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1.
Blood ; 135(1): 41-55, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697823

RESUMO

To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes (NR3C1, NR3C2, TP53, NT5C2, FPGS, CREBBP, MSH2, MSH6, PMS2, WHSC1, PRPS1, and PRPS2) involved in drug response. Their prevalence was 17% in very early relapse (<9 months from diagnosis), 65% in early relapse (9-36 months), and 32% in late relapse (>36 months) groups. Convergent evolution, in which multiple subclones harbor mutations in the same drug resistance gene, was observed in 6 relapses and confirmed by single-cell sequencing in 1 case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently a 2-step process in which a persistent clone survived initial therapy and later acquired bona fide resistance mutations during therapy. In contrast, very early relapses arose from preexisting resistant clone(s). Two novel relapse-specific mutational signatures, one of which was caused by thiopurine treatment based on in vitro drug exposure experiments, were identified in early and late relapses but were absent from 2540 pan-cancer diagnosis samples and 129 non-ALL relapses. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy-induced drug resistance mutations facilitate a subset of pediatric ALL relapses.

2.
World Neurosurg ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31866456

RESUMO

BACKGROUND: Percutaneous endoscopic lumbar discectomy has been widely used to treat lumbar disc herniation; its advantages are less trauma, faster recovery, lower costs, and higher percentage of patient satisfaction compared with open surgery. Treatment of lumbar spinal stenosis with percutaneous full-endoscopic surgery is still challenging, especially for elderly patients with multiple comorbidities and complex pathologic factors. The aim of this study was to introduce percutaneous full-endoscopic lumbar foraminoplasty and decompression using a visualization reamer in elderly patients with lateral recess and foraminal stenosis and evaluate efficacy and safety. METHODS: This retrospective review comprised 65 consecutive elderly patients (30 men and 35 women) with lateral recess and foraminal stenosis who underwent percutaneous full-endoscopic lumbar foraminoplasty and discectomy from January 2017 to September 2017. Visual analog scale and Oswestry Disability Index were used to evaluate pain relief and neurologic improvement. RESULTS: Mean patient age was 71.58 years (range, 65-89 years). Mean follow-up period was 16.12 months (range, 12-20 months). Mean operative time was 98.59 minutes per level (range, 55-120 minutes). Mean intraoperative perspective frequency was 3.21 times (range, 2-6 times). Mean hospital stay after the procedure was 2.18 days (range, 1-4 days). Back and leg visual analog scale and Oswestry Disability Index scores at all time points in the postoperative period were significantly lower than preoperatively (P < 0.01). At final follow-up, modified MacNab criteria were rated as follows: excellent, 47 patients (72.31%); good, 12 patients (16.92%); fair, 3 patients (4.62%); and poor, 4 patients (6.15%). Therefore, excellent or good results were obtained in 89.23% of patients. CONCLUSIONS: Percutaneous full-endoscopic lumbar foraminoplasty and discectomy using a visualization reamer is an effective and safe treatment for elderly patients with lumbar lateral recess and foraminal stenosis. It improves safety and efficiency of decompression and reduces intraoperative fluoroscopy.

3.
Biol Pharm Bull ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31776306

RESUMO

Oxaliplatin is a first-line clinical drug in cancer treatment and its side effects of peripheral neuropathic pain have also attracted much attention. Neuroinflammation induced by oxidative stress-mediated activation of Nuclear Factor-kappa B (NF-κB) plays an important role in the course. Current studies have shown that curcumin has various biological activities like antioxidant, anti-inflammatory, antitumor and so on, while few studies were conducted about its role in oxaliplatin-induced peripheral neuropathic pain. The aim of this study is to verify the mechanism of curcumin alleviating oxaliplatin-induced peripheral neuropathic pain. Intraperitoneally injection with oxaliplatin (4 mg/kg body weight) was given to the rats twice a week and last for four weeks to establish the model rats. Gavage administration of curcumin (12.5, 25, and 50 mg/kg body weight, respectively) was conducted for consecutive 28 days to explore the effects and potential mechanism. Our results showed that curcumin administration could increase mechanical withdrawal threshold and decrease the paw-withdrawal times of cold allodynia significantly; meanwhile, motor nerve conduction velocity (MNCV) and sense nerve conduction velocity (SNCV) were both increased and the injured neurons of the spinal cord were repaired. In addition, curcumin administration increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and reduced Malondialdehyde (MDA). Moreover, the curcumin operation inhibited the activated of NF-κB and level of inflammatory factors like Tumor Necrosis Factor-α (TNF-α), Interleukin-1ß (IL-1ß) and Interleukin-6 (IL-6). In conclusion, these findings suggested that curcumin could alleviate oxaliplatin-induced peripheral neuropathic pain; the mechanism might be inhibiting oxidative stress-mediated activation of NF-κB and mitigating neuroinflammation.

4.
Polymers (Basel) ; 11(11)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694160

RESUMO

To fabricate thermoplastic polymers exhibiting improved ductility without the loss of strength, a novel multiple-step melting/irradiation (MUSMI) strategy was developed by taking poly(vinylidene fluoride)/triallyl isocyanate (PVDF/TAIC) as an example, in which alternate melting and irradiation were adopted and repeated for several times. The initial irradiation with a low dose produced some local crosslinked points (not 3-dimensional network). When the specimen was reheated above the melting temperature, they redistributed in the PVDF matrix, which is an efficient way to avoid the high crosslinking density at certain positions and the disappearance of thermoplastic properties. During the subsequent cooling process, the crosslinked domains in the thermoplastic polymer matrix is expected to play double roles in turning crystal structures for enhancing the ductility without reducing strength. On one hand, they can act as heterogeneous nucleation agents, resulting in higher nucleation density and smaller spherulites; on the other hand, the existence of crosslinked structures restricts the lamellar thickening, accounting for the thinner crystal lamellae. Both smaller spherulites and thinner lamellae contribute to better ductility. At the same time, these local crosslinked points enhance the connectivity of crystal structures (including lamellae and spherulites), which is beneficial to the improvement of strength. Based on the influence of local crosslinked points on the ductility and strength, thermoplastic PVDF with much higher elongation at break and comparable yielding stress (relative to the reference specimen upon strong irradiation only once) was prepared via MUSMI successfully.

5.
BMC Infect Dis ; 19(1): 910, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664944

RESUMO

BACKGROUND: On September 4, 2018, a boarding school in the Shunyi District of Beijing, China reported an outbreak of acute gastroenteritis. At least 209 suspected students caused of diarrhea and vomiting. The case was investigated, and control measures were taken to prevent further spread. METHODS: A retrospective cohort study was conducted among the school students and staff in order to test hypothesis that high risk of food served at the school canteen. We collected information on demographics, refectory records, person to person transmission by uniform epidemiological questionnaire. Risk ratios (RR) and 95% confidence intervals (CI) were calculated. Stool specimens of cases and canteen employees, retained food, water, and environmental swabs were investigated by laboratory analysis. RESULTS: We identified 209 cases (including 28 laboratory-confirmed cases) which occurred from August 29 to September 10. All cases were students, and the average age was 20, 52% were male. The outbreak lasted for 13 days, and peaked on September 5. Consumption of Drinks stall and Rice flour stall on September 1 (RR:3.4, 95%CI:1.5-7.8, and RR:7.6, 95%CI:2.8-20.2), Rice flour stall and Fish meal stall on September 2 (RR:4.0, 95%CI:1.2-13.6, and RR:4.6, 95%CI:1.7-12.5), muslim meal stall on September 4 (RR:2.7, 95%CI:1.3-5.4), Barbeque stall on September 5 (RR:3.0, 95%CI:1.2-7.0) were independently associated with increased risk of disease within the following 2 days. Among 35 specimens of rectal swabs or feces from students, 28 specimens were positive. Norovirus GI.6 alone was detected in 23 specimens, Bacillus cereus alone in 3 specimens and both norovirus GI.6 and Bacillus cereus in 2 specimens. Ten specimens of rectal swabs from canteen employees were positive for norovirus GI, and 2 specimens were positive for Bacillus cereus. Four retained food specimens were positive for Bacillus cereus, and environmental samples were negative for any viruses or bacteria. CONCLUSION: Our investigation indicated that canteen employees were infected by two pathogens (norovirus and Bacillus cereus) and transmission may have been possible due to unhygienic practices. Student consumption of food or drink at high-risk stalls was determined as the probable cause of the outbreak.


Assuntos
Bacillus cereus/isolamento & purificação , Infecções por Caliciviridae/epidemiologia , Surtos de Doenças , Doenças Transmitidas por Alimentos/microbiologia , Gastroenterite/epidemiologia , Norovirus/isolamento & purificação , Adolescente , Pequim/epidemiologia , Infecções por Caliciviridae/complicações , Diarreia/complicações , Fezes/microbiologia , Fezes/virologia , Feminino , Contaminação de Alimentos , Doenças Transmitidas por Alimentos/virologia , Gastroenterite/complicações , Higiene das Mãos , Humanos , Masculino , Razão de Chances , Estudos Retrospectivos , Inquéritos e Questionários , Universidades , Vômito/complicações , Adulto Jovem
6.
Clin Transl Sci ; 12(6): 641-647, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31350825

RESUMO

Fms-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations, common in pediatric acute myeloid leukemia (AML), associate with early relapse and poor prognosis. Past studies have suggested additional cooperative mutations are required for leukemogenesis in FLT3-ITD+ AML. Using RNA sequencing and a next-generation targeted gene panel, we broadly characterize the co-occurring genomic alterations in pediatric cytogenetically normal (CN) FLT3-ITD+ AML to gain a deeper understanding of the clonal patterns and heterogeneity at diagnosis and relapse. We show that chimeric transcripts were present in 21 of 34 (62%) of de novo samples, 2 (6%) of these samples included a rare reoccurring fusion partner BCL11B. At diagnosis, the median number of mutations other than FLT3 per patient was 1 (range 0-3), which involved 8 gene pathways; WT1 and NPM1 mutations were frequently observed (35% and 24%, respectively). Fusion transcripts and high variant allele frequency (VAF) mutants, which included WT1, NPM1, SMARCA2, RAD21, and TYK2, were retained from diagnosis to relapse. We did observe reduction in VAF of simple or single mutation clones, but VAFs were preserved or expanded in more complex clones with multiple mutations. Our data provide the first insight into the genomic complexity of pediatric CN FLT3-ITD+ AML and could help stratify future targeted treatment strategies.

7.
Sci Transl Med ; 11(498)2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243155

RESUMO

Cancer arises from the accumulation of genetic alterations, which can lead to the production of mutant proteins not expressed by normal cells. These mutant proteins can be processed and presented on the cell surface by major histocompatibility complex molecules as neoepitopes, allowing CD8+ T cells to mount responses against them. For solid tumors, only an average 2% of neoepitopes predicted by algorithms have detectable endogenous antitumor T cell responses. This suggests that low mutation burden tumors, which include many pediatric tumors, are poorly immunogenic. Here, we report that pediatric patients with acute lymphoblastic leukemia (ALL) have tumor-associated neoepitope-specific CD8+ T cells, responding to 86% of tested neoantigens and recognizing 68% of the tested neoepitopes. These responses include a public neoantigen from the ETV6-RUNX1 fusion that is targeted in seven of nine tested patients. We characterized phenotypic and transcriptional profiles of CD8+ tumor-infiltrating lymphocytes (TILs) at the single-cell level and found a heterogeneous population that included highly functional effectors. Moreover, we observed immunodominance hierarchies among the CD8+ TILs restricted to one or two putative neoepitopes. Our results indicate that robust antitumor immune responses are induced in pediatric ALL despite their low mutation burdens and emphasize the importance of immunodominance in shaping cellular immune responses. Furthermore, these data suggest that pediatric cancers may be amenable to immunotherapies aimed at enhancing immune recognition of tumor-specific neoantigens.

8.
Nat Commun ; 10(1): 2789, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243274

RESUMO

IGH@ proto-oncogene translocation is a common oncogenic event in lymphoid lineage cancers such as B-ALL, lymphoma and multiple myeloma. Here, to investigate the interplay between IGH@ proto-oncogene translocation and IGH allelic exclusion, we perform long-read whole-genome and transcriptome sequencing along with epigenetic and 3D genome profiling of Nalm6, an IGH-DUX4 positive B-ALL cell line. We detect significant allelic imbalance on the wild-type over the IGH-DUX4 haplotype in expression and epigenetic data, showing IGH-DUX4 translocation occurs on the silenced IGH allele. In vitro, this reduces the oncogenic stress of DUX4 high-level expression. Moreover, patient samples of IGH-DUX4 B-ALL have similar expression profile and IGH breakpoints as Nalm6, suggesting a common mechanism to allow optimal dosage of non-toxic DUX4 expression.


Assuntos
Proteínas de Homeodomínio/metabolismo , Cadeias Pesadas de Imunoglobulinas/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Animais , Apoptose , DNA/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Genômica , Histonas , Humanos , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Sequenciamento Completo do Genoma
9.
J Nanosci Nanotechnol ; 19(9): 5790-5795, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30961740

RESUMO

A facile solution combustion and gel calcination process for the preparation of magnetic MnFe²O4 nanoparticles was introduced. The experimental results showed that the volume of absolute alcohol and the calcination temperature were two key factors to grain size, crystallinity and magnetic properties of MnFe²O4 nanoparticles. With the volume of absolute alcohol increasing from 15 to 100 mL, the average grain size of MnFe²O4 nanoparticles calcined at 400 °C for 2 h increased from 13.4 nm to 36.0 nm, and the saturation magnetization (Ms) value of MnFe²O4 nanoparticles increased from 1.2 emu/g to 105.5 emu/g; while, with the calcination temperature increasing from 400 °C to 800 °C, the average grain size increased from 13.4 nm to 32.9 nm, and the saturation magnetization value increased from 1.2 emu/g to 15.3 emu/g. The specific surface area of MnFe²O4 nanoparticles calcined at 400 °C for 2 h with absolute alcohol of 30 mL was measured, which was large of 49.6 m²/g.

10.
Nat Genet ; 51(4): 694-704, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30926971

RESUMO

Acute erythroid leukemia (AEL) is a high-risk leukemia of poorly understood genetic basis, with controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic features of 159 childhood and adult AEL cases with non-AEL myeloid disorders and defined five age-related subgroups with distinct transcriptional profiles: adult, TP53 mutated; NPM1 mutated; KMT2A mutated/rearranged; adult, DDX41 mutated; and pediatric, NUP98 rearranged. Genomic features influenced outcome, with NPM1 mutations and HOXB9 overexpression being associated with a favorable prognosis and TP53, FLT3 or RB1 alterations associated with poor survival. Targetable signaling mutations were present in 45% of cases and included recurrent mutations of ALK and NTRK1, the latter of which drives erythroid leukemogenesis sensitive to TRK inhibition. This genomic landscape of AEL provides the framework for accurate diagnosis and risk stratification of this disease, and the rationale for testing targeted therapies in this high-risk leukemia.


Assuntos
Leucemia Eritroblástica Aguda/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Genômica/métodos , Proteínas de Homeodomínio/genética , Humanos , Lactente , Recém-Nascido , Masculino , Mutação/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas Nucleares/genética , Prognóstico , Proteína Supressora de Tumor p53/genética , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genética
11.
Genome Biol ; 20(1): 50, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30867008

RESUMO

BACKGROUND: Sequencing errors are key confounding factors for detecting low-frequency genetic variants that are important for cancer molecular diagnosis, treatment, and surveillance using deep next-generation sequencing (NGS). However, there is a lack of comprehensive understanding of errors introduced at various steps of a conventional NGS workflow, such as sample handling, library preparation, PCR enrichment, and sequencing. In this study, we use current NGS technology to systematically investigate these questions. RESULTS: By evaluating read-specific error distributions, we discover that the substitution error rate can be computationally suppressed to 10-5 to 10-4, which is 10- to 100-fold lower than generally considered achievable (10-3) in the current literature. We then quantify substitution errors attributable to sample handling, library preparation, enrichment PCR, and sequencing by using multiple deep sequencing datasets. We find that error rates differ by nucleotide substitution types, ranging from 10-5 for A>C/T>G, C>A/G>T, and C>G/G>C changes to 10-4 for A>G/T>C changes. Furthermore, C>T/G>A errors exhibit strong sequence context dependency, sample-specific effects dominate elevated C>A/G>T errors, and target-enrichment PCR led to ~ 6-fold increase of overall error rate. We also find that more than 70% of hotspot variants can be detected at 0.1 ~ 0.01% frequency with the current NGS technology by applying in silico error suppression. CONCLUSIONS: We present the first comprehensive analysis of sequencing error sources in conventional NGS workflows. The error profiles revealed by our study highlight new directions for further improving NGS analysis accuracy both experimentally and computationally, ultimately enhancing the precision of deep sequencing.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/normas , Neoplasias/genética , Reação em Cadeia da Polimerase/normas , Análise de Sequência de DNA/normas , Software , Estudos de Casos e Controles , Humanos , Mutação , Controle de Qualidade
12.
Nanomaterials (Basel) ; 9(2)2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30764561

RESUMO

Polyoxymethylene (POM) blends with excellent stiffness⁻toughness balance are successfully developed using Tributyl(octyl)phosphonium bis(trifloromethanesulfonyl) imide (TBOP-TFSI), one type of room-temperature ionic liquid, as the nucleating agent. Crystallization behaviors of POM blends have been studied by differential scanning calorimetry (DSC) and polarized light microscopy (PLM). The incorporation of TBOP-TFSI induces the crystal nucleation and fine crystal grain of POM, and also a much shorter hemi-crystalline time with only 0.5 wt% addition. The nucleation effect of ionic liquid leads to considerable improvement in the impact strength of POM blends while not sacrificing its tensile strength. Moreover, antistatic properties with a long-time stable performance are achieved by TBOP-TFSI addition as the electrical resistance reaches 1011 Ω/sq.

13.
World Neurosurg ; 2019 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-30648610

RESUMO

PURPOSE: Cervical stenosis with myelopathy caused by ossification of the ligamentum flavum is relatively rare, and surgical treatment is the preferred option. Previous surgical procedures usually require assisted internal fixation, while some problems may occur, such as large trauma, intraoperative bleeding, wound infection and internal fixation failure. The aim of this paper is to introduce a new minimally invasive surgical procedure for the treatment of upper cervical spinal stenosis complicated with myelopathy. METHODS AND RESULTS: A 56-year-old male patient with cervical myelopathy (C2-3) caused by calcification of the ligamentum flavum underwent posterior percutaneous full-endoscopic cervical laminectomy and decompression (PECLD) and achieved a good clinical efficacy. A surgical incision just 1 cm in size was made, and there was little bleeding during the operation. The patient was hospitalized for 2 days and returned to work after 4 weeks. The patient's postoperative recovery of neurological function was significantly improved, the pain was obviously reduced, and the quality of life was remarkably improved. No intra- or postoperative surgical complications were encountered. CONCLUSIONS: PECLD is an effective method for treating cervical stenosis associated with myelopathy due to ossification of the ligamentum flavum. It has the advantages of smaller trauma, less bleeding, shorter postoperative hospital stays and faster recovery. Taken together, this minimally technique can be considered as a good alternative to traditional open surgery.

14.
ACS Appl Mater Interfaces ; 11(5): 5462-5475, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30640429

RESUMO

Ion-containing polymers are of great importance for its unique structure and properties. An ion-containing polyamide 6 (PA6) was prepared by grafting an ionic liquid, 1-vinyl-3-butyl imidazole chloride [VBIM][Cl], onto the main chain of PA6 using radiation-induced grafting. The grafted ions on the PA6 main chain significantly influenced the structure and properties of the PA6 matrix. The ions form nanoscale aggregations without inducing further microphase separation. Acting as a physical "cross-linking point," each aggregation enhanced inter/intrachain interactions, which increased the viscosity, storage modulus, and relaxation time and reduced the ability of PA6 to crystallize. However, the bulky cations of the grafted ionic liquid can also be seen as "spacers," which enlarge the distance among chains and reduce the strength of the hydrogen bonds inherently existing in the PA6 matrix. The "cross-linking points" and "spacers" of ions as well as the hydrogen bonds of PA6 take effect collectively in the system. Moreover, the ion-containing PA6 retains good melt processability compared with PA6, despite increased viscosity, and can be easily melt-spun into fibers. Fibers prepared from ion-containing PA6 showed improved mechanical properties and antistatic performance and exhibited the expected antibacterial properties, especially with regard to Escherichia coli. Inspiringly, covalently bonding ions to the PA6 main chain offers a new strategy for fabricating functional fibers with permanent antistatic and antibacterial properties.

15.
J Int Med Res ; 47(2): 915-925, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30616417

RESUMO

OBJECTIVE: This study was performed to assess the influence of obesity on colorectal cancer (CRC) and investigate the efficacy of Xiaotan Tongfu (XTTF) decoction to CRC treatment. METHODS: BALB/C mice were used to establish an obesity-associated CRC model by a high-fat diet and tumor implantation. The tumors were harvested from mice inoculated with CT26 cell suspension. Body weight, liver weight, hepatic metastasis, and histological changes were observed. Immunohistochemical analysis and real-time polymerase chain reaction were performed to measure the levels of insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), and IGF binding protein 3 (IGFBP-3). RESULTS: Obesity influenced the secretion of IGFs and aggravated CRC, while XTTF decoction inhibited the process of hepatic metastasis in CRC by upregulating the secretion of IGF-1/IGF-1R and downregulating the secretion of IGFBP-3. CONCLUSIONS: This study provides evidence that XTTF decoction can serve as a candidate curative treatment for CRC.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Obesidade/complicações , Animais , Apoptose , Proliferação de Células , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Receptor IGF Tipo 1/metabolismo , Células Tumorais Cultivadas
16.
Inorg Chem ; 57(24): 15361-15369, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30480436

RESUMO

Luminescence efficiency of trivalent lanthanide-doped upconversion (UC) materials is significantly limited by luminescence concentration quenching. In this work, red UC emission is dramatically enhanced in Er3+-sensitized NaLuF4 UC crystals through energy trapping under multiple excitation wavelengths. Cross-relaxation quenching and the energy migration to internal lattice defects are simultaneously suppressed by confining the excitation energy in the Er3+ activator after introducing the Tm3+ or Ho3+ energy trapping center. The enhanced red UC emission (Er3+: 660 nm) mainly comes from the effective excitation energy confinement by Tm3+ and Ho3+ trapping centers through an easy energy transfer between Er3+ and Tm3+/Ho3+: 4I11/2 (Er3+) → 3H5 (Tm3+) → 4I13/2 (Er3+) and 4I11/2 (Er3+) → 5I6 (Ho3+) → 4I13/2 (Er3+). It is found that the confining efficiency of excitation energy in Er3+-sensitized NaLuF4 crystals is higher than that in Yb3+/Er3+ cosensitized NaLuF4 crystals, and the luminescence efficiency of Er3+-sensitized NaLuF4 crystals is much higher than that of Er3+-based host sensitization UC crystals (NaErF4). Moreover, Er3+-sensitized UC particles can be efficiently excited by three different wavelengths (808, 980, and 1532 nm), indicating huge advantages for applications in bioimaging, anticounterfeiting, and solar cells.

17.
Nat Commun ; 9(1): 3962, 2018 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262806

RESUMO

To evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97-99, 99, and 91% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.


Assuntos
Exoma/genética , Genoma Humano , Genômica , Neoplasias/genética , Análise de Sequência de DNA , Transcriptoma/genética , Criança , Variação Genética , Humanos
18.
Biomed Pharmacother ; 108: 95-102, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30218863

RESUMO

In recent years, Chinese medicine has played an important role in the prognosis of gastric cancer. Precancerous lesions of gastric carcinoma (PLGC) is a class of gastric cancer which is closely related to the gastric mucosal pathology changes in the role of carcinogenic incentives, and plays key role in the progression of normal gastric mucosal cells into gastric cancerous cells. In current experiment, we explore the relationship between Chinese traditional medicine (Xiao Tan He Wei Decoction) and gastric cancer in the PLGC rat animal models and epithelial-mesenchymal transitioned GES-1 cells which were induced useing 1- Methyl-3-nitro-1-nitrosoguanidine (MNNG). PLGC rat model showed significant deterioration in the gastric mucosa with terrible growth rate in body weight and more atypical hyperplasia in gastric mucosa. MC cells, MNNG induced GES-1 cells which epithelial- mesenchymal-transition (EMT)-related proteins have a great change compare with normal GES-1 cells. The cells had characteristics of malignant cells including proliferation, invasion and metastasis ability. Our research founds that Xiao Tan He Wei Decoction could inhibit cell proliferation and increased apoptosis by increase the level of pro-apoptotic proteins like Bax and caspase-3 and decreased the level of anti-apoptotic protein Bcl-2, block the cells in G0/G1 phase simultaneously. Furthermore, Xiao Tan He Wei Decoction could inhibit nuclear factor kappa-light-chain-enhancer (NF-kB) activity and inhibit its transfer from the cytoplasm to the nucleus. However, when we incubated with NF-κB activator PMA, the effect of Xiao Tan He Wei Decoction was reversed. These results suggested that Xiao Tan He Wei Decoction could be used as a method for the treatment of gastric precancerous lesions, and possibly provide a theoretical basis for the clinical treatment of gastric cancer and gastric precancerous lesions.


Assuntos
Apoptose , Medicamentos de Ervas Chinesas/uso terapêutico , NF-kappa B/metabolismo , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/patologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Hiperplasia , Metilnitronitrosoguanidina , Ratos Wistar , Acetato de Tetradecanoilforbol/farmacologia
19.
J Orthop Surg Res ; 13(1): 169, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29976224

RESUMO

BACKGROUND: The open microdiscectomy is the most common surgical procedure for the decompression of radiculopathy caused by lumbar disk herniation. To date, a variety of minimally invasive (MI) techniques have been developed. In the last decades, endoscopic techniques have been developed to perform discectomy. The transforaminal endoscopic discectomy (TED) with posterolateral access evolved out of the development of endoscopic techniques. METHODS: A systematic literature search was performed using the PubMed, EMBASE, and Cochrane Library databases for trials written in English. The randomized trials and observational studies that met our inclusion criteria were subsequently included. Two reviewers respectively extracted data and estimated the risk of bias. All statistical analyses were performed using Review Manager 5.3. RESULTS: Five prospective and four retrospective studies involving 1527 patients were included. The results of the meta-analysis indicated that there were significant differences between the two groups in length of hospital stay (MD = - 8.41, 95% CI - 10.26, - 6.56; p value < 0.00001). However, there were no significant differences in the leg visual analog scale (VAS) scores, the Oswestry Disability Index (ODI) scores, and the incidence of complications and recurrence. CONCLUSIONS: The transforaminal endoscopic discectomy is superior to open microdiscectomy in the length of hospital stay. However, there were no differences in leg pain, functional recovery, and incidence of complications between TED and MD in treating LDH.


Assuntos
Discotomia/métodos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Descompressão Cirúrgica , Endoscopia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
20.
ACS Appl Mater Interfaces ; 10(10): 8411-8416, 2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29488745

RESUMO

Physically anchoring carbon nanotubes (CNTs) onto the interface of immiscible polymer blends has been extensively reported; however, enhancement of physical properties of the blends has seldom been achieved. Herein, we used CNTs with reactive epoxide groups and long poly(methyl methacrylate) (PMMA) tails as a thermodynamic compatibilizer for immiscible poly vinylidene fluoride/poly l-lactide (PVDF/PLLA) blends. The CNTs acted as an efficient compatibilizer and bridged the two phases through physical entanglement and chemical reaction. The sea-island structure of the blend transformed into a bicontinuous structure for CNT contents greater than 3 wt %. The mechanical properties, including ductility and tensile strength, thermal properties, and electrical conductivities were all enhanced by the CNTs compatibilizer. This strategy thermodynamically compatibilized by reactive nanofillers paves the way for advanced blend nanocomposites.

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