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In the framework of 2HDM, we explore the wrong-sign Yukawa region with directand indirect searches up to one-loop level. The direct searches include thelatest $H/A \to f\bar f, VV, Vh, hh$ reports at current LHC, and the study ofindirect Higgs precision measurements works with current LHC, future HL-LHC andCEPC. At tree level of Type-II 2HDM, for degenerate heavy Higgs mass$m_A=m_H=m_{H^\pm}<800$ GeV, the wrong-sign Yukawa regions are excluded largelyexcept for the tiny allowed region around $\cos(\beta-\alpha)\in(0.2,0.3)$under the combined constraints. The excluded region is also nearly independentof parameter $m_{12}$ or $\lambda v^2=m_A^2-m_{12}^2/(\sin \beta \cos \beta)$.The situation changes a lot after including loop corrections to the indirectsearches, for example $m_A=800 $ GeV, the region with $\lambda v^2<0$ will bestronger constrained to be totally excluded. Whilst $\lambda v^2>0$ would getlarger survived wrong-sign region, such as $\cos(\beta-\alpha) \in (0,0.3)$ for$\sqrt{\lambda v^2}=400$ GeV, under combined restrictions.

Probing loop effects in wrong-sign Yukawa region of 2HDM