Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

Comparison of dexmedetomidine vs. remifentanil combined with sevoflurane during radiofrequency ablation of hepatocellular carcinoma: a randomized controlled trial.

BACKGROUND: Remifentanil is widely used for ultrasound-guided percutaneous radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC). We determined whether dexmedetomidine could be an alternative to remifentanil for RFA of HCC under general anesthesia with sevoflurane. METHODS: We prospectively randomized patients scheduled to undergo RFA for HCC to a dexmedetomidine (DEX) group or remifentanil (REMI) group (47 patients each). In the DEX group, a bolus infusion (0.4 µg kg- 1) was started 15 min before anesthesia induction and continued at 0.2 µg kg- 1 h- 1 until 10 min before the end of surgery. In the REMI group, 3 µg kg- 1 h- 1 of remifentanil was administered from 15 min before anesthesia induction to the end of the surgery. The primary endpoint was postoperative pain intensity. Secondary endpoints included analgesic requirement, postoperative liver function, patient comfort, and hemodynamic changes. Group allocation was concealed from patients and data analysts but not from anesthesiologists. RESULTS: Postoperative pain intensity, analgesic consumption, comfort, liver function, and time to emergence and extubation did not differ between the two groups. Heart rate, but not mean arterial pressure, was significantly lower in the DEX group than in the REMI group, at 1 min after intubation and from 30 min after the start of the surgery until anesthesia recovery. Sevoflurane concentration and dosage were significantly lower in the DEX group than in the REMI group. CONCLUSION: During RFA for HCC, low-dose dexmedetomidine reduced the heart rate and need for inhalational anesthetics, without exacerbating postoperative discomfort or liver dysfunction. Although it did not exhibit outstanding advantages over remifentanil in terms of pain management, dexmedetomidine could be a safe alternative adjuvant for RFA under sevoflurane anesthesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OPC-15006613 . Registered on 16 June 2015.

ß-arrestin 2 attenuates lipopolysaccharide-induced liver injury via inhibition of TLR4/NF-κB signaling pathway-mediated inflammation in mice.

AIM: To study the role and the possible mechanism of ß-arrestin 2 in lipopolysaccharide (LPS)-induced liver injury in vivo and in vitro. METHODS: Male ß-arrestin 2+/+ and ß-arrestin 2-/- C57BL/6J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-κB signaling pathway. RESULTS: Compared with wild-type mice, the ß-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-10. Compared with the control group, pro-inflammatory cytokines (including IL-1ß, IL-6, TNF-α, and IL-10) produced by RAW264.7 cells in the ß-arrestin 2 siRNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-κB signaling pathway, including phospho-IκBα and phosho-p65, were upregulated. CONCLUSION: ß-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathway-mediated inflammation.

Hypoxia induces TWIST-activated epithelial-mesenchymal transition and proliferation of pancreatic cancer cells in vitro and in nude mice.

The epithelial-mesenchymal transition (EMT) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. TWIST activated by intra-tumoral hypoxia functions to promote the EMT. We hypothesized that TWIST and the downstream gene pathway could mediate PDAC progression under hypoxia. Therefore, 90 PDAC tissue specimens were immunostained for TWIST and other proteins. Pancreatic cancer cell lines were used for in vitro experiments and nude mice were used to confirm the in vivo data. Expression of TWIST and HIF-1α proteins was significantly upregulated, whereas expression of E-cadherin and p16 was down-regulated in PDAC tissues compared to that of non-tumor tissues and in tumor tissues obtained from patients with tumor involving splenic artery than those without splenic artery involvement. Up-regulated TWIST in tumor tissues were associated with worse prognosis in PDAC patients. The in vitro data showed that HIF-1α-induced TWIST overexpression promoted tumor cell growth and EMT under a hypoxic condition via TWIST interaction with Ring1B and EZH2. In vivo data showed that TWIST overexpression or a hypoxic condition induce xenograft growth, abdominal metastasis and low mouse survival, whereas knockdown of either Ring1B or EZH2 expression suppressed tumor xenograft growth and metastasis and prolonged survival of nude mice. TWIST was the key player in promotion of pancreatic cancer development and metastasis under a hypoxic condition through interaction with Ring1B and EZH2 to regulate expression of E-cadherin and p16 proteins in pancreatic cancer cells.

H. pylori-encoded CagA disrupts tight junctions and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2.

Helicobacter pylori encoded CagA is presently the only known virulence factor that is injected into gastric epithelial cells where it destroys apical junctional complexes and induces dedifferentiation of gastric epithelial cells, leading to H. pylori-related gastric carcinogensis. However, little is known about the molecular mechanisms by which CagA mediates these changes. Caudal-related homeobox 2 (Cdx2) is an intestine-specific transcription factor highly expressed in multistage tissues of dysplasia and cancer. One specific target of Cdx2, Claudin-2, is involved in the regulation of tight junction (TJ) permeability. In this study, our findings showed that the activity of Cdx2 binding to Cdx binding sites of CdxA (GTTTATG) and CdxB (TTTTAGG) of probes corresponding to claudin-2 flanking region increased in AGS cells, infected with CagA positive wild-type strain of H. pylori, compared to CagA negative isogenic mutant-type strain. Moreover, Cdx2 upregulated claudin-2 expression at transcriptional level and translational level. In the meantime, we found that TJs of AGS cells, infected with CagA positive wild-type strain of H. pylori, compared to CagA negative isogenic mutant-type strain, were more severely destroyed, leading to wider cell gap, interference of contact, scattering and highly elevated migration of cells. Herein, this study is firstly demonstrated that H. pylori-encoded CagA disrupts TJs and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2. This provides a new mechanism whereby CagA induced dedifferentiation of AGS cells, leading to malignant behavior of biology.

[Chemical structure of capsicuoside A from fruits of Capsicum annuum].

Five compounds were isolated from Capsicum annuum by means of various chromatographic techniques (silica gel, Sephadex LH-20, MCI GEL CHP-20P and HPLC), and their structures were determined as luteolin-7-O-[2"-O-(5"-O-sinapoyl)-beta-D-apiofuranosyl]-beta-D-glucopyranoside (1), uridine (2), adenosine (3), 7-hydroxy-6-methoxy cinnamic acid ethyl ester (4) and 7-hydroxy cinnamic acid ethyl ester (5) by extensive spectroscopic analyses (UV, IR, MS, 1D- and 2D-NMR). Among them, compound 1 is a new flavone glycoside named as capsicuoside A, and cmpounds 2-5 are isolated for the first time from the fruits of C. annuum.

[Effect of Helicobacter pylori-encoded CagA on biological behavior of gastric adenocarcinoma cells in vitro].

OBJECTIVE: To investigate the effect of Helicobacter pylori-encoded CagA on biological behavior of gastric adenocarcinoma AGS cells. METHODS: With experiment-control system of the wild-type CagA positive strain and isogenic CagA negative mutant strain of Helicobacter pyroli (Hp) were used as control and experimental groups, respectively. The cell contact, migration and invasion were examined by light and electron microscopy and invasion assay. RESULTS: The AGS cells infected by Hp strain with positive wild-type CagA showed more severely changed tight junction, wider intercellular space, loss of cell contacts, and higher migrating and invasive ability. CONCLUSION: Hp CagA may lead to loss of cell contacting and higher migrating and invading ability of gastic cells, and accelerates the malignant progress of tumor.

[Expression of syndecan-1 at different stages in the course of gastric carcinoma and its significance].

OBJECTIVE: To investigate the expression of syndecan-1 protein at different stages in the course of gastric carcinoma and its significance in carcinogenesis and metastasis. METHODS: There were 56 cases of chronic gastritis, 50 cases of chronic atrophic gastritis, 59 cases of intestinal metaplasia, 61 cases of displasia, and 112 cases of gastric carcinoma. Among the carcinoma cases, 55 were without and 57 with lymph node metastases. All paraffin-embedded tissue samples were assessed by immunohistochemistry. RESULTS: The syndecan-1 positive rate was 96.43% (54/56) in gastritis, 98.00% (49/50) in chronic atrophic gastritis, 100.00% (59/59) in intestinal metaplasia, 91.80% (56/61) in displasia, 45.45% (25/55) in gastric carcinoma without, and 24.56% (14/57) in gastric carcinoma with lymph node metastases. There was no significant difference among chronic gastritis, chronic atrophic gastritis and intestinal metaplasia (P > 0.05). There was a significant difference between displasia group and gastric carcinoma group (P <0.05), as well as between gastric carcinoma with and without lymph node metastases. There was a significant difference among well, moderately and poorly differentiated carcinoma groups. CONCLUSION: A decreasing expression of syedecan-1 in the development of gastric carcinoma is related with gastric carcinogenesis, and it may further promote metastasis of gastric carcinoma.

[Expression and significance of caudal type transcription factor-2 in gastric mucosa at different stages of gastric carcinogenesis].

OBJECTIVE: To investigate the expression and significance of caudal type transcription factor-2 (Cdx2) in gastric mucosa at different stages of carcinogenesis. METHODS: By using ABC immunohistochemistry, the expression of Cdx2 was detected in the biopsy specimens of 104 cases of chronic superficial gastritis, 98 cases of chronic atrophic gastritis, 112 cases of intestinal metaplasia, 106 cases of dysplasia and 97 cases of intestinal-type gastric carcinoma. RESULTS: Cdx2 was expressed in the specimens of intestinal metaplasia with an expression rate of 86.6% (97/112), significantly higher than those in dysplasia (58.5%, 62/106) and intestinal-type gastric carcinoma (56.9%, 53/93) (both P < 0.01), while was not expressed in the specimens of chronic superficial gastritis and chronic atrophic gastritis. No significant difference was found between the expression rate of Cdx2 was between the specimens of dysplasia and those of intestinal-type gastric carcinoma (P > 0.05). CONCLUSION: Cdx2 may be a novel marker of intestinal metaplasia and may play an important role in the carcinogenesis of the intestinal-type gastric carcinoma.

[The risk factors and impact of gastroesophageal reflux disease on quality of life in general population].

OBJECTIVES: To assess the risk factors of gastroesophageal reflux disease (GERD) in the general population and its impact on health-related quality of life (HRQOL). METHODS: A face-to-face interview was carried out in Guangdong Province using a validated Chinese version Reflux Disease Questionnaire (RDQ) to assess the prevalence of GERD. Random clustered sampling of permanent inhabitants aged 18 to 90 years was carried out under stratification of urban and suburban areas. The impact of GERD on HRQOL was evaluated using the Chinese version of SF-36. The statistical analysis was performed with SPSS 10.0 programs. RESULTS: A total of 83 GERD patients were collected and 166 healthy subjects were selected as control. There was no difference in prevalence between male (2.6%) and female (2.4%). There was no significant association between age and prevalence of GERD symptoms. Divorced/widowed/separated subjects (OR 4.61) and subjects with severe working burden (OR 3.43) were significantly more likely to report GERD symptoms. As compared with the general population, subjects with GERD symptoms experienced considerable impairment in quality of life. CONCLUSIONS: Psychosocial factors may play important roles in the production of GERD symptoms. GERD has a negative impact on HRQOL.

[Expression of microvessel density in multistep tissues of gastric carcinoma and significance thereof].

OBJECTIVE: To investigate the expression of microvessel density (MVD) in multistep tissue of gastric carcinoma and CD34 in the multistep tissue of gastric carcinogens. METHODS: 277 specimens of gastric diseases, 56 specimens of chronic gastritis, 50 specimens of chronic atrophic gastritis, 59 specimens of intestinal metaplasia, 61 specimens of dysplasia, 57 specimens of gastric carcinoma with lymph node metastases, and 55 specimens of gastric carcinoma without lymph node metastases, obtained from pathological department, Sun Yat-sen university, underwent pathological examination and immunohistochemistry to detect the expression of CD34 antigen that is expressed only in the endothelial cells in tumor. RESULTS: The mean MVD was 13 +/- 10 in the specimens of chronic gastritis, 11 +/- 7 in the chronic atrophic gastritis group, 13 +/- 9 in the intestinal metaplasia group, 17 +/- 10 in the dysplasia group, 27 +/- 11 in the gastric carcinoma without lymph node metastases group, and 28 +/- 10 in the gastric carcinoma with lymph node metastases group. There were not significant differences in MVD among the chronic gastritis group, chronic atrophic gastritis group, and intestinal metaplasia group (all P > 0.05), there was a significant difference in MVD between the chronic gastritis group and dysplasia group (P < 0.05). In the specimens of gastric carcinoma, there were no significant difference in MVD between those with and without lymph node metastases (P > 0.05), and between those of high and low differentiation degrees (both P < 0.05). CONCLUSION: The increase of expression of CD34 in the multistage tissues of gastric carcinoma is associated with the genesis of gastric cancer, and not be related to the gastric carcinoma metastases.

[Evaluation of the quality of life of patients with irritable bowel syndrome].

OBJECTIVE: To explore and assess the health-related quality of life (HRQOL) of irritable bowel syndrome (IBS) patients in the population. METHODS: Random clustered sampling involving permanent inhabitants aged 18 - 80 yr was carried out under stratification of urban and suburban areas in Guangdong Province. Altogether 231 IBS patients fulfilling the Rome II criteria and 636 Non-IBS as control were collected. The impact of IBS on HRQOL was evaluated using the Chinese version of SF-36. RESULTS: (1) There were no statistically significant differences between IBS and Non-IBS groups in aspects of sex, age educational level, and distribution according to areas (P > 0.05). (2) IBS patients reported significantly poorer HRQOL than controls (Non-IBS) on all SF-36 subscales (P < 0.05). The patients had poorer HRQOL than the Non-patients, but their differences weren't significant (P > 0.05). (3) The scores on all SF-36 subscales were highly associated with the frequency of abdominal pain in IBS patients (P < 0.05); They were also correlated to degree of effects of IBS symptoms on life reported by IBS patients (P < 0.05); The association between the scores and the symptom of fatigue which is the most extra-intestinal symptom in IBS was significant (P < 0.05); (4) Copying style was highly correlated to the eight SF-36 subscales; IBS still had a significant impact on patients after partialing out the effect of copying style. CONCLUSIONS: IBS symptoms had a negative impact on HRQOL and the SF-36 could be adopted to detect the differences between IBS group and Non-IBS group, which may be used as an outcome measure in future treatment studies. However, the development of IBS-specific measures of quality of life is necessary.

[A population-based epidemiologic study of irritable bowel syndrome in Guangdong province].

OBJECTIVE: To explore the prevalence of irritable bowel syndrome (IBS) and its risk factors in Guangdong province. METHODS: A questionnaire was used to screen IBS by face-to-face interviews according to Manning (modified including symptoms of constipation) and Rome II criteria. Random clustered sampling involving permanent inhabitants aged 18 - 80 years was carried out under stratification of urban and suburban areas. Potential risk factors were explored by comparing the frequencies among IBS group and non-IBS group using chi(2) and logistic analysis of multivariate adjusted for age and gender. RESULTS: A total of 4178 residents (male 1907, female 2271) were investigated. Mean age among the responders was (43 +/- 14) years. The response rate was 98%. The adjusted prevalence of IBS in Guangdong province is 5.67% according to the modified Rome II criteria, and is 11.50% according to Manning criteria. There is no difference between urban and suburban areas. The female was predominant in IBS, and the ratio of male to female was 1:1.25 (Rome II) and 1:1.34 (Manning). The age was poorly correlated with the prevalence. Events including history of analgesic use such as NSAID (OR = 3.83), history of food allergies (OR = 2.68), psychological distress (OR = 2.18), life events (OR = 1.89), history of dysentery (OR = 1.63) and negative coping style (OR = 1.28) are highly associated with IBS (P < 0.05). CONCLUSION: IBS is a common disorder in Guangdong Province which deserves greater care and further investigation.

[Value and economic analysis of emergency endoscopy in the diagnosis and treatment of massive upper gastrointestinal hemorrhage].

OBJECTIVE: To study the application value of emergency endoscopy in the diagnosis and treatment of massive upper gastrointestinal hemorrhage, and to evaluated by the economic analysis whether the emergency endoscopy was safe and effective,or shorten the hospitalization days and reduced the medical costs. METHODS: Ninety-one patients with massive upper gastrointestinal hemorrhage were randomly divided into emergency endoscopy group (group A) and non-emergency endoscopy group (group B). The patients in group A underwent endoscopy as soon as the blood pressures were normal and the patients of group B underwent endoscopy at 24-48 hours after hospitalization. They would be treated depending on the conditions by endoscopy. Then the correct diagnosis rates, rebleeding rates, complication rates, mean hospitalization days, the endoscopy costs, the blood transfusion costs, the drugs costs and the total hospitalization costs of two groups were evaluated and the cost-effect ratio (C/E) was calculated. RESULTS: The correct diagnosis rates and the endoscopy costs of group A were higher than the group B (100.0 percent vs.90.2 percent, P<0.05; (714.78+/-263.54) yuan vs. (383.57+/-251.72) yuan, P<0.01), and the rebleeding rates, the mean hospitalizations days, the blood transfusion costs and the drugs costs and the total hospitalization costs were all lower compared to the group B (6.1 percent vs. 26.8 percent, P<0.05; (5.42+/-1.70) days vs. (8.51+/-2.30) days, P<0.01; (791.80+/-258.35) yuan vs. (1270.29+/-569.21) yuan, P<0.01; (945.22+/-125.82) yuan vs. (1223.81+/-254.44) yuan, P<0.01; (2785.76+/-353.26) yuan vs. (3 527.76+/-555.62)yuan, P<0.01. The C/E of group A was lower than the group B (2785.76 yuan per patient vs. 3527.76 yuan per patient, P<0.01). CONCLUSION: Emergency endoscopy is not only safe and effective but also economical in the diagnosis and treatment of massive upper gastrointestinal hemorrhage.