Objective To investigate the association of serum total testosterone(TT),free testosterone(FT),sex hormone-binding globulin(SHBG),and estradiol(E_2)with all-cause mortality rate(AMR)in males and to evaluate their predictive value. Methods Based on data from the National Health and Nutrition Examination Survey(NHANES)cycles(1999—2004 and 2013—2016),the relationships between different sex hormones and AMR was analyzed with Cox proportional hazards regression models. The dose-response relationships between different sex hormones and male AMR were assessed with restricted cubic splines(RCS). The predictive performances of different sex hormones for male AMR were compared with receiver operating characteristic(ROC)curves and the area under the curve(AUC). The survival differences across varying sex hormone levels were evaluated with Kaplan-Meier survival curves and log-rank tests. Results This study involved 3632 adult male participants with a median follow-up of 6.5 years,during which 320 AMR occurred(8.8%). Cox univariate analysis indicated that TT,FT and SHBG were risk factors for AMR(P＜0.001). Cox multivariate analysis revealed that FT and SHBG were independent risk factors for AMR(FT:HR=0.90,95%CI:0.86-0.94; SHBG:HR=1.01,95%CI:1.01-1.02). RCS revealed a U-shaped nonlinear relationship between TT,FT and AMR(P＜0.001); SHBG showed a positive dose-response relationship with AMR(P＜0.001). The AUCs of FT predicting the 5-year,10-year,and 15-year AMR were 0.78(95%CI:0.73-0.82),0.80(95%CI:0.76-0.84),and 0.84(95%CI: 0.80-0.88),respectively,significantly outperforming other indicators. Subgroup analysis revealed that FT was negatively correlated with male AMR,but this association was modulated by age,race,smoking status and diabetes status(P_(interaction)＜0.05). Kaplan-Meier survival analysis showed that different levels of TT and FT(Q1-Q4)were significantly positively correlated with survival rate(P＜0.001),while different levels of SHBG were significantly negatively correlated with survival rate,with patients in the Q4 group having the highest risk of death(P＜0.001). Conclusion Based on US NHANES,studies have shown that the FT and SHBG are independent risk factors for male AMR,and FT demonstrates greater predictive value for male AMR than TT.

Acute lung injury（ALI）is a common，deadly complication of sepsis，involving multiple pathophysiological mechanisms.Research on prevention and treatment strategies for ALI has always been a key focus in critical-care medicine field.In recent years，the role of reactive oxygen species in ALI has received extensive attention.This review summarized the research on reactive oxygen species processes in sepsis-induced ALI，to provide new insights for ALI prevention and treatment.

Breast cancer has emerged as the leading cause of cancer incidence and mortality among women globally,with approximately 70%of cases being estrogen receptor(ER)and/or progesterone receptor(PR)positive.The primary treatment for hormone receptor(HR)positive breast cancer is endocrine therapy;however,endocrine therapy resistance remains a critical area of ongoing research.Cyclin D1 is recognized as a biomarker for tumor phenotype and disease progression,and it has been established to correlate with the onset,progres-sion,and prognosis of breast cancer.Recently,studies have also reported the significant role of Cyclin D1 in endocrine resistance in breast cancer.This article provides an overview of the research progress on Cyclin D1 in breast cancer,with a particular emphasis on its relation-ship with endocrine therapy resistance,aiming to offer novel insights for the endocrine treatment of breast cancer.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.

Objective:To screen differentially expressed circular RNAs(circRNA)associated with lymph node metastasis in cervical cancer and investigate their molecular mechanism and biological function.Methods:Cancer tissue samples were collected from 40 cervical cancer patients(20 with lymph node metastasis and 20 without lymph node metastasis).Three specimens were randomly selected from each group,and the circRNA expression profile was analyzed using high-throughput sequencing technology,and perform KEGG and GO enrichment analy-sis was performed on the differentially expressed circRNA derived mother genes.Real-time fluorescence quantita-tive PCR(qRT-PCR)technology was used to validate four significantly upregulated circRNAs with high differential multiples,and a ceRNA network was constructed for database prediction.The relationship between circRNA with the most significant differential expression and clinical pathological features was analyzed.Transfect circRNA small interfering RNA(siRNA)into cervical cancer cell lines.Cell lines were divided into circRNA knockdown group and negative control(si-NC)group.The proliferation of SiHa cells and HeLa cells in cervical cancer was detected by Cell Counting Kit-8(CCK-8).Results:①A total of 2039 differentially expressed circRNAs were detec-ted.The differentially expressed circRNA derived mother genes are mainly enriched in ubiquitin mediated protein hydrolysis,MAPK signaling pathway,endocytosis,apoptosis and other signaling pathways.②Four significantly up-regulated circRNAs with high differential multiples in the transfer group were selected,which are hsa_circ_0067492,hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718.qRT-PCR showed that hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718 were all highly expressed in cervical cancer tissues with lymph node metas-tasis(P<0.01).Hsa_circ_0004904 could interact with microRNAs(miRNAs)such as hsa-miR-3916.Hsa_circ_0085465 could interact with miRNAs such as hsa-miR-4659b-3p,and hsa_circ_0007718 could interact with miRNAs such as hsa-miR-127-5p.③The high and low expression groups of hsa_circ_0004904 showed statistically signigi-cant differences in lymph node metastasis and lymphovascular invasion status(P<0.05).Compared with the si-NC group,the proliferation ability of SiHa cells and HeLa cells was significantly reduced after transfection with hsa_circ_0004904 at 24,48,and 72 hours(P<0.05).Conclusions:Differentially expressed circRNAs were identi-fied in cervical cancer patients with lymph node metastasis.Silencing these circRNAs significantly inhibited the proliferation of cervical cancer cells,suggesting their potential involvement in the progression of lymph node me-tastasis.These circRNAs may serve as specific biomarkers for predicting lymph node metastasis.

Acute lung injury（ALI）is a common，deadly complication of sepsis，involving multiple pathophysiological mechanisms.Research on prevention and treatment strategies for ALI has always been a key focus in critical-care medicine field.In recent years，the role of reactive oxygen species in ALI has received extensive attention.This review summarized the research on reactive oxygen species processes in sepsis-induced ALI，to provide new insights for ALI prevention and treatment.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.

Objective:To screen differentially expressed circular RNAs(circRNA)associated with lymph node metastasis in cervical cancer and investigate their molecular mechanism and biological function.Methods:Cancer tissue samples were collected from 40 cervical cancer patients(20 with lymph node metastasis and 20 without lymph node metastasis).Three specimens were randomly selected from each group,and the circRNA expression profile was analyzed using high-throughput sequencing technology,and perform KEGG and GO enrichment analy-sis was performed on the differentially expressed circRNA derived mother genes.Real-time fluorescence quantita-tive PCR(qRT-PCR)technology was used to validate four significantly upregulated circRNAs with high differential multiples,and a ceRNA network was constructed for database prediction.The relationship between circRNA with the most significant differential expression and clinical pathological features was analyzed.Transfect circRNA small interfering RNA(siRNA)into cervical cancer cell lines.Cell lines were divided into circRNA knockdown group and negative control(si-NC)group.The proliferation of SiHa cells and HeLa cells in cervical cancer was detected by Cell Counting Kit-8(CCK-8).Results:①A total of 2039 differentially expressed circRNAs were detec-ted.The differentially expressed circRNA derived mother genes are mainly enriched in ubiquitin mediated protein hydrolysis,MAPK signaling pathway,endocytosis,apoptosis and other signaling pathways.②Four significantly up-regulated circRNAs with high differential multiples in the transfer group were selected,which are hsa_circ_0067492,hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718.qRT-PCR showed that hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718 were all highly expressed in cervical cancer tissues with lymph node metas-tasis(P<0.01).Hsa_circ_0004904 could interact with microRNAs(miRNAs)such as hsa-miR-3916.Hsa_circ_0085465 could interact with miRNAs such as hsa-miR-4659b-3p,and hsa_circ_0007718 could interact with miRNAs such as hsa-miR-127-5p.③The high and low expression groups of hsa_circ_0004904 showed statistically signigi-cant differences in lymph node metastasis and lymphovascular invasion status(P<0.05).Compared with the si-NC group,the proliferation ability of SiHa cells and HeLa cells was significantly reduced after transfection with hsa_circ_0004904 at 24,48,and 72 hours(P<0.05).Conclusions:Differentially expressed circRNAs were identi-fied in cervical cancer patients with lymph node metastasis.Silencing these circRNAs significantly inhibited the proliferation of cervical cancer cells,suggesting their potential involvement in the progression of lymph node me-tastasis.These circRNAs may serve as specific biomarkers for predicting lymph node metastasis.

Objective:To investigate the expression of Cullin associated NEDD8 dissociated protein 1 in colorectal cancer and its effect on the biological behavior of colorectal cancer.Method:A total of 70 pairs of colorectal cancer and paired normal tissue specimens were collected from Jun to Dec 2017 at the Department of Gastrointestinal Surgery at Peking University People's Hospital. Immunohistochemistry was used to detect the expression of Cullin associated NEDD8 dissociated protein 1 and analyze its relationship with clinical pathological indicators and prognosis. CCK8, colony formation assay, transwell assay, and wound healing assay were used to evaluate the effects of Cullin associated NEDD8 dissociated protein 1 on the proliferation, migration, and invasion ability of colon cancer cells.Result:Compared with normal tissues, Cullin associated NEDD8 dissociated protein 1 was highly expressed in colorectal cancer (Immunohistochemistry score: 3.685±1.257 vs. 2.000±0.851, Z=6.536, P<0.001). The expression level of Cullin associated NEDD8 dissociated protein 1 was significantly correlated with T stage ( χ2=5.67, P=0.017), N stage ( χ2=7.20, P=0.007), and pathology stage ( χ2=4.66, P=0.031). Patients with high expression of Cullin associated NEDD8 dissociated protein 1 had a worse prognosis than those with low expression ( χ2=4.80, P=0.037). Knocking down Cullin associated NEDD8 dissociated protein 1 significantly reduced the proliferation, colony formation, and invasive migration ability of DLD1 cells (all P<0.05). Conclusion:Cullin associated NEDD8 dissociated protein 1 is significantly overexpressed in colorectal cancer and has a promoting effect on the occurrence and development of colorectal cancer.

Objective:To develop and validate a diagnostic model for pancreatic benign and malignant tumors using radiomics technology.Methods:A retrospective analysis was conducted on the clinical data of 113 patients with pancreatic tumors who underwent surgical treatment at the Hepatobiliary and Pancreatic Surgery Departments of the Second Hospital and the First Hospital of Hebei Medical University from January 2020 to December 2022. There were 59 male and 54 female patients, aged (55.3±16.8) years. Preoperative enhanced thin-slice computed tomography (CT) data and postoperative pathological diagnosis results were collected. Data from 74 patients at the Second Hospital were selected, and according to the random classification principle of 7∶3, the data of 52 patients were determined as the training set for model construction, while the remaining 22 patients' data served as the internal validation set. Data from 39 patients at the First Hospital of Hebei Medical University were used as the external validation set to assess the generali-zability of the established model. The region of interest in the lesions on CT images was analyzed using three-dimensional radiomics feature extraction, and the top 5 features were selected using feature selection methods. Radiomics models were established for the selected features using 17 classifiers. The performance of the models was evaluated using the area under curve (AUC) of the receiver operating characteristic (ROC).Results:Two hundred and fifty-five models were established with 15 feature selection methods and 17 classifiers. 7 models with the AUC greater than 0.7 were selected, among which the best one was LASSO-K neighbors classifier model, constructed using the LASSO feature selection method and the k-nearest neighbors algorithm, achieving AUC values of 0.933 (95% CI: 0.859-0.984) in the training set, 0.973 (95% CI: 0.896-1.000) in the validation set, and 0.774 (95% CI: 0.624-0.908) in the external validation set, with satisfactoryclassification and generalization ability. Conclusion:The radiomics-based diagnostic model for pancreatic benign and malignant tumors can effectively distinguish the benignancy and malignancy of tumors. The LASSO-K neighbors classifier model demonstrated high accuracy and reliability in this study.