regenerative medicine.Although combined therapies for the treatment of chronic SCI have attracted attention of researchers and its potential importance is also widely recognized,there had been very few studies involving rehabilitative treatments to date.In a recent study,we have demonstrated for the first time that treadmill training combined with cell transplantation significantly promotes functional recovery even in chronic SCI,not only in additive but also in synergistic manner.Even though we have succeeded to outline the profiles of recovery secondary to the combination therapy,the mechanism underlying the effects remain unsolved.In this review article,we summarize the present progress and consider the prospect of the cell-based regenerative medicine particularly combined with rehabilitative approaches for chronic SCI animal models.展开更多
No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, ...No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, or branch, in the embolic middle cerebral artery. In this experiment, cerebral infarction models were established at M1, and on the upper and lower trunks on the contralateral side of the handedness of rhesus monkeys by using endovascular intervention. The results confirmed a high animal survival rate in stroke models of middle cerebral artery upper trunk occlusion. There was pronounced paralysis at the acute phase, long-term upper extremity dysfunction at the chronic phase, and the models showed good repeatability and consistency. Thus, this study describes a safe and effective model of chronic stroke.展开更多
文摘Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.
基金supported by the National Key Research and Development Program of China,No.2017YFA0105403(to LMR)the Key Research and Development Program of Guangdong Province of China,No.2019B020236002(to LMR)+4 种基金The Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China,No.2018GZR0201006(to LMR)the National Natural Science Foundation of China,Nos.81772349(to BL),31470949(to BL)the Guangzhou Science and Technology Project of China,Nos.201704020221(to LMR),201707010115(to BL)the Natural Science Foundation of Guangdong Province of China,No.2017A030313594(to BL)the Medical Scientific Research Foundation of Guangdong Province of China,No.A2018547(to MP)
文摘Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.
文摘The study was conducted to explore the effect of imatinib,nilotinib,and dasatinib in the treatment of chronic myeloid leukemia(CML)patients.Around 66 patients with CML in chronic phase were selected,subsequently the patients were subdivided into 3 groups with 22 patients in each group:Group A were treated with imatinib;Group B were treated with nilotinib;and Group C were treated with dasatinib.The study showed that,at 18 months of treatment,compared with group A,the molecular biology remission rates of group B and group C were significantly higher,p<0.05;at 6 months and 18 months of treatment,compared with group A,the complete cytogenetic remission rates of group B and group C were significantly higher,p<0.05;and compared with group A,the incidences of vomiting,headache and edema in groups B and C were significantly lower,p<0.05.However,no significant different p>0.05 were observed in the complete hematologic remission rates,and the incidences of neutropenia and thrombocytopenia among the three groups.In summary,nilotinib and dasatinib are effective in the treatment of patients with CML in the chronic phase,which is significantly better than imatinib treatment.
文摘Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.
文摘Objective To evaluate the pharmacokinetics and bioequivalence of generic dasatinib in patients with chronic myeloid leukemia in the choronie phase(CML-CP).Methods Using randomized,parallel,overlapping,self-
文摘Objective To explore the impact of patient reported outcome of tyrosine kinase inhibitor(TKI)related side effects on daily life in Chinese patients with chronic myceloid leukemia(CML)in the chronic phase(CP).Methods From May to November in 2014。
文摘Objective To compare the efficacy and safety between Chinese generic imatinib(Xinwei~,Jiansu Hansoh Pharmaceutical Group Co.,Ltd.)and branded imatinib(Glivec~,Novartis)in patients with newly-diagnosed chronic myeloid leukemia in chronic phase(CML-CP).Methods Patients with newly diagnosed CML-CP
文摘目的:研究双侧经颅直流电刺激(dual-hemispheric transcranial direct current stimulation,Dual-tDCS)对慢性期脑卒中患者上肢运动功能的影响,为治疗慢性期脑卒中上肢功能障碍提供基于神经机制的理论依据。方法:选取某院24例慢性期脑卒中上肢运动功能障碍患者,按照随机数字表法将其分为研究组(n=13)和对照组(n=11)。对照组采用tDCS伪刺激联合常规康复治疗,研究组采用Dual-tDCS联合常规康复治疗。治疗前后,采用Fugl-Meyer运动功能评定量表上肢部分(Fugl-Meyer assessment upper limb scale,FMA-UL)及日常生活活动能力(activities of daily living,ADL)测评量表对患者活动能力进行评估。对比治疗前后初级运动皮层(M1区)与全脑功能连接(functional connectivity,FC)的变化。使用SPSS 24.0统计学软件进行数据分析。结果:治疗后,2组患者的FMA-UL、ADL评分比治疗前均显著提高,且研究组评分明显高于对照组,差异有统计学意义(P<0.05)。M1区与全脑FC分析显示,治疗后对照组健侧M1区到患侧枕中回、健侧舌回、健侧角回FC降低(P<0.01);患侧M1区未见FC变化脑区。治疗后研究组健侧M1区到健侧小脑、健侧小脑蚓部FC降低,到患侧中央前回FC增加(P<0.01);患侧M1区到患侧小脑、患侧颞中回FC增加,到健侧中央前回FC降低(P<0.01)。结论:Dual-tDCS对大脑的神经调控作用可改善慢性期卒中患者运动和非运动相关脑区的FC,可能是慢性期脑卒中上肢运动功能障碍的康复机制。
基金the Japan Science and Technology-California Institute for Regenerative Medicine collaborative programthe Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science(SPS)+5 种基金the Ministry of Education,Culture,Sports,Science,and Technology of Japan(MEXT)supported by the Research Centre Network for Realization of Regenerative Medicine of the Japan Science and Technology Agency(JST)the Japan Agency for Medical Research and Development(AMEDto HO and MN)the General Insurance Association of Japanthe Keio Gijuku Academic award as a Grant-in-Aid for Scientific Research on Innovative Areas(Comprehensive Brain Science Network)from MEXT
文摘Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury（SCI）.By contrast,there are still only a few studies have focused on the treatment of the chronically injured spinal cord,in which cell-based regenerative medicine seems less effective.Since the majority of SCI patients are in the chronic phase,representing a major challenge for the clinical application of cellbased regenerative medicine.Although combined therapies for the treatment of chronic SCI have attracted attention of researchers and its potential importance is also widely recognized,there had been very few studies involving rehabilitative treatments to date.In a recent study,we have demonstrated for the first time that treadmill training combined with cell transplantation significantly promotes functional recovery even in chronic SCI,not only in additive but also in synergistic manner.Even though we have succeeded to outline the profiles of recovery secondary to the combination therapy,the mechanism underlying the effects remain unsolved.In this review article,we summarize the present progress and consider the prospect of the cell-based regenerative medicine particularly combined with rehabilitative approaches for chronic SCI animal models.
基金the National Key Technology Research and Development Program during Eleventh Five-Year Plan, No. 2006BAI01A14
文摘No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, or branch, in the embolic middle cerebral artery. In this experiment, cerebral infarction models were established at M1, and on the upper and lower trunks on the contralateral side of the handedness of rhesus monkeys by using endovascular intervention. The results confirmed a high animal survival rate in stroke models of middle cerebral artery upper trunk occlusion. There was pronounced paralysis at the acute phase, long-term upper extremity dysfunction at the chronic phase, and the models showed good repeatability and consistency. Thus, this study describes a safe and effective model of chronic stroke.
