Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy

Additional file 2: Table S2. Stratified univariate analysis of DFS and OS between LG* and HG* in Chinese ESCC patients

Rare-earth-doped fluoride nanoparticles with engineered long luminescence lifetime for time-gated: In vivo optical imaging in the second biological window

Biomedicine is continuously demanding new luminescent materials to be used as optical probes for the acquisition of high resolution, high contrast and high penetration in vivo images. These materials, in combination with advanced techniques, could constitute the first step towards new diagnosis and therapy tools. In this work, we report on the synthesis of long lifetime rare-earth-doped fluoride nanoparticles by adopting different strategies: core/shell and dopant engineering. The here developed nanoparticles show intense infrared emission in the second biological window with a long luminescence lifetime close to 1 millisecond. These two properties make the here presented nanoparticles excellent candidates for time-gated infrared optical bioimaging. Indeed, their potential application as optical imaging contrast agents for autofluorescence-free in vivo small animal imaging has been demonstrated, allowing high contrast real-time tracking of gastrointestinal absorption of nanoparticles and transcranial imaging of intracerebrally injected nanoparticles in the murine brainThis work was supported in part by the grants from the Fundamental Research Funds for the Central Universities, China (HIT. BRETIV.201503 and AUGA5710052614) and the National Natural Science Foundation of China (51672061). We thank Dr Lina Wu at the Fourth Hospital of Harbin Medical University for her kind help with the MTT assay, and Dr Tymish Y. Ohulchanskyy at Shenzhen University for his kind help with the fluorescence lifetime measurement. The work was also supported by the Ministerio de Economia y Competitividad of Spain (grant MAT2016-75362-C3-1-R). Jie Hu acknowledges the scholarship from the China Scholarship Council (No. 201506650003). Dirk H. Ortgies is grateful to the Spanish Ministry of Economy and Competitiveness for a Juan de la Cierva scholarship (No. FJCI-2014-21101) and the Spanish Institute of Health (ISCIII) for a Sara Borell Fellowship (No. CD17/00210

What Influences Family Migration Decision of China’s New Generation Rural-urban Migrants? A Multilevel Logistic Regression Analysis

The massive scale of new-generation rural-urban migrants in China has attracted extensive scholarly attention in recent years. While previous studies on China’s rural migrant workers focus on migrants’ individual settlement intentions, migrant’s family migration decision-making and the intergenerational differences between the old-generation migrants and new-generation migrants are underexplored. Based on the data of 2017 China Migrants Dynamic Survey, this paper adopts a multilevel logistic regression approach to explore family and destination factors influencing family migration decision of China’s new generation rural migrant workers. The empirical results reveal that both the migrants’ family and destination attributes significantly influence their family migration decision. The demographic and socioeconomic characteristics of family have been pivotal factors underlying family migration decision of China’s new generation rural-urban migrants, while 16.9% of the chances is explained by between-destination differences. Self-employed migrants with housing properties in host cities, long migration duration and high-income level are more likely to migrate with their family members. Yet, the possibility of family migration is found to be significantly and negatively correlated with the age, education level, number of children and inter-provincial mobility of the new generation migrant workers. In addition, new generation rural-urban migrants’ family migration is more likely to be found in cities with service-oriented industry structure, better environmental quality, and higher hukou barriers which is possibly related to more job opportunities. These research findings not only complement the existing literature on China’s new generation rural-urban migrants, but also have important policy implications for reforming hukou system and enhancing social integration of rural-to-urban migrant population

Serum mitochondrial-encoded NADH dehydrogenase 6 and Annexin A1 as novel biomarkers for mortality prediction in critically ill patients with sepsis

ObjectivesFormyl peptide receptor 1 (FPR1) is a member of G protein-coupled receptor (GPCR) family that detects potentially danger signals characterized by the appearance of N-formylated peptides which originate from either bacteria or host mitochondria during organ injury, including sepsis. Mitochondrial-encoded NADH dehydrogenase 6 (MT-ND6) and Annexin A1 (ANXA1), as mitochondrial damage-associated molecular patterns (mtDAMPs) agonist and endogenous agonist of FPR1 respectively, interact with FPR1 regulating polymorphonuclear leukocytes (PMNs) function and inflammatory response during sepsis. However, there is no direct evidence of MT-ND6 or ANXA1 in the circulation of patients with sepsis and their potential role in clinical significance, including diagnosis and mortality prediction during sepsis.MethodsA prospective cohort study was conducted in ICU within a large academic hospital. We measured serum MT-ND6 or ANXA1 in a cohort of patients with sepsis in ICU (n=180) and patients with non-sepsis in ICU (n=60) by Enzyme-linked immunosorbent assays (ELISA). The ROC curve and Kaplan Meier analysis was used to evaluate the diagnostic and prognostic ability of two biomarkers for patients with sepsis.ResultsThe concentration of MT-ND6 and ANXA1 were significantly elevated in the patients with sepsis, and the diagnostic values of MT-ND6 (0.789) for sepsis patients was second only to SOFA scores (AUC = 0.870). Higher serum concentrations of MT-ND6 (>1.41 ng/ml) and lower concentrations of ANXA1 (< 8.09 ng/mL) were closely related to the higher mortality in patients with sepsis, with the predictive values were 0.705 and 0.694, respectively. When patients with sepsis classified based on four pro-inflammation and two anti-inflammation cytokines, it was shown that combination of MT-ND6 and ANXA1 obviously improved the predictive values in the septic patients with mixed hyperinflammation or immunosuppression phenotypes.ConclusionOur findings provide valuable models testing patient risk prediction and strengthen the evidence for agonists of FPR1, MT-ND6 and ANXA1, as novel biomarker for patient selection for novel therapeutic agents to target mtDAMPs and regulator of GPCRs in sepsis

Advances in the treatment of intracranial neoplastic lesions in children with neurofibromatosis 1

Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant genetic diseases of the nervous system, which occurs predominantly in children. It is a multi-system damage caused by genetic defects that cause abnormal development of neural crest cells. The penetrance of NF1 is almost 100%, and the main clinical features are cafe-au-lait spots on the skin and multiple neurofibromas in peripheral nerves. NF1 can lead to intracranial neoplastic lesions, which can be divided into low grade tumors, high grade tumors and tumor-like lesions according to pathology. Most intracranial tumors with NF1 are low grade tumors, and optic pathway gliomas are the most universal, followed by brainstem gliomas, but other types of low grade tumors can also occur on other sites. High grade tumors are uncommon. Although tumor-like lesions/ unidentified bright objects are not tumors, they are the most widespread intracranial abnormalities with partial tumor nature in NF1 children. These neoplastic lesions can be treated by observation, surgery, chemotherapy, radiotherapy, targeted therapy, etc. The best treatment for different lesions is different, and their prognosis is also distinct. At present, the treatment of intracranial neoplastic lesions of NF1 in children is still controversial. This article reviews the characteristics and treatment progress of this disease, aiming to improve the public′s awareness of NF1 neoplastic lesions, provide professional plans of diagnosis and treatment, and finally promote the perfect neurosurgical therapy of NF1 patients

Chemical constituents and hypoglycemic mechanisms of Dendrobium nobile in treatment of type 2 diabetic rats by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experimental verification

Abstract: This study aimed to systematically explore the chemical constituents of D. nobile and its hypoglycemic effect by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experiment. The chemical constituents of D. nobile were qualitatively analyzed, and the hypoglycemic compounds were quickly identified. Network pharmacological analysis and molecular docking technique were applied to assist in the elucidation of the hypoglycemic mechanisms of D. nobile. A type 2 diabetic mellitus (T2DM) rat model was established using the HFD and STZ method for in vivo experimental verification, and these T2DM rats were treated with D. nobile extract and D. nobile polysaccharide for two months by gavage. The results showed that a total of 39 chemical constituents of D. nobile, including alkaloids, bibenzyls, phenanthrenes and other types of compounds, were identified. D. nobile extract and D. nobile polysaccharide could significantly ameliorate the body weight, hyperglycemia, insulin resistance, dyslipidemia and morphological impairment of the liver and pancreas in the T2DM rats. α-Linolenic acid, dihydroconiferyl dihydro-p-coumarate, naringenin, trans-N-feruloyltyramine, gigantol, moscatilin, 4-O-methylpinosylvic acid, venlafaxine, nordendrobin and tristin were regarded as the key hypoglycemic compounds of D. nobile, along with the hypoglycemic effect on the PI3K-AKT signaling pathway, the insulin signaling pathway, the FOXO signaling pathway, the improvement of insulin resistance and the AGE-RAGE signaling pathway. The Western blotting experiment results confirmed that D. nobile activated the PI3K/AKT pathway and insulin signaling pathway, promoted glycogen synthesis via regulating the expression of glycogen synthase kinase 3 beta (GSK-3) and glucose transporter 4 (GLUT4), and inhibited liver gluconeogenesis by regulating the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6pase) in the liver. The results suggested that the hypoglycemic mechanism of D. nobile might be associated with liver glycogen synthesis and gluconeogenesis, contributing to improving insulin resistance and abnormal glucose metabolism in the T2DM rats

SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma

Purpose: Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemotherapy is currently the main method of RB treatment. Unfortunately, RB often becomes chemoresistant and turns lethal. Here, we used in vitro cell immunotherapy to explore whether adoptive immunotherapy could be used as a potential treatment for RB. We focused on spleen tyrosine kinase (SYK), which is significantly upregulated in RB cells and serves as a marker for RB cells. Methods: Using lentiviruses, we genetically modified dendritic cells (DCs) to express and present the SYK peptide antigen to cytotoxic T lymphocytes (CTLs) in vitro. We used SYK-negative cell lines (MDA-MB-231, MCF-10A, and hTERT-RPE1) and SYK-positive cell lines (MCF-7 and RB-Y79) to evaluate the specificity and cytotoxicity of DC presented CTLs using FACS, live-cell imaging, and RNA interference. Results: The cytotoxicity of CTLs induced by SYK-overexpressing DCs (SYK-DC–CTLs) was enhanced more than three times in SYK-positive cell lines compared with SYK-negative cell lines. DCs primed with SYK could drive CTL cytotoxicity against SYK-positive cell lines but not against SYK-negative cell lines. Moreover, SYK-silenced RB-Y79 cells successfully evaded the cytotoxic attack from SYK-DC–CTLs. However, SYK-DC–CTLs could target SYK overexpressed hTERT-RPE1 cells, suggesting that SYK is a specific antigen for RB. Furthermore, SYK-DC–CTL exhibited specific cytotoxicity against carboplatin-resistant RB-Y79 cells in vitro. Conclusions: Our data showed that SYK could be a potential immunotherapy target mediated by DCs. We propose SYK as a candidate target for treatment of chemoresistant RB.Fil: Chen, Xuemei. Xi'an Jiaotong University; ChinaFil: Kunda, Patricia Elena. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Lin, Jianwei. Shenzhen University; ChinaFil: Zhou, Meiling. Shenzhen Luohu Peoples Hospital; China. Shenzhen University; ChinaFil: Huang, Jinghan. Shenzhen Luohu Peoples Hospital; ChinaFil: Zhang, Huqin. Xi'an Jiaotong University; ChinaFil: Liu, Tao. Shenzhen University; China. Shenzhen Luohu Peoples Hospital; Chin

Association between daytime nap duration and risks of frailty: Findings from the China Health and Retirement Longitudinal Study

IntroductionNight sleep duration and total sleep duration are associated with frailty. However, the association between daytime nap duration and the risks of frailty has not been explored thoroughly.MethodsThis study used data from the China Health and Retirement Longitudinal Study (CHARLS). Participants aged 60 years and older at baseline were included in this study. Individuals with daytime nap duration were categorized into four groups: no napping, short napping (< 30 min), moderate napping (30–89 min), and extended napping (≥90 min). Frailty was assessed using a modified Physical Frailty Phenotype (PFP) scale. Non-frail participants at baseline were followed up for 4 years. The association between nap duration and risks of frailty at baseline and incident frailty was evaluated by logistic regression and discrete-time Cox regression analyses, respectively.ResultsIn total, 5,126 participants were included in this study. For individuals with night sleep duration of ≥9 h, short nappers showed higher odds [odds ratio (OR) = 4.08, 95% confidence interval (CI): 1.30–12.78] for frailty compared with non-habitual nappers at baseline, while moderate nappers were less likely to be frail (OR = 0.18, 95% CI: 0.04–0.73). In the follow-up study, short nappers showed higher risks for frailty compared with participants of the no napping group with night sleep duration of < 6 h [hazard ratio (HR) = 1.91, 95% CI: 1.07–3.43] or 6–9 h (HR = 1.97, 95% CI: 1.18–3.30). Compared with short nappers, older adults with extended napping (HR = 0.41, 95% CI: 0.22–0.77) showed lower risks for frailty in those with night sleep duration of 6–9 h. For individuals with night sleep duration of ≥9 h, moderate napping (HR = 0.20, 95% CI: 0.05–0.77) decreased the risks for frailty compared with short napping.ConclusionAmong older adults with night sleep duration of < 9 h, short nappers posed higher risks for frailty compared with non-habitual nappers. Extended naps for those with a night sleep duration of 6–9 h or moderate naps for those with night sleep duration of ≥9 h could lower the risk of frailty compared with short naps. Future studies on the timing, purpose, frequency, and quality of daytime napping and objectively measured nap duration are needed to explore the association between daytime napping and risks of frailty