[Hippocampal Development Deviation and Its Relationship With Cognition in Major Psychiatric Disorders].

Objective: To investigate hippocampal development deviation and its association with cognition in patients with major psychiatric disorders (MPDs), including schizophrenia, bipolar disorder and major depressive disorder. Methods: The T1-weighted MRI data of 174 first-episode drug-naïve schizophrenia (FES) atients, 169 bipolar disorder (BD) patients, 184 major depressive disorder (MDD) patients, and 321 healthy controls were collected and their hippocampal volume was extracted after preprocessing with Freesurfer 5.3. A normative neurodevelopment model was applied to calculate the hippocampal deviation scores. Data on cognitive functions, including visual memory, attention, spatial working memory, were collected. Comparison by different sexes was made to identify difference between the hippocampal development deviation scores of the control group and those of the disease groups. We also investigated the moderating effect of age on the deviation score and explored the association between the deviation score and cognitive function. Results: The hippocampal development deviation scores of patients with MPDs were significantly lower than those of the healthy controls (false discovery rate [FDR]-P<0.05). Analysis of the moderating effect of age revealed lower deviation scores in young patients (<[25.83-28.56] yr.) and higher deviation scores in old patients (>[35.87-54.35] yr.) in comparison with those of the healthy controls. The right hippocampal deviation scores in male FES patients were positively correlated with the number of errors for tasks concerning spatial working memory ( r=0.32, FDR-P=0.04). Conclusion: Our findings suggest abnormal hippocampal development in MPDs patients and its different distribution in MPDs patients of different age groups. The hippocampal development deviation score may provide a new perspective for further understanding of etiology in MPDs.

[Frequency-Specific Alterations of Spontaneous Brain Activity in First-Episode Drug-Naïve Schizophrenia].

Objective: To investigate frequency-specific alterations of spontaneous brain activity in first-episode drug-naïve schizophrenia (SZ) patients and the associations with clinical symptoms. Methods: We collected the resting-state functional MRI (rs-fMRI) data from 84 first-episode drug-naïve SZ patients and 94 healthy controls (HCs) and calculated the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of four frequency bands, including slow-2, slow-3, slow-4, and slow-5. Two-sample t-tests were used to evaluate the intergroup differences in ALFF and ReHo, while partial correlation analyses were conducted to explore the associations between abnormal ALFF and ReHo and the severity of clinical symptoms in the SZ group. Results: Compared with HCs, the SZ group showed reduced ALFF in superior cerebellum and cerebellar vermis across slow-2, slow-3, and slow-4 bands, while increased ALFF was found in left superior temporal gyrus, middle temporal gyrus, and superior temporal pole at slow-4 band. Moreover, reduced ReHo was observed in the right precentral and postcentral gyri at slow-3 band in the SZ group. Additionally, the ALFF of left superior temporal gyrus, middle temporal gyrus, and superior temporal pole in slow-4 band showed a trend of positive correlation with the excited factor score of Positive and Negative Syndrome Scale (PANSS) in the SZ group. Conclusion: Our results suggest that local alterations of spontaneous brain activity were frequency-specific in first-episode drug-naïve SZ patients.

Preoperative LMR and Serum CA125 Level as Risk Factors for Advanced Stage of Ovarian Cancer.

Objectives: This study was to analyze the relationships between lymphocyte-to-monocyte ratio (LMR) alone or combined with serum CA125 (COLC) and advanced stage of ovarian cancer (OC). Methods: The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC staging OC were constructed by a retrospective study. Furthermore, a binary logistic regression model was used to assay the independent risk factors for OC staging. Results: Two hundred and twenty-five patients with OC were identified in this cohort. Eighty-five OC patients were diagnosed at an early stage, and 140 OC patients were diagnosed at an advanced stage. The median of LMR in the early stage was higher than that in advanced stage (4.4 vs. 2.8), and the median of serum CA125 was lower than that in advanced stage (80 U/mL vs. 251.3 U/mL). Multivariate logistic regression LMR≤3.7 (OR=0.299, 95% CI: 0.093-0.962, P=0.043) and CA125>95.7 U/mL (OR=4.317, 95% CI: 1.436-12.977, P=0.009) were risk factors for stage of advanced OC whether presence or absence of malignant ascites. Furthermore, the area under the curve of COLC was higher than that of LMR (0.782 vs. 0.732) or serum CA125 (0.782 vs. 0.708) in staging OC. The specificity of COLC was higher than that of LMR (87.1% vs. 70.6%) or serum CA125 (87.1% vs. 61.2%) in staging OC. Conclusion: LMR alone or in combination with serum CA125 might be associated with OC staging. Besides, as a predictive factor, COLC may have a high specificity in staging OC.

Combined Preoperative LMR and CA125 for Prognostic Assessment of Ovarian Cancer.

Objectives: To investigate the role of inflammation-related factors, lymphocyte-to-monocyte ratio (LMR) alone and combined detection with cancer antigen 125 (CA125), in the prognostic assessment of ovarian cancer (OC). Methods: A retrospective clinicopathologic review was performed. The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC predicting mortality in OC patients were constructed. Besides, Kaplan-Meier and Cox logistic regression models were used to plot the survival curves and determine the independent prognostic factors. Results: A total of 214 OC patients were identified in this cohort. The mean duration of follow-up was 64 months (minimum 8 months, maximum 116 months). In this cohort, 135 cases died (63.1%), and the median progression-free survival (PFS) and overall survival (OS) were 20 and 39.5 months, respectively. Results of the multivariate Cox regression model showed that LMR≤3.8 (HR = 0.494, 95% CI: 0.329-0.742, P = 0.001) and CA125>34 U/ml (HR = 1.641, 95% CI: 1.057-2.550, P = 0.027) were significantly associated with poor PFS; and LMR≤3.8 (HR = 0.459, 95% CI: 0.306-0.688, P = <0.001) and CA125>34 U/ml (HR = 1.946, 95% CI: 1.256-3.015, P = 0.003) were significantly associated with OS. Furthermore, the area under the curve of COLC was higher (0.713) than that of LMR (0.709) or CA125 (0.583), the specificity of COLC was higher (75.9%) than that of LMR (62%) or CA125 (40.5%) in predicting mortality in OC patients. Conclusions: LMR alone and combined with CA125 might be used as predictive markers in OC. Furthermore, as a prognostic factor, COLC might have a higher specificity to predict the outcome.

Self-assembled targeted folate-conjugated eight-arm-polyethylene glycol-betulinic acid nanoparticles for co-delivery of anticancer drugs.

In this study, a targeted nanoparticle platform for co-delivery of anticancer drugs based on folate-conjugated eight-arm-polyethylene glycol-betulinic acid (F-8arm-PEG-BA) was first presented. F-8arm-PEG-BA was synthesized by introducing target molecules (folate) and drug molecules (betulinic acid, BA) to hydrophilic molecules (8arm-PEG). Then another anticancer drug, hydroxycamptothecin (HCPT), was encapsulated into the self-assembled nanoparticles from the conjugate by a simple nanoprecipitation method. These F-8arm-PEG-BA/HCPT nanoparticles (NPs) had a small size (∼120 nm), acceptable critical aggregation concentration (∼64.8 µg mL-1), and high drug loading (∼18 wt% BA and ∼16 wt% HCPT). Compared to the free drugs, the nanoparticles significantly improved the cellular cytotoxicity and exhibited an obvious synergistic effect by the co-delivery of two different anticancer drugs, BA and HCPT. Pharmacokinetics study revealed the nanoparticles could prolong the circulation of BA and HCPT in the blood. In vivo studies indicated that the nanoparticles enhanced tumor targeting and antitumor activity with lower systemic toxicity. In conclusion, F-8arm-PEG-BA/HCPT NPs have great potential for targeted chemotherapy for cancer.

Detoxification of corncob acid hydrolysate with SAA pretreatment and xylitol production by immobilized Candida tropicalis.

Xylitol fermentation production from corncob acid hydrolysate has become an attractive and promising process. However, corncob acid hydrolysate cannot be directly used as fermentation substrate owing to various inhibitors. In this work, soaking in aqueous ammonia (SAA) pretreatment was employed to reduce the inhibitors in acid hydrolysate. After detoxification, the corncob acid hydrolysate was fermented by immobilized Candida tropicalis cell to produce xylitol. Results revealed that SAA pretreatment showed high delignification and efficient removal of acetyl group compounds without effect on cellulose and xylan content. Acetic acid was completely removed, and the content of phenolic compounds was reduced by 80%. Furthermore, kinetic behaviors of xylitol production by immobilized C. tropicalis cell were elucidated from corncob acid hydrolysate detoxified with SAA pretreatment and two-step adsorption method, respectively. The immobilized C. tropicalis cell showed higher productivity efficiency using the corncob acid hydrolysate as fermentation substrate after detoxification with SAA pretreatment than by two-step adsorption method in the five successive batch fermentation rounds. After the fifth round fermentation, about 60 g xylitol/L fermentation substrate was obtained for SAA pretreatment detoxification, while about 30 g xylitol/L fermentation substrate was obtained for two-step adsorption detoxification.

A novel cleaning process for industrial production of xylose in pilot scale from corncob by using screw-steam-explosive extruder.

Steam explosion is the most promising technology to replace conventional acid hydrolysis of lignocellulose for biomass pretreatment. In this paper, a new screw-steam-explosive extruder was designed and explored for xylose production and lignocellulose biorefinery at the pilot scale. We investigated the effect of different chemicals on xylose yield in the screw-steam-explosive extrusion process, and the xylose production process was optimized as followings: After pre-impregnation with sulfuric acid at 80 °C for 3 h, corncob was treated at 1.55 MPa with 9 mg sulfuric acid/g dry corncob (DC) for 5.5 min, followed by countercurrent extraction (3 recycles), decoloration (activated carbon dosage 0.07 g/g sugar, 75 °C for 40 min), and ion exchange (2 batches). Using this process, 3.575 kg of crystal xylose was produced from 22 kg corncob, almost 90 % of hemicellulose was released as monomeric sugar, and only a small amount of by-products was released (formic acid, acetic acid, fural, 5-hydroxymethylfurfural, and phenolic compounds were 0.17, 1.14, 0.53, 0.19, and 1.75 g/100 g DC, respectively). All results indicated that the screw-steam-explosive extrusion provides a more effective way to convert hemicellulose into xylose and could be an alternative method to traditional sulfuric acid hydrolysis process for lignocellulose biorefinery.

Vascular Endothelial Growth Factor and Its Receptor KDR/flk-1 Play Important Roles in Hematopoiesis / 中国实验血液学杂志

It is widely accepted that hematopoietic and endothelial cell lineages are initiated from the same precursor cells (named as hemangioblast), although hemangioblast has not been proved. Vascular endothelial growth factor (VEGF) and its receptor KDR/flk-1 is a prime regulator of endothelial cell proliferation, angiogenesis, vasculogenesis and vascular permeability. It is speculated that VEGF and its receptor KDR/flk-1 may also play an important role in embryonic and postnatal hematopoiesis. But the exact role and mechanism are not well known. Some latest developed cellular and molecular techniques can be used to prove the existence of hemangioblast and to investigate its biologic feature and the effect of VEGF and receptor KDR/flk-1 on its biologic feature.