ObjectiveThe present study aimed to investigate alterations in white matter microstructure and spontaneous neural activity in male college smokers, and to further explore their associations with nicotine dependence. Given that adolescence and early adulthood represent critical periods for brain maturation, particularly for white matter development, understanding the neural correlates of smoking behavior during this stage is of substantial importance for both neuroscience and public health. MethodsA total of 115 male undergraduate students were initially recruited for this study. After quality control and exclusion procedures, 52 male college smokers and 42 demographically matched healthy non-smokers were included in the final analysis. All participants underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI). White matter fiber tracts were reconstructed using the automated fiber quantification (AFQ) method, which enables precise identification and quantification of major fiber bundles. Eighteen major white matter tracts were segmented for each participant. Along the core trajectory of each tract, 100 equidistant nodes were sampled. Fractional anisotropy (FA) was calculated at each node to assess white matter microstructural integrity, while amplitude of low-frequency fluctuation (ALFF) was computed to evaluate spontaneous neural activity within white matter tracts. Between-group differences in FA and ALFF were assessed using two-sample t-tests, with appropriate corrections applied for multiple comparisons. Furthermore, Pearson correlation analyses were conducted to examine the relationships between imaging-derived metrics (FA and ALFF values in regions showing significant group differences) and nicotine dependence severity, as measured by the Fagerström test for nicotine dependence (FTND). ResultsCompared with healthy non-smokers, male college smokers exhibited significantly increased FA values in several white matter tracts, including the left thalamic radiation, right corticospinal tract, forceps major of the corpus callosum, left uncinate fasciculus, and right arcuate fasciculus. These findings suggest altered microstructural organization or increased directional coherence within these pathways. In addition, smokers demonstrated significantly elevated ALFF values in the forceps major, right uncinate fasciculus, and left arcuate fasciculus, indicating enhanced spontaneous neural activity in these white matter regions. Correlation analyses revealed that FA values in the left thalamic radiation and right corticospinal tract were negatively correlated with FTND scores, suggesting that higher levels of nicotine dependence were associated with reduced microstructural integrity or altered fiber organization in these regions. In contrast, ALFF values in the forceps major and right uncinate fasciculus were positively correlated with FTND scores, indicating that greater nicotine dependence was associated with increased spontaneous neural activity in specific white matter pathways. ConclusionThe present study provides evidence that male college smokers exhibit distinct alterations in both white matter microstructure and functional activity. These abnormalities are not uniformly distributed but rather localized to specific fiber tracts implicated in sensorimotor processing, interhemispheric communication, and higher-order cognitive and emotional regulation. Importantly, the observed associations between imaging metrics and nicotine dependence severity suggest that these structural and functional alterations may reflect neurobiological mechanisms underlying addiction. The combination of AFQ-based tract profiling and multimodal MRI offers a sensitive approach for detecting subtle changes along white matter pathways, highlighting its potential utility in identifying neuroimaging biomarkers of nicotine dependence. Overall, these findings indicate that smoking during early adulthood may disrupt ongoing white matter maturation, potentially leading to long-term consequences for brain function. This study provides novel insights into the neural basis of nicotine dependence and underscores the importance of early intervention and prevention strategies targeting young smokers.

Objective: To investigate the efficacy and safety of centrifugal and membrane double plasma molecular adsorption systems (DPMAS) combined with low-dose plasma exchange in the treatment of liver failure. Methods: A retrospective analysis was performed on 60 patients with liver failure treated in our hospital from April 2024 to June 2025. Based on different plasma separation methods, they were divided into the centrifugal DPMAS group (n=30) and the conventional membrane DPMAS group (n=30). The operational parameters, laboratory indicators, and adverse reactions were compared between the two groups. Results: Under the same plasma volume for adsorption and exchange (P>0.05), the centrifugal group showed lower total circulating blood volume, total blood flow rate, and treatment duration compared to the membrane group [10 794 (9 532, 12 637) vs 19 000 (19 000, 21 000) mL, 60 (60, 65) vs 125 (120, 130) mL/min, 169 (141, 193) vs 207 (183, 210) min, P<0.001]. The centrifugal group also had a lower rate of central venous catheter use [(24/30, 80.00%) vs (30/30, 100.00%), P=0.024] and required more calcium supplementation due to sodium citrate anticoagulation [6 (6, 8) vs 2 (2, 2) g, P<0.001]. No significant changes were observed in WBC, Hb, HCT, and PLT levels before and after treatment with the centrifugal group (P>0.05). There was no statistically significant difference in WBC levels before and after membrane group treatment (P=0.199), but the values of Hb, HCT, and PLT showed significant decreases post-treatment compared to pre-treatment [106.50 (102.75, 126.75) vs 123.00 (109.75, 132.00) g/L, 33.20 (29.90, 34.92) vs 34.85 (31.55, 37.52)%, 85.00 (43.25, 139.50) vs 93.00 (61.50, 145.00)×10 /L, P<0.05]. There was no significant difference in coagulation function indexes before and after treatment with centrifugal group (P>0.05). The membrane group showed reduction in fibrinogen (Fib) levels post-treatment [1.50 (1.20, 1.60) vs 1.60 (1.25, 1.80) g/L, P=0.033]. Both groups demonstrated significant decreases in total bilirubin (TBil) and direct bilirubin (DBil) levels after treatment (centrifugal group: 194.70 (107.50, 276.00) vs 239.15 (173.00, 304.17) μmol/L, 101.00 (64.00, 182.30) vs 157.00 (101.00, 195.00) μmol/L; membrane group: 211.50 (118.00, 240.00) vs 263.50 (204.75, 314.00) μmol/L, 188.00 (122.75, 232.25) vs 219.00 (178.50, 267.25) μmol/L, P<0.05]. The incidence of catheter-related complications was lower in the centrifugal group [(2/30, 6.67%) vs (8/30, 26.67%), P=0.038]. Conclusion: The centrifugal DPMAS system demonstrates advantages such as lower blood flow velocity requirements, shorter treatment duration, minimal impact on platelets, and reduced adverse event rates, indicating promising clinical applications.

Five compounds were isolated and purified from the water extract of Elaeagnus oxycarpa Schlechtend leaf by multi-dimensional reversed-phase preparative liquid chromatographic system based on the separation and enrichment model. Their structures were identified by spectral analysis such as NMR, MS, UV, IR and by comparison with literature information as 2,4(1H,3H)-pyrimidinedione (1), elaeagnussugarester B (2), elaeagnussugarester A (3), elaeagnussugarester C (4), gallic acid (5). Compounds 2-4 are new compounds, compound 1 was isolated from Elaeagnus oxycarpa Schlechtend for the first time. The antioxidant and anti-tyrosinase activities of these compounds were evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical method, the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical method, the potassium ferricyanide reduction method and the colorimetric method with L-tyrosine as substrate. The results showed that compounds 2-5 have good antioxidant activities and inhibitory effect on tyrosinase. Compound 4 exhibited the most strong antioxidant activities, with IC₅₀ = 3.59 ± 0.06 μmol·L^-1 for DPPH free radical scavenging ability, IC₅₀ = 10.04 ± 0.20 μmol·L^-1 for ABTS free radical scavenging ability, and total reduction capacity of compound 4 was better than vitamin C respectively. Compound 3 possessed better inhibitory effect on tyrosinase with IC₅₀ = 0.25 ± 0.06 mmol·L^-1.

Objective: To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

Objective:To establish a model of reactive Th17 cells proliferation induced by collagen type Ⅱ(C Ⅱ)in vitro and investigate its influencing factors.Methods:The splenic lymphocytes of normal and CIA mice were isolated and divided into groups.They were given inactivated or non-inactivated C Ⅱ or different concentrations of IL-23(2,10,50 ng/mL),or IL-23p19 antibody.Culturing for 60 hours,the ratio of CD4+RORγt+Th17 cells was detected by flow cytometry.Then,the results obtained are ana lyzed,and the corresponding conclusions are drawn.Results:After 60 hours of culture in vitro,the ratio of Th 17 cells stimulated by inactivated or non-inactivated C Ⅱ in normal mouse spleen lymphocytes was significantly lower than that before culture,and the ratio of Th17 cells not stimulated by C Ⅱ in CIA mouse spleen lymphocytes was also significantly lower than that before culture,while the ratio of Th17 cells stimulated by inactivated C Ⅱ or non-inactivated C Ⅱ in CIA mouse spleen lymphocytes was significantly higher than that before culture,and there was a significant difference compared with the CIA control group(P＜0.05).However,there was no statistical difference in the ratio of Th17 cells between the two groups without inactivated C Ⅱ and inactivated C Ⅱ(P=0.44).After the analysis of the data obtained from the study,it was further concluded that different concentrations of IL-23 did not affect the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro,but after adding IL-23p19 antibody neutralization reagent,the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro decreased significantly,with a statistical difference compared with the blank control group(P＜0.01).Conclusions:This study established an in vitro Th17 cell proliferation model induced by type Ⅱ collagen,exploring the effects of IL-23 and collagen activity on Th17 cell proliferation.The results showed that CⅡ stimulation significantly promoted Th17 cell proliferation in CIA mice,with both active and inactivated CⅡ inducing proliferation.IL-23 was found to be essential for the maintenance of Th17 cells,although its direct proliferative effect was limited.These findings provide new experimental evidence and theoretical support for the mechanism research of rheumatic diseases and IL-23/IL-17 pathway-targeted therapies,with important implications for immune regulation and drug development.

BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

Objective:To investigate the characteristics of cell subsets in rheumatoid arthritis patients complicated with interstitial lung disease (RA-ILD).Methods:The clinical data of 344 patients with RA admitted to the Affiliated Hospital of Nantong University from June 2022 to November 2023 were analyzed. The patients were categorized into two groups based on the diagnostic criteria of ILD: 120 cases in the RA associated with ILD group (RA-ILD group) were included and 224 cases in the RA without ILD group (RA group), the clinical characteristics were compared between the RA-ILD group and the RA group. The influence factors of RA-ILD were analyzed by univariate and multivariate logistic regression.Results:Compared with RA patients, RA-ILD patients were more common in males, with older age, longer course of disease, and higher smoking rate ( P<0.05). The high titer anti-cyclic citrullinated peptide (CCP) antibody, white blood cells, neutrophil, neutrophil to lymphocyte count ratio, aspartate aminotr-ansferase(AST), creatinine (Cr) and lactate dehydrogenase (LDH) levels in RA-ILD patients were higher than those in RA patients. The triglyceride level was lower than that of RA patients ( P<0.05). The percentage of total T cells in peripheral blood lymphocyte subsets in RA-ILD patients [68.65%(62.22%, 76.78%)] was lower than that in RA patients [71.88%(65.83%, 78.39%)] ( Z=-2.26, P=0.024). The percentage of CD4 +T cells [40.2% (32.10%, 45.23%)] was lower than that of RA patients [46.5% (39.74%, 53.19%)] ( Z=-6.29, P<0.001). CD4 +T cell count [486.50 (324.25, 636.75)cells/μl] was lower than that of RA patients [564.50 (438.25, 752.00)cells/μl] ( Z=-4.50, P<0.001). CD4 +/CD8 + levels [1.86 (1.26, 2.18)] were lower than those of RA patients [2.03 (1.40, 2.94)] ( Z=-2.79, P=0.005). B cell count [127.00 (78.00, 207.25)cells/μl] was lower than that of RA patients [163.50 (91.25, 231.50)cells/μl] ( Z=-2.11, P=0.035), The percentage of NK cells in peripheral blood lymphocyte subsets in RA-ILD patients [19.72%(13.14%, 25.83%)] was higher than that in RA patients [12.55% (8.23%, 17.80%)] ( Z=6.13, P<0.001). NK cell count [182.50 (109.00, 293.75)cells/μl] was higher than that of RA patients [156.00 (89.00, 194.75)cells/μl] ( Z=3.17, P=0.002). The percentage of CD8 +T cells [25.10 %(18.74%, 29.86%)] was higher than that of RA patients [22.27% (17.32%, 29.21%)] ( Z=2.00, P=0.046). Imaging types of RA-ILD patients showed that usual interstitial pneumonia (UIP) was more common, followed by non-specific interstitial pneumonia (NSIP). CD8 + T cell count and percentage expression level in UIP were higher than NSIP, and CD4 +/CD8 + expression level was lower than NSIP ( P<0.05). Multivariate logistic regression analysis of indicators with statistical differences were male gender [ OR(95% CI)=2.888 (1.556, 5.360), P=0.001], age [ OR(95% CI)=1.065 (1.033, 1.098), P<0.001], disease duration [ OR(95% CI)=1.004 (1.001, 1.007), P=0.013], high titer anti-CCP antibody [ OR(95% CI)=2.764 (1.214, 6.292), P=0.015], LDH [ OR(95% CI)=1.006 (1.002, 1.009), P=0.001], CD4 +T cell percentage [ OR(95% CI)=0.964 (0.929, 1.000), P=0.049], CD4 +T cell count [ OR(95% CI)=0.998 (0.996, 1.000), P=0.011] and NK cell count [ OR(95% CI)=1.004 (1.001, 1.007), P=0.003]. These indicators were correlated factors for RA-ILD. Conclusion:Male patients with older age, history of smoking and a long disease course are more likely to develop ILD. Male gender with older, long disease course, high titer anti-CCP antibody, increased LDH and NK cell count, CD4 +T cell percentage and decreased CD4 +T cell count are correlation factors for RA-ILD, which may help RA patients to recognize ILD early.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones