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1.
Cell ; 182(3): 713-721.e9, 2020 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-32778225

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 µg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.


Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Evaluación Preclínica de Medicamentos/métodos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Vacunas de Productos Inactivados/uso terapéutico , Vacunas Virales/uso terapéutico , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Betacoronavirus/genética , COVID-19 , Vacunas contra la COVID-19 , Chlorocebus aethiops , Infecciones por Coronavirus/virología , Modelos Animales de Enfermedad , Femenino , Cobayas , Inmunogenicidad Vacunal , Macaca fascicularis , Macaca mulatta , Masculino , Ratones , Ratones Endogámicos BALB C , Filogenia , Neumonía Viral/virología , Conejos , Ratas , Ratas Wistar , SARS-CoV-2 , Vacunas de Productos Inactivados/efectos adversos , Células Vero , Vacunas Virales/efectos adversos
2.
Nature ; 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-37019149

RESUMEN

SARS-CoV-2, the causative agent of COVID-19, emerged in December 2019. Its origins remain uncertain. It has been reported that a number of the early human cases had a history of contact with the Huanan Seafood Market. Here we present the results of surveillance for SARS-CoV-2 within the market. From January 1st 2020, after closure of the market, 923 samples were collected from the environment. From 18th January, 457 samples were collected from 18 species of animals, comprising of unsold contents of refrigerators and freezers, swabs from stray animals, and the contents of a fish tank. Using RT-qPCR, SARS-CoV-2 was detected in 73 environmental samples, but none of the animal samples. Three live viruses were successfully isolated. The viruses from the market shared nucleotide identity of 99.99% to 100% with the human isolate HCoV-19/Wuhan/IVDC-HB-01/2019. SARS-CoV-2 lineage A (8782T and 28144C) was found in an environmental sample. RNA-seq analysis of SARS-CoV-2 positive and negative environmental samples showed an abundance of different vertebrate genera at the market. In summary, this study provides information about the distribution and prevalence of SARS-CoV-2 in the Huanan Seafood Market during the early stages of the COVID-19 outbreak.

3.
Nature ; 583(7818): 830-833, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32380511

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Pulmón/patología , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/patología , Neumonía Viral/virología , Transgenes , Enzima Convertidora de Angiotensina 2 , Animales , Antígenos Virales/inmunología , Antígenos Virales/metabolismo , Betacoronavirus/inmunología , Betacoronavirus/metabolismo , Bronquios/patología , Bronquios/virología , COVID-19 , Infecciones por Coronavirus/inmunología , Modelos Animales de Enfermedad , Células Epiteliales/patología , Células Epiteliales/virología , Femenino , Humanos , Inmunoglobulina G/inmunología , Pulmón/inmunología , Pulmón/virología , Linfocitos/inmunología , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/virología , Masculino , Ratones , Ratones Transgénicos , Pandemias , Neumonía Viral/inmunología , Receptores de Complemento 3d/genética , Receptores de Complemento 3d/metabolismo , SARS-CoV-2 , Replicación Viral , Pérdida de Peso
4.
PLoS Genet ; 18(10): e1010366, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36288387

RESUMEN

BACKGROUND: Bladder cancer (BCa) is one of the most prevalent malignancies globally. Previous study has reported the inhibitory effect of methyltransferase-like 14 (METTL14) on BCa tumorigenesis, but its role in the cell migration, invasion and epithelial-mesenchymal transition (EMT) in BCa remains unknown. MATERIALS AND METHODS: Quantitative real-time PCR (RT-qPCR) and western blot were applied to measure RNA and protein expression respectively. Cell migration, invasion and EMT were evaluated by wound healing, Transwell, and immunofluorescence (IF) assays as well as western blot of EMT-related proteins. In vivo experiments were performed to analyze metastasis of BCa. Mechanism investigation was also conducted to study METTL14-mediated regulation of BCa progression. RESULTS: METTL14 overexpression prohibits BCa cell migration, invasion in vitro and tumor metastasis in vivo. METTL14 stabilizes USP38 mRNA by inducing N6-methyladenosine (m6A) modification and enhances USP38 mRNA stability in YTHDF2-dependent manner. METTL14 represses BCa cell migration, invasion and EMT via USP38. Additionally, miR-3165 inhibits METTL14 expression to promote BCa progression. CONCLUSIONS: Our study demonstrated that METTL14 suppresses BCa progression and forms a feedback loop with USP38. In addition, miR-3165 down-regulates METTL14 expression to promote BCa progression. The findings may provide novel insight into the underlying mechanism of METTL14 in BCa progression.


Asunto(s)
MicroARNs , Neoplasias de la Vejiga Urinaria , Humanos , Transición Epitelial-Mesenquimal/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Retroalimentación , Línea Celular Tumoral , Movimiento Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero , Metiltransferasas/genética , Metiltransferasas/metabolismo , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismo , Proteasas Ubiquitina-Específicas/farmacología
5.
Opt Express ; 32(10): 16809-16822, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38858878

RESUMEN

The X-ray sources for Compton radiography of ICF experiments are generated by using intense picosecond lasers to irradiate wire targets. The wire diameter must be designed thin enough, for example ∼ 10 µm in many published works, to comply a high spatial resolution. This results in a low laser-target interception, which limits the photon yield. We investigated a technique of coded-source radiography based on laser-driven annular sources via Monte Carlo and PIC simulations. The annular X-ray source is formed by laser irradiating tube target in which the effect of electron recirculation plays an important role. We proved that this technique has an increased spatial resolution and contrast than that using the Gaussian source produced by wire targets. Therefore, the diameter of the backlighter target can be significantly increased to uplift laser-target interception without compromising on spatial resolution. This contributes towards a reconciliation between the spatial resolution and photon yield for Compton radiography. The results predict the possibility of improving source photon yield by several times in future experiments.

6.
Opt Express ; 32(6): 9602-9609, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571190

RESUMEN

The thin flyer is a small-scale flying object, which is well known as the core functional element of the initiator. Understanding how flyers perform has been a long-standing issue in detonator science. However, it remains a significant challenge to explore how the flyer is formed and functions in the barrel of the initiator via tabletop devices. In this study, we present dynamic and unprecedented images of flyer in barrel via high intensity short-pulse laser. Advanced radiography, coupled with a high-intensity picosecond laser X-ray source, has enabled the provision of state-of-the-art radiographs in a single-shot experiment for observing micron-scale flyer formation in a hollow cylinder in nanoseconds. The flyer was clearly visible in the barrel and was accelerated and restricted differently from that without the barrel. This first implementation of a tabletop X-ray source provided a new approach for capturing dynamic photographs of small-scale flying objects, which were previously reported to be accessible only via an X-ray phase-contrast imaging system at the advanced photon source. These efforts have led to a significant improvement of radiographic capability and a greater understanding of the mechanisms of "burst" of exploding foil initiators for this application.

7.
Opt Lett ; 49(15): 4114-4117, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090872

RESUMEN

High-power laser interacting with matter generates intense electromagnetic pulses (EMPs), which are closely associated with laser and target parameters. In this study, EMPs induced by picosecond (ps) laser coupling with solid targets are recorded at the XG-III laser facility. Gold wire targets produce more intense EMPs with a maximum EMP value of 608 kV/m compared to some planar targets. EMP propagation in the normal direction is highly coincident with the expansion of detected hot electrons, which is verified by the particle-in-cell simulations. This work is expected to pave, to our knowledge, a new avenue for directional guidance of laser-driven EMPs.

8.
J Asthma ; 61(10): 1252-1264, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38647226

RESUMEN

Objective: The aim of this study was to identify genetic biomarkers and cellular communications associated with severe asthma in microarray data sets and single cell data sets. The potential gene expression levels were verified in a mouse model of asthma.Methods: We identified differentially expressed genes from the microarray datasets (GSE130499 and GSE63142) of severe asthma, and then constructed models to screen the most relevant biomarkers to severe asthma by machine learning algorithms (LASSO and SVM-RFE), with further validation of the results by GSE43696. Single-cell datasets (GSE193816 and GSE227744) were identified for potential biomarker-specific expression and intercellular communication. Finally, The expression levels of potential biomarkers were verified with a mouse model of asthma.Results: The 73 genes were differentially expressed between severe asthma and normal control. LASSO and SVM-RFE recognized three genes BCL3, DDIT4 and S100A14 as biomarkers of severe asthma and had good diagnostic effect. Among them, BCL3 transcript level was down-regulated in severe asthma, while S100A14 and DDIT4 transcript levels were up-regulated. The transcript levels of the three genes were confirmed in the mouse model. Infiltration of neutrophils and mast cells were found to be increased in severe asthma and may be associated with bronchial epithelial cells through BMP and NRG signalingConclusions: We identified three differentially expressed genes (BCL3, DDIT4 and S100A14) of diagnostic significance that may be involved in the development of severe asthma and these gene expressions could be serviced as biomarker of severe asthma and investigating the function roles could bring new insights into the underlying mechanisms.


Asunto(s)
Asma , Biomarcadores , Asma/genética , Asma/inmunología , Animales , Ratones , Biomarcadores/metabolismo , Humanos , Modelos Animales de Enfermedad , Factores de Transcripción/genética , Análisis de la Célula Individual , Aprendizaje Automático , Perfilación de la Expresión Génica
9.
Ann Vasc Surg ; 104: 307-314, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38599487

RESUMEN

BACKGROUND: This study aims to conduct a comparative analysis of the clinical efficacy and safety between pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) in the context of acute lower-extremity deep venous thrombosis (LEDVT). METHODS: A retrospective review of our institution's patient database spanning from February 2011 to December 2019 was performed to identify cases of acute LEDVT. The patients were categorized into 2 distinct groups based on the thrombolytic interventions administered: the PMT group, specifically denoting PMT with AngioJet in our investigation, and the CDT group. Comprehensive data sets encompassing patient demographics, risk factors, procedural specifics, thrombolysis grading, and complications were collected. Subsequent follow-up evaluations at the 2-year mark posttreatment included assessments of postthrombotic syndrome (PTS) and the quality of life. RESULTS: Among the 348 patients identified (mean age: 50.12 ± 15.87 years; 194 females), 200 underwent CDT during the early stage (2011 to 2017), while 148 received PMT between 2017 and 2019. Baseline data between the 2 groups exhibited no statistically significant differences. Thrombus scores significantly decreased in both cohorts posttherapy (each P < 0.001).Patients subjected to PMT demonstrated higher thrombolysis rates (77.35 ± 9.44% vs. 50.85 ± 6.72%), reduced administration of the thrombolytic agent urokinase [20 (20€20) vs. 350 (263€416), P < 0.001], larger limb circumference differences (above the knee: 6.03 ± 1.76 cm vs. 4.51 ± 1.82 cm, P < 0.001; below the knee: 2.90 ± 1.16 cm vs. 2.51 ± 0.90 cm, P < 0.001), and shorter lengths of stay (7.19 ± 3.11 days vs. 12.33 ± 4.77 days, P < 0.001). However, the PMT group exhibited a higher decline in hemoglobin levels (13.41 ± 10.59 g/L vs. 10.88 ± 11.41 g/L, P = 0.038) and an increase in creatinine levels [9.58 (2.32€15.82) umol/L vs. 4.53 (2.87€6.08) umol/L, P < 0.001] compared to the CDT group. No statistically significant differences were observed in the numbers of balloon angioplasty, stent implantation (each P > 0.050), and minor and major complications between the 2 groups. At the 1-year follow-up, PTS occurred in 13.51% of the PMT group compared to 26% of the CDT group (P = 0.025), with a higher incidence of moderate-severe PTS in the CDT group (8% vs. 2.7%, P = 0.036). At the 2-year follow-up, PTS was observed in 16.2% of the PMT group and 31.5% in the CDT group, P = 0.004. Preoperative and postoperative D-values of 36-Item Short Form Health Survey (SF-36) Physical Component Summary and SF-36 Mental Component Summary showed no statistically significant between-group differences. CONCLUSIONS: In our institutional experience, both PMT and CDT have proven to be effective and safe therapeutic approaches for managing acute LEDVT. PMT, in particular, demonstrated superior efficacy in achieving thrombosis resolution and mitigating the risk of PTS, affirming its role as a favorable intervention in this clinical context.


Asunto(s)
Bases de Datos Factuales , Fibrinolíticos , Trombectomía , Terapia Trombolítica , Trombosis de la Vena , Humanos , Estudios Retrospectivos , Masculino , Femenino , Terapia Trombolítica/efectos adversos , Trombosis de la Vena/terapia , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/fisiopatología , Persona de Mediana Edad , Resultado del Tratamiento , Trombectomía/efectos adversos , Trombectomía/instrumentación , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Adulto , Factores de Tiempo , Anciano , Síndrome Postrombótico/etiología , Síndrome Postrombótico/terapia , Cateterismo Periférico/efectos adversos , Factores de Riesgo , Calidad de Vida , Enfermedad Aguda
10.
Ann Vasc Surg ; 104: 315-323, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38599492

RESUMEN

BACKGROUND: The Talos stent-graft has extended length to improve aortic remodeling, and distal porous design to decrease the rate of spinal cord ischemia (SCI). This study retrospectively analyzed its mid-term outcomes for uncomplicated type B aortic dissection in a multicenter study. METHODS: The primary safety end point was 30-day major adverse events, including all-cause mortality, dissection-related mortality, conversion to open surgery, and device-related adverse events. The primary efficacy end point was treatment success at 12 months postoperation, defined as no technical failure or secondary dissection-related reintervention. The survival status of the patients was visualized using the Kaplan-Meier curve. Aortic growth was assessed at 4 levels, and SCI was evaluated at 12 months. RESULTS: 113 patients participated with a mean age of 54.4 (11.1) years and 71.7% (81/113) were male. The 30-day mortality was 0.9% (1/113), no conversions to open surgery or device-related adverse events were recorded. The 12-month treatment success rate was 99.1% (112/113), with no dissection-related reinterventions. There was no spinal cord or visceral ischemia at 12 months. At a median of 34 months follow-up, 9 further deaths were recorded and the 3-year survival rate was 91.7%. The percentage of aortic growth was 1.8% (2/111) at the tracheal bifurcation, 3.6% (4/111) below the left atrium, 6.0% (5/83) above the celiac artery, and 12.1% (9/74) below the lower renal artery. The total thrombosis rate of the false lumen at the stented segment was 80.5% (91/113). CONCLUSIONS: The results showed satisfactory results of Talos stent-graft in terms of safety and efficacy. More data are needed to confirm the long-term performance.


Asunto(s)
Disección Aórtica , Implantación de Prótesis Vascular , Prótesis Vascular , Procedimientos Endovasculares , Diseño de Prótesis , Stents , Humanos , Masculino , Persona de Mediana Edad , Femenino , Disección Aórtica/cirugía , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/mortalidad , Estudios Retrospectivos , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Resultado del Tratamiento , Factores de Tiempo , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Adulto , Anciano , Factores de Riesgo , Porosidad , Aneurisma de la Aorta/cirugía , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/mortalidad , Complicaciones Posoperatorias/etiología , Japón
11.
Opt Express ; 31(19): 30486-30494, 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37710589

RESUMEN

Traditional spiral zone plates (SZPs) have been widely used to generate optical vortices, but this structure suffers from multiple focuses. To eliminate high-order foci, the current method is to design a binary structure that has a sinusoidal transmittance function along the radial direction. With the rapid development of artificial neural networks, they can provide alternative methods to design novel SZPs with a single focus. In this paper, we first propose the concept of generalized binary spiral zone plates (GBSZPs), and train a feedforward neural network (FNN) to obtain the mapping relationship between the relative intensity of each focus and the structural parameters of GBSZPs. Then the structural parameters of GBSZPs with a single focus were predicted by the trained FNN. It is found by simulations and experiments that the intensities of high-order foci can be as low as 0.2% of the required first order. By analyzing the radial transmittance function, it is found that this structure has a different distribution function from the previous radial sinusoidal function, which reveals that the imperfect radial sinusoidal form also can guide the design of binary zone plates to eliminate high-order foci diffraction. These findings are expected to direct new avenue towards improving the performance of optical image processing and quantum computation.

12.
Opt Express ; 31(12): 19266-19277, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37381345

RESUMEN

The axiparabola is a novel reflective element proposed in recent years, which can generate a long focal line with high peak intensity, and has important applications in laser plasma accelerators. The off-axis design of an axiparabola has the advantage of separating the focus from incident rays. However, an off-axis axiparabola designed by the current method always produces a curved focal line. In this paper, we propose a new method to design its surface by combining geometric optics design and diffraction optics correction, which can effectively convert a curved focal line into a straight foal line. We reveal that the geometric optics design inevitably introduces an inclined wavefront, which leads to the bending of the focal line. To compensate for the tilt wavefront, we use an annealing algorithm to further correct the surface through diffraction integral operation. We also carry out numerical simulation verification based on scalar diffraction theory, which proves that the surface of this off-axis mirror designed by this method can always obtain a straight focal line. This new method has wide applicability in an axiparabola with any off-axis angle.

13.
Phys Rev Lett ; 130(9): 095101, 2023 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-36930918

RESUMEN

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft x-ray regime. We use the tricellulose acetate (C_{9}H_{16}O_{8}) foam of 2 mg/cm^{3} density and 1 mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. We diagnose the plasma parameters to be T_{e}=17 eV and n_{e}=4×10^{20} cm^{-3}. We observe the average charge states passing through the plasma to be higher than those predicted by the commonly used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects, which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. The underlying physics is actually the balancing of the lifetime of excited states versus the collisional frequency. In previous measurement with partially ionized plasma from gas discharge and z pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we are able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-glass laser radiation. The finding is important for heavy ion beam driven high-energy-density physics and fast ignitions. The method provides a new approach to precisely address the beam-plasma interaction issues with high-intensity short-pulse lasers in dense plasma regimes.

14.
BMC Cancer ; 23(1): 943, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37803307

RESUMEN

BACKGROUND: Nephrectomy, whether in the era of cytokine therapy or targeted therapy, has an important role in the treatment of metastatic renal cell carcinoma. With the advent of immunotherapy, immunotherapy combined with targeted therapy has become the mainstream of systemic therapy, but the role of nephrectomy in metastatic renal cell carcinoma is unclear. In this study, we retrospectively analyzed the impact of nephrectomy on survival in patients with metastatic renal cell carcinoma who received immune-targeted therapy. METHODS: Patients with metastatic renal cell carcinoma who received immune-targeted therapy at three centers between May 17, 2019 and August 1, 2022 were collected, who were divided into two groups based on whether nephrectomy was performed or not. Survival, response rate and adverse event were compared between the two groups. The primary end point was progression free survival, Subgroup analysis and univariate and multivariable prognostic analyses were also assessed. RESULTS: With a median follow-up time of 29.3 months (95% CI 28.5-30.2), 165 patients were recruited and divided into two groups based on whether they underwent nephrectomy or not. There were 68 patients in the non-nephrectomy group, 97 in the nephrectomy group. Compared to patients treated with immune-targeted therapy, patients treated with immune-targeted therapy plus nephrectomy were able to achieve survival benefits, with a median PFS of 10.8 months (95% CI 8.3-13.3) and 14.4 months (95% CI 12.6-16.2), respectively, as well as an HR of 0.476 (95% CI 0.323-0.701, p = 0.0002). The 12-month and 18-month PFS rates were 30.9% versus 60.8% and 7.4% versus 25.8%, respectively. The objective response rate (ORR) was 52.9% and 60.8%, respectively, in the non-nephrectomy and nephrectomy groups (p = 0.313), and the disease control rate (DCR) was 75% and 83.5%, respectively (p = 0.179). The most common adverse events related to treatment were hypothyroidism, immune-related pneumonitis and rash. Multivariate analysis showed that primary tumor nephrectomy prior to immune-targeted therapy, clear cell renal carcinoma and oligo metastasis were independent prognostic factors. CONCLUSIONS: Nephrectomy may provide PFS benefit with tolerable safety for patients with metastatic renal cell carcinoma who receive immune-targeted therapy. In multivariate analysis, nephrectomy, clear cell carcinoma, and oligo-organ metastasis were found to be favorable independent prognostic factors.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Estudios Retrospectivos , Pronóstico , Nefrectomía
15.
Biochem Genet ; 61(6): 2222-2241, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37184686

RESUMEN

As severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is becoming more infectious and less virulent, symptoms beyond the lungs of the Coronavirus Disease 2019 (COVID-19) patients are a growing concern. Studies have found that the severity of COVID-19 patients is associated with an increased risk of ischemic stroke (IS); however, the underlying pathogenic mechanisms remain unknown. In this study, bioinformatics approaches were utilized to explore potential pathogenic mechanisms and predict potential drugs that may be useful in the treatment of COVID-19 and IS. The GSE152418 and GSE122709 datasets were downloaded from the GEO website to obtain the common differentially expressed genes (DEGs) of the two datasets for further functional enrichment, pathway analysis, and drug candidate prediction. A total of 80 common DEGs were identified in COVID-19 and IS datasets for GO and KEGG analysis. Next, the protein-protein interaction (PPI) network was constructed and hub genes were identified. Further, transcription factor-gene interactions and DEGs-miRNAs coregulatory network were investigated to explore their regulatory roles in disease. Finally, protein-drug interactions with common DEGs were analyzed to predict potential drugs. We successfully identified the top 10 hub genes that could serve as novel targeted therapies for COVID-19 and screened out some potential drugs for the treatment of COVID-19 and IS.


Asunto(s)
COVID-19 , Accidente Cerebrovascular Isquémico , MicroARNs , Humanos , COVID-19/genética , SARS-CoV-2 , Accidente Cerebrovascular Isquémico/genética , Biología Computacional
16.
Lancet ; 395(10224): 565-574, 2020 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-32007145

RESUMEN

BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Genoma Viral , Neumonía Viral/epidemiología , Neumonía Viral/virología , Receptores Virales/metabolismo , Betacoronavirus/metabolismo , Líquido del Lavado Bronquioalveolar/virología , COVID-19 , China/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/transmisión , ADN Viral/genética , Reservorios de Enfermedades/virología , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Filogenia , Neumonía Viral/diagnóstico , Neumonía Viral/transmisión , SARS-CoV-2 , Alineación de Secuencia
17.
Opt Lett ; 46(11): 2795-2798, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34061116

RESUMEN

This Letter demonstrates a novel, to the best of our knowledge, method to measure the fluence distribution of an intense short laser pulse based on the radiochromic effect. We discovered that an intense short laser pulse can induce the color reaction with a radiochromic film (RCF). Further, the net optical density of an irradiated RCF is proportional to the fluence of the incident laser pulse in a large range (${2 {-} 120}\;{{{\rm mJ}/{\rm cm}}^2}$). This method supports a large detection area up to near square-meter scale by splicing multi-pieces of RCFs (${8} \times 10\;{{\rm inch}^2}$ each). The spatial resolution reaches as high as 60 lines/mm. It offers a thin-film (${\sim}{100}\;{\unicode{x00B5}{\rm m}}$ thick), flexible, vacuum-compatible solution to intense short laser measurements, especially to laser facilities above petawatt, with beam sizes up to near square-meter scale, e.g., extreme light infrastructure.

18.
BMC Pregnancy Childbirth ; 21(1): 272, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33794807

RESUMEN

BACKGROUND: The preferable choice of anesthesia for the patients with congenital atlantoaxial dislocation (CAAD) and type I Arnold Chiari malformations (ACM-I) has been a very confusing issue in clinical practice. We describe the successful administration of combined spinal-epidural anesthesia for a woman with CAAD and ACM-1 accompanied by syringomyelia. CASE PRESENTATION: Our case report presents the successful management of a challenging obstetric patient with CAAD and ACM-1 accompanied by syringomyelia. She had high risks of difficult airway and aspiration. The injection of bolus drugs through the spinal or epidural needle may worsen the previous neurological complications. The patient was well evaluated with a multidisciplinary technique before surgery and the anesthesia was provided by a skilled anesthesiologist with slow spinal injection. CONCLUSIONS: An interdisciplinary team approach is needed to weigh risks and benefits for patients with CAAD and ACM-1 undergoing cesarean delivery. Therefore, an individual anesthetic plan should be made basing on the available anesthetic equipments and physicians' clinical experience on anesthetic techniques.


Asunto(s)
Anestesia Obstétrica/métodos , Malformación de Arnold-Chiari/complicaciones , Articulación Atlantoaxoidea/anomalías , Cesárea/efectos adversos , Luxaciones Articulares/complicaciones , Dolor Asociado a Procedimientos Médicos/prevención & control , Adulto , Anestesia Epidural/métodos , Articulación Atlantoaxoidea/diagnóstico por imagen , Femenino , Humanos , Inyecciones Espinales/métodos , Luxaciones Articulares/congénito , Angiografía por Resonancia Magnética , Dimensión del Dolor , Dolor Asociado a Procedimientos Médicos/diagnóstico , Dolor Asociado a Procedimientos Médicos/etiología , Embarazo , Resultado del Tratamiento
19.
Clin Exp Pharmacol Physiol ; 48(1): 64-71, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32663323

RESUMEN

Interleukin (IL)-33 is associated with vascular restenosis after carotid artery balloon injury. This work aims to investigate the involvement of IL-33 in carotid artery balloon injury. We first constructed carotid artery balloon injury model in male Wistar rats. Then, we found that IL-33 was highly expressed in the rats with carotid artery balloon injury 3, 14 and 21 days after surgery. Furthermore, IL-33 treatment promoted inflammatory response and carotid artery intimal hyperplasia in the rats with carotid artery balloon injury, which was effectively improved by anti-IL-33 treatment. In addition, IL-33 treatment enhanced proliferation, migration, inflammatory response and tube formation of human umbilical vein endothelial cells in a concentration-dependent way. In summary, our study demonstrates that IL-33 treatment promotes the progression of vascular restenosis after carotid artery balloon injury by enhancing carotid artery intimal hyperplasia and inflammatory response. Thus, our findings suggest that IL-33 maybe a valuable target for carotid artery balloon injury therapies.

20.
Entropy (Basel) ; 23(2)2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33499279

RESUMEN

We investigated the adiabatic compression along the axial direction of a spinning Van der Waals gas by applying theoretical analysis and molecular dynamics (MD) simulations. Based on the analytical results, the rotation-induced compressibility increase effect is significant in a Van der Waals gas, while the attraction term in the Van der Waals equation of states (EOS) contributes significantly to the compressibility increase in a spinning system. We conducted MD simulations to the axial compression of a spinning gas, whose state is far from the ideal gas state, and further demonstrated that the rotation-induced compressibility increase effect in a dense state is robust, implying that such a phenomenon can be detected in experiments under high-energy-density conditions.

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