OBJECTIVE: To investigate the etiological factors of Alzheimer disease (AD) and the advance in drug treatment. DATA SOURCES: Using the terms "Alzheimer disease, etiology, drug treatment", we searched Medline...OBJECTIVE: To investigate the etiological factors of Alzheimer disease (AD) and the advance in drug treatment. DATA SOURCES: Using the terms "Alzheimer disease, etiology, drug treatment", we searched Medline database for AD treatment-related English literatures which were published between January 1993 and September 2006. Other literatures were obtained by searching concrete magazines and papers by hand. STUDY SELECTION: The data were selected primarily. Epidemiologic study and randomized controlled clinical trials were selected, and those studies with repetitive or similar contents were excluded. DATA EXTRACTION: Totally 1 537 AD and its treatment-related literatures were collected, and 32 of them were involved. Altogether 1 505 non-randomized controlled clinical trials, repetitive studies and reviews were excluded. DATA SYNTHESIS: The restriction of curative effect is a progressive neural degenerative disease. Although the etiological hypothesis of this disease has been introduced, the etiological factors of this disease are still unclear. The current treatments mainly involve: preventing against Aβ formation and clearing Aβ, application of antioxidant and free radical scavengers, application of anti-inflammatory preparation, application of cholinergic preparation, hormonal therapy, application of metabolic enhancer, application of neurotrophic factor and nerve protectant, gene therapy and so on. CONCLUSION: The etiological factors of AD are still unclear, and symptomatic treatment is much taken in clinical therapy. Therefore, the curative effects of AD are still not very ideal.展开更多
Purpose:To evaluate the feasibility and efficacy of a transmesenteric vein extrahepatic portosystemic shunt(TmEPS)for the treatment of cavernous transformation of the portal vein(CTPV).Materials and methods:The clinic...Purpose:To evaluate the feasibility and efficacy of a transmesenteric vein extrahepatic portosystemic shunt(TmEPS)for the treatment of cavernous transformation of the portal vein(CTPV).Materials and methods:The clinical data of 20 patients with CTPV who underwent TmEPS between December 2020and January 2022 at Henan Provincial People’s Hospital were retrospectively collected.The superior mesenteric vein(SMV)trunk was patent or partially occluded in these patients.An extrahepatic portosystemic shunt between the inferior vena cava and the SMV was established using a stent graft through an infraumbilical median longitudinal mini-laparotomy.The technical success,efficacy,and complication rates were evaluated,and the preand postoperative SMV pressures were compared.Patients’clinical outcomes and shunt patency were assessed.Results:TmEPS was successfully performed in 20 patients.The initial puncture success rate of the balloon-assisted puncture technique is 95%.The mean SMV pressure decreased from 29.1±2.9 mmHg to 15.6±3.3 mmHg(p<0.001).All symptoms of portal hypertension resolved.No fatal procedural complications occurred.During the follow-up period,hepatic encephalopathy occurred in two patients.The remaining patients remained asymptomatic.All shunts were patent.Conclusions:TmEPS is a feasible,safe,and effective treatment option for patients with CTPV.展开更多
At present,ischemic stroke seriously affects people's life and health,and its occurrence,development and therapeutic effect are affected by many factors.With the deep research on ischemic cerebral apoplexy disease...At present,ischemic stroke seriously affects people's life and health,and its occurrence,development and therapeutic effect are affected by many factors.With the deep research on ischemic cerebral apoplexy disease,people have a deeper understanding of its virulence genes.The apolipoprotein E genotype is the research focus recently,its genetic type is not only involved in the occurrence and development of ischemic cerebral apoplexy,but also causes different therapeatic effects.In this paper,we reviewed the relationship between apolipoprotein E gene polymorphism and lipid metabolism and atherosclerosis in ischemic stroke,as well as the differences in the therapeutic effects of thrombolysis,thrombectomy and lipid-lowering among different genotypes.展开更多
Background:Previous single-center studies have demonstrated that drug-coated balloons(DCBs)may reduce restenosis rates,which is an important factor affecting the prognosis for intracranial interventional therapy.Howev...Background:Previous single-center studies have demonstrated that drug-coated balloons(DCBs)may reduce restenosis rates,which is an important factor affecting the prognosis for intracranial interventional therapy.However,currently available cardiac DCBs are not always suitable for the treatment of intracranial atherosclerotic stenosis(ICAS).This study aimed to evaluate the safety and efficacy of a novel DCB catheter designed for patients with severely symptomatic ICAS.Methods:This prospective,multicenter,single-arm,target-value clinical trial was conducted in 9 Chinese stroke centers to evaluate the safety and efficacy of a novel DCB catheter for treating symptomatic severe ICAS.Primary metrics and other indicators were collected and analyzed using SAS version 9.4(SAS Institute,Cary,NC,USA).Results:A total of 155 patients were enrolled in this study.The preliminary collection of follow-up data has been completed,while data quality control is ongoing.Conclusion:Results of this study demonstrated the patency rate,safety,and effectiveness of a novel on-label paclitaxel DCB designed for the treatment of ICAS.Ethics and dissemination:This study,involving human participants,was reviewed and approved by the Ethics Committee of Drugs(Devices)Clinical Experiment at Henan Provincial People’s Hospital(reference number:2020-145-03)and other research centers participating in the clinical trial.The results of this study will be presented at international conferences and sent to peer-reviewed journals for publication.Standard protocol items:The Recommendations for Interventional Trials checklist was used when drafting the study protocol.Trial registration number:Registered with the Chinese Clinical Trial Registry on June 11,2021(Chi CTR2100047223).展开更多
Objective:To summarize the nursing treatment of patients who underwent implantation of a blood flow diverter to treat complex intracranial aneurysms.Methods:Data from 22 patients with complex aneurysms,diagnosed at an...Objective:To summarize the nursing treatment of patients who underwent implantation of a blood flow diverter to treat complex intracranial aneurysms.Methods:Data from 22 patients with complex aneurysms,diagnosed at an interventional center for blood flow diverter implantation between February 2015 and February 2016,treated in the Henan Provincial People’s Hospital(Zhengzhou,China),were retrospectively analyzed.Nursing methods,including preoperative,intraoperative,and postoperative care,were analyzed.Results:All 22 patients underwent successful surgery,with no related complications or hospital mortality,and were cured in hospital.Conclusion:Interventional flow diverter therapy for patients with complex intracranial aneurysms is a new technology,and involves intensive care by nursing staff and appears to be a promising new treatment method.展开更多
Background: The balloon-guiding catheter(BGC) reportedly reduces the number of retrievals and occurrence of distal emboli, achieving superior revascularization results and improved clinical outcomes in acute stroke. T...Background: The balloon-guiding catheter(BGC) reportedly reduces the number of retrievals and occurrence of distal emboli, achieving superior revascularization results and improved clinical outcomes in acute stroke. This study will aim to examine the efficacy and safety of the new Separ GateTM BGC.Design: This prospective multicenter single-arm clinical trial will aim to include 128 patients who fulfill its inclusion and exclusion criteria. All patients will receive endovascular interventional therapy with BGC assistance.The primary endpoint will be the immediate surgical success rate, while the secondary endpoint will be product performance. The safety evaluation will include serious adverse events such as puncture site hematoma and bleeding, cerebral vasospasm, vessel dissection, vessel perforation, air embolism, thrombus(acute or subacute),vessel occlusion, distal embolization, infection, adverse reaction to antiplatelet and anticoagulant drugs, intracranial hemorrhage, stroke, death, and device defect.Discussion: The prospective multicenter trial will provide safety and efficacy information for the Separ GateTM BGC.Its findings will provide a clinical reference for endovascular adjuvant therapy of cerebrovascular disease.Trial registration: Chi CTR1800014459.展开更多
BACKGROUND:Previous studies have demonstrated that Piper futokadsura stem selectively inhibits expression of amyloid precursor protein(APP) at the mRNA level.In addition,the piperlonguminine(A) and dihydropiperlongumi...BACKGROUND:Previous studies have demonstrated that Piper futokadsura stem selectively inhibits expression of amyloid precursor protein(APP) at the mRNA level.In addition,the piperlonguminine(A) and dihydropiperlonguminine(B) components(1:0.8),which can be separated from Futokadsura stem,selectively inhibit expression of the APP at mRNA and protein levels. OBJECTIVE:Based on previous findings,the present study investigated the effects ofβ-site amyloid precursor protein cleaving enzyme(BACE1) and APP genes on the production ofβ-amyloid peptide 42(Aβ42) in human neuroblastoma cells(SK-N-SH cells) using small interfering RNAs (siRNAs) and A/B components separated from Futokadsura stem,respectively. DESIGN,TIME AND SETTING:A gene interference-based randomized,controlled,in vitro experiment was performed at the Key Laboratory of Cardiovascular Remodeling and Function Research,Ministries of Education and Public Health,and Institute of Pharmacologic Research, School of Pharmaceutical Science & Department of Biochemistry,School of Medicine,Shandong University between July 2006 and December 2007. MATERIALS:SK-N-SH cells were provided by Shanghai Institutes of Biological Sciences,Chinese Academy of Sciences,Shanghai,China;mouse anti-human BACE1 monoclonal antibody was purchased from R&D Systems,USA;mouse anti-human APP monoclonal antibody was purchased from Cell Signaling Technology,USA;and horseradish peroxidase(HRP)-conjugated goat anti-mouse IgG was provided by Sigma,USA. METHODS:The human BACE1 cDNA sequence was obtained from NCBI website (www.ncbi.nlm.nih.gov/sites/entrez).Three pairs of siRNAs,specific to human BACE1 gene,were synthesized through the use of Silencer^(?) pre-designed siRNA specification,and were transfected into SK-N-SH cells with siPORT NeoFX transfection agent to compare the effects of different concentrations of siRNAs(10-50 nmol/L) on SK-N-SH cells.Futokadsura stem was separated and purified with chemical methods,and the crystal was composed of A/B components,with an A to B ratio of 1:0.8.The A/B(1:0.8) components were added to the SK-N-SH cells at different concentrations(13.13,6.56,and 3.28 mg/mL). MAIN OUTCOME MEASURES:Using RT-PCR and Western blot methods,BACE1 and APP expression at mRNA and protein levels was detected in SK-N-SH cells following treatment with different siRNAs and concentrations of Futokadsura stem-separated A/B components,respectively. Altered Aβ42 secretion by SK-N-SH cells was determined by ELISA. RESULTS:BACE1 mRNA and protein levels were significantly suppressed by 40 and 50 nmol/L siRNAs at 48 hours post-transfection.A/B components(1:0.8),which were separated from Futokadsura stem,selectively inhibited mRNA and protein expression of APP in SK-N-SH cells. Aβ42 secretion by SK-N-SH cells was significantly decreased following treatment with siRNAs or A/B components. CONCLUSION:Inhibition of BACE1 and APP genes by various materials and methods efficiently decreased production of Aβ42.展开更多
Background and purpose:Stent retriever thrombectomy is the standard therapeutic approach for ischemic stroke with acute large-vessel occlusion.This study evaluated the safety and efficacy of a new thrombectomy device(...Background and purpose:Stent retriever thrombectomy is the standard therapeutic approach for ischemic stroke with acute large-vessel occlusion.This study evaluated the safety and efficacy of a new thrombectomy device(Skyflow)in the treatment of acute ischemic stroke.Methods:After an arterial occlusion model was established,stent-retriever thrombectomy was performed.Digital subtraction angiography(DSA)and autopsy were carried out immediately after thrombectomy in six animals in the acute experimental group.Simulated stent-retriever thrombectomy was performed for three animals in the subacute experimental group,and follow-up angiography and vascular pathological examination were assessed 90 days after the operation.In the clinical trial,192 patients with intracranial anterior circulation large vessel occlusion,within 8 h of symptom onset,were included to undergo thrombectomy with either Skyflow or Solitaire FR stent retriever.Efficacy and safety endpoints were recorded(including successful reperfusion,favorable clinical outcomes,time from puncture to reperfusion,instrument operation success rates and National Institutes of Health Stroke Scale(NIHSS)scores at 7 days for efficacy endpoints,and symptomatic intracranial hemorrhage(sICH),subarachnoid hemorrhage(SAH)and all-cause mortality rates for safety endpoints).Results:All blood vessels achieved successful recanalization in the animal models.In the clinical trial,successful recanalization was attained in 88.4%of patients of the Skyflow group,which was comparable to that of the Solitaire FR group(82.5%)in the full analysis set of the clinical trial.There were no severe complications on DSA,an animal autopsy,or vessel pathological examination in animal experiments.Additionally,no statistically significant difference was observed between the Skyflow and Solitaire FR groups in the clinical trial regarding the safety endpoints.Conclusion:This study showed that the new Skyflow stent retriever is safe and effective for the treatment of acute large vessel occlusion,as demonstrated in our animal study and human trial.展开更多
Background:To establish a canine model of aortic arch aneurysm that is suitable for research on new devices and techniques applied to the aortic arch.Materials and methods:Fifteen mongrel dogs underwent surgery.The au...Background:To establish a canine model of aortic arch aneurysm that is suitable for research on new devices and techniques applied to the aortic arch.Materials and methods:Fifteen mongrel dogs underwent surgery.The autologous pericardial patch was sewn on the aortotomy site in the anterior wall of the aortic arch.The animals were followed up for 3 months postoperatively.Computed tomography angiography was used to visualize and measure the aneurysm model.Hematoxylin and eosin staining was used to observe the histological characteristics of the aneurysm model.Changes in aneurysm diameter over time were analyzed using analysis of variance.Results:One dog died of hemorrhage during surgery.Fourteen dogs survived the surgical procedure.Two of them died on the first postoperative day because of ruptures at the suturing margin.The diameter of the aneurysm model was twice as large as that of the aortic arch.There was no significant change in the maximum diameter of the aneurysm model during the follow-up period.Conclusions:We established a controllable and stable aortic arch aneurysm model created with an autologous pericardium patch.The aneurysm model can be used to research endoleaks after thoracic endovascular aortic repair and new endovascular techniques can be applied to the aortic arch.展开更多
Objective:To evaluate the safety and efficacy of the SeparGateballoon-guiding catheter(BGC)for blocking flow and delivering devices in neurointerventional surgery.Method:This prospective multicenter single-arm trial e...Objective:To evaluate the safety and efficacy of the SeparGateballoon-guiding catheter(BGC)for blocking flow and delivering devices in neurointerventional surgery.Method:This prospective multicenter single-arm trial enrolled patients who received BGC adjuvant therapy to provide temporary blood flow arrest of the supra-aortic arch arteries and their branch vessels in interventional therapy.The primary endpoint was immediate procedural success rate in flow arrest,device delivery,and withdrawal.The efficacy endpoints were intraoperative product performance,including rigidity,smoothness,fracture resistance of the catheter wall,catheter push performance,compatibility and radiopaque display,integrity,adhesion thrombus after withdrawal and balloon rupture.The safety endpoints were adverse and serious adverse events associated with the test device and serious adverse events resulting in death or serious health deterioration.Result:A total of 129 patients were included;of them,128 were analyzed in the full analysis set(FAS)and per protocol set(PPS).Immediate procedural success was achieved in 97.7%of patients with FAS and PPS.The lower bound of the 95%confidence interval was 94.6%,higher than the preset efficacy margin of 94%.Device-related adverse events occurred in 2(1.6%)cases.One was mild adverse event of vasospasm,which resolved spontaneously.The other was serious adverse event of dissection aggravation,which was treated with stenting angioplasty.No device defects were observed.Conclusion:In neurointerventional surgery,the SeparGateBGC can be used to temporarily block the flow of the supra-aortic arch arteries and their branch vessels and guide the interventional device to the target vascular position.展开更多
Genome-wide association studies have found that rs17612742 increases the risk of large artery atherosclerotic stroke.The rs17612742 was located in the intron region of Endothelin receptor type A(NRA),which was cellula...Genome-wide association studies have found that rs17612742 increases the risk of large artery atherosclerotic stroke.The rs17612742 was located in the intron region of Endothelin receptor type A(NRA),which was cellular and gender-heterogeneous.Functional genomics studies of rs17612742 were carried out through some public databases,and it was found that rs17612742 was located in the chromatin open region and promoted the expression of NRA.Compared with the control group,EDNRA expression increased in middle cerebral artery occlusion exposed rodents.However,age heterogeneity of EDNRA expression under physiological and pathological conditions was not observed.In addition,we also discussed how to conduct further empirical studies to provide evidence that rs17612742 confers the risk of large artery atherosclerotic stroke by increasing the expression of NRA.展开更多
Herpes simplex virus 1(HSV-1)is highly infectious.More than 70%of the world's population has been infected with HSV-1.1 Most patients with HSV-1 have no obvious clinical symptoms.However,HSV-1 infection can lead t...Herpes simplex virus 1(HSV-1)is highly infectious.More than 70%of the world's population has been infected with HSV-1.1 Most patients with HSV-1 have no obvious clinical symptoms.However,HSV-1 infection can lead to serious complications in people with an underlying genetic susceptibility,various causes of immunodeficiency.展开更多
Circular RNAs (circRNAs) are generated by head-to-tail splicing and are ubiquitously expressed in all multicellular organisms. Their important biological functions are increasingly recognized. Cerebral ischemia reperf...Circular RNAs (circRNAs) are generated by head-to-tail splicing and are ubiquitously expressed in all multicellular organisms. Their important biological functions are increasingly recognized. Cerebral ischemia reperfusion injury-induced brain microvascular endothelial cell dysfunction is an initial stage of blood-brain barrier disruption. The expression profile and potential function of circRNAs in brain microvascular endothelial cells is unknown. Rat brain microvascular endothelial cells were extracted and cultured in glucose-free medium for 4 hours with 5% CO2 and 95% N2, and the medium was then replaced with complete growth medium for 6 hours. The RNA in these cells was then extracted. The circRNA was identified by Find_circ and CIRI2 software. Functional and pathway enrichment analysis of genes that were common to differentially expressed mRNAs and circRNA host genes was performed by the Database for Annotation, Visualization and Integrated Discovery Functional Annotation Tool. Miranda software was used to predict microRNAs that were potentially sponged by circRNAs. Furthermore, cytoscape depicted the circR-NA-microRNA interaction network. The results showed that there were 1288 circRNAs in normal and oxygen-glucose deprived/recovered primary brain microvascular endothelial cells. There are 211 upregulated and 326 downregulated differentially expressed circRNAs. The host genes of these differentially expressed circRNAs overlapped with those of differentially expressed mRNAs. The shared genes were further studied by functional enrichment analyses, which revealed that circRNAs may contribute to calcium ion function and the cyclic guanosine 3′,5′-monophosphate (CAMP) dependent protein kinase (PKα) signaling pathway. Next, quantitative reverse transcription polymerase chain reaction assays were performed to detect circRNA levels transcribed from the overlapping host genes. Eight out of the ten circRNAs with the highest fold-change identified by sequencing were successfully verified. Subsequently, the circRNA-microRNA interaction networks of these eight circRNAs were explored by bioinformatic analysis. These results demonstrate that altered circRNAs may be important in the pathogenesis of cerebral ischemia reperfusion injury and consequently may also be potential therapeutic targets for cerebral ischemia diseases. All animal experiments were approved by the Chongqing Medical University Committee on Animal Research, China (approval No. CQMU20180086) on March 22, 2018.展开更多
The champagne bottle neck(CBN) sign refers to a reduction in the diameter of the proximal portion of the internal carotid artery that resembles a CBN, and is a characteristic feature of Moyamoya disease. A 43-yearold ...The champagne bottle neck(CBN) sign refers to a reduction in the diameter of the proximal portion of the internal carotid artery that resembles a CBN, and is a characteristic feature of Moyamoya disease. A 43-yearold woman with an infarction of the posterior limb of the left internal capsule was diagnosed with Moyamoya syndrome associated with Graves' disease. The CBN sign was observed bilaterally. Cerebral revascularization surgery was performed, including left-sided superficial temporal artery to middle cerebral artery anastomosis. During four years of follow-up, she maintained a euthyroid state and did not have any further cerebral ischemic events. The CBN signs remained unchanged on both sides during this time. This is the first report of the CBN sign in a patient with Moyamoya syndrome associated with Graves' disease.展开更多
Objective:The objective of this study was to evaluate the feasibility and outcomes of transvenous endovascular embolization(TVE) for superficial intracranial arteriovenous malformations(AVMs).Methods:After collecting ...Objective:The objective of this study was to evaluate the feasibility and outcomes of transvenous endovascular embolization(TVE) for superficial intracranial arteriovenous malformations(AVMs).Methods:After collecting clinical and imaging data,a prospective series of 11 patients presenting with superficial AVMs were treated by endovascular embolization using a transvenous approach between November 2016 and October 2018.Results:Ten patients(90.9%) had ruptured AVMs before TVE.The mean nidus size was 3.27 ± 1.47 cm,and the median Spetzler-Martin grade was II.The rate of immediate angiographic occlusion of the AVMs was 90.9%(10/11).One patient was treated with transarterial embolization since TVE was not achieved due to an unsuccessful positioning of the microcatheter.Two patients(cases 8 and 11) suffered a intracranial hemorrhage and a cerebral infarction with encephaledema,respectively,but no procedure-related mortalities were observed.Eight patients(72.7%) were independent with a modified Rankin Score(mRS) 2 at discharge and the m RSs of all patients,which were collected 30 days postintervention,were not more than 2.The mean follow-up period was 17 months.There were no nidus recurrences during the follow-up period.Conclusions:The curative transvenous embolization of superficial AVMs seems feasible and effective while carefully monitoring for embolization-related complications.展开更多
Injury to the brain after intracerebral hemorrhage(ICH)results from numerous complex cellular mechanisms.At present,effective therapy for ICH is limited and a better understanding of the mechanisms of brain injury is ...Injury to the brain after intracerebral hemorrhage(ICH)results from numerous complex cellular mechanisms.At present,effective therapy for ICH is limited and a better understanding of the mechanisms of brain injury is necessary to improve prognosis.There is increasing evidence that ion channel dysregulation occurs at multiple stages in primary and secondary brain injury following ICH.Ion channels such as TWIK-related K+channel 1,sulfonylurea 1 transient receptor potential melastatin 4 and glutamate-gated channels affect ion homeostasis in ICH.They in turn participate in the formation of brain edema,disruption of the blood-brain barrier,and the generation of neurotoxicity.In this review,we summarize the interaction between ions and ion channels,the effects of ion channel dysregulation,and we discuss some therapeutics based on ion-channel modulation following ICH.展开更多
Rationale Haematoma growth is common early after intracerebral haemorrhage(ICH),and is a key determinant of outcome.Tranexamic acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce...Rationale Haematoma growth is common early after intracerebral haemorrhage(ICH),and is a key determinant of outcome.Tranexamic acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce haematoma growth.Methods and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units(STOP-MSU)is a phase Ⅱ double-blind,randomised,placebo-controlled,multicentre,international investigator-led clinical trial,conducted within the estimand statistical framework.Hypothesis In patients with spontaneous ICH,treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimates A sample size of 180 patients(90 in each arm)would be required to detect an absolute difference in the primary outcome of 20%(placebo 39%vs treatment 19%)under a two-tailed significance level of 0.05.An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.Intervention Participants will receive 1 g intravenous tranexamic acid over 10 min,followed by 1 g intravenous tranexamic acid over 8 hours;or matching placebo.Primary efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours,defined as either≥33%relative increase or≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.Discussion We describe the rationale and protocol of STOP-MSU,a phase Ⅱ trial of tranexamic acid in patients with ICH within 2 hours from onset,based in participating mobile stroke units and emergency departments.展开更多
Ferroptosis,as a newly discovered cell death form,has become an attractive target for precision cancer therapy.Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing int...Ferroptosis,as a newly discovered cell death form,has become an attractive target for precision cancer therapy.Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione(GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4(GPX4).However,the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported.Herein,novel tumor microenvironments(TME)-activated metal-organic frameworks involving Fe&Cu ions bridged by disulfide bonds with PEGylation(FCSP MOFs)were developed,which would be degraded specifically under the redox TME,simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS via Fenton reaction,therefore causing ferroptosis.More ROS could be generated by the acceleration of Fenton reaction due to the released Cu ions and the intrinsic photothermal capability of FCSP MOFs.The overexpressed GSH and H2O2 in TME could ensure the specific TME self-activated therapy.Better tumor therapeutic efficiency could be achieved by doxorubicin(DOX)loading since it can not only cause apoptosis,but also indirectly produce H2O2 to amplify Fenton reaction.Remarkable anti-tumor effect of obtained FCSP@DOX MOFs was verified via both in vitro and in vivo assays.展开更多
Spontaneous intracerebral haemorrhage(ICH)is a devastating type of stroke with high mortality and morbidity and for which no effective treatments are available to date.Much experimental and clinical research have been...Spontaneous intracerebral haemorrhage(ICH)is a devastating type of stroke with high mortality and morbidity and for which no effective treatments are available to date.Much experimental and clinical research have been performed to explore its mechanisms regard the subsequent inflammatory cascade and to seek the potential therapeutic strategies.The aim of this review is to discuss insights from clinical settings that have led to the development of numerous animal models of ICH.Some of the current and future challenges for clinicians to understand ICH are also surveyed.展开更多
文摘OBJECTIVE: To investigate the etiological factors of Alzheimer disease (AD) and the advance in drug treatment. DATA SOURCES: Using the terms "Alzheimer disease, etiology, drug treatment", we searched Medline database for AD treatment-related English literatures which were published between January 1993 and September 2006. Other literatures were obtained by searching concrete magazines and papers by hand. STUDY SELECTION: The data were selected primarily. Epidemiologic study and randomized controlled clinical trials were selected, and those studies with repetitive or similar contents were excluded. DATA EXTRACTION: Totally 1 537 AD and its treatment-related literatures were collected, and 32 of them were involved. Altogether 1 505 non-randomized controlled clinical trials, repetitive studies and reviews were excluded. DATA SYNTHESIS: The restriction of curative effect is a progressive neural degenerative disease. Although the etiological hypothesis of this disease has been introduced, the etiological factors of this disease are still unclear. The current treatments mainly involve: preventing against Aβ formation and clearing Aβ, application of antioxidant and free radical scavengers, application of anti-inflammatory preparation, application of cholinergic preparation, hormonal therapy, application of metabolic enhancer, application of neurotrophic factor and nerve protectant, gene therapy and so on. CONCLUSION: The etiological factors of AD are still unclear, and symptomatic treatment is much taken in clinical therapy. Therefore, the curative effects of AD are still not very ideal.
基金supported by the Henan medical science and technology research projects(222102310014)
文摘Purpose:To evaluate the feasibility and efficacy of a transmesenteric vein extrahepatic portosystemic shunt(TmEPS)for the treatment of cavernous transformation of the portal vein(CTPV).Materials and methods:The clinical data of 20 patients with CTPV who underwent TmEPS between December 2020and January 2022 at Henan Provincial People’s Hospital were retrospectively collected.The superior mesenteric vein(SMV)trunk was patent or partially occluded in these patients.An extrahepatic portosystemic shunt between the inferior vena cava and the SMV was established using a stent graft through an infraumbilical median longitudinal mini-laparotomy.The technical success,efficacy,and complication rates were evaluated,and the preand postoperative SMV pressures were compared.Patients’clinical outcomes and shunt patency were assessed.Results:TmEPS was successfully performed in 20 patients.The initial puncture success rate of the balloon-assisted puncture technique is 95%.The mean SMV pressure decreased from 29.1±2.9 mmHg to 15.6±3.3 mmHg(p<0.001).All symptoms of portal hypertension resolved.No fatal procedural complications occurred.During the follow-up period,hepatic encephalopathy occurred in two patients.The remaining patients remained asymptomatic.All shunts were patent.Conclusions:TmEPS is a feasible,safe,and effective treatment option for patients with CTPV.
基金Major Science and Technology Project of Hainan Province(ZDKJ202004)。
文摘At present,ischemic stroke seriously affects people's life and health,and its occurrence,development and therapeutic effect are affected by many factors.With the deep research on ischemic cerebral apoplexy disease,people have a deeper understanding of its virulence genes.The apolipoprotein E genotype is the research focus recently,its genetic type is not only involved in the occurrence and development of ischemic cerebral apoplexy,but also causes different therapeatic effects.In this paper,we reviewed the relationship between apolipoprotein E gene polymorphism and lipid metabolism and atherosclerosis in ischemic stroke,as well as the differences in the therapeutic effects of thrombolysis,thrombectomy and lipid-lowering among different genotypes.
基金funded by The Henan Province Young and Middle-aged Health Science and Technology Innovation Young Talent Training Project(,Grant/Award Number:YXKC20200041)National Health Commission Capacity Building and Continuing Education Project(Grant/Award Number:GWJJ2023100101)
文摘Background:Previous single-center studies have demonstrated that drug-coated balloons(DCBs)may reduce restenosis rates,which is an important factor affecting the prognosis for intracranial interventional therapy.However,currently available cardiac DCBs are not always suitable for the treatment of intracranial atherosclerotic stenosis(ICAS).This study aimed to evaluate the safety and efficacy of a novel DCB catheter designed for patients with severely symptomatic ICAS.Methods:This prospective,multicenter,single-arm,target-value clinical trial was conducted in 9 Chinese stroke centers to evaluate the safety and efficacy of a novel DCB catheter for treating symptomatic severe ICAS.Primary metrics and other indicators were collected and analyzed using SAS version 9.4(SAS Institute,Cary,NC,USA).Results:A total of 155 patients were enrolled in this study.The preliminary collection of follow-up data has been completed,while data quality control is ongoing.Conclusion:Results of this study demonstrated the patency rate,safety,and effectiveness of a novel on-label paclitaxel DCB designed for the treatment of ICAS.Ethics and dissemination:This study,involving human participants,was reviewed and approved by the Ethics Committee of Drugs(Devices)Clinical Experiment at Henan Provincial People’s Hospital(reference number:2020-145-03)and other research centers participating in the clinical trial.The results of this study will be presented at international conferences and sent to peer-reviewed journals for publication.Standard protocol items:The Recommendations for Interventional Trials checklist was used when drafting the study protocol.Trial registration number:Registered with the Chinese Clinical Trial Registry on June 11,2021(Chi CTR2100047223).
基金National Natural Science Foundation of China(81601583).
文摘Objective:To summarize the nursing treatment of patients who underwent implantation of a blood flow diverter to treat complex intracranial aneurysms.Methods:Data from 22 patients with complex aneurysms,diagnosed at an interventional center for blood flow diverter implantation between February 2015 and February 2016,treated in the Henan Provincial People’s Hospital(Zhengzhou,China),were retrospectively analyzed.Nursing methods,including preoperative,intraoperative,and postoperative care,were analyzed.Results:All 22 patients underwent successful surgery,with no related complications or hospital mortality,and were cured in hospital.Conclusion:Interventional flow diverter therapy for patients with complex intracranial aneurysms is a new technology,and involves intensive care by nursing staff and appears to be a promising new treatment method.
文摘Background: The balloon-guiding catheter(BGC) reportedly reduces the number of retrievals and occurrence of distal emboli, achieving superior revascularization results and improved clinical outcomes in acute stroke. This study will aim to examine the efficacy and safety of the new Separ GateTM BGC.Design: This prospective multicenter single-arm clinical trial will aim to include 128 patients who fulfill its inclusion and exclusion criteria. All patients will receive endovascular interventional therapy with BGC assistance.The primary endpoint will be the immediate surgical success rate, while the secondary endpoint will be product performance. The safety evaluation will include serious adverse events such as puncture site hematoma and bleeding, cerebral vasospasm, vessel dissection, vessel perforation, air embolism, thrombus(acute or subacute),vessel occlusion, distal embolization, infection, adverse reaction to antiplatelet and anticoagulant drugs, intracranial hemorrhage, stroke, death, and device defect.Discussion: The prospective multicenter trial will provide safety and efficacy information for the Separ GateTM BGC.Its findings will provide a clinical reference for endovascular adjuvant therapy of cerebrovascular disease.Trial registration: Chi CTR1800014459.
基金the National Natural Science Foundation of China,No. NSFC-3027164
文摘BACKGROUND:Previous studies have demonstrated that Piper futokadsura stem selectively inhibits expression of amyloid precursor protein(APP) at the mRNA level.In addition,the piperlonguminine(A) and dihydropiperlonguminine(B) components(1:0.8),which can be separated from Futokadsura stem,selectively inhibit expression of the APP at mRNA and protein levels. OBJECTIVE:Based on previous findings,the present study investigated the effects ofβ-site amyloid precursor protein cleaving enzyme(BACE1) and APP genes on the production ofβ-amyloid peptide 42(Aβ42) in human neuroblastoma cells(SK-N-SH cells) using small interfering RNAs (siRNAs) and A/B components separated from Futokadsura stem,respectively. DESIGN,TIME AND SETTING:A gene interference-based randomized,controlled,in vitro experiment was performed at the Key Laboratory of Cardiovascular Remodeling and Function Research,Ministries of Education and Public Health,and Institute of Pharmacologic Research, School of Pharmaceutical Science & Department of Biochemistry,School of Medicine,Shandong University between July 2006 and December 2007. MATERIALS:SK-N-SH cells were provided by Shanghai Institutes of Biological Sciences,Chinese Academy of Sciences,Shanghai,China;mouse anti-human BACE1 monoclonal antibody was purchased from R&D Systems,USA;mouse anti-human APP monoclonal antibody was purchased from Cell Signaling Technology,USA;and horseradish peroxidase(HRP)-conjugated goat anti-mouse IgG was provided by Sigma,USA. METHODS:The human BACE1 cDNA sequence was obtained from NCBI website (www.ncbi.nlm.nih.gov/sites/entrez).Three pairs of siRNAs,specific to human BACE1 gene,were synthesized through the use of Silencer^(?) pre-designed siRNA specification,and were transfected into SK-N-SH cells with siPORT NeoFX transfection agent to compare the effects of different concentrations of siRNAs(10-50 nmol/L) on SK-N-SH cells.Futokadsura stem was separated and purified with chemical methods,and the crystal was composed of A/B components,with an A to B ratio of 1:0.8.The A/B(1:0.8) components were added to the SK-N-SH cells at different concentrations(13.13,6.56,and 3.28 mg/mL). MAIN OUTCOME MEASURES:Using RT-PCR and Western blot methods,BACE1 and APP expression at mRNA and protein levels was detected in SK-N-SH cells following treatment with different siRNAs and concentrations of Futokadsura stem-separated A/B components,respectively. Altered Aβ42 secretion by SK-N-SH cells was determined by ELISA. RESULTS:BACE1 mRNA and protein levels were significantly suppressed by 40 and 50 nmol/L siRNAs at 48 hours post-transfection.A/B components(1:0.8),which were separated from Futokadsura stem,selectively inhibited mRNA and protein expression of APP in SK-N-SH cells. Aβ42 secretion by SK-N-SH cells was significantly decreased following treatment with siRNAs or A/B components. CONCLUSION:Inhibition of BACE1 and APP genes by various materials and methods efficiently decreased production of Aβ42.
基金supported by the Co-construction of Provincial and Ministry Youth Project(SBGJ202003004)Key Research and Development Program of Henan Province(Scientific and Technological Project of Henan Province)(202102310037)
文摘Background and purpose:Stent retriever thrombectomy is the standard therapeutic approach for ischemic stroke with acute large-vessel occlusion.This study evaluated the safety and efficacy of a new thrombectomy device(Skyflow)in the treatment of acute ischemic stroke.Methods:After an arterial occlusion model was established,stent-retriever thrombectomy was performed.Digital subtraction angiography(DSA)and autopsy were carried out immediately after thrombectomy in six animals in the acute experimental group.Simulated stent-retriever thrombectomy was performed for three animals in the subacute experimental group,and follow-up angiography and vascular pathological examination were assessed 90 days after the operation.In the clinical trial,192 patients with intracranial anterior circulation large vessel occlusion,within 8 h of symptom onset,were included to undergo thrombectomy with either Skyflow or Solitaire FR stent retriever.Efficacy and safety endpoints were recorded(including successful reperfusion,favorable clinical outcomes,time from puncture to reperfusion,instrument operation success rates and National Institutes of Health Stroke Scale(NIHSS)scores at 7 days for efficacy endpoints,and symptomatic intracranial hemorrhage(sICH),subarachnoid hemorrhage(SAH)and all-cause mortality rates for safety endpoints).Results:All blood vessels achieved successful recanalization in the animal models.In the clinical trial,successful recanalization was attained in 88.4%of patients of the Skyflow group,which was comparable to that of the Solitaire FR group(82.5%)in the full analysis set of the clinical trial.There were no severe complications on DSA,an animal autopsy,or vessel pathological examination in animal experiments.Additionally,no statistically significant difference was observed between the Skyflow and Solitaire FR groups in the clinical trial regarding the safety endpoints.Conclusion:This study showed that the new Skyflow stent retriever is safe and effective for the treatment of acute large vessel occlusion,as demonstrated in our animal study and human trial.
基金supported by the Henan medical science and technology research projects(222102310014 and LGHJ20200058)。
文摘Background:To establish a canine model of aortic arch aneurysm that is suitable for research on new devices and techniques applied to the aortic arch.Materials and methods:Fifteen mongrel dogs underwent surgery.The autologous pericardial patch was sewn on the aortotomy site in the anterior wall of the aortic arch.The animals were followed up for 3 months postoperatively.Computed tomography angiography was used to visualize and measure the aneurysm model.Hematoxylin and eosin staining was used to observe the histological characteristics of the aneurysm model.Changes in aneurysm diameter over time were analyzed using analysis of variance.Results:One dog died of hemorrhage during surgery.Fourteen dogs survived the surgical procedure.Two of them died on the first postoperative day because of ruptures at the suturing margin.The diameter of the aneurysm model was twice as large as that of the aortic arch.There was no significant change in the maximum diameter of the aneurysm model during the follow-up period.Conclusions:We established a controllable and stable aortic arch aneurysm model created with an autologous pericardium patch.The aneurysm model can be used to research endoleaks after thoracic endovascular aortic repair and new endovascular techniques can be applied to the aortic arch.
基金supported by the Co-construction of Provincial and Ministry Youth Project(SBGJ202003004)Scientific and Technological Project of Henan Province(202102310037)。
文摘Objective:To evaluate the safety and efficacy of the SeparGateballoon-guiding catheter(BGC)for blocking flow and delivering devices in neurointerventional surgery.Method:This prospective multicenter single-arm trial enrolled patients who received BGC adjuvant therapy to provide temporary blood flow arrest of the supra-aortic arch arteries and their branch vessels in interventional therapy.The primary endpoint was immediate procedural success rate in flow arrest,device delivery,and withdrawal.The efficacy endpoints were intraoperative product performance,including rigidity,smoothness,fracture resistance of the catheter wall,catheter push performance,compatibility and radiopaque display,integrity,adhesion thrombus after withdrawal and balloon rupture.The safety endpoints were adverse and serious adverse events associated with the test device and serious adverse events resulting in death or serious health deterioration.Result:A total of 129 patients were included;of them,128 were analyzed in the full analysis set(FAS)and per protocol set(PPS).Immediate procedural success was achieved in 97.7%of patients with FAS and PPS.The lower bound of the 95%confidence interval was 94.6%,higher than the preset efficacy margin of 94%.Device-related adverse events occurred in 2(1.6%)cases.One was mild adverse event of vasospasm,which resolved spontaneously.The other was serious adverse event of dissection aggravation,which was treated with stenting angioplasty.No device defects were observed.Conclusion:In neurointerventional surgery,the SeparGateBGC can be used to temporarily block the flow of the supra-aortic arch arteries and their branch vessels and guide the interventional device to the target vascular position.
文摘Genome-wide association studies have found that rs17612742 increases the risk of large artery atherosclerotic stroke.The rs17612742 was located in the intron region of Endothelin receptor type A(NRA),which was cellular and gender-heterogeneous.Functional genomics studies of rs17612742 were carried out through some public databases,and it was found that rs17612742 was located in the chromatin open region and promoted the expression of NRA.Compared with the control group,EDNRA expression increased in middle cerebral artery occlusion exposed rodents.However,age heterogeneity of EDNRA expression under physiological and pathological conditions was not observed.In addition,we also discussed how to conduct further empirical studies to provide evidence that rs17612742 confers the risk of large artery atherosclerotic stroke by increasing the expression of NRA.
基金supported by Joint Funds for the innovation of science and Technology,Fujian province(China)(No.2018Y9064)Shenzhen Science and Technology Program(No.RCBS20210706092409017)Shenzhen University Program(China)(No.827000615).
文摘Herpes simplex virus 1(HSV-1)is highly infectious.More than 70%of the world's population has been infected with HSV-1.1 Most patients with HSV-1 have no obvious clinical symptoms.However,HSV-1 infection can lead to serious complications in people with an underlying genetic susceptibility,various causes of immunodeficiency.
基金supported by the National Natural Science Foundation for Young Scientists of China,No.81601058(to WL)Basic Research and Frontier Science Exploration Foundation of Yuzhong District,Chongqing,China,No.20180106(to FFS)
文摘Circular RNAs (circRNAs) are generated by head-to-tail splicing and are ubiquitously expressed in all multicellular organisms. Their important biological functions are increasingly recognized. Cerebral ischemia reperfusion injury-induced brain microvascular endothelial cell dysfunction is an initial stage of blood-brain barrier disruption. The expression profile and potential function of circRNAs in brain microvascular endothelial cells is unknown. Rat brain microvascular endothelial cells were extracted and cultured in glucose-free medium for 4 hours with 5% CO2 and 95% N2, and the medium was then replaced with complete growth medium for 6 hours. The RNA in these cells was then extracted. The circRNA was identified by Find_circ and CIRI2 software. Functional and pathway enrichment analysis of genes that were common to differentially expressed mRNAs and circRNA host genes was performed by the Database for Annotation, Visualization and Integrated Discovery Functional Annotation Tool. Miranda software was used to predict microRNAs that were potentially sponged by circRNAs. Furthermore, cytoscape depicted the circR-NA-microRNA interaction network. The results showed that there were 1288 circRNAs in normal and oxygen-glucose deprived/recovered primary brain microvascular endothelial cells. There are 211 upregulated and 326 downregulated differentially expressed circRNAs. The host genes of these differentially expressed circRNAs overlapped with those of differentially expressed mRNAs. The shared genes were further studied by functional enrichment analyses, which revealed that circRNAs may contribute to calcium ion function and the cyclic guanosine 3′,5′-monophosphate (CAMP) dependent protein kinase (PKα) signaling pathway. Next, quantitative reverse transcription polymerase chain reaction assays were performed to detect circRNA levels transcribed from the overlapping host genes. Eight out of the ten circRNAs with the highest fold-change identified by sequencing were successfully verified. Subsequently, the circRNA-microRNA interaction networks of these eight circRNAs were explored by bioinformatic analysis. These results demonstrate that altered circRNAs may be important in the pathogenesis of cerebral ischemia reperfusion injury and consequently may also be potential therapeutic targets for cerebral ischemia diseases. All animal experiments were approved by the Chongqing Medical University Committee on Animal Research, China (approval No. CQMU20180086) on March 22, 2018.
文摘The champagne bottle neck(CBN) sign refers to a reduction in the diameter of the proximal portion of the internal carotid artery that resembles a CBN, and is a characteristic feature of Moyamoya disease. A 43-yearold woman with an infarction of the posterior limb of the left internal capsule was diagnosed with Moyamoya syndrome associated with Graves' disease. The CBN sign was observed bilaterally. Cerebral revascularization surgery was performed, including left-sided superficial temporal artery to middle cerebral artery anastomosis. During four years of follow-up, she maintained a euthyroid state and did not have any further cerebral ischemic events. The CBN signs remained unchanged on both sides during this time. This is the first report of the CBN sign in a patient with Moyamoya syndrome associated with Graves' disease.
基金funded by the National Natural Science Foundation of China(No.81601583)the Scientific and Technological Project(No.2018020424)Aboard Research Project(2016054) of Henan Provincial Health Commission.
文摘Objective:The objective of this study was to evaluate the feasibility and outcomes of transvenous endovascular embolization(TVE) for superficial intracranial arteriovenous malformations(AVMs).Methods:After collecting clinical and imaging data,a prospective series of 11 patients presenting with superficial AVMs were treated by endovascular embolization using a transvenous approach between November 2016 and October 2018.Results:Ten patients(90.9%) had ruptured AVMs before TVE.The mean nidus size was 3.27 ± 1.47 cm,and the median Spetzler-Martin grade was II.The rate of immediate angiographic occlusion of the AVMs was 90.9%(10/11).One patient was treated with transarterial embolization since TVE was not achieved due to an unsuccessful positioning of the microcatheter.Two patients(cases 8 and 11) suffered a intracranial hemorrhage and a cerebral infarction with encephaledema,respectively,but no procedure-related mortalities were observed.Eight patients(72.7%) were independent with a modified Rankin Score(mRS) 2 at discharge and the m RSs of all patients,which were collected 30 days postintervention,were not more than 2.The mean follow-up period was 17 months.There were no nidus recurrences during the follow-up period.Conclusions:The curative transvenous embolization of superficial AVMs seems feasible and effective while carefully monitoring for embolization-related complications.
基金supported by the National Natural Science Foundation of China(82071331,81870942,and 81520108011)the National Key Research and Development Program of China(2018YFC1312200)the Canadian Institutes of Health Research(VWY).
文摘Injury to the brain after intracerebral hemorrhage(ICH)results from numerous complex cellular mechanisms.At present,effective therapy for ICH is limited and a better understanding of the mechanisms of brain injury is necessary to improve prognosis.There is increasing evidence that ion channel dysregulation occurs at multiple stages in primary and secondary brain injury following ICH.Ion channels such as TWIK-related K+channel 1,sulfonylurea 1 transient receptor potential melastatin 4 and glutamate-gated channels affect ion homeostasis in ICH.They in turn participate in the formation of brain edema,disruption of the blood-brain barrier,and the generation of neurotoxicity.In this review,we summarize the interaction between ions and ion channels,the effects of ion channel dysregulation,and we discuss some therapeutics based on ion-channel modulation following ICH.
基金Medical Research Future Fund,Australia(APP1152282).
文摘Rationale Haematoma growth is common early after intracerebral haemorrhage(ICH),and is a key determinant of outcome.Tranexamic acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce haematoma growth.Methods and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units(STOP-MSU)is a phase Ⅱ double-blind,randomised,placebo-controlled,multicentre,international investigator-led clinical trial,conducted within the estimand statistical framework.Hypothesis In patients with spontaneous ICH,treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimates A sample size of 180 patients(90 in each arm)would be required to detect an absolute difference in the primary outcome of 20%(placebo 39%vs treatment 19%)under a two-tailed significance level of 0.05.An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.Intervention Participants will receive 1 g intravenous tranexamic acid over 10 min,followed by 1 g intravenous tranexamic acid over 8 hours;or matching placebo.Primary efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours,defined as either≥33%relative increase or≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.Discussion We describe the rationale and protocol of STOP-MSU,a phase Ⅱ trial of tranexamic acid in patients with ICH within 2 hours from onset,based in participating mobile stroke units and emergency departments.
基金supported by the National Natural Science Foundation of China(Grant Nos.81371559,81671709,81601550,81871371,81701711,and 82072056)Guangzhou Municipal Science and Technology Project(No.201804010106,China)National College Students Innovation and Entrepreneurship Training Program(No.201812121007,China)。
文摘Ferroptosis,as a newly discovered cell death form,has become an attractive target for precision cancer therapy.Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione(GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4(GPX4).However,the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported.Herein,novel tumor microenvironments(TME)-activated metal-organic frameworks involving Fe&Cu ions bridged by disulfide bonds with PEGylation(FCSP MOFs)were developed,which would be degraded specifically under the redox TME,simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS via Fenton reaction,therefore causing ferroptosis.More ROS could be generated by the acceleration of Fenton reaction due to the released Cu ions and the intrinsic photothermal capability of FCSP MOFs.The overexpressed GSH and H2O2 in TME could ensure the specific TME self-activated therapy.Better tumor therapeutic efficiency could be achieved by doxorubicin(DOX)loading since it can not only cause apoptosis,but also indirectly produce H2O2 to amplify Fenton reaction.Remarkable anti-tumor effect of obtained FCSP@DOX MOFs was verified via both in vitro and in vivo assays.
基金The authors acknowledge operating grant support from the National Natural Science Foundation of China(grants no:81870942,81471174 and 81520108011)National Key Research and Development ProgramProgramme of China(grant no:2018YFC1312200)+1 种基金Innovation Scientists and Technicians Troop Constructions Projects of Henan Province of China(for MX)and from the Canadian Institutes of Health Sciences(VWY).
文摘Spontaneous intracerebral haemorrhage(ICH)is a devastating type of stroke with high mortality and morbidity and for which no effective treatments are available to date.Much experimental and clinical research have been performed to explore its mechanisms regard the subsequent inflammatory cascade and to seek the potential therapeutic strategies.The aim of this review is to discuss insights from clinical settings that have led to the development of numerous animal models of ICH.Some of the current and future challenges for clinicians to understand ICH are also surveyed.
