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 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
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
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
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 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
OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.METHODS:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predic...OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.METHODS:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predicted by molecular docking.The effects of emodin on the invasion,migration,and proliferation of human umbilical vein endothelial cells(HUVEC)were determined by cell counting kit-8,Transwell,and tube formation assays.Analysis of apoptosis was performed by flow cytometry.CD31 levels were examined by immunofluorescence.The abundance and phosphorylation state of VEGFR2,protein kinase B(Akt),signal transducer and activator of transcription 3(STAT3),and P38 were examined by immunoblot analysis.Corneal alkali burn was performed on 40 mice.Animals were divided randomly into two groups,and the alkali-burned eyes were then treated with drops of either 10μM emodin or phosphate buffered saline(PBS)four times a day.Slitlamp microscopy was used to evaluate inflammation and corneal neovascularization(CNV)in all eyes on Days 0,7,10,and 14.The mice were killed humanely 14 d after the alkali burn,and their corneas were removed and preserved at-80℃ until histological study or protein extraction.RESULTS:Molecular docking confirmed that emodin was able to target VEGFR2.The findings revealed that emodin decreased the invasion,migration,angiogenesis,and proliferation of HUVEC in a dose-dependent manner.In mice,emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali burn.Compared to those of the PBS-treated group,lower VEGFR2 expression and CD31 levels were found in the emodintreated group.Emodin dramatically decreased the expression of VEGFR2,p-VEGFR2,p-Akt,p-STAT3,and p-P38 in VEGF-treated HUVEC.CONCLUSION:This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization.Emodin might be a promising new therapeutic option for corneal alkali burns.展开更多
BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment ep...BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.展开更多
Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player le...Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.展开更多
In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,incl...In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,including bevacizumab,in treating patients with colorectal cancer(CRC).Through neutralization of vascular endothelial growth factor(VEGF),bevacizumab inhibits tumor angiogenesis,impairing neovascularization and thereby depriving the tumor of essential nutrients and oxygen.Conversely,PD-L1 binding to VEGF receptor 2 promotes angiogenesis,supporting tumor vasculature.The interplay between these pathways complicates the assessment of bevacizumab’s efficacy in cancer therapy,notably in CRC,where VEGF and PD-L1 significantly affect treatment response.This review examines metastatic CRC treatment strategies,focusing on bevacizumab’s mechanism of action and the role of PD-L1 in this therapeutic context.展开更多
BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldw...BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldwide.AIM To investigate the expression levels of serum vascular endothelial growth factor(VEGF)and interleukin(IL)-17 in patients with PHC and evaluate their diagnostic value while exploring their relationship with patients’clinical characteristics.METHODS The study included 50 patients with confirmed PHC who visited Wuhan Han-yang Hospital from January 2021 to January 2022,and 50 healthy individuals from the same period served as the control group.Serum VEGF and IL-17 levels in both groups were measured by Enzyme-Linked Immunosorbent Assay,and their diagnostic value was assessed using receiver operating characteristic(ROC)curves.Pearson correlation analysis was performed to examine the relationship between serum VEGF and IL-17 levels.Pathological data of the PHC patients were analyzed to determine the relationship between serum VEGF and IL-17 levels and pathological characteristics.RESULTS Serum VEGF and IL-17 levels were significantly higher in the study group com-pared to the control group(P<0.05).No significant association was observed between serum VEGF and IL-17 levels and gender,age,combined cirrhosis,tumor diameter,or degree of differentiation(P>0.05).However,there was a significant relationship between clinical TNM stage,tumor metastasis,and serum VEGF and IL-17 levels(P<0.05).Correlation analysis revealed a positive correlation between serum VEGF and IL-17(P<0.05).ROC analysis demonstrated that both serum VEGF and IL-17 had good diagnostic efficacy for PHC.CONCLUSION Serum VEGF and IL-17 levels were significantly higher in PHC patients compared to healthy individuals.Their levels were closely related to pathological features such as tumor metastasis and clinical TNM stage,and there was a significant positive correlation between VEGF and IL-17.These biomarkers may serve as valuable reference in-dicators for the early diagnosis and treatment guidance of PHC.展开更多
BACKGROUND Anti-vascular endothelial growth factor(anti-VEGF)therapy is critical for managing neovascular age-related macular degeneration(nAMD),but understanding factors influencing treatment efficacy is essential fo...BACKGROUND Anti-vascular endothelial growth factor(anti-VEGF)therapy is critical for managing neovascular age-related macular degeneration(nAMD),but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes.AIM To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response.METHODS In this study,65 eyes of exudative AMD patients after anti-VEGF treatment for≥1 mo were observed using optical coherence tomography angiography.Patients were classified into non-responders(n=22)and responders(n=43).Logistic regression was used to determine independent risk factors for treatment response.A predictive model was created using the Akaike Information Criterion,and its performance was assessed with the area under the receiver operating characteristic curve,calibration curves,and decision curve analysis(DCA)with 500 bootstrap re-samples.RESULTS Multivariable logistic regression analysis identified the number of junction voxels[odds ratio=0.997,95%confidence interval(CI):0.993-0.999,P=0.010]as an independent predictor of positive anti-VEGF treatment outcomes.The predictive model incorporating the fractal dimension,number of junction voxels,and longest shortest path,achieved an area under the curve of 0.753(95%CI:0.622-0.873).Calibration curves confirmed a high agreement between predicted and actual outcomes,and DCA validated the model's clinical utility.CONCLUSION The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy,enhancing personalized treatment planning.展开更多
The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic mac...The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).展开更多
AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)follo...AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of conbercept.METHODS:This study included 72 PDR patients and 8 cataract patients as controls.PDR patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)performed.Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was studied.RESULTS:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all intervals.Liquid chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC samples.GO and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling pathways.PPI analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC groups.CONCLUSION:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with PDR.Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response,stress response,and cellular metabolism.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 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.
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.
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.
基金Fujian Major Research Grants for Young and Middle-aged Health Professionals(No.2021ZQNZD012,Research and Development of Anti-Keratitis Protein Drug Sgp130)National Natural Science Foundation of China(No.81774369,Study on Mechanism of Yijing Decoction in Preventing Microvascular Damage of Early Diabetic Retinopathy based on MMPs/TIMPs)。
文摘OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.METHODS:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predicted by molecular docking.The effects of emodin on the invasion,migration,and proliferation of human umbilical vein endothelial cells(HUVEC)were determined by cell counting kit-8,Transwell,and tube formation assays.Analysis of apoptosis was performed by flow cytometry.CD31 levels were examined by immunofluorescence.The abundance and phosphorylation state of VEGFR2,protein kinase B(Akt),signal transducer and activator of transcription 3(STAT3),and P38 were examined by immunoblot analysis.Corneal alkali burn was performed on 40 mice.Animals were divided randomly into two groups,and the alkali-burned eyes were then treated with drops of either 10μM emodin or phosphate buffered saline(PBS)four times a day.Slitlamp microscopy was used to evaluate inflammation and corneal neovascularization(CNV)in all eyes on Days 0,7,10,and 14.The mice were killed humanely 14 d after the alkali burn,and their corneas were removed and preserved at-80℃ until histological study or protein extraction.RESULTS:Molecular docking confirmed that emodin was able to target VEGFR2.The findings revealed that emodin decreased the invasion,migration,angiogenesis,and proliferation of HUVEC in a dose-dependent manner.In mice,emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali burn.Compared to those of the PBS-treated group,lower VEGFR2 expression and CD31 levels were found in the emodintreated group.Emodin dramatically decreased the expression of VEGFR2,p-VEGFR2,p-Akt,p-STAT3,and p-P38 in VEGF-treated HUVEC.CONCLUSION:This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization.Emodin might be a promising new therapeutic option for corneal alkali burns.
基金The study was approved by the Ethics Committee of the Second People's Hospital of Chengdu.
文摘BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.
文摘Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.
基金The Natural Science Foundation of Zhejiang Province,No.LQ23H050005The Scientific Research Project of Zhejiang Provincial Education Department,No.Y202250731 and No.Y202353130+1 种基金China Students’Innovation and Entrepreneurship Training Program,No.202310338044China Postdoctoral Science Foundation,No.2022M721720.
文摘In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,including bevacizumab,in treating patients with colorectal cancer(CRC).Through neutralization of vascular endothelial growth factor(VEGF),bevacizumab inhibits tumor angiogenesis,impairing neovascularization and thereby depriving the tumor of essential nutrients and oxygen.Conversely,PD-L1 binding to VEGF receptor 2 promotes angiogenesis,supporting tumor vasculature.The interplay between these pathways complicates the assessment of bevacizumab’s efficacy in cancer therapy,notably in CRC,where VEGF and PD-L1 significantly affect treatment response.This review examines metastatic CRC treatment strategies,focusing on bevacizumab’s mechanism of action and the role of PD-L1 in this therapeutic context.
文摘BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldwide.AIM To investigate the expression levels of serum vascular endothelial growth factor(VEGF)and interleukin(IL)-17 in patients with PHC and evaluate their diagnostic value while exploring their relationship with patients’clinical characteristics.METHODS The study included 50 patients with confirmed PHC who visited Wuhan Han-yang Hospital from January 2021 to January 2022,and 50 healthy individuals from the same period served as the control group.Serum VEGF and IL-17 levels in both groups were measured by Enzyme-Linked Immunosorbent Assay,and their diagnostic value was assessed using receiver operating characteristic(ROC)curves.Pearson correlation analysis was performed to examine the relationship between serum VEGF and IL-17 levels.Pathological data of the PHC patients were analyzed to determine the relationship between serum VEGF and IL-17 levels and pathological characteristics.RESULTS Serum VEGF and IL-17 levels were significantly higher in the study group com-pared to the control group(P<0.05).No significant association was observed between serum VEGF and IL-17 levels and gender,age,combined cirrhosis,tumor diameter,or degree of differentiation(P>0.05).However,there was a significant relationship between clinical TNM stage,tumor metastasis,and serum VEGF and IL-17 levels(P<0.05).Correlation analysis revealed a positive correlation between serum VEGF and IL-17(P<0.05).ROC analysis demonstrated that both serum VEGF and IL-17 had good diagnostic efficacy for PHC.CONCLUSION Serum VEGF and IL-17 levels were significantly higher in PHC patients compared to healthy individuals.Their levels were closely related to pathological features such as tumor metastasis and clinical TNM stage,and there was a significant positive correlation between VEGF and IL-17.These biomarkers may serve as valuable reference in-dicators for the early diagnosis and treatment guidance of PHC.
基金the Longyan First Affiliated Hospital of Fujian Medical University(approval No.202014).
文摘BACKGROUND Anti-vascular endothelial growth factor(anti-VEGF)therapy is critical for managing neovascular age-related macular degeneration(nAMD),but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes.AIM To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response.METHODS In this study,65 eyes of exudative AMD patients after anti-VEGF treatment for≥1 mo were observed using optical coherence tomography angiography.Patients were classified into non-responders(n=22)and responders(n=43).Logistic regression was used to determine independent risk factors for treatment response.A predictive model was created using the Akaike Information Criterion,and its performance was assessed with the area under the receiver operating characteristic curve,calibration curves,and decision curve analysis(DCA)with 500 bootstrap re-samples.RESULTS Multivariable logistic regression analysis identified the number of junction voxels[odds ratio=0.997,95%confidence interval(CI):0.993-0.999,P=0.010]as an independent predictor of positive anti-VEGF treatment outcomes.The predictive model incorporating the fractal dimension,number of junction voxels,and longest shortest path,achieved an area under the curve of 0.753(95%CI:0.622-0.873).Calibration curves confirmed a high agreement between predicted and actual outcomes,and DCA validated the model's clinical utility.CONCLUSION The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy,enhancing personalized treatment planning.
基金supported by Science and Technology Research Project of Jilin Provincial Department of Education,No.JJKH20220072KJ(to XL)Science and Technology Development Program of Jilin Province,No.20200201495JC(to YL)。
文摘The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).
文摘AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of conbercept.METHODS:This study included 72 PDR patients and 8 cataract patients as controls.PDR patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)performed.Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was studied.RESULTS:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all intervals.Liquid chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC samples.GO and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling pathways.PPI analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC groups.CONCLUSION:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with PDR.Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response,stress response,and cellular metabolism.
