Objective:To study reflux characteristics of patients with endoscopic negative heartburn and their manifestation under probe-based confocal laser endoscopy (pCLE) based on the Rome Ⅳ standard.Methods:Thirty-six endoscopic negative outpatients with typical heartburn at the Department of Gastroenterology of the Second Affiliated Hospital of Baotou Medical College from September 2020 to March 2021 were included, and underwent 24-hour multichannel intraluminal impedance-pH monitor and pCLE. According to Rome Ⅳ diagnostic process, patients were divided into non-erosive reflux disease (NERD) group ( n=16), reflux hypersensitivity (RH) group ( n=8) and functional heartburn (FH) group ( n=12). The Gerd-Q scale score, 24-hour pH monitoring results and microstructure changes under pCLE were compared among the three groups. Results:There was no significant difference in the total score, positive symptom score, negative symptom score or positive influence score of Gerd-Q scale among the three groups ( P>0.05). DeMeester score [28.45 (20.08, 34.53)] and acid reflux times (24.88±9.05) in the NERD group were significantly higher than those in the RH group [7.30 (3.90, 11.38), P<0.001; 13.63±5.76, P=0.003] and FH group [6.90 (4.80, 9.73), P<0.001; 7.42±8.32, P<0.001]. But there was no significant difference between the RH group and the FH group ( P>0.05). The diameter of intra-papillary capillary loop (IPCL) (18.68±2.12 μm) and dilation of intercellular space (3.95±0.97 μm) in the NERD group were significantly higher than those in the RH group (13.91±1.99 μm, P<0.001; 2.97±0.55 μm, P=0.006) and FH group (13.83±2.00 μm, P<0.001; 2.31±0.54 μm, P<0.001), but there was no significant difference between the RH group and the FH group ( P>0.05). The number of IPCL in the NERD group, RH group and FH group were 2.0 (1.00, 2.75), 2.0 (1.00, 2.75) and 1.5 (1.00, 2.00), respectively with no significant difference ( P=0.697). Conclusion:Gerd-Q scale is not suitable for differential diagnosis of patients with endoscopic negative heartburn. Compared with functional esophageal diseases (RH and FH), acid reflux and mucosal microstructure changes are of more important pathogenic significance in NERD.

Objective:To quantify the diagnostic index of probe-based confocal laser endomicroscopy (pCLE) for diagnosing Helicobacter pylori ( HP)-associated chronic atrophic gastritis (HpCAG), and to evaluate the efficacy of the quantified diagnostic index for HpCAG. Methods:The study was divided into two stages. The first stage prospectively included patients undergoing gastroscopy, endoscopic biopsy and 13C breath test from November 2021 to September 2022 at the Second Affiliated Hospital of Baotou Medical College. The capillary diameter (CD), cells spacing (CS), gland spacing (GS), and gland area (GA) in the pCLE field of offline video was measured with Image J. The diagnostic criteria of HpCAG by quantitative indicators under pCLE was established by analyzing the area under the receiver operating characteristic (ROC) curve (AUC). In the second stage, the cases with pCLE examination and 13C breath test at the Second Affiliated Hospital of Baotou Medical College from October 2021 to October 2022 were included. The cases that overlapped with the first stage were excluded. The trial was single-blind, with endoscopists and pathologists blind to each other's diagnoses. The diagnosis of pCLE was conducted according to the criteria obtained in the first stage, and the consistency between pCLE diagnosis and the results of histopathology and 13C breath test was analyzed. Results:The first stage enrolled 191 specimens from 35 patients. According to the pathological results of endoscopic biopsy and 13C breath test results, patients and gastric mucosa samples were divided into 4 groups, HP-positive CAG group ( n=59), HP-positive non-CAG group ( n=52), HP-negative CAG group ( n=40), and HP-negative non-CAG group ( n=40). ROC curve analysis results showed that in HP-positive patients, the optimal critical value of GS to distinguish between CAG and non-CAG gastric mucosa was 29.68 μm, and the AUC was the largest among the 4 parameters. In HP-negative patients, the optimal critical value of GS for distinguishing gastric mucosa from CAG and non-CAG was 23.57 μm, and the AUC was the largest among the 4 parameters. In patients with non-CAG, the optimal critical value for GS to distinguish HP-positive and HP-negative gastric mucosa was 20.57 μm, and the AUC was the largest among the 4 parameters. In patients with CAG, the optimal critical values of CD, CS, GS and GA to distinguish between HP-positive and HP-negative gastric mucosa were 13.23 μm, 1.38 μm, 34.03 μm and 6 066.5 μm 2, respectively, and the AUC were 0.608, 0.888, 0.849 and 0.900, respectively. Finally, GS was selected to distinguish between HpCAG and non-HpCAG gastric mucosa, and the optimal critical value was 31.71 μm. However, considering that it was difficult to measure the distance of 31.71 μm by the ruler below the image, the critical value was changed to 30 μm, so GS>30 μm was used as the diagnostic criteria for HpCAG in pCLE, and the diagnostic sensitivity and the specificity were 91.5% and 76.0%, respectively. In the second phase 224 specimens from 80 patients were observed. The sensitivity, the specificity, the positive predictive value, the negative predictive value and accuracy of pCLE (GS>30 μm) in the diagnosis of HpCAG were 96.5% (164/170), 88.9% (48/54), 96.5% (164/170), 88.9% (48/54) and 94.6% (212/224), respectively, with excellent diagnostic agreement with histopathology and 13C breath test (Kappa=0.854). Conclusion:The quantitative monitoring of gastric mucosal microstructure can be achieved under pCLE, and the quantifying indicators are helpful to improve the accuracy of HpCAG diagnosis.