BACKGROUND: Ferroptosis-related genes play a crucial role in regulating intracellular iron homeostasis and lipid peroxidation, and they are involved in the regulation of tumor growth and drug resistance. The expression of ferroptosis-related genes in tumor tissues can be used to predict patients' future survival times, aiding doctors and patients in anticipating disease progression. Based on the sequencing data of lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA) database, this study identified genes involved in the regulation of ferroptosis, constructed a prognostic model, and evaluated the predictive performance of the model. METHODS: A total of 1467 ferroptosis-related genes were obtained from the GeneCards database. Gene expression profiles and clinical data from 541 LUAD patients were collected from the TCGA database. The expression data of all ferroptosis-related genes were extracted, and differentially expressed genes were identified using R software. Survival analysis was performed on these genes to screen for those with prognostic value. Subsequently, a prognostic risk scoring model for ferroptosis-related genes was constructed using LASSO regression model. Each LUAD patient sample was scored, and the patients were divided into high-risk and low-risk groups based on the median score. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated. Kaplan-Meier survival curves were generated to assess model performance, followed by validation in an external dataset. Finally, univariate and multivariate Cox regression analyses were conducted to evaluate the independent prognostic value and clinical relevance of the model. RESULTS: Through survival analysis, 121 ferroptosis-related genes associated with prognosis were initially identified. Based on this, a LUAD prognostic risk scoring model was constructed using 12 ferroptosis-related genes (ALG3, C1QTNF6, CCT6A, GLS2, KRT6A, LDHA, NUPR1, OGFRP1, PCSK9, TRIM6, IGF2BP1 and MIR31HG). The results indicated that patients in the high-risk group had significantly shorter survival time than those in the low-risk group (P<0.001), and the model demonstrated good predictive performance in both the training set (1-yr AUC=0.721) and the external validation set (1-yr AUC=0.768). Risk scores were significantly associated with the prognosis of LUAD patients in both univariate and multivariate Cox regression analyses (P<0.001), suggesting that this score is an important prognostic factor for LUAD patients. CONCLUSIONS This study successfully established a LUAD risk scoring model composed of 12 ferroptosis-related genes. In the future, this model is expected to be used in conjunction with the tumor-node-metastasis (TNM) staging system for prognostic predictions in LUAD patients.
Humans ; Ferroptosis/genetics* ; Prognosis ; Adenocarcinoma of Lung/pathology* ; Lung Neoplasms/pathology* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Middle Aged ; ROC Curve

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

Aging is a complex process triggered by multiple factors,characterized by the gradual decline of physiological and behavioral capabilities.Among various organs,the brain is particularly susceptible to aging effects.Brain aging not only leads to cognitive decline in the elderly but also increases the risk of neurodegen-erative diseases,resulting in reduced quality of life and increased social aging burdens.Therefore,it is essential to thoroughly investigate the mechanisms and biomarkers of both physiological and pathological brain aging to enable early prevention,monitoring,and intervention.Mitochondria play a crucial role in both physiological and pathological brain aging processes,making mitochondrial-related mechanisms and biomarkers key research directions in this field.This article reviews the main manifestations and mechanistic differences between physi-ological and pathological brain aging,summarizes mitochondrial mechanisms in brain aging,identifies mito-chondrial-associated biomarkers,and proposes health-promoting,mitochondria-targeting interventions.

With the rising prevalence of chronic diseases and an aging population,China's traditional segmented health-care delivery model is increasingly inadequate for meeting the growing demand for long-term,systematic health management.In response,the"Physician-Pharmacist Co-management"model has emerged,aiming to enhance the quality and continuity of care through close collaboration between physicians and pharmacists.This paper starts from the concept and origin of"Physician-Phar-macist Co-management"model,focusing on its China-specific advantages shaped by national healthcare policies and clinical real-ities.Unlike the internationally recognized Collaborative Drug Therapy Management(CDTM)model,the Chinese approach re-flects local healthcare structures and needs.Using obstructive pulmonary disease(COPD)as a case study,we examine the mod-el's application and value in managing chronic respiratory diseases.Data indicate that,after the implementation of"physician-pharmacist co-management"model in COPD patients,the CAT score decreased by approximately 24％,the annual rate of acute exacerbation-related hospitalizations declined by about 72％,and the proportion of patients with regular pulmonary rehabilitation exercise habits increased by roughly 3.3-fold.Additionally,the percentage of patients without adverse reactions rose from 47.37％to 64.41％,and the vaccination rate increased by about 2.7-fold.These findings demonstrate the model's significant advantages in improving clinical outcomes,enhancing patient adherence,and reducing healthcare costs.Despite benefits,howev-er,the"Physician-Pharmacist Co-management"model in China faces several challenges,including limited public awareness,gaps in pharmacist training,and insufficient policy support.To address these challenges,this study recommends strengthening public education,establishing comprehensive evaluation systems for pharmaceutical professionals,and improving incentive mech-anisms.Overall,the findings suggest that the"Physician-Pharmacist Co-management"model holds considerable promise for im-proving the quality of chronic disease management,enhancing patient adherence,and optimizing healthcare resource utilization in China.

With the rising prevalence of chronic diseases and an aging population,China's traditional segmented health-care delivery model is increasingly inadequate for meeting the growing demand for long-term,systematic health management.In response,the"Physician-Pharmacist Co-management"model has emerged,aiming to enhance the quality and continuity of care through close collaboration between physicians and pharmacists.This paper starts from the concept and origin of"Physician-Phar-macist Co-management"model,focusing on its China-specific advantages shaped by national healthcare policies and clinical real-ities.Unlike the internationally recognized Collaborative Drug Therapy Management(CDTM)model,the Chinese approach re-flects local healthcare structures and needs.Using obstructive pulmonary disease(COPD)as a case study,we examine the mod-el's application and value in managing chronic respiratory diseases.Data indicate that,after the implementation of"physician-pharmacist co-management"model in COPD patients,the CAT score decreased by approximately 24％,the annual rate of acute exacerbation-related hospitalizations declined by about 72％,and the proportion of patients with regular pulmonary rehabilitation exercise habits increased by roughly 3.3-fold.Additionally,the percentage of patients without adverse reactions rose from 47.37％to 64.41％,and the vaccination rate increased by about 2.7-fold.These findings demonstrate the model's significant advantages in improving clinical outcomes,enhancing patient adherence,and reducing healthcare costs.Despite benefits,howev-er,the"Physician-Pharmacist Co-management"model in China faces several challenges,including limited public awareness,gaps in pharmacist training,and insufficient policy support.To address these challenges,this study recommends strengthening public education,establishing comprehensive evaluation systems for pharmaceutical professionals,and improving incentive mech-anisms.Overall,the findings suggest that the"Physician-Pharmacist Co-management"model holds considerable promise for im-proving the quality of chronic disease management,enhancing patient adherence,and optimizing healthcare resource utilization in China.

OBJECTIVE To know about the perception and current status of drug risk management among pharmacists in Chinese medical institutions,providing insights and recommendations for enhancing the drug risk management system in medical institutions.METHODS A questionnaire survey was conducted across 28 provinces,cities,and autonomous regions;stratified radom sampling was employed to study the population of medical workers and pharmaceutical professionals in medical institutions nationwide.The survey included information on the survey population,the current status of drug risk management implementation in medical institutions,the cognition,definition and process of drug risk management related concepts,and the content and mode of drug risk management work in medical institutions.Finally,suggestions were collected from various medical institutions on the system construction of drug risk management.Descriptive statistical analysis was adopted to summarize the obtained data.RESULTS A total of 446 questionnaires were collected in this survey,including 420 valid questionnaires and 26 invalidquestionnaires.The questionnaire collection rate was 100％,and the effective rate was 94.17％.51.19％ of the respondents based their understanding of drug risk management on Management Measures for Adverse Drug Reaction Reports and Monitoring,while 87.38％ recognized the need for drug risk management throughout the drug use process.63.33％ of the participants stated that their medical institutions had dedicatedpositions related to drug risk management,with the highest proportion (72.17％) was in third-grade class A medical institutions.66.43％ reported implementing risk management across all drug use stages.Suggestions for the development of drug risk management systems in medical institutions by the research participants focused on enhancing guiding documents,clarifying concepts,establishing information-sharing mechanisms.CONCLUSIONS The overall awareness of drug risk management in China's medical institutions is high,with practices in place across various stages in multiple forms.However,there remains a need to strengthen institutional documents,management regulations,system development,and information-sharing mechanisms to improve collaborative governance,improve drug management levels,and ensure patient safety.

Objective:To evaluate knee biomechanics of patients about 12 months after anterior cruciate ligament(ACL)reconstruction during cutting and determine the abnormal biomechanical characteristics.Methods:Sixteen males about 12 months after ACL reconstruction were recruited for this study.Three-dimensional kinematic and kinetic data were collected during cutting movement.Knee joint angles and moments were calculated.Paired t-tests were used to compare the differences in knee biomechanics be-tween the surgical leg and nonsurgical leg.Results:The peak posterior ground reaction force(surgical leg:0.380±0.071;nonsurgical leg:0.427±0.069,P=0.003)and vertical ground reaction force(surgical leg:1.996±0.202,nonsurgical leg:2.110±0.182,P=0.001)were significantly smaller in the surgical leg than in the nonsurgical leg.When compared with the uninjured leg,the surgical leg demonstrated a smaller knee flexion angle(surgical leg:38.3°±7.4°;nonsurgical leg:42.8°±7.9°,P＜0.001)and larger external rotation angle(surgical leg:10.3°±2.4°;nonsurgical leg:7.7°±2.1°,P=0.008).The surgical leg also demonstrated a smaller peak knee extension moment(surgical leg:0.092±0.031;nonsurgical leg:0.133±0.024,P＜0.001)and peak knee external rotation moment(surgical leg:0.005±0.004;nonsurgical leg:0.008±0.004,P=0.015)when com-pared with the nonsurgical leg.Conclusion:The individuals with ACL reconstruction mainly showed asymmetrical movements in the sagittal and horizontal planes.The surgical leg demonstrated a smaller peak knee flexion angle,knee extension moment,and knee external rotation moment,with greater knee external rotation angle.

Objective:To investigate the treatment strategy for pediatric humeral supracondylar fractures with callus formation and displacement neglected for over 1 week.Methods:A retrospective analysis was made of the clinical data of 36 children who had been treated at Department of Pediatric Orthopaedics, Medical Center, The Second Affiliated Hospital, Inner Mongolia Medical University from January 2011 to January 2021 for humeral supracondylar fractures with callus formation and displacement neglected for over 1 week. There were 22 boys and 14 girls, with an age of (6.7±2.7) years (from 2.3 to 12.8 years). All fractures were Gartland type Ⅲ. The patients were divided into 2 groups according to their treatment methods: a closed reduction and percutaneous pinning (CRPP) group of 15 patients subjected to the CRPP treatment only, and a leverage group of 21 patients subjected to CRPP assisted by the "lever technique" with posterior elbow Kirschner wire prying and pulling. The 2 groups were compared in terms of operation time, fluoroscopy frequency, quality of reduction, and recovery time for elbow range of motion; the elbow range of motion, visual analogue scale (VAS), Mayo elbow performance score (MEPS) and complications were assessed at the last follow-up.Results:The 2 groups were comparable because there was no significant difference between them in the general information before operation ( P>0.05). All patients were followed up for (26.2±16.3) months (from 6 to 96 months). All the fractures obtained acceptable reduction and clinical union 4 to 6 weeks after operation. The operation time [(28.2±6.8) min] and fluoroscopy frequency [(27.0±6.0) times] in the leverage group were significantly less than those in the CRPP group [(40.8±10.8) min and (43.3±11.4) times] ( P<0.05). The CRPP group was significantly better than the leverage group in the intraoperative Baumann angle (78.1°±1.6° versus 73.7°±4.1°), lateral capitellohumeral angle (58.3°±2.6° versus 49.6°±5.2°) and horizontal rotation rate (109.5%±3.0% versus 103.2%±4.9%) ( P<0.05). The intraoperative reduction in the CRPP group was significantly closer to the normal mean value than that in the leverage group ( P<0.05). There was no significant difference in the recovery time for elbow range of motion between the CRPP and the leverage groups ( P>0.05). At the last follow-up, the Baumann angle (75.4°±2.8°) and the lateral capitellohumeral angle (53.2°±3.6°) in the leverage group were still significantly better than those in the CRPP group (78.3°±1.5° and 57.5°±2.3°) ( P<0.05). However, there was no significant difference in the elbow range of motion, VAS, MEPS or incidence of complications between the 2 groups ( P>0.05). Conclusion:To treat humeral supracondylar fractures with callus formation and displacement neglected for over 1 week in children, CRPP assisted by the "lever technique" with posterior elbow Kirschner wire prying and pulling is an efficient and accurate method, because it can lead to more satisfactory reduction than CRPP only.

Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT). Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the non-confirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared. Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group(9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282).The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+ and B27+/-)was significantly higher than that in the control group(χ2=16.579,P<0.001;χ2=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SSP. Conclusion:PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province.The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

Objective:To analyze the antigenicity and genetic characteristics of two strains of Eurasian avian H1N1 swine influenza virus (EAS-H1N1) isolated from 2 human cases found in Gansu province to provide scientific reference for disease prevention and control.Methods:Two cases of human infection with EAS-H1N1 discovered in Gansu province since February 2021 were analyzed for antigenicity and genome comparison, and their genome characteristics were analyzed using software such as Mega7.0.Results:Two human infections with EAS-H1N1 had related environmental exposure history. Two strains were obtained: A/Gansu-Xifeng/1143/2021 and A/Gansu-Xifeng/1194/2021. The two strains of HA, NA genes were all from the Eurasian avian H1N1 swine influenza virus, and are closely related to the human infection EAS-H1N1 virus in Hebei and Tianjin and the EAS-H1N1 virus isolated from the mink in Shandong; the HA receptor binding sites of 2 strains E190D and D225E mutations occurred in all spots, and there were no H274Y and N294S mutations in NA protein.Conclusions:Some important molecular mutations occurred in the genome of people infected with EAS-H1N1 virus in Gansu province, which may lead to increased virulence and potential human-to-human transmission. Strengthening the research and analysis of EAS-H1N1 gene characteristics will help to monitor the mutation and mutation of the virus at the molecular level and scientifically prevent and control the epidemic.