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Systemic sclerosis (SSc) is a connective tissue disease with ethnic differences. Single-nucleotide polymorphisms (SNPs) in the ARID3A, CXCR5, and TNFSF8 genes have been reported to be associated with various autoimmune diseases. The aim of this study was to investigate the association between these SNPs and susceptibility to SSc in a Chinese Han population.A case-control study was conducted in 342 patients with SSc and 694 ethnically matched healthy controls. SNPs in ARID3A, CXCR5, and TNFSF8 were genotyped using a Sequenom MassArray iPLEX system, and allele association analyses were performed using the PLINK v1.90 software.Our study demonstrated that the ARID3A rs10415976 G and CXCR5 rs77871618 T alleles were suggestively associated with patients with SSc (P = 0.049 and P = 0.024, respectively) and TNFSF8 rs1555457 T allele was strongly associated with SSc (P = 0.003). Patients carrying the ARID3A rs350146 TT and TNFSF8 rs1555457 TT genotypes had a significant increased risk of SSc (P = 0.03 and P = 0.004, respectively). Moreover, rs10415976, rs77871618, and rs1555457 were associated with SSc in an additive genetic model (P 0.05). rs62132345 and rs1555457 were associated with SSc in the dominant genetic model (P 0.05). rs350146 was associated with SSc in the recessive genetic model (P = 0.029).ARID3A rs10415976, ARID3A rs350146, and CXCR5 rs77871618 were suggestively associated with SSc and TNFSF8 rs1555457 was strongly associated with SSc in the Chinese Han population in this study. Key Points • This case-control study determined that ARID3A rs10415976, ARID3A rs350146 and CXCR5 rs77871618 were suggestively associated with SSc and TNFSF8 rs1555457 was strongly associated with SSc in the Chinese Han population. • The differences in these results compared with previous studies may be a result of ethnic and racial differences.

Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5Recent relative studies related to blood biomarkers in PubMed were reviewed.An increasing number of studies have demonstrated that dysregulated expression of blood biomarkers related to ILD such as ferritin, Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and cytokines, and some tumor markers in MDA5Therefore, this review may provide insight to guide treatment decisions for MDA5

Aim To evaluate the diagnostic value of anti‐citrullinated α‐enolase peptide 1 (anti‐CEP 1) antibody in patients with rheumatoid arthritis (RA) by conducting a systematic review and meta‐analysis. Methods The PubMed, Web of Science, Embase, Scopus, and Cochrane Library databases were searched for relevant studies published until September 23, 2020. A bivariate mixed‐effects model was used to calculate the diagnostic indices from primary data of eligible studies. We performed meta‐regression and subgroup analysis to explore the sources of heterogeneity. Results Twenty‐four articles, with a total of 17 380 patients with RA and 7505 control participants, met the criteria for inclusion in the meta‐analysis. The pooled sensitivity, specificity, and positive and negative likelihood ratios for the anti‐CEP 1 antibody were 44% (95% CI: 38%‐51%), 97% (95% CI: 96%‐98%), and 14.81 (95% CI: 10.66‐20.57) and 0.57 (95% CI: 0.52‐0.64), respectively. The pooled positive and negative predictive values were 0.96 (95% CI: 0.95‐0.97) and 0.53 (95% CI: 0.43‐0.63), respectively. The area under the summary receiver operating characteristic curve was 0.86. Meta‐regression indicated that the anti‐CEP 1 antibody detection method may be a source of heterogeneity. The subgroup analysis of the group in which the anti‐CEP 1 antibody was detected by using a commercial enzyme‐linked immunosorbent assay (ELISA) kit had a sensitivity of 59% (95% CI: 50%‐68%) and a specificity of 93% (95% CI: 85%‐97%). Conclusions The anti‐CEP 1 antibody had moderate RA diagnostic value with relatively low sensitivity and high specificity. An ELISA may increase the RA diagnostic sensitivity.

We aim to elucidate the pathogenesis and heterogeneity of patients with Behçet's syndrome (BS) involving different organs using in-depth proteomics and identify the biomarkers for clinical assessment and treatment of patients.The expression levels of proteins in plasma samples from 98 patients with BS and 31 healthy controls (HC) were measured using our in-depth proteomic platform with a data-independent acquisition mass spectrometer and antibody microarray. Bioinformatic analyses of the biological processes and signaling pathways that were changed in the BS group were performed. Furthermore, the proteomic landscape of the organ-resolved BS pathogenesis was constructed. Biomarkers that indicate the disease severity and the vascular subset were validated in an independent cohort of 108 patients with BS and 29 HCs by using enzyme-linked immunosorbent assay.The BS group had 220 differentially expressed proteins, which discriminate 88.6% of the patients and 95.5% of the HCs. The bioinformatic analyses revealed different biological processes associated with BS pathogeneses, including complement activation, wound healing, angiogenesis, leukocyte-mediated immunity, and so on. Furthermore, the first proteomic landscape of the organ-resolved BS was constructed, providing the proteomic features of BS associated with different organs and protein targets for the development of therapeutic treatment. HABP2, TNC, and SERPINA3 were validated as potential biomarkers for the clinical assessment of vascular BS and treatment targets.Our results provide valuable insight into the pathogenesis of organ-resolved BS in terms of proteomic characteristics and potential biomarkers for vascular BS clinical assessment and treatment in the future.

Objectives The objective of the current study was to detect plasma profiles of inflammatory cytokines for determining potential biomarkers indicating cancer presence among the anti-TIF1-γ antibody-positive dermatomyositis (DM) patients. Methods Twenty-seven cancer-associated anti-TIF1-γ antibody-positive DM (Cancer TIF1-γ-DM) patients were compared with 20 anti-TIF1-γ antibody-positive DM patients without cancer (Non-cancer TIF1-γ-DM) and 10 healthy controls (HC). The plasma levels of 17 cytokines were determined using the Luminex 200 system. The ability of plasma VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ levels to distinguish the presence of cancer was evaluated through the area under the curve (AUC) analysis. Potential protein interactions of TIF1-γ and the five cytokines were analyzed using the STRING database. Results VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ plasma levels were significantly higher in the Cancer TIF1-γ-DM group, especially those without any anticancer treatment, than those in the non-cancer TIF1-γ-DM and HC groups. Meanwhile, anti-TIF1-γ antibody and the five cytokines could distinguish cancer presence in anti-TIF1-γ antibody-positive DM patients. The STRING network indicated that TIF1-γ potentially interacted with the cytokines. Positive correlations of VEGF-A among CCL2, IL-6, and IFN-γ and between IFN-γ and IL-6 were observed in Cancer TIF1-γ-DM patients. VEGF-A, TNF-α, CCL2, and IL-6 were positively associated with muscle-associated enzymes among the Cancer TIF1-γ-DM patients. Conclusion The present study identified VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as significant potential biomarkers indicating the presence of cancer and demonstrated a more detailed cytokine profile during diagnosis. These biomarkers could provide better screening strategies and insight into the Cancer TIF1-γ-DM pathogenesis. Key Points• VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ are potential biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis. Graphical abstract

Behcet’s disease (BD) is a systemic and chronic inflammatory vasculitis with unknown etiology. Diagnosis is determined by evaluating several clinical criteria, but the lack of specific laboratory diagnostic markers makes the diagnosis of BD more difficult. Therefore, the aim of this study was to determine the changes in hematological parameters in BD patients to investigate their relationship with BD clinical features. A total of 48 BD patients and 96 healthy controls were included in this study. The severity of each BD patient was associated to a severity score according to the entire spectrum of disease manifestations. Several laboratory tests were assessed, and the difference in their results between BD patients and healthy controls was evaluated. Correlation analysis was performed to reveal the interaction of these parameters. C-reactive protein (CRP), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), neutrophil count, platelet count, and plateletcrit significantly increased in BD patients compared with healthy controls (P < 0.05). CRP was higher in patients with skin lesions, MCH and MCHC were lower in patients with vascular involvement, and the neutrophil count was higher in patients with skin lesions and genital ulcers. In addition, higher CRP and lower MCH and MCHC were associated with a severe condition. Besides, MCH and MCHC were negatively correlated with the platelet count, plateletcrit, and neutrophil count. This study revealed that MCH and MCHC are valuable parameters for BD. Their levels help assess the disease severity and indicate the vascular involvement in BD.

The objectives of this study are to analyze the association between anti-nuclear matrix protein 2 (NXP2) autoantibody and idiopathic inflammatory myopathies (IIMs) and to assess the diagnostic and prognostic relevance of anti-NXP2 autoantibody in patients with IIMs. A systematic search was performed in PubMed, Web of Science, EMBASE, the Cochrane Library, and Scopus to identify studies published as of February 29, 2020. Data was analyzed using Stata 12.0 and Meta-DiSc 1.4. Twenty-eight studies (4764 patients with IIMs and 1981 controls) were included in the meta-analysis. Anti-NXP2 autoantibody showed a significant association with IIMs (odds ratio (OR) = 26.36, 95% confidence interval (CI): 12.05–57.67, P

Innate lymphoid cells (ILCs), a novel group of innate immune cells, play a key role in the early immune response via rapidly reacting to signals expressed by tissue-resident cells. ILCs contribute to some autoimmune diseases. We aim to investigate the proportions of circulating ILC subgroups in patients with primary biliary cholangitis (PBC). Overall, 48 patients with PBC and 24 healthy controls (HCs) were enrolled. Circulating ILCs and cytokine production were detected by flow cytometry. The proportions of total ILCs, ILC precursors (ILCPs) and ILCP/ILC2 ratio increased and that of ILC2s decreased in patients with PBC. ILC2 proportion was negatively correlated with gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The proportion of ILCPs and ILCP/ILC2 ratio were positively correlated with alkaline phosphatase, GGT, ALT and AST. ILC2 proportion was significantly decreased in the ursodeoxycholic acid (UDCA) -non-responder group compared with the UDCA-responder group, whereas the proportion of ILCPs and ILCP/ILC2 were ratio significantly increased. The proportions of CD38

Objectives An immunoglobulin G4 (IgG4) level above 1350 mg/L is one of the comprehensive criteria for the diagnosis of IgG4-related disease (IgG4-RD). The purpose of this study was to evaluate the differences in IgG4 levels determined using reagents from two main manufacturers and their concordance with clinical diagnosis. Methods IgG4 levels were measured in 309 patients, including 146, 40, 42, 41, and 40 patients with untreated IgG4-RD, pancreatic cancer, primary Sjogren syndrome, systemic lupus erythematosus, and idiopathic retroperitoneal fibrosis, respectively, and 141 healthy controls. The results obtained using the Binding Site and Siemens reagents were compared in patients with IgG4-RD. Results The serum IgG4 level measured using the Siemens reagent was almost two times that measured using the Binding Site reagent. The rate of IgG4-negative patients, which was 19.9% based on measurement using the Binding Site reagent, was only 4.8% based on measurement using the Siemens reagent (p Conclusions There were significant differences in serum IgG4 levels based on commonly used reagents from different manufacturers. The IgG4 cut-off level of 1350 mg/L was not suitable for all detection reagents. Clinicians and patients should be cognizant of these differences associated with the specific detection reagents when evaluating the test results.

The prognostic role of hypercoagulability in COVID-19 patients is ambiguous. D-dimer, may be regarded as a global marker of hemostasis activation in COVID-19. Our study was to assess the predictive value of D-dimer for the severity, mortality and incidence of venous thromboembolism (VTE) events in COVID-19 patients. PubMed, EMBASE, Cochrane Library and Web of Science databases were searched. The pooled diagnostic value (95% confidence interval [CI]) of D-dimer was evaluated with a bivariate mixed-effects binary regression modeling framework. Sensitivity analysis and meta regression were used to determine heterogeneity and test robustness. A Spearman rank correlation tested threshold effect caused by different cut offs and units in D-dimer reports. The pooled sensitivity of the prognostic performance of D-dimer for the severity, mortality and VTE in COVID-19 were 77% (95% CI: 73%-80%), 75% (95% CI: 65%-82%) and 90% (95% CI: 90%-90%) respectively, and the specificity were 71% (95% CI: 64%-77%), 83% (95% CI: 77%-87%) and 60% (95% CI: 60%-60%). D-dimer can predict severe and fatal cases of COVID-19 with moderate accuracy. It also shows high sensitivity but relatively low specificity for detecting COVID-19-related VTE events, indicating that it can be used to screen for patients with VTE.

Prealbumin is a blood component tested for nutrition monitoring, which could be affected during inflammation. This study aimed to investigate the relationships between prealbumin and C-reactive protein (CRP) in inflammatory rheumatic musculoskeletal diseases (RMDs), including Takayasu arteritis, antineutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosus, Behcet's disease and polymyositis/dermatomyositis.A total of 52 healthy controls and 508 RMD patients were included. We collected 3714 clinical and laboratory records from June 2011 to August 2019, and the longest follow-up period was eleven years. The associations between prealbumin and CRP, the globulin gap, the albumin-to-globulin ratio, and IgG were evaluated.Prealbumin had a high correlation coefficient (r=-0.497,Prealbumin is closely related to CRP in Chinese patients with five chronic inflammatory RMDs, which may be due to the influence of chronic inflammation during the course of disease.

Supplemental Material, sj-pdf-2-cat-10.1177_10760296211010976 for Diagnostic Value of D-Dimer in COVID-19: A Meta-Analysis and Meta-Regression by Haoting Zhan, Haizhen Chen, Chenxi Liu, Linlin Cheng, Songxin Yan, Haolong Li and Yongzhe Li in Clinical and Applied Thrombosis/Hemostasis

Supplemental Material, sj-pdf-3-cat-10.1177_10760296211010976 for Diagnostic Value of D-Dimer in COVID-19: A Meta-Analysis and Meta-Regression by Haoting Zhan, Haizhen Chen, Chenxi Liu, Linlin Cheng, Songxin Yan, Haolong Li and Yongzhe Li in Clinical and Applied Thrombosis/Hemostasis

ObjectiveDue to common exposure to yeast in the alcoholic and baking industry, positive rate of anti-Saccharomyces cerevisiae antibodies (ASCA) is reportedly high in patients with Behçet’s disease (BD) who have gastrointestinal symptoms (gastrointestinal BD (GIBD)). We performed a meta-analysis to assess the diagnostic value of ASCA in differentiating patients with BD from those with other chronic inflammatory bowel diseases.MethodsThe meta-analysis is presented with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology checklist. Relevant studies that investigated ASCA levels in patients with BD were retrieved from PubMed, EMBASE, Web of Science, SCOPUS and the Cochrane Library on 12 July 2019; the search was rerun on 12 February 2020. Stata/SE V.12.0 and Meta-DiSc V.1.4 were used to perform the meta-analysis and sensitivity analysis, disaggregated by isotypes of ASCA.ResultsNine studies were included in the meta-analysis. The results revealed a strong association between ASCA and GIBD, especially ASCA-IgG (OR=5.50 (95% CI 2.58 to 11.55), p=0.000) and ASCA-IgG+IgA (OR=5.36 (95% CI 1.40 to 20.45), p=0.014). The positivity rate of ASCA in GIBD was significantly higher than that in ulcerative colitis (UC): IgA (OR=2.13 (95% CI 1.30 to 3.50), p=0.003); IgG+IgA (OR=2.19 (95% CI 1.03 to 4.66), p=0.042); IgG/IgA ((=2.03 (95% CI 1.30 to 3.17), p=0.002). However, the frequency of ASCA-IgG was significantly higher in patients with Crohn's disease than GIBD (OR=0.48 (95% CI 0.28 to 0.83), p=0.009). There was no significant difference in ASCA positivity between BD without gastrointestinal involvement and healthy controls and between GIBD and intestinal tuberculosis (iTB) (p>0.05).ConclusionASCA may play a role in the pathogenesis of gastrointestinal involvement. Negative result of IgG favours the diagnosis of GIBD/BD when differentiated from Crohn’s disease. ASCA-IgA showed moderate diagnostic performance in distinguishing GIBD and UC and the diagnostic performance was better in combination with IgG. However, ASCA may not be a useful serologic marker distinguishing GIBD and iTB.PROSPERO registration numberCRD42020115245.

Objective The coronavirus disease 2019 (COVID‐19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID‐19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID‐19. Methods Studies investigating ferritin in COVID‐19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta‐analysis was performed to compare the ferritin level between different patient groups: non‐survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non‐ICU; with mechanical ventilation versus without mechanical ventilation. Results A total of 52 records involving 10 614 COVID‐19‐confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta‐analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non‐severe patients [WMD 397.77 (95% CI 306.51‐489.02), P, Serum ferritin resulted as a valuable biomarker in COVID‐19. Indeed, this meta‐analysis revealed the association between the serum ferritin level and clinical characteristics of COVID‐19 patients including disease severity, mortality, comorbidities, and certain treatment. Thus, ferritin was associated with poor prognosis and could predict the worsening of COVID‐19 patients.

Highlights • Significant negative correlation between IL-6 and platelet parameters was discovered. • Correlation between multiple cytokines and coagulation indicators was found. • Pro-inflammatory factors were found to be more associated to coagulation parameters. • Cytokines play an important role in the pathogenesis and evaluation of the condition of COVID-19., Background The novel SARS-CoV-2 caused a large number of infections and deaths worldwide. Thus, new ideas for an appropriated assessment of patients’ condition and clinical treatment are of utmost importance. Therefore, in this study, the laboratory parameters of patients with coronavirus disease 2019 (COVID-19) were evaluated to identify the correlation between cytokine expression and other laboratory parameters. Methods A retrospective and single-center study was performed in Wuhan, involving 83 severe or critical COVID-19 patients admitted to the intensive care unit (ICU). Laboratory parameters in ICU patients with laboratory-confirmed infection of SARS-CoV2 were collected. The association between parameters was assessed by Spearman's rank correlation. Results Patients’ median age was 66 years (IQR, 57–73), and 55 (66%) were men. Among the 83 patients, 61 (73%) had 1 or more coexisting medical condition. The median concentration of IL-2R, IL-6, IL8, IL10, and TNFα were above the normal range, without IL-1β. A significant negative correlation between IL-6 and platelet count was discovered (r2 = −0.448, P

The objectives of this study are to analyze the association between anti-nuclear matrix protein 2 (NXP2) autoantibody and idiopathic inflammatory myopathies (IIMs) and to assess the diagnostic and prognostic relevance of anti-NXP2 autoantibody in patients with IIMs. A systematic search was performed in PubMed, Web of Science, EMBASE, the Cochrane Library, and Scopus to identify studies published as of February 29, 2020. Data was analyzed using Stata 12.0 and Meta-DiSc 1.4. Twenty-eight studies (4764 patients with IIMs and 1981 controls) were included in the meta-analysis. Anti-NXP2 autoantibody showed a significant association with IIMs (odds ratio (OR) = 26.36, 95% confidence interval (CI): 12.05-57.67, P 0.001), especially juvenile IIMs (OR = 62.48, 95% CI: 16.97-229.98, P 0.001). The pooled sensitivity, specificity, and area under the curve were 0.19 (95% CI = 0.16-0.21), 1.00 (95% CI = 1.00-1.00), and 0.95 for patients with juvenile IIMs versus controls. Anti-NXP2 autoantibody was associated with an increased risk of developing five characteristics (edema, muscle weakness, myalgia/myodynia, dysphagia, and calcinosis) and reduced risk of interstitial lung disease (ILD) (P 0.001). Anti-NXP2 autoantibody showed no association with increased risk of death in IIMs (P = 0.463). These findings suggest that anti-NXP2 autoantibody is specially related to IIMs and is related to edema, muscle weakness, myalgia/myodynia, dysphagia, calcinosis, and ILD in patients with IIMs. However, there is no evidence to suggest that the presence of anti-NXP2 autoantibody confers a poor prognosis with respect to overall survival. Key Points • This study summarized the diagnostic and prognostic accuracies of anti-NXP2 autoantibody for patients with IIMs. Anti-NXP2 autoantibody is related to edema, muscle weakness, myalgia/myodynia, dysphagia, calcinosis, and ILD in patients with IIMs.

Although microRNA (miR)-145 has been identified to be a tumor suppressor in various types of tumor, it promotes the progression of non-small cell lung cancer (NSCLC). However, the precise underlying molecular mechanism of its action remains unclear. The present study investigated the effects of miR-145 on the proliferation, invasion, metastasis and apoptosis of the NSCLC A549 cell line and the underlying molecular mechanism of its action. In vitro cell proliferation, invasion, migration and apoptosis assays were employed, and the expression levels of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3and poly(ADP-ribose) polymerase (PARP) were evaluated by western blot analysis. The results demonstrated that ectopic expression of miR-145 inhibited the proliferation, invasion and migration of A549 cells, but promoted the apoptosis of A549 cells. Western blot analysis indicated that increased miR-145 levels led to a marked decrease in the expression of MMP-2, MMP-9 and Bcl-2. Upregulation of miR-145 expression increased the expression of Bax, thus increasing the Bax/Bcl-2 ratio. Additionally, the results indicated that miR-145 over expression promoted the cleavage of caspase-3 and PARP. Taken together, these results indicated that miR-145 suppresses the proliferative, invasive and migratory ability of A549 cells. Additionally, miR-145 upregulation induced apoptosis of A549 cells possibly by decreasing MMP-2 and MMP-9 expression, the Bax/Bcl-2 ratio and the activity of the caspase-3 cascade.

Objectives This study aimed to assess the prevalence and clinical correlation of anti-RNA polymerase III antibodies (anti-RNAP III) in Chinese Han systemic sclerosis (SSc) patients. Methods Serum samples from 236 patients with SSc, 125 patients with connective tissue diseases (CTD), and 166 healthy controls (HCs), recruited from Peking Union Medical College Hospital and 21 other medical centers in China, were tested for antibodies to RNA polymerase III by means of a line immunoassay (LIA) or an enzyme-linked immunosorbent assay (ELISA) kit. Results Anti-RNAP III antibodies were found in 14/236 SSc patients (5.93%), 1/125 (0.80%) CTD patients, and 0/166 (0.00%) HCs. The prevalence of anti-RNAP III was higher in SSc patients than in the CTD and HC groups (p = 0.02, p = 0.001, respectively). Renal crisis was significantly more common in patients with anti-RNAP III than patients without anti-RNAP III (42.9 vs. 4.1%, p < 0.0001). Gastrointestinal involvement was significantly more common in patients without anti-RNAP III than patients with anti-RNAP III (53.6 vs. 21.4%, p = 0.039). There was good agreement between the ELISA and line immunoassay (LIA) detection capabilities for anti-RNAP III. Conclusions The anti-RNAP III antibody, which was detected by ELISA, has diagnostic value for SSc and predictive value for SSc-related renal crisis. Both ELISA and LIA are very reliable methods for anti-RNAP III.Key Points• The prevalence of anti-RNAP III antibody was determined in Chinese SSc patients and performed ethnic differences.• The clinical association between anti-RNAP III antibody and Chinese SSc patients was evaluated in this research.• Methodological consistency of detection of anti-RNAP III antibody using commercial ELISA and LIA methods was evaluated in this research.

Table S1. hnRNP K interacting proteins identified in this study (DOCX 17 kb)

Background This study was conducted to identify potential seminal plasma metabolic markers associated with disease activity in Kallmann syndrome (KS). Methods We collected medical records and seminal plasma samples from 17 KS patients and 20 age-matched healthy controls (HC) and performed metabolomics analysis using the UPLC-QTOF-MS method. Results Partial least squares discriminant analysis (PLS-DA) showed that the metabolomics profile of KS patients was clearly separated from HC. Statistical analysis of the data indicates that there are differential metabolites between KS patients and HC. The main metabolic pathways focus on linoleic acid (LA) metabolism, Glycerophospholipid metabolism. Conclusions The seminal plasma metabolomics profile of KS patients has changed. Glycerophospholipids and LA are promising biomarkers for KS diagnosis.

Surgical and medical treatments usually fail to completely remove the primary lesions of salivary adenoid cystic carcinoma (SACC), resulting in local recurrence due to its strong infiltration, hematogenous metastasis and other unique biological behaviors. Targeted gene therapy, including hypoxia‑inducible factor‑1α (HIF‑1α) therapy, sheds new light on the treatment of salivary gland tumors. However, the mechanisms underlying the downregulation of HIF‑1α expression in SACC have not been well studied. The present study aimed to determine the effects of HIF‑1α downregulation on the proliferation, invasion, apoptosis, cell cycle and angiogenesis of hypoxic SACC‑83 cells, and to elucidate the molecular mechanisms underlying these effects. Western blot analysis was used to evaluate the protein expression levels of HIF‑1α and matrix metalloproteinase‑2 (MMP‑2). Angiogenesis and the protein expression of vascular endothelial growth factor (VEGF) were detected by tube formation assay of human umbilical vein endothelial cells and ELISA, respectively. It was revealed that short hairpin RNA was considerably downregulated following overexpression of HIF‑1α. In addition, downregulation of HIF‑1α inhibited the expression of VEGF and MMP‑2, as well as the proliferation, invasion, migration, and tube formation of hypoxic SACC‑83 cells, while inducing apoptosis in these cells. These results suggest that the downregulation of HIF‑1α may be a novel targeted therapy for SACC.