AIM： To explore the influence of portal vein hemodynamic changes after portal venous arterialization （PVA） on peribiliary vascular plexus （PVP） morphological structure and hepatic pathology, and to establish a th...AIM： To explore the influence of portal vein hemodynamic changes after portal venous arterialization （PVA） on peribiliary vascular plexus （PVP） morphological structure and hepatic pathology, and to establish a theoretical basis for the clinical application of PVA. METHODS： Sprague-Dawley rats were randomly divided into control and PVA groups. After PVA, hemodynamic changes of the portal vein and morphological structure of hepatohilar PVP were observed using Doppler ultrasound, liver function tests, ink perfusion transparency management and three-dimensional reconstruction of computer microvisualization, and pathological examination was performed on tissue from the bile duct wall and the liver. RESULTS： After PVA, the cross-sectional area and blood flow of the portal vein were increased, and the increase became more significant over time, in a certain range. If the measure to limit the flow in PVA was not adopted, the high blood flow would lead to dilatation of intrahepatic portal vein and its branches, increase in collagen and fiber degeneration in tunica intima. Except glutamic pyruvic transaminase （GPT）, other liver function tests were normal. CONCLUSION： Blood with a certain flow and oxygen content is important for filling the PVP and meeting the oxygen requirement of the bile duct wall. After PVA, It is the anatomic basis to maintain normal morphology of hepatohilar bile duct wall that the blood with high oxygen content and high flow in arterialized portal vein may fill PVP by collateral vessel reflux. A adequate measure to limit blood flow is necessary in PVA.展开更多
BACKGROUND:Liver revascularization is frequently required during the enlarged radical operation for hilar cholangio carcinoma involving the hepatic artery.Researchers have carried out a number of experiments applying ...BACKGROUND:Liver revascularization is frequently required during the enlarged radical operation for hilar cholangio carcinoma involving the hepatic artery.Researchers have carried out a number of experiments applying partial porta vein arterialization(PVA)in clinical practice.In this study we aimed to establish a theoretical basis for clinical application o partial PVA and to investigate the effects of partial PVA on ra hilar bile duct and hepatic functions.METHODS:Thirty rats were randomly and equally assigned into 3 groups:control(group A),hepatic artery ligation+bile duct recanalization(group B),and partial PVA+bile duc recanalization(group C).Proliferation and apoptosis o rat hilar bile duct epithelial cells,arteriolar counts of the peribiliary plexus(PBP)of the bile duct wall,changes in serum biochemistry,and pathologic changes in the bile duc were assessed 1 month after operation.RESULTS:The proliferation of hilar bile duct epithelial cells in group B was greater than in groups A and C(P<0.01).No apoptotic hilar bile duct epithelial cells were detected in any of the groups.The PBP arteriolar counts of the hilar bile duc wall were similar in groups A and C(P>0.05),but the coun was lower in group B than in group A(P<0.01).No statistically significant differences in alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and albumin were found in the 3 groups.The gamma-glutamyltransferase value was higher in group B than in groups A and C(P<0.01)The hepatic tissues of groups A and C showed no significan abnormality.Chronic inflammatory changes in the hilar bile duct walls were observed only in group B.CONCLUSION:Partial PVA can restore the arterial blood supply of the hilar bile duct and significantly extenuate the injury to hilar bile duct epithelial cells resulting from hepatic artery ligation.展开更多
In the current study, we sought to establish a novel rat model of portal vein artefialization （PVA） and evaluate its impact on liver regeneration after extended partial hepatectomy （PH）. A total of 105 Sprague-Daw...In the current study, we sought to establish a novel rat model of portal vein artefialization （PVA） and evaluate its impact on liver regeneration after extended partial hepatectomy （PH）. A total of 105 Sprague-Dawley rats were randomly assigned to three groups： 68% hepatectomy （the PH group）, portal arterialization after 68% hepatectomy （the PVA group）, and fight nephrectomy only （the control group）. Liver regeneration rate （LRR）, 5-bromo-2-deoxyuridine （BrdU） labeling index, and liver functions were assessed on postoperative day 2, 7, 14 and 28. The 28-day survival rates were compared among the three groups. The 28-day survival rates were similar in all groups （P = 0.331）, and the anastomotic patency was 100%. The LRR in the PVA group was significantly higher than that of the PH group within postoperative 14 days （P 〈 0.05）. The PVA and PH group had increased serum alanine aminotransferase levels （232 ±61 U/L and 212 ±53 U/L, respectively） compared with the control group （101 ±13 U/L） on postoperative day 2, whereas from postoperative day 7 to day 28 there were no differences among the three groups. Serum albumin values were higher after the PVA procedure within postoperative day 14, which gradually became comparable on postoperative day 28 among the three groups. The peaks of BrdU labeling index appeared on postoperative day 2 in all rats, and the PVA procedure was associated with increased BrdU labeling index from postoperative day 7 to 28. The 28-day survival of the PVA rats was comparable. Our findings demonstrate that the PVA procedure utilizing portal vein trunk-renal artery microvascular reconstruction promotes remnant liver regeneration and confers beneficial effects on maintaining and even optimizing liver function after extended partial hepatectomy in rats.展开更多
Liver transplantations were performed on two patients with hepatic failure caused by liver cirrhosis.Hard obsolete thrombi and portal venous sclerosis were observed in the major portal veins of both patients.The arter...Liver transplantations were performed on two patients with hepatic failure caused by liver cirrhosis.Hard obsolete thrombi and portal venous sclerosis were observed in the major portal veins of both patients.The arteria colica media of one recipient and the portal vein of the donor were anastomosed end-to-end.The hepatic artery of the first donor was anastomosed end-to end with the gastroduodenal artery of the first recipient;meanwhile,the portal vein of the second donor was simultaneously anastomosed end-to-end with the common hepatic artery of the second recipient.The blood flow of the portal vein,the perfusion of the donor liver and liver function were satisfactory after surgery.Portal vein arterialization might be an effective treatment for patients whose portal vein reconstruction was difficult.展开更多
To the Editor:Establishing dual arterial and portal inflow is essential for liver transplantation[1].Inadequate portal inflow compromises graft function and graft survival[2].Portal hypoperfusion is usually a conseque...To the Editor:Establishing dual arterial and portal inflow is essential for liver transplantation[1].Inadequate portal inflow compromises graft function and graft survival[2].Portal hypoperfusion is usually a consequence of spontaneous portosystemic shunt,ligation of which展开更多
BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for co...BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis(PVT).The effect of PVA on portal perfusion and primary graft dysfunction(PGD)has not been assessed.All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed.To account for the time-sensitive effects of graft perfusion,patients were classified into two groups:prereperfusion(pre-PVA),if the arterioportal anastomosis was performed before graft revascularization,and postreperfusion(post-PVA),if PVA was performed afterward.The pre-PVA rationale contemplated poor portal hemodynamics,severe vascular steal,or PVT.Post-PVA was considered if graft hypoperfusion became evident.Conservative interventions were attempted before PVA.展开更多
Background Hilar cholangiocarcinoma is a malignant tumor that is difficult to cure. The aim of this study was to observe the effects of flow-controlled partial portal vein arterializations （PPVA） on liver regenerati...Background Hilar cholangiocarcinoma is a malignant tumor that is difficult to cure. The aim of this study was to observe the effects of flow-controlled partial portal vein arterializations （PPVA） on liver regeneration after hepatectomy in minipigs with chronic obstructive jaundice. Methods Eight minipigs were made into chronic obstructive jaundice models. United semi-hepatectomy, which imitates extended radical surgery for treatment of hilar cholangiocarcinoma, was then performed. The eight minipigs were randomly divided into groups A and B （n=4 minipigs each）. PPVA was performed in Group A but not in Group B. The effects of flow-controlled PPVA on live regeneration after hepatectomy were observed for 30 days after hepatectomy. Results The portal vein PO2 at the immediate time point and on postoperative day 30 was higher in Group A （（47.33±2.43） and （48.50±4.44） mmHg） than in Group B （（35.38±4.06） and （35.55±2.55） mmHg respectively, all P 〈0.01）. The mitotic index of liver cells on postoperative days 14 and 21 was higher in Group A （12.55%±2.85% and 15.25%±1.99% respectively） than in Group B （6.85%±2.10% and 11.88%±1.15% respectively, all P 〈0.05）. The regeneration rate of residual liver on postoperative days 14 and 21 was higher in Group A （24.56%±6.15% and 70.63%±9.83% respectively） than in Group B （11.96%±5.43% and 44.92%±7.42% respectively, P 〈0.05 and P 〈0.01 respectively）.Conclusion Flow-controlled PPVA can promote liver regeneration after hepatectomy and prevent liver failure in minipigs with chronic obstructive jaundice.展开更多
Background A fatal complication after liver transplantation is anastomotic embolization of the hepatic artery. In order to solve this problem, the portal venous arterialization （PVA） is used to reconstruct the hepat...Background A fatal complication after liver transplantation is anastomotic embolization of the hepatic artery. In order to solve this problem, the portal venous arterialization （PVA） is used to reconstruct the hepatic arterial blood flow. The purpose of this study was to investigate the influence of PVA on rats with acute occlusion of hepatic artery. Methods Rat PVA models were established and then randomly divided into Group 1 （control group）, Group 2 （jaundice group）, Group 3 （bile duct recanalization group）, and Group 4 （portal vein arterilization group）. Recanalization of the common bile duct and PVA were performed 5 days after bile duct ligation in the rats. The influence of the PVA on general conditions, hepatic changes of structure and function, portal vein pressure and hepatic micrangium were observed for one month. Results Five days after common bile duct ligation the serum bilirubin, transaminase and alkaline phosphatase levels were significantly increased. Compared with group 1, there was a statistically significant difference （P 〈0.01）. These rats then underwent bile duct recanalization and PVA. After a month, the liver functions and microscopic structures completely returned to normal and, compared with group 1, there was no statistically significant difference in portal vein pressure （P 〉0.05）. Vascular casting samples showed that hepatic sinusoids were slightly thicker and more filled than normal ones and although they had some deformations, the hepatic sinusoids were still distributed around the central vein in radial form. Conclusion Within a month after operation, bile duct recanalization and PVA do not show obvious adverse effects on liver hemodynamics and hepatic micrangium, and the liver function and microscopic structure can return to normal.展开更多
Background Off-pump coronary artery bypass surgery （OPCAB） has been widely applied in recent years as a less invasive method of myocardial revascularization. This study evaluated the sequential bilateral internal ma...Background Off-pump coronary artery bypass surgery （OPCAB） has been widely applied in recent years as a less invasive method of myocardial revascularization. This study evaluated the sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system during OPCAB.Methods From April 2004 to August 2010, patients with diffuse right coronary lesions were studied retrospectively and divided into two groups. Group 1 included seventeen patients who underwent this surgery while group 2 included twenty-one patients without right coronary artery surgical therapy. All patients presented with symptoms of angina. Blood flow of bridged vessels was measured. The perioperative ventricular parameters including left ventricular ejection fraction and end diastolic diameter were compared. During follow-up, myocardial nuclide imaging and coronary angiography were carried out.Results Off-pump coronary artery bypass was performed with an average of 3.6 grafts per patient. Hospital mortality was zero. At the time of follow-up, the patients in group 1 recovered better than in group 2 （P〈0.05）. In both groups, the mean New York Heart Association （NYHA） class and ejection fraction increased significantly （P〈0.001） and the mean left ventricular end-diastolic diameter decreased significantly （P 〈0.05）. Myocardial blood supply of inferior wall in group 1 was obviously improved by myocardial nuclide imaging. Coronary angiography for eight patients in group 1 verified that there was blood flow to myocardium in the arterialized vein.Conclusions Sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system can be performed during OPCAB. A postoperative improvement in the cardiac functions and the quality of life was documented, increasing our expectation for extensive application.展开更多
Currently coronary artery bypass grafting （CABG） is the most commonly used procedure for revascularization of coronary heart disease. However it may not be suitable for the patients with diffuse coronary artery dise...Currently coronary artery bypass grafting （CABG） is the most commonly used procedure for revascularization of coronary heart disease. However it may not be suitable for the patients with diffuse coronary artery diseases. Under this circumstance, retrograde perfusion via cardiac venous system, namely retrograde coronary venous bypass graft （CVBG）,展开更多
平均动脉压(mean arterial pressure,MAP)和脉压是反映脑灌注的两项指标,其在急性缺血性脑卒中后能否指导降压治疗策略的选择尚不明确。本研究基于中国急性缺血性脑卒中降压试验(the China antihypertensive trial in acute ischemic st...平均动脉压(mean arterial pressure,MAP)和脉压是反映脑灌注的两项指标,其在急性缺血性脑卒中后能否指导降压治疗策略的选择尚不明确。本研究基于中国急性缺血性脑卒中降压试验(the China antihypertensive trial in acute ischemic stroke,CATIS),根据MAP和脉压水平进行分层,探讨早期降压干预对缺血性脑卒中后不良临床结局的影响。方法:该试验将4 071例收缩压升高的急性缺血性脑卒中患者随机分配至降压治疗组(目标是在随机化后24h内收缩压降低10%~25%,7 d内血压将至<140/90 mm Hg,并在住院期间维持该水平,1 mm Hg=0.133 k Pa)或住院期间停止降压治疗的对照组。展开更多
Background There is still limited data on predictive value of coronary computed tomography angiography(CCTA)–derived fractional flow reserve(CT-FFR) for long term outcomes. We examined the long-term prognostic value ...Background There is still limited data on predictive value of coronary computed tomography angiography(CCTA)–derived fractional flow reserve(CT-FFR) for long term outcomes. We examined the long-term prognostic value of CT-FFR combined with CCTA–defined atherosclerotic extent in diabetic patients with coronary artery disease(CAD).Methods A retrospective pooled analysis of individual patient data was performed. Deep-learning-based vessel-specific CTFFR was calculated. All patients enrolled were followed-up for at least 5 years. Predictive abilities for major adverse cardiac events(MACE) were compared among three models(model 1), constructed using clinical variables;model 2, model 1+CCTA–derived atherosclerotic extent(Leiden risk score);and model 3, model 2+CT-FFR.Results A total of 480 diabetic patients [median age, 61(55–66) years;52.9% men] were included. During a median follow-up time of 2197(2126–2355) days, 55 patients(11.5%) experienced MACE. In multivariate-adjusted Cox models, Leiden risk score(HR: 1.06;95% CI: 1.01–1.11;P = 0.013) and CT-FFR ≤ 0.80(HR: 6.54;95% CI: 3.18–13.45;P < 0.001) were the independent predictors. The discriminant ability was higher in model 2 than in model 1(C-index, 0.75 vs. 0.63;P < 0.001) and was further promoted by adding CT-FFR to model 3(C-index, 0.81 vs. 0.75;P = 0.002). Net reclassification improvement(NRI) was 0.19(P = 0.009) for model 2 beyond model 1. Of note, adding CT-FFR to model 3 also exhibited significantly improved reclassification compared with model 2(NRI = 0.14;P = 0.011).Conclusion In diabetic patients with CAD, CT-FFR provides robust and incremental prognostic information for predicting longterm outcomes. The combined model exhibits improved prediction abilities, which is beneficial for risk stratification.展开更多
Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms...Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.展开更多
Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.Ho...Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.How trisomy 21 causes lung diseases remains poorly understood.In this study,we use the Dp16 mouse model,which contains a segmental chromosomal duplication of the entire Hsa21 syntenic region on mouse chromosome 16,to explore the gene dosage effects on DS-related lung diseases.The Dp16 mice present impaired alveolar development and inflammatory-like pathological changes.Single-cell RNA sequencing(scRNA-seq)analysis highlights increased APP-related interactions among male Dp16 lung cells.Specifically,altered antigen processing and presentation with increased MHC-II signaling are found in Dp16 immune cells.Reduced angiogenesis and altered inflammatory responses of Dp16 endothelial cells are also suggested.Moreover,scRNA-seq indicates hyperplasia of Dp16 vascular smooth muscle cells,which is validated by tissue immunofluorescence assessment.Transthoracic echocardiography further shows the existence of pulmonary hypertension in young Dp16 mice.Independent scRNA-seq analysis of the female lung cells recapitulates the majority of key findings identified in male mice,confirming the reproducibility of the results.Collectively,our results provide important clues for the further development of therapeutic approaches for DS-related lung diseases.展开更多
Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms o...Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.展开更多
Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a ...Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a major type of liver cancer worldwide.In advanced stages,portal vein tumor thrombosis(PVTT)and jaundice are common,whereas obstructive jaundice(OJ)is relatively rare.Both co...BACKGROUND Hepatocellular carcinoma(HCC)is a major type of liver cancer worldwide.In advanced stages,portal vein tumor thrombosis(PVTT)and jaundice are common,whereas obstructive jaundice(OJ)is relatively rare.Both conditions markedly reduce survival and increase therapeutic complexity.Recently,hepatic artery infusion chemotherapy(HAIC)in combination with targeted immunotherapy has shown promise for advanced HCC.CASE SUMMARY We report a 47-year-old male with advanced HCC complicated by PVTT and OJ,who was admitted with marked jaundice of the skin and sclera.Imaging revealed a large hepatic mass(14.5 cm×11.3 cm)in the right lobe with associated portal vein tumor thrombus.The tertiary bile duct was only mildly dilated,making percutaneous transhepatic cholangiography drainage infeasible.The patient underwent reduced-dose HAIC,which resulted in significant tumor shrinkage and marked reduction in serum bilirubin.This improvement enabled sequential treatment with lenvatinib and camrelizumab.After six cycles,both liver function and alphafetoprotein levels improved.The patient achieved a progression-free survival of 20 months and an overall survival of 29 months.CONCLUSION HAIC can treat high-bilirubin HCC with PVTT and OJ,allowing for subsequent targeted immunotherapy.展开更多
White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet li...White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.展开更多
Background In patients with coronary artery disease,age is of known significance in predicting outcomes.Data on clinical outcomes in patients≥85 years undergoing percutaneous coronary intervention(PCI)remain scarce.T...Background In patients with coronary artery disease,age is of known significance in predicting outcomes.Data on clinical outcomes in patients≥85 years undergoing percutaneous coronary intervention(PCI)remain scarce.The study aim was to determine clinical characteristics,risk of adverse cardiovascular events,and mortality in patients aged≥85 years compared to those aged<85 undergoing PCI.Methods In this retrospective study,data were obtained from the nationwide Netherlands Heart Registration on patients undergoing PCI between January 1st,2017 and January 1st,2021.The primary endpoint was all-cause mortality at long-term followup.Results A total of 155,683 patients underwent PCI,of which 100,209(64.4%)acute coronary syndrome cases.Compared to patients aged<85 years,patients aged≥85 were more often female and showed a higher number of cardiovascular comorbidities,including impaired left ventricle ejection fraction and reduced kidney function.Mortality at short-term and long-term follow-up were significantly higher in those aged≥85(P<0.001).Patients aged≥85 were more likely to have a myocardial infarction within 30 days following the index intervention(0.9%vs.0.7%;P=0.024),though they less often underwent revascularization at longterm follow-up compared to patients aged<85(P<0.001).Conclusions The elderly(≥85 years)patient requiring PCI carries an extensive cardiovascular risk profile,translating in significant risk of recurrent cardiovascular events and increased mortality rate.Clinicians should carefully weigh perceived risks and potential benefits in the individual patient,considering the patients’age,cardiovascular risk profile,and associated risk of morbidity and mortality.展开更多
BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such a...BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.展开更多
基金Supported by Science and Technology Plan of Xiamen City,No.3502Z20064005Health Bureau of Xiamen City,No.WSk0521
文摘AIM： To explore the influence of portal vein hemodynamic changes after portal venous arterialization （PVA） on peribiliary vascular plexus （PVP） morphological structure and hepatic pathology, and to establish a theoretical basis for the clinical application of PVA. METHODS： Sprague-Dawley rats were randomly divided into control and PVA groups. After PVA, hemodynamic changes of the portal vein and morphological structure of hepatohilar PVP were observed using Doppler ultrasound, liver function tests, ink perfusion transparency management and three-dimensional reconstruction of computer microvisualization, and pathological examination was performed on tissue from the bile duct wall and the liver. RESULTS： After PVA, the cross-sectional area and blood flow of the portal vein were increased, and the increase became more significant over time, in a certain range. If the measure to limit the flow in PVA was not adopted, the high blood flow would lead to dilatation of intrahepatic portal vein and its branches, increase in collagen and fiber degeneration in tunica intima. Except glutamic pyruvic transaminase （GPT）, other liver function tests were normal. CONCLUSION： Blood with a certain flow and oxygen content is important for filling the PVP and meeting the oxygen requirement of the bile duct wall. After PVA, It is the anatomic basis to maintain normal morphology of hepatohilar bile duct wall that the blood with high oxygen content and high flow in arterialized portal vein may fill PVP by collateral vessel reflux. A adequate measure to limit blood flow is necessary in PVA.
文摘BACKGROUND:Liver revascularization is frequently required during the enlarged radical operation for hilar cholangio carcinoma involving the hepatic artery.Researchers have carried out a number of experiments applying partial porta vein arterialization(PVA)in clinical practice.In this study we aimed to establish a theoretical basis for clinical application o partial PVA and to investigate the effects of partial PVA on ra hilar bile duct and hepatic functions.METHODS:Thirty rats were randomly and equally assigned into 3 groups:control(group A),hepatic artery ligation+bile duct recanalization(group B),and partial PVA+bile duc recanalization(group C).Proliferation and apoptosis o rat hilar bile duct epithelial cells,arteriolar counts of the peribiliary plexus(PBP)of the bile duct wall,changes in serum biochemistry,and pathologic changes in the bile duc were assessed 1 month after operation.RESULTS:The proliferation of hilar bile duct epithelial cells in group B was greater than in groups A and C(P<0.01).No apoptotic hilar bile duct epithelial cells were detected in any of the groups.The PBP arteriolar counts of the hilar bile duc wall were similar in groups A and C(P>0.05),but the coun was lower in group B than in group A(P<0.01).No statistically significant differences in alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and albumin were found in the 3 groups.The gamma-glutamyltransferase value was higher in group B than in groups A and C(P<0.01)The hepatic tissues of groups A and C showed no significan abnormality.Chronic inflammatory changes in the hilar bile duct walls were observed only in group B.CONCLUSION:Partial PVA can restore the arterial blood supply of the hilar bile duct and significantly extenuate the injury to hilar bile duct epithelial cells resulting from hepatic artery ligation.
文摘In the current study, we sought to establish a novel rat model of portal vein artefialization （PVA） and evaluate its impact on liver regeneration after extended partial hepatectomy （PH）. A total of 105 Sprague-Dawley rats were randomly assigned to three groups： 68% hepatectomy （the PH group）, portal arterialization after 68% hepatectomy （the PVA group）, and fight nephrectomy only （the control group）. Liver regeneration rate （LRR）, 5-bromo-2-deoxyuridine （BrdU） labeling index, and liver functions were assessed on postoperative day 2, 7, 14 and 28. The 28-day survival rates were compared among the three groups. The 28-day survival rates were similar in all groups （P = 0.331）, and the anastomotic patency was 100%. The LRR in the PVA group was significantly higher than that of the PH group within postoperative 14 days （P 〈 0.05）. The PVA and PH group had increased serum alanine aminotransferase levels （232 ±61 U/L and 212 ±53 U/L, respectively） compared with the control group （101 ±13 U/L） on postoperative day 2, whereas from postoperative day 7 to day 28 there were no differences among the three groups. Serum albumin values were higher after the PVA procedure within postoperative day 14, which gradually became comparable on postoperative day 28 among the three groups. The peaks of BrdU labeling index appeared on postoperative day 2 in all rats, and the PVA procedure was associated with increased BrdU labeling index from postoperative day 7 to 28. The 28-day survival of the PVA rats was comparable. Our findings demonstrate that the PVA procedure utilizing portal vein trunk-renal artery microvascular reconstruction promotes remnant liver regeneration and confers beneficial effects on maintaining and even optimizing liver function after extended partial hepatectomy in rats.
基金Supported by Natural Science Foundation of Fujian Province,China,No.2011Y0046
文摘Liver transplantations were performed on two patients with hepatic failure caused by liver cirrhosis.Hard obsolete thrombi and portal venous sclerosis were observed in the major portal veins of both patients.The arteria colica media of one recipient and the portal vein of the donor were anastomosed end-to-end.The hepatic artery of the first donor was anastomosed end-to end with the gastroduodenal artery of the first recipient;meanwhile,the portal vein of the second donor was simultaneously anastomosed end-to-end with the common hepatic artery of the second recipient.The blood flow of the portal vein,the perfusion of the donor liver and liver function were satisfactory after surgery.Portal vein arterialization might be an effective treatment for patients whose portal vein reconstruction was difficult.
文摘To the Editor:Establishing dual arterial and portal inflow is essential for liver transplantation[1].Inadequate portal inflow compromises graft function and graft survival[2].Portal hypoperfusion is usually a consequence of spontaneous portosystemic shunt,ligation of which
文摘BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis(PVT).The effect of PVA on portal perfusion and primary graft dysfunction(PGD)has not been assessed.All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed.To account for the time-sensitive effects of graft perfusion,patients were classified into two groups:prereperfusion(pre-PVA),if the arterioportal anastomosis was performed before graft revascularization,and postreperfusion(post-PVA),if PVA was performed afterward.The pre-PVA rationale contemplated poor portal hemodynamics,severe vascular steal,or PVT.Post-PVA was considered if graft hypoperfusion became evident.Conservative interventions were attempted before PVA.
基金This research was supported by the National Natural Science Foundation of China （No. 81072014）.
文摘Background Hilar cholangiocarcinoma is a malignant tumor that is difficult to cure. The aim of this study was to observe the effects of flow-controlled partial portal vein arterializations （PPVA） on liver regeneration after hepatectomy in minipigs with chronic obstructive jaundice. Methods Eight minipigs were made into chronic obstructive jaundice models. United semi-hepatectomy, which imitates extended radical surgery for treatment of hilar cholangiocarcinoma, was then performed. The eight minipigs were randomly divided into groups A and B （n=4 minipigs each）. PPVA was performed in Group A but not in Group B. The effects of flow-controlled PPVA on live regeneration after hepatectomy were observed for 30 days after hepatectomy. Results The portal vein PO2 at the immediate time point and on postoperative day 30 was higher in Group A （（47.33±2.43） and （48.50±4.44） mmHg） than in Group B （（35.38±4.06） and （35.55±2.55） mmHg respectively, all P 〈0.01）. The mitotic index of liver cells on postoperative days 14 and 21 was higher in Group A （12.55%±2.85% and 15.25%±1.99% respectively） than in Group B （6.85%±2.10% and 11.88%±1.15% respectively, all P 〈0.05）. The regeneration rate of residual liver on postoperative days 14 and 21 was higher in Group A （24.56%±6.15% and 70.63%±9.83% respectively） than in Group B （11.96%±5.43% and 44.92%±7.42% respectively, P 〈0.05 and P 〈0.01 respectively）.Conclusion Flow-controlled PPVA can promote liver regeneration after hepatectomy and prevent liver failure in minipigs with chronic obstructive jaundice.
文摘Background A fatal complication after liver transplantation is anastomotic embolization of the hepatic artery. In order to solve this problem, the portal venous arterialization （PVA） is used to reconstruct the hepatic arterial blood flow. The purpose of this study was to investigate the influence of PVA on rats with acute occlusion of hepatic artery. Methods Rat PVA models were established and then randomly divided into Group 1 （control group）, Group 2 （jaundice group）, Group 3 （bile duct recanalization group）, and Group 4 （portal vein arterilization group）. Recanalization of the common bile duct and PVA were performed 5 days after bile duct ligation in the rats. The influence of the PVA on general conditions, hepatic changes of structure and function, portal vein pressure and hepatic micrangium were observed for one month. Results Five days after common bile duct ligation the serum bilirubin, transaminase and alkaline phosphatase levels were significantly increased. Compared with group 1, there was a statistically significant difference （P 〈0.01）. These rats then underwent bile duct recanalization and PVA. After a month, the liver functions and microscopic structures completely returned to normal and, compared with group 1, there was no statistically significant difference in portal vein pressure （P 〉0.05）. Vascular casting samples showed that hepatic sinusoids were slightly thicker and more filled than normal ones and although they had some deformations, the hepatic sinusoids were still distributed around the central vein in radial form. Conclusion Within a month after operation, bile duct recanalization and PVA do not show obvious adverse effects on liver hemodynamics and hepatic micrangium, and the liver function and microscopic structure can return to normal.
文摘Background Off-pump coronary artery bypass surgery （OPCAB） has been widely applied in recent years as a less invasive method of myocardial revascularization. This study evaluated the sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system during OPCAB.Methods From April 2004 to August 2010, patients with diffuse right coronary lesions were studied retrospectively and divided into two groups. Group 1 included seventeen patients who underwent this surgery while group 2 included twenty-one patients without right coronary artery surgical therapy. All patients presented with symptoms of angina. Blood flow of bridged vessels was measured. The perioperative ventricular parameters including left ventricular ejection fraction and end diastolic diameter were compared. During follow-up, myocardial nuclide imaging and coronary angiography were carried out.Results Off-pump coronary artery bypass was performed with an average of 3.6 grafts per patient. Hospital mortality was zero. At the time of follow-up, the patients in group 1 recovered better than in group 2 （P〈0.05）. In both groups, the mean New York Heart Association （NYHA） class and ejection fraction increased significantly （P〈0.001） and the mean left ventricular end-diastolic diameter decreased significantly （P 〈0.05）. Myocardial blood supply of inferior wall in group 1 was obviously improved by myocardial nuclide imaging. Coronary angiography for eight patients in group 1 verified that there was blood flow to myocardium in the arterialized vein.Conclusions Sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system can be performed during OPCAB. A postoperative improvement in the cardiac functions and the quality of life was documented, increasing our expectation for extensive application.
文摘Currently coronary artery bypass grafting （CABG） is the most commonly used procedure for revascularization of coronary heart disease. However it may not be suitable for the patients with diffuse coronary artery diseases. Under this circumstance, retrograde perfusion via cardiac venous system, namely retrograde coronary venous bypass graft （CVBG）,
文摘平均动脉压(mean arterial pressure,MAP)和脉压是反映脑灌注的两项指标,其在急性缺血性脑卒中后能否指导降压治疗策略的选择尚不明确。本研究基于中国急性缺血性脑卒中降压试验(the China antihypertensive trial in acute ischemic stroke,CATIS),根据MAP和脉压水平进行分层,探讨早期降压干预对缺血性脑卒中后不良临床结局的影响。方法:该试验将4 071例收缩压升高的急性缺血性脑卒中患者随机分配至降压治疗组(目标是在随机化后24h内收缩压降低10%~25%,7 d内血压将至<140/90 mm Hg,并在住院期间维持该水平,1 mm Hg=0.133 k Pa)或住院期间停止降压治疗的对照组。
文摘Background There is still limited data on predictive value of coronary computed tomography angiography(CCTA)–derived fractional flow reserve(CT-FFR) for long term outcomes. We examined the long-term prognostic value of CT-FFR combined with CCTA–defined atherosclerotic extent in diabetic patients with coronary artery disease(CAD).Methods A retrospective pooled analysis of individual patient data was performed. Deep-learning-based vessel-specific CTFFR was calculated. All patients enrolled were followed-up for at least 5 years. Predictive abilities for major adverse cardiac events(MACE) were compared among three models(model 1), constructed using clinical variables;model 2, model 1+CCTA–derived atherosclerotic extent(Leiden risk score);and model 3, model 2+CT-FFR.Results A total of 480 diabetic patients [median age, 61(55–66) years;52.9% men] were included. During a median follow-up time of 2197(2126–2355) days, 55 patients(11.5%) experienced MACE. In multivariate-adjusted Cox models, Leiden risk score(HR: 1.06;95% CI: 1.01–1.11;P = 0.013) and CT-FFR ≤ 0.80(HR: 6.54;95% CI: 3.18–13.45;P < 0.001) were the independent predictors. The discriminant ability was higher in model 2 than in model 1(C-index, 0.75 vs. 0.63;P < 0.001) and was further promoted by adding CT-FFR to model 3(C-index, 0.81 vs. 0.75;P = 0.002). Net reclassification improvement(NRI) was 0.19(P = 0.009) for model 2 beyond model 1. Of note, adding CT-FFR to model 3 also exhibited significantly improved reclassification compared with model 2(NRI = 0.14;P = 0.011).Conclusion In diabetic patients with CAD, CT-FFR provides robust and incremental prognostic information for predicting longterm outcomes. The combined model exhibits improved prediction abilities, which is beneficial for risk stratification.
文摘Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.
基金supported by the Fundamental Research Funds for the Central Universities(226-2022-00035)the National Natural Science Foundation of China(81600986).
文摘Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.How trisomy 21 causes lung diseases remains poorly understood.In this study,we use the Dp16 mouse model,which contains a segmental chromosomal duplication of the entire Hsa21 syntenic region on mouse chromosome 16,to explore the gene dosage effects on DS-related lung diseases.The Dp16 mice present impaired alveolar development and inflammatory-like pathological changes.Single-cell RNA sequencing(scRNA-seq)analysis highlights increased APP-related interactions among male Dp16 lung cells.Specifically,altered antigen processing and presentation with increased MHC-II signaling are found in Dp16 immune cells.Reduced angiogenesis and altered inflammatory responses of Dp16 endothelial cells are also suggested.Moreover,scRNA-seq indicates hyperplasia of Dp16 vascular smooth muscle cells,which is validated by tissue immunofluorescence assessment.Transthoracic echocardiography further shows the existence of pulmonary hypertension in young Dp16 mice.Independent scRNA-seq analysis of the female lung cells recapitulates the majority of key findings identified in male mice,confirming the reproducibility of the results.Collectively,our results provide important clues for the further development of therapeutic approaches for DS-related lung diseases.
基金supported by the National Key R&D Program of China,Nos.2021YFA1101703/2021YFA1101700(to YD).
文摘Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.
基金supported by the Chinese Medicine"Dual Chain Integration"Young and Middle-aged Scientific Research and Innovation Teams(No.2022-SLRH-YQ-006)the Key R&D Programme Projects of Xianyang Municipality(No.L2023-ZDYF-SF-014)+1 种基金the Shaanxi University of Traditional Chinese Medicine Science,Education and Research Collaborative Educational Achievement Transformation Project(No.2024KC03)the open research topic from the Key Laboratory of Neurological Diseases in Traditional Chinese Medicine,Shaanxi Province(No.KF202315).
文摘Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a major type of liver cancer worldwide.In advanced stages,portal vein tumor thrombosis(PVTT)and jaundice are common,whereas obstructive jaundice(OJ)is relatively rare.Both conditions markedly reduce survival and increase therapeutic complexity.Recently,hepatic artery infusion chemotherapy(HAIC)in combination with targeted immunotherapy has shown promise for advanced HCC.CASE SUMMARY We report a 47-year-old male with advanced HCC complicated by PVTT and OJ,who was admitted with marked jaundice of the skin and sclera.Imaging revealed a large hepatic mass(14.5 cm×11.3 cm)in the right lobe with associated portal vein tumor thrombus.The tertiary bile duct was only mildly dilated,making percutaneous transhepatic cholangiography drainage infeasible.The patient underwent reduced-dose HAIC,which resulted in significant tumor shrinkage and marked reduction in serum bilirubin.This improvement enabled sequential treatment with lenvatinib and camrelizumab.After six cycles,both liver function and alphafetoprotein levels improved.The patient achieved a progression-free survival of 20 months and an overall survival of 29 months.CONCLUSION HAIC can treat high-bilirubin HCC with PVTT and OJ,allowing for subsequent targeted immunotherapy.
基金supported by the National Natural Science Foundation of China,Nos.82172546(to XH),82172547(to ZZ)the Natural ScienceFoundation of Guangdong Province,Nos.2023A1515012695(to XH),2024A1515010419(to ZZ)the Science and Technology Plan Project of Guangzhou,Nos.202201020413(to ZZ),2023A04J1099(to ZZ).
文摘White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.
文摘Background In patients with coronary artery disease,age is of known significance in predicting outcomes.Data on clinical outcomes in patients≥85 years undergoing percutaneous coronary intervention(PCI)remain scarce.The study aim was to determine clinical characteristics,risk of adverse cardiovascular events,and mortality in patients aged≥85 years compared to those aged<85 undergoing PCI.Methods In this retrospective study,data were obtained from the nationwide Netherlands Heart Registration on patients undergoing PCI between January 1st,2017 and January 1st,2021.The primary endpoint was all-cause mortality at long-term followup.Results A total of 155,683 patients underwent PCI,of which 100,209(64.4%)acute coronary syndrome cases.Compared to patients aged<85 years,patients aged≥85 were more often female and showed a higher number of cardiovascular comorbidities,including impaired left ventricle ejection fraction and reduced kidney function.Mortality at short-term and long-term follow-up were significantly higher in those aged≥85(P<0.001).Patients aged≥85 were more likely to have a myocardial infarction within 30 days following the index intervention(0.9%vs.0.7%;P=0.024),though they less often underwent revascularization at longterm follow-up compared to patients aged<85(P<0.001).Conclusions The elderly(≥85 years)patient requiring PCI carries an extensive cardiovascular risk profile,translating in significant risk of recurrent cardiovascular events and increased mortality rate.Clinicians should carefully weigh perceived risks and potential benefits in the individual patient,considering the patients’age,cardiovascular risk profile,and associated risk of morbidity and mortality.
文摘BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.
