Objective To investigate the inhibitory effects and related mechanisms of NOD like receptor protein 3 (NLRP-3) inflammasome inhibitor MCC950 on oxidative stress, inflammation, and pyroptosis in human esophageal epithelial cells (HEECs). MethodsHEECs cells were passaged and divided into blank control group, acid stimulation group (stimulated 3 times a day with pH 4 acidic medium for 15 minutes each time, cultured for 48 hours), bile salt stimulation group (stimulated 3 times a day with 400 μmol/L bile salt mixture for 15 minutes each time, cultured for 48 hours), lipopolysaccharide (LPS) group (stimulated with 10 μL of 100 ng/mL LPS for 48 hours), MCC950 group (stimulated with 10 μL of 7.5 ng/mL MCC950 for 4 hours, then stimulated with acid, bile hydrochloric acid, and LPS for 48 hours), and N-acetyl-L-cysteine (NAC) group (stimulated with 1 mmol/L NAC for 4 hours, then stimulated with acid, bile hydrochloric acid, and LPS 48 hours). Three culture dishes were used in each group to detect the mRNA and protein expression levels of oxidative protein/antioxidant protein [Nox-4 (NADPH oxidase 4), nuclearfactor erythroidderived 2-like 2 (Nrf-2), heme oxygenase-1 (HO-1)], NLRP-3 signaling pathway [NLRP-3/caspase-1/intereukin (IL)-1β/IL-18], and cell apoptosis pathway [caspase-4/caspase-5/GSDMD] using real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting experiments. Cell apoptosis were observed through Hoechst33342 staining. ResultsMCC950 intervention (0.023) and NAC intervention (0.031) effectively inhibited HEECs apoptosis induced by acid (0.042), bile salt (0.047), and LPS (0.054). The results of RT-PCR experiments showed that MCC950 intervention and NAC intervention significantly inhibited the high expression of Nox-4 mRNA (MCC950: 1.68; NAC: 1.62) in HEECs cells induced by acid (2.40), bile salt (3.07), and LPS (3.52), and significantly upregulated the mRNA expression levels of antioxidant proteins Nrf-2 (MCC950: 0.72; NAC: 0.57) and HO-1 (MCC950: 0.74; NAC: 0.57). MCC950 intervention and antioxidant NAC intervention effectively inhibited the mRNA expression levels of NLRP-3 (MCC950: 1.58; NAC: 1.47), ASC (MCC950: 1.56; NAC: 1.93), caspase-1 (MCC950: 1.64; NAC: 1.96), IL-1β (MCC950: 1.66; NAC: 1.82), IL-18 (MCC950: 1.58; NAC: 1.84) in HEECs cells induced by acid stimulated, bile salt stimulated, and LPS. MCC950 intervention and antioxidant NAC intervention effectively inhibited the mRNA expression levels of apoptosis pathway markers such as caspase-4 (MCC950: 1.51; NAC: 1.61), caspase-5 (MCC950: 1.38; NAC: 1.64), and GSDMD (MCC950: 1.41; NAC: 1.54) induced by acid stimulation, bile salt stimulation, and LPS in HEECs cells. The electrophoresis results were similar with RT-PCR. ConclusionAcid, bile salt, and LPS can all induce the overexpression of oxidative stress markers in HEECs, reduce the expression of antioxidant proteins, and activate the NLRP-3 inflammasome signaling pathway and cell pyroptosis pathway, promoting cellular inflammatory damage, but MCC950 has a protective effect.
Abstract: Objective To evaluate the effect on gastroesophageal reflux and gastric emptying in the different route of gastroesophageal anastomosis objectively after esophagectomy for patients with midesophageal carcinoma. Methods Forty patients with midesophageal carcinoma were randomly divided into two groups. Esophageal bed group (n=20): the gastroesophageal anastomosis were performed while the stomach were pulled on through the esophageal bed after esophagectomy; endothoracic group (n=20): gastroesophageal anastomosis were performed while the stomach were pulled on in the thoracic cavity. Ten persons had no disease of digestive system and healthy volunteers were recruited as normal control group. 24-hour esophageal pH monitoring and radioisotope gastric emptying checkup were carried out in all experimental subjects 3 months after operation, so as to observe the changes of gastroesophageal reflux and gastric emptying. Results All of the patients’s operation were success. And no anastomotic leakage and no anastomotic stenosis. Three months after operation, the patients in both operation groups were with different level of reflux. DeMeester total appraise score, the times of regurgitation of gastric juice in 24h, gt;5 min reflux frequency, the longest time of keep reflux, pHlt;4.00 total time and pHlt;4.00 of total time percent, these targets in both operation groups were higher than those in control group (Plt;0.01) DeMeester total appraise score, the times of regurgitation of gastric juice in 24 hours, the longest time of keeping reflux, pHlt;4.00 of total time and pHlt;4.00 of total time percent in esophageal bed group were lower than those in endothoracic group(Plt;0.01). The recent period of gastric emptying percentage (GE) in both operative groups were lower than that in normal control group. GE in esophageal bed group experimental meal in the stomach after entering the 30,60,90,120,180 and 240 min were higher than those in endothoracic group. Conclusion After the operation of esophagogastric anastomosis through esophageal bed in upper aortic site,gastroesophageal reflux and delayed gastric emptying exist objectively, However, the technique is superior to the traditional technique to reduce the extent of gastroesophageal reflux and delayed gastric emptying, its mechanism might be the result of mechanical factors.
ObjectiveTo summarize basic research progress and current status of clinical diagnosis and therapy for gastroesophageal reflux disease. MethodRelated literatures were collected to review the pathogenesis, clinical manifestations, diagnosis and therapy of gastroesophageal reflux disease. ResultsGastroesophageal reflux disease was caused by many factors, such as hiatus hernia, hypotensive lower esophageal sphincter pressure, acid pocket, prolonged esophageal clearance, and delayed gastric emptying. Extra-esophageal symptoms was a common clinical presentation to gastroesophageal reflux disease. The diagnosis methods for gastroesophageal reflux disease included the symptom observation, gastroscopy examination, 24 h pH monitoring of esophageal, proton pump inhibitor test, questionnaire of gastroesophageal reflux disease and so on. The laparoscopic fundoplication could essentially treat the pathophysiologic abnormalities of gastroesophageal reflux disease, which had an obvious curative effect and wide application prospect. ConclusionPathogenesis, diagnosis, and therapy of gastroesophageal reflux disease are associated with multiple factors, which is still controversial and remains to be further studied.
ObjectiveTo investigate the clinical effects of laparoscopic hiatus reconstruction with Bard Crurosoft patch associated with Nissen fundoplication in elderly patients with gastroesophageal reflux disease (GERD). MethodsFrom July 2006 to July 2009, 22 consecutive elderly patients （≥65 years） with GERD underwent laparoscopic hiatus reconstruction associated with Nissen fundoplication， 10 of them underwent laparoscopic Crurosoft patch hiatus reconstruction (hiatus diameter≥5 cm in 2 patients， lt;5 cm in 8 patients) and 12 underwent laparoscopic simple sutured hiatus reconstruction (hiatus diameter≥5 cm in 2 patients， lt;5 cm in 10 patients). Intra and perioperative data including symptoms (heartburn, regurgitation, dysphagia, and respiratory complications), functional evaluations (esophagogastroscopy, manometric evaluations in lower esophageal segment, and 24 h pH-monitoring values) were compared and analyzed. ResultsPatients in 2 groups had similar preoperative values in demographics, symptom scores, functional evaluations, as well as operative data except for mean operative time. Three-month and 1-year follow-up after operation, the results of symptoms scores and functional evaluations of patients in 2 groups compared with preoperative values wear improved （Plt;0.05）, but symptoms scores and functional evaluations of patients in patch group were evaluated to demonstrate more significant improvement than suture group （Plt;0.05）. In suture group, the results of 3 months after operation were better than 1 year after operation, with statistically significant difference （Plt;0.05）. Two patients underwent postoperative intrathoracic immigration of wrap in suture group, but this complication did not happen in patch group （Plt;0.05）. ConclusionsLaparoscopic hiatus reconstruction with Bard Crurosoft patch associated with Nissen fundoplication is a safe and effective treatment for elderly patients(≥65 years) with GERD.
胃食管反流(GER)是指胃酸和其他胃内容物反流进入食管，正常人存在一定程度的反流，称为生理性反流。GER 可以引起临床症状，甚至组织病理学的改变。当出现胃烧灼、反酸、胸骨后疼痛等临床症状和(或)组织病理学的改变时，也被称为胃食管反流病(GERD)。以慢性咳嗽为主要临床表现的GERD称为胃食管反流性咳嗽(GERC)。2006年蒙特利尔会议提出了反流性咳嗽综合征的定义 。GERC 是慢性咳嗽的常见原因，发生率为5％~41％ ，存在一定的地区差异。欧美报道极为常见，而日本极为少见，国内 GERC占慢性咳嗽病因的12％。
ObjectiveTo analyze the causal relationship between the intake of cheese or tea and the risk of gastroesophageal reflux disease (GERD). MethodsUsing a two-sample Mendelian randomization approach, single nucleotide polymorphisms (SNPs) associated with milk or tea intake were used as instrumental variables. The causal effect of milk or tea intake on the risk of GERD was investigated using the MR Egger method, the weighted median method, the inverse-variance weighted (IVW) random-effects model, and the IVW fixed-effects model. Multivariable analysis was conducted using the MR Egger method, and leave-one-out sensitivity analysis was performed to validate the reliability of the data. ResultsCheese intake could reduce the occurrence of GERD [IVW random-effects model β=–1.010, 95%CI (0.265, 0.502), P<0.05], while tea intake could lead to the occurrence of GERD [IVW random-effects model β=0.288, 95%CI (1.062, 1.673), P<0.05]. ConclusionCheese intake may have a positive causal relationship with reducing the risk of GERD occurrence, while tea intake may have a positive causal relationship with increasing the risk of GERD occurrence.
Objective To investigate the clinical characteristics of upper airway cough syndrome ( UACS) and the relationship of UACS with upper airway diseases, cough variant asthma ( CVA) , and gastroesophageal reflux disease ( GERD) . Methods 92 subjects with chronic cough and throat symptoms and signs were included in the study. The medical records were collected fromall subjects, and 49 subjects suspected for CVA undertook bronchial provocation test. Then the efficacy was evaluated and etiology were analyzed based on the efficacy of targeted treatment. Results Bronchial provocation test yielded positive results in 14 subjects suspected of CVA, accounting for 15. 2% of all cases ( 14/92) . 18. 5% ( 17 /92) of patients had a history of chronic gastritis or combined symptoms of GERD, of whom anti-gastroesophagealreflux treatment was effective. The patients with rhinitis, sinusitis history and/ or symptoms accounted for 33. 7% of cases ( 31 cases) . 51. 1% ( 47/92) of patients had only signs and symptoms of chronic pharyngitis. Conclusions UACS is not only due to the rhinitis and/ or sinusitis but also chronic pharyngitis. Chronic pharyngitis may be secondary to chronic rhinitis/ sinusitis with post nasal drip and gastroesophageal reflux, also may be an independent cause of chronic cough.
Objective To review the clinical experience of Heller myotomy for treatment of achalasia through a small thoracotomy. Methods Twenty-five patients with achalasia (9 moderate, 16 severe) underwent Heller myotomy without concomitant antireflux procedure through a small incision. A left thoracotomy was carried out through either the seventh or eighth intercostals space. The length of skin incision was 6 to 8 cm. Results There was no hospital death and severe postoperative complications. The mean operating time was 50 minutes. Mean hospital stay was 10 days. There was one intraoperative perforation and repaired successfully. All patients reported good to excellent relief of dysphagia and no symptom of gastroesophageal reflux after surgery. Eight patients were subsequently studied with a 24-hour esophageal pH monitoring and no evidence of pathologic reflux found. Conclusions Transthoracic Heller myotomy with a small incision is effective and safe method for treatment of achalasia with minimal invasion, quick recovery, less postoperative complication and shorter hospital stay. Proper extent of the myotomy may decrease the risk of subsequent gastroesophageal reflux in the postoperative period.