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Lei-Si Zhang,1,2,* Jun Wang,1,2,* Ming-Zhu Xu,1,2,* Tian-Mei Wu,1,2 Si-Man Huang,1,2 Han-Yu Cao,1,2 Ai-Ning Sun,1,2 Song-Bai Liu,3 Sheng-Li Xue1,2 1National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of China; 3Suzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song-Bai Liu, Suzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, No. 28, Kehua Road, Suzhou, 215009, People’s Republic of China, Tel +86-13862145806, Email liusongbai@126.com Sheng-Li Xue, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, 215006, People’s Republic of China, Tel +86-512-67781856, Email slxue@suda.edu.cnAbstract: The presence of FLT3-ITD mutation is associated with relapse and poor survival in AML patients. Venetoclax combined with hypomethylating agents (VEN+HMA) was approved for the frontline treatment of elderly or unfit AML patients, which leads to noteworthy impacts on AML management. The combination therapy is associated with encouraging efficacy in FLT3-mutated AML among both newly diagnosed unfit and relapsed/refractory patients. However, we found that two AML patients with FLT3-ITD mutation did not respond to venetoclax plus azacitidine (VEN+AZA). Given that the combined efficacy of venetoclax and the FLT3 inhibitor has been proved in pre-clinical models of FLT3+ AML, it is a scientific rationale to investigate venetoclax combined with the FLT3 inhibitor in AML patients with FLT3-ITD mutation. This is the first report of assessing the safety and response of gilteritinib (the first and only targeted second-generation FLT3 tyrosine kinase inhibitor approved by the US FDA) and venetoclax-based therapy in two AML patients with FLT3-ITD mutation unresponsive to VEN+AZA, which may bring new hope to FLT3 mutated patients who are unresponsive to VEN+HMA.Keywords: acute myeloid leukaemia, FLT3-ITD, gilteritinib, venetoclax

This paper aims to address the problem of geometric state control of large-segment steel box girders in offshore hoisting during the construction of large-span bridges. First, the geometric state control indexes of a large-segment steel box girder are determined, such as the manufacturing parameters of the top and bottom slabs, the width of the annular joint, and the support position. Second, the geometric state equations and state transfer matrixes of large-segment steel box girders under different conditions are deduced by taking the mileage and elevation of control points as basic state variables. In application of the geometric state transfer method in the construction control of the Hong Kong-Zhuhai-Macao Bridge, the width of the annular joint and the position parameters for the support of the large-segment steel box girder are predicted precisely. Moreover, the manufacturing parameters of the top and bottom slabs of the steel box girders are calculated reliably. The measured values show that the width of the annular joint is basically the same with the difference of less than 2 mm, the eccentricity of bridge support is less than 20 mm, and the elevation error of the bridge deck is within −10 mm to +15 mm, which meets the construction accuracy. Using the geometric state transfer method, the rapid and accurate installation of the Hong Kong-Zhuhai-Macao Bridge has been realized, demonstrating that the precise control of the geometric state of a steel box girder with ectopic installation and multi-state transition can be realized by using the geometric state transfer method.

A model for analyzing laminated plates is proposed, considering the interlayer slip. The proposed model is suitable for civil engineering structures, such as undertrack structures and layered pavements. The interlayer slip at the interface was introduced in the model to reflect the effect of imperfect bonding between adjacent layers. The deformation of each layer follows the Kirchhoff–Love assumption of the classical plate theory. The principle of virtual work and the reciprocal theorem of laminated plates were established to account for interlayer slip, based on which the principles of minimum potential and complementary energy were derived and proven. Two- and three-field generalized variational principles were then developed by introducing the Lagrange multiplier method. Moreover, the variational principles for the free vibration and buckling of laminated plates were obtained. Finally, analytical solutions of the bending, free vibration and buckling responses of a simply supported laminated plate were obtained, and they were consistent with the numerical results.