Abstract:Objective To investigate the protective effect of astragaloside IV on radiation-induced esophageal epithelial cell(Het-1A)injury and explore its underlying mechanism.Methods A radiation-induced esophagitis model was established by irradiating Het-1A cells with 6MV-X-rays(2,4,6 Gy).The model cells were treated with different concentrations of astragaloside IV(0,5,10,20,40,80,160 μmol/L).Cell proliferation was assessed using the CCK-8 method to determine the optimal intervention concentration.Het-1A cells were divided into the following groups:normal control group,radiation injury model group,astragaloside IV(40 μmol/L)group,phosphatidylinositol 3-kinase(PI3K)inhibitor LY294002(10 μmol/L)group,and astragaloside IV(40 μmol/L)+LY294002(10 μmol/L)group.The levels of tumour necrosis factor-α(TNF-α)and interleukin-6(IL-6)were measured by ELISA.The cell proliferation was evaluated using the EdU method.The apoptosis was detected by flow cytometry,phosphorylated PI3K(p-PI3K)protein expression was assessed by immunofluorescence,and the expression of caspase-3,Bcl-2,Bax,PI3K,protein kinase B(AKT),mammalian target of rapamycin(mTOR),and their cleaved or phosphorylated proteins were determined by Western blotting.Results A radiation-induced Het-1A injury cell model was constructed using a 4 Gy radiation dose.Compared with the 0 μmol/L astragaloside IV group,the viability of radiation-injured Het-1A cells treated with 10,20,40,and 80 μmol/L astragaloside IV was significantly increased(P<0.05).Compared with the normal control group,the radiation injury model group exhibited elevated levels of TNF-α,IL-6,apoptosis rate,cleaved caspase-3/caspase-3,and Bax protein,as well as reduced cell proliferation rate,Bcl-2,p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR protein levels(P<0.05).Compared with the radiation injury model group,the astragaloside IV group showed significantly reduced levels of the aforementioned inflammatory factors,apoptosis rate,and related pro-apoptotic protein expression,while the proliferation ability and the phosphorylation levels of proteins related to the PI3K/AKT/mTOR pathway were increased(P<0.05).Compared with astragaloside IV group,astragaloside IV+LY294002 group showed significantly increased inflammatory response,apoptosis level,and pro-apoptotic protein expression,while the proliferation ability and activation level of the PI3K/AKT/mTOR pathway were decreased(P<0.05),suggesting that LY294002 could inhibit the protective effect of astragaloside IV on radiation-injured Het-1A cells.Conclusion Astragaloside IV can alleviate 6MV-X-ray-induced Het-1A cell injury,promote cell proliferation,and suppress inflammatory responses and apoptosis.Its mechanism may be related to the activation of the PI3K/AKT/mTOR pathway.

Abstract:Objective To systematically evaluate the clinical value of contrast-enhanced ultrasound(CEUS)and single-photon emission computed tomography/computed tomography(SPECT/CT)in diagnosing cervical lymph node metastasis in postoperative patients with differentiated thyroid carcinoma(DTC).Methods The clinical data of 56 postoperative DTC patients from September 2021 to December 2023 were retrospectively analyzed.All patients underwent both CEUS and SPECT/CT examinations,and the pathological results of lymph node puncture served as the gold standard to compare the diagnostic efficacy of the two imaging methods.Results Among the 56 patients,pathology confirmed lymph node metastasis in 41 cases and no metastasis in 15 cases.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of CEUS were 75.6%,86.7%,93.9%,and 56.5%,respectively,while those of SPECT/CT were 48.8%,100%,100%,and 41.7%,respectively.The sensitivity of CEUS was significantly higher than that of SPECT/CT(P<0.05),whereas the difference in specificity was not statistically significant(P>0.05).CEUS image characteristic analysis revealed that most metastatic lymph nodes exhibited centripetal(80.5%,33/41)and heterogeneous(75.6%,31/41)enhancement patterns.Quantitavive analysis results showed that contrast agent clearance time in metastatic lymph nodes was significantly longer than that in benign lymph nodes[(195.61±49.27)s vs.(163.20±43.65)s,P<0.05].Lymph node region analysis indicated that metastatic lymph nodes were predominantly located in the lateral cervical region,with Level Ⅲ having the highest metastasis rate(92.9%).The typical SPECT/CT image presentation was focal iodine uptake increase,corresponding to the enhanced areas on CEUS.Conclusion CEUS demonstrates high sensitivity in diagnosing cervical lymph node metastasis after DTC surgery,making it suitable for early screening;SPECT/CT exhibits extremely high specificity,rendering it more conducive to confirmation.The combined application of both modalities can complement their advantages,improve diagnostic accuracy,and provide a reliable basis for formulating individualized clinical treatment plans.

Abstract:Objective To analyze the expression of integrin β1(ITGB1)in oral squamous cell carcinoma(OSCC)and its effects on the proliferation,invasion and migration of OSCC cells.Methods GEPIA2 and TIMER2 databases were utilized to analyze the expression of ITGB1 in head and neck squamous cell carcinoma(HNSC)tissues.A total of 42 patients with OSCC who underwent surgical treatment in the Third Affiliated Hospital of Xinxiang Medical University were included.According to the median expression level of ITGB1 protein,the patients were divided into the high ITGB1 group and the low ITGB1 group,and the relationship between the expression level of ITGB1 and the clinicopathological characteristics was analyzed.The mRNA and protein expression levels of ITGB1 in OSCC tissues and cells were detected by quantitative reverse transcription PCR(RT-qPCR)and Western blotting.The expression of ITGB1 was down-regulated by siRNA technology,and then the proliferation,apoptosis,migration and invasion abilities of OSCC cells were detected through CCK-8 assay,flow cytometry,scratch assay,and Transwell assay.Further,the expression of apoptosis and epithelial-mesenchymal transition(EMT)-related proteins was examined by Western blotting.Results The database results showed that ITGB1 was highly expressed in HNSC tissues compared with adjacent normal tissue(P<0.05).The RT-qPCR and Western blotting results showed that the expression levels of ITGB1 in OSCC tissues were higher than in adjacent cells(P<0.001).There were significant differences in the degree of tumor differentiation and TNM stage between the high ITGB1 group and the low ITGB1 group(all P<0.05).At the cellular level,the expression levels of ITGB1 in OSCC cells lines followed the order:HOK<CAL-27<SCC-25 in sequence(all P<0.001).After transfection with si-ITGB1,the expression levels of ITGB1 in SCC-25 cells were inhibited(P<0.001).Compared with the si-NC group,the proliferation activity of cells in the si-ITGB1 group at 24 h,48 h,72 h and 96 h was significantly decreased(P<0.05),a significantly increased apoptosis rate(P<0.001),accompanied by increased Bax expression and decreased Bcl-2 expression(P<0.05).The wound healing assay showed a significantly increased relative wound width at 24 h(P<0.05).The Transwell assay showed a significant decrease in the number of invading cellst(P<0.01).After co-transfection with si-ITGB1,the expression level of E-cadherin significantly increased(P<0.001),while the expression levels of N-cadherin and Vimentin significantly decreased(P<0.001).Conclusion ITGB1 is highly expressed in OSCC,and down-regulating ITGB1 expression can inhibit the proliferation of SCC-25 cells while promoting cell apoptosis.It can also inhibit the migration and invasion of OSCC cells by regulating the expression levels of EMT-related proteins.

Abstract:Venous thromboembolism(VTE)includes deep vein thrombosis(DVT)and pulmonary embolism(PE),with PE predominantly arising from DVT-related thrombus embolization into the pulmonary circulation.PE is characterized by rapid onset and high mortality,posing significant clinical challenges.Biliary tract carcinoma(BTC)represents highly aggressive malignancies within the gastrointestinal system.The global incidence of BTC has been steadily increasing,yet patient prognosis remains poor,primarily due to the challenges associated with early detection.VTE,as a notable complication of BTC,markedly reduces patient survival.This article provides a comprehensive review of the current literature on the intersection of BTC-associated VTE,focusing on epidemiology,pathological mechanisms,risk factors,prevention and treatment,with the aim of offering valuable insights for clinical practice.

Abstract:Objective To explore the roles of long non-coding RNA RP11-757G1.5 in regulating biological behaviors and cisplatin sensitivity of gastric cancer cells.Methods The expression levels of RP11-757G1.5 in gastric epithelial cells(GES-1)and human gastric cancer cells(MKN-45,NCI-N87,AGS,and HGC-27)were detected by real-time quantitative PCR(RT-qPCR).Two small interfering RNA(siRNA)sequences targeting RP11-757G1.5(si-757G1.5#1 and si-757G1.5#2)and a negative control sequence(si-NC)were designed and synthesized,and then transfected into MKN-45 and HGC-27 cells.The cells were divided into Control,si-NC,and two interference groups(si-757G1.5#1 and si-757G1.5#2).To investigate the effects of RP11-757G1.5 on malignant behavior and drug sensitivity,the following experiments were performed:cell viability and the half-maximal inhibitory concentration(IC50)of cisplatin were assessed using the Cell Counting Kit-8(CCK-8)assay;cell migration ability was evaluated by wound healing assay;cell invasion ability was analyzed by Transwell assay;and the protein expression levels of matrix metalloproteinase(MMP)-2/9 were detected by Western blot.Results RT-qPCR results showed that the expression of RP11-757G1.5 was significantly upregulated in various gastric cancer cell lines compared with the normal gastric epithelial cell line GES-1(P<0.05).The MKN-45 and HGC-27 cell lines,which exhibited the highest expression levels,were selected for subsequent functional studies.After successful establishment of RP11-757G1.5 knockdown models,a series of functional experiments were performed.The CCK-8 assay revealed that cell proliferation viability was significantly decreased in the two interference groups(si-757G1.5#1 and si-757G1.5#2)compared with the Control and si-NC groups(P<0.05).Meanwhile,drug sensitivity tests based on the CCK-8 method indicated that the interference groups exhibited significantly enhanced chemosensitivity to cisplatin,with IC50 values decreased by approximately 2.3-2.7-fold(P<0.05).In addition,wound healing and Transwell assays demonstrated that the migration and invasion abilities of the cells were also significantly inhibited in the interference groups,as evidenced by markedly reduced wound closure rates and number of invading cells(P<0.05).At the mechanistic level,Western blot analysis showed that the protein expression levels of MMP-2 and MMP-9 were significantly downregulated in the interference groups(P<0.05).Conclusion RP11-757G1.5 is highly expressed in gastric cancer and promotes malignant phenotypes of tumor cells by regulating MMP-2 and MMP-9 expression,while also affecting chemotherapy sensitivity.These findings suggest its potential as a novel therapeutic target for gastric cancer.

Abstract:Objective To identify causal proteins and develop a prognostic model for gastric cancer,with the ultimate goal of unraveling the biological basis of risk stratification and its implications for drug sensitivity.Methods Utilizing an integrative multi-omics strategy,this study systematically combined cross-cohort gastric cancer genome-wide association study and protein quantitative trait loci(pQTL)data for Mendelian randomization analysis.This approach was integrated with Kyoto Encyclopedia of Genes and Genomes and Gene Ontology functional annotations to identify key biological pathways.A prognostic model was constructed using Least Absolute Shrinkage and Selection Operator(LASSO)-Cox and multivariate Cox regression analyses,and a risk score was calculated.All patients were divided into high-risk and low-risk cohorts based on the median risk score.The model was trained and validated using the GSE62254,GSE15459,and TCGA-STAD datasets.Gene Set Enrichment Analysis,immune microenvironment analysis,and drug sensitivity prediction were used to reveal the molecular characteristics of the high-and low-risk groups.Results Gastric cancer risk-associated pQTLs were significantly enriched in immune response(cytokine receptor interactions,complement cascade)and metabolic pathways(phosphatidylinositol 3-kinase-protein kinase B,mitogen-activated protein kinase).LASSO-Cox and multivariate Cox regression analyses,based on causally associated pQTLs and prognostic genes,revealed that seven genes including inhibin subunit beta B,matrilin 3,TATA-box binding protein like 1,calmegin,chondroitin sulfate proteoglycan 4,lipopolysaccharide binding protein and ST3 beta-galactoside alpha-2,3-sialyltransferase 6 were included in the prognostic model.Kaplan-Meier analysis and area under the receiver operating characteristic curve analysis validated the model's robust predictive performance in both the training and validation sets.The high-risk group exhibited a proinflammatory microenvironment.Furthermore,this group exhibited significantly higher sensitivity to 10 drugs,including 5-fluorouracil,compared with the low-risk group.Conclusion The 7-gene prognostic model established in this study achieves survival risk stratification for gastric cancer,reveals that immune-metabolic imbalance is the core mechanism of risk stratification,and provides a potential biomarker basis for the selection of personalized drug treatment options for high-risk gastric cancer patients.

Abstract:Objective To investigate the effects of insulin-like growth factor 2mRNA-binding protein 3(IGF2BP3)on the malignant phenotype of esophageal cancer cells and its upstream regulatory mechanisms.Methods Bioinformatics analysis combined with real-time quantitative PCR and Western blot were employed to detect the expression of IGF2BP3 and Tet methylcytosine dioxygenase1(TET1),while the correlation between IGF2BP3 and TET1 expression was analyzed in public databases.In esophageal cancer cells TE-15 and ESC-410 transfected with IGF2BP3-specific small interference RNA(siRNA;si-IGF2BP3 group)and negative control siRNA(si-NC group),cell viability,cell proliferation ability and migration and invasion capacities were assessed by Cell Counting Kit-8,5-ethynyl-2'-deoxyuridine(EdU)and Transwell migration and Matrigel invasion assays,and apoptosis was determined by flow cytometry.Western blot was performed to detect the protein expression levels of Ki67,matrix metalloproteinase(MMP)-7/9,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and cleaved caspase-3(CC3).In cells transfected with TET1 overexpression plasmid(Oe-TET1 group)and empty vector plasmid(Oe-NC group),or TET1-specific siRNA(si-TET1 group)and si-NC group,Western blot and RNA methylated immunoprecipitation were utilized to evaluate the protein expression level of IGF2BP3 and the N6-methyladenosine(m6A)methylation degree.Results Compared to normal tissues,the expression of both IGF2BP3 and TET1 was significantly up-regulated in esophageal cancer tissues(P<0.001),and a significant positive correlation was observed between their expression levels(r=0.220,P<0.001).Experimental validation demonstrated that in esophageal cancer cell lines(Eca-109,TE-1,EC-1,ESC-410),the mRNA and protein expression levels of IGF2BP3 and TET1 were higher than those in the normal human esophageal epithelial cell line HET-1A,with the highest expression observed in TE-15 and ESC-410 cells(P<0.001).In functional studies,results showed that compared to the si-NC group,the si-IGF2BP3 group exhibited significantly reduced proliferative activity,decreased EdU-positive rate,weakened migration and invasion abilities,and a significantly increased apoptosis rate(P<0.001).The protein expression levels of Ki-67,MMP-7,MMP-9,and Bcl-2 were down-regulated in the si-IGF2BP3 group,while the expression levels of Bax and CC3 were up-regulated(P<0.001).In mechanistic studies,compared to the Oe-NC group,the Oe-TET1 group showed significantly increased m6A methylation level and protein expression of IGF2BP3;whereas compared to the si-NC group,the si-TET1 group exhibited significantly reduced m6A methylation level and protein expression of IGF2BP3(P<0.001).Conclusion In esophageal cancer,TET1 potentially upregulates IGF2BP3 by enhancing its m⁶A methylation,thereby driving malignant progression.Consequently,the TET1/IGF2BP3 axis represents a promising potential therapeutic target.

Abstract:Cell cycle checkpoints ensure the orderly progression of the cell cycle by precisely monitoring the fidelity of DNA replication and division.Their dynamic regulation is highly dependent on the spatiotemporally specific protein degradation mediated by the ubiquitin-proteasome system(UPS).Aberrant degradation of tumor suppressors or excessive accumulation of oncoproteins are key mechanisms driving uncontrolled cell proliferation,increased genomic instability,and ultimately tumorigenesis and cancer progression.This article systematically reviews the molecular mechanisms by which the UPS regulates cell cycle checkpoints through ubiquitination,examines its dysregulated patterns in the context of tumors,and summarizes the functional roles of E3 ubiquitin ligases and deubiquitinating enzymes in the regulation of cell cycle checkpoints.This review aims to provide a new theoretical basis for developing anticancer strategies targeting cell cycle regulation.

Abstract:Objective To investigate the expression of immunoglobulin superfamily member 9(IGSF9)in endometrial carcinoma(EC)and its relationship with prognosis and immune cell infiltration.Methods A total of 106 EC patients who underwent radical surgery at the Fourth Hospital of Shijiazhuang between January 2016 and December 2019 were enrolled.From the surgical specimens,106 tumor tissues and 58 paired adjacent normal endometrial tissues were collected for the study.Immunohistochemistry(IHC)was used to detect the expression level of IGSF9 in tissues,and its relationship with clinicopathological characteristics was evaluated.The Gene Expression Profiling Interactive Analysis(GEPIA)database was employed to analyze IGSF9 mRNA expression.Real-time quantitative PCR(RT-qPCR)and Western blot were performed to determine mRNA and protein expression levels of IGSF9,respectively.Kaplan-Meier survival analysis with the log-rank test and Cox proportional hazards regression models were applied to assess the association between IGSF9 expression and patient prognosis.The Tumor Immune Estimation Resource(TIMER)database was utilized to explore the relationship between IGSF9 expression and immune cell infiltration.Results Immunohistochemical analysis revealed a positive expression rate of IGSF9 protein in EC tissues of 55.7%(59/106),significantly higher than the 20.7%(12/58)observed in adjacent non-cancerous tissues,with a statistically significant difference(P<0.001).Moreover,high IGSF9 expression was closely associated with adverse clinicopathological features,including lymph node metastasis,advanced(Stage Ⅲ and Ⅳ)FIGO staging,and deep myometrial invasion.Validation via the GEPIA database,RT-qPCR,and Western blot experiments consistently demonstrated that both mRNA and protein expression levels of IGSF9 were significantly elevated in EC tissues compared to normal tissues(all P<0.01).Survival analysis indicated that the median overall survival of IGSF9-positive patients was 44 months,significantly shorter than the 57 months in the IGSF9-negative group,with a statistically significant difference(P=0.001).Multivariate analysis confirmed that IGSF9 positivity is an independent significant risk factor for patient prognosis,with a hazard ratio of 5.684(P=0.039),indicating that the risk of death in positive patients was 5.684 times that of negative patients.Furthermore,analysis of the TIMER database revealed that IGSF9 expression was significantly negatively correlated with the infiltration levels of B cells,CD8⁺ T cells,CD4⁺ T cells,macrophages,and dendritic cells in the tumor microenvironment(all P<0.05).Conclusion IGSF9 is highly expressed in EC,and its expression level is associated with poor patient prognosis and an immunosuppressive microenvironment,suggesting its potential as a biomarker for prognostic assessment and a target for immunotherapy in EC.

Abstract:Objective To explore the clinical significance of serum thrombospondin-1(TSP-1)and microRNA-21(miR-21)expression levels and their relationship with survival outcomes in patients with esophageal squamous cell carcinoma(ESCC).Methods Serum samples were collected from 100 patients with pathologically confirmed ESCC after treatment at Huai'an Hospital between January 2020 and December 2022.Serum TSP-1 levels were measured using enzyme-linked immunosorbent assay,and miR-21 expression was detected by real-time quantitative PCR.Patients were stratified into high and low expression groups based on the median expression levels of serum TSP-1 and miR-21.The correlation between the expression of these biomarkers and clinicopathological features was analyzed.Kaplan-Meier method with Log-rank test was used to compare overall survival(OS)between groups,and Cox proportional hazards regression model was applied to evaluate prognostic factors.Results The serum levels of TSP-1 and miR-21 in 100 ESCC patients were(103.32±14.26)ng/mL and 16.60±2.52,respectively.Based on the median expression levels(TSP-1:103.3 ng/mL;miR-21:16.6),patients were divided into high-and low-expression groups.The TSP-1 level in the high-expression group(117.53±11.02)ng/mL was significantly higher than that in the low-expression group(89.10±10.36)ng/mL(t=13.104,P<0.001).Similarly,the miR-21 level in the high-expression group(18.92±1.17)was significantly higher than that in the low-expression group(14.27±1.57)(t=17.274,P<0.001),and a negative correlation was observed between the two markers(r=-0.202,P=0.048).In terms of clinicopathological features,except for a significant association between miR-21 expression and gender(P<0.001),no notable correlations were found between the two markers and age,TNM stage,lymph node metastasis,or depth of invasion.Survival analysis revealed that the median OS in the high TSP-1 expression group was 32.6 months,which was significantly longer than the 27.1 months in the low-expression group(P<0.05).In contrast,the median OS in the high miR-21 expression group was 27.5 months,significantly shorter than the 33.6 months in the low-expression group(P<0.05).Multivariate analysis further confirmed that high TSP-1 expression was a protective factor for OS(HR=0.342,95%CI:0.193-0.606),while high miR-21 expression(HR=1.754,95%CI:1.039-2.963),lymph node metastasis,and TNM stage Ⅲ-Ⅳ were identified as risk factors.Conclusion In ESCC,serum TSP-1 as a protective factor shows a negative correlation with miR-21 as a risk factor.Both have potential prognostic value,and the efficacy of their combined application requires further validation in future studies.

Abstract:Objective To construct a prognostic risk model based on lactate metabolism-related genes using The Cancer Genome Atlas(TCGA)database,and to identify key biomarkers while validating their clinical significance in endometrial carcinoma(EC).Methods Transcriptionic,clinical,and survival data from 35 normal endometrial tissues and 546 EC tissues were obtained from the Uterine Corpus Endometrial Carcinoma(UCEC)project of TCGA.The 546 cancer tissue samples were randomly divided into a training set and a validation set at a 1:1 ratio.By comparing transcriptionic data between normal tissues and the cancer tissues in the training cohort,differentially expressed genes were identified and intersected with 344 lactate metabolism-related genes from the Molecular Signatures Database to derive a candidate gene set.Subsequently,univariate Cox regression analysis was initially used to screen for prognosis-related genes,followed by Least Absolute Shrinkage and Selection Operator(LASSO)-Cox regression for further dimensionality reduction,ultimately constructing a final risk score model.Patients were stratified into high-risk and low-risk groups based on the median risk score from the model.Differences in clinical characteristics between the high-risk and low-risk groups were compared using the Wilcoxon rank-sum test and the chi-square test,while survival differences between the groups were assessed via Kaplan-Meier survival analysis and the log-rank test.Additionally,the oncoPredict R package was employed to predict and compare the sensitivity to commonly used anticancer drugs,measured by the half-maximal inhibitory concentration value,between the high-risk and low-risk groups.Results A total of 7 008 differentially expressed genes were identified from the TCGA-UCEC database.Focusing on lactate metabolism-related genes,a prognostic risk model comprising three genes,solute carrier family 16 member 1(SLC16A1),GATA binding protein 2(GATA2),and anaplastic lymphoma kinase(ALK),was constructed using univariate and LASSO-Cox regression analyses.The results showed that patients in the high-risk group were older and had more advanced FIGO stages(all P<0.05).Survival analysis confirmed that,compared to the low-risk group,patients in the high-risk group had significantly shorter overall survival in both the training set(P<0.001)and the validation set(P=0.034).Drug sensitivity analysis further revealed that the low-risk group exhibited higher sensitivity to paclitaxel,docetaxel,and cyclophosphamide(all P<0.05),whereas no statistically significant differences in sensitivity to platinum-based drugs or topotecan were observed between the two groups(P>0.05).Conclusion The three-gene risk model,comprising SLC16A1,GATA2,and ALK,establishes lactate metabolism as a key predictor of prognosis in endometrial carcinoma and lays the groundwork for personalized treatment strategies.

Abstract:Objective To construct a risk model of lymph node metastasis of breast cancer based on dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Methods A total of 81 breast cancer patients who underwent surgical treatment at Lu'an People's Hospital from July 2021 to December 2024 were retrospectively enrolled.According to a 7:3 ratio,the patients were randomly allocated into a training set(n=57)and a validation set(n=24).Based on postoperative pathological results,patients in each dataset were further categorized into a lymph node metastasis group and a non-metastasis group.DCE-MRI results from preoperative examinations of all enrolled patients were collected.Binary logistic regression analysis was employed to identify DCE-MRI findings associated with breast cancer lymph node metastasis.Based on these findings,a risk prediction model was developed.The predictive performance of the model for evaluating lymph node metastasis in breast cancer was assessed using statistical methods including receiver operating characteristic(ROC)curve analysis,calibration curve evaluation,decision curve analysis,and external validation.Results In the training set,29 patients(50.88%)were pathologically confirmed to have lymph node metastasis,while 12 patients(50.00%)in the validation set had lymph node metastasis.Univariate analysis revealed no statistically significant differences in baseline characteristics between the two groups(P>0.05),while significant differences were observed in multiple DCE-MRI parameters(all P<0.05).).Specifically,the metastatic group exhibited predominant irregular/round lymph node morphology(58.62%vs.32.14%),reduced long-to-short-axis ratio(1.74±0.43 vs.2.08±0.24),increased cortical-medullary thickness ratio(1.15±0.35 vs.0.87±0.21),higher incidence of hilum absence(58.62%vs.25.00%),and elevated signal enhancement ratio(SER)values(185.01%±8.16%vs.176.94%±8.02%).Regression analysis identified the following as independent influencing factors for lymph node metastasis,including lymph node morphology(OR=13.173,95%CI:1.069-162.335,P=0.044),long-to-short-axis ratio(OR=0.024,95%CI:0.002-0.380,P=0.008),cortical-medullary thickness ratio(OR=1.927,95%CI:1.205-3.083,P=0.006),absent lymph node hilum(OR=18.241,95%CI:1.476-225.458,P=0.024),and SER(OR=1.205,95%CI:1.050-1.383,P=0.008).A risk scoring model constructed based on these factors demonstrated that a higher total score was associated with an increased risk of metastasis.Model validation in the training set showed strong agreement between the calibration curve and the ideal curve,an area under the ROC curve of 0.953(95%CI:0.905-1.000),and a positive net benefit in the decision curve within the threshold probability range of 0.03-0.99,with a maximum net benefit of 0.509.External validation further confirmed the model's generalizability,with an area under the ROC curve of 0.946(95%CI:0.894-0.998)in the validation set.Conclusion A DCE-MRI-based risk model for breast cancer lymph node metastasis demonstrates satisfactory performance in predicting nodal involvement and may serve as a non-invasive method for preoperative assessment of lymph node status in breast cancer patients.

Abstract:Objective To observe the short-term and long-term efficacy of sintilimab combined with hyperthermic intraperitoneal chemotherapy(HIPEC)as first-line treatment for advanced gastric cancer.Methods A total of 87 patients with advanced gastric cancer admitted to Hengshui People's Hospital from January 2019 to August 2020 were enrolled in this study.Based on treatment regimens,patients were divided into the combination group(n=43)and the HIPEC group(n=44).All patients received the XELOX(capecitabine/oxaliplatin)regimen.The HIPEC group additionally underwent HIPEC(containing 5-fluorouracil),while the combination group received intravenous sintilimab(200 mg per dose,once every three weeks)in addition to the HIPEC group's regimen.Therapeutic efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1,while adverse events were graded for severity using the Common Terminology Criteria for Adverse Events version 5.0 from the National Cancer Institute.Serum levels of carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199),and carbohydrate antigen 724(CA724)were measured before and after treatment.Survival analysis was performed using the Kaplan-Meier method,with between-group comparisons conducted by the Log-rank test.Results The objective response rate(ORR)for the entire cohort of 87 patients was 51.72%(45/87).Specifically,the ORR in the combination group reached 62.79%(27/43),significantly higher than the 40.91%(18/44)observed in the HIPEC group(χ²=4.170,P=0.041).Analysis of tumor markers revealed that post-treatment serum levels of CEA,CA199,and CA724 in the combination group were(8.57±2.04)ng/mL,(194.22±45.07)mg/L,and(9.26±2.89)μg/L,respectively,all significantly lower than(12.36±3.81)ng/mL,(261.58±52.17)mg/L,and(13.47±4.45)μg/L in the HIPEC group(t=5.765,6.438,5.219,respectively;all P<0.001).Survival analysis indicated that the combination group achieved a median overall survival of 16.6 months and a 2-year survival rate of 44.19%(19/43),both significantly superior to the HIPEC group's 13.8 months and 25.00%(11/44)with a Log-rank χ² value of 5.186(P=0.023).In terms of safety,adverse reactions were predominantly grade 1-2 in both groups,with no statistically significant differences in the incidence or severity of fatigue,gastrointestinal reactions,myelosuppression,hepatorenal dysfunction,or rash(all P>0.05).Conclusion The administration of sintilimab-assisted HIPEC therapy in patients with advanced gastric cancer significantly enhances antitumor efficacy,effectively reduces serum tumor marker levels,and improves long-term survival.This treatment strategy demonstrates promising clinical application prospects and offers a new direction for comprehensive treatment of advanced gastric cancer.

Abstract:The incidence of melanoma has been steadily increasing,and treatment modalities have improved accordingly.Historically,any patient with a positive sentinel lymph node was recommended to undergo a completion lymph node dissection.However,recent studies have shown that completion lymph node dissection in sentinel lymph node-positive patients is associated with higher complication rates and confers no survival benefit,while yielding only improved regional disease control and additional prognostic information.Therefore,risk stratification models incorporating sentinel lymph node tumor burden and primary tumor characteristics have been developed to predict the status of non-sentinel lymph nodes,potentially allowing the omission of completion lymph node dissection in select patients.This review summarizes recent research on risk factors for non-sentinel lymph node involvement in melanoma and discusses their prognostic implications,with the aim of informing clinical practice.

Abstract:Objective To investigate the regulatory role of osteopontin(OPN)on stemness and angiogenic capacity in triple-negative breast cancer(TNBC)and the involvement of the Notch signaling pathway.Methods Based on in vitro cultures of human normal mammary epithelial cells(MCF-10A),luminal breast cancer cells(MCF-7),and TNBC cells(MDA-MB-436),an OPN-overexpressing(OPN-OE)vector was transfected into MDA-MB-436 cells to establish a stable OPN-overexpressing cell line(OPN-OE group).Control groups included untreated cells(Control group)and empty vector-transfected cells(Vector group).To investigate the role of the Notch signaling pathway,an additional OPN-OE+DAPT group was set up,in which cells were pretreated with the γ-secretase inhibitor DAPT prior to transfection.Subsequently,stemness characteristics were assessed using a tumor sphere formation assay,and pro-angiogenic capacity was evaluated through a tube formation assay with human umbilical vein endothelial cells(HUVECs).Meanwhile,the expression levels of stemness markers,including cluster of differentiation(CD)44,CD24,and aldehyde dehydrogenase 1,as well as vascular endothelial markers such as von Willebrand factor and CD31,were determined by Western blot analysis.Results MDA-MB-436 cells exhibited the highest tumor sphere-forming capacity and expression levels of stemness markers.Their conditioned medium also induced the highest tube formation in HUVECs and expression of vascular endothelial markers.Moreover,the protein levels of OPN and Notch1 in these cells were significantly higher than those in MCF-7 and MCF-10A cells(P<0.05).Compared with the Control and Vector groups,the OPN-OE group showed enhanced tumor sphere formation,upregulation of stemness markers,and significantly increased pro-angiogenic capacity along with related marker expression(P<0.05).However,these OPN overexpression-enhanced stemness properties and pro-angiogenic effects were significantly inhibited by treatment with the Notch pathway inhibitor DAPT(P<0.05).Conclusion OPN enhances stemness and pro-angiogenic capacity in TNBC cells by activating the Notch signaling pathway.Inhibition of the Notch pathway reverses these effects,suggesting that the OPN-Notch axis may represent a potential therapeutic target for TNBC.

Abstract:Objective To explore the changes in intestinal flora in people after cholecystectomy and their correlation with colorectal cancer.Methods This study enrolled a total of 41 Han Chinese subjects from Baotou Central Hospital who had long-term residence in the Inner Mongolia Autonomous Region.From October 2022 to October 2023,their basic information and fecal samples were collected.This included 15 fecal samples from healthy individuals,designated as the healthy control group;16 fecal samples from patients who had undergone cholecystectomy 1-5 years prior,designated as the cholecystectomy group;and 10 fecal samples from colorectal cancer patients without a history of cholecystectomy,designated as the colorectal cancer group.16S rRNA gene sequencing technology was used to analyze the composition,richness and diversity of their intestinal flora,and the differences between groups were compared.Results A total of 3 293 390 high-quality sequences were obtained by sequencing,with good data coverage.At the phylum level,both the post-cholecystectomy group and the colorectal cancer group showed an increase in the relative abundance of Bacteroidota,Proteobacteria,Verrucomicrobiota and Fusobacteria,while the relative abundance of Actinobacteriota showed a decreasing trend.At the genus level,both groups showed increased abundances of Escherichia and Ruminococcus,While Faecalibacterium,Bifidobacterium,Collinsella,and Agathobacter were generally decreased.In addition,the post-cholecystectomy group independently exhibited a significant increase in Blautia and Gemmiger.The healthy control group had higher Chao1 index and Observed species index than the post-cholecystectomy group(P<0.05),and there was also a significant distinction in gut microbiota β-diversity between the healthy control group and the colorectal cancer group(P<0.05).In the inter-group comparison,Lachnospiraceae,Ruminococcus,Faecalimonas and Burkholderiaceae were the main marker flora in the post-cholecystectomy group;while the colorectal cancer group was mainly characterized by Porphyromonadaceae,Peptostreptococcus and Fusobacteriota.Further analysis showed that the abundances of Collinsella,Coriobacteriaceae,and Chloroflexota in the healthy control group were significantly higher than those in the post-cholecystectomy group.In contrast,the colorectal cancer group had higher abundances of Porphyromonas,Anaeroglobus,Fusobacterium,Peptostreptococcus,Ruthenibacterium,Peptoniphilus,Tissierella,and Micromonascompared with the post-cholecystectomy group.Conclusion The changes in intestinal flora composition in people 1-5 years after cholecystectomy are associated with an increased risk of colorectal cancer.Both groups show a trend of decreased bacteria producing short-chain fatty acids and probiotics,along with increased pathogenic bacteria.Additionally,colorectal cancer patients are also accompanied by a significant reduction in intestinal flora richness and separation of community structure.

Abstract:Objective To investigate the expression levels of sequestosome 1(P62)and phosphatase and tensin homolog deleted on chromosome 10(PTEN)in nasal cavity malignant melanoma(MM)tissues and analyze their relationships with clinicopathological characteristics and patient prognosis.Methods A total of 20 patients with pathologically confirmed nasal cavity MM(malignant group)and 20 with nasal inverted papilloma(benign group)were enrolled from the Second Affiliated Hospital of Hebei North University between October 2018 and October 2022.The protein and gene expression levels of P62 and PTEN were detected using immunohistochemical SP and real-time quantitative PCR methods,respectively.Systematic comparisons were made of P62 and PTEN expression among malignant tissues,adjacent tissues,and benign lesions.The relationships between their expression levels and clinicopathological features in the malignant group were analyzed.All malignant group patients were followed up for 1 year postoperatively to record recurrence and disease-free survival.Differences in P62 and PTEN expression between patients with and without recurrence were compared.Restricted cubic spline analysis was employed to evaluate the nonlinear relationship between gene expression and recurrence risk,while Kaplan-Meier method with Log-rank test was used to analyze differences in prognosis between patients with different P62 and PTEN expression levels.Results P62 and PTEN exhibited dynamic and opposing expression patterns across nasal tissue types.P62 levels were lowest in benign lesions(protein-positive rate:15.0%;gene expression:0.98±0.12),increased in paracancerous tissues(50.0%;1.25±0.27),and peaked in cancerous tissues(80.0%;1.83±0.25).Conversely,PTEN showed a progressive decline from the highest level in benign lesions(95.0%;1.67±0.33)to the lowest in cancerous tissues(35.0%;0.76±0.21),with all intergroup differences being statistically significant(all P<0.001).Clinicopathological analysis demonstrated that P62 expression increased with higher tumor stage(stage Ⅰ-Ⅲ:1.60±0.28 to 2.00±0.18)and lymph node metastasis(without 1.61±0.25 vs.with metastasis 1.90±0.21),while PTEN expression correspondingly decreased(Stage Ⅰ-Ⅲ:0.91±0.22 to 0.62±0.18;without 0.92±0.19 vs.with metastasis 0.71±0.19).Postoperative 1-year recurrent patients(9/20)showed higher P62 expression(2.01±0.17 vs.1.67±0.19)and lower PTEN expression(0.60±0.18 vs.0.89±0.14)in cancerous tissues,with recurrence risk demonstrating a nonlinear dose-response relationship with P62(≥1.760)and PTEN(≤0.815)expression levels.Survival analysis indicated that P62-positive patients had significantly shorter median disease-free survival(8.0 months vs.12.0 months),while PTEN-positive patients showed better prognosis(12.0 months vs.7.0 months),with all differences being statistically significant(P<0.05).Conclusion Elevated P62 and reduced PTEN expression were significantly correlated with malignant progression and postoperative recurrence in nasal MM.These two markers show promise as potential molecular biomarkers for assessing tumor biological behavior and prognosis,demonstrating considerable clinical translational value.

Abstract:Cancer-related sarcopenia is a common complication in patients with malignant tumors,characterized by progressive loss of skeletal muscle mass,reduced muscle strength,and decline in physical function.It significantly impacts patients'quality of life,the efficacy of anti-tumor treatments,and overall survival prognosis.The Expert Committee on Cancer Nutrition Therapy of Chinese Society of Clinical Oncology(CSCO)and the Expert Committee on Supportive and Rehabilitative Care in Oncology of CSCO,organized a national panel of national experts to develop this consensus,based on the current status of diagnosis and treatment of cancer-related sarcopenia in China,evidence from domestic and international publications,as well as expert experience and opinions.This consensus systematically elaborates on the definition,epidemiological characteristics,etiology and pathogenesis,screening and diagnosis methods,nutrition and multimodal management,prevention strategies and future research directions related to cancer-related sarcopenia.The aim is to provide standardized and individualized diagnosis and treatment guidance for clinical practice and to promote comprehensive,full-cycle management of cancer patients.

Abstract:Objective To investigate the expression of transient receptor potential anchor protein 1(TRPA1)and transient receptor potential vanillin 1(TRPV1)in cervical cancer tissues and their clinical significance.Methods A total of 90 patients with primary cervical cancer admitted to Guangyuan Central Hospital from January 2020 to December 2021 were selected,and cervical cancer tissues and corresponding adjacent tissue samples were collected.The expressions of TRPA1 and TRPV1 were detected by immunohistochemistry,and their relationships with the clinicopathological characteristics of patients were analyzed.The survival curve was plotted using the Kaplan-meier method,and the survival difference was tested by Log-rank.The Cox proportional hazards regression model was used to analyze the factors influencing the overall survival(OS)of cervical cancer.Results The high expression rate of TRPA1 in cervical cancer tissues was 69.2%(63/91),significantly higher than 33.0%(30/91)in adjacent tissues.The high expression rate of TRPV1 in cervical cancer tissues was 63.7%(58/91),which was also significantly higher than 29.7%(27/91)in adjacent tissues.High expression of TRPA1 was significantly correlated with the degree of differentiation(χ2=4.670,P=0.031),FIGO stage(χ2=6.742,P=0.009),depth of invasion(χ2=7.892,P=0.005),and distant metastasis(χ2=5.663,P=0.017).High expression of TRPV1 was significantly correlated with the degree of differentiation(χ2=8.987,P=0.003),FIGO stage(χ2=4.138,P=0.042),depth of invasion(χ2=4.701,P=0.036),and distant metastasis(χ2=5.968,P=0.015).Kaplan-Meier survival analysis showed that the median OS in the high-expression group of TRPA1 was 20 months,which was not reached in the low-expression group(P=0.001).The median OS in the high-expression group of TRPV1 was 17.5 months,which was not reached in the low-expression group(P=0.006).Univariate COX regression analysis indicated that TRPA1 was highly expressed(HR=2.081,95%CI:1.071-3.025),TRPV1 was highly expressed(HR=1.402,95%CI:1.113-2.558),and poorly differentiated(HR=1.661,95%CI:1.143-2.769),advanced FIGO stage(HR=1.538,95%CI:1.136-2.952),deep muscular layer infiltration(HR=1.368,95%CI:1.064-2.526),and presence of distant metastasis(HR=1.337,95%CI:1.203-2.436)are factors influencing the OS of patients with cervical cancer.Conclusion TRPA1 and TRPV1 are upregulated in cervical cancer tissues.Their high expression is closely related to adverse clinicopathological features and prognosis,and can be used as potential molecular markers for evaluating the prognosis of patients with cervical cancer.

Abstract:Objective To explore the efficacy of surgery,radiotherapy[three-dimensional conformal radiotherapy(3D-CRT)/fractionated stereotactic radiotherapy(FSRT)]and chemotherapy[temozolomide(TMZ)/nimostine(ACNU)]in the treatment of primary and recurrent gliomas.Methods A retrospective analysis was conducted on the clinical medical records of 78 patients with glioma admitted to the Rocket Force Specialized Medical Center from June 2017 to April 2023.Results The median age of all patients in the group was 50 years old(ranging from 13 to 76 years old),and there were 39 male patients.At the initial treatment,69 cases underwent surgical resection,21 cases received FSRT,and 47 cases received 3D-CRT.Thirteen cases received ACNU monotherapy chemotherapy,and 38 cases received TMZ chemotherapy.Multivariate analysis showed that radiotherapy at the initial treatment(HR=0.325,95%CI:0.118-0.816,P=0.018)and chemotherapy(HR=0.516,95%CI:0.284-0.968,P=0.039)can reduce the risk of recurrence.Among them,3D-CRT is superior to FSRT,and TMZ is superior to ACNU.Among the 39 relapsed patients,neither radiotherapy(P=0.480)nor chemotherapy(P=0.830)after relapse could reduce the risk of secondary relapse.Although surgery showed a reducing trend,it did not reach a significant difference(HR=0.296,95%CI:0.075-1.171,P=0.083).In terms of overall survival,surgery could reduce the risk of death(HR=0.246,95%CI:0.063-0.829,P=0.025),while radiotherapy(P=0.142)and chemotherapy(P=0.539)had no significant effect.Conclusion Adjuvant chemoradiotherapy can reduce the recurrence risk of primary glioma.Among them,the efficacy of 3D-CRT is superior to that of FSRT,and TMZ is superior to ACNU.Surgery may help reduce the risk of secondary progression after recurrence and significantly improve overall survival.In addition,3D-CRT and multi-cycle chemotherapy can prolong the overall survival time of patients with WHO grade IV glioma.