Aim To explore the action mechanism of isoquercitrin(IQ)in ameliorating anxiety based on network pharmacology,cellular transcriptomics,molecu-lar docking and animal experiments.Methods The common targets of anxiety disorders and IQ were ob-tained by using relevant databases.The protein-protein interaction network,the biological function and signa-ling pathway enrichment analysis were conducted by u-sing the common targets.Primary hippocampal neurons were cultured in vitro,and corticosterone was added to induce neurons to establish a corticosterone injury mod-el.IQ treatment was added to the culture system,and transcriptomics was used to screen for differentially ex-pressed genes and enrich for differentially expressed pathways.Subsequently,the results were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Possible targets and signaling pathways for IQ treatment on anxiety were speculated and screened u-sing network pharmacology,transcriptomics and molec-ular docking.The anxiety rat model was constructed,and the anxiety state of rats was evaluated after IQ in-tervention,and the protein expression level of hippo-campus was detected to verify the relevant mechanism.Results Network pharmacology,cellular transcrip-tome,and molecular docking analyses revealed that the key mechanism of IQ for anxiety may be related to the BDKRB2/PI3K/Akt signaling pathway.Animal exper-iments showed that IQ was effective in improving anxie-ty behaviour and learning memory ability in rats.IQ increased the movement distance and residence time in the central area of the open field,the time and number percentage of entries into the open arm in the elevated plus maze,and the spontaneous alternations score in the Y maze in rats,and significantly elevated protein expression of BDKRB2,PI3K,Akt and decreased pro-tein expression of NF-κB in the hippocampus.Conclu-sions Isoquercitrin can effectively treat anxiety,and the mechanism of action may be related to the regula-tion of BDKRB2/PI3K/Akt signaling pathway in hip-pocampus.

Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

Objective To observe the correlation between brain abnormal glucose metabolism and striatal dopaminergic neuron damage in early-stage Parkinson disease(PD)patients.Methods Thirty-two early-stage PD patients(PD group)and 18 healthy individuals(control group)were prospectively enrolled,and 18F-FDG and 18F-9-fluoropropyl-(+)-dihydrotetrabenazine(18 F-FP-DTBZ)PET/MR brain imaging were performed.The degrees of uptake were compared between groups,and the correlation between brain abnormal glucose metabolism and striatal dopaminergic neuron damage was analyzed.Results Compared with control group,18F-FDG PET showed that in PD group glucose metabolism decreased in bilateral frontal and parietal lobes but increased in bilateral putamen,pons and bilateral cerebellum(all P＜0.05),while18 F-FP-DTBZ PET showed that in PD group glucose metabolism decreased in bilateral caudate nucleus,anterior putamen and posterior putamen(all P＜0.05).In PD group,the mean standard uptake value(SUVmean)of putamen was positively correlated with the standard uptake value ratio(SUVR)of contralateral caudate nucleus(r=0.305,P=0.014),while SUVmean of frontal cortex was positively correlated with SUVR of contralateral and symptomatic caudate nucleus(r=0.352,0.324,both P＜0.05)as well as anterior putamen(r=0.300,0.314,both P＜0.05),SUVmean of the partial cortex in parietal lobe was positively correlated with SUVR of contralateral and symptomatic caudate nucleus and contralateral anterior putamen(r=0.329,0.303,0.330,all P＜0.05).Conclusion Brain abnormal glucose metabolism had certain correlation with striatal dopaminergic neuron damage in early-stage PD patients.

Objective To observe the correlation between brain abnormal glucose metabolism and striatal dopaminergic neuron damage in early-stage Parkinson disease(PD)patients.Methods Thirty-two early-stage PD patients(PD group)and 18 healthy individuals(control group)were prospectively enrolled,and 18F-FDG and 18F-9-fluoropropyl-(+)-dihydrotetrabenazine(18 F-FP-DTBZ)PET/MR brain imaging were performed.The degrees of uptake were compared between groups,and the correlation between brain abnormal glucose metabolism and striatal dopaminergic neuron damage was analyzed.Results Compared with control group,18F-FDG PET showed that in PD group glucose metabolism decreased in bilateral frontal and parietal lobes but increased in bilateral putamen,pons and bilateral cerebellum(all P＜0.05),while18 F-FP-DTBZ PET showed that in PD group glucose metabolism decreased in bilateral caudate nucleus,anterior putamen and posterior putamen(all P＜0.05).In PD group,the mean standard uptake value(SUVmean)of putamen was positively correlated with the standard uptake value ratio(SUVR)of contralateral caudate nucleus(r=0.305,P=0.014),while SUVmean of frontal cortex was positively correlated with SUVR of contralateral and symptomatic caudate nucleus(r=0.352,0.324,both P＜0.05)as well as anterior putamen(r=0.300,0.314,both P＜0.05),SUVmean of the partial cortex in parietal lobe was positively correlated with SUVR of contralateral and symptomatic caudate nucleus and contralateral anterior putamen(r=0.329,0.303,0.330,all P＜0.05).Conclusion Brain abnormal glucose metabolism had certain correlation with striatal dopaminergic neuron damage in early-stage PD patients.

Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

Objective To establish and evaluate a nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer.Methods A retrospective study was conducted on 1298 patients with HBV-related primary liver cancer hospitalized in the Kunming Third People's Hospital from January 2012 to December 2022.General data and serological indicators were collected,and patients were divided into infection group(n=262)and control group(n=1036)based on the occurrence of spontaneous peritonitis.Univariate and LASSO regression analyses were used to screen variables,followed by binary logistic regression to analyze the influencing factors of spontaneous peritonitis in HBV-related primary liver cancer patients,leading to the establishment of a nomogram prediction model.Finally,the Hosmer-lemeshow(H-L)goodness of fit test,receiver operating characteristic(ROC)curve,calibration curve,decision curve analysis(DCA)and clinical impact curve(CIC)were utilized to evaluate the fit degree,accuracy,calibration,and clinical practicability of the nomogram prediction model.Results Single factor analysis revealed significant differences between infection group and control group in portal vein cancer thrombus(PVTT),Child-Pugh grade,China Liver Cancer Staging(CNLC)stage,alcohol consumption history,smoking history,white blood cell count(WBC),neutrophil count(NE),hemoglobin(Hb),fibrinogen(FIB),abnormal prothrombin(PIVKA-Ⅱ),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total protein(TP),prealbumin(PA),γ-glutamyltransferase(GGT),alkaline phosphatase(ALP),cholinesterase(CHE),total bile acid(TBA),total cholesterol(TC),low density lipoprotein(LDL),creatinine(Cr),HBV DNA,CD3+T cells count,CD4+T cells count,CD8+T cells count,CD4+T cells/CD8+T cells ratio,procalcitonin(PCT),serum amyloid A(SAA),interleukin-6(IL-6),high-sensitivity C-reactive protein(hs-CRP),alpha-fetoprotein(AFP),and IL-4(P＜0.05).LASSO regression analysis identified 5 variables:Child-Pugh grade,PVTT,WBC,CHE and hs-CRP.Binary logistic regression analysis indicated that Child-Pugh grade(Grade B:OR=5.780,95％CI 3.271-10.213,P＜0.001;Grade C:OR=14.818,95％CI 7.697-28.526,P＜0.001),PVTT(OR=2.893,95％CI 2.037-4.108,P＜0.001),WBC(OR=1.088,95％CI 1.031-1.148,P=0.002),and hs-CRP(OR=1.005,95％CI 1.001-1.010,P=0.026)were the independent risk factors of spontaneous peritonitis in HBV-related primary liver cancer patients.Using these 4 variables,a nomogram prediction model was constructed and evaluated.The P-value of the H-L goodness of fit test was 0.760.Moreover,the area under ROC curve(AUC)was 0.866,with a sensitivity of 0.870 and a specificity of 0.716.The average absolute error of the calibration curve is 0.022.DCA and CIC analyses demonstrated that the nomogram prediction model possessed some clinical utility.Conclusion The nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer patients,constructed using Child-Pugh grade,PVTT,WBC and hs-CRP,exhibits a high fitting degree and accuracy,with the prediction probability highly consistent with the actual occurrence probability,and possesses certain clinical practicability.

Objective To investigate the expression of myelin transcription factor 1-like(MYT1L)during amyotrophic lateral sclerosis(ALS)progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus(GEO)database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene(hSOD1G93A)compared to the wild-type(WT)mice.hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting.Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease.An ALS cellular model was established using hSOD1G93A mutant NSC34 cells,with hSOD1WT NSC34 cells as controls.MYT1L expression and distribution were assessed in these cells via Real-time PCR,Western blotting,and immunofluorescent staining.Based on the GSE76220 dataset from the GEO database,differentially expressed genes(DEGs)between MYT1L high-and low-expression groups in lumbar spinal motor neurons of ALS patients were identified,followed by Gene Ontology(GO)functional enrichment analysis.MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.Results In the GSE106803 dataset,MYT1L expression was significantly down-regulated in the spinal cord of ALS mice.Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid-and late-disease stages.Compared to the WT group,MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice,while it increased in astrocytes.In vitro,hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls,with MYT1L localized to both the cytoplasm and nucleus.DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients(GSE76220 dataset)were enriched in synaptic-related functions through GO analysis.Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis.Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons,suggesting its therapeutic potential.

To investigate the transcriptionally regulatory mechanism of the senp8 promoter in yellow cat-fish(Pelteobagrus fulvidraco);this study used P.fulvidraco as the research subject.Dual-luciferase re-porter assay and electrophoretic mobility shift assay were employed to analyze the functional activity of the promoter;coupled with in vivo experiments.The results indicated that the 2 045 bp senp8 promoter se-quence contained key transcription factor binding sites such as SP1;TATA-Box;CCAAT-Box;SREBP1;PPARα;and PPARγ.The binding sites of SREBP1(-901/-910 bp);PPARα(-1 291/-1 308 bp);and PPARγ(-1 292/-1 306 bp)in the senp8 promoter positively regulate its activity;and oleic acid or palmitic acid promote this binding.Furthermore;high-fat feeding promoted the expression of the senp8 gene and its protein in the liver of P.fulvidraco;oleic acid or palmitic acid treatment significantly en-hanced the activity of the senp8 promoter;and this enhancement could be achieved through the regulatory effects of SREBP1;PPARα;and PPARγ response elements.Additionally;high-fat feeding influenced the mRNA and protein expression levels of genes related to deSUMOylation modification in the liver of P.fulvidraco.This study provides new insights into the relationship between deSUMOylation modification and the regulation of lipid metabolism in the vertebrates.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To analyze the effect of altitude on NIH-CPSI score in patients with chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)Methods:Clinical data and the results of NIH-CPSI Questionnaire of the 321 patients with CP/CPPS at different altitudes were collected from March 2021 to March 2022.And the influence of altitudes on NIH-CPSI score of CP/CPPS was analyzed.Result:The NIH-CPSI score of patients living at an altitude of 4 300 m was significantly higher than that of patients living at an altitude of 1 500 m and 2 200 m.The CP/CPPS patients who lived in the higher altitude had more severe symptoms of pain and urination as well as lower scores of life quality(P＜0.05).Conclusion:NIH-CPSI score increased significantly with higher alti-tude,indicating more severe symptoms and decreased quality of life in CP/CPPS patients.These findings highlight the need for man-agement strategies for specific heights in patients with CP/CPPS.