HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Global public health faces substantial challenges from malignant tumors and infectious diseases. Vaccination provides an approach for treating and preventing these diseases. Oral vaccinations are particularly advantageous in disease treatment and prevention due to their non-invasive nature, high patient compliance, convenience, cost-effectiveness, and capacity to stimulate comprehensive and adaptive immune responses. However, the overwhelming majority of oral vaccines remain in experimental development, struggling with clinical and commercial translation due to their suboptimal efficacy. Thus, enhancing scientists' understanding of the interaction between vaccines and gastrointestinal immune system, creating antigen delivery systems suitable for the gut mucosal environment, developing more potent antigenic epitopes, and using personalized combination therapies are critical for advancing the next generation of oral vaccines. This article explores the fundamental principles and applications of current oral anti-tumor and anti-infective vaccines and discusses considerations necessary for designing future oral vaccines.

OBJECTIVE To analysis the clinical and pathological characteristics of lymph nodes metastasis in pediatric patients with differentied thyroid carcinoma(pDTC),and to develop a nomogram for predicting lymph nodes metastasis in patients with pDTC.METHODS Four cohorts were integrated in this study,including internal training cohort(1419 cases)and validation cohort(609 cases)from the Surveillance,Epidemiology,and End Results(SEER)database of the National Cancer Institute,TCGA-pDTC cohort(20 cases from the Cancer Genome Atlas Program)and YHD-pDTC cohort(39 cases from true world).The least absolute shrinkage and selection operator(Lasso)and logistic regression were used to screen factors related to lymph nodes metastasis in the presence and exclusion of T stage in pDTCs based on internal training cohort and construct nomograms.Calibration curve,receiver operating characteristic(ROC)curve,area under the ROC curve(AUC)and decision curve analysis(DCA)were used to evaluate model performance in the other three cohorts.RESULTS Multivariate logistic regression results showed that pathology[OR(95%CI):0.020(0.010-0.060),P<0.001],M stage[OR(95%CI):29.550(3.190-273.490),P=0.003],and T stage[OR(95%CI):2.210(1.820-2.680),P<0.001]were independent factors affecting lymph nodes metastasis in pDTCs.Through the internal training set,internal validation set,YHD-pDTC cohort and TCGA-pDTC cohort,the AUC values were 0.734(0.709,0.758),0.752(0.716,0.788),0.969(0.920,1),and 0.600(0.342,0.858)in that order,and the calibration curves are close to the perfect reference line.T stage is a better predictor of lymph nodes metastasis than extraperitoneal intrusion and tumor size.CONCLUSION Pathology,M stage,and T stage are risk factors for predicting lymph nodes metastasis in pDTCs.The nomogram established on this basis can make individualized predictions of the probability of lymph nodes metastasis in pDTCs.

Objective To develop and compare the predictive performance of five machine learning models for adverse postoperative outcomes in cardiac surgery patients, and to identify key decision factors through SHapley Additive exPlanations (SHAP) interpretability analysis. Methods A retrospective collection of perioperative data (including demographic information, preoperative, intraoperative, and postoperative indicators) with 88 variables was conducted from adult cardiac surgery patients at the First Affiliated Hospital of Xinjiang Medical University in 2023. Adverse postoperative outcomes were defined as the occurrence of acute kidney injury and/or in-hospital mortality during the postoperative hospitalization period following cardiac surgery. Patients were divided into an adverse outcome group and a favorable outcome group based on the presence of adverse postoperative outcomes. After screening feature variables using the least absolute shrinkage and selection operator (LASSO) regression method, five machine learning models were constructed: eXtreme gradient boosting (XGBoost), random forest (RF), gradient boosting machine (GBM), light gradient boosting machine (LightGBM), and generalized linear model (GLM). The dataset was randomly divided into a training set and a test set at a 7 : 3 ratio using stratified sampling, with postoperative outcome as the stratification factor. Model performance was evaluated using receiver operating characteristic curves, decision curve analysis, and F1 Score. The SHAP method was applied to analyze feature contribution. Results A total of 639 patients were included, comprising 395 males and 244 females, with a median age of 62 (55, 69) years. The adverse outcome group consisted of 191 patients, while the favorable outcome group included 448 patients, resulting in an adverse postoperative outcome incidence of 29.9%. Univariate analysis showed no significant differences between the two groups for any variables (P>0.05). Using LASSO regression, 16 feature variables were selected (including cardiopulmonary bypass support time, blood glucose on postoperative day 3, creatine kinase-MB isoenzyme, systemic inflammatory response index, etc.), and five machine learning models (GLM, RF, GBM, LightGBM, XGBoost) were constructed. Evaluation results demonstrated that the XGBoost model exhibited the best predictive performance on both the training set (n=447) and test set (n=192), with area under the curve values of 0.761 [95%CI (0.719, 0.800) ] and 0.759 [95%CI (0.692, 0.818) ], respectively. It also significantly outperformed other models in positive predictive value, and balanced accuracy in the test set. Decision curve analysis further confirmed its clinical utility across various risk thresholds. SHAP analysis indicated that variables such as cardiopulmonary bypass support time, blood glucose on postoperative day 3, creatine kinase-MB isoenzyme, and inflammatory markers (SIRI, NLR, CAR) had high contributions to the prediction. Conclusion The XGBoost model effectively predicts adverse postoperative outcomes in cardiac surgery patients. Clinically, attention should be focused on cardiopulmonary bypass support time, postoperative blood glucose control, and monitoring of inflammatory levels to improve patient prognosis.

Locally advanced rectal cancer(LARC)is associated with a high risk of local recurrence and distant metastasis,making it difficult to be cured by surgery alone.Neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for LARC,with reduced local recurrence rates.However,neoadjuvant chemoradiotherapy is associated with patients' urogenital and sexual dysfunction,which severely affecting their quality of life.Therefore,determining the optimal timing of surgery to balance oncologic and functional outcomes is crucial and challenging.We proposed that choosing the optimal timing of surgery based on preoperative risk assessment of LARC is an effective strategy.The patients with low to moderate risk of recurrence can be considered to perform surgery directly or have preoperative chemotherapy followed by radical surgery.Patients with high risk of recurrence should extend neoadjuvant therapy before surgery to improve oncologic outcomes.In this study we explored the optimal timing of radical surgery for LARC,providing a new idea for individualized and precise treatment of LARC.

Objective:To compare the diagnostic efficacy of ultrasound and MRI in fibro-adipose vascular anomaly (FAVA).Methods:The clinical data of patients with suspected FAVA who underwent ultrasound and MRI examinations at Henan Provincial People’s Hospital from January 2011 to October 2021 were retrospectively analyzed. The imaging findings from ultrasound and MRI were analyzed, and then compared with the pathological findings. To evaluate the diagnostic efficacy of ultrasound and MRI in diagnosing FAVA by assessing sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate. Paired χ2 test (McNemar test) was used to compare the coincidence rate of ultrasound and MRI, as well as their combined diagnosis. A significance level of P < 0.05 was considered statistically significant. Results:A total of 50 patients were included in the study, comprising 24 males and 26 females, with their ages ranging from 1 to 50 years and an average age of (16.2 ± 10.5) years. Pathology confirmed 43 FAVA patients and 7 non-FAVA patients. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of ultrasound in the diagnosis of FAVA were 83.7%, 71.4%, 94.7%, 41.7%, and 82.0%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of MRI in the diagnosis of FAVA were 69.8%, 85.7%, 96.8%, 31.6%, and 72.0%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of FAVA were 90.7%, 71.4%, 95.1%, 55.6%, and 88.0%, respectively. The diagnostic accuracy of ultrasound was higher than that of MRI, but the difference was not statistically significant ( χ2 = 1.41, P = 0.235). The coincidence rate of combined diagnosis was higher than that of ultrasound ( χ2= 0.71, P = 0.401) and MRI ( χ2= 4.00, P = 0.039), with a statistically significant difference. Conclusion:Both ultrasound and MRI are highly valuable in diagnosing FAVA. The combined usage of ultrasound and MRI can enhance the accuracy of preoperative FAVA diagnosis.

Objective:To compare the diagnostic efficacy of ultrasound and MRI in fibro-adipose vascular anomaly (FAVA).Methods:The clinical data of patients with suspected FAVA who underwent ultrasound and MRI examinations at Henan Provincial People’s Hospital from January 2011 to October 2021 were retrospectively analyzed. The imaging findings from ultrasound and MRI were analyzed, and then compared with the pathological findings. To evaluate the diagnostic efficacy of ultrasound and MRI in diagnosing FAVA by assessing sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate. Paired χ2 test (McNemar test) was used to compare the coincidence rate of ultrasound and MRI, as well as their combined diagnosis. A significance level of P < 0.05 was considered statistically significant. Results:A total of 50 patients were included in the study, comprising 24 males and 26 females, with their ages ranging from 1 to 50 years and an average age of (16.2 ± 10.5) years. Pathology confirmed 43 FAVA patients and 7 non-FAVA patients. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of ultrasound in the diagnosis of FAVA were 83.7%, 71.4%, 94.7%, 41.7%, and 82.0%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of MRI in the diagnosis of FAVA were 69.8%, 85.7%, 96.8%, 31.6%, and 72.0%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of FAVA were 90.7%, 71.4%, 95.1%, 55.6%, and 88.0%, respectively. The diagnostic accuracy of ultrasound was higher than that of MRI, but the difference was not statistically significant ( χ2 = 1.41, P = 0.235). The coincidence rate of combined diagnosis was higher than that of ultrasound ( χ2= 0.71, P = 0.401) and MRI ( χ2= 4.00, P = 0.039), with a statistically significant difference. Conclusion:Both ultrasound and MRI are highly valuable in diagnosing FAVA. The combined usage of ultrasound and MRI can enhance the accuracy of preoperative FAVA diagnosis.

Objective:To explore the association between postoperative radiotherapy for bladder cancer and the risk of second primary rectal cancer.Methods:Eligible 75 120 patients with bladder cancer from the Surveillance, Epidemiology, and End Result database (SEER) of the National Cancer Institute (NCI) (1975-2017) were enrolled in this study. The second primary cancers referred to rectal cancers patients suffered after more than five years post-treatment for bladder cancer, and the cumulative incidence was estimated using Fine-Gray competing risk regression. The relative risk (RR) of rectal cancer in patients treated with or without radiotherapy (the RT group or the NRT group) was evaluated using Poisson regression.Results:Among the 75 120 patients, 70 045 (92.4%) were Caucasian, with a median age of 65.8 years (54-74 years). A total of 2 236 (3%) received postoperative radiotherapy, while 72 884 (97%) received surgery alone. The 30-year follow-up revealed a cumulative incidence of rectal cancer of 0.93% in the RT group and 0.43% in the NRT group ( P = 0.004). The competing risk regression analysis identified a significant association between radiotherapy and rectal cancer ( HR: 1.86; 95% CI 1.26-2.74, P < 0.009). Furthermore, the RR of radiotherapy-associated rectal cancer significantly increased as the diagnosis occurred earlier (1975-1985 vs. 1985-1994: RR 2.59; 95% CI 1.20-4.86, P < 0.001), and a lower age at the time of radiotherapy was associated with a higher probability of second primary tumors (≤50-year old vs. > 50 year old : RR 7.89, 95% CI 2.97-21.30, P < 0.001). As calculated using the Poisson distribution, the RR of second rectal tumors was higher in the RT group ( RR: 2.20, 95% CI 1.45-3.18, P < 0.001), even after adjusting the date of diagnosis ( RR: 1.77, 95% CI 1.17-2.57, P = 0.009). Conclusions:An increased risk of rectal cancer following bladder cancer radiotherapy necessitates aggressive follow-ups for the purpose of early detecting second primary rectal cancer associated with bladder cancer radiotherapy.

Objective To develop a self-assessment scale for medication literacy in patients with coronary heart disease comorbidity diabetes and to test its reliability and validity.Methods According to medication literacy theory model,the initial scale was formed through literature review,the qualitative interview and expert inquiry.Cognitive interview was used to optimize the expression of item text.421 patients with coronary heart disease comorbidity diabetes in a tertiary hospital in Zhejiang province from November 2022 to April 2023 were selected to investigate the reliability and validity of the scale by convenience sampling.Results The self-assessment scale of drug literacy for coronary heart disease comorbidity diabetes mellitus included 23 items in 5 dimensions including acquisition,understanding,communication,evaluation and calculation.The total Cronbach's α coefficient of the scale was 0.911;the retest reliability was 0.948;the average content validity index was 0.997;the correlation coefficients between each dimension and total score of the scale and the calibration scale ranged from 0.485 to 0.926.The exploratory factor analysis was employed to extract 5 common factors,and the cumulative variance contribution rate was 73.753％.Confirmatory factor analysis showed that the scale factor structure was stable.Conclusion The scale has good reliability and validity,and it can be used as an effective tool to evaluate the self-rated medication literacy level of patients with coronary heart disease comorbidity diabetes.

Objective To develop a self-assessment scale of home volume management for patients with chronic heart failure(CHF),and to test its reliability and validity.Methods With the self-care theory as the theoretical framework,the initial scale was developed through literature analysis,qualitative interview and expert consultation.A questionnaire survey was conducted on 598 patients with CHF who were treated or reviewed in a tertiary hospital in Hangzhou from September 2022 to January 2023 to test the reliability and validity of the scale.Results The exploratory factor analysis extracted 4 common factors with the cumulative variance contribution rate of 61.268％.The results of confirmatory factor analysis showed that the main evaluation indicators were all within the acceptable range of the judgment standard.The item-level content validity index ranged from 0.853 to 1.000;the scale-level content validity index/average was 0.951.The Cronbach's a coefficient,half reliability and retest reliability of the overall scale were 0.930,0.723 and 0.867,respectively.Conclusion The self-rating scale of home volume management for CHF patients has good reliability and validity,and it can effectively assess the level of home volume management for CHF patients.