1.Clinical characteristics and electrogastrogram analysis of patients with functional dyspepsia overlapping lower gastrointestinal symptoms
Fei LI ; Ting YU ; Meifeng WANG ; Lin LIN ; Liuqin JIANG
Chinese Journal of Postgraduates of Medicine 2024;47(1):6-12
		                        		
		                        			
		                        			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.
		                        		
		                        		
		                        		
		                        	
2. AGEs in DRG Participates in Gastric Hypersensitivity by Regulating Expression of Kv4.2 in Diabetes Mellitus Rat Model
Jiahao WANG ; Ting YU ; Liuqin JIANG
Chinese Journal of Gastroenterology 2023;27(5):263-269
		                        		
		                        			
		                        			 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. 
		                        		
		                        		
		                        		
		                        	
3. Advances in Study on Role of Vagus Nerve in Gut-brain Interaction Disorder in Irritable Bowel Syndrome
Qi CHEN ; Ya JIANG ; Yurong TANG ; Liuqin JIANG
Chinese Journal of Gastroenterology 2023;28(5):307-311
		                        		
		                        			
		                        			 The vagus nerve serves as an important part of the gut-brain axis, which regulates intestinal movement and secretion, emotional and immune response, and is involved in gut-brain interaction disorder in patients with irritable bowel syndrome (IBS). This article provides an overview of the vagus nerve function, the relationship between vagus nerve dysfunction in gut-brain axis and pathogenesis of IBS, and the application of vagus nerve in IBS treatment, with the aim for helping clinicians to better understand the correlation between vagus nerve and gut - brain interaction disorder, and shedding light on potential treatment in IBS. 
		                        		
		                        		
		                        		
		                        	
4. Progress of Research on Role of Eosinophils in Irritable Bowel Syndrome
Sainan SHI ; Lin LIN ; Liuqin JIANG
Chinese Journal of Gastroenterology 2023;28(1):49-52
		                        		
		                        			
		                        			 Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by repeated abdominal pain and changes in defecation habits, which seriously affects the quality of life of patients. The occurrence and development of IBS are affected by many factors. As an inherent component of the gastrointestinal tract, eosinophils play a role in maintaining the local homeostasis of intestine. The activation of intestinal eosinophils plays a direct or indirect role in the occurrence and development of IBS. This article reviewed the progress of research on the potential role of eosinophils in IBS. 
		                        		
		                        		
		                        		
		                        	
5.Randomized Controlled Trial of Anti-reflux Mucosectomy Versus Radiofrequency Energy Delivery for Proton Pump Inhibitor-refractory Gastroesophageal Reflux Disease
Yan WANG ; Meihui LV ; Lin LIN ; Liuqin JIANG
Journal of Neurogastroenterology and Motility 2023;29(3):306-313
		                        		
		                        			 Background/Aims:
		                        			The efficacy and safety of anti-reflux mucosectomy (ARMS) or radiofrequency energy delivery in the treatment of gastroesophageal reflux disease (GERD) have been reported, but the difference between the 2 remains unclear. 
		                        		
		                        			Methods:
		                        			This was a single center, randomized, comparative clinical study. Patients with symptoms of heartburn and/or regurgitation despite proton pump inhibitor treatment were randomly assigned to either ARMS group (n = 20) or radiofrequency group (n = 20).Primary outcome was the standardized GERD questionnaire (GERDQ) at 2 years after the procedures. Secondary outcomes were the proportions of patients with complete proton pump inhibitor (PPI) cessation and patients satisfied with the treatment. 
		                        		
		                        			Results:
		                        			A total of 18 patients randomized to ARMS and 16 to radiofrequency were analyzed in this study. The operation success rate of the 2 groups was 100%. In both ARMS and radiofrequency groups, GERDQ scores at 2 years after the procedures were significantly lower than that before operation (P = 0.044 and P = 0.046). At 2 years postoperatively, the scores of GERDQ did not differ between the 2 groups (P = 0.755). There was no significant difference in the rate of discontinuation of PPIs and patient satisfaction in the ARMS and radiofrequency groups (P = 0.642 and P = 0.934). 
		                        		
		                        			Conclusions
		                        			The clinical efficacy of ARMS and radiofrequency for the PPI-refractory GERD is equivalent. ARMS, the efficacy of which could be maintained for at least 2 years, is promising endoscopic management for the treatment of refractory GERD. 
		                        		
		                        		
		                        		
		                        	
6.The diagnostic value of salivary pepsin test in gastroesophageal reflux disease
Rongrong CHEN ; Hui MAO ; Benchang FENG ; Meifeng WANG ; Lin LIN ; Liuqin JIANG
Chinese Journal of Digestion 2023;43(10):670-676
		                        		
		                        			
		                        			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.
		                        		
		                        		
		                        		
		                        	
7.Efficacy and influencing factors of linaclotide in functional defecation disorders
Benchang FENG ; Rongrong CHEN ; Feng ZHU ; Lin LIN ; Meifeng WANG ; Liuqin JIANG
Chinese Journal of Digestion 2023;43(12):828-833
		                        		
		                        			
		                        			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.
		                        		
		                        		
		                        		
		                        	
8. Clinical Characteristics of Gastroesophageal Reflux Disease Patients With Laryngopharyngeal Symptoms
Rongrong CHEN ; Benchang FENG ; Jiahao WANG ; Meifeng WANG ; Lin LIN ; Liuqin JIANG
Chinese Journal of Gastroenterology 2022;27(7):392-398
		                        		
		                        			
		                        			 Background: The laryngopharyngeal symptoms of gastroesophageal reflux disease (GERD) include hoarseness, foreign body sensation, chronic cough, dysphagia, etc. Its pathogenic mechanisms and reflux characteristics may be different from those of GERD patients simply with typical esophageal symptoms. Aims: To explore the clinical characteristics of GERD patients complicated with laryngopharyngeal symptoms. Methods: Fifty-nine patients having a gastroesophageal reflux disease questionnaire (GerdQ) score ≥8 and abnormal reflux identified by 24 h esophageal impedance-pH monitoring were selected from the outpatients at the First Affiliated Hospital of Nanjing Medical University from January 2019 to December 2021. Twenty-nine cases simply with typical esophageal symptoms were allocated into typical symptom group, and 30 cases complicated with laryngopharyngeal symptoms were allocated into laryngopharyngeal reflux (LPR) group. The general information, results of gastroscopy, 24 h esophageal impedance - pH monitoring and esophageal manometry, as well as the efficacy of proton pump inhibitor (PPI) were collected and compared between the two groups. Results: The proportion of esophagitis in GERD patients in typical symptom group was significantly increased than that in LPR group (P<0.05), while the values of mean nocturnal baseline impedance at 7-3 cm above lower esophageal sphincter (LES) were significantly lower (all P<0.05). Compared with typical symptom group, increased frequency of weak acid reflux, prolonged mean acid clearance time, higher LES relaxation rate, lower velocity of peristaltic waves at 11-7 cm above LES, and poor efficacy of PPI treatment were observed in LPR group (all P<0.05). The severity of heartburn was positively correlated with the percentage of total acid exposure time and DeMeester score (all P<0.05); while the severity of foreign body sensation was positively correlated with the frequency of weak acid reflux and mean time of acid clearance (all P<0.05). Conclusions: The esophageal mucosal injury was mild in GERD patients complicated with laryngopharyngeal symptoms. Laryngopharyngeal symptoms are more likely to be associated with the decreased acid clearance capacity due to esophageal body dysmotility. Strengthened acid suppression therapy should be recommended. 
		                        		
		                        		
		                        		
		                        	
9. Advances in Study on Role of Food Intolerance in Pathogenesis of Irritable Bowel Syndrome
Chinese Journal of Gastroenterology 2022;27(2):97-101
		                        		
		                        			
		                        			 At present,many studies showed that food intolerance (FI) is one of the important factors for the occurrence and aggravation of irritable bowel syndrome (IBS). The FI in IBS patients is related to low grade inflammation of intestine. Fermentable oligo‑,di‑,monosaccharides and polyols (FODMAPs) diet can improve the symptoms of IBS and provide a new idea for exploring the pathogenesis and treatment of IBS. This article reviewed the advances in study on role of FI in pathogenesis of IBS. 
		                        		
		                        		
		                        		
		                        	
10. Influence of Ineffective Swallows on Esophageal Motility and Gastroesophageal Reflux
Xuemin YAO ; Bixing YE ; Meifeng WANG ; Lin UN ; Liuqin JIANG ; Xuemin YAO ; Ying JIN ; Liuqin JIANG
Chinese Journal of Gastroenterology 2022;27(1):9-16
		                        		
		                        			
		                        			 Background : Studies showed that esophageal body dysmotility is associated with gastroesophageal reflux disease (GERD), however, their interactions are still unclear. Aims: To explore the influence of proportion of ineffective swallows on esophageal motility and gastroesophageal reflux in esophageal high-resolution manometry (HRM). Methods: Patients who completed esophageal HRM and 24 h esophageal impedanee-pH monitoring and were identified as normal esophageal motility or mild dysmotility from March 2018 to December 2019 at the First Affiliated Hospital of Nanjing Medical University were recruited retrospectively. According to the times of ineffective swallows in 10 warm water swallows in HRM, these patients were allocated into four groups; Group A (0 times), Group B (1-4 times), Group C (5-7 times), Group D (8-10 times). The parameters of esophageal HRM and 24 h esophageal impedance-pH monitoring were analyzed, and the value of ineffective swallows for assistant diagnosis of pathological acid reflux was assessed. Results: A total of 142 patients were included. There were no significant differences in abnormal manometric parameters between the four groups (all P > 0. 05). In Group D, the number of weak and non-peristalsis were increased, while the mean and maximum value of distal contractile integral (DCI) were decreased as compared with those in Group A and Group B (all P < 0. 05). Between Group C and Group D, the differences in mean and maximum DCI value were significant (all P < 0. 05). As the times of ineffective swallows increased, the acid exposure time (AET) and DeMeester score gradually increased from Group A to Group D (all P < 0. 05). Times of ineffective swallows and weak peristalsis were moderately and positively correlated with AET, DeMeester score, and the total number of acid exposure (all P < 0. 05). ROC curve analysis revealed that the area under the curve (AUC) of ineffective swallows for assistant diagnosis of pathological acid reflux was 0. 625 (95 % CI; 0.523-0. 727, P = 0. 027); the optimal cut-off value was 4. 5, and the sensitivity and specificity were 62. 9% and 61. 7 %, respectively. The diagnostic performance of weak peristalsis was superior to that of non-peristalsis (AUC: 0. 625 vs. 0. 590). Conclusions: Different proportions of ineffective swallows suggest different clinical significance. The clinical relevance of ineffective swallows > 70 % might be most significant, and to a certain extent, can predicts pathological acid reflux. 
		                        		
		                        		
		                        		
		                        	
            
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