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 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.

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.

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 construct and validate the application effect of a standardized nursing protocol for transoral endoscopic thyroidectomy via vestibular approach(TOETVA)led by nurses in operating room under guidance of enhanced recovery after surgery(ERAS).Methods Based on Del-phi method,a TOETVA protocol led by operating room nurses under ERAS guidance was constructed.Eighty patients were randomly divided into control group and experimental group using random number table method,with 40 cases in each group.The control group received routine nursing interventions,while the experimental group received the standardized TOETVA nursing protocol led by operating room nurses under ERAS guidance.The number of days of drainage tube indwelling,length of hospital stay,incidence of complications,anxiety levels,and nursing satisfaction were compared between the two groups.Results Compared with the control group,the experimental group had a shorter number of days of drainage tube indwelling and length of hospital stay,as well as higher nursing satisfaction(P＜0.05).There was no statistically significant difference in anxiety levels between the two groups before intervention(P＞0.05).After intervention,the score of the Self-Rating Anxiety Scale(SAS)in the experimental group decreased and was lower than that in the control group(P＜0.05).However,there was no statistically significant difference in the incidence of complications between the two groups(P＞0.05).Conclusion The construction of a standardized TOETVA nursing protocol led by nurses in operating room under ERAS guidance is scientific and effective.It has positive significance in shortening the drainage tube indwelling time and hospital stay,improving patients' anxiety,and en-hancing patients' nursing satisfaction.

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.

This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.
Chromatography, High Pressure Liquid ; Ginkgo biloba ; Lactones/analysis* ; Least-Squares Analysis ; Spectroscopy, Near-Infrared/methods*

Objective:To explore the effect of thin endometrial thickness (EMT) on the low birth weight (LBW) of singleton in fresh embryo transfer cycle.Methods:It was a retrospective cohort study. The data of singleton deliveries achieved after fresh cleavage embryo transfer in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2015 to February 2019 were included. A total of 2247 cycles were included and were divided into three groups depending on the EMT: group A≤7.5 mm, group B 7.6-12.0 mm and group C>12.0 mm. The major outcome measure was LBW. Binary logistic regression was performed to correct for confounding factors.Results:Singleton birthweight was lower in group A [3000(2525, 3350) g] compared with group B and group C [3350(3050, 3650) g, 3400(3100, 3690) g, all P<0.001]. The incidence of LBW in group A [24.7% (20/81)] was significantly higher than that in groups B and C [4.0% (57/1414), 5.3% (40/752), all P<0.001], while there was no statistical difference between groups B and C ( P>0.05). Body mass index ( P=0.029), estrogen level on the human chorionic gonadotropin (hCG) trigger day ( P=0.027), EMT ( P<0.001), gestational age ( P<0.001) and the gender of the newborn ( P<0.001) were independent factors of LBW. The incidence of LBW increased when the body mass index and gestational age were smaller and estrogen level on the hCG trigger day was ≥4000 ng/L. Taking group B as control group, the incidence of LBW in group A increased significantly and was an independent risk factor for LBW (a OR=4.39, 95% CI=1.85-10.46, P<0.001), while the incidence of LBW in group C had no significant difference (a OR=0.90, 95% CI=0.51-1.59, P=0.723). Conclusion:In the fresh cleavage stage embryo transfer cycle, singleton birth weight was lower in thin EMT group. And thin EMT was an independent risk factor for LBW of singleton delivery.

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