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G protein-coupled receptors (GPCRs) are the largest family of membrane receptors in animals and humans, which transmit various signals from the extracellular environment into cells. Studies have reported that several GPCRs transmit the same signal; however, the mechanism is unclear. In the present study, we identified all 122 classical GPCRs from the genome of Helicoverpa armigera, a lepidopteran pest species. Twenty-four GPCRs were identified as upregulated at the metamorphic stage by comparing the transcriptomes of the midgut at the metamorphic and feeding stages. Nine of them were confirmed to be upregulated at the metamorphic stage. RNA interference in larvae revealed the prolactin-releasing peptide receptor (PRRPR), smoothened (SMO), adipokinetic hormone receptor (AKHR), and 5-hydroxytryptamine receptor (HTR) are involved in steroid hormone 20-hydroxyecdysone (20E)-promoted pupation. Frizzled 7 (FZD7) is involved in growth, while tachykinin-like peptides receptor 86C (TKR86C) had no effect on growth and pupation. Via these GPCRs, 20E regulated the expression of different genes, respectively, including Pten (encoding phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase), FoxO (encoding forkhead box O), BrZ7 (encoding broad isoform Z7), Kr-h1 (encoding Krüppel homolog 1), Wnt (encoding Wingless/Integrated) and cMyc, with hormone receptor 3 (HHR3) as their common regulating target. PRRPR was identified as a new 20E cell membrane receptor using a binding assay. These data suggested that 20E, via different GPCRs, regulates different gene expression to integrate growth and development.

Purpose. To evaluate the diagnostic performance of deep learning with a multichannel fusion three-dimensional convolutional neural network (MCF-3DCNN) in the differentiation of the pathologic grades of hepatocellular carcinoma (HCC) based on dynamic contrast-enhanced magnetic resonance images (DCE-MR images). Methods and Materials. Fifty-one histologically proven HCCs from 42 consecutive patients from January 2015 to September 2017 were included in this retrospective study. Pathologic examinations revealed nine well-differentiated (WD), 35 moderately differentiated (MD), and seven poorly differentiated (PD) HCCs. DCE-MR images with five phases were collected using a 3.0 Tesla MR scanner. The 4D-tensor representation was employed to organize the collected data in one temporal and three spatial dimensions by referring to the phases and 3D scanning slices of the DCE-MR images. A deep learning diagnosis model with MCF-3DCNN was proposed, and the structure of MCF-3DCNN was determined to approximate clinical diagnosis experience by taking into account the significance of the spatial and temporal information from DCE-MR images. Then, MCF-3DCNN was trained based on well-labeled samples of HCC lesions from real patient cases by experienced radiologists. The accuracy when differentiating the pathologic grades of HCC was calculated, and the performance of MCF-3DCNN in lesion diagnosis was assessed. Additionally, the areas under the receiver operating characteristic curves (AUC) for distinguishing WD, MD, and PD HCCs were calculated. Results. MCF-3DCNN achieved an average accuracy of 0.7396±0.0104 with regard to totally differentiating the pathologic grade of HCC. MCF-3DCNN also achieved the highest diagnostic performance for discriminating WD HCCs from others, with an average AUC, accuracy, sensitivity, and specificity of 0.96, 91.00%, 96.88%, and 89.62%, respectively. Conclusions. This study indicates that MCF-3DCNN can be a promising technology for evaluating the pathologic grade of HCC based on DCE-MR images.

Background With the development of new magnetic resonance imaging (MRI) techniques, an increasing number of articles have been published regarding hepatocellular carcinoma magnetic resonance imaging (HCCMRI) in the past decade. However, few studies have statistically analyzed these published articles. In this study, we aim to systematically evaluate the scientific outcomes of HCCMRI research and explore the research hotspots from 2008 to 2017. Methods The included articles regarding HCCMRI research from 2008 to 2017 were downloaded from the Web of Science Core Collection and verified by two experienced radiologists. Excel 2016 was used to analyze the literature data, including the publication years and journals. CiteSpace V was used to perform co-occurrence analyses for authors, countries/regions and institutions and to generate the related collaboration network maps. Reference co-citation analysis (RCA) and burst keyword detection were also performed using CiteSpace V to explore the research hotspots in the past decade. Results A total of 835 HCCMRI articles published from 2008 to 2017 were identified. Journal of Magnetic Resonance Imaging published the most articles (79 publications, 9.46%). Extensive cooperating relationship were observed among countries/regions and among authors. South Korea had the most publications (199 publications, 21.82%), followed by the United States of America (USA) (190 publications, 20.83%), Japan (162 publications, 17.76%), and the People's Republic of China (148 publications, 16.23%). Among the top 10 co-cited authors, Bruix J (398 citations) was ranked first, followed by Llovet JM (235 citations), Kim YK (170 citations) and Forner A (152 citations). According to the RCA, ten major clusters were explored over the last decade; "LI-RADS data system" and "microvascular invasion" (MVI) were the two most recent clusters. Forty-seven burst keywords with the highest citation strength were detected over time. Of these keywords, "microvascular invasion" had the highest strength in the last 3 years. The LI-RADS has been constantly updated with the latest edition released in July 2018. However, the LI-RADS still has limitations in identifying certain categories of lesions by conceptual and non-quantitative probabilistic methods. Plenty of questions still need to be further answered such as the difference of diagnostic efficiency of each major/ancillary imaging features. Preoperative prediction of MVI of HCC is very important to therapeutic decision-making. Some parameters of Gd-EOB-DTPA-enhanced MRI were found to be useful in prediction of MVI, however, with a high specificity but a very low sensitivity. Comprehensive predictive model incorporating both imaging and clinical variables may be the more preferable in prediction of MVI of HCC. Conclusions HCCMRI-related publications displayed a gradually increasing trend from 2008 to 2017. The USA has a central position in collaboration with other countries/regions, while South Korea contributed the most in the number of publications. Of the ten major clusters identified in the RCA, the two most recent clusters were "LI-RADS data system" and "microvascular invasion", indicative of the current HCCMRI research hotspots.

BACKGROUND: The accurate assessment of liver fibrosis is essential for patients with chronic liver disease. A liver biopsy is an invasive procedure that has many potential defects and complications. Therefore, noninvasive assessment techniques are of considerable value for clinical diagnosis. Liver and spleen magnetic resonance elastography (MRE) and serum markers have been proposed for quantitative and noninvasive assessment of liver fibrosis. This study aims to compare the diagnostic performance of liver and spleen stiffness measured by MRE, fibrosis index based on the 4 factors (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and their combined models for staging hepatic fibrosis. METHODS: One hundred and twenty patients with chronic liver disease underwent MRE scans. Liver and spleen stiffness were measured by the MRE stiffness maps. Serum markers were collected to calculate FIB-4 and APRI. Liver biopsies were used to identify pathologic grading. Spearman’s rank correlation analysis evaluated the correlation between the parameters and fibrosis stages. Receiver operating characteristic (ROC) analysis evaluated the performance of the four individual parameters, a liver and spleen stiffness combined model, and an all-parameters combined model in assessing liver fibrosis. RESULTS: Liver stiffness, spleen stiffness, FIB-4, and APRI were all correlated with fibrosis stage (r=0.87, 0.64, 0.65, and 0.51, respectively, all P0.05). CONCLUSIONS: Liver stiffness measured with MRE had better diagnostic performance than spleen stiffness, APRI, and FIB-4 for fibrosis staging. The combined models did not significantly improve the diagnostic value compared with liver stiffness in staging fibrosis.

Interstitial pneumonia (IP) is a lethal complication in lymphoma patients undergoing chemotherapy. A total of 2212 consecutive patients diagnosed with lymphoma between 2009 and 2014 were enrolled in the present study. IP was defined as diffuse pulmonary interstitial infiltrate found on computed tomography scans. IP was observed in 106 patients. Of these, 23 patients were excluded from the study. Finally, 83 patients with IP were included in this study. The incidence of IP was 3.9% (7/287) in Hodgkin lymphoma and 2.4% (76/1925) in non-Hodgkin lymphoma (P = 0.210). The median number of chemotherapy cycles before IP was 3. The median time from the cessation of chemotherapy to IP was 17 days. Eighty-two (98.8%) patients recovered after the treatment with glucocorticoids. Sixty-six (79.5%) patients had a delay in chemotherapy, and 14 (16.9%) patients had premature termination of chemotherapy. Sixty-nine patients were re-treated with chemotherapy after remission from IP, of which 22 (31.9%) experienced IP recurrence. The incidence of IP recurrence was significantly higher in patients re-treated with a similar regimen than in those re-treated with an alternative regimen (65.4 vs. 11.6%, P

Primary membranous nephropathy (PMN) is an antibody-mediated autoimmune glomerular disease. The incidence of PMN is 10/million populations/year and mostly adult patients present with nephrotic syndrome (NS). Moreover, the patients with persistent NS progressed to end-stage renal disease in 5–15 years. A number of studies proved the efficiency of immunosuppressant. Combinations of corticosteroid with alkylating agents or calcineurin inhibitor (CNI) have been proved to be effective to induce remission of PMN with persistent heavy proteinuria. However, there are still 30% PMN patients refractory or dependent to immunosuppressant. A few studies showed rituximab (RTX) may be effective to treat refractory PMN with the protocol varies. The doses of 375 mg/m2 every week for 4 weeks and 1 g fixed dose with a repeat dose in 2 weeks were commonly used. Nonetheless, some studies about anti-neutrophil cytoplasmic antibody-associated vasculitis, rheumatoid arthritis (RA), autoimmune cytopenias, focal segmental glomerulosclerosis, and so on showed a low-dose or single-dose RTX can be effective on proteinuria remission and peripheral blood B-cells elimination. Hereon, we present a 51-year-old refractory PMN patient who was induced complete remission by a low-dose RTX. A 51-year-old Chinese man was admitted to our hospital complaining persistent edema of lower extremities for 2 years. He was diagnosed as NS and received renal biopsy in another hospital 2 years ago. Pathologic study showed membranous nephropathy [Figure 1]. A full dose of ACE inhibitors, prednisolone in combination with cyclophosphamide (“Ponticelli Regimen”) for 6 months failed to induce remission. One year ago, the man was referred to our clinic department. Combination of prednisolone (10 mg/d) with tacrolimus (2–2.5 mg/d) was initiated. Diltiazem were added to increase tacrolimus trough concentration to the range of 5.5–9.8 ng/ml. After 7-month treatment, the patient had not improved and was admitted to our inpatient department. Figure 1 Pathology of renal biopsy. (a) electron microscopy: Subepithelial deposits of immunocomplex, thickening of glomerular basement membrane, effacement of podocyte foot. (b) Light microscopy: Inflammatory cells infiltration and part of the renal tubular atrophy. ... Physical examination was nonspecific except edema of lower extremities. The urine protein was 6.5 g/d, urine protein-to-creatinine (Cr) ratio was 0.663 g/mmol Cr, serum Cr was 15.8 mg/L, and serum albumin was 28 g/L. The blood lipid levels suggested hyperlipidemia. The plasma trough concentration of tacrolimus was 8.7 ng/ml. The CD19CD5 B-cells was 314 cell/μl (12.20%). The blood routine tests were normal and immune indices were negative. Markers and imaging tests for tumor were normal. Hepatitis B surface antigen was negative. Anti-hepatitis B core, anti-hepatitis B e antibody were positive and hepatitis B virus-DNA 0.6 g/mmol Cr. 100 mg rituximab was given to him combining with the former immunosuppresive protocol at 7 months. Six ... RTX is a B-cell depleting monoclonal antibody targets at CD20, a transmembrane protein expressed on virtually all B-cells except when B-cells differentiate into antibody secreting plasma cells. RTX binding to CD20 initiates B-cells apoptosis, complement dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. RTX was first used to treat non-Hodgkin lymphoma in 1997 and be confirmed to be effective in RA, idiopathic thrombocytopenic purpura, pemphigus, and so on. RTX was also gradually used in a wide variety of glomerular diseases including lupus nephritis, IgA nephropathy, minimal change disease and focal segmental glomeruloslcerosis, fibrillary glomerulonephritis, and membranous nephropathy. Recently, a systematic review[1] which searched the available data on RTX therapy for MN from inception to August 1, 2008, recruited 21 case reports or case series and 85 patients without control. Among the 21 reports, the patients were given RTX at a high dose of 375 mg/m2 once weekly for 4 weeks or 1 g RTX on days 1 and 15. RTX treatment can be repeated if the circulating B-cells and proteinuria not reach the remission rang (>3.5 g/d or

To explore the clinical characteristics and prognosis of patients with angioimmunoblastic T cell lymphoma (AITL).The clinical features and prognostic factors of 42 cases newly diagnosed as AITL at Peking University Cancer Hospital from January 2007 to August 2012 were retrospectively analyzed.Their median age was 59(34-76) years. Among them, 97.6% cases (41/42) belonged to Ann Arbor stage III/IV, 73.8% (31/42) cases presented with B symptoms, 85.7% (36/42)cases had painless lymphadenopathy, 52.4% (22/42)cases extranodal involvement, 64.3% (27/42) cases elevated lactate dehydrogenase and 45.2% (19/42) cases elevated β2-microglobulin at diagnosis. And 40.5% (17/42) cases had 3 points of international prognostic index (IPI) score with the highest proportion.First-line chemotherapy was predominantly CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone) or CHOP-like-based and complete response was achieved in 44.7% (17/38) of them. The median follow-up time was 40 (2-106) months The 1, 2, 5-year survival rates were 78%, 57% and 39% respectively.Statistical analysis showed that IPI was an independent prognostic factor (P = 0.009).Other factors included gender (P = 0.311), age (P = 0.263), with or without B symptoms (P = 0.102), Ki-67 index (P = 0.146) as well as the choice of first-line chemotherapy (P = 0.292) each had a tendency of affecting; the survival rate, but failed to reach statistical significance.Angioimmunoblastic T-cell lymphoma is a major type of peripheral T-cell lymphoma. Most AITL patients are elders with a late stage. The disease generally displays an aggressive clinical course and poor prognosis.

To explore the clinical characteristics and prognosis of patients with primary testicular non-Hodgkin's lymphoma.The clinical profiles and prognostic factors of 21 cases newly diagnosed as primary testicular non-Hodgkin's lymphoma at Peking University Cancer Hospital from January 2005 to December 2012 were retrospectively analyzed.Their median age was 59 (34-86) years. And they were classified as Ann Arbor stage I (n = 8), stage II (n = 2) and stage IV (n = 11). There were B symptoms (n = 4), extranodal involvement outside testis (n = 12) and elevated lactate dehydrogenase (LDH) at diagnosis (n = 6). The scores of international prognostic index (IPI) were 0-1 point (n = 10), 3 points (n = 10) and 4 points (n = 1). The regimens included orchidectomy as the initial treatment (n = 15), chemotherapy followed by radiotherapy (n = 7) and CNS prophylaxis during treatment (n = 15). All patients were pathologically diagnosed as diffuse large B-cell lymphoma. And 11 cases belonged to the non-germinal center B cell-like subgroup.First-line chemotherapy was either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) or CHOP-like-based regimen. Complete response was achieved in 85.7% of patients. The median follow-up period was 18 (6-58) months. The 1, 2 and 3-year survival rates were 100%, 80% and 60% respectively. Statistical analysis showed that the first-line chemotherapy with rituximab was a prognostic factor (P = 0.038).Other factors included stage (P = 0.275), LDH level (P = 0.179) , β2-microglobulin level (P = 0.229) and IPI (P = 0.275) .The prognosis of primary testicular non-Hodgkin's lymphoma is usually poor. The first-line chemotherapy with rituximab is a prognostic factor.

To analyze the safety and adverse event profiling of pegylated L-asparaginase (PEG-asp) combined chemotherapy in the treatment of lymphoma patients.The clinical data of 32 lymphoma patients on PEG-asp-based chemotherapy from January 2008 to March 2012 were retrospectively collected and analyzed.There were 22 males and 10 females with a median age of 40 years. They were diagnosed as NK/T cell lymphoma (n = 22) and lymphoblastic lymphoma (n = 10). The overall response rate was 71.9% (23/32). And complete remission was 40.6% (13/32) and partial remission 31.3% (10/32). Myelosuppression was the most common adverse event at an incidence of 81.2% (26/32). Other adverse events included a low level of fibrinogen (n = 13, 40.6%), hypoalbuminemia (n = 8, 25%) and hyperlipidemia (n = 9, 28.1%). No instance of anaphylaxis, acute pancreatitis and thrombosis occurred.PEG-asp is both effective and safe in the treatment of lymphoma and it is well-tolerated.

To evaluate the prognostic value of maximum standard uptake (SUVmax) on pretreatment (18)F-fluoro-2-deoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) scan in patients with newly diagnosed diffuse large B cell lymphoma (DLBCL).The clinical data of 39 DLBCL patients undergoing a PET/CT scan at pre-treatment from December 2009 to October 2011 were analyzed retrospectively. SUVmax on PET/CT was evaluated by SPSS 13.0 for the associations with patient characteristics, prognostic factors, treatment efficacy and survival time.The median SUVmax was higher in non-germinal center B cell-like (non-GCB) patients than that in GCB ones (18.0(2.2 - 40.5) vs 11.6 (5.3 - 18.7), P = 0.039). No difference of SUVmax was observed between the patients with and without bulky disease (P = 0.539). SUVmax was not associated with such patient characteristics as international protein index, age, stage, Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, number of extranodal involvement and Ki-67 (all P0.05). No significant difference in median SUVmax existed between complete remission (CR) and non-CR patients (P = 0.312). The difference of SUVmax was insignificant for the patients with efficacy and no efficacy (P = 0.243). With the cut-off values of 10, 15, 20, the CR rate, response rate, 2-year progression-free survival (PFS) rate and 2-year overall survival (OS) rate were not different between the patients with SUVmax below and above cut-off value (all P0.05).The prognostic value of SUVmax on PET/CT is indeterminate. And it can not be used to predict the patient prognosis.

Crude oil destined for Philadelphia-area refineries is transferred to lighters from the tankers in Delaware Bay because the channel in the Delaware River is too shallow for fully loaded tankers. We developed a simulation model for studying the effects of various policies on service levels. The results were used by Maritrans, the provider of the lightering services, and its largest customer to examine ways in which they could improve their working relationship. Although the customer valued Maritrans' services, it was considering alternative lightering solutions and most seriously considering doing its own lightering. The results of the model provided a deeper understanding of the role of lightering in the customer's crude-oil logistics system, showing that acquiring a separate fleet would be costly and allowing both parties to evaluate other alternatives for reducing costs and improving response times.

To explore the clinical features, diagnosis, treatment and prognosis of central nervous system lymphoma (CNSL).Retrospective analysis was conducted for 31 CNSL cases from January 2007 to December 2009 in our hospital. Their clinical data were analyzed by statistical software package SPSS 16.0.Accounting for around 4.7% of all lymphomas at our institution, the present cohort had 21 males and 10 females with a median age of 38 years old. The major clinical manifestations were focal neurological deficits associated with the site of disease or increased intracranial pressure. Most patients were treated with chemotherapy-based regimens. The overall response rate was 67.7% (21/31) with 32.3% (10/31) complete remission rate (CR) and 35.5% (11/31) partial remission rate (PR). Involvement outside CNS or bone marrow, high international prognostic index (IPI) and B symptoms had significant effects on the therapeutic efficacy (P0.05). The overall survival rates were 80.7%, 74.2%, 64.5% and 58.1% at 3, 6, 12, 24 months respectively. The median survival time was 22.5 months. Univariate analysis showed that the clinical efficacy had significant effects on the overall survival of patients (OR = 0.030, 95%CI: 0.003 - 0.270, P = 0.000).The prognosis of CNSL remains poor. New diagnostic tools and treatment modality need to be explored.