Predicting the probability of converting from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) is still a challenging task. This study aims at providing a personalized MCI-to-AD conversion estimation by using a multipredictor nomogram that integrates neuroimaging features, cerebrospinal fluid (CSF) biomarker, and clinical assessments. To do so, 290 MCI patients were collected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), of whom 76 has converted to AD and 214 remained with MCI. All subjects were randomly divided into a primary and validation cohort. Radiomics signature (Rad-sig) was obtained based on 17 cerebral cortex features selected by using Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. Clinical factors and amyloid-beta peptide (Aβ) concentration were selected by using Spearman correlation between the converted and not-converted patients. Then, a nomogram that combines image features, clinical factor, and Aβ concentration was constructed and validated. Furthermore, we explored the associations between various predictors from the macro- to the microperspective by assessing gene expression patterns. Our results showed that the multipredictor nomogram (C-index 0.978 and 0.956 in both cohorts, respectively) outperformed the nomogram using either Rad-sig or Aβ concentration as individual predictors. Significant associations were found between neuropsychological scores, cerebral cortex features, Aβ levels, and underlying gene pathways. Our study may have a clinical impact as a powerful predictive tool for predicting the conversion probability of MCI and providing associations between cognitive impairment, structural changes, Aβ levels, and underlying biological patterns from the macro- to the microperspective.

Germ cells give rise to all cell lineages in the next-generation and are responsible for the continuity of life. In a variety of organisms, germ cells and stem cells contain large ribonucleoprotein granules. Although these particles were discovered more than 100 years ago, their assembly and functions are not well understood. Here we report that glycolytic enzymes are components of these granules in Drosophila germ cells and both their mRNAs and the enzymes themselves are enriched in germ cells. We show that these enzymes are specifically required for germ cell development and that they protect their genomes from transposable elements, providing the first link between metabolism and transposon silencing. We further demonstrate that in the granules, glycolytic enzymes associate with the evolutionarily conserved Tudor protein. Our biochemical and single-particle EM structural analyses of purified Tudor show a flexible molecule and suggest a mechanism for the recruitment of glycolytic enzymes to the granules. Our data indicate that germ cells, similarly to stem cells and tumor cells, might prefer to produce energy through the glycolytic pathway, thus linking a particular metabolism to pluripotency.

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The flavonoids in Ageratum conyzoides L. have been used in traditional medicine due to its anti-inflammatory and antibacterial properties. However, the specific mechanism of its antibacterial effect, and the potential therapeutic effect on vaginitis have not been well explained. The growth curves of E. coli, S. aurues, and P. aeruginosa after treatment with flavonoids were measured. The influences of flavonoids on the conductivity of bacterial culture medium and exudation of bacterial nucleic acid were also detected. Transcriptomics analysis was applied to analyze the potential mechanism of flavonoids. Flavonoids significantly suppressed the growth curves of E. coli, S. aurues, and P. aeruginosa, and increased the conductivity of bacteria and nucleic acid exudation. Transcriptomics analysis indicated that flavonoids could suppress bacteria by affecting the transcription and metabolism pathways. The obvious therapeutic effect of flavonoids on bacterial vaginitis was also observed. This study systematically analyzed the bacteriostatic mechanism of flavonoids, which should be helpful to develop new drugs based on the bacteriostatic effect of flavonoids.

Many inconsistent findings are reported on the correlation between circulating betatrophin and insulin resistance in the different population. The aim of this analysis was to explore the correlation between the level of betatrophin and insulin resistance in the general population. The databases of PubMed, EMBASE, and the Cochrane Library (inception to October 26, 2016) were searched without language restrictions for publications that reported studies on associations between betatrophin and insulin resistance in adults. Subgroup analyses were performed to investigate potential sources of heterogeneity. The pooled effect size was calculated using a random-effects model. Twenty-five studies were included in this meta-analysis. Meta-analysis showed that betatrophin was positively and significantly correlated with insulin resistance (r=0.16, 95% CI: 0.08-0.25). When all participants were divided into DM, GDM, and Non-DM groups, this association was also significant in T2DM, GDM, and Non-DM participants (T2DM: r=0.09, 95% CI: 0.01-0.17; I =45.1%; GDM: r=0.39, 95% CI: 0.24-0.55; I=0.0%; non-DM: r=0.15, 95% CI: 0.04-0.26; I =89.3%), and it was obvious that heterogeneity existed in Non-DM group (I=89.3%, p<0.001). Subgroup analysis revealed that gender, serum sample and ELISA kits for full-length betatrophin had significant influence on the association between betatrophin and insulin resistance. In conclusion, the level of circulating betatrophin is positively associated with insulin resistance in the general population, especially in T2DM and GDM patients. Gender, serum sample, and ELISA kits for full-length betatrophin may affect this association. More large-scale studies are needed to determine whether improving insulin resistance concomitantly declines betatrophin levels in different diseases.

Stem cells for pancreatitis 425 Gastric injury and bacterial overgrowth 433 The effect of visceral fat on SMA configuration 451 Antiplatelet agents in ulcerative colitis 459 Differentiation of BMSCs into intestinal ce 466 GERDOFF ® efficacy in patients with GERD

Background and study aims Preoperative biliary drainage of hilar cholangiocarcinoma (HC) is controversial. The goal of this study was to compare the clinical outcome and associated complications for types II, III, and IV HC managed by percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP). Patients and methods Between January 2011 and June 2017, a total of 180 patients with II, III, and IV HC were enrolled in this retrospective cohort study. According to the drainage method, patients were divided into two groups: PTBD (n = 81) and ERCP (n = 99). This study was registered with ClinicalTrials.gov, NCT03104582, and was completed. Results Compared with the PTBD group, the ERCP group had a higher incidence of post-procedural cholangitis (37 [37.37 %] vs. 18 [22.22 %], P = 0.028) and pancreatitis (17 [17.17 %] vs. 2 [2.47 %], P = 0.001); required more salvaged biliary drainage (18 [18.18 %] vs. 5 [6.17 %], P  = 0.029), and incurred a higher cost (P < 0.05). Patients with type III and IV HC in the ERCP group had more cholangitis than those in the PTBD group (26 [36.62 %] vs. 11 [18.03 %], P = 0.018). The rate of cholangitis in patients who received endoscopic bilateral biliary stents insertion was higher than patients with unilateral stenting (23 [50.00 %] vs. 9 [26.47 %], P = 0.034), and underwent PTBD internal-external drainage had a higher incidence of cholangitis than those with only external drainage (11 [34.36 %] vs. 7 [14.29 %], P = 0.034). No significant difference in the rate of cholangitis was observed between the endoscopic unilateral stenting group and the endoscopic nasobiliary drainage group (9 [26.47 %] vs. 5 [26.32 %], P = 0.990). Conclusion Compared to ERCP, PTBD reduced the rate of cholangitis, pancreatitis, salvage biliary drainage, and decreased hospitalization costs in patients with types II, III, and IV HC. Risk of cholangitis for patients with types III and IV was significantly lower in the PTBD group.