Karen Khachanov's Chengdu Open title defence was brought to a grinding halt by Denis Istomin as several seeds tumbled on Wednesday.

Russian Khachanov, who beat Albert Ramos-Vinolas in last year's final to claim his maiden ATP Tour title, suffered a 6-3 6-2 loss as Istomin progressed to a last-eight meeting with Next Gen ATP Finals hopeful Jared Donaldson.

"It's really disappointing for me," said Khachanov. "It just didn't go the way I wanted in terms of playing the way I wanted. I just couldn't find exactly my game.

"I wasn't aggressive and I was missing a lot. I haven't been as consistent as I'd like in some tournaments this year, but that's something I can improve, so that's a positive thing."

Second seed Ramos-Vinolas joined Kyle Edmund in suffering a surprise exit, the Spaniard succumbing 6-2 6-3 to Dusan Lajovic.

Edmund, seeded sixth, was dumped out by Donaldson in a see-saw contest that saw the American prevail 6-0 1-6 6-4.

A bad day for the seeds was compounded by Leonardo Mayer's loss to Peter Gojowczyk, although Yuichi Sugita did make it through.

In Shenzhen, Australian Open quarter-finalist David Goffin overcame Evgeny Donskoy 7-6 (7-5) 6-3 and Damir Dzumhur proved too strong for John Millman in a 6-4 7-5 success.

Fourth seed Paolo Lorenzi was beaten 4-6 6-3 7-6 (7-4) by qualifier Zhang Zhizhen, while Donald Young saw off Jeremy Chardy 7-6 (7-5) 6-4.

Finally, Henri Laaksonen enjoyed a 4-6 6-4 6-3 victory over Marius Copil.