Objective To explore the antimicrobial activity of the bacteriocin(tentatively named garvicin LG6)se-creted by Lactococcus garvieae(L.garvieae)SHAMU-LG6 against Staphylococcus aureus(S.aureus)of different hemolytic phenotypes.Methods S.aureus isolated from clinical patients in a hospital of Anhui from 2021 to 2023 were collected.The hemolytic phenotypes of S.aureus were detected by three-point inoculation method.S.aureus of different hemolytic phenotypes were further categorized into methicillin-sensitive S.aureus(MSSA)and methi-cillin-resistant S.aureus(MRSA)according to antimicrobial susceptibility testing results.The antagonistic activity of L.garvieae SHAMU-LG6 against S.aureus of different hemolytic phenotypes was assayed by Oxford cup me-thod.The whole-genome sequencing of L.garvieae SHAMU-LG6 was performed.Biosynthetic gene cluster of gar-vicin LG6 was searched by online databases antiSMASH 7.0 and BAGEL4.Through macroporous resin adsorption,ethanol gradient elution,rotary evaporation,and dried material reconstitution,antimicrobial activity of garvicin LG6 crude extract against S.aureus was detected by the inhibitory testing of Oxford cup method.Results L.garvieae SHAMU-LG6 could significantly antagonize MSSA and MRSA of different hemolytic phenotypes.Biosynthetic gene cluster of garvicin LG6 was present on the chromosomal genome of L.garvieae SHAMU-LG6.The antimicrobial activity of garvicin LG6 secreted by a single colony or 6 mL fermentation fluid of L.garvieae SHAMU-LG6 were at least equal to that of antibiotic disc of 30 pg cefoxitin.Conclusion Garvicin LG6 can efficiently kill MSSA and MR-SA of different hemolytic phenotypes,and has the potential to be developed into a novel antimicrobial agent,which has great prospects for clinical application.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

AIM To explore the protective mechanism of Tangzhiqing Decoction on cognitive function in diabetic mice.METHODS Male C57BL/6 mice were randomly divided into blank group,model group,Tangzhiqing Decoction group,no-load virus group,lncRNA Pvt1 knock-down group,Tangzhiqing Decoction+lncRNA Pvt1 knock-down group.The lncRNA Pvt1 knock-down group and Tangzhiqing Decoction+lncRNA Pvt1 knock-down group were injected with lncRNA Pvt1 knock-down virus in the lateral ventricle,and the Tangzhiqing Decoction group and Tangzhiqing Decoction+lncRNA Pvt1 knock-down group were given 12 g/kg Tangzhiqing Decoction by gavage for 12 weeks.The cognitive function of mice was detected after administration.Nissl staining was used to observe the damage of hippocampal neurons.TUNEL staining was used to detect the degree of neuronal apoptosis in CA1 area of hippocampus.Western blot was used to detect the protein expressions of Atg16L1,SQSTM1/P62,Beclin1 and LC3 in hippocampus.RT-qPCR method was used to detect the expressions of lncRNA Pvt1 and Beclin1,P62 and LC3 mRNA in hippocampus.RESULTS Compared with the blank group,the blood sugar in the model group increased(P＜0.01)and the body weight decreased(P＜0.01).The escape latency was prolonged(P＜0.01),and the times of crossing the platform and the ratio of staying time in the target quadrant were decreased(P＜0.01).The volume of neurons in CA1 area of hippocampus decreased,the number of Nissl bodies decreased and the apoptosis rate of neurons increased(P＜0.01).The expressions of Atg16L1,Beclin1 and LC3Ⅱ/Ⅰ proteins,lncRNA Pvt1 and Beclin1 and LC3 mRNA in hippocampus decreased(P＜0.05,P＜0.01),while the expressions of P62 protein and mRNA increased(P＜0.05,P＜0.01).Compared with the model group,the improvement of blood sugar in Tangzhiqing Decoction group decreased(P＜0.01)and the body weight increased(P＜0.01).The escape latency was shortened(P＜0.01),and the crossing platform times and the ratio of staying time in target quadrant were increased(P＜0.05).The structure and morphology of neurons in CA1 area of hippocampus were normal,the nucleus was obvious,Nissl bodies were abundant,and the apoptosis rate of neurons decreased(P＜0.01).The expressions of Atg16L1,Beclin1,LC3 Ⅱ/Ⅰ proteins,lncRNA Pvt1 and Beclin1,LC3 mRNA in hippocampus increased(P＜0.05,P＜0.01),while the expressions of P62 protein and mRNA decreased(P＜0.05,P＜0.01).Compared with Tangzhiqing Decoction group,the blood sugar of Tangzhiqing Decoction+lncRNA Pvt1 knock-down group increased(P＜0.01).The escape latency was prolonged(P＜0.05);the number of Nissl bodies in hippocampal CA1 area decreased,and the apoptosis rate of neurons increased(P＜0.05).The expressions of Atg16L1,Beclin1,LC3Ⅱ/Ⅰ proteins,lncRNA Pvt1 and Beclin1,LC3 mRNA decreased(P＜0.05,P＜0.01),and P62 mRNA expression increased(P＜0.01).CONCLUSION Tangzhiqing decoction can improve the cognitive function of diabetic mice and alleviate neuronal apoptosis,and its mechanism may be related to the activation of hippocampal lncRNA Pvt1 mediated autophagy.

Objectives:To investigate the predictive value of epicardial fat volume(EFV)and atrioventricular groove fat thickness(AVGT)—morphological biomarkers of epicardial adipose tissue—for major adverse cardiovascular events(MACE)in patients with dilated cardiomyopathy(DCM).Methods:This study enrolled 216 DCM patients.EFV and AVGT were obtained from cardiac magnetic resonance imaging(CMR).Patients were divided into event-free group(n=142)and event group(n=74)based on MACE occurrence during follow-up.Receiver operating characteristic(ROC)curve analysis was used to determine optimal cutoff values.Survival differences were assessed using Kaplan-Meier analysis,Cox proportional hazards regression analysis was used to identify independent risk factors,and restricted cubic spline(RCS)models were used to evaluate dose-response relationships.Results:AVGT and EFV were significantly higher in the event group than in event-free group(both P<0.05).ROC analysis identified optimal MACE-predicting cutoffs as follows:AVGT≥7.74 mm(area under the curve[AUC]=0.57)and EFV≥78.6 ml(AUC=0.62).Kaplan-Meier analysis revealed significantly lower MACE-free survival rates in patients with AVGT≥7.74 mm and EFV≥78.6 ml(both P<0.05).Cox regression analysis confirmed that AVGT(HR=2.18,95%CI:1.34-3.54)and EFV(HR=1.81,95%CI:1.11-2.96)were independent MACE risk factors(both P<0.05)in this patient cohort.RCS models demonstrated the significant linear associations between EFV/AVGT and MACE risk(bothoverall P<0.05).Conclusions:EFV and AVGT,the non-invasive imaging biomarkers quantifying and characterizing fat distribution,are independently correlated with elevated MACE risk in DCM patients.These metrics serve as potential prognostic indicators,enriching risk stratification indicators for early identification of high-risk patients and guiding personalized medication strategies.

Objective:To investigate the effects of 3 D laparoscopic radical resection prostatectomy(LRP)on urinary control and sexual function of patients with prostatic cancer.Methods:A total of 268 patients who were treated with LRP in the Fifth People's Hospital of Huai an City from January 2019 to May 2022 were selected and divided into 2 groups according to surgical methods,with 134 cases in each group.The patients in the control group were treated with traditional LRP,and the 3D LRP was used in the observa-tion group.The clinical effects of the two groups were compared.Results:The patients in observation group had less blood loss([135.62±13.58]mL vs[143.18±14.89]mL)and shorter indwelling catheter time([8.26±1.47]d vs[9.78±1.73]d)compared with control group,but the operation time([160.52±10.78]min vs[154.47±10.41]min)was longer than that in the control group(P＜0.05).The recovery of sexual function and urinary control in the observation group was better than that in the con-trol group after 3,6 and 12 months of the surgery(P＜0.05).After one month of surgery,the scores of ICIQ-SF and 1 h urine pad test were lower than those of the control group.The EPIC-UIN score([72.63±6.85]points vs[67.15±5.09]points)of the observation group was higher than that of the control group(P＜0.05).The patients in the observation group had lower level of residual urine volume([60.26±6.63]mL vs[76.89±7.89]mL),higher maximum urine flow rate([7.52±0.46]mL/s vs[6.17±0.43]mL/s)and detrusor pressure([85.19±7.18]mL vs[76.29±6.85]mL)at maximum urine flow rate compared with the control group(P＜0.05).There was no difference in the incidence of complications between the observation group and the control group(5.97％vs 8.27％,P＞0.05).The recurrence rate of tumor 3 years after operation in the observation group was lower than that in the control group(11.94％vs 29.10％,x2=12.102,P＜0.05).Conclusion:3D LRP has obvious advantages in surgical clarity and preci-sion,which reduces the risk of postoperative complications and improves urinary control ability and sexual function of patients.

Patent foramen ovale(PFO)demonstrates significant comorbidity with migraine,but its causal relationship and the efficacy of transcatheter closure remain controversial.This systematic review examines potential biomarkers and relevant imaging assessments for PFO-associated migraine,aiming to provide a theoretical foundation for clinical diagnosis and treatment.Key biomarkers include platelet activation markers,calcitonin gene-related peptide,homocysteine,and platelet-to-lymphocyte ratio.Imaging evaluations encompass right-to-left shunt grading(transthoracic echocardiography,transcranial Doppler ultrasound),cerebrovascular breath-holding index,characteristics of white matter hyperintensities,alterations in resting-state functional magnetic resonance imaging(rs-f-MRI)brain networks,in-situ thrombi detected by optical coherence tomography,and electroencephalogram(EEG)power spectral features.Research indicates that integrating biomarkers with imaging technologies enhances diagnostic discrimination and treatment outcome prediction.Current challenges include unclear causal relationships and insufficient standardization of detection methods.Future efforts require multidisciplinary collaboration to establish personalized diagnostic and therapeutic frameworks through multimodal indicators,thereby advancing precise prevention and treatment strategies for PFO-related migraine.

Objective To explore the relationship between levels of vascular endothelial growth factor(VEGF),insulin-like growth factor 1(IGF-1),and transforming growth factor-β1(TGF-β1)in the synovial fluid of children with avascular necrosis of the femoral head(also known as Perthes disease)and the efficacy of postoperative revascularization,aiming to provide a basis for subsequent diagnosis and treatment.Methods A retrospective study was conducted on 262 children with Perthes disease admitted to the Affiliated Hospital of Gansu University of Chinese Medicine from January 2023 to June 2024.Based on postoperative revascularization efficacy,patients were divided into good revascularization group(n=228)and poor revascularization group(n=34).For poor revascularization group,a 1:2 matched case-control design was used to select 68 age-matched children with hip synovitis who underwent hip joint fluid puncture as control group.Additionally,82 children with Perthes disease treated at the hospital from June 2024 to January 2025 were enrolled as a validation cohort for nomogram model verification.The expression levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of three groups were compared.Confounding biases were controlled through univariate and stratified analyses.Binary logistic regression analysis was used to identify independent factors affecting the revascularization effect.R software was utilized to draw and verify the nomogram model for predicting the postoperative revascularization effect.Results The levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children in poor revascularization group were all higher than those in control group and good revascularization group(P<0.05).After three types of reconstructive surgeries,the levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children with poor revascularization were all higher than those in children with good revascularization(P<0.05);however,there was no statistically significant difference in the above indicators among different surgical types(P>0.05).Binary logistic regression analysis showed that the levels of VEGF,IGF-1,and TGF-β1 in the synovial fluid were independent risk factors for poor postoperative revascularization in children with Perthes disease.The area under the ROC curve of the nomogram model established accordingly for predicting poor postoperative revascularization in children with Perthes disease was 0.875(95%CI 0.805-0.945),with a sensitivity of 0.874 and a specificity of 0.851.Moreover,the calibration curve and decision curve analysis(DCA)indicated that the model had good clinical applicability.Conclusions The increased levels of VEGF,IGF-1 and TGF-β1 in synovial fluid are associated with poor postoperative revascularization in children with Perthes disease.These three factors are expected to become prognostic indicators for children with Perthes disease.

Patent foramen ovale(PFO)demonstrates significant comorbidity with migraine,but its causal relationship and the efficacy of transcatheter closure remain controversial.This systematic review examines potential biomarkers and relevant imaging assessments for PFO-associated migraine,aiming to provide a theoretical foundation for clinical diagnosis and treatment.Key biomarkers include platelet activation markers,calcitonin gene-related peptide,homocysteine,and platelet-to-lymphocyte ratio.Imaging evaluations encompass right-to-left shunt grading(transthoracic echocardiography,transcranial Doppler ultrasound),cerebrovascular breath-holding index,characteristics of white matter hyperintensities,alterations in resting-state functional magnetic resonance imaging(rs-f-MRI)brain networks,in-situ thrombi detected by optical coherence tomography,and electroencephalogram(EEG)power spectral features.Research indicates that integrating biomarkers with imaging technologies enhances diagnostic discrimination and treatment outcome prediction.Current challenges include unclear causal relationships and insufficient standardization of detection methods.Future efforts require multidisciplinary collaboration to establish personalized diagnostic and therapeutic frameworks through multimodal indicators,thereby advancing precise prevention and treatment strategies for PFO-related migraine.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation