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1.
Thorac Cancer ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31794146

RESUMO

BACKGROUND: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of lung cancer. However, the prevalence of driver alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, and the response of tyrosine kinase inhibitor (TKIs) in PLELC has not been thoroughly investigated. METHOD: We retrospectively reviewed the genetic profiles and treatment course of 330 PLELC patients at the Guangdong Lung Cancer Institute (GLCI) from 1st January, 2008 to 30th December, 2018. We searched and analyzed related literature published in PubMed and Web of Science from 1st January, 2000 and 31th August, 2019 based on their mention of "driver mutations" and "the response of TKIs to mutant PLELC". RESULTS: Genetic alterations of EGFR/ALK were tested in 203 patients (203/330, 61.5%). Five patients (5/175, 2.9%) had EGFR mutation and three patients (3/140, 2.1%) had ALK alteration. From the total of 15 articles identified from electronic searches, 1071 PLELC cases mentioned the driver mutations. EGFR mutation and ALK rearrangement were detected in 15 patients and one patient, respectively. In total, there were four EGFR/ALK mutant PLELC patients who received targeted therapy as palliative treatment at the GLCI and in the literature. However, there was disease progression in all cases one month after use of TKIs. CONCLUSION: The mutation rates of EGFR and ALK were low in PLELC. EGFR and ALK TKIs showed limited response in EGFR/ALK mutant PLELC. Further studies are needed to explore other molecular targets to optimize the therapeutic strategy for PLELC.

2.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31696219

RESUMO

PURPOSE: In the degenerated intervertebral disc (IVD), matrix acidity challenges transplanted bone marrow mesenchymal stem cells (BMSCs). The Ca2+-permeable acid-sensing ion channel 1a (ASIC1a) is responsible for acidosis-mediated tissue injury. The aim of our study was to confirm whether ASIC1a activation induces BMSC apoptosis under conditions that mimic the acidic microenvironment of the degenerated IVD. METHODS: ASIC1a expression in rat BMSCs was investigated by real time-PCR, Western blot (WB) and immunofluorescence. The proliferation and apoptosis of BMSCs under acidic conditions were analyzed by MTT and TUNEL assays. Ca2+-imaging was used to assess the acid-induced increase in the intracellular Ca2+ concentration ([Ca2+]i). The activation of calpain and calcineurin was analyzed using specific kits, and WB analysis was performed to detect apoptosis-related proteins. Ultrastructural changes in BMSCs were observed using transmission electron microscopy (TEM). RESULTS: Acid exposure led to the activation of ASIC1a and increased BMSC apoptosis. The Ca2+ imaging assay showed a significant increase in the [Ca2+]i in response to a solution at pH 6.0. However, BMSC apoptosis and [Ca2+]i elevation were alleviated in the presence of an ASIC1a inhibitor. Moreover, ASIC1a mediated the Ca2+ influx-induced activation of calpain and calcineurin in BMSCs. WB analysis and TEM revealed mitochondrial apoptosis, which was inhibited by an ASIC1a inhibitor, in BMSCs under acidic conditions. CONCLUSIONS: The mimical acidic microenvironment of the degenerated IVD can induce BMSC apoptosis by activating Ca2+-permeable ASIC1a. An acid-induced elevation of [Ca2+]i in BMSCs leads to the subsequent activation of calpain and calcineurin, further resulting in increased mitochondrial permeability and mitochondrial-mediated apoptosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31735331

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. Protein tyrosine phosphatase 1B (PTP1B) is a member of protein tyrosine phosphatases (PTPs) family. In our previous work, PTP1B was found to be overexpressed in ESCC tissues and made contributions to the the cell migration and invasion as well as lung metastasis of ESCC. In this study, we explored the underlying molecular mechanisms. PTP1B enhanced cell migration and invasion by promoting epidermal growth factor receptor (EGFR) expression in ESCC, which was relied on phosphatase activity of PTP1B. Using GST-pulldown combined with LC/MS/MS, we found that nonmuscle myosin IIA (MYH9) was a novel substrate of PTP1B in ESCC cells. PTP1B dephosphorylated MYH9 at Y1408, by which PTP1B up-regulated EGFR expression and enhanced cell migration and invasion in ESCC. In conclusion, our study first reported that PTP1B was the positive regulator of EGFR by dephosphorylating MYH9 at Y1408 to promote cell migration and invasion, which revealed the regulatory mechanism of PTP1B-MYH9-EGFR axis in ESCC.

4.
Oncol Lett ; 18(5): 4563-4572, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31611964

RESUMO

Portal vein (PV) involvement is common in patients with pancreatic ductal adenocarcinoma (PDAC). To the best of our knowledge, pancreatectomy combined with PV resection (PVR) is the only radical therapy for patients with PV involvement. However, there remains a debate on whether patients with PV involvement could benefit from PVR or not. The present study aimed to compare the survival outcomes between patients receiving pancreatoduodenectomy (PD) with PVR and those receiving PD alone. A total of 377 patients with PDAC were enrolled, 138 patients with PV involvement were placed in the PVR group, while the other 239 patients were in the non-PVR group. To reduce selection bias and estimate the causal effect, 123 pairs of propensity score matched (PSM) patients were selected and compared for the survival outcomes. Before PSM, the survival of patients in the PVR group was worse compared with those in the non-PVR group (mean survival, 25.1 vs. 29.3 months; P=0.038). After balancing the baseline characteristics using the PSM method, the significant survival difference between the two groups was insignificant (mean survival, 25.9 vs. 31.2 months; P=0.364). Tumor stage, body mass index, serum albumin, R1 resection, lymph node metastasis, carbohydrate antigen (CA)125 and CA19-9 were significant independent prognostic factors. The incidence of serious postoperative complications was similar between the two groups. PVR is safe and effective for patients with PDAC. Patients with PV involvement could achieve the similar survival outcome as patients without PV involvement, through radical resection combined with PVR, without increasing the risk of serious complications.

5.
New Phytol ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596964

RESUMO

Wood (secondary xylem) formation in tree species is dependent on auxin-mediated vascular cambium activity in stems. However, the complex regulatory networks underlying xylem formation remain elusive. Xylem development in Populus was characterized based on microscopic observations of stem sections in transgenic plants. Transcriptomic, quantitative real-time PCR, chromatin immunoprecipitation PCR, and electrophoretic mobility shift assay analyses were conducted to identify target genes involved in xylem development. Yeast two-hybrid, pull-down, bimolecular fluorescence complementation, and co-immunoprecipitation assays were used to validate protein-protein interactions. PaC3H17 and its target PaMYB199 were found to be predominantly expressed in the vascular cambium and developing secondary xylem in Populus stems and play opposite roles in controlling cambial cell proliferation and secondary cell wall thickening through an overlapping pathway. Further, PaC3H17 interacts with PaMYB199 to form a complex, attenuating PaMYB199-driven suppression of its xylem targets. Exogenous auxin application enhances the dual control of the PaC3H17-PaMYB199 module during cambium division, thereby promoting secondary cell wall deposition. Dual regulation of xylem formation by an auxin-mediated PaC3H17-PaMYB199 module represents a novel regulatory mechanism in Populus, increasing our understanding of the regulatory networks involved in wood formation.

6.
Biomolecules ; 9(10)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658691

RESUMO

As a disease characterized by severe liver necrosis and hemorrhage, duck viral hepatitis (DVH) is mainly caused by duck hepatitis A virus (DHAV). The positive-strand RNA genome of DHAV type 1 (DHAV-1) contains an internal ribosome entry site (IRES) element within the 5' untranslated region (UTR), structured sequence elements within the 3' UTR, and a poly(A) tail at the 3' terminus. In this study, we first examined that insulin-like growth factor-2 mRNA-binding protein-1 (IGF2BP1) specifically interacted with the DHAV-1 3' UTR by RNA pull-down assay. The interaction between IGF2BP1 and DHAV-1 3' UTR strongly enhanced IRES-mediated translation efficiency but failed to regulate DHAV-1 replication in a duck embryo epithelial (DEE) cell line. The viral propagation of DHAV-1 strongly enhanced IGF2BP1 expression level, and viral protein accumulation was identified as the key point to this increment. Collectively, our data demonstrated the positive role of IGF2BP1 in DHAV-1 viral proteins translation and provided data support for the replication mechanism of DHAV-1.

7.
Nano Lett ; 19(10): 7035-7042, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502461

RESUMO

Nanosized oncolytic viral light particles (L-particles), separated from progeny virions, are composed of envelopes and several tegument proteins of viruses, free of nucleocapsids. The noninfectious L-particles experience the same internalization process as mature oncolytic virions, which exhibits great potential to act as targeted therapeutic platforms. However, the clinical applications of L-particle-based theranostic platforms are rare due to the lack of effective methods to transform L-particles into nanovectors. Herein, a convenient and mild strategy has been developed to transform L-particles into near-infrared (NIR) fluorescence Ag2Se quantum dot (QD)-labeled active tumor-targeting nanovectors for real-time in situ imaging and drug delivery. Utilizing the electroporation technique, L-particles can be labeled with ultrasmall water-dispersible NIR fluorescence Ag2Se QDs with a labeling efficiency of ca. 85% and loaded with antitumor drug with a loading efficiency of ca. 87%. Meanwhile, by harnessing the infection mechanism of viruses, viral L-particles are able to recognize and enter tumor cells without further modification. In sum, a trackable and actively tumor-targeted theranostics nanovector can be obtained efficiently and simultaneously. Such multifunctional nanovectors transformed from viral L-particles have exhibited excellent properties of active tumor-targeting, in vivo tumor imaging, and antitumor efficacy, which opens a new window for the development of natural therapeutic nanoplatforms.

8.
J Thorac Oncol ; 14(11): 1912-1923, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446140

RESUMO

BACKGROUND: Understanding the genomic landscape and immune microenvironment features of preinvasive and early invasive lung adenocarcinoma may provide critical insight and facilitate development of novel strategies for early detection and intervention. METHODS: A total of 80 tumor tissue samples and 30 paired histologically normal lung tissue samples from 30 patients with adenocarcinoma in situ (AIS) (n = 8), minimally invasive adenocarcinoma (MIA) (n = 8), and invasive adenocarcinoma (IAC) (n = 14) were subjected to multiregion whole exome sequencing and immunohistochemistry staining for CD8 and programmed death ligand 1 (PD-L1). RESULTS: All tumors, including AIS, exhibited evidence of genomic intratumor heterogeneity. Canonical cancer gene mutations in EGFR, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), NRAS, and BRAF were exclusively trunk mutations detected in all regions within each tumor, whereas genes associated with cell mobility, gap junction, and metastasis were all subclonal mutations. EGFR mutation represented the most common driver alterations across AIS, MIA, and IAC, whereas tumor protein p53 gene (TP53) was identified in MIA and IAC but not in AIS. There was no difference in PD-L1 expression among AIS, MIA, and IAC, but the CD8 positivity rate was higher in IAC. Tumors positive for both PD-L1 and CD8 had a larger proportion of subclonal mutations. CONCLUSIONS: Mutations in EGFR, ERBB2, NRAS, and BRAF are early clonal genomic events during carcinogenesis of lung adenocarcinoma, whereas TP53 and cell mobility, gap junction, and metastasis-related genes may be late events associated with subclonal diversification and neoplastic progression. Genomic intratumor heterogeneity and immunoediting are common and early phenomena that may have occurred before the acquisition of invasion.

9.
CNS Neurosci Ther ; 25(10): 1162-1172, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31436915

RESUMO

AIM: To determine the effect of osteopontin (OPN) on autophagy and autophagy-apoptosis interactions after SAH. METHODS: The endovascular perforation model of SAH or sham surgery was performed in a total of 86 Sprague-Dawley male rats. The temporal expressions of endogenous OPN and autophagy-related proteins (Beclin 1, ATG5, LC3 II to I ratio) were measured in sham and SAH rats at different time points (3, 6, 12, 24, and 72 hours). Rats were randomly divided into three groups: Sham, SAH + Vehicle (PBS, phosphate-buffered saline), and SAH + rOPN (5 µg/rat recombinant OPN). Neurobehavioral tests were performed 24 hours after SAH, followed by the collection of brain samples for assessment of autophagy and apoptosis proteins. These tests assessed whether an autophagy-apoptosis relationship existed on the histological level in the brain. RESULTS: Endogenous OPN and autophagy-related proteins all increased after SAH. rOPN administration improved neurological dysfunction, increased the expression of autophagy-related proteins (Beclin 1, ATG5, LC3 II to I ratio) and antiapoptotic protein Bcl-2, while decreasing the expression of proapoptotic proteins (cleaved Caspase-3 and Bax). rOPN also regulated autophagy-apoptosis interactions 24 hours after SAH. CONCLUSION: rOPN attenuates early brain injury and inhibits neuronal apoptosis by activating autophagy and regulating autophagy-apoptosis interactions.

10.
ACS Omega ; 4(7): 11832-11837, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31460292

RESUMO

In this study, we detail the development of a concise and efficient three-component protocol for the regioselective synthesis of highly functionalized bis-indoles through a one-pot, two-step sequential process starting from enaminones 1, indoles 2, and acenaphthylene-1,2-dione 3 that is catalyzed by piperidine and p-methyl benzenesulfonic acid. This protocol has several advantages including simplicity of experimental operation, high efficiency of bond formation, ready availability and low cost of starting materials, environmentally benign conditions, and target molecular diversity.

11.
Acta Neuropsychiatr ; 31(6): 316-324, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31405402

RESUMO

OBJECTIVE: To explore whether and how group cognitive-behavioural therapy (GCBT) plus medication differs from medication alone for the treatment of generalised anxiety disorder (GAD). METHODS: Hundred and seventy patients were randomly assigned to the GCBT plus duloxetine (n=89) or duloxetine group (n=81). The primary outcomes were Hamilton Anxiety Scale (HAMA) response and remission rates. The explorative secondary measures included score reductions from baseline in the HAMA total, psychic, and somatic anxiety subscales (HAMA-PA, HAMA-SA), the Hamilton Depression Scale, the Severity Subscale of Clinical Global Impression Scale, Global Assessment of Functioning, and the 12-item Short-Form Health Survey. Assessments were conducted at baseline, 4-week, 8-week, and 3-month follow-up. RESULTS: At 4 weeks, HAMA response (GCBT group 57.0% vs. control group 24.4%, p=0.000, Cohen's d=0.90) and remission rates (GCBT group 21.5% vs. control group 6.2%, p=0.004; d=0.51), and most secondary outcomes (all p<0.05, d=0.36-0.77) showed that the combined therapy was superior. At 8 weeks, all the primary and secondary significant differences found at 4 weeks were maintained with smaller effect sizes (p<0.05, d=0.32-0.48). At 3-month follow-up, the combined therapy was only significantly superior in the HAMA total (p<0.045, d=0.43) and HAMA-PA score reductions (p<0.001, d=0.77). Logistic regression showed superiority of the combined therapy for HAMA response rates [odds ratio (OR)=2.12, 95% confidence interval (CI) 1.02-4.42, p=0.04] and remission rates (OR=2.80, 95% CI 1.27-6.16, p=0.01). CONCLUSIONS: Compared with duloxetine alone, GCBT plus duloxetine showed significant treatment response for GAD over a shorter period of time, particularly for psychic anxiety symptoms, which may suggest that GCBT was effective in changing cognitive style.

12.
Virus Res ; 270: 197670, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31330206

RESUMO

The nuclear localization signals (NLS) were usually composed of basic residues (K and R) and played an important role in delivery of genomes and structural protein into nucleus. In this research, we identified that 3Dpol/3CD entered into nucleus during viral propagation of duck hepatitis A virus type 1 (DHAV-1). To investigate the reason that 3Dpol/3CD entered into nucleus, the amino acid sequence of 3CD was analyzed through NLS Mapper program. The basic region 17PRKTAYMRS25 was subsequently proved to be a functional NLS to guide 3Dpol/3CD into nucleus. 18R, 19K and 24R were found essential for maintaining the nuclear targeting activity, and exchange between 24R and 24K had no impact on cellular localization of 3Dpol. Since the entry of 3Dpol/3CD into nucleus was essential for shutoff of host cell transcription and maintaining the viral propagation of picornavirus numbers, our study provided new insights into the mechanism of DHAV-1 propagation.

13.
Int J Biol Sci ; 15(8): 1755-1770, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360117

RESUMO

Diselenide-containing paclitaxel nanoparticles (SePTX NPs) indicated selectivity of cytotoxicity between cancerous and normal cells in our previous work. Herein, the mechanism is revealed by molecular biology in detail. Cancer cells and normal cells were treated with the SePTX NPs and cell proliferation was measured using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cell morphology. Measurement of reactive oxygen species (ROS) levels and biochemical parameters were employed to monitor oxidative stress of the cells. JC-1 assay was used to detect the mitochondrial dysfunction of the cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis was used to detect apoptosis of the cells. Immunofluorescence analysis and western blotting were employed to monitor changes in signaling pathway-related proteins. Compared with PTX, SePTX NPs has a good selectivity to cancer cells and can obviously induce the proliferation damage of cancer cells, but has no significant toxicity to normal cells, indicating that SePTX NPs has a specific killing effect on cancer cells. The results of mechanism research show that SePTX NPs can successfully inhibit the depolymerization of microtubules and induce cell cycle arrest, which is related to the upregulation of p53 and CyclinB1. Simultaneously, SePTX NPs can successfully induce oxidative stress, cause mitochondrial dysfunction, resulting in mitochondrial pathway-mediated apoptosis, which is related to the upregulation of autophagy-related protein LC3-II. On the other hand, lewis lung cancer C57BL/6 mice were used to evaluate the anti-tumor effects of SePTX NPs in vivo. Our data show that SePTX NPs exhibited high inhibiting efficiency against the growth of tumors and were able to reduce the side effects. Collectively, these data indicate that the high antitumor effect and selective cytotoxicities of SePTX NPs is promising in future cancer therapy.

14.
Mikrochim Acta ; 186(8): 529, 2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-31302797

RESUMO

The accurate determination of the molar concentration or the number concentration of particles in a defined volume is important but challenging. Since particle diversity and heterogeneity cannot be ignored in particle quantification, single particle counting has become quite important. However, most methods require standard samples (calibrators) which are usually difficult to obtain. The authors describe a method for single particle counting that is based on the combination of digital counting and formation of microdroplets in a microchip. By compartmentalizing particles into picoliter droplets, positive droplets encapsulating particles were counted and particle concentrations were calculated by Poisson statistics. The concentration of particles over a wide range (from 5.0 × 103 to 1.8 × 107 particles per mL) were accurately determined without the need for using a calibrator. A microdroplet chip including a T-junction channel achieved a 9-fold increase of signal-to-background ratio compared to the traditional flow-focusing chip. This makes the digital counting system a widely applicable tool for quantification of fluorescent particles. Various particles including differently sized fluorescent microspheres and bacteria with large heterogeneity in shape such as Escherichia coli DH5α-pDsRed were accurately quantified by this method. Graphical abstract Schematic representation of the digital single particle counting system for absolute quantification of particles. Particles compartmentalized in picoliter droplets were counted and the number concentration of particles was determined using digital analysis.

15.
J Exp Bot ; 70(19): 5507-5516, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31270545

RESUMO

LysM receptor-like kinases (LYKs) of Arabidopsis thaliana (namely LYK1, LYK4 and LYK5) play a major role in chitin perception and immunity against pathogenic fungi. Chitin-induced heterodimerization of LYK1 and LYK5 has been previously reported, but protein interaction partners of LYK4 have not yet been identified. In this study, by analysing mutants we confirmed a role of LYK4 in chitin perception, and found that the ectodomain of LYK4 homodimerizes and also interacts with the ectodomain of LYK5 in vitro. Pull-down experiments with proteins expressed in protoplasts indicated LYK4-LYK4 and LY4-LYK5 interactions in planta. When protoplasts were treated with chitoheptaose or chitin, a protein complex was immunoprecipitated that appeared to be composed of LYK1, LYK4, and LYK5. Similar experiments with proteins expressed in lyk mutant plants suggested that elicitor treatment induced a physical interaction between LYK1 and LYK5 but not between LYK1 and LYK4. Bimolecular fluorescence complementation experiments substantiated these findings. Overall, our data suggest that LYK4 functions as a LYK5-associated co-receptor or scaffold protein that enhances chitin-induced signaling in Arabidopsis.

16.
Arch Virol ; 164(9): 2385-2388, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31209596

RESUMO

The discovery and analysis of pathogens carried by non-human primates are important for understanding zoonotic infections in humans. We identified a highly divergent astrovirus (AstV) from fecal matter from a rhesus monkey in China, which has been tentatively named "monkey-feces-associated AstV" (MkAstV). The full-length genome of MkAstV was determined to be 7377 nt in length. It exhibits the standard genomic AstV organization of three open reading frames (ORFs) and is most closely related to duck AstV (28%, 49%, and 35% amino acid sequence identity in ORF1a, ORF1b, and ORF2, respectively). Coincidentally, while this report was being prepared, an astrovirus sequence from Hainan black-spectacled toad became available in the GenBank database, showing 95%, 94% and 92% aa sequence identity in ORF1a, ORF1b and ORF2, respectively, to the corresponding ORFs of MkAstV. Phylogenetic analysis of ORF1a, ORF1b, and ORF2 indicated that MkAstV and the amphibian-related astroviruses formed an independent cluster in the genus Avastrovirus. The host of MkAstV remains unknown. Epidemiological and serological studies of this novel virus should be undertaken in primates, including humans.


Assuntos
Astroviridae/isolamento & purificação , Fezes/virologia , Macaca mulatta/virologia , Sequência de Aminoácidos , Animais , Astroviridae/classificação , Astroviridae/genética , China , Genoma Viral , Fases de Leitura Aberta , Filogenia , Alinhamento de Sequência , Proteínas Virais/genética
17.
Mol Cell Probes ; 46: 101413, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31202830

RESUMO

Dengue virus (DENV), a member of the genus Flavivirus within the family Flaviviridae, is one of the most significant mosquito-borne viruses that causing dengue fever in human. A rapid diagnostic would be helpful to detect DENV infection in a timely manner. In the last decade, recombinase polymerase amplification (RPA) technique has been experiencing rapid development and widely employed to detect various other pathogens. In present study, a reverse transcription RPA (RT-RPA) assay combined with lateral flow dipstick (LFD) was established for rapid detection of DENV. The assay could detect DENV-1, -2, -3 and -4. The minimal detection limit of the RT-RPA-LFD assay was 10 copies RNA molecules. The assay was DENV-specific since it had no non-specific reactions with other common human pathogens. The clinical performance of the RT-RPA assay was validated using 120 clinical samples. The coincidence rate between RT-RPA-LFD and qRT-PCR for the clinical samples was 100%, indicating the RT-RPA-LFD assay had good diagnostic performance on clinical samples. The RT-RPA-LFD assay required no sophisticated instrument, providing a possible solution for DENV diagnosis in recourse-limited settings where DENV infection is epidemic.

18.
Huan Jing Ke Xue ; 40(3): 1512-1520, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-31088004

RESUMO

With the rapid development of the economy, the atmospheric pollution in China has become very severe, and poses a great threat to human health. On the basis of relevant research achievements at home and abroad, this paper summarizes the impact of atmospheric pollution on the health of residents from the two aspects of research content and method. It was found that current research is mainly focused on calculating the health losses, evaluating the economic cost of health losses, and analyzing the health benefits of controlling atmospheric pollutants at the macro level, while studies at the micro level are relatively scarce. Moreover, current studies at the micro individual level is mostly empirical research related to epidemic cases abroad; however, domestic research at the micro individual level is still at the initial stage of qualitative analysis. In addition, the quantitative assessment method of atmospheric pollution on the health of residents is also improving. Apart from methods in common use (meta-analysis, Poisson regression model, human capital method, willingness to pay method and disease cost method), there are other methods that are widely used (input-output model and computable general equilibrium model). In general, the effects of atmospheric pollution on resident health include both chronic and short-term acute effects, and involve many other factors as well, such as socioeconomics, natural conditions, behavioral preferences, and personal physiology. Although the depth and breadth of the research are expanding, and the level of discipline integration is being continuously improved, it is necessary to strengthen domestic epidemiological studies, to pay attention to the integration of macro (regions) and micro (individuals), to focus on the reduction and distribution of atmospheric pollutants from a health perspective, and to attach importance to the construction of a basic database in the future to provide a scientific basis for establishing a systematic framework for the analysis of the effects of atmospheric pollution on the health of residents.


Assuntos
Poluição do Ar/efeitos adversos , Nível de Saúde , China , Humanos
19.
Medicine (Baltimore) ; 98(19): e15542, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083208

RESUMO

ON1 is a novel genotype of human respiratory syncytial virus (HRSV) subtype A, in children with acute respiratory tract infections (ARTIs). However, there is not much data on the prevalence and clinical and molecular characterization in China.Our study is based on the children who had respiratory infections positive for RSV-A admitted by Gansu Provincial Maternity and Child-care Hospital in Lanzhou (northwestern China) during the last 7 epidemic seasons from 2010 to 2017.In our study, different strains of the novel RSV-A genotype ON1, first identified in Canada in December 2010, were first detected in Gansu Provincial Maternity and Child-care Hospital in August 2012 and then followed by an abrupt expansion in the number of ON1 variants in the beginning of 2014 and eventually replaced all other RSV-A strains from 2015 to 2017. ON1 is characterized by a 72-nt duplication in the C-terminal region of the highly variable attachment glycoprotein (G), predicted to lengthen the polypeptide with 24 amino acids, including a 23-aa duplication, which likely changes antigenicity. New N-glycosylation sites occurred within the 23-aa duplication and 24-aa insertion of the ON1 viruses in our study. Notably, RSV infections occurred later, but peaked sooner from the 2014/2015 to 2016/2017 epidemic seasons, compared with the previous 4 seasons.Our study concluded that genotype ON1 has caused larger outbreaks and became the predominate genotype for HRSV subgroup A in Lanzhou from 2013 to 2017, and became the sole genotype of RSV-A in 2015/2016 and 2016/2017. Our data indicate that northwest of China and the world will eventually be dominated by the ON1 RSV-A genotype, including the possibility for vaccine development. Based on trends seen in RSV-B BA genotype, which predominated for decades, there is a possibility to develop a vaccine for children in the next 10 years.


Assuntos
Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/genética , Pré-Escolar , China/epidemiologia , Genótipo , Humanos , Lactente , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estudos Retrospectivos
20.
Int J Mol Med ; 44(1): 79-88, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115490

RESUMO

In hepatolithiasis, chronic proliferative cholangitis (CPC), an active and longstanding inflammation of stone­containing bile ducts with enhanced mucin­producing activity, not only affects the progression of the disease, it can also induce biliary carcinogenesis. The present study aimed to examine the effect of the epidermal growth factor receptor (EGFR) monoclonal antibody panitumumab (Pani) on CPC. Following the establishment of CPC rat models, periodic acid Schiff staining was used to observe the positive rate of EGFR expression. The expression levels of EGFR, mucin 5AC (MUC5AC), Ki­67, type I collagen and mammalian target of rapamycin (mTOR), and the activity of ß­glucuronidase (ß­G), were measured. The rats treated with Pani demonstrated a significantly lower degree of hyperproliferation of the epithelium and submucosal glands of the bile duct and collagen fibers of the bile duct wall, a significantly decreased positive rate of EGFR, reduced phosphorylation of mTOR, decreased expression of EGFR, MUC5AC, Ki­67 and type I collagen, and reduced ß­G activity. The therapeutic effects in rats treated with 4 and 6 mg/kg of Pani were more marked than those in rats treated with 2 mg/kg of Pani. Collectively, the data obtained in the present study suggest that the EGFR monoclonal antibody Pani can effectively inhibit the excessive proliferation and stone­forming potential of bile duct mucosa in CPC with a receptor saturation effect. Therefore, Pani offers promise as a treatment for the prevention and control of intrahepatic choledocholithiasis caused by CPC.


Assuntos
Ductos Biliares/metabolismo , Proliferação de Células/efeitos dos fármacos , Colangite/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Receptores ErbB/biossíntese , Panitumumabe/farmacologia , Animais , Ductos Biliares/patologia , Colangite/metabolismo , Colangite/patologia , Doença Crônica , Masculino , Ratos , Ratos Sprague-Dawley
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