Short-chain fatty acids(SCFAs)are metabolites of intestinal microbiota produced from dietary fiber fermentation.They regulate the intestinal motility through multiple mechanisms including modulation of intestinal hormones,enteric nervous system,smooth muscle cells and interstitial cells of Cajal(ICC).Alterations in SCFAs content have been observed in patients with intestinal motivity disorders.Therapeutic interventions such as SCFAs supplementation,high-fiber diets,probiotics/prebiotics,and fecal bacteria transplantation(FMT)have demonstrated efficacy in improving clinical symptoms.This article reviewed research progress on the roles and mechanisms of SCFAs in intestinal motility.

Objective:To analyze the characteristics and electrogastrogram features of patients with functional dyspepsia (FD) overlapping lower gastrointestinal symptoms (LGS).Methods:The clinical data of 61 patients with FD from January 2018 to December 2020 in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. Among them, FD overlapping LGS was in 33 cases (FD overlapping LGS group), and simple FD in 28 cases (simple FD group). The manifestations of patients with FD overlapping LGS were recorded. The dyspeptic symptom score was assessed using the Rome Ⅳ criteria. Anxiety and depression status were evaluated using the hospital anxiety and depression scale (HADS), and sleep disorder was assessed using the Pittsburgh sleep quality index (PSQI). The electrogastrogram was performed, and the normal slow wave percentage (N%), bradygastria percentage (B%), tachygastria percentage (T%), arrhythmia percentage (A%), dominant frequency, dominant power and postprandial-to-fasting power ratio (PR) were recorded.Results:The most common symptom in FD patients overlapping LGS was lower abdomen distention, the incidence was 84.85% (28/33). The upper abdominal bloating score in FD overlapping LGS group was significantly higher than that in simple FD group: 7.00 (6.50, 7.00) scores vs. 5.00 (0.50, 7.00) scores, and there was statistical difference ( P<0.01); there were no statistical differences in other dyspeptic symptoms scores and total score between the two groups ( P>0.05). The incidences of depression and sleep disorder in FD overlapping LGS group were significantly higher than those in simple FD group: 42.42% (14/33) vs. 14.29% (4/28) and 69.70% (23/33) vs. 39.29% (11/28), and there were statistical differences ( χ2 = 5.77 and 5.68, P<0.05); there was no statistical difference in the incidence of anxiety between the two groups ( P>0.05). In FD overlapping LGS group, the postprandial T% in the gastric fundus and postprandial A% in the gastric body were significantly lower than those before meal: 13.79% (6.79%, 21.46%) vs. 20.69% (12.45%, 27.59%) and 3.45% (0, 6.90%) vs. 6.90% (3.45%, 13.79%), and there were statistical differences ( P<0.01). In simple FD group, the postprandial N% in the gastric fundus was significantly lower than that before meal: 55.92% (43.71%, 70.02%) vs. 69.27% (48.07%, 78.45%), and there was statistical difference ( P<0.05). In the gastric fundus, the preprandial N% in FD overlapping LGS group was significantly lower than that in simple FD group, preprandial B% and T% were significantly higher than those in simple FD group, and there were statistical differences ( P<0.01 or <0.05). In the gastric body, the preprandial N% in FD overlapping LGS group was significantly lower than that in simple FD group, and there was statistical difference ( P<0.05). In the pyloric region, the PR in FD overlapping LGS group was significantly lower than that in simple FD group, and there was statistical difference ( P<0.05). In the overall stomach, the preprandial N% in FD overlapping LGS group was significantly lower than that in simple FD group, the preprandial B% and T% were significantly higher than those in simple FD group, and there were statistical differences ( P<0.01 or <0.05). Spearman correlation analysis result showed that the disease course was not correlated with electrogastrogram parameters in patients with FD overlapping LGS ( P>0.05); the total score of dyspeptic symptoms was positively correlated with postprandial A% in the overall stomach ( r = 0.345, P<0.05), and negatively correlated with postprandial dominant frequency in the overall stomach and pyloric region ( r = -0.357 and -0.473, P<0.05 or <0.01). Conclusions:FD patients can overlap with various LGS. The patients with FD overlapping LGS have more severe dyspepsia symptoms, higher proportions of comorbid depression and sleep disorders, and more severe abnormalities in fasting proximal gastric electrical rhythm and emptying function. The severity of dyspeptic symptoms in patients with FD overlapping LGS is correlated with postprandial gastric electrical rhythm abnormalities.

Objective:To explore the occurrence of alexithymia in patients with functional constipation (FC) and its influence on the symptoms, anorectal function and treatment efficacy.Methods:From July 4, 2022 to September 30, 2023, a total of 118 FC patients who visited the outpatient Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University and underwent high-resolution anorectal manometry (HR-ARM) were selected. According to twenty-item Toronto alexithymia scale, a total score of <51 was classified as without alexithymia, and a total score of ≥51 was classified as with alexithymia. The combination of osmotic laxatives and probiotic agents was used for the treatment for 4 weeks. The efficacy of the medication was compared before and after treatment in FC patients with and without alexithymia, as well as the scores of patient assessment of constipation-symptom (PAC-SYM), patient assessment of constipation-quality of life (PAC-QoL), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and HR-ARM results.Independent sample t-test, Mann-Whitney U test and chi-square test were used for statistical analysis. Multivariate logistic regression analysis was performed to analyze the related factors affecting the efficacy of FC treatment. Results:Among the 118 FC patients, 43.2% (51/118) of FC patients had alexithymia, and 56.8% (67/118) of FC patients had no alexithymia. Among them, 43 patients without alexithymia and 32 patients with alexithymia completed the evaluation of treatment efficacy, respectively. There was no statistically significant difference in the frequency of spontaneous defecation before and after treatment in patients with alexithymia ( P>0.05). The frequency of complete spontaneous defecation after treatment was higher than that before treatment in FC patients without alexithymia (5.0 (3.0, 7.0) vs. 3.0 (2.0, 3.0)), and the increased times of total spontaneous defecation after treatment compared to before treatment in patients with alexithymia was less than that in patients without alexithymia (0.0 (0.0, 0.0) vs. -2.0 (-3.0, 0.0)), and the differences were statistically significant ( Z=-4.49 and -3.79, both P < 0.001). The scores of PAC-SYM, PAC-QoL, SAS and SDS in FC patients without alexithymia after treatment were all lower than those before treatment (2.0 (0.0, 8.0) vs. 14.0 (11.0, 16.0), 9.0 (1.1, 16.0) vs. 22.0 (18.0, 40.0), 26.0 (25.0, 30.0) vs. 29.0 (25.0, 34.0), 28.0 (26.0, 30.0) vs. 30.0 (29.0, 35.0)), and the differences were statistically significant ( Z=-5.24, -5.08, -3.60, and -5.21, all P<0.001). Among all the scores, only the PAC-SYM score after treatment was lower than that before treatment in FC patients with alexithymia (14.0 (9.5, 19.0) vs. 17.0 (12.5, 21.0)), and the difference was statistically significant ( Z=-2.66, P=0.008). The effective rate of FC patients without alexithymia was higher than that of patients with alexithymia (72.1%, 31/43 vs. 18.8%, 6/32), and the difference was significant ( χ2=22.09, P<0.001). The reduction of PAC-SYM, PAC-QoL, SAS and SDS scores in FC patients with alexithymia after treatment were all lower than those of FC patients without alexithymia (0.0 (0.0, 2.8) vs. 9.0 (2.0, 14.0), 0.0 (0.0, 0.8) vs. 15.0 (2.0, 19.0), 0.0 (-1.0, 1.0) vs. 0.0 (0.0, 4.0), 0.0 (0.0, 1.0) vs. 3.0 (1.0, 5.0)), and the differences were statistically significant ( Z=-4.24, -4.31, -2.59, and -4.60, all P<0.05). The results of multivariate logistic regression analysis showed that alexithymia was an independent risk factor of ineffective medication treatment of constipation in FC patients ( OR=8.930, 95% confidence interval 2.011 to 39.658, P=0.004). Conclusions:There is a high incidence of alexithymia in FC patients. Alexithymia affects the perception of symptoms and the efficacy of medication treatment of constipation in FC patients.

Objective:To analyze the factors associated with the occurrence of dysphagia after endoscopic submucosal dissection(ESD) treatment in patients with early esophageal cancer or precancerous lesions, and to explore their clinical predictive value.Methods:From March 1, 2020 to March 31, 2021, 35 patients diagnosed with early esophageal cancer or precancerous lesions without dysphagia before ESD treatment were recruited. All the patients were followed up for 2 years after ESD, and were divided into the non-dysphagia group (22 cases) and dysphagia group (13 cases) according to the occurrence of postoperative dysphagia. The demographic characteristics(such as gender and age), ESD-related data (such as the range of circumferential resection), the parameters of high resolution esophageal manometry such as distal contraction integral(DCI), the amplitude of peristaltic waves in various esophageal segments, and the psychological states such as self-rating anxiety scale (SAS) scores of the 2 groups were analyzed. Multivariate logistic regression was used to analyze the independent influencing factors for the occurrence of dysphagia after ESD and receiver operating characteristic curve (ROC) of the independent risk factors was plotted to assess the diagnostic efficacy.Results:The result of multivariate logistic regression analysis showed that the range of circumferential resection ( OR=23.881, 95% confidence interval (95% CI) 4.073 to 140.022), the SAS score ( OR=1.157, 95% CI 1.029 to 1.300), the mean value of DCI ( OR=0.864, 95% CI 0.750 to 0.995) and the maximum value of DCI ( OR=0.914, 95% CI 0.837 to 0.998) were independent influencing factors for postoperative dysphagia (all P<0.05).The result of ROC analysis showed that the area under the curve for the range of circumferential resection predicting dysphagia after ESD was 0.895 (95% CI 0.788 to 0.987, P<0.001), with an optimal cut-off value of 72.50, and the area under the curve for SAS score was 0.811 (95% CI 0.660 to 0.962, P=0.001), with an optimal cut-off value of 34.38. Conclusions:Reduced distal esophageal pressure, and(or) contractile weakness may contribute to dysphagia after ESD. Postoperative dysphagia risk increases when the range of circumferential esophageal resection exceeds 72.5% of the lumen circumference or the SAS score is over 34.

Short-chain fatty acids(SCFAs)are metabolites of intestinal microbiota produced from dietary fiber fermentation.They regulate the intestinal motility through multiple mechanisms including modulation of intestinal hormones,enteric nervous system,smooth muscle cells and interstitial cells of Cajal(ICC).Alterations in SCFAs content have been observed in patients with intestinal motivity disorders.Therapeutic interventions such as SCFAs supplementation,high-fiber diets,probiotics/prebiotics,and fecal bacteria transplantation(FMT)have demonstrated efficacy in improving clinical symptoms.This article reviewed research progress on the roles and mechanisms of SCFAs in intestinal motility.

Objective:To explore the occurrence of alexithymia in patients with functional constipation (FC) and its influence on the symptoms, anorectal function and treatment efficacy.Methods:From July 4, 2022 to September 30, 2023, a total of 118 FC patients who visited the outpatient Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University and underwent high-resolution anorectal manometry (HR-ARM) were selected. According to twenty-item Toronto alexithymia scale, a total score of <51 was classified as without alexithymia, and a total score of ≥51 was classified as with alexithymia. The combination of osmotic laxatives and probiotic agents was used for the treatment for 4 weeks. The efficacy of the medication was compared before and after treatment in FC patients with and without alexithymia, as well as the scores of patient assessment of constipation-symptom (PAC-SYM), patient assessment of constipation-quality of life (PAC-QoL), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and HR-ARM results.Independent sample t-test, Mann-Whitney U test and chi-square test were used for statistical analysis. Multivariate logistic regression analysis was performed to analyze the related factors affecting the efficacy of FC treatment. Results:Among the 118 FC patients, 43.2% (51/118) of FC patients had alexithymia, and 56.8% (67/118) of FC patients had no alexithymia. Among them, 43 patients without alexithymia and 32 patients with alexithymia completed the evaluation of treatment efficacy, respectively. There was no statistically significant difference in the frequency of spontaneous defecation before and after treatment in patients with alexithymia ( P>0.05). The frequency of complete spontaneous defecation after treatment was higher than that before treatment in FC patients without alexithymia (5.0 (3.0, 7.0) vs. 3.0 (2.0, 3.0)), and the increased times of total spontaneous defecation after treatment compared to before treatment in patients with alexithymia was less than that in patients without alexithymia (0.0 (0.0, 0.0) vs. -2.0 (-3.0, 0.0)), and the differences were statistically significant ( Z=-4.49 and -3.79, both P < 0.001). The scores of PAC-SYM, PAC-QoL, SAS and SDS in FC patients without alexithymia after treatment were all lower than those before treatment (2.0 (0.0, 8.0) vs. 14.0 (11.0, 16.0), 9.0 (1.1, 16.0) vs. 22.0 (18.0, 40.0), 26.0 (25.0, 30.0) vs. 29.0 (25.0, 34.0), 28.0 (26.0, 30.0) vs. 30.0 (29.0, 35.0)), and the differences were statistically significant ( Z=-5.24, -5.08, -3.60, and -5.21, all P<0.001). Among all the scores, only the PAC-SYM score after treatment was lower than that before treatment in FC patients with alexithymia (14.0 (9.5, 19.0) vs. 17.0 (12.5, 21.0)), and the difference was statistically significant ( Z=-2.66, P=0.008). The effective rate of FC patients without alexithymia was higher than that of patients with alexithymia (72.1%, 31/43 vs. 18.8%, 6/32), and the difference was significant ( χ2=22.09, P<0.001). The reduction of PAC-SYM, PAC-QoL, SAS and SDS scores in FC patients with alexithymia after treatment were all lower than those of FC patients without alexithymia (0.0 (0.0, 2.8) vs. 9.0 (2.0, 14.0), 0.0 (0.0, 0.8) vs. 15.0 (2.0, 19.0), 0.0 (-1.0, 1.0) vs. 0.0 (0.0, 4.0), 0.0 (0.0, 1.0) vs. 3.0 (1.0, 5.0)), and the differences were statistically significant ( Z=-4.24, -4.31, -2.59, and -4.60, all P<0.05). The results of multivariate logistic regression analysis showed that alexithymia was an independent risk factor of ineffective medication treatment of constipation in FC patients ( OR=8.930, 95% confidence interval 2.011 to 39.658, P=0.004). Conclusions:There is a high incidence of alexithymia in FC patients. Alexithymia affects the perception of symptoms and the efficacy of medication treatment of constipation in FC patients.

Objective:To analyze the factors associated with the occurrence of dysphagia after endoscopic submucosal dissection(ESD) treatment in patients with early esophageal cancer or precancerous lesions, and to explore their clinical predictive value.Methods:From March 1, 2020 to March 31, 2021, 35 patients diagnosed with early esophageal cancer or precancerous lesions without dysphagia before ESD treatment were recruited. All the patients were followed up for 2 years after ESD, and were divided into the non-dysphagia group (22 cases) and dysphagia group (13 cases) according to the occurrence of postoperative dysphagia. The demographic characteristics(such as gender and age), ESD-related data (such as the range of circumferential resection), the parameters of high resolution esophageal manometry such as distal contraction integral(DCI), the amplitude of peristaltic waves in various esophageal segments, and the psychological states such as self-rating anxiety scale (SAS) scores of the 2 groups were analyzed. Multivariate logistic regression was used to analyze the independent influencing factors for the occurrence of dysphagia after ESD and receiver operating characteristic curve (ROC) of the independent risk factors was plotted to assess the diagnostic efficacy.Results:The result of multivariate logistic regression analysis showed that the range of circumferential resection ( OR=23.881, 95% confidence interval (95% CI) 4.073 to 140.022), the SAS score ( OR=1.157, 95% CI 1.029 to 1.300), the mean value of DCI ( OR=0.864, 95% CI 0.750 to 0.995) and the maximum value of DCI ( OR=0.914, 95% CI 0.837 to 0.998) were independent influencing factors for postoperative dysphagia (all P<0.05).The result of ROC analysis showed that the area under the curve for the range of circumferential resection predicting dysphagia after ESD was 0.895 (95% CI 0.788 to 0.987, P<0.001), with an optimal cut-off value of 72.50, and the area under the curve for SAS score was 0.811 (95% CI 0.660 to 0.962, P=0.001), with an optimal cut-off value of 34.38. Conclusions:Reduced distal esophageal pressure, and(or) contractile weakness may contribute to dysphagia after ESD. Postoperative dysphagia risk increases when the range of circumferential esophageal resection exceeds 72.5% of the lumen circumference or the SAS score is over 34.

Objective:To explore the clinical application value of salivary pepsin test (Peptest) in the diagnosis of gastroesophageal reflux disease (GERD).Methods:From April to October 2022, at the Department of Gastroenterology of the First Affiliated Hospital of Nanjing Medical University, a total of 81 patients with typical reflux and (or) heartburn symptoms for more than 1 month, who were diagnosed with GERD and completed 24-hour esophageal pH impedance monitoring (24 h MII-pH) and high-resolution esophageal manometry were enrolled. Salivary samples were collected after lunch, at the onset of symptoms, and at random time point on the day of intubation, and all patients received standard dose of proton pump inhibitor (PPI) for 2 weeks. The 24 h MII-pH results were taken as the gold standard for diagnosing GERD. The optimal time point of Peptest and the diagnostic value of combination of Peptest and PPI test in GERD diagnosis were analyzed. The 24 h MII-pH negative patients were further divided into Peptest-positive group and Peptest-negative group. The heartbrun scores, gastroesophageal reflux disease questionnaire (GERD-Q), reflux characteristics, and esophageal motility between the 2 groups were compared and to investigate the differential diagnostic value of Peptest in 24 h MII-pH negative patients. Chi-square test and non-parametric test were used for statistical analysis.Results:The results of 24 h MII-pH indicated that 21 patients (25.9%, 21/81) were diagnosed GERD and 60 patients were negative for 24 h MII-pH. The onset of symptoms was the optimal time point for Peptest, with a sensitivity of 80.9%, a specificity of 50.0%, and an accuracy of 58.0%. The specificity and accuracy of Peptest at the onset of symptoms combined with PPI test in GERD diagnosis were higher than those of Peptest at the onset of symptoms alone (75.0% vs. 50.0%, 74.1% vs. 58.0%), and the differences were statistically significant ( χ2=8.00 and 4.65, P=0.005 and 0.031). Among 60 cases of 24 h MII-pH negative patients, 30 were positive for Peptest at the onset of symptoms and 30 were negative for Peptest at the onset of symptoms. The heartburn scores and GERD-Q scores of Peptest-positive group were both higher than those of Peptest-negative group (3.0 (2.0, 3.0) vs. 1.0 (0.0, 2.3), 12.0 (9.8, 13.0) vs. 9.0 (6.0, 11.0) ); the clearance time of acid reflux of Peptest-positive group was longer than that of Peptest-negative group (57.0 s (22.3 s, 88.0 s) vs. 18.3 s (9.6 s, 32.1 s) ); the lower esophageal sphincter resting pressure and integrated relaxation pressure were lower than those of Peptest-negative group (10.40 mmHg (5.75 mmHg, 18.95 mmHg) vs. 21.45 mmHg (10.65 mmHg, 31.70 mmHg), 3.90 mmHg (2.05 mmHg, 5.35 mmHg) vs. 4.90 mmHg (3.76 mmHg, 8.25 mmHg); 1 mmHg=0.133 kPa); the distal mean nocturnal baseline impedance, the distal contractile integral and esophagogastric junction contractile integral were all lower than those of Peptest-negative group ( 1 783 Ω (1 660 Ω, 2 157 Ω) vs. 2 300 Ω(1 805 Ω, 2 370 Ω), 1 416 mmHg·s·cm (919 mmHg·s·cm, 2 176 mmHg·s·cm) vs. 1 858 mmHg·s·cm (1 395 mmHg·s·cm, 2 880 mmHg·s·cm), 27.7 mmHg·cm (19.8 mmHg·cm, 39.5 mmHg·cm) vs. 52.6 mmHg·cm (27.7 mmHg·cm, 74.6 mmHg·cm) ), and the differences were statistically significant ( Z=-4.00, -3.53, -3.31, -2.34, -2.13, -2.75, -2.14 and -2.43; P<0.001, <0.001, =0.001, =0.019, =0.033, =0.006, =0.032 and =0.015). Conclusions:Peptest may be better at diagnosing GERD at the onset of symptoms compared to postprandial, random time points, and the accuracy of diagnosing GERD further improves when combined with PPI test. Peptest at the onset of symptoms may have differential diagnostic value for GERD patients in 24 h MII-pH negative patients.

Objective:To explore the efficacy and influencing factors of linaclotide in patients with functional defecation disorder (FDD).Methods:From June 1, 2021 to February 28, 2023, at the First Affiliated Hospital of Nanjing Medical University, 160 patients with FDD were enrolled and randomly divided into linaclotide group and polyethylene glycol group by using a random number table method, with 80 cases in each group, and the treatment course both was 4 weeks. The efficacy, weekly complete spontaneous bowel movement (CSBM), patient assessment of constipation symptom (PAC-SYM), numerical rating scale (NRS), Zung′s self-rating anxiety scale (SAS) and Zung′s self-rating depression scale (SDS) before and after treatment of linaclotide group and polyethyetylene glycol group were recorded and compared. Multivariate logistic regression analysis was performed to analyze the factors affected linaclotide in the treatment of FDD (including anorectal manometry). Receiver operating characteristic curve (ROC) was used to analyze the predictive value of risk factors on the efficacy of linaclotide in FDD. Independent sample t-test, paired t-test and chi-square test were used for statistical analysis. Results:After treatment, the weekly CSBM frequencies of linaclotide group and polyethylene glycol group were both higher than those before treatment in the same group (3.20±2.03 vs. 2.44±2.09, 3.10±2.26 vs. 2.58±2.06), and the differences were statistically significant ( t=-4.85 and -5.91, both P<0.001). After treatment, PAC-SYM score of stool shape, rectal symptom, abdominal symptom and total score, NRS score, SAS score and SDS score of linaclotide group and polyethylene glycol group were all lower than those before treatment in the same group (1.41±0.96 vs. 1.89±1.13, 0.95±0.49 vs. 1.14±0.46, 0.69±0.57 vs. 1.00±0.58, 0.96±0.43 vs. 1.23±0.40, 1.54±1.11 vs. 2.48±1.24, 43.54±6.26 vs. 45.13±7.30, 42.10±7.95 vs. 43.78±9.15 and 1.36±1.09 vs. 1.88±1.17, 0.83±0.40 vs. 1.10±0.45, 0.81±0.60 vs. 1.01±0.69, 0.91±0.42 vs. 1.21±0.41, 1.90±1.17 vs. 2.23±1.27, 43.55±7.72 vs. 44.61±8.51, 40.00±6.71 vs. 41.18±7.50), and the differences were statistically significant ( t=7.08, 7.73, 7.15, 9.26, 7.66, 7.96, 8.46, 7.26, 7.16, 5.78, 8.37, 6.17, 4.67 and 7.13, all P< 0.001). After treatment, the NRS score of linaclotide group was lower than that of polyethylene glycol group, and the difference was statistically significant ( t=-2.01, P=0.046). The total effective rate of linaclotide group was higher than that of polyethylene glycol group (77.5%, 62/80 vs. 62.5%, 50/80), and the difference was statistically significant ( χ2=4.29, P=0.038). The results of multivariate logistic regression analysis showed that the threshold of initial sensory volume and maximum tolerable volume were independent risk factors for linaclotide treatment of FDD ( OR=0.965, 95% confidence interval 0.936 to 0.995, P=0.022; OR=0.980, 95% confidence interval 0.962 to 0.999, P=0.041). The results of ROC analysis showed that the efficacy of linaclotide was poor in FDD patients with the threshold of initial sensory volume >67.5 mL or maximum tolerable volume > 117.5 mL. The combined predictive value of initial sensory volume and maximum tolerable volume threshold was higher than that of individual prediction, with an area under the curve of 0.722, sensitivity of 79.0% and specificity of 55.6%. Conclusions:Linaclotide can improve CSBM, constipation symptoms, abdominal pain and psychological status of FDD patients. The initial sensory volume threshold and maximum tolerable volume threshold are independent risk factors of the efficacy of linaclotide in FDD treatment and have certain predictive value in efficacy.

Background: Diabetic gastroparesis (DGP) is one of the most common complications of diabetes mellitus (DM), and its main symptoms include upper abdominal pain, nausea, vomiting, abdominal distension, etc. Gastric hypersensitivity is the main pathogenesis of DGP. Advanced glycation end products (AGEs) is the initiating factor of chronic complications of DM, and its relationship with gastric hypersensitivity has not yet been clear. Kv4.2 channel plays an important role in regulating visceral sensation. Subunit inactivation of Kv4.2 can reduce potassium current, enhance pain sensation, and increase gastric sensitivity. Aims: To investigate the mechanism of AGEs participating in gastric hypersensitivity by regulating the expression or activity of Kv4.2 channel in DM rat model. Methods: Fifty⁃four rats were randomly divided into control group, DM group and DM+AG group. Streptozocin (STZ) was intraperitoneally injected to induce DM rat model. Blood glucose, body weight, gastric sensitivity and gastric emptying rate were monitored. Western blotting and ELISA were used to detect CML content in stomach tissue and serum, respectively. The expression of RAGE and its co⁃expression with Kv4.2 in dorsal root ganglia (DRG) neurons were detected by immunofluorescence. Western blotting was used to detect RAGE expression and phosphorylation levels of ERK1/2 and Kv4.2 in DRG neurons. Results: Compared with control group, gastric sensitivity was significantly increased in DM group (P<0.01), gastric emptying rate was significantly decreased (P<0.05), AGEs marker CML content in serum and gastric tissue were significantly increased (P<0.05), co ⁃ expression rate of RAGE and Kv4.2 in DRG neurons was significantly increased (P<0.01), and phosphorylation levels of ERK1/2 and Kv4.2 were up⁃regulated (P<0.05). After intervention with AG, above⁃mentioned indices were significantly ameliorated (P<0.05). Conclusions: AGEs is an upstream factor leading to gastric hypersensitivity in DM rat model. AGEs increases the excitability of DRG neurons by inhibiting Kv4.2 channel, leading to gastric hypersensitivity. RAGE and ERK1/2 signal may be involved in the above process.