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.

BACKGROUND:Mesenchymal stem cells have been widely used in the treatment of various diseases due to their wide range of sources,their ease of proliferation in vitro and their ability to secrete a range of immunomodulatory factors to suppress inflammation and promote tissue repair and regeneration.However,in the treatment of many diseases,the therapeutic effect is limited.The effort to engineer and modify mesenchymal stem cells for specific disease pathogenesis or intervention targets is an important development for cell therapy in the future.OBJECTIVE:Interleukin-10 is a typical anti-inflammatory cytokine that helps to modulate the immune response and induces macrophage polarization towards an anti-inflammatory phenotype.This study investigated the therapeutic effect of interleukin-10 engineered human umbilical cord mesenchymal stem cells on inflammatory bowel disease.METHODS:Human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were established by electro-transfection,and screened for clinical-grade cells based on the cell therapy product criteria.C57BL/6J mice were given 5%aqueous dextran sulfate sodium ad libitum to establish a model of acute colitis.Empty plasmid-transfected human umbilical cord mesenchymal stem cells or interleukin-10-human umbilical cord mesenchymal stem cells(1×106 cells/each mouse)were injected on day 1 before modeling(tail vein injection)and day 4(intraperitoneal injection)after modeling,respectively.On day 6 after modeling,colon tissue sections were taken for hematoxylin-eosin staining to assess histological changes.Immunofluorescence staining was performed to detect the expression of proliferating cell nuclear antigen and CD31.RESULTS AND CONCLUSION:The engineered human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were constructed,and met the quality standard of clinical-grade human umbilical cord mesenchymal stem cells.Human umbilical cord mesenchymal stem cells could repair acute colitis in mice.The therapeutic effect of interleukin-10-human umbilical cord mesenchymal stem cells was more efficacious,which more significantly suppressed body weight loss(P<0.05),colon shortening(P<0.05),and damage of colonic tissues(P<0.05)in acute colitis mice.In interleukin-10-human umbilical cord mesenchymal stem cell treatment group,there were significantly more proliferating cell nuclear antigen-positive cells and CD31-positive cells in the colon sections than in the human umbilical cord mesenchymal stem cell treatment group,suggesting that interleukin-10-overexpressing human umbilical cord mesenchymal stem cells contributed to the repair of colon tissue by significantly promoting the proliferation of intestinal tissues and angiogenesis.

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.

BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

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.

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.