Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
Ischemic stroke(IS)presents a major threat to human life and health due to its high disability and mortality rates.3-n-Butylphthalide(NBP),derived from celery seeds of the Apiaceae family native to the Mediterranean r...Ischemic stroke(IS)presents a major threat to human life and health due to its high disability and mortality rates.3-n-Butylphthalide(NBP),derived from celery seeds of the Apiaceae family native to the Mediterranean region,was first introduced in China for acute IS treatment in 2004.NBP demonstrates multiple therapeutic actions,including reconstruction of microcirculation in the cerebral ischemia area,inhibition of platelet aggregation,reduction of cerebral infarction volume,maintenance of blood-brain barrier(BBB)integrity,and enhancement of cerebral blood perfusion.However,its overall efficacy remains moderate,limited by poor water solubility and low bioavailability,which constrains its clinical application.To address these limitations,researchers have actively pursued the development of NBP derivatives and analogs,achieving notable progress.These efforts,including substituent introduction,ring opening derivatization,esterification,and atom substitution,have generated diverse NBP derivatives.Several of these derivatives have advanced to clinical studies.Specifically,potassium 2-(1-hydroxypentyl)-benzoate(PHPB),brozopentyl sodium(BZP),and XY-03-EA(ZONK1103)have reached phase II clinical trials,while(S)-2-(1-acetoxypentyl)benzoic acid L-arginine salt(AAPB)has received clinical trial approval for 2024.This review examines the structural modification and optimization of NBP over the past two decades from a medicinal chemistry perspective,aiming to facilitate the development of superior derivatives and advance cerebral ischemia treatment.展开更多
Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal var...Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal varying characteristics,remains poorly understood.Here,we collected cortical resting-state CBF in rats with left carotid artery blockage during occlusion–reperfusion,and measured the temporal variability and changes in laterality using a novel state-space method.This method was also applied to stroke EEG datasets to validate its effectiveness.After arterial occlusion,the left marginal motor,sensory,auditory,and visual cortices exhibited severe temporal variability impairments.The laterality analysis indicated that affected left regions showed inferior unilateral mean,inter-hemispheric transition probability,time fraction,and laterality duration,while the right side had a higher laterality time fraction and duration.These impairments recovered partially following blood flow restoration.Besides,the ischemic state-space metrics were positively correlated with the pre-occlusion baseline appearance.Stroke patients exhibited impaired temporal variability in the affected ischemic hemisphere.The state-space analysis revealed damaged CBF temporal variability during cerebral ischemia and predicted baseline-ischemia connections.展开更多
Objective To develop QingNangTCM,a specialized large language model(LLM)tailored for expert-level traditional Chinese medicine(TCM)question-answering and clinical reasoning,addressing the scarcity of domain-specific c...Objective To develop QingNangTCM,a specialized large language model(LLM)tailored for expert-level traditional Chinese medicine(TCM)question-answering and clinical reasoning,addressing the scarcity of domain-specific corpora and specialized alignment.Methods We constructed QnTCM_Dataset,a corpus of 100000 entries,by integrating data from ShenNong_TCM_Dataset and SymMap v2.0,and synthesizing additional samples via retrieval-augmented generation(RAG)and persona-driven generation.The dataset comprehensively covers diagnostic inquiries,prescriptions,and herbal knowledge.Utilizing P-Tuning v2,we fine-tuned the GLM-4-9B-Chat backbone to develop QingNangTCM.A multidimensional evaluation framework,assessing accuracy,coverage,consistency,safety,professionalism,and fluency,was established using metrics such as bilingual evaluation understudy(BLEU),recall-oriented understudy for gisting evaluation(ROUGE),metric for evaluation of translation with explicit ordering(METEOR),and LLM-as-a-Judge with expert review.Qualitative analysis was conducted across four simulated clinical scenarios:symptom analysis,disease treatment,herb inquiry,and failure cases.Baseline models included GLM-4-9BChat,DeepSeek-V2,HuatuoGPT-II(7B),and GLM-4-9B-Chat(freeze-tuning).Results QingNangTCM achieved the highest scores in BLEU-1/2/3/4(0.425/0.298/0.137/0.064),ROUGE-1/2(0.368/0.157),and METEOR(0.218),demonstrating a balanced and superior normalized performance profile of 0.900 across the dimensions of accuracy,coverage,and consistency.Although its ROUGE-L score(0.299)was lower than that of HuatuoGPT-II(7B)(0.351),it significantly outperformed domain-specific models in expert-validated win rates for professionalism(86%)and safety(73%).Qualitative analysis confirmed that the model strictly adheres to the“symptom-syndrome-pathogenesis-treatment”reasoning chain,though occasional misclassifications and hallucinations persisted when dealing with rare medicinal materials and uncommon syndromes.展开更多
Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active comp...Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active component,have significant antioxidant,neuroprotective,and cardioprotective effects.Clinically,myocardial ischemia(MI)and depression often interact,which has increasing morbidity and mortality rates.However,the mechanism of PQS on MI with depression remains unclear.Methods:The study employed both in vivo and in vitro experiments.Depression-like behaviour changes and cardiac function were observed in mice with MI and depression induced by a high-fat diet(HFD)and intraperitoneal injection of isoproterenol(ISO)plus chronic unpredictable mild stress(CUMS).Both ISO-exposed H9c2 cells and corticosterone(CORT)-induced HT22 cells were selected for in vitro experiments.Biochemical indices and PI3K/Akt/eNOS pathway-related proteins were measured through enzyme-linked immunosorbent assay(ELISA)and Western blotting.Results:PQS significantly improved depression-like behaviour and heart damage in mice and substantially increased H9c2 and HT22 cell activities in vitro.Western blotting analysis showed that PQS could dramatically reverse the changes in the PI3K/AKT/eNOS signalling pathway both in vivo and in vitro.In addition,applying the PI3K inhibitor LY294002 weakened the neuroprotective and cardioprotective effects of PQS.Conclusion:PQS can effectively improve MI with depression,probably through activating PI3K/Akt/eNOS pathway.展开更多
Objective:To observe the efficacy and safety of TCM syndrome differentiation-guided herbal intervention for patients with five constitutions during the high-risk window period of acute exacerbation of chronic obstruct...Objective:To observe the efficacy and safety of TCM syndrome differentiation-guided herbal intervention for patients with five constitutions during the high-risk window period of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)based on TCM constitution theory.Methods:A total of 300 AECOPD patients in the high-risk window period(54-66 cases for each constitution)were randomly divided into two groups(150 cases each).The control group received fluticasone furoate/umeclidinium/vilanterol inhalation therapy,while the experimental group was additionally given constitution-specific TCM decoctions(e.g.,Erchen Decoction combined with Sanzi Yangqin Decoction for Phlegm-Dampness constitution).The treatment course was 8 weeks with a 6-month follow-up.CAT score,TCM syndrome score,pulmonary function,6-minute walking distance(6MWD),and levels of CRP and IL-6 were observed.Recurrence and safety indicators were recorded.Results:After treatment,all indicators improved significantly in both groups(p<0.05),with the experimental group showing superior improvements in CAT score,TCM syndrome score,FEV1,6MWD,and inflammatory indicators(p<0.01).The recurrence rate was lower in the experimental group during follow-up(p<0.05).No severe adverse reactions or abnormalities in liver/kidney function were observed in either group.Conclusion:TCM syndrome differentiation treatment guided by constitution theory can improve symptoms,quality of life,and pulmonary function,reduce inflammatory levels and recurrence rate in AECOPD patients during the high-risk window period,with good safety.展开更多
Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cereb...Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.展开更多
The prevention and treatment of myocardial ischemia is a hot and difficult point in clinical research and animal experimental research in the cardiovascular field.The combined disease and syndrome animal model with th...The prevention and treatment of myocardial ischemia is a hot and difficult point in clinical research and animal experimental research in the cardiovascular field.The combined disease and syndrome animal model with the disease characteristics of Western medicine and guided by the theory of Chinese medicineto replicate the"syndrome"of Chinese medicine on the model animals by using experimental methods is an effective tool for the research of Chinese medicine.This article summarized the methoding methods and evaluation index of the animal model combined disease of coronary heart disease myocardial ischemia with cold blood stasis,phlegm and blood stasis,qi deficiency and blood stasis syndrome,kidney deficiency and blood stasis,and concluded the treatment of Traditional Chinese medicine.At the same time,it analyzed the main deficiencies of myocardial ischemia syndrome combined with animal models to provide reference for the establishment and research of related animal models.展开更多
Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expre...Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.展开更多
Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necr...Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necroptosis,and phagoptosis,among which autophagy is the most studied.We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury.To the best of our knowledge,this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke.The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.展开更多
Brain injuries like ischemic stroke induce endogenous stem cell production. Although the precise traits of stem cells in pathological brains remain unclear, we previously demonstrated that injury/ischemia-induced stem...Brain injuries like ischemic stroke induce endogenous stem cell production. Although the precise traits of stem cells in pathological brains remain unclear, we previously demonstrated that injury/ischemia-induced stem cells(iSCs)are present in the post-stroke mouse(Nakagomi et al.,2009)and human brains(Beppu et al.,2019).展开更多
Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats wer...Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats were divided into the Control,Model,AMI positive control(Propranolol hydrochloride,30 mg/kg),low dose TFSB(50 mg/kg),and high dose TFSB(100 mg/kg)groups.Rats received the corresponding treatment by intragastric administration once daily for 10 consecutive days.Electrocardiogram,myocardial enzyme,triphenyltetrazolium chloride staining,hematoxylin-eosin,and enzyme-linked immunosorbent assay were performed to evaluate the protective effect of TFSB on AMI rats.Then,the UHPLC-Q-Orbitrap MS method based on serum metabolomics was utilised to search for metabolic biomarkers and metabolic pathways.Subsequently,Western blot and RT-PCR techniques were employed to identify the respective genes and proteins.Results:Pharmacodynamics revealed that TFSB could ameliorate AMI in rats.The results of the metabolomics analysis indicated that the alterations in metabolic profile observed in rats with AMI were partially improved by treatment with TFSB.Moreover,the mRNA expression levels of 5-lipoxygenase(5-LOX)and 15-lipoxygenase(15-LOX)and the protein expression levels of 5-LOX,15-LOX,interleukin-1β(IL-1β),and NF-κB p65 were reduced following treatment with TFSB.Conclusion:The potential treatment of TFSB in AMI may be ascribed to its ability to regulate arachidonic acid metabolism.展开更多
BACKGROUND Acute mesenteric ischemia is a life-threatening disease.Intrasplenic gas is an extremely rare finding in such cases.CASE SUMMARY We report a case of a 79-year-old woman with a history of end-stage renal dis...BACKGROUND Acute mesenteric ischemia is a life-threatening disease.Intrasplenic gas is an extremely rare finding in such cases.CASE SUMMARY We report a case of a 79-year-old woman with a history of end-stage renal disease on hemodialysis for approximately 20 years,type 2 diabetes mellitus,and atrial fibrillation who presented with two days of epigastric pain.A computed tomography scan of the abdomen revealed intraperitoneal free air and significant intrasplenic gas.Laparoscopy revealed diffuse intestinal gangrene,and acute superior mesenteric ischemia was diagnosed.The patient died within 24 hours owing to profound shock.CONCLUSION Intrasplenic gas is an extremely rare finding on computed tomography imaging in cases of acute mesenteric ischemia.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
基金supported by the National Natural Science Foundation of China(Nos.21977058 and 82473840)the Key R&D Program of Jiangsu Province(No.BE2021677)+2 种基金China Postdoctoral Science Foundation(No.2018T110533)the Key Natural Science Foundation of Jiangsu Higher Education Institutions(No.20KJA350002)Jiangsu Province Innovation Project of Postgraduate Training(No.KYCX22_3380).
文摘Ischemic stroke(IS)presents a major threat to human life and health due to its high disability and mortality rates.3-n-Butylphthalide(NBP),derived from celery seeds of the Apiaceae family native to the Mediterranean region,was first introduced in China for acute IS treatment in 2004.NBP demonstrates multiple therapeutic actions,including reconstruction of microcirculation in the cerebral ischemia area,inhibition of platelet aggregation,reduction of cerebral infarction volume,maintenance of blood-brain barrier(BBB)integrity,and enhancement of cerebral blood perfusion.However,its overall efficacy remains moderate,limited by poor water solubility and low bioavailability,which constrains its clinical application.To address these limitations,researchers have actively pursued the development of NBP derivatives and analogs,achieving notable progress.These efforts,including substituent introduction,ring opening derivatization,esterification,and atom substitution,have generated diverse NBP derivatives.Several of these derivatives have advanced to clinical studies.Specifically,potassium 2-(1-hydroxypentyl)-benzoate(PHPB),brozopentyl sodium(BZP),and XY-03-EA(ZONK1103)have reached phase II clinical trials,while(S)-2-(1-acetoxypentyl)benzoic acid L-arginine salt(AAPB)has received clinical trial approval for 2024.This review examines the structural modification and optimization of NBP over the past two decades from a medicinal chemistry perspective,aiming to facilitate the development of superior derivatives and advance cerebral ischemia treatment.
基金supported by the National Natural Science Foundation of China(82250410380 and 62171101)the Natural Science Foundation of Sichuan Province(24NSFSC6257)the China MOST2030 Brain Project(2022ZD0208500).
文摘Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal varying characteristics,remains poorly understood.Here,we collected cortical resting-state CBF in rats with left carotid artery blockage during occlusion–reperfusion,and measured the temporal variability and changes in laterality using a novel state-space method.This method was also applied to stroke EEG datasets to validate its effectiveness.After arterial occlusion,the left marginal motor,sensory,auditory,and visual cortices exhibited severe temporal variability impairments.The laterality analysis indicated that affected left regions showed inferior unilateral mean,inter-hemispheric transition probability,time fraction,and laterality duration,while the right side had a higher laterality time fraction and duration.These impairments recovered partially following blood flow restoration.Besides,the ischemic state-space metrics were positively correlated with the pre-occlusion baseline appearance.Stroke patients exhibited impaired temporal variability in the affected ischemic hemisphere.The state-space analysis revealed damaged CBF temporal variability during cerebral ischemia and predicted baseline-ischemia connections.
基金Hebei Province Higher Education Scientific Research Project(QN2025367)Zhangjiakou City 2022 Municipal Science and Technology Plan Self-raised Fund Project(221105D)Hebei Province Education Science“14th Five-Year Plan”Project(2404224).
文摘Objective To develop QingNangTCM,a specialized large language model(LLM)tailored for expert-level traditional Chinese medicine(TCM)question-answering and clinical reasoning,addressing the scarcity of domain-specific corpora and specialized alignment.Methods We constructed QnTCM_Dataset,a corpus of 100000 entries,by integrating data from ShenNong_TCM_Dataset and SymMap v2.0,and synthesizing additional samples via retrieval-augmented generation(RAG)and persona-driven generation.The dataset comprehensively covers diagnostic inquiries,prescriptions,and herbal knowledge.Utilizing P-Tuning v2,we fine-tuned the GLM-4-9B-Chat backbone to develop QingNangTCM.A multidimensional evaluation framework,assessing accuracy,coverage,consistency,safety,professionalism,and fluency,was established using metrics such as bilingual evaluation understudy(BLEU),recall-oriented understudy for gisting evaluation(ROUGE),metric for evaluation of translation with explicit ordering(METEOR),and LLM-as-a-Judge with expert review.Qualitative analysis was conducted across four simulated clinical scenarios:symptom analysis,disease treatment,herb inquiry,and failure cases.Baseline models included GLM-4-9BChat,DeepSeek-V2,HuatuoGPT-II(7B),and GLM-4-9B-Chat(freeze-tuning).Results QingNangTCM achieved the highest scores in BLEU-1/2/3/4(0.425/0.298/0.137/0.064),ROUGE-1/2(0.368/0.157),and METEOR(0.218),demonstrating a balanced and superior normalized performance profile of 0.900 across the dimensions of accuracy,coverage,and consistency.Although its ROUGE-L score(0.299)was lower than that of HuatuoGPT-II(7B)(0.351),it significantly outperformed domain-specific models in expert-validated win rates for professionalism(86%)and safety(73%).Qualitative analysis confirmed that the model strictly adheres to the“symptom-syndrome-pathogenesis-treatment”reasoning chain,though occasional misclassifications and hallucinations persisted when dealing with rare medicinal materials and uncommon syndromes.
基金supported by the study on the material basis and mechanism of action of American ginseng in the treatment of myocardial ischaemia comorbid depression(2024JH2/102500059).
文摘Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active component,have significant antioxidant,neuroprotective,and cardioprotective effects.Clinically,myocardial ischemia(MI)and depression often interact,which has increasing morbidity and mortality rates.However,the mechanism of PQS on MI with depression remains unclear.Methods:The study employed both in vivo and in vitro experiments.Depression-like behaviour changes and cardiac function were observed in mice with MI and depression induced by a high-fat diet(HFD)and intraperitoneal injection of isoproterenol(ISO)plus chronic unpredictable mild stress(CUMS).Both ISO-exposed H9c2 cells and corticosterone(CORT)-induced HT22 cells were selected for in vitro experiments.Biochemical indices and PI3K/Akt/eNOS pathway-related proteins were measured through enzyme-linked immunosorbent assay(ELISA)and Western blotting.Results:PQS significantly improved depression-like behaviour and heart damage in mice and substantially increased H9c2 and HT22 cell activities in vitro.Western blotting analysis showed that PQS could dramatically reverse the changes in the PI3K/AKT/eNOS signalling pathway both in vivo and in vitro.In addition,applying the PI3K inhibitor LY294002 weakened the neuroprotective and cardioprotective effects of PQS.Conclusion:PQS can effectively improve MI with depression,probably through activating PI3K/Akt/eNOS pathway.
基金Longquan Yi District Health Bureau Project(Project No.:WJKY2023009)。
文摘Objective:To observe the efficacy and safety of TCM syndrome differentiation-guided herbal intervention for patients with five constitutions during the high-risk window period of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)based on TCM constitution theory.Methods:A total of 300 AECOPD patients in the high-risk window period(54-66 cases for each constitution)were randomly divided into two groups(150 cases each).The control group received fluticasone furoate/umeclidinium/vilanterol inhalation therapy,while the experimental group was additionally given constitution-specific TCM decoctions(e.g.,Erchen Decoction combined with Sanzi Yangqin Decoction for Phlegm-Dampness constitution).The treatment course was 8 weeks with a 6-month follow-up.CAT score,TCM syndrome score,pulmonary function,6-minute walking distance(6MWD),and levels of CRP and IL-6 were observed.Recurrence and safety indicators were recorded.Results:After treatment,all indicators improved significantly in both groups(p<0.05),with the experimental group showing superior improvements in CAT score,TCM syndrome score,FEV1,6MWD,and inflammatory indicators(p<0.01).The recurrence rate was lower in the experimental group during follow-up(p<0.05).No severe adverse reactions or abnormalities in liver/kidney function were observed in either group.Conclusion:TCM syndrome differentiation treatment guided by constitution theory can improve symptoms,quality of life,and pulmonary function,reduce inflammatory levels and recurrence rate in AECOPD patients during the high-risk window period,with good safety.
基金supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG)Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH)+1 种基金Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX)Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。
文摘Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.
基金National Natural Science Foundation of China(No.81960861)Funded by Guangxi Graduate Education Innovation Program(No.YCXJ2021035)。
文摘The prevention and treatment of myocardial ischemia is a hot and difficult point in clinical research and animal experimental research in the cardiovascular field.The combined disease and syndrome animal model with the disease characteristics of Western medicine and guided by the theory of Chinese medicineto replicate the"syndrome"of Chinese medicine on the model animals by using experimental methods is an effective tool for the research of Chinese medicine.This article summarized the methoding methods and evaluation index of the animal model combined disease of coronary heart disease myocardial ischemia with cold blood stasis,phlegm and blood stasis,qi deficiency and blood stasis syndrome,kidney deficiency and blood stasis,and concluded the treatment of Traditional Chinese medicine.At the same time,it analyzed the main deficiencies of myocardial ischemia syndrome combined with animal models to provide reference for the establishment and research of related animal models.
文摘Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.
基金Shanghai Rehabilitation Medical Association,Grant/Award Number:2023JGKT24China Rehabilitation Medical Association,Grant/Award Number:KFKT-2023Shanghai“14th Five-Year Plan”Traditional Chinese Medicine Specialty and Traditional Chinese Medicine Emergency Capacity Improvement Project,Grant/Award Number:ZYTSZK2-7。
文摘Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necroptosis,and phagoptosis,among which autophagy is the most studied.We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury.To the best of our knowledge,this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke.The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.
基金partially supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (15K0672318K07380)the Japan Agency for Medical Research and Development (AMED) (21nk0101538h0002) (to TN)。
文摘Brain injuries like ischemic stroke induce endogenous stem cell production. Although the precise traits of stem cells in pathological brains remain unclear, we previously demonstrated that injury/ischemia-induced stem cells(iSCs)are present in the post-stroke mouse(Nakagomi et al.,2009)and human brains(Beppu et al.,2019).
基金sponsored by Shandong Provincial Key Research and Development Program(Major Technological Innovation Project)([2021]CXGC010508)Guizhou Province Youth Science and Technology Talent Plan(YQK[2023]038)+1 种基金Science and Technology Department of Zunyi City of Guizhou province of China([2020]7)Key project at central government level:the ability establishment of sustainable use for valuable Chinese medicine resources(2060302).
文摘Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats were divided into the Control,Model,AMI positive control(Propranolol hydrochloride,30 mg/kg),low dose TFSB(50 mg/kg),and high dose TFSB(100 mg/kg)groups.Rats received the corresponding treatment by intragastric administration once daily for 10 consecutive days.Electrocardiogram,myocardial enzyme,triphenyltetrazolium chloride staining,hematoxylin-eosin,and enzyme-linked immunosorbent assay were performed to evaluate the protective effect of TFSB on AMI rats.Then,the UHPLC-Q-Orbitrap MS method based on serum metabolomics was utilised to search for metabolic biomarkers and metabolic pathways.Subsequently,Western blot and RT-PCR techniques were employed to identify the respective genes and proteins.Results:Pharmacodynamics revealed that TFSB could ameliorate AMI in rats.The results of the metabolomics analysis indicated that the alterations in metabolic profile observed in rats with AMI were partially improved by treatment with TFSB.Moreover,the mRNA expression levels of 5-lipoxygenase(5-LOX)and 15-lipoxygenase(15-LOX)and the protein expression levels of 5-LOX,15-LOX,interleukin-1β(IL-1β),and NF-κB p65 were reduced following treatment with TFSB.Conclusion:The potential treatment of TFSB in AMI may be ascribed to its ability to regulate arachidonic acid metabolism.
文摘BACKGROUND Acute mesenteric ischemia is a life-threatening disease.Intrasplenic gas is an extremely rare finding in such cases.CASE SUMMARY We report a case of a 79-year-old woman with a history of end-stage renal disease on hemodialysis for approximately 20 years,type 2 diabetes mellitus,and atrial fibrillation who presented with two days of epigastric pain.A computed tomography scan of the abdomen revealed intraperitoneal free air and significant intrasplenic gas.Laparoscopy revealed diffuse intestinal gangrene,and acute superior mesenteric ischemia was diagnosed.The patient died within 24 hours owing to profound shock.CONCLUSION Intrasplenic gas is an extremely rare finding on computed tomography imaging in cases of acute mesenteric ischemia.
