Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

Noninvasive Detection of Cerebral Blood Flow and Blood Oxygen Based on Inductive Sensing Technology and Near Infrared Spectroscopy

The synchronous monitoring of cerebral blood flow and blood oxygen levels plays a pivotal role in the prevention,diagnosis,and treatment of cerebrovascular diseases.This study introduces a novel noninvasive device utilizing inductive sensing and near-infrared spectroscopy technology to facilitate simultaneous monitoring of cerebral blood flow and blood oxygen levels.The device consists of modules for cerebral blood flow monitoring,cerebral blood oxygen monitoring,control,communication,and a host machine.Through experiments conducted on healthy subjects,it was confirmed that the device can effectively achieve synchronous monitoring and recording of cerebral blood flow and blood oxygen signals.The results demonstrate the device’s capability to accurately measure these signals simultaneously.This technology enables dynamic monitoring of cerebral blood flow and blood oxygen signals with potential clinical applications in preventing,diagnosing,treating cerebrovascular diseases while reducing their associated harm.

Preparation of Tartary Buckwheat Seed Coating Agent and Its Effect on Germination

To mitigate the wastage of seed resources and reduce the usage of pesticides and fertilizers, seed coating agentshave gained popularity. This study employs single-factor and multi-index orthogonal experimental design methodsto investigate the seed coating formula and physical properties of Tartary buckwheat. The specific effects ofeach component on Tartary buckwheat seed germination are analyzed. The findings reveal that the seed coatingagent formulated with 1.5% polyvinyl alcohol, 0.15% sodium alginate, 0.2% op-10, 0.1% polyacrylamide, 8% colorant,3% ammonium sulfate, 1% potassium dihydrogen phosphate, and 0.15% carbendazim exhibits the mosteffective coating. It demonstrates optimal physical properties and promotes seed germination efficiently. The suspensionrate of this seed coating agent reaches 91.12%, with a mere 2.13% coating shedding rate and 2.5% coatingseed rot rate. Furthermore, it achieves a germination percentage of 99.17%, which is 20.84% higher than the lowestgroup. The germination potential and index are also significantly higher than the lowest group, with anincrease of 20.84% and 26.56%, respectively. Additionally, the vitality index is 553.08, a 15.75% increase comparedto the lowest group. The application of seed coating agents helps reduce seed resource loss, increase plant numbers,and ultimately enhance agricultural yields. This finding holds practical significance in agriculturalproduction.

Berberine inhibits hepatic gluconeogenesis via the LKB1-AMPK-TORC2 signaling pathway in streptozotocin-induced diabetic rats

AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.

Jiao-tai-wan Up-regulates Hypothalamic and Peripheral Circadian Clock Gene Cryptochrome and Activates PI3K/AKT Signaling in Partially Sleep-deprived Rats

This study aims to explore the effect and mechanism of Jiao-tai-wan （JTW） on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant （OR） rats with chronic partial sleep deprivation （PSD）. OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose （FPG）, fasting insulin （FINS）, homeostasis model assessment-insulin resistance （HOMA-IR） and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 （Cryl） and cryptochrome 2 （Cry2） in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B （NF-κB） p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3＇, 5＇-monophosphate （cAMP） and activity of vasodilator-stimulated phosphoprotein （VASP） in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.

Berberine Inhibits Gluconeogenesis in Skeletal Muscles and Adipose Tissues in Streptozotocin-induced Diabetic Rats via LKB1-AMPK-TORC2 Signaling Pathway

The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.

Fenugreek lactone attenuates palmitate-induced apoptosis and dysfunction in pancreatic β-cells

AIM: To investigate the effect of fenugreek lactone(FL) on palmitate(PA)-induced apoptosis and dysfunction in insulin secretion in pancreatic NIT-1 β-cells. METHODS: Cells were cultured in the presence or absence of FL and PA(0.25 mmol/L) for 48 h. Then, lipid droplets in NIT-1 cells were observed by oil red O staining, and the intracellular triglyceride content was measured by colorimetric assay. The insulin content in the supernatant was determined using an insulin radioimmunoassay. Oxidative stress-associated parameters, including total superoxide dismutase, glutathione peroxidase and catalase activity and malondialdehyde levels in the suspensions were also examined. The expression of upstream regulators of oxidative stress, such as protein kinase C-α(PKC-α), phospho-PKC-α and P47 phox, were determined by Western blot analysis and real-time PCR. In addition, apoptosis was evaluated in NIT-1 cells by flow cytometry assays and caspase-3 viability assays.RESULTS: Our results indicated that compared to the control group, PA induced an increase in lipid accumulation and apoptosis and a decrease in insulin secretion in NIT-1 cells. Oxidative stress in NIT-1 cells was activated after 48 h of exposure to PA. However, FL reversed the above changes. These effects were accompanied by the inhibition of PKC-α, phosphoPKC-α and P47 phox expression and the activation of caspase-3. CONCLUSION: FL attenuates PA-induced apoptosis and insulin secretion dysfunction in NIT-1 pancreatic β-cells. The mechanism for this action may be associated with improvements in levels of oxidative stress.

Berberine retarded the growth of gastric cancer xenograft tumors by targeting hepatocyte nuclear factor 4α

BACKGROUND Gastric cancer is the third deadliest cancer in the world and ranks second in incidence and mortality of cancers in China.Despite advances in prevention,diagnosis,and therapy,the absolute number of cases is increasing every year due to aging and the growth of high-risk populations,and gastric cancer is still a leading cause of cancer-related death.Gastric cancer is a consequence of the complex interaction of microbial agents,with environmental and host factors,resulting in the dysregulation of multiple oncogenic and tumor-suppressing signaling pathways.Global efforts have been made to investigate in detail the genomic and epigenomic heterogeneity of this disease,resulting in the identification of new specific and sensitive predictive and prognostic biomarkers.Trastuzumab,a monoclonal antibody against the HER2 receptor,is approved in the first-line treatment of patients with HER2+tumors,which accounts for 13%-23%of the gastric cancer population.Ramucirumab,a monoclonal antibody against VEGFR2,is currently recommended in patients progressing after first-line treatment.Several clinical trials have also tested novel agents for advanced gastric cancer but mostly with dis-appointing results,such as anti-EGFR and anti-MET monoclonal antibodies.Therefore,it is still of great significance to screen specific molecular targets for gastric cancer and drugs directed against the molecular targets.AIM To investigate the effect and mechanism of berberine against tumor growth in gastric cancer xenograft models and to explore the role of hepatocyte nuclear factor 4α(HNF4α)-WNT5a/β-catenin pathways played in the antitumor effects of berberine.METHODS MGC803 and SGC7901 subcutaneous xenograft models were established.The control group was intragastrically administrated with normal saline,and the berberine group was administrated intragastrically with 100 mg/kg/d berberine.The body weight of nude mice during the experiment was measured to assess whether berberine has any adverse reaction.The volume of subcutaneous tumors during this experiment was recorded to evaluate the inhibitory effect of berberine on the growth of MGC803 and SGC7901 subcutaneous transplantation tumors.Polymerase chain reaction assays were conducted to evaluate the alteration of transcriptional expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.Western blotting and IHC were performed to assess the protein expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.RESULTS In the both MGC803 and SGC7901 xenograft tumor models,berberine significantly reduced tumor volume and weight and thus retarded the growth rate of tumors.In the SGC7901 and MGC803 subcutaneously transplanted tumor models,berberine down-regulated the expression of HNF4α,WNT5a andβ-catenin in tumor tissues from both transcription and protein levels.Besides,berberine also suppressed the protein expression of HNF4α,WNT5a andβ-catenin in liver tissues.CONCLUSION Berberine retarded the growth of MGC803 and SGC7901 xenograft model tumors,and the mechanism behind these anti-growth effects might be the downregulation of the expression of HNF4α-WNT5a/β-catenin signaling pathways both in tumor tissues and liver tissues of the xenograft models.

Analysis on Forming Reason of RMB Appreciation Expectation

Since 2003, there has been a strong RMB appreciation expectation in the market. RMB exchange rate becomes the world focus again. This paper insists that the depreciation pressure of US dollar is the main reason that causes RMB appreciation expectation; the ＂double price action＂ of the Chinese tradable goods and non-tradable goods is the special reason that leads to RMB appreciation expectation; furthermore, the asymmetric foreign exchange rate management system in China strengthens RMB appreciation expectation.

基于高阶图融合的多视图聚类算法

基于图的多视图聚类算法通过探索样本点之间的邻近关系,受到了广泛的关注.尽管在实际应用中已经取得了较好的聚类性能,但是观察到大多数算法只是利用一阶邻近关系去构建相似图,这导致信息探索不足和多视图数据表征能力下降.为了解决这个挑战,本文提出了一种新颖的基于高阶图融合的多视图聚类算法(high-order graph fusion for multi-view clustering,HCDMC).具体地,所提出的算法通过一种新颖的隐式权重学习策略,从每个视图对应的一阶和二阶邻近图中学习相应的高阶图.引入希尔伯特-施密特(Hilbert-Schmidt)独立性准则作为一种差异性正则化项,旨在加强一致性高阶图的互补信息.最后,对学习到的一致性高阶图施加连通性约束,直接得到聚类标签矩阵,无需任何后处理步骤.使用交替方向乘子法去解决模型的优化问题.在6个真实的数据集上进行了一系列的实验,相较于最新的算法,本文提出的算法具有更好的聚类性能.

拉丁美洲的世界主义思想探微

拉丁美洲的世界主义思想是在其追求民族独立与解放的历史演进过程中逐步形成,呈现了一种协调自我与他者关系的可能,并在个体价值与人类价值的思辨中升华了植根本土的世界主义思想观照。拉丁美洲的世界主义思想表现为拉丁美洲本身即是世界主义的、由关注个体价值向关注人类整体性渐近发展、从属于民族化世界主义的鲜明地区文化特征,以去殖民化思想、种族融合思想、以泛美主义为代表的共同体思想为核心价值。拉丁美洲的世界主义思想因而展现出多维样态,即去殖民化的世界主义、强调道德教化的世界主义、倡导种族交融的世界主义与寻求全球正义分配的世界主义。拉丁美洲的世界主义思想不仅依凭其独特的文明特性丰富了人类世界主义思想,而且为推动全世界文明的交流互鉴与弘扬全人类共同价值贡献了独具一格的思想智慧。

火星降落伞开伞过程形态参数辨识与应用

针对柔性目标降落伞开伞过程的形态变化大、光照强度变化大、运动规律性差、存在遮挡等问题,提出了一种基于多算法融合的视觉测量技术的降落伞开伞过程形态参数辨识方法。首先,设计了具有视觉测量靶标功能的降落伞图案,提供了丰富的具有可区分度的标记点,能够准确地对定位点进行跟踪和测量,并开展了双目相机内、外参标定。其次,提出了应用对极几何原理,采用基于暗通道的图像增强技术,提高了图像质量,有效地减轻了各种噪声和过曝光等环境因素的影响;采用稀疏编码超分辨率重建算法,改进了特征点的像素级提取,实现了高精度的亚像素级特征提取;采用特征跟踪扩展卡尔曼滤波算法,提升了特征匹配跟踪的精度和效率。最后,通过全尺寸高空开伞试验的验证,结果表明该方法能够达到较高的辨识精度,具有较好的准确性和鲁棒性。此方法在中国首次火星探测“天问一号”探测器上成功得到了应用,精确地从双目影像中辨识出降落伞开伞过程形态参数,对设计和分析降落伞开伞工况提供了重要的技术参考和数据积累。

Inhibition of Abnormal Grain Growth in Stir Zone via In‑Situ Intermetallic Particle Formation During Friction Stir Welding of AA6061

Abnormal grain growth(AGG)has been widely observed in many friction stir welded(FSWed)joints during post-weld heat treatment(PWHT).The coarse grain structure not only reduces the strength of the joint but also limits its usage in superplastic forming.Several methods have been reported in previous studies to inhibit AGG,but all of them can only mitigate AGG.Complete inhibition of AGG was not achieved.In the current research,AGG was widely observed during the PWHT of friction stir welded AA6061.Multi-pass FSW enhanced the thermal stability of the as-welded grain structure but did not eliminate the occurrence of AGG.A new welding method was developed with the ball-milled Al–Ti powder mixture introduced into the stir zone and proved effective in inhibiting AGG in FSWed AA6061 during PWHT.The adoption of 5-pass FSW with an alternate rotation mode succeeded in producing an AGG-free sample.Microscopic characterizations conducted in the stir zone showed an evolution of Al–Ti powder mixture into different particle formations and Al3Ti new phase.Quantitative analysis of the second phase particles(SPPs)in the stir zone confirmed the increases in both particle number and average size.The quantitative results fit well with Humphreys’grain growth model,which theoretically explains the mechanism for AGG inhibition,i.e.,the significantly enhanced particle pinning effect.

Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

It has been known that,the novel coronavirus,2019-nCoV,which is considered similar to SARS-CoV,invades human cells via the receptor angiotensin converting enzyme II(ACE2).Moreover,lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection.However,some patients also exhibit non-respiratory symptoms,such as kidney failure,implying that 2019-nCoV could also invade other organs.To construct a risk map of different human organs,we analyzed the single-cell RNA sequencing(scRNA-seq)datasets derived from major human physiological systems,including the respiratory,cardiovascular,digestive,and urinary systems.Through scRNA-seq data analyses,we identified the organs at risk,such as lung,heart,esophagus,kidney,bladder,and ileum,and located specific cell types(i.e.,type II alveolar cells(AT2),myocardial cells,proximal tubule cells of the kidney,ileum and esophagus epithelial cells,and bladder urothelial cells),which are vulnerable to 2019-nCoV infection.Based on the findings,we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection.This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.

Decoupling Scheme for Virtual Synchronous Generator Controlled Wind Farms Participating in Inertial Response

In this paper,the dynamic coupling between the wind turbine rotor speed recovery(WTRSR)and inertial response of the conventional virtual synchronous generator(VSG)controlled wind farms(WFs)is analyzed.Three distinguishing features are revealed.Firstly,the inertial response characteristics of VSG controlled WFs(VSG-WFs)are impaired by the dynamic coupling.Secondly,when the influence of WTRSR is dominant,the inertial response characteristics of VSG-WFs are even worse than the condition under which WFs do not participate in the response of grid frequency.Thirdly,this phenomenon cannot be eliminated by only enlarging the inertia parameter of VSG-WFs,because the influence of WTRSR would also increase with the enhancement of inertial response.A decoupling scheme to eliminate the negative influence is then proposed in this paper.By starting the WTRSR process after inertial response period,the dynamic coupling is eliminated and the inertial response characteristics of WFs are improved.Finally,the effectiveness of the analysis and the proposed scheme are verified by simulation results.

Tianwen-1 Mars entry vehicle trajectory and atmosphere reconstruction preliminary analysis

The Tianwen-1 Mars entry vehicle successfully landed on the surface of Mars in southern Utopia Planitia on May 15,2021,at 7:18(UTC+8).To acquire valuable Martian flight data,a scientific instrumentation package consisting of a flush air data system and a multilayer temperature-sensing system was installed aboard the entry vehicle.A combined approach was applied in the entry,descent,and landing trajectory reconstruction using all available data obtained by the inertial measurement unit and the flush air data system.An aerodynamic database covering the entire flight regime was generated using computational fluid dynamics methods to assist in the reconstruction process.A preliminary analysis of the trajectory reconstruction result,along with the atmosphere reconstruction and aerodynamic performance,was conducted.The results show that the trajectory agrees closely with the nominal trajectory and the wind-relative attitude.Suspected wind occurred at the end of the trajectory.

Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological abnormalities

Haemorheological abnormalities have been described in diabetes mellitus,as well as in non-alcoholic fatty liver disease(NAFLD).However,the relationship between the changes in liver fat content and haemorheology is unknown.The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content(IHLC)in patients with type 2 diabetes.The serum biochemical markers,such as fasting plasma glucose(FPG),haemoglobin A1c(HbA1c),liver enzymes,lipid profiles,and haemorheological properties,were examined.IHLC was quantified using proton magnetic resonance spectroscopy(1 H-MRS)scanning of the liver.A significant correlation was observed between IHLC and whole blood viscosity at high,middle,and low shear rates.IHLC also positively correlated with haematocrit,the reduced whole blood viscosity at low and middle shear rates,and the erythrocyte aggregation index.Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD.In summary,haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.

Circulating MicroRNAs as Potential Biomarkers in the Diagnosis of Neurosyphilis: A Case Control Study

Objective:Laboratory diagnosis of neurosyphilis(NS)remains a great challenge.This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS,non-neurosyphilis,and healthy controls(HCs).Methods:We analyzed miRNA expression profiles in peripheral blood mononuclear cells(PBMCs)from six patients with NS,eight patients with secondary syphilis(SS),and five HCs using microarray technology.The differentially expressed miRNAs were validated in 33 NS samples,31 SS samples,and 30 HC samples using TaqMan miRNA real-time qPCR(qRT-PCR).Results:Thirty-nine miRNAs were differentially expressed in SS and NS patients compared with HCs.Thirteen miRNAs were randomly selected to validate their expression levels in the same samples used in microarray assay by qRT-PCR.All miRNAs were upregulated in SS and NS samples compared with HC.qRT-PCR analysis of the expression of the 13 miRNAs in a second cohort(76 samples)showed that the average expression levels of nine miRNAs were higher in SS than in NS(SS:0.185,NS:0.136,P=3.8E-10),while the expressions of the other four miRNAs were lower in SS than in NS(SS:0.000757,NS:0.000873,P=0.022).ROC curve analysis of the 13 miRNAs showed the area under the curve value to be 1.00 for distinguishing SS patients from HCs,1.00 for distinguishing NS patients from HCs,1.00 for distinguishing SS and NS patients from HCs,and 0.968 for distinguishing NS from SS patients.Conclusion:The present study is the first one that identified differentially expressed miRNAs in PBMCs from patients with NS.Our results suggest that the 13 candidate miRNAs in PBMCs may be novel noninvasive biomarkers for NS diagnosis.