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1.
Curr Neurovasc Res ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34636310

RESUMO

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is a contributing factor for neurodegenerative diseases. As a recently identified heptapeptide of the brain renin-angiotensin system, angiotensin-(1-7) was revealed to activate its receptor MAS1 and thus ameliorated cognitive impairments in rats with CCH. Since hippocampal synaptic degeneration represents an important pathological basis of cognitive deficits, we hypothesize that activation of MAS1-mediated signaling may alleviate CCH-induced synaptic degeneration in the hippocampus. METHODS: In this study, we tested this hypothesis and uncovered the underlying mechanisms in a rat model of CCH induced by bilateral common carotid artery ligation surgery. At 1 week after the surgery, rats received a daily intraperitoneal injection of vehicle or a non-peptidic MAS1 agonist AVE0991 for 8 weeks. During this procedure, cerebral blood flow (CBF) was recorded. The levels of MAS1, amyloid-ß (Aß), neuroinflammatory cytokines, glial cell markers and synaptophysin in the hippocampus were assessed at the end of the treatment period. RESULTS: We showed that AVE0991 significantly alleviated hippocampal synaptic degeneration in rats with CCH. This protection might be achieved by facilitating CBF recovery, reducing hippocampal Aß levels and suppressing neuroinflammatory responses. CONCLUSIONS: These findings indicate that MAS1-mediated signaling may represent a novel therapeutic target for CCH-related neurodegenerative diseases.

2.
Beilstein J Org Chem ; 17: 2505-2510, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646399

RESUMO

A base- and catalyst-free C(sp3)-H allylic alkylation of 2-alkylpyridines with Morita-Baylis-Hillman (MBH) carbonates is described. A plausible mechanism of the reaction might involve a tandem SN2' type nucleophilic substitution followed by an aza-Cope rearrangement. Various alkyl substituents on 2-alkylpyridines were tolerated in the reaction to give the allylation products in 26-91% yields. The developed method provides a straightforward and operational simple strategy for the allylic functionalization of 2-alkypyridine derivatives.

3.
Radiother Oncol ; 164: 163-166, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34619235

RESUMO

We assessed the impact of different PCI fractionation schedules (30 Gy in 10 versus 15 fractions) on brain metastases-free survival (BMFS) and toxicity in stage III NSCLC. Our results suggest that 30 Gy in 10 fractions is associated with increased toxicity, while no conclusive evidence of improving BMFS was seen with this schedule.

4.
BMC Microbiol ; 21(1): 283, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663233

RESUMO

BACKGROUND: The widespread use of shared bicycles has increased the demand and sanitary requirements for shared bicycles. Previous studies have identified potentially pathogenic bacteria on the surfaces of shared bicycles, but fungal communities have not been investigated. METHODS: We sampled shared-bicycle handles and saddles from five selected locations in a metropolis (Chengdu, China, n = 98) and used surrounding air deposition samples as controls (n = 12). Full-length ITS sequencing and multiple bioinformatic analyses were utilized to reveal fungal community structures and differences. RESULTS: Aspergillus was dominant on both the handles and saddles of shared bicycles, and Alternaria and Cladosporium were the most abundant families in the air samples. Significant differences in fungal community structures were found among the three groups. The handle samples contained higher abundances of Aureobasidium melanogenum and Filobasidium magnum than the saddle and air samples. The saddle samples had a higher abundance of Cladosporium tenuissimum than the other two sample types (P < 0·05). A higher abundance of fungal animal pathogens on shared-bicycle surfaces than in air by FUNGuild (P < 0·05). Moreover, the co-occurrence network of fungi on handles was more stable than that on saddles. CONCLUSION: There were more potential pathogens, including Aspergillus pseudoglaucus, Aureobasidium melanogenum, Kazachstania pintolopesii, Filobasidium magnum, Candida tropicalis, and Malassezia globose were found on shared bicycles than in air, suggesting that hands should not contact mucous membrane after cycling, especially in susceptible individuals, and hygiene management of shared bicycles should be given more attention by relevant organizations worldwide.

5.
Plant Physiol ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34618054

RESUMO

Measuring leaf area index (LAI) is essential for evaluating crop growth and estimating yield, thereby facilitating high-throughput phenotyping of maize (Zea mays). LAI estimation models use multi-source data from unmanned aerial vehicles (UAVs), but using multimodal data to estimate maize LAI, and the effect of tassels and soil background, remain understudied. Our research aims to (1) determine how multimodal data contribute to LAI and propose a framework for estimating LAI based on remote-sensing data, (2) evaluate the robustness and adaptability of an LAI estimation model that uses multimodal data fusion and deep neural networks (DNNs) in single- and whole growth stages, and (3) explore how soil background and maize tasseling affect LAI estimation. To construct multimodal datasets, our UAV collected red-green-blue, multispectral, and thermal infrared images. We then developed partial least square regression (PLSR), support vector regression, and random forest regression models to estimate LAI. We also developed a deep learning model with three hidden layers. This multimodal data structure accurately estimated maize LAI. The DNN model provided the best estimate (coefficient of determination [R2] = 0.89, relative root mean square error [rRMSE] = 12.92%) for a single growth period, and the PLSR model provided the best estimate (R2 = 0.70, rRMSE = 12.78%) for a whole growth period. Tassels reduced the accuracy of LAI estimation, but the soil background provided additional image feature information, improving accuracy. These results indicate that multimodal data fusion using low-cost UAVs and DNNs can accurately and reliably estimate LAI for crops, which is valuable for high-throughput phenotyping and high-spatial precision farmland management.

6.
Sci Total Environ ; 805: 150266, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34536864

RESUMO

Potentially toxic element (PTE) pollution is widespread in road dust across China, and the effects of PTEs in road dust on health cannot be ignored. In this study, the concentrations of six PTEs (Pb, Cd, Cr, Cu, Zn and Ni) in 4336 road dust samples from 58 cities in 31 provincial regions of China taken after 2000 were obtained from the literatures. Based on these data, the spatial distribution, pollution sources, and ecological and human health risks of PTEs in road dust were comprehensively assessed and the main pollution factors and areas of high risk were identified. The results revealed that PTE levels are generally higher in eastern cities than western cities in China. The key driving factors are socioeconomic factors, including those related to transportation, industry, and population, for which the contribution rates are 57.80%, 55.39% and 37.19%, respectively. PTEs in the road dust with high ecological risks are mainly distributed in the southeastern coastal areas and the Beijing-Tianjin-Hebei region. No obvious noncarcinogenic risk was found for PTEs in road dust, but Cd and Pb may have potential noncarcinogenic risk, mainly distributed in cities in western China. Therefore, regions and pollution sources contributing to Pb and Cd levels should be monitored. The control of PTE pollution in China is a priority for ecological and environmental protection.

7.
Abdom Radiol (NY) ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34549331

RESUMO

PURPOSE: To characterize and investigate PET/CT findings in the omentum in the differentiation of tuberculous peritonitis (TBP) and peritoneal carcinoma (PC). METHODS: Thirty-nine patients with TBP and 113 patients with PC who underwent PET/CT were retrospectively enrolled. The omental uptake intensity, distribution characteristics, contracture, size and boundary of soft-tissue lesions, and CT patterns were reviewed. RESULTS: Absent and focal FDG uptake in the lesser omentum was more common in the PC patients (P = 0.034 and P = 0.017, respectively), and diffuse FDG uptake in the lesser omentum was more common in the TBP patients (P < 0.001). An apron-like pattern in the greater omentum commonly occurred in the TBP patients (P = 0.004). Micronodules (< 5 mm) were more common in the TBP patients (P < 0.001), and masses (> 3 cm) were more common in the PC patients (P = 0.001). Smudged and nodular patterns occurred more frequently in the TBP patients than in the PC patients (P < 0.001 and P = 0.003, respectively), and the caked pattern occurred more frequently in the PC patients (P < 0.001). There was no significant difference in the FDG uptake intensity and the boundary of soft-tissue lesions between the TBP and PC patients (P = 0.191 and P = 0.061, respectively). CONCLUSION: Diffuse FDG uptake, an apron-like pattern, micronodules, and a smudged and nodular pattern might be significant differential features of TBP. Absent and/or focal FDG uptake, mass, and a caked pattern might be significant differential features of PC.

8.
Nanoscale ; 13(34): 14417-14425, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473184

RESUMO

The recurrence and metastasis of tumor after surgery is the main cause of death for patients with breast cancer. Systemic chemotherapy suffered from low delivery efficiency to tumors and the side effects of chemo drugs. Localized chemotherapy using drug-containing implants is an alternative, while the reconstruction of breast tissue is generally considered after chemotherapy, resulting in a second surgery for patients. Here, we describe a strategy using implantable drug-containing polymeric scaffolds to deliver chemo drugs directly to the post-resection site, and simultaneously provide mechanical support and regenerative niche for breast tissue reconstruction. When doxorubicin was loaded in mesoporous silica nanoparticles and subsequently incorporated into polycaprolactone scaffolds (DMSN@PCL), a 9-week sustained drug release was achieved post implantation in mice. The local recurrence of residual tumor after surgery was significantly inhibited within 4 weeks in a post-surgical mouse model bearing xenograft MDA-MB-231 tumor. DMSN@PCL scaffolds exhibited good biocompatibility in mice during the treatment. We believe our strategy holds great promise as an adjuvant localized chemotherapy in clinics for combating post-resection breast cancer recurrence.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Feminino , Humanos , Camundongos , Poliésteres
10.
Nat Commun ; 12(1): 5431, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521849

RESUMO

Small cell lung cancer (SCLC) is a highly malignant tumor which is eventually refractory to any treatment. Intratumoral heterogeneity (ITH) may contribute to treatment failure. However, the extent of ITH in SCLC is still largely unknown. Here, we subject 120 tumor samples from 40 stage I-III SCLC patients to multi-regional whole-exome sequencing. The most common mutant genes are TP53 (88%) and RB1 (72%). We observe a medium level of mutational heterogeneity (0.30, range 0.0~0.98) and tumor mutational burden (TMB, 10.2 mutations/Mb, range 1.1~51.7). Our SCLC samples also exhibit somatic copy number variation (CNV) across all patients, with an average CNV ITH of 0.49 (range 0.02~0.99). In terms of mutation distribution, ITH, TMB, mutation clusters, and gene signatures, patients with combined SCLC behave roughly the same way as patients with pure SCLC. This condition also exists in smoking patients and patients with EGFR mutations. A higher TMB per cluster is associated with better disease-free survival while single-nucleotide variant ITH is linked to worse overall survival, and therefore these features may be used as prognostic biomarkers for SCLC. Together, these findings demonstrate the intratumoral genetic heterogeneity of surgically resected SCLC and provide insights into resistance to treatment.


Assuntos
Heterogeneidade Genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Proteínas de Ligação a Retinoblastoma/genética , Carcinoma de Pequenas Células do Pulmão/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Variações do Número de Cópias de DNA , Receptores ErbB/genética , Receptores ErbB/metabolismo , Exoma , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Proteínas de Ligação a Retinoblastoma/metabolismo , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/cirurgia , Fumar/fisiopatologia , Análise de Sobrevida , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
11.
Nat Commun ; 12(1): 5328, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493725

RESUMO

Aliphatic esters are essential constituents of biologically active compounds and versatile chemical intermediates for the synthesis of drugs. However, their preparation from readily available olefins remains challenging. Here, we report a strategy to access aliphatic esters from olefins through a photocatalyzed alkoxycarbonylation reaction. Alkyloxalyl chlorides, generated in situ from the corresponding alcohols and oxalyl chloride, are engaged as alkoxycarbonyl radical fragments under photoredox catalysis. This transformation tolerates a broad scope of electron-rich and electron-deficient olefins and provides the corresponding ß-chloro esters in good yields. Additionally, a formal ß-selective alkene alkoxycarbonylation is developed. Moreover, a variety of oxindole-3-acetates and furoindolines are prepared in good to excellent yields. A more concise formal synthesis of (±)-physovenine is accomplished as well. With these strategies, a wide range of natural-product-derived olefins and alkyloxalyl chlorides are also successfully employed.


Assuntos
Alcenos/química , Técnicas de Química Sintética , Ésteres/química , Indóis/síntese química , Oxindóis/síntese química , Álcoois/química , Catálise , Cloretos/química , Humanos , Estrutura Molecular , Oxalatos/química , Oxirredução , Processos Fotoquímicos , Fisostigmina/análogos & derivados , Fisostigmina/síntese química , Estereoisomerismo
12.
Mol Genet Genomic Med ; : e1802, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480426

RESUMO

BACKGROUND: Fetal cardiac rhabdomyoma (CR) is strongly associated with tuberous sclerosis complex (TSC), which is caused by variants in TSC1 and TSC2. However, in 10%-15% of patients with clinically confirmed TSC, no TSC1/TSC2 variants are identified by panel sequencing or multiplex ligation-dependent probe amplification (MLPA). METHODS: We analyzed eight fetuses with CR and their families. No TSC1/TSC2 variants had previously been identified for six of these fetuses, and we suspected the other two families of gonadal mosaicism. We performed next-generation sequencing (NGS) using CR tissue, umbilical cord tissue, and parental blood. All positive results, involving two paternal semen, were verified by droplet digital polymerase chain reaction (ddPCR). RESULTS: Four fetuses carried low-level mosaic variants (0.05%-14.89%), and two only exhibited somatic mosaic variants in the CR tissue (15.76% and 37.69%). Two fathers had gonadal mosaicism (9.07% and 4.86%). We identified nine pathogenic variants in eight fetuses, including one fetus with a second-hit variant. CONCLUSION: The fetuses assessed in this study carried low-level and somatic mosaic variants, and CR tissue from one fetus exhibited a second-hit variant. Heterozygous gonadal variants can exist in patients with low-level mosaicism. Combining NGS with ddPCR improves the accuracy of prenatal TSC diagnosis.

13.
Chemosphere ; 287(Pt 2): 132060, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34507145

RESUMO

Freshwater resilience is facing to an increasing challenge, while carbon neutral wastewater reclamation has been put onto agenda in more and more countries. The activated sludge-microfiltration (MF)-reverse osmosis (RO) process has been currently adopted for reclamation of municipal wastewater to high-grade product water (e.g. NEWater). However, the conventional activated sludge (CAS) unit in this process has the drawbacks of excessive sludge generation, high energy consumption, greenhouse gases (GHGs) emissions etc. To address these emerging issues, an integrated anaerobic fixed-film membrane bioreactor (AnfMBR)-RO-chlorination process was developed in this study. Results showed that about 99.9% of COD, 99.3% of phosphate and 95.3% of NH4+-N were removed in the AnfMBR-RO process, while breakpoint chlorination served as a polishing step when the NH4+-N concentration in RO permeate exceeded the typical NH4+-N concentration (e.g. 1 mg/L) of NEWater. The net energy consumption and total GHG emissions in the proposed integrated process were estimated to be 0.33 kWh/m3 and 310.2 g CO2e/m3 influent wastewater treated, respectively, which were 64% and 74% less than those in the current municipal wastewater reclamation process. Consequently, this study offers an alternative path to bring municipal wastewater reclamation one step closer to carbon neutrality and water sustainability.

14.
Phytomedicine ; 91: 153700, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34425474

RESUMO

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a standard therapy to treat hepatocellular carcinoma (HCC), but often limited for its complications. Ginsenosides, including total ginsenosides (GS), Rg3, Rh2 and CK, have been clinically used as adjuvants of TACE in HCC therapy. However, partial clinical observations concerning the efficacy and safety of the combinational treatment were contradictory. PURPOSE: To investigate the efficacy and safety of TACE and ginsenosides combination for HCC therapy. METHODS: Randomized controlled trials (RCTs) regarding TACE and ginsenosides for HCC up to May 2021 were screened from six databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information and Web of Science). The outcomes of tumor response, adverse reactions (ADRs), quality of life (QOL), survival rates (OS) and liver function were extracted and evaluated by meta-analysis, respectively. RESULTS: A total of 18 RCTs with 1308 HCC patients were enrolled, and most of the eligible studies had unclear bias risk. Compared with TACE, combining ginsenosides improved objective response rate [ORR, risk ratio (RR) 1.39, 95% confidence intervals (CI) 1.20∼1.61], disease control rate (DCR, RR 1.21, 95% CI 1.12∼1.30), QOL (RR 1.54, 95% CI 1.25∼1.90), one- (RR 1.37, 95% CI 1.16∼1.62) and two- (RR 1.43, 95% CI 1.06∼1.95) year OS, and A level of Child-pugh, as well as reduced the risks of nausea and vomiting, pyrexia, ache, hyperbilirubinemia, anorexia, fatigue, leukopenia, thrombocytopenia and myelosuppression. Subgroup analyses showed that both short- and long- treatment durations of ginsenosides enhanced the A level of Child-pugh, and reduced nausea and vomiting, ache and hyperbilirubinemia. Besides, combining Rg3 benefited DCR, ORR and QOL, and alleviated nausea and vomiting, hyperbilirubinemia, leukopenia, myelosuppression, thrombocytopenia and α-fetoprotein, while combining GS alleviated nausea and vomiting, ache and hyperbilirubinemia, combining Rh2 alleviated thrombocytopenia, and combining CK alleviated nausea and vomiting, pyrexia, ache and leukopenia, respectively. CONCLUSION: The results suggested that combining ginsenosides could continuously benefit the efficacy and safety of TACE in HCC treatment, and Rg3 is the prior selection during the combination.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Ginsenosídeos , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Terapia Combinada , Ginsenosídeos/farmacologia , Humanos , Neoplasias Hepáticas/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-34380082

RESUMO

BACKGROUND: Previous sleep EEG studies have detected abnormalities in sleep architecture and sleep spindle deficits in schizophrenia (SCZ), but the consistency of these results was not robust, which might be due to the small sample size and the influence of clinical factors, such as the various medication therapy and symptom heterogeneity. The current study aimed to regard AVHs as a pointcut to downscale the heterogeneity of SCZ, and explore whether some of sleep architecture and spindle parameters were more severely impaired in SCZ with auditory verbal hallucinations (AVHs) compared to those without AVHs. METHODS: 90 SCZ with AVHs, 92 SCZ without AVHs and 91 healthy controls were recruited and parameters of sleep architecture and spindle activities were compared between groups. The correlation between significant sleep parameters and clinical indicators were analyzed. RESULTS: Deficits of sleep spindle activities at prefrontal electrodes and intra-hemispheric spindle coherence were observed in both AVHs and non-AVHs groups, several of which were more serious in AVHs group. In addition, deficits of spindle activities at central and occipital electrodes and inter-hemispheric spindle coherence mainly manifested accompanying AVHs symptoms, most of which were retained in the medication-naïve first-episode patients, and were associated with Auditory Hallucination Rating Scale scores. CONCLUSIONS: Our results suggested that the underlying mechanism of spindle deficits might be different between SCZ patients with and without AVHs. In the future, the sleep feature of SCZ patients with different symptoms and the influence of clinical factors, such as medication therapy, should be further illustrated.

16.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(4): 464-468, 2021 Aug 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34409804

RESUMO

OBJECTIVES: This study aimed to explore the short-term clinical efficacy and factors influencing low-dose superficial X-ray for treating infantile maxillofacial hemangioma. METHODS: Retrospective analysis was conducted on 161 cases of infants with maxillofacial hemangioma treated with superficial X-ray in the Laser Center of Dermatology Department of Sichuan Provincial People's Hospital from January 2015 to December 2017. Clinical efficacy was analyzed by comparing the photos before and after treatment. Patients were further divided into groups according to different genders, age at the start of treatment, preterm birth or low birth weight, hemangioma site, longest diameter of hemangioma, and type of hemangioma to analyze whether differences existed in clinical efficacy and therapeutic dose between different groups. RESULTS: Twelve months after the end of treatment, the overall cure rate was 93.8%, and the significant efficiency was 97.5%. The clinical efficacy was related to the age of children at the beginning of treatment and the type of hemangioma (P<0.05). The clinical efficacy of children aged less than or equal to 12 months and superficial hemangioma group was better than that of children aged more than 12 months and deep subtype or mixed hemangioma group, respectively. Therapeutic doses associa-ted with hemangioma treatment with diameter, category, age (P<0.05), diameter greater than or equal to 4 cm hemangioma group, the mixed type or deep in the group, the children older than 12 months hemangioma group, respectively, the dia-meter is less than 4 cm hemangioma, superficial hemangioma group and age less than or equal to 12 months hemangioma total treatment group exposure dose is greater. CONCLUSIONS: Low-dose superficial X-ray is safe and effective for the treatment of infantile maxillofacial hemangioma. Age and type of hemangioma at the time of treatment are the factors influencing therapeutic dose and clinical efficacy.


Assuntos
Hemangioma , Nascimento Prematuro , Neoplasias Cutâneas , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Raios X
17.
Acta Biomater ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34329782

RESUMO

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. The primary treatment for CRC is surgical resection, along with chemotherapy in more advanced or inoperable cases. There is a growing interest to complement both curative and palliative treatment with immunotherapies such as the programmed cell death-1 (PD-1) and PD-ligand 1 (PDL1) checkpoint inhibitors and transforming growth factor (TGF) ß inhibitors. However, the clinical outcomes of current immunotherapeutic strategies are limited by tumor heterogeneity and drug resistance. Nanomedicine-based photothermal therapy (PTT) has shown encouraging results for solid tumor ablation. Herein, we designed and synthesized gold nanocages functionalized with primary macrophage membrane and surface anti-PDL1 antibody, and loaded with a TGFß inhibitor, galunisertib. The GNC-Gal@CMaP nanocomposites achieved low-temperature PTT and immunogenic cell death, which subsequently enhanced the anti-tumor efficacy of anti-PDL1 antibody and galunisertib via activation of antigen-presenting cells that primed tumor-specific effector T cells. This study provides experimental proof for a combination of immunotherapy and PTT against CRC. STATEMENT OF SIGNIFICANCE: The combination of photothermal therapy (PTT) with immunotherapy can achieve an inherently synergistic anti-tumor effect. Here we integrated low-temperature PTT, PDL1 antibody and TGF-ß inhibitor in hollow gold nanocage nanocomposites (GNC-Gal@CMaP) that selectively targeted colon cancer cells and accumulated in the tumor microenvironment. The GNC-Gal@CMaP nanocomposites achieved low-temperature PTT and immunogenic cell death, which subsequently enhanced the anti-tumor efficacy of anti-PDL1 antibody and galunisertib via activation of antigen-presenting cells that primed tumor-specific effector T cells. This study provides experimental proof for a combination of immunotherapy and PTT against CRC.

18.
Medicine (Baltimore) ; 100(28): e26525, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260528

RESUMO

ABSTRACT: Catheter ablation of atrial fibrillation sometimes encounters difficulty in passing the interatrial septum. This study reports a modified percutaneous atrial balloon septoplasty with short balloon to gain access to left atrium (LA) during challenging transseptal puncture (TSP).We retrospectively analyzed 20 patients (61.75 ±â€Š7.31 years, 45% male) who received modified percutaneous atrial balloon septoplasty from August 2015 to October 2018. Soft-headed balance middle weight (BMW) guidewire was inserted into left superior pulmonary vein (LSPV) and short non-compliant balloon (15 mm in length and 4.0 or 5.0 mm in diameter) was used for atrial balloon septoplasty (ABS). Interatrial septum was located with inflated balloon and contrast "Hitting Wall" sign. All patients were followed-up for iatrogenic atrial septal defect (iASD) and other related complications.ABS and LA access were performed successfully without complications in all 20 patients. Time needed for ABS was correlated to the number of prior TSP (P = .007). During the 6-month follow-up, no remaining iASD was found by echocardiography.For atrial fibrillation patients with difficulty in passing the interatrial septum, this modified percutaneous ABS might be an alternative strategy which is safe to obtain transseptal access without short or long term complications.


Assuntos
Angioplastia Coronária com Balão/métodos , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Pract Radiat Oncol ; 11(5): 374-383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34157448

RESUMO

PURPOSE: We aimed to explore the efficacy and toxicity of split-course hypofractionated radiation therapy with concurrent chemotherapy (HRT-CHT) in patients with locally advanced non-small cell lung cancer (LANSCLC) in this single-arm, phase II study. METHODS AND MATERIALS: Patients with LANSCLC were considered eligible if their forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC%) and carbon monoxide diffusing capacity (DLCO%) were ≥40% and ≥45%, respectively. HRT-CHT using the intensity modulated radiation therapy technique was administered with 51 Gy in 17 fractions as the first course followed by a break. Patients without disease progression or persistent ≥grade 2 toxicities had an HRT-CHT of 15 to 18 Gy in 5 to 6 fractions as a boost. The primary endpoint was progression-free survival, and the secondary endpoint was overall survival (OS). RESULTS: Eighty-nine patients were enrolled and analyzed. The median follow-up was 29.5 months for all patients and 35.3 months for the survivors. The objective response rate was 97.8%; the median progression-free survival and OS were 11.0 and 27.0 months, respectively. Grade 3 acute esophagitis/pneumonitis occurred in 15 (16.9%)/7 (7.9%) patients. Grade 3/5 late pneumonitis occurred in 2 (2.2%)/1 (1.1%) patients. Of the 78 (87.6%) who completed the split-course HRT-CHT per protocol, patients with better FEV1/FVC% and DLCO% after the break had significantly better OS (for the FEV/FVC1% ≥ 80% vs 60%-79% vs 41%-59% groups, 2-year OS values were 57.2% vs 56.9% vs 0%, respectively, P = .024; for the DLCO% ≥ 80% vs 60%-79% vs 45%-59% groups, 2-year OS values were 70.4% vs 48.4% vs 37.5%, respectively, P = .049). CONCLUSIONS: Split-course HRT-CHT achieved a promising response rate and survival with tolerable toxicity in LANSCLC. Pulmonary function tests are necessary indicators for radiation treatment planning and dose escalation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Estudos Prospectivos
20.
Geophys Res Lett ; 48(10): e2021GL093668, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34149110

RESUMO

Economic activities and the associated emissions have significantly declined during the 2019 novel coronavirus (COVID-19) pandemic, which has created a natural experiment to assess the impact of the emitted precursor control policy on ozone (O3) pollution. In this study, we utilized comprehensive satellite, ground-level observations, and source-oriented chemical transport modeling to investigate the O3 variations during the COVID-19 pandemic in China. Here, we found that the significant elevated O3 in the North China Plain (40%) and Yangtze River Delta (35%) were mainly attributed to the enhanced atmospheric oxidation capacity (AOC) in these regions, associated with the meteorology and emission reduction during lockdown. Besides, O3 formation regimes shifted from VOC-limited regimes to NOx-limited and transition regimes with the decline of NOx during lockdown. We suggest that future O3 control policies should comprehensively consider the effects of AOC on the O3 elevation and coordinated regulations of the O3 precursor emissions.

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