1.Expert consensus on perioperative nursing care for myasthenia gravis patients undergoing thymectomy
Huimin DONG ; Ting ZHOU ; Yingmei ZHONG ; Wei LI ; Xiaoyan LI ; Chunfang ZHANG ; Guoyan QI ; Yangchun LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):1-12
Myasthenia gravis is an autoimmune disorder characterized by impaired neuromuscular transmission. Thymectomy is one of the therapeutic options for acetylcholine receptor antibody-positive myasthenia gravis patients. The quality of perioperative care is directly associated with surgical safety and patient outcomes. However, there is currently a lack of specialized nursing consensus or guidelines specifically addressing the care of these patients domestically or internationally. To promote the standardization and normalization of perioperative nursing care for myasthenia gravis patients undergoing thymectomy and to ensure treatment efficacy, a panel of 57 experts from relevant fields was convened. Based on evidence-based medicine and clinical practice experience, discussions were held on various aspects including condition assessment, nutritional support, medication management, and airway care, resulting in a consensus with 18 final recommendations by using the Delphi method through two rounds of expert consultation. This consensus aims to provide a scientific reference for the perioperative nursing care of myasthenia gravis patients undergoing thymectomy.
2.Study on the correlation between HLA antibodies and pregnancy-related factors, and the predictive value of a random-forest model among female blood donors in Nanning
Fang LU ; Huihui MO ; Wujin SU ; Zhoulin ZHONG ; Hengcong LI ; Yuchen HUANG ; Yuxi CHEN ; Lilan LI ; Yan ZHOU
Chinese Journal of Blood Transfusion 2026;39(3):367-372
Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.
3.Olfactory Receptors Expressed in The Intestine and Their Functions
Pei-Wen YANG ; Meng-Meng YUAN ; Ying ZHOU ; Peng LI ; Gui-Hong QI ; Ying YANG ; Zhong-Yi MAO ; Meng-Sha ZHOU ; Xiao-Shuang MAO ; Jian-Ping XIE ; Yi-Nan YANG ; Shi-Hao SUN
Progress in Biochemistry and Biophysics 2026;53(3):534-549
Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.
4.Effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparo-scopic cholecystectomy
Zhangzhen ZHONG ; Xian ZHENG ; Ting XU ; Jie WANG ; Hui CAO ; Xinggen ZHOU ; Hui LI ; Jiacheng ZHAO ; Hui LIU ; Chao ZHANG
China Pharmacy 2026;37(2):204-209
OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group (n=100) and observation group (n=100). One minute before the initiation of anesthesia, patients in the control group received intravenous injections of Propofol emulsion injection, Sufentanil citrate injection, and Succinylcholine chloride injection. On this basis, patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared, along with their general intraoperative conditions (including sufentanil dosage, duration of pneumoperitoneum, operative time, anesthesia time, and extubation time), postoperative recovery, incidence of adverse reactions, and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure, entropy index (state entropy and response entropy), inflammatory marker levels [interleukin-6 (IL-6) and C-reactive protein (CRP)], numerical rating scale (NRS) for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration, operative time, anesthesia time,extubation time, incidence of postoperative dry mouth, entropy index or length of stay in the post-anesthesia care unit (P>0.05). Compared with the control group, the observation group showed significantly lower postoperative STAI-S scores, reduced intraoperative sufentanil consumption, decreased incidence of postoperative nausea, vomiting, and shivering, the need for dezocine rescue analgesia, as well as lower plasma IL-6 and CRP levels at 24 h after surgery, and NRS (P<0.05). The heart rate and mean arterial pressure of patients in the observation group at the start of surgery, end of surgery, and during extubation were all significantly higher than those in the control group (P<0.05). CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety, reduce intraoperative opioid consumption, suppress postoperative inflammatory response, relieve postoperative pain, and promote recovery in patients undergoing laparoscopic cholecystectomy.
5.NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9
Xiaolong LI ; Yan CAI ; Zhu ZHONG ; Maolin LI ; Dong HUANG ; Zhifei QIAO ; Hongli ZHOU ; Zuo ZHANG ; Jiyin ZHOU
Diabetes & Metabolism Journal 2026;50(1):47-61
Background:
Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear.
Methods:
Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA).
Results:
In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939.
Conclusion
The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.
6.Mechanism of silibinin derivative Sil-1 modulating MAPK signaling pathway to inhibit acute myocardial infarction in rats
Yi-fan LIU ; Meng LI ; De-yu CUI ; Xiao-yan LU ; Ting-bo NING ; Chun-xiu XU ; Jing-chun YAO ; Ji-dong ZHOU ; Zhong LIU
Chinese Pharmacological Bulletin 2025;41(8):1453-1462
Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.
7.Preparation of nano BaTiO 3@Au Schottky junction coatings on titanium implant and the influence on osteogenic properties of rat bone marrow stem cells
Xiaoling GUO ; Danhe SUN ; Luying LI ; Linfeng ZHONG ; Xiaoyan WANG ; Quan ZHOU ; Lingzhou ZHAO
Chinese Journal of Stomatology 2025;60(11):1264-1273
Objective:To prepare a nano-barium titanate@gold Schottky junction (nano-BaTiO 3@Au) coating and investigate its effects on the adhesion, proliferation, and osteogenic differentiation of bone marrow stem cells (BMSCs), aiming to explore a titanium surface modification strategy with superior osteogenic activity. Methods:Pure titanium specimens served as the control group (Ti group). Titanium dioxide coatings were prepared on their surfaces via anodic oxidation. Nano-barium titanate (nBTO group) was further synthesized using the hydrothermal method. Gold nanoparticles were grown in situ on the nano-BaTiO 3 via high-temperature reduction of chloroauric acid using sodium citrate, yielding the nano-barium titanate@gold Schottky junction coating (nBTO@Au group). Surface morphology was observed by scanning electron microscopy (SEM). Elemental composition was analyzed using X-ray energy dispersive spectrum (EDS) and X-ray photoelectron spectroscopy (XPS). Crystal structure was analyzed using X-ray diffraction (XRD) and Raman spectroscopy. Hydrophilicity was assessed via water contact angle measurement. Specimens were co-cultured with BMSCs to evaluate biocompatibility and osteogenic properties. Cell proliferation on days 1, 3, 5, and 7 was assessed using the cell counting kit-8 (CCK-8) assay. Cytotoxicity towards BMSCs was assessed using live/dead cell staining. Cell morphology and adhesion were observed using cytoskeleton staining. Alkaline phosphatase (ALP) expression in BMSCs after 7 days was quantified using an ALP activity assay and ALP staining. Extracellular matrix mineralization after 7 days was evaluated using alizarin red staining and quantification assay. Each experiment was performed using three specimens per group. Results:Scanning electron microscopy revealed that gold nanoparticles with the diameter of(14.838±0.718) nm, uniform in size and homogeneously distributed, were successfully grown in situ on the surface of the nBTO coating. EDS and XPS confirmed the presence of Ba, Ti, O, and Au elements in the nBTO@Au composite coating. XRD and Raman spectroscopy analysis indicated that the nanostructured barium titanate (nBTO) coating was synthesized via a hydrothermal method.Water contact angle measurements showed that the contact angle was 66.8°± 0.45° for the control group, 22.55°±0.42° for the nBTO group, and 26.78°±1.15° for the nBTO@Au group, indicating good hydrophilicity of both nBTO and nBTO@Au coatings. On day 1 and day 3 of culture, the cell proliferation in the nBTO group was significantly lower than that in the control group ( P<0.05). In contrast, no significant differences were observed between the nBTO@Au group and either the control group or the nBTO group (all P>0.05). By day 5, the cell proliferation of nBTO@Au groups was significantly lower than that of the control group ( P<0.05), and the cell proliferation of nBTO group was significantly lower than that of the control group and that of the nBTO@Au group ( P<0.05). By day 7, there were no statistically significant differences in cell proliferation among all experimental groups ( F=1.62, P>0.05).Live/dead cell staining demonstrated that the cell survival rate exceeded 90% in all groups, with normal morphology and few dead cells, indicating good biocompatibility of the nBTO@Au coating. Compared to the control group, both nBTO and nBTO@Au groups promoted cell adhesion and spreading, although no significant difference in cell morphology was noted between the two modified groups. ALP staining revealed a larger stained area and deeper coloration in the nBTO@Au group. Quantitative results showed that ALP activity in the nBTO@Au group was significantly higher than that in both the nBTO and control groups ( P<0.05), and the nBTO group also exhibited significantly higher activity than the control group( P<0.05). Alizarin red staining indicated the deepest coloration in the nBTO@Au group, followed by the nBTO group, and the lightest in the control group. Quantitative analysis further confirmed that the amount of calcium nodule deposition in the nBTO@Au group was significantly greater than that in the other two groups ( P<0.05), and the nBTO group also showed significantly more deposition than the control group( P<0.05). Conclusions:This study successfully prepared an nBTO@Au coating possessing good biocompatibility and enhanced osteogenic properties.
8.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.
9.2024 annual report of interventional treatment for heart failure
Chang-dong ZHANG ; Yu-cheng ZHONG ; Geng LI ; Jie WU ; Jun TIAN ; Zhi-cheng JING ; Wei MA ; Nian-guo DONG ; Yong-jian WU ; Da-xin ZHOU ; Xiao-ke SHANG
Chinese Journal of Interventional Cardiology 2025;33(10):581-587
China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7%at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.
10.BRD4 regulates m6A of ESPL1 mRNA via interaction with ALKBH5 to modulate breast cancer progression.
Haisheng ZHANG ; Linlin LU ; Cheng YI ; Tao JIANG ; Yunqing LU ; Xianyuan YANG ; Ke ZHONG ; Jiawang ZHOU ; Jiexin LI ; Guoyou XIE ; Zhuojia CHEN ; Zongpei JIANG ; Gholamreza ASADIKARAM ; Yanxi PENG ; Dan ZHOU ; Hongsheng WANG
Acta Pharmaceutica Sinica B 2025;15(3):1552-1570
The interaction between m6A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m6A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m6A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

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