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 construct a radiomics model for identifying clinical high-risk carotid plaques. Methods     A retrospective analysis was conducted on patients with carotid artery stenosis in China-Japan Friendship Hospital from December 2016 to June 2022. The patients were classified as a clinical high-risk carotid plaque group and a clinical low-risk carotid plaque group according to the occurrence of stroke, transient ischemic attack and other cerebrovascular clinical symptoms within six months. Six machine learning models including eXtreme Gradient Boosting, support vector machine, Gaussian Naive Bayesian, logical regression, K-nearest neighbors and artificial neural network were established. We also constructed a joint predictive model combined with logistic regression analysis of clinical risk factors. Results    Finally 652 patients were collected, including 427 males and 225 females, with an average age of 68.2 years. The results showed that the prediction ability of eXtreme Gradient Boosting was the best among the six machine learning models, and the area under the curve (AUC) in validation dataset was 0.751. At the same time, the AUC of eXtreme Gradient Boosting joint prediction model established by clinical data and carotid artery imaging data validation dataset was 0.823. Conclusion     Radiomics features combined with clinical feature model can effectively identify clinical high-risk carotid plaques.

Objective     To identify the preoperative risk factors for prolonged mechanical ventilation (PMV) after pulmonary thromboendarterectomy (PTE). Methods    The clinical data of patients who underwent PTE from December 2016 to August 2021 in our hospital were retrospectively analyzed. The patients were divided into two groups according to the postoperative mechanical ventilation time, including a postoperative mechanical ventilation time≤48 h group (≤48 h group) and a postoperative mechanical ventilation time>48 h (PMV) group (>48 h group). Univariable and logistic regression analysis were used to identify the preoperative risk factors for postoperative PMV. Results    Totally, 90 patients were enrolled in this study. There were 40 patients in the ≤48 h group, including 30 males and 10 females, with a mean age of 45.48±12.72 years, and there were 50 patients in the >48 h group, including 29 males and 21 females, with a mean age of 55.50±10.42 years. The results showed that in the ≤48 h group, the median postoperative ICU stay was 3.0 days, and the median postoperative hospital stay was 15.0 days; in the >48 h group, the median postoperative ICU stay was 7.0 days, and the median postoperative hospital stay was 20.0 days. The postoperative PMV was significantly correlated with tricuspid annular plane systolic excursion (TAPSE) [OR=0.839, 95%CI (0.716, 0.983), P=0.030], age [OR=1.082, 95%CI (1.034, 1.132), P=0.001] and pulmonary vascular resistance (PVR) [OR=1.001, 95%CI (1.000, 1.003), P=0.028]. Conclusion    Age and PVR are the preoperative risk factors for PMV after PTE, and TAPSE is the preoperative protective factor for PMV after PTE.

Objective To explore the diagnostic value of Young's modulus obtained by real-time shear wave elastography (SWE) for liver fibrosis in autoimmune hepatitis (AIH) patients. Methods A total of 75 AIH patients in the First Affiliated Hospital of Zhengzhou University from January 2013 to April 2022 were retrospectively enrolled. Scheuer scoring system was used to evaluate degrees of liver fibrosis (S0-S4). By using pathological examination of liver tissues as the golden standard, the receiver operating characteristic curve (ROC) was plotted and the area under the curve (AUC) was used to evaluate the diagnostic value of SWE for the significant fibrosis (≥S2), advanced liver fibrosis (≥S3), and liver cirrhosis (S4), respectively. Independent sample t test was used for comparison of continuous data with normal distribution between the two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and Bonferroni method was used for further comparison between two groups. The Spearman correlation coefficient was used for correlation analysis. The logistic regression analysis was used to predict the impact factors in diagnosis accuracy. Results The Young's modulus measured by SWE was statistically significant different among various fibrosis groups ( H =35.186, P < 0.001) although there was no statistical significance in patients' age and platelet, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, and glutamyl transpeptidase levels (all P > 0.05). The Young's modulus measurement was positively correlated with liver fibrosis ( r =0.675, P < 0.05). The AUCs of SWE in the diagnosis of≥S2, ≥S3, and S4 were 0.839, 0.820 and 0.898, respectively and the corresponding optimum cut-off values were 9.2, 10.9, and 14.4 kPa, respectively. The overall concordance rate of the liver Young' s modulus measurements vs . fibrosis stages was 57.33%. Moreover, the alkaline phosphatase level was an independent predictor for diagnostic accuracy of SWE for stage 0-1 fibrosis ( OR =1.009, 95% CI : 1.001-1.018, P =0.029). Conclusion The SWE possessed a diagnosis value for the significant fibrosis (≥S2), advanced liver fibrosis (≥S3) and liver cirrhosis (S4), although there was a low overall concordance rate in the liver Young's modulus measurements obtained using SWE vs. fibrosis stages.

Objective     To investigate the safety and feasibility of day surgery for patients with palmar hyperhidrosis based on the principles of enhanced recovery after surgery (ERAS). Methods     We retrospectively reviewed the medical records of consecutive patients who underwent endoscopic thoracic sympathicotomy (ETS) in the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to December 2021. Patients were divided into a day surgery group and a conventional group according to their perioperative management methods. The patients in the day surgery group underwent an optimized perioperative procedure under the guidance of ERAS, and were ventilated with a laryngeal or face mask during the operation. The patients in the conventional group completed the preoperative examination, operation and postoperative observation according to the conventional procedures, and were intubated with a single-lumen endotracheal tube. The demographic characteristics, operation time, hospital stay, postoperative complications, and hospitalization cost were compared between the two groups. Results     Finally 172 patients were collected, including 90 males and 82 females, with an average age of 25.97±7.43 years. There were 86 patients in each group. All patients ceased suffering from palmar sweating after surgery. No patient experienced massive bleeding or conversion to thoracotomy. There was no statistical difference in operation time between the two groups (P=0.534). Patients in the day surgery group were discharged within 24 hours. The average hospital stay in the conventional group was 2.09±0.41 days. Incidence of postoperative respiratory complications, and the hospitalization cost of the day surgery group were significantly lower than those of the conventional group (P<0.001). The satisfaction rate in both groups was greater than 95%. Conclusion     Day surgery for patients with palmar hyperhidrosis based on the principles of ERAS is safe and feasible, which can reduce postoperative complications, shorten the length of hospital stay and save the cost of hospitalization.

OBJECTIVE: To observe the correlation between the four limbs perfusion index (PI) and blood lactic acid in patients with neurosis, and evaluate the predictive value of PI on microcirculation perfusion metabolic disorder in patients with neurosis. METHODS: A prospective observational study was conducted. Adult patients admitted to the department of neurological intensive care unit (NICU) of the First Affiliated Hospital of Xinjiang Medical University from July 1 to August 20 in 2020 were enrolled. Under the condition of indoor temperature controlled at 25 centigrade, all patients were placed in the supine position, and the blood pressure, heart rate, PI of both fingers and thumb toes and arterial blood lactic acid were measured within 24 hours and 24-48 hours after NICU. The difference of four limbs PI at different time periods and its correlation with lactic acid were compared. Receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of four limbs PI on patients with microcirculatory perfusion metabolic disorder. RESULTS: A total of 44 patients with neurosis were enrolled, including 28 males and 16 females; average age (61.2±16.5) years old. There were no significant differences in PI of the left index finger and the right index finger [2.57 (1.44, 4.79) vs. 2.70 (1.25, 5.33)], PI of the left toe and the right toe [2.09 (0.85, 4.76) vs. 1.88 (0.74, 4.32)] within 24 hours after entering the NICU, and the PI of the left index finger and the right index finger [3.17 (1.49, 5.07) vs. 3.14 (1.33, 5.36)], PI of the left toe and the right toe [2.07 (0.75, 5.20) vs. 2.07 (0.68, 4.67)] at 24-48 hours after NICU admission (all P > 0.05). However, compared to the PI of the upper and lower limbs on the same side, except for the 24-48 hours after ICU of the PI difference between the left index finger and the left toe (P > 0.05), the PI of the toe was lower than that of the index finger at the other time periods (all P < 0.05). The correlation analysis showed that the PI value of four limbs of patients in both time periods were significantly negatively correlated with arterial blood lactic acid (the r values of the left index finger, the right index finger, the left toe and the right toe were -0.549, -0.482, -0.392 and -0.343 respectively within 24 hours after entering the NICU; the r values of the left index finger, the right index finger, the left toe and the right toe were -0.331, -0.292, -0.402 and -0.442 respectively after entering the NICU 24-48 hours, all P < 0.05). Taking lactic acid ≥ 2 mmol/L as the diagnostic standard for metabolic disorder of microcirculation perfusion (total 27 times, accounting for 30.7%). The efficacy of four limbs PI in predicting microcirculation perfusion metabolic disorder were compared. ROC curve analysis showed that the area under the curve (AUC) and 95% confidence interval (95%CI) of left index finger, right index finger, left toe and right toe predicting microcirculation perfusion metabolic disorder were 0.729 (0.609-0.850), 0.767 (0.662-0.871), 0.722 (0.609-0.835), 0.718 (0.593-0.842), respectively. There was no significant difference in AUC compare with each other (all P > 0.05). The cut-off value of PI of right index finger for predicting microcirculation perfusion metabolic disorder was 2.46, the sensitivity was 70.4%, the specificity was 75.4%, the positive likelihood ratio was 2.86, and the negative likelihood ratio was 0.30. CONCLUSIONS There are no significant differences in PI of bilateral index fingers, bilateral toes in patients with neurosis. However, unilateral upper and lower limbs showed lower PI in the toe than in the index finger. There is a significantly negatively correlation between PI and arterial blood lactic acid in all four limbs. PI can predict the metabolic disorder of microcirculation perfusion, and its cut-off value is 2.46.
Adult ; Female ; Male ; Humans ; Middle Aged ; Aged ; Lactic Acid ; Microcirculation ; Perfusion Index ; Lower Extremity ; Area Under Curve ; Nervous System Diseases

Objective    To explore the utility of machine learning-based radiomics models for risk stratification of severe asymptomatic carotid stenosis (ACS). Methods    The clinical data and head and neck CT angiography images of 188 patients with severe carotid artery stenosis at the Department of Cardiovascular Surgery, China-Japan Friendship Hospital from 2017 to 2021 were retrospectively collected. The patients were randomly divided into a training set (n=131, including 107 males and 24 females aged 68±8 years), and a validation set (n=57, including 50 males and 7 females aged 67±8 years). The volume of interest was manually outlined layer by layer along the edge of the carotid plaque on cross-section. Radiomics features were extracted using the Pyradiomics package of Python software. Intraclass and interclass correlation coefficient analysis, redundancy analysis, and least absolute shrinkage and selection operator regression analysis were used for feature selection. The selected radiomics features were constructed into a predictive model using 6 different supervised machine learning algorithms: logistic regression, decision tree, random forest, support vector machine, naive Bayes, and K nearest neighbor. The diagnostic efficacy of each prediction model was compared using the receiver operating characteristic (ROC) curve and the area under the curve (AUC), which were validated in the validation set. Calibration and clinical usefulness of the prediction model were evaluated using calibration curve and decision curve analysis (DCA). Results    Four radiomics features were finally selected based on the training set for the construction of a predictive model. Among the 6 machine learning models, the logistic regression model exhibited higher and more stable diagnostic efficacy, with an AUC of 0.872, a sensitivity of 100.0%, and a specificity of 66.2% in the training set; the AUC, sensitivity and specificity in the validation set were 0.867, 83.3% and 78.8%, respectively. The calibration curve and DCA showed that the logistic regression model had good calibration and clinical usefulness. Conclusion    The machine learning-based radiomics model shows application value in the risk stratification of patients with severe ACS.

This study established a rapid ECG screening system through the application of wearable ECG equipment. The closed-loop and self-service process of ECG inspection, data collection, transmission and printing have been realized. The new rapid ECG screening system docking with HIS system in the hospital, forming a new intelligent mode of rapid ECG screening. This paper introduces the design of the intelligent mode of ECG rapid screening from the aspects of hardware, software, wearable ECG examination equipment, and briefly describes its implementation path and technical scheme. With the rapid ECG screening system, human power can be saved, the timeliness of ECG examination can be enhanced. The level of ECG diagnosis in the basic units can be improved through building a multiple medical centers which is rely on the cloud platform.
Electrocardiography ; Equipment Design ; Humans ; Research ; Software ; Wearable Electronic Devices

Objective:To explore the efficacy of fluorescent retroperitoneal lymph node dissection in the comprehensive treatment of lymph node recurrence after radical prostatectomy (RP).Methods:From January 2017 to December 2020, 25 patients with lymph node recurrence diagnosed by 68Ga-PSMA PET/CT after RP in our hospital were enrolled in this study. The patients were 67 (59-77) years old. The median PSA was 7.7 (0.5-12.6) ng/ml at lymph node recurrence, and was treated with androgen deprivation therapy (ADT), suggesting hormone-sensitive prostate cancer. Before recurrence, 4 cases were in T 2 stage, 17 cases in T 3, 4 cases in T 4, 10 cases in N 0, and 15 cases in N 1stage, 25 cases in M 0stage. 2 cases diagnosed as ISUP grade group <3, 9 cases in group 4, and 14 cases in group 5. The median time from radical resection to recurrence was 43 (27-56) months. All 25 cases were diagnosed as lymph node recurrence by 68Ga-PSMA PET/CT examination. Fluorescence retroperitoneal lymph node dissection was performed. Pelvic lymph nodes were detected in the dark field under the fluorescence mode, and positive lymph nodes were found. The white light mode was switched, and the lymph nodes were cleaned, and recorded. For metastatic lymph nodes indicated by preoperative PSMA PET/CT, routine dissection was performed regardless of whether the lymph nodes were fluorescently positive or not. The only routine examination was performed if there were no lymph nodes with fluorescently positive staining in other sites. Perioperative data, biochemical recurrence (BCR) rate, radiological recurrence (RAR) rate, and follow-up data were collected and analyzed. Results:25 patients were pathologically diagnosed with lymph node metastasis. The median lymph node dissection time was 21(15-28) min, estimated blood loss was 30(20-50) ml, hospital days was 4(3-5)d without any severe complications (

Objective:To investigate the feasibility of magnetic anchor technique for endoscopic submucosal dissection (ESD) in the treatment of early esophageal cancer.Methods:A self-designed magnetic anchoring device (including an anchor magnet and a target magnet) was used to perform ESD on the hypothesized esophageal lesion mucosa of six isolated esophagus of Beagle dogs. The feasibility and convenience of the operation was evaluated.Results:ESD of 6 isolated esophagus of dogs was successfully completed. Through adjusting the position of anchor magnet, the pulling direction and force of the target magnet on the mucosa could be flexibly controlled, the mucosal peeling surface was fully exposed, and tissue tension was provided to ensure the smooth removal of the diseased mucosa. The entire operation was smooth, and the target magnet was conveniently retained. No target magnet slippage or mucosal laceration occurred during the operation.Conclusion:The magnetic anchor technique is safe and feasible for the ESD, effectively pulling the diseased mucosa in treatment of early esophageal cancer, which can greatly improve the endoscopic operation experience.