The Protective Role of TLR3 and TLR9 Ligands in Human Pharyngeal Epithelial Cells Infected with Influenza A Virus.

In this study we aim to extensively investigate the anti-influenza virus immune responses in human pharyngeal epithelial cell line (Hep-2) and evaluate the protective role of Toll-like receptor (TLR) ligands in seasonal influenza A H1N1 (sH1N1) infections in vitro. We first investigated the expression of the TLRs and cytokines genes in resting and sH1N1 infected Hep-2 cells. Clear expressions of TLR3, TLR9, interleukin (IL)-6, tumour necrosis factor (TNF)-α and interferon (IFN)-ß were detected in resting Hep-2 cells. After sH1N1 infection, a ten-fold of TLR3 and TLR9 were elicited. Concomitant with the TLRs activation, transcriptional expression of IL-6, TNF-α and IFN-ß were significantly induced in sH1N1-infected cells. Pre-treatment of cells with poly I:C (an analog of viral double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide) resulted in a strong reduction of viral and cytokines mRNA expression. The results presented indicated the innate immune response activation in Hep-2 cells and affirm the antiviral role of Poly I:C and CpG-ODN in the protection against seasonal influenza A viruses.

The protective effect of social support on all-cause and cardio-cerebrovascular mortality among middle-aged and older adults in the US.

The relationship between social support and mortality, especially cardio-cerebrovascular mortality, still has some limitations in the assessment of social support, sample selection bias, and short follow-up time. We used the data from 2005 to 2008 National Health and Nutrition Examination Survey to examine this relationship. The study analyzed a total of 6776 participants, divided into Group 1, Group 2, and Group 3 according to the social support score (0-1; 2-3; 4-5). Multivariable adjusted COX regression analyses of our study showed that Group 3 and Group 2 had a reduced risk of all-cause and cardio-cerebrovascular mortality (Group 3 vs 1, HR: 0.55, P < 0.001; HR: 0.4, P < 0.001; Group 2 vs 1, HR: 0.77, P = 0.017; HR: 0.58, P = 0.014) compared with Group 1. The same results were observed after excluding those who died in a relatively short time. Additionally, having more close friends, being married or living as married, and enough attending religious services were significantly related to a lower risk of mortality after adjustment. In brief, adequate social support is beneficial in reducing the risk of all-cause mortality and cardio-cerebrovascular mortality in middle-aged and older adults, especially in terms of attending religious services frequency, the number of close friends, and marital status.

Myotonic dystrophy type 1 presenting with dyspnea: A case report.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a genetic neuromuscular disease involving multiple systems, especially the cardiopulmonary system. The clinical phenotype of DM1 patients is highly variable, which limits early diagnosis and treatment. In the present study, we reported a 35-year-old female DM1 patient with dyspnea as the primary onset clinical manifestation, analyzed her family's medical history, and reviewed related literature. CASE SUMMARY: A 35-year-old woman was admitted to the hospital with dyspnea of 1 mo duration, and sleep apnea for 3 d. Her respiratory pattern and effort were normal, but limb muscle tension was low. Investigation into the patient's medical history revealed that she might have hereditary neuromuscular disease. Electromyography showed that her myotonia potentials were visible in the resting state of the examined muscles, with decreased motor unit potential time limit and amplitude. Genetic testing for DM1 revealed that the cytosine-thymine-guanine (CTG) repeat number of the DMPK gene exceeded 50, while cytosine-CTG expansion in intron 1 of ZNF9 gene was < 30 repeats. The patient was diagnosed with DM1. CONCLUSION: DM1 is a genetic neuromuscular disease involving multiple systems, and the clinical phenotype in DM1 is extremely variable. Some patients with DM1 may be presented at the respiratory department because of dyspnea, which should be cautioned by the pulmonologists. There may be no obvious or specific symptoms in the early stage of disease, and clinicians should improve their understanding of DM1 and make an early diagnosis, which will improve patients' quality of life.

Metabolite identification, tissue distribution, excretion and preclinical pharmacokinetic studies of ET-26-HCl, a new analogue of etomidate.

ET-26-HCl, a novel anaesthetic agent with promising pharmacological properties, lacks extensive studies on pharmacokinetics and disposition in vitro and in vivo. In this study, we investigated the metabolic stability, metabolite production and plasma protein binding (PPB) of ET-26-HCl along with its tissue distribution, excretion and pharmacokinetics in animals after intravenous administration. Ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry identified a total of eight new metabolites after ET-26-HCl biotransformation in liver microsomes from different species. A hypothetical cytochrome P450-metabolic pathway including dehydrogenation, hydroxylation and demethylation was proposed. The PPB rate was highest in mouse and lowest in human. After intravenous administration, ET-26-HCl distributed rapidly to all tissues in rats and beagle dogs, with the highest concentrations in fat and liver. High concentrations of ET-26-acid, a major hydroxylation metabolite of ET-26-HCl, were found in liver, plasma and kidney. Almost complete clearance of ET-26-HCl from plasma occurred within 4 h after administration. Only a small fraction of the parent compound and its acid form were excreted via the urine and faeces. Taken together, the results added to a better understanding of the metabolic and pharmacokinetic properties of ET-26-HCl, which may contribute to the further development of this drug.

Comparison of the effects of different growth standards on infants in Urban Shanghai: a cluster-randomized controlled trial.

BACKGROUND: The Shanghai growth standards are higher than World Health Organization (WHO) growth standards, which may influence the feeding practices of the caregivers and increase the risk of overweight in these infants. This study aimed to compare the effects of different growth standards on childhood obesity in Shanghai metropolitan area. METHODS: This was a cluster-randomized controlled trial conducted in 2 downtown areas with 19 community health service centers in Shanghai from November 2013 to December 2015. Randomization was done at the level of the community. Infants (health newborns) were assessed and monitored by the Shanghai growth standards (S-group) and the 2006 WHO growth standards (W-group), respectively. Measurements were taken at 1.0, 2.0, 4.0, 6.0, 9.0 and 12.0 months of age during follow-up period. Based on the values of length and weight measurements, according to the group's growth standards, doctors provided the caregivers with corresponding clinical consultation. Changes in weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and weight-for length z-score (WLZ) between 2 groups were assessed using mixed regression models. Overweight was compared between 2 group at all follow-up measurements. RESULTS: A total of 6509 infants (52.1% were boys) were in the W-group, and 8510 infants (51.4% were boys) were in the S-group. The overweight ratios between two groups were distinct at 9 months of age (3.4% in W-group and 4.3% in S-group) and 12 months of age (2.2% in W-group and 3.8% in S-group), and the differences were statistically significant (P = 0.020 and P < 0.001, respectively). Compared to W-group, the increase in WAZ (coefficient = 0.04, P = 0.004) and WLZ (coefficient = 0.09, P < 0.001) were significantly greater, and the LAZ was lower (coefficient = -0.04, P = 0.047) in S-group (W-group values were used as reference in mixed regression models). CONCLUSION: Compared to the Shanghai growth standards, the adoption of WHO 2006 growth standards would reduce the risk of infant overweight in Shanghai metropolitan area up to 1 year of age. TRIAL REGISTRATION NUMBER: ChiCTR1800015371, http://www.chictr.org.cn/ Chinese Clinical Trial Registry.