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 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.

ObjectiveTo investigate the mechanism of Huazhuo Jiedu prescription in treating ulcerative colitis （UC） by regulating mitophagy. MethodsThe genes related to mitophagy and UC were retrieved from GeneCards， and then the common genes of mitophagy and UC were analyzed by metascape to identify the genes related to mitophagy in UC. Animal experiments were carried out to decipher the mechanism by which Huazhuo Jiedu prescription treated UC by regulating mitophagy. Sixty C57BL/6 male mice were randomized into normal， model， high-， medium-， and low-dose （50， 25， 12.5 g·kg^-1， respectively） Huazhuo Jiedu prescription， and mesalazine （0.52 g·kg^-1·d^-1） groups， with 10 mice in each group. After successful modeling by the dextran sulfate sodium-free drinking method， the colonic mucosal damage was observed by hematoxylin-eosin staining， and the ultracellular structure of colon mucosa was observed by transmission electron microscopy. The expression levels of mitophagy-related proteins PTEN-induced putative kinase 1 （PINK1） and Parkin protein were determined by Western blot. The expression of prohibitin 2 （PHB2）， ubiquitin-specific protease 15 （USP15）， ubiquitin-specific protease 30 （USP30） in the colon tissue was detected by immunofluorescence （IF）. ResultsAll the drug intervention groups showed ameliorated pathological manifestations of the colonic mucosa and improved mitochondrial structures in UC mice. Compared with the normal group， the model group demonstrated up-regulated protein levels of PINK1 and Parkin （P<0.05）， enhanced average fluorescence intensity of PHB2 （P<0.05）， and weakened average fluorescence intensity of USP15 and USP30 （P<0.05）. Compared with the model group， the mesalazine group and the high- and medium-dose Huazhuo Jiedu prescription groups showcased down-regulated protein levels of PINK1 and Parkin （P<0.05）， decreased average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. The low-dose Huazhuo Jiedu prescription group showed down-regulated protein levels of PINK1 and Parkin （P<0.05）， weakened average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. ConclusionHuazhuo Jiedu prescription can attenuate the intestinal mucosal injury and improve the mitochondrial cell ultrastructure in UC mice by regulating the expression of PINK1-Parkin pathway and inhibiting excessive mitophagy.

ObjectiveTo investigate the mechanism of Huazhuo Jiedu prescription in treating ulcerative colitis （UC） by regulating mitophagy. MethodsThe genes related to mitophagy and UC were retrieved from GeneCards， and then the common genes of mitophagy and UC were analyzed by metascape to identify the genes related to mitophagy in UC. Animal experiments were carried out to decipher the mechanism by which Huazhuo Jiedu prescription treated UC by regulating mitophagy. Sixty C57BL/6 male mice were randomized into normal， model， high-， medium-， and low-dose （50， 25， 12.5 g·kg^-1， respectively） Huazhuo Jiedu prescription， and mesalazine （0.52 g·kg^-1·d^-1） groups， with 10 mice in each group. After successful modeling by the dextran sulfate sodium-free drinking method， the colonic mucosal damage was observed by hematoxylin-eosin staining， and the ultracellular structure of colon mucosa was observed by transmission electron microscopy. The expression levels of mitophagy-related proteins PTEN-induced putative kinase 1 （PINK1） and Parkin protein were determined by Western blot. The expression of prohibitin 2 （PHB2）， ubiquitin-specific protease 15 （USP15）， ubiquitin-specific protease 30 （USP30） in the colon tissue was detected by immunofluorescence （IF）. ResultsAll the drug intervention groups showed ameliorated pathological manifestations of the colonic mucosa and improved mitochondrial structures in UC mice. Compared with the normal group， the model group demonstrated up-regulated protein levels of PINK1 and Parkin （P<0.05）， enhanced average fluorescence intensity of PHB2 （P<0.05）， and weakened average fluorescence intensity of USP15 and USP30 （P<0.05）. Compared with the model group， the mesalazine group and the high- and medium-dose Huazhuo Jiedu prescription groups showcased down-regulated protein levels of PINK1 and Parkin （P<0.05）， decreased average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. The low-dose Huazhuo Jiedu prescription group showed down-regulated protein levels of PINK1 and Parkin （P<0.05）， weakened average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. ConclusionHuazhuo Jiedu prescription can attenuate the intestinal mucosal injury and improve the mitochondrial cell ultrastructure in UC mice by regulating the expression of PINK1-Parkin pathway and inhibiting excessive mitophagy.

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.

Senile trichiasis is primarily manifested by eyelid laxity, decreased horizontal elasticity and tension of the eyelids, leading to friction between the eyelashes and the cornea, which subsequently causes corneal damage and vision decline. Surgical intervention remains the most effective therapeutic approach for senile trichiasis. This article elaborates on the epidemiological characteristics, pathological mechanisms, and clinical manifestations of senile trichiasis and systematically reviews the surgical treatment method for upper and lower eyelid trichiasis, including traditional surgical techniques and emerging minimally invasive procedures combined with personalized therapies. Through a literature review, the effectiveness and recurrence rates of surgical treatment are summarized, emphasizing the importance of preoperative assessment and individualized treatment. Additionally, strategies and recommendations for preventing senile trichiasis are proposed.

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

[Objective]To analyze the prescriptions for the differentiation,treatment and application in the Treatise on Three Categories of Pathogenic Factors regarding low back pain by using data mining technology,and to explore CHEN Wuze's understanding of low back pain as well as the rules for prescribing medications.[Methods]Prescriptions that met the inclusion criteria were screened to establish a database.The IBM SPSS Modeler 18.0 software was used for association rule analysis,and the SPSS statistics 26.0 software was adopted for drug frequency statistics and cluster analysis.Combined with ancient literature records,CHEN's understanding of low back pain,treatment ideas and medication rules were analyzed.[Results]A total of 63 prescriptions were included,involving 143 types of Chinese medicinal herbs with a total frequency of 581 applications.Seventeen high-frequency herbs were identified,primarily including roasted licorice(Glycyrrhiza uralensis),poria(Poria cocos),ginger(Zingiber officinale),aconite(Aconitum carmichaelii),white peony root(Paeonia lactiflora),and cinnamon bark(Cinnamomum cassia).Common herb pairs included"Atractylodes macrocephala-Poria cocos","Poria cocos-Cinnamomum cassia"and"Cinnamomum cassia-Angelica sinensis".The predominant therapeutic effects involved tonifying and deficiency-replenishing medicinals.Medicinal properties were mainly warm,neutral and cold,with sweet,pungent and bitter flavors predominating.Herbs primarily entered the spleen,kidney and lung meridians.Cluster analysis categorized high-frequency herbs into three groups associated with functions such as dispelling wind and eliminating dampness,tonifying the liver and kidney,relaxing tendons and nourishing blood and warming Yang to resolve dampness.[Conclusion]CHEN's approach to treating low back pain emphasizes differentiation and treatment based on the three etiological factors(internal,external and non-internal/external causes),and a spleen-stomach-focused treatment strategy.Core therapeutic principles included strengthening the spleen to eliminate dampness,warming Yang to resolve dampness and warming/unblocking blood vessels.This article summarizes and extracts the medication rules and academic thoughts of CHEN from the Yongjia medical school in treating lumbago,which has reference value for the clinical treatment of lumbago.