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I'm not sure if this is an issue for mupload or plupload, but at the moment the alert message "You must at least upload one file." is being triggered from line 79 of sites/all/modules/plupload/plupload.js when trying to edit a node. The field already has images.
There are of coarse times when you just want to edit the body text or re-order images, without uploading new images. To reproduce, just edit a node with a mupload field, then click save.