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Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis

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Journal of Pharmaceutical Analysis 2023年第7期13卷 817-829页

作者： Jiayun Chen Xueling He Yunmeng Bai Jing Liu Yin Kwan Wong Lulin Xie Qian Zhang Piao Luo Peng Gao Liwei Gu Qiuyan Guo Guangqing Cheng Chen Wang Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhenGuangdong518020China

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ *** on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain *** study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental *** scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during *** could restore neutrophils’chemotaxis and immune function in the septic *** inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during *** also promoted the differentiation and activity of splenic B cells in mice with *** results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the ***,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

关键词： Artesunate Sepsis Single-cell RNA sequencing Immunomodulatory activity

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Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy

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World Journal of Clinical Cases 2024年第20期12卷 4091-4107页

作者： Yu-Ning Li Jia-Lin Su Shu-Hua Tan Xing-Long Chen Tian-Li Cheng Zhou Jiang Yong-Zhong Luo Le-Meng Zhang School of Life and Health Sciences Hunan University of Science and TechnologyXiangtan 411201Hunan ProvinceChina Department of Thoracic medicine Hunan Cancer HospitalChangsha 410013Hunan ProvinceChina

BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this ***,the emergence of drug resistance significantly limits the effectiveness of these therapeutic ***,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these *** To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC *** In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were *** first investigated the characteristics influencing clinical *** levels of NETs and cytokines were measured by commercial *** chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were *** absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were *** using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were *** First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line *** were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were *** metabolites were primarily involved in arachidonic acid and purine *** key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy *** The identified metabolic signatures may effectively distinguish NET levels and predict clinical

关键词： Non-small cell lung cancer Chemoimmunotherapy Neutrophil extracellular traps Metabolomics Machine learning

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Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

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Journal of Pharmaceutical Analysis 2023年第8期13卷 908-925页

作者： Qiuyan Guo Jiangpeng Wu Qixin Wang Yuwen Huang Lin Chen Jie Gong Maobo Du Guangqing Cheng Tianming Lu Minghong Zhao Yuan Zhao Chong Qiu Fei Xia Junzhe Zhang Jiayun Chen Feng Qiu Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China School of chinese Materia Medica and State Key Laboratory of Component-Based Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin301617China Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China College of Food Science and Engineering Institute of OceanBohai UniversityJinzhouLiaoning121013China State Key Laboratory of Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Institute of chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China The Fourth Clinical Medical College of Guangzhou University of chinese medicine ShenzhenGuangdong518033China

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii *** been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune ***,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing *** present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)*** TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total *** the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate *** analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling ***,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

关键词： Tripterygium glycosides tablet Acute liver injury scRNA-seq

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Modulation of expression of P16 and Her2 in rat breast tissues of mammary hyperplasia model by external use of Rupifang Extract

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Journal of traditional chinese medicine 2012年第4期32卷 651-656页

作者： Guijuan Zhang Dehui Li Hui Guo Rui Liao Bizhu Tan Suyi Zhang Yubin Liu Min Ma Xiaoting Zeng Zhuolong Peng Si Huang Yinghui Zheng Yi Ma The School Outpatient Department the First Affiliated Hospital of Jinan University Department of traditional chinese medicine Medical College of Jinan University College of Life Science and Technology Jinan University

tract in external use on expression of proto-onco- genes her2 and tumor suppression genes p16 in rat breast tissues of mammary hyperplasia model. To explore the mechanisms of Rupifang Extract in external use for preventing and treating mammary hyperplasia. METHODS Thirty virginal female Wistar rats were randomized into 5 groups, 6 in each, A： blank con- trol group; B： model group; C： the low dose group of Rupifang; D： the middle dose group of Rupifang; and E： The high dose group of Rupifang. The mam- mary hyperplasia rat models were produced by in- jecting estradiol benzoate and progesterone and ir- ritating by tail nipping. Drug intervention was also launched during the model formation. After 30 days, the expression of her2 and p16 in breast tis- sues of rats in each group were detected by the SP immunohistochemical method. RESULTS： Compared with Blank control group, the expression of her2 in breast tissues in Model group was higher, and the expression of p16 was lower （P〈O.05 or P〈O.01）. After intervention with Rupi- fang Extract, compared with Model group, the ex- pression of her2 in breast tissues in Rupifang groups was lower, and the expression of p16 higher （P〈O.05 or P〈O.01）. CONCLUSION： The mechanisms of Rupifang Ex- tract in external application for preventing and treating mammary hyperplasia may be reducing the expression of proto-oncogenes her2 and in- creasing the expression of tumor suppression genes p16.

关键词： Fibrocystic Breast Disease Receptor,Epidermal Growth Factor Rupifang extract

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决明子水提物对氯氮平所致大鼠体质量增加及糖脂代谢紊乱防治作用研究

决明子水提物对氯氮平所致大鼠体质量增加及糖脂代谢紊乱防治作用...

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2014浙江省医学会心身医学分会学术年会暨精神病学分会司法精神病学组学术年会

作者：董介正沈鉴清邱龄山刘义宋旦哥徐莲莲杭州市第七人民医院

目的:探讨决明子水提物对氯氮平所致大鼠体质量增加、糖脂代谢紊乱及肝脏脂质沉着的效果。方法:选用取2月龄SD大鼠50只,清洁级,雌雄各半,体质量17000g,按其体质量用随机数字表法分为5组,每组10只,即正常对照组,氯氮平组,氯氮平辛伐他汀... 详细信息

目的:探讨决明子水提物对氯氮平所致大鼠体质量增加、糖脂代谢紊乱及肝脏脂质沉着的效果。方法:选用取2月龄SD大鼠50只,清洁级,雌雄各半,体质量17000g,按其体质量用随机数字表法分为5组,每组10只,即正常对照组,氯氮平组,氯氮平辛伐他汀组,氯氮平小剂量决明子组及氯氮平大剂量决明子组。氯氮平的使用方法为1天5mg·kg-1·d-1,第5日起加至25 mg·kg-1·d-1,总共使用时间为8周。2周后在使用氯氮平的同时分别予辛伐他汀1 mg·kg-1·d-1、决明子水提液1000mg·kg-1·d-1及4000mg·kg-1·d-1干预,氯氮平组不予其它药物,正常对照组仅予生理盐水;取基线、3d、1w、2w、4w、6w、8w等7个时间点,称取大鼠体质量(Wt.),测空腹血糖(FBS)及餐后两小时血糖(2hPBG);于实验第8w末采血,检测血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C),并测血清果糖胺(FA)及胰岛素(IRS)水平,并取大鼠肝脏进行常规HE染色。结果:第6w、8w末,氯氮平组大鼠体质量与正常对照组大鼠体质量比较增加明显,FBS及2hPBG升高,血IRS、FA、TC、TG、LDL-C升高、HDL-C降低,表明氯氮平可引起大鼠体重增加,空腹血糖升高、糖耐量异常及脂代谢紊乱;第6w、8w末,与氯氮平组相比,氯氮平+辛伐他汀组、氯氮平+决明子大、小剂量组体质量较轻,FBS及2hPBG升高幅度小、IRS、FA、TC、TG、LDLC水平低、HDL-C略高;与阳性对照氯氮平+辛伐他汀组比较,氯氮平决明子大、小剂量组在减轻体质量增加,降血脂方面均无明显差异,决明子大剂量组在降低血糖方面优于氯氮平辛伐他汀组,表明决明子可以防治氯氮平所致体重增加,且较大剂量效果更明显。肝脏病理示与正常对照组比,氯氮平组镜下可见大鼠肝细胞形态紊乱,血管周围见多量白色脂肪细胞胞,且在距离血管较远的肝细胞也可见到脂质沉着,氯氮平+小剂量决明子组大鼠肝细胞形态正常,血管周围见较多量白色脂肪细胞胞,氯氮平+辛伐他汀组及氯氮平+大剂量决明子组大鼠肝脏小血管周围见少量白色脂肪细胞胞,血管较远处肝细胞无明显脂质沉着。结论:非典型抗精神病药物氯氮平可造成大鼠体质量增加、糖脂代谢紊乱及肝脏脂质沉着,决明子水提物能有效地防治非典型抗精神病药氯氮平所致的大鼠体质量增加、糖脂代谢紊乱及肝脏脂质沉着。

关键词：决明子氯氮平体质量增加糖脂代谢紊乱,脂质沉着

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Methodology Validation of Microbial Limit Test of Bupi Qiangli Ointment

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Agricultural Science & Technology 2017年第2期18卷 365-367页

作者：李江萍杨亮蒋玲贵阳中医学院第二属医院贵州贵阳550001

[Objective] This study was conducted to establish a microbial limit test method for Bupi Qiangli Ointment. [Method] The conventional method and medium dilution method were used for bacterial, mold and yeast counting in sample recovery test. [Result] The medium dilution method （1：10 test solution, 0.5 ml/plate） could effectively eliminate the inhibition effect of the Bupi Qiangli Ointment, and the recovery of Staphylococcus aureus was greater than 70% in the 3 batches of samples; and the conventional method exhibited the recoveries of E. coil, Bacillus subtilis, Candida albicans and Aspergillus greater than 70% in the 3 batches of samples. [Conclusion] Due to Bupi Qiangli Ointment has strongly antibacterial effect on Staphylococcus au- reus, the medium dilution method was used for bacterial counting, and the conventional method was used for mold and yeast counting; and the conventional method was used for controlled bacterium examination of E. coll.

关键词： Bupi Qiangli Ointment Microbial limit tests Method validation Medium dilution method

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Fuzheng Kang'ai decoction(扶正抗癌方) inhibits cell proliferation,migration and invasion by modulating mir-21-5p/human phosphatase and tensin homology deleted on chromosome ten in lung cancer cells

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Journal of traditional chinese medicine 2022年第3期42卷 344-352页

作者： LI Jinhua LIU Chunping ZHAO Yueyang WU Wanyin SUN Pengtao LI Longmei YANG Xiaobing ZHOU Yushu Department of Ultrasound Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Ultrasound Institute of Ultrasound in Musculoskeletal Sports MedicineGuangdong Second Provincial General HospitalGuangzhou 510317China State Key Laboratory of Dampness Syndrome of chinese medicine Guangdong Provincial Hospital of Chinese MedicineThe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Hematology Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Oncology Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLCGuangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China

OBJECTIVE:To elucidate the potential molecular mechanism by which Fuzheng Kang’ai decoction(扶正抗癌方,FZKA)inhibits proliferation,migration,and invasion of lung cancer ***:Varying FZKA concentrations were used to manage lung cancer cells(A549 and PC9).We employed:cell counting kit-8(CCK-8)and plate clone formation assays to examine the cell viability;flow cytometry(FCM)to analyze the cycle arrest;transwell and woundhealing assays to assess the cell invasion and migration,***,a quantitative real-time polymerase chain reaction(q RT-PCR)assay was adopted to evaluate the miR-21-5p *** protein expression analysis,we employed the Western blot *** miR-21-5p overexpression adenovirus vector harboring GFP was constructed and transfected into A549 and PC9,after which we explored the effect of FZKA on miR-21-5p ***:Notably,treatment with FZKA inhibited viability,clone-formation ability,invasion,and migration of lung cancer ***,FZKA markedly suppressed miR-21-5p expression but elevated the human phosphatase and tensin homology deleted on chromosome ten(PTEN)protein level in both A549 and PC9 ***-expression of miR-21-5p lowered PTEN protein ***,overexpressed miR-21-5p levels with adenovirus antagonized FZKA-upregulated PTEN protein ***:The present study demonstrates how FZKA modulates cell biological behaviors,for instance,it impedes the proliferation by upregulating PTEN expression with miR-21-5p as the *** findings unveil the potential novel molecular mechanisms from the micro RNA aspect by which FZKA suppresses the growth of human lung cancer cells.

关键词： lung neoplasms miR-21-5p PTEN phosphohydrolase Fuzheng Kang’ai decoction

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NTE Treatment Results in Increased Fpn Expression in Hippocampus of Rats Subjected to Cerebral Ischemia

NTE Treatment Results in Increased Fpn Expression in Hippoca...

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第九次全国中西医结合基础理论研究学术研讨会

作者： Jun Liao Xing Xia Guo-zuo Wang Yong-mei Shi Jin-wen Ge Department of Anatomy Hunan University of Chinese Medicine Campus Network Center Hunan University of Chinese Medicine College of Integrated medicine Hunan University of Chinese Medicine Hunan province Key Laboratory of Integrated medicine for Cardi-Cerebrovascular Disease Hunan University of Chinese Medicine

Objective:To observe the expression of Ferroportin(Fpn) at different time points in rats after focal cerebral ischemia treated with or without chinese medicine NTE(extract of HuangQi,Chuan Xiong,Di Long,Jiang Can) Methods:The experiment is carried out by two steps:Firstly,SD rats were randomly divided into 2 h,6h,12 h,24 h,72 h groups after operation of Middle cerebral artery occlusion(MCAO),mRNA and protein level of Fpn were detected by immunohistochemistry and RT-PCR at above time points;Secondly,the rats were randomly allotted five groups as following: sham operation group,model group,low dose group of NTE(3 g/kg),medial dose group of NTE (9/kg),large dose group of NTE(27 g/kg).After three days of corresponding therapy by intragastric administration once a day,the regional cerebral ischemia model was reproduced by middle cerebral artery occlusion(MCAO)with suture *** days later,the rats treated by previous *** third day,Neurological behavior of rats were detected by neurobehavioral *** in Hippocampal C region was measured by immunohistochemical method and mRNA of Fpn was detected by RT-PCR. Results:Expression of Fpn in hippocamp C reaches the highest point at 12 h after operation(P<0.05);compared with model group,the large dose group of NTE(27 g/kg) displays a lower Neurological behavior score(P<0.05);and large dose group of NTE showes higher lever expression of Fpn both at mRNA and protein level compared with sham operation group and model group(P<0.05). Conclusion:Disregulation of intracellular iron balance perhaps is the new mechanism of cerebral ischemia injury,the NTE can protect the neuron in Hippocampal C area by adjusting the expression of Fpn to balance the iron after cerebral ischemia.

关键词： Ferroportin(Fpn) Naotaifang extract(NTE) cerebral ischemia

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Clinical efficacy and gene chip expression analysis of Shenzhu Guanxin recipe granules(参术冠心方颗粒) in patients with intermediate coronary lesions

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Journal of traditional chinese medicine 2024年第3期44卷 545-553页

作者： JIN Xiao WU Bingxin LIN Miaoyang ZHONG Biying LIN Luoqi XU Danping Department of traditional chinese medicine the First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou 510630.510630China Department of Cardiology Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510000China Department of traditional chinese medicine the Eighth Affiliated HospitalSun Yat-Sen UniversityShenzhen 518033China

OBJECTIVE: To evaluate the clinical efficacy and safety of Shenzhu Guanxin recipe granules(参术冠心颗粒, SGR) in treating patients with intermediate coronary lesions(ICL), and to investigate the potential mechanism though a transcriptome sequencing approach. METHODS: ICL patients with Qi deficiency and phlegm stasis were adopted and randomly assigned to a case group or a control by random number generator in a 1∶1 randomization ratio to evaluate the clinical efficacy. RESULTS: There was no significant difference between the two groups in coronary computed tomography angiography related indexes in the two groups before and after intervention. Through the gene chip expression analysis, it is finally concluded that there are 355 differential mRNAs(190 up-regulated genes and 165 down regulated genes) when compared the SGR group and placebo group. Through protein-protein interaction network analysis of differentially expressed genes, 10 hub genes were finally obtained: CACNA2D2, CACNA2D3, DNAJC6, FGF12, SGSM2, CACNA1G, LRP6, KIF25, OXTR, UPB1. CONCLUSIONS: SGR combined with Western medicine can be safely used to treat ICL patients with Qi deficiency and phlegm stasis. The possible mechanism of action and relevant gene loci and pathway were proposed.

关键词： intermediate coronary lesions gene expression profiling Qi deficiency and phlegm stasis Shenzhu Guanxin recipe granules

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Differential expression of immune-related genes between healthy volunteers and type 2 diabetic patients with spleen-deficiency pattern

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Journal of traditional chinese medicine 2015年第6期35卷 646-652页

作者： Chen Longhui Yang Zemin Chen Weiwen Li Ruliu Lin Chuanquan Guan Lihua Zhu Zhangzhi Chen Ruifang Li Saimei Zhao Lingbo Zeng Jinhao Wang Jianhua Pi-wei Institute Guangzhou University of Chinese Medicine School of Basic Courses Guangdong Pharmaceutical University the First Affiliated Hospital of Guangzhou University of chinese medicine Clinical Medical College of Acupuncture Moxibustion and RehabilitationGuangzhou University of Chinese Medicine

OBJECTIVE: To investigate the clinical differentiation of spleen-deficiency pattern(SDP), a group of symptoms and signs defined in terms of traditional chinese medicine for its clinical ***: Peripheral venous blood(> 3 m L) was collected from each of six type 2 diabetes mellitus(T2DM)-SDP patients and six healthy volunteers. After the isolation of peripheral white blood cells(PWBCs), total RNA was extracted, and quality control was performed on all RNA samples. Microarray experiments were conducted using the Agilent human whole genome gene chip, and genes demonstrating differential expression were screened. Bioinformatics analysis was conducted on these genes using several online ***: We screened a total of 175 differentially expressed genes(DEGs), of which 111(63%) were down-regulated and 64(37%) were up-regulated in T2DM-SDP patients compared with healthy controls. Among the 175 genes, 158 had biological function annotations: 46(29%) were directly related to an individual's immune regulation or response, 25(16%) were associated with substance and energy metabolism of PWBCs which could also indirectly influence immunity, and the remaining87(55%) were involved in a variety of PWBC biological processes that might eventually influence the immune function. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DEGs were predominantly enriched in seven immune-related pathways. Hierarchical cluster analysis identified gene expression patterns that were distinguishable between the two study ***: Our results suggest that T2DM-SDP patients experience significant hypoimmunity and/or immune dysfunctions, and possess a specific gene expression profile. These findings offer new insights into SDP and the clinical pattern differentiation of T2DM-SDP.

关键词： Diabetes mellitus, Type 2 Immunity Metabolism Leukocytes Oligonucleotide array se-quence analysis Spleen-deficiency pattern

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