Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py ...Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py for ischemic peripheral nerve injuries,this study utilized glucose-modified near-infrared-II(NIR-II)quantum dots(QDs)to label adipose-derived stem cell exosomes(QDs-ADSC-Exos),enabling long-term in vivo NIR-II imaging of exosome treatment for ischemic peripheral nerve damage.Experimental results confirmed that QDs can be used for non-invasive in vitro labeling of exosomes,with QDs-ADSC-Exos exhibiting strong fluorescence signals in the NIR-II window and demonstrating favorable NIR-II imaging characteristics in vivo.Notably,QDsADSC-Exos showed accumulation at the site of nerve injury in cases of ischemic peripheral nerve damage.Func⁃tional neurological assessments indicated that QDs-ADSC-Exos effectively promoted neural regeneration.This study highlights the potential of exosomes in treating ischemic peripheral nerve injuries and elucidates the spatio⁃temporal characteristics of exosome therapy,providing objective evidence for the further optimization of exosomebased treatment protocols.展开更多
Parkinson’s disease(PD)is a common neurodegenerative disorder with profound impact on patients’quality of life and long-term health,and early detection and intervention are particularly critical.In recent years,the ...Parkinson’s disease(PD)is a common neurodegenerative disorder with profound impact on patients’quality of life and long-term health,and early detection and intervention are particularly critical.In recent years,the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD.In this paper,we systematically evaluated potential biomarkers,including proteins,metabolites,epigenetic markers,and exosomes,in the peripheral blood of PD patients.Protein markers are one of the main directions of biomarker research in PD.In particular,α‑synuclein and its phosphorylated form play a key role in the pathological process of PD.It has been shown that aggregation ofα-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD.In terms of metabolites,uric acid,as a metabolite,plays an important role in oxidative stress and neuroprotection in PD.It has been found that changes in uric acid levels may be associated with the onset and progression of PD,showing its potential as an early diagnostic marker.Epigenetic markers,such as DNA methylation modifications and miRNAs,have also attracted much attention in Parkinson’s disease research.Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease,providing new research perspectives for the early diagnosis of PD.In addition,exosomes,as a potential biomarker carrier for PD,are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation.Studies have shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide a new breakthrough for early diagnosis.It has been shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide new breakthroughs in early diagnosis.In summary,through in-depth evaluation of biomarkers in the peripheral blood of PD patients,this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms.Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.展开更多
OBJECTIVE The proteasome inhibitor bortezomib(BTZ)is a first-line anti-multi⁃ple myeloma drug.BTZ-induced peripheral neu⁃ropathy(BIPN)is a main adverse effect that char⁃acterized by neuropathic pain.There is still no ...OBJECTIVE The proteasome inhibitor bortezomib(BTZ)is a first-line anti-multi⁃ple myeloma drug.BTZ-induced peripheral neu⁃ropathy(BIPN)is a main adverse effect that char⁃acterized by neuropathic pain.There is still no strategy to prevent or treat BIPN,attributed to the unidentified mechanisms underlying BIPN.Previous studies suggested that BTZ impairs Schwann cells and thus leads to axonal demye⁃lination,whereas it remained not fully understood how BTZ cause Schwann cell death.It was observed that BTZ upregulates the autophagy marker LC3-Ⅱprotein in Schwann cells.However,it remains unclear whether BTZ causes autopha⁃gy-lysosome dysfunction in Schwann cells.METHODS The male C57BL/6 mice were intra⁃venous injection of BTZ(1 mg·kg-1 per day,twice weekly for a total of 4 weeks).The paw withdraw⁃al latency was tested by the Von Frey test and Hargreaves test to reflect the neuropathic pain.The conduction velocity and the action potential amplitude of the tail nerve were tested by neuro⁃physiological assessment to reflect peripheral nerve function.The histomorphology of the sciat⁃ic nerves was detected by immunofluorescence and transmission electron microscopy to reflect the demyelination and axonal degeneration.The RSC96 cells,the Schwann cell-like immortal cells,were cultured and exposed to BTZ.The lysosomal function was determined by Lyso⁃Tracker and DQ-BSA staining.Autophagy-relat⁃ed proteins,including p62 and LC3,and lysosom⁃al hydrolase cathepsin B were determined by Western blotting.RESULTS①BTZ induced mechano-allodynia,neurological conduction abnormalities of the tail nerve,demyelination and axonal degeneration of the sciatic nerves.②BTZ caused lysosomal dysfunction,resulting in the blockade of autophagy flux in Schwann cells and sciatic nerves.③The lysosomal activator Torin1 reversed lysosomal dysfunction caused by BTZ in Schwann cells.④Torin1 improved BTZ-induced mechano-allodynia and demyelination of sciatic nerves.CONCLUSION BTZ led to lyso⁃somal dysfunction in Schwann cells and contrib⁃uted to BIPN.Lysosomal activation could be a promising strategy for BIPN intervention.展开更多
Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with AMI, but the safety of intracoronory infusion of autologous peripheral blood stem-cell(PBSCs) in patients wit...Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with AMI, but the safety of intracoronory infusion of autologous peripheral blood stem-cell(PBSCs) in patients with AMI is unknown. For this reason, we observe the feasibility and safety of PBSCs transplantation by intracoronory infusion in such patients.Method Fourty one patients with AMI were allocated to receive Granulocyte Colony-Stimulating Factor (G-CSF:Filgrastim,300 μg) with the dose of 300 μg-600 μg/day to mobilize the stem cell, and the duration of applying G-CSF was 5 days . On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then the suspend liquid was infused into the infarct related artery (IRA)by occluding the over the wire balloon and infusing artery through balloon center lumen. In the process of the intracoronary infusion of PBSCs, the complications should be observed, which were arrhythmias including of bradycardia, sinus arrest or atrial ventricular block, premature ventricular beats ,ventricular tachycardia, ventricular fibrillation; and hypotention, etc. Results There were total 10 cases with complications during the intracoronary infusion of PBSCs. The incidence of complications was 24.4%(10/41), including bradycardia is 2.4 %(1/41), sinus arrest or atrial ventricular block is 4.9%(2/41), ventricular fibrillation is 2.4 %( 1/41), hypotention is14.6 % (6 /41).Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.展开更多
Estimate of the Deterministic Neutron RBE for Radiation-induced Pseudo-Pelger Huët Cell Formation R.E.Goans1,2,C.J.Iddins1,R.E.Goans,Jr.3(1.Radiation Emergency Assistance Center/Training Site,Oak Ridge,TN;2.MJW C...Estimate of the Deterministic Neutron RBE for Radiation-induced Pseudo-Pelger Huët Cell Formation R.E.Goans1,2,C.J.Iddins1,R.E.Goans,Jr.3(1.Radiation Emergency Assistance Center/Training Site,Oak Ridge,TN;2.MJW Corporation,Amherst,NY;3.LMU Debusk School of Medicine,Harrogate,TN)Abstract:Using archival peripheral blood slides from radiation accident patients,we have recently described the pseudo-Pelger Huët anomaly(PPHA)in neutrophils as a new radiation-induced biomarker,useful for dosimetry not only immediately after a radiation incident but also potentially helpful as a tool in retrospective dosimetry.展开更多
目的探讨5F鞘组在经外周静脉穿刺置入中心静脉导管(peripherally inserted central catheter,PICC)中临床应用的效果。方法回顾性分析并总结2012年12月至2013年2月哈尔滨医科大学附属第一医院收治的应用5F鞘组10例行PICC患者的临床资料...目的探讨5F鞘组在经外周静脉穿刺置入中心静脉导管(peripherally inserted central catheter,PICC)中临床应用的效果。方法回顾性分析并总结2012年12月至2013年2月哈尔滨医科大学附属第一医院收治的应用5F鞘组10例行PICC患者的临床资料。结果 10例患者均顺利完成PICC,有2例患者术后出现静脉炎,其余患者均未发生严重的并发症。结论静脉穿刺条件差的患者应用5F鞘组行PICC导管有利于提高置管成功率。展开更多
The Himalayan peripheral foreland basin developed when India and Asia collided.Previous studies in the Himalayan foreland were mostly concentrated on Neogene continental clastic sedimentation in sub-Himalaya or Paleog...The Himalayan peripheral foreland basin developed when India and Asia collided.Previous studies in the Himalayan foreland were mostly concentrated on Neogene continental clastic sedimentation in sub-Himalaya or Paleogene shallow marine sedimentation along Pakistan,India,and Nepal in Lesser Himalaya. The lack of early stage of underfilled。展开更多
OBJECTIVE To evaluate the effect of aqueousstem extract of Tinsporacordifolia(TCSE)on 1.experimentally induced diabetic peripheral neuropathy(DPN)2.Serum triglycerides(TG),high density lipoproteins(HDL)and atherogenic...OBJECTIVE To evaluate the effect of aqueousstem extract of Tinsporacordifolia(TCSE)on 1.experimentally induced diabetic peripheral neuropathy(DPN)2.Serum triglycerides(TG),high density lipoproteins(HDL)and atherogenic index(AI)in type 2 diabetic patients.METHODS Experimental study:TCSE was evaluated on streptozotocin induced diabetic Wistar albino rats on the reaction time(RT)to radiant heat in tail flick test.The diabetic animals were grouped into diabetic control group(DC),standard control group(SC)that received glibenclamide+metformin;TCSE 1,TCSE2,and TCSE 3 that received 100,200 and 400mg·kg-1 of TCSE respectively.Another group served as the normal control group(NC).The medications were administered once daily orally for 2 weeks after the induction of diabetes.RT was compared among these groups.Clinical study:20 Type 2 diabetes mellitus patients with TG >200mg·dL-1 and HDL<50mg·dL-1 were randomised to receive either Rosuvastatin 10 mg or TCSE 300 mg per day once daily for 12weeks.After 12 weeks,TG,HDL and AI(calculated as the log 10 of the ratio of TG with HDL)were analysed within the group and compared between the groups.Mann Whitney U test was applied for analysis for both.RESULTS Experimental study:RT was 10.0±0.7sin the NC,7.83±1.19 sin DC(P<0.05 compared to NC)indicating hyperalgesia.SC,TC1,TC2,and TC3 showed 12.83±0.31,13.33±0.88;13.67±1.09and15.25±0.23 s,respectively(P<0.05 compared to DC).Clinical study:In the clinical study,in theTCSE group,TG reduced from 251.62±15.22 to 212.2±11.83 mg·dL-1;HDL increased from 34.53±0.74to40.81±0.71mg·dL-1 and mean AI reduced from 0.83±0.028 to 0.70±0.027.In the rosuvastatin group TG levels decreased from 255.8±13.03 to 196.3±12.84 mg·dL-1;HDL increased from 37.38±0.77to43.3±1.21mg·dL-1 and mean AI reduced from 0.83±0.02 to 0.65±0.03.The change was statistically significant within each groups but not between the groups.CONCLUSION The aqueous extract of Tinosporacordifolia appears to be effective in reducing the diabetic peripheral neuropathy and atherogenic index.展开更多
基金Supported by the National Natural Science Foundation of China(82371373,W2412120)the Shanghai Natural Science Foundation(21ZR1436100).
文摘Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py for ischemic peripheral nerve injuries,this study utilized glucose-modified near-infrared-II(NIR-II)quantum dots(QDs)to label adipose-derived stem cell exosomes(QDs-ADSC-Exos),enabling long-term in vivo NIR-II imaging of exosome treatment for ischemic peripheral nerve damage.Experimental results confirmed that QDs can be used for non-invasive in vitro labeling of exosomes,with QDs-ADSC-Exos exhibiting strong fluorescence signals in the NIR-II window and demonstrating favorable NIR-II imaging characteristics in vivo.Notably,QDsADSC-Exos showed accumulation at the site of nerve injury in cases of ischemic peripheral nerve damage.Func⁃tional neurological assessments indicated that QDs-ADSC-Exos effectively promoted neural regeneration.This study highlights the potential of exosomes in treating ischemic peripheral nerve injuries and elucidates the spatio⁃temporal characteristics of exosome therapy,providing objective evidence for the further optimization of exosomebased treatment protocols.
文摘Parkinson’s disease(PD)is a common neurodegenerative disorder with profound impact on patients’quality of life and long-term health,and early detection and intervention are particularly critical.In recent years,the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD.In this paper,we systematically evaluated potential biomarkers,including proteins,metabolites,epigenetic markers,and exosomes,in the peripheral blood of PD patients.Protein markers are one of the main directions of biomarker research in PD.In particular,α‑synuclein and its phosphorylated form play a key role in the pathological process of PD.It has been shown that aggregation ofα-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD.In terms of metabolites,uric acid,as a metabolite,plays an important role in oxidative stress and neuroprotection in PD.It has been found that changes in uric acid levels may be associated with the onset and progression of PD,showing its potential as an early diagnostic marker.Epigenetic markers,such as DNA methylation modifications and miRNAs,have also attracted much attention in Parkinson’s disease research.Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease,providing new research perspectives for the early diagnosis of PD.In addition,exosomes,as a potential biomarker carrier for PD,are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation.Studies have shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide a new breakthrough for early diagnosis.It has been shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide new breakthroughs in early diagnosis.In summary,through in-depth evaluation of biomarkers in the peripheral blood of PD patients,this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms.Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.
文摘OBJECTIVE The proteasome inhibitor bortezomib(BTZ)is a first-line anti-multi⁃ple myeloma drug.BTZ-induced peripheral neu⁃ropathy(BIPN)is a main adverse effect that char⁃acterized by neuropathic pain.There is still no strategy to prevent or treat BIPN,attributed to the unidentified mechanisms underlying BIPN.Previous studies suggested that BTZ impairs Schwann cells and thus leads to axonal demye⁃lination,whereas it remained not fully understood how BTZ cause Schwann cell death.It was observed that BTZ upregulates the autophagy marker LC3-Ⅱprotein in Schwann cells.However,it remains unclear whether BTZ causes autopha⁃gy-lysosome dysfunction in Schwann cells.METHODS The male C57BL/6 mice were intra⁃venous injection of BTZ(1 mg·kg-1 per day,twice weekly for a total of 4 weeks).The paw withdraw⁃al latency was tested by the Von Frey test and Hargreaves test to reflect the neuropathic pain.The conduction velocity and the action potential amplitude of the tail nerve were tested by neuro⁃physiological assessment to reflect peripheral nerve function.The histomorphology of the sciat⁃ic nerves was detected by immunofluorescence and transmission electron microscopy to reflect the demyelination and axonal degeneration.The RSC96 cells,the Schwann cell-like immortal cells,were cultured and exposed to BTZ.The lysosomal function was determined by Lyso⁃Tracker and DQ-BSA staining.Autophagy-relat⁃ed proteins,including p62 and LC3,and lysosom⁃al hydrolase cathepsin B were determined by Western blotting.RESULTS①BTZ induced mechano-allodynia,neurological conduction abnormalities of the tail nerve,demyelination and axonal degeneration of the sciatic nerves.②BTZ caused lysosomal dysfunction,resulting in the blockade of autophagy flux in Schwann cells and sciatic nerves.③The lysosomal activator Torin1 reversed lysosomal dysfunction caused by BTZ in Schwann cells.④Torin1 improved BTZ-induced mechano-allodynia and demyelination of sciatic nerves.CONCLUSION BTZ led to lyso⁃somal dysfunction in Schwann cells and contrib⁃uted to BIPN.Lysosomal activation could be a promising strategy for BIPN intervention.
文摘Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with AMI, but the safety of intracoronory infusion of autologous peripheral blood stem-cell(PBSCs) in patients with AMI is unknown. For this reason, we observe the feasibility and safety of PBSCs transplantation by intracoronory infusion in such patients.Method Fourty one patients with AMI were allocated to receive Granulocyte Colony-Stimulating Factor (G-CSF:Filgrastim,300 μg) with the dose of 300 μg-600 μg/day to mobilize the stem cell, and the duration of applying G-CSF was 5 days . On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then the suspend liquid was infused into the infarct related artery (IRA)by occluding the over the wire balloon and infusing artery through balloon center lumen. In the process of the intracoronary infusion of PBSCs, the complications should be observed, which were arrhythmias including of bradycardia, sinus arrest or atrial ventricular block, premature ventricular beats ,ventricular tachycardia, ventricular fibrillation; and hypotention, etc. Results There were total 10 cases with complications during the intracoronary infusion of PBSCs. The incidence of complications was 24.4%(10/41), including bradycardia is 2.4 %(1/41), sinus arrest or atrial ventricular block is 4.9%(2/41), ventricular fibrillation is 2.4 %( 1/41), hypotention is14.6 % (6 /41).Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.
文摘Estimate of the Deterministic Neutron RBE for Radiation-induced Pseudo-Pelger Huët Cell Formation R.E.Goans1,2,C.J.Iddins1,R.E.Goans,Jr.3(1.Radiation Emergency Assistance Center/Training Site,Oak Ridge,TN;2.MJW Corporation,Amherst,NY;3.LMU Debusk School of Medicine,Harrogate,TN)Abstract:Using archival peripheral blood slides from radiation accident patients,we have recently described the pseudo-Pelger Huët anomaly(PPHA)in neutrophils as a new radiation-induced biomarker,useful for dosimetry not only immediately after a radiation incident but also potentially helpful as a tool in retrospective dosimetry.
文摘目的探讨5F鞘组在经外周静脉穿刺置入中心静脉导管(peripherally inserted central catheter,PICC)中临床应用的效果。方法回顾性分析并总结2012年12月至2013年2月哈尔滨医科大学附属第一医院收治的应用5F鞘组10例行PICC患者的临床资料。结果 10例患者均顺利完成PICC,有2例患者术后出现静脉炎,其余患者均未发生严重的并发症。结论静脉穿刺条件差的患者应用5F鞘组行PICC导管有利于提高置管成功率。
文摘The Himalayan peripheral foreland basin developed when India and Asia collided.Previous studies in the Himalayan foreland were mostly concentrated on Neogene continental clastic sedimentation in sub-Himalaya or Paleogene shallow marine sedimentation along Pakistan,India,and Nepal in Lesser Himalaya. The lack of early stage of underfilled。
基金The project supported by the management of Vydehi Institute of Medical Sciences and Research Centre,Bangalore,India.The standardised aqueous extract of Tinospora cordifolia was obtained from Natural Remedies Pvt.Ltd.Bangalore as a support towards this project
文摘OBJECTIVE To evaluate the effect of aqueousstem extract of Tinsporacordifolia(TCSE)on 1.experimentally induced diabetic peripheral neuropathy(DPN)2.Serum triglycerides(TG),high density lipoproteins(HDL)and atherogenic index(AI)in type 2 diabetic patients.METHODS Experimental study:TCSE was evaluated on streptozotocin induced diabetic Wistar albino rats on the reaction time(RT)to radiant heat in tail flick test.The diabetic animals were grouped into diabetic control group(DC),standard control group(SC)that received glibenclamide+metformin;TCSE 1,TCSE2,and TCSE 3 that received 100,200 and 400mg·kg-1 of TCSE respectively.Another group served as the normal control group(NC).The medications were administered once daily orally for 2 weeks after the induction of diabetes.RT was compared among these groups.Clinical study:20 Type 2 diabetes mellitus patients with TG >200mg·dL-1 and HDL<50mg·dL-1 were randomised to receive either Rosuvastatin 10 mg or TCSE 300 mg per day once daily for 12weeks.After 12 weeks,TG,HDL and AI(calculated as the log 10 of the ratio of TG with HDL)were analysed within the group and compared between the groups.Mann Whitney U test was applied for analysis for both.RESULTS Experimental study:RT was 10.0±0.7sin the NC,7.83±1.19 sin DC(P<0.05 compared to NC)indicating hyperalgesia.SC,TC1,TC2,and TC3 showed 12.83±0.31,13.33±0.88;13.67±1.09and15.25±0.23 s,respectively(P<0.05 compared to DC).Clinical study:In the clinical study,in theTCSE group,TG reduced from 251.62±15.22 to 212.2±11.83 mg·dL-1;HDL increased from 34.53±0.74to40.81±0.71mg·dL-1 and mean AI reduced from 0.83±0.028 to 0.70±0.027.In the rosuvastatin group TG levels decreased from 255.8±13.03 to 196.3±12.84 mg·dL-1;HDL increased from 37.38±0.77to43.3±1.21mg·dL-1 and mean AI reduced from 0.83±0.02 to 0.65±0.03.The change was statistically significant within each groups but not between the groups.CONCLUSION The aqueous extract of Tinosporacordifolia appears to be effective in reducing the diabetic peripheral neuropathy and atherogenic index.
