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Objective To assess clinical efficacy of vedolizumab （VDZ） in the treatment of inflammatory bowel disease（IBD） and analyze whether VDZ combined with immunomodulator and/or corticosteroids can achieve better outcomes. Methods Twenty-nine patients with active IBD including 21 cases of ulcerative colitis （UC） and 8 cases of Crohn’s disease （CD） were recruited. They were assigned to receive VDZ （at a dose of 300 mg） intravenously at 0, 2, 6 weeks as induction therapy and every 8 or 4 weeks as maintenance therapy. The primary endpoint was clinical response at week 14/22, while the secondary endpoints were clinical remission and mucosal healing at week 54 （VDZ administration every 8 weeks） or week 30 （VDZ administration every 4 weeks）. Based on the concomitant medications, all patients were divided into the VDZ monotherapy and combination groups （VDZ combined with immunomodulator and/or corticosteroids）. The therapeutic effect was compared between two groups. Results Among UC patients,clinical response and endoscopic remission rates at week 14/22 were 81% （13/16） and 63% （10/16）, respectively. At week 54, clinical remission rate was 80% （4/5）and mucosal healing rate was 40% （2/5）. Among CD patients, clinical response rates at week 14/22 and week 30 were 75% （6/8） and 100% （1/1）, respectively. There was no significant difference in clinical response rate at week 14/22 between the VDZ monotherapy and combination groups. Conclusions VDZ is an effective biologic agent as induction and maintenance therapy for UC and CD. VDZ combined with immunomodulator and/or corticosteroids brings no additional benefit in the induction therapy. Therefore, VDZ monotherapy may be a better choice in clinical practice.

Objective To investigate the effect of infliximab （IFX） combination therapy on inflammatory biomarkers and intestinal mucosal healing in patients with extensive Crohn’s disease（CD）. Methods According to the evaluation criteria of endoscopic grading score and mucosal healing of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, inflammatory biomarkers and mucosal healing data of 160 patients with extensive CD were retrospectively analyzed. All patients were assigned into the IFX combination therapy group （n = 98） and conventional drug therapy group （n = 62）. Results The C-reactive protein （CRP） level, erythrocyte sedimentation rate （ESR） and interleukin 6 （IL-6） level began to decline, but the serum TNF-α level increased during the second cycle of IFX treatment. In the IFX combination therapy group, the healing rate of colonic mucosa in patients treated for 12 times had statistical significance compared with that of those treated for less than 12 times （P < 0.05）. In the IFX combination therapy group, the endoscopic total effective rate was 80.3% （57/71）, significantly higher than 64.5% （40/62） in the conventional drug therapy group （P = 0.041）. Conclusions IFX combination regimen can significantly increase the serum TNF-α level, whereas it exerts no effect upon intestinal mucosal healing. IFX combination therapy can more effectively promote colonic mucosal healing than conventional therapy.

The present experiment was conducted to study the effects of different levels of oligosaccharide(FOS) and complex CPP preparation(CPP) in diets on growth performance and serum biochemical parameters for weaned piglets. 240 crossbred DLY( Duroc× Landrace× Yorkshire) 21-day-old weaning piglets, about 7.2 kg in initial body weight were selected and randomly divided into 6 groups, with 2 repeats for each group, 20 each repeat(half male and half female.). Group 1, as the control group, was fed base diet(BD), group 2 was fed BD adding 0.10% aureomycin, group 3, 4, 5, 6, respectively, was fed BD adding 0.05% CPP, 0.05% FOS, 0.20% FOS and 0.10% FOS + 0.05% of CPP. Feeding trial was conducted for 35 days. Results: (1) The combination of 0.10%FOS and 0.05%CPP(group 6) were added, the average daily gain of weaned pigs increased by 13.71 % (P < 0.05) and the feed conversion ratio was reduced by 7.41 % (P < 0.05) compared with control. The diarrhea rate of piglets decreased by 94.63 % (P < 0.01) compared with the control (p < 0.05), and decreased by 62.86 % (P 0.05).(3) There was no significant difference in serum biochemical indexes, such as serum total protein, albumin, urea nitrogen, cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase and sugar by adding FOS and CPP individually or jointly in diet of weaned piglets (P > 0.05);there was no significant effect in serum immunoglobulin IgG and IgM (P> 0.05), but the serum IgE content was increased in different degrees. Conclusion: Adding FOS and CPP in diet for weaned piglets can improve the growth performance, reduce diarrhea rate of piglets, and promote digestion and absorption of feed nutrients, without significant difference between them and diet adding antibiotics. Among them, the effect of adding 0.10%FOS+0.05%CPP was the best.

The present experiment was conducted to study the effects of different levels of oligosaccharide(FOS) and complex CPP preparation(CPP) in diets on growth performance and serum biochemical parameters for weaned piglets. 240 crossbred DLY( Duroc× Landrace× Yorkshire) 21-day-old weaning piglets, about 7.2 kg in initial body weight were selected and randomly divided into 6 groups, with 2 repeats for each group, 20 each repeat(half male and half female.). Group 1, as the control group, fed base diet(BD) , group 2 fed BD adding 0.10% aureomycin, group 3, 4, 5, 6, respectively, fed BD adding 0.05% CPP, 0.05% FOS, 0.20% FOS and 0.10% FOS + 0.05% of CPP. Feeding trial was conducted for 35 days.Results: (1) Intestinal pH: Compared with the control group, the pH values of jejunum, ileum, cecum and colon in the 3, 4, 5 and 6 groups were significantly lower (P < 0.05), while there was no significant difference between the antibiotic group and the control group (P > 0.05).(2) Small intestinal villus morphology: Duodenal segment, villus length of 6 groups was significantly increased compared with the control group (P < 0.05), villus height to recess depth ratio (V/C) was significantly increased (P < 0.05). There was no significant difference in villus length between groups in jejunal segment (P > 0.05). Groups five V/C was significantly higher than that in the control group (P < 0.05). Compared with the control group and the antibiotic group, the ileal segment in the six groups significantly increased V/C (P < 0.05).(3) Intestinal flora Adding FOS, CPP and their combination could reduce the number of E. coli and Salmonella in different intestinal segments, and increase the number of Lactobacillus and Bifidobacteria. Among them, the effect of joint addition is the most obvious. Conclusion: Adding FOS and C PP to the diet of weaned piglets could effectively reduce the intestinal pH value of piglets, increase the length of intestinal villi and V/C, reduce the number of harmful bacteria and increase the number of beneficial bacteria. It is beneficial to maintain the balance of intestinal morphology and microflora and improve the intestinal health of piglets. Among them, the combination of 0.10% FOS and 0.05% CPP is the best, followed by 0.20% FOS.

24-week-old local yellow broiler breeder hens were selected to study the effects of dietary fructo-oligosaccharides(FOS)or antibiotics(bacitracin zinc)on laying performance, serum biochemical indices and dietary mutrient metabolizability. The results showed that: compared with the control group, dietary FOS supplemented with 0.2%, 0.4%, 0.6% could increase the laying rate, average egg weight, feed egg ratio, eggs percent of pass, fertility rate and hatchability of qualified egg, and reduce serum levels of total cholesterol and triglyceride, and improve the apparent metabolizability of dietary nutrients. The effects of diet supplemented with FOS was better than those of diet supplement with 0.05% antibiotics.It was suggested that the appropriate additive amount of FOS in diets for yellow broiler breeder hens should be 0.4%.

Background: Colorectal cancer (CRC) is a disease with high morbidity and mortality rates globally. Long noncoding RNAs (lncRNAs) play a fundamental role in tumor progression, and increasing attention has been paid to their role in CRC. This study aimed to determine the function of lncRNA DICER1 antisense RNA 1 (DICER1‐AS1) in CRC and confirm its potential regulatory mechanisms in CRC. Methods: The publicly available dataset was used to assess DICER1‐AS1 function and expression in CRC. RT–qPCR or western blot assays were performed to verify DICER1‐AS1, miR‐650, and mitogen‐activated protein kinase 1 (MAPK1) expression in CRC cells or tissues. To determine the function of DICER1‐AS1, we performed CCK‐8, colony formation, transwell, cell cycle, and in vivo animal assays. Using RNA sequence analysis, luciferase reporter assays, and bioinformatics analysis, the connection between DICER1‐AS1, MAPK1, and miR‐650 was investigated. Results: DICER1‐AS1 was significantly upregulated in CRC tissue compared to normal colon tissue. High DICER1‐AS1 expression suggested a poor prognosis in CRC patients. Functionally, upregulation of DICER1‐AS1 effectively promoted CRC proliferation, migration, and invasion ex vivo and tumor progression in vivo. Mechanistically, DICER1‐AS1 functions as a competitive endogenous RNA (ceRNA) that sponges miR‐650 to upregulate MAPK1, promotes ERK1/2 phosphorylation, and sequentially activates the MAPK/ERK signaling pathway. Conclusion: Our investigations found that upregulation of DICER1‐AS1 activates the MAPK/ERK signaling pathway by sponging miR‐650 to promote CRC progression, revealing a possible clinically significant biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

The influence mechanism of colorants, admixtures and mix parameters on the surface color and workability of concrete were studied. In addition, the distribution of colorants in hydration products and the effects on the formation of hydration products were studied by means of microscopic measurement. The results show that iron oxide pigments have little effect on slurry fluidity, but high content of iron oxide pigments causes complex problems such as white surface of concrete and deterioration of mechanical durability. Carbon black pigments have higher coloring ability than iron black pigments, but it significantly deteriorates the fluidity of fresh concrete paste. Carbon black pigment particles mainly adhere to hydrated calcium hydroxide and matrix pore through adhesion, which is conducive to the nucleation and crystallization of hydrated products: iron black pigment particles consolidate in concrete structure through mechanical and electrostatic action, but it inhibits the formation of calcium hydroxide to a certain extent: Considering the slurry fluidity and color, the concrete can meet the requirements of fluidity, color and excellent performance by choosing the complex colorant scheme of carbon black and iron black pigments. [ABSTRACT FROM AUTHOR]

The prognosis of pancreatic cancer is still very poor. No specific effective gene therapy for pancreatic cancer has been found. As a key enzyme of the metabolic process of arachidonic acid, cyclooxygenase-2 (COX-2) has been found to be closely related to the tumorigenesis of epithelial cancers. However, the antitumor effect of small interfering RNA (siRNA) targeting COX-2 in pancreatic cancer has not yet been verified. Therefore, the aim of this study was to investigate the effects of COX-2 gene silencing by siRNA on cell proliferation, cell apoptosis, cell cycle and tumorigenicity of pancreatic cancer cells. COX-2 mRNA was detected by RT-PCR and real-time PCR. COX-2 protein was detected by Western blotting. The cell proliferation was measured by cell counting using microscopy. The cell apoptosis and cell cycle were measured by flow cytometry. The tumorigenicity of Capan-2 pancreatic cancer cells transfected with COX-2 siRNA was evaluated using a nude mouse xenograft model. The expression of COX-2 mRNA as well as COX-2 protein were downregulated after COX-2 siRNA transfection. COX-2 siRNA could inhibit the growth of Capan-2 cells significantly by decreasing the cell proliferation, increasing cell apoptosis and regulating cell cycle as well. In vivo experiments demonstrated that the mean volume and weight of subcutaneous xenografts in nude mice derived from Capan-2 cells transfected with COX-2 siRNA were significantly decreased. COX-2 siRNA could inhibit the growth of Capan-2 pancreatic cancer cells and also decrease the tumorigenicity of Capan-2 cells, implicating a new potential therapeutic target in pancreatic cancer.

Colon cancer is one of the most common cancers in the world. Overexpression of MDR1 mRNA and P-gp is associated with the classic multidrug resistance of colon cancer cells. In our previous study, we reported on the transient specific reversal of MDR1/P-gp-dependent multi-drug resistance by RNA interference (RNAi) in colon cancer cells. In this study, RNAi targeting the MDR1 gene stably reversed MDR1/P-gp-dependent multidrug resistance in colon cancer cells. The plasmid vectors pSilencer-#4029, encoding #4029 MDR1 siRNA, and pSilencer-#4123, encoding #4123 MDR1 siRNA, were constructed and then transfected into COLO 320DM, a colon cancer multidrug-resistant cell line. Clone cells were screened by G418 and identified by RT-PCR and Western blot analysis. Cellular viability was measured using the MTT assay. Cell cycle analysis and intracellular adriamycin accumulation were assessed by flow cytometry. MDR1 mRNA and P-gp expression in positive clone cells, those stably transfected with MDR1 siRNA, was inhibited. The IC50 values of the antitumor drugs were significantly decreased in the positive clones compared to the COLO 320DM parent cell line, and the PI/AI values of positive clones treated with antitumor drugs were significantly decreased compared to the parent cells. In addition, the intracellular adriamycin accumulation of positive clones treated with adriamycin was significantly increased compared with COLO 320DM. This demonstrates that the stable transfection of plasmid vectors encoding MDR1 siRNA can stably reverse the MDR1/P-gp-dependent multidrug resistance of colon cancer cells.

No control cell line was available for previous RNA interference studies on reversal of multidrug resistance (MDR) in colon cancer cells. Here, human COLO 320DM, with HT-29 as the control, colon cancer cell lines were used to investigate the reversal of MDR1/P-gp-dependent MDR by siRNA (#4123 and #4029 MDR1 siRNAs) targeting to MDR1 mRNA. Both siRNAs inhibited expression of MDR1 and P-gp in COLO 320DM. The minimum inhibition concentrations were 5 nmol/l of #4123 and 25 nmol/l of #4029. #4123 MDR1 siRNA took effect in 4, 5 and 6 days at doses of 5, 25 and 100 nmol/l, respectively. Increased cytotoxicity of the antitumor drugs adriamycin and vincristine with increased intracellular adriamycin accumulation accompanied inhibition of MDR1 mRNA and P-gp expression. No such effects were found in the HT-29 control. MDR1 siRNAs specifically reversed the MDR of colon cancer cells demonstrating a possible new approach for treating MDR1/P-gp-dependent multidrug resistance.