Long-read sequencing unveils novel somatic variants and methylation patterns in the genetic information system of early lung cancer.

Lung cancer poses a global health challenge, necessitating advanced diagnostics for improved outcomes. Intensive efforts are ongoing to pinpoint early detection biomarkers, such as genomic variations and DNA methylation, to elevate diagnostic precision. We conducted long-read sequencing on cancerous and adjacent non-cancerous tissues from a patient with lung adenocarcinoma. We identified somatic structural variations (SVs) specific to lung cancer by integrating data from various SV calling methods and differentially methylated regions (DMRs) that were distinct between these two tissue samples, revealing a unique methylation pattern associated with lung cancer. This study discovered over 40,000 somatic SVs and over 180,000 DMRs linked to lung cancer. We identified approximately 700 genes of significant relevance through comprehensive analysis, including genes intricately associated with many lung cancers, such as NOTCH1, SMOC2, CSMD2, and others. Furthermore, we observed that somatic SVs and DMRs were substantially enriched in several pathways, such as axon guidance signaling pathways, which suggests a comprehensive multi-omics impact on lung cancer progression across various biological investigation levels. These datasets can potentially serve as biomarkers for early lung cancer detection and may hold significant value in clinical diagnosis and treatment applications.

Abhd2, a Candidate Gene Regulating Airway Remodeling in COPD via TGF-ß.

Purpose: The typical characteristic of COPD is airway remodeling, affected by environmental and genetic factors. However, genetic studies on COPD have been limited. Currently, the Abhd2 gene is found to play a critical role in maintaining alveolar architecture and stability. The research aims to investigate the predictive value of Abhd2 for airway remodeling in COPD and its effect on TGF-ß regulation. Methods: In humans, Abhd2 protein was obtained from peripheral blood monocytes. Peripheral blood TGF-ß, pulmonary surfactant proteins (SPs), metalloproteinases, inflammatory indicators (WBC, NEU, NLR, EOS, CRP, PCT, D-Dimer), chest CT (airway diameter and airway wall thickness), pulmonary function, and blood gas analysis were used to assess airway remodeling. In animals, Abhd2 deficient mice (Abhd2Gt/Gt) using gene trapping and C57BL6 mice were injected intraperitoneally with CSE to construct COPD models. HE staining, Masson staining and immunohistochemistry were used to observe the pathological changes of airway in mice, and RT-PCR, WB, ELISA and immunofluorescence were used to detect the expression of secreted proteins and EMT markers. Results: COPD patients with worse pulmonary function and higher airway remodeling-related inflammatory factors had lower Abhd2 protein expression. Moreover, indicators followed the same trend for COPD patients grouped by prognosis (Group A vs Group B). Serum TGF-ß was negatively correlated with Abhd2 protein expression, FEV1/FVC, FEV1, and FEV1% PRED. In mice, Abhd2 depletion promoted deposition of TGF-ß, leading to more pronounced emphysema, airway thickening, increased alveolar macrophage infiltration, decreased AECII number and SPs, and EMT phenomenon. Conclusion: Downregulation of Abhd2 can promote airway remodeling in COPD by modulating repair after injury and EMT via TGF-ß. This study suggests that Abhd2 may serve as a biomarker for assessing airway remodeling and guiding prognosis in COPD.

Rational design of a near-infrared dual-emission fluorescent probe for ratiometric imaging of glutathione in cells.

Sensors for which the output signal is an intensity change for a single-emission peak are easily disturbed by many factors, such as the stability of the instrument, intensity of the excitation light, and biological background. However, for ratiometric fluorescence sensors, the output signal is a change in the intensity ratio of two or more emission peaks. The fluorescence intensity of these emission peaks is similarly affected by external factors; thus, these sensors have the ability to self-correct, which can greatly improve the accuracy and reliability of the detection results. To accurately image glutathione (GSH) in cells, gold nanoclusters (AuNCs) with intrinsic double emission at wavelengths of 606 nm and 794 nm were synthesized from chloroauric acid. With the emission peak at 606 nm as the recognition signal and the emission peak at 794 nm as the reference signal, a near-infrared dual-emission ratio fluorescence sensing platform was constructed to accurately detect changes in the GSH concentration in cells. In vitro and in vivo analyses showed that the ratiometric fluorescent probe specifically detects GSH and enables ultrasensitive imaging, providing a new platform for the accurate detection of active small molecules.

Magnetic resonance imaging for evaluation of bowel inflammation and disease activity in Crohn's disease: A systematic review and meta-analysis / Imágenes por resonancia magnética para la evaluación de la inflamación intestinal y la actividad de la enfermedad en la enfermedad de Crohn: una revisión sistemática y un metaanálisis

Background: The aim of this systematic review and meta-analysis was to determine the performance of magnetic resonance imaging (MRI) in the diagnosis of bowel inflammation and disease activity in Crohn's disease (CD). Methods: MEDLINE, Embase and Web of Science databases of biomedical literature were systematically searched to identify studies that investigated the diagnostic accuracy of MRI in diagnosing bowel inflammation and disease activity in CD by comparing it with reference standards. Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality. The summary sensitivity and specificity were estimated using the bivariate model, and hierarchical summary receiver operating characteristic (HSROC) parameters were calculated and plotted. Results: Of 5492 citations of interest, 34 articles contained the diagnostic accuracy data. Of these, results for the small bowel and the colorectum were reported separately in 19 studies and jointly by 21 studies. The meta-analytic summary sensitivity and specificity under the bivariate model were 90.9% (95% CI, 85.8%–94.2%) and 90.2% (95% CI, 81.9%–95.0%), respectively. The sensitivities and specificities of individual studies ranged from 55% to 100% and 51% to 100%, respectively. Substantial heterogeneity was observed in both sensitivity (I2=84.9%) and specificity (I2=78.8%). The HSROC curve also showed considerable heterogeneity between studies. Conclusion: Although the meta-analytic summary accuracy of MRI was high for the diagnosis of bowel inflammation in CD, the summary estimates might be unreliable due to the presence of high heterogeneity.(AU)

Antecedentes: El objetivo de esta revisión sistemática y metaanálisis fue determinar el rendimiento de la resonancia magnética nuclear (RM) en el diagnóstico de la inflamación intestinal y la actividad de la enfermedad en la enfermedad de Crohn (EC). Métodos: Se realizaron búsquedas sistemáticas en las bases de datos de literatura biomédica de MEDLINE, Embase y Web of Science para identificar estudios que investigaran la precisión diagnóstica de la RM en el diagnóstico de la inflamación intestinal y la actividad de la enfermedad en la EC comparándola con estándares de referencia. Evaluación de la calidad de los estudios de precisión diagnóstica: se utilizó la herramienta 2 para evaluar la calidad del estudio. La sensibilidad y la especificidad resumidas se estimaron mediante el modelo bivariado, y se calcularon y trazaron los parámetros de características operativas del receptor resumidas jerárquicas (HSROC). Resultados: De 5.492 citas de interés, 34 artículos contenían datos de precisión diagnóstica. De estos, los resultados para el intestino delgado y el colorrectal se informaron por separado en 19 estudios y en forma conjunta en 21 estudios. La sensibilidad y la especificidad del resumen metanalítico bajo el modelo bivariado fueron del 90,9% (IC del 95%, 85,8%-94,2%) y el 90,2% (IC del 95%, 81,9%-95,0%), respectivamente. Las sensibilidades y especificidades de los estudios individuales variaron del 55 al 100% y del 51 al 100%, respectivamente. Se observó heterogeneidad sustancial tanto en la sensibilidad (I2=84,9%) como en la especificidad (I2=78,8%). La curva HSROC también mostró una considerable heterogeneidad entre los estudios. Conclusión: Aunque la precisión del resumen metaanalítico de la RM fue alta para el diagnóstico de inflamación intestinal en la EC, las estimaciones del resumen pueden no ser confiables debido a la presencia de una gran heterogeneidad.(AU)

Magnetic resonance imaging for evaluation of bowel inflammation and disease activity in Crohn's disease: A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to determine the performance of magnetic resonance imaging (MRI) in the diagnosis of bowel inflammation and disease activity in Crohn's disease (CD). METHODS: MEDLINE, Embase and Web of Science databases of biomedical literature were systematically searched to identify studies that investigated the diagnostic accuracy of MRI in diagnosing bowel inflammation and disease activity in CD by comparing it with reference standards. Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality. The summary sensitivity and specificity were estimated using the bivariate model, and hierarchical summary receiver operating characteristic (HSROC) parameters were calculated and plotted. RESULTS: Of 5492 citations of interest, 34 articles contained the diagnostic accuracy data. Of these, results for the small bowel and the colorectum were reported separately in 19 studies and jointly by 21 studies. The meta-analytic summary sensitivity and specificity under the bivariate model were 90.9% (95% CI, 85.8%-94.2%) and 90.2% (95% CI, 81.9%-95.0%), respectively. The sensitivities and specificities of individual studies ranged from 55% to 100% and 51% to 100%, respectively. Substantial heterogeneity was observed in both sensitivity (I2=84.9%) and specificity (I2=78.8%). The HSROC curve also showed considerable heterogeneity between studies. CONCLUSION: Although the meta-analytic summary accuracy of MRI was high for the diagnosis of bowel inflammation in CD, the summary estimates might be unreliable due to the presence of high heterogeneity.

Hyperpolarized 3 helium MRI measured apparent diffusion coefficient and its correlations with pulmonary functions tests in patients with chronic obstructive pulmonary disease: A meta-analysis.

BACKGROUND: This study evaluates role of hyperpolarized 3 helium (3 He) MRI measured apparent diffusion coefficient (ADC) in examining pulmonary function of chronic obstructive pulmonary disease (COPD) patients. METHODS: After literature search in electronic databases, studies were selected by following precise eligibility criteria. Meta-analyses were performed to estimate mean difference in ADC between COPD patients and healthy individuals and to seek correlations between lung ADC and pulmonary function. Metaregression analyses were performed to seek relationships between ADC and age, gender, BMI, cigarette pack-years, and pulmonary function tests. RESULTS: Twenty-five studies (622 COPD patients and 469 healthy controls) were included. Lung ADC was 0.402 (95% confidence interval [CI]: 0.374, 0.429) in COPD patients and 0.228 (95% CI: 0.205, 0.252) in healthy individuals (mean difference 0.160 [95% CI: 0.127, 0.193]; p < 0.001). In metaregression, age (coefficient: 0.006; p = 0.004), pack-years (coefficient: 0.005; p = 0.018), forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio (coefficient: -1.815; p = 0.007), percent predicted diffusion capacity of carbon monoxide (DLCO) (coefficient: -0.004; p = 0.008), and percent predicted inspiratory capacity (coefficient: -0.004; p = 0.012) were significantly associated with ADC in COPD patients. In meta-analysis of correlation coefficients, ADC was significantly correlated with FEV1 (r = -0.62; p < 0.00001), FEV1/FVC (r = -0.80; p < 0.00001), DLCO (r = -0.85; p < 0.00001), functional residual capacity (r = 0.71; p < 0.00001), reserve volume (r = 0.53; p = 0.0001), and emphysema index (r = 0.89; p < 0.00001). CONCLUSION: Hyperpolarized 3 He MRI measured ADC was higher in COPD patients than in healthy individuals and was inversely associated with FEV1, FEV1/FVC, DLCO, and inspiratory capacity.

miR129-1 regulates protein phosphatase 1D protein expression under hypoxic conditions in non-small cell lung cancer cells harboring a TP53 mutation.

Protein phosphatase 1D (PPM1D), which functions as an oncogene, is a known target of the tumor suppressor p53 and is involved in p53-regulated genomic surveillance mechanisms. PPM1D dephosphorylates both p53 and its ubiquitin ligase mouse double minute 2 homolog, as well as the RNA-binding protein (RBM)38, which turns RBM38 from an inducer to inhibitor of TP53 translation. In addition, RBM38 induces PPM1D translation. Hence, the PPM1D-RBM38-p53 axis is important in maintaining genomic integrity and is often altered during tumorigenesis. TP53, which encodes p53, is deleted or mutated in >50% of cancer types, including lung cancer. Mutant p53 has been revealed to complex with hypoxia-inducible factor 1α (HIF1α) and upregulate transcription of pro-metastatic genes. However, the mechanism underlying the action of the PPM1D-RBM38-p53 axis in the context of mutant p53 under normoxic and hypoxic conditions is yet to be elucidated. In the present study, using non-small cell lung cancer (NSCLC) cell lines harboring wild-type (A549 cells) or hot-spot mutant (NCI-H1770 and R249WΔ-TP53-A549 cells) TP53, it was demonstrated that in cells harboring mutant p53, RBM38 was not the primary regulator of PPM1D translation under hypoxic conditions. Knockdown of RBM38 in TP53 mutant cells did not affect the PPM1D protein expression under hypoxic conditions. Instead, in NCI-H1770 cells maintained under normoxic conditions, PPM1D was revealed as a target of micro RNA (miR)-129-1-3p, a known tumor suppressor in lung cancer. Hypoxia resulted in the downregulation of miR-129-1-3p expression, and thus, in the downregulation of PPM1D messenger RNA (mRNA) translation. In NCI-H1770 cells grown under hypoxic conditions, the transient transfection of miR-129-1-3p mimic, and not control mimic, repressed the expression of a reporter containing wild-type, but not miR-129-1-3p binding mutant, of the PPM1D 3'-untranslated region (UTR). Analysis of NSCLC cell lines from the Broad Institute Cancer Cell Encyclopedia and patients with NSCLC from The Cancer Genome Atlas dataset revealed significant co-occurrence of PPM1D/RBM38 and PPM1D/HIF1A mutations. However, there was no significant difference in the overall survival of patients with NSCLC with or without genomic alterations in TP53, RBM38, PPM1D and HIF1A. In summary, the current study demonstrated hypoxia-dependent miR-129-1-3p-mediated regulation of PPM1D protein expression in NSCLC cell line harboring mutant TP53.

RBM38 induces SIRT1 expression during hypoxia in non-small cell lung cancer cells by suppressing MIR34A expression.

OBJECTIVE: The study is to research how miR-34-SIRT1 is regulated during hypoxia in lung cancer cells. RESULTS: Analysis of publicly available datasets from patients with NSCLC did not reveal significant genomic alterations in RBM38, SIRT1, HIF1A, MIR34A, MIR34B, and MIR34C, but expectedly revealed alterations in TP53. Overall survival in NSCLC patients with or without alterations in these genes was not significantly different. When expanded to include all lung cancer patients, overall survival was significantly lower in patients with genomic alterations in these genes. CONCLUSIONS: Cumulatively, our results reveal a novel mechanism of RBM38-mediated regulation of the HIF1A/miR-34a/SIRT1/p53 axis under hypoxia in NSCLC cells.

Mechanism and morphology control of underwater femtosecond laser microgrooving of silicon carbide ceramics.

Silicon carbide (SiC) ceramics have been widely used for microelectronics, aerospace, and other industrial fields due to their excellent chemical stability and thermal tolerance. However, hard machinability and low machining precision of SiC ceramics are the key limitations for their further applications. To address this issue, a novel method of underwater femtosecond laser machining was introduced in this study to obtain high precision and smooth surface of the microgrooves of SiC ceramics. The removal profiles were characterized in terms of width, depth, and surface morphology, which exhibited high dependence on the femtosecond laser processing parameters. The instability during the underwater processing affected by laser-induced gas bubbles and material deposition, however, limits the high surface accuracy of microgrooves and processing efficiency. The process condition transformation from a bubble-disturbed circumstance to a disturbance-free model was carefully investigated through a high speed camera for the femtosecond laser processing of SiC ceramics in water. The experiment results indicated that degree of disturbed effect was heavily dependent on size, distribution, and motion of laser-induced gas bubble. Furthermore, some typical evolution mechanisms of gas bubble and their influence on the removal profiles of microgrooves were discussed in detail. Bubble evolution has been proven to be mainly responsible for the behavior of laser propagation (focus model, total reflection, etc.), which notably affects microstructural characteristic of the microgrooves.

Prevalence of comorbidities in chronic obstructive pulmonary disease patients: A meta-analysis.

BACKGROUND: This study compares the prevalence rates of comorbidities between chronic obstructive pulmonary disease (COPD) and non-COPD control patients reported in literature. METHOD: Literature was searched in several electronic databases. After the selection of studies by following précised eligibility criteria, meta-analyses of odds ratios (ORs) were carried out with subgroup and sensitivity analyses under random effects model. RESULTS: Eleven studies (47,695,183 COPD and 47,924,876 non-COPD control patients' data) were used for meta-analysis. Average age of COPD patients was 66.66 ±â€Š8.72 years of whom 55.4 ±â€Š11.9% were males. The prevalence of cardiovascular comorbidities [OR 1.90, 95% confidence interval (95% CI) 1.59-2.28; P < .00001], cerebrovascular comorbidities (OR 1.84, 95% CI 1.47-2.31; P < .00001), hypertension (OR 1.45, 95% CI 1.31-1.61; P < .00001), diabetes mellitus (OR 1.22, 95% CI 1.07-1.38; P = .003), neurological and psychiatric disorders (OR 1.78, 95% CI 1.48-2.14; P < .00001), gut and renal disorders (OR 1.96, 95% CI 1.43-2.68; P < .00001), musculoskeletal disorders (OR 1.51, 95% CI 1.27-1.78; P < .00001), non-COPD respiratory comorbidities (OR 2.81, 95% CI 2.52-3.14; P < .00001), and cancer (OR 1.67, 95% CI 1.25-2.23; P = .0005) were significantly higher in COPD patients than in non-COPD controls. CONCLUSION: COPD is associated with significantly higher comorbidities than in other diseases that should be taken into consideration in COPD control strategies.

Serum apoprotein A1 levels are inversely associated with disease activity in gout: From a southern Chinese Han population.

To analyze the alteration of lipid profile and inflammatory markers in the serum of patients with gouty arthritis (GA), the levels of serum lipid profile, C-reactive protein (CRP), and erythrocyte sedimentation rates (ESRs) were measured in the serum of 69 gout patients, 35 patients with rheumatoid arthritis (RA), 23 patients with ankylosing spondylitis (AS)/spondyloarthropathy (SpA), and 25 patients with osteoarthritis (OA). The serum levels of apoprotein A1 (Apo-A1) were significantly decreased in patients with gout when compared with RA, AS/SpA, and OA patients. The serum levels of CRP were significantly increased in gouty patients when compared with RA, AS/SpA, and OA patients. Furthermore, the serum levels of ESR were significantly increased in patients with gout compared to patients with OA. Correlation analysis indicated that the levels of Apo-A1 were negatively correlated with serum ESR and CRP (r = -0.475, P < .001; r = -0.380, P = .001, respectively) in the patients with GA. Taken together, this study gives us a better understanding of the relationships between serum lipid profile and inflammatory markers in gout patients.

Autoantibody to MDM2: A potential serological marker of primary Sjogren's syndrome.

INTRODUCTION: Primary Sjogren's Syndrome (pSS) is one of the autoimmune diseases characterized by polyclonal autoantibody production. The human homologue of the mouse double minute 2 (MDM2) is an important negative regulator of p53. Our previous study indicated that autoantibody to MDM2 can be detected in systemic lupus erythematosus patients. The purpose of this study is to study anti-MDM2 autoantibody in pSS patients. METHODS: Anti-MDM2 autoantibody in sera from 100 pSS patients and 74 normal controls was investigated by ELISA. Positive samples were further confirmed by western blotting. Expression of MDM2 in labial gland tissue from pSS patients and normal controls was checked by immunohistochemistry. The difference in clinical characteristics and laboratory findings between anti-MDM2 positive and anti-MDM2 negative pSS patients was analyzed. RESULTS: The presence of anti-MDM2 autoantibody in pSS patients was 21.0%, significantly higher than normal controls (5.40%). MDM2 was overexpressed in labial gland from pSS patients. pSS patients with positive anti-MDM2 were characterized by longer disease duration and more lymphocytes focal gathering in labial gland. Prevalence of anemia, thrombocytopenia and anti-SSB was significantly higher in pSS patients with anti-MDM2 autoantibody. Titer of anit-MDM2 was negatively associated with hemoglobin level, platelet count, complement 3 level and complement 4 level, positively associated with European Sjogren's syndrome disease activity index (ESSDAI) and level of IgG. CONCLUSIONS: Anti-MDM2 autoantibody may be used as a potential serological biomarker in pSS disease activity evaluation. Study on the role of anti-MDM2 or MDM2 in pSS may help us know the pathogenesis mechanism of pSS better.

Clinical characteristics of immune thrombocytopenia associated with autoimmune disease: A retrospective study.

To clarify clinical characteristics of immune thrombocytopenia (ITP) subsets associated with autoimmune diseases (AIDs).Five thousand five hundred twenty patients were reviewed retrospectively. One hundred four ITP patients were included for analysis. Clinical manifestations at first thrombocytopenic episode were recorded.Systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) accounted for a large part in AIDs associated with secondary ITP. SLE-ITP, pSS-ITP, and primary ITP (pITP) patients were different in several aspects in clinical and immunological characteristics. A subgroup of patients in pITP patients with some obvious autoimmune features (defined as AIF-ITP) such as positive ANA but failing to meet the diagnosis criteria now used for a specific kind of connective tissue diseases were also different with other pITP patients in some immunological features, indicating the difference in the pathogenesis mechanism of those autoimmune featured ITP patients.ITP patients were heterogeneous in clinical characteristics. Further study about the different pathogenesis of ITP subsets especially those AIF-ITP patients who only presented with thrombocytopenia will help us have a better understanding of pathogenesis of ITP and a better management of ITP patients.

Potential of IL-33 for Preventing the Kidney Injury via Regulating the Lipid Metabolism in Gout Patients.

Interleukin-33 (IL-33), the most recently discovered member of the IL-1 superfamily, has been linked to several human pathologies including autoimmune diseases, sepsis, and allergy through its specific IL-1 receptor ST2. However, there is little information regarding the role of IL-33 in gout. In this study, we investigated the potential role of IL-33 in gout patients. The serum level of IL-33 was measured by ELISA, and the clinical and laboratory parameters, serum creatinine, urea, and lipid, were extracted from medical record system. The serum IL-33 expression was predominantly increased in gout patients compared to healthy controls, and the IL-33 levels were higher in patients without kidney injury. Furthermore, IL-33 showed a negative correlation with biomarkers of kidney injury, such as CRE and urea. The lipid metabolism dysfunction, tophi, and hypertension are the common reasons for kidney injury in gout. Interestingly, inverse and positive correlation of IL-33 expression was observed in LDL and HDL, respectively. However, there was no significant alteration in the gout patients with hypertension and tophi. These data suggested that IL-33 might act as a protective role in kidney injury through regulating the lipid metabolism in gout.

Association of BAFF and IL-17A with subphenotypes of primary Sjögren's syndrome.

AIM: Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting exocrine glands. Both autoreactive T cells and B cells are involved in the development of pSS, but their exact contribution to the pathogenesis is not clear. Here, we aimed to investigate the association of B-cell activating factor (BAFF) and interleukin (IL)-17A with subphenotypes of pSS. METHODS: Peripheral blood samples were collected from 31 pSS patients and 28 healthy controls. The serum levels of BAFF and IL-17A were quantified by sandwich ELISA. RESULTS: The increased circulating BAFF levels are associated with higher immunoglobulin G (IgG) levels (P = 0.0167) and anti-Ro/SS antigen A autoantibody (P = 0.032), while the elevated circulating levels of IL-17A are associated with lower C3 levels (P = 0.0213) and higher focus score of salivary gland tissue (P = 0.002). CONCLUSION: Our results show that BAFF and IL-17A are associated with different subphenotypes of pSS, suggesting both humoral and cellular immune response are involved in the pathogenesis of pSS.

Biomarkers of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVE: Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication. METHODS: Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA-no ILD, RA-mild ILD, or RA-advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest. RESULTS: MMP-7 and interferon-γ-inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA-no ILD, 41 RA-ILD, 42 RA-indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA-no ILD, 49 RA-ILD, 15 RA-indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses. CONCLUSION: Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication.

Vitamin D deficiency and low bone mineral density in native Chinese rheumatoid arthritis patients.

OBJECTIVE: We aimed to examine the risk factors related to the development of osteoporosis in rheumatoid arthritis (RA) patients and whether there is an association among the changes in bone mineral density (BMD), disease activities (modified DAS28), serum 25-hydroxyvitamin D (25OHD) levels, and disease duration. METHODS: There were 110 patients with RA and 110 age- and sex-matched healthy controls who were concurrently studied. All of the patients underwent the following measurements: erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and serum 25OHD. Dual-energy X-ray absorptiometry (DEXA) was also used to measure the BMD of the left femur at the time of recruitment. Patients taking vitamin D supplement or corticosteroids were excluded. RESULTS: The incidences of osteopenia (45.6% vs. 36.4%, P = 0.170) and osteoporosis (33.6% vs. 5.45%, P = 0.000) were higher in the RA patients than in the healthy controls. There was a significant negative correlation between vitamin D levels and DAS28 (r = -0.325, P = 0.001) and a significant positive correlation between vitamin D levels and BMD (r = 0.422, P = 0.000). The multiple regression analysis revealed that 25OHD levels were significantly correlated with disease activity and BMD (F = 11.087, P = 0.000). Stepwise multiple regression analysis showed that serum 25OHD levels were the significant predictors for low BMD and high disease activity (DAS28) in RA patients. CONCLUSION: The incidences of osteoporosis and osteopenia were higher in RA patients compared to the age- and gender-matched healthy controls. Low serum 25OHD levels correlate with low BMD and high disease activity in RA patients.