Comparison of two methods for CT-guided pulmonary nodule location before thoracoscopic surgery.

Introduction: Preoperative computed tomography (CT)-guided localization can shorten the time of video-assisted thoracoscopic surgery (VATS) and accurately aid in pulmonary nodule removal. Aim: To discuss the application value and safety of 2 kinds of breast localization needles and anchor localization needles in clinical practice for pulmonary nodules under CT guidance before VATS. Material and methods: We retrospectively studied 215 patients with 247 pulmonary nodules, who underwent CT-guided pulmonary nodule location before VATS. The 2 kinds of localization needles were randomly used, and we collected and analysed the clinical data. Results: We used breast and anchor localization needles in 27.9% and 72.1% of cases, respectively. Differences were observed in puncture localization time, detachment rate, and visual analogue scale (VAS). The detachment rate (0%) and positioning time (median: 12 min) were less in the anchor than in the breast localization needle group (8.7% and median: 13 min, respectively). The median VAS was approximately 2 and 5 in the anchor and breast localization needle groups, respectively. Surgical pathology revealed that 155 (62.8%) pulmonary nodules were malignant while 92 (37.2%) were benign. The primary distinction in surgical procedures is the higher proportion of segmental resections in the middle and inner band group (19.3%) compared to the periphery band group (4.2%). Conclusions: Unlike breast localization needles, anchor localization needles can reduce pain and discomfort after positioning, and they are not easy to decouple. These 2 needles are safe for CT-guided localization, which can shorten the time of VATS and accurately aid in pulmonary nodule removal.

Biomarkers of interstitial lung disease associated with primary Sjögren's syndrome.

OBJECTIVES: The aim of this study was to investigate serum biomarkers linked to primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD). METHODS: 69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs). RESULTS: Among consecutively enrolled patients with pSS, the presence of pSS-ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS-ILD group (ILA 2 + ILA 3) than in the pSS-no-ILD and pSS-indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p < 0.05 for all variables). A binary logistic regression model revealed that disease duration and KL-6 levels were associated with the presence of pSS-ILD (p < 0.05). Complementary least absolute shrinkage and selection operator (LASSO) modeling showed that age, KL-6, and TNF-α effectively differentiated pSS-ILD (ILA 2 + ILA3) from pSS without ILD (ILA 0 + ILA 1), with an area under the curve (AUC) of 0.883 (p value < 0.0001). CONCLUSIONS: Patient age, disease duration, and serum levels of both KL-6 and TNFα were the most discriminating factors associated with the presence of ILD in our pSS patients. Higher levels of CRP, IgM, eotaxin, TGFα, and TNFα should also prompt the search for occult as well as clinically evident lung involvement based on statistically significant univariate associations with pSS-ILD. CLINICAL TRIAL REGISTRATION: None.

Serum MUC5AC protein levels are correlated with the development and severity of connective tissue disease-associated pulmonary interstitial lesions.

Background: Mucin 5AC (MUC5AC) and mucin 5B (MUC5B) are the major components of airway mucins. The expression levels of MUC5AC and MUC5B are related to connective tissue disease-associated interstitial lung disease (CTD-ILD) in the promoter region of MUC5AC and MUC5B and the relevant bronchoalveolar lavage fluid. However, the serum protein levels of MUC5AC and MUC5B have not been tested in CTD-ILD patients. In this study, we tested the serum levels of MUC5AC and MUC5B proteins in CTD-ILD patients and assessed their relationship with the occurrence and development of ILD. Methods: Serum samples were obtained from 168 CTD and 80 healthy participants from the First Affiliated Hospital of Xiamen University. The serum levels of MUC5AC and MUC5B proteins were measured by enzyme-linked immunosorbent assay. Results: Of the 168 individuals with CTD, 70 had primary Sjögren's syndrome (pSS), 64 had systemic sclerosis (SSc), and 34 had polymyositis/dermatomyositis (PM/DM). There were 116 cases with concurrent ILD; ILD scores were 1 (n=23), 2 (n=41), and 3 (n=52). Serum MUC5AC and MUC5B protein levels were considerably higher in CTD-ILD than CTD-only individuals or healthy controls (both p<0.005). Among the CTD subgroups, MUC5AC was higher in individuals with concurrent ILD than in those without ILD (all p<0.05). MUC5AC was positively correlated with ILD severity in all three CTD subgroups (all R>0.47 and all p<0.05). The MUC5B levels varied substantially between SSc and SSc patients with concurrent ILD (p=0.032) and were related to ILD severity only in PM/DM patients (R=0.346 and p=0.045). Conclusion: MUC5AC is correlated with the occurrence and development of ILD, while MUC5B is associated with ILD diagnosis and severity in CTD subgroups. Serum MUC5AC levels present a definite diagnostic utility for CTD-ILD and as proxies for its severity.

The serum uric acid is longitudinally related to patients global assessment of disease activity in male patients with axial spondyloarthritis.

OBJECTIVES: To investigate longitudinal relationship between serum uric acid (SUA) and disease activity among Chinese males with axial spondyloarthritis (axSpA). METHODS: Two-year data from the NASA study cohort of male patients with axial spondyloarthritis were analyzed. Patients global assessment of disease activity (PtGA), BASDAI, ASDAS-CRP, BASFI, and SF-36 were used as the outcomes. The autoregressive Generalized Estimation Equation (GEE) model was used to investigate the longitudinal relationship between SUA and the above outcomes. Age and gender and symptom duration were tested as effect modifiers or confounders. RESULTS: In total, 102 male axSpA patients were included, 33.3% of who were hyperuricemia at baseline. Over time,serum uric acid levels associated with the global assessment of patient global assessment of disease activity (PtGA)[P=0.041, ß=-2.059,95%CI(-4.032, -0.086)], SF-36: Vitality (VT) [P=0.01, ß=1.751, 95%CI (0.415,3.087)], SF-36: Social Functioning (SF)[P=0.002, ß= 2.968,95%CI (1.067,4.869)]). And these relationgships were independent of age, symptom duration, baseline uric acid levels, and medication use. CONCLUSIONS: In summary, SUA levels is longitudinally related to PtGA and mental health assessment. Age, gender and symptom duration do not have an impact on the relationships.

Use of Computed Tomography-Guided Percutaneous Biopsy of Invasive Non-Mucinous Lung Adenocarcinoma to Predict the Degree of Histological Differentiation.

Background: The International Association for the Study of Lung Cancer (IASLC) published a grading system for invasive pulmonary adenocarcinoma that is closely associated with prognosis. This study aimed to investigate the accuracy of computed tomography (CT)-guided biopsy specimen grading and surgery-guided grading systems for detecting invasive non-mucinous lung adenocarcinoma and to determine whether CT-guided biopsy can predict the degree of histological differentiation. Methods: In total, 130 patients with invasive non-mucinous lung adenocarcinoma who underwent CT-guided biopsy before surgical excision were retrospectively studied. Biopsy and surgical specimen pathologies were compared. Grading was performed according to different subtypes proposed by the International Association for the Study of Lung Cancer. Sensitivity, specificity, positive and negative predictive values (PPV/NPV), and accuracy were calculated for each subtype and grade. Results: The concordance rates of biopsy and surgical pathology subtypes and grades were 73.1% and 72.3%, respectively. Sensitivity, specificity, PPV, NPV, and accuracy of grade 3 were 54.8%, 100%, 100%, 87.6%, and 89.2%, respectively. Pathology grades were primarily discrepant with respect to two aspects of biopsy and surgical samples in the same patient. First, the biopsy and surgical specimen pathology findings indicated lepidic and acinar subtypes as the main subtypes in the same patient, respectively. Second, biopsy specimen histology did not find solid types; however, >20% of solid subtypes were identified in surgical pathology samples in the same patient. Conclusions: The preoperative CT-guided biopsy specimen grading system showed relatively high accuracy and could predict the prognosis of invasive non-mucinous lung adenocarcinoma.

Predictors of long-term prognosis in rheumatoid arthritis-related interstitial lung disease.

The aim of the study was to identify specific clinical and serum protein biomarkers that are associated with longitudinal outcome of RA-associated interstitial lung disease (RA-ILD). 60 RA patients with clinical and serological profiles were assessed by HRCT and pulmonary function tests (PFTs) at baseline (Year 0) and 5 years post enrollment (Year 5). Progression versus non-progression was defined based on changes in Quantitative Modified HRCT scores and PFTs over time. Specific serum protein biomarkers were assessed in serum samples at baseline and Year 5 by Multiplex enzyme-linked immunosorbent assays (ELISAs). At Year 5, 32% of patients demonstrated progressive RA-ILD, 35% were stable, and 33% improved. Baseline age and rheumatoid factor (RF) were significantly different between RA-ILD outcomes of progression vs. no-progression (p < 0.05). Changes in levels of CXCL11/I-TAC and MMP13 over 5 years also distinguished pulmonary outcomes (p < 0.05). A final binary logistic regression model revealed that baseline age and changes in serum MMP13 as well as CXCL11/I-TAC were associated with RA-ILD progression at Year 5 (p < 0.01), with an AUC of 0.7772. Collectively, these analyses demonstrated that baseline clinical variables (age, RF) and shifts in levels of selected serum proteins (CXCL11/I-TAC, MMP13) were strongly linked to RA-ILD outcome over time.

A Dual-Dimer method for training physics-constrained neural networks with minimax architecture.

Data sparsity is a common issue to train machine learning tools such as neural networks for engineering and scientific applications, where experiments and simulations are expensive. Recently physics-constrained neural networks (PCNNs) were developed to reduce the required amount of training data. However, the weights of different losses from data and physical constraints are adjusted empirically in PCNNs. In this paper, a new physics-constrained neural network with the minimax architecture (PCNN-MM) is proposed so that the weights of different losses can be adjusted systematically. The training of the PCNN-MM is searching the high-order saddle points of the objective function. A novel saddle point search algorithm called Dual-Dimer method is developed. It is demonstrated that the Dual-Dimer method is computationally more efficient than the gradient descent ascent method for nonconvex-nonconcave functions and provides additional eigenvalue information to verify search results. A heat transfer example also shows that the convergence of PCNN-MMs is faster than that of traditional PCNNs.

Autoreactive T cells to citrullinated HSP90 are associated with interstitial lung disease in rheumatoid arthritis.

AIM: Previous analysis of comparative anti-citrullinated heat shock protein 90 (citHSP90) antibody profiles between bronchoalveolar lavage fluid and serum indicates that the lung plays a direct role in shaping the immune repertoire of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: To address the contribution of citHSP90ß-specific T cells in this process, we evaluated in vitro cytokine responses to citHSP90ß in RA patients with different stages of ILD as well as in controls with non-RA connective tissue disease-associated ILD (CTD-ILD). Cultures derived from whole blood were individually stimulated with HSP90ß, citHSP90ß, citrullinated BSA, or no antigen. The concentrations of 13 cytokines and chemokines in the plasma supernatant were then measured using Luminex xMAP technology. RESULTS: CitHSP90ß induced significantly higher levels of interferon-γ (IFN-γ) levels in RA-ILD (interstitial lung abnormalities = 2 + 3) groups compared to the RA-no ILD group (P = 0.01), but did not stimulate the production of other cytokines (P > 0.05). Furthermore, citHSP90ß did not stimulate the production of IFN-γ or other cytokines in those individuals with non-RA CTD-ILD. CONCLUSION: Overall, the production of IFN-γ by T cells stimulated with citHSP90ß demonstrates a bias toward TH1 immune responses that are likely involved in the pathogenesis of RA-ILD.

[Value of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Evaluating Diffuse Tumor Infiltration of Bone Marrow in Patients with Acute Leukemia].

OBJECTIVE: To analyze the value of dynamic contrast-enhanced magnetic resonance imaging (CEMRI) for evaluating diffuse tumor infiltration of bone marrow in patients with acute leukemia (AL). METHODS: From January 2010 to February 2016, 80 AL patients admitted in our hospital were chosen as AL patient group, 100 healthy people were chosen as control group, and all subjects were diagnosed with MRI and CEMRI. The Emax and Slope of ilium and vertebra lumbalis were compared between AI patient and control groups. The relation of Emax and Slope with protocells % was analyzed. RESULTS: The Emax and Slope of AL patients were significantly higher than those of control group (P<0.05). After treatment, the Emax and Slope of CR/PR patients decreased significantly (P<0.05). Multiple regression analysis showed that the protocells %=-0.5632+0.0540 Emax+0.0056 Slope. The Emax and Slope of AL patients had significant correlation with Protocells %(P<0.05). CONCLUSION: The results of CEMRI relate with pathological examination and treatment effect.

CIP2A mediates prostate cancer progression via the c-Myc signaling pathway.

Recent evidence suggests that cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a novel therapeutic target in a variety of tumors. In this study, we investigated the clinical significance of CIP2A and its function in our large collection of prostate samples. Between August 2000 and December 2013, 126 patients with histologically confirmed prostate cancer (PCa) and 92 with benign prostate hyperplasia (BPH) were recruited into the study. Quantitative real-time PCR (RT-PCR), Western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in PCa clinical samples and cell lines. The relationships between CIP2A expression and clinicopathological features were analyzed. The functional role of CIP2A in PCa cells was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and invasion. High expression of CIP2A staining was 86.51 % (109/126) in 126 cases of PCa and 17.39 % (16/92) in 92 cases of BPH; the difference of CIP2A expression between PCa and BPH was statistically significant. CIP2A was significantly elevated in all five PCa cell lines when compared to the RWPE-1 cells at both the messenger RNA (mRNA) and protein levels. Silencing of CIP2A inhibited the proliferation of DU-145 cells which have a relatively high level of CIP2A in a time- and concentration-dependent manner, and the invasion and migration of DU-145 cells were distinctly suppressed. Furthermore, CIP2A knockdown led to substantial reductions in c-Myc levels in DU-145 cells, but no significant change in phosphorylated Akt expression after CIP2A knockdown in DU-145 cells. Our data suggest that the pathogenesis of human PCa maybe mediated by CIP2A, and CIP2A inhibition treatment may provide a promising strategy for the antitumor therapy of PCa, and thus, CIP2A could represent selective targets for the molecularly targeted treatments of PCa.

CIP2A mediates prostate cancer progression via the c-MYC signaling pathway.

Recent evidence suggests that cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a novel therapeutic target in a variety of tumors. In this study, we investigated the clinical significance of CIP2A and its function in our large collection of prostate samples. Between August 2000 and December 2013, 126 patients with histologically confirmed PCa and 92 with benign prostate hyperplasia (BPH) were recruited into the study. Quantitative RT-PCR, Western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in PCa clinical samples and cell lines. The relationships between CIP2A expression and clinicopathological features were analyzed. The functional role of CIP2A in PCa cells was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and invasion. High expression of CIP2A staining was 86.51 % (109/126) in 126 cases of PCa and 17.39 % (16/92) in 92 cases of BPH, and the difference of CIP2A expression between PCa and BPH was statistically significant. CIP2A was significantly elevated in all five PCa cell lines when compared to the RWPE-1 cells at both the messenger RNA (mRNA) and protein levels. Silencing of CIP2A inhibited the proliferation of DU-145 cells which have a relatively high level of CIP2A in a time- and concentration-dependent manner, and the invasion and migration of DU-145 cells were distinctly suppressed. Furthermore, CIP2A knockdown led to substantial reductions in c-Myc levels in PCa cell lines, but no significant change in phosphorylated Akt expression after CIP2A knockdown in DU-145 cells. Our data suggest that the pathogenesis of human PCa maybe mediated by CIP2A, and CIP2A inhibition treatment may provide a promising strategy for the antitumor therapy of PCa, and thus CIP2A could represent selective targets for the molecularly targeted treatments of PCa.