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.

Traumatic intracranial hematoma progresses rapidly and may cause quick increase of intracranial pressure and even brain hernia, ultimately leading to coma or death. Therefore, traumatic intracranial hematoma needs prompt treatment, but the prerequisite of treatment is early examination and diagnosis. Due to the limited transportation and other reasons, the existing large-scale detection devices such as CT and MRI cannot be deployed on the rescue site or during patient transportation. Instead, the portable diagnosis devices have the characteristics of miniaturization and high flexibility, which is conducive to promoting early detection, assisting diagnosis and further guiding the formulation of treatment plans. At present, more and more attention has been paid to the portable diagnosis devices in the diagnosis of intracranial hematoma. The authors summarized the conventional diagnosis methods and application of portable diagnosis devices for traumatic intracranial hematoma, aiming to provide a reference for the diagnosis of traumatic intracranial hematoma.

Objective:To construct of a computed tomography (CT) based radiomics model for predicting the prognosis of patients with gastric neuroendocrine neoplasm (GNEN) and inves-tigate its application value.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 182 patients with GNEN who were admitted to 2 medical centers, including the First Affiliated Hospital of Zhengzhou University of 124 cases and the Affiliated Cancer Hospital of Zhengzhou University of 58 cases, from August 2011 to December 2020 were collected. There were 130 males and 52 females, aged 64(range, 56-70)years. Based on random number table, all 182 patients were divided into the training dataset of 128 cases and the validation dataset of 54 cases with a ratio of 7:3. All patients underwent enhanced CT examination. Observation indicators: (1) construction and validation of the radiomics prediction model; (2) analysis of prognostic factors for patients with GNEN in the training dataset; (3) construction and evaluation of the prediction model for prognosis of patients with GNEN. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and the chi-square test, corrected chi-square test or Fisher exact probability were used for comparison between groups. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. The R software (version 4.0.3) glmnet software package was used for least absolute shrinkage and selection operator (LASSO)-COX regression analysis. The rms software (version 4.0.3) was used to generate nomogram and calibration curve. The Hmisc software (version 4.0.3) was used to calculate C-index values. The dca.R software (version 4.0.3) was used for decision curve analysis. Results:(1) Construction and valida-tion of the radiomics prediction model. One thousand seven hundred and eighty-one radiomics features were finally extracted from the 182 patients. Based on the feature selection using intra-group correlation coefficient >0.75, and the reduce dimensionality using LASSO-COX regression analysis, 14 non zero coefficient radiomics features were finally selected from the 1 781 radiomics features. The radiomics prediction model was constructed based on the radiomics score (R-score) of these non zero coefficient radiomics features. According to the best cutoff value of the R-score as -0.494, 128 patients in the training dataset were divided into 64 cases with high risk and 64 cases with low risk, 54 patients in the validation dataset were divided into 35 cases with high risk and 19 cases with low risk. The area under curve (AUC) of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the training dataset was 0.83[95% confidence interval ( CI ) as 0.76-0.87, P<0.05], 0.84(95% CI as 0.73-0.91, P<0.05), 0.91(95% CI as 0.78-0.95, P<0.05), respectively. The AUC of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the validation dataset was 0.84(95% CI as 0.75-0.92, P<0.05), 0.84 (95% CI as 0.73-0.91, P<0.05), 0.86(95% CI as 0.82-0.94, P<0.05), respectively. (2) Analysis of prognostic factors for patients with GNEN in the training dataset. Results of multivariate analysis showed gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression were independent factors influencing prognosis of patients with GNEN in the training dataset ( P<0.05). (3) Construction and evaluation of the prediction model for prognosis of patients with GNEN. The clinical prediction model was constructed based on the independent factors influen-cing prognosis of patients with GNEN including gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression. The C-index value of clinical prediction model in the training dataset and the validation dataset was 0.86 (95% CI as 0.82-0.90) and 0.80(95% CI as 0.72-0.87), respectively. The C-index value of radiomics prediction model in the training dataset and the validation dataset was 0.80 (95% CI as 0.74-0.86, P<0.05) and 0.75(95% CI as 0.66-0.84, P<0.05), respectively. The C-index value of clinical-radiomics combined prediction model in the training dataset and the validation dataset was 0.88(95% CI as 0.85-0.92) and 0.83 (95% CI as 0.77-0.89), respectively. Results of calibration curve show that clinical prediction model, radiomics prediction model and clinical-radiomics combined prediction model had good predictive ability. Results of decision curve show that the clinical-radiomics combined prediction model is superior to the clinical prediction model, radiomics prediction model in evaluating the prognosis of patients with GNEN. Conclusions:The predection model for predicting the prognosis of patients with GNEN is constructed based on 14 radiomics features after selecting. The prediction model can predict the prognosis of patients with GNEN well, and the clinical-radiomics combined prediction model has a better prediction efficiency.

Abstract Psychological stress and coping strategies are important factors affecting physical and mental health. Unhealthy eating behavior caused by stress is common in children and adolescents, which has not been fully clarified. In this paper, studies on the association of psychological stress with general eating behavior, abnormal eating behavior or eating disorders among children and adolescents were reviewed. The epidemiology and influencing factors were elaborated, and the possible physiological mechanism was summarized, in order to provide reference for the future research.

Objective:To retrieve and summarize evidence for prevention of hypothermia at birth in newborn.Methods:Databases such as Up To Date, BMJ Best Practice, National Institute for Health and Care Excellence(NICE), Joanna Briggs Institute (JBI), Cochrane Library, Registered Nurses′Association of Ontario (RNAO), American Heart Association(AHA), Web of Science, PubMed, Chinese Biology Medical Literature database, Wanfang Med Online were searched to collect relevant evidence for prevention of hypothermia at birth in newborn, including guidelines, systematic reviews, evidence summaries and expert consensus. Two researchers independently evaluated the quality of the literature and extracted the data of the literature which met the criteria.Results:Six articles were selected, including 1 clinical decision support system, 2 guidelines, 1 systematic review and 2 expert consensuses. Nineteen pieces of best evidence were summarized.Conclusions:This study summarized the best evidence for the prevention of hypothermia at birth in newborn, and provided evidence-based support for clinical practice.

Objective:To explore the association between resting heart rate(RHR) and all-cause mortality among the Chinese oldest-old aged more than 80.Methods:Using a total of seven surveys or follow-ups data (1998, 2000, 2002, 2005, 2008, 2011 and 2014) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 17 886 elderly over 80 years old were selected as subjects, their resting heart rate were measured though baseline survey and the survival outcome and death time of the subjects were followed up. The subjects were divided into 6 groups according to their resting heart rate. Cox regression model was used to estimate the effect of resting heart rate on mortality risk. The interaction of age, gender and resting heart rate was also analyzed by likelihood ratio test.Results:The age of subjects M( P25, P75) was 92 (86, 100) years old, including 10 531 females (58.9%) and there were 13 598 participants died, the mortality rate was 195.5 per 1 000 person-years. Multivariate Cox regression analysis showed that compared to the control group (60-69 pbm/min), the hazard ratio of the elderly are 1.06 (95% CI: 1.02, 1.11), 1.09 (95% CI: 1.04, 1.15), 1.23 (95% CI: 1.14, 1.34), 1.25 (95% CI: 1.08, 1.44) in the group of RHR between 70-79, 80-89, 90-99 and ≥100 pbm/min and Pvalues are all less than 0.05. Likelihood ratio test showed that RHR and age had an interaction effect. ( P for interaction=0.011). Conclusion:The risk of all-cause death increased with the increase of resting heart rate and this relationship was stronger between the 80-89 years old people.

Objective:To explore the association between resting heart rate(RHR) and all-cause mortality among the Chinese oldest-old aged more than 80.Methods:Using a total of seven surveys or follow-ups data (1998, 2000, 2002, 2005, 2008, 2011 and 2014) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 17 886 elderly over 80 years old were selected as subjects, their resting heart rate were measured though baseline survey and the survival outcome and death time of the subjects were followed up. The subjects were divided into 6 groups according to their resting heart rate. Cox regression model was used to estimate the effect of resting heart rate on mortality risk. The interaction of age, gender and resting heart rate was also analyzed by likelihood ratio test.Results:The age of subjects M( P25, P75) was 92 (86, 100) years old, including 10 531 females (58.9%) and there were 13 598 participants died, the mortality rate was 195.5 per 1 000 person-years. Multivariate Cox regression analysis showed that compared to the control group (60-69 pbm/min), the hazard ratio of the elderly are 1.06 (95% CI: 1.02, 1.11), 1.09 (95% CI: 1.04, 1.15), 1.23 (95% CI: 1.14, 1.34), 1.25 (95% CI: 1.08, 1.44) in the group of RHR between 70-79, 80-89, 90-99 and ≥100 pbm/min and Pvalues are all less than 0.05. Likelihood ratio test showed that RHR and age had an interaction effect. ( P for interaction=0.011). Conclusion:The risk of all-cause death increased with the increase of resting heart rate and this relationship was stronger between the 80-89 years old people.

Objective: To investigate the relationship between the epidemic of Coronavirus Disease in 2019 (COVID-19) in China and population migration from Wuhan before the city implemented strict migration restrictions. Methods: We collected the cumulative number of confirmed cases with COVID-19 up to January 31, 2020 from the official website of the health administrative departments, and information on population migration out of Wuhan during January 10, 2020 and January 24, 2020, approximately half months prior to the implementation of strict migration restrictions by the city, from Baidu population-migration big data platform. Population migration data were provided for the top 100 cities in the form of percentage values, calculated as the number of migrants from Wuhan into these cities divided by the total number of migrants out of Wuhan during the same period multiplied by 100%. The two-independent sample non-parametric Wilcoxon rank-sum test was used to compare the distribution of cumulative number of cases between the top 100 cities and the remaining 205 non-top 100 cities of China. The relationship between the cumulative number of cases and the percentage of migrants from Wuhan into the top 100 cities were further assessed by Pearson correlation and by multiple linear regression with adjustment for population size, population density, and GDP per capita. Results: The top 100 cities accounted for 91.6% of total migrants out of Wuhan, and the top 14 cities were all in Hubei province. There were a total of 5,869 cases in the top 100 cities, with a median (interquartile range) of 21.5 (12~55) cases, whereas in the 205 non-top 100 cities there were a total of 1,063 cases, with a median (interquartile range) of 4 (2~7) cases. The median cumulative number of cases differed significantly between the two types of cities (P<0.001). Among the top 100 cities, there was a strong correlation between the percentage of migrants from Wuhan and the cumulated number of cases (Pearson correlation coefficient=0.92), and for every 1 percentage point increase in migrants from Wuhan the cumulative number of cases increased by approximately 42 (95%CI, 39 to 45). The number of cumulative number of cases in Wenzhou and Chongqing was detected as potential outliers in regression diagnosis (P<0.001, corresponding standardized residuals were 5.2 and 3.5, respectively), suggesting that the number of cases in these two cities was substantially higher than others with similar amount of migrants from Wuhan. Conclusions There is a strong positive association between the percentage of migrants from Wuhan and the epidemic status of COVID-19 infections in cities in China.

Objective: To explore the correlation between pull-up ability and upper body composition of male college students in a college in Guangxi, and to provide scientific guidance for college students’ exercise. Methods: A total of 685 male college students were randomly selected from a college in Guangxi.Pull up tests were implemented according to the national physical health test standards. Measurements of muscle mass, fat mass, fat percentage, etc. of the upper limbs were conducted by using the Ogilvy Body Composition Meter (TANITA MC-180). Data entry and analysis were performed by using SPSS 23.0. Results: The pass rate of male college students in the region was 21.7%; There was a statistically significant difference in the fat mass and percentage of body fat between males with different pull-up ability (F=11.30，14.18，12.91，15.22，P<0.01).After controlling age, height, weight and BMI, partial correlation analysis showed that there was a negative correlation between the pull-up ability of male college students and the fat mass and limb fat rate of both upper limbs(r=-0.22, -0.33, -0.31, -0.38, P<0.01). Conclusion The ability of male students in Guangxi to pull up is needed to be improved. Pull-up exercises can reduce fat mass and fat percentage in the upper limbs and improve body composition.

Objective To investigate the clinical efficacy of enhanced recovery after surgery (ERAS) in the radical gastrectomy for gastric cancer.Methods The clinical data of 140 patients undergoing radical gastrectomy for gastric cancer at the Affiliated Hospital of Qingdao University from April 2011 to June 2013 were prospectively analyzed.A double-blind,randomized,controlled study was performed in the 140 patients,and all of them were divided into the ERAS group (patients undergoing perioperative management according to enhanced recovery rehabilitation program) and the control group (patients undergoing perioperative management) based on a random numble table.The inflammatory markers,nutritional index and postoperative recovery of patients were observed.Patients of the ERAS group were followed up by telephone interview within the first 24 hours after discharge,and by outpatient examination since the second week after discharge.The follow-up was ended at postoperative day 30.Patients of the control group were reexamined at the third week after discharge.The measurement data with normal distribution was presented as x ± s.The comparison between groups was evaluated with an independent sample t test.The trend analyses for variables were done using repeated measures ANOVA.The count data were analyzed using the chi-square test or Fisher exact probability.Results Eighty patients were screened for eligibility,and were allocated into the ERAS group (40 patients) and the control group (40 patients).The total protein in serum (TP),albumin (Alb),prealbumin,TNF-α,IL-6,c-reactive protein,resting energy expenditure (REE),glycemic index,insulin index and Insulin resistance index in the 2 groups showed a range of variations at postoperative day 1,3,and 5,and these were (61 ±5)g/L,(34 ±3)g/L,(160 ± 18)g/L,(12.3 ±2.3)mmol/L,(101 ±34)ng/L,(43 ± 11)g/L,(1 336 ± 105)kal/d,(7.6 ±0.8)mmol/L,(16.8 ±3.5)mU/L and 5.7 ±1.3 in the ERAS group at postoperative day 1,and (58 ± 4) g/L,(31 ± 4) g/L,(147 ± 18) g/L,(15.3 ± 2.2) mmol/L,(122 ±37)ng/L,(56 ±27) g/L,(1 450 ± 164)kal/d,(9.3 ± 1.4) mmol/L,(30.5 ±6.8) mU/L and 12.5 ±3.2 in the control group,respectively,showing a significant difference between the 2 groups (F =31.63,8.03,67.36,147.04,9.63,6.84,16.10,54.85,104.51,139.47,P ＜0.05).The duration of fever,time to flatus,duration of hospital stay,hospital expenses,numeric rating scale and quality of life (QOL) were (2.9 ±0.9) days,(2.9 ± 0.6) days,(7.6 ± 2.1) days,(28 495 ± 4 722) yuan,1.4 ± 1.0 and 15.4 ± 0.9 in the ERAS group after operation,and (3.8 ±0.6)days,(3.5 ±0.7)days,(8.9 ±2.6)days,(35 318 ±7 610)yuan,2.4 ± 1.1 and 14.4 ± 1.2 in the control group,respectively,with a significant difference between the 2 groups (t =-0.91,-3.66,-2.85,-4.82,-4.20,3.92,P ＜0.05).Two patients were complicated with respiratory diseases,1 patient received reoperation and 1 was readmitted to the hospital at postoperative day 30 in the ERAS group.Three patients had respiratory diseases,1 received reoperation and 2 were readmitted to the hospital at postoperative day 30 in the control group,with no significant difference between the 2 groups (P ＞ 0.05).Conclusions ERAS is safe and feasible for the perioperative treatment of patients with gastric cancer,meanwhile it could reduce the surgical stress,shorten the duration of hospital stay and improve QOL and postoperative complications,ERAS might take effects by reducing insulin resistance and decreasing REE.Registry This study was registered with the Chinese Clinical Trial Registry with the registry number of ChiCTR-TRC-10001611.