Coffee consumption might be associated with lower potential risk and severity of metabolic syndrome: national health and nutrition examination survey 2003-2018.

BACKGROUND: Metabolic syndrome (MetS) is a clinical syndrome characterized by multiple metabolic disorders and is a serious global health problem. The coffee effect, acting as one of the most prevalent beverages on metabolic syndrome, is debatable. METHODS: We included patients from the National Health and Nutrition Examination Survey 2003-2018 and used a comprehensive evaluation called the MetS z-score to assess the severity of metabolic syndrome. The relationship between coffee, decaffeinated coffee, tea, and MetS z-scores was explored using a weighted linear regression. We also divided the participants into metabolic and non-metabolic syndrome groups according to the NCEP/ATP III criteria for the subgroup analysis. RESULTS: A total of 14,504 participants were included in this study. The results demonstrated that drinking more than three cups of coffee daily was significantly linked to lower MetS z-scores (p < 0.001). Daily coffee consumption was also associated with lower BMI (p = 0.02), systolic blood pressure (p < 0.001), Homeostatic Model Assessment for Insulin Resistance (p < 0.001), and triglycerides (p < 0.001), while it was positively correlated with HDL-C (p = 0.001). Participants who consumed more than three cups of coffee daily had a lower MetS z-score in the MetS (p < 0.001) and non-MetS (p = 0.04) groups. CONCLUSION: This research indicates that coffee consumption is linked to MetS severity. However, decaffeinated coffee and tea intake were unrelated to MetS severity.

Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status. METHODS: The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model. RESULTS: The patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer-Lemeshow goodness-of-fit test (χ2 = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable. CONCLUSION: Micro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.

Clinical characteristics and prognosis in systemic lupus erythematosus-associated pulmonary arterial hypertension based on consensus clustering and risk prediction model.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE). This study aims to explore the clinical characteristics and prognosis in SLE-PAH based on consensus clustering and risk prediction model. METHODS: A total of 205 PAH (including 163 SLE-PAH and 42 idiopathic PAH) patients were enrolled retrospectively based on medical records at the First Affiliated Hospital of Zhengzhou University from July 2014 to June 2021. Unsupervised consensus clustering was used to identify SLE-PAH subtypes that best represent the data pattern. The Kaplan-Meier survival was analyzed in different subtypes. Besides, the least absolute shrinkage and selection operator combined with Cox proportional hazards regression model were performed to construct the SLE-PAH risk prediction model. RESULTS: Clustering analysis defined two subtypes, cluster 1 (n = 134) and cluster 2 (n = 29). Compared with cluster 1, SLE-PAH patients in cluster 2 had less favorable levels of poor cardiac, kidney, and coagulation function markers, with higher SLE disease activity, less frequency of PAH medications, and lower survival rate within 2 years (86.2% vs. 92.8%) (P < 0.05). The risk prediction model was also constructed, including older age at diagnosis (≥ 38 years), anti-dsDNA antibody, neuropsychiatric lupus, and platelet distribution width (PDW). CONCLUSIONS: Consensus clustering identified two distinct SLE-PAH subtypes which were associated with survival outcomes. Four prognostic factors for death were discovered to construct the SLE-PAH risk prediction model.

Effects of organic pollutants on struvite crystallization kinetics and the molecular mechanism of inhibition on crystal growth.

The abilities of improving phosphorus (P) resources sustainability and reducing water eutrophication make struvite crystallization technology attract increasing interest in wastewater treatment, but struvite crystallization process may be affected by various impurities in wastewater. In this study, the effects of nine representative ionic surfactants including three types (anionic, cationic and zwitterionic) on crystallization kinetics and product quality of struvite were investigated, and the influencing mechanism was further probed. The results demonstrated that anionic surfactants significantly inhibit crystal growth so as to reduce crystal size especially in a-axis direction, change crystal morphology and decrease P recovery efficiency, and also lead to a slight decline in product purity. In contrast, cationic and zwitterionic surfactants have no obvious influence on the formation of struvite. A series of experimental characterizations and molecular simulations collectively revealed that the inhibition of crystal growth by anionic surfactants is attributed to the adsorption of anionic surfactant molecules on struvite crystal surface and subsequent blockage of active growth sites. The binding ability of surfactant molecules with the Mg2+ exposed on struvite crystal surface was highlighted to be the most essential factor determining the adsorption behavior and adsorption capacity. Anionic surfactants with stronger binding ability with Mg2+ have more intense inhibitory effect, but a large molecular volume of anionic surfactants will weaken the adsorption capacity on crystal surface so as to reduce the inhibitory effect. Contrastively, cationic and zwitterion surfactants without binding ability with Mg2+ have no inhibitory effect. These findings enable us to have a clearer understanding of the impact of organic pollutants on struvite crystallization and make a preliminary judgment on the organic pollutants that may have the ability to inhibit the crystal growth of struvite.

Tumor markers are associated with rapidly progressive interstitial lung disease in adult-dermatomyositis.

OBJECTIVES: DM-associated rapidly progressive interstitial lung disease (DM-RP-ILD) has been the clinical conundrum. We assess the serum levels of tumor markers (TMs) in different types of ILD, and explore the diagnostic utility of TMs for DM/ADM-RP-ILD. METHODS: This was a retrospective cohort study, data including clinical and laboratory records were collected from the first affiliated hospital of Zhengzhou University from December 2015, to June 2020. Tumor markers (TMs) include CEA, CA153, CA724, CA125, and CA199. Spearman analysis, ROC, and Kaplan-Meier curve were used for data analysis. RESULTS: Total 272 patients (149 DM and 123 ADM) were enrolled, 152 (55.88%) with ILD (116 with chronic ILD, 36 with RP-ILD) and 120 (44.12%) without ILD among them. The serum levels of CEA and ferritin were significantly higher in patients with RP-ILD than in the other two groups. Serum CA125, CA199, and CA153 levels in patients with RP-ILD were higher than those without ILD. CEA levels were associated with the ferritin, KL-6 and anti-MDA5 levels, and CEA concentration was significantly negatively correlated with DLco (P = 0.016, R2 = - 0.281). CEA [AUC = 0.7, 95% CI = (0.594, 0.806)] and ferritin [AUC = 0.737, 95% CI = (0.614, 0.860)] had diagnosed value for patients developing RP-ILD. Patients with high serum CEA levels had higher mortality rate within the DM-ILD population. CONCLUSIONS: TMs and ferritin were increased in DM/ADM-RP-ILD, and serum CEA and CA153 levels can evaluate disease severity of DM. And CEA and ferritin can be used as noninvasive diagnostic biomarkers for patients with DM-RP-ILD. Key Points • Interstitial lung disease (ILD) is a serious complication of DM, and is a leading cause of mortality, especially rapidly progressive ILD. • Tumor markers as a kind of noninvasive detection can reflect the disease severity of DM, and CEA and ferritin can be used to identify patients with RP-ILD.

Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Systemic Lupus Erythematosus and Pulmonary Arterial Hypertension: Evidence From Transcriptome Data.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple systems. Pulmonary arterial hypertension (PAH) has a close linkage with SLE. However, the inter-relational mechanisms between them are still unclear. This article aimed to explore the shared gene signatures and potential molecular mechanisms in SLE and PAH. Methods: The microarray data of SLE and PAH in the Gene Expression Omnibus (GEO) database were downloaded. The Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify the co-expression modules related to SLE and PAH. The shared genes existing in the SLE and PAH were performed an enrichment analysis by ClueGO software, and their unique genes were also performed with biological processes analyses using the DAVID website. The results were validated in another cohort by differential gene analysis. Moreover, the common microRNAs (miRNAs) in SLE and PAH were obtained from the Human microRNA Disease Database (HMDD) and the target genes of whom were predicted through the miRTarbase. Finally, we constructed the common miRNAs-mRNAs network with the overlapped genes in target and shared genes. Results: Using WGCNA, four modules and one module were identified as the significant modules with SLE and PAH, respectively. A ClueGO enrichment analysis of shared genes reported that highly activated type I IFN response was a common feature in the pathophysiology of SLE and PAH. The results of differential analysis in another cohort were extremely similar to them. We also proposed a disease road model for the possible mechanism of PAH secondary to SLE according to the shared and unique gene signatures in SLE and PAH. The miRNA-mRNA network showed that hsa-miR-146a might regulate the shared IFN-induced genes, which might play an important role in PAH secondary to SLE. Conclusion: Our work firstly revealed the high IFN response in SLE patients might be a crucial susceptible factor for PAH and identified novel gene candidates that could be used as biomarkers or potential therapeutic targets.

Enhancing continuous reactive crystallization of lithium carbonate in multistage mixed suspension mixed product removal crystallizers with pulsed ultrasound.

In this work, pulsed ultrasound was used to facilitate steady-state reactive crystallization and increase the final yield and productivity of lithium carbonate in continuously operated single and multistage mixed suspension mixed product removal (MSMPR) crystallizers. Experimental analyses of the stirred tank MSMPR cascade were performed to investigate the effects of ultrasound field, residence time and temperature which contributed to the steady-state yield, crystal size distribution and crystal morphology. The results show that pulsed ultrasound can not only significantly enhance the reaction rate, but also help to improve the particle size distribution and the crystal habit. Subsequently, a population balance model was developed and applied to estimate the final yield of the continuous process of the lithium bicarbonate thermal decomposition reaction coupling lithium carbonate crystallization. The consistency of the final yield between the experiments and the simulations proved the reliability of the established model. Through the experimental and simulation analyses, it is demonstrated that the use of pulsed ultrasound, higher final stage temperature, MSMPR cascade design and appropriate residence time help to achieve higher yield and productivity. Furtherly, based on the conclusion drawn, pulsed ultrasound enhanced three-stage MSMPR cascaded lithium carbonate continuous crystallization processes were designed, and the maximum productivity of 44.0 g/h was obtained experimentally.

Development of a Novel Highly Spontaneous Metastatic Model of Esophageal Squamous Cell Carcinoma Using Renal Capsule Technology.

PURPOSE: Increasing evidence has demonstrated that animal models are imperative to investigate the potential molecular mechanism of metastasis and discover anti-metastasis drugs; however, efficient animal models to unveil the underlying mechanisms of metastasis in esophageal squamous cell carcinoma (ESCC) are limited. METHODS: ESCC cell EC9706 with high invasiveness was screened by repeated Transwell assays. Its biological characteristics were identified by flow cytometry as well as by the wound healing and CCK-8 assays. Besides, the levels of epithelial-mesenchymal transition-related markers were examined using Western blotting. Parental (EC9706-I0) and subpopulation (EC9706-I3) cells were employed to establish the renal capsule model. Next, the tumor growth was detected by a live animal imaging system, and hematoxylin and eosin staining was applied to evaluate the metastatic status in ESCC. RESULTS: EC9706-I3 cells showed rapid proliferation ability, S phase abundance, and high invasive ability; obvious upregulation in N-cadherin, Snail, Vimentin, and Bit1; and downregulation in E-cadherin. EC9706-I3 cells were less sensitive to the chemotherapy drug 5-fluorouracil than EC9706-I0 cells; however, both cell lines reached a tumorigenesis rate of 100% in the renal capsule model. The live animal imaging system revealed that the tumors derived from EC9706-I0 cells grew more slowly than those from EC9706-I3 cells at weeks 3-14. The EC9706-I3 xenograft model displayed a spontaneous metastatic site, including kidney, heart, liver, lung, pancreas, and spleen, with a distant metastatic rate of 80%. CONCLUSION: Our data suggested that the metastatic model was successfully established, providing a novel platform for further exploring the molecular mechanisms of metastasis in ESCC patients.

Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN. METHODS: Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining. RESULTS: 159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in the renal tissues of patients with LN (P = 0.014). Bio-informatics analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-ß1 (TGF-ß1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018). CONCLUSION: Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.

Behcet's disease with peripheral nervous system involvement successfully treated with golimumab: a case report and review of the literature.

Nervous system involvement is a rare and serious complication of Behcet's disease (BD), and the peripheral type is rarer. This article aimed to describe a case of BD with the peripheral nervous system (PNS) involvement and present a comprehensive literature review. One case of BD with PNS involvement was reported and related literature was retrospectively reviewed via PubMed/MEDLINE and Scopus database. The patient was resistant to traditional treatments, such as glucocorticoids and immunosuppressants, but had rapid quiescence after using golimumab. Our literature review suggests that the involved peripheral nerves in BD were diverse, the most common were the tibial nerves and peroneal nerves, vasculitis might be the main cause, and prednisone was still the cornerstone of treatment. TNF-α inhibitors have been increasingly used for refractory BD in recent years. This well-illustrated case demonstrates the potential benefit of golimumab to the patient with PNS involvement. Given the diversity and complexity of PNS involvement, we recommend golimumab as a new trial treatment in clinical practice.

Identification of Molecular Markers Associated With the Pathophysiology and Treatment of Lupus Nephritis Based on Integrated Transcriptome Analysis.

Lupus nephritis (LN) is a well-known complication of systemic lupus erythematosus and is its leading cause of morbidity and mortality. Our study aimed to identify the molecular markers associated with the pathophysiology and treatment of LN. The renal tissue gene expression profiles of LN patients in the GSE32591 dataset were downloaded as a discovery cohort from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified; weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules of DEGs; and gene function enrichment analysis, molecular crosstalk analysis, and immune cell infiltration analysis were performed to explore the pathophysiological changes in glomeruli and tubulointerstitia of LN patients. The crosstalk genes were validated in another RNA-sequencing cohort. DEGs common in RNA-sequencing dataset and GSE32591 were uploaded to the Connectivity Map (CMap) database to find prospective LN-related drugs. Molecular docking was used to verify the targeting association between candidate small molecular compounds and the potential target. In all, 420 DEGs were identified; five modules and two modules associated with LN were extracted in glomeruli and tubulointerstitia, respectively. Functional enrichment analysis showed that type I interferon (IFN) response was highly active, and some biological processes such as metabolism, detoxification, and ion transport were impaired in LN. Gene transcription in glomeruli and tubulointerstitia might affect each other, and some crosstalk genes, such as IRF7, HLA-DRA, ISG15, PSMB8, and IFITM3, play important roles in this process. Immune cell infiltration analysis revealed that monocytes and macrophages were increased in glomeruli and tubulointerstitia, respectively. CMap analysis identified proscillaridin as a possible drug to treat LN. Molecular docking showed proscillaridin forms four hydrogen bonds with the SH2 domain of signal transducer and activator of transcription 1 (STAT1). The findings of our study may shed light on the pathophysiology of LN and provide potential therapeutic targets for LN.