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A total of 130 adult patients with PPI-refractory symptoms of suspicious GERD who were admitted to the Beijing Tongren Hospital were enrolled in the study. Patients who had at least a 2-week history of symptoms of heartburn with or without regurgitation were eligible for enrollment as patients suspicious for GERD. Those patients who did not respond to twice-daily PPI therapy for at least 8 weeks were diagnosed with PPI-refractory symptoms [46,19]. As HRM and impedance-pH/manometry are valuable tools in clinical and esophageal investigation [20], all patients underwent a salivary pepsin test, endoscopy, HRM and 24-h multichannel intraluminal impedance and pH recording (24-h MII-pH). Patients who had histories of thoracic, esophageal, or gastric surgery, eosinophilic or infectious esophagitis, and severe esophageal motility disorders, such as achalasia and scleroderma, or were pregnant were excluded. The study was approved by the Beijing Tongren Hospital Medical Ethics Committee (No. TRECKY2015-114). All participants signed the informed consent prior to participating the study.

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