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We establish a general form of sum-difference inequality in two variables, which includes both two distinct nonlinear sums without an assumption of monotonicity and a nonconstant term outside the sums. We employ a technique of monotonization and use a property of stronger monotonicity to give an estimate for the unknown function. Our result enables us to solve those discrete inequalities considered by Cheung and Ren (2006). Furthermore, we apply our result to a boundary value problem of a partial difference equation for boundedness, uniqueness, and continuous dependence.