Objective:Osteoarthritis(OA)and sarcopenia are significant health concerns in the elderly,substantially impacting their daily activities and quality of life.However,the relationship between them remains poorly underst...Objective:Osteoarthritis(OA)and sarcopenia are significant health concerns in the elderly,substantially impacting their daily activities and quality of life.However,the relationship between them remains poorly understood.This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia.Methods:Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)between disease and control groups were identified using R software.Common DEGs were extracted via Venn diagram analysis.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs.Protein-protein interaction(PPI)networks were constructed,and candidate hub genes were ranked using the maximal clique centrality(MCC)algorithm.Further validation of hub gene expression was performed using 2 independent datasets.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia.Mouse models of OA and sarcopenia were established.Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model.The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement.Real-time reverse transcription PCR(real-time RT-PCR)was employed to assess the mRNA expression levels of candidate key genes in both models.Gene set enrichment analysis(GSEA)was conducted to identify pathways associated with the selected shared key genes in both diseases.Results:A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia,including 76 upregulated and 13 downregulated genes.These 89 DEGs were significantly enriched in protein digestion and absorption,the PI3K-Akt signaling pathway,and extracellular matrix-receptor interaction.PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes.Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets,AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases,both of which showed a significant upregulation trend in the disease groups(all P<0.05).The value of area under the curve(AUC)for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7,indicating that both genes have potential value in predicting OA and sarcopenia.Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups(all P<0.05),consistent with the results observed in the bioinformatics analysis.GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction,ribosome,and oxidative phosphorylation in OA and sarcopenia.Conclusion:AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia.The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.展开更多
Currently,research on N^(6)-methyladenine(m^(6)A)is extensive in the field of oncology,while studies involving m^(6)A and skin diseases remain relatively limited.Based on existing reports,we searched PubMed and Web of...Currently,research on N^(6)-methyladenine(m^(6)A)is extensive in the field of oncology,while studies involving m^(6)A and skin diseases remain relatively limited.Based on existing reports,we searched PubMed and Web of Science for literature related to m^(6)A and dermatological conditions.Analysis of citation counts and journal impact factors revealed a significant upward trend in the volume of m^(6)A-related research.Term frequency analysis of titles and abstracts indicated that studies mainly focus on skin tumors and inflammatory or immune-related skin diseases,particularly melanoma,psoriasis,and skin development.Transcriptomic data from the Gene Expression Omnibus(GEO)were analyzed,revealing differential expression of m^(6)A-related genes in 4 types of skin tumors(including squamous cell carcinoma and basal cell carcinoma)as well as in inflammatory skin diseases such as psoriasis and atopic dermatitis,and potential mechanisms of action were also explored.Findings suggest that m^(6)A modifications exhibit heterogeneity between neoplastic and nonneoplastic skin diseases.However,the regulatory mechanisms of m^(6)A dynamic modifications on key genes involved in dermatological disorders remain unclear and warrant further investigation.展开更多
Critical care medicine focuses on understanding the pathophysiological mechanisms and treatment approaches for life-threatening conditions,including sepsis,severe trauma/burns,hemorrhagic shock,heatstroke,and acute pa...Critical care medicine focuses on understanding the pathophysiological mechanisms and treatment approaches for life-threatening conditions,including sepsis,severe trauma/burns,hemorrhagic shock,heatstroke,and acute pancreatitis,all of which have high incidence rates.These conditions are primarily characterized by acute multi-organ dysfunction,with sudden onset,severe illness,and high mortality rates.Additionally,critical care treatment demands substantial medical resources,imposing significant economic burdens on patients’families and society.In recent years,critical care medicine has achieved notable progress,especially in multidisciplinary integration with immunology-based fields.Collaboration across disciplines has not only accelerated advancements in critical care but also propelled the rapid development of modern immunology.This paper provides an overview and assessment of the cross-disciplinary fusion between critical care medicine and immunology,exploring how these fields related extensions mutually enhance each other.It further analyzes China’s potential to become a global leader in this area within the next 5 to 10 years.展开更多
Objective:Compared with long-term renal replacement therapy,kidney transplantation is the ideal treatment for end-stage renal disease(ESRD),significantly extending patient life and improving quality of life.Kidney tra...Objective:Compared with long-term renal replacement therapy,kidney transplantation is the ideal treatment for end-stage renal disease(ESRD),significantly extending patient life and improving quality of life.Kidney transplant patients need to adhere to lifelong immunosuppressive medication regimens,but their medication adherence is generally poor compared with other organ transplant recipients.Medication adherence is closely related to medication literacy and psychological status,yet related studies are limited.This study aims to investigate the current status of medication adherence,inner strength,and medication literacy in kidney transplant patients,analyze the relationships among these 3 factors,and explore the mediating role of inner strength in the relationship between medication literacy and medication adherence.Methods:A cross-sectional survey was conducted from March to October 2023 involving 421 patients aged≥18 years who visited kidney transplantation outpatient clinics at 4 tertiary hospitals in Hunan Province.The inner strength,medication literacy,and medication adherence of kidney transplant patients were investigated using the Inner Strength Scale(ISS),the Chinese version of the Medication Literacy Assessment in Spanish and English(MedLitRxSE),and the Chinese version of the Morisky Medication Adherence Scale-8(C-MMAS-8),respectively.Univariate analysis was performed to examine the effects of demographic and clinical data on medication adherence.Correlation analysis was conducted to explore the relationships among medication literacy,medication adherence,and inner strength.Significant variables from univariate and correlation analyses were further analyzed using multiple linear regression,and the mediating effect of inner strength was explored.Results:Among the 421 questionnaires collected,408 were valid,with an effective rate of 96.91%.The scores of C-MMAS-8,MedLitRxSE,and ISS were 6.64±1.16,100.63±14.67,and 8.47±4.03,respectively.Among the 408 patients,only 86(21.08%)patients had a high level of medication adherence,whereas 230(56.37%)patients had a medium level of medication adherence,and 92(22.55%)patients had poor medication adherence.Univariate analysis indicated that the kidney transplant patients’age,marital status,education levels,years since their kidney transplant operation,number of hospitalizations after the kidney transplant,and adverse drug reactions showed significant differences in medication adherence(all P<0.05).Correlation analysis showed that inner strength positively correlated with both medication literacy(r=0.183,P<0.001)and medication adherence(r=0.201,P<0.001).Additionally,there was a positive correlation between medication adherence and medication literacy(r=0.236,P<0.001).Inner strength accounted for 13.22%of the total effect in the mediating role between medication literacy and medication adherence.Conclusion:The level of medication adherence among kidney transplant patients needs improvement,and targeted intervention measures are essential.Inner strength mediates the relationship between medication literacy and medication adherence in these patients.Healthcare professionals should focus on enhancing medication literacy and supporting patients’inner strength to improve medication adherence.展开更多
Methylenetetrahydrofolate reductase(MTHFR)deficiency is a rare autosomal recessive genetic disorder caused by mutations in the MTHFR gene,leading to a variety of clinical manifestations.In October 2022,the Second Xian...Methylenetetrahydrofolate reductase(MTHFR)deficiency is a rare autosomal recessive genetic disorder caused by mutations in the MTHFR gene,leading to a variety of clinical manifestations.In October 2022,the Second Xiangya Hospital of Central South University admitted a 21-year-old male patient with neuropsychiatric disorders,presenting primarily with cognitive decline,limb tremors,abnormal mental and behavioral symptoms,seizures,and gait disturbances.These symptoms had gradually developed over 5 years,worsening significantly in the past year.The patient’s plasma homocysteine levels were 10 times higher than normal,and brain MRI revealed brain atrophy and significant abnormal signals in the bilateral paraventricular nuclei and heads of the bilateral caudate nuclei.Further genetic testing identified a paternal mutation c.1604G>A(p.R535Q)and a maternal mutation c.227T>G(p.L76R)of the MTHFR gene.After betaine supplementation,the plasma homocysteine levels decreased within a week,and the symptoms improved.The patient was ultimately diagnosed with severe hyperhomocysteinemia due to MTHFR deficiency.The c.227T>G(p.L76R)mutation represents a novel missense mutation in the MTHFR gene associated with MTHFR deficiency,but further research is needed to confirm its potential pathogenicity.Early treatment with betaine can fully reverse the symptoms.展开更多
Objective:IgA nephropathy(IgAN)is the most common primary glomerular disease in China,but its pathogenesis remains unclear.This study aims to explore the regulatory role of the mammalian target of rapamycin(mTOR)signa...Objective:IgA nephropathy(IgAN)is the most common primary glomerular disease in China,but its pathogenesis remains unclear.This study aims to explore the regulatory role of the mammalian target of rapamycin(mTOR)signaling pathway in autophagy and mesangial proliferation during renal injury in IgA.Methods:The activity of mTOR and autophagy was evaluated in kidney samples from IgAN patients and in an IgAN mouse model induced by oral bovine serum albumin and carbon tetrachloride(CCl4)injection.mTOR inhibitors(rapamycin)and activators[bpV(phen)]were administered to the IgAN mouse model to observe the effects of mTOR on autophagy and renal lesions.In human mesangial cells treated with polymeric IgA1(p IgA1)and mTOR modulators,the expression and distribution of cell cycle proteins were assessed,along with the effects of mTOR on mesangial cell proliferation and autophagy.Results:Increased mTOR activity and decreased autophagy were observed in kidney tissues from IgAN patients and the mouse model,as evidenced by elevated phosphorylated mTOR(p-mTOR)levels and reduced LC3 expression.In the IgAN mouse model,rapamycin inhibited mTOR,restored autophagy,reduced mesangial IgA deposition,alleviated mesangial cell proliferation,and decreased proteinuria(all P<0.05).In contrast,bpV(phen)activated mTOR,further suppressed autophagy,exacerbated kidney damage,and increased proteinuria(all P<0.05).In vitro,p-IgA1 induced mesangial cell proliferation and inhibited autophagy,effects that were reversed by rapamycin and aggravated by bpV(phen)(all P<0.05).mTOR regulated mesangial cell proliferation by altering cell cycle distribution,with rapamycin inducing G1 phase arrest and bpV(phen)promoting cell cycle progression.Additionally,cyclinD1 expression in renal cortex was up-regulated in the IgAN mouse model,further increased by bpV(phen),and reduced by rapamycin(all P<0.05).Conclusion:Inhibition of the mTOR signaling pathway enhances renal autophagy,reduces mesangial cell proliferation,and improves renal injury in IgAN.展开更多
The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South Univers...The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions.Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan.Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung.Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases.Immunohistochemical(IHC)staining demonstrated positivity for thyroid transcription factor 1(TTF-1)and ALK-D5F3 in tumor cells,while negativity for P40.The next-generation sequencing(NGS)tests identified a PNPT1-ALK(Exon22:Exon20)fusion variant in case 1 and a TCEAL2-ALK(Exon3:Exon19)fusion variant in case 2.The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system(ARMS)-PCR at the mRNA level.Both patients were treated with oral alectinib at a dosage of 600 mg twice daily.The tumors in both patients were significantly decreased after alectinib treatment,achieving partial response.At the time of submission,there was an absence of disease progression and the progression-free survival(PFS)had surpassed 1 year.It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK(Exon22:Exon20)fusion or a TCEAL2-ALK(Exon3:Exon19)fusion,experience favorable therapeutic outcomes through the administration of alectinib.This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors(TKIs).展开更多
Objective:Healthcare workers,as a high-stress professional group,face long-term high intensity workloads and complex medical environments,resulting in increasingly prominent mental health issues.In particular,the wide...Objective:Healthcare workers,as a high-stress professional group,face long-term high intensity workloads and complex medical environments,resulting in increasingly prominent mental health issues.In particular,the widespread presence of anxiety symptoms and somatic pain has become a major factor affecting both the quality of care and the career development of healthcare workers.This study aims to investigate the mediating and moderating roles of psychological resilience and sleep in the relationship between somatic pain and anxiety among healthcare workers.Methods:A cross-sectional questionnaire survey was conducted among 1661 healthcare workers.The instruments used included the Generalized Anxiety Disorder-7(GAD-7),item 3 from the Patient Health Questionnaire-9(PHQ-9),the 10-item Connor-Davidson Resilience Scale(CD-RISC-10)for psychological resilience,and the Visual Analogue Scale(VAS)for assessing anxiety,sleep disturbance,psychological resilience,and somatic pain.Results:The detection rate of anxiety symptoms among healthcare workers was 38.95%.Psychological resilience was significantly negatively correlated with anxiety symptoms(r=−0.451,P<0.01),sleep disturbance(r=−0.313,P<0.01),and somatic pain(r=−0.214,P<0.01).Moreover,psychological resilience partially mediated the relationship between somatic pain and anxiety(β=−0.103,P<0.01),and sleep quality moderated the latter part of the mediation model(“somatic pain-psychological resilience-anxiety”).Conclusion:Under high-intensity workloads,healthcare workers generally experience severe anxiety symptoms.Psychological resilience plays an important protective mediating role in their mental health,and sleep quality serves as a moderator in this relationship.Enhancing healthcare workers’psychological resilience and improving their sleep may promote both their physical and mental well-being.展开更多
Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum c...Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum creatinine(Scr)levels,the incidence of ARC is high in intensive care unit(ICU)settings.ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics.However,limited research exists on the incidence and risk factors of ARC in the ICU,and even fewer data are available specifically for neurological ICU(NICU).This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients.Methods:We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023.Creatinine clearance(CrCl)was calculated using the Cockcroft-Gault equation.ARC was defined as a CrCl≥130 mL/(min·1.73 m^(2))sustained for more than 50%of the duration of the NICU stay.A total of 208 neurocritically ill patients were assigned into an ARC group(n=52)and a non-ARC(N-ARC)group(n=156).Clinical characteristics were compared between the 2 groups.Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC.Results:The incidence of ARC among neurocritically ill patients was 25.00%.Of the 74 patients with normal CrCl,20(27.03%)gradually developed ARC during hospitalization.Compared with the N-ARC group,the patients of the ARC group were younger(P<0.001),with a higher proportion of females(P=0.048)and a lower admission mean arterial pressure(MAP)(P=0.034).Moreover,patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group(P<0.001).In binary Logistic regression analysis,younger age(OR=0.903,95%CI 0.872 to 0.935)and severe bacterial infections(OR=6.270,95%CI 2.568 to 15.310)were significant predictors of ARC.Conclusion:ARC is relatively common in the NICU.A considerable number of patients with initially normal renal function developed ARC during hospitalization.Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.展开更多
Objective:Existing research shows that psychotherapists may experience secondary trauma and burnout,often neglecting self-care.This study aims to examine the effectiveness of self-care education in enhancing self-care...Objective:Existing research shows that psychotherapists may experience secondary trauma and burnout,often neglecting self-care.This study aims to examine the effectiveness of self-care education in enhancing self-care efficacy among psychotherapists and explore factors affecting improvements in their self-care abilities.Methods:A self-care workshop was conducted for 159 psychotherapists from various fields.Participants’demographic information and self-care ability data were collected.The Exercise of Self-Care Agency Scale(ESCA)was used to assess the participant’s self-care levels before and after the workshop.Results:Post-workshop,ESCA total scores and subscale scores of participants showed significant increases(all P<0.001).Notably,score improvement levels differed by gender and years of practice,with female therapists showing greater improvement than male therapists(t=2.069,P=0.040)and those with longer work experience showing greater improvement than those with shorter experience(F=2.537,P=0.042).Conclusion:Providing self-care education for psychotherapists is essential.Future self care education programs or interventions for psychotherapists should consider gender and work experience factors to better support their self-care enhancement.展开更多
Objective:Long noncoding RNAs(lncRNA)play important roles in the pathological processes of angiogenesis-related diseases such as cancer and diabetic retinopathy.This study aims to identify global research trends and h...Objective:Long noncoding RNAs(lncRNA)play important roles in the pathological processes of angiogenesis-related diseases such as cancer and diabetic retinopathy.This study aims to identify global research trends and hotspots in the field of lncRNAs in angiogenesis-related diseases and to explore future research directions.Methods:Relevant literature published between 2012 and 2022 was retrieved from the Web of Science Core Collection(WoSCC).A total of 1516 articles on lncRNAs and angiogenesis-related diseases were included for bibliometric analysis.CiteSpace and VOSviewer were used to analyze publication countries,institutions,journals,authors,co cited references,and key words.Results:The number of publications in this field has shown a steadily increasing trend from 2012 to 2022,peaking in 2021.China has the highest number of publications,while the United States ranked highest in centrality.Nanjing Medical University was the most prolific institution.Liu Y was the most productive author,while Wang Y ranked first in co citation frequency.Cell was the most frequently cited journal.The latest terms of burst key words were vascular remodeling,dysfunction,heart,target,suppress,and pulmonary arterial hypertension.Conclusion:From 2012 to 2022,research on lncRNAs in angiogenesis-related diseases has grown significantly.China leads in publication volume,while the United States holds the most academic influence.Emerging research hotspots such as vascular remodeling and dysfunction point to key directions for future research.展开更多
Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remai...Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma.Methods:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin tissues.Results:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m^(6)A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway.Conclusion:This study reveals the m^(6)A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m^(6)A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.展开更多
基金supported by the National Natural Science Foundation of China(82060418).
文摘Objective:Osteoarthritis(OA)and sarcopenia are significant health concerns in the elderly,substantially impacting their daily activities and quality of life.However,the relationship between them remains poorly understood.This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia.Methods:Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)between disease and control groups were identified using R software.Common DEGs were extracted via Venn diagram analysis.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs.Protein-protein interaction(PPI)networks were constructed,and candidate hub genes were ranked using the maximal clique centrality(MCC)algorithm.Further validation of hub gene expression was performed using 2 independent datasets.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia.Mouse models of OA and sarcopenia were established.Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model.The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement.Real-time reverse transcription PCR(real-time RT-PCR)was employed to assess the mRNA expression levels of candidate key genes in both models.Gene set enrichment analysis(GSEA)was conducted to identify pathways associated with the selected shared key genes in both diseases.Results:A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia,including 76 upregulated and 13 downregulated genes.These 89 DEGs were significantly enriched in protein digestion and absorption,the PI3K-Akt signaling pathway,and extracellular matrix-receptor interaction.PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes.Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets,AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases,both of which showed a significant upregulation trend in the disease groups(all P<0.05).The value of area under the curve(AUC)for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7,indicating that both genes have potential value in predicting OA and sarcopenia.Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups(all P<0.05),consistent with the results observed in the bioinformatics analysis.GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction,ribosome,and oxidative phosphorylation in OA and sarcopenia.Conclusion:AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia.The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
基金supported by the National Natural Science Foundation,China(82103704).
文摘Currently,research on N^(6)-methyladenine(m^(6)A)is extensive in the field of oncology,while studies involving m^(6)A and skin diseases remain relatively limited.Based on existing reports,we searched PubMed and Web of Science for literature related to m^(6)A and dermatological conditions.Analysis of citation counts and journal impact factors revealed a significant upward trend in the volume of m^(6)A-related research.Term frequency analysis of titles and abstracts indicated that studies mainly focus on skin tumors and inflammatory or immune-related skin diseases,particularly melanoma,psoriasis,and skin development.Transcriptomic data from the Gene Expression Omnibus(GEO)were analyzed,revealing differential expression of m^(6)A-related genes in 4 types of skin tumors(including squamous cell carcinoma and basal cell carcinoma)as well as in inflammatory skin diseases such as psoriasis and atopic dermatitis,and potential mechanisms of action were also explored.Findings suggest that m^(6)A modifications exhibit heterogeneity between neoplastic and nonneoplastic skin diseases.However,the regulatory mechanisms of m^(6)A dynamic modifications on key genes involved in dermatological disorders remain unclear and warrant further investigation.
基金supported by the National Science Foundation for Distinguished Young Scholars,China(82025021).
文摘Critical care medicine focuses on understanding the pathophysiological mechanisms and treatment approaches for life-threatening conditions,including sepsis,severe trauma/burns,hemorrhagic shock,heatstroke,and acute pancreatitis,all of which have high incidence rates.These conditions are primarily characterized by acute multi-organ dysfunction,with sudden onset,severe illness,and high mortality rates.Additionally,critical care treatment demands substantial medical resources,imposing significant economic burdens on patients’families and society.In recent years,critical care medicine has achieved notable progress,especially in multidisciplinary integration with immunology-based fields.Collaboration across disciplines has not only accelerated advancements in critical care but also propelled the rapid development of modern immunology.This paper provides an overview and assessment of the cross-disciplinary fusion between critical care medicine and immunology,exploring how these fields related extensions mutually enhance each other.It further analyzes China’s potential to become a global leader in this area within the next 5 to 10 years.
基金This work was supported by the Natural Science Foundation of Hunan Province,China (2024JJ9201)。
文摘Objective:Compared with long-term renal replacement therapy,kidney transplantation is the ideal treatment for end-stage renal disease(ESRD),significantly extending patient life and improving quality of life.Kidney transplant patients need to adhere to lifelong immunosuppressive medication regimens,but their medication adherence is generally poor compared with other organ transplant recipients.Medication adherence is closely related to medication literacy and psychological status,yet related studies are limited.This study aims to investigate the current status of medication adherence,inner strength,and medication literacy in kidney transplant patients,analyze the relationships among these 3 factors,and explore the mediating role of inner strength in the relationship between medication literacy and medication adherence.Methods:A cross-sectional survey was conducted from March to October 2023 involving 421 patients aged≥18 years who visited kidney transplantation outpatient clinics at 4 tertiary hospitals in Hunan Province.The inner strength,medication literacy,and medication adherence of kidney transplant patients were investigated using the Inner Strength Scale(ISS),the Chinese version of the Medication Literacy Assessment in Spanish and English(MedLitRxSE),and the Chinese version of the Morisky Medication Adherence Scale-8(C-MMAS-8),respectively.Univariate analysis was performed to examine the effects of demographic and clinical data on medication adherence.Correlation analysis was conducted to explore the relationships among medication literacy,medication adherence,and inner strength.Significant variables from univariate and correlation analyses were further analyzed using multiple linear regression,and the mediating effect of inner strength was explored.Results:Among the 421 questionnaires collected,408 were valid,with an effective rate of 96.91%.The scores of C-MMAS-8,MedLitRxSE,and ISS were 6.64±1.16,100.63±14.67,and 8.47±4.03,respectively.Among the 408 patients,only 86(21.08%)patients had a high level of medication adherence,whereas 230(56.37%)patients had a medium level of medication adherence,and 92(22.55%)patients had poor medication adherence.Univariate analysis indicated that the kidney transplant patients’age,marital status,education levels,years since their kidney transplant operation,number of hospitalizations after the kidney transplant,and adverse drug reactions showed significant differences in medication adherence(all P<0.05).Correlation analysis showed that inner strength positively correlated with both medication literacy(r=0.183,P<0.001)and medication adherence(r=0.201,P<0.001).Additionally,there was a positive correlation between medication adherence and medication literacy(r=0.236,P<0.001).Inner strength accounted for 13.22%of the total effect in the mediating role between medication literacy and medication adherence.Conclusion:The level of medication adherence among kidney transplant patients needs improvement,and targeted intervention measures are essential.Inner strength mediates the relationship between medication literacy and medication adherence in these patients.Healthcare professionals should focus on enhancing medication literacy and supporting patients’inner strength to improve medication adherence.
基金supported by the National Natural Science Foundation(81971696)the Natural Science Foundation of Hunan Province(2022JJ30861),China.
文摘Methylenetetrahydrofolate reductase(MTHFR)deficiency is a rare autosomal recessive genetic disorder caused by mutations in the MTHFR gene,leading to a variety of clinical manifestations.In October 2022,the Second Xiangya Hospital of Central South University admitted a 21-year-old male patient with neuropsychiatric disorders,presenting primarily with cognitive decline,limb tremors,abnormal mental and behavioral symptoms,seizures,and gait disturbances.These symptoms had gradually developed over 5 years,worsening significantly in the past year.The patient’s plasma homocysteine levels were 10 times higher than normal,and brain MRI revealed brain atrophy and significant abnormal signals in the bilateral paraventricular nuclei and heads of the bilateral caudate nuclei.Further genetic testing identified a paternal mutation c.1604G>A(p.R535Q)and a maternal mutation c.227T>G(p.L76R)of the MTHFR gene.After betaine supplementation,the plasma homocysteine levels decreased within a week,and the symptoms improved.The patient was ultimately diagnosed with severe hyperhomocysteinemia due to MTHFR deficiency.The c.227T>G(p.L76R)mutation represents a novel missense mutation in the MTHFR gene associated with MTHFR deficiency,but further research is needed to confirm its potential pathogenicity.Early treatment with betaine can fully reverse the symptoms.
基金supported by the Key Funding Project of Hunan Provincial Health Commission(A202303057091)the Nephrology Medical Development Research Fund Project(20220316ZN),China.
文摘Objective:IgA nephropathy(IgAN)is the most common primary glomerular disease in China,but its pathogenesis remains unclear.This study aims to explore the regulatory role of the mammalian target of rapamycin(mTOR)signaling pathway in autophagy and mesangial proliferation during renal injury in IgA.Methods:The activity of mTOR and autophagy was evaluated in kidney samples from IgAN patients and in an IgAN mouse model induced by oral bovine serum albumin and carbon tetrachloride(CCl4)injection.mTOR inhibitors(rapamycin)and activators[bpV(phen)]were administered to the IgAN mouse model to observe the effects of mTOR on autophagy and renal lesions.In human mesangial cells treated with polymeric IgA1(p IgA1)and mTOR modulators,the expression and distribution of cell cycle proteins were assessed,along with the effects of mTOR on mesangial cell proliferation and autophagy.Results:Increased mTOR activity and decreased autophagy were observed in kidney tissues from IgAN patients and the mouse model,as evidenced by elevated phosphorylated mTOR(p-mTOR)levels and reduced LC3 expression.In the IgAN mouse model,rapamycin inhibited mTOR,restored autophagy,reduced mesangial IgA deposition,alleviated mesangial cell proliferation,and decreased proteinuria(all P<0.05).In contrast,bpV(phen)activated mTOR,further suppressed autophagy,exacerbated kidney damage,and increased proteinuria(all P<0.05).In vitro,p-IgA1 induced mesangial cell proliferation and inhibited autophagy,effects that were reversed by rapamycin and aggravated by bpV(phen)(all P<0.05).mTOR regulated mesangial cell proliferation by altering cell cycle distribution,with rapamycin inducing G1 phase arrest and bpV(phen)promoting cell cycle progression.Additionally,cyclinD1 expression in renal cortex was up-regulated in the IgAN mouse model,further increased by bpV(phen),and reduced by rapamycin(all P<0.05).Conclusion:Inhibition of the mTOR signaling pathway enhances renal autophagy,reduces mesangial cell proliferation,and improves renal injury in IgAN.
基金supported by the National Natural Science Foundation(81900070)the Natural Science Foundation of Hunan Province(2020JJ5813)China。
文摘The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions.Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan.Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung.Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases.Immunohistochemical(IHC)staining demonstrated positivity for thyroid transcription factor 1(TTF-1)and ALK-D5F3 in tumor cells,while negativity for P40.The next-generation sequencing(NGS)tests identified a PNPT1-ALK(Exon22:Exon20)fusion variant in case 1 and a TCEAL2-ALK(Exon3:Exon19)fusion variant in case 2.The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system(ARMS)-PCR at the mRNA level.Both patients were treated with oral alectinib at a dosage of 600 mg twice daily.The tumors in both patients were significantly decreased after alectinib treatment,achieving partial response.At the time of submission,there was an absence of disease progression and the progression-free survival(PFS)had surpassed 1 year.It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK(Exon22:Exon20)fusion or a TCEAL2-ALK(Exon3:Exon19)fusion,experience favorable therapeutic outcomes through the administration of alectinib.This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors(TKIs).
基金supported by the Natural Science Foundation of Hunan Province,China(2023JJ60076)。
文摘Objective:Healthcare workers,as a high-stress professional group,face long-term high intensity workloads and complex medical environments,resulting in increasingly prominent mental health issues.In particular,the widespread presence of anxiety symptoms and somatic pain has become a major factor affecting both the quality of care and the career development of healthcare workers.This study aims to investigate the mediating and moderating roles of psychological resilience and sleep in the relationship between somatic pain and anxiety among healthcare workers.Methods:A cross-sectional questionnaire survey was conducted among 1661 healthcare workers.The instruments used included the Generalized Anxiety Disorder-7(GAD-7),item 3 from the Patient Health Questionnaire-9(PHQ-9),the 10-item Connor-Davidson Resilience Scale(CD-RISC-10)for psychological resilience,and the Visual Analogue Scale(VAS)for assessing anxiety,sleep disturbance,psychological resilience,and somatic pain.Results:The detection rate of anxiety symptoms among healthcare workers was 38.95%.Psychological resilience was significantly negatively correlated with anxiety symptoms(r=−0.451,P<0.01),sleep disturbance(r=−0.313,P<0.01),and somatic pain(r=−0.214,P<0.01).Moreover,psychological resilience partially mediated the relationship between somatic pain and anxiety(β=−0.103,P<0.01),and sleep quality moderated the latter part of the mediation model(“somatic pain-psychological resilience-anxiety”).Conclusion:Under high-intensity workloads,healthcare workers generally experience severe anxiety symptoms.Psychological resilience plays an important protective mediating role in their mental health,and sleep quality serves as a moderator in this relationship.Enhancing healthcare workers’psychological resilience and improving their sleep may promote both their physical and mental well-being.
基金supported by the Natural Science Foundation of Hunan Province(2023JJ60087)the Clinical Medical Technology Innovation Guidance Project of Hunan Province(2021SK53501),China。
文摘Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum creatinine(Scr)levels,the incidence of ARC is high in intensive care unit(ICU)settings.ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics.However,limited research exists on the incidence and risk factors of ARC in the ICU,and even fewer data are available specifically for neurological ICU(NICU).This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients.Methods:We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023.Creatinine clearance(CrCl)was calculated using the Cockcroft-Gault equation.ARC was defined as a CrCl≥130 mL/(min·1.73 m^(2))sustained for more than 50%of the duration of the NICU stay.A total of 208 neurocritically ill patients were assigned into an ARC group(n=52)and a non-ARC(N-ARC)group(n=156).Clinical characteristics were compared between the 2 groups.Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC.Results:The incidence of ARC among neurocritically ill patients was 25.00%.Of the 74 patients with normal CrCl,20(27.03%)gradually developed ARC during hospitalization.Compared with the N-ARC group,the patients of the ARC group were younger(P<0.001),with a higher proportion of females(P=0.048)and a lower admission mean arterial pressure(MAP)(P=0.034).Moreover,patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group(P<0.001).In binary Logistic regression analysis,younger age(OR=0.903,95%CI 0.872 to 0.935)and severe bacterial infections(OR=6.270,95%CI 2.568 to 15.310)were significant predictors of ARC.Conclusion:ARC is relatively common in the NICU.A considerable number of patients with initially normal renal function developed ARC during hospitalization.Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.
基金supported by the Natural Science Foundation of Hunan Province,China(2023JJ60076).
文摘Objective:Existing research shows that psychotherapists may experience secondary trauma and burnout,often neglecting self-care.This study aims to examine the effectiveness of self-care education in enhancing self-care efficacy among psychotherapists and explore factors affecting improvements in their self-care abilities.Methods:A self-care workshop was conducted for 159 psychotherapists from various fields.Participants’demographic information and self-care ability data were collected.The Exercise of Self-Care Agency Scale(ESCA)was used to assess the participant’s self-care levels before and after the workshop.Results:Post-workshop,ESCA total scores and subscale scores of participants showed significant increases(all P<0.001).Notably,score improvement levels differed by gender and years of practice,with female therapists showing greater improvement than male therapists(t=2.069,P=0.040)and those with longer work experience showing greater improvement than those with shorter experience(F=2.537,P=0.042).Conclusion:Providing self-care education for psychotherapists is essential.Future self care education programs or interventions for psychotherapists should consider gender and work experience factors to better support their self-care enhancement.
基金supported by the Natural Science Foundation of Hunan Province,China(2022JJ30869).
文摘Objective:Long noncoding RNAs(lncRNA)play important roles in the pathological processes of angiogenesis-related diseases such as cancer and diabetic retinopathy.This study aims to identify global research trends and hotspots in the field of lncRNAs in angiogenesis-related diseases and to explore future research directions.Methods:Relevant literature published between 2012 and 2022 was retrieved from the Web of Science Core Collection(WoSCC).A total of 1516 articles on lncRNAs and angiogenesis-related diseases were included for bibliometric analysis.CiteSpace and VOSviewer were used to analyze publication countries,institutions,journals,authors,co cited references,and key words.Results:The number of publications in this field has shown a steadily increasing trend from 2012 to 2022,peaking in 2021.China has the highest number of publications,while the United States ranked highest in centrality.Nanjing Medical University was the most prolific institution.Liu Y was the most productive author,while Wang Y ranked first in co citation frequency.Cell was the most frequently cited journal.The latest terms of burst key words were vascular remodeling,dysfunction,heart,target,suppress,and pulmonary arterial hypertension.Conclusion:From 2012 to 2022,research on lncRNAs in angiogenesis-related diseases has grown significantly.China leads in publication volume,while the United States holds the most academic influence.Emerging research hotspots such as vascular remodeling and dysfunction point to key directions for future research.
基金supported by the National Natural Science Foundation(82071036,82000973)the Natural Science Foundation of Hunan Province(2022JJ30821,2019JJ50967)the Special Project for the Construction of Innovative Provinces in Hunan Province(2023SK4030),China。
文摘Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma.Methods:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin tissues.Results:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m^(6)A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway.Conclusion:This study reveals the m^(6)A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m^(6)A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.
