[Effects of probiotics on the intestinal microecological abnormalities and colorectal cancer of mice induced by high-fat diet].

Objective: To establish the mice colorectal cancer (CRC) model induced by AOM/DSS with the intervention of high fat diet and probiotics, and to explore the potential mechanism of probiotics intervention in regulating intestinal flora disturbance and antitumor efficiency. Methods: Forty 8-week-old male C57BL/6J mice were randomly divided into 4 groups with 10 mice in each group: HFD group, HDF with probiotics intervention (HFD+P) group, normal diet (ND) group, normal diet with probiotics intervention (ND+P) group. The probiotic groups were administered with probiotics preparation by gavage. During the experiment, AOM/DSS was used to induce mouse colorectal cancer model. The mouse body weight was regularly recorded and the body status was evaluated weekly. High-throughput 16S rDNA sequencing was used to analyze the changes of fecal flora in bacterial structure before and after cancer induction. At the end of the experiment, intestinal tissues of mice were collected and the epididymis adipose mass (EAM) and tumor burden were recorded. The Alpha diversity index was used to analyze the abundance and diversity of the intestinal flora (higher chaol index means higher abundance of bacteria and greater Simpson index means lower diversity in flora structure). The Beta diversity index was used to analyze the significance of the difference in the distribution of intestinal flora among the four groups (When R>0, the difference in the distribution of bacteria among the groups is greater than the difference within the group). Results: After 15 weeks of experiment, the body weight of mice in HFD group, HFD+P group, ND group and ND+P group was (33.70±0.52) g, (28.70±0.32) g, (25.90±0.34) g and (25.60±0.40) g, whose difference was statistically significant (F=700.89, P<0.01). The body weight of HFD group was higher than that of ND group and HFD+P group while the body weight of HFD+P group was still higher than that of ND group, and the differences were statistically significant (all P<0.017). The average EAM of HFD group, HFD+P group, ND group and ND+P group was (1.36±0.15) g, (0.67±0.08) g, (0.58±0.10) g and (0.54±0.05) g, whose difference was statistically significant (F=114.03, P<0.01). Pairwise comparisons showed that EAM in HFD group was higher than that in ND group and HFD+P group respectively, with statistically significant difference (both P<0.01), while average EAM of HFD+P group was similar to ND group (P=0.09). Under the diet intervention, the Chao1 index of HFD group, HFD+P group, ND group and ND+P group was 217.62, 235.32, 301.51 and 305.71 respectively, and the Simpson index was 0.93, 0.89, 0.91 and 0.90. At the same time, the Anosim analysis of Beta diversity analysis showed that the difference in the flora distribution among four groups was greater than the difference with in each group with statistically significant difference (R=0.655, P=0.001). Species abundance analysis revealed that, compared with ND group, at phylum level, HFD group had a higher proportion of Bacteroides phylum and Firmicutes phylum in the intestinal flora and lower proportion of Verrucomicrobia; at genus level, the proportion of Bacteroides and Oscillibacter in HFD group was higher while the proportion of Akkermansia and Alloprevotella was lower. After the intervention of probiotics, the flora mentioned above was improved significantly except for Alloprevotella. The average number of tumor in HFD group, HFD+P group, ND group and ND+P group was 4.63±1.19, 2.33±0.52, 2.56±0.73 and 2.38±0.52 with statistically significant difference (F=14.92, P<0.01). Conclusion: Probiotics therapy can reduce obesity and flora imbalance caused by HFD and reduce the incidence of CRC by regulating intestinal flora disturbance.

The diagnostic and prognostic values of serum and urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in sepsis induced acute renal injury patients.

OBJECTIVE: The kidney injury molecule-1 (uKIM-1) and neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) have been demonstrated to be diagnostic biomarkers for acute kidney injury (AKI) in a variety of diseases. However, both of them were not well validated in sepsis patients with acute kidney injury. PATIENTS AND METHODS: This was a prospective and observational study which was performed in the three intensive care units of the Beijing Chao-Yang Hospital. Over a 12-month period, 174 patients (70 sepsis patients, 69 sepsis with AKI and 35 controls) were enrolled. Blood and urinary specimens were collected at admission as soon as possible (within 24 hours) and KIM-1 and NGAL levels were tested. RESULTS: Levels of uKIM-1, uNGAL, sNGAL were significantly higher in the sepsis patients who developed AKI compared to those sepsis with no-AKI (0.88 ng/ml (0.37, 2.14) vs. 1.21 ng/ml (0.67, 3.26) p=0.003, 63.54 ng/ml (21.66, 125.45) vs. 249.85 ng/ml (86.60, 585.97) p<0.001, and 108.08 ng/ml (67.74, 212.22) vs. 200.01 ng/ml (102.76, 300.77) p=0.001, respectively). sKIM-1 also had significant differences between the two groups (83.98 pg/ml (54.00,147.08) vs. 193.41 pg/ml (106.90, 430.60) p<0.001). The four biomarkers (uKIM-1, sKIM-1, uNGAL, sNGAL) all could be predictive for AKI, and the areas under the receiver operating characteristic curves (AUROC) were 0.607, 0.754, 0.768, 0.658, respectively. The uNGAL was an independent risk factor for septic AKI, and the AUROC was 0.768 (95% CI: 0.689 to 0.835). The uNGAL and sNGAL were related to the prognosis of sepsis. CONCLUSIONS: Our results showed that NGAL was a promising biomarker of septic AKI. Like the uKIM-1, the sKIM-1 could early predict the occurrence of septic AKI too, but both of them did not have the predictive value in judging the severity of AKI and the prognosis of sepsis.

[Enantiomeric separations of 1-1,2,4-triazole compounds by micro-high performance liquid chromatography].

The enantiomeric separations of sixteen novel 1-1,2,4-triazole chiral compounds were investigated by micro-HPLC with a 200 mm x 100 microns i.d. capillary chiral OD column. The detection was performed at 223 nm. The mobile phase was a mixture of iso-propyl alcohol and n-hexane(20:80, V/V) at a flow rate of 30 microL/min and column head pressure of 6.9 MPa. Some of the enantiomers could be separated on baseline. In comparing with the separation results by the conventional HPLC method, the micro-HPLC method had the advantages of high-speed, economy, environmental friendliness etc. The effect of solute structure on enantio-selectivity was investigated and the chiral recognition mechanism was also discussed. It was found that the main separation mechanisms involve the pi-pi association and inclusion between the substituent R and the spiral pocket of OD-CSP.