AIM:To investigate the regulatory mechanism of silent information regulator 6(Sirt6)on nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway and ferroptosis in skeletal muscle aging in-duced by D-galactose(D-Gal)in mice.METHODS:A D-Gal-induced mouse aging model was established and randomly divided into control and D-Gal groups.In vitro,D-Gal-treated C2C12 mouse myoblasts were treated with ferroptosis ago-nist erastin(Era)and inhibitor ferrostatin-1(Fer-1),Sirt6 agonist MDL-800 and inhibitor OSS-128167,and Nrf2 siRNA.Mouse body weight and forelimb relative grip strength were monitored.RT-qPCR and Western blot were used to measure the expression of Sirt6,Nrf2,HO-1,P53,P21,P16,muscle ring finger protein 1,muscle atrophy F-box,solute carrier family 7 member 11,and glutathione peroxidase 4 in gastrocnemius muscle and myoblasts.Hematoxylin-eosin staining was performed to examine muscle fiber diameter.Levels of reactive oxygen species(ROS),mitochondrial ROS,mitochon-drial membrane potential,senescence-associated β-galactosidase activity,glutathione,lipid peroxidation,and Fe2? con-centration were measured in myoblasts and myotubes.Immunofluorescence staining was used to detect myosin heavy chain(MyHC)expression in myotubes.RESULTS:Mice in the D-Gal group exhibited significant reductions in body weight and forelimb grip strength(P<0.01),upregulation of aging and muscle atrophy markers,and decreased mRNA and pro-tein levels of ferroptosis markers and Sirt6(P<0.01).Additionally,gastrocnemius muscle fiber diameter significantly de-creased(P<0.01).In D-Gal-treated myoblasts and myotubes,aging and muscle atrophy markers were elevated(P<0.01),MyHC expression was reduced,and protein levels of ferroptosis-related markers,Sirt6,Nrf2,and HO-1 were de-creased(P<0.05 or P<0.01).Fer-1 pre-treatment alleviated these changes(P<0.05 or P<0.01).MDL-800 significantly improved D-Gal-induced aging and muscle atrophy in myoblasts and myotubes,while increasing the expression of ferropto-sis-related proteins(P<0.05 or P<0.01).However,the addition of Erastin abolished the beneficial effects of MDL-800(P<0.05 or P<0.01).Following Nrf2 siRNA transfection,the ability of MDL-800 to improve ferroptosis and the quality of myotube formation was significantly diminished(P<0.05 or P<0.01).CONCLUSION:Sirt6 inhibits ferroptosis in myo-blasts through the Nrf2/HO-1 signaling pathway,thereby alleviating age-related changes in myoblasts and the decline in myotube formation quality,which is beneficial for improving skeletal muscle aging.

Objective This study aims to conduct a retrospective analysis of the malignant tumor mortality cases at a specialized oncology hospital,providing a reference for rationally allocating medical resources and early diagnosis and treatment of malignant tumors.Methods Demographic data and clinical records of deceased patients with malignant tumor at the hospital from 2019 to 2024 was collected and analyzed with SPSS 25.0 and R studio in terms of gender,age,mortality rate and death causes.Results Totally,862 inpatients were reported dead from 2019 to 2024,with a mortality rate of 0.32％.Among them,500(58.0％)had not received surgical treatments,and 561(65.1％)were documented as clinical/pathological stage Ⅳ.Overall,531 deaths occurred in men and 331 in women;the male mortality rate was significantly higher than the female(0.54％vs.0.19％,(x2=236.93,P=0.000).The highest annual tumor-related mortality rate was recorded in 2019(0.46％).The 75-and-older age group had the greatest mortality,with 113 deaths accounting for 1.23％;the age-specific distribution differed sig-nificantly between sexes(P＜0.05).The top five causes of cancer death were lung cancer(206 cases,23.90％),liver cancer(88 cases,10.21％),gastric cancer(75 cases,8.70％),malignant lymphoma(73 cases,8.47％),pancreatic cancer(72 cases,8.35％).Conclusion The malignant tumor mortality rate is higher in males than in females,with the highest mortality observed in those aged 75 and above.Lung,liver and gastric cancers account for most cancer deaths.The hospital managers should strengthen health education for the elderly and simultaneously strengthen the diagnosis and treatment of these key cancers.

Objective This study aims to conduct a retrospective analysis of the malignant tumor mortality cases at a specialized oncology hospital,providing a reference for rationally allocating medical resources and early diagnosis and treatment of malignant tumors.Methods Demographic data and clinical records of deceased patients with malignant tumor at the hospital from 2019 to 2024 was collected and analyzed with SPSS 25.0 and R studio in terms of gender,age,mortality rate and death causes.Results Totally,862 inpatients were reported dead from 2019 to 2024,with a mortality rate of 0.32％.Among them,500(58.0％)had not received surgical treatments,and 561(65.1％)were documented as clinical/pathological stage Ⅳ.Overall,531 deaths occurred in men and 331 in women;the male mortality rate was significantly higher than the female(0.54％vs.0.19％,(x2=236.93,P=0.000).The highest annual tumor-related mortality rate was recorded in 2019(0.46％).The 75-and-older age group had the greatest mortality,with 113 deaths accounting for 1.23％;the age-specific distribution differed sig-nificantly between sexes(P＜0.05).The top five causes of cancer death were lung cancer(206 cases,23.90％),liver cancer(88 cases,10.21％),gastric cancer(75 cases,8.70％),malignant lymphoma(73 cases,8.47％),pancreatic cancer(72 cases,8.35％).Conclusion The malignant tumor mortality rate is higher in males than in females,with the highest mortality observed in those aged 75 and above.Lung,liver and gastric cancers account for most cancer deaths.The hospital managers should strengthen health education for the elderly and simultaneously strengthen the diagnosis and treatment of these key cancers.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

AIM:To investigate the regulatory mechanism of silent information regulator 6(Sirt6)on nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway and ferroptosis in skeletal muscle aging in-duced by D-galactose(D-Gal)in mice.METHODS:A D-Gal-induced mouse aging model was established and randomly divided into control and D-Gal groups.In vitro,D-Gal-treated C2C12 mouse myoblasts were treated with ferroptosis ago-nist erastin(Era)and inhibitor ferrostatin-1(Fer-1),Sirt6 agonist MDL-800 and inhibitor OSS-128167,and Nrf2 siRNA.Mouse body weight and forelimb relative grip strength were monitored.RT-qPCR and Western blot were used to measure the expression of Sirt6,Nrf2,HO-1,P53,P21,P16,muscle ring finger protein 1,muscle atrophy F-box,solute carrier family 7 member 11,and glutathione peroxidase 4 in gastrocnemius muscle and myoblasts.Hematoxylin-eosin staining was performed to examine muscle fiber diameter.Levels of reactive oxygen species(ROS),mitochondrial ROS,mitochon-drial membrane potential,senescence-associated β-galactosidase activity,glutathione,lipid peroxidation,and Fe2? con-centration were measured in myoblasts and myotubes.Immunofluorescence staining was used to detect myosin heavy chain(MyHC)expression in myotubes.RESULTS:Mice in the D-Gal group exhibited significant reductions in body weight and forelimb grip strength(P<0.01),upregulation of aging and muscle atrophy markers,and decreased mRNA and pro-tein levels of ferroptosis markers and Sirt6(P<0.01).Additionally,gastrocnemius muscle fiber diameter significantly de-creased(P<0.01).In D-Gal-treated myoblasts and myotubes,aging and muscle atrophy markers were elevated(P<0.01),MyHC expression was reduced,and protein levels of ferroptosis-related markers,Sirt6,Nrf2,and HO-1 were de-creased(P<0.05 or P<0.01).Fer-1 pre-treatment alleviated these changes(P<0.05 or P<0.01).MDL-800 significantly improved D-Gal-induced aging and muscle atrophy in myoblasts and myotubes,while increasing the expression of ferropto-sis-related proteins(P<0.05 or P<0.01).However,the addition of Erastin abolished the beneficial effects of MDL-800(P<0.05 or P<0.01).Following Nrf2 siRNA transfection,the ability of MDL-800 to improve ferroptosis and the quality of myotube formation was significantly diminished(P<0.05 or P<0.01).CONCLUSION:Sirt6 inhibits ferroptosis in myo-blasts through the Nrf2/HO-1 signaling pathway,thereby alleviating age-related changes in myoblasts and the decline in myotube formation quality,which is beneficial for improving skeletal muscle aging.

Liver cancer is one of the most common cancers,and its common surgical treatment methods include tran-scatheter arterial chemoembolization,radiofrequency ablation,and liver transplantation surgery.However,the treatment effect of these surgeries on patients with mid-to late-stage liver cancer is not ideal.In recent years,with the continuous development of tumor gene therapy and tumor immunology,tumor treatment methods have transitioned from traditional models to targeted onco-lytic virus therapy.With the advantages of fast replication,the oncolytic virus can kill tumor cells without damaging other normal cells and realize the targeted treatment of liver cancer through mechanisms such as activating the immune system and improving the tumor microenvironment.In addition,immunotherapy can reduce tumor recurrence and metastasis,thereby exerting therapeutic effects on liver cancer.This article reviews the research progress of oncolytic virus and immunotherapy for liver cancer,aiming to provide a reference for the clinical treatment of liver cancer.

Objective:To investigate the risk factors of postoperative recurrence of parastomal hernia repair.Methods:The clinical and follow-up data of 128 patients undergoing parastomal hernia repair at the the Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology from Jan 1, 2013 to Dec 31, 2022 was analyzed retrospectively.Results:Postoperative recurrence was confirmed in 32 patients during follow-up, and the recurrence rates were 13.8% , 24.8% and 25.0% at 1',3' and 5 years .Univariate analysis showed that body mass index (BMI) , chronic obstructive pulmonary disease (COPD), type of stoma, prophylactic stoma displacement, and surgical options were the risk factors for recurrence after parastomal hernia repair. Multiple Logistic regression analysis showed that BMI, COPD, prophylactic stoma displacement, and surgical options were independent risk factors for the recurrence after parastomal hernia ( P< 0.05). Conclusion:The occurrence of hernia recurrence after parastomal hernia repair is closely related to patients' BMI, COPD, prophylactic stoma displacement and the surgical options.

Objective To explore the application of MRI in the differential diagnosis of high-and low-risk thymoma.Methods The data of patients with pathologically confirmed thymoma were collected bidirectionally,and the differences in clinical data,MRI image characteristics of lesions,signal characteristics and apparent diffusion coefficient(ADC)values were compared and analyzed between high-and low-risk thymoma according to the pathological subtype.The receiver operating characteristic(ROC)curve analysis was used to screen out meaningful features,then the diagnostic efficacy and combined prediction probability of indicators were evaluated.Results There was no significant difference in clinical data(P＞0.001).The morphology of high-risk lesions was mainly irregular,while that of low-risk lesions was mainly regular.The edges of high-risk lesions were mostly not smooth,and the edges of low-risk lesions were mostly smooth.The enhancement degree of high-risk lesions was higher than that of low-risk lesions,and the ADC value was lower than that of low-risk lesions,with statistical significance(P＜0.001),in which the ADC value area under the curve(AUC)was higher than other indicators(AUC=0.968),and the combined prediction probability of indicators was the highest(AUC=0.981).Conclusion MRI shows great potential application value in preoperative differential diagnosis of high-and low-risk thymoma.

Objective:To compare the differences in distribution and prognosis of cervical cancer patients in the 2009 and 2018 editions of International Federation of Gynecology and Obstetrics (FIGO) staging, and to analyze the prognostic factors of cervical cancer patients.Methods:The clinical data of 524 cervical cancer patients admitted to the First Affiliated Hospital of Soochow University from January 2010 to December 2018 were retrospectively analyzed. The cases were staged according to the 2009 and 2018 FIGO staging, and the Kendall τb coefficient was calculated to compare the consistency of the distribution of the two stages. Kaplan-Meier was used for survival analysis, and log-rank test was used to test the difference of prognosis in each stage. Cox-regression was used to analyze the prognostic factors of cervical cancer patients.Results:In the 2009 FIGO edition of staging, 1 case of stage ⅠB1 was reduced to stage ⅠA1 due to the microscopic infiltration depth <5 mm, 51 cases of stage ⅠB1 were raised to stage ⅠB2 due to 2 cm4 cm. A total of 119 cases raised to stage ⅢC1 due to pelvic lymph node metastasis, and 11 cases raised to stage ⅢC2 due to para-aortic lymph node metastasis. The distribution of cases in the two stages was consistent (τb=0.61, P<0.001). There were statistically significant differences in overall survival (OS) ( χ2=107.13, P<0.001; χ2=93.02, P<0.001; χ2=92.74, P<0.001) and progression-free survival (PFS) ( χ2=91.95, P<0.001; χ2=77.69, P<0.001; χ2=73.27, P<0.001) among patients with different stages of FIGO in 2018 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, ⅢC1, ⅢC2, Ⅳ) and 2009 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, Ⅳ) and patients with different T stages (T 1, T 2, T 3, T 4). There were statistically significant differences in OS ( χ2=20.71, P<0.001) and PFS ( χ2=24.25, P<0.001) in 2018 FIGOⅠB and ⅢC stages, and there was a statistically significant difference in OS between stage ⅢC1 and stage ⅠB2 ( χ2=6.18, P=0.013). Multivariate analysis showed that age ( HR=1.88, 95% CI: 1.08-3.28, P=0.026), pathological type ( HR=2.11, 95% CI: 1.04-4.27, P=0.038), lymph node metastasis ( HR=2.18, 95% CI: 1.34-3.56, P=0.002), parametrial spread ( HR=2.56, 95% CI: 1.52-4.29, P<0.001), maximum tumor diameter ( HR=1.98, 95% CI: 1.18-3.30, P=0.009), squamous cell carcinoma antigen (SCCA) positive after treatment ( HR=4.49, 95% CI: 2.09-9.68, P<0.001) and Hemoglobin (HB) level before treatment ( HR=0.58, 95% CI: 0.35-0.96, P=0.035) were independent risk factors for OS in patients with cervical cancer. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅠB1, ⅠB2, ⅠB3 were 100%, 97.1% and 87.9% respectively, with a statistically significant difference ( χ2=7.79, P=0.020), and there was a statistically significant difference between stage ⅠB1 and ⅠB3 ( χ2=5.55, P=0.019). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅠB1 and ⅠB2 were 95.7% and 84.3% respectively, with a statistically significant difference ( χ2=9.08, P=0.003). For patients with 2018 FIGO stage ⅠB, SCCA positive after treatment ( HR=1 172.50, 95% CI: 10.37-132 554.51, P=0.003) was an independent risk factor for OS, and differentiation degree ( HR=0.09, 95% CI: 0.01-0.81, P=0.032), treatment method ( HR=0.17, 95% CI: 0.04-0.71, P=0.015) and SCCA positive after treatment ( HR=190.68, 95% CI: 14.27-2 547.67, P<0.001) were independent risk factors for PFS. For patients with 2018 FIGO stage ⅠB, stage ( HR=9.56, 95% CI: 2.38-38.32, P=0.001), SCCA positive after treatment ( HR=126.32, 95% CI: 12.36-1 290.60, P<0.001) and lymph node metastasis ( HR=20.07, 95% CI: 3.63-111.11, P=0.001) were independent risk factors for OS, and differentiation degree ( HR=0.11, 95% CI: 0.02-0.63, P=0.013), treatment method ( HR=0.22, 95% CI: 0.06-0.75, P=0.015) and SCCA positive after treatment ( HR=43.83, 95% CI: 7.94-241.84, P<0.001) were independent risk factors for PFS. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 95.7% and 75.6% respectively, with a statistically significant difference ( χ2=13.96, P<0.001). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 83.1% and 67.1% respectively, with a statistically significant difference ( χ2=7.61, P=0.006). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 90.9% and 75.0% respectively, with a statistically significant difference ( χ2=8.85, P=0.003). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 75.7% and 66.7% respectively, with a statistically significant difference ( χ2=4.07, P=0.044). For patients with 2018 FIGO stage Ⅱ, pathological type ( HR=20.28, 95% CI: 2.93-140.32, P=0.002) and stage ( HR=4.35, 95% CI: 1.02-18.55, P=0.047) were independent risks factors for OS. For patients with 2009 FIGO stage Ⅱ, pathological type ( HR=5.82, 95% CI: 1.62-20.94, P=0.007) was an independent risk factor for OS, and pathological type ( HR=3.09, 95% CI: 1.22-7.85, P=0.017) and lymph node metastasis ( HR=2.07, 95% CI: 1.22-3.51, P=0.007) were independent risk factors for PFS. For patients with 2018 FIGO stage Ⅲ, maximum tumor diameter ( HR=3.31, 95% CI: 1.45-7.56, P=0.005) and SCCA positive after treatment ( HR=4.67, 95% CI: 1.22-17.86, P=0.024) were independent risk factors for OS, and pathological type ( HR=4.15, 95% CI: 1.47-11.77, P=0.007) and SCCA positive after treatment ( HR=3.96, 95% CI: 1.45-10.86, P=0.007) were independent risk factors for PFS. Conclusion:The 2018 and 2009 FIGO staging have a good distribution consistency in the cervical cancer patients, and the 2018 FIGO stage ⅠB has more advantages in judging the prognosis, but stage ⅢC cannot accurately judge the prognosis. Lymph node metastasis and maximum tumor diameter are more important prognostic factors.

Humans ; Nephrectomy ; Hemostatics/therapeutic use* ; Laparoscopy ; Kidney Neoplasms/surgery* ; Minimally Invasive Surgical Procedures