1.Preliminary application of histological evaluation of donor pancreas biopsy tissue in simultaneous pancreas-kidney transplantation
Jiao WAN ; Hui GUO ; Jiali FANG ; Guanghui LI ; Luhao LIU ; Yunyi XIONG ; Wei YIN ; Tong YANG ; Junjie MA ; Zheng CHEN
Organ Transplantation 2026;17(2):250-256
Objective To preliminarily investigate the safety and efficacy of donor pancreas needle biopsy in simultaneous pancreas-kidney transplantation. Methods Clinical data of 7 cases undergoing donor pancreas biopsy were collected retrospectively. All cases underwent donor pancreas biopsy before or during simultaneous pancreas-kidney transplantation. Frozen section or paraffin sectioning techniques were used for tissue preparation, and hematoxylin-eosin and Masson staining were performed to histologically evaluate the donor pancreas. The quality of donor pancreas was comprehensively assessed by combining histological findings with the donor's clinical data. Postoperative follow-up data of 5 simultaneous pancreas-kidney transplant recipients were collected to summarize the safety of donor pancreas biopsy and the prognosis of transplant recipients. Results The 7 pancreas donors were aged 28 to 62 years, with a body mass index ranging from 20.76 to 27.68 kg/m2. Liver ultrasound indicated fatty liver in 3 cases, while pancreatic ultrasound did not reveal any significant abnormalities. Among them, biopsy was performed on 2 donors after completion of pancreatic procurement and processing, and the frozen section histology showed moderate acute pancreatitis changes (edema of acinar cells, necrosis and inflammatory cell infiltration). Combined with a serum amylase level elevated more than 3 times the upper limit of normal value, these two donor pancreases were finally discarded. The remaining 5 cases underwent biopsy immediately after pancreatic vascular anastomosis during simultaneous pancreas-kidney transplantation, and histological evaluation was performed on paraffin-embedded sections. No biopsy-related complications (such as bleeding, pancreatic fistula, etc.) occurred after transplantation. One recipient died of severe infection 2 months after transplantation, while the other 4 recipients were followed up for more than 5 years, with well-functioning transplant kidneys and pancreases. Conclusions Donor pancreas biopsy is relatively safe, and the risk of biopsy-related complications after transplantation is controllable. Comprehensive assessment of donor pancreas quality by combining histological evaluation with the donor's clinical indicators is conducive to improving the accuracy of donor pancreas selection and organ utilization.
2.Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"
Dan LI ; Xiaoxia LIU ; Xiaofen WANG ; Zuxin HE ; Junnan WEI ; Yanqing LIU ; Yuxuan GAO ; Ping LUO ; Fang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):201-209
ObjectiveBased on the theory of "spleen governing transportation and transformation", this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice(AMR-AFI) in improving slow-transit constipation(STC), as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis, thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group, model group, positive drug(mosapride) group(3 mg·kg-1), and low-, medium-, and high-dose groups of AMR-AFI(3.9, 7.8, 15.6 g·kg-1). Except for the control group, the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling, interventions were administered. All groups received continuous administration for 15 d, during which fecal samples, colon tissue, and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate, histological morphology of colonic tissue was observed via hematoxylin-eosin(HE) staining, and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, and IL-2 in serum were detected using enzyme-linked immunosorbent assay(ELISA). Furthermore, the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing, while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue, followed by gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Finally, Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group, the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased(P<0.01), while serum levels of IL-6, TNF-α, and IL-2 were significantly elevated(P<0.01). HE staining showed damage and shedding of colonic mucosal epithelial cells, along with a reduction in goblet cells in the model group. In comparison with the model group, all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6, TNF-α, and IL-2(P<0.01). Among these, the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats(P<0.05, P<0.01). Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group, as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis, such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice, increased species richness, downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella, and enriched beneficial and butyrate-producing bacteria, including Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast, pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota, arachidonic acid-mediated inflammatory metabolism, and aldosterone-regulated water-salt balance pathways.
3.Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"
Dan LI ; Xiaoxia LIU ; Xiaofen WANG ; Zuxin HE ; Junnan WEI ; Yanqing LIU ; Yuxuan GAO ; Ping LUO ; Fang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):201-209
ObjectiveBased on the theory of "spleen governing transportation and transformation", this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice(AMR-AFI) in improving slow-transit constipation(STC), as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis, thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group, model group, positive drug(mosapride) group(3 mg·kg-1), and low-, medium-, and high-dose groups of AMR-AFI(3.9, 7.8, 15.6 g·kg-1). Except for the control group, the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling, interventions were administered. All groups received continuous administration for 15 d, during which fecal samples, colon tissue, and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate, histological morphology of colonic tissue was observed via hematoxylin-eosin(HE) staining, and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, and IL-2 in serum were detected using enzyme-linked immunosorbent assay(ELISA). Furthermore, the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing, while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue, followed by gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Finally, Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group, the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased(P<0.01), while serum levels of IL-6, TNF-α, and IL-2 were significantly elevated(P<0.01). HE staining showed damage and shedding of colonic mucosal epithelial cells, along with a reduction in goblet cells in the model group. In comparison with the model group, all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6, TNF-α, and IL-2(P<0.01). Among these, the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats(P<0.05, P<0.01). Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group, as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis, such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice, increased species richness, downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella, and enriched beneficial and butyrate-producing bacteria, including Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast, pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota, arachidonic acid-mediated inflammatory metabolism, and aldosterone-regulated water-salt balance pathways.
4.Association between screen behaviors with overweight and obesity among children and adolescents
Chinese Journal of School Health 2026;47(4):486-489
Objective:
To investigate the prevalence of overweight and obesity among children and adolescents in Yangzhou City, and its association with screen behaviors, so as to provide scientific evidence for weight management among students.
Methods:
In May 2025, an electronic questionnaire survey was conducted among children and adolescents in Yangzhou City. A total of 3 722 participants were selected from grades 4 to 12 in 18 primary and secondary schools (108 classes) by using stratified cluster random sampling. The Chi square test was used to compare the differences in the detection rates of overweight and obesity among children and adolescents with 5 types of screen behaviors (watching TV, playing electronic games, scrolling short videos, screen based learning, electronic socializing) in different time groups each day (never, >0~<2 h, ≥2 h). Multivariate Logistic regression analysis was performed to examine the associations of five types of screen behaviors, presence of electronic devices in the bedroom, and screen use during meals on the weight status of children and adolescents.
Results:
The prevalence of overweight and obesity among children and adolescents was 37.3%. For all five types of screen behaviors, the differences in the distribution of overweight and obesity detection rates among children and adolescents across the three time spent categories were statistically significant ( χ 2=30.76- 70.78 , all P <0.01). After adjusting for confounding factors, multivariate Logistic regression analysis revealed that frequent or always using screens during meals( OR =1.63, 95% CI =1.14~2.31), playing video games ( OR =1.28, 95% CI =1.11-1.48), browsing short videos ( OR =1.29, 95% CI=1.09-1.54), and screen based learning ( OR =1.26, 95% CI =1.10-1.44) were significantly associated with overweight and obesity among children and adolescents (all P <0.05).
Conclusions
Excessive screen use is positively correlated with the incidence of overweight and obesity in children and adolescents. Targeted interventions on screen behaviors among children and adolescents are therefore warranted.
5.Strategies of HIV-1 Vaccines Based on mRNA Platforms
Pei LIU ; Zhong-Yue FANG ; Xin-Xin CHEN ; Shao-Wei LI ; Ying GU
Progress in Biochemistry and Biophysics 2026;53(4):826-839
Since its emergence in the 1980s, the human immunodeficiency virus (HIV) has caused a global pandemic, posing a severe threat to human life and health as well as social development. Although pre-exposure prophylaxis (PrEP) effectively curbs HIV transmission and antiretroviral therapy (ART) significantly extends the lifespan of patients, vaccines remain a pivotal tool for blocking transmission and ending the pandemic. The high genetic variability of HIV-1, the glycan shield of its envelope glycoproteins, and the long-term persistence of latent reservoirs have repeatedly led to bottlenecks in traditional vaccine strategies. In recent years, mRNA technology has offered a novel approach to addressing these challenges, leveraging advantages such as sequence programmability, short production cycles, native conformational expression of antigens, and self-adjuvant effects. In recent years, mRNA vaccine technology has emerged as a transformative solution to longstanding vaccinology challenges, characterized by its sequence programmability, rapid production cycles, native conformational antigen expression, and intrinsic self-adjuvanting properties. Unlike traditional platforms reliant on pathogen culture or recombinant proteins, mRNA vaccines can be expeditiously designed and updated based solely on viral genomic sequences. Lipid nanoparticle (LNP)-encapsulated mRNA facilitates endogenous antigen expression and presentation, simultaneously eliciting potent humoral and cellular immune responses. Within this landscape, self-amplifying mRNA (saRNA) further extends in vivo antigen expression to enhance the persistence of immune responses. Moreover, the LNP delivery system not only protects mRNA from degradation and mediates endosomal escape but also synergizes with mRNA to optimize immune activation via self-adjuvant effects. Importantly, mRNA platforms circumvent the pre-existing immunity associated with viral vectors and the genomic integration risks of DNA vaccines, positioning them as a cornerstone for global pandemic preparedness. This review systematically delineates recent advances in mRNA technology for HIV-1 vaccine development, focusing on four pivotal research frontiers. First, mRNA innovations building upon the RV144 trial optimize antigens through codon modification and multivalent designs to induce more durable and broad-spectrum immunity. Second, particulate mRNA vaccine strategies, utilizing virus-like particles (VLPs) and ferritin nanoparticles, achieve in situ antigen self-assembly, significantly enhancing B cell activation and reducing infection risks in non-human primate models. Third, germline-targeting mRNA vaccines address the low-affinity barrier of broadly neutralizing antibody (bNAp) precursors, efficiently activating rare precursor B cells and promoting affinity maturation. Fourth, therapeutic mRNA vaccines offer unique advantages for an HIV functional cure; combining immunogens with mRNA-encoded adjuvants potentiates cellular immunity, while LNP-mediated “shock-and-kill” strategies specifically activate latent reservoirs to guide immune clearance. Comparative analyses with traditional platforms reveal that mRNA technology redefines antigen production and presentation, simulating chronic infection through sustained expression and enabling dual-pathway presentation via endogenous synthesis. Furthermore, we explore the mechanistic innovations of mRNA vaccines in inducing bNAps: sustained in vivo production prolongs the activation window for precursor B cells and maintains germinal center (GC) reactions; endogenously expressed antigens adopt native conformations to expose conserved epitopes; and self-adjuvanting effects modulate the functions of antigen-presenting cells (APCs) and follicular helper T cells (Tfh), driving somatic hypermutation and affinity maturation. We also address critical clinical translation challenges, including immune durability, adaptability to special populations, and large-scale LNP manufacturing, while proposing targeted optimization strategies. In conclusion, this review establishes a theoretical framework for utilizing mRNA technology to overcome HIV-1 immune escape, transitioning from a descriptive paradigm to a problem-solving-based synthesis of evidence. By integrating preclinical and early clinical data, we bridge the gap between basic design and translational verification. mRNA technology is poised to become a central pillar inHIV-1 prevention and therapy, providing a robust toolset to achieve the global goal of ending the AIDS pandemic and offering a blueprint for vaccine development against other recalcitrant infectious diseases.
6.A panel study on association of short-term air pollution exposure and peripheral blood microparticles in healthy adults
Bin ZHANG ; Xinghou HE ; Jiahui LIU ; Xuyang SHAN ; Yan FANG ; Huiying XU ; Erlu ZHAO ; Shengcong LIU ; Hongbing XU ; Jianping LI ; Wei HUANG
Journal of Environmental and Occupational Medicine 2026;43(1):1-7
Background Microparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human. Objective To evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs. Method A panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA). Results The results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM2.5 (IQR=64.9 μg·m−3) at prior 18 h and NO (IQR=40.5 μg·m−3) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05). Conclusion Short-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.
7.Comparative analysis of the characteristics of imported malaria cases in Nanning City in 2024 and the same period of the previous year
Shu-lin WEI ; Zhi-qiang QU ; Yuan-yuan LUO ; Yan-cui HUANG ; Shu-qin DIAO ; Xue LI ; Sheng-long YANG ; Xiao-yu HUANG ; Mi-fang LUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):81-84
Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.
8.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
9.Expert consensus on prognostic evaluation of cochlear implantation in hereditary hearing loss.
Xinyu SHI ; Xianbao CAO ; Renjie CHAI ; Suijun CHEN ; Juan FENG ; Ningyu FENG ; Xia GAO ; Lulu GUO ; Yuhe LIU ; Ling LU ; Lingyun MEI ; Xiaoyun QIAN ; Dongdong REN ; Haibo SHI ; Duoduo TAO ; Qin WANG ; Zhaoyan WANG ; Shuo WANG ; Wei WANG ; Ming XIA ; Hao XIONG ; Baicheng XU ; Kai XU ; Lei XU ; Hua YANG ; Jun YANG ; Pingli YANG ; Wei YUAN ; Dingjun ZHA ; Chunming ZHANG ; Hongzheng ZHANG ; Juan ZHANG ; Tianhong ZHANG ; Wenqi ZUO ; Wenyan LI ; Yongyi YUAN ; Jie ZHANG ; Yu ZHAO ; Fang ZHENG ; Yu SUN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(9):798-808
Hearing loss is the most prevalent disabling disease. Cochlear implantation(CI) serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system(Favorable, Marginal, Poor). The consensus focuses on common hereditary non-syndromic hearing loss(such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1) and syndromic hereditary hearing loss(such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome), which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans
;
Cochlear Implantation
;
Prognosis
;
Hearing Loss/surgery*
;
Consensus
;
Connexin 26
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Mutation
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Sulfate Transporters
;
Connexins/genetics*
10.Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.
Bin LIU ; Wen-Zhe DENG ; Wen-Hua HU ; Rong-Xi LU ; Qing-Yu ZHANG ; Chen-Feng GAO ; Xiao-Jie HUANG ; Wei-Guo LIAO ; Jin GAO ; Yang LIU ; Hiroshi KURIHARA ; Yi-Fang LI ; Xu-Hui ZHANG ; Yan-Ping WU ; Lei LIANG ; Rong-Rong HE
Acta Pharmaceutica Sinica B 2025;15(6):3149-3162
Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.


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