Objective To construct mice hepatocellular carcinoma models with different tumor immune microenvironments(TIME)and explore the differences.Methods H22 and hepa1-6 were used to construct subcutaneous transplantation tumor model of C57 mice as homologous hepatocellular carcinoma cell lines(denoted as H22 group and hepal-6 group,each n=8),and the differences of TIME were evaluated.Immunohistochemistry was used to detect and quantify the infiltration of T cells,CD4+T cells,CD8+T cells,regulatory T cells and B cells in TIME.Flow cytometry was performed to detect the differences of composition of immune cell subpopulations in peripheral blood and tumor parenchyma.Gene expression profile characteristics of tumor tissue were analyzed based on high-throughput transcriptome sequencing technology,and enrichment analyses of immune-related signaling pathways were evaluated combined with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG).Results H22 group showed cold and hepa1-6 group showed hot TIME characteristics.The number of T cells,CD4+T cells and CD8+T cells in tumor tissue of H22 group were all lower,while the proportion of T cells,CD4+T cells and CD8+T cells in peripheral blood were all higher than those of hepa1-6 group(all P＜0.05).Compared with H22 group,up-regulated genes of tumor tissue in hepa1-6 group expressed significantly enriched in tumor immune activation-related signaling pathways.Conclusion H22 and hepa1-6 hepatocellular carcinoma models showed distinct TIME characteristics of cold and hot tumors,respectively,and the amount of immune cells in tumor tissue of the former were significantly lower than those in the latter.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Objective:To determine the safety and efficacy of the modified off-pump biatrial mini-maze procedure to treat isolated atrial fibrillation.Methods:This study retrospectively included isolated atrial fibrillation patients who underwent the modified off-pump biatrial mini-maze procedure at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University from January 2021 to December 2023. These patients underwent a mini-maze procedure using the Dallas lesion set protocol. A purse-string suture was then performed on the right atrium, and 4 ablation lesions were made to the superior vena cava, the inferior vena cava, the appendix of the right atrium and the tricuspid valve annulus from the purse-string suture point using the bipolar radiofrequency clamp. After the operation, the patients were followed up at 3, 6 and 12months and every year thereafter.Results:A total of 301 patients were followed up. There were no deaths or strokes. A follow-up at intervals of 3, 6, 12, 24 and 36 months showed that the cumulative success rate free from isolated atrial fibrillation was 96.0%、91.0%、85.9%、79.5% and 72.7%.Conclusion:The modified off-pump biatrial mini-maze procedure is safe and effective and can be considered as an off-pump ablation option for patients and cardiac surgeons.

BACKGROUND: The proportion of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is relatively high in China. However, these patients currently lack significant benefits from available neoadjuvant treatment options. This study aims to explore the potential application value of neoadjuvant targeted therapy by evaluating its efficacy and safety in patients with EGFR-mutant resectable lung adenocarcinoma. METHODS: A multicenter retrospective study was used to analyze the treatment effect of patients with stage IIA-IIIB EGFR-mutant lung adenocarcinoma who underwent surgical resection after receiving neoadjuvant targeted therapy from July 2019 to October 2024. RESULTS: A total of 24 patients with EGFR-mutant lung adenocarcinoma from three centers were included in this study. All patients successfully underwent surgery and achieved R0 resection of 100.0%. The objective response rate (ORR) was 83.3% (20/24) . The major pathologic response (MPR) rate was 37.5% (9/24), with 2 patients (8.3%) achieving pathological complete response (pCR). During neoadjuvant therapy, 13 out of 24 patients (54.2%) experienced adverse events of grade 1-2, with no occurrences of ≥ grade 3. The most common treatment-related adverse events were rash (n=4, 16.7%), mouth sores (n=2, 8.3%), and diarrhea (n=2, 8.3%). The median follow-up time was 33.0 months, no deaths occurred in all patients, and the overall survival (OS) rate was 100.0%. The 1-year disease-free survival (DFS) rate was 91.1%, and the 2-year DFS rate remained at 86.2%. CONCLUSIONS The application of neoadjuvant targeted therapy in patients with EGFR-mutant resectable lung adenocarcinoma is safe and feasible, and is expected to become a highly promising neoadjuvant treatment option for the patients with EGFR-mutant lung adenocarcinoma.
Humans ; ErbB Receptors/metabolism* ; Male ; Female ; Middle Aged ; Adenocarcinoma of Lung/surgery* ; Neoadjuvant Therapy ; Lung Neoplasms/surgery* ; Aged ; Retrospective Studies ; Mutation ; Adult

Objective To construct mice hepatocellular carcinoma models with different tumor immune microenvironments(TIME)and explore the differences.Methods H22 and hepa1-6 were used to construct subcutaneous transplantation tumor model of C57 mice as homologous hepatocellular carcinoma cell lines(denoted as H22 group and hepal-6 group,each n=8),and the differences of TIME were evaluated.Immunohistochemistry was used to detect and quantify the infiltration of T cells,CD4+T cells,CD8+T cells,regulatory T cells and B cells in TIME.Flow cytometry was performed to detect the differences of composition of immune cell subpopulations in peripheral blood and tumor parenchyma.Gene expression profile characteristics of tumor tissue were analyzed based on high-throughput transcriptome sequencing technology,and enrichment analyses of immune-related signaling pathways were evaluated combined with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG).Results H22 group showed cold and hepa1-6 group showed hot TIME characteristics.The number of T cells,CD4+T cells and CD8+T cells in tumor tissue of H22 group were all lower,while the proportion of T cells,CD4+T cells and CD8+T cells in peripheral blood were all higher than those of hepa1-6 group(all P＜0.05).Compared with H22 group,up-regulated genes of tumor tissue in hepa1-6 group expressed significantly enriched in tumor immune activation-related signaling pathways.Conclusion H22 and hepa1-6 hepatocellular carcinoma models showed distinct TIME characteristics of cold and hot tumors,respectively,and the amount of immune cells in tumor tissue of the former were significantly lower than those in the latter.

Objective:To determine the safety and efficacy of the modified off-pump biatrial mini-maze procedure to treat isolated atrial fibrillation.Methods:This study retrospectively included isolated atrial fibrillation patients who underwent the modified off-pump biatrial mini-maze procedure at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University from January 2021 to December 2023. These patients underwent a mini-maze procedure using the Dallas lesion set protocol. A purse-string suture was then performed on the right atrium, and 4 ablation lesions were made to the superior vena cava, the inferior vena cava, the appendix of the right atrium and the tricuspid valve annulus from the purse-string suture point using the bipolar radiofrequency clamp. After the operation, the patients were followed up at 3, 6 and 12months and every year thereafter.Results:A total of 301 patients were followed up. There were no deaths or strokes. A follow-up at intervals of 3, 6, 12, 24 and 36 months showed that the cumulative success rate free from isolated atrial fibrillation was 96.0%、91.0%、85.9%、79.5% and 72.7%.Conclusion:The modified off-pump biatrial mini-maze procedure is safe and effective and can be considered as an off-pump ablation option for patients and cardiac surgeons.

Objective:To investigate the correlation between CHA 2DS 2-VASC score and the recurrence risk of paroxysmal atrial fibrillation after radiofrequency ablation. Methods:It was a retrospective cohort study. A total of 150 patients who underwent radiofrequency ablation for paroxysmal atrial fibrillation in Xingtai People′s Hospital from January 2017 to January 2021 were consecutively included in the study. According to the preoperative CHA 2DS 2-VASC score, patients were divided into high score group (≥3 points, n=90) and low score group (<3 points, n=60). Baseline clinical data was collected. All patients underwent circumferential pulmonary vein isolation, and those with atrial flutter before ablation also underwent tricuspid isthmus isolation. Holter and electrocardiogram examinations were performed at 3, 6 months and 1 year after ablation to evaluate whether there was recurrence of atrial fibrillation. Univariate and multivariate Cox regression was used to analyze the risk factors for recurrence of atrial fibrillation after radiofrequency ablation. Results:Among 150 patients 90 were males and 60 were females with a mean age of (64.0±3.6) years. There were no significant differences in age, sex, and proportion of hypertension, diabetes, chronic heart failure and stroke or transient ischemic attack (TIA), medication of antiarrhythmic and anticoagulant drugs between the two groups (all P>0.05). The longest duration of atrial fibrillation in the high score group was significantly longer than that in the low score group (26.0±6.1) hours vs. (10.0±2.1) hours, P<0.05). There were no patients with cardiac tamponade, atrial esophageal fistula and severe vascular puncture complications in the two groups. During the follow-up period, the recurrence rate in the high score group was significantly higher than that in the low score group (16.7% (15/90) vs. 8.3% (5/60), P<0.05). Multivariate Cox regression analysis showed that CHA 2DS 2-VASC score≥3 was an independent risk factor for atrial fibrillation recurrence in patients with paroxysmal atrial fibrillation after radiofrequency ablation ( HR=3.84, 95% CI: 1.87-7.89, P=0.02). Conclusion:CHA 2DS 2-VASC score≥3 is an independent risk factor for atrial fibrillation recurrence in patients with paroxysmal atrial fibrillation after radiofrequency ablation.