BACKGROUND： Thrombolysis therapy is not suitable for the elderly patients with acute ischemic stroke who delayed to be diagnosed for more than 3 hours, but traditional medicine is also not very ideal. OBJECTIVE： To ...BACKGROUND： Thrombolysis therapy is not suitable for the elderly patients with acute ischemic stroke who delayed to be diagnosed for more than 3 hours, but traditional medicine is also not very ideal. OBJECTIVE： To observe the clinical therapeutic effect of modified hemodilution combined therapy applied in elderly patients with acute cerebral thrombosis and analyze the mechanism of this therapeutic method. DESIGN： 1：1 paired grouping according to gender and controlled observation SETTING： Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University. PARTICIPANTS： Totally 90 elderly patients with acute ischemic stroke who received the treatment in the Cadre Ward and Mental Ward, Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University from March 1996 to June 2004 were recruited. They all met the diagnosis criteria revised by the Fourth Academic Conference of National Cerebrovascular Diseases in 1995 and were diagnosed as acute ischemic stroke by skull CT. They were informed of therapeutic plan and detected items. According to 1：1 paired principle in gender, 90 enrolled patients were assigned into treated group （n=45） and control group （n=45）. There were 39 male and 6 female in the treatment group, and they were aged （76±6）years, ranging from 71 to 84 years, and hospitalized at the 14^th to 76^th hours after onset. There were 39 male and 6 female in the control group, and they were aged （76±6）years , ranging from 70 to 82 years, and hospitalized at the 16^th to 72^th hours after onset. METHODS： Therapeutic method： Patients of treated group received modified hemodilution combined therapy. 200 mL whole blood of patients was exchanged with 500 mL dextran-40 （including 20 mL danshen parenteral solution and 32 mg heparin） at the beginning of therapy; From the 2^nd day, compound huangqi tea bag （Huangqi mainly, including danshen, honghua, chuanxiong, shishao and a little acetyl salicylic acid） was made, twice a day, 1 bag once. At the same time, the above-mentioned dextran-40 liquid of 500 mL was intravenously injected, once a day, 14 days in total; On the 6^th day after therapy, the above-mentioned aseptic autoblood stored in refrigerator at 4℃ was transfused back into the patients following pre-treatment of high-concentration oxygenation and ultraviolet irradiation by light quantum instrument. Patients of control group were intravenously injected of 0.4 g venoruton（Traditional Chinese medicine compound parenteral solution for promoting blood circulation and removing blood stasis ） and 50 g/L glucose of 500 mL, 75 mg acetosal was taken orally, once a day, 14 days in total. ② Measurement and observation of index： Blood coagulation index, change of platelet aggregation rate and change of hemorrheology of patients in two groups were monitored before and after therapy. The level of blood lipid of patients in two groups was measured with American Beckman automatic biochemistry analyzer. Blood flow rate of middle cerebral artery of resting electrocardiogram were measured with American HP SONOS 2500 sonoscope. Neuro-dysfunction score revised in the national conference （1995） was used to evaluate the recovery of neurological function of the patients in two groups at the 3rd, 5^th, 7^th and 14^th days after therapy. ③Therapeutic effect and adverse effect were observed at the same time. MAIN OUTCOME MEASURES ： ① Changes of coagulation index, blood lipid level and hemorheology; ② Blood flow rate of middle cerebral artery and NDS of patients with acute ischemic stroke in two groups; ③Adverse effect of drug. RESULTS： Totally 90 patients were enrolled in the experiment. One patient from treated group died of hyperosmolar nonketotic diabetic coma of complicated diabetes mellitus. One patient from control group died of severe pulmonary infection. The rest 88 patients entered the stage of result analysis. ① Change of coagulation index and platelet aggregation rate： prothrombin time （PT）, activated partial thromboplastin time （APTT） and thrombin time （TT） of patients after therapy were significantly longer than those before therapy in the treated group and those after therapy in control group [After therapy in treated group： （18.4±1.9）, （41.8±2.1）, （19.7±1.7） s, Before therapy in treated group： （13.4±1.3）, （35.8±1.3）, （12.5±0.9） s, After therapy in control group： （16.9±1.5）, （39.1±1.1）, （11.9±2.1） s, P〈 0.05]：Concentration of fibrinogen （Fbg） after therapy was significantly lower than that before therapy in the treated group and that after therapy in control group[After therapy in treated group： （3.4±0.4） g/L; Before therapy in treated group： （4.3±0.7） g/L; After therapy in control group：（4.0±0.6） g/L; P 〈 0.05]. Platelet aggregation rate decreased from （37.92 ±0.85）% before therapy to （26.42±1.01）% after therapy （P 〈 0.01）. ②Change of blood lipid level： Levels of total cholesterol （TC）, triacylglycerol（TG） and low density lipoprotein cholesterol （LDL-C） of patients after therapy were significantly lower than those before therapy in treated group and those after therapy in control group [After therapy in treated group： （5.2±0.9）, （1.9±0.9）, （2.08±1.1） mmol/L, before therapy in treated group： （5.9±1.2）, （2.8±0.9）, （3.94±0.5） mmol/L, After therapy in control group： （6.0±1.1）, （2.6±0.8）, （3.84±0.9） mmol/L, P 〈 0.05]. ③Change of hemorheology index： Hematocrit of patients of treated group was significantly lower after therapy than before therapy [Before therapy： （43.84±4.55）% ;After therapy： （40.48±4.02）%;P 〈 0.05]. Blood flow rate of middle cerebral artery of patients of treated group was significantly lower before therapy than after therapy [（90±1.2）, （97±2.1） cm/s,P〈 0.01]. ⑤NDS of patients in treated group was significantly lower than of control group 14 days after therapy. The total effective rate after therapy was significantly higher in the treated group than in the control group （93%,78%, P 〈 0.05）. ⑥There was no obvious adverse effect. CONCLUSION： Modified hemodilution combined therapy can improve hemorheology, decrease hematocrit, increase blood flow rate of middle cerebral artery, so as to improve the impaired clinical neurological function of elderly patients with acute cerebral thrombosis through anticoagulation and antiplatelet aggregative activity as well as regulating blood lipid.展开更多
At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of pa...At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of patients receive tissue plasminogen activator. Transcranial laser therapy has been shown to be effective in animal models of acute ischemic stroke, resulting in significant improvement in neurological score and function. NEST-1 and NEST-2 clinical trials in human patients have demonstrated the safety and positive trends in efficacy of transcranial laser therapy for the treatment of ischemic stroke when initiated close to the time of stroke onset. Combining intravenous tissue plasminogen activator treatment with transcranial laser therapy may provide better functional outcomes. Statins given within 4 weeks of stroke onset improve stroke outcomes at 90 days compared to patients not given statins, and giving statins following transcranial laser therapy may provide an effective treatment for patients not able to be given tissue plasminogen activator due to time constraints.展开更多
Objective: To research the protective effect of acupuncture on the cardiac performance and cerebral function in acute ischemic stroke (AIS) patients. Methods: Forty AIS patients were randomly divided into acupuncture ...Objective: To research the protective effect of acupuncture on the cardiac performance and cerebral function in acute ischemic stroke (AIS) patients. Methods: Forty AIS patients were randomly divided into acupuncture group (n=20) and medication group (n=20) according to their admission sequence. Acupoints, bilateral Neiguan (PC 6) and Tongli (HT 5) were punctured with Gauge-28 filiform needles, once daily, with 10 sessions being a therapeutic course. Patients of the medication group were treated with oral administration of persantine and aspirin as well as intravenous drip of 20% mannitol, low molecular dextran and compound Danshen (red sage root) injectio. Cerebral infarction volume, ECG (heart rate, ST Ⅱ and T Ⅱ), plasma CGRP, thromboxane (TX) B 2 and 6-Keto-prostanglandin (PG) F1a and scores of the neurological deficit were used as the indexes. Results: After 2 courses of treatment, self comparison of pre-and post treatment of each group showed that the therapeutic effects of acupuncture in reducing infarction volume ( P<0.01), lowering heart rate (HR, P<0.01) and ST Ⅱ ( P<0.01), raising T Ⅱ wave amplitude ( P<0.01), elevating plasma CGRP ( P<0.001) and 6-keto-PGF 1a ( P<0.01) and reducing plasma TXB 2 ( P< 0.01) were superior to those of medication group. Conclusion: Acupuncture of acupoints of the Pericardium Meridian and Heart Meridian has a significant protective action on the cardiac performance and cerebral function in acute ischemic stroke patients.展开更多
Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke.The contact-kinin pathway,initiated by plasma kallikrein(PK)and activated factor XII(FXIIa),functions bidirectionall...Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke.The contact-kinin pathway,initiated by plasma kallikrein(PK)and activated factor XII(FXIIa),functions bidirectionally with the coagulation and inflammation cascades,providing a novel target for therapeutic drug development in ischemic stroke.In this study,we identified a bat-derived oligopeptide from Myotis myotis(Borkhausen,1797),designated LE6(Leu-Ser-Glu-Glu-Pro-Glu,702 Da),with considerable potential in stroke therapy due to its effects on the contact kinin pathway.Notably,LE6 demonstrated significant inhibitory effects on PK and FXIIa,with inhibition constants of 43.97μmol/L and 6.37μmol/L,respectively.In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time.In murine models,LE6 effectively inhibited carrageenan-induced mouse tail thrombosis,FeCl3-induced carotid artery thrombosis,and photochemically induced intracerebral thrombosis.Furthermore,LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models.Notably,the low toxicity,hemolytic activity,and bleeding risk of LE6,along with its synthetic simplicity,underscore its clinical applicability.In conclusion,as an inhibitor of FXIIa and PK,LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.展开更多
Ischemic stroke is the leading cause of disability and mortality worldwide.The blood‒brain barrier(BBB)is the first line of defense after ischemic stroke.Disruption of the BBB induced by brain microvascular endothelia...Ischemic stroke is the leading cause of disability and mortality worldwide.The blood‒brain barrier(BBB)is the first line of defense after ischemic stroke.Disruption of the BBB induced by brain microvascular endothelial cells(BMECs)dysfunction is a key event that triggers secondary damage to the central nervous system,where blood-borne fluids and immune cells penetrate the brain parenchyma,causing cerebral edema and inflammatory response and further aggravating brain damage.Here,we develop a novel artificial mesenchymal stem cell(MSC)extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers,which encapsulated miR-132-3p with protective effects on BMECs.The artificial extracellular vesicles(MSCo/miR-132-3p)had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system(MPS)and could target ischemia Apoptosis;Ischemic stroke therapy injured BMECs.After internalization into the damaged BMECs,MSCo/miR-132-3p escaped the lysosomes via the H_(Ⅱ) phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine(DOPE)and decreased cellular reactive oxygen species(ROS)and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway.In the transient middle cerebral artery occlusion(tMCAO)models,MSCo/miR-132-3p targeted impaired brain regions(approximately 9 times the accumulation of plain liposomes at 12 h),reduced cerebral vascular disruption,protected BBB integrity,and decreased infarct volume(from 44.95% to 6.99%).展开更多
基金the Grant from Science and Technology Development Foundation of Railway Bureau of Shanghai, No. 3402052304/A
文摘BACKGROUND： Thrombolysis therapy is not suitable for the elderly patients with acute ischemic stroke who delayed to be diagnosed for more than 3 hours, but traditional medicine is also not very ideal. OBJECTIVE： To observe the clinical therapeutic effect of modified hemodilution combined therapy applied in elderly patients with acute cerebral thrombosis and analyze the mechanism of this therapeutic method. DESIGN： 1：1 paired grouping according to gender and controlled observation SETTING： Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University. PARTICIPANTS： Totally 90 elderly patients with acute ischemic stroke who received the treatment in the Cadre Ward and Mental Ward, Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University from March 1996 to June 2004 were recruited. They all met the diagnosis criteria revised by the Fourth Academic Conference of National Cerebrovascular Diseases in 1995 and were diagnosed as acute ischemic stroke by skull CT. They were informed of therapeutic plan and detected items. According to 1：1 paired principle in gender, 90 enrolled patients were assigned into treated group （n=45） and control group （n=45）. There were 39 male and 6 female in the treatment group, and they were aged （76±6）years, ranging from 71 to 84 years, and hospitalized at the 14^th to 76^th hours after onset. There were 39 male and 6 female in the control group, and they were aged （76±6）years , ranging from 70 to 82 years, and hospitalized at the 16^th to 72^th hours after onset. METHODS： Therapeutic method： Patients of treated group received modified hemodilution combined therapy. 200 mL whole blood of patients was exchanged with 500 mL dextran-40 （including 20 mL danshen parenteral solution and 32 mg heparin） at the beginning of therapy; From the 2^nd day, compound huangqi tea bag （Huangqi mainly, including danshen, honghua, chuanxiong, shishao and a little acetyl salicylic acid） was made, twice a day, 1 bag once. At the same time, the above-mentioned dextran-40 liquid of 500 mL was intravenously injected, once a day, 14 days in total; On the 6^th day after therapy, the above-mentioned aseptic autoblood stored in refrigerator at 4℃ was transfused back into the patients following pre-treatment of high-concentration oxygenation and ultraviolet irradiation by light quantum instrument. Patients of control group were intravenously injected of 0.4 g venoruton（Traditional Chinese medicine compound parenteral solution for promoting blood circulation and removing blood stasis ） and 50 g/L glucose of 500 mL, 75 mg acetosal was taken orally, once a day, 14 days in total. ② Measurement and observation of index： Blood coagulation index, change of platelet aggregation rate and change of hemorrheology of patients in two groups were monitored before and after therapy. The level of blood lipid of patients in two groups was measured with American Beckman automatic biochemistry analyzer. Blood flow rate of middle cerebral artery of resting electrocardiogram were measured with American HP SONOS 2500 sonoscope. Neuro-dysfunction score revised in the national conference （1995） was used to evaluate the recovery of neurological function of the patients in two groups at the 3rd, 5^th, 7^th and 14^th days after therapy. ③Therapeutic effect and adverse effect were observed at the same time. MAIN OUTCOME MEASURES ： ① Changes of coagulation index, blood lipid level and hemorheology; ② Blood flow rate of middle cerebral artery and NDS of patients with acute ischemic stroke in two groups; ③Adverse effect of drug. RESULTS： Totally 90 patients were enrolled in the experiment. One patient from treated group died of hyperosmolar nonketotic diabetic coma of complicated diabetes mellitus. One patient from control group died of severe pulmonary infection. The rest 88 patients entered the stage of result analysis. ① Change of coagulation index and platelet aggregation rate： prothrombin time （PT）, activated partial thromboplastin time （APTT） and thrombin time （TT） of patients after therapy were significantly longer than those before therapy in the treated group and those after therapy in control group [After therapy in treated group： （18.4±1.9）, （41.8±2.1）, （19.7±1.7） s, Before therapy in treated group： （13.4±1.3）, （35.8±1.3）, （12.5±0.9） s, After therapy in control group： （16.9±1.5）, （39.1±1.1）, （11.9±2.1） s, P〈 0.05]：Concentration of fibrinogen （Fbg） after therapy was significantly lower than that before therapy in the treated group and that after therapy in control group[After therapy in treated group： （3.4±0.4） g/L; Before therapy in treated group： （4.3±0.7） g/L; After therapy in control group：（4.0±0.6） g/L; P 〈 0.05]. Platelet aggregation rate decreased from （37.92 ±0.85）% before therapy to （26.42±1.01）% after therapy （P 〈 0.01）. ②Change of blood lipid level： Levels of total cholesterol （TC）, triacylglycerol（TG） and low density lipoprotein cholesterol （LDL-C） of patients after therapy were significantly lower than those before therapy in treated group and those after therapy in control group [After therapy in treated group： （5.2±0.9）, （1.9±0.9）, （2.08±1.1） mmol/L, before therapy in treated group： （5.9±1.2）, （2.8±0.9）, （3.94±0.5） mmol/L, After therapy in control group： （6.0±1.1）, （2.6±0.8）, （3.84±0.9） mmol/L, P 〈 0.05]. ③Change of hemorheology index： Hematocrit of patients of treated group was significantly lower after therapy than before therapy [Before therapy： （43.84±4.55）% ;After therapy： （40.48±4.02）%;P 〈 0.05]. Blood flow rate of middle cerebral artery of patients of treated group was significantly lower before therapy than after therapy [（90±1.2）, （97±2.1） cm/s,P〈 0.01]. ⑤NDS of patients in treated group was significantly lower than of control group 14 days after therapy. The total effective rate after therapy was significantly higher in the treated group than in the control group （93%,78%, P 〈 0.05）. ⑥There was no obvious adverse effect. CONCLUSION： Modified hemodilution combined therapy can improve hemorheology, decrease hematocrit, increase blood flow rate of middle cerebral artery, so as to improve the impaired clinical neurological function of elderly patients with acute cerebral thrombosis through anticoagulation and antiplatelet aggregative activity as well as regulating blood lipid.
文摘At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of patients receive tissue plasminogen activator. Transcranial laser therapy has been shown to be effective in animal models of acute ischemic stroke, resulting in significant improvement in neurological score and function. NEST-1 and NEST-2 clinical trials in human patients have demonstrated the safety and positive trends in efficacy of transcranial laser therapy for the treatment of ischemic stroke when initiated close to the time of stroke onset. Combining intravenous tissue plasminogen activator treatment with transcranial laser therapy may provide better functional outcomes. Statins given within 4 weeks of stroke onset improve stroke outcomes at 90 days compared to patients not given statins, and giving statins following transcranial laser therapy may provide an effective treatment for patients not able to be given tissue plasminogen activator due to time constraints.
文摘Objective: To research the protective effect of acupuncture on the cardiac performance and cerebral function in acute ischemic stroke (AIS) patients. Methods: Forty AIS patients were randomly divided into acupuncture group (n=20) and medication group (n=20) according to their admission sequence. Acupoints, bilateral Neiguan (PC 6) and Tongli (HT 5) were punctured with Gauge-28 filiform needles, once daily, with 10 sessions being a therapeutic course. Patients of the medication group were treated with oral administration of persantine and aspirin as well as intravenous drip of 20% mannitol, low molecular dextran and compound Danshen (red sage root) injectio. Cerebral infarction volume, ECG (heart rate, ST Ⅱ and T Ⅱ), plasma CGRP, thromboxane (TX) B 2 and 6-Keto-prostanglandin (PG) F1a and scores of the neurological deficit were used as the indexes. Results: After 2 courses of treatment, self comparison of pre-and post treatment of each group showed that the therapeutic effects of acupuncture in reducing infarction volume ( P<0.01), lowering heart rate (HR, P<0.01) and ST Ⅱ ( P<0.01), raising T Ⅱ wave amplitude ( P<0.01), elevating plasma CGRP ( P<0.001) and 6-keto-PGF 1a ( P<0.01) and reducing plasma TXB 2 ( P< 0.01) were superior to those of medication group. Conclusion: Acupuncture of acupoints of the Pericardium Meridian and Heart Meridian has a significant protective action on the cardiac performance and cerebral function in acute ischemic stroke patients.
基金supported by the National Natural Science Foundation of China(32200397,23SWAQ09,and 31930015)Yunnan Province Grant(202302AA310032,202302AA310035,and 202003AD150008)+5 种基金Ministry of Science and Technology of China(2018YFA0801403)Chinese Academy of Sciences(SAJC202103 and KFJ-BRP-008-003)New Cornerstone Investigator Program(NCI202238)Kunming Science and Technology Bureau(2022SCP007)Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University(202101AC070461)Basic Research Program of Yunnan Province Science and Technology Department(202301AT070083)。
文摘Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke.The contact-kinin pathway,initiated by plasma kallikrein(PK)and activated factor XII(FXIIa),functions bidirectionally with the coagulation and inflammation cascades,providing a novel target for therapeutic drug development in ischemic stroke.In this study,we identified a bat-derived oligopeptide from Myotis myotis(Borkhausen,1797),designated LE6(Leu-Ser-Glu-Glu-Pro-Glu,702 Da),with considerable potential in stroke therapy due to its effects on the contact kinin pathway.Notably,LE6 demonstrated significant inhibitory effects on PK and FXIIa,with inhibition constants of 43.97μmol/L and 6.37μmol/L,respectively.In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time.In murine models,LE6 effectively inhibited carrageenan-induced mouse tail thrombosis,FeCl3-induced carotid artery thrombosis,and photochemically induced intracerebral thrombosis.Furthermore,LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models.Notably,the low toxicity,hemolytic activity,and bleeding risk of LE6,along with its synthetic simplicity,underscore its clinical applicability.In conclusion,as an inhibitor of FXIIa and PK,LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.
基金supported by the National Science Foundation of China(82473862 and 82304414)the open fund of National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers(2024-KFA-007,China)+2 种基金Top Talent Support Program for young and middle-aged people of Wuxi Health Committee(HB2023103,China)Wuxi Young Science and Technology Talent Support Program(TJXD-2024-107,China)Key Science Foundation of Jiangyin Health Committee(K202101,China).
文摘Ischemic stroke is the leading cause of disability and mortality worldwide.The blood‒brain barrier(BBB)is the first line of defense after ischemic stroke.Disruption of the BBB induced by brain microvascular endothelial cells(BMECs)dysfunction is a key event that triggers secondary damage to the central nervous system,where blood-borne fluids and immune cells penetrate the brain parenchyma,causing cerebral edema and inflammatory response and further aggravating brain damage.Here,we develop a novel artificial mesenchymal stem cell(MSC)extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers,which encapsulated miR-132-3p with protective effects on BMECs.The artificial extracellular vesicles(MSCo/miR-132-3p)had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system(MPS)and could target ischemia Apoptosis;Ischemic stroke therapy injured BMECs.After internalization into the damaged BMECs,MSCo/miR-132-3p escaped the lysosomes via the H_(Ⅱ) phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine(DOPE)and decreased cellular reactive oxygen species(ROS)and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway.In the transient middle cerebral artery occlusion(tMCAO)models,MSCo/miR-132-3p targeted impaired brain regions(approximately 9 times the accumulation of plain liposomes at 12 h),reduced cerebral vascular disruption,protected BBB integrity,and decreased infarct volume(from 44.95% to 6.99%).
