Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact...After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.展开更多
BACKGROUND:Sepsis may increase the risk of long-term cardiovascular outcomes.This study aims to investigate association between sepsis survivorship and cardiovascular outcomes and to identify risk factors.METHODS:We c...BACKGROUND:Sepsis may increase the risk of long-term cardiovascular outcomes.This study aims to investigate association between sepsis survivorship and cardiovascular outcomes and to identify risk factors.METHODS:We conducted a comprehensive systematic search of MEDLINE,EMBASE,the Cochrane Library,Wanfang,and CNKI from database inception through May 2025,without language restrictions.The primary outcome was a composite of myocardial infarction,stroke,congestive heart failure,or cardiovascular death.To evaluate the association between sepsis survivors and cardiovascular outcomes,we calculated cumulative incidence rates and hazard ratios(HRs)with corresponding 95%confi dence intervals(95%CIs).RESULTS:Twenty-fi ve observational studies comprising 7,525,271 participants were included.The pooled cumulative incidence of major cardiovascular events was 9.0%(95%CI:6.1%-11.9%),myocardial infarction 2.4%(95%CI:1.6%-3.1%),stroke 4.9%(95%CI:3.8%-6.1%),and congestive heart failure 8.6%(95%CI:4.6%-12.6%).Compared with non-sepsis controls,sepsis survivors had a signifi cantly higher risk of major cardiovascular events(HR:1.54;95%CI:1.32-1.79),myocardial infarction(HR:1.41;95%CI:1.29-1.54),stroke(HR:1.45;95%CI:1.32-1.60),and congestive heart failure(HR:1.51;95%CI:1.46-1.56).Risk factors associated with increased cardiovascular events in sepsis survivors included age≤45 years,male,hyperlipidemia,and multiple comorbidities.CONCLUSION:Adult sepsis survivors may face significantly increased risks of long-term cardiovascular outcomes.Both common cardiovascular risk factors and sepsis-related pathophysiological changes contribute to this association.展开更多
BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the g...BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the gene expression alterations in the lymphatic system and the effectiveness of platelet-mediated lymphangiogenesis in improving liver cirrhosis and PHT.AIM To investigate the role of lymphangiogenesis in preclinical PHT models.METHODS Immunohistochemistry and transcriptome sequencing of bile duct ligation(BDL)and control lymphatic samples were conducted to reveal the indicated signaling pathways.Functional enrichment analyses were performed on the differentially expressed genes and hub genes.Adenoviral infection of vascular endothelial growth factor C(VEGF-C),plateletrich plasma(PRP),and VEGF3 receptor(VEGFR)inhibitor MAZ-51 was used as an intervention for the lymphatic system in PHT models.Histology,hemodynamic tests and western blot analyses were performed to demonstrate the effects of lymphatic intervention in PHT patients.RESULTS Lymphangiogenesis was increased in the BDL rat model.Transcriptome sequencing analysis of the extrahepatic lymphatic system revealed its close association with platelet adherence,aggregation,and activation.The role of PHT in the rat model was investigated by activating(PRP)and inhibiting(MAZ-51)the lymphatic system.PRP promoted lymphangiogenesis,which increased lymphatic drainage,alleviated portal pressure,reduced liver fibrosis,inhibited inflammation,inhibited angiogenesis,and suppressed mesenteric artery remodeling.MAZ-51 reversed the above improvements.CONCLUSION Via VEGF-C/VEGFR-3,platelets impede fibrosis,angiogenesis,and mesenteric artery remodeling,ultimately alleviating PHT.Thus,platelet intervention is a therapeutic approach for cirrhosis and PHT.展开更多
AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young pati...AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young patients(≤50 years old)diagnosed with RVO-related macular edema(RVO-ME)who had been undergoing IVC at the 474 Hospital in Xinjiang between January 2022 and October 2023.Patients were categorized into two groups:70 eyes in the effective group and 30 eyes in the ineffective group.The effective group comprised patients exhibiting a visual acuity improvement of≥2 lines at the last follow-up,with resolved ME and central macular thickness(CMT)<300μm.Conversely,the ineffective group included patients with visual acuity improvement of<1 line,persistent ME,and CMT≥300μm at the last follow-up.Serological parameters,including white blood cell count,neutrophil count,lymphocyte count,monocyte count,and mean platelet volume were assessed before treatment.The correlation between bestcorrected visual acuity(BCVA)and neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune inflammation index(SII),and systemic immune response index(SIRI)was analyzed.Additionally,the association between these serological parameters and the efficacy of IVC was explored.RESULTS:Three months after treatment,the effective group demonstrated a significant improvement in BCVA from 0.82±0.20 to 0.36±0.10,with a concurrent decrease in CMT from 661.28±163.90 to 200.61±82.45μm(P<0.001).Conversely,the ineffective group exhibited minimal changes in BCVA(0.86±0.25 to 0.82±0.14)and CMT(669.84±164.95 to 492.13±138.67μm,P<0.001).The differences in BCVA and CMT between the two groups were statistically significant(P<0.001).According to subgroup analysis,in patients with central RVO(CRVO),BCVA improved from 0.82±0.23 to 0.49±0.12 in the effective group and from 0.80±0.18 to 0.76±0.22 in the ineffective group(P<0.001).The CMT changes followed a similar pattern.In patients with branch RVO(BRVO),comparable trends in BCVA and CMT changes were observed between the effective and ineffective groups(P<0.001).Additionally,the effective group exhibited higher PLR and SII values than the ineffective group(P<0.05).Further CRVO and BRVO subgroups analysis exhibited consistent PLR and SII value trends.CONCLUSION:Compared to other inflammatory factors,elevated PLR and SII levels before treatment are better predictors of outcomes in young RVO-ME patients undergoing IVC treatment.展开更多
BACKGROUND Diabetic retinopathy(DR)is the leading cause of vision loss in patients with diabetes.The vascular endothelial growth factor(VEGF)pathway plays a critical role in the pathogenesis of DR,and ranibizumab,an a...BACKGROUND Diabetic retinopathy(DR)is the leading cause of vision loss in patients with diabetes.The vascular endothelial growth factor(VEGF)pathway plays a critical role in the pathogenesis of DR,and ranibizumab,an anti-VEGF agent,has shown promise in its treatment.Signal transducer and activator of transcription 3(STAT3)is involved in inflammatory processes and cellular signaling,while glial fibrillary acidic protein(GFAP)is a marker of glial cell activation,both contributing to retinal damage in DR.However,the mechanisms by which ranibizumab affect early-stage DR through the VEGF/STAT3/GFAP pathway are not fully understood.AIM To investigate the role of ranibizumab in early DR via the VEGF/STAT3/GFAP pathway.METHODS Adult retinal pigment epithelial 19(ARPE-19)cells and human retinal microvascular endothelial cells(HRMECs)were cultured under high-glucose conditions to simulate a diabetic environment.The effects of ranibizumab on cytokine mRNA and protein expression were analyzed by quantitative polymerase chain reaction and Western blot analysis.A diabetic rat model was induced with streptozotocin(60 mg/kg).Retinal changes,including retinal ganglion cell(RGC)apoptosis,vascular alterations,and cytokine expression,were evaluated using fundus fluorescein angiography,hematoxylin and eosin and periodic acid Schiff staining,immunofluorescence,confocal imaging,and Western blot analysis.RESULTS High-glucose conditions significantly increased the mRNA and protein levels of VEGF,STAT3,GFAP,and other cytokines in ARPE-19 and HRMECs.However,these levels were partially suppressed by ranibizumab.RGC apoptosis,vascular leakage,and elevated cytokine expression were observed during early-stage DR in diabetic rats.Ranibizumab treatment in diabetic rats reduced cytokine expression,restored RGCs,and repaired vascular networks.CONCLUSION Intravitreal ranibizumab modulates the VEGF/STAT3/GFAP pathway,suppresses cytokine expression,and promotes retinal repair,effectively delaying or preventing early DR progression.展开更多
Adipose-derived stem cell,one type of mesenchymal stem cells,is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery.However,its application has been limited b...Adipose-derived stem cell,one type of mesenchymal stem cells,is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery.However,its application has been limited by the complexities of the ischemic microenvironment.Hydrogel scaffolds,which are composed of hyaluronic acid and chitosan,exhibit excellent biocompatibility and biodegradability,making them promising candidates as cell carriers.Vascular endothelial growth factor is a crucial regulatory factor for stem cells.Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells,thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke.Here,we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells.Subsequently,we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemiareperfusion injury.When loaded with adipose-derived stem cells,this vascular endothelial growth factor–loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology.Further in vivo experiments revealed that this vascular endothelial growth factor–loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells,leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion.It also helped maintain mitochondrial integrity and axonal morphology,greatly improving rat motor function and angiogenesis.Therefore,utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.展开更多
Objective To investigate the effects of WenFei JiangZhuo Formula on cognitive function,serum neurofactors,and cerebral blood flow status in patients with mild-to-moderate vascular dementia(VaD),providing evidence for ...Objective To investigate the effects of WenFei JiangZhuo Formula on cognitive function,serum neurofactors,and cerebral blood flow status in patients with mild-to-moderate vascular dementia(VaD),providing evidence for clinical treatment.Methods A total of 80 patients with mild-to-moderate VaD admitted to our hospital from January 2022 to December 2023 were randomly divided into a control group(40 cases)and an observation group(40 cases)using a random number table.The control group received oral administration of butylphenidyl soft capsules,while the observation group received WenFei JiangZhuo Formula decoction as adjunct therapy.Both groups underwent continuous treatment for 12 weeks.Clinical outcomes were compared including cognitive function scores(MMSE,MoCA),serum neurofactors[brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)],and cerebral hemodynamics parameters[peak systolic velocity(Vs),end-diastolic velocity(Vd),mean velocity(Vm)of the middle cerebral artery(MCA)and anterior cerebral artery(ACA)].Clinical efficacy and adverse reactions were statistically analyzed.Results:After treatment,both groups showed significantly improved MMSE and MoCA scores compared to baseline levels(P<0.05),with the observation group demonstrating greater improvement than the control group(P<0.05).Serum BDNF and NGF levels increased significantly in both groups(P<0.05),while TNF-αand IL-6 levels decreased markedly(P<0.05),with the observation group showing better improvement than the control group(P<0.05).Both groups showed significant increases in MCA,ACA,Vs,Vd,and Vm compared to baseline levels(P<0.05),with the observation group outperforming the control group(P<0.05).The overall effective rate in the observation group was 87.50%,significantly higher than the control group's 67.50%(P<0.05).No statistically significant differences were observed in adverse reaction rates between the groups(P>0.05).Conclusion:WenFei JiangZhuo Formula can effectively improve cognitive function in patients with mild-to-moderate VaD.This mechanism may involve upregulating neurotrophic factors,suppressing inflammatory responses,and enhancing cerebral blood flow perfusion,with demonstrated safety profile.展开更多
Panvascular diseases(PVD)are a group of systemic disorders characterized by vascular pathologies,posing a significant threat to human health.Traditional risk factors for PVD include advanced age,male gender,hypertensi...Panvascular diseases(PVD)are a group of systemic disorders characterized by vascular pathologies,posing a significant threat to human health.Traditional risk factors for PVD include advanced age,male gender,hypertension,diabetes mellitus,dyslipidemia,hyperuricemia,smoking,and excessive alcohol consumption.Emerging risk factors encompass chronic inflammatory diseases,Helicobacter pylori infection,air pollution,sleep disorders,and psychological stress.These factors interact synergistically,accelerating vascular dysfunction and increasing the risk of cardiovascular and cerebrovascular events.This review integrated multidisciplinary knowledge to systematically delineate PVD risk factors,thereby establishing a scientific foundation for precise risk assessment and preventive strategies.Ultimately,these efforts may advance panvascular research,improve patient prognosis,reduce healthcare burdens,and enhance population vascular health.展开更多
Microvascular invasion(MVI)is a critical factor in hepatocellular carcinoma(HCC)prognosis,particularly in hepatitis B virus(HBV)-related cases.This editorial examines a recent study by Xu et al who developed models to...Microvascular invasion(MVI)is a critical factor in hepatocellular carcinoma(HCC)prognosis,particularly in hepatitis B virus(HBV)-related cases.This editorial examines a recent study by Xu et al who developed models to predict MVI and high-risk(M2)status in HBV-related HCC using contrast-enhanced computed tomography(CECT)radiomics and clinicoradiological factors.The study analyzed 270 patients,creating models that achieved an area under the curve values of 0.841 and 0.768 for MVI prediction,and 0.865 and 0.798 for M2 status prediction in training and validation datasets,respectively.These results are comparable to previous radiomics-based approaches,which reinforces the potential of this method in MVI prediction.The strengths of the study include its focus on HBV-related HCC and the use of widely accessible CECT imaging.However,limitations,such as retrospective design and manual segmentation,highlight areas for improvement.The editorial discusses the implications of the study including the need for standardized radiomics approaches and the potential impact on personalized treatment strategies.It also suggests future research directions,such as exploring mechanistic links between radiomics features and MVI,as well as integrating additional biomarkers or imaging modalities.Overall,this study contributes significantly to HCC management,paving the way for more accurate,personalized treatment approaches in the era of precision oncology.展开更多
Kidney transplantation remains the best treatment option for patients with endstage kidney disease,offering superior outcomes and improved quality of life.However,as in the general population,cardiovascular disease re...Kidney transplantation remains the best treatment option for patients with endstage kidney disease,offering superior outcomes and improved quality of life.However,as in the general population,cardiovascular disease remains the leading cause of mortality among kidney transplant recipients.While traditional cardiovascular risk factors—such as hypertension,diabetes,dyslipidemia,and tobacco use—are prevalent in this population,they are often compounded by transplant-specific and non-traditional risk factors unique to the post-transplant setting.This review aims to explore these non-traditional and transplant-related cardiovascular risk factors,including allograft dysfunction and acute rejection episodes.Moreover,we will provide an overview of the cardiovascular implications of immunosuppressive therapy,including its association with opportunistic infections such as cytomegalovirus.Finally,we will touch upon considerations for special populations of kidney transplant recipients based on our current understanding of these non-traditional cardiovascular risks with the currently available data.展开更多
A systematic review and meta-analysis study was conducted to assess the effectiveness of probiotic/prebiotic/synbiotic supplementation on the effects of cardiovascular risk factors in patients with type 2 diabetes mel...A systematic review and meta-analysis study was conducted to assess the effectiveness of probiotic/prebiotic/synbiotic supplementation on the effects of cardiovascular risk factors in patients with type 2 diabetes mellitus(T2DM)based on data from randomized controlled trials(RCTs).We searched electronic databases including PubMed,Cochrane Library,Embase,and Web of Science to identify clinical trials published up to 31 March 2023.Data was pooled using a random-effects model if significant heterogeneity(I2>50%),otherwise use a fixed-effects model.Fifty-six trials that included 3317 patients were enrolled for analysis.Meta-analysis reported that probiotic/prebiotic/synbiotic supplementation significantly reduced systolic blood pressure(SBP)(weighted mean difference(WMD):-3.57 mmHg,95% confidence interval(CI):-5.36,-1.78;P=0.000),diastolic blood pressure(DBP)(WMD:-2.05 mmHg,95%CI:-3.07,-1.04;P=0.000),triglycerides(TG)(WMD:-16.10 mg/dL,95%CI:-20.16,-12.05;P=0.000),total cholesterol(TC)(WMD:-14.00 mg/dL,95%CI:-20.46,-7.55;P=0.000),low-density lipoprotein cholesterol(LDL-C)(WMD:-7.03 mg/dL,95%CI:-9.25,-4.81;P=0.000),fasting plasma glucose(FPG)(WMD:-16.57 mg/dL,95%CI:-20.39,-12.74;P=0.000),hemoglobin A1c(HbA1c)(WMD:-0.44%,95%CI:-0.68,-0.20;P=0.000),insulin(standardized mean difference(SMD):-0.37,95%CI:-0.53,-0.21;P=0.000),homeostatic model assessment of insulin resistance(HOMA-IR)(WMD:-1.05,95%CI:-1.56,-0.54;P=0.000),C-reactive protein(CRP)(SMD:-0.35,95%CI:-0.57,-0.13;P=0.002),tumor necrosis factor-α(TNF-α)(SMD:-1.07,95%CI:-1.57,-0.56;P=0.000),interleukin-6(IL-6)(SMD:-0.37,95%CI:-0.61,-0.13;P=0.003)levels,they also increased the high-density lipoprotein cholesterol(HDL-C)(WMD:3.70 mg/dL,95%CI:1.80,5.60;P=0.000)levels in T2DM patients,as compared to the placebo groups.This meta-analysis supports the use of probiotic/prebiotic/synbiotic supplementation as an adjunctive therapy to improve blood pressure,glycemic control parameters,lipid profile and inflammatory markers in patients with T2DM,which are well-known cardiovascular risk factors.展开更多
BACKGROUND Cardiovascular(CV)complications are common in intensive care unit(ICU)patients after gastrointestinal surgery and are associated with increased mortality and prolonged hospital stay.The optimization of post...BACKGROUND Cardiovascular(CV)complications are common in intensive care unit(ICU)patients after gastrointestinal surgery and are associated with increased mortality and prolonged hospital stay.The optimization of postoperative nursing interventions,particularly pain management,is crucial for reducing such complications.AIM To investigate the effects of enhanced recovery nursing on CV complications after gastrointestinal surgery in ICU patients and associated risk factors.METHODS A retrospective analysis was conducted on 78 adult patients who underwent gastrointestinal surgery in the ICU of our hospital between February 2023 and September 2024.Among them,40 patients received standard care(control group),while 38 received enhanced recovery nursing(observation group).We compared the incidence of CV complications and nursing satisfaction between the two groups.Patients were divided into CV complication and non-complication groups based on complication occurrence,and logistic regression analysis was used to identify risk factors.RESULTS In the control and observation groups,the incidence of CV complications was 30.0%(12/40)and 18.4%(7/38),with a nursing satisfaction rate of 70.0%(28/40)and 92.1%(35/38),respectively.The postoperative pain score at 14 days was significantly lower in the observation group(0.27±0.15)compared to the control group(1.65±0.37),with all differences being statistically significant(P<0.05).Univariate analysis indicated significant differences in age,body mass index,hypertension,diabetes,smoking history,history of heart failure,and previous myocardial infarction(P<0.05).Multivariate logistic regression identified heart failure history,previous myocardial infarction,age,hypertension,and diabetes as independent risk factors,with odds ratios of 1.195,1.528,1.062,1.836,and 1.942,respectively(all P<0.05).CONCLUSION Implementing enhanced recovery nursing for ICU patients after gastrointestinal surgery is beneficial in reducing the incidence of CV complications and improving nursing satisfaction.展开更多
BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and dep...BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
Background The association of systemic inflammatory response index(SIRI)with prognosis of coronary artery disease(CAD)patients has never been investigated in a large sample with long-term follow-up.This study aimed to...Background The association of systemic inflammatory response index(SIRI)with prognosis of coronary artery disease(CAD)patients has never been investigated in a large sample with long-term follow-up.This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States.Methods A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey(NHANES)1999-2018 were included in this study.Cox proportional hazards model,restricted cubic spline(RCS),and receiver operating characteristic curve(ROC)were performed to investigate the association of SIRI with all-cause and cause-specific mortality.Piecewise linear regression and sensitivity analyses were also performed.Results During a median follow-up of 7.7 years,1454 all-cause mortality occurred.After adjusting for confounding factors,higher lnSIRI was significantly associated with higher risk of all-cause(HR=1.16,95%CI:1.09-1.23)and CVD mortality(HR=1.17,95%CI:1.05-1.30)but not cancer mortality(HR=1.17,95%CI:0.99-1.38).The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI,respectively.ROC curves showed that lnSIRI had robust predictive effect both in short and long terms.Conclusions SIRI was independently associated with all-cause and CVD mortality,and the dose-response relationship was Jshaped.SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.展开更多
Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability...Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzhe...Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).展开更多
Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-me...Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-ments in karst hydrology,significant gaps remain in long-term trends,underlying processes,and quantitative effects of environmental changes.This is especially true in areas like the Wujiang River(WJ)in China,where human activities such as reservoir construction and land use/cover changes have accelerated hydrochemical changes.We combined recent and historical monitoring data to provide a detailed analysis of the spatial and temporal characteristics,evolution,and controlling factors of major ions in WJ.These findings are important for local water management and contribute to global efforts to manage similar karst systems facing human-induced pressures.Our research shows clear seasonal differences in solute concentrations,with higher levels during the dry season.WJ’s water is rich in calcium,with Ca-HCO_(3) ion pairs being the most common.Reservoir monitor-ing stations show much higher levels of NO_(3)^(−)and SO_(4)^(2−)compared to river-type stations,likely due to longer hydraulic retention time and increased acid deposition.The study confirms the significant role of pH and water temperature in rock weathering processes.Land use/cover changes were identified as the primary drivers of solute variations(46.37%),followed by lithology(13.92%)and temperature(8.35%).Over the past two decades,in-tense carbonate weathering has been observed,especially during wet seasons.Among karstic provinces,Guizhou Province stands out with the highest ion concentrations,indicative of its extensive karst coverage and heightened weathering processes.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by European Regional Development Funds RE0022527 ZEBRATOX(EU-Région Réunion-French State national counterpart,to Nicolas Diotel and Jean-Loup Bascands).
文摘After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.
基金supported by Zhejiang Province Medical and Health Science and Technology Plan Project(2022KY241)Hangzhou Health Science and Technology Plan Project(ZD20230017).
文摘BACKGROUND:Sepsis may increase the risk of long-term cardiovascular outcomes.This study aims to investigate association between sepsis survivorship and cardiovascular outcomes and to identify risk factors.METHODS:We conducted a comprehensive systematic search of MEDLINE,EMBASE,the Cochrane Library,Wanfang,and CNKI from database inception through May 2025,without language restrictions.The primary outcome was a composite of myocardial infarction,stroke,congestive heart failure,or cardiovascular death.To evaluate the association between sepsis survivors and cardiovascular outcomes,we calculated cumulative incidence rates and hazard ratios(HRs)with corresponding 95%confi dence intervals(95%CIs).RESULTS:Twenty-fi ve observational studies comprising 7,525,271 participants were included.The pooled cumulative incidence of major cardiovascular events was 9.0%(95%CI:6.1%-11.9%),myocardial infarction 2.4%(95%CI:1.6%-3.1%),stroke 4.9%(95%CI:3.8%-6.1%),and congestive heart failure 8.6%(95%CI:4.6%-12.6%).Compared with non-sepsis controls,sepsis survivors had a signifi cantly higher risk of major cardiovascular events(HR:1.54;95%CI:1.32-1.79),myocardial infarction(HR:1.41;95%CI:1.29-1.54),stroke(HR:1.45;95%CI:1.32-1.60),and congestive heart failure(HR:1.51;95%CI:1.46-1.56).Risk factors associated with increased cardiovascular events in sepsis survivors included age≤45 years,male,hyperlipidemia,and multiple comorbidities.CONCLUSION:Adult sepsis survivors may face significantly increased risks of long-term cardiovascular outcomes.Both common cardiovascular risk factors and sepsis-related pathophysiological changes contribute to this association.
基金Supported by the National Natural Science Foundation of China,No.82100639,No.82200630,and No.81970526Postdoctoral Scientific Research Foundation of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,No.202401023+3 种基金Clinical Research Program of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,No.JYLJ202124Shanghai Municipal Commission of Health and Family Planning,No.20244Y0195 and No.20234Y0132the Fundamental Research Program Funding of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.JYZZ162Science Foundation of Xinjiang Uygur Natural Autonomous Region,No.2022D01F17.
文摘BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the gene expression alterations in the lymphatic system and the effectiveness of platelet-mediated lymphangiogenesis in improving liver cirrhosis and PHT.AIM To investigate the role of lymphangiogenesis in preclinical PHT models.METHODS Immunohistochemistry and transcriptome sequencing of bile duct ligation(BDL)and control lymphatic samples were conducted to reveal the indicated signaling pathways.Functional enrichment analyses were performed on the differentially expressed genes and hub genes.Adenoviral infection of vascular endothelial growth factor C(VEGF-C),plateletrich plasma(PRP),and VEGF3 receptor(VEGFR)inhibitor MAZ-51 was used as an intervention for the lymphatic system in PHT models.Histology,hemodynamic tests and western blot analyses were performed to demonstrate the effects of lymphatic intervention in PHT patients.RESULTS Lymphangiogenesis was increased in the BDL rat model.Transcriptome sequencing analysis of the extrahepatic lymphatic system revealed its close association with platelet adherence,aggregation,and activation.The role of PHT in the rat model was investigated by activating(PRP)and inhibiting(MAZ-51)the lymphatic system.PRP promoted lymphangiogenesis,which increased lymphatic drainage,alleviated portal pressure,reduced liver fibrosis,inhibited inflammation,inhibited angiogenesis,and suppressed mesenteric artery remodeling.MAZ-51 reversed the above improvements.CONCLUSION Via VEGF-C/VEGFR-3,platelets impede fibrosis,angiogenesis,and mesenteric artery remodeling,ultimately alleviating PHT.Thus,platelet intervention is a therapeutic approach for cirrhosis and PHT.
基金Supported by Youth Cultivation Research Program of Beijing Road Medical Area,Xinjiang Military Region General Hospital,Xinjiang,China(No.2022jzbj105)Science and Technology Program of Urumqi Municipal Health and Wellness Commission(No.202360).
文摘AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young patients(≤50 years old)diagnosed with RVO-related macular edema(RVO-ME)who had been undergoing IVC at the 474 Hospital in Xinjiang between January 2022 and October 2023.Patients were categorized into two groups:70 eyes in the effective group and 30 eyes in the ineffective group.The effective group comprised patients exhibiting a visual acuity improvement of≥2 lines at the last follow-up,with resolved ME and central macular thickness(CMT)<300μm.Conversely,the ineffective group included patients with visual acuity improvement of<1 line,persistent ME,and CMT≥300μm at the last follow-up.Serological parameters,including white blood cell count,neutrophil count,lymphocyte count,monocyte count,and mean platelet volume were assessed before treatment.The correlation between bestcorrected visual acuity(BCVA)and neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune inflammation index(SII),and systemic immune response index(SIRI)was analyzed.Additionally,the association between these serological parameters and the efficacy of IVC was explored.RESULTS:Three months after treatment,the effective group demonstrated a significant improvement in BCVA from 0.82±0.20 to 0.36±0.10,with a concurrent decrease in CMT from 661.28±163.90 to 200.61±82.45μm(P<0.001).Conversely,the ineffective group exhibited minimal changes in BCVA(0.86±0.25 to 0.82±0.14)and CMT(669.84±164.95 to 492.13±138.67μm,P<0.001).The differences in BCVA and CMT between the two groups were statistically significant(P<0.001).According to subgroup analysis,in patients with central RVO(CRVO),BCVA improved from 0.82±0.23 to 0.49±0.12 in the effective group and from 0.80±0.18 to 0.76±0.22 in the ineffective group(P<0.001).The CMT changes followed a similar pattern.In patients with branch RVO(BRVO),comparable trends in BCVA and CMT changes were observed between the effective and ineffective groups(P<0.001).Additionally,the effective group exhibited higher PLR and SII values than the ineffective group(P<0.05).Further CRVO and BRVO subgroups analysis exhibited consistent PLR and SII value trends.CONCLUSION:Compared to other inflammatory factors,elevated PLR and SII levels before treatment are better predictors of outcomes in young RVO-ME patients undergoing IVC treatment.
基金Supported by the Natural Science Foundation of Jiangxi Province,No.20242BAB25489National Natural Science Foundation of China,No.82260211 and No.81460092+1 种基金Key Research and Development Project in Jiangxi Province,No.20203BBG73058Chinese Medicine Science and Technology Project in Jiangxi Province,No.2020A0166。
文摘BACKGROUND Diabetic retinopathy(DR)is the leading cause of vision loss in patients with diabetes.The vascular endothelial growth factor(VEGF)pathway plays a critical role in the pathogenesis of DR,and ranibizumab,an anti-VEGF agent,has shown promise in its treatment.Signal transducer and activator of transcription 3(STAT3)is involved in inflammatory processes and cellular signaling,while glial fibrillary acidic protein(GFAP)is a marker of glial cell activation,both contributing to retinal damage in DR.However,the mechanisms by which ranibizumab affect early-stage DR through the VEGF/STAT3/GFAP pathway are not fully understood.AIM To investigate the role of ranibizumab in early DR via the VEGF/STAT3/GFAP pathway.METHODS Adult retinal pigment epithelial 19(ARPE-19)cells and human retinal microvascular endothelial cells(HRMECs)were cultured under high-glucose conditions to simulate a diabetic environment.The effects of ranibizumab on cytokine mRNA and protein expression were analyzed by quantitative polymerase chain reaction and Western blot analysis.A diabetic rat model was induced with streptozotocin(60 mg/kg).Retinal changes,including retinal ganglion cell(RGC)apoptosis,vascular alterations,and cytokine expression,were evaluated using fundus fluorescein angiography,hematoxylin and eosin and periodic acid Schiff staining,immunofluorescence,confocal imaging,and Western blot analysis.RESULTS High-glucose conditions significantly increased the mRNA and protein levels of VEGF,STAT3,GFAP,and other cytokines in ARPE-19 and HRMECs.However,these levels were partially suppressed by ranibizumab.RGC apoptosis,vascular leakage,and elevated cytokine expression were observed during early-stage DR in diabetic rats.Ranibizumab treatment in diabetic rats reduced cytokine expression,restored RGCs,and repaired vascular networks.CONCLUSION Intravitreal ranibizumab modulates the VEGF/STAT3/GFAP pathway,suppresses cytokine expression,and promotes retinal repair,effectively delaying or preventing early DR progression.
基金supported by a grant from the Excellent Young Scholars Cultivation Project of Fujian Medical University Union Hospital,No.2022XH026(to HC)Joint Funds for the Innovation of Science and Technology in Fujian Province,No.2019Y9058(to XL)the Natural Science Foundation of Fujian Province,No.2020J011017(to XL)。
文摘Adipose-derived stem cell,one type of mesenchymal stem cells,is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery.However,its application has been limited by the complexities of the ischemic microenvironment.Hydrogel scaffolds,which are composed of hyaluronic acid and chitosan,exhibit excellent biocompatibility and biodegradability,making them promising candidates as cell carriers.Vascular endothelial growth factor is a crucial regulatory factor for stem cells.Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells,thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke.Here,we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells.Subsequently,we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemiareperfusion injury.When loaded with adipose-derived stem cells,this vascular endothelial growth factor–loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology.Further in vivo experiments revealed that this vascular endothelial growth factor–loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells,leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion.It also helped maintain mitochondrial integrity and axonal morphology,greatly improving rat motor function and angiogenesis.Therefore,utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.
文摘Objective To investigate the effects of WenFei JiangZhuo Formula on cognitive function,serum neurofactors,and cerebral blood flow status in patients with mild-to-moderate vascular dementia(VaD),providing evidence for clinical treatment.Methods A total of 80 patients with mild-to-moderate VaD admitted to our hospital from January 2022 to December 2023 were randomly divided into a control group(40 cases)and an observation group(40 cases)using a random number table.The control group received oral administration of butylphenidyl soft capsules,while the observation group received WenFei JiangZhuo Formula decoction as adjunct therapy.Both groups underwent continuous treatment for 12 weeks.Clinical outcomes were compared including cognitive function scores(MMSE,MoCA),serum neurofactors[brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)],and cerebral hemodynamics parameters[peak systolic velocity(Vs),end-diastolic velocity(Vd),mean velocity(Vm)of the middle cerebral artery(MCA)and anterior cerebral artery(ACA)].Clinical efficacy and adverse reactions were statistically analyzed.Results:After treatment,both groups showed significantly improved MMSE and MoCA scores compared to baseline levels(P<0.05),with the observation group demonstrating greater improvement than the control group(P<0.05).Serum BDNF and NGF levels increased significantly in both groups(P<0.05),while TNF-αand IL-6 levels decreased markedly(P<0.05),with the observation group showing better improvement than the control group(P<0.05).Both groups showed significant increases in MCA,ACA,Vs,Vd,and Vm compared to baseline levels(P<0.05),with the observation group outperforming the control group(P<0.05).The overall effective rate in the observation group was 87.50%,significantly higher than the control group's 67.50%(P<0.05).No statistically significant differences were observed in adverse reaction rates between the groups(P>0.05).Conclusion:WenFei JiangZhuo Formula can effectively improve cognitive function in patients with mild-to-moderate VaD.This mechanism may involve upregulating neurotrophic factors,suppressing inflammatory responses,and enhancing cerebral blood flow perfusion,with demonstrated safety profile.
文摘Panvascular diseases(PVD)are a group of systemic disorders characterized by vascular pathologies,posing a significant threat to human health.Traditional risk factors for PVD include advanced age,male gender,hypertension,diabetes mellitus,dyslipidemia,hyperuricemia,smoking,and excessive alcohol consumption.Emerging risk factors encompass chronic inflammatory diseases,Helicobacter pylori infection,air pollution,sleep disorders,and psychological stress.These factors interact synergistically,accelerating vascular dysfunction and increasing the risk of cardiovascular and cerebrovascular events.This review integrated multidisciplinary knowledge to systematically delineate PVD risk factors,thereby establishing a scientific foundation for precise risk assessment and preventive strategies.Ultimately,these efforts may advance panvascular research,improve patient prognosis,reduce healthcare burdens,and enhance population vascular health.
文摘Microvascular invasion(MVI)is a critical factor in hepatocellular carcinoma(HCC)prognosis,particularly in hepatitis B virus(HBV)-related cases.This editorial examines a recent study by Xu et al who developed models to predict MVI and high-risk(M2)status in HBV-related HCC using contrast-enhanced computed tomography(CECT)radiomics and clinicoradiological factors.The study analyzed 270 patients,creating models that achieved an area under the curve values of 0.841 and 0.768 for MVI prediction,and 0.865 and 0.798 for M2 status prediction in training and validation datasets,respectively.These results are comparable to previous radiomics-based approaches,which reinforces the potential of this method in MVI prediction.The strengths of the study include its focus on HBV-related HCC and the use of widely accessible CECT imaging.However,limitations,such as retrospective design and manual segmentation,highlight areas for improvement.The editorial discusses the implications of the study including the need for standardized radiomics approaches and the potential impact on personalized treatment strategies.It also suggests future research directions,such as exploring mechanistic links between radiomics features and MVI,as well as integrating additional biomarkers or imaging modalities.Overall,this study contributes significantly to HCC management,paving the way for more accurate,personalized treatment approaches in the era of precision oncology.
文摘Kidney transplantation remains the best treatment option for patients with endstage kidney disease,offering superior outcomes and improved quality of life.However,as in the general population,cardiovascular disease remains the leading cause of mortality among kidney transplant recipients.While traditional cardiovascular risk factors—such as hypertension,diabetes,dyslipidemia,and tobacco use—are prevalent in this population,they are often compounded by transplant-specific and non-traditional risk factors unique to the post-transplant setting.This review aims to explore these non-traditional and transplant-related cardiovascular risk factors,including allograft dysfunction and acute rejection episodes.Moreover,we will provide an overview of the cardiovascular implications of immunosuppressive therapy,including its association with opportunistic infections such as cytomegalovirus.Finally,we will touch upon considerations for special populations of kidney transplant recipients based on our current understanding of these non-traditional cardiovascular risks with the currently available data.
基金Jiangsu College of Nursing 2023 Special Fund for Research and Development of Medical-Educational Integration。
文摘A systematic review and meta-analysis study was conducted to assess the effectiveness of probiotic/prebiotic/synbiotic supplementation on the effects of cardiovascular risk factors in patients with type 2 diabetes mellitus(T2DM)based on data from randomized controlled trials(RCTs).We searched electronic databases including PubMed,Cochrane Library,Embase,and Web of Science to identify clinical trials published up to 31 March 2023.Data was pooled using a random-effects model if significant heterogeneity(I2>50%),otherwise use a fixed-effects model.Fifty-six trials that included 3317 patients were enrolled for analysis.Meta-analysis reported that probiotic/prebiotic/synbiotic supplementation significantly reduced systolic blood pressure(SBP)(weighted mean difference(WMD):-3.57 mmHg,95% confidence interval(CI):-5.36,-1.78;P=0.000),diastolic blood pressure(DBP)(WMD:-2.05 mmHg,95%CI:-3.07,-1.04;P=0.000),triglycerides(TG)(WMD:-16.10 mg/dL,95%CI:-20.16,-12.05;P=0.000),total cholesterol(TC)(WMD:-14.00 mg/dL,95%CI:-20.46,-7.55;P=0.000),low-density lipoprotein cholesterol(LDL-C)(WMD:-7.03 mg/dL,95%CI:-9.25,-4.81;P=0.000),fasting plasma glucose(FPG)(WMD:-16.57 mg/dL,95%CI:-20.39,-12.74;P=0.000),hemoglobin A1c(HbA1c)(WMD:-0.44%,95%CI:-0.68,-0.20;P=0.000),insulin(standardized mean difference(SMD):-0.37,95%CI:-0.53,-0.21;P=0.000),homeostatic model assessment of insulin resistance(HOMA-IR)(WMD:-1.05,95%CI:-1.56,-0.54;P=0.000),C-reactive protein(CRP)(SMD:-0.35,95%CI:-0.57,-0.13;P=0.002),tumor necrosis factor-α(TNF-α)(SMD:-1.07,95%CI:-1.57,-0.56;P=0.000),interleukin-6(IL-6)(SMD:-0.37,95%CI:-0.61,-0.13;P=0.003)levels,they also increased the high-density lipoprotein cholesterol(HDL-C)(WMD:3.70 mg/dL,95%CI:1.80,5.60;P=0.000)levels in T2DM patients,as compared to the placebo groups.This meta-analysis supports the use of probiotic/prebiotic/synbiotic supplementation as an adjunctive therapy to improve blood pressure,glycemic control parameters,lipid profile and inflammatory markers in patients with T2DM,which are well-known cardiovascular risk factors.
文摘BACKGROUND Cardiovascular(CV)complications are common in intensive care unit(ICU)patients after gastrointestinal surgery and are associated with increased mortality and prolonged hospital stay.The optimization of postoperative nursing interventions,particularly pain management,is crucial for reducing such complications.AIM To investigate the effects of enhanced recovery nursing on CV complications after gastrointestinal surgery in ICU patients and associated risk factors.METHODS A retrospective analysis was conducted on 78 adult patients who underwent gastrointestinal surgery in the ICU of our hospital between February 2023 and September 2024.Among them,40 patients received standard care(control group),while 38 received enhanced recovery nursing(observation group).We compared the incidence of CV complications and nursing satisfaction between the two groups.Patients were divided into CV complication and non-complication groups based on complication occurrence,and logistic regression analysis was used to identify risk factors.RESULTS In the control and observation groups,the incidence of CV complications was 30.0%(12/40)and 18.4%(7/38),with a nursing satisfaction rate of 70.0%(28/40)and 92.1%(35/38),respectively.The postoperative pain score at 14 days was significantly lower in the observation group(0.27±0.15)compared to the control group(1.65±0.37),with all differences being statistically significant(P<0.05).Univariate analysis indicated significant differences in age,body mass index,hypertension,diabetes,smoking history,history of heart failure,and previous myocardial infarction(P<0.05).Multivariate logistic regression identified heart failure history,previous myocardial infarction,age,hypertension,and diabetes as independent risk factors,with odds ratios of 1.195,1.528,1.062,1.836,and 1.942,respectively(all P<0.05).CONCLUSION Implementing enhanced recovery nursing for ICU patients after gastrointestinal surgery is beneficial in reducing the incidence of CV complications and improving nursing satisfaction.
文摘BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
基金National Key Research and Development Program of China(2022YFC2503500 and 2022YFC2503504)。
文摘Background The association of systemic inflammatory response index(SIRI)with prognosis of coronary artery disease(CAD)patients has never been investigated in a large sample with long-term follow-up.This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States.Methods A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey(NHANES)1999-2018 were included in this study.Cox proportional hazards model,restricted cubic spline(RCS),and receiver operating characteristic curve(ROC)were performed to investigate the association of SIRI with all-cause and cause-specific mortality.Piecewise linear regression and sensitivity analyses were also performed.Results During a median follow-up of 7.7 years,1454 all-cause mortality occurred.After adjusting for confounding factors,higher lnSIRI was significantly associated with higher risk of all-cause(HR=1.16,95%CI:1.09-1.23)and CVD mortality(HR=1.17,95%CI:1.05-1.30)but not cancer mortality(HR=1.17,95%CI:0.99-1.38).The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI,respectively.ROC curves showed that lnSIRI had robust predictive effect both in short and long terms.Conclusions SIRI was independently associated with all-cause and CVD mortality,and the dose-response relationship was Jshaped.SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.
文摘Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
基金supported by National Institute on Aging(NIH-NIA)R01AG054459(to ALL).
文摘Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).
基金supported by Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515110824 and 2025A1515011839)Shenzhen Science and Technology Program(No.RCBS20231211090638066).
文摘Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-ments in karst hydrology,significant gaps remain in long-term trends,underlying processes,and quantitative effects of environmental changes.This is especially true in areas like the Wujiang River(WJ)in China,where human activities such as reservoir construction and land use/cover changes have accelerated hydrochemical changes.We combined recent and historical monitoring data to provide a detailed analysis of the spatial and temporal characteristics,evolution,and controlling factors of major ions in WJ.These findings are important for local water management and contribute to global efforts to manage similar karst systems facing human-induced pressures.Our research shows clear seasonal differences in solute concentrations,with higher levels during the dry season.WJ’s water is rich in calcium,with Ca-HCO_(3) ion pairs being the most common.Reservoir monitor-ing stations show much higher levels of NO_(3)^(−)and SO_(4)^(2−)compared to river-type stations,likely due to longer hydraulic retention time and increased acid deposition.The study confirms the significant role of pH and water temperature in rock weathering processes.Land use/cover changes were identified as the primary drivers of solute variations(46.37%),followed by lithology(13.92%)and temperature(8.35%).Over the past two decades,in-tense carbonate weathering has been observed,especially during wet seasons.Among karstic provinces,Guizhou Province stands out with the highest ion concentrations,indicative of its extensive karst coverage and heightened weathering processes.
