Combinatorial Chemistry & High Throughput Screening - Volume 21, Issue 10, 2018

The association between vitamin D receptor (VDR) genetic polymorphism and lung cancer risk has been evaluated by the previous meta-analyses. Due to the emergence of novel studies and inappropriate inclusion of overlapping populations, an updated meta-analysis on recent evidences is necessarily needed. We comprehensively searched databases of PubMed, Web of Science and Chinese National Knowledge Infrastructure and finally obtained 7 eligible studies according to the inclusion criteria. Four positions on VDR gene, namely ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810) and TaqI (rs731236), were considered in this investigation. Data pooling found no significant association of lung cancer risk with ApaI or FokI. In contrast, it was indicated that the BsmI A allele was negatively related to the lung cancer risk, compared with the G allele (OR = 0.51, 95% CI = 0.33-0.79). Individuals with BsmI AA (OR = 0.53, 95% CI = 0.26-1.11) and AG genotypes (OR = 0.46, 95% CI = 0.30−0.71) showed decreased risk of lung cancer, compared with those of GG genotype. Regarding the TaqI polymorphism, the T allele carriers were at increased risk of lung cancer (OR = 1.25, 95% CI = 1.04-1.50). Compared with the TaqI TC+CC genotype, the TT genotype was positively associated with lung cancer risk (OR = 1.42, 95% CI = 1.11-1.82). No publication bias was identified in any of the analysis. In conclusion, VDR genetic polymorphism may be correlated to lung cancer risk. Given limited number of the included studies, more observations are warranted to draw a safer conclusion.

Background: Patients with previously treated non-small-cell lung cancer (NSCLC) have limited treatment options. A novel treatment based on programmed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors has emerged as promising therapeutic options for advanced NSCLC. We assessed oncological outcomes of PD-L1 antibody versus docetaxel in previously treated NSCLC. Objectives: The purpose of this meta-analysis was to analyse the oncological outcomes of anti-PD1 to chemotherapy in the treatment of non-small-cell lung cancer. Results: Overall survival (OR=0.68,95%CI=0.61-0.75, P<0.00001) and progression-free survival (OR=0.84,95%CI=0.77-0.92, P=0.0002) were longer with anti-PD1 than with docetaxel in NSCLC. Anti-PD1 was associated with even greater objective response rate than docetaxel (OR=1.61,95%CI=1.16-2.24, P=0.004). Treatment-related adverse events of grade 3-5 did favor anti-PD1 over docetaxel (OR=0.21,95%CI=0.10-0.42, P<0.00001). Conclusions: Among patients with advanced NSCLC, we found that there was a superior survival benefit and with a favorable safety profile with anti-PD1 than with docetaxel. More large-scale randomized controlled trials are needed to identify relevant biomarkers that have an effect on predicting the population that would most likely benefit from PD-1/PD-L1 for pretreated advanced NSCLC patients.

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

Background: Circulating endothelial progenitor cells (EPCs) have regenerative capacities and play an important role in vessel wall homeostasis. When attracted to the site of vessel wall injury, EPCs rapidly differentiate into a functional layer as part of the healing process. The Genous TM endothelial progenitor cell (EPC) capturing stent is coated with anti-human CD34+ antibodies which combine with circulating EPCs from the peripheral blood to the stent surface. Objective: This meta-analysis aims to explore the Genous TM endothelial progenitor cell capturing stent in coronary artery disease (CAD) adverse event rate after one-year follow-up. Methods: PubMed, EMBASE and, Google Scholar databases were searched for eligible studies. CAD survival data and clinicopathological features were analyzed by expected shortfall (ES) and 95% CI. Fixed-effect model and random-effect model are used for summary statistics. Results: 12 studies, including 15985 coronary artery disease (CAD) patients who received PCI treatment were included in this study. After 1-year follow-up, the rate of adverse event showed that the target vessel failure (TVF) was 8.5% (7.6%-17.4%), target vessel revascularization was 4.1% (TVR, 0-15.6%), target lesion revascularization was 4.2% (TLR, 3.7%-22%), myocardial infarction was 2.0% (MI, 1.8%-5.2%), major adverse cardiac events was 8.7% (MACE, 6.4%-28%), and the all-cause death was 4.0% (0-9.2). Conclusion: After one-year follow-up, the incidence rate of Genous stent adverse events was stable in CAD patients. The study showed a better evaluation of Genous stent, and it provides a better reference for CAD clinical treatment.

Aim and Objective: Lung cancer is a highly heterogeneous cancer, due to the significant differences in molecular levels, resulting in different clinical manifestations of lung cancer patients there is a big difference. Including disease characterization, drug response, the risk of recurrence, survival, etc. Method: Clinical patients with lung cancer do not have yet particularly effective treatment options, while patients with lung cancer resistance not only delayed the treatment cycle but also caused strong side effects. Therefore, if we can sum up the abnormalities of functional level from the molecular level, we can scientifically and effectively evaluate the patients' sensitivity to treatment and make the personalized treatment strategies to avoid the side effects caused by over-treatment and improve the prognosis. Result & Conclusion: According to the different sensitivities of lung cancer patients to drug response, this study screened out genes that were significantly associated with drug resistance. The bayes model was used to assess patient resistance.

Aim: To analyze the clinical characteristics and antibiotic resistance of Mycoplasma pneumoniae pneumonia (MP) in Chinese patients, providing valuable information for the management of patients with MP. Methods: A total of 120 children who were hospitalized in The First Hospital of Huzhou between January and December 2016 for respiratory tract infection due to M. pneumoniae were enrolled in this study. Infection with M. pneumoniae was confirmed by ELISA for M. pneumoniae antibody, PCR, and throat culture. Antibiotic resistance was measured from the minimum inhibitory concentrations (MICs) of antibiotics. The 23S rRNA gene of M. pneumoniae was also examined for mutations using DNA sequencing. Patients with MP were classified into antibiotic resistance (n = 98) and no resistance (n = 20) groups. For the 98 patients showing antibiotic resistance, they were further stratified into subgroups based on the antibiotics initially prescribed: azithromycin or erythromycin (n = 78) and cephalosporin or penicillin (n = 20). Clinical characteristics were compared between the patient groups. Results: Antibiotic resistance group presented significantly longer febrile days compared to the no resistance group (P = 0.007). The number of febrile days after macrolide treatment was also longer in antibiotic resistance group than in no resistance group (P = 0.042). MP patients initially treated with azithromycin or erythromycin showed a longer average duration of respiratory symptoms (P = 0.046) and had a fever for more days after macrolide treatment (P = 0.009) compared to those received cephalosporin or penicillin. The average white blood cell count of patients treated with azithromycin or erythromycin was nearly half of those treated with cephalosporin or penicillin (P < 0.001). Nearly 90% of the resistant M. pneumoniae strains showed A to G substitution at position 2063 of the 23S rRNA gene. Conclusion: The clinical characteristics and antibiotic resistance of MP were analyzed in 120 Chinese patients. DNA sequencing revealed a highly prevalent A2063G mutation in the 23S rRNA gene.

Objective: To determine the levels of α-1 acid glycoprotein (ORM1) in the sera of advanced lung adenocarcinoma (LUAD) patients with epidermal growth factor receptor (EGFR) mutation before treatment and after acquirement of EGFR tyrosine kinase inhibitor (EGFR-TKI) resistance, and to explore the clinical cut off value of ORM1 for targeted therapy resistance in LUAD. Methods: Enzyme-linked immunosorbent assay was used to determine serum ORM1 levels. Receiver operating characteristic curve was applied to evaluate the serum ORM1 level in the resistance of EGFR-TKI and the cut off value of ORM1 for the diagnosis of EGFR-TKI resistance. Results: The serum ORM1 concentrations in the healthy group, before and after drug resistance were 1.687 ± 0.103, 1.868 ± 0.101, and 1.731 ± 0.088 μg/ml, respectively. The serum ORM1 concentrations before and after drug resistance were higher than that of the healthy group, whereas the serum ORM1 concentrations in the resistant group were lower than those before drug treatment. In comparison to healthy group, the area under curve (AUC) of the serum ORM1 concentration was 0.918 ± 0.029 with sensitivity of 90.5% and specificity of 78.6% in the patient before EGFR-TKI treatment, while the AUC was 0.644 ± 0.062 with sensitivity of 69.0% and specificity of 66.7% in the resistance group. When compared to those before treatment, the AUC of serum ORM1 concentration was 0.880 ± 0.038 with a sensitivity of 92.9% and specificity of 73.8% in the resistance group. The cutoff value of serum ORM1 was 1.778 μg/ml for advanced EGFR-positive LUAD and 1.723 μg/ml after resistance to EGFR-TKI. Conclusion: Serum ORM1 has an important diagnostic value for the diagnosis of EGFR-positive LUAD and EGFR-TKI resistance in patients especially with advanced EGFR-positive LUAD. Our findings suggest that serum ORM1 is a biomarker in the prediction of EGFR-TKI resistance in EGFR-positive LUAD.

Background: Cereal hull color is an important quality specification characteristic. Many studies were conducted to identify genetic changes underlying cereal hull color diversity. However, these studies mainly focused on the gene level. Recent studies have suggested that metabolomics can accurately reflect the integrated and real-time cell processes that contribute to the formation of different cereal colors. Methods: In this study, we exploited published metabolomics databases and applied several advanced computational methods, such as minimum redundancy maximum relevance (mRMR), incremental forward search (IFS), random forest (RF) to investigate cereal hull color at the metabolic level. First, the mRMR was applied to analyze cereal hull samples represented by metabolite features, yielding a feature list. Then, the IFS and RF were used to test several feature sets, constructed according to the aforementioned feature list. Finally, the optimal feature sets and RF classifier were accessed based on the testing results. Results and Conclusion: A total of 158 key metabolites were found to be useful in distinguishing white cereal hulls from colorful cereal hulls. A prediction model constructed with these metabolites and a random forest algorithm generated a high Matthews coefficient correlation value of 0.701. Furthermore, 24 of these metabolites were previously found to be relevant to cereal color. Our study can provide new insights into the molecular basis of cereal hull color formation.

Aim and Objective: Integrating multi-omics data to identify driver genes and key biological functions for tumorigenesis remains a major challenge. Method: A new computational pipeline was developed to identify the Driver Mutation-Differential Co-Expression (DM-DCE) modules based on dysfunctional networks across 11 TCGA cancers. Results: Functional analyses provided insight into the properties of various cancers, and found common cellular signals / pathways of cancers. Furthermore, the corresponding network analysis identified conservations or interactions across different types of cancers, thus the crosstalk between the key signaling pathways, immunity and cancers was found. Clinical analysis also identified key prognostic / survival patterns. Conclusion: Taken together, our study sheds light on both cancer-specific and cross-cancer characteristics systematically.

Background: Transverse colostomy is commonly performed to create temporary stoma in rectal cancer patients after neoadjuvant chemoradiotherapy. Conventional methods are either difficult to implement or to care for. To resolve these problems, we herein describe a modified transverse colostomy method. Material and Methods: Two sutures of peritoneum were made as “bridges” to support the stoma. Absorbable sutures were utilized to reinforce the stoma. Once the stoma was created, the stoma bag was immediately placed on the skin. 120 patients who received conventional or modified transverse colostomy between 2008 and 2014 were selected. Then, the two groups of patients were compared for stoma-related complications. Results: The operation time of stoma construction was 34±10 minutes for the conventional method and 28±7 minutes for the modified method (P= 0.009). There were no significant differences between the two groups with respect to postoperative bleeding, bowel obstruction or stoma retraction. Patients with conventional transverse colostomy were remarkably more likely to experience parastoma hernia (P= 0.048) and stoma prolapse (P= 0.038). Conclusion: In comparison with conventional methods, the modified transverse colostomy is a safe and effective diverting technique. It can be readily performed by all kinds of surgeons, especially those in underdeveloped areas. The technique represents a preferred method for constructing temporary stoma in rectal cancer patients treated with neoadjuvant chemoradiotherapy.

Aim and Objective: There are several diseases having a complicated mechanism. For such complicated diseases, a single drug cannot treat them very well because these diseases always involve several targets and single targeted drugs cannot modulate these targets simultaneously. Drug combination is an effective way to treat such diseases. However, determination of effective drug combinations is time- and cost-consuming via traditional methods. It is urgent to build quick and cheap methods in this regard. Designing effective computational methods incorporating advanced computational techniques to predict drug combinations is an alternative and feasible way. Method: In this study, we proposed a novel network embedding method, which can extract topological features of each drug combination from a drug network that was constructed using chemical-chemical interaction information retrieved from STITCH. These topological features were combined with individual features of drug combination reported in one previous study. Several advanced computational methods were employed to construct an effective prediction model, such as synthetic minority oversampling technique (SMOTE) that was used to tackle imbalanced dataset, minimum redundancy maximum relevance (mRMR) and incremental feature selection (IFS) methods that were adopted to analyze features and extract optimal features for building an optimal support machine vector (SVM) classifier. Results and Conclusion: The constructed optimal SVM classifier yielded an MCC of 0.806, which is superior to the classifier only using individual features with or without SMOTE. The performance of the classifier can be improved by combining the topological features and essential features of a drug combination.

Background: Hemolymphangioma is a rare benign tumor. To the best of our knowledge, there were only 10 reports of this tumor of the pancreas until March 2018. Case Report: Here, we reported a large invasive hemolymphangioma of the pancreas in a young woman with a complaint of abdominal distension and an epigastric mass about 3 weeks. She was found to have a huge multilocular cystic tumor at the neck and body of pancreas on computed tomography. She was eventually diagnosed with hemolymphangioma of the pancreas after operation. After 2 years of follow-up, there was no signs of recurrence. Conclusion: From our case and literature, we can conclude that hemolymphangioma of the pancreas is uncommon benign tumor, and it is hard to make an accurate diagnosis preoperatively. Radical surgical resection should be performed whenever possible. The prognosis of this disease seems good.

Background: Esophageal cancer (EC) is a common digestive system tumor, characterized by high invasion, apparent lethality, and poor prognosis. Direct diffusion is the major metastatic mechanism of early EC, whereas advanced EC is spread mainly by lymphatic metastasis, but also can be transferred to the liver, lungs, bones, and so on, by hematogenous metastasis. The incidence of bone metastasis in esophageal cancer is low, and maxillary metastasis of EC is more rare. Objective: To explore the differential diagnosis in ECMM, the rare metastasis of EC, and the possible mechanisms and predictors of bone metastasis. Methods: The clinical materials of a male patient with maxillary metastasis of esophageal cancer (ECMM) were analyzed. Then, the possible mechanism of the ECMM was discussed. Conclusion: ECMM may belong to the hematogenous metastasis. The early detection of rare sites of metastasis of EC should be prioritized in tumor marker detection, imaging, pathology, and other diagnostic techniques.

Objective: To explore the application and diagnostic value of high-resolution CT in the process of lymphocytic interstitial pneumonia clinical diagnosis, and analyze one case of CT-guided percutaneous lung biopsy lymphocytic interstitial pneumonia. Methods: The medical record of a patient with lymphocyte interstitial pneumonia (LIP) who came to the clinic on 2014-04-22 were analyzed and summarized retrospectively. Results: The patient was a 55 years old female farmer. The CT-guided percutaneous lung biopsy was performed at her first visit; on 2014-07-09, the patient returned to our outpatient clinic with the main complaint of "1 week of coughing and blood in sputum and phlegm". Pathology consultation report from the PLA General Hospital on 2014-07-29 showed: (right lower lung) pneumonic pseudo-tumor; Zhejiang First Hospital’s pathology consultation report on 2014-08-11 showed: lymphocyte interstitial pneumonia. Conclusion: The diagnosis of lymphocyte interstitial pneumonia (LIP) with high-resolution CT may be used to increase its clinical diagnosis rate, reduce misdiagnosis and improve early detection.