Mevalonate inhibits acid sphingomyelinase activity, increases sphingomyelin levels and inhibits cell proliferation of HepG2 and Caco-2 cells.

BACKGROUND: Sphingomyelin (SM) and cholesterol are two types of lipid closely related biophysically. Treating the cells with exogenous sphingomyelinase (SMase) induces trafficking of cholesterol from membrane to intracellular pools and inhibition of cholesterol synthesis. In the present work, we address a question whether increased cholesterol synthesis affects hydrolysis of SM by endogenous SMases. METHODS: Both HepG2 and Caco-2 cells were incubated with mevalonate. The SMase activity was determined and its mRNA examined by qPCR. The cellular levels of cholesterol, SM, and phosphatidylcholine (PC) were determined and cell proliferation rate assayed. RESULTS: We found that mevalonate dose-dependently decreased acid but not neutral SMase activity in both HepG2 and Caco-2 cells with HepG2 cells being more sensitive to mevalonate. Kinetic examination in HepG2 cells revealed that acid SMase activity was increasing with cell proliferation, and such an increase was reversed by mevalonate treatment. Acid SMase mRNA was not significantly decreased and Western blot showed signs of proteolysis of acid SMase by mevalonate. After mevalonate treatment, the levels of cholesterol were significantly increased associated with increases in SM and PC. The cell growth was retarded by mevalonate and the effect was more obvious in HepG2 cells than in Caco-2 cells. CONCLUSION: Mevalonate can trigger a mechanism to enhance SM levels by inhibition of acid SMase. The effect may ensure the coordinate changes of SM and cholesterol in the cells. Mevalonate also affects cell growth with mechanism required further characterization.

The characteristics of oesophageal squamous cell carcinoma: an analysis of 1317 cases in southeastern China.

AIM OF THE STUDY: To research the demographic and histopathological features of ESCC in southeastern China. MATERIAL AND METHODS: We retrospectively reviewed the ESCC cases in the biobank of the National Engineering Centre for Biochip in Shanghai, which cooperates with lots of hospitals and research institutions in southeastern China. The patients were pathologically confirmed as having ESCC. The demographic and histopathological features of these cases were analysed subsequently. RESULTS: A total of 1317 patients were enrolled. The overall male: female ratio was 2.88: 1. 74.34% of these cases occurred in people aged between 50-70 years. Dysphagia was the most common symptom, which accounted for 93.40% of all the patients. Stage II and III were predominant (79.73%). 72.89% of patients had a tumour length greater than 3 cm. Most of the tumours (65.83%) were located in middle third of the oesophagus. There was a significant difference among the tumour stage, length, and location in different sex groups (P < 0.05), but not between different age groups (P > 0.05). In males, ESCC is usually located in the lower parts, with a longer tumour length and higher tumour stage. 24.15% of patients had lymph nodes ratio (LNR) > 0.2. CONCLUSIONS: In our analysis, dysphagia was more common in ESCC patients, to whom more attention should be paid. Additionally, males had a higher incidence, with longer and more distant disease, which gives a poor prognosis.

Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress.

AIMS: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. METHODS: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety- and depression-like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. RESULTS: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety-like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety-like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N-methyl-D-aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety-like behaviors. CONCLUSIONS: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS-like symptoms. These findings may give insight into the treatment of IBS and related psychological distress.

Hybrid argon plasma coagulation for the treatment of Barrett's esophagus: A prospective, multicenter study.

BACKGROUND: The incidence of Barrett's esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success. AIM: To determine the efficacy and safety of HybridAPC in the treatment of BE. METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded. RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min. CONCLUSION: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.

Optical enhancement mode 2 improves the detection rate of gastric neoplastic lesion in high-risk populations: A multicenter randomized controlled clinical study.

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

Maintenance treatment of mild gastroesophageal reflux disease with proton pump inhibitors taken on-demand: a meta-analysis.

BACKGROUND/AIMS: To evaluate the efficacy of on-demand strategy with proton pump inhibitors (PPIs) in mild gastroesophageal reflux disease (GERD). METHODOLOGY: A literature search was conducted to identify randomized controlled clinical trials which investigating on-demand treatment with PPIs in mild GERD. The control group should be placebo or once-daily treatment. Comparison of treatment effect was performed. RESULTS: Eight studies met the inclusion criteria, of which six were compared with placebo, two others with once-daily treatment. The percentage of patients unwilling to continue the study was 12.1% in the on-demand group while 39.6% in the placebo group. The meta-analysis revealed a statistically significant difference between the two groups (RR: 0.32; 95% CI: 0.23, 0.43). We obtained a similar result when compared with once-daily treatment (RR: 0.52; 95% CI: 0.34, 0.79). CONCLUSIONS: This meta-analysis indicates that on-demand therapy with PPIs is superior to placebo or once-daily treatment in terms of mild GERD.

Clinical guideline on magnetically controlled capsule gastroscopy (2021 edition).

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.

[The diagnostic value of multichannel intraluminal esophageal impedance and pH monitoring in gastroesophageal reflux-related cough].

OBJECTIVE: To evaluate the diagnostic value and limitation of multichannel intraluminal esophageal impedance and pH (MII-pH) monitoring on the diagnosis of gastroesophageal reflux-related chronic cough (GERC). METHODS: The patients with suspicious GERC consecutively referred to our respiratory clinic between May 2010 and July 2011 underwent a MII-pH monitoring, and received anti-reflux drug therapy, irrespective of the laboratory findings. Chronic cough due to gastroesophageal reflux was determined when there was a favorable response to anti-reflux therapy. Then, the sensitivity, specificity, false positive and negative rate, total consistence, positively and negatively predictive value, the area under the curve of ROC and the Kappa value of the laboratory investigation were calculated for the diagnosis of GERC. RESULTS: During the research period, 56 patients completed MII-pH monitoring. Among them, the abnormal reflux was found in 35 patients, and GERC was finally confirmed in 30 patients (85.7%) including 25 patients (83.3%) due to acid reflux and 5 patients (16.7%) due to non-acid reflux. In the remaining 21 patients with normal reflux episodes, 6 patients (28.6%) could be explained by non-acid reflux for their cough because of a relatively predominant weakly acid reflux and favorable response to empirical anti-reflux therapy. For the diagnosis of GERC, MII-pH monitoring had the sensitivity of 83.3%, the specificity of 75.0%, false positive rate of 25.0%, false negative rate of 16.7%, total consistence of 80.4%, positive predictive value of 85.7%, negative predictive value of 71.4%, the area under the curve of ROC of 0.792 and Kappa value of 0.577 respectively. CONCLUSION: MII-pH is a sensitive and reliable tool for the diagnosis of GERC due to its ability to detect both acid and non-acid reflux.

Effects of Cyclooxygenase-2 Inhibitors on Gastrointestinal Malignancies: a Systematic Review and Meta-analysis.

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a reduced risk of gastrointestinal malignancies, which is thought to be mediated mainly through the inhibition of cyclooxygenases-2 (COX-2). Due to the severe side effects of aspirin/NSAIDs, selective COX-2 inhibitors may be a more ideal choice. The objective is to evaluate the association of selective COX-2 inhibitors with gastrointestinal (GI) malignancies and premalignant lesions. We searched for published manuscripts evaluating the association between COX-2 inhibitors and GI malignancies or precancerous lesion. Two investigators independently abstracted the data; then, we conducted the analysis by Review Manager V.5.0; evaluation of effectiveness was performed by an intention to treat (ITT) method. Selective COX-2 inhibitors had no beneficial effects on the progression or regression of esophageal and gastric dysplasia (OR = 1.06, 95% CI 0.63-1.78, P = 0.83 for regression of esophageal dysplasia; OR = 1.06, 95% CI 0.58-1.91, P = 0.86 for progression of esophageal dysplasia; OR = 1.95, 95%CI 0.92-4.17, P = 0.08 for regression of gastric dysplasia; and OR = 0.99, 95%CI 0.68-1.43, P = 0.94 for progression of gastric dysplasia). There is no protective effect on colorectal cancer (OR = 0.89, 95% CI 0.77-1.03, P = 0.11), and the use could not improve the effect of chemoradiation (OR = 1.20, 95% CI 0.46-3.19, P = 0.71). This pooled analysis indicates no meaningful association between selective COX-2 inhibitors and GI malignancies.

Melanosis coli: A factor not associated with histological progression of colorectal polyps.

OBJECTIVE: In this study we aimed to investigate the association of melanosis coli (MC) and the colorectal polyp detection rate (PDR). METHODS: In all, 1104 MC patients and 62 181 non-MC participants were enrolled. And 2208 controls were matched by participants' age and gender, and quality of bowel preparation using the propensity score matching (PSM) method. Additionally, 490 polyps in MC and 980 in controls matched by age and gender, and size and location of polyps were analyzed. The association of PDR and pathological features of polyps with MC were also analyzed. RESULTS: MC patients showed a higher PDR (44.3% vs 39.3%, P = 0.006) and detection rate of low-grade adenoma (45.4% vs 36.7%, P = 0.002) but fewer large polyps (≥10 mm) (18.8% vs 26.9%, P = 0.001), fewer polyps in the left colon (33.5% vs 40.0%, P = 0.018), and a lower detection rate of advanced adenoma/adenocarcinoma (17.4% vs 24.3%, P = 0.003) than the matched controls. On multivariate logistic regression analysis, MC was independently associated with an increased PDR (odds ratio 1.184, 95% confidence interval 1.045-1.343, P = 0.008). Analysis targeting polyps showed that there were significant differences in age, gender, location, and pathology (P < 0.001) between polyps with and without MC. However, after adjusting for participants' age and gender, size and location of polyps, there was no difference between the two groups in pathology (P = 0.635). CONCLUSION: MC is independently associated with increased colorectal PDR, but not with histological progression of polyps.

Efficacy of Endoscopic Radiofrequency Ablation for Treatment of Reflux Hypersensitivity: A Study Based on Rome IV Criteria.

Objective: Effective therapies for reflux hypersensitivity are lacking. Endoscopic radiofrequency ablation may reduce the sensitivity of the distal esophagus through direct interference with nociceptors or vagal afferent fibers and thus may be useful in reflux hypersensitivity. The aim of this study is to assess the effectiveness and possible mechanisms of endoscopic radiofrequency ablation in reflux hypersensitivity patients. Methods: Patients with reflux hypersensitivity who fulfilled the Rome IV criteria and who wished to receive further treatment were recruited. Endoscopic radiofrequency ablation was delivered to the gastroesophageal junction. Data were collected by questionnaire using a 6-point Likert scale. The primary outcome measure was effect on symptoms including heartburn, regurgitation, and chest pain. The secondary outcomes were degree of satisfaction, medication use, acid exposure time (AET), low esophageal sphincter (LES) pressure, and total reflux episodes. We also assessed positive cell density of transient receptor potential vanilloid type 1 receptor (TRPV1) and calcitonin gene-related peptide (CGRP), both of which are biomarkers of afferent fibers, in biopsies obtained from esophageal mucosa 0.5 cm-1 cm above the Z line. These scales will be administered at baseline, 3-month follow-up, 6-month follow-up, and 12-month follow-up. Results: A total of 22 reflux hypersensitivity patients were enrolled (14 males, median age 50.0 years). A significant improvement in symptom scores (heartburn, regurgitation, and chest pain) was noted at 3 months, 6 months, and 12 months (P < 0.001). Satisfaction with life increased to 72.7% (16/22), 72.7% (16/22), and 68.2% (15/22) at 3, 6, and 12 mo, respectively, compared with baseline (P < 0.001). Nineteen patients reduced their medication use after treatment. Of these, 22.7% (5/22), 31.8% (7/22), and 40.9% (9/22) subjects stopped medication use at 3 mo, 6 mo, and 12 mo, respectively. No statistical differences were noted in AET, LES pressure, or total reflux episodes from preoperation to 12 mo postoperation. After treatment, the positive cell density of both TRPV1 and CGRP decreased significantly; however, only TRPV1 had a positive correlation with heartburn (r = 0.51, P = 0.03) and chest pain (r = 0.77, P < 0.01). Conclusion: Endoscopic radiofrequency ablation was an effective and safe therapeutic option in reflux hypersensitivity patients. Further studies with large sample size are required to validate the role of radiofrequency in reflux hypersensitivity.

Tandospirone prevents stress-induced anxiety-like behavior and visceral hypersensitivity by suppressing theta oscillation enhancement via 5-HT1A receptors in the anterior cingulate cortex in rats.

Tandospirone, a third-generation of antianxiety agent with fewer side effects, has been widely used in the treatment of anxiety. Moreover, it is interesting that tandospirone has been found to relieve gastrointestinal symptoms in patients with refractory irritable bowel syndrome who also have psychological dysfunctions. However, the underlying mechanism remains unclear. In this study, using a visceral hypersensitivity rat model induced by chronic water avoidance stress to mimic the symptoms of irritable bowel syndrome, we found that tandospirone relieved anxiety-like behavior and visceral hypersensitivity induced by stress. Meanwhile, stressed rats had increased 5-HT concentration, less 5-HT1A receptor expression, and enhanced theta oscillations in the anterior cingulate cortex (ACC). Furthermore, the power of the theta band in ACC is positively correlated with the level of visceral sensitivity. Activation of 5-HT1A receptors by its agonist, 8-OH-DPAT, to compensate for their effect in ACC reduced the enhancement of theta oscillations in ACC slices in stressed rats, whereas 5-HT1A receptor antagonist, WAY100135, facilitates theta oscillations in slices of normal rats. Tandospirone reduced the enhancement of theta band power in ACC in vitro and in vivo, thus alleviating anxiety-like behavior and visceral hypersensitivity through 5-HT1A receptors in stressed rats. These results suggest a novel mechanism by which tandospirone activates 5-HT1A receptors to relieve stress-induced anxiety and visceral hypersensitivity by suppressing theta oscillation enhancement in ACC.

Rarely fast progressive memory loss diagnosed as Creutzfeldt-Jakob disease: A case report.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare degenerative disease of the central nervous system that can be contagious or hereditary and is a rare cause of rapidly progressive dementia. It almost always results in death within 1-2 years from symptom onset. CASE SUMMARY: Here, we report the case of a 57-year-old male who initially experienced dizziness followed by a 1-mo fast decline in memory function. He presented to the local hospital and underwent magnetic resonance imaging and cerebrospinal fluid (CSF) examination, with no definitive diagnosis. However, the symptoms of progressive forgetting worsened. In addition, he exhibited progressive involuntary tremor of the limbs. Then, he came to our hospital, and according to the results of CSF examination, electroencephalography (EEG) and magnetic resonance imaging (MRI) tests and clinical manifestations of cerebellar ataxia, dementia, and myoclonus that rapidly progressed, with a short duration of illness, he was finally diagnosed with sporadic CJD (sCJD). CONCLUSION: This case report aims to create awareness among physicians to emphasize auxiliary examination, CSF examination, EEG and MRI tests and recognition of cerebellar ataxia, dementia, and myoclonus that rapidly progress to prompt pursuit of an early diagnosis and identification of sCJD and to reduce complications.

Hypothyroidism with elevated pancreatic amylase and lipase without clinical symptoms: A case report.

BACKGROUND: Hypothyroidism is an endocrine disorder that has worldwide prevalence and can affect multiple organ systems. We report a case of hypothyroidism with elevated pancreatic amylase and trypsin without acute pancreatitis. No such case has been previously reported. CASE SUMMARY: A 29-year-old woman did not pay much attention to a fever 4 d prior. During this time, she experienced anorexia and only drank a small amount of water every day. She did not present with abdominal distension, postprandial nausea, vomiting, cough or expectoration. After physical and laboratory examinations, the patient was diagnosed with hypothyroidism. During the course of the disease, hypothyroidism was generally accompanied by constantly increased pancreatic amylase and trypsin. After admission, the possible etiology of the patient was excluded and the concentrations of pancreatic lipase and amylase in serum were > 2000U/L (reference range 23-300 U/L) and 410 U/L (reference range 30-110 U/L), respectively. So we highly suspected that it may be acute pancreatitis. Interestingly, she never developed any complications associated with acute pancreatitis despite high levels of serum pancreatic amylase and trypsin, and she reported no symptoms of abdominal pain. Serum amylase and lipase decreased gradually after active thyroxine supplementation, and the patient was discharged from the hospital after active treatment. CONCLUSION: This case suggests that clinicians should pay attention to hypothyroidism with elevated pancreatic amylase and trypsin, even if no complications of acute pancreatitis are reported.

[The effect of ligand of peroxisome proliferators-activated receptor gamma 15d-PGJ2 on the proliferation and activation of hepatic stellate cells].

OBJECTIVE: To observe the effect of ligand of peroxisome proliferators-activated receptor gamma (PPAR gamma) 15d-PGJ2 on the proliferation and activation of hepatic stellate cells (HSC) and to study the role played by PPAR gamma during the process of HSC activation. METHODS: By using RT-PCR and cell culture, we investigated the effects of 5 micro mol/L and 10 micro mol/L 15d-PGJ2 on culture-activated HSC and on PDGF-induced HSC proliferation, production of extracellular matrix and expression of chemokines. RESULTS: The expression of alpha-SMA was significantly suppressed by 5mumol/L 15d-PGJ2, and the expression of PPAR gamma was significantly higher in the 15d-PGJ2 treated group than in the untreated group (0.64+/-0.03 vs 0.09+/-0.01, t=36.0517, P<0.01); PDGF-induced HSC proliferation was dose-dependently suppressed by 15d-PGJ2; the expressions of PPAR gamma in 5 micro mol/L and also in 10 micro mol/L 15d-PGJ2 plus PDGF pre-treated group increased much more than those in the PDGF-treated group (0.03+/-0.02 vs 0.60+/-0.03, t=42.6616, P<0.01 and 0.03+/-0.02 vs 0.69+/-0.04, t=33.83, P<0.01); the expressions of alpha-SMA, alpha 1 (I)-collagen and MCP-1 were suppressed. CONCLUSION: Activation of PPAR gamma can modulate pro-fibrotic and pro-inflammatory roles of HSC and the increased expression of PPAR gamma may become a new target for antifibrosis.

Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice.

Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor (PAF) and was previously suggested to have anticancer properties. The direct evidence is still lacking. We studied colonic tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced AOM/DSS method. ß-Catenin was determined by immunohistochemistry, PAF levels by ELISA, and sphingomyelin metabolites by mass spectrometry. Without treatment, spontaneous tumorigenesis was not identified but the intestinal mucosa appeared thicker in KO than in wild-type (WT) littermates. AOM alone induced more ACF in KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS treatments induced colonic tumors and the incidence was significantly higher in KO than in WT mice. By the enhanced AOM/DSS method, tumor number per mouse increased 4.5 times and tumor size 1.8 times in KO compared with WT mice. Although all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO mice. Compared with WT mice, cytosol expression of ß-catenin was significantly increased and nuclear translocation in tumors was more pronounced in KO mice. Lipid analysis showed decreased ceramide in small intestine and increased sphingosine-1-phosphate (S1P) in both small intestine and colon in nontreated KO mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS treatment. In conclusion, lack of alk-SMase markedly increases AOM/DSS-induced colonic tumorigenesis associated with decreased ceramide and increased S1P and PAF levels.

Protective effects of quercetin against chronic mixed reflux esophagitis in rats by inhibiting the nuclear factor-κB p65 and interleukin-8 signaling pathways.

OBJECTIVE: To observe the effects of quercetin on chronic mixed reflux esophagitis (RE) in rats by inhibiting the nuclear factor-κB p65 (NF-κBp65) and interleukin-8 (IL-8) signaling pathways. METHODS: Forty-eight healthy male Sprague-Dawley rats were randomly divided into six groups, with 8 rats in each group: the normal intact group, the sham operation group, the RE control group, the RE group treated with omeprazole or 100 mg/kg and 200 mg/kg quercetin. The animals were sacrificed after 6 weeks of different interventions. The pathological characteristics of esophageal mucosa were observed according to the diagnostic criteria and the expressions of NF-κBp65 and IL-8 were assessed by immunohistochemistry and real-time polymerase chain reaction. RESULTS: Compared with the RE control group, esophageal mucosal injury was improved and the expressions of NF-κBp65 and IL-8 were significantly decreased in the RE group treated with omeprazole or quercetin (P < 0.05). Compared with the omeprazole group, the gross and microscopic scores of esophageal mucosal injury and the expressions of NF-κBp65 and IL-8 in the 100 mg/kg and 200 mg/kg quercetin groups were not increased (P > 0.05). There was no statistically significant difference between the RE groups treated with 100 mg/kg quercetin and 200 mg/kg quercetin. CONCLUSION: Quercetin can prevent esophageal mucosal injury in RE rats by suppressing the NF-κBp65 and IL- 8 signaling pathways.

[The role of peroxisome proliferators-activated receptor gamma (PPARgamma) during activation of hepatic stellate cells].

OBJECTIVES: To observe the role of PPARgamma during the activation process of hepatic stellate cells (HSC). METHODS: By morphology and RT-PCR, we study the changes of expression of PPARgamma in culture-activated HSC or in vivo activated HSC induced by dimethylnitrosamine (DMN). RESULTS: In vitro, the expression level of PPARgamma in freshly isolated HSC (0.72+/-0.01) significantly reduced to 0.48+/-0.03 on the third day of culture (t = 19.8372, P<0.01), and reduced 70% on the seventh culture-day and could not be detected after the second passage. In vivo, HSC freshly isolated from normal control rats expressed PPARgamma (0.76+/-0.01). During the development of rat liver fibrosis induced by DMN, the expression level significantly reduced to 0.46+/-0.02 after the third injection of DMN (t = 29.5318, P<0.01), and reduced 66% on the end of first week and could not be detected on the end of second and third week. CONCLUSION: The expression of PPARgamma might play an important role on the maintenance of resting-form of HSC, and the reduction of expression of PPARgamma might be an early event during the activation process of HSC.

Dietary intake and risk for reflux esophagitis: a case-control study.

Background. Specific dietary components have been associated with gastroesophageal reflux disease (GERD) in Europe and the United States. However, the relationship between dietary components and GERD in Chinese still remains unclear. Methods. A total of 268 patients who were newly diagnosed as reflux esophagitis (RE) in Outpatient Endoscopy Center of Tongji Hospital were recruited. In addition, 269 sex- and age-matched subjects were also recruited as controls. The body measurements were determined, and the dietary intake during the previous year was evaluated using food frequency questionnaire (FFQ). Stepwise multiple logistic regression analysis was performed to examine the association between nutrients and RE. Results. After adjustment for WC, WHR, total energy intake, and demographics, there were a positive dose-response relationship between RE and calcium, meat, oils, and salt and a negative dose-response relationship between RE and protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs. Conclusion. High intake of meat, oils, salt, and calcium is associated with an increased risk for RE while high intake of protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs correlates with a reduced risk for RE.