Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial...Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.展开更多
BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the ...BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the efficacy of texture analysis based on multi-parametric magnetic resonance(MR)imaging(MRI)in predicting microvascular invasion(MVI)in preoperative HCC.METHODS This study included 105 patients with pathologically confirmed HCC,categorized into MVI-positive and MVI-negative groups.We employed Original Data Analysis,Principal Component Analysis,Linear Discriminant Analysis(LDA),and Non-LDA(NDA)for texture analysis using multi-parametric MR images to predict preoperative MVI.The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software,with results expressed as the misjudgment rate(MCR).RESULTS Texture analysis using multi-parametric MRI,particularly the MI+PA+F dimensionality reduction method combined with NDA discrimination,demonstrated the most effective prediction of MVI in HCC.Prediction accuracy in the pulse and equilibrium phases was 83.81%.MCRs for the combination of T2-weighted imaging(T2WI),arterial phase,portal venous phase,and equilibrium phase were 22.86%,16.19%,20.95%,and 20.95%,respectively.The area under the curve for predicting MVI positivity was 0.844,with a sensitivity of 77.19%and specificity of 91.67%.CONCLUSION Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI,portal venous,and equilibrium phases.This study provides an objective,non-invasive method for preoperative prediction of MVI,offering a theoretical foundation for the selection of clinical therapy.展开更多
The analysis of experimental data demonstrates that platelets and neutrophils are involved in the no-reflow phenomenon,also known as microvascular obstruction(MVO).However,studies performed in the isolated perfused he...The analysis of experimental data demonstrates that platelets and neutrophils are involved in the no-reflow phenomenon,also known as microvascular obstruction(MVO).However,studies performed in the isolated perfused hearts subjected to ischemia/reperfusion(I/R)do not suggest the involvement of microembolization and microthrombi in this phenomenon.The intracoronary administration of alteplase has been found to have no effect on the occurrence of MVO in patients with acute myocardial infarction.Consequently,the major events preceding the appearance of MVO in coronary arteries are independent of microthrombi,platelets,and neutrophils.Endothelial cells appear to be the target where ischemia can disrupt the endothelium-dependent vasodilation of coronary arteries.However,reperfusion triggers more pronounced damage,possibly mediated by pyroptosis.MVO and intra-myocardial hemorrhage contribute to the adverse post-infarction myocardial remodeling.Therefore,pharmacological agents used to treat MVO should prevent endothelial injury and induce relaxation of smooth muscles.Ischemic conditioning protocols have been shown to prevent MVO,with L-type Ca2+channel blockers appearing the most effective in treating MVO.展开更多
Hepatocellular carcinoma(HCC)is one of the most lethal tumors in the world.Liver resection(LR)and liver transplantation(LT)are widely considered as radical treatments for early HCC.However,the recurrence rates after c...Hepatocellular carcinoma(HCC)is one of the most lethal tumors in the world.Liver resection(LR)and liver transplantation(LT)are widely considered as radical treatments for early HCC.However,the recurrence rates after curative treatment are still high and overall survival is unsatisfactory.Microvascular invasion(MVI)is considered to be one of the important prognostic factors affecting postoperative recurrence and long-term survival.Unfortunately,whether HCC patients with MVI should receive postoperative adjuvant therapy remains unknown.In this review,we summarize the therapeutic effects of transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,tyrosine protein kinase inhibitor-based targeted therapy,and immune checkpoint inhibitors in patients with MVI after LR or LT,aiming to provide a reference for the best adjuvant treatment strategy for HCC patients with MVI after LT or LR.展开更多
AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulate...AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulated by HG for 48h to establish the in vitro cell model.Different concentrations of Api(2.5,5,and 10μmol/L)were applied for treatment.Cell counting kit-8(CCK-8),Transwell,and tube formation assays were performed to examine the effects of Api on the viability,migration,and angiogenesis in HG-induced HRMECs.Vascular permeability was evaluated by Evans blue dye.The inflammatory cytokines and oxidative stress-related factors were measured using their commercial kits.Protein expression of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)and p38 mitogen-activated protein kinase(MAPK)was measured by Western blot.RESULTS:Api prevented HG-induced HRMECs viability,migration,angiogenesis,and vascular permeability in a concentration-dependent manner.Meanwhile,Api also concentration-dependently inhibited inflammation and oxidative stress in HRMECs exposed to HG.In addition,HG caused an elevated expression of NOX4,which was retarded by Api treatment.HG stimulation facilitated the activation of p38 MAPK signaling in HRMECs,and Api could weaken this activation partly via downregulating NOX4 expression.Furthermore,overexpression of NOX4 or activation of p38 MAPK signaling greatly weakened the protective role of Api against HG-stimulated HRMECs.CONCLUSION:Api might exert a beneficial role in HGstimulated HRMECs through regulating NOX4/p38 MAPK pathway.展开更多
OBJECTIVE To investigate the regulatory effects of icariin(ICA)on cardiac micro⁃vascular endothelial cells(CMEC)after oxygenglucose deprivation reperfusion(OGD/R)injury.METHODS CMEC were subjected to OGD/R treatment t...OBJECTIVE To investigate the regulatory effects of icariin(ICA)on cardiac micro⁃vascular endothelial cells(CMEC)after oxygenglucose deprivation reperfusion(OGD/R)injury.METHODS CMEC were subjected to OGD/R treatment to construct a myocardial ischemiareperfusion model,and were divided into normal,model,low(10μmol·L^(-1)),medium(20μmol·L^(-1))and high(40μmol·L^(-1))ICA group,and high ICA+inhibitor group(40μmol·L^(-1)+20 nmol·L^(-1)).CCK-8 assay was used to assess the protective ability of ICA against CMEC,and cell migration assay and tube-formation assay were used to detect the migration and generation ability of CMEC.The TCMSP database,Swiss-Target database and literature mining methods were used to col⁃lect ICA-related targets,the GeneCards data⁃base was used to collect target genes related to myocardial ischemia/reperfusion,and Cytoscape 3.8.0 software was used to construct a"drug-tar⁃get-disease"network.The potential targets were imported into STRING 11.5 database to obtain the PPI network.GO and KEGG enrichment analyses were performed on the potential targets using the DAVID database.Molecular docking was performed using AutoDock-vina 1.1.2 soft⁃ware.Western blot detected the expression of related proteins.RESULTS After CMEC was subjected to OGD/R treatment,ICA had a protec⁃tive effect at 10^(-1)60μmol·L^(-1);the results of the cell migration assay showed that each group of ICA could promote the migratory effect of CMEC(P<0.01,P<0.01);and the results of tube-for⁃mation assay showed that each group of ICA could significantly promote the generation of branches(P<0.01)and the capillary length exten⁃sion(P<0.05).Network pharmacology collected a total of 23 ICA action targets,1500 disease tar⁃gets and 12 key targets.GO function enrichment analysis found 85 results.KEGG pathway enrich⁃ment analysis found 53 results,involving AGERAGE signaling pathway,sphingolipid signaling pathway and VEGF signaling pathway.Molecu⁃lar docking results showed that ICA had better binding with core targets PRKCB,PRKCA and PTGS2.Western blot results showed that ICA could regulate the expression of PRKCB,PRKCA and PTGS2 proteins.The results of cell migra⁃tion assay,tube-formation assay and protein expression were reversed after addition of PKC inhibitor.CONCLUSION The potential mecha⁃nism of action of ICA against myocardial isch⁃emia-reperfusion injury may be related to the reg⁃ulation of processes such as CMEC migration and angiogenesis,and it functions through the key target gene PKC.展开更多
Objective To investigate the impact of microvascular obstruction(MVO)on the global and regional myocardial function by cardiac magnetic resonance feature-tracking(CMR-FT)in ST-segment-elevation myocardial infarction(S...Objective To investigate the impact of microvascular obstruction(MVO)on the global and regional myocardial function by cardiac magnetic resonance feature-tracking(CMR-FT)in ST-segment-elevation myocardial infarction(STEMI)patients after percutaneous coronary intervention.Methods Consecutive acute STEMI patients who underwent cardiac magnetic resonance imaging 1-7 days after successful reperfusion by percutaneous coronary intervention treatment were included in this retrospective study.Based on the presence or absence of MVO on late gadolinium enhancement images,patients were divided into groups with MVO and without MVO.The infarct zone,adjacent zone,and remote zone were determined based on a myocardial 16-segment model.The radial strain(RS),circumferential strain(CS),and longitudinal strain(LS)of the global left ventricle(LV)and the infarct,adjacent,and remote zones were measured by CMRFT from cine images and compared between patients with and without MVO using independent-samples t-test.Logistic regression analysis was used to assess the association of MVO with the impaired LV function.Results A total of 157 STEMI patients(mean age 56.66±11.38 years)were enrolled.MVO was detected in 37.58%(59/157)of STEMI patients,and the mean size of MVO was 3.00±3.76 mL.Compared with patients without MVO(n=98),the MVO group had significantly reduced LV global RS(t=-4.30,P<0.001),global CS(t=4.99,P<0.001),and global LS(t=3.51,P=0.001).The RS and CS of the infarct zone in patients with MVO were significantly reduced(t=-3.38,P=0.001;t=2.64,P=0.01;respectively)and the infarct size was significantly larger(t=8.37,P<0.001)than that of patients without MVO.The presence of LV MVO[OR=4.10,95%CI:2.05-8.19,P<0.001]and its size[OR=1.38,95%CI:1.10-1.72,P=0.01],along with the heart rate and LV infarct size were significantly associated with impaired LV global CS in univariable Logistic regression analysis,while only heart rate(OR=1.08,95%CI:1.03-1.13,P=0.001)and LV infarct size(OR=1.10,95%CI:1.03-1.16,P=0.003)were independent influencing factors for the impaired LV global CS in multivariable Logistic regression analysis.Conclusion The infarct size was larger in STEMI patients with MVO,and MVO deteriorates the global and regional LV myocardial function.展开更多
AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the...AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the retinal tissue in diabetic rats.METHODS:The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot.LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities.Cell count kit-8(CCK-8),5-ethynyl2’-deoxyuridine(EdU),flow cytometry,scratch test,Transwell test and tube formation assay were used to examine the ability of cell proliferation,migration,and angiogenesis.Finally,a preliminary exploration of its mechanism was performed by Western blot.RESULTS:The expression of HDAC7 was both upregulated in retinal tissues of diabetic rats and high glucosetreated HRMECs.Down-regulation of HDAC7 expression significantly reduced the ability of proliferation,migration,and tube formation,and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs.CONCLUSION:High glucose can up-regulate the expression of HDAC7 in HRMECs.Down-regulation of HDAC7 can inhibit HRMECs activities.HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.展开更多
BACKGROUND Septic arthritis of the manubriosternal joint is a diagnostic challenge due to its rarity and anatomical characteristic.Conventional ultrasound,plain radiographs,and computed tomography are not able to conf...BACKGROUND Septic arthritis of the manubriosternal joint is a diagnostic challenge due to its rarity and anatomical characteristic.Conventional ultrasound,plain radiographs,and computed tomography are not able to confirm or even suspect arthritis early.Superb microvascular imaging is a new advanced Doppler technique in evaluating low-flow microvascular patterns.The higher sensitivity for increased perisynovial vascularity helps to suspect septic arthritis and forms a methodical approach to using magnetic resonance imaging(MRI).CASE SUMMARY A 34-year-old immunocompetent woman presented with a fever and a dull ache in the chest radiating to the right arm.Traumatic injury and the most common respiratory and cardiac disorders were ruled out.Blood cultures came back positive for Staphylococcus aureus,and sepsis was confirmed.A small lump was noted on the chest during the first week of hospitalization.Superb microvascular imaging was performed and septic arthritis of the manubriosternal joint was detected.MRI confirmed the diagnosis and showed septic arthritis of the manubriosternal joint with several localized abscesses behind the sternum.The patient was treated for three weeks with intravenous antibiotics and the outcome was favorable:Inflammatory markers became normal,and the lump disappeared.Three months later,the patient was examined for a new episode of mild pain in the sternum and was diagnosed with persistent perichondritis by ultrasound in comparison with MRI.CONCLUSION Superb microvascular imaging is a useful tool for the early diagnosis of septic arthritis of the manubriosternal joint and following-up.展开更多
BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study...BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and LMPI.AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study.The patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were collected.In order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was constructed.Diagnostic performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy.RESULTS There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of NF-PNETs.The area under the receiver value for the predictive performance of combined predictive factors was 0.855.The sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,respectively.CONCLUSION Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.展开更多
BACKGROUND Microvascular invasion(MVI)is an important predictor of poor prognosis in patients with hepatocellular carcinoma(HCC).Accurate preoperative prediction of MVI in HCC would provide useful information to guide...BACKGROUND Microvascular invasion(MVI)is an important predictor of poor prognosis in patients with hepatocellular carcinoma(HCC).Accurate preoperative prediction of MVI in HCC would provide useful information to guide the choice of therapeutic strategy.Shear wave elastography(SWE)plays an important role in hepatic imaging,but its value in the preoperative prediction of MVI in HCC has not yet been proven.AIM To explore the value of conventional ultrasound features and SWE in the preoperative prediction of MVI in HCC.METHODS Patients with a postoperative pathological diagnosis of HCC and a definite diagnosis of MVI were enrolled in this study.Conventional ultrasound features and SWE features such as maximal elasticity(Emax)of HCCs and Emax of the periphery of HCCs were acquired before surgery.These features were compared between MVI-positive HCCs and MVI-negative HCCs and between mild MVI HCCs and severe MVI HCCs.RESULTS This study included 86 MVI-negative HCCs and 102 MVI-positive HCCs,including 54 with mild MVI and 48 with severe MVI.Maximal tumor diameters,surrounding liver tissue,color Doppler flow,Emax of HCCs,and Emax of the periphery of HCCs were significantly different between MVI-positive HCCs and MVI-negative HCCs.In addition,Emax of the periphery of HCCs was significantly different between mild MVI HCCs and severe MVI HCCs.Higher Emax of the periphery of HCCs and larger maximal diameters were independent risk factors for MVI,with odds ratios of 2.820 and 1.021,respectively.CONCLUSION HCC size and stiffness of the periphery of HCC are useful ultrasound criteria for predicting positive MVI.Preoperative ultrasound and SWE can provide useful information for the prediction of MVI in HCCs.展开更多
BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angioge...BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastasis of liver tumors.展开更多
AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer(BCLC) early...AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer(BCLC) early(A) and intermediate(B) stage hepatocellular carcinoma(HCC) patients with microvascular invasion(MVI).METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival(RFS) and overall survival(OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/m L, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/m L, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/m L, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early-and intermediate-stage HCC patients with MVI.展开更多
AIM: To identify the hepatic vascular architecture of patients with hepatitis C virus(HCV) using superb microvascular imaging(SMI) and investigate the use of SMI in the evaluation of liver fibrosis.METHODS: SMI was pe...AIM: To identify the hepatic vascular architecture of patients with hepatitis C virus(HCV) using superb microvascular imaging(SMI) and investigate the use of SMI in the evaluation of liver fibrosis.METHODS: SMI was performed in 100 HCV patients. SMI images were classified into five types according to the vascular pattern, and these patterns were compared with the fibrosis stage. Moreover, the images were analyzed to examine vascularity by integrating the number of SMI signals in the region of interest ROI [number of vascular trees(VT)]. The number of VT, fibrosis stage, serum parameters of liver function, and CD34 expression were investigated.RESULTS: There was a significant difference between SMI distribution pattern and fibrosis stage(P < 0.001). The mean VT values in each of the fibrosis stages were as follows: 26.69 ± 7.08 in F0, 27.72 ± 9.32 in F1, 36.74 ± 9.23 in F2, 37.36 ± 5.32 in F3, and 58.14 ± 14.08 in F4. The VT showed excellent diagnostic ability for F4 [area under the receiver operator characteristic(AUROC): 0.911]. The VT was significantly correlated with the CD34 labeling index(r = 0.617, P < 0.0001).CONCLUSION: SMI permitted the detailed delineation of the vascular architecture in chronic liver disease. SMI appears to be a reliable tool for noninvasively detecting significant fibrosis or cirrhosis in HCV patients.展开更多
Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay k...Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay kit and dihydroethidine(DHE) staining were used to assess oxidative stress.TENEL staining and caspase 3 expression were used to assess the apoptosis of CMECs.H89 was used to inhibit eAMP/PKA pathway:fasudil was used to inhibit Rho/ROCK pathway.The protein expressions of Rho.ROCK uere examined by Western blol analysis.lesults:High glucose increased the production of ROS.the activity of NADPH.the apoptosis rate and the expression level of Rho/ROCK in CMECs.while GLP- 1 decreased high glucose-induced ROS production.the NADPH activity and the apoptosis rate and the expression level of Rho/ROCK in CMECs,the difference were statistically significant(P<0.05).Conclusions:GLP-1 could protect the cardiac microvessels against oxidative stress and apoptosis.The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-dependent manner,resulting in a subsequent decrease in the expression of NADPH oxidase.展开更多
Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotect...Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.展开更多
Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary micro...Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation,but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography(MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction,respectively,and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall,MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice,but the approval of regulatory authorities is lacking.展开更多
BACKGROUND Microvascular invasion(MVI)is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma(HCC)patients after hepatectomy and liver transplantation,but it can b...BACKGROUND Microvascular invasion(MVI)is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma(HCC)patients after hepatectomy and liver transplantation,but it can be determined only in surgical specimens.Accurate preoperative prediction of MVI is conducive to clinical decisions.AIM To develop and validate a preoperative prediction model for MVI in patients with HCC.METHODS Data from 454 patients with HCC who underwent hepatectomy at the First Affiliated Hospital of Nanjing Medical University between May 2016 and October 2019 were retrospectively collected.Then,the patients were nonrandomly split into a training cohort and a validation cohort.Logistic regression analysis was used to identify variables significantly associated with MVI that were then included in the nomogram.We evaluated the discrimination and calibration ability of the nomogram by using R software.RESULTS MVI was confirmed in 209(46.0%)patients by a pathological examination.Multivariate logistic regression analysis identified four risk factors independently associated with MVI:Tumor size[odds ratio(OR)=1.195;95%confidence interval(CI):1.107–1.290;P<0.001],number of tumors(OR=4.441;95%CI:2.112–9.341;P<0.001),neutrophils(OR=1.714;95%CI:1.036–2.836;P=0.036),and serumα-fetoprotein(20–400 ng/mL,OR=1.955;95%CI:1.055–3.624;P=0.033;>400 ng/mL,OR=3.476;95%CI:1.950–6.195;P<0.001).The concordance index was 0.79(95%CI:0.74–0.84)and 0.81(95%CI:0.74–0.89)in the training and validation cohorts,respectively.The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes.CONCLUSION We have developed and validated a preoperative prediction model for MVI in patients with HCC.The model could aid physicians in clinical treatment decision making.展开更多
The aim of this research was to study the clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus(T2DM).We analyzed the clinical data from 1421 T2DM inpatients at Wuhan U...The aim of this research was to study the clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus(T2DM).We analyzed the clinical data from 1421 T2DM inpatients at Wuhan Union Hospital.Subjects were divided into early-onset T2DM group(diagnostic age<40 years)and late-onset T2DM group(diagnostic age>40 years).All subjects underwent a standardized assessment of microvascular complications.Data were compared with independent-samples t test or Chi-square test.Multiple logistic regression was used to determine the risk factors of microvascular complications.Patients with early-onset T2DM were more inclined to have a lower systolic blood pressure(SBP),a longer duration of diabetes and higher levels of body mass index(BM1),uric acid(UA),fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG)and glycosylated hemoglobin(HbAlc)than those with lateonset T2DM(P<0.05).The prevalence of diabetic retinopathy(DR)was significantly higher and that of diabetic peripheral neuropathy(DPN)was significantly lower in early-onset group than in late-onset group(P<0.05).For DN,UA was an independent risk factor in early-onset T2DM.SBP and TG were independent risk factors in late-onset T2DM.For DR,duration of diabetes and SBP were independent risk factors in early-onset T2DM.Duration of diabetes,SBP and HbAlc were independent risk factors in late-onset T2DM.This study demonstrated that the clinical characteristics of early-onset T2DM were metabolic disorders,including glucose metabolism,lipid metabolism and amino acid metabolism.Early-onset T2DM was more likely to be associated with DR.The potential pathogenesis of early and late-onset T2DM might be different.The management of metabolic risk factors especially HbA1c,SBP,TG and UA is advised to be performed in the early stage of diabetes.展开更多
Diabetic complications including diabetic nephropathy,retinopathy,and neuropathy are as major causes of morbidity and mortality in diabetes individuals worldwide and current therapies are still unsatisfactory.One of t...Diabetic complications including diabetic nephropathy,retinopathy,and neuropathy are as major causes of morbidity and mortality in diabetes individuals worldwide and current therapies are still unsatisfactory.One of the reasons for failure to develop effective treatment is the lack of fundamental understanding for underlying mechanisms.Genetic studies are powerful tools to dissect disease mechanism.The heritability(h2) was estimated to be 0.3-0.44 for diabetic nephropathy and 0.25-0.50 for diabetic retinopathy respectively.Previous linkage studies for diabetic nephropathy have identified overlapped linkage regions in 1q43-44,3q21-23,3q26,10p12-15,18q22-23,19q13,22q11-12.3 in multiple ethnic groups.Genome-wide association studies(GWAS) of diabetic nephropathy have been conducted in several populations.However,most of the identified risk loci could not be replicated by independent studies with a few exceptions including those in ELMO1,FRMD3,CARS,MYO16/IRS2,and APOL3-MYH9 genes.Functional studies of these genes revealed the involvement of cytoskeleton reorganization(especially non-muscle type myosin),phagocytosis of apoptotic cells,fibroblast migration,insulin signaling,and epithelial clonal expansion in the pathogenesis of diabetic nephropathy.Linkage analyses of diabetic retinopathy overlapped only in 1q36 region and current results from GWAS for diabetic retinopathy are inconsistent.Conclusive results from genetic studies for diabetic neuropathy are lacking.For now,small sample sizes,confounding by population stratification,different phenotype definitions between studies,ethnic-specific associations,the influence of environmental factors,and the possible contribution of rare variants may explain the inconsistencies between studies.展开更多
基金Program of Natural Science Foundation of Shanghai,Grant/Award Number:21ZR1453800 and 22ZR1452400Program of National Natural Science Foundation of China,Grant/Award Number:82370057+3 种基金Fundamental Research Funds for the Central Universities,Grant/Award Number:22120220562Program of Shanghai Municipal Health Commission,Grant/Award Number:20204Y0384Program of National Key Research and Development Project of China,Grant/Award Number:2023YFC2509500。
文摘Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.
基金Supported by National Natural Science Foundation of China,No.81560278the Health Commission of Guangxi Zhuang Autonomous Region,No.Z-A20221157,No.Z20200953,and No.G201903023.
文摘BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the efficacy of texture analysis based on multi-parametric magnetic resonance(MR)imaging(MRI)in predicting microvascular invasion(MVI)in preoperative HCC.METHODS This study included 105 patients with pathologically confirmed HCC,categorized into MVI-positive and MVI-negative groups.We employed Original Data Analysis,Principal Component Analysis,Linear Discriminant Analysis(LDA),and Non-LDA(NDA)for texture analysis using multi-parametric MR images to predict preoperative MVI.The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software,with results expressed as the misjudgment rate(MCR).RESULTS Texture analysis using multi-parametric MRI,particularly the MI+PA+F dimensionality reduction method combined with NDA discrimination,demonstrated the most effective prediction of MVI in HCC.Prediction accuracy in the pulse and equilibrium phases was 83.81%.MCRs for the combination of T2-weighted imaging(T2WI),arterial phase,portal venous phase,and equilibrium phase were 22.86%,16.19%,20.95%,and 20.95%,respectively.The area under the curve for predicting MVI positivity was 0.844,with a sensitivity of 77.19%and specificity of 91.67%.CONCLUSION Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI,portal venous,and equilibrium phases.This study provides an objective,non-invasive method for preoperative prediction of MVI,offering a theoretical foundation for the selection of clinical therapy.
基金supported by the Russian Science Foundation(Grant No.23-65-10017)The mini-chapter on treatment of MVO was supported by state assignment 122020300042-4.
文摘The analysis of experimental data demonstrates that platelets and neutrophils are involved in the no-reflow phenomenon,also known as microvascular obstruction(MVO).However,studies performed in the isolated perfused hearts subjected to ischemia/reperfusion(I/R)do not suggest the involvement of microembolization and microthrombi in this phenomenon.The intracoronary administration of alteplase has been found to have no effect on the occurrence of MVO in patients with acute myocardial infarction.Consequently,the major events preceding the appearance of MVO in coronary arteries are independent of microthrombi,platelets,and neutrophils.Endothelial cells appear to be the target where ischemia can disrupt the endothelium-dependent vasodilation of coronary arteries.However,reperfusion triggers more pronounced damage,possibly mediated by pyroptosis.MVO and intra-myocardial hemorrhage contribute to the adverse post-infarction myocardial remodeling.Therefore,pharmacological agents used to treat MVO should prevent endothelial injury and induce relaxation of smooth muscles.Ischemic conditioning protocols have been shown to prevent MVO,with L-type Ca2+channel blockers appearing the most effective in treating MVO.
基金Supported by the National Natural Science Foundation of China,No.81902839.
文摘Hepatocellular carcinoma(HCC)is one of the most lethal tumors in the world.Liver resection(LR)and liver transplantation(LT)are widely considered as radical treatments for early HCC.However,the recurrence rates after curative treatment are still high and overall survival is unsatisfactory.Microvascular invasion(MVI)is considered to be one of the important prognostic factors affecting postoperative recurrence and long-term survival.Unfortunately,whether HCC patients with MVI should receive postoperative adjuvant therapy remains unknown.In this review,we summarize the therapeutic effects of transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,tyrosine protein kinase inhibitor-based targeted therapy,and immune checkpoint inhibitors in patients with MVI after LR or LT,aiming to provide a reference for the best adjuvant treatment strategy for HCC patients with MVI after LT or LR.
文摘AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulated by HG for 48h to establish the in vitro cell model.Different concentrations of Api(2.5,5,and 10μmol/L)were applied for treatment.Cell counting kit-8(CCK-8),Transwell,and tube formation assays were performed to examine the effects of Api on the viability,migration,and angiogenesis in HG-induced HRMECs.Vascular permeability was evaluated by Evans blue dye.The inflammatory cytokines and oxidative stress-related factors were measured using their commercial kits.Protein expression of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)and p38 mitogen-activated protein kinase(MAPK)was measured by Western blot.RESULTS:Api prevented HG-induced HRMECs viability,migration,angiogenesis,and vascular permeability in a concentration-dependent manner.Meanwhile,Api also concentration-dependently inhibited inflammation and oxidative stress in HRMECs exposed to HG.In addition,HG caused an elevated expression of NOX4,which was retarded by Api treatment.HG stimulation facilitated the activation of p38 MAPK signaling in HRMECs,and Api could weaken this activation partly via downregulating NOX4 expression.Furthermore,overexpression of NOX4 or activation of p38 MAPK signaling greatly weakened the protective role of Api against HG-stimulated HRMECs.CONCLUSION:Api might exert a beneficial role in HGstimulated HRMECs through regulating NOX4/p38 MAPK pathway.
基金National Natural Science Foundation of China(82030124)National Natural Science Foundation of China(82174015)Science and Technology Innovation Project of China Academy of Traditional Chinese Medicine(CI2021A04609)。
文摘OBJECTIVE To investigate the regulatory effects of icariin(ICA)on cardiac micro⁃vascular endothelial cells(CMEC)after oxygenglucose deprivation reperfusion(OGD/R)injury.METHODS CMEC were subjected to OGD/R treatment to construct a myocardial ischemiareperfusion model,and were divided into normal,model,low(10μmol·L^(-1)),medium(20μmol·L^(-1))and high(40μmol·L^(-1))ICA group,and high ICA+inhibitor group(40μmol·L^(-1)+20 nmol·L^(-1)).CCK-8 assay was used to assess the protective ability of ICA against CMEC,and cell migration assay and tube-formation assay were used to detect the migration and generation ability of CMEC.The TCMSP database,Swiss-Target database and literature mining methods were used to col⁃lect ICA-related targets,the GeneCards data⁃base was used to collect target genes related to myocardial ischemia/reperfusion,and Cytoscape 3.8.0 software was used to construct a"drug-tar⁃get-disease"network.The potential targets were imported into STRING 11.5 database to obtain the PPI network.GO and KEGG enrichment analyses were performed on the potential targets using the DAVID database.Molecular docking was performed using AutoDock-vina 1.1.2 soft⁃ware.Western blot detected the expression of related proteins.RESULTS After CMEC was subjected to OGD/R treatment,ICA had a protec⁃tive effect at 10^(-1)60μmol·L^(-1);the results of the cell migration assay showed that each group of ICA could promote the migratory effect of CMEC(P<0.01,P<0.01);and the results of tube-for⁃mation assay showed that each group of ICA could significantly promote the generation of branches(P<0.01)and the capillary length exten⁃sion(P<0.05).Network pharmacology collected a total of 23 ICA action targets,1500 disease tar⁃gets and 12 key targets.GO function enrichment analysis found 85 results.KEGG pathway enrich⁃ment analysis found 53 results,involving AGERAGE signaling pathway,sphingolipid signaling pathway and VEGF signaling pathway.Molecu⁃lar docking results showed that ICA had better binding with core targets PRKCB,PRKCA and PTGS2.Western blot results showed that ICA could regulate the expression of PRKCB,PRKCA and PTGS2 proteins.The results of cell migra⁃tion assay,tube-formation assay and protein expression were reversed after addition of PKC inhibitor.CONCLUSION The potential mecha⁃nism of action of ICA against myocardial isch⁃emia-reperfusion injury may be related to the reg⁃ulation of processes such as CMEC migration and angiogenesis,and it functions through the key target gene PKC.
文摘Objective To investigate the impact of microvascular obstruction(MVO)on the global and regional myocardial function by cardiac magnetic resonance feature-tracking(CMR-FT)in ST-segment-elevation myocardial infarction(STEMI)patients after percutaneous coronary intervention.Methods Consecutive acute STEMI patients who underwent cardiac magnetic resonance imaging 1-7 days after successful reperfusion by percutaneous coronary intervention treatment were included in this retrospective study.Based on the presence or absence of MVO on late gadolinium enhancement images,patients were divided into groups with MVO and without MVO.The infarct zone,adjacent zone,and remote zone were determined based on a myocardial 16-segment model.The radial strain(RS),circumferential strain(CS),and longitudinal strain(LS)of the global left ventricle(LV)and the infarct,adjacent,and remote zones were measured by CMRFT from cine images and compared between patients with and without MVO using independent-samples t-test.Logistic regression analysis was used to assess the association of MVO with the impaired LV function.Results A total of 157 STEMI patients(mean age 56.66±11.38 years)were enrolled.MVO was detected in 37.58%(59/157)of STEMI patients,and the mean size of MVO was 3.00±3.76 mL.Compared with patients without MVO(n=98),the MVO group had significantly reduced LV global RS(t=-4.30,P<0.001),global CS(t=4.99,P<0.001),and global LS(t=3.51,P=0.001).The RS and CS of the infarct zone in patients with MVO were significantly reduced(t=-3.38,P=0.001;t=2.64,P=0.01;respectively)and the infarct size was significantly larger(t=8.37,P<0.001)than that of patients without MVO.The presence of LV MVO[OR=4.10,95%CI:2.05-8.19,P<0.001]and its size[OR=1.38,95%CI:1.10-1.72,P=0.01],along with the heart rate and LV infarct size were significantly associated with impaired LV global CS in univariable Logistic regression analysis,while only heart rate(OR=1.08,95%CI:1.03-1.13,P=0.001)and LV infarct size(OR=1.10,95%CI:1.03-1.16,P=0.003)were independent influencing factors for the impaired LV global CS in multivariable Logistic regression analysis.Conclusion The infarct size was larger in STEMI patients with MVO,and MVO deteriorates the global and regional LV myocardial function.
基金Supported by the Shaanxi Province Traditional Chinese Medicine Project(No.SZY-KJCYC-2023-028)。
文摘AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the retinal tissue in diabetic rats.METHODS:The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot.LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities.Cell count kit-8(CCK-8),5-ethynyl2’-deoxyuridine(EdU),flow cytometry,scratch test,Transwell test and tube formation assay were used to examine the ability of cell proliferation,migration,and angiogenesis.Finally,a preliminary exploration of its mechanism was performed by Western blot.RESULTS:The expression of HDAC7 was both upregulated in retinal tissues of diabetic rats and high glucosetreated HRMECs.Down-regulation of HDAC7 expression significantly reduced the ability of proliferation,migration,and tube formation,and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs.CONCLUSION:High glucose can up-regulate the expression of HDAC7 in HRMECs.Down-regulation of HDAC7 can inhibit HRMECs activities.HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.
文摘BACKGROUND Septic arthritis of the manubriosternal joint is a diagnostic challenge due to its rarity and anatomical characteristic.Conventional ultrasound,plain radiographs,and computed tomography are not able to confirm or even suspect arthritis early.Superb microvascular imaging is a new advanced Doppler technique in evaluating low-flow microvascular patterns.The higher sensitivity for increased perisynovial vascularity helps to suspect septic arthritis and forms a methodical approach to using magnetic resonance imaging(MRI).CASE SUMMARY A 34-year-old immunocompetent woman presented with a fever and a dull ache in the chest radiating to the right arm.Traumatic injury and the most common respiratory and cardiac disorders were ruled out.Blood cultures came back positive for Staphylococcus aureus,and sepsis was confirmed.A small lump was noted on the chest during the first week of hospitalization.Superb microvascular imaging was performed and septic arthritis of the manubriosternal joint was detected.MRI confirmed the diagnosis and showed septic arthritis of the manubriosternal joint with several localized abscesses behind the sternum.The patient was treated for three weeks with intravenous antibiotics and the outcome was favorable:Inflammatory markers became normal,and the lump disappeared.Three months later,the patient was examined for a new episode of mild pain in the sternum and was diagnosed with persistent perichondritis by ultrasound in comparison with MRI.CONCLUSION Superb microvascular imaging is a useful tool for the early diagnosis of septic arthritis of the manubriosternal joint and following-up.
基金Supported by Beijing Hospitals Authority Youth Program,No.QML20231103.
文摘BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and LMPI.AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study.The patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were collected.In order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was constructed.Diagnostic performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy.RESULTS There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of NF-PNETs.The area under the receiver value for the predictive performance of combined predictive factors was 0.855.The sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,respectively.CONCLUSION Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.
基金Supported by the Key Program of Science and Technology Commission Foundation of Changning,No.CNKW2022Y61.
文摘BACKGROUND Microvascular invasion(MVI)is an important predictor of poor prognosis in patients with hepatocellular carcinoma(HCC).Accurate preoperative prediction of MVI in HCC would provide useful information to guide the choice of therapeutic strategy.Shear wave elastography(SWE)plays an important role in hepatic imaging,but its value in the preoperative prediction of MVI in HCC has not yet been proven.AIM To explore the value of conventional ultrasound features and SWE in the preoperative prediction of MVI in HCC.METHODS Patients with a postoperative pathological diagnosis of HCC and a definite diagnosis of MVI were enrolled in this study.Conventional ultrasound features and SWE features such as maximal elasticity(Emax)of HCCs and Emax of the periphery of HCCs were acquired before surgery.These features were compared between MVI-positive HCCs and MVI-negative HCCs and between mild MVI HCCs and severe MVI HCCs.RESULTS This study included 86 MVI-negative HCCs and 102 MVI-positive HCCs,including 54 with mild MVI and 48 with severe MVI.Maximal tumor diameters,surrounding liver tissue,color Doppler flow,Emax of HCCs,and Emax of the periphery of HCCs were significantly different between MVI-positive HCCs and MVI-negative HCCs.In addition,Emax of the periphery of HCCs was significantly different between mild MVI HCCs and severe MVI HCCs.Higher Emax of the periphery of HCCs and larger maximal diameters were independent risk factors for MVI,with odds ratios of 2.820 and 1.021,respectively.CONCLUSION HCC size and stiffness of the periphery of HCC are useful ultrasound criteria for predicting positive MVI.Preoperative ultrasound and SWE can provide useful information for the prediction of MVI in HCCs.
基金This study was supported in part by grant from the KeyProject Foundation of Medical Sciences of Jiangsu province(RC2003100)
文摘BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastasis of liver tumors.
基金Supported by Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor,Ministry of Education,No.GKZ201604Key Project of Guangxi Health and Family Planning Commission,China,No.S201513Key Project of Guangxi Science and Technology Department,China,No.Gui Ke AB16380242
文摘AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer(BCLC) early(A) and intermediate(B) stage hepatocellular carcinoma(HCC) patients with microvascular invasion(MVI).METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival(RFS) and overall survival(OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/m L, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/m L, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/m L, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early-and intermediate-stage HCC patients with MVI.
文摘AIM: To identify the hepatic vascular architecture of patients with hepatitis C virus(HCV) using superb microvascular imaging(SMI) and investigate the use of SMI in the evaluation of liver fibrosis.METHODS: SMI was performed in 100 HCV patients. SMI images were classified into five types according to the vascular pattern, and these patterns were compared with the fibrosis stage. Moreover, the images were analyzed to examine vascularity by integrating the number of SMI signals in the region of interest ROI [number of vascular trees(VT)]. The number of VT, fibrosis stage, serum parameters of liver function, and CD34 expression were investigated.RESULTS: There was a significant difference between SMI distribution pattern and fibrosis stage(P < 0.001). The mean VT values in each of the fibrosis stages were as follows: 26.69 ± 7.08 in F0, 27.72 ± 9.32 in F1, 36.74 ± 9.23 in F2, 37.36 ± 5.32 in F3, and 58.14 ± 14.08 in F4. The VT showed excellent diagnostic ability for F4 [area under the receiver operator characteristic(AUROC): 0.911]. The VT was significantly correlated with the CD34 labeling index(r = 0.617, P < 0.0001).CONCLUSION: SMI permitted the detailed delineation of the vascular architecture in chronic liver disease. SMI appears to be a reliable tool for noninvasively detecting significant fibrosis or cirrhosis in HCV patients.
基金supported by Shanghai Municipal Health Bureau Youth Subject(NO.20134y116)
文摘Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay kit and dihydroethidine(DHE) staining were used to assess oxidative stress.TENEL staining and caspase 3 expression were used to assess the apoptosis of CMECs.H89 was used to inhibit eAMP/PKA pathway:fasudil was used to inhibit Rho/ROCK pathway.The protein expressions of Rho.ROCK uere examined by Western blol analysis.lesults:High glucose increased the production of ROS.the activity of NADPH.the apoptosis rate and the expression level of Rho/ROCK in CMECs.while GLP- 1 decreased high glucose-induced ROS production.the NADPH activity and the apoptosis rate and the expression level of Rho/ROCK in CMECs,the difference were statistically significant(P<0.05).Conclusions:GLP-1 could protect the cardiac microvessels against oxidative stress and apoptosis.The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-dependent manner,resulting in a subsequent decrease in the expression of NADPH oxidase.
基金supported in part by the National Natural Science Foundation of China,No.81573644(to LMH),81573733(to SWX)the Tianjin 131 Innovative Team Project,China(to HW)+5 种基金the National Major Science and Technology Project of China,No.2012ZX09101201-004(to SWX)the Science and Technology Plan Project of Tianjin of China,No.16PTSYJC00120(to LMH)the Applied Foundation and Frontier Technology Research Program of Tianjin of China(General Project),No.14JCYBJC28900(to SXW)the National International Science and Technology Cooperation Project of China,No.2015DFA30430(to HW)the Key Program of the Natural Science Foundation of Tianjin of China,No.16ICZDJC36300(to HW)the Scientific Research and Technology Development Plan Project of Guangxi Zhuang Autonomous Region of China,No.14125008-2-5(to SXW)
文摘Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.
文摘Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation,but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography(MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction,respectively,and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall,MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice,but the approval of regulatory authorities is lacking.
基金the National Natural Science Foundation of China,No.81672100the Key Laboratory for Laboratory Medicine of Jiangsu Province of China,No.ZDXKB2016005.
文摘BACKGROUND Microvascular invasion(MVI)is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma(HCC)patients after hepatectomy and liver transplantation,but it can be determined only in surgical specimens.Accurate preoperative prediction of MVI is conducive to clinical decisions.AIM To develop and validate a preoperative prediction model for MVI in patients with HCC.METHODS Data from 454 patients with HCC who underwent hepatectomy at the First Affiliated Hospital of Nanjing Medical University between May 2016 and October 2019 were retrospectively collected.Then,the patients were nonrandomly split into a training cohort and a validation cohort.Logistic regression analysis was used to identify variables significantly associated with MVI that were then included in the nomogram.We evaluated the discrimination and calibration ability of the nomogram by using R software.RESULTS MVI was confirmed in 209(46.0%)patients by a pathological examination.Multivariate logistic regression analysis identified four risk factors independently associated with MVI:Tumor size[odds ratio(OR)=1.195;95%confidence interval(CI):1.107–1.290;P<0.001],number of tumors(OR=4.441;95%CI:2.112–9.341;P<0.001),neutrophils(OR=1.714;95%CI:1.036–2.836;P=0.036),and serumα-fetoprotein(20–400 ng/mL,OR=1.955;95%CI:1.055–3.624;P=0.033;>400 ng/mL,OR=3.476;95%CI:1.950–6.195;P<0.001).The concordance index was 0.79(95%CI:0.74–0.84)and 0.81(95%CI:0.74–0.89)in the training and validation cohorts,respectively.The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes.CONCLUSION We have developed and validated a preoperative prediction model for MVI in patients with HCC.The model could aid physicians in clinical treatment decision making.
文摘The aim of this research was to study the clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus(T2DM).We analyzed the clinical data from 1421 T2DM inpatients at Wuhan Union Hospital.Subjects were divided into early-onset T2DM group(diagnostic age<40 years)and late-onset T2DM group(diagnostic age>40 years).All subjects underwent a standardized assessment of microvascular complications.Data were compared with independent-samples t test or Chi-square test.Multiple logistic regression was used to determine the risk factors of microvascular complications.Patients with early-onset T2DM were more inclined to have a lower systolic blood pressure(SBP),a longer duration of diabetes and higher levels of body mass index(BM1),uric acid(UA),fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG)and glycosylated hemoglobin(HbAlc)than those with lateonset T2DM(P<0.05).The prevalence of diabetic retinopathy(DR)was significantly higher and that of diabetic peripheral neuropathy(DPN)was significantly lower in early-onset group than in late-onset group(P<0.05).For DN,UA was an independent risk factor in early-onset T2DM.SBP and TG were independent risk factors in late-onset T2DM.For DR,duration of diabetes and SBP were independent risk factors in early-onset T2DM.Duration of diabetes,SBP and HbAlc were independent risk factors in late-onset T2DM.This study demonstrated that the clinical characteristics of early-onset T2DM were metabolic disorders,including glucose metabolism,lipid metabolism and amino acid metabolism.Early-onset T2DM was more likely to be associated with DR.The potential pathogenesis of early and late-onset T2DM might be different.The management of metabolic risk factors especially HbA1c,SBP,TG and UA is advised to be performed in the early stage of diabetes.
文摘Diabetic complications including diabetic nephropathy,retinopathy,and neuropathy are as major causes of morbidity and mortality in diabetes individuals worldwide and current therapies are still unsatisfactory.One of the reasons for failure to develop effective treatment is the lack of fundamental understanding for underlying mechanisms.Genetic studies are powerful tools to dissect disease mechanism.The heritability(h2) was estimated to be 0.3-0.44 for diabetic nephropathy and 0.25-0.50 for diabetic retinopathy respectively.Previous linkage studies for diabetic nephropathy have identified overlapped linkage regions in 1q43-44,3q21-23,3q26,10p12-15,18q22-23,19q13,22q11-12.3 in multiple ethnic groups.Genome-wide association studies(GWAS) of diabetic nephropathy have been conducted in several populations.However,most of the identified risk loci could not be replicated by independent studies with a few exceptions including those in ELMO1,FRMD3,CARS,MYO16/IRS2,and APOL3-MYH9 genes.Functional studies of these genes revealed the involvement of cytoskeleton reorganization(especially non-muscle type myosin),phagocytosis of apoptotic cells,fibroblast migration,insulin signaling,and epithelial clonal expansion in the pathogenesis of diabetic nephropathy.Linkage analyses of diabetic retinopathy overlapped only in 1q36 region and current results from GWAS for diabetic retinopathy are inconsistent.Conclusive results from genetic studies for diabetic neuropathy are lacking.For now,small sample sizes,confounding by population stratification,different phenotype definitions between studies,ethnic-specific associations,the influence of environmental factors,and the possible contribution of rare variants may explain the inconsistencies between studies.
