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1.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3022-3034, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602849

RESUMO

To characterize the chemical constituents of Huanbei Zhike Prescription by ultra-high performance liquid chromatography-time of flight mass spectrometry( UPLC-Q-TOF-MS/MS). A Thermo Syncronls C18 column( 2. 1 mm×100 mm,1. 7 µm) was used with methanol( A)-0. 1% formic acid solution( B) as the mobile phase for gradient elution. The injection volume was 2 µL; the column temperature was 40 ℃; the flow rate was 0. 3 m L·min-1; and electrospray ionization( ESI) source was used to collect data in positive and negative ion modes. The ion scanning range was m/z 50-1 200,with capillary voltage of 3 000 V,ion source temperature of100 ℃,atomization gas flow rate of 50 L·h-1,desolvent gas flow rate of 800 L·h-1,desolvent temperature of 400 ℃,cone hole voltage of 40 V,with argon as the collision gas and the collision energy was 20-35 V. The excimer ion peak information was analyzed by Waters UNIFI data processing software. The molecular formula with error within 1×10-5 was compared with the data in database to identify the compounds. The secondary fragment ion information of the target compound was selected,and then compared with the retention time and fragmentation patterns provided by the database and the existing literature to further confirm the compositions and structures of the compounds. A total of 68 main compounds in Huanbei Zhike Prescription were identified,including 38 flavonoids,10 organic acids,6 terpenoids and 10 nitrogen-containing compounds,of which 12 compounds were verified by the control substances. This method is rapid and accurate,which provides a new strategy for the qualitative analysis of the chemical constituents of Huanbei Zhike Prescription,and lays a foundation for the further study and quality control of the compound pharmacodynamic substance.


Assuntos
Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Espectrometria de Massas em Tandem , Terpenos/análise
2.
Acta Pharmacol Sin ; 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31607752

RESUMO

T cell metabolic activation plays a crucial role in inflammation of atherosclerosis. Shikonin (SKN), a natural naphthoquinone with anti-inflammatory activity, has shown to exert cardioprotective effects, but the effect of SKN on atherosclerosis is unclear. In addition, SKN was found to inhibit glycolysis via targeting pyruvate kinase muscle isozyme 2 (PKM2). In the present study, we investigated the effects of SKN on hyperhomocysteinemia (HHcy)-accelerated atherosclerosis and T cell inflammatory activation in ApoE-/- mice and the metabolic mechanisms in this process. Drinking water supplemented with Hcy (1.8 g/L) was administered to ApoE-/- mice for 2 weeks and the mice were injected with SKN (1.2 mg/kg, i.p.) or vehicle every 3 days. We showed that SKN treatment markedly attenuated HHcy-accelerated atherosclerosis in ApoE-/- mice and significantly decreased inflammatory activated CD4+ T cells and proinflammatory macrophages in plaques. In splenic CD4+ T cells isolated from HHcy-ApoE-/- mice, SKN treatment significantly inhibited HHcy-stimulated PKM2 activity, interferon-γ secretion and the capacity of these T cells to promote macrophage proinflammatory polarization. SKN treatment significantly inhibited HHcy-stimulated CD4+ T cell glycolysis and oxidative phosphorylation. Metabolic profiling analysis of CD4+ T cells revealed that Hcy administration significantly increased various glucose metabolites as well as lipids and acetyl-CoA carboxylase 1, which were reversed by SKN treatment. In conclusion, our results suggest that SKN is effective to ameliorate atherosclerosis in HHcy-ApoE-/- mice and this is at least partly associated with the inhibition of SKN on CD4+ T cell inflammatory activation via PKM2-dependent metabolic suppression.

3.
Environ Res ; 179(Pt A): 108778, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629946

RESUMO

BACKGROUND: Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans. OBJECTIVE: To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men. METHOD: Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers. RESULTS: Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend<0.05), except for monoethyl phthalate (MEP) in relation to HNE-MA. Additionally, significantly or suggestively inverse dose-dependent relationships were exhibited between urinary 8-isoPGF2α and sperm concentration (p for trend = 0.05), and between urinary 8-OHdG and percent of normal sperm morphology (p for trend = 0.01). Mediation analysis showed that urinary 8-isoPGF2α suggestively mediated 12% of the inverse association between monobutyl phthalate (MBP) and sperm concentration, and that urinary 8-OHdG suggestively mediated 32% of the inverse association of MEP with percent of normal sperm morphology (both p < 0.10). CONCLUSIONS: Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality.

4.
Cancer Res ; 79(22): 5758-5768, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31585940

RESUMO

Angiogenesis is a hallmark of cancer that promotes tumor progression and metastasis. However, antiangiogenic agents have limited efficacy in cancer therapy due to the development of resistance. In clear cell renal cell carcinoma (ccRCC), AXL expression is associated with antiangiogenic resistance and poor survival. Here, we establish a role for GAS6/AXL signaling in promoting the angiogenic potential of ccRCC cells through the regulation of the plasminogen receptor S100A10. Genetic and therapeutic inhibition of AXL signaling in ccRCC tumor xenografts reduced tumor vessel density and growth under the renal capsule. GAS6/AXL signaling activated the expression of S100A10 through SRC to promote plasmin production, endothelial cell invasion, and angiogenesis. Importantly, treatment with the small molecule AXL inhibitor cabozantinib or an ultra-high affinity soluble AXL Fc fusion decoy receptor (sAXL) reduced the growth of a pazopanib-resistant ccRCC patient-derived xenograft. Moreover, the combination of sAXL synergized with pazopanib and axitinib to reduce ccRCC patient-derived xenograft growth and vessel density. These findings highlight a role for AXL/S100A10 signaling in mediating the angiogenic potential of ccRCC cells and support the combination of AXL inhibitors with antiangiogenic agents for advanced ccRCC. SIGNIFICANCE: These findings show that angiogenesis in renal cell carcinoma (RCC) is regulated through AXL/S100A10 signaling and support the combination of AXL inhibitors with antiangiogenic agents for the treatment of RCC.

5.
Environ Sci Technol ; 53(20): 12026-12034, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525872

RESUMO

The effects of disinfection byproducts (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n = 1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC versus GG (Pint = 0.07) and associations with decreased birth length, ponderal index, and gestational age were observed only among subjects with GSTZ1 rs7975 GA/AA versus GG (Pint = 0.07, 0.02, and 0.02, respectively). Our results suggested that prenatal DBP exposure was negatively associated with birth weight and ponderal index, and maternal genetic polymorphisms in CYP2E1 and GSTZ1 might modify these associations.

6.
Phys Chem Chem Phys ; 21(38): 21262-21266, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31538166

RESUMO

Binary skutterudite-type IrP3 possesses a unique structural configuration that exhibits unusual electronic, thermoelectric, and dynamical properties and can be applied in thermoelectric generators; IrP3 has unique square (P4) rings stacked with a relatively loose arrangement and thus has been expected to exhibit fascinating evolution in the bonding patterns and electronic properties under high pressure. Herein, we systematically investigated the global energetically stable structures of IrP3 under ambient- and high-pressure conditions using the swarm intelligence-based structure searching technique in combination with first-principles calculations. Our theoretical prediction shows that the skutterudite-type structure with the Im3[combining macron] symmetry is most stable under ambient conditions. An orthorhombic structure with the Pmma space group was predicted to be energetically superior to the Im3[combining macron] phase above 47.60 GPa. The abrupt volume collapse at the corresponding phase boundaries even reached 14.67%, stemming from the abrupt collapse of large voids in the Im3[combining macron] phase. To explore the possibility of the occurrence of pressure-induced metallization and superconducting states under compressive conditions, the electronic band structures were investigated. Our results showed that the Im3[combining macron] phase was a narrow-gap semiconductor with the band gap of 1.04 eV, whereas the high-pressure Pmma IrP3 was a metallic phase with the superconducting transition temperature of 2.40 K. The current results are beneficial for the further understanding of other skutterudite-type compounds under high pressure.

7.
Bioresour Technol ; 293: 122020, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31470231

RESUMO

A lab-scale acidogenic sulfate-reducing reactor with N2 stripping was continuously operated to uncover its microbial mechanism treating highly sulfate-containing organic wastewaters. Results showed that sulfate reduction efficiency decreased with the influent COD/sulfate ratios. Microbial community analysis showed that VFA accumulation mainly caused by the predominance of fermentative bacteria including Streptococcus and Oceanotoga. Genus Desulfovibrio was the most predominant SRB and enriched at low influent COD/sulfate ratios. Although Bifidobacterium, Atopobium, Wohlfahrtiimonas, Dysgonomonas etc. had low average abundance, they were identified keystone genera by the co-occurrence network analysis. The functions of the microbial community were not insignificantly influenced by COD/sulfate ratios. All predicted functional genes involved in dissimilatory sulfate reduction reached their maximum abundances at influent COD/sulfate ratio of 1.5, while the assimilatory sulfate reduction was favored at the COD/sulfate ratio lower than 2.


Assuntos
Carbono , Desulfovibrio , Reatores Biológicos , Sulfatos , Águas Residuárias
8.
J Med Genet ; 56(11): 758-764, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31413119

RESUMO

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a heterogenous neurodegenerative disorder named after its pathological features. It has long been considered a disease of genetic origin. Recently, the GGC repeated expansion in the 5'-untranslated region (5'UTR) of the NOTCH2NLC gene has been found in adult-onset NIID in Japanese individuals. This study was aimed to investigate the causative mutations of NIID in Chinese patients. METHODS: Fifteen patients with NIID were identified from five academic neurological centres. Biopsied skin samples were analysed by histological staining, immunostaining and electron microscopic observation. Whole-genome sequencing (WGS) and long-read sequencing (LRS) were initially performed in three patients with NIID. Repeat-primed PCR was conducted to confirm the genetic variations in the three patients and the other 12 cases. RESULTS: Our patients included 14 adult-onset patients and 1 juvenile-onset patient characterised by degeneration of multiple nervous systems. All patients were identified with intranuclear inclusions in the nuclei of fibroblasts, fat cells and ductal epithelial cells of sweat glands. The WGS failed to find any likely pathogenic variations for NIID. The LRS successfully identified that three patients with adult-onset NIID showed abnormalities of GGC expansion in 5'UTR of the NOTCH2NLC gene. The GGC repeated expansion was further confirmed by repeat-primed PCR in seven familial cases and eight sporadic cases. CONCLUSION: Our findings provided evidence that confirmed the GGC repeated expansion in the 5'UTR of the NOTCH2NLC gene is associated with the pathogenesis of NIID. Additionally, the GGC expansion was not only responsible for adult-onset patients, but also responsible for juvenile-onset patients.

9.
Water Res ; 165: 115008, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31461682

RESUMO

Stormwater biofilters have been increasingly used to mitigate the impact of climate change on the export of contaminants including nitrate to water bodies. Yet, their performance is rarely tested under high-intensity rainfall events, which are predicted to occur more frequently under climate change scenarios. We examined the potential of biochar to improve the resilience of woodchip biofilters under simulated high-intensity rainfall events and linked denitrification to biochar-mediated changes in hydrological (physical), chemical, and biological properties of woodchip biofilters. Results showed that nitrate removal capacity of woodchip biofilters decreased with increases in rainfall intensity or duration and decreases in antecedent drying time. However, adding biochar to woodchips significantly decreased the exhaustion rate of woodchips, only when the hydraulic residence time (HRT) was less than 5 h. At longer HRT (>5 h), the benefits of biochar became less apparent. We attributed the improved denitrification during high nitrate loading to biochar's ability to decrease dissolved oxygen in pore water and increase water holding capacity and retention of dissolved organic carbon and nitrate-all of which could increase nitrate utilization. Biochar increased the net microbial biomass but did not affect the relative abundance of denitrifying genes, which indicates that a shift in microbial biomass could not fully explain the observed increase in nitrate removal in biochar-augmented woodchip biofilters. Overall, the results showed that biochar could increase the resiliency of woodchip biofilters for denitrification in high-intensity rainfall events, a worst-case scenario, thereby mitigating the water quality degradation during climate change.


Assuntos
Reatores Biológicos , Desnitrificação , Carvão Vegetal , Nitratos
10.
Sci Rep ; 9(1): 11055, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363137

RESUMO

Current brain spheroids or organoids derived from human induced pluripotent stem cells (hiPSCs) still lack a microglia component, the resident immune cells in the brain. The objective of this study is to engineer brain region-specific organoids from hiPSCs incorporated with isogenic microglia-like cells in order to enhance immune function. In this study, microglia-like cells were derived from hiPSCs using a simplified protocol with stage-wise growth factor induction, which expressed several phenotypic markers, including CD11b, IBA-1, CX3CR1, and P2RY12, and phagocytosed micron-size super-paramagnetic iron oxides. The derived cells were able to upregulate pro-inflammatory gene (TNF-α) and secrete anti-inflammatory cytokines (i.e., VEGF, TGF-ß1, and PGE2) when stimulated with amyloid ß42 oligomers, lipopolysaccharides, or dexamethasone. The derived isogenic dorsal cortical (higher expression of TBR1 and PAX6) and ventral (higher expression of NKX2.1 and PROX1) spheroids/organoids displayed action potentials and synaptic activities. Co-culturing the microglia-like cells (MG) with the dorsal (D) or ventral (V) organoids showed differential migration ability, intracellular Ca2+ signaling, and the response to pro-inflammatory stimuli (V-MG group had higher TNF-α and TREM2 expression). Transcriptome analysis exhibited 37 microglia-related genes that were differentially expressed in MG and D-MG groups. In addition, the hybrid D-MG spheroids exhibited higher levels of immunoreceptor genes in activating members, but the MG group contained higher levels for most of genes in inhibitory members (except SIGLEC5 and CD200). This study should advance our understanding of the microglia function in brain-like tissue and establish a transformative approach to modulate cellular microenvironment toward the goal of treating various neurological disorders.

11.
PLoS One ; 14(7): e0219406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31283774

RESUMO

Postoperative shed autologous blood reinfusion techniques have been used for decades in total knee arthroplasty (TKA), but the effectiveness of this procedure is still a matter of debate. This multicenter retrospective study investigated the medical records of patients who underwent unilateral and bilateral TKA from January 1, 2015 to December 31, 2017 in three hospitals. According to whether postoperative shed autologous blood reinfusion was used, the patients were divided into the control group and the shed autologous blood reinfusion group. The volume of perioperative infusion of red blood cells and plasma, the blood transfusion-related costs, and the postoperative hospital stay were compared between the two groups of patients. A total of 200 unilateral and 74 bilateral TKA were included after successful matching. Among the patients who underwent unilateral TKA, the control group and the shed autologous blood reinfusion group had 95 and 91 patients, respectively, who received allogeneic blood infusion (P = 0.268). There was no significant difference in the number of units of allogeneic red blood cells infused (P = 0.154), while the transfusion-related cost was increased (P<0.001). The same phenomena were observed over the patients underwent bilateral TKA. Shed autologous blood reinfusion does not reduce the need for infusing allogeneic red blood cells. In addition, the procedure increases patient expense and may also lead to an extended postoperative hospital stay.

12.
Org Biomol Chem ; 17(30): 7172-7181, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31310252

RESUMO

A new dinuclear zinc cooperative catalytic enantioselective three-component reaction via a domino Knoevenagel /Michael/cyclization sequence has been developed. A series of chiral 3,3'-dihydrofuran spirooxindoles are obtained in excellent yields (up to 99%) and enantioselectivities (up to 99% ee). In addition, the reaction is carried out smoothly on a gram scale under mild conditions.

13.
Phytochemistry ; 166: 112058, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31280093

RESUMO

Isatis indigotica Fortune is a popular herb in traditional Chinese medicine, and various types of metabolites are the basis for its pharmacological efficacy. The biosynthesis and accumulation of these metabolites are closely linked to nitrogen availability; the benefits of low nitrogen application on the environment and herb quality are increasingly prominent. To analyze metabolic changes in the leaves and roots of I.indigotica in nitrogen deficiency conditions, and to identify the pathways and metabolites induced by low nitrogen availability, we used untargeted liquid chromatography coupled with mass spectrometry (UHPLC-TripleTOF) to obtain metabolomics profiling of I.indigotica under two N-deficiency treatments (0 kg/hm2; 337.5 kg/hm2) and normal nitrogen treatment (675 kg/hm2). A total of 447 metabolites were annotated. Principal component analysis separated the three nitrogen treatments. A greater diversity of metabolites was observed in roots than in leaves under N-deficiency treatments, suggesting that roots have a more important function in low N tolerance. Differential metabolites were mainly enriched in purine metabolism, phenylpropanoid biosynthesis, the shikimate pathway, tryptophan metabolism, and flavonoid biosynthesis that notably induced only in leaves in low nitrogen stress. Moderate N-deficiency benefits carbohydrate accumulation, whereas accumulation of most amino acids decreases. Uniquely, L-tryptophan was maintained at a high concentration in N-deficiency conditions. Low nitrogen stress induced the accumulation of some specialized metabolites (matairesinol, dictamnine, 5-hydroxyindoleacetate (serotonin) in roots and vitexin, xanthohumol, sinapyl alcohol in leaves). N-deficiency also increased the accumulation of adenosine and quality indicators of I.indigotica (indirubin-indigo, epigoitrin and anthranilic acid) in a certain degree. Our findings showed that nitrogen deficiency modified roots and leaves conditions of I.indigotica, affecting both the primary and secondary metabolism. Moderate nitrogen reduction was beneficial to the accumulation of active ingredients. Our methods and analysis are expected to provide an insight regarding the diversity of metabolites and regulation of their synthesis in low nitrogen application, and better investigate the nitrogen deficiency effect on I.indigotica.


Assuntos
Isatis/metabolismo , Metabolômica , Nitrogênio/deficiência , Cromatografia Líquida , Espectrometria de Massas
14.
Artif Cells Nanomed Biotechnol ; 47(1): 2298-2305, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31174440

RESUMO

Photothermal therapy (PTT) is a rapidly developing approach for cancer therapy, which has been widely recognized to exert high efficacy as compared to chemotherapy. However, the limited tumour homing property of currently available drug delivery systems (DDSs) is the bottleneck for the efficient delivery of photothermal agents. Here in this study, we surface modified silica nanoparticles (SLN) with the cell membrane (CM) derived from 143B cells to construct a platform (CM/SLN) capable of targeting the homogenous 143B cells. In addition, indocyanine green (ICG) as a photothermal agent was encapsulated into CM/SLN to finally construct a DDS suitable for tumour-targeted PTT of osteosarcoma. Our results revealed that CM/SLN/ICG was mono-dispersed core-shell nanoparticles with advanced stability in a physiological environment. Moreover, due to the modification of CM, CM/SLN/ICG could specifically target the homogenous 143B cells both in vitro and in vivo, which demonstrated superior anticancer efficacy when compared with either SLN/ICG or free ICG. Hence, CM/SLN/ICG could be a promising DDS for tumour targeted PTT of osteosarcoma.


Assuntos
Membrana Celular/metabolismo , Portadores de Fármacos/química , Verde de Indocianina/química , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Fotoquimioterapia , Dióxido de Silício/química , Animais , Transporte Biológico , Linhagem Celular Tumoral , Portadores de Fármacos/metabolismo , Feminino , Humanos , Verde de Indocianina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Osteossarcoma/patologia
15.
Phys Rev Lett ; 122(10): 104801, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30932681

RESUMO

We demonstrate a laser-driven, tunable electron lens fabricated in monolithic silicon. The lens consists of an array of silicon pillars pumped symmetrically by two 300 fs, 1.95 µm wavelength, nJ-class laser pulses from an optical parametric amplifier. The optical near field of the pillar structure focuses electrons in the plane perpendicular to the pillar axes. With 100±10 MV/m incident laser fields, the lens focal length is measured to be 50±4 µm, which corresponds to an equivalent quadrupole focusing gradient B^{'} of 1.4±0.1 MT/m. By varying the incident laser field strength, the lens can be tuned from a 21±2 µm focal length (B^{'}>3.3 MT/m) to focal lengths on the centimeter scale.

17.
Bioinformatics ; 35(22): 4586-4595, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30994904

RESUMO

MOTIVATION: The Oxford Nanopore sequencing enables to directly detect methylation states of bases in DNA from reads without extra laboratory techniques. Novel computational methods are required to improve the accuracy and robustness of DNA methylation state prediction using Nanopore reads. RESULTS: In this study, we develop DeepSignal, a deep learning method to detect DNA methylation states from Nanopore sequencing reads. Testing on Nanopore reads of Homo sapiens (H. sapiens), Escherichia coli (E. coli) and pUC19 shows that DeepSignal can achieve higher performance at both read level and genome level on detecting 6 mA and 5mC methylation states comparing to previous hidden Markov model (HMM) based methods. DeepSignal achieves similar performance cross different DNA methylation bases, different DNA methylation motifs and both singleton and mixed DNA CpG. Moreover, DeepSignal requires much lower coverage than those required by HMM and statistics based methods. DeepSignal can achieve 90% above accuracy for detecting 5mC and 6 mA using only 2× coverage of reads. Furthermore, for DNA CpG methylation state prediction, DeepSignal achieves 90% correlation with bisulfite sequencing using just 20× coverage of reads, which is much better than HMM based methods. Especially, DeepSignal can predict methylation states of 5% more DNA CpGs that previously cannot be predicted by bisulfite sequencing. DeepSignal can be a robust and accurate method for detecting methylation states of DNA bases. AVAILABILITY AND IMPLEMENTATION: DeepSignal is publicly available at https://github.com/bioinfomaticsCSU/deepsignal. SUPPLEMENTARY INFORMATION: Supplementary data are available at bioinformatics online.

18.
Med Sci Monit ; 25: 1788-1799, 2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30850575

RESUMO

BACKGROUND Studies have shown inconsistent associations of nitrite and nitrate intake with the risk of gastric cancer or its associated mortality. We performed a meta-analysis of observational studies to evaluate the correlation of nitrite and nitrate intake with the risk of gastric cancer. MATERIAL AND METHODS We searched for studies reporting effect estimates and 95% confidence intervals (CIs) of gastric cancer in PubMed, EMBASE, and the Cochrane Library through November 2018. The summary results of the included studies were pooled using a random-effects model. RESULTS Eighteen case-control and 6 prospective cohort studies recruiting 800 321 participants were included in this study. The summary results indicated that the highest (odds ratio [OR], 1.27; 95%CI, 1.03-1.55; P=0.022) or moderate (OR: 1.12; 95%CI, 1.01-1.26; P=0.037) nitrite intake were associated with a higher risk of gastric cancer. However, we noted that high (OR, 0.81; 95%CI, 0.68-0.97; P=0.021) or moderate (OR, 0.86; 95%CI, 0.75-0.99; P=0.036) nitrate intakes were associated with a reduced risk of gastric cancer. These associations differed when stratified by publication year, study design, country, the percentage of male participants, assessment of exposure, adjusted model, and study quality. CONCLUSIONS High or moderate nitrite intake was associated with higher risk of gastric cancer, whereas high or moderate nitrate intake was correlated with lower risk of gastric cancer.


Assuntos
Nitratos/efeitos adversos , Nitritos/efeitos adversos , Neoplasias Gástricas/metabolismo , Nitrito de Amila/efeitos adversos , Estudos de Casos e Controles , Humanos , Nitratos/metabolismo , Nitritos/metabolismo , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/fisiopatologia
19.
Front Immunol ; 10: 395, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30899265

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) can be classified into primary HLH and secondary HLH. Primary HLH usually occurs in infants and children with an underlying genetic defect, and there are also teens and occasional adults with primary HLH. Most cases with secondary HLH are adult patients with secondary triggers including infections, malignancies, and autoimmune diseases. The distinction between primary HLH and secondary HLH seems to be less straightforward, as patients with secondary HLH may also have genetic defects while primary HLH can be triggered by secondary causes. In this study, using amplicon-based targeted gene sequencing (TGS), we sequenced eighteen HLH-related genes in 112 adult HLH cases, which were mostly secondary HLH. Mutations or rare variants were identified in 48 cases (42.9%). All the variants except one were missense variants, and biallelic gene mutations were identified in 3 cases in which only one case harbored homogenous missense mutation. Recurrent variants including UNC13D p.G863D and AP3B1 p.T359A are much more prevalent in our cohort than in normal East Asian population, and in silico analysis predicted pathogenicity of these variants. In conclusion, according to our study, genetic defects may also contribute to the development of adult HLH cases or secondary HLH cases.

20.
Asian J Surg ; 42(10): 899-906, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30914154

RESUMO

To provide a meta-analysis of studies evaluating long-term all-cause mortality, aneurysm-related mortality and re-intervention after open or endovascular repair for abdominal aortic aneurysm. Electronic bibliographic sources were interrogated using a combination of free text and controlled vocabulary searches to identify studies comparing the long-term outcomes of open and endovascular repair for abdominal aortic aneurysm. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Fixed effect or random effects models were used. We retrieved 4 randomized controlled trials (RCTs; 2,783 patients), 7 nonrandomized trials (86,035 patients). The primary outcome was all-cause mortality. Heterogeneity was high and publication bias could not be excluded. Despite these limitations, the analysis showed that open and endovascular abdominal aortic aneurysm repair had similar all-cause mortality (OR 1.16, 95% CI, 0.89-1.51) over 5 years follow up, which was maintained after at least 10 years of follow-up (OR 0.87, 95% CI, 0.73-1.03). There was no significant difference in aneurysm-related mortality by 5 years or longer follow-up. A significantly lower proportion of patients undergoing open repair required reintervention (OR 0.38, 95% CI 0.24-0.64), which was maintained over 5 years of follow-up. There is no long-term survival difference between the patients who underwent open or endovascular aneurysm repair. There is significantly higher risk of reinterventions after endovascular aneurysm repair.

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