ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease （RA-ILD） in DBA/1 mice using Porphyromonas gingivalis （Pg） infection combined with collagen-induced arthritis （CIA）， and to comprehensively evaluate pathological characteristics in joints， lungs， and serum. MethodsForty DBA/1 mice were randomly divided into four groups， i.e.， Control， Pg infection （Pg）， CIA， and Pg infection combined with CIA （Pg+CIA）， with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin （α-SMA）， typeⅠ collagen （ColⅠ）， and fibronectin （FN） in lung tissues. Real-time quantitative polymerase chain reaction（Real-time PCR）was used to measure mRNA expression levels of α-SMA， ColⅠ， FN， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in lung tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of Pg， cyclic citrullinated peptide （CCP）， and immunoglobulin G （IgG）. ResultsJoint lesions： The CIA and Pg+CIA groups showed 100% arthritis incidence， with evident joint redness， swelling， and deformity. The number of affected limbs was 27 and 28， and clinical scores were 68 and 70， respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups， with significantly increased histopathological scores， bone mineral density， bone volume fraction， trabecular thickness， and trabecular number compared to the Control group （P<0.01）. No obvious joint pathology was observed in the Pg group. Lung lesions： The Pg+CIA group exhibited marked alveolar inflammation， interstitial inflammatory cell infiltration， and alveolar wall thickening， with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control， Pg， and CIA groups （P<0.05）. Lung protein and mRNA expression levels of α-SMA， ColⅠ， and FN were markedly increased， and mRNA levels of IL-6， TNF-α， and IL-1β were significantly elevated compared to the Control group （P<0.05）. Serology： The Pg+CIA group showed significantly higher levels of CCP， Pg， and IgG compared with the Control， Pg， and CIA groups （P<0.05）. ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD， along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model， providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics， and serves as a basis for establishing anti-cyclic citrullinated peptide antibody （ACPA）-positive RA-ILD animal models.

ObjectiveTo verify the association between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis by constructing an in vitro co-culture system of testis. MethodsTesticular tissue blocks from 20-25-day-old male rats were placed in an in vitro culture system， and the culture medium was replaced every 2 to 3 days. PCR was used to verify the expression of marker genes of various spermatogenic cells. RNA interference technology was employed to verify the correlation between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis. ResultsThe co-culture system could be continuously cultured for more than 2.5 months in vitro. RT-PCR showed that specific marker genes of spermatogonia， spermatocyte and spermoblast were expressed. The RNA and protein expression of Trib3 and Akt changed after the knocking down of Ddit3 and Trib3， respectively. It demonstrated the existence of Ddit3-Trib3-Akt signaling pathway in rat spermatogenesis. ConclusionThe culture time of more than 2.5 months indicates that the culture system can temporarily maintain the proliferation and differentiation of stem cells， and simultaneously maintain and stabilize spermatogenesis in a simple system. The successful validation of the Ddit3-Trib3-Akt signaling pathway also confirms that this culture system can be used to study possible molecular mechanisms of spermatogenesis in vitro.

Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population，so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018，a cross-sectional design was employed，and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations，subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001)，and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females，participants younger than 55 years，and non-diabetic individuals (P<0.05). Furthermore，smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB，with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study，based on the NHANES 2005-2018 database，found a linear positive correlation between METS-IR and OAB.

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.

BackgroundPrenatal depression has an important impact on maternal health and pregnancy outcomes. Previous studies have shown that maternal prenatal depression is associated with social support， and social support is related to fear of childbirth. However， there is limited research on the relationship among maternal prenatal depression， social support and fear of childbirth， and no studies have specifically explored the influence of social support and fear of childbirth on prenatal depression in primiparous women. ObjectiveTo investigate the current status of prenatal depression among primiparous women， and to analyze the correlation between social support and fear of childbirth， and to further explore the influence of social support and fear of childbirth on prenatal depression in this population， so as to provide references for improving their mental health. MethodsA total of 380 primiparous women admitted to the inpatient department of Chengdu Wenjiang District People's Hospital from December 2022 to September 2023 were enrolled as study subjects. A self-made questionnaire， Edinburgh Postnatal Depression Scale （EPDS）， Social Support Rating Scale （SSRS） and Childbirth Attitudes Questionnaire （CAQ） were used to conduct the survey. Pearson correlation analysis was employed to examine the relationships between scale scores. Multiple linear regression analysis was conducted to identify influencing factors of prenatal depression. ResultsA total of 380 questionnaires were distributed， with 372 （97.89%） valid responses collected. Among the participants， 222 cases （59.68%） were identified with prenatal depression. Pearson correlation analysis revealed that EPDS score was negatively correlated with SSRS score （r=-0.283， P<0.01） and positively correlated with CAQ score （r=0.341， P<0.01）. Multiple linear regression analysis indicated that social support （β=-0.166， P<0.01） and fear of childbirth （β=0.269， P<0.01） were influencing factors of prenatal depression in primiparous women. ConclusionThe prevalence of prenatal depression among primiparous women is concerning， with depression levels showing significant associations with both social support and fear of childbirth.

In order to clarify the effects of drought stress training on the quality and drought resistance of Codonopsis pilosula, this study used PEG to simulate drought stress and employed potting with water control for the drought stress training of C. pilosula plants. The polysaccharide content, secondary metabolites, antioxidant system, and photosynthetic pigment system of C. pilosula after drought stress training were analyzed. The results showed that the content of fructans in the root of C. pilosula increased after two rounds of drought stress treatment, and it was significantly higher than that of the control group. The accumulation of fructans in the root of C. pilosula showed an upward trend during the rehydration treatment. The content of lobetyolin and tangshenoside Ⅰ increased after drought stress treatment compared with that of the control group. The rehydration treatment caused first increasing and then decreasing in the content of lobetyolin, while it had no significant effect on the tangshenoside Ⅰcontent. The content of photosynthetic pigments decreased after drought stress treatment, and it gradually increased during the first round of rehydration and the second round of rehydration. Moreover, the increase was faster in the second round of rehydration than in the first round of rehydration. The content of the peroxidation product malondialdehyde(MDA) and the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) increased after drought stress treatment compared with those of the control group, and they showed a tendency of decreasing during rehydration. Moreover, the decrease was faster in the second round of rehydration than in the first round of rehydration. When the plants of C. pilosula after drought stress training were again subjected to severe drought stress, the wilting rate decreased significantly, and the biomass increases significantly. This study showed that the drought stress training could promote the accumulation of polysaccharides and secondary metabolites in the root of C. pilosula. When encountering drought stress again, C. pilosula plants could quickly regulate the antioxidant system and delay the decomposition of chlorophyll to respond to drought stress. The findings provide a theoretical basis for the ecological cultivation of C. pilosula in arid and semi-arid areas.
Codonopsis/growth & development* ; Droughts ; Polysaccharides/metabolism* ; Stress, Physiological ; Water/metabolism* ; Antioxidants/metabolism* ; Photosynthesis ; Drought Resistance

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics