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Gastroesophageal reflux disease (GERD) is a gastrointestinal motility disorder that results from the reflux of stomach contents into the esophagus or oral cavity, causing symptoms or complications. The typical symptoms of GERD are heartburn and regurgitation of gastric contents into the oropharynx. Heartburn is the sensation of burning or discomfort behind the sternum. Heartburn may radiate into the neck, is typically worse after meals or when in a reclining position, and may be eased by antacids. Regurgitation is the backflow of gastric contents into the mouth or hypopharynx. Epigastric pain can also be a symptom of GERD. Extraesophageal symptoms of GERD include dental erosions, laryngitis, cough, and asthma. In recent years, great progress has been made in understanding the molecular basis of GERD, suggesting that its pathogenesis is more complex and multifactorial. In this paper, the molecular pathogenesis was taken as the starting point, including the mechanism of genes in the pathogenesis and development of GERD, the mechanism of NF-κB pathway in the pathogenesis and development of GERD, the role of proteinase-activated receptor-2 in the pathogenesis of GERD, the association between abnormal serotonin pathway and GERD, and the relationship between reactive oxygen species and GERD, to summarize the pathogenesis of gastroesophageal reflux disease.
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Gastroesophageal reflux disease (GERD) is a global digestive system disease caused by the reflux of gastric contents into the esophagus and the injury of esophageal mucosa. At present, the pathogenesis of GERD is not completely clear. Studies have found that GERD is closely related to intestinal flora disorder and small intestine bacterial overgrowth (SIBO). Changes in intestinal flora can participate in the occurrence and development of GERD by activating immune and inflammatory reactions, affecting gastroesophageal motility and other mechanisms. In addition, intestinal flora can also indirectly regulate and affect the pathogenesis of GERD by causing some metabolic diseases. This paper aims to review the relationship between GERD and intestinal flora.
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There are more than 3 000 kinds of volatile organic compounds (VOCs) in human exhaled gas, which are directly or indirectly related to the pathophysiological process of the body. Therefore, the detection and quantitative analysis of VOCs in vivo is helpful for the early detection, diagnosis and evaluation of treatment results. Breath analysis is a simple, noninvasive, painless, economic and time-saving detection method. It is a new field of rapid development, and has great potential in disease screening and clinical diagnosis. In this paper, the application of human exhaled gas analysis in clinical disease diagnosis and the latest progress in this field will be summarized.
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Objective To investigate the association of the polymorphisms of the FGB gene rs4220 and rs1044291 loci with plasma fibrinogen (Fg) level and gallstones in Xinjiang, China. Methods Blood samples were collected from 150 Uygur and Han patients with gallstones and 150 Uygur and Han individuals without gallstones who were hospitalized or underwent physical examination in The People's Hospital of Xinjiang Uygur Autonomous Region from December 2017 to May 2020. Plasma Fg level was measured, and based on the previous results of whole exon sequencing of the FGB gene, the SNaPshot method was used to identify the genotype at rs4220 and rs1044291 loci of the FGB gene. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to investigate the association between each variable and gallstones. Results For the Chinese Han population, the gallstones group had a significantly higher plasma Fg level than the control group [2.90 (2.43-3.49) g/L vs 2.47 (2.06-3.02) g/L, Z =-3.62, P 0.05). For the Chinese Han population, the subjects carrying GG genotype at the rs4220 locus in the gallstones group had a significantly higher plasma Fg level than those in the control group [2.84(2.32-3.61) g/L vs 2.34(2.05-2.75) g/L, Z =-3.04, P 0.05). Conclusion The influence of FGB gene polymorphism on plasma Fg level may be associated with race, and FGB gene polymorphisms at the rs4220 and rs1044291 loci may be involved in the pathogenesis of gallstones by regulating Fg level in the population in Xinjiang.
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Objective:To investigate the chronic restraint stress induced expressions of acid sensitive receptors and its role in the esophageal inflammation and oxidative stress.Methods:Twenty male specific pathogen free (SPF) Kunming mice were randomly divided into two groups: stress group and control group (each group, n=10). Stress mice were restrained in self-made restraint device for 2 hours per day and lasted for total 14 days. The histopathological changes of esophageal mucosa were observed by hematoxylin eosin (HE) staining under light microscope. The expression of nicotinamide adenine dinucleotide phosphate (Nox-4) was detected by immunohistochemistry, real time fluorescent quantitative polymerase chain reaction (qRT-PCR) and enzyme linked immunosorbent assay (ELISA). The mRNA expressions of acid sensitive receptors were detected by qRT-PCR. Results:HE staining showed that stress mice had obvious infiltrations of neutrophils and eosinophils, and also showed inflammatory change in esophgus, while no significant abnormality was found in the esophagus of control mice. The inflammotory scores in stress group were significantly higher than that in control group ( P<0.001). Immunohistochemistry showed that Nox-4 was mainly expressed in the lamina propria, mucosa and submucosa of esophagus. The mRNA expression levels of Nox-4 in stress group was (2.67±0.62) times higher than control group, with statistically significant difference ( P<0.001). In addition, the plasma concentration of Nox-4 in stress group was significantly higher than that of control group [(0.42±0.01)ng/ml vs (2.13±0.35)ng/ml, P<0.001]. The transcription levels of acid sensitive receptors in stressed mice, such as transient receptor potential vanilloid-1 (TRPV-1), TRPV-4, acid-sensing ion channel-1 (ASIC-1), ASIC-2 and ASIC-3 were significantly higher than those in the control group, with statistically significant difference ( P<0.001). Pearson correlation analysis showed that there was a positive correlation between Nox-4 mRNA expression and TRPV-1, TRPV-4, ASIC-1, ASIC-2, ASIC-3 mRNA expression in stress group ( r=0.97, 0.94, 0.98, 0.95 and 0.99, P<0.01). Conclusions:Stress may increases the expression of acid sensitive receptors and result in an esophageal inflammation and oxidative stress, which may contribute to the formation of esophageal hypersensitivity.
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Objective:To investigate the clinical efficacy of laparoscopic sleeve gastrectomy (LSG) for obesity complicated with obstructive sleep apnea syndrome (OSAS).Methods:The retrospective and descriptive study was conducted. The clinical data of 74 patients with obesity complicated with OSAS who were admitted to People's Hospital of Xinjiang Uygur Autonomous Region from January 2017 to June 2018 were collected. There were 40 males and 34 females, aged (39±10)years, with a range from 20 to 56 years. Observation indicators: (1) surgical and postoperative situations; (2) follow-up; (3) correlation analysis between obesity indicators and OSAS indicators; (4) analysis of factors influencing the postoperative efficacy of OSAS. Follow-up using hospitalization examination was conducted to detect the incidence of complications and the improvement of obesity and OSAS indicators after patients discharge. The follow-up was up to June 2019. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages. Repeated measurement data was analyzed using the mixed-effects model. Correlation analysis was conducted using the Pearson correlation coefficients. Multivariate analysis was conducted using the COX proportional risk regression model. Results:(1) Surgical and postoperative situations: 74 patients underwent LSG successfully, without conversion to open surgery, including 12 cases undergoing LSG combined with laparoscopic cholecystectomy and 9 cases undergoing LSG combined with esophageal hiatal hernia repair. The operation time and volume of intraoperative blood loss of 74 patients were (88±22)minutes and (57±25)mL. There was no severe postoperative complications and perioperative mortality. The duration of postoperative hospital stay of 74 patients were 5 days (range, 3-8 days). (2) Follow-up: among 74 patients, 71 were followed up at 1 month, 68 were followed up at 3 months, 64 were followed up at 6 months and 61 were followed up at 12 months after operation, respectively. The body mass, body mass index (BMI), abdominal circumference, chest circumference, neck circumference, apnea hypopnea index (AHI), average oxyhemoglobin saturation (ASaO 2), lowest oxygen saturation, epworth sleepiness scale score, excess weight loss rate of the 71 patients who were followed up at 1 month after operation were (108±16)kg, (38±5)kg/m 2, (121±14)cm, (122±13)cm, (41.3±2.5)cm, (25±15)times/hour, 88.1%±3.8%, 70.0%±9.3%, 17.8±2.3, 30%±8%, respectively. The above indicators of the 68 patients who were followed up at 3 month after operation were (96±14)kg, (33±5)kg/m 2, (113±13)cm, (120±12)cm, (39.7±2.3)cm, (17±11)times/hour, 90.2%±3.1%, 78.5%±7.1%, 15.0±2.2, 52%±13%, respectively. The above indicators of the 64 patients who were followed up at 6 month after operation were (88±11)kg, (31±4)kg/m 2, (105±11)cm, (113±11)cm, (37.5±1.7)cm, (10±7)times/hour, 92.4%±2.2%, 84.2%±3.5%, 13.6±1.7, 63%±14%, respectively. The above indicators of the 61 patients who were followed up at 12 month after operation were (80±8)kg, (28±3)kg/m 2, (97±8)cm, (108±10)cm, (36.5±1.4)cm, (6±4)times/hour, 93.7%±1.4%, 88.0%±3.1%, 9.2±1.5, 75%±16%, respectively. There were significant differences in the body mass, BMI, abdominal circumference, chest circumference, neck circumference, AHI, ASaO 2, lowest oxygen saturation, epworth sleepiness scale score of patients before and after operation ( F=109.855, 108.632, 90.565, 27.846, 96.353, 49.969, 48.561, 115.938, 257.762, P<0.05). There were 39 cases with AHI<5 times/hour in the 61 patients who were followed up at 12 month after operation, and the clinical complete response rate of OSAS was 63.93%(39/61). (3) Correlation analysis between obesity indicators and OSAS indicators: results of the Pearson correlation analysis showed that the AHI was positively correlated with the body mass and BMI ( r=0.267, 0.317, P<0.05) and negatively correlated with the ASaO 2 and lowest oxygen saturation ( r=-0.525, -0.551, P<0.05), and there was no correlation between AHI and neck circumference ( P>0.05) in the 74 patients before operation. The lowest oxygen saturation was negatively correlated with the body mass and BMI ( r=-0.330, -0.400, P<0.05), and there was no correlation between lowest oxygen saturation and neck circumference ( P>0.05) in the 74 patients before operation. The AHI was negatively correlated with the ASaO 2 and lowest oxygen saturation ( r=-0.406, -0.373, P<0.05), and there was no correlation between AHI and the body mass, BMI or neck circumference ( P>0.05) in the 61 patients who were followed up at 12 month after operation. There was no correlation between lowest oxygen saturation and the body mass, BMI or neck circumference ( P>0.05) in the 61 patients who were followed up at 12 month after operation. (4) Analysis of factors influencing the postoperative efficacy of OSAS: results of the multivariate analysis showed that preoperative AHI was an independent influence factor for postoperative efficacy of OSAS ( hazard ratio=1.039, 95% confidence interval: 1.016-1.063, P<0.05). Conclusion:LSG can effectively reduce the body mass and improve OSAS of patients with obesity complicated with OSAS in the short term.
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Objective To investigate the expression of NADPH oxidase Nox-4 induced by stress in gastric mucosa and its role in inflammation.Methods Twenty male SPF Kunming mice were randomly divided into chronic restraint stress group(stress group) and control group.Stress mice were restrained in selfmade restraint device for 2 hours each day.The rest of the time,the mice in the two groups had free access to food and water normally,experiment lasted 14 days.The histopathological changes of gastric mucosa were assessed by HE staining under light microscope.The expression of Nox-4 in gastric mucosa of mice was carried out by immunohistochemical method.The relative expression levels of Nox-4,antioxidant protein (Mn-SOD,GSH,Catalase) and inflammatory factors(IL-8,IL-1β,TNF-α) in gastric mucosa were detected by real-time quantitative RT-PCR and ELISA.Results Basal cell proliferation,neutrophil,eosinophil and plasma cell infiltration and inflammatory changes were observed in the lamina propria and glandular epithelium of stress mice,while no obvious abnormalities were found in control mice.The expression of Nox-4 in stress group was deeper and more abundant than that in control group,mainly expressed in lamina propria and glandular epithelium.The mRNA expression levels of Nox-4 in gastric mucosa of stress group was(2.42±0.51) times higher than that of control group,and blood concentration of stress group was(2.23±0.67) times higher than that of control group(t=-46.32,P＜0.001).The RT-PCR of antioxidant proteins in gastric mucosa showed that the transcription levels of Mn SOD,GSH and Catalase in stress group were significantly lower than that of control group (Mn-SOD:0.59± 0.10,GSH:0.58± 0.11,Catalase:0.57± 0.09),and there were significant differences between the two groups(t=13.57,11.67,15.01,P＜0.01).RT-PCR results showed that the transcription levels of IL-8,IL-1β,TNF-α in stress group were significantly higher than those in control group (IL-8:1.47±0.34,IL-1β:1.48 ± 0.42,TNF-α:1.51 ± 0.37),and there were significant differences in two groups(t=-18.45,-19.14,-20.85,P＜0.01).ELISA results showed that the serum levels of inflammatory factors in stress group were significantly higher than those in control group(2.25±0.37,3.59±0.45,3.41±0.34),and the differences were statistically significant(t=-47.11,-79.36,-96.32,P＜0.01).Pearson correlation analysis showed that there was a positive correlation between serum concentration of Nox-4 and inflammatory factors(IL-8,IL-1β,TNF-αt) in stress group(r=0.97,0.99,0.98,P＜0.01).Spearman rank correlation analysis showed that the grade of gastric mucosal inflammation was positively correted with serum levels of Nox-4 and inflammatory factors (IL-8,IL-1β,TNF-α) (r =0.96,0.92,0.91,0.94,all P＜ 0.01)Conclusion Stress may lead to gastric mucosal lesion by overexpression of proinflammatory factors through destroying the balance of oxidation/antioxidant system in gastric mucosa.
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Objective To investigate stress induced Nox-4 expression and to explore its role in adipose inflammation. Methods Twenty male Kunming mice were randomly divided into two groups ( n=10 each) , chronic restraint stress group and control group. Stress mice were restrained in self-made restraint device for 2 hours per day for 14 days. HE staining, immunohistochemistry, RT-PCR, and ELISA were used to analyze the expression of Nox-4, CD11b, antioxidant protein ( Mn SOD, GSH-Px, Catalase), adipocytokines ( adiponectin, MCP-1, IL-6, TNF-a). Results White adipose tissue (WAT) of stress mice inguinal fat pad significantly shrank compared to control group. HE staining showed that there were a large number of mononuclear cells, neutrophils, eosinophils, and cell infiltration reactions and inflammatory changes in WAT of stress mice. The stress significantly increased CD11b-positive cells and the expression of mF4/80, CD68. The concentration of serum FFA in stress group increased significantly, nearly twice of the control group ( P<0.01) . Nox-4 positive staining cells in stress WAT were deeper and more abundant. The level of Nox-4 in stress WAT was significantly higher than that of control group(P<0.01). The levels of antioxidant proteins such as Mn-SOD, GSH-Px, and catalase in stress WAT were significantly lower than those of control group (P<0.01). The expression levels of adiponectin in stress WAT were significantly reduced as compared to control group ( P<0.01) . The levels of MCP-1, IL-6 and TNF-α in stress WAT were significantly higher than those in control group (P<0.01). Conclusion Stress may lead to imbalance of adipose oxidation/antioxidant system and abnormal expression of adipocytokines, which may result in adipose inflammation.
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Objective To investigate the expression of malondialdehyde ( MDA) in esophageal mu-cosa of different types of gastroesophageal reflux disease ( GERD) patients and its role in the esophageal in-flammation. Methods According to the inclusion and exclusion criteria, 42 patients hospitalized in the the Xinjiang Uygur Autonomous Region People's Hospital from December 2017 to October 2018 were selected as the research group. 8 healthy subjects completed physical examination were set up as healthy control group. GERD completed GERDQ score, 24 h pH monitoring, and taken 3 cm on the dentate line of the esophagus as a specimen. The study group was divided into non-erosive reflux disease (NERD) group (17 cases) and Ero-sive reflux disease [erosive esophagitis (RE)] group (25 cases). Then hematoxylin-eosin (HE) staining, immunohistochemistry, real-time polymerase chain reaction ( qPCR ) , enzyme-linked immunosorbent assay (ELISA) methods were used to detect inflammation, oxidative stress (MDA), antioxidant enzyme [manga-nese superoxide dismutase (Mn SOD), glutathione (GSH), catalase (CAT)], and proinflammatory cyto-kines [monocyte chemotactic protein-1 (MCP-1), interlukin-8 (IL-8), tumor necrosis factorα(TNF-α)]. Results There was no significant difference in body mass index ( BMI ) between the three groups ( P >0. 05). 24 h pH monitoring of esophagus showed that the indexes of weak acid reflux (4<pH<7), acid re-flux ( pH<4 ) , esophageal near end acid reflux (％) and DeMeester score in RE group were significantly higher than those in NERD group, with statistical significance between the groups (P<0. 05). There was no significant difference in esophageal pressure between high resolution groups (P>0. 05). In RE group , the infiltration of immune cells (neutrophils, eosinophils), nipple lengthening, edema and other inflammatory changes were found in the esophageal mucosa, and the inflammation score reached the peak, which was signif-icantly higher than that in NERD group, with statistical significant difference (P<0. 001). The positive ex-pression of MDA in the two groups ( NERD, RE) was higher than that in the control group, and the MDA ex-pression in the RE group was almost covered with the full layer esophagus. The serum MDA concentration in the NERD and RE groups was significantly higher than that in the control group (P<0. 001). Compared with the NERD group, the serum MDA in the RE group reached the peak (P<0. 01). The relative expression of mRNA ( Mn SOD, GSH and CAT) in NERD group and RE group was significantly decreased, and there was a significant difference between the three groups (P<0. 001). Compared with the NERD group, the mRNA expression level of Mn SOD and CAT in RE group was significantly decreased (P<0. 01). The relative ex-pression of mRNA (MCP-1, IL-8, TNF- α) increased significantly in the two groups (NERD, RE), and there was a statistically significant difference between the three groups ( P <0. 001 ) . Compared with the NERD group, the expression of its inflammatory factors in the RE group significantly increased (P<0. 01). Conclusions The expression level of MDA in different types of GERD is significantly higher, which may be closely related to esophageal inflammation induced by acid reflux.
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Objective To detect the expression levels of collagen1 (colla-1),transforming growth factor-β1 (TGF-β1),a-smooth muscle actin (α-SMA) and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX-4) in mouse esophagus submitted to chronic restraint stress (CRS),in order to discuss stress-induced esophageal fibrosis and the role of oxidative stress.Methods 20 male Kunming mice were randomly divided into two groups,CRS and normal control (NC).The mice in CRS group were submitted to 2 h per day of restraint stress using home-made device for a period of 14 days,and the mice in both group were treated the same at rest of the time.Fibrotic changes of esophageal tissue were observed using Masson staining.The expression levels of NOX-4 and related fibrotic cytokines in esophageal tissues were detected by several methods such as immunohistochemistry,enzyme-linked immunosorbent assay (ELISA) and realtime polymerase chain reaction (qRT-PCR).Results Body weight in CRS group was significantly lower than NC group (8.75 ± 1.69 vs 12.69 ± 3.16),with statistically significant difference (t =3.11,P ＜ 0.05).Masson staining revealed that CRS mice showed distinct fibrosis of epithelial interstitium,while there was no distinct changes observed in NC mice.Immunohistochemical staining revealed intense staining for NOX-4 in epithelial,mucosal and submucosal layers of esophagi in CRS mice.ELISA showed that the serum level of NOX-4 in CRS mice was higher than NC mice (1.442 ± 0.05 vs 0.449 ± 0.08),with statistically significant difference (t =-27.32,P ＜ 0.01).Real-time PCR results showed that the expression of colla-1,TGF-β1,α-SMA and NOX-4 in CRS mice were as (2.443 ±0.36,2.78 ±0.13,2.244 ±0.18,2.448 ±0.440) times higher than NC mice,with statistically significant difference (t =-11.19,-38.86,-19.90,-10.37,P ＜ 0.01).Conclusions Fibrotic cytokines such as colla-1,TGF-β1 and α-SMA may participate in formation of stress induced esophageal fibrosis,and oxidative stress may play crucial role in the process of esophageal fibrosis.