Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 577
Filtrar
1.
Chemosphere ; 287(Pt 2): 132150, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34826896

RESUMO

A few studies reported the impact of mineral conductivity properties on contaminant-mineral-microbe interactions and microbial community structure changes in the interaction process. To fill the gap, conductive minerals (magnetite/hematite) and an insulative mineral (quartz) were introduced into Cr(VI) reduction systems to investigate the effect of mineral conductivity properties on Cr(VI) removal. Results showed that conductive minerals enhanced Cr(VI) reduction rate as compared to insulative minerals. Higher reduction percentage (>86%) was observed when both ERB (extracellular respiratory bacteria) and conductive minerals were presence than those with only minerals (<10%) or ERB (<55%), indicating a synergistic effect existed in this bio-remediation system. Moreover, surface elements detection manifested higher Fe-containing groups and Fe(III)-Cr(III) complexes covered on conductive minerals surface when ERB was present. Electrochemical data suggested that ERB facilitated the activity of electron transference on the surface of conductive minerals. Our results indicated that conductive minerals did act as an "electron shuttle" while insulative minerals increased adsorption sites to accelerate Cr(VI) reduction. 16S rRNA sequences results demonstrated that conductive minerals changed the microbial community structure and increased the diversity of the functional microbes including Pseudomonas spp. and Exiguobacterium spp. This work is of deep significance for better understanding the process of elements biogeochemical and elimination of pollutants.

2.
Environ Res ; : 112326, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748776

RESUMO

Along with rapid development of sulfate radicals-based advanced oxidation process, efficient, alternatively eco-friendly and cost-effective catalyst is of uppermost priority. However, expensive chemicals are used as source of metal in most of these catalysts, and lose sight of the abundant natural mineral resources on immediate surroundings. In this work, montmorillonite and hematite, two of abundantly natural minerals were utilized to prepare a persulfate catalyst (TMH@M) for sulfamethoxazole (SMX) degradation. The results indicated more than 91% of SMX was removed within 60 min in TMH@M/PS system. The degradation efficiency of SMX of TMH@M/PS combined system was impacted by SMX concentration, PS dosage and natural organic matters, and can remain stable in a certain concentration of HA/chelating agent and a wide pH range (3.01-9.06). Radical scavenging and EPR tests demonstrated 1O2, OH, and SO4- were major reactive oxygen species in the TMH@M/PS system, while the latter seems more important for degradation of SMX. The results of SEM-EDS, XRD and XPS conformed that low valence iron species (Fe0, Fe2+ and Fe3O4) on TMH@M surface are the main driving force behind PS activation to generate reactive species. Furthermore, the iron species on TMH@M surface were transformed during reaction, that in favor of mitigating metal leaching. This work presented a method based on ubiquitous natural minerals to prepare catalyst with excellent PS activate performance for organic wastewater treatment implying a new strategy in minerals utilization deeply and a promisingly alternative process for organic wastewater treatment based on mineral materials.

3.
Medicine (Baltimore) ; 100(45): e27812, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766592

RESUMO

RATIONALE: Takotsubo syndrome (TTS) is characterized by transient and reversible left ventricular systolic dysfunction, which are often associated with acute physical or emotional stressors. Cancer is one of the comorbidities in TTS, and TTS is even considered as a paraneoplastic syndrome, but its mechanism remains unclear. We report a patient in whom cancer and untreated mental disorders triggered TTS. PATIENT CONCERNS: A 59-year-old man was transferred to the Department of Cardiology because of acute onset of severe chest pain and dyspnea before cystoscopy. He presented with hematuria, had been diagnosed with a high-grade urothelial bladder cancer, and underwent transurethral resection of bladder tumors 4 months previously. He had severe anxiety regarding recurrence and death from cancer, especially after the hematuria recurred. DIAGNOSIS: TTS and severe anxiety. INTERVENTIONS: The results of coronary angiography, a left ventriculogram, echocardiography, and the clinical outcome led to the diagnosis of TTS. The patient was treated with extracorporeal membrane oxygenation support, mechanical ventilation, and drugs for heart failure and anxiety. OUTCOMES: Echocardiography showed normal wall motion on day 6 of symptom onset. Six months after symptom onset, the anxiety score was reduced from 12 to 11, and the patient had no episodes of any discomfort, and no evidence of cancer recurrence was observed. LESSONS: Patients with cancer and TTS have a higher level of stress, and physicians need to pay more attention to early screening and early treatment of mental disorders in these patients. Prompt and effective multidisciplinary treatment, including psychological counseling and antianxiety drugs, can improve the prognosis in such cases.

4.
Sci Total Environ ; : 151711, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34800457

RESUMO

The outbreak of COVID-19 has led to the large-scale usage of chlorinated disinfectants in cities. Disinfectants and disinfection by-products (DBPs) enter rivers through urban drainage and surface runoff. We investigated the variations in residual chlorine, DBPs, and different aquatic organisms in the Hanjiang, Fuhe, and Qinglinghe Rivers in Wuhan during the COVID-19 pandemic. The sampling sites were from the wastewater treatment plant outlets to the downstream drinking water treatment plant intakes. Total residual chlorine and DBPs (dichloromethane and trichloromethane) detected in the river water ranged from 0 to 0.84 mg/L and 0 to 0.034 mg/L, respectively. The residual chlorine and DBPs showed a gradual reduction pattern related to water flow, and the concentration at intakes did not exceed the Chinese drinking water source quality standards. Phytoplankton and zooplankton densities were not significantly correlated with residual chlorine and DBPs. The fluctuations in phytoplankton resource use efficiency (RUE) and zooplankton RUE in the Fuhe River, with the highest residual chlorine, and the Qinglinghe River with the highest DBPs, were higher than those in the Hanjiang River. For benthic macroinvertebrates, the number of functional feeding groups in the Hanjiang River was higher than that in the Fuhe and Qinglinghe Rivers. The water and sediment bacterial communities in the Hanjiang River differed significantly from those in the Fuhe and Qingling Rivers. The denitrification function involved in N metabolism was stronger in the Fuhe and Qinglinghe Rivers. Structural equation modelling revealed that residual chlorine and DBPs impacted the diversity of benthos through direct and indirect effects on plankton. Although large-scale chlorine-containing disinfectants use occurred during the investigation, it did not harm the density of the detected aquatic organisms in water sources. With the regular use of chlorinated disinfectants for indoor and outdoor environments in response to the SARS-CoV-2 globally, it is still necessary to study the long-term and accumulated responses of water ecosystems exposed to chlorine-containing disinfectants.

5.
Biomed Res Int ; 2021: 2899043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621893

RESUMO

Objective: To test the biomechanical properties of 3D printed tantalum and titanium porous scaffolds. Methods: Four types of tantalum and titanium scaffolds with four alternative pore diameters, #1 (1000-700 µm), #2 (700-1000 µm), #3 (500-800 µm), and #4 (800-500 µm), were molded by selective laser melting technique, and the scaffolds were tested by scanning electronic microscope, uniaxial-compression tests, and Young's modulus tests; they were compared with same size pig femoral bone scaffolds. Results: Under uniaxial-compression tests, equivalent stress of tantalum scaffold was 411 ± 1.43 MPa, which was significantly larger than the titanium scaffolds (P < 0.05). Young's modulus of tantalum scaffold was 2.61 ± 0.02 GPa, which was only half of that of titanium scaffold. The stress-strain curves of tantalum scaffolds were more similar to pig bone scaffolds than titanium scaffolds. Conclusion: 3D printed tantalum scaffolds with varying pore diameters are more similar to actual bone scaffolds compared with titanium scaffolds in biomechanical properties.

7.
Sci Total Environ ; 807(Pt 2): 150898, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653457

RESUMO

Methane (CH4) is the second most important greenhouse gas, contributing approximately 17% of radiative forcing, and CH4 emissions from river networks due to intensified human activities have become a worldwide issue. However, there is a dearth of information on the CH4 emission potentials of different rivers, especially those draining contrasting watershed landscapes. Here, we examined the spatial variability of diffusive CH4 emissions and discerned the roles of environmental factors in influencing CH4 production in different river reaches (agricultural, urban, forested and mixed-landscape rivers) from the Chaohu Lake Basin in eastern China. According to our results, the urban rivers most frequently exhibited extremely high CH4 concentrations, with a mean concentration of 5.46 µmol L-1, equivalent to 4.1, 9.7, and 7.2 times those measured in the agricultural, forested, and mixed-landscape rivers, respectively. The availability of carbon sources and total phosphorus were commonly identified as the most important factors for CH4 production in agricultural and urban rivers. Dissolved oxygen and oxidation-reduction potential were separately discerned as important factors for the forested and mixed-landscape rivers, respectively. Monte Carlo flux estimations demonstrated that rivers draining contrasting landscapes exhibit distinct potentials to emit CH4. The urban rivers had the highest CH4 emissions, with a flux of 9.44 mmol m-2 d-1, which was 5.1-10.4 times higher than those of the other river reaches. Overall, our study highlighted that management actions should be specifically targeted at the river reaches with the highest emission potentials and should carefully consider the influences of different riverine environmental conditions as projected by their watershed landscapes.

8.
Phys Med Biol ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715678

RESUMO

Coronavirus disease 2019 (COVID-19) has brought huge losses to the world, and it remains a great threat to public health. X-ray computed tomography (CT) plays a central role in the management of COVID-19. Traditional diagnosis with pulmonary CT images is time-consuming and error-prone, which could not meet the need of precise and rapid COVID-19 screening. Nowadays, deep learning (DL) has been successfully applied to CT image analysis, which assists radiologists in workflow scheduling and treatment planning for patients with COVID-19. Traditional method uses Cross-Entropy (CE) as loss function with Softmax layer following fully-connected layer. Most DL-based classification methods target intraclass relationship in certain class (early, progressive, severe, or dissipative phases), ignoring the natural order of different phases of the disease progression; i.e., from an early stage and progress to a late stage. To learn both intraclass and interclass relationship among different stages and improve accuracy of classification, this paper proposes an ensemble learning method based on ordinal regression, which leverages the ordinal information on COVID-19 phases. The proposed method uses multi-binary, neuron stick-breaking (NSB) and soft labels (SL) techniques, and ensembles the ordinal outputs through a median selection. To evaluate our method, we collected 172 confirmed cases. In 2-fold cross-validation experiment, the accuracy is increased by 22% compared with traditional method when we use modified Resnet-18 as backbone. And precision, recall and F1-score are also improved. The experimental results show that our proposed method achieves a better performance than the traditional methods, which helps establish guidelines for classification of COVID-19 chest CT images.

9.
ACS Biomater Sci Eng ; 7(11): 5165-5174, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34704735

RESUMO

A DNA structure-based nanoreactor has emerged as a promising biomaterial for antitumor therapy with its intrinsic biodegradability, biocompatibility, and tunable multifunctionality. Herein, the intelligent DNA nanohydrogel was reported to target cancer cells, control the size, be pH-responsive, and be loaded with glucose oxidase (GOx). Two kinds of X-shaped DNA monomers and DNA linkers were assembled to form a DNA nanohydrogel by hybridization. GOx was successfully encapsulated in the DNA nanohydrogel. The DNA linker was designed with i-motif sequences and modified with ferrocene (Fc). The i-motif-like quadruplex structures were formed in acidic tumor microenvironments, resulting in the disassembly of the DNA nanohydrogel to release GOx. The GOx could oxidize the intratumoral glucose to produce gluconic acid and H2O2. The generated H2O2 was catalyzed by Fc to induce toxic hydroxyl radicals (•OH), which could effectively kill cancer cells. Both the in vitro and the in vivo results demonstrated that the multifunctional DNA nanohydrogel had high-efficiency tumor suppression through combined chemodynamic and starvation cancer therapies.


Assuntos
Neoplasias , Microambiente Tumoral , DNA/genética , Glucose Oxidase , Humanos , Peróxido de Hidrogênio , Neoplasias/tratamento farmacológico
10.
Nanomaterials (Basel) ; 11(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34361187

RESUMO

SiC particulate reinforced aluminum metal matrix composites (SiCp/Al MMCs) are characterized by controllable thermal expansion, high thermal conductivity and lightness. These properties, in fact, define the new promotional material in areas and industries such as the aerospace, automotive and electrocommunication industries. However, the poor weldability of this material becomes its key problem for large-scale applications. Sintering bonding technology was developed to join SiCp/Al MMCs. Cu nanoparticles and liquid Ga were employed as self-fluxing filler metal in air under joining temperatures ranging from 400 °C to 500 °C, with soaking time of 2 h and pressure of 3 MPa. The mechanical properties, microstructure and gas tightness of the joint were investigated. The microstructure analysis demonstrated that the joint was achieved by metallurgical bonding at contact interface, and the sintered layer was composed of polycrystals. The distribution of Ga was quite homogenous in both of sintered layer and joint area. The maximum level of joint shear strength of 56.2 MPa has been obtained at bonding temperature of 450 °C. The specimens sintering bonded in temperature range of 440 °C to 460 °C had qualified gas tightness during the service, which can remain 10-10 Pa·m3/s.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34370193

RESUMO

The occurrence of ten target pharmaceuticals was investigated in drinking water sources and tap water in a city in the middle reaches of the Yangtze River, including erythromycin (ERY), roxithromycin (RTM), ciprofloxacin (CPX), ofloxacin (OFX), sulfadiazine (SDZ), sulfamethoxazole (SMX), oxytetracycline (OTC), tetracycline (TC), ibuprofen (IBF), and naproxen (NPX). And the corresponding ecological risk for three classes of aquatic organisms and human health risk for different life stages were estimated. Results demonstrated that nine pharmaceuticals except for TC were detected with the frequencies of 20-100% and the concentrations of

12.
Sci Total Environ ; 791: 148240, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34412383

RESUMO

Vanadium (V) can have toxic effects on human organs and physiological systems, yet tracing V sources remains challenging. Here, two methods were used for V source tracing in soil based on speciation characteristics and isotope compositions. According to the sequential extraction method of the European Communities Bureau of Reference (BCR), the analysis of speciation distributions offers a possible means of distinguishing V sources. Here, the isotope compositions of polluted soils around a coal-fired power plant and smelter in China were used to identify the sources of V. Significant V isotope variation (δ51V range = -0.74 ± 0.07; mean ± 2SD = -0.52 ± 0.05‰) was observed in the soil samples, attributed to coal-burning (Δ51VCoal-Fly ash 1 = -0.31 ± 0.05‰; mean ± 2SD; n = 1) and smelting processes (Δ51VSlag-Fly ash 2 = -0.31 ± 0.07‰; mean ± 2SD; n = 1). All of the soil V isotope ratios plotted within the range of end-member components corresponding to potential V contributors in the environment. Among these, δ51V ranged from -0.74 ± 0.07 to -0.55 ± 0.02‰ in topsoil, the average δ51V was -0.52 ± 0.05‰ in the deep soils, and the δ51V of the end-member components ranged from -0.52 ± 0.05 to -0.94 ± 0.11‰. The primary anthropogenic source of V in the topsoil was fly ash from coal-burning that was consistent with the BCR method results. Furthermore, the downward migration of V was identified in the soil profile adjacent to the smelting plant, and V in the deep soils was dominated by natural sources relative to anthropogenic sources in the surface soils.


Assuntos
Poluentes do Solo , Solo , Monitoramento Ambiental , Humanos , Isótopos , Poluentes do Solo/análise , Vanádio
13.
Front Med (Lausanne) ; 8: 699502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381800

RESUMO

Objective: We sought to explore if there is an association between neutrophil-to-lymphocyte ratio (NLR) and treatment failure in patients with peritoneal dialysis-associated peritonitis (PDAP). Methods: Our cohort involved 337 episodes of PDAP experienced by 202 patients who were undergoing continuous ambulatory peritoneal dialysis at a single center from 1 July 2013 to 30 June 2018. The exposures were log-transformed NLR and a categorical variable grouped by the tertiles of NLR levels (T1, <3.75; T2, 3.75-6.53; and T3, >6.53) at baseline. Generalized estimating equation (GEE) and restricted cubic spline (RCS) analyses were done to determine the association between NLR and treatment failure, defined as catheter removal or all-cause mortality during therapy. Results: After adjusting for other potential predictors, the log-transformed NLR exhibited an incremental relationship with the risk of treatment failure (odds ratio, 1.82; 95% confidence interval, 1.05-3.15). RCS analyses showed that the relationship was positively and linearly correlated (P for nonlinearity = 0.104). As a three-level categorical variable, in reference to T1, the T3 of NLR showed a 3.41-fold increased venture of treatment failure in fully adjusted model. Subgroup analyses suggested that the prognostic relevance of NLR in PDAP was particularly significant in gram-negative peritonitis. Conclusions: A greater level of NLR at baseline was remarkably associated with a higher incidence of treatment failure among PDAP episodes regardless of other potential risk factors.

14.
World J Gastrointest Oncol ; 13(8): 893-914, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34457194

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with a poor prognosis, and its treatment remains a great challenge. Dihydrotanshinone I (DHTS) has been reported to exert antitumor effect in many cancers. However, the role of DHTS in ESCC remains unclear. AIM: To investigate the antitumor effect of DHTS in ESCC and the underlying mechanisms. METHODS: CCK-8 assay and cell cycle analysis were used to detect proliferation and cell cycle in ESCC cells. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining were used to detect apoptosis in ESCC cells. Western blot was used to detect the expression of proteins associated with the mitochondrial pathway. Immunofluorescence was used to detect the expression of phosphorylated STAT3 (pSTAT3) in DHTS-treated ESCC cells. ESCC cells with STAT3 knockdown and overexpression were constructed to verify the role of STAT3 in DHTS induced apoptosis. A xenograft tumor model in nude mice was used to evaluate the antitumor effect of DHTS in vivo. RESULTS: After treatment with DHTS, the proliferation of ESCC cells was inhibited in a dose- and time-dependent manner. Moreover, DHTS induced cell cycle arrest in the G0/1 phase. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining revealed that DHTS induced obvious apoptosis in KYSE30 and Eca109 cells. At the molecular level, DHTS treatment reduced the expression of pSTAT3 and anti-apoptotic proteins, while increasing the expression of pro-apoptotic proteins in ESCC cells. STAT3 knockdown in ESCC cells markedly promoted the activation of the mitochondrial pathway while STAT3 overexpression blocked the activation of the mitochondrial pathway. Additionally, DHTS inhibited tumor cell proliferation and induced apoptosis in a xenograft tumor mouse model. CONCLUSION: DHTS exerts antitumor effect in ESCC via STAT3-mediated activation of the mitochondrial pathway. DHTS may be a novel therapeutic agent for ESCC.

15.
Ann Transl Med ; 9(12): 963, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277763

RESUMO

Background: Sagliker syndrome (SS) is characterized by a severe uglifying facial appearance resulting from untreated or inadequately treated secondary hyperparathyroidism (SHPT). To date, the craniofacial morphology of patients with SS has yet to be analyzed. The present research sought to cephalometrically evaluate the craniofacial features of patients with SS and to perform an in-depth analysis of their serum biochemical parameters, with the aim of furthering the theoretical basis for the early diagnosis and prevention of SS. Methods: A retrospective chart review of 9 patients who fulfilled the diagnostic criteria for SS were included in this study, and their serum biochemical parameters were collected. After subjecting standard lateral cephalometric radiographic images to correction for distortions caused by magnification followed by digitization, we conducted a cephalometric analysis. Student's two-tailed t tests or Mann-Whitney U tests were used to analyze the data. Thirty-three patients with patients with SHPT alone were also included as controls. Results: The lower anterior facial height (ANS-ME) and total anterior facial height (N-Me) measurements of patients with SS were significantly increased compared to those of the controls. The angles between the Frankfort horizontal, palatal, and occlusal planes and the mandibular plane, were greater in the SS group than in the control group, as was the gonial angle. Patients with SS also exhibited a significantly larger maxillary protrusion angle and relative position of the maxilla to the mandible. Most patients with SS had class II malocclusion, whereas most of the controls exhibited normal occlusion. Soft tissue largely followed the same pattern as craniofacial changes. Our investigation also showed that among patients with SHPT, female sex, longer duration of dialysis, and higher serum levels of alkaline phosphatase and intact parathyroid hormone were associated with development to SS. Conclusions: Patients with SS show facial and biochemical differences compared to patients with SHPT. Female sex, long dialysis duration, and high serum levels of intact parathyroid hormone and alkaline phosphatase may be potential risk factors for SS.

16.
Front Oncol ; 11: 660320, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307134

RESUMO

The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for Lu-177 or Ra-223 treatment. Drug repurposing as a cost-effective and time-saving alternative to traditional drug development has been increasingly discussed. Proton pump inhibitors (PPIs) such as pantroprazole, which are commonly used as antacids, have also been shown to be effective in cancer chemoprevention via induction of apoptosis in multiple cancer cell lines. Vitamin C is an essential micronutrient for human body, has been proposed as a potential anti-cancer agent. In this context, have we investigated the combination of vitamin C and pantoprazole for the management of metastatic castration-resistant prostate cancer (mCRPC). Six chosen human adenocarcinoma cell lines were used to investigate the influence of pantoprazole on the microenvironment of cancer cells (extracellular pH and production of exosomes). Tumor growth and tumor 18F-FDG uptake in PC3 xenografts were analyzed following varied treatment. Our in vitro Results have suggested that pantoprazole enhanced the cytotoxic activity of vitamin C by regulating pH values and production of exosomes in cancer cells. Moreover, the synergistic effect of pantoprazole and vitamin C was pH-dependent since pantoprazole was more effective at a slightly acidic pH. In vivo, the combined treatment using pantoprazole and vitamin C produced better therapeutic outcomes than treatment with vitamin C or pantoprazole alone, as demonstrated via tumor growth and uptake of 18F-FDG. Therefore, we suggest that pantoprazole combined with vitamin C could be as a possible strategy to manage mCRPC.

17.
ACS Appl Mater Interfaces ; 13(32): 38866-38876, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34318673

RESUMO

Cu/SiO2 hybrid bonding with planarized dielectric and isolated metal connections can realize ultradense interconnects (e.g., ≤1 µm) by eliminating the microbumps and underfill through the direct bonding of Cu-Cu and SiO2-SiO2. However, the low-temperature bonding of Cu-Cu (oxide-free surface) and SiO2-SiO2 (hydroxylated surface) is difficult to be compatible in a mechanism. We circumvent this contradiction by constructing a co-hydroxylated functional surface on a Cu/SiO2 hybrid platform. By combining and optimizing the protocol of Ar/O2 plasma activation and formic acid solution immersion, an -OH active layer was successfully established on the Cu and SiO2 surfaces simultaneously, and the increased total surface area provided more adsorption sites for hydroxyl groups. A Cu-Cu interface with sufficient atom diffusion, substantial grain growth, and fewer microvoids was obtained at 200 °C. Notably, the carbon-related interlayer that may degrade the interfacial performance could be effectively inhibited across the optimized SiO2-SiO2 interface even if organic acid was introduced in the protocol. This low-temperature Cu/SiO2 hybrid bonding via a co-hydroxylated strategy may inspire the development of a memory-centric chip architecture and functional integrated circuits delivering a monolithic-like performance in the future hyperscaling era.

18.
Chin Med J (Engl) ; 134(16): 1967-1976, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34310400

RESUMO

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).


Assuntos
COVID-19 , Idoso , Anticorpos Antivirais , COVID-19/terapia , Vacinas contra COVID-19 , Método Duplo-Cego , Humanos , Imunização Passiva , Proteínas Recombinantes de Fusão , SARS-CoV-2
19.
Atherosclerosis ; 331: 6-11, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34252837

RESUMO

BACKGROUND AND AIMS: Although ticagrelor exerts an antibacterial activity, its effect on infections in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) is unclear. We aimed to assess whether ticagrelor and clopidogrel affect infections in these patients during hospitalization. METHODS: A total of 2116 consecutive patients with STEMI undergoing PCI were divided into the ticagrelor (n = 388) and clopidogrel (n = 1728) groups. The primary outcome was infection onset. Secondary outcomes were in-hospital all-cause death and major adverse cardiovascular and cerebrovascular events (MACCE). Propensity score analyses were conducted to test the robustness of the results. RESULTS: Infections developed in 327 (15.4%) patients. There was no significant difference in infection between both groups (ticagrelor vs. clopidogrel: 13.1% vs. 16.0%, p = 0.164). Patients in the ticagrelor group had lower rates of in-hospital all-cause death and MACCE than patients in the clopidogrel group. Multivariate logistic regression analysis determined that ticagrelor and clopidogrel had a similar preventive effect on infections during hospitalization (adjusted odds ratio [OR] = 1.20; 95% confidence interval [CI] = 0.80-1.78, p = 0.380). Compared to the patients treated with clopidogrel, patients treated with ticagrelor had a slightly lower risk of other outcomes, but no statistical difference. Propensity score analyses demonstrated similar results for infections and other outcomes. CONCLUSIONS: Compared with clopidogrel treatment, ticagrelor treatment did not significantly alter the risk of infections during hospitalization among STEMI patients undergoing PCI, but was associated with a slightly lower risk of in-hospital all-cause death and MACCE.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Hospitalização , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Ticagrelor/efeitos adversos , Resultado do Tratamento
20.
J Oncol ; 2021: 6687291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239564

RESUMO

Objective: To investigate the association between KRAS/NRAS/BRAF mutations and metabolic parameters of pretreatment 18F-FDG PET/CT in colorectal cancer (CRC). Methods: A total of 85 patients with CRC were included in the study. PET/CT was performed in all the patients before surgery. The histopathological examination and analysis of the gene mutational status of the primary tumor were conducted. The associations among clinical features, PET metabolic parameters, and the gene mutational status were investigated. Moreover, receiver operating characteristic (ROC) curves for maximum standard uptake value (SUVmax) of the primary tumor were generated along with analysis of the target tissue to nontarget tissue ratio (T/NT) for predicting the efficacy of KRAS/NRAS/BRAF mutations in CRC. Finally, the corresponding area under the curve, the optimal cutoff value, and the corresponding sensitivity and specificity were obtained. Results: The mutation rate of KRAS/NRAS/BRAF was 54.12% (46/85). In addition, both SUVmax and T/NT were significantly higher in the KRAS/NRAS/BRAF-mutation groups compared to the wild-type group (15.88 ± 6.71 vs. 12.59 ± 5.79, 8.04 ± 3.03 vs. 6.38 ± 2.80; P=0.012 and 0.004, respectively). Results from the ROC curve also showed that the cutoff values for T/NT and SUVmax were 5.14 and 12.40, respectively, while the predictive accuracy was 0.682 and 0.647, respectively. On the other hand, the sensitivity was 91.30% and 65.22% while the specificity was 43.59% and 64.10%, respectively. Moreover, univariate analysis showed that the KRAS/NRAS/BRAF mutation was not significantly associated with gender, age, lesion location, tumor length, pathological type, tissue differentiation, and UICC staging (all P > 0.05). Conclusion: T/NT ratio and SUVmax could be the potential surrogate imaging indicators to predict the KRAS/NRAS/BRAF mutational status in CRC patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...