[摘 要] 目的：探讨胃肝样腺癌（HAS）的临床病理特征与免疫微环境异质性，筛选预后标志物，阐释其高侵袭性与疗效差的机制，为精准诊疗策略提供理论依据。方法:​​ 回顾性收集2013年1月至2025年5月期间海军军医大学第一附属医院与第二附属医院收治的65例HAS患者的临床信息及病理资料。采用免疫组织化学技术检测HAS​​肝样分化标志物、神经内分泌标志物​​等分子表达情况，通过Kaplan-Meier生存分析法明确与预后相关的靶点。利用多色免疫荧光技术鉴定肿瘤区域内免疫细胞亚群分布情况，以阐明其免疫微环境特征。结果：65例患者中，男性54例（83.1%），女性11例（16.9%），中位年龄68岁。肿瘤好发于贲门（40%），其次为胃窦（32.3%）和胃体（27.7%）。中位随访时间23.18个月，15例患者死亡，46例生存，4例失访。HAS的胃镜及手术标本大体观呈灰白色实性质硬肿物，镜下可见中低分化胃腺癌与肝细胞癌（HCC）样分化区交错分布。表达神经内分泌相关分子的HAS患者呈现出更多的淋巴结转移数量及更短的总生存期。免疫微环境解析显示，HAS总体缺乏免疫细胞浸润，呈现“冷肿瘤”特征；免疫细胞主要聚集于胃癌腺体周围区域，而在HCC样分化区域罕见淋巴细胞浸润。结论：HAS侵袭性强，根治性手术是主要治疗手段；神经内分泌转化提示不良预后，是个体化治疗的关键标志；免疫细胞浸润缺乏，可能是其免疫治疗响应不佳的原因。

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To explore the prognostic implications of coagulation-fibrinolysis biomarkers in intracerebral hemorrhage(ICH)and to construct a multivariable logistic regression model for individualized risk prediction.Methods A total of 101 ICH patients who were admitted to Nanfang Hospital of Southern Medical University from January 2020 to December 2023 were retrospectively enrolled.These patients were stratified into a poor outcome group(ΔGCS≤0)and a good outcome group(ΔGCS>0)according to the difference in Glasgow Coma Scale(GCS)scores between discharge and admission.Coagulation and fibrinolysis markers collected upon admission were analyzed.The Least Absolute Shrinkage and Selection Operator(LASSO)regression was employed to screen variables.A logistic regression model was constructed using 70%of the cases(the training set),while the remaining 30%were utilized for validation.The performance of the model was evaluated through receiver operating characteristic(ROC)curves,calibration plots,Hosmer-Lemeshow goodness-of-fit test,and decision curve analysis(DCA).Results Univariate analysis indicated that thrombin-antithrombin complex(TAT),D-dimer,and age exhibited significant differences between the two outcome groups(P<0.05).These three variables were selected via LASSO regression and incorporated into the logistic model.The final model equation was expressed as:logit(P)=-6.234+1.132×TAT+0.867×D-dimer+0.699×Age.In the training set,the area under the ROC curve(AUC)was 0.795.The calibration curve demonstrated excellent agreement between the predicted and observed outcomes,with a Hosmer-Lemeshow test P-value of 0.8568.DCA revealed that the model achieved net clinical benefit across a broad range of risk thresholds(0.1～0.8).Conclusions TAT,D-dimer,and age are independent predictors of poor prognosis in patients with ICH.The logistic regression model based on these variables demon-strates favorable discriminatory ability and clinical utility.The nomogram derived from this model enables individu-alized risk assessment and may aid clinicians in early prognostic evaluation and treatment planning.

Objective To explore the prognostic implications of coagulation-fibrinolysis biomarkers in intracerebral hemorrhage(ICH)and to construct a multivariable logistic regression model for individualized risk prediction.Methods A total of 101 ICH patients who were admitted to Nanfang Hospital of Southern Medical University from January 2020 to December 2023 were retrospectively enrolled.These patients were stratified into a poor outcome group(ΔGCS≤0)and a good outcome group(ΔGCS>0)according to the difference in Glasgow Coma Scale(GCS)scores between discharge and admission.Coagulation and fibrinolysis markers collected upon admission were analyzed.The Least Absolute Shrinkage and Selection Operator(LASSO)regression was employed to screen variables.A logistic regression model was constructed using 70%of the cases(the training set),while the remaining 30%were utilized for validation.The performance of the model was evaluated through receiver operating characteristic(ROC)curves,calibration plots,Hosmer-Lemeshow goodness-of-fit test,and decision curve analysis(DCA).Results Univariate analysis indicated that thrombin-antithrombin complex(TAT),D-dimer,and age exhibited significant differences between the two outcome groups(P<0.05).These three variables were selected via LASSO regression and incorporated into the logistic model.The final model equation was expressed as:logit(P)=-6.234+1.132×TAT+0.867×D-dimer+0.699×Age.In the training set,the area under the ROC curve(AUC)was 0.795.The calibration curve demonstrated excellent agreement between the predicted and observed outcomes,with a Hosmer-Lemeshow test P-value of 0.8568.DCA revealed that the model achieved net clinical benefit across a broad range of risk thresholds(0.1～0.8).Conclusions TAT,D-dimer,and age are independent predictors of poor prognosis in patients with ICH.The logistic regression model based on these variables demon-strates favorable discriminatory ability and clinical utility.The nomogram derived from this model enables individu-alized risk assessment and may aid clinicians in early prognostic evaluation and treatment planning.

BACKGROUND: 3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction. Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues. The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction. METHODS: In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF). The biological scaffolds were constructed using desktop-stereolithography.The physicochemical properties of the hydrogels were evaluated; Some experiments have been conducted to evaluate exosomes’ effect of promotion vaginal reconstruction and to explore the mechanism in this process. RESULTS: It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue. Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats, which may through the PI3K/AKT signaling pathway. CONCLUSION The use of exosome-hydrogel composites improved the epithelial regeneration of vaginal tissue, increased angiogenesis, and promoted smooth muscle tissue regeneration. 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.

Within traditional teaching models,students frequently assume a passive role in acquiring knowledge,potentially resulting in diminished motivation and limited engagement,particularly within the realm of Medical Immunology education.The inte-gration of role-playing,informed by constructivist learning theory,situated learning theory,and multiple intelligences theory,has demonstrated encouraging outcomes within clinical medical education settings.However,the extent to which this approach has been explored within the context of Immunology instruction remains insufficiently examined.This study investigates the utilization of role-playing as a pedagogical approach in Medical Immunology education,wherein students are assigned specific scenarios to simulate the functions of various immune components.The primary objective is to augment interactivity and the overall appeal of the learning pro-cess.Efficacy of this instructional method was evaluated through in-class quizzes,surveys,and performance analysis.The findings demonstrate that role-playing substantially enhances student engagement,comprehension,knowledge retention,and examination per-formance.In practical application,the integration of role-playing with ideological and political elements has the potential to enhance learning outcomes and foster students'enthusiasm for engaging in cutting-edge literature and immunological research.This approach also necessitates greater proficiency in teachers'professional competencies and organizational skills,as well as increased allocation of class time and spatial resources.Future research should investigate the applicability of role-playing across various educational levels and examine its potential integration with classroom ideological and political education.

Objective:To analyze the epidemiological distribution characteristics, influencing factors, and infection rates of pertussis in the population of Henan Province.Methods:From 2022 to 2023, a cross-sectional survey was conducted to investigate the permanent population in Henan Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-pertussis toxin IgG (PT-IgG), analyze the antibody positivity rate (≥20 IU/ml) and median concentration (MC), and estimate the pertussis infection rate based on PT IgG ≥40 IU/ml. The rank sum test was used to compare antibody levels among groups, and the χ2 test was used to compare antibody positive rates and infection rates among groups. Results:A total of 4 810 research subjects were included in this study. The overall positive rate of PT-IgG was 12.10% and MC was 3.04 (0.35, 10.36) IU/ml. There were significant differences both in positive rates and antibody levels of PT-IgG among different regions or age groups (region positive rate: χ2=134.06, P<0.001, MC: H=337.74, P<0.001; age group positive rate: χ2=45.27, P<0.001, MC: H=134.49, P<0.001). Both the positive rate of PT-IgG (25.26%) and MC (8.01 IU/ml) were the highest within one year after completing a full course of vaccination. There were significant differences in positive rates and antibody levels among people receiving different types of pertussis vaccines (positive rate: χ2=12.38, P=0.006, MC: H=17.93, P<0.001). The antibody positivity rate (35.71%) and MC (8.88 IU/ml) of the people who received cell-free pertussis inactivated poliomyelitis influenza type b (combined) vaccine throughout the course were higher than those who received other types of vaccines. The natural infection rate of pertussis was evaluated for individuals aged≥3 years who had no history of pertussis vaccine immunization within the year prior to sampling. With a high vaccination rate, the estimated infection rate of pertussis in the population was 5 757.22/100 000. The infection rates in the 3-year-old (1 940.16/100 000) and 4-year-old (1 765.68/100 000) populations were at a low level among the entire population, reaching their peak at the age of 6 (12 656.71/100 000). Subsequently, although the infection rate continued to decline, it remained at a high level and peaked again at the age of 40-49 years (8 740.39/100 000). There was a statistically significant difference in the estimated infection rate of pertussis among different age groups ( χ2=53.21, P<0.001). Conclusion:The PT-IgG level of pertussis in the population of Henan Province is generally at a low level. The estimated infection rate of pertussis is much higher than the reported incidence rate. A booster dose of pertussis vaccine is recommended at 6 years old.

Objective:To analyze the epidemiological distribution characteristics, influencing factors, and infection rates of pertussis in the population of Henan Province.Methods:From 2022 to 2023, a cross-sectional survey was conducted to investigate the permanent population in Henan Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-pertussis toxin IgG (PT-IgG), analyze the antibody positivity rate (≥20 IU/ml) and median concentration (MC), and estimate the pertussis infection rate based on PT IgG ≥40 IU/ml. The rank sum test was used to compare antibody levels among groups, and the χ2 test was used to compare antibody positive rates and infection rates among groups. Results:A total of 4 810 research subjects were included in this study. The overall positive rate of PT-IgG was 12.10% and MC was 3.04 (0.35, 10.36) IU/ml. There were significant differences both in positive rates and antibody levels of PT-IgG among different regions or age groups (region positive rate: χ2=134.06, P<0.001, MC: H=337.74, P<0.001; age group positive rate: χ2=45.27, P<0.001, MC: H=134.49, P<0.001). Both the positive rate of PT-IgG (25.26%) and MC (8.01 IU/ml) were the highest within one year after completing a full course of vaccination. There were significant differences in positive rates and antibody levels among people receiving different types of pertussis vaccines (positive rate: χ2=12.38, P=0.006, MC: H=17.93, P<0.001). The antibody positivity rate (35.71%) and MC (8.88 IU/ml) of the people who received cell-free pertussis inactivated poliomyelitis influenza type b (combined) vaccine throughout the course were higher than those who received other types of vaccines. The natural infection rate of pertussis was evaluated for individuals aged≥3 years who had no history of pertussis vaccine immunization within the year prior to sampling. With a high vaccination rate, the estimated infection rate of pertussis in the population was 5 757.22/100 000. The infection rates in the 3-year-old (1 940.16/100 000) and 4-year-old (1 765.68/100 000) populations were at a low level among the entire population, reaching their peak at the age of 6 (12 656.71/100 000). Subsequently, although the infection rate continued to decline, it remained at a high level and peaked again at the age of 40-49 years (8 740.39/100 000). There was a statistically significant difference in the estimated infection rate of pertussis among different age groups ( χ2=53.21, P<0.001). Conclusion:The PT-IgG level of pertussis in the population of Henan Province is generally at a low level. The estimated infection rate of pertussis is much higher than the reported incidence rate. A booster dose of pertussis vaccine is recommended at 6 years old.

Objective To observe the value of nomogram based on enhanced cortical phase CT Radscore combined with CT features for predicting synchronous distant metastasis(SDM)of renal cell carcinoma(RCC).Methods Totally 139 RCC patients from center A were retrospectively enrolled and divided into SDM group(n=46)and non-SDM group(n=93),also classified as training set(n=97)and test set(n=42)at a ratio of 7∶3.Additionally,20 RCC patients from center B were included as validation set(8 cases with SDM and 12 cases without SDM).Radiomics features were extracted and screened based on enhanced cortical phase CT images to calculate Radscore.Multivariate logistic regression analysis was performed to identify independent predictors of RCC SDM among clinical and CT features.Then a logistic regression model was constructed combining Radscore and independent predictors of RCC SDM and visualized as a nomogram.The receiver operating characteristic curve and the area under the curve(AUC)was used to assess the efficacy of the nomogram for predicting RCC SDM.Results The maximum tumor diameter,CT-T stage and perirenal adipose stranding were all independent predictors of RCC SDM(all P＜0.01).Radscore was calculated based on 5 optimal features.The nomogram was constructed based on perirenal adipose stranding,CT-T stage and Radscore.AUC of the model for predicting RCC SDM in training set,test set and validation set was 0.964,0.921 and 0.885,respectively.Conclusion Enhanced cortical phase CT Radscore combined with perirenal adipose stranding and CT-T stage could effectively predict RCC SDM.

Objective To observe the value of nomogram based on enhanced cortical phase CT Radscore combined with CT features for predicting synchronous distant metastasis(SDM)of renal cell carcinoma(RCC).Methods Totally 139 RCC patients from center A were retrospectively enrolled and divided into SDM group(n=46)and non-SDM group(n=93),also classified as training set(n=97)and test set(n=42)at a ratio of 7∶3.Additionally,20 RCC patients from center B were included as validation set(8 cases with SDM and 12 cases without SDM).Radiomics features were extracted and screened based on enhanced cortical phase CT images to calculate Radscore.Multivariate logistic regression analysis was performed to identify independent predictors of RCC SDM among clinical and CT features.Then a logistic regression model was constructed combining Radscore and independent predictors of RCC SDM and visualized as a nomogram.The receiver operating characteristic curve and the area under the curve(AUC)was used to assess the efficacy of the nomogram for predicting RCC SDM.Results The maximum tumor diameter,CT-T stage and perirenal adipose stranding were all independent predictors of RCC SDM(all P＜0.01).Radscore was calculated based on 5 optimal features.The nomogram was constructed based on perirenal adipose stranding,CT-T stage and Radscore.AUC of the model for predicting RCC SDM in training set,test set and validation set was 0.964,0.921 and 0.885,respectively.Conclusion Enhanced cortical phase CT Radscore combined with perirenal adipose stranding and CT-T stage could effectively predict RCC SDM.