Objective To investigate the effect and underlying mechanism of bufalin regulating ferroptosis on extracellular matrix synthesis in renal tubular epithelial cells(RTECs)under high glucose(HG)conditions.Methods RTECs were cultured in vitro and exposed to HG.The experimental groups included:the control group,the HG group,the HG+dimethyl sulfoxide(DMSO)group,the HG+bufalin group,the HG+ferrostatin-1(Fer-1)group,the HG+bufalin+DMSO group and HG+bufalin+erastin group.The expression levels of fibronectin(FN),type Ⅰ collagen(Col Ⅰ),acyl-CoA synthetase long-chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)were detected using Western blot assay and quantitative real-time PCR(qRT-PCR).The potential molecular targets of bufalin were predicted using SwissTargetPrediction,and functional enrichment analysis was conducted using Metascape.FerrDb was employed to analyze ferroptosis-related gene sets.The levels of ferrous ions(Fe2+),malondialdehyde(MDA)and glutathione(GSH)were measured using micro-methods to evaluate the occurrence of ferroptosis.Results Compared with the control group,the mRNA and protein relative expression levels of FN,Col Ⅰand ACSL4 were increased in the HG group,while the mRNA and protein expression levels of GPX4 and SLC7A11 were decreased(P＜0.05).Compared with the HG+DMSO group,the mRNA and protein expression levels of FN,Col Ⅰand ACSL4,as well as levels of Fe2+and MDA were decreased in the HG+bufalin group,while the mRNA and protein expression levels of GPX4 and SLC7A11,and the level of GSH were increased(P＜0.05).In the HG+Fer-1 group,the mRNA and protein expression levels of GPX4 and SLC7A11 were increased,while the mRNA and protein expression levels of ACSL4,FN and Col Ⅰ were decreased(P＜0.05).The SwissTargetPrediction database and Metascape analysis function showed that the downstream functions of bufalin were closely related to lipid metabolism,inflammatory response,programmed cell death and ferroptosis-related pathways.The FerrDb analysis results indicated that the target sites of bufalin were closely related to ferroptosis markers.Compared with the HG+bufalin+DMSO group,the mRNA and protein expression levels of GPX4 and SLC7A11 were decreased in the HG+bufalin+Erastin group,while the mRNA and protein expression levels of ACSL4,FN and Col Ⅰ were increased(P＜0.05).Conclusion Bufalin attenuates extracellular matrix synthesis in HG-induced RTECs by inhibiting ferroptosis.

Objective The biomechanical performance of Ilizarov fixator models with different configurations for humeral shaft defect was compared,so as to provide a biomechanical basis for selecting the appropriate circular external fixation structure for the clinical treatment of humeral shaft defects using Ilizarov technology.Methods Based on CT data of the humerus from a healthy volunteer,the external fixators with three configurations,namely,hybrid frame,semi-ring frame and 90° fan frame were established.The finite element method was used to simulate the displacement and stress distribution under different loading conditions,and the finite element results were validated by biomechanical tests.Results Finite element analysis results:in terms of displacement,under compression,tensile and torque conditions,the displacement of 90° fan model was smaller than that of hybrid and semi-ring models.In terms of stress,the 90° fan model had the smallest displacement under tensile condition.In compression and torque tests,the semi-annular model had the lowest stress.Biomechanical test results:the semi-ring model exhibited the smallest displacement under axial compression,but there was no significant difference between the three models(P＞0.05).Conclusions The semi-ring and 90° fan frames can achieve a similar stability as the traditional hybrid frame through the strategy of'reducing the ring and increasing the stem'.The unilateral structure of the 90° fan frame has the advantages of small size,light weight,and structural stability,as well as a small impact on the shoulder and elbow joints,which makes it more valuable in clinical applications.

Objective To explore the efficacy and safety of one-stage flexible ureteroscopic lithotripsy for bilateral kidney stones.Methods Retrospectively analyzed 112 patients with bilateral kidney stones treated by flexible ureteroscopic lithotripsy from January 2018 to October 2023.Based on the treatment procedure,the participants were divided into an observation group and a control group.The observation group(60 cases)underwent one-stage lithotripsy using flexible ureteroscopy for bilateral kidney stones,the control group(52 cases)received staged lithotripsy for bilateral kidney stones.The operation time,intraoperative blood loss,stone clearance rate one month after operation,postoperative hematuria time,duration of lumbar and abdominal pain,creatinine level one day after operation and incidence of postoperative complications were compared between the two groups of patients.Results Findings indicated that the observation group had a mean operation time of(103.68±27.46)min,which was significantly shorter compared to the control group's mean operation time of(132.51±39.74)min,the difference was statistically significant(P<0.01).Additionally,the stone clearance rate after one month post-operation was 91.67%in the observation group and 90.38%in the control group(P=0.920);The average blood loss of the observation group was(15.29±5.15)mL,and the duration of postoperative lumbar and abdominal pain was(6.18±1.40)d,while the average blood loss of the control group was(12.00±3.62)mL,and the duration of postoperative lumbar and abdominal pain was(4.56±1.12)d,with significant difference(P<0.01);The duration of postoperative hematuria in the observation group was(3.07±0.92)d,the incidence of postoperative irritation sign of bladder was 65.00%,the incidence of postoperative moderate and low fever was 25.00%,and the creatinine level on the first day after surgery was(73.47±17.80)μmol/L,while the duration of postoperative hematuria in the control group was(2.73±1.28)d,the incidence of postoperative irritation sign of bladder was 53.85%,the incidence of postoperative moderate and low fever was 17.31%,and the creatinine level on the first day after surgery was(68.61±17.38)μmol/L,the differences were not statistically significant(P>0.05).Conclusion One stage flexible ureteroscopic lithotripsy for bilateral kidney stones is safe and effective,moreover,the surgical outcome is close to that of staged surgery,but postoperative nursing and pain management should be strengthened in order to improve the effect of comprehensive treatment.

Objective To investigate the effect and underlying mechanism of bufalin regulating ferroptosis on extracellular matrix synthesis in renal tubular epithelial cells(RTECs)under high glucose(HG)conditions.Methods RTECs were cultured in vitro and exposed to HG.The experimental groups included:the control group,the HG group,the HG+dimethyl sulfoxide(DMSO)group,the HG+bufalin group,the HG+ferrostatin-1(Fer-1)group,the HG+bufalin+DMSO group and HG+bufalin+erastin group.The expression levels of fibronectin(FN),type Ⅰ collagen(Col Ⅰ),acyl-CoA synthetase long-chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)were detected using Western blot assay and quantitative real-time PCR(qRT-PCR).The potential molecular targets of bufalin were predicted using SwissTargetPrediction,and functional enrichment analysis was conducted using Metascape.FerrDb was employed to analyze ferroptosis-related gene sets.The levels of ferrous ions(Fe2+),malondialdehyde(MDA)and glutathione(GSH)were measured using micro-methods to evaluate the occurrence of ferroptosis.Results Compared with the control group,the mRNA and protein relative expression levels of FN,Col Ⅰand ACSL4 were increased in the HG group,while the mRNA and protein expression levels of GPX4 and SLC7A11 were decreased(P＜0.05).Compared with the HG+DMSO group,the mRNA and protein expression levels of FN,Col Ⅰand ACSL4,as well as levels of Fe2+and MDA were decreased in the HG+bufalin group,while the mRNA and protein expression levels of GPX4 and SLC7A11,and the level of GSH were increased(P＜0.05).In the HG+Fer-1 group,the mRNA and protein expression levels of GPX4 and SLC7A11 were increased,while the mRNA and protein expression levels of ACSL4,FN and Col Ⅰ were decreased(P＜0.05).The SwissTargetPrediction database and Metascape analysis function showed that the downstream functions of bufalin were closely related to lipid metabolism,inflammatory response,programmed cell death and ferroptosis-related pathways.The FerrDb analysis results indicated that the target sites of bufalin were closely related to ferroptosis markers.Compared with the HG+bufalin+DMSO group,the mRNA and protein expression levels of GPX4 and SLC7A11 were decreased in the HG+bufalin+Erastin group,while the mRNA and protein expression levels of ACSL4,FN and Col Ⅰ were increased(P＜0.05).Conclusion Bufalin attenuates extracellular matrix synthesis in HG-induced RTECs by inhibiting ferroptosis.

Objective To investigate the characteristics of changes in hepatitis B surface antigen(HBsAg),hepatitis B virus(HBV)deoxyribonucleic acid(DNA),and alanine aminotransferase(ALT)levels following the cessation of nucleos(t)ide analogues(NAs)therapy in hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)patients with baseline HBsAg levels<1000 IU/ml.Methods This retrospective cohort study analyzed 73 HBeAg-negative CHB patients treated at the Fifth Medical Centre of Chinese PLA General Hospital from January 2020 to June 2023.Patients were divided into 3 groups according to baseline HBsAg level and discontinuation strategy:HBsAg-negative discontinuation group(n=14),HBsAg-positive discontinuation group(n=25),and HBsAg-positive continuation group(n=34).All patients were followed for 48 weeks.Baseline clinical characteristics and changes in virological and hepatic biochemical indicators during follow-up were compared among the 3 groups.Univariate logistic regression analysis was performed to assess the correlation between clinical indicators and HBV DNA reappearance in HBsAg-positive discontinuation group,and between clinical indicators and HBsAg decline>0.5 log IU/ml in this group.Results There were no significant differences in the baseline levels of gender,age,albumin,and total bilirubin among the 3 groups(P>0.05).The baseline direct bilirubin level was significantly higher in HBsAg-positive discontinuation group than that in other groups(P<0.05),while the lymphocyte counts were significantly higher in HBsAg-negative discontinuation group(P<0.05).During the 48-week follow-up period,the HBV DNA reappearance rate in HBsAg-positive discontinuation group(72.0%)was significantly higher than that in other groups(P<0.001).There was no significant difference in the incidence of ALT elevation among the three groups(P=0.260).The proportion of patients with HBsAg decline>0.5 log IU/ml in HBsAg-positive discontinuation group(24.0%)was significantly higher than that in HBsAg-positive continuation group(5.9%,P<0.05).The proportion of patients with HBsAg increase>0.5 log IU/ml in HBsAg-positive discontinuation group(12.0%)was also significantly higher than that in HBsAg-positive continuation group(0%,P<0.05).Univariate logistic regression analysis revealed no significant association between the analyzed clinical indicators and HBsAg decline(P>0.05).Conclusions Discontinuation of NAs therapy in HBsAg-negative patients demonstrates high safety,with sustained HBsAg negativity post-cessation and low risks of viral relapse and liver function abnormalities.For HBsAg-positive patients,discontinuation may promote HBsAg decline in some individuals but is associated with risks of HBV DNA reappearance and HBsAg elevation.The decision to discontinue therapy should be comprehensively evaluated based on patients'baseline HBsAg levels and clinical characteristics.

Objective:To investigate the association between different types of lung nodules and the risk of lung cancer in a population at high risk of lung cancer and to provide an epidemiologic basis for the comprehensive management of lung nodules.Methods:Using the free lung cancer screening program of low-dose CT (LDCT) in Wenling, Zhejiang Province, we collected baseline and imaging information of high-risk groups for lung cancer who underwent LDCT screening from April 2019 to October 2021 and patients with previous history of lung cancer, tuberculosis, pneumoconiosis, and silicosis were excluded. A total of 28 539 study subjects were included in the analysis, and the follow-up ended on 31 December 2023. Based on the characteristics of the detected pulmonary nodules, the study subjects were classified with no nodules, with solid nodules, with pure ground glass nodules, and with part solid nodules groups. The association between different characteristics of lung nodules and the risk of lung cancer development was analyzed using the Cox proportional hazard regression model with a new diagnosis of lung cancer during the follow-up period as the outcome.Results:The overall detection rate of lung nodules with a mean diameter of ≥3 mm was 76.5%, of which 53.7%, 18.2%, and 4.6% were detected in the solid nodule, pure ground glass nodule, and partially solid nodule groups, respectively. There were statistically significant differences between the different nodule groups in terms of age, gender, BMI, history of toxic exposure education level, smoking status, history of lung disease, and family history of lung cancer (all P<0.05). The median follow-up time of the study population was 3.4 years, and 485 new lung cancer cases were diagnosed during the follow-up period. After adjusting for covariates, the results of multifactorial Cox proportional hazard regression model analysis showed that the risk of lung cancer was higher in pure ground glass nodules and part solid nodules compared with solid nodules, with HR values (95% CI) of 1.89 (1.52-2.35) and 6.49 (5.18-8.14), respectively. The results of subgroup analysis showed that patients in the group of part solid nodules had the highest risk of lung cancer in all strata of the population, followed by patients with pure ground glass nodules. Patients in the solid nodule group who were older or had previous lung disease had a higher risk of lung cancer, and the risk of lung cancer in the part solid nodule group differed between genders. Conclusions:The proportion of lung nodules detected is high in the high-risk group of lung cancer, and among them, patients with pure ground glass and part solid nodules have a higher risk of developing lung cancer. Attention should be paid to the annual follow-up management for patients with solid nodules who are older or who have had lung diseases, as well as for female patients with part solid nodules.

Objective:To systematically review the prediction models for extubation failure in critically ill patients undergoing mechanical ventilation, providing a reference for healthcare professionals in selecting appropriate models to identify high-risk populations.Methods:Literature on the construction of prediction models for extubation failure risk in critically ill patients undergoing mechanical ventilation was retrieved from China National Knowledge Infrastructure, Wanfang Database, VIP, SinoMed, PubMed, Web of Science, Embase, and Cochrane Library. The search was limited from database inception to February 2024. Two researchers independently screened the literature and extracted data, using bias risk assessment tools to evaluate the bias risk and applicability of the prediction models.Results:A total of nine studies were included, with the most common predictive factors being mechanical ventilation duration, Glasgow Coma Scale score, cough reflex strength, age, and 24-hour input/output volume. The area under the receiver operating characteristic curve for the models ranged from 0.689 to 0.926, indicating good predictive performance. However, the risk of bias was high, mainly due to small sample sizes, the selection of predictive factors based on univariate analysis, and lack of proper internal validation.Conclusions:Existing prediction models show good predictive performance, but they carry high bias risk. Future studies should improve research design, adhere to model development and reporting guidelines, and develop well-performing, user-friendly prediction models to more accurately identify high-risk populations for extubation failure.

Mild cognitive impairment(MCI)is a clinical condition that lies between normal aging and dementia and can be considered as the initial stage of dementia development.Executive dysfunction is one of the core symptoms of dementia, the maintenance and improvement of executive function play a central role in delaying the onset of dementia.At present, many studies have shown that cognitive training can improve executive function in MCI patients, but there are few researches and no consensus on the underlying mechanisms.This paper provides a review of the effects of cognitive training on executive function in patients with MCI, explores the impact of executive function deficits and cognitive training on the behavioral and neural levels of executive function in patients with MCI, and points out the limitations of current MCI intervention strategies and potential development directions, with the aim of providing new insights into the intervention and treatment of MCI.

Objective:To investigate the association between different types of lung nodules and the risk of lung cancer in a population at high risk of lung cancer and to provide an epidemiologic basis for the comprehensive management of lung nodules.Methods:Using the free lung cancer screening program of low-dose CT (LDCT) in Wenling, Zhejiang Province, we collected baseline and imaging information of high-risk groups for lung cancer who underwent LDCT screening from April 2019 to October 2021 and patients with previous history of lung cancer, tuberculosis, pneumoconiosis, and silicosis were excluded. A total of 28 539 study subjects were included in the analysis, and the follow-up ended on 31 December 2023. Based on the characteristics of the detected pulmonary nodules, the study subjects were classified with no nodules, with solid nodules, with pure ground glass nodules, and with part solid nodules groups. The association between different characteristics of lung nodules and the risk of lung cancer development was analyzed using the Cox proportional hazard regression model with a new diagnosis of lung cancer during the follow-up period as the outcome.Results:The overall detection rate of lung nodules with a mean diameter of ≥3 mm was 76.5%, of which 53.7%, 18.2%, and 4.6% were detected in the solid nodule, pure ground glass nodule, and partially solid nodule groups, respectively. There were statistically significant differences between the different nodule groups in terms of age, gender, BMI, history of toxic exposure education level, smoking status, history of lung disease, and family history of lung cancer (all P<0.05). The median follow-up time of the study population was 3.4 years, and 485 new lung cancer cases were diagnosed during the follow-up period. After adjusting for covariates, the results of multifactorial Cox proportional hazard regression model analysis showed that the risk of lung cancer was higher in pure ground glass nodules and part solid nodules compared with solid nodules, with HR values (95% CI) of 1.89 (1.52-2.35) and 6.49 (5.18-8.14), respectively. The results of subgroup analysis showed that patients in the group of part solid nodules had the highest risk of lung cancer in all strata of the population, followed by patients with pure ground glass nodules. Patients in the solid nodule group who were older or had previous lung disease had a higher risk of lung cancer, and the risk of lung cancer in the part solid nodule group differed between genders. Conclusions:The proportion of lung nodules detected is high in the high-risk group of lung cancer, and among them, patients with pure ground glass and part solid nodules have a higher risk of developing lung cancer. Attention should be paid to the annual follow-up management for patients with solid nodules who are older or who have had lung diseases, as well as for female patients with part solid nodules.