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Hello.
When you ask someone how they are and they reply "I'm not good", which of the following are correct and better replies?

1. What happened?
2. What's up?
3. What's up with you?
4. What's wrong?
5. What's wrong with you?

Thanks.

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#2

#4

Also, you could say What's the matter?

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Karen151. What happened?
2. What's up?
3. What's up with you?
4. What's wrong?
5. What's wrong with you?

"What happened?" implies that the speaker already knows that the other person has undergone some kind of experience, and sees that this apparently did not turn out well. In that context it is possible.

Otherwise, #2 and #4 are OK to use in a general setting.

"... with you?" can sound accusing (depending to some extent on intonation).

(Cross-posted.)