A new sight to acute pancreatitis through paracolic gutter exudation, a multicenter retrospective study.

Objectives: Paracolic gutter exudation (PGE) may influence the severity of acute pancreatitis, but no study has explored it extensively. The objective of this study was to evaluate PGE for assessing the severity of disease. Methods: We performed a retrospective analysis of 488 patients from three tertiary hospitals in Guangxi, China. General clinical information, severity, and clinical courses were recorded. The PGE score were classified as follows: 0 for no exudation, 1 for unilateral exudation, and 2 for bilateral exudation. We used ROC curves to assess the predictive value of the PGE score, and logistic regression analysis to determine risk factors associated with death, ICU admission, and the occurrence of MODS. Results: This study included 352 patients with moderately severe acute pancreatitis (MSAP) and 136 patients with severe acute pancreatitis (SAP). Patients who had PGE experienced higher total hospitalization costs, longer hospital stays, a higher incidence of SAP, higher mortality rates, higher ICU admission rates, a higher incidence of MODS, and higher incidence of infections than those without (P < 0.05). Diagnostic efficacy in predicting severity in patients with MSAP and SAP increased after BISAP, MCTSI, modified Marshall, and SOFA scores combined with PGE score respectively. The PGE score of >1 is an independent risk factor for ICU admission and MODS occurrence. (P < 0.05). Conclusion: The PGE provides reliable and objective information for assessing severity and clinical course of patients with MSAP and SAP.

Ossicular Reconstruction With Various Degrees of Malleus Preservation in Patients With Chronic Otitis Media.

Objective: We examined the relationship between factors of middle ear conditions and the outcome of ossiculoplasty in chronic otitis media (COM) by measuring the improvement in the air-bone gap (ABG) and air conduction threshold (TAC). Methods: This retrospective study analyzed 76 patients (77 ears) who underwent ossiculoplasty from among 520 COM patients who underwent tympanoplasty based on the maximum preservation of the original ossicles. The reconstructed ossicular chain was performed by preserving or utilizing the remaining malleus in all cases with the presence of the malleus manubrium. Patients with eardrum adhesion, cholesteatoma, and cholesterol granuloma were defined as having a compromised middle ear condition (Group A), and those without as having an uncompromised middle ear condition (Group B). In each group, pure-tone audiometry was performed preoperatively and postoperatively, and improvements in the ABG and TAC were compared. The effects of the types of tympanoplasty and the method of ossiculoplasty (columella versus incus interposition) on postoperative ABG and TAC were also compared. Results: The postoperative ABG improvement in Group B was significantly higher than that in Group A [ß = 7.31, 95% confidence interval (CI) = 1.93-12.69, P < .05]. Type III minor columella tympanoplasty yielded significantly better results than type III major and type Vb tympanoplasty (ß = 11.42, 95% CI = 5.16-17.68, P < .01). There were no significant differences in the postoperative ABG or TAC between the reconstruction groups with and without preservation of malleus. Conclusions: Our results indicate that complex cases compromised by adhesions, cholesteatoma, and cholesterol granuloma have worse outcomes regarding hearing improvement and success rates, while those with intact stapes suprastructure have better outcomes. Malleus was maximally preserved in the patients of this study; however, this showed no significant prognostic benefit in hearing.

LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior.

This study aimed to clarify the role of la-related protein 1 (LARP1) in cell cycle progression and metastatic behavior of cultured gastric carcinoma (GC) cells. To do that, LARP1 expression was detected in clinical GC tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The cell viability, apoptosis, cell cycle, migration, invasion, and cell growth were examined using a Cell Counting Kit-8, Annexin V-FITC staining, propidium iodide staining, Transwell migration and invasion assays, and colony formation assays after LARP1 knockdown. Phosphatidyl inositol 3-kinase (PI3K) and AKT1 mRNA and protein expression levels of PI3K, p-AKT1, AKT1, p-BAD, p-mTOR, and p21 in si-LARP1 transfected GC cells were determined using qRT-PCR and western blotting. Here, we've shown that LARP1 expression was upregulated in human GC tissues and KATO III cells. LARP1 knockdown inhibited GC cell proliferation, cell cycle progression, migration, invasion, and colony formation and promoted apoptosis. In si-LARP1-transfected KATO III cells, the mRNA expression levels of PI3K and AKT1, PI3K protein expression, and the p-AKT1/AKT1 ratio were significantly suppressed. p-mTOR and p-BAD were significantly decreased, whereas p21 was significantly increased in si-LARP1-transfected KATO III cells. In conclusion LARP1 knockdown induces apoptosis and inhibits cell cycle progression and metastatic behavior via PI3K/AKT1 signaling in GC cells.

Stages of psychological change among patients with non-alcoholic fatty liver disease in China: a national cross-sectional study.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease worldwide. However, treatment of NAFLD is potentially influenced by psychological conditions. Using the simplified version of the University of Rhode Island Change Assessment (URICA-SV) scale, this study aimed to evaluate the stage of psychological change as a prerequisite to refining implementation strategies for psychological change. DESIGN: A multicentre cross-sectional survey. SETTING: Ninety hospitals in China. PARTICIPANTS: 5181 patients with NAFLD were included in this study. OUTCOME MEASURES: All patients completed the URICA-SV questionnaire and were assigned to one of the three stages of change (precontemplation, contemplation or action) according to their readiness scores. A stepwise multivariate logistic regression analysis was used to identify independent factors associated with the stage of psychological change. RESULTS: A total of 4832 (93.3%) patients were included in the precontemplation stage and only 349 (6.7%) considered making a change or preparing to make one. There were significant differences in gender (Cohen's d=0.039, p=0.005), age (Cohen's d=-0.327, p<0.001), waist circumference (Cohen's d=0.143, p=0.003), alanine transaminase (Cohen's d=0.347, p=0.001), triglyceride (Cohen's d=0.351, p=0.002), body mass index (BMI; Cohen's d=0.056, p<0.001), proportion of hyperlipidaemia (Cohen's d=0.068, p<0.001) and cardiovascular disease (Cohen's d=0.032, p=0.029), therapeutic regimen (Cohen's d=0.136, p<0.001), and Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease overall score (Cohen's d=-0.420, p<0.001) between patients with NAFLD in the precontemplation stage and those in the contemplation/action stage. Logistic regression identified BMI (HR 0.659, 95% CI 0.469 to 0.928, p=0.017), cardiovascular disease (HR 2.161, 95% CI 1.089 to 4.287, p=0.027) and triglyceride (HR 0.751, 95% CI 0.591 to 0.955, p=0.020) as independent factors predicting psychological change. CONCLUSIONS: The results demonstrated that very few patients with NAFLD presented psychological condition in the stage of action. Psychological condition was found to be significantly related to BMI, cardiovascular disease and triglyceride factors. Integrated diversity considerations for evaluating psychological change are necessary.

Reliability and validity of the Chinese version of chronic liver disease questionnaire-nonalcoholic fatty liver disease in patients with nonalcoholic fatty liver disease: a multicenter cross-sectional survey in China.

PURPOSE: The Chronic Liver Disease Questionnaire (CLDQ)-Nonalcoholic Fatty Liver Disease (NAFLD) is a disease-specific instrument to assess the health-related quality of life (HRQL) of patients with NAFLD. In order to provide further evidence for the cross-cultural utility of this instrument in the Chinese population, we translated the CLDQ-NAFLD into Chinese and examined its reliability and validity. METHODS: Patients with NAFLD in 90 hospitals across China were enrolled in this multicenter cross-sectional survey. Eligible patients completed the Chinese version of CLDQ-NAFLD at enrollment to assess HRQL. Internal consistency of the questionnaire was assessed using Cronbach's alpha coefficient and split-half reliability. Convergent and discriminant validity were assessed using Spearman correlation coefficient. Factor analysis was used to test the construct validity. RESULTS: Between March and August 2019, 5181 patients with a mean age of 43.8 ± 13.3 years were enrolled. All domains exhibited good internal consistency, with Cronbach's alpha and split-half reliability greater than 0.70. The scaling success rate of all domains was 100% for convergent validity and 99.4% (179/180) for discriminant validity. The inter-scale correlations indicated a significant correlation between all CLDQ-NAFLD domains (r = 0.608 to 0.832, all p < 0.001). Factor analysis of 36 items extracted 6 factors, which explained 69.14% of the total variance. CONCLUSION: The Chinese version of CLDQ-NAFLD is a reliable and valid instrument for assessing the HRQL of Chinese patients with NAFLD.

Pou3f1 mediates the effect of Nfatc3 on ulcerative colitis-associated colorectal cancer by regulating inflammation.

BACKGROUND: Ulcerative colitis-associated colorectal cancer (UC-CRC) is an important complication of ulcerative colitis. Pou3f1 (POU class 3 homeobox 1) is a critical regulator for developmental events and cellular biological processes. However, the role of Pou3f1 in the development of UC-CRC is unclear. METHODS: In vivo, a UC-CRC mouse model was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS). Body weight, colon length, mucosal damage, tumor formation, and survival rate were assessed to determine the progression of UC-CRC. Western blot, quantitative real-time PCR, ELISA, immunohistochemistry, immunofluorescence and TUNEL were performed to examine the severity of inflammation and tumorigenesis. In vitro, LPS-treated mouse bone marrow-derived macrophages (BMDMs) and RAW264.7 cells were used to study the role of Pou3f1 in inflammation. ChIP and luciferase reporter assays were used to confirm the interaction between Nfatc3 and Pou3f1. RESULTS: Pou3f1 expression was increased in the colons of UC-CRC mice, and its inhibition attenuated mucosal injury, reduced colon tumorigenesis and increased survival ratio. Knockdown of Pou3f1 suppressed cell proliferation and increased cell death in colon tumors. Both the in vivo and in vitro results showed that Pou3f1 depletion reduced the production of proinflammation mediators. In addition, ChIP and luciferase reporter assays demonstrated that Nfatc3 directly bound with the Pou3f1 promoter to induce its expression. The effect of Nfatc3 on the inflammatory response in macrophages was suppressed by Pou3f1 knockdown. CONCLUSION: Overall, it outlines that Pou3f1 mediates the role of Nfatc3 in regulating macrophage inflammation and carcinogenesis in UC-CRC development.

Optimal N-acetylcysteine concentration for intratympanic injection to prevent cisplatin-induced ototoxicity in guinea pigs.

BACKGROUND: Cisplatin is a chemotherapy drug that can induce sensorineural hearing loss. At present, no otoprotective agent is approved for use. OBJECTIVES: This study investigated the optimal concentration of intratympanic N-acetylcysteine (NAC) to prevent cisplatin-induced ototoxicity in a guinea pig model. MATERIALS AND METHODS: Guinea pigs (n = 64) were treated with a single intratympanic injection containing different NAC concentrations or saline (control) 3 days prior to intraperitoneal injection with cisplatin. The threshold change in the auditory brainstem response was assessed. RESULTS: Four weeks after intraperitoneal cisplatin injection, only the group that received 2% NAC exhibited significant otoprotection (p < .05) compared with the control. Otoprotection was observed at all the frequencies tested (1k, 2k, 4k, and 8k Hz). The 2% NAC group also exhibited significant otoprotection (p < .05) compared with the other NAC groups (at 1k, 2k, 4k, and 8k Hz). The 4% NAC group exhibited significantly reduced hearing capacity (p < .05) in the fourth week compared with controls. CONCLUSIONS AND SIGNIFICANCE: Intratympanic NAC administration is an efficient and safe means of preventing cisplatin-induced ototoxicity. In our animal model, the optimal intratympanic NAC concentration was 2%; concentrations of 4% loss of otoprotection.

Health-related quality of life in Chinese population with non-alcoholic fatty liver disease: a national multicenter survey.

BACKGROUND: Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient's health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. METHODS: In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. RESULTS: A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330-2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001-1.011), triglyceride (HR, 1.184; 95% CI, 1.074-1.305), disease severity (HR, 3.203; 95% CI, 1.418-7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074-8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. CONCLUSIONS: This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.

Blocking NFATc3 ameliorates azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer in mice via the inhibition of inflammatory responses and epithelial-mesenchymal transition.

Ulcerative colitis-associated colorectal cancer (UC-CRC) is the most serious complication of ulcerative colitis (UC). Nuclear factor of activated T cells 3 (NFATc3) is participated in inflammation and cancer. In this study, we investigated the effects of NFATc3 on experimental UC-CRC in vivo and in vitro, and explored the underlying mechanisms. Administration of azoxymethane (AOM) and dextran sulfate sodium (DSS) induced UC-CRC model in C57BL/6 mice. Body weight was monitored weekly. Colon tissues were harvested at week 14. We examined changes in the histopathology, inflammatory cytokines, carcinogenesis factors, and epithelial-mesenchymal transition (EMT) markers in colon tissues. We found that NFATc3 expression was significantly up-regulated in AOM/DSS treated mice compared with control. Mice lacking NFATc3 showed decreased tumor number and size, decreased mucosal damage, and increased survival rate. Moreover, down-regulation of NFATc3 could inhibit the proliferation and EMT of UC-CRC, decrease the levels of pro-inflammatory cytokines, reduce the colonic infiltration by neutrophils and macrophages, and suppress the activation of P38 and JNK signal pathway in mice. In In vitro experiments, silencing NFATc3 suppressed the proliferation and EMT of CRC cells, and reduced the activation of P38 and JNK. In addition, miR-370-3p could bind to NFATc3. Down-regulation of miR-370-3p promoted proliferation and EMT of CRC cells, while silencing NFATc3 could reverse these effects. In conclusion, NFATc3 was involved in the pathogenesis of experimental UC-CRC and NFATc3 knockdown ameliorated experimental UC-CRC progression via the inhibition of inflammatory responses and EMT. NFATc3 mediated the inhibitory effects of miR-370-3p on CRC cells proliferation and EMT. Targeting NFATc3 may be effective in treating UC-CRC.

miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition.

INTRODUCTION: Ulcerative colitis (UC) is a chronic and inflammatory bowel disease. UC-associated colorectal cancer (UC-CRC) is one of the most severe complications of long-standing UC. In the present study, we explored the effects of miR-370-3p on UC-CRC in vivo and investigated its underlying mechanisms in vivo and in vitro. METHODS: Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to induce UC-CRC in C57BL/6 mice. AOM/DSS-induced mice were treated with 5×108 pfu miR-370-3p overexpressing-adenovirus via tail-vein injection every two weeks. RESULTS: We found that miR-370-3p significantly improved the body weights and survival rates and inhibited the tumorigenesis of UC-CRC in AOM/DSS mice. Mechanically, miR-370-3p inhibited AOM/DSS-induced inflammatory response by decreasing tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) through targeting toll-like receptor 4 (TLR4), as demonstrated by down-regulation of TLR4, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and phosphorylated epidermal growth factor receptor (pEGFR). miR-370-3p decreased the expression of tumor-associated proteins, including p53, ß-catenin, and ki67 in AOM/DSS-treated mice. Additionally, miR-370-3p remarkably inhibited epithelial-mesenchymal transition (EMT) via increasing E-cadherin expression and reducing N-cadherin and Vimentin expression in vivo. Further studies showed that miR-370-3p repressed proliferation and EMT of colon cancer cells in vitro. Moreover, we proved that miR-370-3p decreased the expression of tumor-associated proteins and reversed EMT by regulating ß-catenin in colon cancer cells. CONCLUSION: Taken together, miR-370-3p alleviated UC-CRC by inhibiting the inflammatory response and EMT in mice, which suggested miR-370-3p as a novel potential target for UC-CRC therapy.

Utility of Transabdominal Ultrasonography Enhanced by Oral Cellulose-Based Contrast Agent in Depicting Varices at Cardia and Fundus.

The use of transabdominal color Doppler ultrasound after oral administration of an oral cellulose-based contrast agent (TUS-OCCA) in depicting varices at the cardia and fundus was explored. Both gastroscopy and transabdominal color Doppler ultrasound (TUS) were performed for this purpose, with gastroscopy serving as the gold standard. Patients were assigned by TUS protocol to one of three groups: TUS + empty stomach (TUS-ES); TUS + oral water intake (TUS-OW); and TUS-OCCA. TUS-based grading of varices reflected venous diameters and blood flow velocities, designated as follows: Ux = difficulty discerning gastric fundus and cardia or delineating varices; U0 = no detectable varices; U1 = diameter <5 mm, flow rate <10 cm/s; U2 = diameter <5 mm, flow rate ≥10 cm/s; U3 = diameter 5-10 mm, flow rate <10 cm/s; U4 = diameter 5-10 mm, flow rate ≥10 cm/s; and U5 = diameter >10 mm, any flow rate. Between August 2016 and August 2019, 239 patients with cirrhosis were enrolled prospectively, including bleeding (n = 71) and non-bleeding (n = 168) groups. Varices were directly observed in 10.5% (25/239) of TUS-ES group members, compared with 59.2% (58/98) of the TUS-OW group and 89.6% (104/116) of the TUS-OCCA group; all detection rates differed significantly (TUS-OCCA > TUS-OW > TUS-ES, p < 0.05). TUS-based grading (as defined) revealed the following patient distribution: Ux, n = 34; U0, n = 18; U1, n = 50; U2, n = 41; U3, n = 16; U4, n = 46; U5, n = 34. In grading by variceal diameter, overall correspondence between TUS and gastroscopy was 93% (174/187). TUS-OCCA greatly improved rates of detection of varices at the cardia and fundus, offering a new method by which diagnosis and quantitative grading may be achieved and affording an excellent, non-invasive approach to dynamic follow-up.

Evaluation of ultrasound-guided Freka-Trelumina enteral nutrition tube placement in the treatment of acute pancreatitis.

BACKGROUND: Enteral nutrition should be implemented as early as possible in patients with moderate or severe acute pancreatitis. This study was designed to evaluate the feasibility and Deffectiveness of ultrasound-guided Freka-Trelumina tube placement for enteral nutrition in acute pancreatitis. METHODS: Patients with severe acute pancreatitis admitted to Shengjing Hospital of China Medical University who needed Freka-Trelumina tube placement for enteral nutrition and gastrointestinal decompression were included in the current study. The relevant evaluation indicators of tube placement included the success rate of tube placement, tube placement time, tube shift rate, and blocking rate. In addition, the evaluation indicators of ultrasound-guided tube placement (from 1 January 2018 to 31 July 2019) were compared with those of previous endoscope-guided placement (from 1 January 2015 to 31 December 2017) by analysing the data from the electronic medical record system. RESULTS: The success rate of ultrasound-guided tube placement was 90.7% (49/54). All 49 patients tolerated the Freka-Trelumina feeding tube. The average ultrasound-guided tube placement time for the 49 patients was 18.4 ± 12.8 min (range, 5-36 min). The Freka-Trelumina feeding tube had a shift rate of 10.2% (5/49). The blocking rate of the Freka-Trelumina feeding tube was 12.2% (6/49). The success rate of tube placement, tube shift rate and blocking rate for endoscope-guided tube placement were 100% (62/62), 11.3% (7/62), and 12.9% (8/62), respectively. The average endoscope-guided tube placement time for the 62 patients was 16.5 ± 5.7 min (range, 12-31 min). The comparison between the ultrasound-guided group and the endoscope-guided group showed that the success rate of tube placement, tube placement time, tube shift rate and blocking rate were similar. CONCLUSION: The ultrasound-guided method can be done non-invasively at the bedside, which is safe and convenient, and the Freka-Trelumina feeding tube can be placed in time to achieve the goal of early enteral nutrition and gastrointestinal decompression.

Correction to: Liaoning Score for Prediction of Esophageal Varices in Cirrhotic Patients Who Had Never Undergone Endoscopy: A Multicenter Cross-Sectional Study in Liaoning Province, China.

Unfortunately, the fourteenth author's name was incorrectly published in the Original Article. The correct author name is Cen Hong.

Liaoning Score for Prediction of Esophageal Varices in Cirrhotic Patients Who Had Never Undergone Endoscopy: A Multicenter Cross-Sectional Study in Liaoning Province, China.

BACKGROUND AND AIMS: Endoscopy is necessary for assessment of esophageal varices (EVs) in cirrhotic patients, but its use is limited because of the poor compliance of patients and shortage of public health resources at primary hospitals or rural areas, especially in less well developed countries. A multicenter cross-sectional study aimed to establish a novel non-invasive score for prediction of EVs in cirrhotic patients who had never undergone endoscopy. METHODS: Patients with liver cirrhosis regardless of acute upper gastrointestinal bleeding (AUGIB) who underwent the first-time upper gastrointestinal endoscopy at 11 hospitals in Liaoning Province, China were considered. Independent predictors for EVs were identified by multivariate logistic regression analysis and then combined into an equation. The diagnostic performance with area under curve (AUC) was further evaluated by receiver operating characteristic curve analysis. RESULTS: Overall, 363 patients were included, of whom 260 had EVs and 180 presented with AUGIB. In all patients, AUGIB, ascites, and platelets were the independent predictors for EVs. The equation (i.e., Liaoning score) was 0.466 + 1.088 × AUGIB (1 = yes; 0 = no) + 1.147 × ascites (1 = yes; 0 = no) - 0.012 × platelets, which had an AUC of 0.807 (p < 0.0001). In patients with AUGIB, ascites and platelets were the independent predictors for EVs. The equation was as follows: 1.205 + 1.557 × ascites (1 = yes; 0 = no) - 0.008 × platelets, which had an AUC of 0.782 (p < 0.0001). In patients without AUGIB, platelets was the only independent predictor for EVs, which had an AUC of 0.773 (p < 0.0001). CONCLUSION: The Liaoning score is based on easy-to-access regular clinical and laboratory data and has a good diagnostic performance for non-invasive prediction of EVs in cirrhotic patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02593799.

The Attenuation of Scutellariae radix Extract on Oxidative Stress for Colon Injury in Lipopolysaccharide-induced RAW264.7 Cell and 2,4,6-trinitrobenzene Sulfonic Acid-induced Ulcerative Colitis Rats.

BACKGROUND: Oxidative stress (OS) has been regarded as one of the major pathogeneses of ulcerative colitis (UC) through damaging colon. It has been shown that Scutellariae radix (SR) extract has a beneficial effect for the prevention and treatment of UC. OBJECTIVE: The aim of this study was to investigate whether SR had a potential capacity on oxidant damage for colon injury both in vivo and in vitro. MATERIALS AND METHODS: The 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce UC rats model while 1 µg/ml lipopolysaccharide (LPS) was for RAW264.7 cell damage. Disease activity index (DAI) was determined to response the severity of colitis. The myeloperoxidase (MPO) activity in rat colon was also estimated. The 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid assay was performed to evaluate the total antioxidant capacity of SR. Furthermore, the activity of glutathione peroxidase (GSH-PX), catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation malondialdehyde (MDA) in cell supernatant and rat serum were detected by appropriate kits. In addition, an immunohistochemical assay was applied to examine transforming growth factor beta 1 (TGF-ß1) protein expression in colon tissue. RESULTS: The treatment with SR could significantly increase the activity of GSH-PX, CAT, and SOD associated with OS in LPS-induced RAW264.7 cell damage and TNBS-induced UC rats. However, the level of MDA was markedly reduced both in vitro and in vivo. Furthermore, SR significantly decreased DAI and reversed the increased MPO activity. Thus, SR could decrease the severity of acute TNBS-induced colitis in rats. Immunohistochemical assay showed that SR significantly downregulated TGF-ß1 protein expression in colon tissue. CONCLUSION: Our data provided evidence to support this fact that SR attenuated OS in LPS-induced RAW264.7 cell and also in TNBS-induced UC rats. Thus, SR may be an interesting candidate drug for the management of UC. SUMMARY: Scutellariae radix (SR) could significantly increase the activity of glutathione peroxidase, catalase, and superoxide dismutase associated with OS in lipopolysaccharide-induced RAW264.7 cell damage and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis ratsThe level of malondialdehyde was markedly reduced by SR both in vitro and in vivo SR could decrease the severity of acute TNBS-induced colitis in ratsSR could significantly downregulate the expression of transforming growth factor beta 1 protein in colon tissue. Abbreviations used: OS: Oxidative stress, UC: Ulcerative colitis, SR: Scutellariae radix, TNBS: 2,4,6-trinitrobenzene sulfonic acid, DAI: Disease activity index, MPO: Myeloperoxidase, GSH-PX: Glutathione peroxidase, CAT: Catalase, SOD: Superoxide dismutase, MDA: Malondialdehyde, TGF-ß1: Transforming growth factor beta 1, OD: Optical density, ROS: Reactive oxygen species.

Overexpression of WNT5B promotes COLO 205 cell migration and invasion through the JNK signaling pathway.

WNT5B is a member of the WNT family that has been reported to be overexpressed in a variety of cancer cell lines and tissues, including colorectal cancer (CRC). However, the potential roles of WNT5B in tumorigenesis have not been reported. In the present study, the WNT5B gene was transfected into CRC cells and generated a COLO 205 cell line with stable overexpression of WNT5B. MTT, wound healing and Transwell assays showed that overexpression of WNT5B significantly increased cell proliferation, migration and invasion capacities of the COLO 205 cells in vitro. Meanwhile, western blotting demonstrated that cells with stable expression of WNT5B showed increased protein expression levels and activities of matrix metalloproteinase (MMP) 2 and MMP 9. In addition, we also observed activation of the WNT/JNK signaling pathway in WNT5B-overexpressing cells. Subsequently, c-jun NH2-terminal kinase (JNK) was knocked down by RNA interference in the WNT5B-overexpressing COLO 205 cells. Knockdown of JNK significantly reduced the migratory capacity of the COLO 205 cells and decreased protein expression levels and activities of MMP 2 and 9 in vitro. In conclusion, our findings suggest that WNT5B may play an important role in the tumorigenesis of CRC.

Carcinoembryonic antigen related cellular adhesion molecule 1 alleviates dextran sulfate sodium-induced ulcerative colitis in mice.

AIMS: To investigate the effects of exogenous carcinoembryonic antigen related cellular adhesion molecule 1 (CEACAM1) on ulcerative colitis (UC) in a dextran sulfate sodium (DSS)-induced mouse model. MAIN METHODS: UC mice model was induced by administration of DSS in drinking water for 7days. Treatment of CEACAM1 was performed by a transrectal injection of CEACAM1 gene packed adenovirus in the mice. The severity of UC was evaluated using disease activity index and colon length. Histological changes were observed after hematoxylin and eosin staining. ELISA was used to measure secretion of pro-inflammatory cytokines in the colon tissue. The expression of mRNA and protein were detected using real-time PCR and western blotting. The effect of CEACAM1 on epithelial cell restitution was evaluated using wound-healing test in Caco-2 cells. KEY FINDINGS: CEACAM1 overexpression attenuated the symptoms of UC as evidenced by decreased DAI score, increased colon length and histopathologic score. In addition, exogenous CEACAM1 reduced the levels of inflammatory cytokines and downregulated COX-2 and iNOS expression levels. Moreover, CEACAM1 overexpression decreased colonic permeability by upregulating expression of tight junction proteins. In the in vitro study, exogenous CEACAM1 promoted proliferation and migration of Caco-2 cell. SIGNIFICANCE: Exogenous CEACAM1 effectively rescues the symptoms of UC in DSS mice through preventing inflammatory responses, improving epithelial barrier and promoting epithelial cells restitution.

Adipose-Derived Mesenchymal Stem Cells Ameliorate Ulcerative Colitis Through miR-1236 Negatively Regulating the Expression of Retinoid-Related Orphan Receptor Gamma.

Mesenchymal stem cells (MSCs) were reported to accelerate the curing of ulcerative colitis (UC). Altered expression of microRNAs (miRNAs) has recently revealed association with UC. However, the effect of adipose-derived MSCs (ASCs) on UC and the mechanism of how miRNAs regulate UC remain unclear. We investigated the effect of ASCs on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced UC in rat colon tissues. qRT-PCR and immunofluorescence analyses were performed to monitor the expression of miR-1236 and its target molecule, retinoid-related orphan receptor γ (RORγ). Regulation of the expression of RORγ by miR-1236 was assessed using luciferase reporter construct assays and miR-1236 mimic transfection. The relationship between miR-1236 and RORγ was further investigated in HT29 cells induced by TNF-α. ASCs highly ameliorated UC and decreased the inflammation markers in rats with TNBS-induced UC. In addition, ASCs upregulated the expression of miR-1236 and decreased the expression of RORγ in the TNBS-induced rat model of UC. The luciferase reporter assay and bioinformatic analysis demonstrated that the expression of RORγ was directly targeted and regulated by miR-1236. Specifically, the expression of RORγ was suppressed by miR-1236 mimic and enhanced by miR-1236 inhibitor. Furthermore, we demonstrated that exogenous miR-1236 mimic could inhibit the expression of RORγ in HT29 cell induced by TNF-α. ASCs effectively alleviated UC in rats with the expression of miR-1236 alteration, and miR-1236 may play important roles in UC by downregulating the expression of RORγ.

Meta-analysis of the effectiveness and safety of vedolizumab for ulcerative colitis.

AIM: To conduct a meta-analysis examining the effectiveness and safety of vedolizumab for the treatment of ulcerative colitis (UC). METHODS: A search was conducted of MEDLINE, Cochrane, EMBASE, and Google Scholar on July 31, 2013. Inclusion criteria were: (1) Randomized controlled trial (RCT); (2) Patients treated for UC; and (3) Intervention was vedolizumab. The following information/data were extracted from studies that met the inclusion criteria: the name of the first author, year of publication, study design, patient demographic information, response rate, remission rate, and adverse events. The primary outcome was clinical response rate, and the secondary outcomes were clinical remission rate and serious adverse events. Odds ratio (OR) with 95%CI were calculated for each outcome. RESULTS: Of 224 studies initially identified, three RCTs examining the use of vedolizumab meeting the inclusion criteria were included in the meta-analysis. All studies examined the use of vedolizumab at dosages ranging from 0.5 to 10 mg/kg body weight (one study used a standard dose of 300 mg). The follow-up periods were approximately 6 wk. The total number of patients in the intervention groups was 901, and in the control groups was 221. The mean age of the patients was approximately 41 years, and approximately half were males. The follow-up periods ranged from 43 d to 6 wk. The clinical response and remission rates were significantly higher for patients who received vedolizumab as compared to control patients (clinical response: OR = 2.69; 95%CI: 1.94-3.74, P < 0.001 and remission rate: OR = 2.72; 95%CI: 1.76-4.19, P < 0.001). Serious adverse events were not higher in patients that received vedolizumab. CONCLUSION: This analysis supports the use of vedolizumab for the treatment of UC.