查看更多>>摘要：Objective:Osteoarthritis(OA)is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation.This study aimed to investigate the anti-OA effect of scutellarein(SCU),a single-unit flavonoid compound obtained from Scutellaria barbata D.Don,in rats.Methods:The extracted rat chondrocytes were treated with SCU and IL-1β.The chondrocytes were divided into control group,IL-1β group,IL-1β+SCU 50 μmol/L group,and IL-1β+SCU 100 pmol/L group.Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining.CCK-8 method was used to detect the cytotoxicity of SCU.ELISA,qRT-PCR,Western blotting,immunofluorescence,SAβ-gal staining,flow cytometry,and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1β intervention.Additionally,anterior cruciate ligament transection(ACL-T)was used to establish a rat OA model.Histological changes were detected by safranin O/fast green,hematoxylin-eosin(HE)staining,and immunohistochemistry.Results:SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms.Specifically,it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation.In addition,SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase(NF-κB/MAPK)pathway,thereby reducing inflammatory cytokine production in the joint cartilage.Furthermore,SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes,further highlighting its potential role in OA treatment.In vivo experiments revealed that SCU(at a dose of 50 mg/kg)administered for 2 months could significantly delay the progression of cartilage damage,which was reflected in a lower Osteoarthritis Research Society International(OARSI)score,and reduced expression of matrix metalloproteinase 13(MMP13)in cartilage.Conclusion:SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.
查看更多>>摘要：Objective:Matrix metalloproteinase 13(MMP13)is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens,modifying protein structures and regulating inflammatory responses,but its role in deep vein thrombosis(DVT)has not been determined.The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT.Methods:We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT.After screening genes possibly related to MMP13 in DVT mice,the expression levels of candidate genes in human umbilical vein endothelial cells(HUVECs)and the venous wall were evaluated.The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro.Results:Among the differentially expressed genes,interleukin 1 beta,podoplanin(Pdpn),and factor Ⅷvon Willebrand factor(F8VWF)were selected for analysis in mice.When MMP13 was inhibited,the expression level of PDPN decreased significantly in vitro.In HUVECs,overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation,while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation.Conclusions:Inhibiting the expression of MMP13 could reduce the burden of DVT in mice.The mechanism involves downregulating the expression of Pdpn through MMP13,which could provide a novel gene target for DVT diagnosis and treatment.
查看更多>>摘要：Objective:A novel technique was explored using an airbag-selective portal vein blood arrester that circumvents the need for an intraoperative assessment of anatomical variations in patients with complex intrahepatic space-occupying lesions.Methods:Rabbits undergoing hepatectomy were randomly assigned to 4 groups:intermittent portal triad clamping(PTC),intermittent portal vein clamping(PVC),intermittent portal vein blocker with an airbag-selective portal vein blood arrester(APC),and without portal blood occlusion(control).Hepatic ischemia and reperfusion injury were assessed by measuring the 7-day survival rate,blood loss,liver function,hepatic pathology,hepatic inflammatory cytokine infiltration,hepatic malondialdehyde levels,and proliferating cell nuclear antigen levels.Results:Liver damage was substantially reduced in the APC and PVC groups.The APC animals exhibited transaminase levels similar to or less oxidative stress damage and inflammatory hepatocellular injury compared to those exhibited by the PVC animals.Bleeding was significantly higher in the control group than in the other groups.The APC group had less bleeding than the PVC group because of the avoidance of portal vein skeletonization during hepatectomy.Thus,more operative time was saved in the APC group than in the PVC group.Moreover,the total 7-day survival rate in the APC group was higher than that in the PTC group.Conclusion:Airbag-selective portal vein blood arresters may help protect against hepatic ischemia and reperfusion injury in rabbits undergoing partial hepatectomy.This technique may also help prevent liver damage in patients requiring hepatectomy.
查看更多>>摘要：Objective:The objective of this research was to explore the difference and correlation of the morphological and hemodynamic features between sidewall and bifurcation aneurysms in anterior circulation arteries,utilizing computational fluid dynamics as a tool for analysis.Methods:In line with the designated inclusion criteria,this study covered 160 aneurysms identified in 131 patients who received treatment at Union Hospital of Tongji Medical College,Huazhong University of Science and Technology,China,from January 2021 to September 2022.Utilizing follow-up digital subtraction angiography(DSA)data,these cases were classified into two distinct groups:the sidewall aneurysm group and the bifurcation aneurysm group.Morphological and hemodynamic parameters in the immediate preoperative period were meticulously calculated and examined in both groups using a three-dimensional DSA reconstruction model.Results:No significant differences were found in the morphological or hemodynamic parameters of bifurcation aneurysms at varied locations within the anterior circulation.However,pronounced differences were identified between sidewall and bifurcation aneurysms in terms of morphological parameters such as the diameter of the parent vessel(Dvessel),inflow angle(θF),and size ratio(SR),as well as the hemodynamic parameter of inflow concentration index(ICI)(P＜0.001).Notably,only the SR exhibited a significant correlation with multiple hemodynamic parameters(P＜0.001),while the ICI was closely related to several morphological parameters(R＞0.5,P＜0.001).Conclusions:The significant differences in certain morphological and hemodynamic parameters between sidewall and bifurcation aneurysms emphasize the importance to contemplate variances in threshold values for these parameters when evaluating the risk of rupture in anterior circulation aneurysms.Whether it is a bifurcation or sidewall aneurysm,these disparities should be considered.The morphological parameter SR has the potential to be a valuable clinical tool for promptly distinguishing the distinct rupture risks associated with sidewall and bifurcation aneurysms.
查看更多>>摘要：Objective:Complete resection of malignant gliomas is often challenging.Our previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the total removal of brain lesions.This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.Methods:A total of 64 patients diagnosed with malignant glioma(WHO grade Ⅲ and Ⅳ)who underwent surgery between 2012 and 2018 were included.Among them,29 patients received ICEUS.The effects of ICEUS on overall survival(OS)and progression-free survival(PFS)of patients were evaluated.A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.Results:The ICEUS group showed better survival rates both in OS and PFS than the control group.The univariate analysis revealed that age,pathology and ICEUS were significant prognostic factors for PFS,with only age being a significant prognostic factor for OS.In multivariate analysis,age and ICEUS were significant prognostic factors for both OS and PFS.The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.Conclusion:ICEUS facilitates the identification of residual tumors.Age and ICEUS are prognostic factors for malignant glioma surgery,and use of ICEUS offers a better prognosis for patients with malignant glioma.
查看更多>>摘要：Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women's health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression on β-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase in β-catenin and p-GSK-3β caused by the suppression of ZNF554.In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown.Additionally,when RBM5 was overexpressed,it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels.Conclusion:ZNF554 functions as a tumor suppressor in UCEC.Furthermore,ZNF554 regulates UCEC progression through the RBM5/WNT/β-catenin signaling pathway.ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.
查看更多>>摘要：Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl-channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T＞C(chr11:61722628,p.Y68H)and c.867+97G＞A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T＞C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G＞A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.
查看更多>>摘要：Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C＞A(p.Asn58Lys)and c.1538G＞T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.
查看更多>>摘要：Objective:Hemophilia carriers(HCs),who are heterozygous for mutations in the clotting factor Ⅷ/clotting factor Ⅸ gene(F8 or F9),may have a wide range of clotting factor levels,from very low,similar to afflicted males,to the upper limit of normal,and may experience mental health issues.The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs.Additionally,we aimed to investigate the mental health status of HCs in China.Methods:A total of 127 hemophilia mothers,including 93 hemophilia A(HA)mothers and 34 hemophilia B(HB)mothers,were enrolled in this study.Long distance PCR,multiplex PCR,and Sanger sequencing were used to analyze mutations in F8 or F9.Coagulation factor activity was detected by a one-stage clotting assay.The Symptom Checklist 90(SCL-90,China/Mandarin version)was given to HCs at the same time to assess their mental health.Results:A total of 90.6％of hemophilia mothers were diagnosed genetically as carriers,with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers,respectively.The median clotting factor level in carriers was 0.74 IU/mL(ranging from 0.09 to 1.74 IU/mL)compared with 1.49 IU/mL(ranging from 0.93 to 1.89 IU/mL)in noncarriers,of which 14.3％of HCs had clotting factor levels of 0.40 IU/mL or below.A total of 53.8％(7/13)of HA carriers with low clotting factor levels(less than 0.50 IU/mL)had a history of bleeding,while none of the HB carriers displayed a bleeding phenotype.The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00(±60.37)and 1.78(±0.59),respectively.A total of 67.7％of the respondents had psychological symptoms,with obsessive-compulsive disorder being the most prevalent and severe.The pooled estimates of all nine factors were significantly higher than those in the general population(P＜0.05).Conclusions:The detection rate of gene mutations in hemophilia mothers was 90.6％,with a median clotting factor level of 0.74 IU/mL,and 14.3％of HCs had a clotting factor level of 0.40 IU/mL or below.A history of bleeding was present in 41.2％of HCs with low clotting factor levels(less than 0.50 IU/mL).Additionally,given the fragile mental health status of HCs in China,it is critical to develop efficient strategies to improve psychological well-being.
查看更多>>摘要：Objective:This study aimed to explore the risk factors and outcomes of hypokalemia during the recovery period from anesthesia in the gynecological population.Methods:This retrospective cohort study included 208 patients who underwent gynecological surgery at our institution between January 2021 and March 2022.Data were collected for each patient,including demographics,disease status,surgical data,and clinical information.Preoperative bowel preparation,postoperative gastrointestinal function,and electrolyte levels were compared between the two groups using propensity score matching(PSM).Results:The incidence of hypokalemia(serum potassium level＜3.5 mmol/L)during the recovery period from anesthesia was approximately 43.75％.After PSM,oral laxative use(96.4％vs.82.4％,P=0.005),the number of general enemas(P=0.014),and the rate of＞2 general enemas(92.9％vs.77.8％,P=0.004)were identified as risk factors for hypokalemia,which was accompanied by decreased PaCO2 and hypocalcemia.There were no significant differences in postoperative gastrointestinal outcomes,such as the time to first flatus or feces,the Ⅰ-FEED score(a scoring system was created to evaluate impaired postoperative gastrointestinal function),or postoperative recovery outcomes,between the hypokalemia group and the normal serum potassium group.Conclusion:Hypokalemia during postanesthesia recovery period occurred in 43.75％of gynecological patients,which resulted from preoperative mechanical bowel preparation;however,it did not directly affect clinical outcomes,including postoperative gastrointestinal function,postoperative complications,and length of hospital stay.
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