Objective This study was based on the network pharmacology to explore the mechanisms whereby Tribulus terrestris affects vitiligo.Methods The screening criteria for oral bioavailability(OB)and drug-likeness(DL)were set as OB≥30％and DL≥O.18,respectively.The databases of Traditional Chinese Medicine Systems Pharmacology and analysis platforms of OMIM,Swiss Target Prediction and GeneCards were used to screen out target genes of main active ingredients of Tribulus terrestris and construct an"active ingredients-target"network using Cyto-scape 3.9.1 software.Then the target genes of the main active ingredients of Tribulus terrestris and the target genes of vitiligo were intersected to construct a"disease-pathway-target-component-drug"network.In addition,the intersection targets were respectively imported into the STRING platform to construct Protein-Protein Interaction(PPI)Networks,and into the DAVID database for GO and KEGG pathway enrichment analyses.The structure of small molecules of key drug compo-nents and vitiligo-related protein structure were searched on PubChem and PBD.After setting up receptors and ligands,the molecular docking of these two was performed.Results Through screening,we identified 12 active ingredients,including kaempferol,terrestramide,isorhamnetin,sitosterol,which possibly affect 71 targets.PPI network analysis showed ten major targets,inclu-ding AKT1,TNF,ESR1,PPARG,HPGDS,CASP3,and PTGS2.These targets were involved in many biological processes,such as apoptosis,peptide serine phosphorylation,and cell response to reactive oxygen species,through various signaling pathways,including apoptosis,tumor necrosis factor and reactive oxygen species signaling.Molecular docking results showed that the main active components such as kaverol and isorhamnetin were stably bound to the core targets,such as AKT1,TNF and ESR1,the core components regulating key targets.Conclusion Tribulus terres-tris may improve vitiligo through regulating inflammation,apoptosis,immune function and oxida-tive stress.

ObjectiveTo estimate long-term trends in kidney cancer morbidity,mortality,and disability-adjusted life years rates（DALY rates）in five Asian countries and regions from 1990 to 2019 and the current disease burden of kidney cancer in China in 2019,and to project future trends through 2029.MethodsData were obtained from the Global Burden of Disease Study 2019（GBD 2019）,from which burden of disease indicators was obtained for China′s mainland,Taiwan of China,South Korea,Japan,and Singapore,analyzing trends of disease burden from 1990 to 2019. Using ARIMA models,morbidity and mortality trends were projected for China′s mainland from 2020 to 2029.ResultsAmong the five Asian countries and regions from 1990 to 2019,the age-standardized morbidity,mortality,and DALY rates of China′s mainland,Taiwan of China,and South Korea showed an upward trend（EAPC 95% CI ＞ 0）. Taiwan of China had the largest change of growth,followed by China′s mainland. In 2019,the DALY rates of kidney cancer in five Asian countries and regions showed an upward trend with the increase in age. The disease burden of male kidney cancer in each country and region was higher than that of females. The DALY rate of kidney cancer caused by three risk factors,high body mass index（BMI）,smoking,and trichloroethylene occupational exposure,was the highest in Taiwan of China. The prediction results of the ARIMA model showed that the morbidity and mortality of kidney cancer in China′s mainland would continue to increase from 2020 to 2029.ConclusionsSince 1990,the morbidity of kidney cancer has been showing an increasing trend in the five Asian countries and regions. And morbidity and mortality will continue to increase in China′s mainland by 2029.

Objective To explore changing trend of disease burden of neonatal diseases in China from 1990 to 2019 and to provide evidence for prevention and treatment of neonatal diseases.Methods The data on neonatal diseases in China for years of 1990 and 2019 were extracted from the Global Burden of Disease Study 2019（GBD 2019）.The number of patients,standardized prevalence,mortality,standardized mortality,years of life lost（YLLs）,standardized YLLs,years lived with disability（YLDs）,standardized YLDs,disability adjusted life years（DALYs）,standardized DALYs,and estimated annual percent change（EAPC） were adopted to evaluate variations in disease burden of neonatal diseases between 1990 and 2019.Results Compared with those in 1990,both the number of patients and standardized prevalence rate of neonatal diseases in China increased,with the EAPC of 2.83%（95% uncertainty interval [UI]:2.59%,3.07%） and 2.52%（95%UI:2.33%,2.72%）;while the mortality and standardized mortality rates were both on the decline,with the EAPC of-6.40%（95%UI:-6.64%,-6.16%） and-5.10%（95%UI:-5.59%,-4.62%）,respectively.The neonatal diseases-related YLDs and standardized YLDs rate increased,with the EAPC of 4.05%（95%UI:3.88%,4.21%） and 3.86%（95%UI:3.68%,4.04%）;but the YLLs,standardized YLLs rate,the DALYs,and standardized DALYs rate decreased,with the EAPC of-6.40%（95%UI:-6.16%,-6.64 %）,-5.11%（95%UI:-4.62%,-5.59%）,-4.75%（95%UI:-4.48%,-5.02%）,and-4.09%（95%UI:-3.74%,-4.45%）.Among the neonatal diseases,preterm birth was the leading category as ranked by standardized rate of prevalence,mortality,YLLs,and DALYs;nonspecific neonatal infections was the leading category as ranked by standardized YLDs.Conclusion The prevalence and YLDs rate of neonatal diseases in China increased in 2019 compared with those in 1990.Early diagnosis and treatment of neonatal diseases should be improved to reduce the burden caused by the diseases.

Objective:To investigate the potential pathogenic biomarkers associated with psoriasis and cellular heterogeneity at the level of single cells.Methods:Single cell sequencing data from psoriatic skin biopsies were subjected to quality control, dimensional-reduction clustering and cell annotation. Cell clusters were analyzed for differentially expressed genes (DEGs), cell communication and pseudotime analysis. And TFs-miRNA-hub genes regulatory networks were constructed.Results:6 hub genes were identified by multialgorithm, SPRR2A, SPRR2D, IL7R, IL1RN, IER3, and LCN2. NF-κB, TNF and MAPK signaling pathway were shown to be significantly enriched. The expression of SPRRs was significantly upregulated in endothelial cells, fibroblasts and immune cells such as Langerhans cells, CD8 + T cells, M1 macrophages, resting T cells, while IL7R was predominantly expressed in immune cells. A dramatic increase of the proportion of fibroblasts, dendritic cells, Treg cells and CD8 + T cells in psoriatic skin lesions (LS) ( P=0.023, P=0.007, P=0.046, P=0.028). The activeness of interactions number, interaction strength and level of pathway enrichment of cell communication were higher in LS than in the healthy control group. Fibroblasts, dendritic cells and resting T cells only interact with other cells in LS. Pseudotime analysis showed that immune cells were mainly distributed in early trajectory, and monocytes involved in the whole trajectory and increased in later trajectory. The expression of hub genes (except IL7R) were all increased along with pseudotime. Transcription factors, NFKB1, was involved in the regulation of hub genes ( SPRR2A, IL1RN, IL7R and IER3) transcription. Conclusion:Overexpression of SPRRs and IL7R, and interactive effects of immune cells may be involved in the pathogenic processes of psoriasis via the NF-κB and MAPK pathways, which lays the theoretical basis for further in-depth study of the pathogenic mechanism of psoriasis.

Objective:To screen the potential biomarkers and key signal pathways associated with transient receptor potential vanillin 3 ( TRPV3) mutations by bioinformatic analysis, and explore the effects of epidermal functions and keratinocyte differentiation among focal palmoplantar keratoderma and Olmsted syndrome caused by TRPV3 mutations. Methods:HEK293T cells transfected with TRPV3 mutant were sequenced by Sanger DNA. The differentially expressed genes associated with TRPV3 mutation were screened and the modules most related to sample characteristics were screened by weighted gene co-expression network analysis (WGCNA). Further enrichment and functional annotation were carried out. The protein interaction network was constructed by STRING database, and the key genes related to TRPV3 mutation were screened by multiple algorithms. Results:24 hours after transfection of HEK293T cells with wild type or TRPV3 mutants, it was found that the number of living cells in each cell line decreased, especially Gly573Cys, Gly573Ser and Trp692Gly. A total of 30 differentially expressed genes related to TRPV3 mutations were screened by WGCNA differential analysis, among which GO enrichment showed that they were mainly involved in the positive regulation of transcription by RNA polymerase Ⅱ and positive regulation of nucleic acid-templated transcription; while KEGG pathway enrichment analysis showed that they were mainly concentrated in mitogen-activated protein kinase signal pathway, inflammatory mediator regulation of TRP channel, cell senescence and sphingolipid metabolism. The results of four CytoHubba algorithms were crossed and four key target genes were identified, including FOS, EGR1, ATF3 and EGR2. Conclusion:This study found that TRPV3 mutations inhibit cell activity, which is closely related to skin keratosis such as Olmsted syndrome and focal palmoplantar keratosis. The differentially expressed genes related to TRPV3 mutations were screened by bioinformatics methods, which can provide a reference basis for the follow-up study of the pathogenesis and treatment of related diseases caused by TRPV3 mutations.

Objective:Pancreatic adenocarcinoma (PAAD) is one of the more malignant tumors of the digestive system with a poor prognosis. The aim of this study was to investigate the clinical significance and analyse the relationship between lactate metabolism genes and the tumor microenvironment.Methods:Pancreatic cancer and non-lesioned pancreatic cancer data were downloaded from the TCGA and GTEx databases, respectively, and lactate metabolism genes were downloaded from the GeneCards database. Lactate metabolism genes were identified as PAAD differentially expressed lactate metabolism genes and then prognostic models for pancreatic cancer lactate metabolism genes were constructed by univariate and LASSO-Cox methods. ssGSEA and ESTIMATE algorithms were used to assess the lactate risk gene relationship with the tumor microenvironment.Results:The prognostic model consisting of seven key lactate genes ( UCA1, ARNT2, PNPLA6, ATP6V0A1, MET, PRPF8, KRT7) is of great clinical value in independently predicting the prognosis of PAAD patients. In the tumor microenvironment, a variety of immune cell infiltrates showed a suppressed state in the group at high risk of lactate metabolism, including NK cells, regulatory T cells and eosinophils. Conclusion:The prognostic model of PAAD constructed through lactate metabolism-related genes and analysis of the tumor microenvironment provide new evidence for the prognosis and clinical treatment of patients with PAAD.

Objective To analyze the active ingredients of Xiaoyao Pill and its molecular mechanisms in the treatment of chloasma. Methods The active ingredients of Xiaoyao Pill, its target proteins and the targets related to human chloasma were searched through BATMAB-TCM database, GeneCards database, CTD database and GEO database, and the network diagram of active ingredient-disease targets was constructed. STRING database was used to construct protein interaction network, followed by GO and KEGG enrichment analysis. Finally, the active ingredients and common targets were verified by molecular docking. Results Xiaoyao Pill contained many key active ingredients such as angelica, 1-methyl-2-dodecyl-4-quinolone, ergotamine, palmitic acid, behenic acid, azelaic acid, and retinol, which possibly regulated expression of proteins related to core genes such as AKT1, INS, TNF, TP53, IL1B, KCNA1, PPARG, and JUN, resulting in the improvement of melasma. KEGG enrichment analysis revealed that the pathways involved in the action of Xiaoyao Pill included neuroactive ligand-receptor interactions, retrograde endocannabinoid signaling, dopaminergic synapses, CAMP signaling, nonalcoholic fatty liver disease, and gonadotropin-releasing hormone secretion. Molecular docking showed that the binding energies of TNF-ergotamine, IL1B-ergotamine, PPARG-ergotamine and JUN-ergotamine were all <-9 kcal/mol. Conclusions In addition to scavenge of free radicals, inhibition of melanin synthesis and anti-aging, Xiaoyao Pill can also inhibit nuclear transcription factor and reduce the inflammatory cascade reaction of IL-1β and tumor necrosis factor-α, resulting in anti-inflammation and antioxidation, consequently leading to improvement of chloasma.

目的 通过整合分析多芯片数据,探究与痤疮发病相关的关键基因及免疫细胞浸润水平.方法 从GEO数据库获取基因芯片数据集,采用"limma"R包和加权基因共表达网络分析(WGCNA)筛选与痤疮表型相关基因模块中的差异表达基因(DEGs),并进行GO功能富集和KEGG通路分析;利用STRING在线数据库及Cytoscape软件构建蛋白质互作网络,并筛选出关键基因;基于CIBERSORT算法分析免疫细胞浸润情况.结果 共筛选到154个DEGs.DEGs与信号受体结合、细胞因子活性、趋化因子受体结合等有关,主要集中在病毒蛋白与细胞因子和细胞因子受体的相互作用、细胞因子-细胞因子受体的相互作用、趋化因子信号传导、NF-κB信号传导、IL-17 信号传导等通路.构建的PPI网络中,得到139个节点,1597条边,筛选到两个关键基因(CCR5、CXCL8).22种免疫细胞浸润中,相对于正常对照组,皮损组中有更多的中性粒细胞、活化的肥大细胞、活化的树突状细胞、活化的CD4记忆T细胞等,而调节性T细胞、静息的树突状细胞、静息的肥大细胞等相对更少.结论 本研究利用生物信息学方法筛选的关键基因及免疫细胞浸润水平的变化可能在痤疮发病中起到重要作用.

Objective:To screen out the differentially expressed genes (DEGs) of alopecia areata, explore its immune infiltration mechanism and predict the therapeutic targets of traditional Chinese medicine, so as to provide new ideas for the pathogenesis and traditional Chinese medicine treatment of alopecia areata.Methods:Downloading gene microarray expression profiles related to alopecia areata from the GEO (Gene Expression Omnibus) database; Screening and enrichment analysis of DEGs; Constructing protein interaction network (PPI), screening key genes by Cytoscape software; Analyzing the correlation of infiltrating immunocyte bansed on CIBERSORT deconvolution method; Using Coremine medical database, a medical ontology information retrieval platform, to screen key genes for corresponding traditional Chinese medicine targets.Results:A total of 164 DEGs were screened from three alopecia areata chip samples. GO enrichment analysis showed that the 164th DEGs were mainly enriched in skin development, molecular activity, endopeptidase inhibitor activity, supramolecular fiber, etc.KEGG enrichment analysis screened Staphylococcus aureus infection, estrogen signal pathway, Wnt signal pathway, transforming growth factor β (TGF- β) and other signal pathways. Ten key genes KRT85, BMP2, KRTAP3-1, KRT27, MSX2, KRTAP11-1, HOXC13, DSG4, KRT82 and TCHH were screened by protein interaction network analysis. The correlation analysis between DEGs and immune infiltrating cells showed that there were significant differences inγ δ T cells( P<0.001), M1 macrophages( P<0.001). The potential targets of traditional Chinese medicine such as Huang Qi( P=0.0178), Bie Jia( P=0.0012) and Jiang Xiang( P=0.0033) were mapped by Coremine database. Conclusion:This study used bioinformatics methods to screen candidate genes related to the pathogenesis of alopecia areata, showing that they are closely related to infiltrating immunocyte, and screened potential therapeutic targets for Chinese medicine, providing a theoretical basis for an in-depth study of the pathological mechanisms and therapeutic approaches of alopecia areata.