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.

Objective To investigate the relationship between two-lung ventilation (TLV) with single-lumen endotracheal tube (SLT), one-lung ventilation (OLV) with double-lumen endotracheal tube (DLT) and postoperative pulmonary complications (PPCs) after total thoracoscopic cardiac surgery. Methods The clinical data of patients who underwent totally thoracoscopic cardiac surgeries in the Guangdong Provincial People’s Hospital from October 2019 to October 2021 were retrospectively analyzed. The patients were divided into 2 group according to the type of endotracheal tube, including a SLT group and a DLT group. Baseline data, surgical variables and PPCs were compared. The influencing factors of PPCs in the two groups were analyzed by binary logistic regression analysis. Results Finally 349 patients were enrolled, including 180 males and 169 females with an average age of (50.0±14.8) years. There were 219 patients in the SLT group and 130 patients in the DLT group. There was no statistical difference in baseline data, surgical variables or PPCs between the two groups (P＞0.05). Binary logistic regression analysis showed that PPCs were related to body mass index in the SLT group (OR=0.778, 95%CI 0.637 to 0.951, P=0.014) and preoperative smoking history in the DLT group (OR=0.058, 95%CI 0.004 to 0.903, P=0.042). Conclusion For the patients who undergo totally thoracoscopic cardiac surgery, TLV with SLT and OLV with DLT show no significant association with PPCs. At the same time, PPCs are associated with body mass index in the SLT group, while associated with preoperative smoking history in the DLT group.

Objective To investigate the MRI features of primary retroperitoneal leiomyosarcoma(PRLS).Methods Thirty-three cases of pathologically confirmed PRLS were analyzed retrospectively,and their multi-parameter MRI features were analyzed qualitatively and quantitatively.Results Of the 33 PRLS,24 cases were located in the renal hilum,inferior vena cava,or the area around the bifurcation of the iliac vessels.Twenty-four cases had relatively intact capsule,25 cases had necrosis,and 15 cases had coagulated geographic necrosis.The mean diameter of the tumors was(9.9±5.1)cm,ranging from 3.0 to 20.7 cm,among which 27 cases with a diameter larger than 5 cm.The tumor parenchyma of the 33 PRLS all showed significantly high signal intensity on diffusion weighted imaging(DWI),and significantly low signal intensity on apparent diffusion coefficient(ADC)map.The tumor parenchyma showed moderate to obvious degree of progressive enhancement,and the signal intensity value of the tumor in each phase after contrast injection was higher than that of the psoas major muscle(P＜0.001).Conclusion PRLS are usually large but have a relatively intact capsule and are closely related to the major retroperitoneal veins.The coagulated geographic necrosis,significantly limited diffusion of water molecules,and progressive enhancement pattern all show certain MRI characteristics.

Objective:To assess the effects of the scanning parameters of cone beam computed tomography(CBCT)on image quality,positioning error and additional radiation dose for patients with cervical cancer after tube voltage was reduced,so as to explore scanning conditions that was suitable to patients with cervical cancer.Methods:Seventy-two patients with cervical cancer who received radiotherapy in Deyang People's Hospital from January 2020 to August 2022 were selected.According to different scanning parameters,they were divided into low-dose group A(120 kV,154.4 mAs),low-dose group B(120 kV,228.8 mAs)and conventional group[adopted business-supplied scan sequences(120 kV,675.8 mAs)].The CBCT scan image was obtained by decreasing the tube voltage and tube current,and reducing scanning angle.The registration results of positioning error of low-dose group A,B and conventional group on three directions included left and right(x-axis),head and foot(y-axis)and abdominal and back(z-axis)were respectively obtained,and the results were analyzed by variance analysis.The Catphan503 phantom of X-ray volumetric imaging(XVI)was used to measure the image quality of the corresponding 3 groups,and the further comparison was conducted.Results:There were no significant differences between the three groups in the scanning parameters on x,y and z axis directions for positioning error of patients with cervical cancer(P＞0.05).The scanning times of low-dose group A and B were approximately 1 minute,and the scanning time of conventional group was approximately 2 minutes.The noises of low-dose group A and B,and conventional group were respectively 36.51％,26.09％and 18.37％,and the radiation dose that was generated by CBCT image scanning in group A was correspondingly reduced.Conclusion:The reductions of scanning speed and collimator size of CBCT scanning parameters do not affect the positioning error and image quality,and it can decrease the scanning time and additional radiation dose of patients in undergoing radiotherapy.

Objective:To evaluate the detection performance of left ventricular ejection fraction (LVEF) in patients with chronic renal failure (CRF) by an artificial intelligence (AI) model based on yolox framework integrating left ventricular segmentation and critical point detection.Methods:From January 2019 to June 2023, a total of 4 284 echocardiographic images of 2 000 adults aged 18-80 years without segmental wall motion abnormalities, structural heart disease, cardiac surgery or cardiomyopathy were collected in Henan Provincial People′s Hospital to delineate the endocardial membrane, as a training set, an AI model based on yolox framework integrating left ventricular segmentation and critical point detection was established. The images were divided into the training set( n=1 675) and the test set( n=325) in a ratio of about 5∶1. All 228 echocardiographic images of 100 normal adult volunteers who were treated in Henan Provincial Chest Hospital from May 2020 to May 2021 were collected as external test set validation. All 792 echocardiographic images of 204 patients treated in Henan Provincial People′s Hospital from April 2019 to June 2023 were continuously enrolled to evaluate the measurement efficiency of AI model. Spearman correlation statistical method was used to analyze the consistency of AI model measurement with manual measurement and TomTec software measurement methods of 3 senior echocardiographic professionals. Subjects were divided into clear image group, unclear image group, normal LVEF group and reduced LVEF group, the differences of general data between the two groups were compared. The correlation coefficient(ICC) within the group was calculated to analyze the consistency, so as to evaluate the model performance. Results:LVEF measured by AI model was significantly correlated with both manual measurement and TomTec model measurement ( rs=0.834, 0.826; all P<0.01). ICC values of the clear image group and the unclear image group were 0.96 and 0.97, respectively. ICC values for all subjects, normal LVEF group and reduced LVEF group were 0.96, 0.90 and 0.96, respectively. Conclusions:The AI model based on yolox framework integrating left ventricular segmentation and critical point detection has good diagnostic performance in the automatic measurement of LVEF in patients with CRF.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

OBJECTIVE: To explore the molecular mechanism of a case where RhD genotyping did not match serological results. METHODS: The serological results of 8 members from two generations of this family were analyzed. And according to Mendelian law of inheritance, RhD genotyping, zygotic type determination and gene sequencing were performed for the family members. RESULTS: The proband and one of her cousins have the same RhD alleles, both of them have a 336-1G>A intron variant RhD allele and a complete RhD deletion allele. The variant alleles are inherited from two of their parents with blood relationship, while the complete-deleted alleles come from the other. 336-1G>A means that the last base G of the second intron of the RhD gene is mutated to A, which leads to a negative RhD serology and a positive genotype in the proband. CONCLUSION There was a rare 336-1G> A intron variant gene (RhD * 01N.25) in this family, which was a recessive gene relative to the RhD gene and resulted in RhD phenotype negative.
Alleles ; Female ; Genotype ; Humans ; Introns/genetics* ; Pedigree ; Phenotype ; Rh-Hr Blood-Group System/genetics*

Genetic counseling for ring chromosomes, particularly hereditary ring chromosomes, is still difficult. In recent years, molecular biology has provided more clues for the genetic mechanism of ring chromosomes. In this paper, the epidemiology, pathogenesis, clinical phenotype and prenatal diagnosis of ring chromosomes are reviewed.

With the application of BACs-on-Beads (BoBs) and array-comparative genome hybridization (aCGH) technologies in prenatal diagnosis, microdeletion/microduplications at Xp22.3 have been frequently detected. However, the relatively high prevalence and lack of knowledge of such disorders have brought difficulties for clinical genetic counseling. Here, recent progress of research on microdeletion/microduplications at Xp22.3, including epidemiology, pathogenesis, clinical manifestation, and prenatal diagnosis, is reviewed.
Chromosomes, Human, X ; genetics ; Comparative Genomic Hybridization ; Female ; Genetic Counseling ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Research ; trends

RASopathies are a group of disorders caused by germline variants of genes involved in RAS/MAPK pathway with overlapping features which may complicate their diagnosis. Since almost all RASopathies are autosomal dominant inherited disorders, the affected families may give birth to multiple children with the disease. Owning to the advance in sequencing technology, the genotype-phenotype correlation of RASopathies has become clearer in recent years, and genetic testing is now available in many places, which make prenatal diagnosis for couples with increased risk possible. For de novo variants of RASopathies, prenatal diagnosis is still difficult as the findings in routine ultrasonography are not specific enough. Nevertheless, certain findings may still be used as clues for prenatal diagnosis. This article overviews the common disorders of RASopathies, with an emphasis on the features that can be used as clues for the prenatal diagnosis of RASopathies.
Female ; Genes, ras ; Humans ; MAP Kinase Signaling System/genetics* ; Pregnancy ; Prenatal Diagnosis