Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

BACKGROUND:Medical hydrogels are new functional polymer materials with three-dimensional structural networks and excellent biocompatibility,which have been widely studied in the field of tissue engineering and drug carriers,but the research on the combination of medical hydrogels and Chinese medicine for the treatment of diseases based on tissue engineering is still in the early exploration stage.Therefore,through the analysis of the mechanism of the role of medical hydrogels,the integration of medical hydrogels and Chinese medicine in the research of the joint application of the article,can better provide ideas for scientific researchers,and the joint application of Chinese medicine and medical hydrogels is of great significance. OBJECTIVE:To explore the strategy and significance of Chinese medicine combined with medical hydrogel for disease treatment based on tissue engineering research. METHODS:PubMed and CNKI were used to retrieve articles about the application of Chinese medicine combined with medical hydrogel in tissue engineering from January 2010 to November 2022,with the Chinese and English search terms"hydrogel,traditional Chinese medicine,drug carrier,tissue engineering".After the initial screening of all articles according to the inclusion and exclusion criteria,the 61 articles with high relevance were retained for review. RESULTS AND CONCLUSION:(1)Although the application of Chinese medicine combined with medical hydrogel is involved in intra-articular,intra-tissue organ,soft tissue wounds,tissue engineering,etc.,except for the clinical application of Chinese medicine combined with hydrogel dressing for soft tissue injury,other aspects are still in the experimental stage.(2)The development of Chinese medicine combined with medical hydrogel has great potential and development prospects,but there is a certain difficulty in the manufacture of the gel with high-performance requirements,and it is difficult to master the physical and chemical properties precisely.(3)At present,the comprehensive view of injectable hydrogel with the characteristics of easy to use,its joint use of Chinese medicine can be extended to a wider range,can be used for joint,organ,tissue engineering-related disease treatment.Smart hydrogel has high sensitivity and reversible transformation can also meet the use of the special environment.During the combined use of Chinese medicine,it also needs to understand the mechanism of action of Chinese medicine components.(4)The strategy of combining Chinese medicine with medical hydrogels for disease treatment should start with matching the therapeutic effects of Chinese medicine on organs,tissues and cells combined with appropriate types of medical hydrogels to make up for the shortcomings of traditional Chinese medicine delivery methods and frequent drug delivery.In tissue engineering,hydrogels can be loaded with stem cells after Chinese medicine intervention,or with both Chinese medicine and stem cells for disease treatment.(5)In future research of combined Chinese medicine and medical hydrogel application,we also need to consider:we should ensure that the biological properties of medical hydrogel can be quantified,and grasp the characteristics of hydrogel with different manufacturing processes of different materials to produce the required medical hydrogel that meets the application conditions.In Chinese medicine,we need to comprehensively understand and analyze the therapeutic effects and application mechanisms of known Chinese medicine monomer and Chinese medicine compound extracts,so as to achieve a more perfect combination between Chinese medicine and medical hydrogel under a more clear mechanism.With the continuous improvement of medical science and technology innovation,the medical hydrogel can be innovatively combined with other traditional treatment methods of Chinese medicine,such as acupuncture,massage,cupping and so on,to be used from multiple angles.

Objective:To conduct a retrospective study on the treatment outcomes of patients who underwent artificial temporomandibular joint (TMJ) replacement surgery and to evaluate the effectiveness of artificial TMJ treatment.Methods:This study selected 62 patients who received standard Biomet artificial TMJ treatment at Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University from May 2010 to September 2023 as the study subjects. Among them, there were 15 male patients and 47 female patients. The average age was 33.5 years old(ranging from 18 to 67 years). This study statistically analyzed postoperative indicators, including maximum mouth opening, forward jaw movement, lateral movement, postoperative pain scores, and patient satisfaction.Results:This study included a total of 62 patients with 99 TMJ joints. No infections occurred postoperatively. The average follow-up period was 33.7 months (ranging from 7 to 170 months). At 6 months postoperatively, the mean mouth opening was (36.1±6.2) mm, lateral movement was (2.1±0.9) mm, and forward jaw movement was (1.0±0.9) mm. The pain visual analog scale score at 6 months postoperatively was (2.8±0.6), and patient satisfaction with the surgery was (8.8±1.1). Spiral CT scans conducted after surgery showed no joint dislocation or migration, and the artificial joint remained stable during the follow-up period.Conclusions:Artificial TMJ replacement is a valuable method for effectively restoring TMJ structure and essential functions related to mouth opening and chewing. It is worthy of promotion as a reconstructive approach for the temporomandibular joint

Objective To investigate global optimisation of anterior acetabular column pinning channels can be achieved based on large density point cloud data.Methods Data were collected on the CT scans of the normal pelvis in 40 adults from January 2022 to January 2023,including 22 males and 18 females,aged 20 to 54 years old.Medical imaging data from three of the samples were selected for experimental study.In planning access for anterior acetabular column pinning,to address the is-sue of whether the current CAD planning methods were advanced or not,four combinations of the same point cloud acquisition channels,different directional line creation software,and the same 3D design and virtual experiment software were proposed:Mimics+Imageware+UG,Mimics+3DReshaper+UG,Mimics+ZEISS Quality Suite+UG and Mimics+Design X+UG,and direc-tional lines created based on the centroid point set and solid point cloud of the secondary pruning model,respectively,and it applied to the planning of the left anterior column pinning channel of the three acetabular samples.The maximum internally connected cylinder without acetabular socket and pubic bone penetration was used as a safe passage for nailing of the anterior acetabular column to evaluate the advancement of each method.Results The fitting effect of the directional line was better than that of the unnoised solid point cloud when the central point set with obvious relevant features was selected as the sample points;and the combination of Mimics+Imageware+UG and Mimics+3DReshaper+UG could efficiently and stably obtain the desirable planning results when planning with the central point set,respectively,in the three acetabular samples 1,2,3.The maximum internal joint circle diameters obtained in samples 1,2,and 3 were 10.35 mm,9.62 mm,and 9.24 mm;and when the directional lines were based on the solid point cloud the combined methods of Mimics+ZEISS Quality Suite+UG and Mimics+Design X+UG were not applicable;whereas the Mimics+3 DReshaper+UG the solid point cloud denoising planning method could stably obtain the maximum value of the safe channel for nail placement,and the maximum internal joint circle diameters obtained in acetabular samples 1,2,and 3 are 10.66 mm,10.96 mm,and 9.48 mm,respectively.Conclusion It is recommend-ed that the nail placement channel planners use robust Mimics+Imageware+UG or Mimics+3DReshaper+UG centre point set planning method,and if there is enough time,it is recommended to use the solid point cloud denoising planning method of Mimics+3DReshaper+UG in order to obtain the maximum value of safe channels for nail placement.

Objective To explore the feasibility of integrated imaging of portal vein and hepatic vein with"three low-contrast agents"combined with energy spectrum CT technology.Methods A total of 100 patients with enhanced abdominal CT scans were selected.The patients were randomly divided into two groups.The patients of experimental group(n=50)were injected with the isotonic con-trast agent iodixanol(320 mg I/mL)at a flow rate of 3 mL/s and a total volume of 1.2 mL/kg,and underwent energy spectrum CT scan in the portal venous phase.The patients of control group(n=50)were injected with the sub-hypertonic contrast agent iohexol(350 mg I/mL)at a flow rate of 5 mL/s and a total volume of 1.5 mL/kg,and underwent conventional multi-phase spiral CT enhancement scan.The image quality and radiation dose of portal vein and hepatic vein were compared between the two groups.Results The CT value of main portal vein in the experimental group was higher than that in the control group,and the difference was statistically sig-nificant(P＜0.05).There was no statistical significance in main portal vein contrast-to-noise ratio(CNR),main portal vein signal-to-noise ratio(SNR),hepatic vein CT value,and hepatic vein CNR between the two groups(P＞0.05).The SNR and image standard deviation(SD)of the hepatic vein in the control group were better than those in the experimental group(P＜0.05).There was no statistical significance in the subjective scores of portal vein and hepatic vein between the two groups(P＞0.05).The volume CT dose index(CTDIvol),dose length product(DLP),and effective dose(ED)of the portal venous phase spectrum CT scan in the experimental group were lower than those of the conventional single-phase spiral CT scan in the control group(P＜0.05).Conclusion"Three low-contrast agents"combined with energy spectrum CT technology can realize integrated imaging of portal vein and hepatic vein in late portal vein,and can reduce radiation dose.

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

Objective This paper investigates the effect of a multi-physical field fusion intervention based on transcranial direct current stimulation(tDCS),transcranial magnetic stimulation(TMS)and music on mental fatigue.Methods After fatigue induction,10 subjects received blank group stimulation,music group stimulation and tDCS-TMS-Music stimulation,respectively.tDCS stimulation sites were located in the bilateral frontal regions of the subjects,and TMS stimulation sites were located in the bilateral occipital regions of the hindbrain.Heart rate variability and reaction performance were measured before and after each intervention to determine the elimination effect of different intervention programs on mental fatigue.Results Compared with the control group,the tDCS-TMS-Music group showed significantly greater improvements in subjective mental workload,response performance,and heart rate variability.Conclusion The results of this study support that tDCS-TMS-Music can effectively alleviate mental fatigue induced by long-term cognitive performance tasks,and the intervention effect is better than music intervention and resting-state relief at the same time.

Objective:To investigate the value of multimodal ultrasound features combined with peripheral blood inflammatory cell ratios in evaluating the efficacy of neoadjuvant chemotherapy (NAC) in breast cancer.Methods:A total of 106 breast cancer patients diagnosed and treated with NAC at the Second Affiliated Hospital of Anhui Medical University from May 2021 to April 2024 were retrospectively collected, resulting in the conclusion of 61 patients (61 masses) in the study. All patients underwent multimodal ultrasound and peripheral blood routine examinations before NAC and after two cycles of NAC treatment. The patients were divided into a major histological response (MHR) group and a non-major histological response (NMHR) group as indicators for evaluating NAC efficacy. The differences in multimodal ultrasound features and inflammatory cell ratios before NAC and after two cycles of NAC treatment between the MHR and NMHR groups were compared. Binary logistic multivariate regression analysis was performed to determine the independent predictors of NAC efficacy in breast cancer. ROC curves were plotted to evaluate the diagnostic efficacy of predicting NAC efficacy.Results:Among the 61 breast masses, 25 (40.98%) were in the MHR group, and 36 (59.02%) were in the NMHR group.Multivariate binary logistic regression analysis showed that the change rate of maximum tumor diameter after the second cycle (ΔD 2), change rate of vascular index after the second cycle (ΔVI 2), change rate of elastic strain ratio after the second cycle (ΔE-Strain 2), change rate of reverse imaging score after the second cycle (ΔI-imaging score 2), and platelet-to-lymphocyte ratio (PLR) before NAC were independent predictors of NAC efficacy ( OR=1.145, P=0.019; OR=1.055, P=0.016; OR=1.036, P=0.033; OR=1.276, P=0.016; OR=1.054, P=0.047). The area under the ROC curve (AUC) for the combined diagnosis of the above parameters was 0.928 (95% CI=0.866~0.990), with a sensitivity of 80.0% and a specificity of 91.7%. Conclusions:The combination of ΔD 2, ΔVI 2, ΔE-Strain 2, ΔI-imaging score 2 and PLR before NAC has high clinical application value for early prediction of NAC efficacy in breast cancer.

Objective To compare the advantages of robot assisted and DSA guided PBC for the treatment of trigeminal neuralgia.Methods A retrospective clinical analysis was conducted on 85 patients(28 in robot group and 57 in DSA group)who underwent robot assisted and DSA guided PBC surgery in a same center from September 2021 to February 2024.The single puncture success rate,improvement rate of VAS score,clinical efficacy rate,incidence of complications,average surgical time and fluoroscopy time were compared between the two groups.Results There was no statistically significant difference between the two groups in terms of single puncture success rate(96.43% vs.84.21% ),VAS improvement rate[88.9% (77.78%,100.00% )vs.88.89% (55.56%,100.00% )],clinical effective rate(92.86% vs.94.74% ),and total incidence of complications(35.09% vs.42.11% )(P>0.05).The average surgical time was significantly higher in the robot group[38.50(35.00,48.00)min]than the DSA group[19.00(15.00,25.50)min],and the average fluoroscopy time in the robot group[13.00(12.00,15.75)s]was significantly lower than the DSA group[194.00(152.50,259.50)s].The difference in average surgical and fluoroscopy time between the two groups was statistically significant(P<0.05).Conclusion DSA guided surgery has more advantages in centers with a large number of patients and a pursuit of efficiency.The robot assisted surgical puncture process is safe and controllable and patient radiation exposure time is short,thereby having high clinical application and promotion value.

Objective:To investigate the genotype,mutation type,and ethnic distribution characteristics of thalassemia in the population of Hechi area,Guangxi,and to provide a reference basis for prevention and control of thalassemia and eugenic counseling in the region.Methods:Gap-polymerase chain reaction(gap-PCR)and reverse dot blot(RDB)were used for genetic testing on suspected thalassemia persons,and the results were analyzed.Results:Among 29 136 samples,a total of 17 016(58.40％)positive samples for thalassemia genes were detected,with a higher detection rate in males than in females(X2=49.917,P＜0.001).The detection rates of thalassemia genes were significant different among Zhuang,Han,Yao,Mulao,and Maonan ethnic groups(x2=546.121,P＜0.001).The α-thalassemia genotypes were mainly--SEA/αα(16.67％),-α3.7/αα(8.90％),αCSα/αα(6.00％).Additionally,four rare genotypes were detected,including--THAI/αα(47 cases),HKαα/αα(2 cases),--SEA/-α21.9(2 cases),and--THAI/αcsα(1 case).The β-thalassemia genotypes were mainly βCD17/βN(7.49％),βCD41-42/βN(6.70％),βCD71-72/βN(0.44％).108 cases of moderate and severeβ-thalassemia were detected,of which 81 cases had a history of blood transfusion,the transfusion frequency of 60 cases was more than 10 times/year,and 10 cases received bone marrow transplantation.Conclusion:Thalassemia in Hechi area is predominantly deletion type--SEA/αα,the detection rate of thalassemia in ethnic minorities is higher than that in Han population.In this area,moderate and severe β-thalassemia have certain incidence,these patients mostly need regular blood transfusion and iron removal treatment,and very few patients have received bone marrow transplantation.This study provides a certain reference basis for prevention and control of thalassemia and eugenic counseling in the region.