Combinatorial Chemistry & High Throughput Screening - Volume 22, Issue 4, 2019

Objective: Lung cancer is the most prevalent cancer in the world, and lung adenocarcinoma is the most common lung cancer subtype. Identification and determination of relevant prognostic markers are the key steps to personalized cancer management. Methods: We collected the gene expression profiles from 265 tumor tissues of stage I patients from The Cancer Genome Atlas (TCGA) databases. Using Cox regression model, we evaluated the association between gene expression and the overall survival time of patients adjusting for gender and age at initial pathologic diagnosis. Results: Age at initial pathologic diagnosis was identified to be associated with the survival, while gender was not. We identified that 15 genes were significantly associated with overall survival time of patients (FDR < 0.1). The 15-mRNA signature- based risk score was helpful to distinguish patients of high-risk group from patients of low-risk group. Conclusion: Our findings reveal novel genes associated with lung adenocarcinoma survival and extend our understanding of how gene expression contributes to lung adenocarcinoma survival. These results are helpful for the prediction of the prognosis and personalized cancer management.

Background: Assisted reproductive techniques (ART) have been extensively used to treat infertility. Inaccurate prediction of a couple’s fertility often leads to lowered self-esteem for patients seeking ART treatment and causes fertility distress. Objective: This prospective study aimed to statistically analyze patient data from a single reproductive medical center over a period of 18 months, and to establish mathematical models that might facilitate accurate prediction of successful pregnancy when ART are used. Methods: In the present study, we analyzed clinical data prospectively collected from 760 infertile patients visiting the second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University between June 1, 2016 and December 31, 2017. Various advanced statistical methods, including broken-line regression, were employed to analyze the data. Results: Age remained the most important factor affecting the outcome of IVF/ICSI. Using the broken-line regression model, the fastest clinical pregnancy declining age was between 25 and 32. Female infertility type was found to be a key predictor for the number of good-quality embryos and successful pregnancy, along with the antral follicle count (AFC), total number of embryos, recombinant follicle stimulating hormones (rFSH) dosage, estradiol (E2) on the trigger day, and total number of oocytes retrieved. rFSH dosage was also significantly associated with the number of oocytes retrieved and the number of frozen embryos. Conclusion: The fastest clinical pregnancy declining age is ranged between 25 and 32, and female infertility type is evidenced as another key predictive factor for the cumulative outcome of ART.

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

Aims and Objective: A new library of resveratrol derivatives was designed and synthesized in excellent yield via two-step reaction utilizing Vilsmeier reaction as the first step and subsequent addition of substituted aromatic amine in the second step. Methods: Synthesized compounds were investigated for their antioxidant as well as for in vitro inhibition activity against jack bean urease enzyme. Compounds R3b and R4 with IC50 value 18.85±0.15 and 21.60±0.19μM against urease enzyme and 6.01±0.07 and 7.52±0.14μM in vitro- DPPH free radical scavenging activity have emerged as most active molecules from the selected library. Molecular simulation studies were also carried out for determining the interaction detail of newly synthesized compounds within a protein pocket. Results and Conclusion: Newly synthesized compounds were found to possess better docking score (-5.941 to -6.894) and binding energy (-46.854 to -56.455) as compared to the parent resveratrol (-5.45 and -20.155) which revealed that the newly synthesized compounds bind in a better way as compared to the parent molecule.

Aim and Objective: Lung cancer is a disease with a dismal prognosis and is the major cause of cancer deaths in many countries. Nonetheless, rapid technological developments in genome science guarantees more effective prevention and treatment strategies. Materials and Methods: In this study, genes were pair-matched and screened for lung adenocarcinomaspecific gene relationships. False positives due to fluctuations in single gene expression were avoided and the stability and accuracy of the results was improved. Results: Finally, a deep learning model was constructed with machine learning algorithm to realize the clinical diagnosis of lung adenocarcinoma in patients. Conclusion: Comparing with the traditional methods which takes ingle gene as a feature, the relative difference between gene pairs is a higher order feature, leverage high-order features to build the model can avoid instability caused by a single gene mutation, making the prediction results more reliable.

Objective: A significant proportion of patients with early non-small cell lung cancer (NSCLC) can be cured by surgery. The distant metastasis of tumors is the most common cause of treatment failure. Precisely predicting the likelihood that a patient develops distant metastatic risk will help identify patients who can further intervene, such as conventional adjuvant chemotherapy or experimental drugs. Methods: Current molecular biology techniques enable the whole genome screening of differentially expressed genes, and rapid development of a large number of bioinformatics methods to improve prognosis. Results: The genes associated with metastasis do not necessarily play a role in the pathogenesis of the disease, but rather reflect the activation of specific signal transduction pathways associated with enhanced migration and invasiveness. Conclusion: In this study, we discovered several genes related to lung cancer resistance and established a risk model to predict high-risk patients.

Background: Intrahepatic Biliary Cystadenoma (IBC) is rare but has a high incidence of misdiagnosis, especially for experienceless surgeons. Case: We report a case of IBC located in the caudate lobe and described a typical procedure of misdiagnosing this disease. Finally, the patient was successfully cured, but the procedure of misdiagnosis should attract attention. IBC and atypical biopsy for histological examination are the most important causes of misdiagnosis. Recurrent cystic lesions of the liver and repeated increases in CA 19-9 may suggest a "liver cyst", which is a misdiagnosis. Conclusion: The experience and lessons of misdiagnosis, in this case, may help other clinicians diagnose the rare disease accurately.

Background: Patients with pancreatic adenocarcinoma may develop into duodenal obstruction during the course of their disease. The diagnosis of obstruction can be generally achieved by means of imaging technologies. Case and Outcome: We reported a rare case of pancreatic tumor with duodenal obstruction accompanied by obstructive symptoms, which was finally confirmed by laparotomy. A 68-year-old man was admitted to our department with a 3-day medical history of upper abdominal pain, nausea and vomiting. The diagnosis of duodenal obstruction was established by means of various imagings including computed tomography (CT) scan, gastroscopy and upper gastrointestinal imaging. Upper gastrointestinal imaging and magnetic resonance imaging (MRI) showed extrinsic tumor mass was noted at the second and third portion of the duodenum accompanied by duodenal obstruction and dilatation, respectively. Laparotomy confirmed a tumor mass arising from the head and uncinate process of pancreas, which had invaded the second and third portions of the duodenum and caused closed loop obstruction. A pancreaticoduodenectomy (Whipple procedure) was performed followed by therapeutic trade-off according to intraoperative exploration. Postoperative histopathology revealed pancreatic tumor only infiltrated duodenal wall, while resection margins of pancreas, common bile duct and duodenum were all negative. The patient was cured and discharged home 12 days after surgery. Conclusion: The present case indicated radical operation in our study appeared to be the first choice treatment for patients with malignant duodenal obstruction.