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Background Long non-coding RNAs (lncRNAs) have been consistently reported to be involved in the progression of non-small cell lung cancer (NSCLC). In this study, we aimed to identify aberrantly expressed lncRNAs in NSCLC, in order to explore new therapeutic targets for NSCLC. Methods Two pairs of NSCLC and adjacent normal tissues were first analyzed by RNA sequencing. The expressions of LINC00702 in 40 pairs patient samples and in 4 NSCLC cell lines was measured by quantitative real-time PCR. Putative target miRNAs of LINC00702 were predicted by the bioinformatics tools. The effect of LINC00702 on tumor growth in vivo was evaluated. Results LINC00702 was significantly down-regulated in patients with NSCLC, which was correlated with tumor size and metastasis. In addition, overexpression of LINC00702 markedly suppressed proliferation and metastasis in NSCLC cells via inducing apoptosis in vitro and in vivo. Moreover, bioinformatics and luciferase reporter assays demonstrated that LINC00702 functioned as a competing endogenous RNA (ceRNA) for miR-510 in NSCLC, and upregulated its target gene PTEN. Conclusion Our results indicated that LINC00702 modulated the expression of PTEN gene by acting as a ceRNA for miR-510 in NSCLC. Therefore, LINC00702 may serve as a potential target for the diagnosis and treatment of patients with NSCLC.

Background: The global COVID-19 epidemic remains severe, with the cumulative global death toll reaching more than 207,170 as of May 2, 2020 (1). Purpose: Our research objective is to establish a reliable nomogram to predict mortality in COVID-19 patients. The nomogram can help us distinguish between patients who are at high risk of death and need close attention. Patients and Methods: For the single-center retrospective study, we collected 21 cases of patients who died in the critical illness area of the Optical Valley Branch of Tongji Hospital, Huazhong University of Science and Technology, from February 9 to March 10. Additionally, we selected 99 patients discharged during this period for analysis. The nomogram was constructed to predict the mortality for COVID-19 patients using the primary group of 120 patients and was validated using an independent cohort of 84 patients. We used multivariable logistic regression analysis to construct the prediction model. The nomogram was evaluated for calibration, differentiation, and clinical usefulness. Results: The predictors included in the nomogram were c-reactive protein, PaO2/FiO2, and cTnI. The areas under the curves of the nomogram were 0.988 (95% CI: 0.972–1.000) and 0.956 (95% CI, 0.874–1.000) in the primary and validation groups, respectively. Decision curve analysis suggests that the nomogram may have clinical usefulness. Conclusion: This study provides a nomogram containing c-reactive protein, PaO2/FiO2, and cTnI that can be conveniently used to predict individual mortality in COVID-19 patients. Next, we will collect as many cases as possible from multiple centers to build a more reliable nomogram to predict mortality for COVID-19 patients.

In spite of the unique advantages of minimally invasive treatment, laparoscopic surgery is not recommended in T4 colon cancer patients with the concern of technical feasibility and suboptimal oncologic outcomes. We used the database of our center to reevaluate laparoscopic surgery's value in T4 colon cancer and compared with open surgery in both short- and long-term outcomes.We conducted a retrospective and propensity score-matched study of pathological T4 colon cancer patients who received laparoscopic surgery or open surgery from March 2011 to August 2015.A total of 411 pathological T4 colon cancer patients were identified. Propensity score matching (PSM) resulted in 86 patients in laparoscopic group and 86 patients in open group. Our study showed longer operation time, less blood loss and less length of postsurgical stay compared with open surgeries (167 ± 56 min vs. 111 ± 50.1 min, P 0.001; 72 ± 61.5 mL vs. 113 ± 113.9 mL, P = 0.004; 7.3 ± 2.1 days vs. 7.9 ± 2.1 days, P = 0.046, respectively). 7 (8.2%) patients underwent conversions to open surgery. 5-years of DFS and OS showed no statistic difference between the two groups. The 1-, 3-, and 5-years OS rates were 89.4%, 77.5% and 73.2% for laparoscopic surgery and 95.2%, 82.7% and 73.9% for open surgery (P = 0.618). The 1-, 3-, and 5-years OS rates were 89.5%, 77.2% and 61.7% for laparoscopic surgery and 91.7%, 75.3% and 66.8% for open surgery (P = 0.903).Our analysis demonstrates that there is no statistic difference in short- and long-oncologic outcomes in our center and it is a reliable evidence to support the clinical application of laparoscopic surgery in T4 colon cancer patients. Still, considering the lack of randomized controlled trails, conducting large prospective multi-center population-based studies is not only required, but also pressing.

The present study investigated the intervention efficacies of rosiglitazone (ROS) and retinoin (RET) on bleomycin-induced pulmonary fibrosis in rats. A total of 48 rats were randomly divided into the control group (group C), the model group (group M), the dexamethasone group (group D), the ROS group (group R), the RET group (group W) and the ROS + RET group (group L). Group M and the treatment groups were intratracheally injected with 5 mg/kg bleomycin, while group C was injected with saline. The lungs of rats in each group were inspected using high resolution computed tomography (HRCT), lung tissue hematoxylin and eosin staining and Masson staining; furthermore, lung L-hydroxyproline (Hyp) content and the concentration of transforming growth factor β1 (TGF-β1) serum of each group were also determined. The fibrosis score, Hyp content and TGF-β1 concentration of each treatment group were significantly lower when compared with group M (P0.05). Findings from the present study conclude that ROS and RET are able to suppress bleomycin-induced pulmonary fibrosis with improved efficacies when compared with dexamethasone; furthermore, the combination of these two pharmacological agents may exert synergistic effects.

Objective. To investigate the role of CXXC5 and the CD40/CD40L pathway in lung fibrosis. Methods. (1) We constructed mouse models of bleomycin-induced pulmonary fibrosis and transfected them with a CXXC5 overexpression vector to evaluate the severity of pulmonary fibrosis. (2) Mouse lung fibroblast (MLF) models stably overexpressed or knockout of CXXC5 vector were constructed. After transforming growth factor-β1 (TGF-β1) stimulation, we examined the proliferation and apoptosis of the MLF model and evaluated the expression of mesenchymal markers and the CXXC5/CD40/CD40L pathway. Results. (1) Compared with other groups, the overexpressed CXXC5 group had less alveolar structure destruction, thinner alveolar septum, and lower Ashcroft score. (2) In bleomycin-induced mice, the expression of CD40 and CD40L increased at both transcriptional and protein levels, and the same changes were observed in α-smooth muscle actin (α-SMA) and collagen type I (Colla I). After upregulation of CXXC5, the increase in CD40, CD40L, α-SMA, and Colla I was attenuated. (3) Stimulated with TGF-β1, MLF proliferation was activated, apoptosis was suppressed, and the expression of CD40, CD40L, α-SMA, and Colla I was increased at both transcriptional and protein levels. After upregulation of CXXC5, these changes were attenuated. Conclusion. CXXC5 inhibits pulmonary fibrosis and transformation to myofibroblasts by negative feedback regulation of the CD40/CD40L pathway.

Context: Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown. Objective: This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF. Materials and methods: Rat IPF model was established by endotracheal injection of 5 mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100 mg/kg once daily), prednisone (H, 5 mg/kg once daily) and acetylcysteine (N, 4 mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay. Results: After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p

Increasing evidence indicates that inflammation plays a vital role in tumorigenesis and progression. However, the prognostic value of inflammatory biomarkers in colorectal cancer (CRC) has not been established. In this study, a retrospective analysis was conducted in patients with CRC in Fudan University Shanghai Cancer Center (FUSCC) between April 1, 2007 and April 30, 2014, and 5,336 patients were identified eligible. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and albumin/globulin ratio (AGR) were analyzed. Kaplan-Meier analysis was used to calculate the 5-year overall survival (OS) and disease-free survival (DFS). Cox regression analysis was performed to assess the prognostic factors. Nomograms were established to predict OS and DFS, and Harrell's concordance index (c-index) was adopted to evaluate prediction accuracy. As results, the 5-year OS was 79.2% and the 5-year DFS was 56.0% in the cohort. Patients were stratified into 2 groups by NLR (≤2.72 and >2.72), PLR (≤219.00 and >219.00), LMR (≤2.83 and >2.83) and AGR ( 2.72, PLR > 219.00, LMR ≤ 2.83 and AGR

3062 Background: With the proven success of PD-1 and PD-L1 monoclonal antibodies, exploiting antibody based immune checkpoint strategies has potential to reduce disease burden and improve patient survival outcome. IBI318, as a first-in-class anti-PD-1/PD-L1 bispecific antibody, could provide more potent anti-tumor activity and more durable response. Here we report preliminary results from an ongoing phase 1a/1b study of IBI318 in advanced tumors. Methods: In the dose escalation of Phase 1a, patients with advanced and/or refractory solid tumors or hematological malignancies were enrolled to receive IBI318. Dose escalation was from 0.3 mg to 600 mg (8 cohorts) via an accelerated titration followed by a modified toxicity probability interval-2 design with a 28-day dose-limiting toxicity (DLT) observation period. Patients without DLT will receive IBI318 every two week (Q2W). Tumor assessments were performed every 6 weeks. Results: As of Jan 10, 2020, 15 pts who had failed at least one line of treatment had been enrolled (1 pt each in 0.3 mg, 1 mg, 3 mg and 10 mg; 3 pts in 30 mg; 3 pts in 100 mg, 3 pts in 300 mg and 2 pts in 600 mg) for dose escalation and received at least 1 dose of treatment. Median duration of treatment was 6.1 (range: 2.1-24.7) weeks. IBI318 had been well tolerated with no DLT from 0.3mg to 300mg group. 11 of 15 pts had treatment related AEs (TRAEs) and the most common (≥10%) TRAEs were pyrexia (20.0%, G1/2) and infusion-related reaction (20.0%, G1/2). 1 patient in 300 mg had an immune-related AE (G2 arthritis). No ≥G3 TRAE had been observed. 12 pts had at least one on-study tumor assessment. 3 of 9 pts receiving dose level ≥10mg had achieved partial response (1 confirmed, 1 pending confirmation and the other PD after the first PR scan). A total of 10 pts discontinued treatment due to disease progression (8) and AE (2, G4 lung infection and G4 upper gastrointestinal hemorrhage, both were not related to treatment). Conclusions: IBI318 has shown an acceptable safety profile. Preliminary efficacy results are promising in advanced cancer patients. The study is currently ongoing at dose level of 600 mg Q2W. Clinical trial information: NCT03875157 .

The aim of the present study was to investigate whether the expression of tribbles pseudokinase 3 (TRB3) is involved in pulmonary interstitial fibrosis and to examine the possible mechanisms. The expression of TRB3 in murine alveolar type II epithelial cells (MLE‑12 cells) following transforming growth factor β1 (TGF‑β1) stimulation was assessed using various techniques, including western blot and reverse transcription‑quantitative polymerase chain reaction assays. TRB3 overexpression and downregulation models were used to evaluate the impact of TRB3 on the TGF‑β1‑induced epithelial‑mesenchymal transition (EMT) of MLE‑12 cells. The downregulation of TRB3 was induced by RNA interference. The expression of TRB3 was significantly increased in MLE‑12 cells following the activation of TGF‑β1 (P

Background To assess the level of asthma control achieved with budesonide/formoterol in Chinese patients with asthma, based on the Global Initiative for Asthma (GINA) definition and Asthma Control Test (ACT) score. Methods This multicenter, cross-sectional study (NCT01785901) evaluated asthma control levels in Chinese patients receiving physician-prescribed budesonide/formoterol treatment. Adults with a diagnosis of asthma ≥6 months and receiving budesonide/formoterol treatment ≥3 months before screening were consecutively enrolled. Data including medical and medication history were collected using face-to-face questionnaires and physical examinations during a single visit. Results A total of 1483 asthma out-patients from 27 medical centers were enrolled; 217 (14.6%) were treated with budesonide/formoterol using a fixed-dose strategy and 1266 (85.4%) with the SMART (Symbicort ® Maintenance And Reliever Therapy) strategy. According to GINA criteria, asthma was controlled in 58.6% (95% CI: 56.1%–61.1%) of patients and was either controlled or partly controlled in 94.1% (95% CI: 92.8%–95.3%) of patients. According to ACT score, asthma was completely controlled in 22.4% (95% CI: 20.3%–24.6%) of patients and was either completely or well controlled in 83.3% (95% CI: 81.4%–85.2%) of patients. Multivariate logistic regression analysis revealed that a >5-year history of asthma and an age of >50 years were factors associated with lower levels of asthma control. Conclusions This study demonstrated high levels of asthma control (GINA: controlled and partly controlled and ACT: completely and well controlled) in Chinese patients with asthma treated with budesonide/formoterol. Greater age and a longer disease history were associated with lower levels of asthma control. Trial registration ClinicalTrials.govNCT01785901. Registered February 5, 2013.

The aim of the present study was to investigate the impact of N‑acetylcysteine (NAC) on the expression of reduced nicotinamide adenine dinucleotide phosphate oxidase 1 (Nox1), and the proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) in rats exhibiting monocrotaline (MCT)‑induced pulmonary hypertension, and to investigate the possible mechanisms and treatment roles of NAC in pulmonary vascular remodeling (PVR). A total of 18 Wistar rats were randomly divided into three groups: The control (C) group; the MCT (M) group; and the NAC (N) group. The right ventricular hypertrophy index (RVHI) and other indicators were recorded 6 weeks subsequently. Groups C and M were divided into two subgroups: Groups C1 and M1 (control); and group C2 and M2 group (treated with ML171). Group N was not sub‑divided. PASMCs were isolated, and the vascular remodeling and Nox1 positioning were observed. The expression of Nox mRNA in each group, and the proliferation, apoptosis, and superoxide dismutase (SOD) activity of PASMCs, prior to and following the ML171 treatment, were measured. NAC was able to decrease RVHI and other indicators (P

The aim of the present study was to investigate the effect of pirfenidone on bleomycin-induced lung fibrosis in rats, in order to elucidate the underlying mechanism of periostin-induced fibrosis. The lung fibrosis model was constructed using a single intratracheal instillation of bleomycin in rats. The normal rats without bleomycin administration were used as controls (n=24). Bleomycin-treated rats were randomized into the model (M) or pirfenidone (P) group (n=24 per group). Rats were sacrificed on days 7, 14 and 28 following treatment. Hematoxylin-eosin and Masson's trichrome staining were performed to analyze pulmonary alveolitis and fibrosis. Periostin location was detected by immunohistochemistry. Hydroxyproline content, and expression of periostin and transforming growth factor (TGF)-β1 were detected by ELISA, reverse transcription-quantitative polymerase chain reaction or western blotting. Correlation of periostin expression with hydroxyproline and TGF-β1 content was also analyzed. Histological findings demonstrated that pirfenidone significantly inhibited bleomycin-induced lung fibrosis and reduced the hydroxyproline content on day 14 and day 28 compared with the model group (P