ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

Objective:To investigate the clinical diagnosis and treatment of granulomatous prostatitis（GP）in patients with Prostate Imaging Reporting and Data System（PI-RADS）scores ≥ 4 on magnetic resonance imaging（MRI）.Methods:The data of 12 GP patients with PI-RADS score ≥ 4 who were admitted to Beijing Chaoyang Hospital，Capital Medical University，from February 2015 to February 2025，were retrospectively analyzed. The patients were aged 51?73 years（mean 66 years）. Presenting complaints included elevated prostate-specific antigen（PSA）levels in 6 cases，prostatic mass in 2 cases，urinary retention in 3 cases，and gross hematuria in 1 case. All 12 patients had concomitant lower urinary tract symptoms. Medical history revealed pulmonary tuberculosis in 2 cases，testicular tuberculosis in 1 case，close contact with tuberculosis in 1 case（spouse diagnosed with pulmonary tuberculosis 5 years earlier），allergic granulomatous vasculitis in 1 case，and intravesical bacillus Calmette-Guérin（BCG）instillation in 1 case. Digital rectal examination（DRE）showed gradeⅠprostatic hyperplasia in 2 cases，grade Ⅱ in 9 cases，and grade Ⅲ in 1 case. Nodules were palpable in 6 patients. The median PSA was 7.20 ng/ml（ranging 1.11?21.90 ng/ml），with 2 cases < 4 ng/ml. Transrectal ultrasound was performed in 10 patients，and prostate volumes were ranging from 29.48 to 109.78 cm3，with 6 cases > 45 cm3. All 12 patients underwent MRI，and all demonstrated PI-RADS scores ≥ 4，typically presenting as low signal intensity on T2-weighted imaging，high signal on diffusion-weighted imaging（DWI），and low apparent diffusion coefficient（ADC）values. Contrast-enhanced MRI in 8 cases revealed heterogeneous enhancement. One patient underwent 68Ga-prostate-specific membrane antigen positron emission tomography-computed tomography（ 68Ga-PSMA PET-CT），which showed band-like increased uptake in the central zone. All 12 patients were preoperatively suspected of prostate cancer，of whom 10 underwent transrectal biopsy and 2 underwent transperineal biopsy. Pathological characteristics and follow-up results were analyzed. Treatment outcomes were analyzed，The International Prostate Symptom Score（IPSS），quality of life（QOL）score，maximum urinary flow rate（Q max），and post-void residual urine（PVR）volume were compared before and 1 month after treatment. Results:Histopathology confirmed GP in all cases，with chronic inflammation in 11 cases and acute inflammation in 1 case. Immunohistochemistry demonstrated positivity for CD68（macrophage marker），high-molecular weight cytokeratin（HCK），and reticulin staining；periodic acid-Schiff（PAS）and acid-fast staining were positive in 2 cases，corresponding to 1 patient with a prior history of pulmonary tuberculosis and 1 with testicular tuberculosis. Two patients underwent thulium laser enucleation of the prostate，while 10 received conservative treatment，including 2 patients with tuberculosis infection who were referred for anti-tuberculosis therapy and 8 patients treated with oral tamsulosin 0.2 mg once daily. Follow-up was completed in 10 patients：9 were followed for 1 ? 3 months（mean 2.4 months），and 1 patient was followed for 9 years before being diagnosed with prostate cancer. Two additional patients，whose pathological findings suggested a possible diagnosis of tuberculous granulomatous prostatitis，were advised to undergo anti-tuberculosis treatment at another hospital and were subsequently lost to follow-up. Among the 2 patients who underwent thulium laser enucleation，IPSS decreased from 26 and 25 to 6 and 5 respectively，QOL scores decreased from 6 and 5 to 1 and 0 respectively，Q max increased from 4.5 and 4.3 ml/s to 23.0 and 21.9 ml/s respectively. In the 8 patients treated conservatively，IPSS decreased from 18.45±7.17 to 14.45±5.03，and QOL score decreased from 5.09±1.04 to 4.09±0.70 at 1 month after treatment，showing significant improvement（ P < 0.05）. Additionally，one patient initially diagnosed with GP and managed conservatively remained stable for 9 years，but subsequently developed urinary retention and underwent thulium laser enucleation，with postoperative pathology confirming prostate cancer. Conclusions:Clinical manifestations of GP are nonspecific，and the condition can easily be mistaken for prostate cancer due to elevated PSA levels and PI-RADS scores ≥4. Some patients may present with acute urinary retention，but definitive diagnosis still relies on prostate biopsy and immunohistochemistry. Treatment should be individualized according to the underlying etiology，with medication as the mainstay，while transurethral surgical intervention may be considered in cases with obstruction. Although GP is a benign lesion，its potential association with prostate cancer warrants vigilance and emphasizes the importance of long-term follow-up.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

OBJECTIVES: To elucidate the anti-aging effect of β-sitosterol (BS), an important component in the fruits of Alpinia oxyphylla Miq., in C. elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis. METHODS: C. elegans treated with 10 µg/mL BS were monitored for survival time and changes in body length, motility, and reproductive function. The effect of ETS-5 gene knockdown on survival time of C. elegans was observed, and the changes in fat accumulation and lipid redox homeostasis in the transfected C. elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio. The mRNA expression levels of ferroptosis-related genes (FTN-1, GPX-1 and AAT-9) were detected using qPCR. The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C. elegans were examined. The effect of BS on nuclear localization of FEV (the human homolog of ETS-5) was validated in cultured human umbilical venous endothelial cells (HUVECs). RESULTS: Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan, promoted lipid accumulation and reduced lipid peroxidation in C. elegans. ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1, AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C. elegans. CONCLUSIONS BS inhibits ferroptosis in C. elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme, a key gene for ferroptosis, which in turn prolongs the lifespan of C. elegans.
Animals ; Caenorhabditis elegans/physiology* ; Ferroptosis/drug effects* ; Alpinia/chemistry* ; Sitosterols/pharmacology* ; Longevity/drug effects* ; Fruit/chemistry* ; Humans

Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*

Objective To elucidate the anti-aging effect of β-sitosterol(BS),an important component in the fruits of Alpinia oxyphylla Miq.,in C.elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis.Methods C.elegans treated with 10 μg/mL BS were monitored for survival time and changes in body length,motility,and reproductive function.The effect of ETS-5 gene knockdown on survival time of C.elegans was observed,and the changes in fat accumulation and lipid redox homeostasis in the transfected C.elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio.The mRNA expression levels of ferroptosis-related genes(FTN-1,GPX-1 and AAT-9)were detected using qPCR.The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C.elegans were examined.The effect of BS on nuclear localization of FEV(the human homolog of ETS-5)was validated in cultured human umbilical venous endothelial cells(HUVECs).Results Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan,promoted lipid accumulation and reduced lipid peroxidation in C.elegans.ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1,AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C.elegans.Conclusion BS inhibits ferroptosis in C.elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme,a key gene for ferroptosis,which in turn prolongs the lifespan of C.elegans.

This paper focuses on the formation of Chinese medicine symptoms in late-life depression(LLD).It delves into an interdisciplinary study that combines interoception and the Chinese medicine concept of'holism of physique and spirit'.LLD,as a common psychiatric disorder,has significant differences in clinical characteristics from younger patients,often manifesting physical discomfort and cognitive impairment.As a key link in the body-brain axis,interoception plays a central role in regulating emotions and behaviors,and its abnormalities are closely related to the development of LLD.The Chinese medicine concept of'holism of physique and spirit'provides a therapeutic perspective that unifies the body and the spirit,emphasizing the interaction between visceral functions and emotional states.Psychological interventions,including cognitive-behavioral therapy and mindfulness meditation,are effective in improving interoception and reducing depressive symptoms.In this study,the relationship between interoception and LLD was analyzed through embodied cognition theory and fMRI technology,and the application of'holism of physique and spirit'in treating late-life depression.The challenges and opportunities of interdisciplinary research in the field of late-life depression is discussed,and future research directions is proposed,aiming to provide more scientific and effective strategies for the prevention,diagnosis,and treatment of LLD.

This paper combs through the current situation and influencing factors of the application of action research in nursing undergraduate teaching reform, and puts forward its problems and suggestions, with a view to providing reference for nursing educators in China to carry out nursing undergraduate teaching action research.

Objective:To explore the experiences of nursing undergraduates with the blended teaching model in midwifery courses.Methods:This qualitative study employed purposive sampling to select 17 nursing undergraduates from the 2021 cohort who participated in the "Midwifery Theory and Skills 2" course in December 2023. Face-to-face semi-structured interviews were conducted, and the data were analyzed using Colaizzi's seven-step method.Results:Three main themes and eight subthemes were identified. First, the blended teaching model enhanced professional knowledge and skills in midwifery: online resources expanded professional knowledge; online demonstration videos improved operational skills; offline group collaboration strengthened communication skills. Second, it developed professional awareness and emotions in midwifery: systematic course learning enhanced professional identity; offline role-playing cultivated emotional perception; clinical experience sharing by teachers fostered a sense of responsibility in midwifery. Third, it optimized blended teaching resources: the user experience on online platforms was improved, and offline classroom settings were better designed.Conclusions:The blended teaching model aids in enhancing students' comprehensive knowledge and skills in midwifery and fosters professional emotions related to the field. It is recommended to further optimize blended teaching resources to improve the effectiveness of this teaching model in midwifery courses.