Abstract:Objective To explore the clinical value of magnetic resonance imaging(MRI)radiomics parameters in predicting the risk of radiation-induced temporal lobe injury(RTLI)in patients with locally advanced nasopharyngeal carcinoma(LA-NPC).Methods A retrospective analysis was conducted on 126 patients with LA-NPC who received intensity-modulated radiotherapy(IMRT)and concurrent platinum-based chemotherapy from June 2021 to June 2023.Patients were randomly assigned to the training set(n=88)and the test set(n=38)in a ratio of 7:3.Univariate and multivariate Logistic regression models were used to predict the risk factors for RTLI occurrence.The radiomics feature data in the MRI imaging sequences before treatment were extracted,and the Mann-Whitney,Pearson correlation,minimum absolute shrinkage and selection operator(LASSO)algorithms were used to screen the significant features.The clinical features and radiomics features screened out were integrated into a joint model based on the logistic regression algorithm.The receiver operating characteristic(ROC)curve,calibration curve and decision curve were used to compare and verify the predictive performance of the model.Results A total of 49 patients with LA-NPC developed RTLI,including 34 cases in the training set and 15 cases in the test set.The median latency from the completion of IMRT to the first MRI detection of RTLI in all damaged temporal lobes was 19.12 months.Logistic regression analysis showed that T stage(OR=8.414,95％CI:1.945-36.402,P=0.004)and D0.5cc(OR=5.315,1.610-17.543,P=0.006)were independent risk factors for predicting RTLI in patients with LA-NPC.The Rad-score model was constructed using six MRI texture features significantly associated with RTLI,and the combined model was constructed by combining two independent clinical factors.ROC curve analysis showed that the predictive performance of the combined model in the training set was superior to that of either the clinical model alone or the radiomics model(all P＜0.05).In the test set,the combined model superior to that of the clinical feature model(P=0.017),but showed no statistically significant difference when compared with the MRI-based radiomics model(P＞0.05).The calibration curve indicated good agreement between the predictions of the combined model and actual observations,while the decision curve demonstrated favorable clinical net benefit of the model.Conclusion The combined model constructed by integrating MRI radiomics features and clinical features can effectively predict the risk of RTLI in patients with LA-NPC and is expected to become an important auxiliary tool for RTLI prediction.

Abstract:Objective To explore the impacts of icariin(ICA)on the proliferation,migration,and invasion of liver cancer cells by adjusting long non-coding RNA(lncRNA)OIP5-AS1/miR-338-3p pathway.Methods MTT assay was used to measure the inhibitory effect of ICA on the proliferation of liver cancer SNU182 cells,and screen for the appropriate intervention concentration.Liver cancer SNU182 cells were classified into Control group,ICA group,ICA+pc-NC group,ICA+pc-OIP5-AS1group,ICA+pc-OIP5-AS1+miR-NC group,and ICA+pc-OIP5-AS1+miR-338-3p mimics group.Real-time quantitative PCR was performed to measure the expression of OIP5-AS1 and miR-338-3p.MTT assay was used to detect cell proliferation.Cell scratch assay was used to detect cell migration.Transwell method was used to measure cell invasion.Flow cytometry was used to measure cell apoptosis.Western blot was performed to detect the protein expression of vascular endothelial growth factor A(VEGF-A),vascular endothelial cadherin(VE-cadherin),proliferating cell nuclear antigen(PCNA),cleaved caspase-3,E-cadherin,N-cadherin and vimentin.The dual luciferase activity assay verified the targeting relationship between OIP5-AS1 and miR-338-3p.Results 12.5-100 μmol/L of ICA could inhibit the proliferation of SNU182 cells(P＜0.05),and 50 μmol/L was selected for the subsequent experiments.Compared with the Control group,the OIP5-AS1 expression,the growth activity,scratch healing rate,invasion number,N-cadherin,vimentin,VEGF-A,VE-cadherin,and PCNA protein expression of SNU182 cells in the ICA group reduced,while the miR-338-3p expression,cell apoptosis rates,E-cadherin and cleaved caspase-3 protein expression increased(P＜0.05).Compared with the ICA group and the ICA+pc-NC group,the OIP5-AS1 expression,the growth activity,scratch healing rate,invasion number,N-cadherin,vimentin,VEGF-A,VE-cadherin,and PCNA protein expression in SNU182 cells in the ICA+pc-OIP5-AS1 group increased,while the miR-338-3p expression,cell apoptosis rates,E-cadherin and cleaved caspase-3 protein expression reduced(P＜0.05).Upregulation of miR-338-3p could reduce the promoting effect of overexpression of OIP5-AS1 on the malignant biological behavior of SNU182 cells(P＜0.05).Conclusion ICA may inhibit the proliferation,migration and invasion of SNU182 cells while promoting apoptosis by downregulating the expression of OIP5-AS1 and upregulating the expression of miR-338-3p.

Abstract:Objective To investigate the mutation status of phosphatidylinositol 3-kinase catalytic subunit alpha(PIK3CA)in advanced non-small cell lung cancer(NSCLC)and its impact on the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)and patient prognosis.Methods Clinical data of 64 patients with PIK3CA-mutant advanced NSCLC diagnosed at the Affiliated Brain Hospital of Nanjing Medical University from January 2016 to March 2023 were collected.The association between different mutation sites and clinicopathological characteristics as well as prognosis was analyzed.Furthermore,39 patients with coexisting EGFR and PIK3CA mutations were compared with 84 patients harboring EGFR mutations alone to evaluate the influence of PIK3CA mutations on EGFR-TKI efficacy and prognosis.Univariate and multivariate Cox regression models were used to identify factors associated with prognosis.Results The most frequent PIK3CA mutation sites were E545K(20/64),H1047R(16/64),and E542K(12/64).The most common co-mutations were EGFR(29/64)and TP53(13/64).There were no significant differences in objective response rate(ORR:36.1％vs.28.6％),disease control rate(DCR:61.1％vs.61.9％),1-year survival rate(58.3％vs.57.1％),2-year survival rate(25.0％vs.23.8％),median progression-free survival(PFS:6.9 months vs.5.8 months),or median overall survival(OS:15.4 months vs.14.2 months)between the PIK3CA Exon 9 and Exon 20 mutation groups(all P＞0.05).Compared with the EGFR mutation group,The EGFR and PIK3CA co-mutant group had worse clinical efficacy,including lower ORR(41.0％vs.60.7％)and DCR(76.9％vs.95.2％),reduced 1-year survival rate(71.8％vs.94.0％)and 2-year survival rate(38.5％vs.67.9％),as well as shorter median PFS(7.9 months vs.14.2 months)and median OS(18.8 months vs.28.0 months),and the difference was statistically significant(all P＜0.05).Multivariate analysis identified PIK3CA mutation(HR=2.364,95％CI:1.578-3.542)and ECOG performance status(HR=2.319,95％CI:1.550-3.468)were independent risk factors for OS in EGFR mutation patients(P＜0.05).Conclusion The differential mutation of Exon 9 and Exon 20 of PIK3CA gene had no effect on short-term efficacy and prognosis of patients.The co-mutation of EGFR and PIK3CA affects the therapeutic effect of EGFR-TKI,increases the risk of patient death,and is an independent risk factor for poor prognosis of patients with targeted therapy.

Abstract:Objective To compare the incidence of complications and patient satisfaction between immediate prosthetic breast reconstruction and delayed prosthetic breast reconstruction in patients undergoing radiotherapy after radical mastectomy for breast cancer,and to analyze the influencing factors of complications.Methods This study is a single-center retrospective investigation.According to the inclusion and exclusion criteria,a total of 96 patients who underwent radical mastectomy,prosthetic breast reconstruction,and postoperative radiotherapy at Jiangsu Provincial Hospital of Traditional Chinese Medicine between January 2019 and November 2023 were included.Based on the timing of breast reconstruction,the patients were divided into the immediate prosthetic breast reconstruction group(immediate reconstruction group,n=58)and the delayed prosthetic breast reconstruction group(delayed reconstruction group,n=38).Complications and satisfaction scores were compared between the two groups,and the influence of related factors on the occurrence of complications was evaluated by logistic regression model.Results There were no statistically significant differences between the two groups in terms of age,menopausal status,TNM stage,neoadjuvant chemotherapy,tumor location,tumor number,molecular subtype,and postoperative radiotherapy field(P＞0.05).Regarding complications,the overall complication rate in the immediate reconstruction group was 32.8％(19/58),comparable to the 28.9％(11/38)in the delayed reconstruction group,with no statistically significant difference(P=0.694).However,the incidence of capsular contracture in the immediate reconstruction group was 20.7％(12/58),significantly higher than the 5.3％(2/38)in the delayed reconstruction group(P=0.036).Univariate analysis suggested that diabetes might be associated with an increased risk of complications(immediate reconstruction group:OR=4.306,P=0.016).There were no statistically significant differences between the two groups in breast satisfaction,psychological well-being,satisfaction with the medical process,or total satisfaction scores(P＞0.05).During the follow-up period,no deaths were observed in either group.One patient in the immediate reconstruction group(1/58,1.72％)developed bone metastasis 32 months after surgery,while two patients in the delayed reconstruction group(2/38,5.26％)developed visceral metastases at 18 months and 46 months after surgery,respectively.There was no statistically significant difference in the overall disease recurrence rate between the two groups(P=0.560).Conclusion For patients undergoing radiotherapy after radical mastectomy for breast cancer,delayed prosthetic reconstruction can reduce the risk of capsular contracture,while the overall incidence of complications and patient satisfaction are similar between the two reconstruction timing strategies.Clinical decision-making should comprehensively weigh these factors based on individual patient circumstances.

Abstract:This article aims to systematically elucidate the characteristics of the chemokine family,their mechanisms in the development and progression of colorectal cancer(CRC),clinical relevance,and diagnostic and therapeutic application value,as well as to explore the potential and current challenges of targeting chemokine pathways,in order to provide references for precision diagnosis and treatment of CRC and related research.By integrating research such as the classification and structure of chemokines,CRC-related molecular mechanisms,advances in diagnosis and treatment research,and targeting strategies(e.g,the CXCR4 inhibitor AMD3100),it has been found that chemokines and their receptors can regulate key processes in CRC,such as proliferation and metastasis,demonstrating potential as diagnostic biomarkers and therapeutic targets.Although strategies targeting chemokine pathways show promise for clinical application,existing challenges must be overcome to advance their translational application.

Abstract:Objective To explore the relationship between neuregulin-1(NRG1),lectin galactoside-binding soluble 1(LGALS1),and ubiquitin carboxyl-terminal hydrolase L1(UCHL1)with their clinical pathological features and prognosis in gastric cancer tissue.Methods A total of 105 gastric cancer patients admitted to Hainan Cancer Hospital from January 2017 to January 2022 were selected.Immunohistochemical staining was used to detect the expression of NRG 1,LGALS1,and UCHL1 proteins in the cancer tissue and paired adjacent tissues during surgery.Patients were followed up for 3 years postoperatively,and their survival status were recorded.Kaplan-Meier method was used draw a survival curve,and Cox proportional hazards regression model was employed to analyze prognostic factors in gastric cancer patients.Results The positive expression rates of NRG1,LGALS1 and UCHL1 in gastric cancer tissues were 77.14％,74.29％and 68.57％,respectively,which were significantly higher than 20.00％,15.24％and 18.10％in adjacent tissues,and the differences were statistically significant(x2=68.627,74.032,54.473,all P＜0.05).The expression of NRG1,LGALS1 and UCHL1 showed statistically significant differences among patients with different TNM stages,histological differentiation degrees,lymph node metastasis status,and depths of invasion(all P＜0.05).Survival analysis revealed that the 3-year postoperative survival rates for patients with positive expression of NRG1,LGALS1,and UCHL1 significantly lower than patients with negative expression(58.02％vs.79.17％,57.69％vs.77.78％,56.94％vs.75.76％,x2=4.230,4.107,4.476,all P＜0.05).Multivariate Cox regression analysis indicated that positive expression of NRG1(HR=3.196,95％CI:1.302-7.843,P=0.011),LGALS1(HR=3.824,95％CI:1.449-10.090,P=0.007),UCHL1(HR=4.280,95％CI:1.459-12.553,P=0.008)in tissues,along with lymph node metastasis(HR=2.795,95％CI:1.234-6.329,P=0.014),were significant factors affecting the prognosis of gastric cancer patients.Conclusion NRG1,LGALS1,and UCHL1 are highly expressed in gastric cancer tissue and are closely related with the clinicopathological characteristics and prognosis of patients.

Abstract:Objective To compare the efficacy differences between radical surgery and definitive radiotherapy in the treatment of stage T1-2N0M0 proximal esophageal squamous cell carcinoma,and to provide evidence for clinical treatment selection.Methods General data of patients with proximal esophageal squamous cell carcinoma admitted to the First Affiliated Hospital of Anhui Medical University from January 2013 to December 2022 were retrospectively collected.Patients with stage T1-2N0M0 who received definitive radiotherapy or radical surgery were selected.Propensity score matching(PSM)was applied to balance baseline differences between groups.Survival curves were plotted using the Kaplan-Meier method to compare overall survival(OS)between the two groups.Cox proportional hazards regression model was used to analyze factors related to prognosis.Results A total of 128 patients were included,with 79 in the surgery group and 49 in the radiotherapy group.There were no statistically significant differences in 3-year survival rate(80.93％vs.79.57％),5-year survival rate(64.37％vs.71.37％),or 10-year survival rate(24.41％vs.58.56％)between the radiotherapy and surgery groups(P＞0.05).After PSM,32 patients were included in each group,and the difference in OS between the two groups remained statistically insignificant(P＞0.05).Univariate Cox regression analysis showed that only age was a risk factor affecting OS(P=0.037),while gender,lesion location,smoking history,drinking history,lesion length,comorbidities,and treatment modality were not associated with OS(P＞0.05).Further multivariate Cox regression analysis,including clinically potentially significant variables(age,lesion location,length,comorbidities,and treatment modality),revealed that age(HR=2.865,95％CI:1.398-5.871,P=0.004)and lesion length(HR=2.105,95％CI:1.062-4.174,P=0.033)were independent prognostic factors for OS.Subgroup analysis showed that for patients with lesion length＞2.5 cm,the surgery group had better OS than the radiotherapy group(P=0.045).Recurrence occurred in 31 patients,with 19 in the surgery group and 12 in the radiotherapy group,and there was no statistically significant difference in recurrence rates between the two groups(P＞0.05).Conclusion Definitive radiotherapy and surgery have comparable efficacy in the treatment of stage T1-2N0M0 proximal esophageal carcinoma.Patients with lesion length＞2.5 cm may achieve better outcomes with surgery than with radiotherapy.Further studies are needed to better define the optimal patient populations for different treatment strategies.

Abstract:human epidermal growth factor receptor 2(HER2)gene mutations serve as critical drivers in various malignancies.Due to the diversity of mutation types,the functional changes in the HER2 protein vary significantly.Therefore,different targeted HER2 drugs need to be selected based on the specific mutation type.Current clinical practice and treatment strategies continue to be explored and optimized.This review comprehensively summarizes the diverse spectrum of HER2 gene mutations and evaluates corresponding clinical treatment strategies,aiming to provide insights for the development of personalized therapeutic approaches.

Abstract:Objective To investigate the expression characteristics of syntaxin 16(STX16)in hepatocellular carcinoma(HCC)and analyze its correlation with clinicopathological parameters and prognosis.Methods The differential expression,diagnostic efficacy,and prognostic association of STX16 in HCC and adjacent tissues were analyzed based on the Cancer Genome Atlas(TCGA)database.Clinical specimens from 132 HCC patients at Jiangsu Cancer Hospital were collected.Immunohistochemistry was used to detect STX16 protein expression in tumor and adjacent tissues.Its correlation with clinical-pathological parameters and overall survival(OS)was analyzed.Results In the TCGA cohort,STX16 expression was significantly higher in HCC tissues than in adjacent tissues(5.31±0.60 vs.3.24±0.39,P＜0.01).The receiver operating characteristic(ROC)curve analysis indicated that STX16 has good diagnostic value for HCC,with an area under the curve(AUC)of 0.940,a sensitivity of 87.0％,and a specificity of 90.0％.Survival analysis revealed that patients with high STX16 expression had significantly shorter progression-free interval(PFI:13.1 months vs.29.2 months,P=0.005)and overall survival(OS:48.9 months vs.69.3 months,P=0.035).Multivariate Cox regression confirmed that high STX16 expression was an independent risk factor for both PFI(HR=1.546,95％CI:1.047-2.282,P=0.028)and OS(HR=1.579,95％CI:1.019-2.448,P=0.041).In the clinical cohort,STX16 expression was also significantly higher in HCC tissues than in adjacent tissues(immunohistochemical score:5.99 vs.1.75,P＜0.01).Patients with high STX16 expression had shorter OS(44.0 months vs.not reached,P＜0.01).Cox regression analysis found that STX16 expression level was a risk factor for OS but not an independent prognostic factor.Conclusion STX16 is significantly overexpressed in HCC,closely associated with aggressive tumor features and poor prognosis,and may serve as a potential independent prognostic biomarker for HCC.

Abstract:Objective To investigate the predictive value of serum angiopoietin-2(Ang-2)and hypoxia-inducible factor-1α(HIF-1α)for early recurrence and metastasis in elderly patients with stage Ⅰ-ⅡA non-small cell lung cancer(NSCLC)after thoracoscopic resection.Methods A total of 258 elderly patients with stage Ⅰ-ⅡA NSCLC who underwent uniportal video-assisted thoracoscopic surgery at Yuncheng Central Hospital Affiliated to Shanxi Medical University from April 2022 to April 2023 were included.Serum levels of Ang-2 and HIF-1α were measured preoperatively in all patients.They were followed up for 2 years postoperatively and were divided into groups based on the occurrence of recurrence and metastasis during follow-up.Differences in serum Ang-2,HIF-1α levels,and baseline characteristics were compared between the groups.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of serum Ang-2 and HIF-1α levels for postoperative recurrence and metastasis risk.Results All 258 patients completed follow-up(range:7-24 months).Postoperative recurrence and metastasis occurred in 45 patients(17.44％),with a median recurrence time of 16 months.Compared with the non-recurrence group,the recurrence/metastasis group had a higher proportion of stage ⅡA disease and poorly differentiated tumors,and significantly higher preoperative levels of carcinoembryonic antigen(CEA),carbohydrate antigen 125(CA125),Ang-2,and HIF-1α(P＜0.05).Correlation analysis showed a positive correlation between the risk of postoperative recurrence/metastasis and serum levels of Ang-2 and HIF-1α(P＜0.05).ROC curve analysis revealed that the areas under the curve(AUC)for predicting early postoperative recurrence risk using serum Ang-2 alone,HIF-1α alone,and their combination were 0.849(95％CI:0.778-0.920),0.851(95％CI:0.788-0.914),and 0.917(95％CI:0.876-0.959),respectively.The predictive performance of the combined detection was significantly superior to that of either single indicator(Z=1.702,1.724;P=0.044,0.042).Conclusion Serum levels of Ang-2 and HIF-1α are positively correlated with postoperative recurrence and metastasis in elderly patients with stage I-ⅡANSCLC.Combined detection of these two indicators provides a good prediction of postoperative recurrence and metastasis risk.

Abstract:Objective To systematically evaluate the expression characteristics,prognostic value,and related biological functions of acyl-protein thioesterase 2(LYPLA2)in hepatocellular carcinoma(HCC),and to explore its potential application value in HCC diagnosis and treatment.Methods Transcriptomic data from 374 HCC tissues and 50 normal liver tissues in the Cancer Genome Atlas(TCGA)database were integrated to analyze the differential expression of LYPLA2,its correlation with prognosis and clinicopathological features.The CIBERSORT algorithm was used to assess immune cell infiltration,and Gene Set Enrichment Analysis(GSEA)was employed to screen LYPLA2-related signaling pathways.Fresh cancer tissues and adjacent non-cancerous tissues from 10 HCC patients who underwent surgical treatment at Taizhou First People's Hospital between October 2022 and October 2023 were collected.Immunohistochemical staining was used to verify the differential expression of the LYPLA2 protein.The Kaplan-Meier method was used for survival analysis,and Cox proportional hazards regression models were applied to evaluate prognostic factors.Results Analysis based on TCGA data showed that the mRNA expression level of LYPLA2 was significantly higher in HCC tissues compared to normal liver tissues(P＜0.001).Immunohistochemical staining results from clinical samples further confirmed that LYPLA2 protein expression was higher in HCC tissues than in adjacent tissues,approximately 2.8 times higher(histochemistry score:52.3±8.7 vs.18.6±5.2,P＜0.001).The median overall survival of patients in the high LYPLA2 expression group was significantly shortened by 50.9 months compared to the low LYPLA2 expression group(33.5 months vs.84.4 months,HR=2.37,95％CI=1.66-3.40,P＜0.001).The receiver operating characteristic curve(ROC)curve analysis indicated that LYPLA2 had good predictive efficacy for the 3-year survival rate of HCC patients(AUC=0.844).LYPLA2 expression significantly increased with higher pathological grade and elevated alpha-fetoprotein(AFP)levels(P＜0.05).Univariate Cox regression analysis showed that stage,pathological T stage,pathological M stage,and LYPLA2 expression were all factors affecting the prognosis of HCC patients(P＜0.05).Multivariate Cox regression analysis further confirmed that LYPLA2 expression was an independent prognostic factor for HCC(HR=2.124,95％CI:1.313-3.434,P=0.002).Correlation analysis revealed that high LYPLA2 expression was positively correlated with the infiltration levels of CD56+natural killer cells(r=0.371),macrophages(r=0.133),Th2 cells(r=0.191),and follicular helper T cells(r=0.128),and was co-expressed with immunomodulatory and immunosuppressive molecules.GSEA indicated that LYPLA2-related genes were significantly enriched in pathways such as DNA repair inhibition and metabolic reprogramming.Conclusion LYPLA2 is upregulated in HCC and serves as an independent adverse prognostic factor.Its mechanism may be related to reshaping the tumor immunosuppressive microenvironment.Targeting LYPLA2 holds promise as a novel strategy for HCC immunotherapy.

Abstract:Objective To analyze the predictive value of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI)combined with diffusion kurtosis imaging(DKI)in magnetic resonance imaging(MRI)for postoperative recurrence in rectal cancer patients after total mesorectal excision.Methods A total of 120 rectal cancer patients who underwent total mesorectal excision at Nanjing Tianyinshan Hospital from February 2021 to February 2023 were included.All patients underwent IVIM-DWI and MRI-DKI examinations 7 days after surgery and were followed up for 12 months.Based on postoperative recurrence status,they were divided into a recurrence group(62 cases)and a non-recurrence group(58 cases).The IVIM-DWI parameters[apparent diffusion coefficient(ADC),perfusion fraction(f),pseudo-diffusion coefficient(D*),true diffusion coefficient(D)]and MRI-DKI parameters[mean kurtosis(MK),mean diffusivity(MD)]were compared between the two groups.Logistic multivariate regression was used to analyze risk factors for recurrence after total mesorectal excision.A nomogram prediction model was constructed using R software and internally validated by the Bootstrap method.The Hosmer-Lemeshow test was applied to evaluate the goodness of fit.Receiver operating characteristic(ROC)curves were plotted to assess the predictive performance of individual parameters and their combination for recurrence.Results Compared with the non-recurrence group,the recurrence group showed significantly lower ADC,D*,D,and MD values(P＜0.05),and significantly higher f values(P＜0.05).There was no statistically significant difference in MK values between the two groups(P＞0.05).Logistic multivariate regression analysis indicated that lymph node metastasis,differentiation,ADC,D*,D,f,postoperative chemoradiotherapy,and MD were independent risk factors for recurrence after total mesorectal excision(P＜0.05).The Hosmer-Lemeshow goodness-of-fit test indicated good agreement between the predicted values of the nomogram model and the actual observations(x2=7.826,P=0.449),with a concordance index(C-index)of 0.914 and an area under the curve(AUC)of 0.914(95％CI:0.844-0.947),indicating excellent discriminative ability.The combined prediction using IVIM-DWI and MRI-DKI parameters yielded an AUC of 0.847(95％CI:0.784-0.910),which was significantly higher than that of any single parameter(all P＜0.05).Conclusion Recurrence after total mesorectal excision in rectal cancer patients is closely associated with decreased ADC,D*,D,and MD values and increased f values.Combined detection of these imaging parameters can improve the sensitivity of postoperative recurrence prediction and holds important clinical reference value.

Abstract:Objective To investigate the effects of carcinoembryonic antigen-related cell adhesion molecule 19(CEACAM19)on the proliferation,pyroptosis,and invasion of human gastric cancer cells via modulation of the adenosine monophosphate activated protein kinase(AMPK)/silent information regulator two homolog 1(SIRT1)/nuclear factor kappa B(NF-κB)signaling pathway.Methods The gastric adenocarcinoma cell line AGS was selected and divided into the following groups:Control group(non-transfected with plasmid),siRNA-NC group(transfected with CEACAM19 negative control),si-Cc19 group(transfected with CEACAM19 siRNA),si-Cc1 9+DMSO group(treated with DMSO after CEACAM19 siRNA transfection),and si-Cc1 9+AMPK inhibitor Compound C group(treated with Compound C after CEACAM19 siRNA transfection).Cell proliferation was assessed using the cell counting kit-8(CCK-8)assay and colony formation experiments.Cell pyroptosis was observed via scanning electron microscopy.Cell invasion capability was evaluated using the Transwell assay.Western blot was employed to detect the expression levels of proteins related to gasdermin D(GSDMD),cysteine aspartate-specific protease-1(caspase-1),E-cadherin,N-cadherin,and proteins related to the AMPK/SIRT1/NF-κB signaling pathway(AMPK,p-AMPK,SIRT1,p65,p-p65).Results Compared with the siRNA-NC group,the si-Cc19 group showed significantly decreased AGS cell survival rate,colony formation rate,number of invasive cells,N-cadherin expression,and p-p65/p65 ratio(P＜0.05),while the expression levels of pyroptosis-related proteins(GSDMD,caspase-1,E-cadherin)and pathway-related proteins(p-AMPK/AMPK/SIRT1)as well as interleukin-18(IL-18)in cell supernatant were significantly elevated(P＜0.05).Scanning electron microscopy results revealed that more AGS cells in the si-Cc1 9 group underwent swelling and rupture,with small pores appearing on the cell surface.In contrast,the si-Cc19+Compound C group showed significantly increased colony formation rate,cell survival rate,cell invasion count,p-p65/p65,and N-cadherin levels(P＜0.05),while the expression levels of GSDMD,caspase-1,E-cadherin,p-AMPK/AMPK,SIRT1,and IL-18 in cell supernatant were significantly decreased(P＜0.05),with reduced cell swelling and rupture.Conclusion CEACAM19 may promote the proliferation and invasion of gastric cancer cells and inhibit cell pyroptosis by regulating the AMPK/SIRT1/NF-κB signaling pathway.

Abstract:Objective To quantitatively analyze the impact of positioning errors on dose coverage of tumor target areas during intensity-modulated radiotherapy(IMRT)for lung cancer based on cone-beam computed tomography(CBCT)images,and to assess the risk of under-target area irradiation and over-spinal cord irradiation caused by positioning errors.To provide dosimetric evidence for optimizing the clinical operation process of IMRT for lung cancer and enhancing the safety of treatment.Methods A total of 100 patients with non-small cell lung cancer who received IMRT treatment in our hospital from January 2024 to January 2025 were selected.All patients were placed in the supine position with body immobilization using a vacuum bag.CBCT scans were performed before and during the treatment(once every 5 treatments).Perform gray-scale registration on CBCT images and positioning CT images,and record the positioning errors of patients in the three directions of left and right(X-axis),head and foot(Y-axis),and front and back(Z-axis).The positioning error data was reverse-imported into the original treatment plan through the radiotherapy planning system(TPS)to generate an"error simulation plan".The dosimetric parameters of the target area in the original plan and the error simulation plan[including target area coverage(D95)]were compared and analyzed.The dose received by 95％of the target volume,the average dose of the target area(Dmean),the dose uniformity index of the target area(HI),and the dosimetric parameters of the spinal cord[the maximum dose of the spinal cord(Dmax),the volume of the spinal cord receiving a dose of ≥45 Gy(V45)].The patients were divided into the mild error group(absolute error ≤2 mm),the moderate error group(2 mm＜absolute error≤5 mm),and the severe error group(absolute error＞5 mm)based on the size of the positioning error.The incidences of target area underdose(D95＜95％of the prescribed dose)and spinal cord excess(Dmax＞45 Gy)were compared among the three groups.Results A total of 558 CBCT scans were completed for 100 patients,including 486 pre-treatment scans(87.10％)and 72 in-treatment scans(12.90％).The mean values and distributions of the positioning errors in the X,Y,and Z axes were as follows:The error range of the X-axis(left and right)was-4.35 to 3.92 mm,with an mean value of(1.88±1.26)mm;The Y-axis(head and foot)error range was-5.21 to 5.03 mm,with an average of(2.15±1.38)mm.The error range of the Z-axis(front and back)was-4.12 to 3.85 mm,with an average of(2.01±1.31)mm.The mild error group had 223 times(39.96％),the moderate error group had 214 times(38.35％),and the severe error group had 121 times(21.68％).Among them,the proportion of severe errors in the Y-axis direction was the highest(16.31％,91/558),and the proportion of severe errors in the X-axis direction was the lowest(8.96％,50/558).Compared with the original plan,the levels of planning target volume(PTV)D95,PTV Dmean,clinical target volume(CTV)D95 and gross tumor volume(GTV)D95 in the simulation plan were lower(P＜0.05),while the levels of PTV HI,spinal cord Dmaxand spinal cord V45 were higher(P＜0.05).The incidence of target area under-dose and spinal cord over-dose in the severe error group were both higher than those in the moderate error group and the mild error group(P＜0.05),and the moderate error group was significantly higher than the mild error group(P＜0.05).Pearson correlation analysis showed that the positioning errors in the X,Y,and Z axes were negatively correlated with PTV D95(r=-0.528,-0.682,-0.563,P＜0.001),and positively correlated with spinal cord Dmax(r=0.542,0.715,0.586,P＜0.001).Conclusion Positioning errors(especially in the Y-axis direction)during IMRT treatment for lung cancer can significantly increase the risk of under-target and spinal cord excess,and the degree of error is positively correlated with the risk.Strict control of positioning errors is of great clinical significance for ensuring target dose coverage and reducing spinal cord exposure.

Abstract:Objective To investigate the expression of E74-like ETS transcription factor 3(ELF3)in epithelial ovarian cancer(EOC)tissues and its relationship with clinicopathological features,and to preliminarily analyze the role and molecular mechanism of ELF3 in promoting EOC cell growth and metastasis.Methods Immunohistochemistry was used to detect the expression level of ELF3 in EOC tissues and analyze its correlation with clinicopathological characteristics.ELF3-knockdown A2780 and CAOV3 cell lines,as well as ELF3-overexpressing SKOV3 cell lines,were constructed.The effects of ELF3 on cell proliferation and metastatic ability were assessed using the cell counting kit-8(CCK-8)assay,scratch wound healing assay,and Transwell migration and invasion assays.Subcutaneous xenograft and intraperitoneal metastasis models were established in nude mice to evaluate the role of ELF3 in tumor growth and metastasis in vivo.Western blotting was performed to examine the effects of ELF3 on the expression of epithelial-mesenchymal transition(EMT)markers,namely neural cadherin(N-cadherin)and epithelial cadherin(E-cadherin),and on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.A PI3K inhibitor LY294002 was used to validate the regulatory role of this pathway in EMT.Results Immunohistochemical results showed that high expression of ELF3 was significantly associated with International Federation of Gynecology and Obstetrics(FIGO)stage,lymph node metastasis,peritoneal metastasis and the presence of ascites(P＜0.05).Serum levels of cancer antigen 125,cancer antigen 153,and human epididymis protein 4 were significantly elevated in the high ELF3 expression group(P＜0.05).In vitro experiments demonstrated that ELF3 knockdown significantly inhibited EOC cell proliferation,migration,and invasion(P＜0.001),whereas ELF3 overexpression promoted these processes(P＜0.05).In animal models,the tumor volume and the number of Ki-67 positive cells in the ELF3 knockdown group were significantly lower than those in the control group(58.50±7.06 vs.87.83±3.87,P＜0.05),and the number of intraperitoneal metastatic nodules was also significantly reduced(3.50±0.50 vs.8.50±1.12,P＜0.01).Compared with the control group,N-cadherin protein levels were significantly downregulated,and E-cadherin expression was upregulated in ELF3-knockdown A2780 cells and xenograft tumors from the knockdown group.In ELF3-overexpressing SKOV3 cells,the expression levels of phosphorylated PI3K(p-PI3K)and phosphorylated AKT(p-AKT)were increased,while total PI3K and AKT expression showed no significant change.Following treatment with a PI3K inhibitor(LY294002),p-AKT and N-cadherin expression were significantly downregulated,and E-cadherin expression was upregulated,whereas ELF3 expression remained unchanged.Conclusion ELF3 is highly expressed in EOC tissues and promotes tumor growth and metastasis,potentially regulating EMT-related proteins through the PI3K/AKT pathway to participate in the progression of EOC.

Abstract:Objective To investigate the clinical effects of transurethral resection of prostate(TURP)performed at different time points following transurethral resection of bladder tumor(TURBT)in patients with benign prostatic hyperplasia combined with bladder cancer.Methods A total of 92 patients with benign prostatic hyperplasia and bladder cancer who underwent TURBT between January 2021 and July 2023 were retrospectively analyzed.According to the timing of TURP,they were divided into a study group(TURP performed simultaneously with TURBT,n=46)and a control group(TURP performed 8 weeks after TURBT,n=46).Perioperative parameters,postoperative inflammatory and stress response indicators,and voiding function were compared between the two groups.The perioperative indicators,postoperative inflammation and stress response,and urinary function indexes of the two groups were compared,and the urinary symptom burden(BS)score and international Prostate Symptom Score(IPSS)were recorded.The incidence of postoperative complications and recurrence rate of bladder cancer at 24 months after surgery were followed up.Results The total operative time,intraoperative blood loss during TURP,hospitalization time,and catheter retention time in the study group were(68.15±22.51)min,(74.19±12.01)mL,(15.77±3.02)days,and(4.12±0.51)days,respectively,all of which were lower than those in the control group[(93.16±10.16)min,(109.53±17.43)mL,(28.16±5.66)days,and(6.22±1.56)days]with significant differences(t=6.868,11.302,13.099,8.678,P＜0.05).In contrast,there was no statistically significant difference in intraoperative blood loss during TURBT between the two groups(P＞0.05).On postoperative day 1,levels of interleukin-6,malondialdehyde,and lipid peroxides were higher in the study group(P＜0.05).One week after surgery,the maximum urinary flow rate in the study group was higher than that in the control group[(18.66±2.99)mL/s vs.(15.15±4.21)mL/s,t=4.610,P＜0.05],while the residual urine volume and intravesical pressure were lower than those in the control group[(33.87±7.15)mL vs.(42.08±9.55)mL,(13.31±3.02)cmH2O vs.(18.87±4.11)cmH2O,t=4.667,7.394,P＜0.05)].At 3 months after surgery,BS and IPSS scores were lower in the study group than in the control group(P＜0.05).The total incidence of postoperative complications was 17.39％in the study group and 13.04％in the control group,with no significant difference(P＞0.05).In the study group,5 cases(10.87％)of bladder cancer recurrence occurred within 24 months after surgery,and 4 cases(8.70％)in the control group,with no significant difference(P＞0.05).Conclusion In patients with with benign prostatic hyperplasia combined with bladder cancer,performing TURP simultaneously with TURBT shortens recovery and improves voiding,without significantly increasing 24-month recurrence risk,and is overall safe,though early postoperative inflammatory responses are more pronounced.

Abstract:Objective To investigate the anti-tumor mechanism of simvastatin in pancreatic neuroendocrine neoplasms(pNENs)through regulating Krüppel-like factor 4(KLF4)and subsequently suppressing the mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK)signaling pathway.Methods Differentially expressed genes after simvastatin treatment were screened by RNA sequencing.The expression pattern of KLF4 in various cancers and its correlation with patient prognosis were analyzed using the TIMER2.0 and GEPIA2 databases.Reverse transcription-quantitative PCR(RT-qPCR)and Western blot were performed to validate the effect of simvastatin on KLF4 expression at transcriptional and protein levels.In QGP-1 cells with low endogenous KLF4 expression,a KLF4-overexpressing plasmid was constructed.Cell proliferation was assessed by CCK-8 assay,EdU incorporation assay,and colony formation assay.Western blot was further used to examine changes in key proteins of the MAPK/ERK pathway.Results RNA-seq results showed that KLF4 expression was upregulated after simvastatin treatment.Bioinformatics analyses indicated that KLF4 was lowly expressed in multiple tumor tissues,and its high expression was positively correlated with favorable prognosis in several cancers(P＜0.05).Both RT-qPCR and Western blot confirmed that simvastatin treatment significantly increased KLF4 expression at mRNA and protein levels(P＜0.05).Successful overexpression of KLF4 in stable transfection cells was verified by Western blot(P＜0.001).CCK-8,colony formation,and EdU assays consistently demonstrated that KLF4 overexpression significantly suppressed the proliferation of QGP-1 cells.Furthermore,Western blot analysis revealed that KLF4 overexpression markedly reduced phosphorylated ERK(pERK)levels(P＜0.001).Conclusion Simvastatin exerts anti-tumor effects in pNENs by upregulating KLF4 expression and inhibiting the MAPK/ERK signaling pathway.

Abstract:Objective To investigate the predictive value of cancer-associated fibroblast markers podoplanin(PDPN)and alpha-smooth muscle actin(α-SMA)in evaluating the efficacy and predicting prognosis of breast cancer patients receiving neoadjuvant chemotherapy(NACT).Methods Clinicopathological data were collected from 80 breast cancer patients who underwent NACT followed by surgical resection at Nanjing Drum Tower Hospital between January 2010 and December 2015.Expression of PDPN andα-SMA in tumor tissues was detected by immunohistochemistry and assessed using a semi-quantitative histochemical score(H-score).Based on the mean H-score,patients were categorized into high-and low-expression groups.The associations between PDPN/α-SMA expression and clinicopathological features,NACT efficacy(evaluated using the Miller-Payne pathological grading system),and prognosis were analyzed.Relationships between marker expression and clinicopathological parameters were examined using x2 test or Fisher's exact test.Overall survival(OS)served as the primary prognostic endpoint.Kaplan-Meier curves were plotted,and differences between groups were compared using the Log-rank test.A multivariate Cox proportional hazards regression model was applied to determine independent prognostic factors.Receiver operating characteristic(ROC)curve analysis was used to assess the predictive efficacy of PDPN and α-SMA expression for patient prognosis.Results The H-scores for PDPN and α-SMA in the 80 breast cancer tissues were 73.63±59.04 and 66.50±54.62,respectively.Among the patients,41 had low PDPN expression and 39 had high expression,while 44 had low α-SMA expression and 36 had high expression.Correlation analysis revealed that high expression of both PDPN(x2=8.605,P=0.003)and α-SMA(x2=21.721,P＜0.001)was significantly associated with more advanced lymph node metastasis,but not with NACT efficacy(both P＞0.05).Survival analysis showed that the OS of the high PDPN expression group was significantly lower than that of the low expression group(Log-rank x2=16.945,P＜0.001),and a similar trend was observed for α-SMA(Log-rank x2=11.634,P=0.001).Multivariate Cox analysis further confirmed that PDPN(adjusted HR=1.066,95％CI:1.024-1.110,P=0.002)and α-SMA(adjusted HR=1.034,95％CI:1.001-1.068,P=0.041)were independent risk factors affecting OS.ROC curve analysis indicated that the combined area under the curve for predicting patient prognosis using both markers was 0.784(95％CI:0.664-0.904,P=0.003),which was superior to either marker alone.Conclusion High expression of PDPN and α-SMA in breast cancer patients is significantly associated with lymph node metastasis and poor prognosis following NACT.Combined detection of these markers offers enhanced prognostic value and may serve as a potential clinical evaluation indicator.

Abstract:Objective To investigate the expression,clinical prognostic value,and correlation with immune cell infiltration of Rho GTPase activating protein 9(ARHGAP9)in kidney clear cell carcinoma(KIRC).Methods Based on the The Cancer Genome Atla database,and validation with clinical samples,we compared the expression differences of ARHGAP9 between KIRC tumor tissues and normal tissues.Through stratified analysis,the relationship between ARHGAP9 expression levels and the methylation status of its DNA promoter with patients' clinicopathological characteristics was investigated.The Search Tool for the Retrieval of Interacting Genes/Proteins was utilized to construct a protein interaction network for ARHGAP9,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed on the interacting genes.Furthermore,the Tumor Immune Estimation Resource database algorithm was applied to evaluate the association between ARHGAP9 expression and immune cell infiltration levels in the tumor microenvironment.Combined with Cox proportional-hazards regression models,the independent prognostic value of ARHGAP9 expression and key immune cell infiltration in KIRC patients was assessed.Results ARHGAP9 was differentially expressed in multiple cancers and correlated with patient prognosis(P＜0.05).The mRNA and protein expression levels of ARHGAP9 were upregulated in KIRC(P＜0.05).In KIRC,ARHGAP9 mRNA and protein expression,as well as DNA promoter methylation levels,were associated with histological grade,pathological stage,and lymph node stage(P＜0.05).Functional enrichment analysis results indicated that ARHGAP9 was involved in regulating the sphingolipid signaling pathway,cAMP signaling pathway,Ras signaling pathway,and Wnt signaling pathway.The expression of ARHGAP9 correlated with the infiltration levels of CD4+T cells,CD8+T cells,neutrophils,dendritic cells,B cells,and macrophages(P＜0.05).Univariate and multivariate Cox regression analyses revealed that high expression of ARHGAP9 was an independent prognostic risk factor for KIRC patients.Conclusion ARHGAP9 is highly expressed in KIRC and associated with poor prognosis,suggesting that it may serve as a reliable prognostic biomarker and a potential therapeutic target for KIRC patients.

Abstract:In recent years,nanomaterials have demonstrated unique advantages in thermal,optical,and electrical properties due to their distinctive size effects and surface effects,offering new opportunities for tumor diagnosis and treatment.Copper sulfide(CuS)nanomaterials exhibit significant potential in antitumor research owing to their favorable biocompatibility,efficient Fenton-like catalytic activity,and excellent photothermal conversion performance.Through the synergistic combination of photothermal therapy and chemodynamic therapy,CuS nanomaterials can substantially enhance therapeutic outcomes.Furthermore,these materials can serve as drug delivery carriers,loading chemotherapeutic agents,photothermal agents,photosensitizers,and immune activators to achieve multimodal combination therapy,thereby further improving treatment efficacy.This article systematically reviews recent advances in the application of CuS nanomaterials in tumor therapy,with a focus on their roles in photothermal therapy,chemodynamic therapy,chemotherapy,photodynamic therapy,gas therapy,immunotherapy,and tumor diagnosis.On this basis,current challenges are analyzed,and future development directions are prospected.