1.Preliminary establishment of reference intervals for 12 cytokines in adult plasma by multiplex bead-based flow fluorescent immunoassay
Xinyu WANG ; Xing CHENG ; Lu ZHENG ; Yue ZHANG ; Yuting MA ; Guoping NIU ; Feng GU ; Yongqiang CHEN
Chinese Journal of Immunology 2025;41(5):1202-1207
Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95%reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.
2.Preliminary establishment of reference intervals for 12 cytokines in adult plasma by multiplex bead-based flow fluorescent immunoassay
Xinyu WANG ; Xing CHENG ; Lu ZHENG ; Yue ZHANG ; Yuting MA ; Guoping NIU ; Feng GU ; Yongqiang CHEN
Chinese Journal of Immunology 2025;41(5):1202-1207
Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95%reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.
3.Application and research prospects of experimental animal models of chronic stress
Xiaoqi YUE ; Yuting LI ; Miao JIANG ; Zigang ZHAO ; Chunyu NIU
Chinese Journal of Comparative Medicine 2024;34(4):147-155
The effect and mechanism of chronic stress on psychosomatic diseases are important topics in stress research.The establishment of animal models to simulate human chronic stress is of great significance to investigations of stress responses,the pathogenesis of related diseases,clinical treatment,and drug development.In this paper,animal models of chronic stress commonly used in China and abroad are reviewed;the classification of stressors,animal selection,model construction,pathological manifestations,and evaluation indexes are summarized;and the advantages and disadvantages and application of various models are discussed.The paper provides a reference for the study and selection of models of chronic stress response.
4.Role of NLRP3-pyroptosis in experimental sepsis-induced lung injury
Yuting LI ; Chunyu NIU ; Zigang ZHAO
Chinese Journal of Comparative Medicine 2024;34(8):139-147
The Nod-like receptor pyrin domain-associated protein 3(NLRP3)-mediated pyroptosis of pulmonary parenchymal and immune cells plays a key role in the pathogenesis of lung injury during sepsis.NF-κB,JAK2/STAT3 and MAPK signaling pathways are involved in NLRP3-mediated pyroptosis.Targeting NLRP3-pyroptosis and its related signaling pathways,pharmacological interventions with Physalin B,schisandrin,erythropoietin,and physical therapies such as acupuncture at Zusanli and Feishu points,as well as NLRP3-specific inhibitors like ergolide,have all shown effective anti-septic effects in treating lung injuries.This article reviewed the roles and mechanisms of NLRP3-pyroptosis in sepsis-induced lung injury,as well as the experimental progresses made in targeting NLRP3 pyroptosis as a therapy.We aim to highlight the importance of NLRP3-pyroptosis as a target,providing insights for the prevention and treatment of sepsis-induced lung injury.
5.Analysis of prognostic influencing factors of malignant peritoneal mesothelioma
Yuting FANG ; Zhichao JIANG ; Yaru NIU ; Midan XIANG ; Wei PEI ; Guangwen YUAN ; Yongkun SUN
Cancer Research and Clinic 2024;36(12):933-937
Objective:To investigate the clinical characteristics and prognostic factors of malignant peritoneal mesothelioma (MPeM).Methods:A retrospective case series study was conducted. Clinical and follow-up data of 73 MPeM patients who received pemetrexed and cisplatin (AP regimen)-based treatment at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2004 to December 2022 were collected. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier method was used to perform the survival analysis; univariate and multivariate analyses were performed to identify the influencing factors of prognosis by log-rank test and Cox proportional hazards model.Results:In 73 MPeM patients, there were 33 males and 40 females, with a median age of 57 years old (range: 20-76 years old). Among them, 41 patients (56.2%) were aged ≥55 years old, 5 patients (6.8%) had a history of asbestos exposure, 45 patients (61.6%) presented with ascites, and 32 patients (43.8%) had distant metastasis, 70 patients (95.9%) were epithelioid subtype, 38 patients (52.1%) underwent surgery, and 3 patients (4.1%) received radiotherapy. The median OS time of all patients was 30 months (95% CI: 25-50 months), and the median PFS time was 8 months (95% CI: 6-14 months). Univariate analysis results showed that the differences in OS and PFS between patients with different ages (<55 years old vs. ≥55 years old: the median OS time not reached vs. 25 months, P < 0.001; the median PFS time 13 months vs. 7 months, P = 0.046) and Eastern Cooperative Oncology Group (ECOG) score (1 point vs. 2 points: the median OS time 37 months vs. 21 months, P < 0.001; the median PFS time 14 months vs. 4 months, P = 0.004) were statistically significant. There were statistically significant differences in OS among patients with different status of surgery (with vs. without: the median OS time 37 months vs. 24 months, P = 0.020), history of asbestos exposure (with vs. without: the median OS time 32 months vs. 18 months, P = 0.002) and distant metastasis (with vs. without: the median OS time 58 months vs. 20 months, P < 0.001). Multivariate analysis results showed that ECOG score of 2 points ( HR = 5.04, 95% CI: 1.29-19.73, P = 0.020) and distant metastasis ( HR = 4.26, 95% CI: 1.77-10.24, P = 0.001) were independent risk factors for OS of patients. Conclusions:Most MPeM patients are female, the epithelioid subtype is predominant, and the overall prognosis is poor. However, patients aged <55 years old, without history of asbestos exposure, with a good general condition, with surgery, or without distant metastasis have relatively good prognosis.
6.Analysis of prognostic influencing factors of malignant peritoneal mesothelioma
Yuting FANG ; Zhichao JIANG ; Yaru NIU ; Midan XIANG ; Wei PEI ; Guangwen YUAN ; Yongkun SUN
Cancer Research and Clinic 2024;36(12):933-937
Objective:To investigate the clinical characteristics and prognostic factors of malignant peritoneal mesothelioma (MPeM).Methods:A retrospective case series study was conducted. Clinical and follow-up data of 73 MPeM patients who received pemetrexed and cisplatin (AP regimen)-based treatment at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2004 to December 2022 were collected. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier method was used to perform the survival analysis; univariate and multivariate analyses were performed to identify the influencing factors of prognosis by log-rank test and Cox proportional hazards model.Results:In 73 MPeM patients, there were 33 males and 40 females, with a median age of 57 years old (range: 20-76 years old). Among them, 41 patients (56.2%) were aged ≥55 years old, 5 patients (6.8%) had a history of asbestos exposure, 45 patients (61.6%) presented with ascites, and 32 patients (43.8%) had distant metastasis, 70 patients (95.9%) were epithelioid subtype, 38 patients (52.1%) underwent surgery, and 3 patients (4.1%) received radiotherapy. The median OS time of all patients was 30 months (95% CI: 25-50 months), and the median PFS time was 8 months (95% CI: 6-14 months). Univariate analysis results showed that the differences in OS and PFS between patients with different ages (<55 years old vs. ≥55 years old: the median OS time not reached vs. 25 months, P < 0.001; the median PFS time 13 months vs. 7 months, P = 0.046) and Eastern Cooperative Oncology Group (ECOG) score (1 point vs. 2 points: the median OS time 37 months vs. 21 months, P < 0.001; the median PFS time 14 months vs. 4 months, P = 0.004) were statistically significant. There were statistically significant differences in OS among patients with different status of surgery (with vs. without: the median OS time 37 months vs. 24 months, P = 0.020), history of asbestos exposure (with vs. without: the median OS time 32 months vs. 18 months, P = 0.002) and distant metastasis (with vs. without: the median OS time 58 months vs. 20 months, P < 0.001). Multivariate analysis results showed that ECOG score of 2 points ( HR = 5.04, 95% CI: 1.29-19.73, P = 0.020) and distant metastasis ( HR = 4.26, 95% CI: 1.77-10.24, P = 0.001) were independent risk factors for OS of patients. Conclusions:Most MPeM patients are female, the epithelioid subtype is predominant, and the overall prognosis is poor. However, patients aged <55 years old, without history of asbestos exposure, with a good general condition, with surgery, or without distant metastasis have relatively good prognosis.
7.Application status and trends of health examination data: visualization research based on Citespace
Xinlei MIAO ; Qianqian WANG ; Guimin TANG ; Xiangjun NIU ; Wan ZHAO ; Yuting SUN ; Xuhong GE ; Song LENG
Chinese Journal of Health Management 2023;17(10):750-756
Objective:To explore the application status and trends of the health examination data.Methods:Relevant literatures on health examination data were retrieved from Web of Science from 1 January 2007 to 30 June 2022 and China Knowledge Network Infrastructure from 1 January 1992 to 30 June 2022; and the literature and research contents were visually analyzed by using CiteSpace 6.1 bibliometrics software.Results:Total of 5 517 Chinese articles and 18 563 English articles were selected. The publication volume of health examination data in China increased year by year since 1992, and the international publication volume also showed an increasing trend. The Chinese literature focused on health management, osteoporosis, overweight, and physical examination subjects such as pilots, while the English literature focused on the study of obesity, care and functional cognition after the formation of a cohort of physical examination data. More co-citation papers related to health examination data were published in the journals from developed countries mainly in the United States and the United Kingdom, and the contents of the co-cited journals highly covered disease research on chronic diseases, such as cardiovascular disease, functional cognition and rehabilitation.Conclusions:The number of articles published on health examination data is increasing year by year, and in the future, more studies will use big data algorithms such as machine learning to measure the association between the risk of chronic diseases and related influencing factors.
8.Pulmonary rehabilitation restores limb muscle mitochondria and improves the intramuscular metabolic profile
Shiwei QUMU ; Weiliang SUN ; Jing GUO ; Yuting ZHANG ; Lesi CAI ; Chaozeng SI ; Xia XU ; Lulu YANG ; Xuanming SITU ; Tianyi YANG ; Jiaze HE ; Minghui SHI ; Dongyan LIU ; Xiaoxia REN ; Ke HUANG ; Hongtao NIU ; Hong LI ; Chang'An YU ; Yang CHEN ; Ting YANG
Chinese Medical Journal 2023;136(4):461-472
Background::Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated.Methods::Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results::At the end of 90 days, COPD rats’ weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion::COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.
9.The electrophysiological features of patients with anti-neurofascin 155 IgG4 antibodies positive chronic inflammatory demyelinating polyradiculoneuropathy
Yuting REN ; Zaiqiang ZHANG ; Kang ZHANG ; Na CHEN ; Ying WANG ; Songtao NIU ; Bin CHEN ; Xingao WANG ; Hua PAN
Chinese Journal of Neurology 2022;55(4):312-318
Objective:To investigate the electrophysiological features of patients with anti-neurofascin 155 (NF155) IgG4 antibodies positive chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Methods:The electrophysiological data of 6 anti-NF155 IgG4 antibodies positive CIDP patients in Beijing Tiantan Hospital, Capital Medical University from September 2018 to May 2021 were retrospectively analyzed. Parameters studies included standard motor and sensory nerve conduction studies, electromyography (EMG) and F waves studies. Correlation analysis was made to explore the relationships between clinical indicators and electrophysiological data.Results:There was statistically significant difference in the motor nerve conduction study on abnormal rate of tibial nerve (χ 2=11.08, P=0.011). Motor nerve conduction abnormalities were presented in a majority of patients with decreased motor conduction velocity (MCV) and prolonged distal motor latency (DML). There was no statistically significant difference in the overall abnormal rate between lower limbs and upper limbs (30/32, 93.8% vs 22/22, 100.0%; χ 2=1.43, P=0.508), sensory nerve conduction and motor nerve conduction (52/54, 96.3% vs 42/42, 100.0%; χ 2=1.59, P=0.503). There was statistically significant difference in the overall abnormal rate in median nerve, ulnar nerve and sural nerve (χ 2=14.96, P=0.001;χ 2=10.00, P=0.007; χ 2=9.95, P=0.008),and absent sensory nerve action potential was the most common abnormality in sensory nerve conduction abnormalities. The abnormal rate of EMG was 9/14, which was constituted by upper limbs (4/8) and lower limbs (5/6), and the spontaneous activity accompanied with prolonged duration and increased amplitude of motor unit action potential was common. Significant negative correlations were established between disease duration and compound muscle action potential (CMAP) amplitude and negative area of ulnar nerve ( r=-0.84, P=0.036; r =-0.76, P=0.011), and the correlations between age and MCV of median nerve and ulnar nerve were also found ( r=0.89, P=0.019; r=0.95, P=0.003). The DML of median nerve was negatively correlated with CMAP amplitude ( r=-0.63, P=0.049). Moreover, the correlation analysis revealed associations of the F wave latency with the DML, CMAP amplitude and MCV of tibial nerve ( r= 0.90, P=0.039; r=-0.96, P=0.012; r=-0.96, P=0.010). Conclusions:The motor nerve and sensory nerve, the myelin sheath and axon of peripheral nerves in anti-NF155 IgG4 CIDP patients were largely affected. The CMAP amplitude and negative area of ulnar nerve might be of certain clinical value in reflecting the disease duration.The younger the patients, the more severe the demyelination degree of the upper limbs. The F wave latency of tibial nerve not only reflected the abnormal proximal conduction, but also the distal damage degree of myelin sheath and axon.
10.Differential bone metabolism and protein expression in mice fed a high-fat diet versus Daurian ground squirrels following natural pre-hibernation fattening.
Xuli GAO ; Shenyang SHEN ; Qiaohua NIU ; Weilan MIAO ; Yuting HAN ; Ziwei HAO ; Ning AN ; Yingyu YANG ; Yu ZHANG ; Han ZHANG ; Kenneth B STOREY ; Hui CHANG
Journal of Zhejiang University. Science. B 2022;23(12):1042-1056
This study compared the effects on bone metabolism and morphology of pathological obesity induced by excessive fat intake in a non-hibernator (mice) versus healthy obesity due to pre-hibernation fattening in a hibernator (ground squirrels). Kunming mice were fed a high-fat diet to provide a model of pathological obesity (OB group). Daurian ground squirrels fattened naturally in their pre-hibernation season (PRE group) were used as a healthy obesity model. Micro-computed tomography (micro-CT) and three-point bending tests were used to determine the microstructure and mechanical properties of bone. Western blots were used to analyze protein expression levels related to bone metabolism (Runt-related transcription factor 2 (RunX2), osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), cathepsin K, matrix metallopeptidase 9 (MMP9), patched protein homolog 1 (Ptch1), phosphorylated β-catenin (P-β-catenin), and glycogen synthase kinase-3β (GSK-3β)). Compared with controls, there was no obvious bone loss in the OB mice, and the stiffness of the femur was increased significantly. Compared with summer active squirrels, bone formation was enhanced but the mechanical properties did not change in the PRE group squirrels. In OB mice, western blots showed significantly increased expression levels of all proteins except RunX2, OPG, and Ptch1. PRE ground squirrels showed significantly increased expression of most proteins except OCN and Ptch1, which decreased significantly, and P-β-catenin and OPG, which did not change. In conclusion, for non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, increasing both bone loss and bone formation. For pre-hibernating ground squirrels, the healthy obesity acquired before hibernation had a positive effect on the microstructure of bones, and also enhanced the expression levels of proteins related to bone formation, bone resorption, and Wnt signaling.
Mice
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Animals
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Hibernation
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Core Binding Factor Alpha 1 Subunit/metabolism*
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Glycogen Synthase Kinase 3 beta/metabolism*
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Diet, High-Fat
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X-Ray Microtomography
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Sciuridae/metabolism*
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Obesity

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