Tumor lineage plasticity (LP) is an emerging hallmark of cancer progression. Through pharmacologically probing the function of epigenetic regulators in prostate cancer cells and organoids, we identified bromodomain protein BRD4 as a crucial player. Integrated ChIP-seq and RNA-seq analysis of tumors revealed, for the first time, that BRD4 directly activates hundreds of genes in the LP programs which include neurogenesis, axonogenesis, EMT and stem cells and key drivers such as POU3F2 (BRN2), ASCL1/2, NeuroD1, SOX2/9, RUNX1/2 and DLL3. Interestingly, BRD4 genome occupancy is reprogrammed by anti-AR drugs from facilitating AR function in CRPC cells to activating the LP programs and is facilitated by pioneer factor FOXA1. Significantly, we demonstrated that BRD4 inhibitor AZD5153, currently at clinical development, possesses potent activities in complete blockade of tumor growth of both de novo neuroendocrine prostate cancer (NEPC) and treatment-induced NEPC PDXs and that suppression of tumor expression of LP programs through reduction of local chromatin accessibility is the primary mechanism of action (MOA) by AZD5153. Together, our study revealed that BRD4 plays a fundamental role in direct activation of tumor LP programs and that its inhibitor AZD5153 is highly promising in effective treatment of the lethal forms of the diseases.

OBJECTIVE To explore the construction path and effectiveness of dynamic zoning management model during dengue fever pandemic,and to provide evidence for optimizing hospital-acquired infection control strategies.METHODS Retrospective analysis method was conducted,the practical data of dengue fever epidemic prevention and control in a tertiary general hospital in 2024 as the sample,to evaluate the application effect of the"zoned treatment-dynamic allocation-environmental coordination"trinity prevention and control model.Based on the optimized infection prevention and control strategies implemented during the epidemic,such as the"core ward-specialist collaboration"dynamic zoning,flexible ward expansion,hierarchical disinfection,real-time dynamic re-source allocation mechanism,and precise environmental intervention,a comprehensive evaluation of prevention and control efficiency was conducted across key dimensions including infection control,resource utilization,pre-vention and control costs and patient outcomes.RESULTS Through the construction of flexible wards,the number of expanded isolation beds accounted for 44.13％(331/750)of the total beds,including 144 beds(19.20％)in core wards and 187 beds(24.93％)in specialist collaborative wards.The expansion of specialist collaborative wards increased the isolation admission capacity by 129.86％.The two types of wards admitted 57.27％of single-disease dengue patients and 42.73％of isolated patients with combined diagnosis and treatment needs from inter-nal medicine,surgery,obstetrics,gynecology,and pediatrics.The minimum ratio of flexible buffer isolation beds was 6.34％(21/331),with a maximum daily treatment capacity of 310 patients.Data showed:hospital infec-tion incidence rate was 0,peak adult mosquito density was 0.13 mosquitoes/trap·night,prevention and control cost was 95.22 yuan per case,and patient satisfaction increased by 1.98％(95.09 vs.93.24,P=0.014).CONCLUSIONS The"dynamic zoning"model achieves rapid spatial elastic reconstruction of inpatient wards for"peace-epidemic conversion"through the coordination of three links.Based on effectively blocking in-hospital transmission,it ensures the needs of multi-specialty treatment,enabling the hospital to strike a balance between the bottom line of prevention and control safety and the fulfillment of diversified medical service requirements dur-ing the epidemic outbreak period.It can provide standardized prevention and control solutions for medical institu-tions to respond to public health emergencies of vector-borne infectious diseases,and achieve the goal of zero cross infection of hospital-acquired Dengue.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective To comprehensively evaluate the prevalence of and influencing factors for low-level viraemia(LLV)in Chinese patients receiving antiviral therapy for human immunodeficiency virus(HIV)infection through systematic review and Meta-analysis.Methods Cochrane Library,Web of Science,Embase,PubMed,China Bio-medicine(CBM),VIP,China National Knowledge Infrastructure(CNKI),and Wanfang Data were systematically retrieved.Retrieval time was from the establishment of the database to February 2024.Literatures related to the prevalence of LLV in patients receiving antiviral therapy for HIV infection were retrieved using combination of key-words and free words.Stata 16.0 software was used for Meta-analysis.Random effects model was adopted to calcu-late the combined prevalence and its 95％confidence interval.Results A total of 15 papers were included in analy-sis,involving 191 212 specimens.Meta-analysis random effects model showed that the prevalence of LLV in Chinese patients receiving antiviral therapy for HIV infection was 13.00％(95％CI:7.82％-19.24％).Subgroup analysis showed that cross-sectional studies,northern regions,males,age ≥50 years,heterosexual transmission routes,baseline CD4+T lymphocyte count＜200 cells/μL,and patients who had ever changed therapy regimens had higher LLV prevalence.Conclusion The prevalence of LLV in patients receiving antiviral therapy for HIV infection is re-latively higher.Attention should be paid to such high-risk population,and appropriate antiviral therapy schemes should be selected as early as possible.Timely intervention is necessary when LLV occurs.

Objective To comprehensively evaluate the prevalence of and influencing factors for low-level viraemia(LLV)in Chinese patients receiving antiviral therapy for human immunodeficiency virus(HIV)infection through systematic review and Meta-analysis.Methods Cochrane Library,Web of Science,Embase,PubMed,China Bio-medicine(CBM),VIP,China National Knowledge Infrastructure(CNKI),and Wanfang Data were systematically retrieved.Retrieval time was from the establishment of the database to February 2024.Literatures related to the prevalence of LLV in patients receiving antiviral therapy for HIV infection were retrieved using combination of key-words and free words.Stata 16.0 software was used for Meta-analysis.Random effects model was adopted to calcu-late the combined prevalence and its 95％confidence interval.Results A total of 15 papers were included in analy-sis,involving 191 212 specimens.Meta-analysis random effects model showed that the prevalence of LLV in Chinese patients receiving antiviral therapy for HIV infection was 13.00％(95％CI:7.82％-19.24％).Subgroup analysis showed that cross-sectional studies,northern regions,males,age ≥50 years,heterosexual transmission routes,baseline CD4+T lymphocyte count＜200 cells/μL,and patients who had ever changed therapy regimens had higher LLV prevalence.Conclusion The prevalence of LLV in patients receiving antiviral therapy for HIV infection is re-latively higher.Attention should be paid to such high-risk population,and appropriate antiviral therapy schemes should be selected as early as possible.Timely intervention is necessary when LLV occurs.

OBJECTIVE To explore the construction path and effectiveness of dynamic zoning management model during dengue fever pandemic,and to provide evidence for optimizing hospital-acquired infection control strategies.METHODS Retrospective analysis method was conducted,the practical data of dengue fever epidemic prevention and control in a tertiary general hospital in 2024 as the sample,to evaluate the application effect of the"zoned treatment-dynamic allocation-environmental coordination"trinity prevention and control model.Based on the optimized infection prevention and control strategies implemented during the epidemic,such as the"core ward-specialist collaboration"dynamic zoning,flexible ward expansion,hierarchical disinfection,real-time dynamic re-source allocation mechanism,and precise environmental intervention,a comprehensive evaluation of prevention and control efficiency was conducted across key dimensions including infection control,resource utilization,pre-vention and control costs and patient outcomes.RESULTS Through the construction of flexible wards,the number of expanded isolation beds accounted for 44.13％(331/750)of the total beds,including 144 beds(19.20％)in core wards and 187 beds(24.93％)in specialist collaborative wards.The expansion of specialist collaborative wards increased the isolation admission capacity by 129.86％.The two types of wards admitted 57.27％of single-disease dengue patients and 42.73％of isolated patients with combined diagnosis and treatment needs from inter-nal medicine,surgery,obstetrics,gynecology,and pediatrics.The minimum ratio of flexible buffer isolation beds was 6.34％(21/331),with a maximum daily treatment capacity of 310 patients.Data showed:hospital infec-tion incidence rate was 0,peak adult mosquito density was 0.13 mosquitoes/trap·night,prevention and control cost was 95.22 yuan per case,and patient satisfaction increased by 1.98％(95.09 vs.93.24,P=0.014).CONCLUSIONS The"dynamic zoning"model achieves rapid spatial elastic reconstruction of inpatient wards for"peace-epidemic conversion"through the coordination of three links.Based on effectively blocking in-hospital transmission,it ensures the needs of multi-specialty treatment,enabling the hospital to strike a balance between the bottom line of prevention and control safety and the fulfillment of diversified medical service requirements dur-ing the epidemic outbreak period.It can provide standardized prevention and control solutions for medical institu-tions to respond to public health emergencies of vector-borne infectious diseases,and achieve the goal of zero cross infection of hospital-acquired Dengue.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.

Objective:To preliminarily explore the related factors that affect chimera mosaicism in in vitro fertilization (IVF) treatment. Methods:A case-control study was conducted to retrospectively analyze the clinical data of 2252 blastocysts in 579 preimplantation genetic testing (PGT) cycles in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2020. Biopsy cells were analyzed by next generation sequencing (NGS). According to the analysis results, all embryos were divided into mosaicism group and non-mosaicism group. Mosaicism types included euploid-aneuploid mosaicism, aneuploid-aneuploid mosaicism and complex mosaicism. The population characteristics and laboratory-related parameters of the two groups of embryos were compared, and single-factor and multi-factor analysis of the incidence of mosaicism were performed to evaluate the related factors that affect the development of mosaic embryos.Results:A total of 2252 blastocysts in 579 cycles were included in this study, 905 embryos (40.2%) were euploid, 923 (41.0%) were aneuploid, and 424 (18.8%) were mosaicism. Among them, 228 (10.1%) were euploid-aneuploidy mosaicism, 59 (2.6%) were aneuploidy-aneuploidy mosaicism, and 137 (6.1%) were complex mosaicism. NGS technology was performed in 4 institutions, and the mosaicism rate fluctuated between 7.6% and 26.2%. After adjusting the confounding factors (the age of the male and female partners, the quality of the male partner's sperm, the ovarian stimulation protocols, the type of culture medium, the indications of PGT, the different biopsy operators and the developmental stage of the blastocyst), it was found that the blastocyst trophectoderm cell (TE) score (grade C vs. grade A, P=0.014) and the genetic testing institutions (institution 2 vs. early stage of institution 1, P<0.001; late stage of institution 1 vs. early stage of institution 1, P<0.001) had a significant effect on the occurrence of mosaicism. Compared with the TE score of grade A, the chance of mosaicism in grade C increased by 66% (a OR=1.66, 95% CI=1.11-2.50, P=0.014). Compared with the early stage of institution 1, the incidence of mosaicism in institution 2 and late stage of institution 1 was 2.28 times (a OR=2.28, 95% CI=1.71-3.04, P<0.001), and late stage of institution 1 was 2.17 times that of the early stage (a OR=2.17, 95% CI=1.41-3.34, P<0.001). Conclusion:The incidence of mosaicism during IVF treatment is related to NGS genetic testing institutions and the quality of trophectoderm cells

Objective:To preliminarily explore the related factors that affect chimera mosaicism in in vitro fertilization (IVF) treatment. Methods:A case-control study was conducted to retrospectively analyze the clinical data of 2252 blastocysts in 579 preimplantation genetic testing (PGT) cycles in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2020. Biopsy cells were analyzed by next generation sequencing (NGS). According to the analysis results, all embryos were divided into mosaicism group and non-mosaicism group. Mosaicism types included euploid-aneuploid mosaicism, aneuploid-aneuploid mosaicism and complex mosaicism. The population characteristics and laboratory-related parameters of the two groups of embryos were compared, and single-factor and multi-factor analysis of the incidence of mosaicism were performed to evaluate the related factors that affect the development of mosaic embryos.Results:A total of 2252 blastocysts in 579 cycles were included in this study, 905 embryos (40.2%) were euploid, 923 (41.0%) were aneuploid, and 424 (18.8%) were mosaicism. Among them, 228 (10.1%) were euploid-aneuploidy mosaicism, 59 (2.6%) were aneuploidy-aneuploidy mosaicism, and 137 (6.1%) were complex mosaicism. NGS technology was performed in 4 institutions, and the mosaicism rate fluctuated between 7.6% and 26.2%. After adjusting the confounding factors (the age of the male and female partners, the quality of the male partner's sperm, the ovarian stimulation protocols, the type of culture medium, the indications of PGT, the different biopsy operators and the developmental stage of the blastocyst), it was found that the blastocyst trophectoderm cell (TE) score (grade C vs. grade A, P=0.014) and the genetic testing institutions (institution 2 vs. early stage of institution 1, P<0.001; late stage of institution 1 vs. early stage of institution 1, P<0.001) had a significant effect on the occurrence of mosaicism. Compared with the TE score of grade A, the chance of mosaicism in grade C increased by 66% (a OR=1.66, 95% CI=1.11-2.50, P=0.014). Compared with the early stage of institution 1, the incidence of mosaicism in institution 2 and late stage of institution 1 was 2.28 times (a OR=2.28, 95% CI=1.71-3.04, P<0.001), and late stage of institution 1 was 2.17 times that of the early stage (a OR=2.17, 95% CI=1.41-3.34, P<0.001). Conclusion:The incidence of mosaicism during IVF treatment is related to NGS genetic testing institutions and the quality of trophectoderm cells