Shanghai, China (SportsNetwork.com) - Top-seeded reigning two-time champion Novak Djokovic and former world No. 1 Roger Federer reached the third round, while former top-ranked great Rafael Nadal was sent packing Wednesday at the $4 million Shanghai Masters tennis event. Playing with a bout of appendicitis this week, the second-seeded Nadal lost his second straight match, this time in 6-3, 7-6 (8-6) fashion at the hands of fellow Spanish left-hander Feliciano Lopez. Nadal also came up a quarterfinal loser last week at the China Open, his first tournament back after missing three months of action with a right wrist injury. For sure [I dont feel] perfect, said Nadal. Its the same way that I felt before. A little bit more dizzy now. But thats it. Nothing that I have to worry about. When you lose a match, it is not the moment to talk about obvious things. I lost. Feli played better than me. Nadal, who has been taking antibiotics for the appendicitis, began feeling pain in his abdomen on Saturday, and the next day went to a hospital where he learned he had the early stages of the condition. Nadal said he opted for antibiotics rather than undergo surgery right away. The French Open champion said the risk of his condition getting any worse after a few days of steady improvement is always very, very low. The 2009 Shanghai runner-up said he will talk with his doctors when he returns to Spain about whether hell need to have the appendix removed. Meanwhile, the current world No. 1 Djokovic handled Austrian Dominic Thiem 6-3, 6-4 and the third-seeded Federer barely survived against Argentine Leonardo Mayer, 7-5, 3-6, 7-6 (9-7), in 2 hours, 42 minutes, as Mayer led 5-2 in the third-set tiebreak before the Swiss legend fought back to advance at Qizhong Forest Sports City Arena. The 2010 Shanghai runner-up Federer saved five match points on Wednesday. It was the second-most match points he has saved in his career. Federer saved seven match points in a first-round win over Scott Draper in Cincinnati in 2003. Djokovic is undefeated in his last 11 matches in Shanghai and is looking to lift the trophy here for the third year in a row. Already a Masters winner in Indian Wells, Miami and Rome this season, the 27-year-old star is chasing his 20th Masters title. He dismantled Tomas Berdych for the China Open championship last week. Djokovic beat Juan Martin del Potro in last years Shanghai finale. Another top-five upset came when former top-10 Frenchman Gilles Simon foiled fourth-seeded Australian Open champ Stan Wawrinka, 5-7, 7-5, 6-4, on Day 4. And American Jack Sock posted a big upset by tackling seventh-seeded U.S. Open runner-up Kei Nishikori 7-6 (7-5), 6-4. The Japanese star Nishikori was fresh off his titles in Tokyo and Kuala Lumpur and had won 15 of his previous 16 matches on tour. Eleventh-seeded former world No. 1 Andy Murray continued his recent run of fine play by besting 6-foot-8 Pole Jerzy Janowicz 7-5, 6-2. Murray captured his first title in 15 months on Shenzhen, China, two weeks ago and was a semifinalist in Beijing last week. Murray titled here in Shanghai in 2010 and 2011 and was the runner-up in 2012. In other action involving top-10 seeds, No. 5 David Ferrer overcame Slovak Martin Klizan 4-6, 7-6 (7-4), 6-4; a No. 6 Berdych drubbed Frenchman Richard Gasquet 6-3, 6-1; Argentine wild card Juan Monaco doused No. 8 Canadian Milos Raonic 5-2, retired; and Frenchman Julien Benneteau upended No. 10 Grigor Dimitrov 7-5, 6-3. Raonic, who was last weeks Tokyo runner-up to Nishikori, succumbed to an illness while playing Monaco. Also on Wednesday, 13th-seeded John Isner edged out fellow American Steve Johnson 7-6 (8-6), 7-6 (9-7); 14th-seeded Spaniard Roberto Bautista Agut outlasted Canadian Vasek Pospisil 7-6 (7-1), 3-6, 6-4; Tunisian qualifier Malek Jaziri beat Chinese wild card Chuhan Wang 6-0, 6-4; and Russian Mikhail Youzhny snuck past Croat Ivan Dodig 7-6 (9-7), 6-7 (4-7), 6-3. The third round will be staged on Thursday, as Djokovic will face Kazakhstans Mikhail Kukushkin, Federer will meet Bautista Agut, and the 2011 Shanghai runner-up Ferrer will tangle with the resurgent Murray in some featured matches. This weeks big winner will collect $798,450. White Vapormax Womens Uk . Luke Wileman and I stood in the corridor outside of the Vancouver Whitecaps dressing room at BC Place in Vancouver. Nike Vapormax Mens Trainers Sale . At times during a solid but not spectacular season, they looked all three. 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