Abstract:Objective Urine is a promising biomarker source for clinical proteomics studies. Regional physiological differences are common in multi-center clinical studies. In this study, we investigate whether significant differences are present in the urinary proteomes of individuals from different regions in China. Methods In this study, morning urine samples were collected from healthy urban residents in three regions of China (Haikou, Xi’an and Xining) and urinary proteins were preserved using a membrane-based method (Urimem). The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among three regions. Functional annotation of the differential proteins among the three areas was analyzed using the DAVID online database, and pathway enrichment of the differential urinary proteins was analyzed using KEGG. Results We identified 1898 proteins from Urimem samples using label-free proteome quantification, of which 56 urine proteins were differentially expressed among the three regions (P < 0.05). Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than inter-sex differences. After gender stratification, 16 differential proteins were identified in male samples and 84 differential proteins were identified in female samples. Among these differential proteins, several proteins have been previously reported as urinary disease biomarkers. Conclusions Urimem will facilitate urinary protein storage for large-scale urine sample collection. Regional differences are a confounding factor influencing the urine proteome and should be considered in future multi-center biomarker studies.
Abstract:Objective To explore circulating biomarkers for screening the invasiveness of non-functioning pituitary adenomas (NF-PAs). Methods The exosomal RNAs were extracted from serum of patients with invasive NF-PA (INF-PA) or noninvasive NF-PA (NNF-PA). Droplet digital PCR was adapted to detect the mRNA expression of candidate genes related to tumor progression or invasion, such as cyclin dependent kinase 6 (CDK6), ras homolog family member U (RHOU), and spire type actin nucleation factor 2 (SPIRE2). Student’s t-test was used to analyze the statistical difference in the mRNA expression of candidate genes between the two groups. Receiver operating characteristic (ROC) curve was used to establish a model for predicting the invasiveness of NF-PAs. The accuracy, sensitivity, specificity and precision of the model were then obtained to evaluate the diagnostic performance. Results CDK6 (0.2600±0.0912 vs. 0.1789±0.0628, t=3.431, P=0.0013) and RHOU mRNA expressions (0.2696±0.1118 vs. 0.1788±0.0857, t=2.946, P=0.0052) were upregulated in INF-PAs patients’ serum exosomes as compared to NNF-PAs. For CDK6, the area under the ROC curve (AUC) was 0.772 (95% CI: 0.600-0.943, P=0.005), the accuracy, sensitivity, specificity and precision were 77.27%, 83.33%, 75.00% and 55.56% to predict the invasiveness of NF-PAs. For RHOU, the AUC was 0.757 (95% CI: 0.599-0.915, P=0.007), the accuracy, sensitivity, specificity and precision were 72.73%, 83.33%, 68.75% and 50.00%. In addition, the mRNA levels of CDK6 and RHOU in serum exosomes were significantly positively correlated (r=0.935, P<0.001). After combination of the cut-off scores of the two genes, the accuracy, sensitivity, specificity and precision were 81.82%, 83.33%, 81.25% and 62.50%. Conclusions CDK6 and RHOU mRNA in serum exosomes can be used as markers for predicting invasiveness of NF-PAs. Combination of the two genes performs better in distinguishing INF-PAs from NNF-PAs. These results indicate CDK6 and RHOU play important roles in the invasiveness of NF-PAs, and the established diagnostic method is valuable for directing the clinical screening and postoperative treatment.
Keywords:pituitary adenoma;invasiveness;exosome;droplet digital PCR;biomarkers;CDK6;RHOU
Abstract:Objective To evaluate the instant effects and five-year clinical outcomes of coronary artery disease patients complicated with diabetes mellitus after StentBoost-optimized percutaneous coronary intervention (PCI). Methods From March 2009 to July 2010, 184 patients undergoing PCI at our hospital were found stent underexpansion or malapposition by StentBoost after stents implantation and were divided into the diabetic (n=73, 39.67%) and the non-diabetic group (n=111, 60.33%). All patients received StentBoost-guided post-dilatation after stent implantation. The instant procedural results were measured and clinical outcome after five-year follow-up was analyzed in each group. Between-group comparisons were performed using Chi-square test or Student’s t test. Multivariate logistic regression analysis was carried out to reveal the independent predictors for long-term clinical outcomes of StentBoost-optimized PCI . Results After StentBoost-guided post-dilatation, the minimum diameter (MinLD), maximum diameter (MaxLD) and average diameter in both groups increased significantly than before (P<0.001), the (MaxLD-MinLD)/MaxLD ratio and the in-stent residual stenosis decreased accordingly (P<0.001). The five-year follow-up showed similar mortality rate (4.92% vs. 2.86%, P=0.67) and major adverse cardiac event rate (11.48% vs. 11.43%, P = 1.0) between the diabetic and the non-diabetic group, whereas the recurrence of angina pectoris was higher in the diabetic group compared to the non-diabetic group (47.54% vs. 29.52%; P=0.02). A multivariate logistic regression analysis revealed that age and left ventricular ejection fraction rather than diabetes mellitus were independent predictors for long-term clinical outcomes. Conclusions StentBoost could effectively improve instant PCI results; the long-term clinical outcomes of StentBoost-optimized PCI were similar between diabetic and non-diabetic patients. Age and left ventricular ejection fraction were the independent predictors for long-term clinical outcomes.
Abstract:Objective Our previous study has revealed that iASPP is elevated in human head and neck squamous cell carcinoma (HNSCC) and iASPP overexpression signifcantly correlates with tumor malignant progression and poor survival of HNSCC. This study investigated the function of iASPP playing in proliferation and invasion of HNSCC in vitro. Methods HNSCC cell line Tu686 transfected with Lentiviral vector-mediated iASPP-specific shRNA and control shRNA were named the shRNA-iASPP group and shRNA-NC group, respectively. The non-infected Tu686 cells were named the CON group. CCK-8 assay, flow cytometry, transwell invasion assay were performed to detect the effects of iASPP inhibition in vitro. Results Our results demonstrated that the proliferation of shRNA-iASPP cells at the time of 72 h (F=32.459, P=0.000), 96 h (F=51.407, P=0.000), 120 h (F=35.125, P=0.000) post-transfection, was significantly lower than that of shRNA-NC cells and CON cells. The apoptosis ratio of shRNA-iASPP cells was 9.42% ± 0.39% (F=299.490, P=0.000), which was significantly higher than that of CON cells (2.80% ± 0.42%) and shRNA-NC cells (3.18% ± 0.28%). The percentage of shRNA-iASPP cells in G0/G1 phase was 74.65% ± 1.09% (F=388.901, P=0.000), which was strikingly increased, compared with that of CON cells (55.19% ± 1.02%) and shRNA-NC cells (54.62% ± 0.88%). The number of invading cells was 56 ± 4 in the shRNA-iASPP group (F=84.965, P=0.000), which decreased significantly, compared with the CON group (111 ± 3) and the shRNA-NC group (105 ± 8). The survival rate of shRNA-iASPP cells administrated with paclitaxel was highly decreased, compared with CON cells and shRNA-NC cells (F=634.841, P=0.000). Conclusion These results suggest iASPP may play an important role in progression and aggressive behavior of HNSCC and may be an efficient chemotherapeutic target for the treatment of HNSCC.
Keywords:human head and neck squamous cell carcinoma;iASPP;chemosensitivity;paclitaxel
Abstract:Objective To depict imaging anatomy of bronchial artery (BA) using multidetector CT-angiography (MDCTA) and evaluate the value of MDCTA for management of hemoptysis patients requiring admission to emergency room. Methods We retrospectively studied the clinical and radiological data of patients with severe hemoptysis (≥100 ml of expectorated blood in a 24-hour period) requiring admission to emergency room from Jan 1, 2013 to Dec 31, 2015. Patients’ images of MDCTA, treatment modalities, and outcome were discussed. Results A total of 108 patients underwent MDCTA scans. Etiology of hemoptysis was mainly bronchiectasis (44%), tuberculosis sequelae (26%) and tumor (18%). MDCTA visualized 197 traceable BAs and also suggested the involvement of 35 nonbronchial systemic arteries. The mean diameter of BAs, measured at the level of the bronchial bifurcation in the mediastinum, was 2.8±1.2 mm. The mean diameter of BAs, for 52 patients who only received conservative treatment, was 2.9±1.1 mm, and was not significantly larger than that of BAs for 56 patients who underwent bronchial artery embolization (BAE) for continued bleeding which did not resolve after conservative treatment (2.7±1.1 mm, P = 0.94). The technical success rate of embolization was 95% (53/56). Clinical success rate during follow-up was achieved in 50 (94%) of 53 patients who had undergone embolization. Conclusions MDCTA provides useful information for identifying the anatomical characteristics of bleeding-related BAs and nonbronchial systemic arteries for the management of patients with severe hemoptysis. However, MDCTA could not determine the individuals who need BAE through measuring diameter of BAs.
Abstract:Objective Psoriasis is an immune-mediated inflammatory disease. Despite advances in the study of its pathogenesis, the exact development mechanism of psoriasis remains to be fully elucidated. Hyperproliferative epidermis plays a crucial role in psoriasis. This study aimed to investigate the effects of interleukin-36β (IL-36β) on keratinocyte dysfunction in vitro. Methods Human keratinocyte cell lines, HaCaT cells, were treated with 0 (control), 50 or 100 ng/ml IL-36β respectively for 24 h. Cell viability was determined with a cell counting kit-8 assay. Flow cytometry was used to assess the effects of IL-36β on apoptosis and cell cycle distribution. Expressions of the differentiation markers, such as keratin 10 and involucrin, were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). Expressions of the inflammatory cytokines, IL-1β and IL-6 were tested by ELISA. Results CCK8 assay showed the survival rate had no significant difference between the control and treated group (P > 0.05). Flow cytometry analysis showed cell cycle arrest at S phase in the IL-36β-treated groups compared with the control group (P < 0.05). RT-qPCR verified the decreased mRNA expressions of keratin 10 and involucrin in the IL-36β-treated groups compared with the negative control (P < 0.01). ELISA showed 100 ng/ml IL-36β enhanced levels of IL-1β and IL-6 in culture supernatants of HaCaT cells compared with the negative control (P < 0.05). Conclusion Taken together, these findings suggest that IL-36β could induce cell cycle arrest at S phase, inhibit keratin 10 and involucrin expressions and promote inflammatory activity in HaCaT cell lines.
Abstract:Objective To clarify the possible association of GSTT1 homozygous deletion with the susceptibility to pancreatic cancer. Methods We searched PubMed database, Chinese Journal Full Text Database (CNKI), and EMBASE to find the eligible studies published up to April 18, 2018 for evaluating the relationship between GSTT1 homozygous deletion and pancreatic cancer. The frequency of null genotype for GSTT1 between the pancreatic cancer group and the healthy control group was compared with Chi-square test, and odds ratios (ORs) value and 95% confidence interval (95% CI) were calculated. Results A total of 9 studies met the inclusion criteria, and 5952 cases consisting of 2387 pancreatic cancer patients and 3565 healthy controls were included in the meta analysis. Compared with the control group, frequency of null genotype for GSTT1 in the pancreatic cancer group was higher (33.4% vs. 38.7%, OR = 1.26, 95%CI = 1.01-1.58, P = 0.04). Conclusion GSTT1 homozygous deletion individuals may have higher susceptibility to pancreatic cancer.
Abstract:We review the representatives literatures on chronic osteomyelitis, sum up the new insights in recent years into diagnostic options and treatment regimens, analyze the advantages and disadvantages of various diagnostic approaches and treatment strategies, and propose areas of interest to make current diagnostic and treatment strategies more specific.
Abstract:Here we report a case of heterotopic cornual pregnancy after in vitro fertilization who was diagnosed at 6 weeks after frozen embryos transfer. The heterotopic pregnancy was successfully terminated by transvaginal ultrasound-guided selective fetal reduction. At 38+1 weeks, she underwent a cesarean section and delivered a healthy 3300 g male infant with Apgar score of 10-10’ evaluated at 1 min and 5 min.
Abstract:A 22-year-old man suffered from acute pulmonary hemorrhage and deteriorated renal function occurred within 3 days after traumatic brain injury. Mechanical ventilation cannot correct his severe hypoxemia, therefore, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support was initiated and finally resolved his hypoxemia. Concomitantly, continuous renal replacement therapy was performed to improve his kidney function. Although no anti-glomerular basement membrane (anti-GBM) antibody was detected in serum, Goodpasture’s syndrome was considered. After treated with methylprednisolone pulse therapy and plasmapheresis, his renal function was significantly improved. ECMO was eventually discontinued after 60 hours of treatment and extubated on day 10. He was discharged home with normal pulmonary and renal functions.