OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 （NLRP3） inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3， apoptosis-associated speck-like protein ， containing a CARD （ASC）， and caspase-1 precursor （pro- No.20-21ZY1053） caspase-1） were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group， model group， dexamethasone group （0.002 g/kg）， and Pangshi antai zhixue decoction low-， medium-， and high-dose groups （11.025， 22.05， 44.10 g/kg）， with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically， once a day， for 12 consecutive days. Except for normal group， other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication， serum levels of triiodothyronine （T3）， thyroxine （T4）， interleukin-2 （IL-2）， IL-4， IL-6， IL-10， and interferon-γ （IFN-γ） were all detected； the abortion rate and uterine coefficient were calculated； the pathological morphology of the pregnant uterus was observed； protein expressions of NLRP3， ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3， ASC， and pro-caspase-1 were all less than －5 kJ/moL. The animal experiment results showed that compared with normal group， the uterine coefficient and serum levels of IL-4， IL-6 and IL-10 were decreased significantly in model group （P＜0.05）； the abortion rate and serum levels of T3， T4， IL-2 and IFN-γ as well as protein expressions of NLRP3， ASC and caspase-1 were increased significantly （P＜0.05）； there were abortion lesions in the pregnant endometrium. Compared with the model group， most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups （P＜0.05）， and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome， down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2， and up-regulating anti-inflammatory cytokines such as IL-4， IL-6 and IL-10， thereby improving spontaneous abortion with heat syndrome.

OBJECTIVES: Increasing detection of low-risk papillary thyroid carcinoma (PTC) is associated with overdiagnosis and overtreatment. N6-methyladenosine (m⁶A)-mediated microRNA (miRNA) dysregulation plays a critical role in tumor metastasis and progression. However, the functional role of m⁶A-miRNAs in PTC remains unclear. This study aims to elucidate the regulatory mechanism of m⁶A-miR-139-5p expression in PTC, determine its association with PTC metastasis, and evaluate its potential as a diagnostic biomarker for PTC metastasis, thereby providing experimental evidence for precision diagnosis and therapy. METHODS: Expression profiles of m⁶A-miRNAs were compared between the The Cancer Genome Atlas (TCGA) and GSE130512 cohorts to identify metastasis-associated candidates. Clinical specimens from 13 metastasis and 18 non-metastasis PTC patients were analyzed to assess m⁶A-miR-139-5p expression and its correlation with metastasis. Functional experiments were conducted to investigate the effect of fat mass and obesity-associated protein (FTO) on pri-miR-139 methylation and processing, clarifying its regulatory role in miR-139-5p expression. In TPC-1 cells, MTT assays were performed to evaluate whether miR-139-5p overexpression could counteract FTO-mediated cell proliferation. Transwell invasion assays were used to determine the impact of miR-139-5p on PTC cell invasion, exploring whether it functions through the ZEB1/E-cadherin axis. RESULTS: By comparing TCGA and GSE130512 cohorts, it was found that circulating m⁶A-miR-139-5p could serve as a biological indicator for detecting PTC metastasis. Detection of 13 metastatic and 18 non-metastatic clinical specimens showed that FTO inhibited the processing of pri-miR-139 by reducing its methylation level, leading to the dysregulation of miR-139-5p in PTC (P<0.05). In TPC-1 cells, MTT assay showed that overexpression of miR-139-5p could partially reverse FTO overexpression-mediated cell proliferation (P<0.05). In addition, miR-139-5p inhibited the invasive ability of PTC cells by targeting the ZEB1/E-cadherin axis, while FTO overexpression could partially weaken this inhibitory effect. CONCLUSIONS Circulating miR-139-5p can be a potential marker for evaluating PTC metastasis. FTO affects the expression and function of miR-139-5p by regulating m⁶A modification of pri-miR-139, but its clinical value needs further verification.
Humans ; MicroRNAs/metabolism* ; Thyroid Cancer, Papillary/metabolism* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism* ; Thyroid Neoplasms/metabolism* ; Cell Line, Tumor ; Neoplasm Metastasis ; Adenosine/genetics* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Cadherins/metabolism* ; Cell Proliferation ; Zinc Finger E-box-Binding Homeobox 1/genetics*

OBJECTIVES: Depressive and anxiety disorders are among the most common mental disorders worldwide and are associated with unhealthy lifestyle behaviors. The Life's Simple 7 (LS7) guideline proposed by the American Heart Association aims to reduce cardiovascular risk by improving behaviors such as diet and physical activity, but its impact on mental health is not yet fully clear. This study examined the association between LS7 scores and symptoms of anxiety and depression in adults undergoing routine health examinations. METHODS: Data were collected from individuals who underwent health examinations from May 2015 to December 2024 at the Health Management Center of the Third Xiangya Hospital. All participants completed the LS7 assessments, the Self-Rating Depression Scale (SDS), and the Self-Rating Anxiety Scale (SAS). Participants were categorized into 4 LS7 score groups: Low (≤7), average (8-9), good (10), and excellent (11-14). Those with SDS or SAS≥50 were classified as having mental disorder symptoms; with this group, SAS≥50 indicated anxiety, SDS≥50 indicated depression, and SDS and SAS≥50 indicated comorbid anxiety-depression. Binary logistic regression was used to assess associations between LS7 score and mental symptoms, calculating odds ratio (OR) and 95% confidence interval (CI). A restricted cubic spline (RCS) regression model was used to analyze the dose-response relationship between LS7 score (continuous variable) and the risk of mental symptoms. Nodes were set at the 5th, 35th, 65th, and 95th percentiles of the LS7 score, with the 5th percentile as the reference point. All models were adjusted for covariates such as gender, age, living alone, drinking status, education level, and sleep quality. Logistic regression framework was used to fit and calculate the adjusted OR (aOR) and 95% CI. Nonlinear relationship tests were also conducted. Subgroup analysis was performed to explore the interaction between gender, age, drinking habits, education level, and other factors and the LS7 score in influencing the risk of mental symptoms. RESULTS: A total of 5 449 participants were included; 1 363 (25.01%) had depressive symptoms, 398 (7.30%) had anxiety symptoms, and 259 (4.75%) had comorbid anxiety-depression. The prevalence of mental symptoms decreased significantly as LS7 scores increased. Univariate and multivariate Logistic regression indicated that LS7 score≥8 was protective against mental symptoms. Multivariate Logistic regression demonstrated moderate discriminative ability (AUC=0.672). Among individuals with anxiety, depression, or comorbid symptoms, LS7 score distributions showed a graded decrease from poor to excellent groups. After adjustment, an excellent LS7 score was associated with a 39% lower risk of depression (aOR=0.61, 95% CI 0.47 to 0.78, P<0.001), a 63% lower risk of anxiety (aOR=0.37, 95% CI 0.22 to 0.59, P<0.001), and a 66% lower risk of comorbid anxiety-depression (aOR=0.34, 95% CI 0.17 to 0.62, P=0.001). The AUC values of the anxiety model, depression model, and comorbid anxiety and depression model were 0.632, 0.672, and 0.619, respectively. All models demonstrated moderate discriminatory ability, which was statistically significant, but their capacity to distinguish cases from non-cases was limited. RCS analysis confirmed a linear inverse relationship between LS7 score and mental symptom risk. Not smoking and regular physical activity were the strongest protective behaviors. Subgroup analysis suggested stronger protective effects in men, younger adults (≤60), non-drinkers, and those with higher education levels, and revealed a significant interaction between alcohol use and LS7 score (P for interaction=0.021), indicating that alcohol consumption may weaken the protective effect of LS7. CONCLUSIONS Ideal healthy lifestyle behaviors, as reflected by higher LS7 scores, are associated with lower risks of anxiety and depression in adults. Promoting LS7-based lifestyle practices may serve as a practical and effective strategy for the prevention and management of anxiety and depression in both clinical and daily life settings.
Humans ; Cross-Sectional Studies ; Depression/epidemiology* ; Anxiety/epidemiology* ; Adult ; Male ; Female ; Middle Aged ; Healthy Lifestyle ; Risk Factors ; Anxiety Disorders/epidemiology* ; Exercise ; Physical Examination ; Aged

The clinical application of chemotherapeutic drugs has been limited due to the lack of tumor selectivity which causes different degrees of adverse reactions. Transferrin receptor(TfR) is one of the targets for tumor targeted drug delivery system because it is over-expressed in many kinds of tumor cells and tumor-associated blood vessels, but is low-expressed in normal cells. By modifying drug carriers or coupling antitumor drugs with ligands that have high specific affinity for TfR, it is expected to achieve targeted therapy of TfR over-expressed tumors. In this paper, the application progress of TfR functional ligands in tumor targeted drug delivery in recent years is summarized, in order to provide reference for the research of TfR targeted drug delivery systems.

Objective:To investigate the application value of Th1/Th2 cytokines,interleukin-17(IL-17)and serum tumor markers in the diagnosis,prognosis and recurrence of breast cancer.Methods:A total of 200 patients with breast cancer admitted to Inner Mongolia Hospital of Peking University Cancer Hospital from December 2021 to December 2022 were selected,and they were divided into negative group(60 cases),weakly positive(80 cases)group and positive group(60 cases)according to immunohistochemistry indicators.In addition,another 60 persons who underwent physical examination were selected as healthy control group.The changes of the Th1/Th2,IL-17,CA125,CYFRA21-1,CA153 and CEA levels were observed,and the clinical value of the combined detection of the 6 indicators in predicting the prognosis and recurrence of breast cancer was investigated.Results:The results of comparative analysis indicated that the clinical pathological features related to recurrence,histological grading,tumor diameter and lymph node metastasis(x2=7.552,12.037,12.063,8.543,P＜0.05),respectively.Multivariate analysis showed that tumor recurrence,tissue grading,tumor diameter and lymph node metastasis were the important factors for the prognosis of patients with breast cancer(OR=3.096,3.050,3.425,3.031,P＜0.05).Compared with the single prediction of Th1/Th2,IL-17,CA125,CYFRA21-1,CA153 and CEA,the combined prediction of 6 indicators had higher clinical value for prognosis and recurrence of patients with breast cancer,which sensitivity,accuracy and specificity were respectively 96%,93.46%and 85%.Conclusion:The observation on the changes of the combined predictive levels of 6 items,which include Th1/Th2,IL-17,CA125,CYFRA21-1,CA153 and CEA of patients,indicates that the combined detection has high sensitivity and accuracy.This highly efficient and convenient detection method can provide references for improving the prognosis,reducing the recurrence and enhancing the accuracy of assessment.

Chemokines and their receptors play crucial roles in nervous system diseases,among which the CXC chemokine receptor 3(CXCR3)is an important mediator of intercellular communication.CXCR3 not only participates in inflammatory chemotaxis and malignant behaviors of tumor cells but also regulates the neurologic diseases.CXCR3 and its ligands directly or indirectly contribute to neuroinflammation and neuroimmunity,and potentially serve as therapeutic targets for diseases like multiple sclerosis,Alzheimer's disease,and glioma and so on.This review discusses the expression and impact of CXCR3 and its ligands in neurological diseases such as multiple sclerosis,neurologic tumors,neurodegenerative diseases,and neuropathic pain,as well as their associations with CXCR3 ligands.Understanding the mechanisms linking CXCR3 to these diseases could facilitate its potential as an early diagnostic biomarker and a target for drug intervention,and provide the basis of studying the occurrence and developmant of nervous system disease.

Objective:To observe any effects of repetitive high-frequency transcranial magnetic stimulation (rTMS) on the upper limb motor function of stroke survivors with right hemiplegia.Methods:Forty stroke survivors with right hemiplegia were divided at random into a high-frequency rTMS group and a sham stimulation group, each of 20. In addition to routine rehabilitation, the high-frequency rTMS group was given daily high-frequency rTMS 5d per week for 2 weeks, while the sham stimulation group was provided with sham rTMS. Before and after the treatment, both groups were evaluated using the Fugl-Meyer Upper Extremity motor function evaluation scale (FMA-UE), surface electromyography (sEMG), and electroencephalographic microstatus testing. Any adverse reactions in the course of the treatment were recorded.Results:After the treatment, the average FMA-UE scores of both groups had improved significantly, with the average of the high-frequency rTMS group significantly higher than the other group′s average. After the treatment the peak-to-peak sEMG value of the radial long extensor carpi radialis longus muscle in the high-frequency rTMS group was significantly higher than before the treatment and significantly higher than that of the other group. The temporal coverage of microstate B, the average duration and temporal coverage of microstate C, and the temporal coverage and frequency of occurrence of microstate D after treatment of both groups were also significantly improved. The mean duration of electroencephalographic (EEG) microstate A was negatively correlated with the FMA-UE scale scores ( r=-0.57) and its temporal coverage was positively correlated with the peak-to-peak sEMG value of the ulnar lateral wrist flexor. The mean duration of EEG microstate B was positively correlated with the peak-to-peak sEMG value of the triceps brachii and deltoid, and the mean duration of EEG microstate C was also positively correlated with the peak-to-peak sEMG value of the deltoid muscle. Conclusions:High-frequency rTMS can effectively improve the upper limb motor functioning of stroke survivors with right hemiparesis. After high-frequency rTMS, the functional network activity related to EEG microstate B increases significantly, while that related to microstates C and D decreases significantly.

Combined with teaching practice, this study summarizes the teaching contents, methods and effect evaluation of pathological technology for professional postgraduates majoring in pathology. According to the basic conditions of postgraduates, the pathological technology training program has been formulated, student-centered heuristic teaching is carried out by using diversified teaching methods such as flipped classroom, interactive theoretical teaching is carried out by using the intelligent teaching platform, and practical teaching is carried out by using the problem-based learning mode, aiming to improve the theoretical literacy and practical level of pathological technology of professional postgraduates majoring in pathology, improve their clinical research thinking, and lay a foundation for clinical pathological diagnosis and scientific research in the future.

OBJECTIVE: Immunotherapy has brought significant clinical benefits to a subset of patients, but has thus far been disappointing in the treatment of immunologically "cold" tumors. Existing biomarkers that can precisely identify these populations are insufficient. In this context, a potential cold tumor microenvironment (TME) marker FARSB was investigated to reveal its impact on TME and patients' response to immunotherapy across pan-cancer. METHODS: The expression levels and mutational landscape of FARSB in pan-cancer were investigated. Kaplan-Meier and univariate Cox regression analyses were applied to analyze the prognostic significance of FARSB. Pathways affected by FARSB were investigated by gene set enrichment and variation analysis. The relationship between FARSB expression and immune infiltration was examined using the TIMER2 and R packages. Single-cell RNA sequencing (scRNA-seq) data of several cancer types from GSE72056, GSE131907, GSE132465, GSE125449 and PMID32561858 were analyzed to validate the impact of FARSB on the TME. The predictive effect of FARSB on immunotherapy efficacy was explored in 3 immune checkpoint inhibitors (ICIs)- treated cohorts (PMID32472114, GSE176307, and Riaz2017). RESULTS: FARSB expression was significantly higher in 25 tumor tissues than in normal tissues and was associated with poor prognosis in almost all tumor types. FARSB expression exhibited a strong association with several DNA damage repair pathways and was significantly associated with TP53 mutation in lung adenocarcinoma (P < 0.0001, OR=2.25). FARSB characterized a typical immune desert TME and correlated with impaired expression of chemokines and chemokines receptors. Large-scale scRNA-seq analysis confirmed the immunosuppressive role of FARSB and revealed that FARSB potentially shapes the cold TME by impeding intercellular interactions. In 3 ICI-treated cohorts, FARSB demonstrated predictive value for immunotherapy. CONCLUSION This study provides a pan-cancer landscape of the FARSB gene by integrated single-cell and bulk DNA sequencing analysis and elucidates its biological function to promote DNA damage repair and construct the immune desert TME, suggesting the potential value of FARSB as a novel marker for stratifying patients with poor immunotherapeutic benefits and "cold" TME.
Humans ; Tumor Microenvironment ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Sequence Analysis, RNA