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.

[Abstract] In the early stage of the application of platelet apheresis technology, there was a concern that high-frequency platelet apheresis might lead to the risk of lymphocyte depletion in blood donors. With the advances in platelet apheresis technology and improvements in collection purity and efficiency, this concern was waning. In recent years, with the wide application of leucocyte-reduced platelets apheresis, this issue has once again become a concern and research hotspot in the international blood transfusion research field. We briefly review this concern and focus on the research progress in recent years and put forward some suggestions to reduce this potential risk and of further research.

Objective To evaluate the agreement of four common HEp-2 indirect immunofluorescence assay(IFA)kits in the patients with antinuclear antibody(ANA)-associated rheumatic immune diseases(AARD)and the patients with non-autoimmune diseases(NAD).Methods The experiment in this study included two stages.In stage 1,the serum samples were randomly selected from 134 patients,and ANAs were detected by IFA at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from Janu-ary to June 2023.All of the samples were tested using four kinds of HEp-2 IFA kits,and the consistency of qualitative results was eval-uated by statistical analysis.The kit exhibited highest positive rate was defined as Kit X.In the stageⅡ,a total of 554 serum samples(from 218 AARD and 336 NAD patients)with positive results detected by initial screening of reagent X were selected during the same period,and then the samples were tested by the other three HEp-2 IFA kits.The patterns and titers of ANA were recorded,and a semi-quantitative evaluation system was established.The reproducibility of different patterns of ANA and the consistency of the results among varying clinical characteristics,fluorescence reaction intensities and positive reaction sites in nucleus was statistically analyzed.Results There were no significant differences of qualitative results among the results from four kits(P＞0.05).The highest positive rate ap-peared in the kit m(45.86%)which was deemed as the initial screening kit X.Significant differences in the consistency of ANA pat-terns were observed.The reproducibility scores of centromeric pattern and granular pattern were higher than those of homogeneous pat-tern,dense fine speckled pattern,nuclear cytoplasmic mixed pattern and other mixed pattern with significant difference(P＜0.05).The reproducibility score of simple pattern was higher than that of mixed patterns(P＜0.05).In the nucleoplasmic region,the consistency score of the AARD group was higher than that of NAD group(P＜0.01).The consistency scores of each reaction site increased with the rise of the intensity of reaction.In the three reaction parts(nucleoplasm,nucleolus and equatorial plate),the scores between the weak and strong fluorescence reaction intensity groups showed significant differences(P＜0.001).The lowest consistency score occurred in cytoplasmic region.Conclusion The clinical interpretation for IFA ANA reports should be more cautious for the results showing weak fluorescence intensity,mixed patterns,and staining positive cytoplasmic sites.For the choice for reagents,the clinical laboratories should be also mindful of the impacts of fluorescent secondary antibodies of anti-human immunoglobulin on the test results.The develop-ment of standardized official guidelines for the manufacture of HEp-2 IFA kits should be crucial initiative for enhancing the consistency of ANA detection and promoting mutual recognition for the results between laboratories.

Objective To investigate the induction factors of hypotension during cesarean section for perilous placenta previa under combined spinal-epidural anesthesia (CSEA) and to construct a nomogram prediction model. Methods A total of 130 parturients who underwent cesarean section for perilous placenta previa under CSEA from January 2020 to December 2023 in Yulin Maternity and Child Healthcare Hospital were selected as study subjects. A self-designed general information questionnaire was used to investigate the basic information and the occurrence of hypotension of the subjects. According to the occurrence of intraoperative hypotension, the patients were divided into hypotension group (47 cases) and non-hypotension group (83 cases). Univariate analysis was performed on the general information of the two groups, and multivariate Logistic regression analysis was used to explore the induction factors of intraoperative hypotension. Results Univariate analysis showed that there were statistically significant differences in body mass index, anesthesia level, presence of multiple pregnancy, preoperative systolic blood pressure, operative time, and the occurrence of Bezold-Jarisch reflex between the two groups (P < 0.05). Multivariate Logistic regression analysis revealed that body mass index≥ 24 kg/m², anesthesia level was in the eighth thoracic vertebra(T8) or above, multiple pregnancy, preoperative systolic blood pressure < 90 mmHg, operative time >1.5 h, and the occurrence of Bezold-Jarisch reflex were independent risk factors for hypotension during cesarean section for perilous placenta previa under CSEA (P < 0.05). A regression equation for the induction factors of hypotension during cesarean section for perilous placenta previa under CSEA was constructed: Logit(P)=-23.211+1.079×(body mass index ≥ 24 kg/m²)+1.101×anesthesia level (≥T8)+3.193×multiple pregnancy+2.214×preoperative systolic blood pressure (< 90 mmHg)+4.606×operative time (>1.5 h)+2.011×occurrence of Bezold-Jarisch reflex. The nomogram showed high discrimination and accuracy for patients with preoperative systolic blood pressure < 90 mmHg. After 1, 000 times of Bootstrap resampling for the nomogram model, a calibration curve was obtained, and the consistency index was calculated as 0.850, indicating good calibration of the nomogram model. The receiver operating characteristic (ROC) curve was plotted, with an area under the curve of 0.896 and 95% confidence interval of 0.802 to 0.956, suggesting good predictive performance. Conclusion Body mass index ≥24 kg/m², anesthesia level ≥ T8, multiple pregnancy, preoperative systolic blood pressure < 90 mmHg, operative time >1.5 h, and the occurrence of Bezold-Jarisch reflex are induction factors for hypotension during cesarean section for perilous placenta previa under CSEA.

Objective:To analyze spatiotemporal distribution characteristics of syphilis in Zhejiang province from 2016 to 2020, to explore cluster areas of syphilis cases, and to provide a theoretical basis for accurate prevention and control of syphilis.Methods:Data on reported syphilis cases in Zhejiang province from 2016 to 2020 were collected from the notifiable infectious disease surveillance system in China Disease Control and Prevention Information System. The ArcGIS10.2 software was used as a data management and presentation platform to establish a database for spatial analysis of syphilis in Zhejiang province from 2016 to 2020, and spatial autocorrelation analysis of reported syphilis incidence was conducted. The SaTScan 9.6 software was used for spatiotemporal scanning analysis.Results:A total of 158 420 cases of syphilis were reported in Zhejiang province from 2016 to 2020, and the average annual reported incidence rate was 49.07 per 100 000 in all counties and districts (range: 20.52 per 100 000-124.29 per 100 000) . The overall spatial distribution pattern of syphilis cases in Zhejiang province was characterized by higher reported syphilis incidence in the West area and lower incidence in the middle area. Global autocorrelation analysis showed that all the global Moran′s I indices from 2016 to 2020 were over 0, Z values were over 1.96, and P values were below 0.001, suggesting the spatial clustering of reported syphilis cases. Local autocorrelation analysis showed that there were 2 high-high clustering areas (Tonglu and Chun′an counties in Hangzhou city, Jingning county in Lishui city) , and 1 low-low clustering area (Jindong district, Dongyang and Yongkang county-level cities in Jinhua city) . Local hot-spot analysis with G statistic showed that there were 6 positive hot-spot areas and 8 negative hot-spot areas of syphilis cases in Zhejiang province. SaTScan spatiotemporal scanning analysis revealed 3 clustering areas, mainly distributed in Taizhou and Zhoushan cities along the eastern coast, and some counties and districts in the southwestern mountainous areas. Conclusions:The reported incidence rate of syphilis in Zhejiang province is characterized by spatial clustering. In the future, prevention and control of syphilis should be strengthened in southwestern mountainous areas, eastern islands, and other remote areas as well as areas with poor transportation.

Objective:To compare the use of continuous constant negative pressure drainage and intermittent suction mode drainage in abdominal wall angioplasty to minimize the impact of complications.Methods:From May 2017 to August 2019, the Department of Medical Cosmetology and Plastic Surgery, Wuhan Third Hospital treated 76 female patients after expanded flap repair, aged 27-35 years, with an average age of 30.5±14.2 years, and 58 female patients after abdominal wall plasty, aged 38-55 years, with an average age of 47.8±7.8 years. They were divided into intermittent negative pressure drainage group and continuous negative pressure drainage group. The negative pressure values in different intervals were set according to the type of operation. The drainage volume, drainage time, incidence of hematoma, subcutaneous effusion, flap necrosis rate, primary wound healing rate and drainage related bleeding were recorded and compared between the two groups.Results:After expanded flap repair in 38 cases, flap necrosis occurred in 1 case and hematoma in 3 cases; After abdominal wall plasty in 29 cases, flap necrosis occurred in 0 cases and hematoma in 1 case. The primary healing of incision was higher ( P<0.05), the drainage volume was larger, but the drainage time was shorter ( P<0.05), and no bleeding related to drainage was observed. The effect of monitoring drainage was positively correlated with the effect of operation. Conclusions:Continuous and constant negative pressure drainage is related to the prognosis of patients undergoing expansion flap repair and abdominal wall plasty. It is helpful to improve the effect of plastic surgery and the quality of nursing work. It is an effective method for nursing management after plastic surgery.

Objective: To assess the implementation of National Leprosy Control Plan (2011-2020) in Zhejiang Province, so as to provide insights into leprosy control. Methods: Leprosy control data were collected from the National Leprosy Management Information System of China, and health administrative sectors, centers for disease control and prevention and professional leprosy control institutions at each level in Zhejiang Province. According to the scheme for the final evaluation of National Leprosy Control Plan (2011-2020), the implementation of 12 indicators in Zhejiang Province in 2020 was investigated, including the current number of leprosy patients, prevalence of leprosy, proportion of training on leprosy control skills, proportion of regular leprosy treatment, proportion of treatment of adverse reactions, annual examination rate of close contacts, proportion of early case identification and awareness of leprosy control knowledge. Results: There were 50 registered leprosy cases in Zhejiang Province by the end of 2020, with a decrease of 50.98% relative to in 2010. The prevalence of leprosy was less than 1/105 in 93 counties (districts) of Zhejiang Province, and the rate of training on leprosy control skills, rate of regular leprosy treatment, rate of treatment of adverse reactions, annual examination rate of close contacts, rate of early case identification were all 100% in Zhejiang Province. There were no new confirmed cases with diagnosis of leprosy having grade 2 deformity or disability, or no new cases with deformity or disability within 2 years following anti-leprosy therapy. In addition, the awareness of leprosy control knowledge was 91.67% among the public and 98.12% among the close contacts. All of the 12 indicators reached the requirements of the National Leprosy Control Plan (2011-2020). Conclusions The implementation of the National Leprosy Control Plan (2011-2020) in Zhejiang Province had achieved the targets defined in the final evaluation of the plan. Intensifying multi-sectoral joint leprosy prevention and control and improving early identification and standardized therapy of leprosy cases are recommended for future leprosy control in Zhejiang Province.

Objective:To describe the baseline characteristics of the subjects enrolled in the China Quantitative CT (QCT) big data program in 2018—2019.Methods:Based on baseline data from the Chinese health big data project from January 2018 to December 2019 from the eligible enrolled population, measurements of bone mineral density (BMD) and visceral adipose tissue (VAT) were performed using Mindways′ QCT Pro Model 4 system. The baseline data of age, gender, regional distribution, height, weight, abdominal circumference, blood pressure, blood routine and blood biochemical tests were analyzed. And the single factor analysis of variance (ANOVA) was used to check the age related trend of BMD and VAT in both genders.Results:After screening the inclusion exclusion criteria and outliers of the main indicators, 86 113 people were enrolled in the project. The enrollment rate was 92.47%, including 35 431 (41.1%) women and 50 682 (58.9%) men, and the ratio of men to women was 1.43. The mean age was (50.3±12.7) years in all the subjects, and it was (50.2±12.8) years and (50.4±12.5) years in men and women, respectively, and there was no statistical difference between the two genders ( P>0.05). Total of 43 833 people were enrolled in east China, it was the largest group by region (50.90%), it was followed by central China (16 434 people, 19.08%), and the number of people enrolled in Northeast China was the lowest (2 914 people, 3.38%). The rate of completing of health information indicators related to the main outcome of the study were all above 70%, and there were significant differences between men and women (all P<0.05). The mean BMD was (139.33±46.76) mg/cm 3 in women, (135.90±36.48) mg/cm 3 in men, which showed a decreasing trend with age in both gender (both P<0.001); the mean intra-abdominal fat area was (116.39±56.23) cm 2 in women, (191.67±77.07) cm 2 in men, and there was an increasing trend with age in both men and women (both P<0.001). Conclusions:There are gender differences in BMD and VAT measured by QCT with different age tendency, and there are gender differences in health information index. Regional factors should also be taken into account for regional differences in the inclusion of data.

Objective:To investigate the normal reference values of spinal bone mineral density measured by quantitative computed tomography (QCT) and the differences of bone mineral density (BMD) in different regions of in Chinese adult males.Methods:Men who underwent low-dose CT lung scan for cancer screening in regions of Northeast, North, East, South, Central and Southwest of China from January 2018 to December 2019 were selected. And the lumbar vertebrae BMD values in the male subjects were measured by the QCT system (Mindways Software, Inc.). The mean BMD values and their decline rates were calculated at an age interval of 10 years, and the prevalence of osteoporosis was calculated according to the American College of Radiology spine QCT osteoporosis diagnostic criteria.Results:A total of 50 682 males with a mean age of (50.22±12.79) years (ranged 20 to 98 years) were included in this study. The peak BMD of (173.11±28.56) mg/cm 3 in the healthy Chinese adult male population appeared in the age group of 20 to 29 years and then declined with age. Before the age of 70 years, the BMD was relatively higher in males in South China, and it was lower in Central China and Southwest China, and it was intermediate in Northeast, North and East of China, with statistically significant differences. There was no significant differences in BMD in the males in the two age groups of 70 to 79 years and 80 and older among the regions in China. The overall decline rate of spinal BMD in Chinese males under QCT was about 46.92% over the lifetime, and it declined obviouslyin the 40-49 age group. The overall prevalence of osteoporosis in Chinese male population aged 50 years and above was approximately 11.42%, with the highest prevalence in Southwest China and Central China (14.72% and 13.87%, respectively) and the lowest in North China and South China (8.53% and 7.71%, respectively). Conclusions:A reference of lumbar spine BMD values for healthy males in China based on QCT is established. BMD values were highest in South China and Lowest in Central China.

Objective:To establish the normal reference value of lumbar bone mineral density (BMD) under quantitative CT (QCT) in Chinese healthy adult females and to explore the regional differences.Methods:Total of 35 431 healthy women who met the inclusion criteria of Chinese health quantitative CT big data program were selected in this study. The BMD of the central plane of L 1 and L 2 vertebrae was measured by Mindways′s QCT system, and the mean value was taken. One-way analysis of variance was used to compare the BMD differences of lumbar vertebrae in women of different ages and regions. The subjects were grouped by an age interval of 10 years, and the level of BMD in different regions of the same age group were compaired. Results:The peak BMD of Chinese healthy adult women appeared in the age group of 20-29 years (Northeast China(183.01±24.58) mg/cm 3, North China (188.93±24.80) mg/cm 3, East China (187.54±27.71) mg/cm 3, South China (186.22±33.72) mg/cm 3, Central China (176.33±24.91) mg/cm 3, Southwest China(182.25±28.00) mg/cm 3), and then it decreased with age. The level of BMD in different regions decreased with the age. Before the age of 70 years, BMD in Central and Southwest China was always at a low level((176.23±24.91) to (90.38±28.12) mg/cm 3, 182.25±28.00 to (88.55±25.68) mg/cm 3), lower than those in Northeast China ((183.01±24.58) to (99.69±27.85) mg/cm 3), North China ((188.93±24.80) to (95.89±26.12) mg/cm 3), East China ((187.54±27.71) to (95.65±27.86) mg/cm 3). After 70 years of age, BMD tended to be the same in different regions ( P>0.05). The BMD values in Central China and Southwest China were similar in the age group of 40-60 years ( P>0.05). The BMD values in the health adult femles in the age group of 60 years in different regions of Chinawere all lower than those of bone mass abnormality (all P<0.05). The detection rate of osteoporosis in females over 50 years was the highest in Southwest China (25.65%) and it was the lowest in North China (17.30%). Conclusions:This study establishes reference values of BMD under QCT in healthy Chinese women, which can be used as a reference basis for identifying women with low BMD who are at risk of osteoporosis. The BMD value is the lowest in Southwest China and the highest in South China.