Changes of serum miR-221 and miR-145 levels with papillary thyroid carcinoma and their relationship with invasive activity.

This study aimed to investigate the expression of miR-221 and miR-145 in papillary thyroid carcinoma, and the effect of miR-221 and miR-145 on the invasion ability of thyroid cancer cells and its mechanism. For this purpose, 120 patients with thyroid nodules were divided into the observation group (PTC) of 43 cases and the control group (benign nodules) of 42 cases according to postoperative pathological diagnosis. Total RNA was extracted from serum samples of all patients, and the expression levels of miRNA-145 and miR-221 were detected by fluorescence quantitative PCR. The expression of two kinds of miRNAs in the groups was compared, and their correlation was analyzed. The results showed that the expression of miRNA-145 in thyroid cancer tissues was lower than that in paired adjacent normal tissues (P < 0.001). The expression of miRNA-221 in thyroid cancer tissues was higher than that in paired adjacent normal tissues (P < 0.001). The proliferation and migration ability of miRNA-145 cells were significantly decreased (P < 0.01). The expression of miRNA-221 was up-regulated, and the proliferation and migration ability of cells was significantly enhanced (P < 0.05). High expression of miRNA-145 can inhibit cell proliferation and migration and promote apoptosis, while high expression of miRNA-221 will promote cell proliferation and migration and enhance the invasion ability of cancer cells. In general, the expression of miRNA-22l in serum of PTC patients is significantly up-regulated, while the expression level of miR-145 is down-regulated, which can be used as effective indicators to judge the biological activity of the tumor, and the combined detection of the two can significantly enhance the diagnostic value of PTC. Upregulation of miR-145 inhibits PTC cell proliferation; arrests cell cycle and promotes apoptosis miR-145 may play an important role as a tumor suppressor gene.

Alterations in degree centrality and cognitive function in breast cancer patients after chemotherapy.

The goal of this study was to determine the presence or absence of persistent functional impairments in specific brain regions in breast cancer patients during the recovery period after chemotherapy. We calculated degree centrality (DC) and explored the correlation between brain changes and cognitive scores in 29 female patients with breast cancer who had completed chemotherapy within 1-6 years (C + group) and in 28 age-matched patients with breast cancer who did not receive chemotherapy (C- group). All patients underwent rs-fMRI and cognitive testing. Differences in brain functional activity were explored using DC parameters. Correlations between brain features and cognitive scores were analyzed via correlation analysis. Compared with the C- group, the C + group obtained significantly lower motor and cognitive subscores on the Fatigue Scale for Motor and Cognitive Functions and four subscale scores of the Functional Assessment of Cancer Therapy-Cognitive Function (P < 0.05). Furthermore, the C + group exhibited a significantly higher DC z-score (zDC) in the right superior temporal gyrus and left postcentral gyrus (P < 0.01, FWE-corrected), and a lower zDC in the left caudate nucleus (P < 0.01, FWE-corrected). We found a positive correlation between digit symbol test (DST) scores and zDC values in the right superior temporal gyrus (r = 0.709, P < 0.001), and a negative correlation between DST scores and zDC values in the right angular gyrus (r = -0.784, P < 0.001) and left superior parietal gyrus (r = -0.739, P < 0.001). Chemotherapy can cause abnormal brain activity and cognitive decline in patients with breast cancer, and these effects are likely to persist. DC can be used as an imaging marker for chemotherapy-related cognitive impairment after chemotherapy in breast cancer patients.

Glucagon-Like Peptide-2 Modulates Enteric Paneth Cells Immune Response and Alleviates Gut Inflammation During Intravenous Fluid Infusion in Mice With a Central Catheter.

Background: Glucagon-like peptide-2 (GLP-2) has protective effects on gastrointestinal functions. Our previous study found that GLP-2 could significantly reduce intestinal permeability and bacterial translocation in total parenteral nutrition (TPN) animal model. However, the effects of GLP-2 on the impairment of the intestinal Paneth cells immune function and gut inflammation during intravenous fluid infusion mainly consisted of nutritional materials is currently scattered. Objective: The current study was aimed to investigate the efficacy of the GLP-2 in alleviating gut inflammation and modulating enteric Paneth cells immune response in parenterally fed mice and its underlying mechanisms. Methods: Thirty-six male ICR mice underwent venous catheterization were divided into 3 groups: Chow, TPN, and TPN+GLP-2 groups. GLP-2 was administered intravenously at 60 µg/day for 5 days. The small intestine tissue and serum samples were collected on the 7th day. Results: Compared with the TPN group, the expression of tight junction proteins occludin and claudin-1 were significantly increased in the TPN+GLP-2 group. In addition, the expression of lysozyme, sPLA2, insulin-like growth factor-1, and epithelial protection and repair genes were improved in the TPN+GLP-2 group. The levels of IL-6 and TNF-α proteins and mRNAs in the ileum tissues were remarkably reduced in the TPN+GLP-2 group, while IL-10 protein and mRNA level were elevated in the TPN+GLP-2 group (all p < 0.05). Moreover, the TPN+GLP-2 group has higher levels of serum endotoxin, D-lactic acid, and MPO than those of the TPN group. Conclusions: GLP-2 alleviated gut inflammation and improved enteric Paneth cells immune responses through intravenous fluid infusion, possibly by improving the functioning of epithelial protection and repair, and reducing mucosal inflammatory responses.

Glucagon-like peptide-2 improves intestinal immune function and diminishes bacterial translocation in a mouse model of parenteral nutrition.

Parenteral nutrition (PN) is associated with increased infectious risks due to impaired intestinal immunity. Although glucagon-like peptide-2 (GLP-2) enhances the gut barrier function, it is uncertain whether it improves mucosal immunologic barrier function. We hypothesized that injecting the PN mouse model with GLP-2 improved innate and acquired immunity, and prevented bacterial translocation. Forty-eight hours after venous cannulation, male Institute of Cancer Research mice were randomly divided into 3 groups based on their diet: chow with saline (n = 10), PN (n = 9), or PN + GLP-2 (30 µg bid per mouse, n = 10) provided for 5 days. Compared with chow, PN reduced interleukin (IL)-4 and IL-13 levels (P < .05, respectively), whereas, compared with PN alone, GLP-2 injection increased IL-4 and IL-13 levels (P < .05, respectively). Compared with chow, PN considerably suppressed, whereas GLP-2 improved, secretory phospholipase A2 and cryptdin-4 expression. PN, compared with chow, considerably decreased lysozyme and polymeric immunoglobulin receptor levels, whereas, compared with PN, GLP-2 significantly increased these protein levels (P < .01, respectively). In tissue and luminal samples, compared with chow, PN reduced secretory immunoglobulin A levels (P < .05), whereas, compared with PN alone, GLP-2 increased secretory immunoglobulin A levels (P < .05). Functionally, more bacterial translocation was observed in the PN group compared with the chow group (P < .001), and GLP-2 injection decreased bacterial translocation to chow levels (P < .05). In summary, GLP-2 treatment may improve intestinal innate and acquired immunity, and prevent bacterial translocation in mice on total parenteral nutrition.

Partial enteral nutrition increases intestinal sIgA levels in mice undergoing parenteral nutrition in a dose-dependent manner.

BACKGROUND AND AIMS: Partial enteral nutrition (PEN) protects parenteral nutrition (PN) induced gut mucosal immunity impairment. However, the gastrointestinal function of most patients with PN is too poor to tolerate full dosage of PEN and no guidelines recommend PEN dose. We aimed to identify an optimal PEN dose and to understand the protective mechanism. METHODS: Mice were assigned to groups with total parenteral nutrition (TPN), total enteral nutrition (TEN), or various degrees of PEN with PN. Additionally, AS1517499 was used to inhibit STAT6. Five days after treatment, secretory immunoglobulin A (sIgA) levels of luminal washing fluid and JAK1-STAT6 signalling in ileum tissue of different groups were assessed. RESULTS: We found that TPN lowered luminal sIgA and down-regulated pIgR, phosphorylated JAK1 and STAT6, IL-4 and IL-13 as well relative to TEN. Moreover, 40% EN were lowest dose that reversed these detrimental consequences of PN to an equivalent level as TEN. The rescue of pIgR and luminal sIgA expression was decreased when the JAK1-STAT6 pathway was inhibited. CONCLUSION: We conclude that 40% EN is the optimal PEN dose that reverses PN-induced impairment of gut mucosal immunity. Additionally, we hypothesise that this benefit involves activation of the JAK1-STAT6 pathway.

Effects of n-3 PUFAs on Intestinal Mucosa Innate Immunity and Intestinal Microbiota in Mice after Hemorrhagic Shock Resuscitation.

n-3 polyunsaturated fatty acids (PUFAs) can improve the function of the intestinal barrier after damage from ischemia-reperfusion or hemorrhagic shock resuscitation (HSR). However, the effects of n-3 PUFAs on intestinal microbiota and the innate immunity of the intestinal mucosa after HSR remain unclear. In the present study, 40 C57BL/6J mice were randomly assigned to five groups: control, sham, HSR, HSR + n-3 PUFAs and HSR + n-6 PUFAs. Mice were sacrificed 12 h after HSR. Liver, spleen, mesenteric lymph nodes and terminal ileal tissues were collected. Intestinal mucosae were scraped aseptically. Compared with the HSR group, the number of goblet cells increased, expression of mucin 2 was restored and disturbed intestinal microbiota were partly stabilized in the PUFA-administered groups, indicating that both n-3 and n-6 PUFAs reduced overproliferation of Gammaproteobacteria while promoting the growth of Bacteroidetes. Notably, n-3 PUFAs had an advantage over n-6 PUFAs in improving ileal tissue levels of lysozyme after HSR. Thus, PUFAs, especially n-3 PUFAs, partly improved the innate immunity of intestinal mucosa in mice after HSR. These findings suggest a clinical rationale for providing n-3 PUFAs to patients recovering from ischemia-reperfusion.

Whole Grain Intake Reduces Pancreatic Cancer Risk: A Meta-Analysis of Observational Studies.

Mounting evidence from epidemiology studies suggests that whole grain intake may reduce pancreatic cancer risk, but convincing evidence is scarce. We conducted a meta-analysis to assess the association between whole grain intake and pancreatic cancer risk. Relevant observational studies were identified by searching PubMed, Embase, Scopus, and Cochrane library databases for the period from January 1980 to July 2015, with no restrictions. We calculated the summary odds ratios (ORs) for pancreatic cancer using random-effects model meta-analysis. Between-study heterogeneity was analyzed using the I statistic. A total of 8 studies regarding whole grain intake were included in the meta-analysis. The pooled OR of pancreatic cancer for those with high versus low whole grain intake was 0.76 (95% confidence interval [CI], 0.64-0.91; P = 0.002). There was no significant heterogeneity across these studies (I²â€Š= 11.7%; Pheterogeneity = 0.339). In the subgroup analysis by geographic area, the summary ORs of developing pancreatic cancer were 0.64 (95% CI, 0.53-0.79; P < 0.001; I ²= 0%; Pheterogeneity = 0.482) in the United States (n = 4) and 0.95 (95% CI, 0.63-1.43; P = 0.803; I ²= 45.6%; Pheterogeneity = 0.175) in Europe (n = 2). In the subgroup analysis by type of whole grain, the summary ORs were 0.72 (95% CI, 0.60-0.87; P = .001; I²â€Š= 0; Pheterogeneity = 0.876) for grains (n = 4) and 0.74 (95% CI, 0.27-2.02; P = 0.554; I²â€Š= 86.3%; Pheterogeneity = 0.007) for wheat (n = 2). A high intake of whole grains was associated with a reduced risk of pancreatic cancer. Because of the absent of more cohort studies, further prospective studies need to be conducted to ensure conclusions that are more robust.

Apple-Derived Pectin Modulates Gut Microbiota, Improves Gut Barrier Function, and Attenuates Metabolic Endotoxemia in Rats with Diet-Induced Obesity.

This study was aimed at determining potential effects of apple-derived pectin on weight gain, gut microbiota, gut barrier and metabolic endotoxemia in rat models of diet-induced obesity. The rats received a standard diet (control; Chow group; n = 8) or a high-fat diet (HFD; n = 32) for eight weeks to induce obesity. The top 50th percentile of weight-gainers were selected as diet induced obese rats. Thereafter, the Chow group continued on chow, and the diet induced obese rats were randomly divided into two groups and received HFD (HF group; n = 8) or pectin-supplemented HFD (HF-P group; n = 8) for six weeks. Compared to the HF group, the HF-P group showed attenuated weight gain (207.38 ± 7.96 g vs. 283.63 ± 10.17 g, p < 0.01) and serum total cholesterol level (1.46 ± 0.13 mmol/L vs. 2.06 ± 0.26 mmol/L, p < 0.01). Compared to the Chow group, the HF group showed a decrease in Bacteroidetes phylum and an increase in Firmicutes phylum, as well as subordinate categories (p < 0.01). These changes were restored to the normal levels in the HF-P group. Furthermore, compared to the HF group, the HF-P group displayed improved intestinal alkaline phosphatase (0.57 ± 0.20 vs. 0.30 ± 0.19, p < 0.05) and claudin 1 (0.76 ± 0.14 vs. 0.55 ± 0.18, p < 0.05) expression, and decreased Toll-like receptor 4 expression in ileal tissue (0.76 ± 0.58 vs. 2.04 ± 0.89, p < 0.01). The HF-P group also showed decreased inflammation (TNFα: 316.13 ± 7.62 EU/mL vs. 355.59 ± 8.10 EU/mL, p < 0.01; IL-6: 51.78 ± 2.35 EU/mL vs. 58.98 ± 2.59 EU/mL, p < 0.01) and metabolic endotoxemia (2.83 ± 0.42 EU/mL vs. 0.68 ± 0.14 EU/mL, p < 0.01). These results suggest that apple-derived pectin could modulate gut microbiota, attenuate metabolic endotoxemia and inflammation, and consequently suppress weight gain and fat accumulation in diet induced obese rats.

GLP-2 Prevents Intestinal Mucosal Atrophy and Improves Tissue Antioxidant Capacity in a Mouse Model of Total Parenteral Nutrition.

We investigated the effects of exogenous glucagon-like peptide-2 (GLP-2) on mucosal atrophy and intestinal antioxidant capacity in a mouse model of total parenteral nutrition (TPN). Male mice (6-8 weeks old) were divided into three groups (n = 8 for each group): a control group fed a standard laboratory chow diet, and experimental TPN (received standard TPN solution) and TPN + GLP-2 groups (received TPN supplemented with 60 µg/day of GLP-2 for 5 days). Mice in the TPN group had lower body weight and reduced intestinal length, villus height, and crypt depth compared to the control group (all p < 0.05). GLP-2 supplementation increased all parameters compared to TPN only (all p < 0.05). Intestinal total superoxide dismutase activity and reduced-glutathione level in the TPN + GLP-2 group were also higher relative to the TPN group (all p < 0.05). GLP-2 administration significantly upregulated proliferating cell nuclear antigen expression and increased glucose-regulated protein (GRP78) abundance. Compared with the control and TPN + GLP-2 groups, intestinal cleaved caspase-3 was increased in the TPN group (all p < 0.05). This study shows GLP-2 reduces TPN-associated intestinal atrophy and improves tissue antioxidant capacity. This effect may be dependent on enhanced epithelial cell proliferation, reduced apoptosis, and upregulated GRP78 expression.

Superior mesenteric artery syndrome caused by surgery and radiation therapy for a brain tumor: A case report.

Superior mesenteric artery syndrome (SMAS) is defined as an obstruction of the third part of duodenum due to compression by the superior mesenteric artery. Although traumatic brain injury is a risk factor for SMAS, few cases of SMAS resulting from brain surgery have been reported. SMAS has been observed to occur following neurosurgical surgery in pediatric patients but, to the best of our knowledge, no such cases have been reported in adults. The present study reports the case of a 21-year-old female patient who developed SMAS after persistent vomiting and prolonged weight loss following cerebellar tumor resection and cranial irradiation. The SMAS was confirmed by computed tomography and resolved following successful nutritional management.

Peri-operative immunonutrition in patients undergoing liver transplantation: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: No consensus has been reached concerning the effects of peri-operative immunonutrition in patients undergoing liver transplantation. We conducted a meta-analysis to evaluate the effects of peri-operative immunonutrition on clinical outcomes and liver function in patients undergoing liver transplantation. METHODS AND STUDY DESIGN: The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and google scholar were searched to identify all available randomized controlled studies which compared peri-operative immunonutrition support (glutamine, ω-3 polyunsaturated fatty acids, arginine and ribonucleic acids) with standard nutrition. The data analysis was performed using Revman 5.2 software. RESULTS: A total of 7 randomized controlled trials (RCTs) involving 501 patients were included. Peri-operative immunonutrition significantly reduced the risk of infectious complications (RR: 0.51; 95% CI: 0.27 to 0.98, p=0.04) and shortened the postoperative hospital stay [weighted mean difference (WMD): -3.89; 95% CI: -7.42 to -0.36; p=0.03]. Furthermore, perioperative immunonutrition improved liver function by decreasing the levels of aspartate aminotransferase (AST) in the blood (WMD: -25.4; 95% CI: -39.9 to -10.9, p=0.0006). However, we did not find statistically significant differences in serum alanine aminotransferase (ALT), total bilirubin (TB) and direct bilirubin (DB) levels. There were no statistically significant differences in mortality and rejection reaction. CONCLUSIONS: Peri-operative nutrition support adding immunonutrients like glutamine, ω-3 polyunsaturated fatty acids, arginine and ribonucleic acids may improve outcomes in patients undergoing liver transplantation. Due to the limited sample size of the included trials, further large-scale and rigorously designed RCTs are needed.

Partial Enteral Nutrition Preserves Elements of Gut Barrier Function, Including Innate Immunity, Intestinal Alkaline Phosphatase (IAP) Level, and Intestinal Microbiota in Mice.

Lack of enteral nutrition (EN) during parenteral nutrition (PN) leads to higher incidence of infection because of gut barrier dysfunction. However, the effects of partial EN on intestina linnate immunity, intestinal alkaline phosphatase (IAP) and microbiota remain unclear. The mice were randomized into six groups to receive either standard chow or isocaloric and isonitrogenous nutritional support with variable partial EN to PN ratios. Five days later, the mice were sacrificed and tissue samples were collected. Bacterial translocation, the levels of lysozyme, mucin 2 (MUC2), and IAP were analyzed. The composition of intestinal microbiota was analyzed by 16S rRNA pyrosequencing. Compared with chow, total parenteral nutrition (TPN) resulted in a dysfunctional mucosal barrier, as evidenced by increased bacterial translocation (p < 0.05), loss of lysozyme, MUC2, and IAP, and changes in the gut microbiota (p < 0.001). Administration of 20% EN supplemented with PN significantly increased the concentrations of lysozyme, MUC2, IAP, and the mRNA levels of lysozyme and MUC2 (p < 0.001). The percentages of Bacteroidetes and Tenericutes were significantly lower in the 20% EN group than in the TPN group (p < 0.001). These changes were accompanied by maintained barrier function in bacterial culture (p < 0.05). Supplementation of PN with 20% EN preserves gut barrier function, by way of maintaining innate immunity, IAP and intestinal microbiota.

Laparoscopic Versus Open Colorectal Resection Within Fast Track Programs: An Update Meta-Analysis Based on Randomized Controlled Trials.

The objective of the study was to assess the safety and efficacy of laparoscopic colorectal surgery by comparing open operation within fast track (FT) programs. The Cochrane Library, PubMed, Embase and Chinese Biological Medicine Database were searched to identify all available randomized controlled trials (RCTs) comparing laparoscopic with open colorectal resection within FT programs. A total of seven RCTs were finally included, enrolling 714 patients with colorectal cancer: 373 patients underwent laparoscopic surgery and FT programs (laparoscopic/FT group) and 341 patients received open operation and FT programs (open/FT group). Postoperative hospital stay (weighted mean difference (WMD): 0.66; 95% CI: 0.27 - 1.04; P < 0.05), total hospital stay (WMD: 1.46; 95% CI: 0.40 - 2.51; P < 0.05) and overall complications (RR: 1.31; 95% CI: 1.12 - 1.54; P < 0.05) were significantly lower in laparoscopic/FT group than in open/FT group. However, no statistically significant differences on mortality (risk ratio (RR): 2.26; 95% CI: 0.62 - 8.22; P = 0.21), overall surgical complications (RR: 1.19; 95% CI: 0.94 - 1.51; P = 0.15) and readmission rates (RR: 1.33; 95% CI: 0.79 - 2.22; P = 0.28) were found between both groups. The laparoscopic colorectal surgery combined with FT programs shows high-level evidence on shortening postoperative and total hospital stay, reducing overall complications without compromising patients' safety.

Use of n-3 PUFAs can decrease the mortality in patients with systemic inflammatory response syndrome: a systematic review and meta-analysis.

BACKGROUND: There have been several meta-analyses evaluating the effect of n-3 polyunsaturated fatty acids (PUFAs) in critically ill patients, but of these, none focused on patients with systemic inflammatory response syndrome (SIRS). The objective of this meta-analysis was to evaluate the effect of omega-3 fatty acids (n-3 FAs) on this narrow subset. METHODS: All relevant articles were searched on MEDLINE, EMBASE, SpringerLink, and the Cochrane Database of Systematic Reviews from 1990 to 2014. Meta-analyses were used to evaluate risk ratios and mean differences with 95% confidence intervals between the n-3 PUFA group and the control group. Subgroup analyses were conducted in terms of the route of fish oil. RESULTS: Nine randomized controlled trials (RCTs) with 783 adult patients were included in this study. Compared with control groups, n-3 FA provision can significantly reduce the incidence of mortality (RR: 0.77 [0.60, 0.97]; P=0.03; I2=0%). Secondary outcomes showed no significant differences between groups except for shorter length of hospital stay (weighted mean difference: -10.56 [-19.76, -1.36], p<0.00001, I2=99%). CONCLUSIONS: Overall, this meta-analysis from RCTs indicates that provision of n-3 PUFAs has a therapeutic effect on survival rate in patients with SIRS.