ObjectiveTo construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis (CIP), in order to address the critical issue of the lack of standardized animal models in this research field. MethodsThirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group (n=5), a bleomycin (BLM) group (n=15), and a BLM+programmed death-1 (PD-1) monoclonal antibody (BLM+PD-1) group (n=15). Corresponding drugs were administered via intraperitoneal injection for intervention. The general condition, body weight changes, survival rate, and pulmonary histopathological alterations were systematically monitored. ResultsCompared with the BLM group, the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis, characterized by progressive body weight loss and more severe deterioration of general conditions. Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group. In contrast, pulmonary lesions continued to worsen in the BLM+PD-1 group, with no evidence of resolution of inflammation 28 days post-modeling. Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A (IL-17A) in lung tissues reached 34.28% in the BLM+PD-1 group 14 days post-modeling, which was markedly higher than that in the BLM group (24.02%, P < 0.000 1). The positive expression rate of α-smooth muscle actin (α-SMA) was 12.40% in the BLM+PD-1 group 14 days post-modeling, nearly twice the level in the BLM group (5.87%). 28 days post-modeling, the positive expression rate of α-SMA remained at 7.72% in the BLM+PD-1 group, while it declined to 3.38% in the BLM group. ConclusionThe addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy. Accordingly, this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis. This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.

ObjectiveTo explore the effects of genetic variation of obesity-related biological pathways and gene-obesity interactions on the incidence of gastric cancer, so as to better understand the pathogenesis of gastric cancer and help identify high-risk populations for individualized prevention of gastric cancer. MethodsA case-control study based on the Shanghai Suburban Adult Cohort and Biobank study (SSACB) was conducted on the cases with gastric cancer. A total of 267 cases with gastric cancer and 267 healthy controls matched 1∶1 by age and gender using propensity score were included in the study. After genome-wide genotyping, quality control and imputation, 19 250 single nucleotide polymorphism (SNP) sites from 115 genes in 4 obesity-related biological pathways were extracted. Univariate and multivariate logistic regression analyses were used to evaluate the association between these SNP sites and the risk of gastric cancer, and false positive report probability (FPRP) was used for multiple test correction.Data from Biobank Japan (BBJ) and FinnGen public accessible databases were used to validate significant SNP sites. For validated sites, expression quantitative trait loci (eQTL) analysis and differentially expressed genes analysis were further performed. Additive and multiplicative interactions were used to evaluate the gene-obesity interactions on the incidence of gastric cancer. Additive interaction evaluation indicators included relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI), while multiplicative interaction evaluation indicators include OR_GxE and P_inter. ResultsA total of 41 SNP sites were significantly associated with the onset of gastric cancer (P_adj<0.05, FPRP_0.1<0.1), among which 7 groups of haplotype blocks were formed. ACACB/ rs2268401 [SSACB: P=0.005, BBJ: P=0.049], HRAS/ rs12785860 (SSACB: P<0.001, FinnGen: P=0.045), and PTPN1/ rs6095985 (SSACB: P<0.001, FinnGen: P=0.023) were significantly associated with the risk of gastric cancer after validation in different populations. Among which, the G allele of HRAS/ rs12785860 was correlated with the downregulation of HRAS mRNA expression (P<0.001), and the expression level of HRAS in gastric cancer tissues was higher than that in adjacent normal tissues (P<0.001). Additionaly, JAK1/rs11208559 showed a positive additive interaction with waist circumstance (WC) on the risk of gastric cancer [RERI=2.29(0.06~4.53), AP=0.57(0.23~0.90), SI=4.03(2.20~5.87)]. ConclusionObesity-related biological pathway SNP sites and their haplotypes are associated with the risk of gastric cancer, suggesting that genetic variations in obesity pathways may affect gastric cancer. The HRAS/ rs12785860 is significantly associated with downregulation of HRAS gene expression, which may serve as a potential genetic marker for gastric cancer. JAK1/rs11208559 interacts with obesity additively on the risk of gastric cancer. Individuals with GC+CC genotypes and pre-central or central obesity have an increased risk of gastric cancer, providing clues and evidences for individualized prevention of gastric cancer.

Objective:To analyze serum inflammatory factors associated with antihistamine resistance in patients with chronic spontaneous urticaria (CSU) .Methods:A total of 88 CSU patients were enrolled from Guangzhou Dermatology Hospital from January 2022 to December 2024. All patients received antihistamine treatment according to the "Guideline for diagnosis and treatment of urticaria in China (2022) " . Based on the 7-day urticaria activity score (UAS7) after 4-week treatment, these patients were divided into an antihistamine-sensitive group and an antihistamine-resistant group. Serum levels of inflammatory factors at the initial visit were analyzed using the Olink-targeted proteomics technology. Specific biomarkers associated with antihistamine resistance were identified, and Spearman correlation analysis was carried out to analyze correlations among differentially expressed proteins. A logistic regression model was constructed based on the Olink proteomics data, and the predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis. Measurement data were expressed as mean ± standard deviation or median (lower quartile, upper quartile) .Results:The 88 CSU patients aged 12 to 81 (38.78 ± 13.89) years, with the disease duration being 18 (7.00, 60.00) months. There were 32 patients in the antihistamine-sensitive group and 56 in the antihistamine-resistant group. No significant differences were found between the two groups in terms of age, disease duration, gender, or history of allergic diseases (all P > 0.05) . After 4 weeks of antihistamine treatment, the UAS7 score was significantly higher in the antihistamine-resistant group (25.00 [15.25, 31.00] points) than in the antihistamine-sensitive group (0.50 [0.00, 4.00] points; Z = -7.08, P < 0.001) . The Olink-targeted proteomics identified 5 differentially expressed proteins between the two groups: compared with the antihistamine-sensitive group, the antihistamine-resistant group showed > 2-fold higher expression of fibroblast growth factor 19 (FGF19) , interleukin-15 receptor subunit alpha (IL-15RA) , eotaxin (CCL11) , and monocyte chemoattractant protein-1 (MCP-1) ; in contrast, the expression of sulfotransferase 1A1 (ST1A1) in the antihistamine-sensitive group was 2.54 times that in the antihistamine-resistant group. Among the differentially expressed proteins, MCP-1 showed the highest specificity (1.00) for predicting antihistamine resistance, followed by CCL11 (0.97) . Correlation analysis revealed a significant positive correlation between MCP-1 and CCL11, and a significant negative correlation between IL-15RA and ST1A1. ROC curve analysis showed that MCP-1 and CCL11 had area under the curve values of 0.603 and 0.630, respectively, in predicting antihistamine resistance. Conclusion:MCP-1 and CCL11 may be potential biomarkers for predicting antihistamine resistance in CSU patients.

Objective:To compare the clinical outcomes of immediate breast reconstruction using latissimus dorsi flap with implant versus mesh with implant based on BREAST-Q evaluation.Methods:From the clinical database of the First Affiliated Hospital of Nanjing Medical University, the patients who underwent immediate breast reconstruction after total mastectomy from January 2020 to December 2023 were selected as the research subjects. All breast reconstruction surgeries were performed by the same surgeon. Patients were divided into two groups according to surgical methods: the latissimus dorsi muscle flap combined with implant immediate breast reconstruction group (LD group) and the mesh combined with implant immediate breast reconstruction group (mesh group). Patients were followed up in outpatient clinics or by telephone one year after surgery. The BREAST-Q was used to evaluate the surgical outcomes of both groups from four dimensions: psychosocial well-being, sexual well-being, chest-physical well-being, and breast satisfaction. The score range for each dimension was 0-100, with higher scores indicating greater patient satisfaction with quality of life and surgical outcomes. Statistical analysis was performed using SPSS 22.0 software. Normally distributed measurement data were expressed as Mean ± SD, and comparisons between the two groups were performed using independent sample t-test. Count data were expressed as number of cases and percentages, and comparisons between groups were performed using chi-square test or Fisher’s exact test. P<0.05 was considered statistically significant. Results:A total of 123 patients were included, with 59 patients in the LD group and 64 patients in the mesh group. In the LD group, the mean age was (37.7±7.0) years, body mass index (BMI) was (22.6±2.6) kg/m 2, and clinical tumor staging showed 2, 22, 30, and 5 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. In the mesh group, the mean age was (39.1±7.0) years, BMI was (22.6±2.8) kg/m 2, and clinical tumor staging showed 1, 25, 38, and 0 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. There were no statistically significant differences between the two groups in baseline characteristics including age, BMI, and clinical tumor staging (all P>0.05). One year after surgery, the BREAST-Q result showed no statistically significant differences between the LD group and mesh group in psychosocial well-being [(83.0±19.8) points vs. (80.8±19.3) points] and sexual well-being [(62.1±30.4) points vs. (65.8±25.6) points] (all P>0.05). However, the LD group had lower chest-physical well-being scores than the mesh group [(40.6±9.7) points vs. (45.1±9.6) points, P<0.05], while breast satisfaction scores were higher in the LD group than in the mesh group [(68.0±17.8) points vs. (59.8±12.6) points, P<0.01]. Conclusion:Immediate breast reconstruction by both latissimus dorsi flap with implant and mesh with implant can improve patients’ psychosocial and sexual well-being by enhancing breast appearance. However, LD technique provides better breast satisfaction, while the mesh technique offers advantages in physical well-being of the chest wall and upper body. Surgeons should select the most appropriate breast reconstruction technique based on patients’ anatomical conditions, treatment history, and individual needs to optimize postoperative quality of life and satisfaction.

Objective:This study aims to establish a real world study (RWS) quality evaluation model based on Analytic Hierarchy Process -Fuzzy Comprehensive Evaluation Methods (AHP-FCE), and provide a reference basis for researchers and quality control personnel in medical and health institutions.Methods:The evaluation index framework of RWS quality was obtained by analyzing national RWS regulations. Two rounds of Delphi expert consultation were conducted, while the results were statistically analyzed and weighted using the AHP method by Yaahp software. The comprehensive evaluation model of RWS was established by combining AHP and FCE methods.Results:The RWS quality evaluation model based on AHP-FCE methods was constructed, including 6 primary indicators, 31 secondary indicators, and specific indicator evaluation methods, and validated through RWS case analysis.Conclusions:The RWS quality evaluation model constructed in this study is reasonable and practical, which can provide a reference for institutional researchers and quality managers.

Objective:To analyze serum inflammatory factors associated with antihistamine resistance in patients with chronic spontaneous urticaria (CSU) .Methods:A total of 88 CSU patients were enrolled from Guangzhou Dermatology Hospital from January 2022 to December 2024. All patients received antihistamine treatment according to the "Guideline for diagnosis and treatment of urticaria in China (2022) " . Based on the 7-day urticaria activity score (UAS7) after 4-week treatment, these patients were divided into an antihistamine-sensitive group and an antihistamine-resistant group. Serum levels of inflammatory factors at the initial visit were analyzed using the Olink-targeted proteomics technology. Specific biomarkers associated with antihistamine resistance were identified, and Spearman correlation analysis was carried out to analyze correlations among differentially expressed proteins. A logistic regression model was constructed based on the Olink proteomics data, and the predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis. Measurement data were expressed as mean ± standard deviation or median (lower quartile, upper quartile) .Results:The 88 CSU patients aged 12 to 81 (38.78 ± 13.89) years, with the disease duration being 18 (7.00, 60.00) months. There were 32 patients in the antihistamine-sensitive group and 56 in the antihistamine-resistant group. No significant differences were found between the two groups in terms of age, disease duration, gender, or history of allergic diseases (all P > 0.05) . After 4 weeks of antihistamine treatment, the UAS7 score was significantly higher in the antihistamine-resistant group (25.00 [15.25, 31.00] points) than in the antihistamine-sensitive group (0.50 [0.00, 4.00] points; Z = -7.08, P < 0.001) . The Olink-targeted proteomics identified 5 differentially expressed proteins between the two groups: compared with the antihistamine-sensitive group, the antihistamine-resistant group showed > 2-fold higher expression of fibroblast growth factor 19 (FGF19) , interleukin-15 receptor subunit alpha (IL-15RA) , eotaxin (CCL11) , and monocyte chemoattractant protein-1 (MCP-1) ; in contrast, the expression of sulfotransferase 1A1 (ST1A1) in the antihistamine-sensitive group was 2.54 times that in the antihistamine-resistant group. Among the differentially expressed proteins, MCP-1 showed the highest specificity (1.00) for predicting antihistamine resistance, followed by CCL11 (0.97) . Correlation analysis revealed a significant positive correlation between MCP-1 and CCL11, and a significant negative correlation between IL-15RA and ST1A1. ROC curve analysis showed that MCP-1 and CCL11 had area under the curve values of 0.603 and 0.630, respectively, in predicting antihistamine resistance. Conclusion:MCP-1 and CCL11 may be potential biomarkers for predicting antihistamine resistance in CSU patients.

Objective:To compare the clinical outcomes of immediate breast reconstruction using latissimus dorsi flap with implant versus mesh with implant based on BREAST-Q evaluation.Methods:From the clinical database of the First Affiliated Hospital of Nanjing Medical University, the patients who underwent immediate breast reconstruction after total mastectomy from January 2020 to December 2023 were selected as the research subjects. All breast reconstruction surgeries were performed by the same surgeon. Patients were divided into two groups according to surgical methods: the latissimus dorsi muscle flap combined with implant immediate breast reconstruction group (LD group) and the mesh combined with implant immediate breast reconstruction group (mesh group). Patients were followed up in outpatient clinics or by telephone one year after surgery. The BREAST-Q was used to evaluate the surgical outcomes of both groups from four dimensions: psychosocial well-being, sexual well-being, chest-physical well-being, and breast satisfaction. The score range for each dimension was 0-100, with higher scores indicating greater patient satisfaction with quality of life and surgical outcomes. Statistical analysis was performed using SPSS 22.0 software. Normally distributed measurement data were expressed as Mean ± SD, and comparisons between the two groups were performed using independent sample t-test. Count data were expressed as number of cases and percentages, and comparisons between groups were performed using chi-square test or Fisher’s exact test. P<0.05 was considered statistically significant. Results:A total of 123 patients were included, with 59 patients in the LD group and 64 patients in the mesh group. In the LD group, the mean age was (37.7±7.0) years, body mass index (BMI) was (22.6±2.6) kg/m 2, and clinical tumor staging showed 2, 22, 30, and 5 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. In the mesh group, the mean age was (39.1±7.0) years, BMI was (22.6±2.8) kg/m 2, and clinical tumor staging showed 1, 25, 38, and 0 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. There were no statistically significant differences between the two groups in baseline characteristics including age, BMI, and clinical tumor staging (all P>0.05). One year after surgery, the BREAST-Q result showed no statistically significant differences between the LD group and mesh group in psychosocial well-being [(83.0±19.8) points vs. (80.8±19.3) points] and sexual well-being [(62.1±30.4) points vs. (65.8±25.6) points] (all P>0.05). However, the LD group had lower chest-physical well-being scores than the mesh group [(40.6±9.7) points vs. (45.1±9.6) points, P<0.05], while breast satisfaction scores were higher in the LD group than in the mesh group [(68.0±17.8) points vs. (59.8±12.6) points, P<0.01]. Conclusion:Immediate breast reconstruction by both latissimus dorsi flap with implant and mesh with implant can improve patients’ psychosocial and sexual well-being by enhancing breast appearance. However, LD technique provides better breast satisfaction, while the mesh technique offers advantages in physical well-being of the chest wall and upper body. Surgeons should select the most appropriate breast reconstruction technique based on patients’ anatomical conditions, treatment history, and individual needs to optimize postoperative quality of life and satisfaction.

Objective:This study aims to establish a real world study (RWS) quality evaluation model based on Analytic Hierarchy Process -Fuzzy Comprehensive Evaluation Methods (AHP-FCE), and provide a reference basis for researchers and quality control personnel in medical and health institutions.Methods:The evaluation index framework of RWS quality was obtained by analyzing national RWS regulations. Two rounds of Delphi expert consultation were conducted, while the results were statistically analyzed and weighted using the AHP method by Yaahp software. The comprehensive evaluation model of RWS was established by combining AHP and FCE methods.Results:The RWS quality evaluation model based on AHP-FCE methods was constructed, including 6 primary indicators, 31 secondary indicators, and specific indicator evaluation methods, and validated through RWS case analysis.Conclusions:The RWS quality evaluation model constructed in this study is reasonable and practical, which can provide a reference for institutional researchers and quality managers.

Objective:To investigate the characteristics of gut microbiota in patients with type 2 diabetes (T2DM) complicated by nonalcoholic fatty liver disease (NAFLD).Methods:A total of 74 patients first diagnosed with T2DM at the Endocrinology Department of Peking Union Medical College Hospital from April 2021 to October 2023 were included. Among them, 28 patients had concurrent NAFLD while 46 patients did not. Additionally, 51 healthy controls were matched (HC group). Clinical laboratory parameters were collected, and 16S rRNA sequencing with fecal samples was conducted to compare the differences in gut microbiota across the groups.Results:Compared to the group with T2DM, patients with concurrent T2DM and NAFLD were younger, had higher level of insulin resistance as assessed by the homeostatic model assessment of insulin resistance, higher body mass index (BMI), and higher triglyceride levels. There was no difference in α-diversity across the three groups ( P>0.05), while there was a significant difference in β-diversity ( P=0.03). The Eubacterium coprostanoligenes, Fusicatenibacter, Parasutterella and Tyzzerella 3 were enriched in the group with concurrent T2DM and NAFLD as shown by the relative abundance, while the relative abundance of Flavonifractor was decreased in this group. Tyzzerella 3 abundance was positively correlated with triglyceride and albumin levels and negatively correlated with high-density lipoprotein cholesterol (HDL-C) levels. Conclusion:Patients with T2DM complicated by NAFLD exhibit dysbiosis in gut microbiota composition and specific genera abundance, with Flavonifractor identified as a potential protective factor for T2DM complicated by NAFLD.