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Altered levels of circulating CD8⁺CXCR5⁺PD-1⁺T follicular cytotoxic cells in primary Sjogren's syndrome

CLINICAL RHEUMATOLOGY 2022年第6期41卷 1697-1708页

作者： zhai, xuwen Wang, Yanlin Guo, Hui Liang, Zhaojun Feng, Min Wu, Yanyao Qin, Yan Zhao, Xiangcong Gao, Chong Luo, Jing Shanxi Med Univ Simulat Hosp Clin Skills Teaching Jinzhong 030600 Shanxi Peoples R China Shanxi Med Univ Dept Med Div Rheumatol Hosp 2 Taiyuan 030001 Shanxi Peoples R China Shanxi Med Univ Dept Med Div Nephrol Hosp 2 Taiyuan 030001 Shanxi Peoples R China Shenzhen Baoan Shiyan Peoples Hosp Dept Med Div Nephrol Shenzhen 518005 Guangdong Peoples R China Harvard Med Sch Brigham & Womens Hosp Dept Pathol Boston MA 02115 USA

Background Circulating CD8(+)T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) (CD8(+)CXCR5(+)T), a recently identified follicular cytotoxic T cell subset, are involved in antiviral immunity and autoimmunity, but their abundance and role in the pathogenesis of primary Sjogren syndrome (pSS) are unknown. Methods Circulating CD8(+)CXCR5(+)T cell and CD8(+) regulatory T cells (CD8(+)Treg) were evaluated in 49 pSS patients (19 patients with pulmonary involvement) and 24 age- and sex-matched healthy controls (HCs) by flow cytometry. Orthogonal partial least squares discriminant analysis (OPLS-DA) was performed, and receiver operating characteristic curves (ROC) were generated to identify characteristic cell subsets. Spearman's correlation analysis was conducted to examine the relationships between CD8(+)T cell subsets and clinical features. Results The proportions and numbers of CD8(+)CXCR5(+) , CD8(+)CXCR5(+) programmed death 1-positive (PD-1(+)), and CD8(+)CXCR5 PD-1(+)T cells were significantly higher, whereas those of CD8 +/- Treg were markedly lower, in pSS patients than HCs. The CD8(+)CXCR5(+)PD-1(+)T cell to CD8(+)Treg ratio had the greatest discriminatory power for pSS and HCs according to OPLS-DA and ROC analyses. The increased numbers of CD8(+)CXCR5(+)T cells and CD8(+)CXCR5(+)PD-1(+)T cells were strongly associated with those of CD4(+)CXCR5(+)T and B cells. The proportions and numbers of CD8(+)CXCR5(+)PD-1(+)T cells were increased in pSS patients with lung involvement. Conclusions We identified a new CD8(+)CXCR5(+)PD-1(+)T subset, which was increased in abundance in pSS patients, particularly those with lung involvement, compared with HCs. Also, the CD8(+)CXCR5(+)PD-1(+)T to CD8(+)Treg ratio may be useful for identifying pSS. Our findings suggest that targeting follicular CD8(+)T cell subsets has therapeutic potential for pSS.

关键词： CD8(+)CXCR5(+) follicular cytotoxic T subsets CD8(+) regulatory T cells Lung involvement OPLS-DA Primary Sjogren's syndrome

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Zacopride selectively activates the Kir2.1 channel via a PKA signaling pathway in rat cardiomyocytes

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Science China(Life Sciences) 2013年第9期56卷 788-796页

作者： ZHANG Li LIU QingHua LIU ChengFang zhai xuwen FENG QiLong XU RuiLing CUI XiangLi ZHAO ZhiQing CAO JiMin WU BoWei Department of Physiology and the Key Laboratory of Cellular Physiology Ministry of Education Shanxi Medical University Department of Pathophysiology Shanxi Medical University Department of Biomedical Sciences Mercer University School of Medicine Department of Physiology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College

We recently reported that zacopride is a selective inward rectifier potassium current (IK1 ) channel agonist, suppressing ventricular arrhythmias without affecting atrial arrhythmias. The present study aimed to investigate the unique pharmacological properties of zacopride. The whole-cell patch-clamp technique was used to study IK1 currents in rat atrial myocytes and Kir2.x currents in human embryonic kidney (HEK)-293 cells transfected with inward rectifier potassium channel (Kir)2.1, Kir2.2, Kir2.3, or mutated Kir2.1 (at phosphorylation site S425L). Western immunoblots were performed to estimate the relative protein expression levels of Kir2.x in rat atria and ventricles. Results showed that zacopride did not affect the IK1 and transmembrane potential of atrial myocytes. In HEK293 cells, zacopride increased Kir2.1 homomeric channels by 40.7%±9.7% at 50 mV, but did not affect Kir2.2 and Kir2.3 homomeric channels, and Kir2.1-Kir2.2, Kir2.1-Kir2.3 and Kir2.2-Kir2.3 heteromeric channels. Western immunoblots showed that similar levels of Kir2.3 protein were expressed in rat atria and ventricles, but atrial Kir2.1 protein level was only 25% of that measured in the ventricle. In addition, 5-hydroxytryptamine (5-HT) 3 receptor was undetectable, whereas 5-HT 4 receptor was weakly expressed in HEK293 cells. The Kir2.1-activating effect of zacopride in these cells was abolished by inhibition of protein kinase A (PKA), but not PKC or PKG. Furthermore, zacopride did not activate the mutant Kir2.1 channel in HEK293 cells but selectively activated the Kir2.1 homomeric channel via a PKA-dependent pathway, independent to that of the 5-HT receptor.

关键词： zacopride inward rectifier potassium channel 5-HT receptor protein kinase

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IK1 channel agonist zacopride suppresses ventricular arrhythmias in conscious rats with healing myocardial infarction

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LIFE SCIENCES 2019年第0期239卷 117075-000页

作者： zhai, xuwen Qiao, Xi Zhang, Li Wang, Dongming Zhang, Lijun Feng, Qilong Wu, Bowei Cao, Jimin Liu, Qinghua Shanxi Med Univ Clin Skills Teaching Simulat Hosp Taiyuan Shanxi Peoples R China Shanxi Med Univ Dept Pathophysiol 56 Xinjian South Rd Taiyuan 030001 Shanxi Peoples R China Childrens Hosp Shanxi Clin Lab Taiyuan Shanxi Peoples R China Shanxi Med Univ Hosp 2 Taiyuan Shanxi Peoples R China Shanxi Med Univ Minist Educ Key Lab Cellular Physiol 56 Xinjian South Rd Taiyuan 030001 Shanxi Peoples R China Shanxi Med Univ Dept Physiol 56 Xinjian South Rd Taiyuan 030001 Shanxi Peoples R China

Aims: Arrhythmogenesis of chronic myocardial infarction (MI) is associated with the prolongation of action potential, reduction of inward rectifier potassium (I-K1, Kir) channels and hyper-activity of Calcium/calmodulin-dependent kinase II (CaMKII) in cardiomyocytes. Zacopride, a selective I-K1 agonist, was applied to clarify the cardioprotection of I-K1 agonism via a CaMKII signaling on arrhythmias post-MI. Methods: Male SD rats were implanted wireless transmitter in the abdominal cavity and subjected to left main coronary artery ligation or sham operation. The telemetric ECGs were monitored per day throughout 4 weeks. At the endpoint, isoproterenol (1.28 mg/kg, i.v.) was administered for provocation test. The expressions of Kir2.1 (dominant subunit of I-K1 in ventricle) and CaMKII were detected by Western-blotting. Key findings: In the telemetric rats post-MI, zacopride significantly reduced the episodes of atrioventricular conduction block (AVB), premature ventricular contraction (PVC), ventricular tachycardia (VT) and ventricular fibrillation (VF), without significant effect on superventricular premature contraction (SPVC). In provocation test, zacopride suppressed the onset of ventricular arrhythmias in conscious PMI or sham rats. The expression of Kir2.1 was significantly downregulated and p-CaMKII was upregulated post-MI, whereas both were restored by zacopride treatment. Significance: I-K1/Kir2.1 might be an attractive target for pharmacological controlling of lethal arrhythmias post MI.

关键词： Inward rectifier potassium channel Zacopride Myocardial infarction Arrhythmias Calcium/calmodulin-dependent kinase II

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巨噬细胞抑制因子-1对老年膝骨关节炎软骨细胞增殖代谢影响的实验研究

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中华风湿病学杂志 2019年第12期23卷 839-844,I0004页

作者：王东明翟旭雯耿翔李鹏翠卫小春李璐山西医科大学第二医院骨科山西医科大学第二医院骨与软组织损伤修复山西省重点实验室太原030001 山西医科大学模拟医院晋中030619 山西卫生健康职业学院药学系晋中030619

目的观察不同浓度巨噬细胞抑制因子-1(MIC-1)对老年膝OA患者软骨细胞增殖代谢的影响。方法收集健康年轻人和老年膝OA患者的血清、膝关节软骨标本各10例,检测标本中MIC-1的含量变化。常规培养人软骨细胞,对照组单纯加培养液,实验组培养... 详细信息

目的观察不同浓度巨噬细胞抑制因子-1(MIC-1)对老年膝OA患者软骨细胞增殖代谢的影响。方法收集健康年轻人和老年膝OA患者的血清、膝关节软骨标本各10例,检测标本中MIC-1的含量变化。常规培养人软骨细胞,对照组单纯加培养液,实验组培养液中含不同浓度重组人MIC-1蛋白,其中,实验组1浓度为10 ng/ml,实验组2浓度为100 ng/ml和实验组3浓度为200 ng/ml,培养48 h后,5-乙炔基-2-脱氧尿苷(EdU)检测软骨细胞增殖情况,蛋白质印迹法和实时荧光定量(qRT)-PCR检测软骨细胞pSmad2、Smad2和Col2等指标的表达情况。统计学分析采用t检验,单因素方差分析(ANOVA),Tukey法。结果年轻人血清中MIC-1蛋白相对表达量(0.89±0.11)高于老年人(0.48±0.12),差异有统计学意义(t=2.58,P<0.05)。对照组EdU阳性细胞百分比为(26.8±1.5)%,实验组1为(26.2±1.6)%,实验组2为(35.2±1.8)%,实验组3为(45.6±2.7)%,多组间比较差异有统计学意义(F=21.45,P<0.01)。pSmad2蛋白相对表达量在多组之间比较差异有统计学意义(F=18.32,P<0.01),其中,实验组2(1.25±0.11)和实验组3(0.93±0.22)分别高于对照组(0.54±0.10);多组比较Col2蛋白相对表达量差异有统计学意义(F=17.90,P<0.01),其中,实验组2(1.28±0.14)和实验组3(1.74±0.14)分别高于对照组(0.80±0.04)。Col2的mRNA相对表达量在多组间比较差异有统计学意义(F=17.90,P<0.01),其中,实验组2(1.13±0.16)和实验组3(1.65±0.15)分别高于对照组(0.49±0.10)。结论老年膝OA患者血清和软骨组织MIC-1含量低于年轻人,MIC-1可以促进老年膝关节软骨细胞增殖。

关键词：老年人软骨细胞骨关节炎巨噬细胞

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The impact of radiotherapy on the prognosis of metastatic clear cell renal cell carcinoma after surgery

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Scientific Reports 2025年第1期15卷 1-11页

作者： Li, xuwen Tan, Zhongyu Zhu, Yihao zhai, Yabo Chen, Can Wang, Dong Wang, Mingshuai Xing, Nianzeng Yang, Feiya Ye, Xiongjun Department of Urology National Cancer Center National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China First Clinical Medical College Nanchang University Nanchang China Zunyi Medical University Zunyi China

Clear cell renal cell carcinoma, one of the most common types of renal cell carcinoma, has been increasing in incidence year by year. This study aims to investigate the impact of radiotherapy on the prognosis of patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing cytoreductive surgery. Clinical data of patients with mccRCC who underwent cytoreductive surgery were collected from the SEER database (2000–2021). This study employed propensity score matching (PSM) and R software to evaluate the overall survival (OS) of radiotherapy. Univariate and multivariate COX regression analyses were conducted to explore the impact of different variables on prognosis. Finally, a nomogram was developed to predict patient survival rates. A total of 2076 patients with mccRCC who underwent cytoreductive surgery were included in this study, with 538 (25.92%) in the radiotherapy group and 1539 (74.08%) in the non-radiotherapy group. After propensity score matching (PSM), there were 300 cases in each group. Kaplan-Meier values and the Cox proportional hazards model were used to plot the overall survival (OS) curves, which showed that the median survival time in the radiotherapy group was significantly lower than that in the non-radiotherapy group. Additionally, multivariate Cox regression analysis revealed that tumor grade, N stage, radiotherapy, lung metastasis, and liver metastasis were independent factors affecting the prognosis of patients with mccRCC undergoing cytoreductive surgery. Lastly, a nomogram was developed to estimate the survival rates of patients with mccRCC after cytoreductive surgery. Radiotherapy after cytoreductive surgery may have an adverse impact on the prognosis of patients with mccRCC. © The Author(s) 2025.

关键词： Metastatic clear cell renal cell carcinoma Overall survival Propensity score matching Radiotherapy Surgery

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口腔腺样囊性癌肾转移1例报告

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中华泌尿外科杂志 2025年第2期46卷 145-146页

作者：朱亿豪殷华奇翟亚博王文宽李旭文杨飞亚邢念增叶雄俊国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院泌尿外科北京100021 河南省肿瘤医院泌尿外科郑州450000

口腔腺样囊性癌肾转移十分罕见。本文报道1例口腔腺样囊性癌术后双肾转移患者,左肾接受射频消融术,右肾行根治性肾切除术,手术顺利。术后3个月肌酐74μmol/L。本例采用的多学科综合诊疗模式,为双肾继发恶性肿瘤患者的诊疗提供一定的思路。

关键词：腺样囊性癌肾转移手术治疗综合治疗

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Quantitative isotopic fingerprinting of thallium associated with potentially toxic elements (PTEs) in fluvial sediment cores with multiple anthropogenic sources

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ENVIRONMENTAL POLLUTION 2020年第Part3期266卷 115252-115252页

作者： Liu, Juan Zhou, Yuchen She, Jingye Tsang, Daniel C. W. Lippold, Holger Wang, Jin Jiang, Yanjun Wei, Xudong Yuan, Wenhuan Luo, xuwen zhai, Shujing Song, Lan Guangzhou Univ Innovat Ctr Sch Environm Sci & Engn Inst Environm Res Greater Bay Guangzhou 510006 Peoples R China Minist Educ Key Lab Waters Qual & Conservat Pearl River Delta Guangzhou 510006 Peoples R China Hong Kong Polytech Univ Dept Civil & Environm Engn Kowloon Hung Hom Hong Kong Peoples R China Helmholtz Zentrum Dresden Rossendorf Inst Ressourcenokol D-04318 Leipzig Germany Fujian Normal Univ Sch Geog Sci Key Lab Humid Subtrop Ecogeog Proc Minist Educ Fuzhou Peoples R China Guangdong Prov Key Lab Radionuclides Pollut Contr Guangzhou 510006 Peoples R China Southern Univ Sci & Technol Sch Environm Sci & Engn Guangdong Prov Key Lab Soil & Groundwater Pollut Shenzhen 518055 Peoples R China

Thallium (Tl) is a dispersed trace metal showing remarkable toxicity. Various anthropogenic activities may generate Tl contamination in river sediments, posing tremendous risks to aquatic life and human health. This paper aimed to provide insight into the vertical distribution, risk assessment and source tracing of Tl and other potentially toxic elements (PTEs) (lead, cadmium, zinc and copper) in three representative sediment cores from a riverine catchment impacted by multiple anthropogenic activities (such as steel-making and Pb-Zn smelting). The results showed high accumulations of Tl combined with associated PTEs in the depth profiles. Calculations according to three risk assessment methods by enrichment factor (EF), geoaccumulation index (I-geo) and the potential ecological risk index (PERI) all indicated a significant contamination by Tl in all the sediments. Furthermore, lead isotopes were analyzed to fingerprint the contamination sources and to calculate their quantitative contributions to the sediments using the IsoSource software. The results indicated that a steel-making plant was the most important contamination source (similar to 56%), followed by a Pb-Zn smelter (similar to 20%). The natural parental bedrock was found to contribute similar to 24%. The findings highlight the importance of including multiple anthropogenic sources for quantitative fingerprinting of Tl and related metals by the lead isotopic approach in complicated environmental systems. (C) 2020 Elsevier Ltd. All rights reserved.

关键词： Thallium contamination Spatial distribution Pollution risk assessment Multiple end-members Isotopic tracing

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Downregulation of Skp2 inhibits the growth and metastasis of gastric cancer cells in vitro and in vivo

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TUMOR BIOLOGY 2013年第1期34卷 181-192页

作者： Wei, Zheng Jiang, Xian Liu, Fengjun Qiao, Haiquan Zhou, Baoguo zhai, Bo Zhang, Lianfeng Zhang, xuwen Han, Likun Jiang, Hongchi Krissansen, Geoffrey W. Sun, Xueying Harbin Med Univ Affiliated Hosp 1 Dept Gen Surg Hepatosplen Surg Ctr Harbin 150001 Peoples R China Shandong Univ Qilu Hosp Dept Gen Surg Jinan 250100 Peoples R China Univ Auckland Fac Med & Hlth Sci Dept Mol Med & Pathol Auckland 1005 New Zealand

S-phase kinase-associated protein-2 (Skp2) is overexpressed in human cancers and associated with poor prognosis. Skp2 acts as an oncogenic protein by enhancing cancer cell growth and tumor metastasis. The present study has demonstrated that small hairpin RNA (shRNA)-mediated downregulation of Skp2 markedly inhibits the viability, proliferation, colony formation, migration, invasion, and apoptosis of human gastric cancer MGC803 cells, which express a high level of Skp2. In contrast, Skp2 shRNA had only a slight effect on the above properties of BGC823 cells, which express a low level of Skp2. In accord, knockdown of Skp2 suppressed the ability of MGC803 cells to form tumors and to metastasize to the lungs of mice, and the growth of established tumors, by inhibiting cell proliferation and enhancing cell apoptosis. In contrast, overexpression of Skp2 promoted tumorigenesis of BGC823 cells in mice. Skp2 depletion induced cell cycle arrest in the G(1)/S phase by upregulating p27, p21, and p57 and downregulating cyclin E and cyclin-dependent kinase 2. Skp2 depletion also increased caspase-3 activity, impeded the ability of cells to form filopoidia and locomote, upregulated RECK (reversion-inducing cysteine-rich protein with kazal motifs), and downregulated matrix metalloproteinase (MMP)-2 and MMP-9 activity and expression. The results suggest that downregulating Skp2 warrants investigation as a promising strategy to treat gastric cancers that express high levels of Skp2.

关键词： S-phase kinase-associated protein-2 Gastric cancer Proliferation Cell cycle Metastasis p27

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基于ADAMS/INSIGHT的汽车悬架定位参数优化设计

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汽车技术 2011年第5期 33-36页

作者：丁亚康翟润国井绪文一汽轿车股份有限公司

运用ADAMS/CAR建立某车型前悬架的精确模型,并分析了该悬架定位参数随车轮跳动的变化情况。针对分析中存在前束角和外倾角变化范围较大问题,运用ADAMS/INSIGHT,通过对悬架部分硬点坐标和优化目标多次修改和迭代计算,系统可自动找出最优... 详细信息

运用ADAMS/CAR建立某车型前悬架的精确模型,并分析了该悬架定位参数随车轮跳动的变化情况。针对分析中存在前束角和外倾角变化范围较大问题,运用ADAMS/INSIGHT,通过对悬架部分硬点坐标和优化目标多次修改和迭代计算,系统可自动找出最优结果。对比优化前、后车轮定位参数可知,不仅前束角和外倾角优化目标达到,其它车轮定位参数的变化范围也有所缩小。

关键词：悬架定位参数优化设计 ADAMS/CAR ADAMS/INSIGHT

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Cobalt-decorated 3D hybrid nanozyme: A catalytic amplification platform with intrinsic oxidase-like activity

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ELECTROCHIMICA ACTA 2021年 395卷 139197-139197页

作者： Lu, Nannan Yan, Xiaoyi Gu, Yue Zhang, Tingting Liu, Yu Song, Yu Xu, Zhiqian Xing, Yue Li, xuwen Zhang, Zhiquan zhai, Shengyong Jilin Univ Coll Chem Changchun 130012 Peoples R China Anhui Univ Chinese Med Sch Pharm Hefei 230013 Peoples R China Qingdao Univ Qingdao Canc Inst Qingdao 266071 Peoples R China Changchun Univ Chinese Med Jilin Ginseng Acad Changchun 130117 Peoples R China

Research about constructing multi-dimensional carbon nanomaterials is of great significance in electrocatalytic and sensing fields in order to integrate structural merits of each individual unit. Also, nano-materials with enzyme-like activities are prospective candidates for artificial enzyme design and electrochemical application. Herein, we fabricate Co, N co-doped hierarchical hybrid (Co@NCNTs/NC) nanozyme, which integrates of both N-doped carbon nanotubes (NCNTs) and N-doped carbon sheets (NC). The three-dimensional (3D) porous carbon composite is prepared by thermal treatment of metal-organic framework (MOF) which was synthesized by growing of ZIF-67 on ZIF-L at room temperature. The obtained nanomaterial not only possesses an improved oxidase-like activity that can catalyze 3,3',5,5'-tetramethylbenzidine (TMB) in the absence of hydrogen peroxide (H2O2), but also constructs a signal amplification platform towards dopamine (DA) due to the synergistic catalysis of Co species and N-doped porous carbon architecture. The electrocatalytic performance for DA detection shows a broad linear range from 30 nM to 710 mu M and a detection limit of 9 nM. The Co@NCNTs/NC/GCE is employed to practically detect DA in human serum and artificial cerebrospinal fluid (aCSF) samples with satisfactory results. The present work exhibits a great promising in colorimetric and electrochemical sensing fields and presents a new sight for the fabrication of MOF-derived nanozyme. (C) 2021 Elsevier Ltd. All rights reserved.

关键词： Metal-organic frameworks Oxidase-like activity Nanozyme Electrochemical sensing Dopamine

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