最新刊期

    50 4 2025

      Guideline and Consensus

    • 在应对气候变暖导致的热射病增多问题上,全军热射病防治与研究中心等机构制定了新的防治指南,提出了25条推荐意见,为热射病的防治与研究工作提供指导。
      Song Jing-Chun, Song Qing, Zhang Wei, Li Wei-Qin, Zhang Xi-Jing, Liu Shu-Yuan, Gao Yan, Li Hai-Ling, Heatstroke Prevention and Treatment Research Center of Chinese PLA, Expert Group of Heatstroke Prevention and Treatment of Chinese PLA, and Chinese PLA Professional Committee of Critical Care Medicine
      Vol. 50, Issue 4, Pages: 367-386(2025) DOI: 10.11855/j.issn.0577-7402.0506.2025.0328
      Chinese guideline for the diagnosis and treatment of heatstroke (2025 edition)
      摘要:In recent years, the incidence and mortality of heatstroke have been increasing annually alongside global warming, with a marked rise in cases exhibiting atypical symptoms. To address the increasingly complex challenges in heatstroke prevention and treatment, Heatstroke Prevention and Treatment Research Center of Chinese PLA, Expert Group of Heatstroke Prevention and Treatment of Chinese PLA, and Chinese PLA Professional Committee of Critical Care Medicine have jointly developed this guideline (2025 edition). Utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, Appraisal of Guidelines for Research and Evaluation (AGREE) criteria, and Reporting Items for Practice Guidelines in Healthcare (RIGHT) standards, and based on the 2015 draft "Expert Consensus on the Standardized Diagnosis and Treatment of Heatstroke" and the 2019 "Chinese Expert Consensus on the Diagnosis and Treatment of Heatstroke", this guideline has been crafted. This guideline provides 25 evidence-based recommendations to guide the prevention, treatment and research of heatstroke, which thoroughly covers 8 critical domains: clinical classification, pathophysiological mechanisms, clinical manifestations, diagnostic criteria, differential diagnosis, treatment protocols, rehabilitation and return to work, and prevention.  
      关键词:heatstroke;classic type;exertional type;diagnosis;life chain;heat acclimation;return to work   
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      Expert Review

    • 最新研究揭示无功能垂体瘤新分类,助力精准诊疗和预后评估。
      Sun Tian, Zhang Xue-Dong, Zheng Er-Han, Shen Hao, Zhou Tao, Meng Xiang-Hui, Guo Qing-Hua
      Vol. 50, Issue 4, Pages: 387-392(2025) DOI: 10.11855/j.issn.0577-7402.1810.2025.0304
      摘要:Non-functioning pituitary adenomas (NFPAs) are relatively common. Apart from hyperprolactinemia caused by pituitary compression, they typically lack overt hormonal hypersecretion and usually present with clinical symptoms due to mass effects. Previously considered a uniform entity, NFPAs are actually a highly heterogeneous group of tumors, including aggressive subtypes like silent corticotroph adenomas (SCA) and null cell adenomas. The 2022 WHO new classification of pituitary tumors employs transcription factors [e.‍g., pituitary-specific transcription factor 1 (PIT-1), T-box transcription factor 19 (TBX19, also known as TPIT), steroidogenic factor 1 (SF-1)] for detailed categorization, allowing precise subclassification of NFPAs into multiple subtypes derived from distinct cell lineages, including silent gonadotroph adenomas, SCA, and plurihormonal PIT-1-positive adenomas. This helps identify highly invasive subtypes with high recurrence risk, guiding clinical diagnosis and treatment, prognostic assessment, and individualized management. The new classification also provides a theoretical basis for targeted therapies of NFPAs (e.g., somatostatin analogs and temozolomide). This review comprehensively discusses the latest pathological classification of NFPAs and its clinical implications, aiming to enhance understanding of this disease and offer valuable insights for precise diagnosis, treatment, and prognostic assessment.  
      关键词:non-functioning pituitary tumor;pathological classification;transcription factors;diagnosis;treatment   
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      Clinical Research

    • 在神经外科领域,北京天坛医院专家通过回顾性分析252例高分级无功能垂体神经内分泌肿瘤患者资料,发现年龄小于55岁、T2信号不均匀、Knosp 3B-4级及Ki-67≥3%是肿瘤复发相关的风险因素,为预测肿瘤全切术后复发提供解决方案。
      Zhang Zhe, Bie Zhi-Xu, Liu Pi-Nan, Li Peng
      Vol. 50, Issue 4, Pages: 393-399(2025) DOI: 10.11855/j.issn.0577-7402.1614.2025.0103
      Analysis of recurrent risk factors associated with high-grade non-functional pituitary neuroendocrine tumors
      摘要:ObjectiveTo investigate the risk factors associated with recurrence of high-grade non-functioning pituitary neuroendocrine tumors (NF-PitNETs) following total resection.MethodsA retrospective study was conducted on the clinical data of 252 patients with high-grade NF-PitNETs who underwent surgical treatment at the Department of Neurosurgery, Beijing Tiantan Hospital from January 2012 to December 2023, and met the inclusion criteria. High-grade NF-PitNETs included Knosp 3A, 3B, and4-grade subtypes. Kaplan-Meier curves and Log-rank tests were employed to compare the progression-free survival (PFS) of Knosp 3A, 3B, and 4-grade patients. Cox regression analysis was applied to identify the risk factors associated with the recurrence of high-grade NF-PitNETs. Receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of each recurrence-related factor to evaluate the diagnostic efficiency.ResultsSurvival analysis revealed that there were significant differences in PFS among Knosp 3A, 3B, and 4-grade patients (P<0.001). The PFS of Knosp 3A was significantly better than that of grade 3B and 4-grade (P<0.05), while there was no significant difference between Knosp 3B and 4-grade (P=0.118). After integrating the three groups into Knosp 3A group and 3B-4 group, there were significant differences in PFS and some clinical features between the two groups (P<0.05). Cox regression analysis indicated that age <55 years old (HR=2.883, 95%CI 1.253-6.634; P=0.013), T2 heterogeneous signal (HR=1.842, 95%CI 1.061-3.197; P=0.030), Knosp 3B-4 (HR=2.190, 95%CI 1.069-4.488; P=0.032), and Ki-67≥3% (HR=2.266, 95%CI 1.265-4.061; P=0.006) were risk factors related to tumor recurrence. ROC curve analysis showed that the AUCs of the above-mentioned risk factors were 0.682, 0.706, 0.709 and 0.750, respectively, and the AUC of the multi-factor combined model (age+T2 signal+Knosp grade+Ki-67) was 0.838, which was significantly larger than that of each single risk factor (P<0.05).ConclusionHigh-grade NF-PitNETs patients with age <55 years old, T2 heterogeneous signal, Knosp 3B-4 and Ki-67≥3% have a higher recurrence risk. The combined application of multiple risk factors can improve the predictive value of recurrence.  
      关键词:high grade;non-functioning pituitary neuroendocrine tumors;recurrence;risk factors   
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    • 据美国重症监护医学信息数据库研究,专家构建了重症社区获得性肺炎患者中长期死亡风险预后模型,为临床诊疗提供重要参考。
      Deng Nan-Li, Liu Ren-Huai, Chai Xin, Zhang Xi-Jing, Su Bin-Xiao
      Vol. 50, Issue 4, Pages: 400-408(2025) DOI: 10.11855/j.issn.0577-7402.1759.2025.0305
      Construction and evaluation of a medium- and long-term prognosis model for severe community-acquired pneumonia based on MIMIC-Ⅳ database
      摘要:ObjectiveTo explore the risk factors for medium- and long-term mortality in patients with severe community-acquired pneumonia (SCAP) based on the Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ), construct a prognostic model and evaluate its predictive efficacy.MethodsIn this retrospective cohort study, 1943 SCAP patients from the U.S. MIMIC-Ⅳ database (2008-2019) were randomly divided into training (n=1363) and validation (n=580) sets (7:3 ratio). Primary and secondary endpoints were 1-year and 30-/90-day all-cause mortality, respectively. Prognostic factors were selected using LASSO regression and multivariable Cox proportional hazards modeling, and a visual nomogram model was built. Model performance was assessed viaC-index, receiver operator characteristic (ROC) curves, and calibration curves, and compared with the CURB-65 score. Risk stratification was validated using Kaplan-Meier analysis.ResultsThe 30-day, 90-day, and 1-year all-cause mortality rates for SCAP patients were 25.9%, 34.5%, and 42.6%, respectively. Seven independent risk factors were identified: age (HR=1.037), heart rate (HR=1.007), red blood cell distribution width (RDW, HR=1.092), Acute Physiology Score Ⅲ (APS-Ⅲ, HR=1.013), cerebrovascular disease(HR=1.453), liver disease (HR=1.272), and malignancy (HR=2.007). Based on these factors, Cox regression model was constructed and nomogram was drawn, C-indices of training set and validation set were 0.710 and 0.688, respectively. For 1-year mortality prediction, the model achieved superior area under the ROC curve (AUC) values (training set: 0.768; validation set: 0.738) compared with CURB-65 score (training set: 0.648; validation set: 0.616). Kaplan-Meier survival analysis revealed significantly worse survival in high-risk group than low-risk group (P<0.0001).ConclusionsAge, heart rate, RDW, APS-Ⅲ, cerebrovascular disease, liver disease, and malignant tumor were medium- and long-term mortality risk factors in SCAP patients. The prognostic model constructed based on these factors has high predictive power and provides an important clinical diagnosis and treatment reference.  
      关键词:severe community-acquired pneumonia;MIMIC-Ⅳ database;prognostic model;LASSO regression   
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    • 衢州市人民医院研究团队基于高千伏CT影像组学分析,成功预测关节旁MSU结晶沉积,为临床决策提供参考。
      Huang Wei-Tao, Zhang Guo-Zheng, Han Xiao-Wei
      Vol. 50, Issue 4, Pages: 409-417(2025) DOI: 10.11855/j.issn.0577-7402.0933.2025.0102
      The predictive value of high-kilovoltage CT radiomics for urate crystallization in gouty arthritis
      摘要:ObjectiveTo explore the value of a combined model based on high-kilovoltage CT radiomics and clinical factors for predicting monosodium urate (MSU) crystal deposition in gouty arthritis.MethodsThe clinical data of 136 patients with MSU crystal deposition adjacent to joints confirmed by dual-energy CT (DECT) and 79 patients with non-MSU calcifications adjacent to joints were retrospectively analyzed. The dataset was randomly divided into a training set (n=150) and a validation set (n=65) at a ratio of 7:3 for the construction of predictive models. Radiomic features were extracted from high-kilovolt (135 kV) images, and 20 radiomic features were selected using minimum redundancy-maximum relevance and least absolute shrinkage and selection operator (LASSO) regression. Logistic regression, light gradient boosting machine (LightGBM), and support vector machine models were built based on the selected features, and the best-performing model was identified. Multivariate logistic regression analysis was used to screen for risk factors associated with MSU crystal deposition adjacent to joints. A nomogram model was then constructed by integrating radiomic features and clinical variables. The diagnostic performance of the models was evaluated by means of the receiver operating characteristics (ROC) area under the curve (AUC).ResultsMultivariate logistic regression analysis revealed that CT value was an independent risk factor for MSU crystal deposition adjacent to joints (P<0.001). Among the three machine-learning models, the LightGBM model demonstrated the best predictive performance and good dataset robustness. Therefore, the nomogram was constructed using the LightGBM model. The AUCs of the nomogram model for predicting MSU crystal deposition in the training and validation sets were 0.932 and 0.856, respectively, both exceeding 0.85 and significantly higher than those of the clinical model (De-long test, P<0.05). No statistically significant difference was observed between nomogram model and radiomics model (De-long test, P>0.05).ConclusionsHigh-kilovoltage CT radiomics analysis can predict MSU crystal deposition adjacent to joints. The nomogram model and the radiomics model both demonstrate high diagnostic performance, which can provide valuable references for clinical decision-making.  
      关键词:gouty arthritis;monosodium urate crystals;radiomics;dual energy CT   
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    • 据最新研究,老年脑膜瘤患者术后预后不良的独立危险因素包括脑膜瘤WHO Ⅱ级和Ⅲ级、术后贫血及低蛋白血症,而使用镇痛/镇静药物为其保护因素。研究构建的多因素模型预测效能良好,可用于临床决策参考。
      Gong Yan-Yu, Qu Hong, Feng Si-Zhe, Yu Chun-Yong, Du Jin-Wei, Jiang Jin
      Vol. 50, Issue 4, Pages: 418-426(2025) DOI: 10.11855/j.issn.0577-7402.0115.2024.0929
      Predictive value of albumin, hemoglobin, and multifactorial model for poor postoperative prognosis in elderly patients with meningiomas
      摘要:ObjectiveTo explore the predictive value of albumin, hemoglobin and multifactorial model for poor postoperative prognosis in elderly patients with meningioma.MethodsA retrospective analysis was conducted on 253 elderly patients who underwent meningioma surgery and were transferred to the neurosurgical intensive care unit (NICU) at General Hospital of Northern Theater Command from January 2019 to September 2021, serving as the modeling cohort. Another 227 elderly patients who were treated in NICU after meningioma surgery from November 2021 to June 2023 were used as the validation cohort. Patients in the modeling cohort were categorized into good prognosis group [Glasgow Coma Scale (GCS) score>7, n=161] and poor prognosis group (GCS≤7, n=92) based on the GCS. Univariate and multifactorial logistic regression analyses were performed on the modeling cohort to identify independent risk factors, and a multifactorial model for predicting poor postoperative prognosis in elderly patients with meningioma was constructed based on these factors. The predictive efficacy and accuracy of the model were evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, Hosmer-Lemeshow goodness-of-fit test, and calibration curves. The predictive value of postoperative albumin, hemoglobin, and the multifactorial models for postoperative prognosis in elderly meningioma patients was assessed using restricted cubic spline modeling (RCS), decision curves (DCA), and validated using an external validation cohort to assess the stability of the model.ResultsMeningioma WHO grade Ⅱ and Ⅲ (OR=3.994, 95%CI 1.963-8.126), postoperative hypoalbuminemia (OR=2.194, 95%CI 1.079-4.462), and postoperative anemia (OR=2.117, 95%CI 1.096-4.089) were identified as independent risk factors for poor postoperative prognosis in elderly meningioma patients (P<0.05), while the use of analgesic/sedative medications was a protective factor (OR=0.388, 95%CI 0.201-0.748, P<0.05). The Hosmer-Lemeshow test indicated that the constructed multifactorial model had a good fit accuracy (P=0.161). The AUC for predicting poor postoperative prognosis in elderly meningioma patients for postoperative albumin and hemoglobin were 0.545 (95%CI 0.472-0.617) and 0.632 (95%CI 0.561-0.702), respectively, and showed a nonlinear dose-response relationship with prognosis (P<0.01). DCA analysis results showed that the net benefit rate of multifactorial model was higher than that of postoperative albumin and hemoglobin when the threshold probabilities were between 0.10 and 0.90. The AUC for predicting postoperative prognosis in the elderly meningioma patients in the modeling and validation cohorts were 0.810 and 0.819, respectively, and their calibration curves suggested good discrimination and accuracy.ConclusionsMeningioma WHO grades Ⅱ and Ⅲ, postoperative anemia and hypoalbuminemia are independent risk factors for poor postoperative prognosis in elderly meningioma patients, while the use of analgesic/sedative drugs is a protective factor. The multifactorial model constructed based on these factors has a good predictive efficacy and credibility, and can be used as a reference for clinical decision-making.  
      关键词:hemoglobin;multifactorial model;elderly;meningioma;prognosis   
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    • 中山大学附属第一医院研究团队分析肺腺癌骨转移癌痛患者外周血转录组,发现CXCR3、POMC等关键基因及调控网络,为MBP治疗提供新靶点。
      Zhao Yang, Lin Shi-Qing, Chen Lan-Lan, Dou Yun-Ling, Lin Zhong-Yuan
      Vol. 50, Issue 4, Pages: 427-435(2025) DOI: 10.11855/j.issn.0577-7402.0926.2024.0731
      Transcriptome profiling of peripheral blood and preliminary verification in lung adenocarcinoma patients with metastatic bone pain
      摘要:ObjectiveTo analyze and preliminarily verify key genes and pathways in the transcriptome of peripheral blood of lung adenocarcinoma patients with metastasis bone pain (MBP), and to explore its underlying mechanism.MethodsNine lung adenocarcinoma patients with bone metastasis treated in the First Affiliated Hospital of Sun Yat-sen University from May 2020 to May 2021 were selected for retrospective analysis, including 4 patients with typical MBP clinical manifestations and visual analogue scale (VAS) ≥4 (MBP group) and 5 patients without suffering any pain (control group). Peripheral blood mRNA sequencing was performed to identify differentially expressed genes (DEGs), followed by functional pathways analysis and protein-protein interaction (PPI) network analysis. The most significant modules and hub genes were confirmed and visualized using Cytoscape software. The target miRNAs regulating these hub genes were predicted using Targetscan database, and long non-coding RNA (lncRNA) interacting with these miRNAs were also predicted using lncBase database. The relationships among lncRNA, miRNA and mRNA were visualized to construct a competing endogenous RNA (ceRNA) network through Cytoscape software, and the nodes of this network were verified using quantitative PCR (qPCR).ResultsA total of 1466 DEGs were identified, including 666 up-regulated genes and 800 down-regulated genes. Chemokine receptor 3 (CXCR3), pro-opiomelanocortin (POMC), neuromedin U receptor 1 (NMUR1), chemokine ligand 2 (CCL2) and endocannabinoid receptor 1 (CNR1) were identified as hub genes. The most significant enriched processes and pathways of DEGs included osteoclast differentiation, NOD like receptor signal transduction pathway, type Ⅰ interferon signal pathway, nuclear factor kappa-B (NF-κB) signal pathway, apoptosis/autophagy pathway, chemokine signal pathway, interleukin (IL)-1β pathway. Two ceRNA networks were identified: MALAT1-hsa-miR-124-3p.2-CCL2 and NEAT1-hsa-miR-325-3p-CXCR3. qPCR results showed that the expression levels of CCL2, CXCR3, MALAT1, NEAT1 and hsa-miR-325 were higher in MBP group than these in control group (P<0.05).ConclusionsCXCR3, POMC, NMUR1, CCL2 and CNR1 may serve as key genes in the occurrence of MBP and could be important regulatory targets for MBP. The development of MBP in lung adenocarcinoma may be associated with the dysregulation of the networks: MALAT1-hsa-miR-124-3p.2-CCL2 and NEAT1-hsa-miR-325-3p-CXCR3.  
      关键词:lung adenocarcinoma;metastatic bone pain;transcriptomics;competing endogenous RNA   
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    • 据最新研究,我国女性乳腺癌发病率持续上升,死亡率呈下降趋势,未来防控形势严峻,需优化筛查策略和资源配置。
      Shang Qing, Wang Hai-Peng, Wang Jing
      Vol. 50, Issue 4, Pages: 436-443(2025) DOI: 10.11855/j.issn.0577-7402.1919.2025.0324
      Age-period-cohort model analysis and prediction of breast cancer incidence and mortality among Chinese women from 1992 to 2021
      摘要:ObjectiveTo analyze the trends in incidence and mortality of breast cancer among Chinese women from 1992 to 2021, assess the impact of age, period, and cohort on its incidence and mortality rates, and predict future trends to provide a basis for developing effective intervention strategies.MethodsUtilizing the 2021 Global Burden of Disease (GBD2021) database, the Joinpoint regression model was employed to analyze the trends in age-standardized incidence and mortality rates of breast cancer among Chinese women from 1992 to 2021. The age-period-cohort model was applied to estimate the age, period, and cohort effects on the incidence and mortality of breast cancer among Chinese women during the same period. The autoregressive integrated moving average (ARIMA) model was used to predict the age-standardized incidence and mortality rates of breast cancer among Chinese women from 2022 to 2026. A stratified analysis was conducted to explore the impact of different risk factors [including smoking, alcohol consumption, high body mass index (BMI), hyperglycemia, physical inactivity, and diet] on breast cancer mortality.ResultsFrom 1992 to 2021, the incidence and mortality rates of breast cancer among Chinese women showed an overall upward trend, with incidence rates rising from 15.95/100,000 in 1992 to 55.54/100,000 in 2021, and mortality rates increasing from 7.35/100,000 to 12.41/100,000. The age-standardized incidence rate also exhibited an upward trend, rising from 18.51/100,000 to 37.00/100,000, with an average annual percentage change (AAPC) of 2.43%. However, the age-standardized mortality rate showed an overall downward trend, decreasing from 9.05/100,000 to 8.24/100,000, with an AAPC of -0.35%. The APC model analysis revealed that the age, period, and cohort effects on incidence and mortality were statistically significant (P<0.001). Within the same birth cohort, breast cancer incidence increased in women aged 15-89 years but decreased in those≥90 years. Breast cancer mortality showed a steady increase with age. With the increase in years, the risk of breast cancer incidence gradually increased, reaching the highest between 2017 and 2021, with a relative risk (RR) value of 1.37. Conversely, the risk of breast cancer mortality decreased with the increase in years, with the lowest mortality between 2012 and 2016, and an RR value of 0.86. With the increase in the birth cohort year, the risk of breast cancer incidence gradually increased, while the risk of mortality gradually decreased. The ARIMA model prediction results showed that the age-standardized incidence rate of breast cancer among women would continue to rise from 2022 to 2026, reaching 40.25/100,000 by 2026, while the age-standardized mortality rate would tend to stabilize at 8.28/100,000 by 2026. Among the risk factors for breast cancer, diet was found to have the highest impact on breast cancer mortality.ConclusionsThe incidence rate of breast cancer among Chinese women continues to rise, indicating that the prevention and control situation remains severe. Future efforts should focus on developing precise screening programs for high-risk populations and optimizing early screening strategies and treatment resource allocation based on predicted trend.  
      关键词:breast cancer;incidence;mortality;age-period-cohort model;prediction   
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    • 据最新研究,重庆市社区老年人血红蛋白水平与肌少症及握力降低显著相关,贫血与肌少症相关但非独立危险因素。
      Chen Hong-Zhen, Zheng Kun, Wu Xiao-Xue, Xia Li
      Vol. 50, Issue 4, Pages: 444-451(2025) DOI: 10.11855/j.issn.0577-7402.1458.2024.0521
      Correlation between hemoglobin, anemia and sarcopenia in the elderly population
      摘要:ObjectiveTo analyze the correlation between hemoglobin (Hb), anemia, and sarcopenia in the elderly population in Chongqing communities.MethodsA cross-sectional study was conducted on elderly individuals who underwent healthy examinations at 5 community health service centers in Chongqing from March to August 2023. Demographic characteristics, social factors, body composition measurement, grip strength, 6-meter gait speed and blood tests were assessed. Receiver operating characteristic (ROC) curve was utilized to evaluate the accuracy of Hb in predicting sarcopenia, and the Youden index was employed to determine the optimal Hb cut-off value for diagnosing sarcopenia and its components. Both unadjusted and adjusted logistic regression analyses were performed to examine the relationship between Hb and anemia with sarcopenia and its components.ResultsA total of 531 elderly populations were included, with an average age of (71.1±6.5) years. The overall prevalence of sarcopenia was 13.6% (72/531), including 29 males (40.3%) and 43 females (59.7%). Unadjusted analyses showed that Hb was correlated with sarcopenia, decreased muscle mass, slower gait speed, and reduced grip strength (P<0.05). After adjusting for all potential risk factors, Hb was still significantly associated with sarcopenia and reduced grip strength (P<0.05). For every 10 g/L increase in Hb, the risk of sarcopenia decreased by 2.3%, and the risk of reduced grip strength decreased by 1.7% (P<0.05). Anemia was correlated with sarcopenia, reduced muscle mass, and decreased grip strength in unadjusted analyses (P<0.05), while the correlation between anemia and reduced grip strength remained significant after adjustment for all potential risk factors (P<0.05). The optimal Hb cut-off value for diagnosing sarcopenia in males and females were 148 g/L and 128 g/L, respectively.ConclusionsHb is an independent risk factor for sarcopenia and reduced grip strength. Anemia is associated with sarcopenia, but is not an independent risk factor for sarcopenia.  
      关键词:sarcopenia;anemia;hemoglobin;muscle mass;grip strength;gait speed;elderly population   
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      Basic Research

    • 最新研究发现,二氧化硅诱导的小鼠矽肺模型中,TGF-β1导致成纤维细胞分泌的MMP3增多并潴留在肺ECM中,加重胶原沉积,促进肺纤维化。MMP3可能成为矽肺纤维化的潜在治疗靶点。
      Wang Yu-Meng, Luo Wei, Chao Jie
      Vol. 50, Issue 4, Pages: 458-466(2025) DOI: 10.11855/j.issn.0577-7402.0920.2024.1227
      The role of matrix metalloproteinase 3 to progression of pulmonary fibrosis in mouse silicosis
      摘要:ObjectiveTo investigate the expression of matrix metalloproteinase 3 (MMP3) in a mouse silicosis model induced by SiO2, and explore its role in pulmonary fibrosis.MethodsSix male C57B/6 mice were randomly divided into control and silicosis groups (n=3). The silicosis model was established via intratracheal instillation of SiO2 suspension (0.2 g/kg); the control group were intratracheally instilled with the same amount of normal saline. Human pulmonary fibroblasts (HPF-a) and mouse lung fibroblasts (MLg) were treated with 5 ng/ml of transforming growth factor-β1 (TGF-β1) to construct an ex vivo silicosis cell model. Masson trichrome and Sirius red staining were used to assess the effects of SiO2 on pulmonary tissue and extracellular matrix (ECM) deposition. Single-cell transcriptomics was performed on mouse lung tissue, with bioinformatics analyses identifying ECM-associated cellular composition changes and key genes. The expression and distribution of these key genes were analyzed by spatial transcriptomics. Western blotting was employed to detect Vimentin and MMP3 protein levels in mouse lung tissue and fibroblasts. Immunofluorescence staining was used to localize MMP3 in lung ECM and TGF-‍β1-treated fibroblasts and to evaluate its accumulation in the ECM.ResultsMasson's and Sirius red staining revealed fibrotic changes and significant ECM collagen deposition in mice of silicosis group. Single-cell and spatial transcriptomics identified fibroblast-associated alterations in ECM components, with MMP3 emerging as a key gene. MMP3 mRNA expression was significantly elevated in mouse lungs of silicosis group and was localized primarily to fibrotic lesions. Western blotting showed a significant increase in MMP3 protein levels in the lungs of silicosis group mice compared to control group (P<0.05). TGF-‍β1 treatment led to a time-dependent increase in MMP3 protein levels in HPF-a cells (P<0.05). Immunofluorescence revealed elevated MMP3 expression in the ECM of mouse lungs in silicosis group (P<0.05). When TGF-‍β1 treated MLg cells were seeded onto normal mouse lung ECM, MMP3 expression increased(P<0.05). Similarly, after decellularizing ECM seeded with MLg cells, MMP3 expression levels remained significantly elevated (P<0.01). Co-localization analysis showed enhanced Vimentin and MMP3 signals in and around silicotic nodules in mice of silicosis group (P<0.01).ConclusionsIn the mouse silicosis model, secretion of MMP3 from fibroblasts increased with TGF‑β1 treatment, accumulating in the pulmonary ECM, exacerbating collagen deposition, and promoting fibrosis. MMP3 may serve as a potential therapeutic target for silicosis-induced pulmonary fibrosis.  
      关键词:matrix metalloproteinase 3;extracellular matrix;silicosis;single-cell transcriptome sequencing;spatial transcriptome sequencing   
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    • 最新研究发现,赤芍总苷能有效缓解小鼠哮喘症状并抑制气道重塑,其机制可能与下调气道重塑相关蛋白表达和抑制NLRP3炎性小体激活有关。
      Zhou Yi-Jin, Tian Xin-Lei, Shi Xing-Chan, Hu Wen-Jie, Zhu Shan
      Vol. 50, Issue 4, Pages: 467-474(2025) DOI: 10.11855/j.issn.0577-7402.0474.2024.1120
      Effect and mechanism of total paeony glycoside on airway remodeling in bronchial asthma
      摘要:ObjectiveTo investigate the effect of total paeony glycoside (TPG) on airway remodeling in bronchial asthma mice and its underlying mechanisms.MethodsForty-eight BALB/c mice were randomly divided into control group, model group, ovalbumin+budesonide group (OVA+BUD group), and OVA+TPG group, with 12 mice in each group. Except the control group, mice in other groups were sensitized by intraperitoneal injection of 10% OVA aluminum hydroxide suspension, and then stimulated by atomized inhalation of 1% OVA to establish mouse asthma model. One hour before each inhalation of OVA, mice in OVA+BUD group were atomized with 2 ml BUD suspension, and mice in OVA+TPG group were given 5 g/kg TPG by intragastric administration. Lung tissues and bronchoalveolar lavage fluid (BALF) of mice from each group were collected, and the pathological morphology of the lung tissues was detected by hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining. Inflammatory cell counts [white blood cell (WBC), neutrophil (NEU), eosinophils (EOS), and leukomonocyte (LYM)] in BALF were detected by Wright-giemsa staining. The contents of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in BALF were determined by ELISA. Airway remodeling proteins [fibronectin, α-smooth muscle actin (α-SMA), collagen Ⅰ] and NOD-like receptor protein 3 (NLRP3) inflammasome-related proteins [NLRP3, cleaved caspase-1, apoptosis-associated speck-like protein (ASC)] levels were detected by Western blotting. Human bronchial smooth muscle cells (HBSMCs) were divided into control group (normal culture), transforming growth factor (TGF)-β1 group (culture medium containing 10 ng/ml TGF-β1), and TGF-β1+TPG group (culture medium containing 10 ng/ml TGF-β1 and 50 µg/ml TPG). Cell proliferation was detected by CCK-8 method, and Western blotting was used to detect the expression of airway remodeling proteins and NLRP3 inflammasome-related proteins.ResultsCompared with control group, model group exhibited increased infiltration of inflammatory cell in lung tissues, mucosal epithelium hyperplasia, narrowed bronchial lumen narrowed, tube wall thickened, increased cup cells and mucus secretion, and an elevated pathological score of lung injury (P<0.05); the number of inflammatory cells (WBC, NEU, EOS, and LYM) and the levels of inflammatory factors (TNF-α, IL-1β, and IL-6) in BALF were increased (P<0.05), and the expressions of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC were elevated (P<0.05). Compared with model group, BUD or TPG treatment effectively reduced asthma symptoms, improved lung histopathology injury, inhibited bronchial wall thickening, significantly reduced the number of inflammatory cells (WBC, NEU, EOS, and LYM) and the content of inflammatory factors (TNF-α, IL-1β, and IL-6) in BALF, and inhibited expression of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC (P<0.05). Compared with control group, the proliferation rate of HBSMCs was increased, and the protein expression levels of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC were increased in TGF-β1 group (P<0.05). Compared with TGF-β1 group, TPG treatment decreased cell proliferation and inhibited the protein expression of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC (P<0.05).ConclusionTPG may alleviate airway remodeling and asthma symptoms by decreasing the expression of airway remodeling-related proteins, inhibiting NLRP3 inflammasome activation, and reducing the inflammatory response.  
      关键词:total paeony glycoside;bronchial asthma;airway remodeling;airway inflammation   
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    • 最新研究发现,芒果苷通过Nrf2/HO-1信号通路抑制肌萎缩性侧索硬化细胞模型焦亡,具有细胞保护作用。
      Su Bo-Yang, He Zheng-Qing, Liu Jing, Li Mao, Huang Xu-Sheng
      Vol. 50, Issue 4, Pages: 475-482(2025) DOI: 10.11855/j.issn.0577-7402.1207.2024.1227
      Effect of mangiferin on hSOD1<sup>G93A</sup>-induced pyroptosis in mice <italic style="font-style: italic">via</italic> activating Nrf2/HO-1 signaling pathway
      摘要:ObjectiveTo explore the effect of mangiferin (MF) on pyroptosis in an amyotrophic lateral sclerosis (ALS) cell model by regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway.Methods(1)Mouse NSC-34 cell lines transfected with hSOD1WT and hSOD1G93A plasmids were randomly divided into blank group, model group, MF (100 μmol/L) group, MF (200 μmol/L) group. MF was added into the culture plate for 24 hours. Cell viability was assessed using CCK-8 kit. Lactate dehydrogenase (LDH) release was measured using LDH cytotoxicity detection kit. Levels of inflammatory factors interleukin (IL)-1β and IL-18 in cell supernatant were determined by enzyme-linked immunosorbent assay (ELISA). The expression of Nrf2, HO-1, NADPH quinone oxidoreductase-1 (NQO-1), NOD-like receptor protein 3 (NLRP3), gasdermin D (GSDMD)-N and caspase-1 was detected by Western blotting. (2)Mouse hSOD1G93A NSC-34 cells were randomly divided into model group, MF(200 μmol/L) group, Nrf2-siRNA group and Nrf2-siRNA+MF(200 μmol/L) group. The cells were transiently transfected with Nrf2-siRNA using LipofectamineTM 3000. Western blotting was used to detect the protein expression levels of Nrf2, HO-1, NQO-1, NLRP3, caspase-1 and GSDMD-N.Results(1) The results of the CCK-8 assay showed that after the hSOD1G93A NSC-34 cells were treated with MF at concentrations of 300 μmol/L and below for 24 hours, the changes in cell viability were not significant (P>0.05). Compared with blank group, the release of LDH, the contents of IL-1β and IL-18 in the cell culture supernatant of model group were increased (P<0.001); the protein expression levels of Nrf2, HO-1, and NQO-1 were decreased (P<0.05 or P<0.01); the protein expression levels of NLRP3, caspase-1, and GSDMD-N were increased (P<0.05 or P<0.01 or P<0.001). Compared with model group, the release of LDH, the contents of IL-18 and IL-1β in the culture supernatant in MF(100 μmol/L) and MF(200 μmol/L) groups were decreased (P<0.001); the protein expression levels of NLRP3, caspase-1 and GSDMD-N were decreased (P<0.05 or P<0.001), and the expression levels of Nrf2, HO-1 and NQO-1 were increased (P<0.05 or P<0.01). (2) Compared with model group, the protein expession levels of Nrf2, NO-1 and NQO-1 were increased (P<0.05 or P<0.001) in MF(200 μmol/L) group, while the protein expression levels of NLRP3, caspase-1 and GSDMD-N were decreased (P<0.001); the protein expression levels of Nrf2 and HO-1 were decreased in Nrf2-siRNA group (P<0.01 or P<0.001), while the protein expression levels of NLRP3, caspase-1 and GSDMD-N were increased (P<0.001). Compared with Nrf2-siRNA group, the protein expression levels of Nrf2, HO-1 and NQO-1 in Nrf2-siRNA+MF(200 μmol/L) group were increased (P<0.01 or P<0.001), and the protein expression levels of NLRP3, caspase-1 and GSDMD-N were decreased (P<0.001).ConclusionMF can inhibit pyroptosis in the ALS cell model through Nrf2/HO-1 signaling pathway, playing a protective role.  
      关键词:amyotrophic lateral sclerosis;mangiferin;nuclear factor E2 related factor;pyroptosis;signaling pathway   
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    • 最新研究发现,脓毒症时GLP-1水平升高,通过GLP-1R抑制T淋巴细胞糖酵解,为防治脓毒症T淋巴细胞功能障碍提供新策略。
      Liu Hong-Sheng, Zhang Qing-Hong
      Vol. 50, Issue 4, Pages: 483-489(2025) DOI: 10.11855/j.issn.0577-7402.1112.2024.0813
      Research progress of immunometabolic mechanism for GLP-1 to modulate T cell dysfunction in sepsis
      摘要:Persistent inflammation, immuno-suppression and catabolism syndrome (PICS) occurs at the later stage of sepsis, characterized by T cell dysfunction with severe poor outcome. Recent studies found that T cell function be largely affected by its metabolic status. In sepsis, a variety of signaling molecules, including the nutrients, could trigger T cell to undergo metabolic reprogramming that from oxidative phosphorylation to aerobic glycolysis via phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinases (Akt)-mammalian target of rapamycin (mTOR) pathway, leading to severe alterations of its immune phenotype. Glucagon-like peptide-1 (GLP-1) is a kind of incretin hormone that could regulate nutrients and energy metabolism in the body. It can reduce blood glucose level, suppress the immune and inflammatory responses. Plasma GLP-1 levels were rapidly elevated in sepsis and correlated closely with the outcome in critical care. GLP-1 receptor (GLP-1R) agonist could block the glycolysis of T cells, reduce glucose transporter type 1 mRNA expression, and inhibit T cell proliferation. Therefore, the elevated GLP-1 level may represent the metabolic switch toward "aerobic glycolysis", reflecting the pathological status of PICS. Here, the review elucidates the regulation of GLP-1 on the immune function and metabolic reprogramming of T cells and provides strategies for the prevention and treatment of T cell immune dysfunction in sepsis via GLP-1 receptor.  
      关键词:glucagon-like peptide-1;T cell dysfunction;sepsis;immunometabolism   
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    • 神经血管单元研究进展,为年龄依赖性癫痫治疗提供新思路。
      Liu Xuan, Yin Rong
      Vol. 50, Issue 4, Pages: 490-494(2025) DOI: 10.11855/j.issn.0577-7402.1671.2024.0704
      Research progress on the role of neurovascular unit dysfunction in elderly patients with epileptic seizures
      摘要:The neurovascular unit (NVU) is the smallest structural unit that maintains the integrity of the blood-brain barrier (BBB), regulates cerebral physiological activities, and maintains the homeostasis of the brain's internal environment. It has become a hot topic in the study of brain physiology and pathological changes. NVU plays a crucial role in age-dependent central nervous system diseases such as cerebral white matter lesions, cognitive impairment, and cerebrovascular disease. Its dysfunction can lead to destruction of BBB integrity, with subsequent protein leakage, immune-inflammatory responses, and alterations in cerebral hemodynamics, all of which can trigger seizures or progression of neurodegenerative disorders. Conversely, seizures can also accelerate NVU dysfunction and promote brain aging. The review summarizes the role of dysfunctional constituent cells of the NVU in the pathogenesis of age-dependent epilepsy and the research progress in related molecular pathways, aiming to provide new perspectives for epilepsy treatment research.  
      关键词:epilepsy in the elderly;neurovascular unit;blood-brain barrier;mechanism of action   
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    • 据最新报道,AMPK信号通路在脊髓损伤调控和治疗领域的研究取得进展,为脊髓损伤治疗和药物开发提供新思路。
      Zhang Zhi-Lan, Huang Xiao-Meng, Shang Wen-Ya, Huang Jing, Wei Hui-Lin, Li Bing, Ren Ya-Feng
      Vol. 50, Issue 4, Pages: 495-503(2025) DOI: 10.11855/j.issn.0577-7402.0224.2024.0827
      Research progress on AMPK signaling pathway in the regulation and treatment of spinal cord injury
      摘要:Spinal cord injury (SCI) is a central nervous system disease with high morbidity and disability rates, bringing serious economic and psychological burdens to families and society worldwide. AMP-activated protein kinase (AMPK) is an important sensor in the energy metabolism process in living organisms, which plays a central role in maintaining energy balance. It is currently considered a key target for the prevention and treatment of multiple diseases. Studies have shown that AMPK signaling can regulate autophagy, neuroinflammation, oxidative stress, mitochondrial function and other processes after SCI, thus affecting the pathological process of SCI. This review summarizes the research progress on AMPK signaling pathway involved in the regulation of SCI, in order to provide new ideas for the treatment and drug development of SCI.  
      关键词:spinal cord injury;AMP-activated protein kinase;pathological mechanism;neuroinflammation;axon regeneration   
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