Search

Background The bronchiectasis severity index (BSI) and FACED score are currently used in predicting outcomes of non-cystic fibrosis bronchiectasis (NCFB). Distance-saturation product (DSP), the product of distance walked, and lowest oxygen saturation during the 6-min walk test showed strong predictive power of mortality in non-CF bronchiectasis patients. This study aimed to compare the efficacy of these scores and DSP in predicting mortality. Methods and Patients Our retrospective study included NCFB patients from January 2004 to December 2017. We recorded the basic data, pulmonary function, radiologic studies, sputum culture results, acute exacerbations (AE), emergency department (ED) visits, hospitalization, and mortality. Results A total 130 NCFB patients were analysed. The mean BSI score, FACED score, and DSP were 8.8 ± 4.9, 3.4 ± 1.7, and 413.1 ± 101.5 m%, respectively. BSI and FACED scores had comparable predictive power for AE (p=.011; p=.010, respectively). The BSI score demonstrated a significant correlation with ED visits (p=.0003). There were 12 deaths. Patients were stratified using a DSP cut-off value of 345 m% according to the best area under receiver operator characteristic curve (AUC) value in mortality. DSP was not correlated with AE and ED visits. BSI, FACED scores, and DSP demonstrated statistically significant correlations with hospitalization (p

Background and Objectives: Patients who have advanced lung cancer and bone metastasis (BM) often suffer from skeletal-related events (SREs) that lead to poor quality of life and poor prognosis. Our study aimed to investigate the prognostic factors in patients with BM from epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma. Materials and Methods: This retrospective study included 77 lung adenocarcinoma patients with synchronous BM. These patients had first-line EGFR tyrosine kinase inhibitors (EGFR-TKIs) between January 2017 and December 2019. Among them, 42 patients were treated with 120 mg of subcutaneous denosumab monthly. We investigated their baseline characteristics, cancer management, SREs, progression-free survival (PFS), and overall survival (OS). Results: The PFS in the patients treated with or without denosumab were 10.1 vs. 12.5 months (p = 0.971). The median OS was 26.9 vs. 29.5 months (p = 0.967) in no denosumab and denosumab groups, respectively. Univariate analyses showed benefit of afatinib in PFS and good performance status in OS. Conclusion: Those patients that took afatinib as first-line EGFR-TKIs had significantly longer PFS than those treated with other TKIs. Denosumab had no prognostic effect on PFS or OS.

Psychological resilience is regarded as a critical protective factor for preventing the development of mental illness from experienced adverse events. Personal strength is one key element of resilience that reflects an individual&rsquo, s reactions to negative life events and is crucial for successful adaptation. Previous studies have linked unimodal imaging measures with resilience. However, applying multimodal imaging measures could provide comprehensive organization information at the system level to examine whether an individual&rsquo, s resilience strength is reflected in the brain&rsquo, s structural and functional network. In this study, MRI was used to acquire multimodal imaging properties and subscales of personal strength in terms of resilience from 109 participants (48 females and 61 males). We employed a method of fusion independent component analysis to link the association between multimodal imaging components and personal strength of psychological resilience. The results reveal that a fusion component involving multimodal frontal networks in connecting with the parietal, occipital, and temporal regions is associated with the resilience score for personal strength. A multiple regression model further explains the predictive role of frontal-associated regions that cover a visual-related network regulating cognition and emotion to discern the perceived adverse experience. Overall, this study suggests that frontal-associated regions are related to individual resilience strength.

Background The interaction between the pulmonary function and cardiovascular mechanics is a crucial issue, particularly when treating patients with chronic obstructive pulmonary disease (COPD). Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. Methods This is a cross-sectional and preliminary data from a prospective study, which examines 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on the synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by a six-minute walking test (6MWT). Results The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64–0.97), n = 43) and a desynchronized group (median 0.23 (0.02–0.51), n = 12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r = 0.42, p = 0.001) and distance saturation product (r = 0.41, p = 0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis. Conclusion This is the first result studying the heart–lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.

In Uygur medicine, Huganbuzure granule (HBG) is one of the classical prescriptions for liver protection. However, its role in immune liver injury remains unknown. This study evaluates the effect of HBG on concanavalin-A- (ConA-) induced immune liver injury and investigates its protective underlying mechanism. BALB/c mice were randomly divided into five groups (n = 24 mice per group): control, ConA, 1.6 g/kg HBG + ConA, 3.2 g/kg HBG + ConA, and 6 mg/kg prednisolone + ConA. HBG was intragastrically administrated once daily for ten consecutive days, prior to ConA (20 mg/kg) injection. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), superoxide dismutase (SOD), and malondialdehyde (MDA) in mouse serum were measured after ConA injection. Moreover, liver-related mRNA levels were evaluated by qPCR. The detection of liver-related proteins was assessed by immunohistochemistry and western blot analysis. Compared with the ConA group, HBG reduced the mRNA expression of IL-17A and IFN-γ and the protein expression of T-bet and ROR-γt. In addition, HBG increased the mRNA expression of IL-4 and TGF-β and protein expression of GATA3 and Foxp3, indicating that HBG regulated the balance of Th1/Th2 and Th17/Treg. Furthermore, HBG alleviated immune liver injury by reducing oxidative stress, inhibiting apoptosis, and decreasing the expression of p-JNK, p-ERK, p-p38, p-JAK1, p-STAT1, p-STAT3, and IRF1. Our data suggested that HBG attenuated ConA-induced immune liver injury by regulating the immune balance and inhibiting JAK1/STATs/IRF1 signaling, thereby reducing apoptosis induced by JNK activation. The findings indicate that HBG may be a promising drug for immune liver injury.

Purpose Pseudomonas aeruginosa is associated with pulmonary function decline and high disease severity in non-cystic fibrosis (CF) bronchiectasis. The prevalence of nontuberculous mycobacteria (NTM) in non-CF bronchiectasis patients has increased recently. This study investigated the impact of NTM with or without P. aeruginosa isolates in non-CF bronchiectasis patients. Patients and methods Our retrospective study included 96 non-CF bronchiectasis patients from January 2005 to December 2014. We recorded the presentation, exacerbations, emergency department (ED) visits, hospitalization, serial pulmonary function, radiologic studies, and sputum culture results. All patients were followed up for at least 2 years. Results The 96 patients were divided into four groups: patients with concomitant negative NTM and P. aeruginosa isolates (n=41; group 1), patients with positive NTM isolates (n=20; group 2), patients with positive P. aeruginosa isolates (n=20; group 3), and patients with concomitant positive NTM and P. aeruginosa isolates (n=15; group 4). Compared with group 1 patients, patients in groups 2 and 3 showed a significant decline in forced expiratory volume in 1 second (FEV1). They also had more frequent annual acute exacerbations (AE), ED visits, and hospitalization. Group 4 patients had the greatest FEV1 and forced vital capacity (FVC) decline and the most frequent AE, ED visits, and hospitalization. Conclusion Concomitant NTM and P. aeruginosa isolates in non-CF bronchiectasis are associated with the greatest pulmonary function decline and the worst disease severity. This result suggested that early recognition and prompt treatment of concomitant NTM and P. aeruginosa isolates may improve the outcome in non-CF bronchiectasis patients.

This study aims at examining the hypolipidemic effect of piceatannol on high fat diet (HFD)-induced hypercholesterolemic Sprague-Dawley rats and serum metabolite changes. Piceatannol supplement significantly lowered the total cholesterols, low density lipoprotein cholesterol levels and the atherogenic index as compared to the HFD model which only have increased dietary cholesterol intake. Using untargeted mass spectrometry-based metabolomic platforms, multivariate statistics revealed that HFD significantly perturbed fatty acids, lysophospholipids, bile acids and conjugated bile acids. Reduced CYP7A1 protein expression and increase in glycocholate and taurodeoxycholate after piceatannol treatment suggested the conjugated bile acid might contribute to the cholesterol-lowering effect. For lipid profiles, lysoPC (20:2) and lysoPC (20:0) were decreased while the ratio of esterified arachidonic acid to esterified dihomo-γ linoleic acid was up-regulated for rats after piceatannol supplement. These results indicated that the therapeutic effect of piceatannol is associated with bile acid and fatty acid metabolisms and reduced absorption of dietary cholesterols.

Background and Objectives: Bronchiectasis and chronic obstructive pulmonary disease (COPD) often coexist, although the causality is not currently clear. Currently, the clinical influence of COPD on patients with major bronchiectasis over time has not yet been investigated. Material and Methods: This retrospective study recruited consecutive patients with bronchiectasis from outpatient clinic between January 2006 and December 2007. Under the setting of quantification with HRCT, patients who should undergo multiple pulmonary function and exercise tests with regularclinic follow-up were included. The final analysis consisted of 66 eligible patients who were evaluated for clinical status, treatment, and sputum culture from up to 10-year electronic medical records. Results: Of these 66 patients, 45 (68%) had bronchiectasis without COPD and 21 (32%) had COPD. Patients with COPD group had a higher bronchiectasis extent score (32.21 ± 13.09 points vs. 21.89 ± 10.08 points, p = 0.001). Sputum production was reported more frequently by patients with COPD, however, no significant difference was observed after 3 years of follow-up (82.4% vs. 81.6%, p = 0.945). Bronchiectasis extent score correlated with positive sputum culture with Pseudomonas without a synergistic effect from COPD (odds ratio: 1.06, confidence interval: 1.00–1.12, p = 0.031). Regardless of COPD, after 10 years, the proportion of patients using inhaled corticosteroids and/or long-acting β2-agonist between the two groups was not significantly different. Conclusion: COPD aggravated bronchiectasis extension, which was correlated with chronic Pseudomonas aeruginosa colonisation. Moreover, COPD would affect the medium-term (in 3–5 years) bronchiectasis treatment. Therefore, the COPD phenotype of bronchiectasis could be a clinical predictor of the course of treatment.

Scopoletin is a natural anticarcinogenic and antiviral coumarin component. Many studies have proved its anti-cancer effect, and after the preliminary screening of this study, Scopoletin had the best inhibitory effect on Non-small cell lung cancer (NSCLC). But its mechanism for treating NSCLC is still unclear. Therefore, network pharmacology and molecular docking technology were used to explore the potential anti-NSCLC targets and pathways of Scopoletin. The results were verified in vitro.First, Scopoletin was isolated from Fennel and screened to conduct cell proliferation assay on Human lung cancer cell line A549, Human colon cancer cell line HCT-116 and Human hepatoma cell line HepG2 respectively, through the MTT test. Then, the key targets and related pathways were screened through Protein-protein Interaction (PPI) network and "component-target-pathway" (C-TP) network constructed by network pharmacology. And the key targets were selected to dock with Scopoletin via molecular docking. A549 and Human normal lung epithelial cell BEAS-2B were used to verify the results, finally.Through MTT, A549 was chosen as the test cancer cell. From network pharmacology, 16 targets, 27 signaling pathways and 16 GO items were obtained (P 0.05). The results of PPI network and molecular docking showed that EGFR, BRAF and AKT1 were the key targets of Scopoletin against NSCLC, which were consistent with the western-blot results.Through network pharmacology, molecular docking and experiments in vitro, Scopoletin was verified to against NSCLC through RAS-RAF-MEK-ERK pathway and PI3K/AKT pathway.

Background/Objective Tumor necrosis factor-α (TNF-α) antagonists have become increasingly popular in the treatment of psoriasis. However, the increased risk of latent tuberculosis infection (LTBI) reactivation has also become an important issue in clinical practice. The aim of this study was to evaluate serial QuantiFERON-TB Gold In-Tube (QFT-GIT) testing for detecting LTBI among a cohort of psoriatic patients vaccinated with bacille Calmette-Guerin in a country with an intermediate burden of TB during long-term treatment with TNF-α antagonists. Methods We enrolled psoriatic patients treated with TNF-α antagonists who also accepted yearly serial QFT-GIT testing and regular chest X-ray examinations before and during the anti-TNF-α treatment from January 2010 to August 2014. Patients diagnosed with LTBI received chemoprophylaxis, and QFT-GIT testing was performed in these patients after completion of chemoprophylaxis. Results In this retrospective study, 101 patients had completed baseline and at least 1 year of follow-up. Among these patients, 60 had continued TNF-α antagonists therapy and received examinations in the 2 nd year, whereas 18 had continued the therapy until the 3 rd year. The conversion rate among these patients was 14.29% (13/91). In this study, 23 patients were diagnosed with LTBI according to the positive results obtained in the QFT-GIT test, with 19 of them having completed chemoprophylactic therapy. Follow-up QFT-GIT testing revealed reversion in 11 patients (57.89%) and decreased interferon-γ (IFN-γ) levels (68.42%) in 13 patients. Patients over 45 years of age tended to have a persistent positive result. Conclusion This study demonstrated that 14.29% of psoriatic patients undergoing long-term TNF-α antagonist therapy had a QFT-GIT conversion. Although a decreased IFN-γ level and QFT-GIT reversion were observed in most cases following prophylactic therapy, the value of QFT-GIT for evaluating the effect of LTBI prophylaxis remains controversial.

Background: Previous surveillance methods to monitor the prognoses of patients with bronchiectasis are too complex for use in daily practice. The 6-minute walk test (6MWT) is a simple exercise test to predict the prognosis of chronic obstructive airway disease and numerous chronic lung diseases, including idiopathic pulmonary fibrosis. No studies have investigated exercise-induced oxygen desaturation (EID) and distance-saturation product (DSP) of 6MWT to predict the prognoses of patients with bronchiectasis. Methods: This was a prospective study to identify correlations between variables of 6MWT and mortality in patients with bronchiectasis over a 6-year period. The study cohort included 69 patients with stable non-cystic fibrosis (non-CF) bronchiectasis who were regularly evaluated for functional status via 6-minute walk distance (6MWD), spirometry, BODE index, EID, and DSP. Results: Of the 69 patients, 9 (13%) died and 60 (87%) survived during the 6-year follow-up period. The percentage of EID was higher [seven of nine patients (78%) vs . 22 of 60 patients (27%), P=0.003] in the non-survivors group. The 6MWD (467.9±77.1 vs . 363.7±126.7 m, P=0.001) was higher in the survivors group. DSP was significantly lower in the non-survivors group (411.0±78.4 vs . 283.9±90.0 m%, P 280 m% (P Conclusions: DSP is a simple parameter to predict 6-year mortality in patients with non-CF bronchiectasis.

Introduction The prognostic value of epidermal growth factor receptor (EGFR) mutations and the correlation between EGFR mutations and the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histological classification remain controversial. The current study aimed to investigate the pure prognostic role of EGFR mutations in treatment-naive patients with resected stage I lung adenocarcinoma. Methods We retrospectively reviewed 373 patients with stage I pulmonary non-small-cell lung cancer who underwent complete surgical resection between January 2010 and May 2014. The tumors were classified according to IASLC/ATS/ERS criteria. EGFR mutation status was determined by established methods. Results A total of 120 patients were included for analysis; 87 had tumors with EGFR mutations and 33 had wild-type tumors. More low- and intermediate-grade tumors had EGFR mutations, and nearly half of the high-grade tumors were wild-type (75.7% versus 46.2%, p = 0.041). Patients with low-grade tumors had significantly greater median disease-free survival (DFS) (76.8 versus 13 months, p < 0.0001) and better overall survival (OS) (median OS not reached, p = 0.0003) than those with intermediate- and high-grade tumors. Tumor recurrence was 41.4% and 30.3% in mutant and wild-type patients. The 5-years survival rate was 54% and 71.2%. Multivariate analysis revealed that the new histological classification and the pathologic stage were independent predictors of both DFS and OS. EGFR mutation status had no prognostic implications. Conclusion Low grade tumors according to IASLC/ATS/ERS histological classification and the pathologic stage IA tumors of resected stage I lung adenocarcinomas independently predict better DFS and OS. EGFR mutations were frequently seen in histologically low- and intermediate-grade tumors but not a prognostic factor.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. Methods: This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. Results: Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. Conclusions: Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide promising effect against non-small-cell lung cancer (NSCLC), although most tumors acquire resistance. Our objective was to assess the survival outcome of patients with NSCLC with or without subsequent chemotherapy after acquired TKI resistance.A total of 114 patients with pathologically confirmed stage IIIB or IV NSCLC who had had disease control with TKIs were retrospectively reviewed. After acquired TKI resistance, patients received either best supportive care (BSC) only or BSC plus subsequent chemotherapy. Both groups were well balanced in regard to performance status, age, sex, histology subtype, and smoking status.Sixty-seven patients (58.8%) received subsequent chemotherapy, and 47 patients (41.2%) received BSC only. The median overall survival (OS) and progression-free survival (PFS) from the time of TKI resistance in the subsequent-chemotherapy group (11.2 months and 3.5 months, respectively) were longer than those of the BSC group (3.8 months and 1.5 months, respectively; P.01). Patients who subsequently received taxane-based chemotherapy exhibited higher a response rate and disease control rate (48.7% and 79.5%, respectively) than patients treated with a nontaxane regimen (21.4% and 53.5%, respectively; P.05). Overall survival and PFS in patients after taxane-based subsequent chemotherapy (12.7 months and 5.1 months, respectively) were longer than those of patients given a nontaxane regimen (7 months and 1.8 months, respectively; P.01).This study suggests that acquired TKI resistance should be managed aggressively. The higher antitumor response and survival outcome with a taxane-based regimen in this retrospective study could encourage further prospective investigation to confirm the efficacy of taxane over nontaxane chemotherapy in patients with NSCLC whose disease progresses with EGFR TKI treatment.

Objectives Aspiration of the lower airways due to foreign body is rare in adults. This study aimed to determine the outcome of patients who received flexible bronchoscopy with different modalities for foreign body removal in the lower airways. Patients and Methods Between January 2003 and January 2014, 94 patients diagnosed with foreign body in the lower airways underwent flexible bronchoscopy with different modalities, which included forceps, loop, basket, knife, electromagnet, and cryotherapy. The clinical presentation, foreign body location and characteristics, and applications of flexible bronchoscopy were analyzed. Results Forty (43%) patients had acute aspiration, which developed within one week of foreign body entry and 54 (57%) had chronic aspiration. The most common foreign bodies were teeth or bone. More patients with chronic aspiration than those with acute aspiration were referred from the out-patient clinic (48% vs. 28%), but more patients with acute aspiration were referred from the emergency room (35% vs. 6%) and intensive care unit (18% vs. 2%). Flexible bronchoscopy with different modalities was used to remove the foreign bodies (85/94, 90%). Electromagnet or cryotherapy was used in nine patients to eliminate the surrounding granulation tissue before foreign body removal. In the nine patients with failed flexible bronchoscopy, eight underwent rigid bronchoscopy instead and one had right lower lung lobectomy for lung abscess. Conclusions Flexible bronchoscopy with multiple modalities is effective for diagnosing and removing foreign bodies in the lower respiratory airways in adults, with a high success rate (90%) and no difference between acute and chronic aspirations.

Objectives. Chemotherapy as first-/second-line treatment in different epidermal growth factor receptor (EGFR) mutation lung adenocarcinoma remains controversial.Methods. Consecutive patients were collected between 2009 and 2012. Patients were divided into two groups (1st-line chemotherapy:n= 56 and 2nd-line chemotherapy:n= 55). Their outcomes profiles were analyzed.Results. The overall survival (OS) of all patients (390 versus 662 days,p< 0.0001), as well as both progression-free survival (PFS, 151 versus 252 days,p= 0.0001) and OS (308 versus 704 days,p= 0.0001) of patients withL858Rmutation (n= 63), who received 2nd-line chemotherapy, was significantly poor. By univariate and multivariate analysis, 2nd-line chemotherapy, andL858Rmutation were significantly related to poor PFS and OS.Conclusion. In advanced lung adenocarcinoma,L858Rmutation and 2nd-line chemotherapy caused a poor outcome. It is a consideration to choice of 1st-line chemotherapy in these subjects. A prospective design is warranted to confirm this finding.

To revalidate a means of assessing delirium in intensive care unit patients and to investigate the independent effect of delirium on the mortality of mechanically ventilated patients.A prospective cohort study.A 37-bed medical intensive care unit of a tertiary care hospital.Subjects were 102 of 131 consecutive mechanically ventilated patients.All the enrolled patients were assessed for delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Mortality rate were compared between patients with or without delirium, and the predictors of death were investigated.The two CAM-ICU assessors' sensitivities in diagnosing delirium compared with reference standard were 91% and 95%, whereas their specificities were both 98%. They also demonstrated high interrater reliability with kappa statistics of 0.91. Delirium was present in 22 of 102 (22%) patients in the first 5 days. The delirious patients had higher intensive care unit mortality rate than nondelirious patients (63.6% vs. 32.5%, respectively), with a hazard ratio of 2.57 (95% confidence interval, 1.56-8.15). In multivariate analysis, delirium (odds ratio, 13.0; 95% confidence interval, 2.69-62.91), shock (odds ratio, 12.91; 95% confidence interval, 2.93-56.92), and illness severity (odds ratio, 9.61; 95% confidence interval, 2.24-41.18) were independent predictors of mortality.This study confirms previous work showing that delirium is an independent predictor for increased mortality among mechanically ventilated patients.

Background: The alveolar recruitment maneuver (RM) has been reported to improve oxygenation in acute respiratory distress syndrome (ARDS) and may be related to reduced extravascular lung water (EVLW) in animals. This study was designed to investigate the effects of RM on EVLW in patients with ARDS. Methods: An open label, prospective, randomized controlled trial including patients with ARDS was conducted in hospitals in North Taiwan between 2010 and 2016. The patients were divided into 2 groups (with and without RM). The primary endpoint was the comparison of the EVLW index between the 2 groups. Results: Twenty-four patients with ARDS on mechanical ventilator support were randomized to receive ventilator treatment with RM (RM group, n = 12) or without RM (non-RM group, n = 12). Baseline demographic characteristics were similar between the 2 groups. After recruitment, the day 3 extravascular lung water index (EVLWI) (25.3 ± 9.3 vs 15.5 ± 7.3 mL/kg, P = .008) and the arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FiO2) (132.3 ± 43.5 vs 185.6 ± 38.8 mL/kg, P = .003) both improved over that of day 1. However, both EVLWI and PaO2/FiO2 did not significantly change from day 1 to 3 in the non-RM group. Conclusion: RM is a feasible method for improving oxygenation and the EVLW index in patients with ARDS, as well as for decreasing ventilator days and intensive care unit stay duration.

Study Objectives.The aim of this study is to investigate the correlation between serum high-sensitivity C-reactive protein (hs-CRP) and other clinical tools including high-resolution computed tomography (HRCT) in patients with stable non-CF bronchiectasis.Design.A within-subject correlational study of a group of patients with stable non-CF bronchiectasis, who were recruited from our outpatient clinic, was done over a two-year period.Measurements.Sixty-nine stable non-CF bronchiectasis patients were evaluated in terms of hs-CRP, 6-minute walk test, pulmonary function tests, and HRCT.Results.Circulating hs-CRP levels were significantly correlated with HRCT scores (n=69,r=0.473,P<0.001) and resting oxygenation saturation (r=-0.269,P=0.025). HRCT severity scores significantly increased in patients with hs-CRP level of 4.26 mg/L or higher (mean ± SD28.1±13.1) compared to those with hs-CRP level less than 4.26 mg/L (31.7±9.8,P=0.004). Oxygenation saturation at rest was lower in those with hs-CRP level of 4.26 mg/L or higher (93.5±4.4%) compared to those with hs-CRP level less than 4.26 mg/L (96.4±1.6%,P=0.001).Conclusion.There was a good correlation between serum hs-CRP and HRCT scores in the patients with stable non-CF bronchiectasis.

SD rat C6 brain glioma model is established, and observe its pathological characteristic and MRI. C6 glioma cells were implanted through stereotactic orientator, and C6 brain glioma rat model was established. The change of tumor body growth (MRI) at Week 1, 2 and 3 after the implantation was observed, and compared with gross pathological results. The intracranial implantation via stereotactic orientation had a success rate of 100%, and there was no distal and extracranial metastasis. As shown by T2WI and enhanced T1WI scanning, tumor body grew with peritumor edema at the end of Week 1 after the implantation, and grew rapidly to a volume approximate to gross pathological results two weeks later. It had a high success rate to establish rat C6 brain glioma model through stereotactic orientation. MRI + pathological examination could better reflect the growth way and development process of tumor.

It is the study about the role of 18F-FDG PET imaging technology in differentiating diabetic encephalopathy (DE) rat model. 10 rats were injected with Streptozotocin to use as duplicate DE model rats, and 10 rats were injected with normal saline to use as control rats. The change of rat behavior was observed. HE staining was made to detect the intracerebral pathological changes in rats. In both groups, the conditions of intracerebral glucose metabolism in rats were observed in vivo through 18F-FDG PET imaging technology. Under PET imaging, glucose metabolism decreased in hippocampus in model group, and there were only mild neuron injury and slight glucose hypometabolism in control group. The combination of 18F-FDG PET imaging with behavioral and pathological observation could become one of ways to determine whether the model is successful.

Objectives: Docetaxel and pemetrexed have been validated as therapeutics for previously treated advanced non-small-cell lung cancer (NSCLC), but tolerability is a concern for standard treatment with docetaxel administered once every 3 weeks (tri-weekly 75-mg/m2 schedule). We conducted this retrospective study to compare the efficacy and toxicity of weekly low-dose docetaxel versus tri-weekly pemetrexed for previously treated advanced NSCLC. Methods: Consecutive patients who received low-dose single docetaxel (30 mg/m2 on days 1 and 8 every 3 weeks) or pemetrexed (500 mg/m2 every 3 weeks) at a single university-affiliated hospital following failure of previous treatment were retrospectively reviewed. Their outcomes and toxicity profiles were determined. Results: 179 patients were included between 2005 and 2008 (docetaxel, n = 79; pemetrexed, n = 100). Both groups had similar hematologic (16.5 vs. 15.0%; p = 0.84) and non-hematologic (20.3 vs. 24%; p = 0.55) toxicities. After controlling for confounding factors, docetaxel remained superior to pemetrexed for progression-free survival (median 4.0 vs. 2.4 months; hazard ratio 0.64; 95% CI 0.47–0.87; p = 0.005) and overall survival (median 15.0 vs.8.5 months; hazard ratio 0.54; 95% CI 0.38–0.77; p Conclusion: Although this study showed that weekly low doses of docetaxel were as tolerable as pemetrexed for previously treated advanced NSCLC, a prospective design is needed to confirm this finding.

Homozygous mutations in the Borate Cotransporter SLC4A11 cause two early-onset corneal dystrophies: congenital hereditary endothelial dystrophy (CHED) and Harboyan syndrome. More recently, four sporadic patients with late-onset Fuchs corneal dystrophy (FCD), a common age-related disorder, were also reported to harbor heterozygous mutations at this locus. We therefore tested the hypothesis that SLC4A11 contributes to FCD and asked whether mutations in SLC4A11 are responsible for familial cases of late-onset FCD. We sequenced SLC4A11 in 192 sporadic and small nuclear late-onset FCD families and found seven heterozygous missense novel variations that were absent from ethnically matched controls. Familial data available for one of these mutations showed segregation under a dominant model in a three-generational family. In silico analyses suggested that most of these substitutions are intolerant, whereas biochemical studies of the mutant protein indicated that these alleles impact the localization and/or posttranslational modification of the protein. These results suggest that heterozygous mutations in SLC4A11 are modest contributors to the pathogenesis of adult FCD, suggesting a causality continuum between FCD and CHED. Taken together with a recent model between FCD and yet another early onset corneal dystrophy, PPCD, our data suggest a shared pathomechanism and genetic overlap across several corneal dystrophies.

Glaucoma is a disease frequently associated with elevated intraocular pressure that can be alleviated by filtration surgery. However, the post-operative subconjunctival scarring response which blocks filtration efficiency is a major hurdle to the achievement of long-term surgical success. Current application of anti-proliferatives to modulate the scarring response is not ideal as these often give rise to sight-threatening complications. SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein involved in extracellular matrix (ECM) production and organization. In this study, we investigated post-operative surgical wound survival in an experimental glaucoma filtration model in SPARC-null mice. Loss of SPARC resulted in a marked (87.5%) surgical wound survival rate compared to 0% in wild-type (WT) counterparts. The larger SPARC-null wounds implied that aqueous filtration through the subconjunctival space was more efficient in comparison to WT wounds. The pronounced increase in both surgical survival and filtration efficiency was associated with a less collagenous ECM, smaller collagen fibril diameter, and a loosely-organized subconjunctival matrix in the SPARC-null wounds. In contrast, WT wounds exhibited a densely packed collagenous ECM with no evidence of filtration capacity. Immunolocalization assays confirmed the accumulation of ECM proteins in the WT but not in the SPARC-null wounds. The observations in vivo were corroborated by complementary data performed on WT and SPARC-null conjunctival fibroblasts in vitro. These findings indicate that depletion of SPARC bestows an inherent change in post-operative ECM remodeling to favor wound maintenance. The evidence presented in this report is strongly supportive for the targeting of SPARC to increase the success of glaucoma filtration surgery.

To evaluate the association of epidermal growth factor receptor (EGFR) gene copy number with EGFR and k-ras mutation status and tyrosine kinase inhibitor (TKI) sensitivity in non-small cell lung cancer (NSCLC), EGFR gene copy number of 182 NSCLC tumor specimens were analyzed by chromogenic in situ hybridization (CISH). EGFR and k-ras mutation analyses were also performed for, respectively, 176 and 157 of the 182 patients. Additionally, 36 patients in this study had received TKI monotherapy. The tumor was considered to be CISH positive if the gene copy number wasor=5 signals per nucleus inor=40% of tumor cells. CISH-positive tumors were strongly associated with adenocarcinoma (56.8%) compared with squamous cell carcinoma (15.9%) (p0.0001). The CISH-positive tumors were also strongly associated with EGFR mutations (78%) compared with wild type (20.2%) (p0.0001). Only six tumors had k-ras mutations. None had EGFR mutation and only one was CISH positive. In the patients treated with TKI, EGFR mutation was strongly associated with TKI responsiveness (22/25 responders) (p0.0001), but the CISH-positive tumors were only marginally significant (18/25 responders) (p=0.0665). Patients with EGFR mutations or CISH-positive tumors were all associated with longer median survival, although not statistically significant. Our results suggest Increased EGFR copy number was highly correlated with EGFR mutation in adenocarcinoma. Although it is less correlated with TKI responsiveness when compared with EGFR mutations, it still could be a good alternative molecular predictive marker for TKI responsiveness, since CISH can be done on paraffin section and is much quicker than DNA sequencing.

Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were previously the standard first-line treatments for lung cancers with activating EGFR mutations. The first-generation reversible EGFR TKIs, gefitinib and erlotinib, demonstrated substantial efficacy in the treatment of brain metastases from EGFR-mutated lung adenocarcinoma. However, the efficacy of afatinib, the second-generation irreversible EGFR TKI, as the first-line treatment in lung adenocarcinoma patients with brain metastasis has yet to be evaluated.Here, we report cases of 3 patients who received afatinib alone as the first-line treatment in combination with whole-brain radiotherapy or following surgical resection of brain metastases. All 3 patients had EGFR L858R mutation. The first patient had lung adenocarcinoma with brain metastasis and no neurologic symptoms. After consultation, she received afatinib as a first-line treatment. Chest computed tomography and brain magnetic resonance imaging (MRI) showed partial response. The second patient had lung adenocarcinoma accompanied with a metastatic brain lesion associated with seizures. This patient received whole-brain radiotherapy and afatinib treatment following brain MRI and subsequently showed significant regression of the brain metastasis. The third patient had strabismus of the right eye, and brain MRI showed a single tumor at the cerebellar pontine angle. This patient underwent surgical resection of the tumor followed by afatinib treatment. He refused adjuvant radiotherapy after surgery for brain metastasis. The brain MRI showed no recurrent brain metastasis, and the patient had relatively less neurologic deficiency.This series of 3 cases indicate that afatinib may be an appropriate first-line treatment alternative in patients having lung adenocarcinoma with EGFR mutations. Further retrospective analyses and prospective clinical trials are required to substantiate the efficacy of afatinib in the treatment of brain metastases of lung adenocarcinoma.

We used a congenic C57Bl/6J cystic fibrosis transmembrane conductance regulator ( Cftr)−/− mouse model, which develops cystic fibrosis (CF)-like pathology in all organs, to evaluate the short- and long-term therapeutic effects of dietary docosahexaenoic acid (DHA). Thirty-day-old Cftr−/− mice and wild-type littermates were randomized to receive a liquid diet with or without DHA (40 mg/day). Animals were killed for histological and lipid analysis after 7, 30, and 60 days of therapy. DHA had no significant therapeutic or harmful effect on the lung, pancreas, or ileum of the Cftr−/− mice or their wild-type littermates. In contrast, dietary DHA resulted in highly significant amelioration of the severity of liver disease in the Cftr−/− mice, primarily a reduction in the degree of peri-portal inflammation. Additionally, these detailed measurements confirm our previous findings that Cftr−/− mice have significant alterations in the pancreas (except external acinar diameter), ileum, liver, lung, and salivary (except sublingual) glands at all ages compared with their age-matched wild-type littermates. In conclusion, inhibition of cytokines and/or eicosanoid metabolism and release of endogenous inhibitors of inflammation by DHA may account for the anti-inflammatory effects in the liver of this congenic murine model of CF. The potential therapeutic benefits of DHA in severe CF-associated liver disease remain to be explored.

Objectives The aim of the study was to investigate the risk factors of developing early-onset delirium in mechanically ventilated patients and determine the subsequent clinical outcomes. Methods Confusion assessment method for the intensive care unit (ICU) was used to assess the enrolled mechanically ventilated patients for delirium. The risk factors of developing delirium and clinical outcomes were determined in these subjects. Results Delirium was present in 31 (21.7%) of 143 patients in the first 5 days. In multivariable analysis, hypoalbuminemia (odds ratio, 5.94; 95% confidence interval, 1.23-28.77) and sepsis (odds ratio, 3.65; 95% confidence interval, 1.03-12.9) increased the risk of developing delirium in mechanically ventilated patients. The patients with delirium had a higher in-hospital mortality (67.7% vs 33.9%, respectively; P = .001) and longer duration of mechanical ventilation (19.5 ± 15.8 vs 9.3 ± 8.8 days, respectively; P = .003) than patients without delirium. The incidence of nosocomial pneumonia was increased in delirious patients (64.5% vs 38.4%, P = .01) compared with nondelirious patients, whereas the lengths of ICU or hospital stay were similar between both groups. Conclusions Mechanically ventilated patients with sepsis or hypoalbuminemia were more vulnerable to develop delirium in their early stay in the ICU. Early-onset delirium is associated with prolonged duration of mechanical ventilation and higher incidence of nosocomial pneumonia, leading to a higher mortality.

Objectives Bronchiectasis is characterized by an irreversible dilatation of bronchi and is associated with lung fibrosis. MMP-1 polymorphism may alter its transcriptional activity, and differentially modulate bronchial destruction and lung fibrosis. Design To investigate the association of MMP-1 polymorphisms with disease severity in non-cystic fibrosis (CF) bronchiectasis patients, 51 normal subjects and 113 patients with bronchiectasis were studied. The associations between MMP-1 polymorphisms, lung function, and disease severity evaluated by high resolution computed tomography (HRCT) were analyzed. Results The frequency of MMP-1(-1607G) allele was significantly higher in patients with bronchiectasis than normal subjects (70.8% vs 45.1%, p

Background After the new definition of adjustment disorder (AjD) by the International Classification of Diseases-11(ICD-11), AjD has attracted more and more attention. Adjustment disorder new module-20 (ADNM-20), which is used to diagnose AjD, has been verified in some countries, but it has not been verified in China. As a result, the purpose of this study was to investigate the validity and reliability of the Chinese version of the Adjustment disorder new module-20 (ADNM-20) in female breast cancer patients. Methods The ADNM-20 translated into Chinese employed the translation and back translation technique. Three hundred fifty four newly diagnosed ( Results ADNM-20 core symptoms included 8 items and two factors, which were extracted by using exploratory factor analysis (EFA). It could explain 61.74% of the total variance. ADNM-20 accessory symptoms including 12 items and four factors, which were extracted by using EFA. It could explain 68.34% of the total variance. Cronbach’s α coefficient for ADNM-20 was 0.93, split-half reliability was 0.87, and the test-retest correlation coefficient was 0.74. The correlation coefficient between each subscale was ranged from 0.53 to 0.71 (P P Conclusions The study verified the validity and reliability of the Chinese version of ADNM-20. It is applicable to measure the prevalence of adjustment disorder in the breast cancer population.