Mica Can Alleviate TNBS-Induced Colitis in Mice by Reducing Angiotensin II and IL-17A and Increasing Angiotensin-Converting Enzyme 2, Angiotensin 1-7, and IL-10.

AIM: To explore the treatment effect of mica on 2,4,6-trinitrobenzenesulfonic acid solution- (TNBS-) induced colitis in mice. MATERIALS AND METHODS: Thirty male BALB/C mice were randomly divided into the control group, the TNBS group, and the mica group. Control mice were treated with saline solution. Experimental colitis was induced by TNBS (250 mg/kg/d) in the TNBS group and the mica group. After modeling, the mica group was treated with mica (180 mg/kg/d) for 3 days, while the TNBS group continued the treatment with TNBS. All solutions were injected intrarectally. During treatment, body weight and mice activity were monitored daily. After treatment, the colon tissues of mice were collected; angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), angiotensin 1-7 (Ang (1-7)), IL-17A, and IL-10 expression was analyzed by ELISA and immunohistochemistry. RESULTS: Food intake, activity, and body weight gradually decreased in the TNBS group compared to the control group and the mica group (all P < 0.05). Also, black stool adhesion in the anus and thin and bloody stool were observed in the TNBS group, but not in the other two groups. Moreover, the expression of Ang II, ACE2, Ang (1-7), IL-17A, and IL-10 in the TNBS group increased compared to that in the control group. Compared to the TNBS group, ACE2, Ang (1-7), and IL-10 in the mica group increased, while Ang II and IL-17A decreased (all P < 0.05). CONCLUSION: Mica can alleviate TNBS-induced colitis in mice by regulating the inflammation process; it reduces Ang II and IL-17A and increases ACE2, IL-10, and Ang (1-7).

[Reversal Effect of curcuma wenyujin extract on SGC-7901/VCR induced subcutaneous transplanted tumor in nude mice and its effect on the expression of P-glycoprotein].

OBJECTIVE: To explore the reversal effect of multidrug resistance of Curcuma Wenyujin (CW) and its possible mechanism by establishing Vincristine-resistant gastric cancer SGC-7901 cells (SGC-7901/VCR) induced subcutaneous transplanted tumor in nude mice. METHODS: First we identified the resistance of SGC-7901/VCR by using methyl thiazolyl tetrazolium (MTT). The SGC-7901/VCR induced subcutaneous transplanted tumor model was established in 50 BALB/c nude mice by tissue block method. After 2 -3 weeks 36 mice with similar tumor size were selected and divided into 6 groups by random digit table, i.e., the model group, the Vincristine (VCR) group, the low dose CW group, the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group, 6 in each group. Normal saline was intraperitoneally injected to mice in the model group at 10 mL/kg, once per 2 days. VCR was intraperitoneally injected to mice in the VCR group at 0.28 mg/kg once per 2 days. CW at 1.4 and 2.8 g/kg was administered to mice in the low and high dose CW groups by gastrogavage, 0.2 mL each time, once daily. CW at 1.4 and 2.8 g/kg was administered by gastrogavage and VCR was intraperitoneally injected at 0.28 mg/kg, once per 2 days to mice in the low dose CW combined VCR group and the high dose CW combined VCR group. All medication lasted for 14 days. The tumor growth was observed. The inhibition rate was calculated. Meanwhile, the positioning and expression of P-glycoprotein (P-gp) were detected by immunohistochemistry and Western blot. RESULTS: SGC-7901/VCR had strong resistance to VCR, Adramycin (ADM), fluorouracil (5-FU), and Cisplatin (DDP), especially to VCR. Proliferation activities of SGC-7901/VCR were significantly enhanced after drug elution. The tumor volume gradually increased as time went by. The tumor volume was the minimum in the high dose CW combined VCR group. The tumor volume was obviously reduced in the high dose CW combined VCR group with obviously reduced with increased inhibition rate of 51.56%, when compared with that of the model group and the VCR group (P < 0.05). Western blot test showed that, when compared with the model group, the gray level of P-gp in the VCR group increased (P < 0.05), and the relative expression of P-gp in the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group significantly decreased (P < 0.05). Compared with the VCR group, the gray level of the P-gp decreased in the low dose CW group, the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group (P < 0.05). Results of immunohistochemistry showed that, when compared with the model group, expression scores of P-gp in the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group decreased with statistical difference (P < 0.05). Compared with the VCR group, expression scores of P-gp were obviously lowered in the low dose CW group, the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group (P < 0.05). CONCLUSIONS: CW could reverse the drug resistance of SGC-7901/VCR subcutaneous transplanted tumor. And its mechanism might be related to down-regulating the expression of P-gp, suggesting that CW could be used as a kind of multidrug resistance reversal agent based on P-gp.

[Effect of Weifuchun on inhibiting inflammation of Helicobacter pylori-infected GES-1 cells and NF-kappaB signaling pathway].

OBJECTIVE: To study the effect of Weifuchun on inflammation of Helicobacter pylori (Hp)-infected gastric epithelial cells (GES-1) and its correlation with NF-kappaB signaling pathway. METHODS: Hp standard home-made strain (CagA +, VacA +) NCTCI 1637 infected GES-1 cells were used. Weifuchun was used as intervention. Weifuchun of different concentrations (5,10, and 20 microg/mL) were screened by MTT assay. A blank group and the model group were set up. Then the growth inhibition rate of drugs on gastric epithelial GES-1 cells was detected with MTT assay. Cell cycle was detected using flow cytometry. The supernatant liquid was separated to detect the contents of IL-8 and IL-4 by ELISA.The protein expression level of NF-kappaB was detected by Western blot analysis. RESULTS: MTT assay indicated significantly inhibitory effect of Weifuchun on GES-1 cells [5% inhibiting concentration (IC5)] was 10 microg/ml in the Weifuchun group. After GES-1 and Hp were cultured together,the contents of IL-8 in the supernatant were more obviously higher in the model group than in the blank group (P < 0.05), and then gradually decreased. After treatment with different concentrations of Weifuchun, the levels of IL-8 in the supernatant were less when compared with the model group at 12, 24, 48, and 72 h (P < 0.05). The decrement was the most significant in the high dose Weifuchun group. The IL-4 level in the supernatant was obviously lower in the model group than in the blank group. It obviously increased in the high concentration Weifuchun group (P < 0.05). There was no statistical difference in the IL-4 level between middle, low concentration Weifuchun group and the blank group (P > 0.05). The protein expression of intranuclear P65 increased and that of IkBalpha decreased 60 min after Hp infection. But the protein expression of intranuclear P65 decreased and the protein expression of IkBalpha increased after intervention of Weifuchun. CONCLUSIONS: Weifuchun adjusted H. pylori induced IL-8 and IL-4 production by gastric epithelial cells through blocking NF-kappaB pathways. Its mechanisms might possibly lie in inhibiting p65 from entry into nucleus and the degradation of IkBalpha. Weifuchun was an effective drug for treatment of Hp correlated chronic gastritis.

[Abnormal dendritic cells mediated immune response in a rat model of visceral hypersensitivity].

OBJECTIVE: To explore the role of altered characteristics of intestinal dendritic cell (DC) in the induction of visceral hyperalgesia through the activation of mast cells in a rat model of irritable bowel syndrome (IBS). METHODS: A total of 20 Sprague-Dawley rats were divided into modeling and control groups (n = 10 each). The IBS rat model was established by combining colorectal distention with restraint stress. Abdominal withdrawal reflex (AWR) was employed to evaluate visceral sensitivity. The surface marker of intestinal DC was analyzed by immunohistochemistry. Toluidine blue staining was used to determine the number of mast cells (MC). The expressions of interleukin (IL) -4 and IL-9 in colonic mucosa were measured by enzyme-linked immunosorbent assay (ELISA) and the level of proteinase-activated receptor-2 (PAR-2) was measured by Western blot. Mesenteric lymph node (MLN) DC and splenic CD4(+)/CD8(+)T cells were isolated and purified by magnetic label-based technique. Cytokine production of MLN DC co-culturing with CD4(+) or CD8(+)T cells was determined. RESULTS: The number of colonic MC in modeling group was more than that in control group ((2.73 ± 0.21) vs (1.13 ± 0.10), P = 0.000). The expressions of PAR-2, IL-4 and IL-9 in colonic mucosa were all higher than those in control group (2.13 ± 0.81 vs 0.42 ± 0.29, (7.2 ± 1.2) vs (3.3 ± 1.0) pg/ml, (7.3 ± 1.3) vs (5.2 ± 0.6) pg/ml, P = 0.026, 0.000, 0.001). Co-cultured MLN DC with CD4(+) T cells showed a predominant IL-4 secretion in the modeling group ((1.22 ± 0.33) vs (0.80 ± 0.48) pg/ml, P = 0.000). CONCLUSION: Increased colonic DC may stimulate CD4(+) T cells to secrete a high level of IL-4 to cause the degranulation of mast cells and the generation of visceral hypersensitivity in IBS rats.

Utility of metagenomics next-generation sequencing in the diagnosis and treatment of severe infectious diseases in the intensive care unit.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is a new method that combines high-throughput sequencing and bioinformatics analysis. However, it has not become as popular due to the limited testing equipment and high costs and lack of family awareness with not much relevant intensive care unit (ICU) research data. OBJECTIVE: To explore the clinical use and value of metagenomics next-generation sequencing (mNGS) in patients with sepsis in the ICU. METHODS: We conducted a retrospective analysis of 102 patients with sepsis admitted to the ICU of Peking University International Hospital from January 2018 to January 2022. Based on whether mNGS was performed, the identified patients were divided into the observation group (n= 51) and the control group (n= 51), respectively. Routine laboratory tests, including routine blood test, C-reactive protein, procalcitonin, and culture of suspicious lesion specimens were performed in both groups within 2 hours after admission to the ICU, while mNGS tests were performed in the observation group. Patients in both groups were routinely given initial anti-infective, anti-shock, and organ support treatment. Antibiotic regimens were optimized in a timely manner according to the etiological results. Relevant clinical data were collected. RESULTS: The testing cycle of mNGS was shorter than that of the conventional culture (30.79 ± 4.01 h vs. 85.38 ± 9.94 h, P< 0.001), while the positive rate of mNGS was higher than that of the conventional culture (82.35% vs. 45.1%, P< 0.05), with obvious superiority in the detection of viruses and fungus. There were significant differences in the optimal time of antibiotics (48 h vs.100 h) and length of ICU stay (11 d vs. 16 d) between the observation group and control group (P< 0.01) respectively, with no difference in 28-day mortality (33.3% vs. 41.2%, P> 0.05). CONCLUSION: mNGS is useful in the detection of sepsis-causing pathogens in the ICU with the advantages of short testing time and high positive rate. There was no difference in the 28-day outcome between the two groups, which may be related to other confounding factors such as small sample size. Additional studies with extended sample size are needed.

Effects of Endoscopic Submucosal Excavation With Non-Submucosal Injection on Stromal Tumors in Stomach.

Background and Aim: Endoscopic submucosal excavation (ESE) is commonly used to treat gastrointestinal stromal tumors (GISTs), especially for tumor sizes within 2 cm; compared with the conventical ESE, the efficacy and safety of the no-submucosal injection (NSI) ESE remains unclear. The aim of this study was to assess the clinical efficacy and safety of NSI-ESE for gastric stromal tumors. Methods: ESE was performed in 102 patients at our hospital between January 2018 and January 2020, and the clinical features, surgical outcomes, complications, cost of performance, pathological diagnosis, and risk classification were evaluated. Results: All tumors were completely resected by endoscopic resection (ER), with a complete resection rate of 100%. It was achieved by ESE/EFTR (endoscopic full-thickness resection) in 49 cases with submucosal injection, and by ESE/EFTR in 53 cases with NSI-ESE. The mean surgical time in cases with submucosal injection was 25.86 ± 4.45 min, compared to the cases without submucosal injection (17.23 ± 3.47 min), and the difference was significant (p < 0.001); the exposure time of tumor, the time of complete excavation of tumor, procedure cost, and hospital stay in the NSI-ESE group were all lower than those cases with submucosal injection (p < 0.05). In the risk classification, 95 (93.1%) cases had a very low risk, 4 (4.0%) cases had a low risk, and 2 (2.0%) cases had a high risk. No recurrence or metastasis was observed during the follow-up period of 18 ± 6 months (range: 13-25 months). Conclusions: NSI-ESE is a feasible, effective, and safe treatment for gastric GISTs; compared to the conventional ESE, NSI-ESE has the following advantages: it decreases procedure time, it lowers the risk of perforation, and it is cost-effective.

Effectiveness of a nurse-led Mindfulness-based Tai Chi Chuan (MTCC) program on Posttraumatic Growth and perceived stress and anxiety of breast cancer survivors.

Background: With the development of positive psychology, posttraumatic growth research on cancer patients has attracted increasing attention from researchers. It is immensely important to effectively increase the posttraumatic growth level of cancer patients and improve their quality of life. Objectives: To investigate the effectiveness of a nurse-led mindfulness-based Tai Chi Chuan (MTCC) programme for increasing posttraumatic growth (PTG) and decreasing the perceived stress and anxiety of breast cancer survivors. Methods: A RCT was conducted. Participants were randomly assigned to either the MTCC group or the control group. The programme included 59 women with stage I-III breast cancer. Participants in the intervention group participated in a nurse-led 8-week, twice a week, one-hour per day mindfulness-based exercise programme. The effectiveness of the intervention was measured three times (T1 - before intervention; T2 - after intervention; T3 - one year after intervention) using validated scales, including the PTG inventory (PTGI), Perceived Stress Scale (PSS), and Self-rating Anxiety Scale (SAS). A repeated-measure analysis of variance model was used to analyse the data. Results: Compared with the wait-list control group, the PTG level in the MTCC group was much higher after the 8-week intervention and the follow-up (F = 374.98, P < .000). The results showed that MTCC increased the level of PTG, and the effect persisted 1 year after intervention. In addition, PSS (F = 55.22, P < .000) and SAS (F = 148.92, P < .000) scores were significantly decreased at T2 and T3. Conclusion: The research preliminarily revealed that the MTCC programme was simple, effective, and more suitable to clinical nurses which should be recommended to cancer survivors to promote their recovery.

Antecedentes: Con el desarrollo de la psicología positiva, la investigación de crecimiento postraumático en pacientes con cáncer ha atraído cada vez más la atención de los investigadores. Es sumamente importante aumentar de manera eficaz el nivel de crecimiento postraumático de los pacientes con cáncer y mejorar su calidad de vida.Objetivos: Investigar la efectividad de un programa de Tai Chi Chuan basado en mindfulness (MTCC en sus siglas en inglés) dirigido por enfermeras para aumentar el crecimiento postraumático (PTG en sus siglas en inglés) y disminuir la percepción de estrés y ansiedad de las sobrevivientes de cáncer de mama.Métodos: Se condujo un ECA. Las participantes fueron asignadas al azar al grupo MTCC o al grupo control. El programa incluyó a cincuenta y nueve mujeres con cáncer de mama en estadio I-III. Las participantes en el grupo de intervención participaron en un programa de ejercicios basados en mindfulness dirigido por enfermeras, de 8 semanas, dos veces por semana, de una hora diaria. La efectividad de la intervención se midió tres veces (T1 ­ antes de la intervención; T2 ­ después de la intervención; T3 ­ un año después de la intervención) usando escalas validadas, incluidas el inventario de PTG (PTGI), la Escala de Estrés Percibida (PSS) y la Escala de Ansiedad Auto-reportada (SAS). Para analizar los datos se utilizó un modelo de análisis de varianza de medidas repetidas.Resultados: En comparación con el grupo control de la lista de espera, el nivel de PTG en el grupo MTCC fue mucho más alto después de intervención de 8 semanas y al seguimiento (F = 374.98, P< 0.000). Los resultados mostraron que la MTCC aumentó los niveles de PTG y el efecto persistió un año después de la intervención. Además, las puntuaciones de PSS (F = 55.22, P< 0.000) y SAS (F = 148.92, P< 0.000) disminuyeron significativamente en T2 y T3.Conclusiones: Las investigaciones preliminares revelaron que el programa de MTCC era simple, efectivo y más adecuado para las enfermeras clínicas, lo que debería recomendarse a las sobrevivientes de cáncer para promover su recuperación.

Fluorescence quenching properties of Au-Ag-Pt tri-metallic nanorod: The application in specific detection of alpha-fetoprotein.

In this paper, the fluorescence quenching characteristics of Au-Ag-Pt core-shell nanorods have been studied.Due to nonradiative energy transformation, the fluorescence emission intensity of bovine serum albumin (BSA) could be greatly quenched.It has been found that the quenching effect of Au-Ag-Pt core-shell nanorods could be optimized by adjusting the concentration of chloroplatinic acid.Based on the fluorescence quenching properties of Au-Ag-Pt core-shell nanorods, Au-Ag-Pt trimetal fluorescence quenching nanoprobe has been prepared, and the specificity of alpha-fetoprotein (AFP) detection has also been realized.In order to guarantee the sensing specificity, the surface modification including carboxyl replacement, carboxyl activation and antibody connection have been performed on Au-Ag-Pt core-shell nanorods.By using the principle of specific combination of antigen and antibody, the specific detection of AFP has been realized with a lower detection limit of 4.0 pg/mL, and the linear detection range spans a scope from 0.03 to 0.5 ng/mL.Interference experiments and the actual samples detection results show that the Au-Ag-Pt trimetal core-shell nanorod probes have good anti-interference and repeatability.

Photonic ultrawideband signal generator using an optically injected chaotic semiconductor laser.

We propose and demonstrate a method to generate ultrawideband (UWB) signals in the optical domain based on the chaotic dynamics of an optically injected semiconductor laser with optical feedback. The chaotic-UWB pulses with a fractional bandwidth of 116% and central frequency of 6.88 GHz are experimentally generated by controlling the injection strength and frequency detuning of the chaotic laser. The spectrum of the UWB signals is in full compliance with the Federal Communications Commission spectral mask, and the experimental results are qualitatively consistent with the simulated results.

[Proteomic expression analysis of colonic mucosa in a rat model of irritable bowel syndrome].

OBJECTIVE: To explore the pathogenesis of irritable bowel syndrome (IBS) and the regulation of the network relationship between differential proteins. METHODS: Sixteen female SD rats of clean grade were randomly divided into IBS group (n = 8) and control group (n = 8). A rat model of IBS was established by a special odor of mothball as a conditional stimulation and colorectal distension plus the classic conditions of physical restraint as a non-conditional stimulation in turn. The total proteins were extracted from colon mucosa of two different rat groups. After preparation of total proteins, solubilized proteins were separated by two-dimensional differential gel electrophoresis. Those differential protein spots were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). The identified proteins were classified through an online web gene ontology tool. Some of the valuable differently expressed proteins were chosen for further verification by Western blotting. RESULTS: Intensity changes of 19 spots were detected among 1396 protein spots. A total of 13 different proteins were identified by MALDI-TOF MS successfully; eight of these were up-regulated and five down-regulated in colon mucosa of IBS rat. The eight over-expressed proteins were cytokeratin 8, protein disulfide isomerase A3 (PDIA3), peroxiredoxin-6, cathepsin S, heterogeneous nuclear ribonucleoprotein F, eukaryotic translation initiation factor, carbonyl reductase 1, glyoxalase I; five under-expressed proteins were alpha-enolase, transgelin, serpinB5, cardiac alpha-actin 1 and 40S ribosomal protein SA. The results of Western blotting confirmed that PDIA3 was indeed over-expressed in colonic mucosa of IBS rat. CONCLUSIONS: Some proteins related to immunity of intestinal tract, inflammation and nerve are differently expressed in colonic mucosa of IBS rat. It is suggested that immunity, inflammation and neuro-endocrine network in gut are associated with the pathogenesis of IBS.

[Effect of muscovite on non-steroidal anti-inflammatory drug associated intestinal injury and its influences on tumor necrosis factor-alpha and nuclear factor-kappaB in rats].

OBJECTIVE: To examine the efficacy of muscovite on non-steroidal anti-inflammatory drug (NSAID) associated intestinal injury in rats, and its influences on the expressions of inflammatory factors, tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB), for researching its possible mechanism of intestinal mucosal protection. METHODS: NSAID associated intestinal injury in rat was induced by intra-gastric infusion of diclofenac. Twenty-four male Sprague-Dawley rats were randomly and equally assigned to three groups: normal control group, model control group and Muscovite group, 8 in each group. The normal control group received physiological saline 1 mL/100 g and the other two groups received diclofenac 7.8 mg/kg respectively every day for 5 days; while to the Muscovite group, Muscovite 120 mg/kg was gastric infused once on the day before modeling, followed with 120 mg/kg per day, given an hour before diclofenac infusion in the modeling days. All rats were killed on the 6th day, their gross changes and histological injury of intestinal mucosa were observed and scored, serum level of TNF-alpha was assayed in radioimmunoassay and NF-kappaB activity was determined by immunohistochemistry. RESULTS: The small dosage diclofenac administration can cause intestinal damage, revealing obviously erythema, erosion, multiple ulcer, intestinal stricture, even perforation, etc. Intestinal injury in the Muscovite group was obviously milder than that in the model control group, only showed changes of local congestion, edema and erosion. The scores of gross and histological intestinal features in the model control group were 4.38 +/- 1.41 and 4.00 +/- 1.85, while in the Muscovite group were 1.25 +/- 1.58 and 1.75 +/- 0.71, respectively, all higher than those in the normal control group (0.00 +/- 0.00 and 0.00 +/- 0.00, P < 0.01 and P < 0.05), respectively, but the elevation in the model control group were more significant (P < 0.05). Similar results were shown in comparisons of TNF-alpha and NF-kappaB levels between groups, the values were 6.19 +/- 2.76 and 1.38 +/- 1.19 in normal control; 22.20 +/- 5.42 and 5.75 +/- 0.46 in model control; 9.61 +/- 4.02 and 0.13 +/- 0.35 in the Muscovite group, respectively (all P < 0.01). CONCLUSION: Muscovite could effectively reduce the NSAID associated intestinal mucosal injury by inhibiting the activity of NF-kappaB in intestinal mucosa, and down-regulating the expression of TNF-alpha in blood plasma, so muscovite is proved to have protective function for intestine.

Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl Alcohol Extract Inhibits AGS Cell Helicobacter pyloriCagA+VacA+ Promoted Invasiveness by Down-Regulating Caudal Type Homeobox Transcription Factor and Claudin-2 Expression.

OBJECTIVE: To investigate the effects and possible mechanisms of action of Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl alcohol extract (CWNAE) on repression of human gastric cancer (GC) AGS cell invasion induced by co-culturing with Helicobacter pylori (HP). METHODS: AGS cells were cultured with HP of positive or negative cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) expression (CagA+/- or VacA+/-) and divided into 5 group. Group A was cultured without HP as a control, Group B with HPCagA+VacA+, Group C with HPCagA-VacA-, Group D with HPCagA+VacA+ and CWNAE, and Group E with HPCagA-VacA- and CWNAE. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and tumor invasion assays, examinations of morphology and ultramicroscopic structures, quantitative real-time polymerase chain reaction and Western blots were performed to measure the effects and uncover the mechanisms behind these effects of HPCagA+VacA+ and CWNAE on the epithelial-mesenchymal transition (EMT) of AGS cells. RESULTS: The 10% inhibitory concentration of CWNAE against AGS cells after a 48 h incubation was 19.73±1.30 µg/mL. More AGS cells were elongated after co-culturing with HPCagA+VacA+ than after culturing with HPCagA-VacA-. In tumor invasion assays, HPCagA+VacA+ significantly enhanced the invasiveness of AGS cells compared to the other experimental groups (all P value <0.05), and this effect was inhibited by CWNAE. Treatment with CWNAE normalized tight junctions and reduced the number of pseudopodia of AGS cells co-cultured with HPCagA+VacA+. HPCagA+VacA+ up-regulated zincfinger ebox binding homeobox 1 (ZEB1) in AGS cells after co-culturing for 24 h. Expression of caudal type homeobox transcription factor (CDX-2) and claudin-2 was significantly increased by HPCagA+VacA+ (P<0.05), but not by HPCagA-VacA-. CONCLUSION: HPCagA+VacA+ promoted the invasiveness of AGS cells through up-regulation of ZEB1 transcription and claudin-2 and CDX-2 expression. CWNAE inhibited these effects of HPCagA+VacA+ on AGS cells by down-regulating ZEB1 transcription, and CDX-2 and claudin-2 expression.

IRF1-mediated immune cell infiltration is associated with metastasis in colon adenocarcinoma.

BACKGROUND: Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells. METHODS: We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the "Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data" algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database. RESULTS: The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values. CONCLUSIONS: The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.

[Effect of non-steroidal anti-inflammatory drugs on small intestinal barrier function in rats].

OBJECTIVE: To approach the effect on mechanical barricade of the mucous membrane of small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Thirty-two male SD rats were randomly divided into control group and model group. The rats of the model group were given 7.5 mg/kg diclofenac by gavage, bid; the rats of the control group were given the same dose of saline. Then they were further randomly divided into two subgroups (n=8) at the first day and the fifth day after making the models to observe the scores of anatomical lesion on stomach and small intestine and the scores of tissue damage of mucous membrane and to quantitatively analyze the height of villi, as well as the thickness and the section area of mucous membrane with Carl Zeiss Imaging Systems. Observation of the change of ultrastructural organization of mucous membrane was carried out with transmission electron microscope. RESULTS: The mucous membrane of stomach of the model groups was slightly edematous. There was no difference between the scores of the model groups and control groups. It was seen that the mucous membrane of small intestine of the first day model group presented with erythema, amaurosis and ulcer. The ulcer was distributed along mesentery. The mucous membrane of small intestine of the fifth day model group showed bleeding, perforation and sinus tract formation, and the scores of anatomical lesion was higher than that of the control group (P < 0.05). The scores of the lesions of the first and fifth day model groups were 3.5 and 5.0. The difference had statistical significance when compared with those of the control groups (the scores were 0) (P < 0.05). Cell degeneration and cellular necrosis of epithelial mucosa of small intestine was also seen in the first day model group. The top of villi was ablated. The height of the pile on jejunum was (126.9 +/- 32.0) microm and that on ileum was (118.6 +/- 22.9) microm. They were lower than those of the control group (P < 0.05). However there was no difference of the thickness and section area between them, but the thickness and section area showed a tendency of decrease. It was also seen that there were apomorphosis and sphacelism of epithelial cells in the fifth day model group. Some villi were ablated and laminae propria exposed. The height of villi on jejunum [(73.4 +/- 25.4) microm] and that on ileum [(109.3 +/- 17.6) microm] decreased significantly. The thickness of mucous membrane [(123.8 +/- 51.6) microm and (165.7 +/- 37.4) microm] decreased and the section area [(2.48 +/- 1.01) mm2 and (3.27 +/- 0.76) mm2] became smaller (P < 0.05 vs. control group). The mucous membrane of the villi on small intestine was continuous but arranged disorderly. Cytochondriome swelled, endocytoplasmic reticulin expanded with different degrees, intercellular junction widened partly. The microvilli in the fifth day model group were ablated more obviously and intercellular junctions were broken and destroyed gravely. CONCLUSIONS: Diclofenac can cause damage to the function of mucous membrane barricade of small intestine. It could also lead to shortening of the villi, thinning of the mucous membrane, ablation of the microvilli, and widening of the tight intercellular junction as the characteristic morphological change.

Peripheral blood miR-372 as a biomarker for ulcerative colitis via direct targeting of NLRP12.

The present study aimed to investigate the expression pattern and underlying mechanism of microRNA-372 (miR-372) in the progression of ulcerative colitis (UC). Reverse transcription-quantitative polymerase chain reaction was used to measure miR-372 expression levels in the blood and colonic mucosa tissue samples from patients with UC. The present study demonstrated that levels of miR-372 were significantly increased in the blood and colonic mucosa tissue samples from patients with UC compared with healthy controls. Furthermore, the level of serum miR-372 was positively correlated with the level of serum c-reactive protein. Receiver operating characteristic analysis indicated that levels of miR-372 detected in serum and tissue samples could be used to screen for patients with UC from healthy controls. These results indicated a potential role of miR-372 as a diagnostic marker and therapeutic target for patients with UC. Furthermore, a conserved miR-372 binding site in the 3'untranslated region of the NLR family pyrin domain containing 12 (NLRP12) was identified. Dual luciferase assay demonstrated that overexpression of miR-372 significantly reduced the relative luciferase activity of pmirGLO-NLRP12-3'UTR compared with control pmirGLO. In addition, western blot analysis indicated that overexpression of miR-372 significantly decreased the protein expression level of NLRP12. Therefore it was hypothesized that miR-372 may promote the progression of UC by suppressing NLRP12 protein expression and thereby inducing the excessive production of inflammatory cytokines. In conclusion, high levels of miR-372 detected in peripheral blood samples may serve a role as a potential biomarker to screen potential patients with UC from healthy controls.

Effects Of Modified Mindfulness-Based Stress Reduction (MBSR) On The Psychological Health Of Adolescents With Subthreshold Depression: A Randomized Controlled Trial.

BACKGROUND: Sub-threshold depression (SD) has been associated with impairments in adolescent health which increase the rate of major depression. Researchers have shown the effectiveness of mindfulness on mental health, however whether the traditional mindful skills were suitable for youngsters, it was not clear. This study investigated the effects of a tailed Mindfulness-based stress reduction (MBSR) on their psychological state. METHODS: A double-blind, randomized controlled trial was carried out. 56 participants who met the inclusion criteria agreed to be arranged randomly to either the MBSR group (n=28) or the control group (n=28). Participants in MBSR group received a tailored 8-week, one time per week, one hour each time group intervention. The effectiveness of intervention was measured using validated scales, which including BDI-II, MAAS, RRS at three times (T1-before intervention; T2-after intervention; T3-three months after intervention). A repeated-measures analysis of variance model was used to analyze the data. RESULTS: The results showed significant improvements in MBSR group comparing with control group that depression level decreased after the 8-week intervention and the follow up (F =17.721, p < 0.00). At the same time, RRS score was significantly decreased at T2 and T3(F= 28.277, p < 0.00). The results also showed that MBSR promoted the level of mindfulness and the effect persisted for three months after intervention (F=13.489, p < 0.00). CONCLUSION: A tailored MBSR intervention has positive effects on psychology health among SD youngsters, including decrease depression and rumination level, cultivate mindfulness.

Biopsy strategies for endoscopic screening of pre-malignant gastric lesions.

Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) were adopted to evaluate gastric risk stratification in five biopsy samples. This study aimed to evaluate the degree of gastric atrophy (GA) and intestinal metaplasia (IM) in five locations to detect a more representative biopsy sample in gastric cancer (GC) screening. Our study enrolled 368 patients and 5 biopsy pieces were acquired from them. Gastric risk stratification was calculated by OLGA and OLGIM staging system. The results revealed that the IM score in the incisura angularis was higher than that in the larger and lesser curvature of corpus mucosa (p = 0.037 and p = 0.030, respectively) and the IM score in the lesser curvature of antrum mucosa was higher than that in the incisura angularis mucosa (p = 0.018). IM is more frequently observed in the angulus region than in the lesser curvature of corpus in the mild degree (p = 0.004) and mild IM lesions in the lesser curvature of antrum were more frequently observed than in the incisura angularis mucosa (p = 0.004), Four biopsy pieces protocol (larger curvature and lesser curvature of the antrum, lesser curvature of the corpus and angulus) demonstrated accurate consistency (97.83% and 98.37%, respectively) with a Kendall's tau-b of higher than 0.990, along with low misdiagnosis rates of OLGA and OLGIM (III + IV) (9.76% and 5.00%, respectively). Three biopsy pieces protocol (lesser curvature of the antrum and corpus, angulus biopsy) in OLGA and OLGIM staging system was close to the standard protocol (five biopsy specimens) with a consistency of 94.84% and 94.29% and has a Kendall's tau-b higher than 0.950 and diagnostic omission rates of 9.76% and 5.00%, respectively, which was exactly the same with the four biopsy pieces protocol. Furthermore, it had the second-highest Youden index (0.902 and 0.950, respectively) and area under the ROC curve (0.992 and 0.996, respectively) for the screening of high-risk GC by OLGA and OLGIM stages. Thus, we recommended the angulus and the lesser curvature of antrum as a conventional biopsy and three biopsy pieces for further GC risk screening.

Lactulose improves cognition, quality of life, and gut microbiota in minimal hepatic encephalopathy: A multicenter, randomized controlled trial.

OBJECTIVE: Lactulose is effective in the treatment and prevention of overt hepatic encephalopathy (OHE), but there are limited data on its use on microbiota in relations to minimal hepatic encephalopathy (MHE) recovery. The present study aimed to assess the efficacy of lactulose in recovery of MHE in aspects of cognitive function, quality of life, and impact on intestinal microbiota. METHODS: This multicenter, open-label randomized controlled trial was conducted in 11 teaching hospitals in China. Participants were randomly allocated on a 2:1 basis to receive lactulose (Gp-L) or no therapy as control (Gp-NL) for 60 days. The primary endpoint was the MHE reversal rate. Gut microbiota were compared between MHE patients and healthy volunteers, as well as lactulose-responders and non-responders. RESULTS: A total of 98 cirrhotic patients were included in the study, with 31 patients in the Gp-NL group and 67 patients in the Gp-L group. At day 60, the MHE reversal rate in Gp-L (64.18%) was significantly higher than that in Gp-NL (22.58%) (P = .0002) with a relative risk of 0.46 (95% confidence interval 0.32-0.67). Number needed to treat was 2.4. Further, there was significantly more improvement in physical functioning in Gp-L (4.62 ± 6.16) than in Gp-NL (1.50 ± 5.34) (P = .0212). Proteobacteria was significantly higher in MHE patients compared with healthy volunteers (12.27% vs 4.65%, P < .05). Significant differences were found between lactulose responders and non-responders in Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. CONCLUSIONS: Treatment with lactulose significantly improves MHE recovery rate, and gut microbiota change in MHE patients can modulate the effectiveness of this therapy. Chinese Clinical Trial Register (ChiCTR) (ID: ChiCTR-TRC-12002342).

[A meta-analysis of radiofrequency ablation for early hepatocellular carcinoma].

OBJECTIVE: To compare the effectiveness and safety of radiofrequency ablation (RFA) with other therapeutic methods for patients with early hepatocellular carcinoma (HCC). METHODS: Randomized clinical trials (RCTs) which compared the efficacy or safety of RFA with other therapeutic methods for primary hepatocellular carcinoma in Cochrane library, EMBASE, PubMed, OVID and CBM were searched. Trials were considered of high quality if methodological quality score was 3 or more according to Jadad standard. Statistical heterogeneity between trials was evaluated by STATA 9.0 and considered to exist when P < 0.1. Heterogeneity of the included articles was tested and used to select proper effective model for calculation. Sensitivity analysis was performed and publication bias was investigated through visual inspection of funnel plots and Egger regression model. RESULTS: Six RCTs including 862 cases were analyzed. As compared with other therapeutic approaches, RFA significantly increased 3-year overall survival rate and reduced local recurrence rate of early hepatocellular carcinoma; the total OR were 2.06 (95% CI being 1.54-2.77, P = 0.000) and 0.40 (95% CI being 0.28-0.57, P = 0.000) respectively. As compared with other therapeutic approaches, the total OR of new HCC recurrence rates, extrahepatic metastasis rate and major complications in patients with HCC treated with RFA were 0.92 (95% CI being 0.68-1.24), 0.98 (95% CI being 0.30-3.22), 1.35 (95% CI being 0.49-3.77) respectively, showing no significant differences (P > 0.05). Inspection of the funnel plots for all outcome measures did not reveal evidence of publication bias (P = 0.670, 0.160, 0.884, 0.087, 0.317, respectively, by Egger regression model). CONCLUSIONS: RFA is superior to other treatment methods with respect to local recurrence and 3 year overall survival in early HCC and is the preferred therapeutic method for small HCC because it is minimally invasive, simple and convenient.

Therapeutic Effect of Chang'an I Recipe ( I ) on Irritable Bowel Syndrome with Diarrhea: A Multicenter Randomized Double-Blind Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) decoction Chang'an I Recipe ( I ) in the treatment of irritable bowel syndrome with diarrhea (IBS-D). METHOD: A multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatment group or the placebo control group, administrated with Chang'an I Recipe or placebo, 150 mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score (IBS-SSS) and the differences in adequate relief (AR) responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD) scales. The safety indices included adverse events and related laboratory tests. RESULTS: A total of 216 patients were included, with 109 in the treatment group and 107 in the control group, and finally 206 were included in the full analysis set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total effective rate was 67.6% and 40.2% for the treatment and control groups, respectively, with 95% confidence interval (CI) for difference in the effective rates between the two groups of 14.4%-40.2%; while in PPS, the total effective rate was 71.3% and 41.2% for the treatment and control groups, respectively (95% CI 16.6%-43.4%). The consistent conclusions of FAS and PPS showed a better efficacy in the treatment group. Both FAS and PPS showed higher AR responder in the treatment group (FAS: 59.6% vs. 35.5%; PPS: 62.8% vs. 38.1%). As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the two groups (P>0.05). Both anxiety and depression scales of HAD were not significantly different between the two groups (P>0.05). No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant. CONCLUSION: Chang'an I Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. (No.ChiCTR-TRC-09000328).