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.

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Objective To systematically evaluate the effectiveness and acceptability of antidepressant drugs in the treatment of postpartum depression(PPD).Methods The PubMed,Cochrane Library,Embase,Web of Science,China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Journals of Chinese Scienc were searched,and Chinese Biomedical Literature Service System(SinoMed)database until November 2023.Screen randomized controlled trials(RCTs)of antidepressant drugs for the treatment of PPD.The treatment group was given antidepressant drugs,and the control group was given placebo or another antidepressant drug.Meta-analysis of effectiveness and acceptability is performed using Stata 17.0 software.Results A total of 27 RCTs with a total of 2 202 patients were included.The results of meta-analysis showed:The top three efficacy relative to placebo were mirtazapine[odds ratio(OR)=2.25,95％confidence interval(CI)=(1.20-3.30),P＜0.05],nortriptyline[OR=1.50,95％CI=(0.55-2.44),P＞0.05],venlafaxine[OR=1.35,95％CI=(0.13-2.56),P＞0.05].Acceptability is compared with placebo in the top three Chinese herbal medicine[OR=0.47,95％CI=(-0.72-1.66),P＞0.05],nortriptyline[OR=-0.08,95％CI=(-1.16-1.33),P＞0.05],venlafaxine[OR=-0.12,95％CI=(-1.47-1.24),P＞0.05].Conclusion Nortriptyline,venlafaxine,trazodone,and duloxetine are effective in treating PPD without obvious adverse drug reactions.

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Objective To identify the cuproptosis genes associated with prognosis and immune microenvironment in lung cancer with the use of bioinformatics.Methods The lung cancer dataset used in this study was obtained from the TCGA database.The cuproptosis-related genes(CRGs)were obtained from the previously reported literature.The R software Deseq2 package was used to identify the differentially expressed genes(DEGs)in lung cancer.The intersection of DEGs and CRGs was taken to obtain the differentially expressed CRGs(DE-CRGs).COX analysis and R software rms package were used to identify DE-CRGs associated with the prognosis of lung cancer.Estimate and Cibersort algorithms were applied to identify the correlation of DE-CRGs with the immune microenvironment.Results Compared to the normal tissues,a total of 5,269 DEGs were present in lung cancer tissues in the TCGA database,and there were 11 shared genes between DEGs and CRGs.The 11 DE-CRGs mainly regulated the energy metabolism,carbon metabolism and amino acid metabolism.In the DE-CRGs,LIPT1 was an independent risk factor for lung cancer,and the column chart constructed with the clinical features(age,TNM staging,and residual tumor)predicted the survival of lung cancer patients in a manner similar to their actual outcomes.LIPT1 showed a positive correlation with the infiltration of M1 and M2 type macrophages,activated natural killer cells cells and CD8+T cells,and showed a significant negative correlation with M0 type macrophages,activated mast cells,neutrophils and Treg cells(P<0.05).Conclusion LIPT1 may serve as a prognostic and immune microenvironment-associated cuproptosis gene,which is a novel biomarker for lung cancer therapy.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective:To evaluate the clinical efficacy and safety of an antioxidant gel containing tea polyphenols combined with narrow-band ultraviolet B in the treatment of vitiligo.Methods:A single-center, randomized controlled clinical trial was conducted. From April 25 to June 27, 2024, patients with vitiligo were selected from the Department of Dermatology, Hangzhou Third People's Hospital. An open-label and researcher-blinded design was used. The patients were divided into 3 groups: a phototherapy group receiving phototherapy alone, a tea polyphenols combined group treated with an antioxidant gel containing tea polyphenols combined with phototherapy, and a positive control group treated with an antioxidant gel containing superoxide dismutase combined with phototherapy, with the treatment duration being 3 months. The efficacy was evaluated using the Vitiligo Area Scoring Index (VASI), and when the VASI was improved by ≥ 10%, the treatment would be considered effective. Changes in skin aging and skin barrier function indicators before and after treatment were assessed for 72 vitiligo lesions in the tea polyphenols combined group and for 72 lesions in the phototherapy group. Comparisons between the groups were performed using one-way analysis of variance, Fisher's exact test, chi-square test, or t test. Results:A total of 171 vitiligo patients with 307 target lesions were successfully followed up in this study, including 74 males and 97 females, and their ages ranged from 1 to 64 years. Among the 307 lesions, 95 were treated with phototherapy alone, of which 35 showed improvement, resulting in a total response rate of 36.8% and an average VASI improvement rate of 10.9%; adverse reactions occurred in 29 lesions (30.5%). Of 138 lesions treated with the antioxidant gel containing tea polyphenols combined with phototherapy, 73 showed improvement, resulting in a total response rate of 52.9% and an average VASI improvement rate of 24.0%; adverse reactions occurred in 10 lesions (7.2%). In the positive control group, 74 lesions were treated, and 40 showed improvement, resulting in a total response rate of 54.1% and an average VASI improvement rate of 18.3%; adverse reactions occurred in 5 lesions (6.8%). Compared with the phototherapy group, the tea polyphenols combined group showed a significantly increased total response rate and a VASI improvement rate (both P < 0.01), but a significantly decreased incidence rate of adverse reactions ( P < 0.001). No significant differences in the above indicators were observed between the tea polyphenols combined group and the positive control group (all P > 0.05). In addition, the changes in skin barrier function and skin aging indicators (except for wrinkle depth) before and after treatment were significantly reduced in the tea polyphenols combined group compared to the phototherapy group (all P < 0.05). After the phototherapy alone, the transepidermal water loss significantly increased ( P = 0.004), and the water content of the stratum corneum significantly decreased ( P = 0.012). However, no significant differences in skin barrier function or skin aging indicators were found between pre- and post-treatment in the tea polyphenols combined group ( P > 0.05) . Conclusion:The antioxidant gel containing tea polyphenols could effectively improve the efficacy of narrow-band ultraviolet B in the treatment of vitiligo, and alleviate skin aging and barrier damage caused by phototherapy.

AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P＜0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P＜0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P＜0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P＜0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.