Racial Differences in Plasma Microbial Translocation and Plasma Microbiome, Implications in Systemic Lupus Erythematosus Disease Pathogenesis.

OBJECTIVE: Black groups have increased prevalence and accelerated pathogenicity of systemic lupus erythematosus (SLE) compared to other ethnic/racial groups. The microbiome and systemic microbial translocation are considered contributing factors to SLE disease pathogenesis. However, racial differences in the plasma microbiome and microbial translocation in lupus remain unknown. METHODS: In the current study, we investigated plasma levels of microbial translocation (lipopolysaccharide [LPS] and zonulin) and the plasma microbiome using microbial 16S RNA sequencing of Black and White patients with SLE and Black and White healthy controls. RESULTS: Plasma microbial translocation was increased in Black patients versus in White patients and in patients with SLE versus healthy controls regardless of race. Compared to sex, age, and disease status, race had the strongest association with plasma microbiome differences. Black groups (Black controls and Black patients) had lower α-diversity than White groups (White controls and White patients) and more distinct ß-diversity. Black and White patients demonstrated differences in plasma bacterial presence, including Staphylococcus and Burkholderia. Compared to White patients, Black patients had higher SLE Disease Activity Index (SLEDAI) scores and urinary protein levels as well as a trend for increased anti-double-stranded DNA (dsDNA) antibody levels consistent with the known increased severity of lupus in Black patients overall. Certain plasma bacteria at the genus level were identified that were associated with the SLEDAI score, urinary protein, and anti-dsDNA antibody levels. CONCLUSION: This study reveals racial differences in both quality and quantity of plasma microbial translocation and identified specific plasma microbiome differences associated with SLE disease pathogenesis. Thus, this study may provide new insights into future potential microbiome therapies on SLE pathogenesis.

Correlation between spleen density and prognostic outcomes in patients with colorectal cancer after curative resection.

OBJECTIVE: The objective of this study was to investigate the correlation between spleen density and the prognostic outcomes of patients who underwent curative resection for colorectal cancer (CRC). METHODS: The clinical data of patients who were diagnosed with CRC and underwent radical resection were retrospectively analyzed. Spleen density was determined using computed tomography. Analysis of spleen density in relation to overall survival (OS) and disease-free survival (DFS) utilizing the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors, and a nomogram was constructed to predict OS and DFS. Moreover, internally validated using a bootstrap resamplling method. RESULTS: Two hundred twelve patients were included, of whom 23 (10.85%) were defined as having a diffuse reduction of spleen density (DROSD) based on diagnostic cutoff values (spleen density≦37.00HU). Kaplan-Meier analysis indicated that patients with DROSD had worse OS and DFS than those non-DROSD (P < 0.05). Multivariate Cox regression analysis revealed that DROSD, carbohydrate antigen 199 (CA199) > 37 U/mL, tumor node metastasis (TNM) stage III-IV, laparoscopy-assisted operation and American Society of Anesthesiology (ASA) score were independent risk factors for 3-year DFS. DROSD, CA199 > 37 U/mL, TNM stage III-IV, hypoalbuminemia, laparoscopy-assisted operation and ASA score were chosen as predictors of for 3-year OS. Nomograms showed satisfactory accuracy in predicting OS and DFS using calibration curves, decision curve analysis and bootstrap resamplling method. CONCLUSION: Patients with DROSD who underwent curative resection have worse 3-year DFS and OS. The nomogram demonstrated good performance, particularly in predicting 3-year DFS with a net clinical benefit superior to well-established risk calculator.

Diagnostic efficacy of combining diffusion-weighted magnetic resonance imaging with serum Mucin 1, Mucin 13, and Mucin 16 in distinguishing borderline from malignant epithelial ovarian tumors.

AIMS: To enhance ovarian tumor diagnosis beyond conventional methods, this study explored combining diffusion-weighted magnetic resonance imaging (DWI-MRI) and serum biomarkers (Mucin 1 [MUC1], MUC13, and MUC16) for distinguishing borderline from malignant epithelial ovarian tumors. METHODS: A total of 126 patients, including 71 diagnosed with borderline (BEOTs) and 55 with malignant epithelial ovarian tumors (MEOTs), underwent preoperative DWI-MRI. Region of interest (ROI) was manually drawn along the solid component's boundary of the largest tumor, focusing on areas with potentially the lowest apparent diffusion coefficient (ADC). For entirely cystic tumors, a free-form ROI enclosed the maximum number of septa while targeting the lowest ADC. Serum biomarkers were determined using enzyme-linked immunosorbent assay. RESULTS: Basic morphological traits proved inadequate for malignancy diagnosis, warranting this investigation. BEOTs had an ADC mean of (1.670 ± 0.250) × 103 mm2 /s, while MEOTs had a lower ADC mean of (1.332 ± 0.481) × 103 mm2 /s, with a sensitivity of 63.6% and specificity of 90.1%. Median MUC1 (167.0 U/mL vs. 87.3 U/mL), MUC13 (12.44 ng/mL vs. 7.77 ng/mL), and MUC16 (180.6 U/mL vs. 36.1 U/mL) levels were higher in MEOTs patients. The biomarker performance was: MUC1, sensitivity 50.9%, specificity 100%; MUC13, sensitivity 56.4%, specificity 78.9%; MUC16, sensitivity 83.64%, specificity 100%. Combining serum biomarkers and ADC mean resulted in a sensitivity of 96.4% and specificity of 100%. CONCLUSION: The integration of DWI-MRI with serum biomarkers (MUC1, MUC13, and MUC16) achieves exceptional diagnostic accuracy, offering a powerful tool for the precise differentiation between borderline and malignant epithelial ovarian tumors.

Exploring the Effect of High-Energy Heavy Ion Beam on Rice Genome: Transposon Activation.

High-energy heavy ion beams are a new type of physical mutagen that can produce a wide range of phenotypic variations. In order to understand the mechanism of high-energy heavy ion beams, we resequenced the whole genome of individual plants with obvious phenotypic variations in rice. The sequence alignment results revealed a large number of SNPs and InDels, as well as genetic variations related to grain type and heading date. The distribution of SNP and InDel on chromosomes is random, but they often occur in the up/downstream regions and the intergenic region. Mutagenesis can cause changes in transposons such as Dasheng, mPing, Osr13 and RIRE2, affecting the stability of the genome. This study obtained the major gene mutation types, discovered differentially active transposons, screened out gene variants related to phenotype, and explored the mechanism of high-energy heavy ion beam radiation on rice genes.

The psoas muscle density as a predictor of postoperative complications in elderly patients undergoing rectal cancer resection.

Background: Muscle depletion that impairs normal physiological function in elderly patients leads to poor prognosis. This study aimed to evaluate the association between total abdominal muscle area (TAMA), total psoas area (TPA), psoas muscle density (PMD), and short-term postoperative complications in elderly patients with rectal cancer. Methods: All elderly patients underwent rectal cancer resection with perioperative abdominal computed tomography (CT). Complications were assessed according to the Clavien-Dindo classification. Severe complications were defined as grade III-V following the Clavien-Dindo classification. Univariate and multivariate analyses were performed to evaluate risk factors of short-term severe postoperative complications. Results: The cohort consisted of 191 patients with a mean age of 73.60 ± 8.81 years. Among them, 138 (72.25%) patients had Clavien-Dindo 0- II, 53 (27.75%) patients had severe postoperative complications (Clavien-Dindo III-V), and 1(0.52%) patient died within 30 days of surgery. PMD was significantly higher in the Clavien-Dindo 0-II cohort compared to the Clavien-Dindo III-V cohort (p=0.004). Nevertheless, TAMA and TPA failed to exhibit significant differences. Moreover, the multivariate regression analysis implied that advanced age [OR 1.07 95%CI (1.02-1.13) p=0.013], male [OR 5.03 95%CI (1.76-14.41) p=0.003], high charlson comorbidity index (CCI) score [OR 3.60 95%CI (1.44-9.00) p=0.006], and low PMD [OR 0.94 95%CI (0.88-0.99) p=0.04] were independent risk factors of Clavien-Dindo III-V. Conclusion: Preoperative assessment of the PMD on CT can be a simple and practical method for identifying elderly patients with rectal cancer at risk for severe postoperative complications.

COVID-19 mRNA vaccine, but not a viral vector-based vaccine, promotes neutralizing anti-type I interferon autoantibody production in a small group of healthy individuals.

Coronavirus disease 2019 (COVID-19) vaccines are highly effective but also induce adverse events, in particular, autoimmunity. Findings from several studies revealed that patients with life-threatening SARS-CoV-2 infection had increased, pre-existing, neutralizing antibodies against type I interferons (IFNs). However, whether COVID-19 vaccination induces the anti-type I IFN antibody remains unclear. In the current study, we evaluated plasma levels of 103 autoantibodies against various human self-antigens and 16 antibodies against viral antigens in healthy individuals pre- and post-COVID-19 vaccination. Twelve participants received a COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna), and 8 participants received a viral vector-based vaccine (Janssen). All participants produced increased antibody levels against SARS-CoV-2 antigens following vaccination. Among the 103 autoantibodies, only plasma levels of IgG autoantibodies against type I IFNs increased in participants who received a mRNA vaccine (3/12), but not in those who received the viral vector-based vaccine (0/8) at postvaccination compared to pre-vaccination. Among the three individuals showing increased anti-IFN IgG following vaccination, both plasma samples and plasma-purified total IgGs showed a dose-dependent binding ability to IFN-α; two of the three showed neutralizing activity to IFN-α-2a-induced phosphorated STAT1 responses in human peripheral blood mononuclear cells postvaccination compared to baseline in vitro. Among the 103 autoantibodies tested, the COVID-19 mRNA vaccine, but not the viral vector-based vaccine, specifically induced neutralizing anti-type I IFN autoantibodies in a small group of healthy individuals (~10%). Findings from this study imply that COVID-19 mRNA vaccines may suppress IFN-mediated innate immunity and impair immune defense through induced autoimmunity in some healthy individuals, who may need to switch to another type of COVID-19 vaccine (e.g., a viral vector-based vaccine).

Immune podocytes in the immune microenvironment of lupus nephritis (Review).

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder caused by the loss of tolerance to endogenous nuclear antigens such as double­stranded DNA, leading to the proliferation of T cells and subsequent activation of B cells, which results in serious organ damage and life­threatening complications such as lupus nephritis. Lupus nephritis (LN) develops as a frequent complication of SLE, accounting for >60% of SLE cases, and is characterized by proteinuria and heterogeneous histopathological findings. Glomerular injury serves a role in proteinuria as podocyte damage is the leading contributor. Numerous studies have reported that podocytes are involved in the immune response that promotes LN progression. In LN, immune complex deposition stimulates dendritic cells to secrete inflammatory cytokines that activate T cells and B cells. B cells secrete autoantibodies that attack and damage the renal podocytes, leading to renal podocyte injury. The injured podocytes trigger inflammatory cells through the expression of toll­like receptors and trigger T cells through major histocompatibility complexes and CD86, thereby participating in the local immune response and the exacerbation of podocyte injury. Based on the existing literature, the present review summarizes the research progress of podocytes in LN under the local immune microenvironment of the kidney, explores the mechanism of podocyte injury under the immune microenvironment, and evaluates podocytes as a potential therapeutic target for LN.

Identification of Anti-SNRPA as a Novel Serological Biomarker for Systemic Sclerosis Diagnosis.

Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for clinical diagnosis of the disease. We employed a protein array-based approach to identify and validate SSc-specific autoantibodies. Phase I involved profiled autoimmunity using human proteome microarray (HuProt arrays) with 90 serum samples: 40 patients with SSc, 30 patients diagnosed with autoimmune diseases, and 20 healthy subjects. In Phase II, we constructed a focused array with candidates identified antigens and used this to profile a much larger cohort comprised of serum samples. Finally, we used a western blot analysis to validate the serum of validated proteins with high signal values. Bioinformatics analysis allowed us to identify 113 candidate autoantigens that were significantly associated with SSc. This two-phase strategy allowed us to identify and validate anti-small nuclear ribonucleoprotein polypeptide A (SNRPA) as a novel SSc-specific serological biomarker. The observed positive rate of anti-SNRPA antibody in patients with SSc was 11.25%, which was significantly higher than that of any disease control group (3.33%) or healthy controls (1%). In conclusion, anti-SNRPA autoantibody serves as a novel biomarker for SSc diagnosis and may be promising for clinical applications.

The hub genes and their potential regulatory mechanisms in chronic spontaneous urticaria revealed by integrated transcriptional expression analysis.

Chronic spontaneous urticaria (CSU) is a recurrent disease characterized by wheals and or angioedema, and its pathogenesis is still unclear. The microarray datasets of skin tissue from CSU patients and healthy controls were integrated and analysed in Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the NetworkAnalyst tool. Then, the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Subsequently, a protein-protein interaction (PPI) network of DEGs was constructed by STRING and the related hub genes were identified through the MOCDE tool. The potential miRNAs targeting hub genes were predicted based on the intersection of three online databases, namely TargetScanHuman, TargetBase and miRNet. Differentially expressed lncRNAs (DElncRNAs) was performed using the GEO2R tool. The potential miRNAs targeting DElncRNAs were predicted through miRNet. Finally, the shared miRNAs targeting both hub genes and DElncRNAs were used to construct an mRNA/miRNA/lncRNA regulatory network. A total of 296 DEGs were obtained, which were mainly enriched in inflammatory and immune responses. Further, 14 hub genes were identified by the PPI network of DEGs. Clinical correlation analysis showed that the mRNA expressions of S100A7, S100A8, S100A9, S100A12, IL6 and SOCS3 in CSU were positively correlated with the 7-day urticaria activity score (UAS7), and their potential diagnostic value was supported by the receiver operating characteristic curve (ROC) analysis. Five up-regulated lncRNAs in the cytoplasm were obtained by DElncRNAs analysis. The ROC analysis showed that PVT1, SNHG3 and ZBTB20 - AS1 was of potential diagnostic value for CSU. Eight shared miRNAs targeting both hub genes and DElncRNAs were identified and used to construct a competing endogenous RNA (ceRNA) network. It was found that the IL-6/miR - 149 - 5p/ZBTB20 - AS1 axis might play an important role in the activation of mast cells in CSU. IL-6 and its related regulatory molecules may be used as potential diagnostic markers and therapeutic targets for CSU.

Can the Part Replace the Whole? A Choice Experiment on Organic and Pesticide-Free Labels.

Chemical pesticides are a serious impediment to agricultural sustainability. A large-scale reduction in their use to secure food supplies requires more innovative and flexible production systems. Pesticide-free production standards bring together the strengths of all participants in the food value chain and could be the catalyst for this transition. Using a choice experiment approach and green tea as an example, this study investigated consumers' preferences for organic and pesticide-free labels. According to the findings, organic and pesticide-free labels and brands are all major factors that affect consumers' purchase decisions. Consumers are more willing to pay for organic labels than pesticide-free labels. There is a substitution effect between organic labels and pesticide-free labels. Complementary effects exist between organic labels and national brands, pesticide-free labels, and national brands. Consumer trust has an impact on consumers' choice of organic labels and pesticide-free labels. The use of pesticide-free labels is an alternate approach for small- and medium-sized businesses in a specific market to lower the cost of organic certification.

Hydroxychloroquine prophylaxis for preeclampsia, hypertension and prematurity in pregnant patients with systemic lupus erythematosus: A meta-analysis.

OBJECTIVES: This meta-analysis aimed to evaluate the effectiveness of HCQ in improving the maternal and fetal outcomes in pregnancies with SLE. METHODS: A literature search was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane database for relevant English language articles, and Wanfang, CNKI and VIP for Chinese articles, from the databases' inception to April 30, 2020. These studies compared the maternal and/or fetal outcomes between pregnant patients with SLE who were administered HCQ during pregnancy (HCQ+ group) and those who were not administered HCQ (HCQ- group). Two investigators extracted the data and assessed the quality using the Newcastle-Ottawa Scale (NOS) and GRADE criteria independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. All statistical analyses were conducted using the Stata 12.0 software. RESULTS: Nine studies involving 1132 pregnancies were included in the study (3 case controls, 2 prospective cohorts, 4 retrospective cohorts). Preeclampsia, gestational hypertension, and prematurity were significantly lower in the HCQ+ group than in the HCQ- group (OR 0.35, 95% CI 0.21-0.59), (OR 0.41, 95% CI 0.19-0.89) and (OR 0.55, 95% CI 0.36-0.86), respectively. There were no significant differences in the rates of HELLP Syndrome (OR 0.88, 95% CI 0.19-3.96), gestational diabetes (OR 2.3, 95% CI 0.44-12.12), thrombotic events (OR 0.26, 95% CI 0.05-1.51), spontaneous abortion (OR 1.77, 95% CI 0.96-3.26), premature rupture of membranes (OR 0.58, 95% CI 0.24-1.39), oligohydramnios (OR 0.90, 95% CI 0.38-2.14), live birth (OR 1.22, 95% CI 0.60-2.47), stillbirth (OR 1.00, 95% CI 0.50-2.00), congenital malformation (OR 0.53, 95% CI 0.14-2.04), low birth weight (OR 0.77, 95% CI 0.43-1.39), intrauterine distress (OR 1.07, 95% CI 0.41-2.76,), intrauterine growth restriction (OR 0.57, 95% CI 0.06-5.43), or five-minute APGAR score <7 (OR 0.72, 95% CI 0.20-2.58) between the two groups. CONCLUSIONS: HCQ treatment during pregnancy could reduce the risk of preeclampsia, pregnancy hypertension and prematurity in SLE patients. The certainty of evidence is high but majority of the studies included are retrospective studies and not randomized controlled trials. Therefore, the multidisciplinary management of pregnant patients with SLE should promote HCQ use, irrespective of disease activity or severity.

Strongyloides stercoralis Infection in a Patient with Chronic Renal Failure from North China.

INTRODUCTION: Human strongyloidiasis is a generally neglected parasitic disease of major global distribution, spreading commonly in tropical and subtropical areas. As for China, strongyloidiasis occur mainly in South of China and no relevant information about the parasite infection in North China was available. CASE PRESENTATION: An 84-year-old man from Shanxi province, North China, was admitted to Department of Nephrology with complaints of a 7-month history of intermittent edema of both lower extremity with foam urine and 3-day history of fever, chill and diarrhea. Large numbers of rhabditiform larva of Strongyloides stercoralis (S. stercoralis) were observed in a stool sample. Diagnosis of S. stercoralis infection was established by morphological observations of larvae under the microscope in both wet mount and Wright-Giemsa staining smear and further confirmed by molecular biology identification. CONCLUSIONS: We report a rare case of S. stercoralis infection in a patient with chronic renal failure from North China, which implies the possibility of developing human strongyloidiasis in cooler climates. In addition, our case suggests that clinicians should consider the complication of S. stercoralis infection in immunosuppressed patient populations with chronic renal failure. Morphological details of S. stercoralis in Wright-Giemsa staining was first described in the present case. Our results also support the use of molecular techniques targeting COX1 gene sequence for the diagnosis of S. stercoralis infection, which was prove to be necessary in laboratory practice, especially for those inexperienced morphologists in temperature zone.

The Differential Effects of Physical Activity Calorie Equivalent Labeling on Consumer Preferences for Healthy and Unhealthy Food Products: Evidence from a Choice Experiment.

Background: Since numerical calorie labels have limited effects on less-calorie food ordering, an alternative called physical activity calorie equivalent (PACE) labels, which exhibit calories using visible symbols and the minutes of exercise to burn off the calories, may be more effective in reducing calories ordered. Methods: By using a choice experiment (CE) approach, the aims of this study were to estimate the effects of PACE labels on consumer preferences for healthy and unhealth food. Red date walnuts and potato chips were used as the representatives of healthy and unhealthy foods respectively in this study. Moreover, future time perspective (FTP) is an individual trait variable of consumers, which has been recognized as a significant driver of healthy behaviors. We also included FTP into the interaction with PACE labels. Results: Firstly, the results were opposite between the healthy and unhealthy food groups. Respondents showed significantly more positive attitudes toward red date walnuts (i.e., healthy food) with PACE labels, while they showed significantly more negative preferences for chips (i.e., unhealthy food) with PACE labels. Secondly, people with higher FTP are preferred red date walnuts with PACE labels, while PACE labels on chips could undermine the preferences of respondents with higher FTP. Thirdly, we found that women (vs. men) were less inclined to choose healthy food with standard calorie labels and labels showing the minutes of running to burn off the calories, as well as that the elderly (vs. younger) people in the healthy food group preferred the labels showing the minutes of running to burn off the calories. People with a higher body mass index (BMI) were reluctant to purchase walnuts with the information about the minutes of walking. Conclusions: Results from this study showed that PACE labels have significant effects on consumers' preferences for food products.

Identification of Novel Serological Autoantibodies in Takayasu Arteritis Patients Using HuProt Arrays.

To identify novel autoantibodies of Takayasu arteritis (TAK) using HuProt array-based approach, a two-phase approach was adopted. In Phase I, serum samples collected from 40 TAK patients, 15 autoimmune disease patients, and 20 healthy subjects were screened to identify TAK-specific autoantibodies using human protein (HuProt) arrays. In phase II, the identified candidate autoantibodies were validated with TAK-focused arrays using an additional cohort comprised of 109 TAK patients, 110 autoimmune disease patients, and 96 healthy subjects. Subsequently, the TAK-specific autoantibodies validated in phase II were further confirmed using western blot analysis. We identified and validated eight autoantibodies as potential TAK-specific diagnostic biomarkers, including anti-SPATA7, -QDPR, -SLC25A2, -PRH2, -DIXDC1, -IL17RB, -ZFAND4, and -NOLC1 antibodies, with AUC of 0.803, 0.801, 0.780, 0.696, 0.695, 0.678, 0.635, and 0.613, respectively. SPATA7 could distinguish TAK from healthy and disease controls with 73.4% sensitivity at 85.4% specificity, while QDPR showed 71.6% sensitivity at 86.4% specificity. SLC25A22 showed the highest sensitivity of 80.7%, but at lower specificity of 67.0%. In addition, PRH2, IL17RB, and NOLC1 showed good specificities of 88.3%, 85.9%, and 86.9%, respectively, but at lower sensitivities (<50%). Finally, DIXDC1 and ZFAND4 showed moderate performance as compared with the other autoantibodies. Using a decision tree model, we could reach a specificity of 94.2% with AUC of 0.843, a significantly improved performance as compared with that by each individual biomarker. The performances of three autoantibodies, namely anti-SPATA7, -QDPR, and -PRH2, were successfully confirmed with western blot analysis. Using this two-phase strategy, we identified and validated eight novel autoantibodies as TAK-specific biomarker candidates, three of which could be readily adopted in a clinical setting.

Pentraxin 3 is more accurate than C-reactive protein for Takayasu arteritis activity assessment: A systematic review and meta-analysis.

AIMS: Whether the circulating levels of pentraxin 3 (PTX3), an acute phase reactant (APR), are higher in active Takayasu arteritis (TAK), and if so, whether PTX3 is more accurate than C-reactive protein (CRP) in TAK activity assessment has been investigated in this study. STUDY DESIGN: Research works such as PubMed, Embase, ScienceDirect, Cochrane Library, and two Chinese literature databases (CNKI and WanFang) were searched for studies conducted till August 30th, 2019. Two investigators searched the studies independently, who evaluated the quality of the study using the Newcastle-Ottawa scale (NOS) and extracted data. Pooled standard mean difference (SMD) and diagnostic indexes, with a 95% confidence interval (CI), were calculated using a random-effect model. RESULTS: Totally, 8 studies involving 473 TAK (208 active and 265 inactive TAK) patients and 252 healthy controls were eventually included in the meta-analysis. PTX3 level in the blood in active TAK patients were found to be higher than that in dormant TAK with pooled SMD of 0.761 (95% CI = 0.38-1.14, p<0.0001; I2 = 68%, p of Q test = 0.003). And there was no publication bias. Among the 8 studies, 5 studies identified active TAK with both PTX3 and CRP. The pooled sensitivity, specificity, and AUC values of PTX3 in active TAK diagnosis were higher than those of CRP (0.78 [95% CI = 0.65-0.87] vs. 0.66 [95% CI = 0.53-0.77], p = 0.012; 0.85 [95% CI = 0.77-0.90] vs. 0.77 [95% CI = 0.56-0.90], p = 0.033; 0.88 [95% CI = 0.85-0.90] vs. 0.75 [95% CI = 0.71-0.79], p < 0.0001). It showed potential publication bias using Egger's test (p of PTX3 = 0.031 and p of CRP = 0.047). CONCLUSIONS: PTX3 might be better than CRP in the assessment of TAK activity. Yet, it should be cautious before clinical use for moderate heterogeneity and potential publication bias of the meta-analysis.

Intermedin alleviates the inflammatory response and stabilizes the endothelial barrier in LPS-induced ARDS through the PI3K/Akt/eNOS signaling pathway.

Inflammatory storms and endothelial barrier dysfunction are the central pathophysiological features of acute respiratory distress syndrome (ARDS). Intermedin (IMD), a member of the calcitonin gene-related peptide (CGRP) family, has been reported to alleviate inflammation and protect endothelial cell (EC) integrity. However, the effects of IMD on ARDS have not been clearly elucidated. In the present study, clinical ARDS data were used to explore the relationship between serum IMD levels and disease severity and prognosis, and we then established a model to predict the possibility of hospital survival. Mouse models of ARDS and LPS-challenged endothelial cells were used to analyze the protective effect and underlying mechanism of IMD. We found that in patients with ARDS, increased serum IMD levels were associated with reduced disease severity and increased rates of hospital survival. IMD alleviated the LPS-induced inflammatory response by decreasing proinflammatory cytokines, NF-κB p65 expression and NF-κB p65 nuclear translocation. In addition, IMD stabilized the endothelial barrier by repairing adherens junctions (AJs), cytoskeleton and capillary leakage. IMD exerted protective effects against ARDS on pulmonary endothelial cells, at least partly, through PI3K/Akt/eNOS signaling, while IMD's anti-inflammation effect was mediated through an eNOS-independent mechanism. Our study may provide new therapeutic insight for ARDS treatment.

Circulating Exosomes From Lipopolysaccharide-Induced Ards Mice Trigger Endoplasmic Reticulum Stress in Lung Tissue.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a critical clinical syndrome with high mortality rate, and few effective therapies have been found in the past 50 years, indicating that the pathogenesis of ARDS remains unclear. Exosomes, a novel cross-communication mechanism, are involved in critical diseases. However, the role of circulating exosomes in the development of ARDS remains poorly understood. METHODS: In the present study, naive mice were treated with circulating exosomes from lipopolysaccharide (LPS)-induced ARDS mice or exosome-depleted serum. Histological lung damage, bronchoalveolar lavage fluid (BALF), and endoplasmic reticulum (ER) stress were measured. RESULTS: Increased tumor necrosis factor (TNF)-α, interleukin (IL)-6, total cell counts, polymorphonuclear (PMN) leukocyte proportions and myeloperoxidase (MPO) activity in BALF, and increased wet/dry weight ratios and protein concentrations in BALF were found in mice after exosome injection but not in mice treated with exosome-depleted serum. Furthermore, western blot analysis showed that circulating exosomes from ARDS mice upregulated glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression and downregulated ß-Catenin and VE-cadherin expression in lung tissues. CONCLUSIONS: Collectively, these data demonstrate that circulating exosomes from LPS-induced ARDS mice trigger ER stress in lung tissue, facilitating the development of ARDS, at least partly by promoting endothelial dysfunction.

NAF1 rs4691896 Is Significantly Associated with Coal Workers' Pneumoconiosis in a Chinese Han Population: A Case-Control Study.

BACKGROUND Previous studies have demonstrated the important role of genetic predisposition in coal workers' pneumoconiosis (CWP) in addition to environmental factors. The pathogenesis of pulmonary fibrosis disease is related to telomere activity. We performed this study to assess the association between genetic variants of telomere-related genes and the risk of CWP. MATERIAL AND METHODS We enrolled 652 CWP Chinese Han patients and 648 dust-exposed controls in this case-control design study, genotyping 8 single-nucleotide polymorphisms (SNPs) including TERT (rs2736100), TERC (rs10936599 and rs12696304), and NAF1 (rs7675998, rs3822304, rs12331717, rs936562 and rs4691896) using the Sequenom MassARRAY system. RESULTS We identified a significant allele association between NAF1 rs4691896 and CWP by comparing patients with controls (22.0% vs. 13.0%, odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.54-2.33, Pc=1.14×10⁻8). The genotype frequency of rs4691896 differed significantly between the patients and controls (Pc=1.49×10⁻8). In addition, rs4691896 was correlated with CWP in an additive genetic model (OR: 1.96, 95% CI: 1.58-2.44, Pc=8.96×10⁻9) and a dominant model (OR: 2.15, 95% CI: 1.70-2.73, Pc=2.39×10⁻9). CONCLUSIONS Our study for the first time demonstrates an association between a telomere-related gene (NAF1) and CWP in a Chinese Han population, and provides valuable insight to further understand the possible pathogenetic mechanism of fibrosis in CWP.

Analysis of myositis autoantibodies in Chinese patients with cancer-associated myositis.

BACKGROUND: Cancer-associated myositis (CAM) has poor prognosis and causes higher mortality. In general, myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) have been shown to be useful biomarkers for its diagnosis. METHODS: In the present study, focus was given in assessing the presence, prevalence, and diagnostic values of myositis autoantibodies in Chinese patients diagnosed with CAM. The sera collected from 49 CAM patients, 108 dermatomyositis/polymyositis (DM/PM) patients without cancer, 105 disease controls, and 60 healthy controls were detected for the presence of 16 autoantigens (Jo-1, OJ, EJ, PL-7, PL-12, MDA5, TIF1γ, Mi-2α, Mi-2ß, SAE1, NXP2, SRP, Ku, PM-Scl75, PM-Scl100, and Ro-52) using a commercial Euroline assay. RESULTS: The frequency of anti-TIF1γ was significantly higher in CAM patients than in DM/PM patients without cancer (46.9% vs 14.8%, P < .001). Importantly, the sensitivity and specificity for this MSA were 46.9% and 85.2%, respectively. These helped to differentiate CAM patients from DM/PM patients without cancer. However, there was no difference in other MSAs and MAAs between CAM and DM/PM patients without cancer. CONCLUSION: The present study indicates that anti-TIF1γ levels can serve as important biomarkers for CAM diagnosis and help in distinguishing between CAM and DM/PM patients without cancer.