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.

Cohort study of children and adolescents health is an ideal method to explore health-related problems from childhood to adulthood, to which more attention has been paid. This paper summarizes the progress in cohort study of children and adolescents health conducted both at home and abroad by introducing the study design, main contents. Emphasizing the international exchange and cohort integration, continuously expanding cohort research field, and using multi-source data for high-quality follow-up have become the trend of cohort study of children and adolescents health.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Diabetic retinopathy(DR)is the main cause of blindness and visual impairment.In hyperglycemia,oxidative stress,or hypoxia,IL-1β upregulation mediates retinal inflammation.Sustained low-grade inflammation can cause retinal vascular damage and neurodegeneration,stimulate oxidative damage,disrupt the blood retinal barrier,and induce retinal neovascularization.This article reviews the research progress of IL-1β in the mechanism and clinical treatment of DR.

In China, the prevalence of overweight and obesity among adults is 34.3% and 16.4% respectively. Bariatric/metabolic surgery can effectively relieve morbid obesity by limiting nutrient absorption or regulating metabolism, consequently reducing obesity-related complications such as type 2 diabetes and hypertension and improving the quality of life for patients. Currently, the mainstream surgical methods are sleeve gastrectomy, Roux-en-Y gastric bypass, etc. Other new exploratory surgical methods, including combined laparoscopic sleeve gastrectomy, intragastric balloon, etc., are also undergoing continuous development. Here we reviewed the evolution of mainstream and emerging exploratory methods for bariatric/metabolic surgeries and discussed the merits and limitations of individual surgical methods, in aim to provide clinicians with more options for individualized treatment strategy for patients.

Objective:To investigate the risk factors for early complications after laparoscopy-assisted gastrectomy in patients with gastric cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 196 patients who underwent laparos-copy-assisted radical gastrectomy at Peking Union Medical College Hospital from March 2016 to March 2019 were collected. There were 144 males and 52 females, aged (61±10)years. Observation indicators: (1) early complications after laparoscopy-assisted radical gastrectomy and treatment; (2) analysis of risk factors for early complications after laparoscopy-assisted radical gastrectomy.Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( P25,P75). Count data were represented as absolute numbers. Univariate analysis was conducted using the t test, Mann-Whitney U test or chi-square test. Multivariate analysis was conducted using the Logistic regressional model. Results:(1) Early complications after laparoscopy-assisted radical gastrectomy and treatment: 51 of 196 patients had early postoperative complications, including 7 cases of grade Ⅰ according to Clavien-Dindo classi-fication system, 32 cases of grade Ⅱ, 9 cases of grade Ⅲa, 3 cases of grade Ⅲb. There was no grade Ⅳ or Ⅴ complication. There were 25 cases with abdominal complications, 7 cases with thoracic complications, 3 cases with internal/catheter related complications and 16 cases with other unclassified complications. All patients with complications were improved after symptomatic and supportive treatments. (2) Analysis of risk factors for early complications after laparoscopy-assisted radical gastrectomy: results of univariate analysis showed that the lymphocyte count, neutrophil-to-lymphocyte ratio, radiotherapy, operation time, volume of intraoperative blood loss, T stage, lymph node metastasis were related factors for early complications after laparoscopy-assisted radical gastrectomy in patients with gastric cancer ( Z=?2.048, χ2=6.385, 4.168, 8.068, 6.336, 12.497, 7.522, P<0.05). Results of multivariate analysis showed that the neutrophil/lymphocyte ratio ≥1.96, operation time ≥222 minutes, and lymph node metastasis were independent risk factors for early complica-tions after laparoscopy-assisted radical gastrectomy in patients with gastric cancer ( odds ratio=2.279, 2.245, 2.226, 95% confidence interval as 1.149-4.519, 1.116-4.517, 1.125-4.402, P<0.05). Conclusions:The abdominal complications are the most common early complications after laparoscopy-assisted radical gastrectomy. The neutrophil-to-lymphocyte ratio ≥1.96, operation time ≥222 minutes, and lymph node metastasis are independent risk factors for early complications after laparoscopy-assisted radical gastrectomy in patients with gastric cancer.

Objective To understand the current prevalence of clonorchiasis in Jiangxi Province. Methods A survey was performed according to the scheme of the 3rd Principal Human Parasites of Jiangxi Province. Based on the ecological regions,a stratified cluster sampling method was applied by the economic and geographic situation. In rural areas,the investigation of C. si?nensis was carried out together with the soil?transmitted helminths investigation,and in the urban areas,the random cluster sam?pling method was applied for the C. sinensis investigation. There were 92 survey sites from 32 counties. The eggs of C. sinensis in stool were examined by Kato?Katz technique,and health knowledge was also investigated by questionnaires in some people at the same time. Results A total of 23 606 sample residents were investigated,and 138 were found infected with C. sinensis, with the infection rate of 0.58%. Light infection was found in most of them. Totally 124 C. sinensis infected persons focused in Xinfeng County,and only a few of infected people scattered in the other counties. In Xinfeng County,851 residents were investi?gated. Among them,the infected people were found in all the age groups except the 0?year age group. The highest infection rate appeared in the 70? years group(24.00%). The male infection rate was 20.29%,which was higher than that of the female (6.25%),showing a statistically significant difference(P<0.01). The infection rate was highest in the population who received high school or technical secondary school education(31.48%). For the occupation distribution,the infection rate was highest in public officers(39.39%). The questionnaire survey showed that the infection rate in the populations in Xinfeng County who had the history of eating raw fish or raw shrimp was 33.15%. Conclusions The distribution of C. sinensis infection presents a region?al aggregation in Xinfeng County,but in other areas,the distribution is sporadic. It is necessary to continue to carry out the para?sitic disease screening,and in Xinfeng County,it is necessary to strengthen the comprehensive prevention and control interven?tion.

Objective To explore the immune mechanism of negative results of immune tests of schistosomiasis japonica pa?tients. Methods Totally 142 schistosomiasis patients(positive stool examinations)of Poyang Lake region were tested by ELI?SA method,and the ROC curve was applied to determine the high and low response of the patients. The levels of cellular immu?nity and cytokines of high and low responders were compared. Results Totally eight schistosomiasis patients were found as low responders. Besides SWAP?IgA(t= -1.588,P > 0.1),the levels of isotype antibodies were significantly lower in the low re?sponders compared with those in the high responders(t = -14.517 to -2.866,all P < 0.05). In the low responders,the propor?tion of CD3+T was increased;and the proportions of CD4+T,CD8+T,CD4+CD25+Treg,and the ratio of CD4+/CD8+ were all de?creased,but all of them were not significant(t = -1.72 to 0.974,all P > 0.05)compared with those in the high responders. The differences of IFN?γ and IL?10 between the high and low responders were both not significant(t= -2.426 to 0.216,all P >0.05). Conclusions There is a significant difference between the high and low responders only in the levels of isotype antibod?ies. One of the reasons of low response in the immune tests is the much lower antibody level after the antigen?antibody compound is completely formulated.

Objectives To explore the relationship between illness perceptions and health behavior in the subjects. Methods Revised illness perception questionnaire and health promoting lifestyle profileⅡ (HPLPⅡ) were used to measure 101 patients′illness perception and health behavior between the groups. Results The HPLPⅡscore of LEAD was(2.17 ± 0.29) with the score of dimension. The course of disease, prognosis and perception of emotion were negatively related to health behaviour; personal control and primaty congtion of drsease were postively related to health behaviour (all P<0.01). Conclusion Medical personnel should pay attention to the relationship between illness perceptions and health behavior in patients with LEAD and effective measures should be taken to improve the patients′illness perceptions, promote their choices and persistence in health behavior and improve the quality of life.

Objective To understand the capability of parasitic disease diagnosis among professionals from the clinic labora?tory of Class A tertiary hospitals in Jiangxi Province. Methods The teams that took part in the competition were formed from 20 Class A tertiary hospitals,with 2 contestants per team. The competition contents included written examination and skill opera?tion. The written examination involved the life cycle of parasites,immunological basis,detecting techniques,etiological diagno?sis etc.,and the skill operation involved making and dying thin and thick blood smears,making Kato?Katz’s fecal thick smears, as well as microscopic examinations of smears. Results A total of 40 participants took part in the competition. Their total aver?age score was 97.3±22.4 with the pass rate of 15.0%,in which the mean score of theoretical knowledge was 56.6±12.8 with the pass rate of 52.5%,and the mean score of skill operation was 40.8±12.4 with the pass rate of 5.0%. In the written examination, the scoring rate of the life cycle of soil?transmitted helminths was the highest(90.0%),and the rate of the basic knowledge of food?borne parasites was the lowest(31.5%). Both the pass rates of blood smear making and examination were higher than those of Kato?Katz’s thick smears,and the differences were statistically significant( both P<0.05). The detection rates of Plasmodi?um vivax,Plasmodium falciparum,Plasmodium ovale and negative slides of the contestants were 38.8%,45.0%,35.0%and 25.0% respectively. As to the microscopic examination of helminth eggs,the detection rate of Trichuris trichiura egg was the highest(87.5%),and the rate of the Sparganum mansoni egg was the lowest(2.5%). The scores of Kato?Katz’s thick smear making and examination of the contestants from the provincial level hospitals were higher than those from the city level hospitals (both P<0.05),and the score of those from teaching hospitals in Kato?Katz’s thick smear making was higher than that of those from non?teaching hospitals(P < 0.05). Conclusions The technique level of professionals from the clinic laboratory of the Class A tertiary hospitals cannot meet the needs of the diagnosis of parasitic diseases in Jiangxi Province ,which should arouse the attention of the health authorities and hospitals.