Search

Pathologic features of Alzheimer's disease (AD) include accumulation of amyloid β (Aβ) and hyperphosphorylated tau protein. We have shown previously that the chemokine-like receptor 1 (CMKLR1) is a functional receptor for β), and CMKLR1 contributes to the uptake of β. However, it is unclear whether CMKLR1 ameliorates or aggravates the process of AD. Here, we show that deletion of the gene coding for CMKLR1 significantly increased β deposits in brains of both male and female amyloid P precursor protein/presenilin-1 mice. However, it markedly decreased the mortality of these mice. Behavioral studies found that CMKLR1 deficiency improved cognitive impairment of male and female amyloid P precursor protein/presenilin-1 mice and intracerebroventricular-streptozotocin injection AD mice. We further explored the effect of CMKLR1 on tau pathology. We found that CMKLR1 deficiency or inhibition attenuated the hyperphosphorylation of tau in brains of AD mice in vivo and in the neuronal cells in vitro. The expression of CMKLR1 on the neurons affected tau phosphorylation by participating in tau seeding. Together, these results uncover a novel mechanism of CMKLR1 in the pathologic process of AD and suggest that inhibiting the promotion effect of CMKLR1 on tau seeding may provide a new strategy for the treatment of AD. [ABSTRACT FROM AUTHOR]

A rapid, specific and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous determination of timosaponin B-II (TB-II) and A-III (TA-III) in rat plasma. Plasma samples were pretreated via simple protein precipitation with acetonitrile and ginsenoside Rg2 was used as internal standard. Chromatographic separation was carried out on an Agilent XDB-C8 (150mm×2.1mm i.d., 5µm) column by isocratic elution with acetonitrile-2mmol/L ammonium acetate (55:45, v/v). The detection was performed on a Sciex API 4000+ triple-quadrupole tandem mass spectrometer with TurboIonSpray ionization (ESI) inlet via the negative ion multiple reaction monitoring (MRM) mode. The results showed that the calibration curve was linear in the concentration range of 3-3000ng/mL for TB-II and 0.3-3000ng/mL for TA-III, respectively. The intra- and inter-day precisions were less than 13.25%, and the accuracy ranged from 100.88% to 104.07% at three QC levels for both. The pharmacokinetic profiles of TB-II and TA-III in timosaponins (total timosaponin) at three dose levels (TB-II 150, 300, 600mg/kg and TA-III 0.59, 1.17, 2.34mg/kg, respectively) and in timosaponins-Huangbai alkaloids mixtures (1:1, 1:3, w/w, TB-II 300mg/kg and TA-III 1.17mg/kg) were studied for the first time in rats by this LC-MS/MS method. After single oral administration of timosaponins, mean Cmax and AUC0-t of TB-II and TA-III increased but non-proportional to the oral doses. When timosaponins-Huangbai alkaloids (1:1, 1:3, w/w) mixtures were administered, Cmax and AUC0-t of TB-II in the mixtures were obviously higher than the corresponding values in timosaponins at the same dose level. [ABSTRACT FROM AUTHOR]

Background and aim: Schizophrenia (SCZ) and bipolar disorder (BD) have a high comorbidity of alcohol use disorder (AUD), and both comorbid AUD and excessive alcohol consumption (AC) have been linked to greater illness severity. We aimed to identify genomic loci jointly associated with SCZ, BD, AUD and AC to gain further insights into their shared genetic architecture. Design: We analysed summary data (P values and Z scores) from genome-wide association studies (GWAS) using conjunctional false discovery rate (conjFDR) analysis, which increases power to discover shared genomic loci. We functionally characterized the identified loci using publicly available biological resources. Setting: AUD and AC data provided by the Million Veteran Program, derived from the United States Department of Veterans Affairs Healthcare System. SCZ and BD data provided by the Psychiatric Genomics Consortium, based on cohorts from countries in Europe, North America and Australia. Participants: AUD (34 658 cases, 167 346 controls), AC (n = 200 680), SCZ (31 013 cases and 38 918 controls), BD (20 352 cases and 31 358 controls). All participants were of European ancestry. Measurements: Genomic loci shared between alcohol traits, SCZ and BD at conjFDR <0.05. Findings: Conditional Q-Q plots showed single-nucleotide polymorphism (SNP) enrichment for both alcohol traits across different levels of significance with SCZ and BD, and vice versa. Using conjFDR analysis we leveraged this genetic enrichment and identified several loci shared between SCZ and AUD (n = 28) and AC (n = 24), BD and AUD (n = 2) and AC (n = 8) at conjFDR <0.05. Among these loci, 24 are novel for AUD, 15 are novel for AC, three are novel for SCZ and one is novel for BD. There was a mixture of same and opposite effect directions among the shared loci. Conclusions: Alcohol use disorder and alcohol consumption share genomic loci with the psychiatric disorders schizophrenia and bipolar disorder with a mixed pattern of effect directions, indicating a complex genetic relationship between the phenotypes. [ABSTRACT FROM AUTHOR]

In the past decades, various studies have suggested a possible link between thymidine phosphorylase (TP) level and colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)-based chemotherapy; however, they have arrived at inconsistent results. Therefore, the present meta-analysis aimed to disclose a more comprehensive evaluation of this relationship. PubMed, the Cochrane Library, Ovid MEDLINE, Embase and China National Knowledge Infrastructure were systematically searched for studies that evaluated the prognostic value of TP in CRC. Stata 12.0 software was used to test the heterogeneity and evaluate the overall test performance. A total of 15 studies, including 1,225 patients, were included. The summary estimates of TP for CRC treated with 5-FU-based chemotherapy indicated a moderately positive prognosis with a hazard ratio (HR) of 0.76 (P=0.031) for overall survival and a HR of 0.711 (P=0.022) for relapse-free survival. On the basis of the present meta-analysis, TP could be promising and meaningful in the prognosis of CRC treated with 5-FU-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Southern China is an endemic area for primary liver cancer (PLC), but it is unclear if rates have changed in recent decades. We evaluated PLC incidence and estimated the effects of age, period of diagnosis, and birth cohort in Sihui City, Guangdong Province, China. Methods: Age-standardized rates (ASRs) of PLC were examined for both males and females from 1987 to 2011. Joinpoint regression analysis was conducted to estimate the annual percent changes in PLC incidence. The ageperiod- cohort (APC) model was used to investigate the effects of age, diagnosis period, and birth cohort on the relative risk (RR) of PLC. Results: A total of 2988 PLC cases were identified in this period, with average ASRs of 51.1/100,000 for males and 11.7/100,000 for females. Joinpoint regression analysis revealed increasing PLC incidence throughout the entire period in both males (average annual change of 1.65%) and females (0.20%). RRs increased gradually in both sexes from the youngest age group (30-34 years) to the oldest (80-84 years). In males, the RR decreased during diagnosis period from 1987-1991 to 1997-2001 and remained stable thereafter. In females, RRs fluctuated with diagnosis period throughout the entire period. Incidence tended to increase with birth cohort from 1905-1909 to 1975-1979 in both males and females; however, female incidence plateaued in the youngest cohorts born between 1955 and 1974, while incidence in males increased sharply in the cohorts born between 1965 and 1974. According to APC analysis, the full age-period-cohort (APC) model fit the data best, and the period-cohort (PC) model would be enough to explain variability of rates in females. Conclusion: The PLC incidence rate in males of Sihui City has increased more significantly than female over the last 25 years. Despite the age effect in male, this trend mainly reflects the effects of risk factors that are present in early life (birth cohort) and period change in both genders. [ABSTRACT FROM AUTHOR]

Background: Faced with the challenge of population aging, a prolonged working life is increasingly important in today's society. Maintaining work ability of employees is one of the effective ways to cope with the challenges to sustainability of the workforce presented by population aging. Researchers have shown ongoing interest in exploring the determinants of restricted work ability. The aim of this study was to evaluate the effects of work stress on work ability among power supply workers in Guangdong, China.Methods: A cross-sectional study was conducted among power supply workers during August 2014 to September 2014. A total of 805 subjects were enrolled in the study. Work stress was assessed by the Job Content Questionnaire and the Effort Reward Imbalance Questionnaire. Work ability was assessed by the Work Ability Index (WAI). The structural equation model was applied to test the relationship between different work stress components and work ability simultaneously using the Job Demands-Resources model as a framework.Results: Job resources (measured by job control, reward and social support) were positively and directly associated with work ability (β = 0.70, P < 0.001). The association between job demands and work ability was also statistically significant (β = -0.09, P = 0.030). In addition, the findings also supported previous studies in that job demands were correlated with job resources (β = -0.26, P < 0.001).Conclusions: Our findings suggest that decision makers and health care providers should consider increasing job resources available to power supply workers. Consideration of organizational changes related to the design of the job task also would be useful to improve the employees' work ability. [ABSTRACT FROM AUTHOR]

The article discusses the prognostic value of magnetic resonance imaging (MRI)-detected cranial nerve (CN) involvement in nasopharyngeal carcinoma (NPC). According to the study, the incidence of patients with MRI-detected CN involvement was higher than CN palsy. Moreover, MRI-detected CN involvement has change on the prognosis independent of lesion localization and symptoms.

The article focuses on a study conducted to analyze the spread pattern of lymph node (LN) metastases in patients with nasopharyngeal carcinoma. Researchers used magnetic resonance imaging (MRI) in the study. The efficacy of selective neck irradiation was also assessed during the study. All patients were treated with radiation therapy during the study. It was found in the study that by using MRI, LN metastases spread in an orderly fashion, that is, from higher level LNs to lowe level LNs.