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.

Objective To investigate the protective effect of electrical stimulation-induced auditory brainstem response(EABR)monitoring on the cochlear nerve pathway during acoustic neuroma surgery.Methods The data of 36 patients who underwent acoustic neuroma surgery were studied,all surgeries were performed using the middle fossa approach.Among them,18 cases were monitored intraoperatively using EABR monitoring 4 times as the mo-nitoring group,while the other 18 cases underwent surgery without monitoring as the control group.The monito-ring group,preoperatively,there were 7 ears classified as grade A,6 ears as grade B,and 5 ears as grade C.The preoperative pure tone average thresholds(0.5,1.0,2.0,4.0 kHz)were 37.60±16.95 dB HL,and the maximum tumor diameter was 13.76±4.37 mm.The control group,preoperatively,there were 4 ears classified as grade A,7 ears as grade B,and 7 ears as grade C.The preoperative pure tone average was 46.80±22.64 dB HL,and the max-imum tumor diameter was 13.74±4.26 mm.Results In the monitoring group,except for the first monitoring,the V-wave evoked rate was 72.22％(13/18),and for the remaining three times,it was 100.00％(18/18).The mini-mum current stimulation intensity that could evoke the V-wave was 0.5 mA,and the V-wave latency was 3.97±0.17 ms.Follow-up was conducted for both groups of patients within 1 to 3 months postoperatively.In the monito-ring group,there were 7 ears classified as grade A,4 ears as grade B,4 ears as grade C,and 3 ears as grade D.Among them,3 patients experienced hearing loss after surgery,and the postoperative pure tone average was 52.20±38.35 dB HL.In the control group,there was 1 ear classified as grade A,1 ear as grade B,6 ears as grade C,and 10 ears as grade D.Among them,10 patients experienced hearing loss after surgery,and the postoperative pure tone average was 90.90±37.28 dB HL.Conclusion EABR monitoring during the resection of acoustic neuroma not only has positive significance for improving the hearing protection rate of acoustic neuroma surgery,but also assists the surgeons in identifying the cochlear nerve during surgery.The integrity of the auditory nerve pathway is protec-ted to the greatest extent for possible cochlear implanting.

Objective To analyze the influencing factors for poor prognosis in elderly patients with CHD and left ventricular dysfunction(LVD)treated by CABG,and to construct a logistic predic-tion model.Methods A total of 199 elderly CHD patients with LVD undergoing CABG in Zhu-jiang Hospital from April 2020 to April 2023 were retrospectively enrolled.After 1 year of follow-up,according to whether MACCE occurred after surgery,they were divided into MACCE group(24 cases)and non-MACCE group(175 cases).The clinical data were compared between the two groups.Multivariate logistic regression analysis was used to analyze the influencing factors for poor prognosis,and a logistic prediction model was constructed.Results The MACCE group had significantly larger proportions of hypertension,diabetes,chronic kidney disease,NYHA gradeⅢand multi-vessel disease,and smaller proportion of non-cardiopulmonary bypass than the non-MACCE group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that diabetes(OR=2.328,95％CI:1.469-3.690,P=0.000),NYH A grade(OR=2.181,95％CI:1.184-4.021,P=0.013),multi-vessel disease(OR=1.996,95％CI:1.187-3.355,P=0.009),and non-cardiopulmonary bypass(OR=0.660,95％CI:0.541-0.806,P=0.000)were independent influen-cing factors for poor prognosis in the patients after CABG.The AUC value of the constructed pre-diction model in predicting poor prognosis was 0.822(95％CI:0.721-0.923),with a sensitivity of 66.70％and a specificity of 80.60％.Conclusion Diabetes,NYHA grade,multi-vessel disease and non-cardiopulmonary bypass are independent influencing factors for poor prognosis in elderly CHD patients complicated with LVD after CABG.The constructed logistic prediction model has certain predictive value for poor prognosis in these elderly patients.

Objective To investigate the protective effect of electrical stimulation-induced auditory brainstem response(EABR)monitoring on the cochlear nerve pathway during acoustic neuroma surgery.Methods The data of 36 patients who underwent acoustic neuroma surgery were studied,all surgeries were performed using the middle fossa approach.Among them,18 cases were monitored intraoperatively using EABR monitoring 4 times as the mo-nitoring group,while the other 18 cases underwent surgery without monitoring as the control group.The monito-ring group,preoperatively,there were 7 ears classified as grade A,6 ears as grade B,and 5 ears as grade C.The preoperative pure tone average thresholds(0.5,1.0,2.0,4.0 kHz)were 37.60±16.95 dB HL,and the maximum tumor diameter was 13.76±4.37 mm.The control group,preoperatively,there were 4 ears classified as grade A,7 ears as grade B,and 7 ears as grade C.The preoperative pure tone average was 46.80±22.64 dB HL,and the max-imum tumor diameter was 13.74±4.26 mm.Results In the monitoring group,except for the first monitoring,the V-wave evoked rate was 72.22％(13/18),and for the remaining three times,it was 100.00％(18/18).The mini-mum current stimulation intensity that could evoke the V-wave was 0.5 mA,and the V-wave latency was 3.97±0.17 ms.Follow-up was conducted for both groups of patients within 1 to 3 months postoperatively.In the monito-ring group,there were 7 ears classified as grade A,4 ears as grade B,4 ears as grade C,and 3 ears as grade D.Among them,3 patients experienced hearing loss after surgery,and the postoperative pure tone average was 52.20±38.35 dB HL.In the control group,there was 1 ear classified as grade A,1 ear as grade B,6 ears as grade C,and 10 ears as grade D.Among them,10 patients experienced hearing loss after surgery,and the postoperative pure tone average was 90.90±37.28 dB HL.Conclusion EABR monitoring during the resection of acoustic neuroma not only has positive significance for improving the hearing protection rate of acoustic neuroma surgery,but also assists the surgeons in identifying the cochlear nerve during surgery.The integrity of the auditory nerve pathway is protec-ted to the greatest extent for possible cochlear implanting.

Objective To analyze the influencing factors for poor prognosis in elderly patients with CHD and left ventricular dysfunction(LVD)treated by CABG,and to construct a logistic predic-tion model.Methods A total of 199 elderly CHD patients with LVD undergoing CABG in Zhu-jiang Hospital from April 2020 to April 2023 were retrospectively enrolled.After 1 year of follow-up,according to whether MACCE occurred after surgery,they were divided into MACCE group(24 cases)and non-MACCE group(175 cases).The clinical data were compared between the two groups.Multivariate logistic regression analysis was used to analyze the influencing factors for poor prognosis,and a logistic prediction model was constructed.Results The MACCE group had significantly larger proportions of hypertension,diabetes,chronic kidney disease,NYHA gradeⅢand multi-vessel disease,and smaller proportion of non-cardiopulmonary bypass than the non-MACCE group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that diabetes(OR=2.328,95％CI:1.469-3.690,P=0.000),NYH A grade(OR=2.181,95％CI:1.184-4.021,P=0.013),multi-vessel disease(OR=1.996,95％CI:1.187-3.355,P=0.009),and non-cardiopulmonary bypass(OR=0.660,95％CI:0.541-0.806,P=0.000)were independent influen-cing factors for poor prognosis in the patients after CABG.The AUC value of the constructed pre-diction model in predicting poor prognosis was 0.822(95％CI:0.721-0.923),with a sensitivity of 66.70％and a specificity of 80.60％.Conclusion Diabetes,NYHA grade,multi-vessel disease and non-cardiopulmonary bypass are independent influencing factors for poor prognosis in elderly CHD patients complicated with LVD after CABG.The constructed logistic prediction model has certain predictive value for poor prognosis in these elderly patients.

Objective: To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC. Methods: The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells. Results: A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner. Conclusion RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

Objective To evaluate the quality of treatment planning(TP)and re-optimization planning(RP)of radiotherapy for rectal cancer using PlanIQ software,thereby providing methods and tools for the screening and optimization of radiotherapy plans.Methods Twenty patients with rectal cancer who received radiotherapy were selected retrospectively,with 10 cases of intensity-modulated radiotherapy(IMRT)and 10 of volumetric modulated arc therapy(VMAT).(1)TP:IMRT plan involved 5-field irradiation,and VMAT plan involved two 360°arcs.The prescription doses were 50 Gy/25 f for PTV1 and 45 Gy/25 f for PTV2.All plans underwent direct machine parameter optimization and required 95%isodose lines to cover 100%of the target volume.Organs-at-risk(OAR)were limited by reference to tolerated dose standards.After the planning was completed,the plans were reviewed and confirmed by a physician,and the treatment was implemented after dose verification.(2)RP:a physicist with 10 years of experience re-optimized the 20 TP plans,with the irradiation technique and field setting unchanged.The re-optimization involved adjusting planning conditions and parameters based on individual experience until the dose to OAR was minimized while without affecting PTV coverage.The quality of TP plans and RP plans were quantitatively evaluated using PlanIQ software.Non-parametric Wilcoxon signed rank test was performed for dose-volume histogram parameters and plan quality index between two groups.Results The dose-volume histogram parameters in RP plans were superior to those in TP plans,and the differences in the Dmax of PTV1,the V45 Gy and Dmax of small intestine,and the V45 Gy of colon were statistically significant(P<0.05).The quality scores of RP plans for IMRT group,VMAT group and all patients were significantly higher than those of TP plans(P<0.05),with plan quality index of 88.55±3.35 vs 86.61±4.63(P=0.005),89.72±3.15 vs 87.21±3.04(P=0.028),and 89.14±3.22 vs 86.91±3.22(P=0.001),respectively.Conclusion RP can further improve the quality of radiotherapy plan for rectal cancer.PlanIQ software serves as an effective tool for quality control and screening of radiotherapy planning.

Objective To assess inter-observer variations(IOV)in the delineation of target volumes and organs-at-risk(OAR)for intensity-modulated radiotherapy(IMRT)of nasopharyngeal carcinoma(NPC)among physicians from different levels of cancer centers,thereby providing a reference for quality control in multi-center clinical trials.Methods Twelve patients with NPC of different TMN stages were randomly selected.Three physicians from the same municipal cancer center manually delineated the target volume(GTVnx)and OAR for each patient.The manually modified and confirmed target volume(GTVnx)and OAR delineation structures by radiotherapy experts from the regional cancer center were used as the standard delineation.The absolute volume difference ratio(△V_diff),maximum/minimum volume ratio(MMR),coefficient of variation(CV),and Dice similarity coefficient(DSC)were used to compare the differences in organ delineation among physicians from different levels of cancer centers and among the 3 physicians from the same municipal cancer center.Furthermore,the IOV of GTVnx and OAR among physicians from different levels cancer centers were compared across different TMN stages.Results Significant differences in the delineation of GTVnx were observed among physicians from different levels of cancer centers.Among the 3 physicians,the maximum values of △V_diff,MMR,and CV were 97.23%±83.45%,2.19±0.75,and 0.31±0.14,respectively,with an average DSC of less than 0.7.Additionally,there were considerable differences in the delineation of small-volume OAR such as the left and right optic nerves,chiasm,and pituitary,with average MMR>2.8,CV>0.37,and DSC<0.51.However,relatively smaller differences were observed in the delineation of large-volume OAR such as the brainstem,spinal cord,left and right eyeballs,and left and right mandible,with average△V_diff<42%,MMR<1.55,and DSC>0.7.Compared with the differences among physicians from different levels cancer centers,the differences among the 3 physicians from the municipal cancer center were slightly reduced.Furthermore,there were also differences in the delineation of target volumes for NPC among physicians from different levels cancer centers,depending on the staging of the disease.Compared with the delineation of target volumes for earlier stage patients(stages I or II),the differences among physicians in the delineation of target volumes for advanced stage patients(stages III or IV)were smaller,with average △V_diff and DSC of 98.31%±67.36%vs 69.38%±72.61%(P<0.05)and 0.55±0.08 vs 0.72±0.12(P<0.05),respectively.Conclusion There are differences in the delineation of GTVnx and OAR in radiation therapy for NPC among physicians from different levels of cancer centers,especially in the delineation of target volume(GTVnx)and small-volume OAR for early-stage patients.To ensure the accuracy of multicenter clinical trials,it is recommended to provide unified training to physicians from different levels of cancer centers and review their delineation results to reduce the effect of differences on treatment outcomes.

With the rapid development of artificial intelligence technology,small molecule generation models have emerged as a significant research direction in the field of drug discovery.These models,including Generative Adversarial Networks(GANs),Variational Autoencoders(VAEs),and diffusion models,have proven to possess remarkable capabilities in optimizing drug properties and generating complex molecular structures.This article comprehensively analyzes the application of the aforementioned advanced technologies in the drug discovery process,demonstrating how they supplement and enhance traditional drug design methods.At the same time,it addresses the challenges facing current methods in terms of data quality,model complexity,computational cost,and generalization ability,with a prospect of future research directions.