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 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 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.

This case report described an 80-year-old male patient with Parkinson disease(PD)complicated with myasthenia gravis(MG).Six years ago,the patient was diagnosed with PD based on the motor symptoms including bradykinesia and static tremor and treated with levodopa-benserazide and piribedil sustained-release tablets.He was admitted to the hospital due to left eyelid ptosis one month ago.The result of Neostigmine test was positive and anti-acetylcholine receptor(AChR)antibodies of serum was positive,which met the diagnostic criteria for myasthenia gravis(MG).The symptom of MG improved significantly after treatment with glucocorticoid and pyridostigmine but the PD symptoms worsened.The symptoms of PD were improved after withdrawal of pyridostigmine and use of the levodopa-benserazide and his condition maintained stable at 3 years of follow-up.The PD complicated with MG was fairly rare.We also reviewed the literature on the possible comorbidity mechanism and treatment strategies to improve the comprehensive understanding and ability of diagnosis and treatment of clinicians.

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.

BACKGROUND:At present,measurement osteotomy technique and gap balance technique are the two main surgical methods in total knee arthroplasty.Both methods have their advantages and disadvantages.By adjusting the osteotomy angle,the gap balance technique can reduce the release of soft tissue and obtain a more balanced flexion and extension space.The clinical efficacy of gap balance technique is superior,but this surgical method lacks tools and is easily influenced by the surgeon's surgical experience and subjective judgment,with more errors.Measurement osteotomy technique has a short learning curve,but it relies on anatomic markers and is prone to many complications due to inaccurate positioning.In recent years,many instrument companies have successively developed and launched tools that can improve the quality of surgery.However,there are still few reports about the tool. OBJECTIVE:To compare the clinical efficacy of gap balance technique and measurement osteotomy technique under Offset Repo-Tensor in total knee arthroplasty,and explore the value of Offset Repo-Tensor in total knee arthroplasty. METHODS:The medical records of 85 patients with total knee arthroplasty were collected and divided into two groups according to the operation method.Group A consisted of 44 patients who underwent total knee arthroplasty using a gap balance technique combined with Offset Repo-Tensor.Group B consisted of 41 patients who underwent total knee arthroplasty using measurement osteotomy technique.Surgical time,American Knee Society Score,knee range of motion,changes in lower limb alignment,and postoperative complications were compared between the two groups to evaluate the clinical efficacy of gap balance technique combined with Offset Repo-Tensors in total knee arthroplasty. RESULTS AND CONCLUSION:(1)All 85 patients were followed up.(2)Postoperative knee range of motion in both groups was higher than that before surgery(P<0.05),and the improvement in group A was more significant than that in group B(P<0.05).(3)American Knee Society Score in both groups after surgery was higher than that before surgery(P<0.05),and the American Knee Society Score in group A was higher than that in group B at 2 weeks,1,3 months,and the last follow-up(P<0.05).(4)The operation time of group A was slightly shorter than that of group B,but the difference was not significant(P>0.05).(5)The lower limb alignment in both groups was improved after operation,but there was no significant difference between the two groups(P>0.05).(6)The complication rate of group A(2%)was lower than that of group B(7%),but there was no significant difference between the two groups(P>0.05).(7)It is indicated that compared with the measurement osteotomy technique,the combination of Offset Repo-Tensor and gap balance technique can elevate the clinical effect and improve the function and motion range of the knee joint.

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.