BACKGROUND:Mitochondrial autophagy is closely related to the occurrence and development of steroid-induced osteonecrosis of the femoral head(SONFH),but specific biomarkers and regulatory mechanisms remain unclear. OBJECTIVE:To identify the key biomarkers of mitochondrial autophagy in steroid-induced osteonecrosis of the femoral head using machine learning algorithms and to conduct an immune infiltration analysis. METHODS:The SONFH datasets GSE123568 and GSE74089 were downloaded from the GEO database,serving as the training and validation sets,respectively.Differentially expressed genes between SONFH and control groups were selected,and weighted gene co-expression network analysis was performed.Mitochondrial autophagy-related genes were obtained from MitoCarta3.0 and intersected with differentially expressed genes and module genes.Two machine learning algorithms were utilized to identify key genes of SONFH mitochondrial autophagy,and validated using an external validation set.CIBERSORT and immune infiltration analysis were employed to assess the proportion of immune cells,and ssGSEA was used to analyze the correlation between mitochondrial autophagy genes and immune cells. RESULTS AND CONCLUSION:Differential analysis identified a total of 1 163 differentially expressed genes,including 663 upregulated genes and 500 downregulated genes.Weighted gene co-expression network analysis identified 4 key modules,comprising 1 412 module genes.Intersection with mitochondrial autophagy genes yielded 39 intersecting genes as disease-related mitochondrial autophagy genes.Gene ontology enrichment analysis showed that the biological processes were mainly related to heme metabolism,mitochondrial transport,nucleotide bisphosphate metabolism and thioester metabolism,and the cellular components were mainly related to mitochondrial matrix,mitochondrial outer membrane,organelle outer membrane and mitochondrial inner membrane,and the molecular functions were mainly related to fatty acid ligase activity,iron-sulfur cluster binding,and cofactor A ligase activity.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mapped out a total of six pathways,which were mainly related to fatty acid degradation,mitochondrial autophagy,butyric acid metabolism,fatty acid biosynthesis and cofactor biosynthesis.Through LASSO regression and RFE-SVM algorithm analysis,four intersecting genes(ALDH5A1,FBXL4,MCL1,and STOM)were identified.The receiver operating characteristic curves of the four core genes and the diagnostic column chart validation set were all greater than 0.9.The occurrence and development of SONFH were related to immune cells such as dendritic cells,bone marrow-derived suppressor cells,regulatory T cells,and central memory CD8 T cells.To conclude,the four key mitochondrial autophagy genes ALDH5A1,FBXL4,MCL1,and STOM play a crucial role in the progression of SONFH through osteoclast differentiation and immune mechanisms.Additionally,all four genes have good disease prediction efficacy and can serve as biomarkers for the diagnosis and treatment of SONFH.

Osteoporosis （OP） is a metabolic disorder characterized by microstructural deterioration of bone and increased bone fragility due to reduced bone mass， which can cause the development of bone-related diseases. This condition imposes significant economic and psychological burdens on patients. While modern medicine has extensively researched the pathogenesis of OP， it remains incompletely understood. Current clinical management primarily relies on anti-resorptive drugs and synthetic metabolic agents. However， long-term use of some medications may yield suboptimal therapeutic outcomes and lead to severe adverse reactions. Given the necessity for prolonged or lifelong treatment for OP， there is a critical need to identify highly effective， safe， and cost-effective pharmaceutical interventions. In light of evolving disease management paradigms and recent advancements in OP research， traditional Chinese medicine has demonstrated emerging advantages in addressing this condition. Through literature review， this study delves into the pathogenesis of OP from five perspectives： hormonal dysregulation， autophagy， ferroptosis， oxidative stress， and intestinal flora alteration. Furthermore， it summarizes the therapeutic efficacy and specific mechanisms of traditional Chinese medicine monomers and compound formulas against OP through regulating hormone levels， interfering with autophagy， inhibiting ferroptosis， counteract oxidative stress，and maintain intestinal flora balance. These multifaceted insights are expected to provide theoretical reference and guide future clinical traditional Chinese medicine approaches for preventing and managing OP.

Objective To clarify the changes in CXCL5 in serum and gastric tissues of patients with chronic atrophic gastritis(CAG)and precancerous lesions of gastric cancer(PLGC)and to investigate the predictive value of CXCL5 for the diagnosis of CAG and PLGC.Methods This study enrolled 72 participants of CAG admitted to the Department of Splenology and Gastroenterology of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to June 2023,with gastroscopy and pathologically confirmed diagnosis,as well as 68 healthy participants who underwent gastroscopy in the same period at our department.We collected clinical information and laboratory results from all participants.The logistic regression analysis methods were used to identify the diagnostic value of serum CXCL5.Furthermore,in order to clarify the role of CXCL5 in the developent of CAG,a total of 15 patients each with CAG,intestinal metaplasia,and dysplasia treated at our hospital from June 2023 to December 2023,and 15 healthy participants were selected.The relationship between the expression of CXCL5 and the degree of clinicopathology was analysed in each group using ELISA,PCR,and immunohistochemistry staining to validate and assess the diagnostic efficacy of CXCL5.Results The study found that several factors were associated with CAG,including family history of tumours,smoking and alcohol consumption history,dietary regularity,Helicobacter pylori infection,the number of lesions,gastric function scores and CXCL5(P<0.05).The ROC curve had an AUC of 1.00 and a Youden index of 0.986,indicating excellent predictive ability.The ELISA results indicated a significantly higher serum CXCL5 expression level in the CAG,intestinal metaplasia,and dysplasia groups compared to the normal group.There was a positive correlation between the serum CXCL5 expression level and the degree of pathology.The PCR and immunohistochemistry staining results indicate that the mRNA and pro-tein expression levels of CXCL5 in gastric tissues of patient groups were significantly higher compared to the nor-mal group.Furthermore,the mRNA and protein expression levels of CXCL5 in gastric tissues were positively correlated with the degree of pathology.Conclusions The results indicate that CXCL5 is highly expressed in the serum and gastric tissues of patients with CAG and PLGC,and its expression level is positively correlated with the degree of pathology.Therefore,CXCL5 could serve as a predictive indicator and a potential therapeutic target for the diagnosis of CAG and PLGC.

Objective:To evaluate the effect of workshop-based incontinence associated dermatitis (IAD) training course for geriatric nurse specialists, and to provide references and evidence for the application of workshop teaching model in specialized nursing training.Methods:The convenience sampling method was used to select 40 participants in the 9th Chongqing Geriatric Nurse Specialist Training Program in May 2021 as the intervention group, and IAD training was conducted using the workshop method. The 42 participants in the 8th Chongqing Geriatric Nurse Specialist Training Program in May 2020 were selected as the control group, who received IAD training through traditional teaching methods. After the training, the achievement of teaching objectives and teaching satisfaction were compared between the two groups using questionnaire survey, and IAD nursing knowledge and attitudes were compared using scales. SPSS 27.0 was used for the t-test and chi-square test. Results:The questionnaire survey showed that the intervention group achieved higher teaching objectives in all dimensions compared to the control group ( P<0.05). Compared with the control group, the intervention group had higher scores in teaching satisfaction regarding teaching format, interest in learning, practical skills, theoretical understanding, integration of theory and practice, and problem-solving abilities ( P<0.05). Compared with the control group, the intervention group demonstrated significantly higher scores in IAD nursing knowledge [(11.32±1.56) vs. (9.02±2.26), P<0.05] and attitudes [(37.63±3.54) vs. (32.81±2.97), P<0.05]. Conclusions:The workshop training has been highly recognized by the trainees, contributing to improved implementation effectiveness of teaching, enhancing the scores of IAD nursing knowledge and attitudes. This approach offers a new perspective for training with a practical focus in the specialized nursing field.

Purpose/Significance To explore and implement the automated interpretation of pediatric medical exam answers,so as to enhance the efficiency and quality of answer explanation compilation.Method/Process The paper proposes a method that combines latent semantic indexing(LSI),MC-BERT,and the CoSENT model.Initially,multiple candidate answer explanations are extracted from ref-erence documents using the LSI method and the MC-BERT model.Subsequently,the CoSENT model is employed to calculate the simi-larity between the candidate explanations and the question stems as well as the answer options.The candidate explanation with the highest similarity is then selected as the final answer explanation.Result/Conclusion The experimental results show that the method presented in this paper achieves a precision rate of 72.6％.Compared to single methods or models,it significantly improves the recall and precision of answer parsing,effectively enhances the efficiency of compiling question answer explanations,reduces the burden on educators,and pro-vides significant data support for educational research.

Objective:To explore the patterns of failure after postoperative intensity-modulated radiotherapy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric cancer or gastroesophageal junction carcinoma with pathological stages T 3-4N 0 or T xN 1-3 admitted to Cancer Hospital of Chinese Academy of Medical Sciences from May 2009 to December 2018 were retrospectively analyzed. All patients received postoperative radiotherapy. During the follow-up, tumor recurrence was confirmed by imaging or endoscopic or pathological data, etc. According to the location of tumor recurrence, recurrence patterns were divided into local, regional and distant recurrence. Differences in recurrence patterns among different groups were compared using t-test and Chi-square test. Patient survival was assessed through Kaplan-Meier method. Results:A total of 76 patients were enrolled, with a median age of 49 years old (27-67 years old), 34 cases (45%) were classified as T 3 stage, 40 cases (53%) of T 4 stage, and 75 cases (99%) of N 1-3 stage, respectively. Seventy-three patients (92%) were classified as stage Ⅲ, and 38 patients (50%) underwent D2 dissection. The median follow-up time was 32.8 months (7.1-138.5 months). The median time of recurrence was 17.6 months (2.9-113.6 months). The median survival time after recurrence was 8.19 months (0.6-91.9 months). There were 13 cases (17%) of local recurrence, 6 cases (8%) of regional recurrence, and 72 cases (95%) of distant metastasis in patients. Peritoneal metastasis (33 cases, 43%) and distant lymph node metastasis (12 cases, 16%) were the main patterns of distant recurrence. Conclusions:By intensity-modulated radiotherapy technology, adjuvant radiotherapy yields favorable local and regional control for gastric cancer. Distant metastasis is still the main pattern of recurrence.

Objective:To analyze clinical features, short-term efficacy and side effects of salvage re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy, to investigate the prognostic factors of re-irradiation with precise radiotherapy techniques.Methods:A retrospective analysis was performed on patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy treated in the Fourth Hospital of Hebei Medical University from January 2008 to December 2016. The patients underwent re-irradiation therapy (re-RT) or re-irradiation therapy concurrent chemotherapy (re-CCRT). The main observation index was after-recurrence survival (ARS), which was calculated by Kaplan-Meier method for survival analysis. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox regression model.Results:A total of 109 patients were included, with a median age of 66 years (43-89 years), and a median follow-up time of 120.8 months (79.0-176.5 months). The objective response rates (ORR) and dysphagia improvement rates (DIR) in all patients were 64.2% and 63.0%, respectively. The median ARS and 1-, 3-, 5-, 8-year survival rates in all patients were 7.8 months and 32.1%, 9.2%, 7.3% and 2.3%, respectively. The median ARS and 1-, 3-, 5-years survival rates were 10.8 months and 45.9%, 13.5%, 10.8% for patients with time to recurrence (TTR) ≥24 months, significantly longer than those of 5.7 months and 25.0%, 6.9%, 5.6% for patients with TTR<24 months ( χ2=7.99, P=0.005). The median ARS in groups with re-irradiation dose of ≤50 Gy,>50-54 Gy, and>54 Gy groups were 5.7, 10.0 and 8.1 months, respectively ( χ2=6.94, P=0.031). The 1-, 3- and 5-year survival rates were 30.4%, 5.1%, and 3.8% for re-RT versus 36.7%, 20.0%, and 16.7% for re-CCRT ( χ2=2.12, P=0.145). Multivariate analysis showed that TTR ( HR=0.607, 95% CI=0.372-0.991, P=0.046) and lesion length ( HR=0.603, 95% CI=0.371-0.982, P=0.042) were the independent factors for ARS. There was no significant difference in ≥2 grade pneumonitis and 2-3 grade radiation esophagitis between the re-RT and re-CCRT groups ( χ2=0.25, P=0.619; χ2=0.51, P=0.808). The morbidity of ≥2 grade myelosuppression in the re-RT group was significantly lower than that in the re-CCRT group (3.7% vs. 36.7%, χ2=18.15, P<0.001). Conclusions:Precise re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy can alleviate dysphagia, but ARS remains poor. Re-irradiation dose range from>50-54 Gy may be suitable for locally relapse patients as salvage treatment. Patients with TTR≥24 months and lesion length ≤5 cm obtain favorable prognosis.

Objective:To analyze clinical efficacy of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma and identify prognostic factors.Methods:Clinical data of patients with anal squamous cell carcinoma who received intensity-modulated chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2010 to January 1, 2022 were retrospectively analyzed. Regular follow-up was carried out. The main indexes included disease-free survival (DFS), locoregional failure-free survival (LRFFS) and overall survival (OS), and adverse reactions were recorded. The survival curve was delineated by Kaplan-Meier method and the influencing factors of survival were analyzed by Cox regression models.Results:A total of 65 patients were enrolled with 19 (29%) males and 46 (71%) females. According to the American Joint Committee on Cancer (AJCC) 7 th edition staging, there were 7 (11%), 28 (43%), 10 (15%), and 20 (31%) patients with stage I, II, IIIa, and IIIb, respectively. Before the chemoradiotherapy, 2 (3%) patients received chemotherapy and 12 (18%) patients received local resection. The median dose of radiotherapy was 54 Gy (range: 45-64 Gy) and the main concurrent chemotherapy regimen was capecitabine combined with cisplatin ( n=34, 52%). The completion rate of radiotherapy during concurrent chemoradiotherapy was 100%, and the chemotherapy completion rate was 88%. During the therapy, 5 patients (8%) were interrupted but completed concurrent chemoradiotherapy in full dose, and 8 patients (12%) reduced the dose of concurrent chemotherapy due to the toxicities. During the chemoradiotherapy, 15 cases (23%) experienced grade 3-4 leukopenia, and 17 cases (26%) experienced grade 3-4 radiation dermatitis. No treatment-related death occurred during the treatment. The median follow-up time was 50.4 months (range: 4.4-142.2 months), local recurrence occurred in 7 cases (11%), distant metastasis occurred in 3 cases (5%), and the 5-year DFS, LRFFS and OS rates were 78.8%, 86.5% and 85.1%, respectively. Cox univariate analysis indicated that T stage was significantly associated with DFS ( P=0.006), and tended to be associated with OS ( P=0.054). Conclusions:Intensity-modulated radiotherapy combined with concurrent chemotherapy is an effective treatment for anal squamous cell carcinoma, with tolerable acute toxicities. T stage is an influencing factor of DFS in anal squamous cell carcinoma patients.

BACKGROUND:Ferroptosis-related genes have been found to play an important role in the pathogenesis of rheumatoid arthritis.However,there is currently a lack of immune expression of ferroptosis-related signature genes in rheumatoid arthritis and the construction of competing endogenous RNA(CeRNA)interaction networks.Machine learning,as a powerful signature gene selection algorithm based on bioinformatics,can more accurately identify ferroptosis-related signature genes that dominate the pathogenesis of rheumatoid arthritis. OBJECTIVE:To screen ferroptosis-related signature genes in rheumatoid arthritis using bioinformatics and machine learning methods,and to analyze the correlation between ferroptosis-related signature genes and immune infiltration and the construction of CeRNA network of ferroptosis-related signature genes. METHODS:Rheumatoid arthritis-related microarrays were obtained from the GEO database,and ferroptosis-related genes and their differential gene expression were extracted using R language.The differentially expressed genes were screened using machine learning methods.The LASSO regression and SVM-RFE methods were used for signature gene screening,and the genes filtered by both were re-intersected to finally obtain the signature genes in rheumatoid arthritis.Receiver operating characteristic curves were used to assess the accuracy of the screened signature genes for disease diagnosis.Immune infiltration of rheumatoid arthritis and normal synovial tissues was analyzed using the CIBERSORT algorithm,and the correlation between the signature genes and immune cells was analyzed.Finally,the CeRNA network of ferroptosis-related signature genes for rheumatoid arthritis was constructed and the disease signature genes were validated. RESULTS AND CONCLUSION:A total of 150 ferroptosis-related genes in rheumatoid arthritis were obtained,including 55 up-regulated genes and 95 down-regulated genes.GO and KEGG enrichment analyses identified 18 GO significantly correlated entries and 30 KEGG entries respectively,mainly involving metal ion homeostasis,ferric ion homeostasis and oxidative stress response.Machine learning analysis finally identified disease signature genes GABARAPL1 and SAT1.GSEA analysis found that adipocytokine signaling pathway,drug metabolism cytochrome P450,fatty acid metabolism,PPAR signaling pathway,tyrosine metabolism were mainly concentrated when GABARAPL1 was highly expressed,and chemokine signaling pathway,intestinal immune network on IGA production were mainly concentrated when SAT1 was highly expressed.Immune infiltration analysis found that nine immune cells were significantly different in rheumatoid arthritis and normal synovial tissues,in which plasma cells,T-cell CD8,and T-cell follicular helper were highly expressed and the rest were lowly expressed in the disease group.Single gene and immune cell correlation analysis found that GABARAPL1 was positively correlated with dendritic resting cells,activated NK cells,and macrophage M1,with the most significant correlation with dendritic resting cells,while SAT1 was positively correlated with T cell CD4 and γδ T cells and negatively correlated with NK resting cells.GSVA analysis found that SAT1 was upregulated in ascorbic acid and aldehyde metabolism,while downregulated in B-cell receptor signaling pathway,Toll-like receptor signaling pathway,T-cell receptor signaling pathway,and natural killer cell-mediated cytotoxicity.GABARAPL1 showed a down-regulation trend in PPAR signaling pathway,metabolism of nicotinate and nicotinamide,tryptophan metabolism,fatty acid metabolism,and steroid biosynthesis.Sixty long non-code RNAs may play a key role in the development of rheumatoid arthritis.To conclude,the occurrence of rheumatoid arthritis is significantly correlated with the abnormal expression of rheumatoid arthritis-induced ferroptosis-related signature genes,and the signature genes induce disease development via relevant signaling pathways.By analyzing rheumatoid arthritis-related long non-code RNAs-mediated ceRNA networks,potential therapeutic targets and signaling pathways can be identified to further elucidate its pathogenesis and provide a reference basis for subsequent experimental studies.

Objective:To study the differential gene expression and immune cell infiltration of gout patients,to find the key genes and immune cells of gout pathogenesis,and to explore the relationship between immune cells and gout.Methods:The gout chip GSE160170 was downloaded from the GEO database,and the differential gene expression analysis was carried out with the help of R language.Then,the STRING database was used to analyze the differential gene,and the Cytoscape software was used to screen the key genes,and then carry out enrichment analysis.At the same time,the infiltration of immune cells were analyzed.Results:The study found that IL-6,IL-1β,TNF,CCL3,CXCL8 and CXCL1 were key genes in the pathogenesis of gout,which were mainly exerted by IL-17,Toll-like receptor,NOD-like receptor,NF-κB and other signaling pathways.Processes such as cellular responses to lipo-polysaccharides,bacteria-derived molecules,and biological stimuli lead to disease;immune infiltration results indicate that memory B cells,activated NK cells,activated dendritic cells,activated mast cells and eosinophils were involved in the disease.It was signifi-cantly expressed in gout patients;the correlation analysis between immune cells showed that the expression of follicular helper T cells were positively correlated with the expression of activated mast cells,and the expression of unactivated NK cells and monocyte were negatively correlated.Conclusion:Key genes and differentially expressed immune cells are closely related to the pathogenesis of gout,providing new ideas for the study of the molecular mechanism of gout.