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.

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.

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.

Radiation therapy (RT) is a well-established and widely used treatment modality for prostate cancer. As prostate-rectum proximity contributes to rectal toxicity, there is growing interest in rectal protection. Technical advances have enabled the reduction of rectal injury. To improve the safety of prostate cancer radiotherapy and minimize the rectal toxicity of irradiation, the advances in rectal protection technique during prostate cancer radiotherapy, including technical advances of radiation therapy, image-guided radiotherapy, application of endorectal balloons, and use of rectum spacers, were reviewed, aiming to provide reference for improving the safety of prostate cancer radiotherapy and alleviating rectal radiation injury.

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To observe the expression of GLIS3 in triple negative breast cancer(TNBC)and analyze its relationship with the prognosis of TNBC patients.Methods Bioinformatic analysis was applied to analyze the expression level of GLIS3 in Gene Expression Omnibus(GEO).Kaplan-Meier survival curve was plotted to evaluate the impact of GLIS3 expression on the survival rate of patients based on DNA chip data.A total of 125 patients pathologically diagnosed as TNBC in the Fourth Hospital of Hebei Medical University from January to December 2014 were enrolled by cluster random sampling.Among them,53 patients had complete tissue specimens,medical records and follow-up data.Immunohistochemical assay was used to detect the expression of GLIS3 in TNBC and adjacent tissues to tumors,while the relationships between GLIS3 protein expression in breast cancer tissues and clinicopathological parameters such as age,menstrual status,tumor size,clinical stage,histological grade,pathological type,axillary lymph node metastasis,vascular tumor thrombus,and expression of TP53 and Ki-67 were analyzed.Kaplan-Meier survival curve was plotted to analyze the effect of GLIS3 on the overall and disease-free survival of TNBC patients.Cox regression model was established to identify the risk factors impacting the prognosis of the patients.Results Analysis of GEO data showed that the expression of GLIS3 in TNBC was significantly higher than that in paracancer tissues(P＜0.05).The expression of GLIS3 was notably higher in the TNBC tissue than the adjacent tissue to tumor(P＜0.05).A marked augmentation of GLIS3 expression was observed in both the advanced and larger-sized tumors(P＜0.05).Univariate analysis of Cox regression model revealed that lymph node metastasis,TNM stage and GLIS3 expression were all related to disease-free survival of TNBC patients(P＜0.05).Univariate and multivariate analyses displayed that TNM stage was related to the overall survival of TNBC patients(P＜0.05).The patients with high expression of GLIS3 had significant shorter disease-free survival time than those with low expression(P＜0.05),but had no statistical difference in overall survival(P＞0.05).Conclusion GLIS3 protein is highly expressed in TNBC tissues,and tumor size and TNM stage are correlated with its high expression.The high expression of GLIS3 suggests that the patients have poor prognosis and low disease-free survival rate.

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.