Quantitative analysis with multiphase contrast-enhanced computed tomography to evaluate residual tumor activity of hepatocellular carcinoma after DEB-TACE.

Most hepatocellular carcinomas (HCC) treated by transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE) are characterized by coagulation necrosis; therefore, it is often difficult to distinguish enhancement in the arterial phase that would lead to false negative evaluation. This study aimed to evaluate the specificity and sensitivity of the difference value of multiphase contrast-enhanced computed tomography (CECT) in predicting residual tumor activity in HCC lesions after DEB-TACE. This retrospective diagnostic study analyzed CECT images of 73 HCC lesions in 57 patients 20 to 40 days (average 28 days) after DEB-TACE treatment at our Hospital from January to December 2019. Postoperative pathology or digital subtraction angiography images were used as references. Residual tumor activity after the first intervention was determined based on the presence of tumor staining in digital subtraction angiography or the postoperative pathological discovery of HCC tumor cells. A significant difference was observed between the active and inactive residual groups in ∆ HU difference between CT values of arterial phase and non-contrast scans (AN, P = .000), difference between CT values of venous phase and non-contrast scans (VN, P = .000), difference between CT values of delay phase and non-contrast scans (DN, P = .000), (difference between CT values of venous and arterial phase scans, P = .001), and (difference between CT values of delay and arterial phase scans, P = .005). No statistically significant difference was observed between the delayed and venous phases (difference between CT values of delay and venous phase scans, P = .361). The area under the curve (AUC) of the ROC curve showed that the diagnostic efficacies in difference in CT value of AN (AUC = 0.976), VN (AUC = 0.927), and DN (AUC = 0.924) were higher, and their cutoff values were 4.86, 12.065, 20.19 HU with their sensitivities of 93.3%, 84.4%, 77.8% and specificities of 100%, 96.4%, and 100%, respectively. difference in CT value values of AN, VN, DN, difference between CT values of venous and arterial phase scans and difference between CT values of delay and arterial phase scans can sensitively detect residual tumor activity 20-40 days after DEB-TACE. Thus, more sensitive active residual foci were detected using all 3 enhanced phases rather than only the arterial phase. Quantitative analysis of multiphase CECT can detect residual tumor activity in an early and noninvasive manner, which can provide time for patients to receive early follow-up treatment.

Safety and efficacy of an integrated endovascular treatment strategy for early hepatic artery occlusion after liver transplantation.

BACKGROUND: Hepatic artery occlusion (HAO) after liver transplantation (LT) is typically comprised of hepatic artery thrombosis (HAT) and stenosis (HAS), both of which are severe complications that coexist and interdependent. This study aimed to evaluate an integrated endovascular treatment (EVT) strategy for the resolution of early HAO and identify the risk factors associated with early HAO as well as the procedural challenge encountered in the treatment strategy. METHODS: Consecutive orthotopic LT recipients (n = 366) who underwent transplantation between June 2017 and December 2018 were retrospectively investigated. EVT was performed using an integrated strategy that involved thrombolytic therapy, shunt artery embolization plus vasodilator therapy, percutaneous transluminal angioplasty, and/or stent placement. Simple EVT was defined as the clinical resolution of HAO by one round of EVT with thrombolytic therapy and/or shunt artery embolization plus vasodilator therapy. Otherwise, it was defined as complex EVT. RESULTS: Twenty-six patients (median age 52 years) underwent EVT for early HAO that occurred within 30 days post-LT. The median interval from LT to EVT was 7 (6-16) days. Revascularization time (OR = 1.027; 95% CI: 1.005-1.050; P = 0.018) and the need for conduit (OR = 3.558; 95% CI: 1.241-10.203, P = 0.018) were independent predictors for early HAO. HAT was diagnosed in eight patients, and four out of those presented with concomitant HAS. We achieved 100% technical success and recanalization by performing simple EVT in 19 patients (3 HAT+/HAS- and 16 HAT-/HAS+) and by performing complex EVT in seven patients (1 HAT+/HAS-, 4 HAT+/HAS+, and 2 HAT-/HAS+), without major complications. The primary assisted patency rates at 1, 6, and 12 months were all 100%. The cumulative overall survival rates at 1, 6, and 12 months were 88.5%, 88.5%, and 80.8%, respectively. Autologous transfusion < 600 mL (94.74% vs. 42.86%, P = 0.010) and interrupted suture for hepatic artery anastomosis (78.95% vs. 14.29%, P = 0.005) were more prevalent in simple EVT. CONCLUSIONS: The integrated EVT strategy was a feasible approach providing effective resolution with excellent safety for early HAO after LT. Appropriate autologous transfusion and interrupted suture technique helped simplify EVT.

Drug-eluting beads transarterial chemoembolization by CalliSpheres is effective and well tolerated in treating intrahepatic cholangiocarcinoma patients: A preliminary result from CTILC study.

This study aimed to investigate the efficacy and safety of drug-eluting beads (DEB) transarterial chemoembolization (TACE) treatment in Chinese intrahepatic cholangiocarcinoma (ICC) patients.37 ICC patients underwent DEB-TACE treatment in CTILC study (registered on clinicaltrials.gov with registry No. NCT03317483) were included in this present study. Treatment response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall survival (OS) was calculated from the time of DEB-TACE operation until the date of death from any causes. Liver function change and adverse events (AEs) were recorded during and after DEB-TACE operation.3 (8.1%) patients achieved complete response (CR) and 22 (59.5%) patients achieved partial response (PR), with objective response rate (ORR) of 67.6%. After DEB-TACE treatment, mean OS was 376 days (95%CI: 341-412 days). Multivariate logistic regression analysis revealed that Bilobar disease (P = .040, OR: 0.105, 95% CI: 0.012-0.898) and portal vein invasion (P = .038, OR: 0.104, 95% CI: 0.012-0.881) could independently predict less possibility of ORR. Patients with ALB abnormal, TP abnormal, ALT abnormal and AST abnormal were increased at 1-week post DEB-TACE treatment (P = .034, P = .001, P < .001, P = .006, respectively), while returned to the levels at baseline after 1 to 3 months (all P > .050). Besides, most of the AEs were mild including pain, fever, vomiting, and nausea in this study.DEB-TACE was effective and well tolerated in treating ICC patients, and bilobar disease as well as portal vein invasion were independently correlated with less probability of ORR achievement.

Efficacy and Safety of Drug-Eluting Beads Transarterial Chemoembolization by CalliSpheres® in 275 Hepatocellular Carcinoma Patients: Results From the Chinese CalliSpheres® Transarterial Chemoembolization in Liver Cancer (CTILC) Study.

The purpose of this study was to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Chinese hepatocellular carcinoma (HCC) patients and the prognostic factors for treatment response as well as survival. A total of 275 HCC patients were included in this prospective study. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST), and progression-free survival (PFS) as well as overall survival (OS) were determined. Liver function and adverse events (AEs) were assessed before and after DEB-TACE operation. Complete response (CR), partial response (PR), and objective response rate (ORR) were 22.9%, 60.7%, and 83.6%, respectively. The mean PFS was 362 (95% CI: 34.9-375) days, the 6-month PFS rate was 89.4 ± 2.1%, while the mean OS was 380 (95% CI: 370-389) days, and the 6-month OS rate was 94.4 ± 1.7%. Multivariate logistic regression revealed that portal vein invasion (p = 0.011) was an independent predictor of worse clinical response. Portal vein invasion (p = 0.040), previous cTACE treatment (p = 0.030), as well as abnormal serum creatinine level (BCr) (p = 0.017) were independent factors that predicted worse ORR. In terms of survival, higher Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.029) predicted for worse PFS, and abnormal albumin (ALB) (p = 0.011) and total serum bilirubin (TBIL) (p = 0.009) predicted for worse OS. The number of patients with abnormal albumin, total protein (TP), TBIL, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were augmented at 1 week posttreatment and were similar at 1-3 months compared with baseline. The most common AEs were pain, fever, nausea, and vomiting, and no severe AEs were observed in this study. DEB-TACE was effective and tolerable in treating Chinese HCC patients, and portal vein invasion, previous cTACE treatment, abnormal BCr, ALB, and TBIL appear to be important factors that predict worse clinical outcome.

The Comprehensive Analysis of Efficacy and Safety of CalliSpheres® Drug-Eluting Beads Transarterial Chemoembolization in 367 Liver Cancer Patients: A Multiple-Center, Cohort Study.

This study aimed to investigate the efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization (DEB-TACE) in treating Chinese patients with liver cancer. A total of 367 liver cancer patients from 24 medical centers were consecutively enrolled in this multiple-center, prospective cohort study, including 275 hepatocellular carcinoma (HCC) cases, 37 intrahepatic cholangiocarcinoma (ICC) cases, and 55 secondary liver cancer cases. All the patients received CalliSpheres® DEB-TACE treatment. Treatment response, overall survival (OS), change of liver function, and adverse events (AEs) were assessed. DEB-TACE treatment achieved 19.9% complete response (CR) and 79.6% objective response rate (ORR), with mean OS of 384 days [95% confidence interval (CI): 375-393 days]. CR and ORR were both higher in HCC patients compared with primary ICC patients and secondary liver cancer patients, while no difference was discovered in OS. Portal vein invasion was an independent risk factor for CR, while portal vein invasion, previous conventional TACE (cTACE) treatment, and abnormal blood creatinine (BCr) were independent risk factors for ORR. In addition, largest nodule size ≥5.0 cm, abnormal albumin (ALB), and abnormal total bilirubin (TBIL) independently correlated with unfavorable OS. Most liver function indexes were recovered to baseline levels at 1-3 months after DEB-TACE. Common AEs were pain, fever, vomiting, and nausea; most of them were at mild grade. CalliSpheres® DEB-TACE is efficient and well tolerated in Chinese liver cancer patients. Portal vein invasion, previous cTACE treatment, largest nodule size, abnormal BCr, ALB, and TBIL correlate with worse prognosis independently.

Smartphone-Based Point-of-Care Microfluidic Platform Fabricated with a ZnO Nanorod Template for Colorimetric Virus Detection.

Viruses pose serious infectious disease threats to humans and animals. To significantly decrease the mortality and morbidity caused by virus infections, there is an urgent need of sensitive and rapid point-of-care platforms for virus detection, especially in low-resource settings. Herein, we developed a smartphone-based point-of-care platform for highly sensitive and selective detection of the avian influenza virus based on nanomaterial-enabled colorimetric detection. The 3D nanostructures, which serve as a scaffold for antibody conjugation to capture the avian influenza virus, are made on PDMS herringbone structures with a ZnO nanorod template. After virus capture, the on-chip gold nanoparticle-based colorimetric reaction allows virus detection by naked eyes with a detection limit of 2.7 × 104 EID50/mL, which is one order of magnitude better than that of conventional fluorescence-based ELISA. Furthermore, a smartphone imaging system with data processing capability further improves the detection limit, reaching down to 8 × 103 EID50/mL. The entire virus capture and detection process can be completed in 1.5 h. We envision that this point-of-care microfluidic system integrated with smartphone imaging and colorimetric detection would provide a fast, cheap, sensitive, and user-friendly platform for virus detection in low-resource settings.

Regulatory network of two circRNAs and an miRNA with their targeted genes under astilbin treatment in pulmonary fibrosis.

Circular RNAs (circRNAs) are becoming new therapeutic drug targets. However, their profiles under astilbin treatment have not been reported yet. In this study, we analysed the global reprogramming of circRNA transcriptome and a regulatory network of circRNAs with their targeted genes under astilbin treatment in pulmonary fibrosis. A total of 145 circRNAs were differentially expressed in the astilbin-treated group compared with the bleomycin-treated group using RNA sequencing. In the bleomycin- and astilbin-treated groups, 29 coexpressed circRNAs were found. The maximum number of circRNAs was distributed on chromosome two, and their length varieties were mainly within 1000 bp. Four differentially expressed circRNAs (circRNA-662, 949, 394 and 986) were tested to validate the RNA sequencing data, and their targeted microRNAs and genes were analysed by qRT-PCR, Western blot, Pearson correlation coefficient, a dual-luciferase reporter system and anti-AGO2 RNA immunoprecipitation. The results showed that circRNA-662 and 949 can act as "miR-29b sponges" targeting Gli2 and STAT3 to exert their functions. Our work suggests that the transcriptome complexity at the circRNA level under astilbin treatment. These circRNAs may be potential molecular targets for drug action.

Case report of a 28-year-old man with aortic dissection and pulmonary shadow due to granulomatosis with polyangiitis.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterised by the main violation of the upper and lower respiratory tract and kidney. GPA is considered a systemic vasculitis of medium-sized and small blood vessels where aortic involvement is extremely rare. CASE PRESENTATION: A 28-year-old male was admitted to the hospital due to 4 h of chest pain. Computed tomography scan of the aorta showed a thickened aortic wall, pulmonary lesions, bilateral pleural effusion and pericardial effusion. The aortic dissection should be considered. An emergency operation was performed on the patient. Surgical biopsies obtained from the aortic wall showed destructive changes, visible necrosis, granulation tissue hyperplasia and a large number of acute and chronic inflammatory cells. Nearly a year later, the patient was re-examined for significant pulmonary lesions. His laboratory studies were significantly positive for anti-neutrophilic antibody directed against proteinase 3. Finally, the diagnosis of GPA was obviously established. CONCLUSIONS: Although GPA rarely involves the aorta, we did not ignore the fact that GPA may involve large blood vessels. In addition, GPA should be included in the systemic vasculitis that can give rise to aortitis and even aortic dissection.

Efficacy and safety of CalliSpheres® drug-eluting beads transarterial chemoembolization in patients with secondary liver cancer: a preliminary result from CTILC study.

BACKGROUND: This study aimed to assess the treatment response, short-term overall survival (OS) and safety profiles of drug-eluting beads transarterial chemoembolization (DEB-TACE) in patients with secondary liver cancer. METHODS: Fifty-five patients with secondary liver cancer underwent DEB-TACE were enrolled in this prospective cohort study. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST). OS was calculated from the time of DEB-TACE operation until the date of death. RESULTS: The complete response (CR) and objective response rate (ORR) at 1-3 months post DEB-TACE were 12.7% and 67.3%. Mean OS was 383 d (95% CI: 360-406), and 6-month OS rate was 93.4%±3.7%. Subgroup analysis revealed previous conventional TACE (cTACE) treatment was correlated with worse ORR (P=0.028), and it was a risk factor for ORR achievement (P=0.021). As for liver function, the percentages of abnormal TP (P=0.031), TBIL (P=0.022), ALT (P=0.002) and AST (P=0.035) were increased at 1 week post DEB-TACE compared to baseline, while these four indexes returned to baseline (all P>0.05) at 1-3 months post DEB-TACE. As to safety profiles, 41 (66.1%), 28 (45.2%), 17 (27.4%), 8 (12.9%) and 6 (9.7%) cases had pain, vomiting, fever, nausea and other adverse events (AEs) respectively during DEB-TACE operation, while 26 (41.9%), 9 (14.5%), 8 (12.9%), 4 (6.5%), 1 (1.6%) and 2 (3.2%) cases had pain, fever, vomiting, nausea, bone marrow toxicity and other AEs respectively at 1 month after DEB-TACE operation. CONCLUSIONS: DEB-TACE was efficient and well tolerated in treating patients with secondary liver cancer.

Intratumoral Spatial Heterogeneity at Perfusion MR Imaging Predicts Recurrence-free Survival in Locally Advanced Breast Cancer Treated with Neoadjuvant Chemotherapy.

Purpose To characterize intratumoral spatial heterogeneity at perfusion magnetic resonance (MR) imaging and investigate intratumoral heterogeneity as a predictor of recurrence-free survival (RFS) in breast cancer. Materials and Methods In this retrospective study, a discovery cohort (n = 60) and a multicenter validation cohort (n = 186) were analyzed. Each tumor was divided into multiple spatially segregated, phenotypically consistent subregions on the basis of perfusion MR imaging parameters. The authors first defined a multiregional spatial interaction (MSI) matrix and then, based on this matrix, calculated 22 image features. A network strategy was used to integrate all image features and classify patients into different risk groups. The prognostic value of imaging-based stratification was evaluated in relation to clinical-pathologic factors with multivariable Cox regression. Results Three intratumoral subregions with high, intermediate, and low MR perfusion were identified and showed high consistency between the two cohorts. Patients in both cohorts were stratified according to network analysis of multiregional image features regarding RFS (log-rank test, P = .002 for both). Aggressive tumors were associated with a larger volume of the poorly perfused subregion as well as interaction between poorly and moderately perfused subregions and surrounding parenchyma. At multivariable analysis, the proposed MSI-based marker was independently associated with RFS (hazard ratio: 3.42; 95% confidence interval: 1.55, 7.57; P = .002) adjusting for age, estrogen receptor (ER) status, progesterone receptor status, human epidermal growth factor receptor type 2 (HER2) status, tumor volume, and pathologic complete response (pCR). Furthermore, imaging helped stratify patients for RFS within the ER-positive and HER2-positive subgroups (log-rank test, P = .007 and .004) and among patients without pCR after neoadjuvant chemotherapy (log-rank test, P = .003). Conclusion Breast cancer consists of multiple spatially distinct subregions. Imaging heterogeneity is an independent prognostic factor beyond traditional risk predictors.

Heterogeneous Enhancement Patterns of Tumor-adjacent Parenchyma at MR Imaging Are Associated with Dysregulated Signaling Pathways and Poor Survival in Breast Cancer.

Purpose To identify the molecular basis of quantitative imaging characteristics of tumor-adjacent parenchyma at dynamic contrast material-enhanced magnetic resonance (MR) imaging and to evaluate their prognostic value in breast cancer. Materials and Methods In this institutional review board-approved, HIPAA-compliant study, 10 quantitative imaging features depicting tumor-adjacent parenchymal enhancement patterns were extracted and screened for prognostic features in a discovery cohort of 60 patients. By using data from The Cancer Genome Atlas (TCGA), a radiogenomic map for the tumor-adjacent parenchymal tissue was created and molecular pathways associated with prognostic parenchymal imaging features were identified. Furthermore, a multigene signature of the parenchymal imaging feature was built in a training cohort (n = 126), and its prognostic relevance was evaluated in two independent cohorts (n = 879 and 159). Results One image feature measuring heterogeneity (ie, information measure of correlation) was significantly associated with prognosis (false-discovery rate < 0.1), and at a cutoff of 0.57 stratified patients into two groups with different recurrence-free survival rates (log-rank P = .024). The tumor necrosis factor signaling pathway was identified as the top enriched pathway (hypergeometric P < .0001) among genes associated with the image feature. A 73-gene signature based on the tumor profiles in TCGA achieved good association with the tumor-adjacent parenchymal image feature (R2 = 0.873), which stratified patients into groups regarding recurrence-free survival (log-rank P = .029) and overall survival (log-rank P = .042) in an independent TCGA cohort. The prognostic value was confirmed in another independent cohort (Gene Expression Omnibus GSE 1456), with log-rank P = .00058 for recurrence-free survival and log-rank P = .0026 for overall survival. Conclusion Heterogeneous enhancement patterns of tumor-adjacent parenchyma at MR imaging are associated with the tumor necrosis signaling pathway and poor survival in breast cancer. © RSNA, 2017 Online supplemental material is available for this article.

miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in idiopathic pulmonary fibrosis (IPF) regulation is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 is yet to be investigated. Additionally, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual-luciferase reporter assay system were used to identify the target gene of miR-30a, and cell transfection was utilized to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and miR-30a mimic and inhibitor transfection significantly reduced and increased the TET1 protein expression, respectively. Further experimentation verified that the TET1 siRNA interference could inhibit Drp-1 promoter hydroxymethylation. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit TET1 expression through base pairing with complementary sites in the 3'untranslated region to regulate Drp-1 promoter hydroxymethylation. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Unsupervised Clustering of Quantitative Image Phenotypes Reveals Breast Cancer Subtypes with Distinct Prognoses and Molecular Pathways.

Purpose: To identify novel breast cancer subtypes by extracting quantitative imaging phenotypes of the tumor and surrounding parenchyma and to elucidate the underlying biologic underpinnings and evaluate the prognostic capacity for predicting recurrence-free survival (RFS).Experimental Design: We retrospectively analyzed dynamic contrast-enhanced MRI data of patients from a single-center discovery cohort (n = 60) and an independent multicenter validation cohort (n = 96). Quantitative image features were extracted to characterize tumor morphology, intratumor heterogeneity of contrast agent wash-in/wash-out patterns, and tumor-surrounding parenchyma enhancement. On the basis of these image features, we used unsupervised consensus clustering to identify robust imaging subtypes and evaluated their clinical and biologic relevance. We built a gene expression-based classifier of imaging subtypes and tested their prognostic significance in five additional cohorts with publically available gene expression data but without imaging data (n = 1,160).Results: Three distinct imaging subtypes, that is, homogeneous intratumoral enhancing, minimal parenchymal enhancing, and prominent parenchymal enhancing, were identified and validated. In the discovery cohort, imaging subtypes stratified patients with significantly different 5-year RFS rates of 79.6%, 65.2%, 52.5% (log-rank P = 0.025) and remained as an independent predictor after adjusting for clinicopathologic factors (HR, 2.79; P = 0.016). The prognostic value of imaging subtypes was further validated in five independent gene expression cohorts, with average 5-year RFS rates of 88.1%, 74.0%, 59.5% (log-rank P from <0.0001 to 0.008). Each imaging subtype was associated with specific dysregulated molecular pathways that can be therapeutically targeted.Conclusions: Imaging subtypes provide complimentary value to established histopathologic or molecular subtypes and may help stratify patients with breast cancer. Clin Cancer Res; 23(13); 3334-42. ©2017 AACR.

Infectious Disease Containment Based on a Wireless Sensor System.

Infectious diseases pose a serious threat to public health due to its high infectivity and potentially high mortality. One of the most effective ways to protect people from being infected by these diseases is through vaccination. However, due to various resource constraints, vaccinating all the people in a community is not practical. Therefore, targeted vaccination, which vaccinates a small group of people, is an alternative approach to contain infectious diseases. Since many infectious diseases spread among people by droplet transmission within a certain range, we deploy a wireless sensor system in a high school to collect contacts happened within the disease transmission distance. Based on the collected traces, a graph is constructed to model the disease propagation, and a new metric (called connectivity centrality) is presented to find the important nodes in the constructed graph for disease containment. Connectivity centrality considers both a node's local and global effect to measure its importance in disease propagation. Centrality based algorithms are presented and further enhanced by exploiting the information of the known infected nodes, which can be detected during targeted vaccination. Simulation results show that our algorithms can effectively contain infectious diseases and outperform other schemes under various conditions.

Changes in intestinal microflora in rats with acute respiratory distress syndrome.

AIM: To implement high-throughput 16S rDNA sequencing to study microbial diversity in the fecal matter of rats with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Intratracheal instillation of lipopolysaccharide was used to induce ALI, and the pathological changes in the lungs and intestines were observed. D-lactate levels and diamine oxidase (DAO) activities were determined by enzymatic spectrophotometry. The fragments encompassing V4 16S rDNA hypervariable regions were PCR amplified from fecal samples, and the PCR products of V4 were sequenced by Illumina MiSeq. RESULTS: Increased D-lactate levels and DAO activities were observed in the model group (P < 0.01). Sequencing results revealed the presence of 3780 and 4142 species in the control and model groups, respectively. The percentage of shared species was 18.8419%. Compared with the control group, the model group had a higher diversity index and a lower number of species of Fusobacteria (at the phylum level), Helicobacter and Roseburia (at the genus level) (P < 0.01). Differences in species diversity, structure, distribution and composition were found between the control group and early ARDS group. CONCLUSION: The detection of specific bacteria allows early detection and diagnosis of ALI/ARDS.

Analysing the relationship between lncRNA and protein-coding gene and the role of lncRNA as ceRNA in pulmonary fibrosis.

Long non-coding RNAs (lncRNAs) are involved in various pathophysiologic processes and human diseases. However, their dynamics and corresponding functions in pulmonary fibrosis remain poorly understood. In this study, portions of lncRNAs adjacent or homologous to protein-coding genes were determined by searching the UCSC genome bioinformatics database. This was found to be potentially useful for exploring lncRNA functions in disease progression. Previous studies showed that competing endogenous RNA (ceRNA) hypothesis is another method to predict lncRNA function. However, little is known about the function of ceRNA in pulmonary fibrosis. In this study, we selected two differentially expressed lncRNAs MRAK088388 and MRAK081523 to explore their regulatory mechanisms. MRAK088388 and MRAK081523 were analysed as long-intergenic non-coding RNAs (lincRNAs), and identified as orthologues of mouse lncRNAs AK088388 and AK081523, respectively. qRT-PCR and in situ hybridization (ISH) showed that they were significantly up-regulated, and located in the cytoplasm of interstitial lung cells. We also showed that MRAK088388 and N4bp2 had the same miRNA response elements (MREs) for miR-200, miR-429, miR-29, and miR-30, whereas MRAK081523 and Plxna4 had the same MREs for miR-218, miR-141, miR-98, and let-7. Moreover, the expression levels of N4bp2 and Plxna4 significantly increased in fibrotic rats, and were highly correlated with those of MRAK088388 and MRAK081523, respectively. Among their shared miRNAs, miR-29b-3p and let-7i-5p decreased in the model group, and were negatively correlated with the expression of MRAK088388 and MRAK081523, respectively. MRAK088388 and MRAK081523 could regulate N4bp2 and Plxna4 expression by sponging miR-29b-3p and let-7i-5p, respectively, and possessed regulatory functions as ceRNAs. Thus, our study may provide insights into the functional interactions of lncRNA, miRNA and mRNA, and lead to new theories for the pathogenesis and treatment of pulmonary fibrosis.

Positive network assortativity of influenza vaccination at a high school: implications for outbreak risk and herd immunity.

Schools are known to play a significant role in the spread of influenza. High vaccination coverage can reduce infectious disease spread within schools and the wider community through vaccine-induced immunity in vaccinated individuals and through the indirect effects afforded by herd immunity. In general, herd immunity is greatest when vaccination coverage is highest, but clusters of unvaccinated individuals can reduce herd immunity. Here, we empirically assess the extent of such clustering by measuring whether vaccinated individuals are randomly distributed or demonstrate positive assortativity across a United States high school contact network. Using computational models based on these empirical measurements, we further assess the impact of assortativity on influenza disease dynamics. We found that the contact network was positively assortative with respect to influenza vaccination: unvaccinated individuals tended to be in contact more often with other unvaccinated individuals than with vaccinated individuals, and these effects were most pronounced when we analyzed contact data collected over multiple days. Of note, unvaccinated males contributed substantially more than unvaccinated females towards the measured positive vaccination assortativity. Influenza simulation models using a positively assortative network resulted in larger average outbreak size, and outbreaks were more likely, compared to an otherwise identical network where vaccinated individuals were not clustered. These findings highlight the importance of understanding and addressing heterogeneities in seasonal influenza vaccine uptake for prevention of large, protracted school-based outbreaks of influenza, in addition to continued efforts to increase overall vaccine coverage.

All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by downregulating the TGF-ß1/Smad3 signaling pathway in rats.

The transforming growth factor-ß1 (TGF-ß1)/Smad3 signaling pathway has a central role in pathogenesis of lung fibrosis. In the present study, we investigated if all-trans retinoic acid (ATRA) could attenuate fibrosis in bleomycin (BLM)-induced lung fibrosis in rats through regulating TGF-ß1/Smad3 signaling. Beginning on day 14 after BLM administration, the ATRA I and II groups of rats received daily oral administration of ATRA for 14 days. All rats were killed on day 28. Lung tissue sections were prepared and subject to histological assessment, and expression levels of proteins involved in the TGF-ß1 signaling cascade and epithelial-mesenchymal transition (EMT) were evaluated by transmission electron microscopy (TEM), quantitative real-time polymerase chain reaction (qRT-PCR), western blot procedure, and immunohistochemical or immunofluorescence staining. BLM significantly increased the alveolar septum infiltrates, inflammatory cell infiltrates, and collagen fibers. These BLM-induced changes were significantly ameliorated by ATRA treatment. In addition, BLM significantly increased levels of lung fibrosis markers α-SMA, hydroxyproline (Hyp), collagen I, Snail, and Twist, whereas significantly decreased E-cadherin expression. ATRA treatment largely reversed BLM-induced changes in these lung fibrosis markers. ATRA also blocked BLM-induced activation of the TGF-ß1/Smad3 signaling pathway in lung tissues, including expression of TGF-ß1, Smad3, p-Smad3, zinc-finger E-box-binding homeobox 1 and 2 (ZEB1 and ZEB2), and the high-mobility group AT-hook 2 (HMGA2). Our results suggest that ATRA may have potential therapeutic value for lung fibrosis treatment.

Differential expression of long non-coding RNAs in bleomycin-induced lung fibrosis.

Recent studies suggest that long non­coding RNAs (lncRNAs) are more involved in human diseases than previously realized. A growing body of evidence links lncRNA mutation and dysregulation to diverse human diseases. However, the association of lncRNAs with the pathogenesis of lung fibrosis remains poorly understood. In this study, we detected changes in hydroxyproline and collagen levels, as well as the ultrastructure of lung tissue to develop a rat model of lung fibrosis. The differentially expressed lncRNAs and mRNA profiles between fibrotic lung and normal lung tissue were analyzed using microarrays. Gene Ontology analysis and pathway analysis were performed for further research. Two differentially expressed lncRNAs, namely, AJ005396 and S69206, were detected by in situ hybridization to validate the microarray data. The results revealed that the number of collagen fibers in the interstitial lung tissue significantly increased in the model group compared with the normal group. In total, 210 and 358 lncRNAs were upregulated and downregulated, respectively, along with 415 upregulated and 530 downregulated mRNAs in the rats with lung fibrosis. AJ005396 and S69206 were upregulated in the fibrotic lung tissue, consistent with the microarray data, and were located in the cytoplasm of the interstitial lung cells. In conclusion, the expression profile of the lncRNAs was significantly altered in the fibrotic lung tissue and these transcripts are potential molecular targets for inhibiting the development of lung fibrosis.