BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.

Aim To investigate the effect of Zhenwu decoction on inflammation,oxidative stress and apopto-sis of human glomerular epithelial cells(HGEC)in-duced by lipopolysaccharide(LPS)based on Nrf2/HO-1 signaling pathway,and to explore the underlying mechanism.Methods HGEC were treated with LPS(1.0 mg·L-1)for 24 h to construct an oxidative damage model.On this basis,2.5％,5％and 10％Zhenwu decoction-containing serum were added to the low,medium and high dose groups of Zhenwu decoc-tion,and a normal group was set up.The changes of cell activity were assessed by MTT method and LDH method.The contents of TNF-α,IL-6,IL-10,SOD,CAT,GSH-Px,ROS and MDA in each group were de-tected by ELISA.The apoptosis of each group was de-tected by flow cytometry.The mRNA and protein ex-pressions of Bax,Bcl-2,caspase-3,caspase-9 and Nrf2/HO-1 pathway were detected by RT-qPCR and Western blot,respectively.Results Compared to the normal group,the model group of HGEC exhibited increased levels of inflammatory cytokines,enhanced oxidative stress response and aggravated apoptosis;after inter-vention with various doses of Zhenwu decoction,the in-flammatory levels in HGEC were reduced,oxidative damage and apoptosis were effectively ameliorated,and the mRNA and protein expression levels of the Nrf2/HO-1 signaling pathway were upregulated.Conclu-sions Zhenwu decoction can protect HGEC from LPS-induced inflammation and oxidative damage and im-prove apoptosis.The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

AIM:To analyze the expression of se-creted phosphoprotein 1(SPP1)and programmed cell death-ligand 1(PD-L1)in SMARCA4-deficient non-small cell lung cancer,and to provide a scientif-ic basis for the study of the follow-up treatment of this rare pathological type of lung cancer.METH-ODS:The clinical and pathological characteristics of 12 patients with this disease were analyzed retro-spectively,and the patients were divided into two groups of adenocarcinomas and poorly differentiat-ed carcinomas according to their morphological characteristics,and the relationship between the expression of SPP1 and PD-L1 was analyzed in the two groups.RESULTS:SPP1 expression was detect-ed in all patients and Its expression level was signif-icantly higher in the poorly differentiated carcino-ma group compared with the adenocarcinoma group(P=0.015);PD-L1 expression was found in 6/7 patients(5 cases were not measured),compared with the adenocarcinoma group,PD-L1 was also highly expressed in the poorly differentiated carci-noma group(P=0.048)and the PD-L1 difference be-tween the two groups suggested that the results were similar to those of SPP1.CONCLUSION:SMARCA4-deficient non-small cell lung cancer has high positive expression of SPP1 and PD-L1.It was more pronounced in patients with poorly differenti-ated carcinoma.There may be a positive correla-tion between SPP1 and PD-L1 expression in SMAR-CA4-deficient non-small cell lung cancer and the mechanism of the correlation needs to be further verified in subsequent studies.

Objective:To analyze the factors associated with long-term survival after radical resection of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),and to construct random forest and Cox regression models,to evaluate the two models.Methods:A total of 368 patients with HBV-infected HCC who underwent radical resection were selected retrospectively.These patients were categorized as having a good prognosis(n=266)or a poor prognosis(n=102)based on their survival and mortality status.Univariate and Cox regression analysis were used to identify fac-tors that predict poor prognosis in HCC patients after surgery,and Cox regression and random forest prediction models were constructed and evaluated.Results:There were significant differences in smoking history,Child-Pugh classifica-tion,cirrhosis,microvascular invasion,TNM staging,tumor capsule integrity,platelet-to-lymphocyte ratio(PLR),regular antiviral therapy,HBV-DNA load,alpha-fetoprotein(AFP),neutrophil-to-lymphocyte ratio(NLR),systemic immune in-flammatory index(SII),and albumin-to-globulin ratio(AGR)between the two groups(P<0.05);Cox regression showed that cirrhosis,microvascular invasion,regular antiviral treatment,HBV-DNA load,NLR,PLR,SII,and AGR were related factors that negatively affected the prognosis of patients with HBV-infected HCC after surgery(P<0.05),with an AUC of 0.870 for predicting prognosis;the importance ranking obtained by the random forest model was HBV-DNA load,cirrho-sis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII,with an AUC of 0.926 for predicting prog-nosis;the AUC predicted by the random forest model was greater than that predicted by the Cox regression model(Z=2.411,P=0.016).Conclusion:HBV-DNA load,cirrhosis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII are factors that affect the poor prognosis of patients with HBV-related HCC after surgery.The random for-est prediction model constructed based on these factors has high predictive value and is superior to the Cox regression prediction model.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Objective To analyze the changes in serum immunoglobulin E(IgE),interleukin-6(IL-6),high-mobility group protein B1(HMGB1),β2-microglobulin(β2-M),and T lymphocyte subsets in patients with secretory otitis media(SOM)and to evaluate their clinical significance.Methods A total of 185 patients with SOM admitted to Wuhan First Hospital between March 2023 and March 2025 were enrolled as the patient group,and 185 healthy individuals who underwent routine physical examinations at our hospital during the same period served as the control group.Serum levels of IgE,IL-6,HMGB1,and β2-microglobulin(β2-M),as well as peripheral blood T lymphocyte subsets,were compared between the two groups.Based on disease duration,the patients were further classified into acute(n=43),subacute(n=61),and chronic(n=81)subgroups.Levels of the serum markers and T lymphocyte subsets were compared across these three subgroups.The diagnostic value of the serum markers for SOM was evaluated,and their correlations with peripheral blood T lymphocyte subsets were analyzed.Results he levels of serum IgE,IL-6,HMGB1,β2-M,and peripheral blood CD8+were significantly higher in the disease group than in the control group,whereas the levels of peripheral blood CD4+and CD4+/CD8+were significantly lower(P<0.05).Across the acute,subacute,and chronic subgroups,the levels of serum IgE,IL-6,HMGB1,β2-M,and CD8+exhibited a progressive increasing trend,while CD4+and CD4+/CD8+levels showed a corresponding decreasing trend(P<0.05).The combined measurement of serum IgE,IL-6,HMGB1,and β2-M yielded a higher area under the curve(AUC)for diagnosing SOM compared to each marker alone(P<0.05),with a sensitivity of 88.65%and specificity of 76.76%.Furthermore,serum levels of IgE,IL-6,HMGB1,and β2-M were positively correlated with peripheral blood CD8+levels(r=0.618,0.578,0.622,0.549;P<0.05),and negatively correlated with CD4+and CD4+/CD8+ratios(r=-0.539,-0.573,-0.519,-0.559 for CD4+;r=-0.604,-0.618,-0.559,-0.649 for CD4+/CD8+;P<0.05).Conclusion The progression of SOM is associated with alterations in serum markers and peripheral blood T lymphocyte subsets.Furthermore,the combination of serum IgE,IL-6,HMGB1,and β2-MG demonstrates enhanced diagnostic value in patients with SOM,and a significant correlation exists between these four markers and the levels of peripheral blood T lymphocyte subsets.

Ischemic obstruction is a dangerous condition with a high mortality rate.Professor Jin Shi proposed that vascular intesti-nal obstruction disease is based on the intestinal tract while the structure of mesenteric vascular structure in modern medicine is highly similar to the morphological description of"intestinal collateral"in traditional Chinese medicine.The"hypercoagulable state"of blood is highly consistent with the core of the pathogenesis of"intestinal stasis"in traditional Chinese medicine.Blood stasis is a key patho-logical product and pathogenic factor of vascular intestinal obstruction and it is necessary to pay attention to the combination of disease identification,clarification of urgency,and phased treatment.This study provides a theoretical basis and practical example for the treatment of vascular intestinal obstruction in traditional Chinese medicine.

Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.