Abstract:Objective To investigate the clinical application value of long-acting pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)in the prevention of neutropenia following docetaxel,cisplatin,and fluorouracil(TPF)regimen chemotherapy in patients with head and neck cancer.Methods One hundred and six patients with locally advanced head and neck cancer,who were admitted to the Affiliated Cancer Hospital of Guizhou Medical University between June 2019 and June 2023,were included in this study.All patients received TPF regimen chemotherapy and underwent long-acting neutropenia prevention with PEG-rhG-CSF.After excluding 11 cases with incomplete data,a total of 95 cases were eventually included for analysis,consisting of the primary prevention(PP)group(n=47)and the secondary prevention(SP)group(n=48).The main observation indicators included the incidence of chemotherapy-induced neutropenia(CIN),febrile neutropenia(FN),antibiotic usage,the rate of chemotherapy dose reduction,and the incidence and duration of delays in the next chemotherapy cycle.Results Compared with the PP group,the SP group showed a significantly lower incidence of FN in the first cycle,with a reduction of 23.6％(P＜0.05).During the first cycle,the time to neutrophil nadir was significantly shorter in the SP group than in the PP group[(5.02±3.65)d vs.(6.32±3.42)d,P＜0.05],the time to neutrophil recovery was significantly earlier in the SP group[(5.38±3.94)d vs.(6.98±3.81)d,P＜0.01],and the duration of neutropenia was also shorter in the SP group[(0.35±0.60)d vs.(0.66±0.76)d,P＜0.05].In the second cycle,the duration of neutropenia was shorter in the PP group than in the SP group(P＜0.05).Conclusion Preventive leukocyte elevation therapy with PEG-rhG-CSF can effectively reduce the incidence and severity of CIN and FN in head and neck cancer patients undergoing TPF chemotherapy.

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.

Abstract:Inflammation is considered a key driver of the initiation and progression of colorectal cancer.During the initial stage of colorectal cancer,risk factors such as inflammatory bowel disease,dysbiosis of the gut microbiota,and metabolic abnormalities promote the accumulation of driver gene mutations and the clonal expansion of mutated epithelial cells by inducing oxidative stress,disruption of the intestinal barrier,and abnormal immune responses,thereby triggering early events in the transition from inflammation to cancer.In the progression stage,tumor cells,immune cells,stromal cells,and intratumoral microorganisms together form a self-sustaining inflammatory tumor microenvironment,driving immunosuppression,angiogenesis,and stromal remodeling,thereby endowing the tumor with sustained proliferation and invasive capabilities.During the establishment of the pre-metastatic microenvironment,remote signals such as exosomes and intratumoral bacteria released from the primary tumor,combined with the anatomical features of portal venous drainage in colorectal cancer and the liver's inherent susceptibility to inflammation and immune tolerance,collectively promote the formation of a pre-metastatic niche that facilitates the dissemination,colonization,and growth of tumor cells.Finally,this article summarizes preliminary evidence supporting anti-inflammatory therapeutic strategies in colorectal cancer.In the future,an integrated intervention system centered on inflammation regulation and combined with immunotherapy and targeted therapies will provide new insights and targets for the precise prevention and treatment of colorectal cancer.

Abstract:Objective To develop and validate a combined model integrating clinical,pathological,and plain CT radiomics features for differentiating adrenal metastatic nodules in lung cancer patients.Methods A total of 364 patients admitted to Tangshan People's Hospital from February 2013 to December 2023 were enrolled.Using a 7∶3 random allocation method,they were divided into a training set(254 cases,comprising 124 benign nodules and 130 metastatic nodules)and a test set(110 cases,comprising 54 benign nodules and 56 metastatic nodules).A comparative analysis of clinicopathological characteristics,including sex,age,clinical stage of lung cancer,and histological type,was conducted between patients in the training and test sets.Based on non-enhanced CT images,1316 radiomics features of adrenal indeterminate nodules were extracted.The least absolute shrinkage and selection operator(LASSO)was used to screen statistically significant features,which were then employed to construct a radiomics score(Rad-score).Subsequently,multivariate Logistic regression analysis was further applied to identify independent risk factors for adrenal metastatic nodules in lung cancer.By integrating clinical,pathological,and radiomics information,a combined diagnostic model was developed and visualized as a nomogram.The differential diagnostic performance and calibration accuracy of this nomogram were evaluated using the area under the receiver operating characteristic curve(AUC)and calibration curves,respectively.Results The clinicopathological analysis revealed statistically significant differences in gender,clinical stage of lung cancer,and histologic type distribution between metastatic and benign nodules(all P＜0.05),whereas no statistically significant difference was observed in age(P＞0.05).Specifically,metastatic nodules showed significantly higher proportions in male gender(training set:61.54％vs.43.55％;test set:64.29％vs.37.04％),advanced stage(Ⅲ/Ⅳ)(training set:92.31％vs.51.61％;test set:92.86％vs.40.74％),and small cell lung cancer subtype(training set:34.62％vs.9.68％;test set:32.14％vs.11.11％)compared to benign nodules.Following LASSO screening and collinearity exclusion,four independent features,including original_shape_Flatness,wavelet-LLH_glcm_Imc1,wavelet-LLH_glcm_InverseVariance,and wavelet-LLL_firstorder_Maximum,were incorporated to construct the Rad-score.The Rad-score was significantly higher in the metastatic nodule group than in the benign nodule group(training set:0.746 vs.0.233;test set:0.796 vs.0.245,both P＜0.00 1).In univariate analysis,Rad-score demonstrated the best discriminative performance with an AUC of 0.897.The combined diagnostic model,constructed based on gender,clinical stage of lung cancer,and Rad-score,achieved AUCs of 0.918(95％CI:0.882-0.954)in the training set and 0.910(95％CI:0.857-0.963)in the test set.Sensitivity,specificity,and accuracy were all superior to those of any single variable(all P＜0.05).Using a nomogram cutoff score of 96.30 points,the model exhibited well-fitted calibration curves in both cohorts(P=0.240,0.563),demonstrating good agreement between the predicted results and pathological outcomes.Conclusion The combined clinical-pathological-radiomics diagnostic model,constructed based on Rad-score from non-contrast CT,gender,and clinical stage of lung cancer,can effectively differentiate adrenal metastatic nodules,contributing to precise staging and individualized treatment.

Abstract:The Global Cancer Observatory has reported that the global cancer prevalence rate is continuing to increase,with a predicted surge in the number of new cases from 19.3 million in 2020 to 28.4 million in 2040.The advent of molecular diagnostic technology has led to the widespread utilisation of targeted drugs in the precise management of malignant neoplasms.However,a variety of targeted drugs have been associated with elevated blood pressure,new-onset hypertension,or uncontrolled pre-existing hypertension.Therefore,the management of cancer-related hypertension(CR-HTN)has become an important challenge in the comprehensive oncology treatment.This review outlines the common risk factors for tumors and hypertension.It focuses on summarizing the pathophysiological mechanisms through which targeted drugs in CR-HTN contribute to elevated blood pressure via core pathways such as endothelial dysfunction and imbalance in vascular tone regulation.Additionally,it discusses comprehensive management strategies,including risk stratification,dynamic monitoring,lifestyle interventions,and individualized antihypertensive drug selection.The aim is to provide a reference for optimizing cardiovascular risk management in cancer patients in clinical practice.

Abstract:Objective To investigate the expression of inhibitor of growth family member 4(ING4)in endometrial cancer(EC)and its effect on the biological functions of cancer cells.Methods A total of 138 endometrial tissue specimens were collected,including 30 normal endometrial(NE),31 endometrial hyperplasia without atypia(EHA),30 atypical endometrial hyperplasia(EAH),and 47 EC tissues.The protein expression of ING4,tumor protein p53(p53),cyclin-dependent kinase inhibitor 1A(p21),and cyclin-dependent kinase inhibitor 2A(p16)was detected by immunohistochemistry.Stable ING4-overexpressing cell lines(Ad-ING4 group)and negative control cell lines(NC group)were established in Ishikawa and HEC-1B cells via lentiviral transfection.The mRNA expression levels of ING4,p53,cysteine-containing aspartate-specific protease-3(CASP3),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)were measured by quantitative real-time PCR,while the protein expression levels of ING4,p53,p21,p16,CASP3,Bcl-2,Bax,signal transducer and activator of transcription 3(STAT3),and its phosphorylated form(p-STAT3)were evaluated by Western blot.Cell proliferation,migration,and invasion were assessed using the Cell Counting Kit-8(CCK-8)assay,colony formation assay,wound healing assay,and Transwell invasion assay.Apoptosis and cell cycle distribution were analyzed by flow cytometry.A subcutaneous xenograft tumor model was established in nude mice using ING4-overexpressing HEC-1B cells to observe the effect of ING4 overexpression on in vivo tumor growth.Results In EC tissues,the expression level of ING4 protein(mean optical density:0.288±0.056)was significantly lower than that in NE(0.480±0.077),EHA(0.506±0.084),and EAH(0.406±0.096)tissues(P＜0.001).Furthermore,ING4 expression showed a significant positive correlation with the expression ofp21(r=0.353,P=0.015)and p 16(r=0.451,P=0.002).In cellular experiments,compared with the NC group,the Ad-ING4 group of Ishikawa and HEC-1B cells exhibited inhibited proliferation,migration,and invasion capabilities.Specifically,EC cells in the Ad-ING4 group showed significantly reduced proliferative activity(72 h,96 h),colony formation ability,wound healing rate,and the number of Transwell invading cells,along with an increased proportion of G1-phase cells and early apoptotic cells.In the Ad-ING4 group,the p53/p21/p16 signaling pathway was activated,CASP3 expression was upregulated,the Bax/Bcl-2 ratio increased,while p-STAT3 protein expression was inhibited.In vivo animal experiments demonstrated that the subcutaneous xenograft tumor volume in the Ad-ING4 group was significantly smaller than that in the NC group[(89.00±7.55)mm3 vs.(206.70±8.51)mm3,P＜0.01],and the protein expression levels of ING4,p53,and p16 in the tumor tissues were higher.Conclusion ING4 is downregulated in EC.Its overexpression effectively inhibits tumor cell proliferation,invasion,and in vivo tumorigenesis by activating the p53/p21/p16 pathway,promoting apoptosis,and inhibiting STAT3 phosphorylation,suggesting that ING4 possesses tumor-suppressive functions.

Abstract:Objective To investigate the expression patterns,biological functions,and prognostic value of ephrin-A1(EFNA1)and special AT-rich sequence-binding protein 2(SATB2)in ovarian cancer.Methods A total of 120 patients with ovarian cancer admitted to the Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University from January 2020 to June 2022 were enrolled.According to the Response Evaluation Criteria in Solid Tumors version 1.1 and clinical outcomes by June 30,2025,patients were divided into a favorable prognosis group(n=62)and a poor prognosis group(n=58).Serum EFNA1 levels were measured by enzyme-linked immunosorbent assay,and SATB2 mRNA expression in ovarian cancer tissues was detected by quantitative real-time PCR.Multivariate logistic regression was used to analyze factors influencing poor prognosis in ovarian cancer patients.The diagnostic efficacy of EFNA1 and SATB2 for prognosis was evaluated using receiver operating characteristic(ROC)curve analysis.Bioinformatics databases were employed to analyze the expression profiles of EFNA1 and SATB2 in ovarian cancer tissues and their association with overall survival.EFNA1 and SATB2 overexpression plasmids and silencing vectors were constructed and transfected into the human ovarian cancer cell line SKOV3,with empty vector control,negative siRNA control,and corresponding treatment groups established.Cell viability was assessed using the Cell Counting Kit-8 assay,and cell invasion ability was evaluated by Transwell assay.Results Database analysis revealed upregulated EFNA1 expression in ovarian cancer tissues(P＜0.05),and high EFNA1 expression was associated with reduced overall survival(HR=1.17,P=0.031).In contrast,SATB2 expression was downregulated(P＜0.05),and high SATB2 expression was correlated with improved overall survival(HR=0.83,P＜0.01).Cellular experiments confirmed that EFNA1 promoted SKOV3 cell proliferation and invasion(P＜0.01),whereas SATB2 inhibited these biological behaviors(P＜0.01).Clinical sample analysis showed that serum EFNA1 levels were significantly higher in the poor prognosis group(18.56±8.78 ng/mL)than in the favorable prognosis group(13.52±5.46 ng/mL)with significant difference(t=3.862,P＜0.001).SATB2 mRNA expression in ovarian cancer tissues was significantly lower in the poor prognosis group(3.31±0.77)compared to the favorable prognosis group(4.15±0.79)with significant difference(t=5.871,P＜0.001).ROC curve analysis indicated that the combined predictive model of EFNA1 and SATB2(area under the curve=0.865)outperformed either biomarker alone.Multivariate logistic regression analysis demonstrated that high EFNA1 expression(OR=2.243,P=0.030)and low SATB2 expression(OR=0.388,P=0.012)were independent prognostic factors for ovarian cancer patients.Conclusion EFNA1 and SATB2 genes regulate malignant biological behaviors in ovarian cancer,and their expression levels are closely associated with patient prognosis,serving as valuable biomarkers for prognostic assessment in ovarian cancer.

Abstract:Objective To investigate the application and clinical outcomes of totally laparoscopic digestive tract reconstruction in radical resection for colon cancer.Methods A total of 102 colon cancer patients who underwent surgical treatment at Zhoukou Central Hospital between March 2021 and March 2024 were selected.According to the method of digestive tract reconstruction,they were divided into two groups:the observation group(n=49)underwent totally laparoscopic intestinal anastomosis,and the control group(n=53)underwent intestinal anastomosis via an auxiliary incision.The surgical approach for all patients was based on the Chinese Protocol for Diagnosis and Treatment of Colorectal Cancer,combined with preoperative assessment and tumor pathological characteristics.Clinical data were retrospectively analyzed,including perioperative indicators,visual analogue scale(VAS)pain scores on postoperative days 1,3,and 7,postoperative recovery,levels of diamine oxidase(DAO),D-lactate(DLA),and glutamine(Gln)before and after surgery,gastrointestinal quality of life index(GIQLI)scores,prognostic nutritional index(PNI),and the incidence of postoperative complications.Results The incision length in the observation group was significantly shorter than that in the control group[(3.21±0.52)cm vs.(6.33±1.02)cm,t=19.222,P＜0.001].There were no statistically significant differences between the two groups in operative time,intraoperative blood loss,or number of lymph nodes harvested(P＞0.05).The VAS scores on postoperative days 1,3,and 7 in the observation group were 4.62±1.08,2.66±0.51,and 1.55±0.52,respectively,all significantly lower than those in the control group(5.83±1.12,3.34±0.57,and 1.96±0.43)with statistically siginificant differences(t=5.546,6.330,4.352,all P＜0.001).The time to first flatus,defecation,ambulation,incision healing,and hospital stay were all shorter in the observation group compared to the control group(all P＜0.05).Postoperatively,DAO and DLA levels increased in both groups compared to preoperative levels,but were lower in the observation group.Gln levels decreased in both groups,but were higher in the observation group(all P＜0.05).After 6 months of follow-up,GIQLI scores improved and PNI scores decreased postoperatively in both groups compared to preoperative values(P＜0.05),with no statistically significant difference between the groups(P＞0.05).The incidence of postoperative complications in the observation group was 4.08％(2/49),significantly lower than the 18.87％(10/53)in the control group(x2=5.363,P＜0.05).Conclusion In radical resection for colon cancer,the application of totally laparoscopic digestive tract reconstruction offers advantages including minimal invasiveness,less postoperative pain,faster recovery,a lesser impact on intestinal barrier function,and a lower incidence of complications.

Abstract:Objective To explore the diagnostic value and clinical application potential of combined detection of serum soluble B7-H3(sB7-H3)and periostin(POSTN)in early gastric cancer.Methods A total of 90 gastric cancer patients treated at Shangqiu First People's Hospital between January 2020 and June 2023 were selected as the study subjects(gastric cancer group).Additionally,90 patients with benign gastric lesions admitted during the same period were enrolled as the control group.Baseline data from all participants were collected,and serum levels of sB7-H3 and POSTN were measured using enzyme-linked immunosorbent assay.Differences in baseline characteristics and serum levels of sB7-H3 and POSTN between the two groups were compared.Multivariate logistic regression analysis was employed to identify independent factors influencing the occurrence of early gastric cancer.Receiver operating characteristic(ROC)curves were plotted to evaluate the diagnostic and predictive value of serum levels of sB7-H3 and POSTN,and their combined detection for early gastric cancer.Results There were no statistically significant differences between the two groups in age,body mass index,smoking history,alcohol consumption history,history of hypertension,history of diabetes,or lipid levels(total cholesterol and triglycerides)(all P＞0.05).The proportion of males(71.11％vs.54.44％,P=0.021)and the Helicobacter pylori(Hp)infection rate(93.33％vs.56.67％,P＜0.001)were significantly higher in the gastric cancer group compared to the control group.The serum levels of sB7-H3 and POSTN in the gastric cancer group were(43.42±5.68)ng/mL and(21.51±4.12)ng/mL,respectively,both significantly higher than(36.97±5.31)ng/mL and(17.03±3.86)ng/mL in the control group(all P＜0.001).Subgroup analysis revealed that the expression levels of sB7-H3 and POSTN were significantly higher in patients with poorly/undifferentiated tumors,lymph node metastasis,TNM stage ⅠB,and Hp-negative status(all P＜0.001).Multivariate logistic regression analysis identified Hp infection(OR=2.543,95％CI:1.452-4.454),sB7-H3(OR=3.209,95％CI:1.645-6.261),and POSTN(OR=2.859,95％CI:1.560-5.239)as independent risk factors for early gastric cancer.Diagnostic performance evaluation showed that the areas under the ROC curve(AUC)for diagnosing early gastric cancer using sB7-H3 and POSTN alone were 0.828(95％CI:0.765-0.880)and 0.797(95％CI:0.731-0.853),respectively.The AUC for their combined diagnosis increased to 0.887(95％CI:0.831-0.929),and its diagnostic efficacy was significantly superior to that of either single indicator(all P＜0.05).Conclusion Serum sB7-H3 and POSTN serve as potential biomarkers for early gastric cancer,with their expression levels correlating with malignant tumor characteristics and constituting independent risk factors.The combined detection of these two markers significantly enhances diagnostic efficacy,offering a novel strategy for the non-invasive auxiliary diagnosis of early gastric cancer.

Abstract:Objective To investigate the expression of contactin-associated protein-like 2(CNTNAP2)in pituitary adenoma cells,its effects on cell proliferation,migration,and invasion,and to elucidate the role of the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway in this process.Methods The expression level of CNTNAP2 in mouse pituitary adenoma cell lines was detected using real-time quantitative PCR(RT-qPCR)and Western blot.In pituitary adenoma GT1-1 cells transfected with CNTNAP2 overexpression plasmid(OE-CNTNAP2)and negative control plasmid(OE-NC),or CNTNAP2 small interfering RNA(si-CNTNAP2)and negative control sequence(si-NC),cell viability,apoptosis,migration,and invasion capabilities were assessed using the Cell Counting Kit-8(CCK-8),Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL),and Transwell assays,respectively.Western blot was performed to analyze the expression levels of apoptosis-and epithelial-mesenchymal transition(EMT)-related proteins,as well as the phosphorylation levels of PI3K/Akt.The PI3K/Akt pathway agonist 740 Y-P was used to treat the cells to investigate whether this pathway mediates the regulatory effects of CNTNAP2.Results The expression of CNTNAP2 was significantly lower in mouse pituitary adenoma cells than in normal pituitary cells.In the OE-CNTNAP2 group,cells overexpressing CNTNAP2 exhibited the following significant biological changes:inhibition of cell proliferation(CCK-8 assay showed decreased cell viability),increased apoptosis(elevated TUNEL-positive rate,upregulation of pro-apoptotic proteins Bax and cleaved caspase-3,and downregulation of anti-apoptotic protein Bcl-2),reduced migration and invasion capabilities(decreased number of transmembrane cells in Transwell assays),and suppression of EMT(upregulation of the epithelial marker E-cadherin and downregulation of the mesenchymal marker N-cadherin).Concurrently,the activity of the PI3K/Akt signaling pathway was inhibited in this group,as evidenced by reduced phosphorylation levels of PI3K and Akt.Conversely,in the si-CNTNAP2 group,cells with CNTNAP2 knockdown displayed the opposite biological phenotypes:enhanced proliferation,reduced apoptosis,improved migration and invasion capabilities,and promoted EMT,accompanied by activation of the PI3K/Akt signaling pathway.Treatment with 740 Y-P effectively reversed the effects induced by CNTNAP2 overexpression,including the inhibition of cell proliferation,increased apoptosis,reduced migration and invasion capabilities,and decreased phosphorylation levels of the PI3K/Akt pathway.Conclusion CNTNAP2 functions as a tumor suppressor in pituitary adenoma cells.Its overexpression inhibits the PI3K/Akt signaling pathway,thereby suppressing cell proliferation,migration,invasion,and the EMT process.

Abstract:Objective To evaluate the efficacy and safety of concurrent chemoradiotherapy combined with camrelizumab in the treatment of advanced non-small cell lung cancer(NSCLC)and to analyze the immune response status of patients.Methods A total of 90 patients with advanced NSCLC admitted to Huai'an Second People's Hospital from January 2020 to March 2023 were enrolled.All patients received concurrent chemoradiotherapy(prescribed total radiation dose:60 Gy,delivered in 30 fractions at 2 Gy per fraction).In the combination group(n=50),patients received camrelizumab(200 mg,intravenous infusion,once every 3 weeks)in addition to concurrent chemoradiotherapy,while the control group(n=40)received concurrent chemoradiotherapy alone.Short-term efficacy was assessed after 4 cycles of treatment using the Response Evaluation Criteria in Solid Tumors version 1.1,with objective response rate(ORR)and disease control rate(DCR)calculated.Long-term survival outcomes were evaluated through follow-up to obtain progression-free survival(PFS)and overall survival(OS).Safety was assessed by recording treatment-related adverse events according to the Common Terminology Criteria for Adverse Events version 4.03 of the National Cancer Institute.Flow cytometry was used to detect dynamic changes in the proportions of total T lymphocytes(CD3+),helper/inducer T lymphocytes(CD4),and cytotoxic T lymphocytes(CD8+)in peripheral blood,as well as the CD4+/CD8+ratio before and after treatment.Results Among the 90 patients evaluable for efficacy,the ORR and DCR in the combination group were 32.0％and 80.0％,respectively,while those in the control group were 15.0％and 55.0％,respectively.The difference in ORR between the groups did not reach statistical significance(P=0.062),but the DCR in the combination group was significantly higher than that in the control group(P=0.011).Survival analysis showed that the median PFS and OS in the combination group were 9.7 months and 30.6 months,respectively,both significantly longer than those in the control group(6.4 months and 12.7 months,respectively;all P＜0.05).After treatment,the proportions of CD3+and CD4+T lymphocytes,as well as the CD4+/CD8+ratio,significantly increased in the combination group,while the proportion of CD8+T lymphocytes significantly decreased.Moreover,the improvements in all these indicators were significantly greater in the combination group than in the control group(all P＜0.001).Regarding safety,the main adverse reactions were grade 1-2,with an overall incidence of grade 3 adverse reactions of 5.6％.Furthermore,there were no statistically significant differences in the incidence of any adverse reactions between the two groups(all P＞0.05).Conclusion Concurrent chemoradiotherapy combined with camrelizumab significantly improves the disease control rate and survival outcomes in patients with advanced NSCLC,enhances immune function,and demonstrates a favorable safety profile.This regimen exhibits a synergistic effect between chemoradiotherapy and immunotherapy,indicating promising clinical application prospects.

Abstract:Objective To analyze the efficacy of intensity-modulated radiotherapy(IMRT)in patients with esophageal cancer and the risk factors of acute radiation-induced lung injury(ARILI),and to construct the relevant regression model.Methods The clinical medical records of 312 esophageal cancer patients who underwent IMRT and were admitted to the first affiliated hospital of Henan university of science and technology from January 2021 to June 2024 were collected as the research objects.They were divided into the occurrence group(53 cases,RTOG grades 1-4)and the non-occurrence group(259 cases)based on whether ARILI occurred during the 6-month follow-up after radiotherapy.RTOG grade 0.The therapeutic effects and the occurrence of adverse reactions of the two groups of patients were analyzed.Univariate and multivariate Logistic regression analyses were used to analyze the factors influencing the occurrence of ARILI in patients with esophageal cancer undergoing IMRT,and a model was constructed.Results Among the 312 patients after IMRT,245 cases(78.53%)achieved complete remission,61 cases(19.55%)achieved partial remission,6 cases(1.92%)had no remission,and the total remission rate was 98.08%.There were 29 cases(9.29%)of radiation esophagitis,53 cases(16.99%)of ARILI,31 cases(9.94%)of bone marrow suppression,and 15 cases(4.81%)of gastrointestinal reactions.Compared with the group without ARILI,the proportion of patients with a total radiotherapy dose of≥60 Gy and lymph node metastasis was higher in the group with ARILI,and the levels of lung V5,lung V10,lung V20,lung V30,average lung dose(MLD),serum interleukin(IL)-8,and transforming growth factor-β1(TGF-β1)were all higher(P<0.05).The results of multivariate Logistic regression analysis showed that Lung V5>50%,lung V20>25%,lung V30>20%,elevated serum IL-8 level,and elevated serum TGF-β1 level are all risk factors for ARILI in patients with esophageal cancer after IMRT(OR=1.608,2.523,2.087,1.020,1.014,P<0.05).Based on this,a regression equation was constructed:logit(P)=-109.606+lung V5×0.475+lung V20×0.925+lung V30×0.736+serum IL-8 level×0.019+serum TGF-β1 level×0.014.The results of the receiver operating characteristic curve(ROC)showed that when Logit(P)>0.20,the area under the curve(AUC)value was 0.999,the 95%CI was 0.997 to 1.000,the sensitivity was 100.00%,and the specificity was 98.84%.Conclusion The effect of IMRT in patients with esophageal cancer is good,but the safety is average.The risk factors for ARILI in patients with esophageal cancer undergoing IMRT are lung V5>50%,lung V20>25%,lung V30>20%,high serum IL-8 level,and high serum TGF-β1 level.The model established in this way can take targeted treatment and intervention measures for patients who meet the above characteristics,helping to improve the prognosis of patients.

Abstract:The tumor micro environment(TME)is pivotal for tumor onset,growth,and metastasis,offering a fertile ground for tumor biological activities and comprising stromal cells and extracellular matrix(ECM)that support tumor cell proliferation.Tumor-associated fibroblasts(CAFs),the predominant stromal cells in the TME,are highly heterogeneous and chronically activated,significantly impacting TME remodeling and tumor progression.This article comprehensively explores the heterogeneity of CAFs in terms of their origins,molecular markers,subset functions,and spatiotemporal dynamics.It delves into the complex mechanisms through which CAFs drive TME remodeling via ECM reorganization,immune microenvironment regulation,metabolic reprogramming,and angiogenesis.By leveraging cutting-edge technologies like single-cell RNA sequencing and proteomics to analyze the transcriptional profiles and markers of CAF subsets,the review identifies potential therapeutic targets and proposes multifaceted strategies targeting CAF heterogeneity.These approaches,which include precise CAF targeting,combination therapies,and dynamic monitoring techniques,present novel solutions for overcoming treatment resistance and enhancing therapeutic efficacy in cancer.

Abstract:Objective To explore the efficacy of shear wave elastography(SWE)combined with clinical parameters in predicting axillary lymph node(ALN)metastasis of breast cancer.Methods A total of 305 breast cancer patients admitted to Yuncheng Central Hospital from January 2023 to December 2024 were selected as the research subjects.They were randomly divided into the training set(n=210)and the test set(n=95)in a ratio of 7∶3.According to the histopathological results,the patients were divided into the ALN positive group and the ALN negative group.Before treatment,all patients'conventional ultrasound and SWE images were collected,and laboratory indicators were tested.The receiver characteristic operating curve was used to evaluate the value of predicting ALN positivity,and the area under the curve(AUC),sensitivity and specificity were calculated.Results The training set included 113 cases of ALN-negative and 97 cases of ALN-positive.The test set included 47 ALN-negative cases and 48 ALN-positive cases.In the training set and test set,clinical cT2 stage,positive ALN reported by ultrasound,breast imaging reporting and Data System(BI-RADS)classification,and SWE hard ring sign were associated with histological metastasis of ALN(P<0.05).In both the training set and the test set,the average SWV of ALN in the ALN positive group was significantly higher than that in the ALN negative group(P<0.05).In the training set,the AUC of SWV for differentiating positive and negative ALN metastases was 0.846(95%CI:0.790-0.892),with a sensitivity of 80.41%and a specificity of 92.04%.Furthermore,in the training set and test set,the neutrophil count/lymphocyte count(NLR)in the ALN positive group[training set:3.05(2.47,3.95)vs.1.87(1.56,2.74);test set:2.95(2.20,3.93)vs.1.87(1.37,2.40)],platelet count/lymphocyte count(PLR)[Training set:190.10(138.57,254.82)vs.128.39(107.81,165.92);test set:188.00(143.31,269.78)vs.122.94(104.37,153.26)],systemic immune inflammation index(SII)[Training set:860.81(534.71,1 349.74)vs.639.78(423.18,789.57);test set:691.25(501.42,1 188.75)vs.586.14(417.64,834.54)]was significantly higher than that of the ALN negative group(P<0.05).In the training set,the results of multivariate Logistic regression showed that BI-RADS class 5,SWV,SWE hard ring sign,NLR and PLR were significantly correlated with positive ALN metastasis(P<0.05).These five characteristic variables were included to construct a Logistic regression model:Logit(P)=-14.938+1.675×BI-RADS Category 5+1.958×SWV+2.682×hard ring sign+1.062×NLR+0.017×PLR.Through ROC curve analysis,the AUC value of this model for predicting ALN metastasis was 0.971(95%CI:0.938-0.989),with a sensitivity of 89.69%and a specificity of 96.46%.The AUC value of this model for predicting ALN metastasis in the test set was 0.980(95%CI:0.928-0.998),with a sensitivity of 89.58%and a specificity of 95.74%.Conclusion The prediction model constructed based on BI-RADS5,SWE hard ring sign,SWV,NLR and PLR can effectively predict the risk of ALN metastasis in breast cancer patients,providing a new tool for non-invasive assessment of the risk of ALN metastasis in breast cancer patients.

Abstract:Immunotherapy has made breakthrough progress in the treatment of gastric cancer and adenocarcinoma at the gastroesophageal junction,bringing new hope for patients with advanced gastric cancer.However,clinical studies have shown that the emergence of immune checkpoint inhibitor resistance significantly affects patient response rates and long-term survival benefits.Therefore,it is of great clinical significance and scientific value to delve into the molecular mechanisms of immune therapy resistance in gastric cancer and adenocarcinoma at the gastroesophageal junction.This article systematically reviews the current research progress in gastric cancer immunotherapy,focusing on the potential mechanisms of immune checkpoint inhibitor resistance,aiming to provide theoretical basis for overcoming clinical resistance issues and to guide the development of new therapeutic strategies.

Abstract:Objective To investigate the expression of acyl-CoA synthase long chain family member 4(ACSL4)in ovarian cancer tissues and its relationship with the biological behavior of ovarian cancer cells.Methods The expression of ACSL4 in ovarian cancer tissues was analyzed by TCGA and GTEx databases,and survival analysis was performed using the Kaplan-Meier Plotter database.The ovarian cancer SKOV-3 cell line was cultured in vitro.Ferroptosis was induced by the ferroptosis activator(Erastin),and the lipid peroxidation level,cell viability,migration and invasion abilities of SKOV-3 cells were detected.The ACSL4 overexpression cell line(oe-ACSL4)was constructed to further verify its functions in ferroptosis and cell biological behaviors.Results Compared with normal tissues,the expression of ACSL4 in TCGA-OV tissues was significantly decreased(P=0.029).The median overall survival time(OS)and median progression-free survival time(PFS)of OV patients with high expression of ACSL4 were significantly better than those of the low expression group(OS:62.34 months vs.59.85 months,P=0.048;)PFS:31.68 months vs.26.14 months,P=0.008).In serous ovarian cancer,the OS in the ACSL4 high-expression group was also significantly prolonged(51.36 months vs.45.78 months,P=0.016).In the Erastin group,SKOV-3 cells significantly upregulated the expression of ACSL4(protein:0.42±0.18 vs.0.15±0.09,P=0.017;mRNA:1.99±0.19 vs.1.00±0.11,P<0.001),cell viability decreased by approximately 28%(P<0.001),and lipid peroxides increased[(13.34±3.20)%vs.(5.92±2.14)%]The level of malondialdehyde(MDA)increased[(1.70±0.19)nmol/mgprot vs.(0.91±0.03)nmol/mgprot,P<0.001].The content of reduced glutathione(GSH)decreased[(6.64±1.64)μmol/mgprot vs.(16.84±2.45)μmol/mgprot,P<0.001].Compared with the control group,the number of migratory cells in the Erastin group was significantly reduced(283.20±52.78 vs.410.20±76.01,P=0.015),and the number of invasive cells was significantly reduced(119.60±36.46 vs.240.40±40.20,P=0.001).The results of western blotting showed that compared with the control group,the expression level of E-cadherin protein in the Erastin group was upregulated(1.12±0.10 vs.0.56±0.09,t=9.290,P<0.001).Vimentin(0.81±0.05 vs.1.10±0.10,t=5.605,P<0.001),N-cadherin(0.38±0.06 vs.0.72±0.11,t=6.010,P<0.001)and GPX4(0.15±0.06 vs.0.37±0.07,t=5.862,P<0.001)were downregulated.The lipid peroxidation activity of cells in the oe-ACSL4 group increased,the lipid peroxidation activity in the oe-ACSL4+Erastin group further increased,and the level of lipid peroxidation in the oe-ACSL4+Fer-1 group decreased,and the difference was statistically significant(P<0.001).Compared with the control group,the MDA level in the oe-ACSL4 group increased,while the protein expression levels of GSH and GPX4 decreased.Compared with the oe-ACSL4 group,the MDA level in the oe-ACSL4+Fer-1 group decreased,while the GSH content and GPX4 protein expression increased.Conclusion Low expression of ACSL4 is significantly associated with poor prognosis of ovarian cancer.From a mechanistic perspective,ACSL4 can inhibit the proliferation,migration and invasion of tumor cells by enhancing ferroptosis activity.

Abstract:TAnti-tumor therapy(mainly including drug therapy)often causes the nausea and vomiting,which not only brings obvious discomfort to cancer patients,increases their psychological and mental burden,but also affects the compliance of anti-tumor treatment and the overall therapeutic efficacy.Those nausea and vomiting symptoms often last for a quite long time,usually persisting for more than 120 hours after administration of anti-tumor drugs.However,now clinical commonly used antiemetic drugs have a shorter half-life time,making it difficult to cover the entire risk period of nausea and vomiting with a single anti-tumor treatment cycle.Thus there is an urgent as well as huge unmet need for longer acting,more convenient and safe drugs,to facilitate whole-process management of anti-tumor therapy induced nausea and vomiting in clinical practice.Fosrolapitant and palonosetron hydrochloride for injection is a novel dual-channel,ultra-long acting antiemetic drug approved by the Chinese National Medical Products Administration(NMPA)on May 27,2025,for the effective prevention of acute and delayed nausea and vomiting caused by the adult highly emetic chemotherapy(HEC)drug or regimen.That drug targets both the neurokinin-1(NK-1)receptor and the 5-hydroxytryptamine 3(5-HT3)receptor,achieving strong and dual blockade of those two emetic targets in same time.Its half-life time is up to 188 hours,thus a single administration can cover the acute,delayed,and ultra-delayed phases of nausea and vomiting related to a single anti-cancer treatment cycle.In order to standardize the clinical application of fosrolapitant and palonosetron hydrochloride for injection,Expert Committee on Safety Management of Antitumor Therapy and Expert Committee on Supportive and Rehabilitation Therapy for Tumors,Chinese Society of Clinical Oncology(CSCO)jointly organized an expert group.Based on the latest research evidence and clinical experience,they repeatedly deliberated to formulate these guidelines for reference by physicians.

Abstract:Objective To investigate the prognostic role of tumor suppressor gene septal protein 9 gene methylation(mSEPT9)detection in preoperative fecal samples in predicting early recurrence after endoscopic resection of pT1 colorectal cancer.Methods From March 2021 to June 2023,plasma and fecal samples of 106 patients with pT1 colorectal cancer who underwent endoscopic resection in Baishan Central Hospital were prospectively collected(preoperative baseline and 1 week postoperatively),genome-wide DNA was extracted,and the DNA methylation of SEPT9 target genes was evaluated by bisulfite next-generation directed sequencing,to screen the SEPT9-specific methylation sites.Based on binary Cox proportional hazards regression analysis,CpG methylation sites associated with 2-year postoperative recurrence were identified,and a prognostic model based on mSEPT9 levels in fecal samples was developed to predict recurrence free survival(RFS).All patients will be followed up for at least 2 years.Results In preoperative baseline samples,a consistent trend in methylation rates for all selected CpG sites between plasma and feces was observed,and the average methylation rates were(0.14%-32.75%),which was higher in fecal samples than in plasma samples for almost all selected sites(0.09%-12.93%).At 1 week postoperatively,the methylation rate of 9 CpG sites in the SEPT9 gene was found to be significantly lower compared with preoperative rates(P<0.05).The 2-year RFS rate was 89.62%(95/106).After correcting for some major objective confounders,a higher methylation rate of 15 CpG sites in the SEPT9 gene was associated with a 2-year postoperative recurrence risk(P<0.05)by binary Cox risk-proportional regression analysis.A prognostic model was developed based on these 15 methylated loci.The formula for the regression model was π(x)=1/11+e-ωt+b(π:risk score;x:methylation rate at the locus;ω:coefficient;11+e-ωt+b 1 b:intercept).Based on the Receiver Operating Characteristic curve,the area under the curve of the model predicting 2-year RFS was 0.826(95%CI:0.748-0.903)and had a higher predictive value(P<0.05)relative to conventional tumor markers(0.773).Stratified according to the cut-off value(0.353),40 cases were in the high-risk group and 66 cases were in the low-risk group.The RFS rate of high-risk group patients was significantly lower than that of low-risk group patients(72.50%vs.100.0%,P<0.001).After univariate and multivariate Cox risk proportional regression modeling,fecal mSEPT9 status(HR=3.931,P<0.001)was an independent factor for postoperative colorectal cancer recurrence.According to the Cancer Genome Atlas database and Gene Expression Omnibus data,there was a higher rate of SEPT9 methylation in colon adenocarcinoma(COAD)patients compared with normative colon tissues(P<0.05);furthermore,disease-free survival was shorter in COAD patients with SEPT9 mRNA expression below the median value(P=0.011).Conclusion In this study,a colorectal cancer prognostic model containing 15 SEPT9 gene promoter CpG mutation sites was successfully developed.The model was able to successfully predict the risk of recurrence in the early(within 2 years)after endoscopic resection in patients with pT1 colorectal cancer,thus highlighting the potential of fecal mSEPT9 as a biomarker for colorectal cancer.