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 observe the clinical efficacy of manual therapy based on the Discovery of Posture Secret (DPS) in treating adolescent idiopathic scoliosis (AIS).Methods:Thirty-six AIS patients were randomly divided into an observation group of 17 and a control group of 16. In addition to 10 minutes of side-shift training each week, the control group was given 20 minutes of sling exercise training (SET), while the observation group underwent weekly 20-minute manual therapy sessions based on DPS on the days without SET. Before and after the 4 weeks of treatment spine curvature (Cobb angle), clavicular angle (CA), angle of trunk rotation (ATR) and vertebral rotation (VR) were measured, and the Scoliosis Research Society′s patient questionnaire 22 (SRS-22) was administered.Results:After the treatment the average Cobb angle, CA, ATR and SRS-22 score of the observation group had improved significantly compared with before the treatment. The average Cobb angle, ATR and SRS-22 score of the control group were also significantly higher, but the improvements were not as great as in the observation group. There was no significant difference in VR improvement between the two groups.Conclusion:Manual therapy based on the DPS can effectively ameliorate the scoliosis and shoulder imbalance of AIS patients.

Early identification and intervention of high-risk factors during pregnancy is important for the prevention of maternal mortality. A certain hospital has established a management system for pregnant women undergoing first visit in non-obstetric departments and started applying it in three campus of the hospital in July 2023. Through the information management module for pregnant women undergoing first visit in non-obstetric departments that embedded in the hospital information system, abnormal pregnancy situations could be screened in a timely, comprehensive, and standardized manner, and quality control management could be carried out. At the same time, the hospital established a graded management path based on the severity of the condition of pregnant women, and provided early intervention for critically ill pregnant women reported through standardized management and multidisciplinary collaboration. From July to December 2023, a total of 5 766 pregnant women were first diagnosed and reported in 41 non-obstetric departments. Telephone follow-up showed a true reporting rate of 93.0%, and a total of 11 critical illness case were reported, including 2 cases of misoperation, with an accuracy rate of 81.8%. There were no adverse outcomes caused by failure to detect critical illness cases in a timely manner. In contrast, the relevant statistical data from January to June 2023 showed that there were 257 cases of pregnant women reported by non-obstetric departments, including 0 cases of critical illness and 1 case of missed critical illness. In addition, the time for non-obstetricians to screen for critically illness pregnant women of childbearing age has been reduced from 5-10 min per person before the system application to 15 s-1 min per person. The application of this system has reduced the missed reporting of critical illnesses, effectively ensured the safety of pregnant women, and improved work efficiency. It can provide reference for safety management of pregnant women in other medical institutions.

Objective:To evaluate the relationship between blood transfusion factors (massive transfusion, transfusion of stored red blood cells and anhepatic transfusion) and early postoperative outcomes in the patients undergoing orthotopic liver transplantation.Methods:Patients with end-stage liver disease who underwent orthotopic liver transplantation and intraoperative blood transfusion from January 2021 to March 2022 in our hospital were retrospectively selected, and their clinical data were collected. The patients were divided into massive transfusion group (M group, total red blood cell transfusion ≥10 U) and non-massive transfusion group (NM group) according to the amount of intraoperative blood transfused. The patients were divided into fresh blood group (NS group) and stored blood group (S group, red blood cell storage time > 2 weeks) according to the storage time of red blood cells transfused. The patients were divided into transfusion in anhepatic stage group (group T) and nontransfusion in anhepatic stage group (group NT) according to whether blood was transfused in the anhepatic stage. Multivariate logistic regression, generalized linear model and generalized linear mixed model were used to analyze the relationship between blood transfusion factors and primary outcome measures (postoperative pulmonary complications, circulation overload, acute kidney injury, abdominal infection, thrombosis) and between blood transfusion factors and secondary outcome measures (duration of ICU stay, postoperative hospitalization, postoperative temperature ≥38.5 ℃ at any time point after surgery, postoperative liver and kidney function index, coagulation function index, platelet count and preoperative difference).Results:One hundred and six patients were enrolled in this study. The results of multivariate logistic regression analysis: Massive blood transfusion and infusion of stored blood were risk factors for postoperative pulmonary complications, massive blood transfusion was a risk factor for abdominal infection, Child-Turcotte-Pugh score for liver function and time of anhepatic phase were risk factors for postoperative acute kidney injury, Child-Turcotte-Pugh score was a risk factor for circulatory overload, and age and massive blood transfusion were risk factors for thrombosis ( P<0.05). The results of generalized linear model analysis: Intraoperative stored blood transfusion and blood transfusion during the anhepatic phase were risk factors for prolonged duration of ICU stay, massive blood transfusion, intraoperative stored blood transfusion and blood transfusion during the anhepatic phase were risk factors for prolonged hospitalization ( P<0.05), and there was no correlation between massive blood transfusion, intraoperative stored blood transfusion and blood transfusion during the anhepatic phase and temperature ≥38.5 ℃ at any time point after surgery ( P>0.05). The results of generalized linear mixed model analysis: There was statistically significant difference in the difference between preoperative and postoperative liver and kidney function indexes, coagulation function indexes and platelet counts in the patients with or without massive transfusion, stored blood transfusion or blood transfusion during the anhepatic phase ( P<0.05). Conclusions:Massive blood transfusion and infusion of stored blood are the main risk factors for early adverse outcomes after orthotopic liver transplantation in the patients.

Background Non-occupational carbon monoxide (CO) poisoning is a public health problem that seriously affect people’s health and lives. Objective To describe the prevalence of non-occupational CO poisoning during 2007—2018 in Shanghai, analyze its epidemiological characteristics and potential influencing factors, and explore effective prevention and control measures. Methods Daily reported non-occupational CO poisoning cases and meteorological factors from 2007 to 2018 were collected in Shanghai, epidemiological characteristics were analyzed by descriptive epidemiology methods, and a distributed lag nonlinear model was used to assess the association between temperature and non-occupational CO poisoning. Results A total of 2264 non-occupational CO poisoning events and 3866 cases from 2007 to 2018 were reported in Shanghai, including 59 death cases. More than half of the poisoning cases were female (56.3%), and young adults accounted for more cases than any other age group (54.8%). The poisoning events mainly occurred in winter (from December to next February); however, cases reported in summer increased in recent years. The peak period of the events was from 20:00 to 24:00. Households (85.2%) and restaurants (8.0%) were the common places of non-occupational CO poisoning events, and the main cause was improper use of gas water heater (36.9%). A nonlinear curve was found between daily average temperature of current day and the occurrence of non-occupational CO poisoning. Temperature was negatively associated with the risk of non-occupational CO poisoning when the temperature was lower than 9.6 ℃, while a positive association was found during 9.7-26.0 ℃. Conclusion Winter is a high season for non-occupational CO poisoning in Shanghai, rising cases reported in summer is also worthy of attention. Supervision should be strengthened to ban sales of unqualified gas water heaters, and health education on CO poisoning prevention and control should be conducted through multiple channels, in order to reduce the incidence of CO poisoning.

Objective: To determine the relationship between mental sub-health and dietary behavior among Chinese adolescents, and to provide a scientific basis for improving adolescent mental sub-health through healthy dietary behavior. Methods: A total of 16 545 adolescents aged 13 to 22 years were sampled by random cluster sampling method in six administrative regions of China. A questionnaire survey was conducted to investigate adolescents’ dietary behaviors and mental sub-health status. Results: The proportion of boys consuming breakfast, snacks, carbonated drinks, vegetables, fish and dairy products was 76.2%, 20.2%, 19.0%, 78.4%, 52.4% and 59.2%, respectively, while the proportion of girls was 79.2%, 28.6%, 12.6%, 78.3%, 43.2% and 54.9%, respectively. Except for the "vegetable" option, dietary behaviors showed significant sex differences(χ2=20.79,320.10,229.06,150.27,32.21,P<0.01). In terms of mental sub-health, the detection rates of male adolescents’ mental sub-health status, behavioral sub-health and social sub-health were 20.7%, 26.0% and 17.2%, respectively, while those of female adolescents were 18.6%, 24.1% and 14.8%, respectively. The differences between boys and girls were statistically significant (χ2=17.32,7.66,17.46,P<0.01). Controlling for age and gender, breakfast "normally eating" and "occasionally eat", vegetables "normally eating" and "occasionally eat", fish "normally eating" and "occasionally eat", milk, dairy products "normally drink" and "occasional drink",was negatively associated with teenagers’ psychological sub-health (OR=0.60,0.73;0.50,0.65;0.74,0.77;0.73,0.69,P<0.05). Conclusion Healthy dietary behavior could be protective to avoid adolescent mental sub-health.Nutritional lectures and guideline books are needed among students and their parents.Nutritionists are encouraged to provide healthy nutritional advice to school canteen.

Preoperative neoadjuvant chemoradiotherapy NCR) combined with total mesorectal excision (TME) is the standard treatment mode for locally advanced rectal cancer.Compared with postoperative NCR,preoperative NCR increases the tumor down-staging,sphincter-preserving rate and local control rate.Patients who attain pathological complete response (pCR) after preoperative NCR have better prognosis compared with their counterparts.This article reviews the research progress on preoperative NCR in recent years.

Objective: To explore the related factors of death from severe heat stroke in Shanghai from 2013 to 2017. Methods: The data of 1 152 patients with severe heat stroke who were divided into survival (n=1 037) and death (n=115) groups including gender, age and heat stroke type (heat cramp, heat exhaustion, heat apoplexy and the mixed type) were collected from meteorological bureau and case report system for high temperature heat stroke in Shanghai from 2013 to 2017. Meanwhile, the meteorological data of the onset date of severe heat stroke cases were collected, including maximum temperature, minimum temperature, daily temperature, relative humidity, air pressure, precipitation and wind speed. The differences of individual and meteorological factors between the two groups were compared, and multivariate logistic regression model was used to analyze the related factors of death from severe heat stroke. Results: Among 1 152 cases, the mean±SD of age was (56.29±18.95) years old, 843 (73.18%)were male, 962 (83.51%) were in the heat wave period; 322 cases (27.95%) were heat cramp, 170 cases (14.76%) were heat exhaustion, 533 cases (46.27%) were heat apoplexy and 114 cases (9.90%) were the mixed type. Daily average temperature ((32.81±1.99) ℃), daily maximum and minimum temperatures ((38.20±2.24) ℃ and (29.22±1.94) ℃) in survival group were lower than those in death group (all P values<0.001), which were (33.76±1.17) ℃, (39.19±1.31) ℃ and (29.72±1.66) ℃. Daily average relative humidity ((60.36±9.75)%) and daily minimum relative humidity ((41.26±9.71)%) in survival group were higher than those in death group(allP values <0.05), which were (54.59±6.89)% and (35.60±7.24)%. The results of logistic regression analysis suggested that compared with the cases with daily average humidity <60% and a mixed type heat stroke, the death OR (95%CI) values of cases with daily average humidity >60%, heat cramp, heat exhaustion and heat apoplexy were 0.31 (0.18,0.54), 0.13 (0.05,0.34), 0.68 (0.58,2.30) and 0.87 (0.48,1.58). Conclusion The temperature, relative humidity and the type of heat stroke were the main related factors affecting the prognosis of severe heat stroke.

For the safety problems of internal medicine intravenous infusion,we carry out meticulous management,establish quality control system of intravenous infusion safety management,and formulate quality control plan.We collect and analyse the potential unsafety factors in the various departments of internal medicine.We have revised the intravenous infusion system and procedures,formulated standards for safety inspection of intravenous fluids,and standardized the admission system for nurses.We carry out training on intravenous infusion related knowledge for nursing staff,carry out meticulous management of venous transfusion links,and actively carry out learning and communication.All these measures have greatly enhanced the safety awareness of the nursing staff.The safety index of intravenous infusion for liver diseases was preliminarily summarized.The use rate of the safe indwelling needle was increased from 30.60％ to 92.30％,the rate of appropriate rate of drop speed increased from 68.45％ to 93.20％,the three sign standard rate rose from 75.20％ to 95.10％,and the patient's satisfaction with infusion increased from 85.60％ to 96.82％.Meticulous management can improve the safety of the internal medicine intravenous infusion as a whole.

Objective To investigate the genotype distribution of microsatellite locus CAI among Candida albicans ( C.albicans ) strains and to evaluate its relationship with the epidemic of vulvovaginal candidiasis ( VVC) in Guizhou region .Methods Ninety independent C.albicans strains isolated from pa-tients with VVC in Guizhou were investigated based on single-strand conformation polymorphisms ( SSCP ) and GeneScan analysis .The genotypes of C.albicans strains were identified by microsatellite locus CAI pol-ymorphism analysis .The gene polymorphism and the cluster of C.albicans strains were analyzed by using software SPSS 19.0.A logistic regression model was used to analyze the relationship between genotype distri -bution of CAI microsatellite among C.albicans strains and VVC infection .Results Twenty-seven distinct CAI genotypes with various patterns were identified from 90 C.albicans strains by GeneScan analysis .Clus-ter analysis showed that the C.albicans strains were classified into three clusters ( ClusterⅠto Cluster Ⅲ) . Three predominant genotypes including 30-45, 32-46 and 30-46 and other 7 highly similar genotypes be-longed to clusterⅡthat accounted for 70.0%(63 strains) in all strains.The odds ratio for the predominant genotypes associated with VVC infection was 4.3.Conclusion The predominant distribution of genotypes was observed among the isolated C.albicans strains.The predominant genotypes of C.albicans were highly associated with the occurrence of VVC .