"What's up?" is a very casual form of asking your friend what is happening in their life. You can also say, "What's up and down?" You would not use either of these phrases if you know something is wrong or there is a concern.
"How are we?", as opposed to "How are you?" is an affectionate way of asking the person's situation.
If you know something has happened and if you want to follow up on your friend, you can ask, "How do you feel now? Any better?" This is for example if the friend broke up with his/her partner and after a couple of days you check up on them to see if he/she's doing okay.
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