Objective:To evaluate the role of esophagogastric junction contractile index (EGJ-CI) in distinguishing patients with refractory gastroesophageal reflux disease (RGERD) from functional heartburn (FH).Methods:From March 2014 to January 2018, 82 patients with proton pump inhibitor (PPI) refractory heartburn and/or regurgitation, who visited the Outpatient Department of Gastroenterology at The First Affiliated Hospital with Nanjing Medical University were enrolled, among them 50 patients with RGERD (RGERD group) and 32 patients with FH (FH group). EGJ-CI of RGERD group and FH group were compared. The sensitivity and specificity of EGJ-CI to distinguish RGERD from FH patients. The correlation between EGJ-CI and high resolution esophageal manometry parameters, baseline impedance level and 24 h impedance-pH monitoring parameters were analyzed. Mann-Whitney U test, receiver operator characteristic curve analysis and Spearman correlation analysis were used for statistical analysis. Results:The EGJ-CI of RGERD group was lower than that of FH group (25.8 mmHg·cm (14.1 mmHg·cm, 35.9 mmHg·cm)(1 mmHg=0.133 kPa) vs. 39.2 mmHg·cm (23.0 mmHg·cm, 60.8 mmHg·cm)), and the difference was statistically significant ( Z=-2.833, P=0.005). When the cut-off value of EGJ-CI was 35.8 mmHg·cm, the sensitivity and specificity to distinguish RGERD from FH were 76.0% and 62.5%, respectively; area under the curve was 0.69 (95% CI 0.57 to 0.81). EGJ-CI was positively correlated with lower sphincter resting pressure, integrated relaxation pressure, distal contractile integral, distal esophageal pressure, and mean nocturnal baseline impedance ( r=0.812, 0.631, 0.451, 0.490 and 0.401, all P<0.01). EGJ-CI was negatively correlated with DeMeester score, acid exposure time, total reflux episodes, acid reflux episodes, long reflux episodes and longest reflux time ( r=-0.363, -0.372, -0.346, -0.318, -0.300 and -0.291, all P<0.01). Conclusions:EGJ-CI can help to distinguish patients with FH from RGERD.

[Objective]To explore the possible effects of the apolipoprotein A5(APOA5)gene rs2075291 and rs3135507 poly-morphisms on plasma lipid levels and the severity of coronary stenosis in patients with coronary heart disease(CHD)in Chinese Han people.[Methods]Polymerase chain reaction-restriction fragment length polymorphism method(PCR-RFLP)was used to identify the genotypes of the rs2075291 or rs3135507 polymorphism for the 324 patients with CHD and the 152 CHD-free controls,and the lipid levels between the genotypes were compared. The severity of coronary stenosis was assessed by the Gensini scoring system ,and the associations of the rs2075291 and rs3135507 polymorphisms as well as other factors with the Gensini scores were analyzed by mul-tivariate linear regression.[Results]The CHD patients had higher prevalence of hypertension ,and higher levels of triglycerides (TG),total cholesterol(TC),apolipoprotein B100(APOB100),lipoprotein(a)[Lp(a)],TG/high-density lipoprotein cholesterol (HDL-C),TC/HDL-C,low-density lipoprotein cholesterol(LDL-C)/HDL-C and APOB100/apolipoprotein AI(APOAI),and low-er levels of HDL-C and APOAI than the controls(P < 0.05 for all). The rs2075291 or rs3135507 allele and genotype frequencies were similar between the CHD group and the control group. The subjects with the rs2075291 GT genotype had higher levels of TG and TG/HDL-C,and lower levels of HDL-C than the subjects with the GG genotype in controls(P < 0.05 for all). In CHD patients, those with the rs2075291 GT genotype had higher levels of TG/HDL-C and TC/HDL-C than the patients with the GG genotype(P<0.05 for both). Regarding the rs3135507 polymorphism,the A allele carriers had lower level of APOB100 than the patients with the GG genotype(P<0.05). No significant association between the rs2075291 or rs3135507 polymorphism and the Gensini scores were detected by multivariate linear regression(P > 0.05).[Conclusion]The APOA5 rs2075291 polymorphism had significant effects on plasma lipid levels,but no effects on the occurrence and development of CHD. Further multicenter case-control studies with large samples are needed to validate these findings.

The Rome IIII( criteria were released in May 2016. Based on the development of brain-intestinal axis theory, intestinal microecology, pharmacogenomics and social psychology, the Rome IIII( criteria revise the definition, diagnostic criteria, clinical evaluation process, and treatments of functional constipation (FC). The revisions are as follows: (1) Definition: FC and constipation-predominant irritable bowel syndrome are considered to be on a continuum rather than as independent entities. (2) Diagnostic criteria: the Bristol stool scale type 1, type 2 and spontaneous bowel movements are added in the diagnostic criteria, respectively, refining the criteria for stool consistency and frequency. (3) Clinical evaluation process: the Rome IIII( criteria specifies the clinical assessment procedure for FC. The aim is to exclude organic disease, to detect the structural changes of the combination, to determine the type of guidance therapy, and to reduce unnecessary checks to improve diagnostic efficiency. (4) Pathophysiologic mechanism: much more newly investigated mechanisms are added, including the risk factors, genetics, inadequate colonic propulsion and defecation disorder. (5) Treatment: the treatment regimen summarizes the evidence-based medical evidence of new drugs, such as secretagogues and bile acid transport inhibitors, and evaluates the safety of all the new and old drugs. Compared to the Rome III( standard, the diagnosis of FC will be more stringent and efficient, and the treatment options will be more standardized and reasonable with the Rome IIII(.

[ABSTRACT]AIM:ToobservehowfarnesoidXreceptor(FXR)functionedinconcanavalinA(ConA)-induced hepatitis (CIH) and the regulation of FXR-thyrotropin embryonic factor (TEF) pathway.METHODS:C57BL/6 mice were injected with Con A to induce hepatitis .The expression of FXR and TEF in the liver specimens was determined by qRT-PCR and Western blotting .The concentrations of serum ALT/AST and inflammatory cytokines IFN-γ, TNF-α, IL-4 and IL-2 in the blood samples were tested after Con A injection .RESULTS:FXR was down-regulated in CIH mice .TEF was up-regula-ted when FXR was activated by chenodeoxycholic acid (CDCA).Activation of FXR reduced the levels of aminotransferases and inflammatory cytokines IFN-γ, TNF-α, IL-4 and IL-2 in the CIH mice induced by Con A injection .CONCLUSION:FXR activation attenuates CIH mouse liver injury and reduces inflammatory cytokines .FXR activation results in TEF up-regu-lation.The FXR-TEF pathway may play a protective role in autoimmune hepatitis .

Background/Aims: Achalasia is a rare disease, but the incidence is increasing recently. Peroral esophageal myotomy (POEM) is an effective treatment.Regurgitation is a common symptom before and after POEM. Our aim is to investigate the factors related to preoperative and postoperative reflux symptoms. Methods: Our study was retrospective. The achalasia patients diagnosed by high-resolution manometry and gastroscopy were divided into reflux group and non-reflux group before and after POEM, respectively. General information, symptoms, POEM information, and manometric results were compared. Results: (1) Ninety-six of 130 patients had reflux symptoms before POEM. The lower esophageal sphincter pressure (LESP) in the reflux group was significantly higher than the non-reflux group (P = 0.023), while integrated relaxation pressure (IRP) was similar. The reflux group had longer esophagus than the non-reflux group (P = 0.006). Reflux symptoms were not related to subtypes of achalasia.(2) Twenty-five of 84 patients had reflux symptoms after POEM. Postoperative Eckardt scores, LESP, and 4-second IRP (4sIRP) were significantly lower than the preoperative values (P < 0.001). The preoperative values and POEM information were similar between the postoperative 2 groups and there was no significant difference in the presence of preoperative reflux symptoms between 2 groups.The postoperative LESP and 4sIRP were similar between the 2 groups, however, the postoperative UESP was significantly higher in the reflux group than the non-reflux group (P = 0.042). The non-reflux group had more declines in Eckardt scores and LESP than the reflux group. Conclusions The reflux symptoms of achalasia patients without treatment were mainly due to food retention. The postoperative reflux symptoms were not the sign of the excessive relaxation of lower esophageal sphincter.

Background/Aims: Achalasia is a rare disease, but the incidence is increasing recently. Peroral esophageal myotomy (POEM) is an effective treatment.Regurgitation is a common symptom before and after POEM. Our aim is to investigate the factors related to preoperative and postoperative reflux symptoms. Methods: Our study was retrospective. The achalasia patients diagnosed by high-resolution manometry and gastroscopy were divided into reflux group and non-reflux group before and after POEM, respectively. General information, symptoms, POEM information, and manometric results were compared. Results: (1) Ninety-six of 130 patients had reflux symptoms before POEM. The lower esophageal sphincter pressure (LESP) in the reflux group was significantly higher than the non-reflux group (P = 0.023), while integrated relaxation pressure (IRP) was similar. The reflux group had longer esophagus than the non-reflux group (P = 0.006). Reflux symptoms were not related to subtypes of achalasia.(2) Twenty-five of 84 patients had reflux symptoms after POEM. Postoperative Eckardt scores, LESP, and 4-second IRP (4sIRP) were significantly lower than the preoperative values (P < 0.001). The preoperative values and POEM information were similar between the postoperative 2 groups and there was no significant difference in the presence of preoperative reflux symptoms between 2 groups.The postoperative LESP and 4sIRP were similar between the 2 groups, however, the postoperative UESP was significantly higher in the reflux group than the non-reflux group (P = 0.042). The non-reflux group had more declines in Eckardt scores and LESP than the reflux group. Conclusions The reflux symptoms of achalasia patients without treatment were mainly due to food retention. The postoperative reflux symptoms were not the sign of the excessive relaxation of lower esophageal sphincter.

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.

Background/Aims: It is known that post-reflux swallow-induced peristaltic wave (PSPW) index represents the chemical clearance of the esophagus. However, few studies have explored why some reflux episodes could induce PSPW while others in the same patient could not. The purpose of this study is to investigate the characteristics of reflux episodes which could elicit PSPW. Methods: In this study, 269 reflux episodes were detected, of which 90 with a PSPW and 179 without a PSPW. Comparisons were made between the characteristics of reflux episodes with a PSPW and without a PSPW. The characteristics were including nadir pH, pH drop, proximal extent (cm, sec), ascending velocity (cm/sec), volume clearance time, acid clearance time, percentage acidic (%), 15 to 60-minute acid burden (seconds), and 15- to 60-minute volume burden (seconds). The characteristics between the 2 groups were compared through performing Wilcoxon signed rank test. Results: Reflux episodes followed by a PSPW were significantly associated with a higher proximal extent than those without a PSPW. After the reflux episodes, higher volume clearance time and larger volume burden were more likely to trigger a PSPW. However, there were no significant differences between the 2 groups in nadir pH, pH drop, ascending velocity, acid clearance time, percentage acidic, or acid burden. Conclusions The role of acid seems to be less important in a reflux episode inducing a PSPW. Proximal reflux episodes are more likely to induce a PSPW. The depression of volume clearance may also be an important factor in eliciting a PSPW.

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.