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Objective: BAT1706 is a proposed biosimilar of bevacizumab (BEV). The objective of this phase I clinical trial was to establish pairwise similarity between BAT1706, US-sourced BEV (US-BEV), and EU-sourced BEV (EU-BEV) after a single intravenous (IV) infusion in healthy male subjects. Methods: This phase I clinical trial was a randomized, double-blinded, three-arm study in 128 healthy adult male subjects. Every subject received a single IV infusion of 1 mg/kg of study drug and was subsequently monitored for 14 weeks. Pharmacokinetic, safety, and immunogenicity data were collected from each patient. The primary pharmacokinetic endpoint of this clinical study was area under the concentration curve from time zero to infinity (AUC0–inf). Biosimilarity of the study drugs was confirmed if the two-sided 90% confidence interval (CI) ratios of the geometric means for the three pairwise comparisons were contained within the range 80–125%. Other pharmacokinetic parameters including area under the concentration curve to time t (AUC0–t), maximum concentration of drug in plasma (Cmax), half-life (t½), and time to Cmax (tmax) were also measured. Results: The pharmacokinetic parameters were comparable for the three drug products evaluated. The 90% CI for the AUC0–inf was 99–112% for BAT1706 versus EU-BEV, 97–110% for BAT1706 vs US-BEV and 92–104% for EU-BEV versus US-BEV comparisons, respectively, demonstrating biosimilarity. There were no significant adverse events attributable to BAT1706, as compared to EU-BEV and US-BEV. BAT1706 demonstrated a similar safety profile to EU-BEV and US-BEV. In addition, no anti-drug antibody positive result was reported for any subject included in the study. Conclusion: In this study, BAT1706, a proposed biosimilar of BEV, was shown to be highly similar to EU-BEV and US-BEV in terms of pharmacokinetic equivalence, safety, and immunogenicity in healthy subjects after a single IV infusion. Trial Registration: NCT03030430. [ABSTRACT FROM AUTHOR]

Objectives: Salivary adenoid cystic carcinoma (SACC) is one of the most common malignant salivary gland tumors. Our study aims to investigate whether hypoxia‐induced autophagy was up‐regulated in the progression of SACC. Materials and methods: We performed differentially expressed gene analysis and pathway enrichment analysis and then calculated the correlation analysis on GSE59701 and GSE28996 datasets. The expression of HIF‐1ɑ and MAP1LC3B was analyzed in the paraffin‐embedded specimens by immunohistochemical method and in the hypoxic SACC‐LM cells by immunofluorescence. TEM microscopy was also performed to observe the formation of autophagosomes in SACC tissue and the hypoxic SACC‐LM cells. Results: The autophagy pathway was up‐regulated in SACC datasets, and five genes including MAP1LC3B were positively correlated with HIF‐1ɑ. Immunohistochemistry results showed that autophagy was activated and the expression of HIF‐1ɑ and MAP1LC3B was positively correlated in SACC specimens. In hypoxic SACC‐LM cells, we also identified the up‐regulation of autophagy and the close correlation between HIF‐1ɑ and MAP1LC3B expression. Autophagosomes were observed both in the tissue and the hypoxic SACC‐LM cells by TEM microscopy. Conclusions: Our study showed that autophagy is up‐regulated in dataset, SACC tissue, and hypoxic cell line; hypoxia‐induced autophagy in SACC might play a vital role in the development of SACC. [ABSTRACT FROM AUTHOR]

Urban lakes have tremendous ecological significance to the city and have been under higher and higher pressure of being polluted as the cities develop. In this paper, we improved the fuzzy comprehensive evaluation method by abandoning the results analysis method in the principle of maximum degree of membership in its traditional process, and classifying water quality into two types according to the membership characteristics of water quality to each water level, i. e. single-prominent-type and non-single-prominent-type. Applying this improved fuzzy comprehensive evaluation method and selecting 14 parameters, we evaluate the water environmental condition and evolution trend from 2006 to 2010 of Xuanwu Lake in Nanjing. Results indicated that: the water quality of Xuanwu Lake was single-prominent-type in 2008 and non-single-prominent-type in the other years; overall the water environmental condition was complex and exhibited a fluctuation trend in the years; as a whole, the membership degree of water quality showed a characteristic of bing high for the first, fourth and fifth sort of waters but low for the second and third sorts of waters, and showed an obvious tendency of becoming equalization. Compared with the comprehensive pollution index evaluation method and traditional fuzzy comprehensive evaluation method, the improved fuzzy comprehensive evaluation method can play a full role of the advantage of Fuzzy Mathematics and comprehensively and objectively reflect water environmental condition and its variation trend, thus can provide effective support for city lake water environment renovation. [ABSTRACT FROM AUTHOR]

Objectives: Fibrous dysplasia (FD) is a focal bone lesion composed primarily of immature bone marrow stromal cells along with spicules of immature woven bone. However, cellular differentiation and proliferation in mutant human bone marrow stromal cells (hBMSCs) of FD have not been fully elucidated. Therefore, the aim of this study was to investigate the occurrence of Gsα mutation at the Arg201 codon in hBMSCs and human trabecular bone cells (hTBCs, osteoblast-like cells). In addition, we evaluated the gene expression and protein secretion of amphiregulin from hBMSCs and hTBCs and assessed the biologic activity and possible mechanism of amphiregulin in our system. Study design: Mutant hBMSCs from FD patients and hTBCs from disease-free bone specimens of the same patient were successfully cultured. We studied the Gsα mutations at the Arg201 codon by means of polymerase chain reaction (PCR)–restriction fragment length polymorphism. Gene expression and protein secretion of amphiregulin in hBMSCs and hTBCs was confirmed by reverse-transcription (RT) PCR and Western blotting analysis. The modulation proliferation and possible mechanism of the exogenous addition of amphiregulin and epidermal growth factor receptor tyrosine kinase inhibitor (AG-1478) were assessed by using Wst-1 assays. Results: The Gsα mutations in clonal adherent mutant hBMSCs and hTBCs were successfully identified. We identified amphiregulin to be highly expressed in hBMSCs compared with hTBCs. The growth of hBMSCs was stimulated by the exogenous addition of amphiregulin and inhibited by AG-1478. Conclusions: The Gsα-mutant hBMSCs were successfully identified, and amphiregulin may play a significant role in the proliferation of hBMSCs. [Copyright &y& Elsevier]