The violent collision occurred about 2:30 a.m. just south of Victory Boulevard, according to the California Highway Patrol, which issued a SigAlert.
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Investigators believe the violent sequence of events began when a driver lost control of a black car that crashed. A red Jeep then struck the first vehicle and the driver who had exited the sedan; the impact launched the person into the southbound lanes.
The injured motorist was transported to a medical center in critical condition. Three other people, whose conditions were unclear, were also hospitalized.
All lanes remained closed until shortly after 3 a.m. when the southbound side of the interstate was reopened. After the mangled vehicles were towed from the scene, the CHP canceled the SigAlert about 6:30 a.m. and reopened all northbound lanes.
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The cause of the collision was unknown.