Background:Duodenal papillary adenoma is a benign tumor with relatively low incidence but significant carcinogenesis potential.Despite the minimal invasiveness and low complication rate,endoscopic papillectomy is associated with a definite risk of recurrence for duodenal papillary adenoma.Investigating the driver genes of duodenal papillary adenoma and establishing predictive models for recurrence and malignant progression could facilitate the precision medicine.Aims:To identify the key driver genes for tumor occurrence,carcinogenesis and recurrence in duodenal papillary adenoma by integrating multi-dimensional bioinformatics approaches based on transcriptomics data,and validate clinically.Methods:Expression profiles of duodenal papillary adenoma and adenocarcinoma were obtained from the GEO database(including data sets GSE189035,GSE94919,GSE111156,and GSE102208).Differentially expressed genes(DEGs)between adenomatous and normal tissues were screened.Weighted gene co-expression network analysis(WGCNA)and pseudo-time analysis were combined to identify the core genes exhibiting an"initial rise followed by decline"expression pattern during the dynamic progression from normal tissue to adenoma and adenocarcinoma.Functional annotation,immune microenvironment profiling,and protein-protein interaction network analysis were performed to explore the tumor-promoting mechanisms of these core genes.Clinical validation was conducted using immunohistochemistry to estimate the gene expression level and its relationship with tumor recurrence.Results:A total of 469 common DEGs were identified.WGCNA revealed that the blue module(including 1 051 genes)was associated with adenoma development and progression(Cor=-0.29,0.15,and 0.11 for normal tissue,adenoma,and adenocarcinoma,respectively).Intersection with DEGs pinpointed four key genes:SLC12A2,BEST4,SLC37A2,and SOAT2.Pseudo-time analysis demonstrated that only SLC12A2 maintained sustained high expression in both adenoma and adenocarcinoma tissues.KEGG enrichment analysis indicated that SLC12A2 was linked to various malignant pathways(e.g.,PD-1/PD-L1 signaling pathway),and its high expression correlated with the reduced immune cell infiltration(e.g.,γδ T cells,CD8+T cells,etc.).Clinical validation by immunohistochemistry confirmed the trend of initial upregulation and subsequent downregulation of SLC12A2 expression in normal,adenoma,and adenocarcinoma tissues.Patients with tumor recurrence showed higher SLC12A2 expression level(P=0.004);likewise,SLC12A2 high expression was associated with an elevated recurrence risk(P=0.034).Conclusions:SLC12A2 serves as a critical driver of tumorigenesis and progression for duodenal papillary adenoma,and might be a promising biomarker for recurrence prediction.

Background:Duodenal papillary adenoma is a benign tumor with relatively low incidence but significant carcinogenesis potential.Despite the minimal invasiveness and low complication rate,endoscopic papillectomy is associated with a definite risk of recurrence for duodenal papillary adenoma.Investigating the driver genes of duodenal papillary adenoma and establishing predictive models for recurrence and malignant progression could facilitate the precision medicine.Aims:To identify the key driver genes for tumor occurrence,carcinogenesis and recurrence in duodenal papillary adenoma by integrating multi-dimensional bioinformatics approaches based on transcriptomics data,and validate clinically.Methods:Expression profiles of duodenal papillary adenoma and adenocarcinoma were obtained from the GEO database(including data sets GSE189035,GSE94919,GSE111156,and GSE102208).Differentially expressed genes(DEGs)between adenomatous and normal tissues were screened.Weighted gene co-expression network analysis(WGCNA)and pseudo-time analysis were combined to identify the core genes exhibiting an"initial rise followed by decline"expression pattern during the dynamic progression from normal tissue to adenoma and adenocarcinoma.Functional annotation,immune microenvironment profiling,and protein-protein interaction network analysis were performed to explore the tumor-promoting mechanisms of these core genes.Clinical validation was conducted using immunohistochemistry to estimate the gene expression level and its relationship with tumor recurrence.Results:A total of 469 common DEGs were identified.WGCNA revealed that the blue module(including 1 051 genes)was associated with adenoma development and progression(Cor=-0.29,0.15,and 0.11 for normal tissue,adenoma,and adenocarcinoma,respectively).Intersection with DEGs pinpointed four key genes:SLC12A2,BEST4,SLC37A2,and SOAT2.Pseudo-time analysis demonstrated that only SLC12A2 maintained sustained high expression in both adenoma and adenocarcinoma tissues.KEGG enrichment analysis indicated that SLC12A2 was linked to various malignant pathways(e.g.,PD-1/PD-L1 signaling pathway),and its high expression correlated with the reduced immune cell infiltration(e.g.,γδ T cells,CD8+T cells,etc.).Clinical validation by immunohistochemistry confirmed the trend of initial upregulation and subsequent downregulation of SLC12A2 expression in normal,adenoma,and adenocarcinoma tissues.Patients with tumor recurrence showed higher SLC12A2 expression level(P=0.004);likewise,SLC12A2 high expression was associated with an elevated recurrence risk(P=0.034).Conclusions:SLC12A2 serves as a critical driver of tumorigenesis and progression for duodenal papillary adenoma,and might be a promising biomarker for recurrence prediction.

Objective To construct a predictive model of thrombus clearance rate to guide the selection of therapeutic strategies for acute lower extremity venous thromboembolism patients by studying the clinic data of patients who underwent AngioJet mechanical thromboaspiration surgery.Methods By calculating the thrombus clearance rate in 83 VTE patients treated with AngioJet surgery,correlation analysis of clinical data,combined with the characteristic factors in the LASSO regression model,multiple logistic regression analysis was applied to build a prediction model of thrombus clearance rate column line graph,and the accuracy of the prediction model was evaluated using C index,calibration curve and decision curve.Results VTE type was significantly correlated with thrombus clearance rate,and the predictors in the column line plot contained:age,sex,thrombus type,surgical history,tumor history,and smoking history.The model showed great predictive power and high accuracy with a C-index of 0.795(95％CI:0.682 3-0.905 7).Decision curve analysis showed that prediction of thrombus clearance by column line plot for AngioJet procedure was effective when the threshold probability was in the range of 0.02-0.63.Conclusion In the correlation analysis,VTE type was significantly correlated with thrombus clearance.The results of this study showed that the AngioJet thrombus aspiration procedure was able to achieve a high rate of thrombus clearance in men older than 65 years with a history of tumors,a central thrombus type,no history of surgery,and no history of smoking.

Objective To develop a health belief model(HBM)based adolescent alcohol-related cognition scale to measure adolescent alcohol-related cognition and test its reliability and validity.Methods The adolescents'alcohol-related cognitive scale was developed based on HBM model.By using purposive sampling,three general high schools in Qingpu District,Shanghai were selected.One-third of the classes from grades 10 and 11 in each school were randomly selected,and the students from these classes were surveyed as the research subjects.Exploratory factor analysis and confirmatory factor analysis were used to analyze its reliability(internal consistency reliability and combination reliability)and validity(structural validity,convergent validity,discriminative validity and criterion validity).Results A total of 970 questionnaires were collected,of which 948 were valid,with an effective rate of 97.7%.The adolescents'alcohol-related cognitive scale contained 22 items.Five common factors were extracted from exploratory factor analysis,including perceived susceptibility,perceived severity,perceived benefits,perceived obstacles,and self-efficacy.The cumulative variance contribution rate reached 83.89%.The results of confirmatory factor analysis confirmed the overall fit of the model.The average variance extracted value(AVE)of each dimension was greater than 0.5,and the convergent validity of the model was ideal.The AVE square root of each dimension of the scale was greater than its correlation coefficient,indicating good discrimination validity.Cronbach's α coefficient of the total volume table was 0.892,indicating good overall reliability.Conclusion The adolescents'alcohol-related cognitive scale developed in this study has good reliability and validity,which can be used to measure adolescents'alcohol-related perceptions.

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

OBJECTIVE: To investigate the occurrence of CSF3R mutation in patients with t(8;21) acute myeloid leukemia (AML) and its correlation with some clinical parameters. METHODS: The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21) translocation were analyzed retrospectively. High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations. The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed. RESULTS: Among 167 patients with t(8;21) AML, 15 patients (9.0%) carried CSF3R mutations, including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail. The most common coexisting mutations of CSF3R were KIT (40.0%), TET2 (33.3%), DNMT3A (26.7%), FLT3 (20.0%), CBL (20.0%), IDH1 (13.3%), etc. Compared with the wild type, the CSF3R mutant group had a higher mutation rate of DNA methylation-related genes（P <0.001）. The median peripheral white blood cell (WBC) count of patients with CSF3R gene mutation was 5.80 (3.20-8.56)×10⁹/L at initial diagnosis, which was significantly lower than 8.80 (5.26-19.92)×10⁹/L of the CSF3R wild-type patients (P =0.017). There was no significant difference between the two groups in sex, median age, FAB classification, hemoglobin level, platelet count, etc. (P >0.05). The CR rate of the CSF3R gene mutation group (100%) was significantly higher than that of the wild-type group (86.8%), but the difference was not statistically significant (P >0.05). The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher -X rate than the wild group (86.7% vs 47.4%, P =0.004; 33.3% vs 13.2%, P =0.037). CONCLUSION There is a high incidence of CSF3R mutation in t (8;21) AML patients. The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.
Humans ; Retrospective Studies ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Signal Transduction ; Receptors, Colony-Stimulating Factor/genetics*

Objective:To systematically integrate qualitative research on the decision-making experience of fertility preservation in cancer patients of childbearing age, so as to provide evidence-based basis for improving patients' fertility preservation decision-making ability and formulating targeted intervention plans.Methods:Qualitative research on the decision-making experience of fertility preservation in cancer patients of childbearing age was systematically searched on PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI) , Wanfang Database, VIP and China Biology Medicine disc. The search period was from database establishment to December 2, 2022. The quality of literature was evaluated using the quality evaluation criteria for qualitative research of the Australia Joanna Briggs Institute Evidence-Based Health Care Center. The results were integrated using the Meta-synthesis method.Results:A total of 11 articles were included, 28 results were extracted, summarized into 6 categories, and formed 3 integrated results. The integration results included the challenges and opportunities faced by fertility preservation decision-making, fertility preservation decision-making was influenced by individual, family and social factors, and lack of sufficient decision-making support.Conclusions:Cancer patients of childbearing age lack decision-making support for fertility preservation and face decision-making difficulties. Medical and nursing staff should comprehensively evaluate the fertility needs of cancer patients of childbearing age, pay attention to their cognition and experience, provide professional fertility counseling, and help patients make high-quality decision-making.

Objective:To explore the coexisting gene mutations of FLT3-ITD mutation and its association with partial clinical parameters in acute myeloid leukemia (AML).Methods:The clinical data of 236 newly diagnosed AML outpatients and hospitalized patients of Changzhou No.2 People's Hospital and the Second People's Hospital of Wuxi between December 2012 and August 2019 were retrospectively analyzed. Genome DNA-polymerase chain reaction (PCR) combined with Sanger sequencing was used to detect FLT3-ITD mutations, and 51 tumor target gene mutations in patients with FLT3-ITD mutations were detected by using high-throughput DNA sequencing combined with Sanger sequencing.Results:Among 236 AML patients, FLT3-ITD mutations were found in 71 cases (30.1%). About 97.2% (69/71) patients with FLT3-ITD mutations were accompanied by additional mutations, of which 19 patients harbored double coexisting genes mutations, 24 patients harbored 3 coexisting genes mutations and 26 patients harbored ≥ 4 coexisting genes mutations. The most common coexisting genes mutations were NPM1 (55 cases, 77.5%), followed by DNMT3A (36 cases, 50.7%), TET2 (9 cases, 12.7%), CEBPA (5 cases, 7.0%), IDH1 (4 cases, 5.6%) and NRAS (4 cases, 5.6%). In FLT3-ITD mutation group, the hemoglobin level of patients with DNMT3A mutation type was lower than that of those with DNMT3A wild type ( t = -2.37, P = 0.020); the hemoglobin level of patients with NPM1 mutation type was higher than that of those with NPM1 wild type ( t = 2.04, P = 0.045). The platelet in patients with 3 mutations and ≥ 4 mutations was higher than that in those with double mutations ( χ2 = 7.72, P = 0.021). After chemotherapy in 71 patients, the curative effect of 66 cases was evaluable, and the white blood count of 18 patients who did not reach complete remission was higher than that of 48 patients who reached complete remission ( Z = -2.74, P = 0.006). Conclusions:Most FLT3-ITD mutated patients with AML commonly show coexisting gene mutations, and the mutation types of coexisting genes are correlated with the clinical features of patients.

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Humans ; Neoadjuvant Therapy/adverse effects* ; Paclitaxel/therapeutic use* ; Treatment Outcome ; Triple Negative Breast Neoplasms/pathology*