In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Objective:To construct and verify a prediction and evaluation model based on dual-energy computed tomography(CT)radiomics for lymph node metastasis in gastric cancer,so as to provide more accurate and reliable method before lymph node in gastric cancer occurs metastasis.Methods:A total of eighty patients with gastric cancer admitted to Handan Central Hospital from January 2021 to December 2024 were retrospectively selected,and they were divided into a modeling group(48 cases)and a verification group(32 cases)using a random number table method according to a ratio of 3 to 2.The influencing factors were analyzed,and predictive model was constructed and verified by using univariate and binary logistics regression.The patients'general information,tumor size,differentiation degree,lesion location,and carbohydrate antigen 125(CA125),carbohydrate antigen 199(CA199)and carcinoembryonic antigen(CEA)were compared between two groups.Results:There were not significant differences in age,gender,body mass index(BMI),tumor size,degree of differentiation,lesion location in the modeling group(P>0.05).In the modeling group,the immunity concentration(IC)was(20.66±2.85)μg/mL,and normal immunity concentration(nIC)was(0.45±0.06)μg/mL,and the slope was(3.52±0.30).The three indicators were respectively(21.09±3.25)μg/mL,(0.47±0.05)μg/mL,(3.49±0.42)in verification group.There were significant differences in the three indicators among two groups(t=3.277,5.287,2.918,P<0.05).There were not significant differences in the tumor-related detection indicators between two groups(P>0.05).The results of binary logistics regression analysis showed that IC,nIC,and slope were influential factors in lymph node metastasis of gastric cancer(OR=2.564,1.647,1.786,P<0.05).The constructed prediction model by using Python Scikit-learn showed favorable appearance in the calibration curve with a slope closed to 1,which indicated a high degree of consistency between predicted risks and actual risks.Receiver operating characteristic(ROC)curve analysis showed that the area under curve(AUC)of the modeling group was 0.896(95%CI:0.8154～0.9167),and the sensitivity and specificity were respectively 84.60%and 80.69%.The above three indicators were respectively 0.853(95%CI:0.7982～0.8671),86.66%and 80.00%in the verification group.Conclusion:A prediction and evaluation model for lymph node metastasis of gastric cancer based on dual-energy CT radiomics is successfully constructed,and its predictive efficiency and clinical application value are verified.

BACKGROUND:THZ1,an inhibitor of cyclin-dependent kinase 7,has been shown to inhibit the proliferation of a variety of tumor cells,but whether THZ1 can affect the stemness of glioma stem cells through the Wnt/β-catenin signaling pathway remains unclear.OBJECTIVE:To investigate the effect of THZ1 on stemness of glioma cell U87 and its mechanism.METHODS:U87 adherent cells were cultured to form stem cell mammospheres.The expressions of stemness related proteins were verified by western blot assay.The effect of THZ1 on half maximal inhibitory concentration(IC50)of U87 cells was determined by Cell Counting Kit-8(CCK-8)assays.The effects of THZ1 on proliferation and migration of U87 cells were determined by cell colony-formation assays,cell wound healing assays,and Transwell migration assays.The effect of THZ1 treatment on mammosphere forming rate and mammosphere size of U87 stem cells was analyzed.Stemness associated proteins CD133,ABCG2,Nanog,OCT4,SOX2,epithelial-mesenchymal transformation-related proteins E-cadherin,N-cadherin,Occludin,Snail,and Wnt/β-catenin pathway associated proteins Axin1,β-Catenin,WNT-5A,GSK3β,Cyclind-1,and C-myc were measured by western blot assay.RESULTS AND CONCLUSION:(1)Compared with adherent cells,the expressions of stemness related proteins Nestin,CD133,ABCG2,Nanog,OCT4,and SOX2 were significantly increased.(2)Compared with the control group,THZ1 decreased the proliferation and migration of U87 cells.(3)THZ1 inhibited the mammosphere forming rate and mammosphere size of U87 stem cells.(4)After THZ1 treatment,the expression of N-cadherin and Snail decreased,while the protein expression of E-cadherin and Occludin increased.(5)THZ1 treatment decreased the expression of Wnt/β-catenin pathway related proteins Axin1,β-Catenin,Wnt-5A,GSK3β,Cyclind-1,and C-myc in U87 stem cells.It is concluded that THZ1 can suppress the proliferation and migration of U87 cells,and inhibit the mammosphere forming ability,stemness related protein expression,and epithelial-mesenchymal transformation ability of U87 stem cells by down-regulating the expression of Wnt/β-catenin signaling pathway related molecules.

Objective To investigate the molecular mechanism by which super enhancers(SEs)regulate the expression of the genetic suppressor element 1(GSE1)and influence the proliferation of breast cancer cell line MCF-7.Methods The oncogene GSE1,driven by SEs,was identified through analysis of the ChIP-seq dataset of MCF-7 cells obtained from the GEO database.The protein expression level of GSE1 was assessed via Western blot following treatment with the bromodomain-containing protein 4(BRD4)inhibitor JQ1.The expression of GSE1 across various cancers and different breast cancer subtypes was analyzed using the Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)databases,respectively.Overall survival(OS)of breast cancer patients was compared between the GSE1 high-expression and low-expression groups using the GEPIA database.Immunohis-tochemistry(IHC)was performed to evaluate GSE1 expression in breast cancer tissue samples.The mRNA expres-sion levels of GSE1 in different breast cancer cell lines were validated by RT-qPCR.A GSE1 interference vector was constructed and transfected into MCF-7 cells,and the knockdown efficiency was assessed using Western blot.Cell proliferation and migration were evaluated using CCK-8 assay,colony formation assay,wound healing assay,and Transwell migration assay.Potential GSE1-interacting proteins were predicted using the STRING database.Finally,Western blot analysis was conducted to assess changes in epithelial-mesenchymal transition(EMT)-related proteins and key components of the Wnt/β-catenin signaling pathway.Results The integrative genomics viewer(IGV)was used to visualize ChIP-seq data from MCF-7 cells,and the rank ordering of super enhancers(ROSE)algorithm was applied to predict the SE region of GSE1 in the MCF-7 genome.GSE1 and BRD4 expression levels were significantly reduced following JQ1 treatment(P<0.05).High expression levels of GSE1 in breast cancer were confirmed through analyses using the HPA,TCGA,and GEPIA databases,as well as IHC,and these find-ings were associated with poor prognostic outcomes in breast cancer patients(P<0.05).RT-qPCR results further demonstrated that GSE1 is significantly upregulated in breast cancer cells(P<0.05).Analysis of the STRING database revealed a strong correlation between GSE1 and Snail(Snai1).Transfection of a GSE1-specific interference vector significantly inhibited the proliferation and migration of MCF-7 cells compared to the control group,upregu-lated E-cadherin and Occludin expression,and downregulated N-cadherin and Snail expression(P<0.05).Addi-tionally,knockdown of GSE1 resulted in decreased expression of Wnt/β-catenin signaling pathway-related proteins,including β-catenin,Wnt-5a,and Cyclin-D1,along with increased Axin1 expression(P<0.05).Conclusion SE driven GSE1 promotes the proliferation,migration and EMT of MCF-7 cells via the Wnt/β-catenin signaling pathway.

Objective To explore the effect of phloretin on the proliferation,apoptosis,and tumorigenicity of ovarian cancer cells by regu-lating the Rac1/Akt/NF-κB signaling pathway.Methods The ovarian cancer cell line SKOV3 and the human normal ovarian epithelial cell line IOSE-80 were divided into the following groups:control,low-dose phloretin,medium-dose phloretin,high-dose phloretin,PM A,and high-dose phloretin+PMA.Morphological changes were observed under a microscope.Cell viability and apoptosis were assessed using the CCK-8 assay,colony formation assay,and flow cytometry.Western blotting was performed to detect the expression of proteins related to the Rac1/Akt/NF-κB signaling pathway.Tumor-bearing nude mice were established,tumor weights were measured,and the expres-sion levels of Rae1 and Akt in tumor tissues were analyzed.Results Compared with the control group,SKOV3 cells treated with low-,medium-,and high-dose phloretin showed reduced survival rate,colony formation,and expression of p-NF-κB p65/NF-κB p65,p-Akt/Akt,and Rac 1 in a dose-dependent manner.However,PM A reversed the inhibitory effects of high-dose phloretin on the malignant progression of ovarian cancer.In vivo experiments demonstrated that phloretin significantly inhibited tumor growth and reduced Akt and Rae1 expres-sion in tumor tissues(P＜0.05).Conclusion Phloretin suppresses the malignant progression of ovarian cancer by inhibiting the Rae1/Akt/NF-κB signaling pathway.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

Objective:To construct and verify a prediction and evaluation model based on dual-energy computed tomography(CT)radiomics for lymph node metastasis in gastric cancer,so as to provide more accurate and reliable method before lymph node in gastric cancer occurs metastasis.Methods:A total of eighty patients with gastric cancer admitted to Handan Central Hospital from January 2021 to December 2024 were retrospectively selected,and they were divided into a modeling group(48 cases)and a verification group(32 cases)using a random number table method according to a ratio of 3 to 2.The influencing factors were analyzed,and predictive model was constructed and verified by using univariate and binary logistics regression.The patients'general information,tumor size,differentiation degree,lesion location,and carbohydrate antigen 125(CA125),carbohydrate antigen 199(CA199)and carcinoembryonic antigen(CEA)were compared between two groups.Results:There were not significant differences in age,gender,body mass index(BMI),tumor size,degree of differentiation,lesion location in the modeling group(P>0.05).In the modeling group,the immunity concentration(IC)was(20.66±2.85)μg/mL,and normal immunity concentration(nIC)was(0.45±0.06)μg/mL,and the slope was(3.52±0.30).The three indicators were respectively(21.09±3.25)μg/mL,(0.47±0.05)μg/mL,(3.49±0.42)in verification group.There were significant differences in the three indicators among two groups(t=3.277,5.287,2.918,P<0.05).There were not significant differences in the tumor-related detection indicators between two groups(P>0.05).The results of binary logistics regression analysis showed that IC,nIC,and slope were influential factors in lymph node metastasis of gastric cancer(OR=2.564,1.647,1.786,P<0.05).The constructed prediction model by using Python Scikit-learn showed favorable appearance in the calibration curve with a slope closed to 1,which indicated a high degree of consistency between predicted risks and actual risks.Receiver operating characteristic(ROC)curve analysis showed that the area under curve(AUC)of the modeling group was 0.896(95%CI:0.8154～0.9167),and the sensitivity and specificity were respectively 84.60%and 80.69%.The above three indicators were respectively 0.853(95%CI:0.7982～0.8671),86.66%and 80.00%in the verification group.Conclusion:A prediction and evaluation model for lymph node metastasis of gastric cancer based on dual-energy CT radiomics is successfully constructed,and its predictive efficiency and clinical application value are verified.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

BACKGROUND:THZ1,an inhibitor of cyclin-dependent kinase 7,has been shown to inhibit the proliferation of a variety of tumor cells,but whether THZ1 can affect the stemness of glioma stem cells through the Wnt/β-catenin signaling pathway remains unclear.OBJECTIVE:To investigate the effect of THZ1 on stemness of glioma cell U87 and its mechanism.METHODS:U87 adherent cells were cultured to form stem cell mammospheres.The expressions of stemness related proteins were verified by western blot assay.The effect of THZ1 on half maximal inhibitory concentration(IC50)of U87 cells was determined by Cell Counting Kit-8(CCK-8)assays.The effects of THZ1 on proliferation and migration of U87 cells were determined by cell colony-formation assays,cell wound healing assays,and Transwell migration assays.The effect of THZ1 treatment on mammosphere forming rate and mammosphere size of U87 stem cells was analyzed.Stemness associated proteins CD133,ABCG2,Nanog,OCT4,SOX2,epithelial-mesenchymal transformation-related proteins E-cadherin,N-cadherin,Occludin,Snail,and Wnt/β-catenin pathway associated proteins Axin1,β-Catenin,WNT-5A,GSK3β,Cyclind-1,and C-myc were measured by western blot assay.RESULTS AND CONCLUSION:(1)Compared with adherent cells,the expressions of stemness related proteins Nestin,CD133,ABCG2,Nanog,OCT4,and SOX2 were significantly increased.(2)Compared with the control group,THZ1 decreased the proliferation and migration of U87 cells.(3)THZ1 inhibited the mammosphere forming rate and mammosphere size of U87 stem cells.(4)After THZ1 treatment,the expression of N-cadherin and Snail decreased,while the protein expression of E-cadherin and Occludin increased.(5)THZ1 treatment decreased the expression of Wnt/β-catenin pathway related proteins Axin1,β-Catenin,Wnt-5A,GSK3β,Cyclind-1,and C-myc in U87 stem cells.It is concluded that THZ1 can suppress the proliferation and migration of U87 cells,and inhibit the mammosphere forming ability,stemness related protein expression,and epithelial-mesenchymal transformation ability of U87 stem cells by down-regulating the expression of Wnt/β-catenin signaling pathway related molecules.

Objective To investigate the molecular mechanism by which super enhancers(SEs)regulate the expression of the genetic suppressor element 1(GSE1)and influence the proliferation of breast cancer cell line MCF-7.Methods The oncogene GSE1,driven by SEs,was identified through analysis of the ChIP-seq dataset of MCF-7 cells obtained from the GEO database.The protein expression level of GSE1 was assessed via Western blot following treatment with the bromodomain-containing protein 4(BRD4)inhibitor JQ1.The expression of GSE1 across various cancers and different breast cancer subtypes was analyzed using the Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)databases,respectively.Overall survival(OS)of breast cancer patients was compared between the GSE1 high-expression and low-expression groups using the GEPIA database.Immunohis-tochemistry(IHC)was performed to evaluate GSE1 expression in breast cancer tissue samples.The mRNA expres-sion levels of GSE1 in different breast cancer cell lines were validated by RT-qPCR.A GSE1 interference vector was constructed and transfected into MCF-7 cells,and the knockdown efficiency was assessed using Western blot.Cell proliferation and migration were evaluated using CCK-8 assay,colony formation assay,wound healing assay,and Transwell migration assay.Potential GSE1-interacting proteins were predicted using the STRING database.Finally,Western blot analysis was conducted to assess changes in epithelial-mesenchymal transition(EMT)-related proteins and key components of the Wnt/β-catenin signaling pathway.Results The integrative genomics viewer(IGV)was used to visualize ChIP-seq data from MCF-7 cells,and the rank ordering of super enhancers(ROSE)algorithm was applied to predict the SE region of GSE1 in the MCF-7 genome.GSE1 and BRD4 expression levels were significantly reduced following JQ1 treatment(P<0.05).High expression levels of GSE1 in breast cancer were confirmed through analyses using the HPA,TCGA,and GEPIA databases,as well as IHC,and these find-ings were associated with poor prognostic outcomes in breast cancer patients(P<0.05).RT-qPCR results further demonstrated that GSE1 is significantly upregulated in breast cancer cells(P<0.05).Analysis of the STRING database revealed a strong correlation between GSE1 and Snail(Snai1).Transfection of a GSE1-specific interference vector significantly inhibited the proliferation and migration of MCF-7 cells compared to the control group,upregu-lated E-cadherin and Occludin expression,and downregulated N-cadherin and Snail expression(P<0.05).Addi-tionally,knockdown of GSE1 resulted in decreased expression of Wnt/β-catenin signaling pathway-related proteins,including β-catenin,Wnt-5a,and Cyclin-D1,along with increased Axin1 expression(P<0.05).Conclusion SE driven GSE1 promotes the proliferation,migration and EMT of MCF-7 cells via the Wnt/β-catenin signaling pathway.