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Objective: The lack of appropriate preclinical models of ovarian yolk sac tumor (OYST) is currently hindering the pursuit of new methods of treatment and investigation of the pathogenesis of the disease. We developed and characterized an OYST patient-derived xenograft (PDX) model in this study., Methods: Tumor fragments from a patient with an OYST were implanted subcutaneously into BALB/c Nude mice. Engrafted xenografts were compared with the original tumor according to histology, immunohistochemistry, humanized identified, and drug efficacy testing with in vivo treatment programs., Results: There was a high degree of histologic and immunohistochemical (IHC) resemblance between the established PDX model and its corresponding human tumors. Bleomycin, etoposide, and cisplatin (JEB) chemotherapy regimens were effective in clinical patients and were effective in the OYST PDX model; therefore, the effect of PDX intervention was consistent with clinical outcomes of OYSTs., Conclusion: We have successfully established an OYST PDX model. This OYST model preserves the basic molecular features of the primary human tumor, thereby providing a valuable method to preclinically evaluate new treatments and explore disease pathogenesis.

Aims/hypothesis: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes., Methods: In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 μg) for 12 weeks. The primary endpoint was the change in HbA 1c from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA 1c  < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug., Results: We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 μg, 150 μg and 200 μg groups). At the end of 12 weeks, mean differences in HbA 1c in the treatment groups were -7.76 mmol/mol (95% CI -9.23, -4.63, p < 0.001) (-0.72%, 95% CI -1.01, -0.43), -12.89 mmol/mol (95% CI -16.05, -9.72, p < 0.001) (-1.18%, 95% CI -1.47, -0.89) and -11.14 mmol/mol (95% CI -14.19, -7.97, p <0 .001) (-1.02%, 95% CI -1.30, -0.73) in the 75 μg, 150 μg and 200 μg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA 1c . Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death., Conclusions/interpretation: All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes., Trial Registration: ClinicalTrials.gov NCT03520972 FUNDING: The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.

This paper develops a two-dimensional (2D) radiomics approach with computed tomography (CT) to differentiate between benign and malignant ovarian neoplasms. A retrospective study was conducted from July 2017 to June 2019 for 134 patients with surgically-verified benign or malignant ovarian tumors. The patients were randomly divided in a ratio of 7:3 into two sets, namely a training set (of n = 95) and a test set (of n = 39). The ITK-SNAP software was used to delineate the regions of interest (ROI) associated with lesions of the largest diameters in plain CT image slices. Texture features were extracted by the Analysis Kit (AK) software. The training set was used to select the best features according to the maximum-relevance minimum-redundancy (mRMR) criterion, in addition to the algorithm of the least absolute shrinkage and selection operator (LASSO). Then, we employed a radiomics model for classification via multivariate logistic regression. Finally, we evaluated the overall performance of our method using the receiver operating characteristics (ROC), the DeLong test. and tested in an external validation test sample of patients of ovarian neoplasm. We created a radiomics prediction model from 14 selected features. The radiomic signature was found to be highly discriminative according to the area under the ROC curve (AUC) for both the training set (AUC = 0.88), and the test set (AUC = 0.87). The radiomics nomogram also demonstrated good calibration and differentiation for both the training (AUC = 0.95) and test (AUC = 0.96) samples. External validation tests gave a good performance in radiomic signature (AUC = 0.83) and radiomics nomogram (AUC = 0.95). The decision curve explicitly indicated the clinical usefulness of our nomogram method in the sense that it can influence major clinical events such as the ordering or abortion of other tests, treatments or invasive procedures. Our radiomics model based on plain CT images has a high diagnostic efficiency, which is helpful for the identification and prediction of benign and malignant ovarian neoplasms.

To reduce dependence on petroleum, the biosynthesis of important chemicals from simple substrates using industrial microorganisms has attracted increased attention. Metabolic engineering of Saccharomyces cerevisiae offers a sustainable and flexible alternative for the production of various chemicals. As a key metabolic intermediate, malonyl-CoA is a precursor for many useful compounds. However, the productivity of malonyl-CoA derivatives is restricted by the low cellular level of malonyl-CoA and enzymatic performance. In this review, we focused on how to increase the intracellular malonyl-CoA level and summarize the recent advances in different metabolic engineering strategies for directing intracellular malonyl-CoA to the desired malonyl-CoA derivatives, including strengthening the malonyl-CoA supply, reducing malonyl-CoA consumption, and precisely controlling the intracellular malonyl-CoA level. These strategies provided new insights for further improving the synthesis of malonyl-CoA derivatives in microorganisms., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Avian influenza A (H7N9) virus was first reported in mainland China in 2013, and alarming in 2016-17 due to the surge across a wide geographic area. Our study aimed to identify and explore the spatial and temporal variation across five epidemics to reinforce the epidemic prevention and control., Methods: We collected spatial and temporal information about all laboratory-confirmed human cases of A (H7N9) virus infection reported in mainland China covering 2013-17 from the open source. The autocorrelation analysis and intensity of cases were used to analyse the spatial cluster while circular distribution method was used to analyse the temporal cluster., Results: Across the five epidemics, a total of 1553 laboratory-confirmed human cases with A (H7N9) virus were reported in mainland China. The global Moran's I index values of five epidemic were 0.610, 0.132, 0.308, 0.306, 0.336 respectively, among which the differences were statistically significant. The highest intensity was present in the Yangtze River Delta region and the Pearl River Delta region, and the range enlarged from the east of China to inner provinces and even the west of China across the five epidemics. The temporal clusters of the five epidemics were statistically significant, and the peak period was from the end of January to April with the first and the fifth epidemic later than the mean peak period., Conclusions: Spatial and temporal clusters of avian influenza A (H7N9) virus in humans are obvious, moreover the regions existing clusters may enlarge across the five epidemics. Yangtze River Delta region and the Pearl River Delta region have the spatial cluster and the peak period is from January to April. The government should facilitate the tangible improvement for the epidemic preparedness according to the characteristics of spatial and temporal clusters of patients with avian influenza A (H7N9) virus.

Purpose: Echinococcosis is a chronic neglected zoonotic disease with high endemic in western China. The aim of the study was to evaluate the Health-related Quality of Life (HRQoL) in patients with echinococcosis in Tibetan communities for investigating the physical and mental health challenges faced by the echinococcosis patients and meeting community health needs., Methods: The HRQoL was measured with 36-Item Short Form Health Survey (SF-36) questionnaire in the case-control study. Analysis of variance (ANOVA) method was used to analyze the data., Results: 50 echinococcosis patients were collected in study group and divided into three subgroups by the duration of staying on albendazole tablets. 52 healthy individuals were collected in control group. In physical quality of life, the duration of staying on albendazole tables influenced the PF (F = 6.661, P < 0.001), RP (F = 3.130, P = 0.029), and GH (F = 4.105, P = 0.008). In mental quality of life, the duration of staying on albendazole tables influenced the SF (F = 10.764, P < 0.001) and RE (F = 5.573, P = 0.001). The income level was the important confounder in PF (F = 11.515, P = 0.001), GH (F = 10.315, P = 0.002), VT (F = 5.984, P = 0.016), and MH (F = 5.565, P = 0.020)., Conclusions: The HRQoL in people with echinococcosis is reduced in comparison with the healthy individuals. It is necessary to shorten the duration of treatment and adopt the special methods adapting the local culture to improve the health-related quality of life in Tibetan communities. Meanwhile, the economic improvement is the foundation.