RESUMO
Bimetallic nanomaterials (BNMs) have been used in sensing, biomedicine, and environmental remediation, but their multipurpose and comprehensive applications in molecular logic computing and information security protection have received little attention. Herein, This synthesis method is achieved by sequentially adding reactants under ice bath conditions. Interestingly, Ag-Cr NPs can dynamically selectively sense anions and reductants in multiple channels. Especially, ClO- can be quantitatively detected by oxidizing Ag-Cr NPs with detection limits of 98.37 nM (at 270 nm) and 31.83 nM (at 394 nm). Based on sequential-dependent synthesis process of Ag-Cr NPs, Boolean logic gates and customizable molecular keypad locks are constructed by setting the reactants as the inputs, the states of the resulting solutions as the outputs. Furthermore, dynamically selective response patterns of the Ag-Cr NPs can be converted into binary strings to exploit molecular crypto-steganography to encode, store, and hide information. By integrating the three dimensions of authorization, encryption, and steganography, 3 in 1 advanced information protection based on Ag-Cr nanosensing system can be achieved, which can enhance the anti-cracking ability of information. This research will promote the development and application of nanocomposites in the field of information security and deepen the connection between molecular sensing and the information world.
RESUMO
Emergomyces is a newly described dimorphic fungus genus; it may cause fatal infections in immunocompromised patients, but diagnosis is often delayed. We report a case of disseminated emergomycosis caused by the novel species Emergomyces orientalis in a kidney transplant recipient from Tibet. Infection was diagnosed early by metagenomic next-generation sequencing.
Assuntos
Micoses , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenômica , Micoses/diagnóstico , OnygenalesRESUMO
Inspired by information exchange and logic functions of life based on molecular recognition and interaction networks, ongoing efforts are directed toward development of molecular or nanosystems for multiplexed chem/biosensing and advanced information processing. However, because of their preparation shortcomings, poor functionality, and limited paradigms, it is still a big challenge to develop advanced nanomaterials-based systems and comprehensively realize neuron-like functions from multimode sensing to molecular information processing and safety. Herein, using fish scales derived carbon nanoparticles (FSCN) as a reducing agent and stabilizer, a simple one-step synthesis method of multifunctional silver-carbon nanocomposites (AgNPs-FSCN) is developed. The prepared AgNPs-FSCN own wide antibacterial and multisignal response abilities in five channels (including color, Tyndall, absorption and fluorescence intensities, and absorption wavelength) for quantitative colorimetric and fluorescence sensing of H2 O2 , ascorbic acid, and dopamine. Benefiting from its multicoding stimuli-responsive ability, molecular concealment, and programmability, AgNPs-FSCN can be abstracted as nanoneurons for implementing batch and parallel molecular logic computing, steganography, and cryptography. This research will promote the preparation of advanced multifunctional nanocomposites and the development of their multipurpose applications, including the multireadout-guided multianalyte intelligent sensing and sophisticated molecular computing, communication, and security.
Assuntos
Nanopartículas Metálicas , Nanocompostos , Animais , Carbono , Dopamina , Lógica , PrataRESUMO
Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.
Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Imidazóis/uso terapêutico , Compostos Macrocíclicos/uso terapêutico , Pirrolidinas/uso terapêutico , Quinoxalinas/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Valina/análogos & derivados , Combinação de Medicamentos , Hepatite C/virologia , Humanos , Ribavirina/uso terapêutico , Valina/uso terapêuticoRESUMO
Toxoplasma gondii is a protozoan with worldwide distribution that infects birds and mammals, including humans. The consumption of free-range chicken meat is a common practice in many parts of the world. However, little information is available concerning the molecular prevalence and genotypes of T. gondii infection in free-range chickens intended for human consumption in China. In this study, a total of 1360 serum samples were collected from food markets in Hunan province of China for detecting T. gondii antibodies by indirect hemagglutination assay. In addition, 650 brain tissues were also collected to investigate T. gondii DNA by amplification of B1 gene with a seminested polymerase chain reaction (PCR), and the positive DNA samples were typed at 10 genetic markers using multilocus PCR-restriction fragment length polymorphism. Antibodies to T. gondii were detected in 457 of the examined serum samples (33.6%; 95% confidence interval [CI]: 31.1-36.1), and 72 DNA samples (11.1%; 95% CI: 8.6-13.4) were positive for the T. gondii B1 gene. In this study, region and age of free-range chickens were shown to be risk factors for T. gondii infection (p < 0.01). Two genotypes (ToxoDB#9 and ToxoDB#52) were identified from two samples with complete genotyping results. Our study revealed a high prevalence of T. gondii infection in free-range chickens intended for human consumption in Hunan province, suggesting that recommendations to consumers should be made, especially in some regions of China where consumption of undercooked chicken meat is common. This is the first genetic characterization of T. gondii in free-range chickens intended for human consumption in Hunan province, China, and also the first report of genotype ToxoDB#52 in China.
Assuntos
Galinhas/parasitologia , Microbiologia de Alimentos/estatística & dados numéricos , Doenças das Aves Domésticas/epidemiologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/epidemiologia , Animais , Galinhas/sangue , China/epidemiologia , Genótipo , Humanos , Doenças das Aves Domésticas/parasitologia , Fatores de Risco , Estudos Soroepidemiológicos , Toxoplasma/genética , Toxoplasmose Animal/parasitologiaRESUMO
According to Healthy China, a national strategy of the Government of China, new requirements were put forward for high-quality medical education, high-level surgical research, and precise clinical diagnosis and treatment. In the context of Emerging Medical Discipline, a strategic blueprint of medical education in China, this paper reviews the concept and core value of virtual reality (VR) and its significant role in the medical industry. On that basis, we explore the role of VR technology in medical training against the background of Emerging Medicine Discipline. Furthermore, typical cases are presented to help analyze and illustrate in detail the important role of VR technology in the teaching and training of stomatological and clinical procedures, skills assessment, online self-directed training, and clinical thinking skills training. We herein summarize useful information from past experience so as to help build innovative models of medical education in the context of Emerging Medical Discipline.
Assuntos
Educação Médica , Realidade Virtual , China , Competência Clínica , TecnologiaRESUMO
Compared with adults, children tend to have lower incidence rate, hospitalization rate, and mortality rate of coronavirus disease 2019 (COVID-19), while the cause of such age-based differences in disease severity remains unclear. An investigation of pathogenesis in children may help to analyze the therapies for the high-risk population. Human angiotensin-converting enzyme â ¡ is the main receptor of severe acute respiratory syndrome coronavirus 2 and can limit pulmonary capillary leakage and inflammation mediated by angiotensin 2 and exert a protective effect against acute lung injury. Its expression decreases with age. Regular vaccination and frequent upper respiratory virus infection in children can lead to regular immune activation, and its combination with strong innate immunity can help to achieve virus clearance in the early stage of infection in children with COVID-19. Meanwhile, there are strong regeneration and repair abilities of alveolar epithelial cells in children, which may help with the early recovery of infection. In addition, risk factors, such as underlying cardiopulmonary diseases, obesity, and smoking, are relatively uncommon in children. Social factors, including home quarantine and timely closure of schools, may help to reduce the infection rate in children. However, children with immunodeficiency are a high-risk population and should be closely monitored. Further studies are needed to investigate the immune and protection mechanisms against COVID-19 in children.
Assuntos
COVID-19 , Adulto , Criança , Humanos , Inflamação , Pulmão , Fatores de Risco , SARS-CoV-2RESUMO
OBJECTIVE: To detect pathogens in a critically ill patient using metagenomic sequencing. METHODS: A critically ill patient with severe acute pancreatitis suffered from abdominal pain and progressed into unconsciousness. Tissue smear, culture, automated biochemical identification and antibiotic susceptibility test, viral load determination by real-time fluorescence quantitative PCR, and immunohistochemical pathological tests were performed to detect pathogens, in addition to metagenomic sequencing based on the BGISEQ-100 high throughput sequencing platform. The sequences exclusive of host sequences were searched in the microbial genome database including viruses, bacteria, fungi and parasites. RESULTS: The patient was infected with methicillin-resistant Staphylococcus aureus, carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii, verified by both the routine methods and the metagenomic sequencing. The metagenomic sequencing also detected cytomegalovirus (CMV) with a turn-around time of 5 days. Real-time fluorescent quantitative PCR confirmed 189 000 copies/mL CMV load. CONCLUSION: In this case, three species of bacteria and one virus were detected by metagenomic sequencing quickly and accurately. Metagenomic sequencing may be helpful for diagnosing infectious diseases in critically ill patients.
Assuntos
Acinetobacter baumannii/isolamento & purificação , Infecções Bacterianas/diagnóstico , Klebsiella pneumoniae/isolamento & purificação , Metagenômica , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Estado Terminal , Farmacorresistência Bacteriana , Sequenciamento de Nucleotídeos em Larga Escala , HumanosRESUMO
BACKGROUND: Tremendous efforts have been made to establish the concept of vascular restoration therapy with a fully bioresorbable scaffold for coronary artery disease. With an improved scaffold design and technologies, the novel NeoVas scaffold has shown promising clinical performance at 6 months follow-up. OBJECTIVE: The aim of this study was to investigate the 1 year clinical outcomes and multislice computed tomography (MSCT) angiographic results after implantation of the NeoVas scaffold in patients with single de novo coronary artery lesions. METHODS: The NeoVas first-in-man study was a prospective, two-center, single-arm study enrolling 31 patients who were eligible for the treatment. The composite endpoint of target lesion failure (TLF)-defined as cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization (TLR)-was assessed. Of the 31 patients scheduled for 1 year clinical follow-up, 29 patients received MSCT examinations. RESULTS: At 1 year follow-up, there was only 1 (3.2%) TLF, attributed to 1 patient who suffered ischemia-driven TLR at 181 days postprocedure. No cardiac deaths or scaffold thrombosis were observed. MSCT analysis demonstrated excellent vessel patency, with a median in-scaffold lumen area of 10.6 mm2 (interquartile range [IQR]: 8.2-11.7 mm2 ) and a minimal lumen diameter of 2.7 mm (IQR: 2.4-3.0 mm). CONCLUSIONS: This study demonstrated the safety and efficacy of the NeoVas scaffold for patients with single de novo coronary artery lesions at 1 year of follow-up. Noninvasive MSCT data confirmed vessel patency and the maintenance of vessel dimensions following implantation of the NeoVas bioresorbable sirolimus-eluting scaffold.
Assuntos
Implantes Absorvíveis , Fármacos Cardiovasculares/administração & dosagem , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos , Tomografia Computadorizada Multidetectores , Intervenção Coronária Percutânea/instrumentação , Sirolimo/administração & dosagem , Idoso , Fármacos Cardiovasculares/efeitos adversos , China , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Desenho de Prótese , Sirolimo/efeitos adversos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Ultrassonografia de Intervenção , Grau de Desobstrução VascularRESUMO
OBJECTIVE: To investigate the clinical outcomes influenced by distal extension of false lumen in acute type B aortic dissection (TBAD) patients following thoracic endovascular aortic repair (TEVAR). METHODS: From April 2002 to January 2013, 264 TBAD patients treated with TEVAR were retrospectively enrolled. The IIIa group exhibited a distal false lumen above the diaphragm (n = 70), and the IIIb group exhibited a distal false lumen under the diaphragm (n = 194). The morphological characteristics and adverse events (30-day and >30 days) were recorded and evaluated. RESULTS: There were no significant differences between the two groups regarding the demographics, comorbidity profiles, or initial feature of computed tomography angiography. The incidence of true lumen compression and branch involvement were significantly increased in the IIIb group compared with the IIIa group (8.6% vs. 25.3%, respectively; 15.7% vs. 36.1%, respectively, both P < 0.05). The 30-day mortality rate was 1.0% (2/194) in the IIIb group, whereas the IIIa group was zero. The incidence of early adverse events, the 5-year cumulative freedom from adverse events, and the 5-year cumulative freedom from all-cause mortality rate were not significantly different between the IIIa and IIIb groups (2.9% vs. 6.7%, 81.4%, and 80.4%, and 95.7% vs. 93.8%, respectively, all P > 0.05). Log-rank tests also indicated there was no significant difference. CONCLUSIONS: There was no significant difference between the IIIa and IIIb groups in the 5-year morality and adverse aortic events following TEVAR. The distal extension of false lumen prior to TEVAR does not influence the long-term morality and adverse aortic events in acute TBAD.
Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Complicações Pós-Operatórias/etiologia , Doença Aguda , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aortografia/métodos , Implante de Prótese Vascular/mortalidade , Distribuição de Qui-Quadrado , Angiografia por Tomografia Computadorizada , Dilatação Patológica , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate the feasibility of ultrashort echo time (UTE) magnetic resonance imaging (MRI) for the diagnosis of skull fractures. METHODS: The skull fracture models of ten Bama pigs and 364 patients with craniocerebral trauma were subjected to computed tomography (CT), UTE and conventional MRI sequences. The accuracy of UTE imaging in skull fracture diagnosis was analysed using receiver operating characteristic (ROC) curve analysis, McNemar's test and Kappa values. Differences among CT, UTE imaging and anatomical measurement (AM) values for linear fractures (LFs) and depressed fractures (DFs) were compared using one-way ANOVA and a paired-samples t-test. RESULTS: UTE imaging clearly demonstrated skull structures and fractures. The accuracy, validity and reliability of UTE MRI were excellent, with no significant differences between expert readings (P > 0.05; Kappa, 0.899). The values obtained for 42 LFs and 13 DFs in the ten specimens were not significantly different among CT, UTE MRI and AMs, while those obtained for 55 LFs and ten DFs in 44 patients were not significantly different between CT and UTE MRI (P > 0.05). CONCLUSIONS: UTE MRI sequences are feasible for the evaluation of skull structures and fractures, with no radiation exposure, particularly for paediatric and pregnant patients. KEY POINTS: Despite ionising radiation, CT is standard for skull fracture assessment. Conventional MRI cannot depict skull structures. 3D-UTE sequences clearly demonstrate skull structures and fractures. UTE plus conventional MRI are superior to CT in craniocerebral trauma assessment. Paediatric and pregnant patients will benefit from this imaging modality.
Assuntos
Imagem Ecoplanar/métodos , Imageamento Tridimensional/métodos , Fraturas Cranianas/diagnóstico , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Suínos , Porco Miniatura , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
NS5ATP9, a gene up-regulated by NS5A, plays a crucial oncogenic role in several types of human tumours. However, the underlying mechanisms remain unclear. Autophagy, an evolutionarily conserved catabolic process, maintains cellular homeostasis under stress conditions, such as starvation, and plays a crucial role in tumour initiation and progression. Here, we report that NS5ATP9 mRNA and protein expression was up-regulated in starved HepG2 cells and that the up-regulated NS5ATP9 played a functional role in starvation-induced autophagy. Overexpression or silencing of this gene showed contrasting effects on Beclin 1 and on starvation-induced autophagy. Furthermore, NS5ATP9-mediated autophagy is required for promotion of tumour cell growth, and this effect could be inhibited with 3-methyladenine, chloroquine or by Beclin 1-silencing. Thus, the mechanism for NS5ATP9-promoted autophagy is Beclin 1-dependent in the condition of starvation, and for hepatoblastoma cell growth is also Beclin 1-dependent.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Proteínas de Transporte/genética , Hepatoblastoma/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana/genética , Adenina/análogos & derivados , Adenina/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Proteína Beclina-1 , Proteínas de Transporte/metabolismo , Proliferação de Células , Cloroquina/farmacologia , Proteínas de Ligação a DNA , Células Hep G2 , Hepatoblastoma/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , Estresse FisiológicoRESUMO
Hepatitis C virus (HCV) core protein stimulates many signaling pathways related to apoptosis inhibition resulting in hepatocellular carcinoma (HCC). It has been reported that sirt1 is involved in regulating apoptosis; therefore, we investigated the influence of HCV core protein on sirt1 expression and apoptosis in human HepG2 cells. Our study showed that HCV core protein inhibited apoptosis of HepG2 cells as well as caspase-3 expression and activity (P < 0.05). At the same time, sirt1 expression was increased at both the mRNA (P < 0.05) and protein (P < 0.05) levels. Furthermore, apoptosis inhibition was reversed when sirt1 was knocked down (P < 0.05). Our study provides further evidence that the sirt1-p53-Bax signaling pathway plays an important role in regulating the suppression of cell apoptosis induced by HCV core protein.
Assuntos
Apoptose/efeitos dos fármacos , Células Hep G2/virologia , Hepacivirus/fisiologia , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas do Core Viral/biossíntese , Proteínas do Core Viral/metabolismo , Proteína X Associada a bcl-2/metabolismo , Sequência de Bases , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virologia , Técnicas de Silenciamento de Genes , Células Hep G2/citologia , Hepacivirus/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virologia , Dados de Sequência Molecular , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Transdução de Sinais , Sirtuína 1/farmacocinética , Proteínas do Core Viral/genéticaRESUMO
BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation remains controversial. The primary aim of our study was to evaluate the impact of optimal DAPT duration on bleeding events between 6 and 12 months after biodegradable polymer-coated DES implantation. The secondary aim is to determine the predictors and prognostic implications of bleeding. METHODS: This study is a post hoc analysis of the Multi-Center Registry of EXCEL Biodegradable Polymer Drug Eluting Stents (CREATE) study population. A total of 2,040 patients surviving at 6 months were studied, including 1,639 (80.3%) who had received 6-month DAPT and 401 (19.7%) who had received DAPT greater than 6 months. Bleeding events were defined according to the bleeding academic research consortium (BARC) definitions as described previously and were classified as major/minor (BARC 2-5) and minimal (BARC 1). A left censored method with a landmark at 6 months was used to determine the incidence, predictors, and impact of bleeding on clinical prognosis between 6 and 12 months. RESULTS: At 1-year follow-up, patients who received prolonged DAPT longer than 6 months had a significantly higher incidence of overall (3.0% vs. 5.5%, P = 0.021) and major/minor bleeding (1.1% vs. 2.5%, P = 0.050) compared to the patients who received 6-month DAPT. Multivariate analysis showed that being elderly (OR = 1.882, 95% CI: 1.109-3.193, P = 0.019), having diabetes (OR = 1.735, 95% CI: 1.020-2.952, P = 0.042), having a history of coronary artery disease (OR = 2.163, 95% CI: 1.097-4.266, P = 0.026), and duration of DAPT longer than 6 months (OR = 1.814, 95% CI: 1.064-3.091, P = 0.029) were independent predictors of bleeding. Patients with bleeding events had a significantly higher incidence of cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis. CONCLUSIONS: Prolonged DAPT (greater than 6 months) after biodegradable polymer-coated DES increases the risk of bleeding, and is associated with adverse cardiac events at 1-year follow-up. (J Interven Cardiol 2014;27:119-126).
Assuntos
Stents Farmacológicos , Hemorragia/induzido quimicamente , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Plásticos Biodegradáveis , Clopidogrel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivadosRESUMO
Clostridioides difficile (formerly Clostridium difficile) has been regarded as an 'urgent threat' and a significant global health problem, as life-threatening diarrhoea and refractory recurrence are common in patients with C. difficile infection (CDI). Unfortunately, the available anti-CDI drugs are limited. Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and faecal microbiota transplantation for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g. teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g. Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g. vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g. Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarises current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation.
Assuntos
Antibacterianos , Clostridioides difficile , Infecções por Clostridium , Transplante de Microbiota Fecal , Humanos , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/prevenção & controle , Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Vancomicina/uso terapêutico , Fidaxomicina/uso terapêuticoRESUMO
BACKGROUND: Cartilage defects are some of the most common causes of arthritis. Cartilage lesions caused by inflammation, trauma or degenerative disease normally result in osteochondral defects. Previous studies have shown that decellularized extracellular matrix (ECM) derived from autologous, allogenic, or xenogeneic mesenchymal stromal cells (MSCs) can effectively restore osteochondral integrity. AIM: To determine whether the decellularized ECM of antler reserve mesenchymal cells (RMCs), a xenogeneic material from antler stem cells, is superior to the currently available treatments for osteochondral defects. METHODS: We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70% confluence; 50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition. Decellularized sheets of adipocyte-derived MSCs (aMSCs) and antlerogenic periosteal cells (another type of antler stem cells) were used as the controls. Three weeks after ascorbic acid stimulation, the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints. RESULTS: The defects were successfully repaired by applying the ECM-sheets. The highest quality of repair was achieved in the RMC-ECM group both in vitro (including cell attachment and proliferation), and in vivo (including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues). Notably, the antler-stem-cell-derived ECM (xenogeneic) performed better than the aMSC-ECM (allogenic), while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells. CONCLUSION: Decellularized xenogeneic ECM derived from the antler stem cell, particularly the active form (RMC-ECM), can achieve high quality repair/reconstruction of osteochondral defects, suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.
RESUMO
This study aimed to investigate the impact of different nitrogen forms on soil physicochemical properties and microbial community structure in perennial alpine cultivated grasslands, in order to provide scientific basis for developing nitrogen addition strategies for perennial alpine cultivated grasslands. In June 2022, a 4-year-old Qinghai grassland mixed with Poa pratensis Qinghai and Festuca sinensis Qinghai was established at the Bakatai Farm in Gonghe County, Hainan Tibetan Autonomous Prefecture, Qinghai Province. The study was conducted without fertilization as a control (CK), and three different forms of nitrogen treatments were set up, namely, U:urea (amide nitrogen), A:ammonium sulfate (ammonium nitrogen), and N:calcium nitrate (nitrate nitrogen); the nitrogen application rate for each treatment was 67.5 kg·(hm2·a)-1, and the composition and diversity of soil nutrients and microbial communities under different treatments were analyzed. The results showed that the input of exogenous ammonium nitrogen significantly increased NH4+-N content, AP content, and EC; amide nitrogen input significantly increased SOC content and TN content; and nitrate nitrogen input significantly increased NO3--N content, AN content, and TC content. Exogenous nitrogen input changed the structure of soil bacterial and fungal communities, as well as the relative abundance of dominant phyla and genera, but it did not significantly affect the alpha diversity of bacterial and fungal communities. Principal coordinate analysis (PCoA) showed that different forms of nitrogen addition had a significant impact on the Beta diversity of bacterial communities, whereas the impact on fungal communities was not significant. Redundancy analysis (RDA) indicated that nitrogen addition mainly changed the composition and structure of microbial communities through soil ammonium nitrogen. Overall, ammonium nitrogen fertilizer should be given priority in the soil remediation process of perennial cultivated grasslands in the Qinghai Tibet Plateau.
Assuntos
Fertilizantes , Pradaria , Microbiota , Nitrogênio , Microbiologia do Solo , Solo , Solo/química , China , Poaceae/crescimento & desenvolvimentoRESUMO
The importance of matrix metalloproteinase 8 (MMP8) expression during the progression of thoracic aortic dissection (TAD) has been recently emphasized. Genetic variations that affect proteinase expression or activity might contribute to the pathogenesis of TAD. In this study, we investigated whether the MMP8 C-799T genotype is associated with TAD. The frequency distributions of the MMP8 C-799T polymorphism were determined by direct sequencing. Associations between the polymorphism and disease progression in TAD were investigated. The level of plasma and tissue MMP8 was measured by enzyme-linked immunosorbent assay and western blotting. The MMP8 C-799T polymorphism was significantly associated with susceptibility to disease progression in TAD patients (n = 152) than in controls (n = 147) (P = 0.004, OR = 0.62, 95 % CI 0.45-0.86). The TT homozygotes had a significantly higher risk of TAD compared to C allele carriers in a logistic regression model, after adjustment for the conventional risk factors for TAD. The plasma MMP8 concentration was significantly higher in TAD patients compared to control patients (P < 0.05). TT genotypes had increased MMP8 levels compared to CC and CT genotype carriers in both TAD and control subjects (P < 0.05). The C-799T polymorphism in the MMP8 promoter is part of the genetic variation underlying the susceptibility of individuals to the progression of TAD.
Assuntos
Aorta Torácica/patologia , Dissecção Aórtica/genética , Povo Asiático/genética , Etnicidade/genética , Predisposição Genética para Doença , Metaloproteinase 8 da Matriz/genética , Polimorfismo de Nucleotídeo Único/genética , Dissecção Aórtica/enzimologia , Aorta Torácica/enzimologia , Western Blotting , Estudos de Casos e Controles , Demografia , Ensaio de Imunoadsorção Enzimática , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Background: The burden of alcohol-related liver disease (ARLD) is increasing in China. Patients with ARLD are more likely to have comorbid sarcopenia, which may impair their survival. This study aimed to evaluate the relationship between the prognoses of patients with ARLD and sarcopenia, identified using the skeletal muscle index at the third lumbar vertebra level (L3-SMI). Methods: Hospitalized patients with ARLD were retrospectively enrolled between 2015 and 2018 and followed up for 24 months to evaluate their survival profiles. Cox proportional hazards regression models were used to estimate patient survival factors. A receiver operating characteristic curve was created to identify the cut-off point of the L3-SMI for predicting the prognoses of Chinese patients with ARLD. Results: The study enrolled 168 male patients with ARLD who were followed-up for 24 months or until a study endpoint was met. The overall L3-SMI in patients with ARLD was 42.61 ± 9.15 cm2/m2, and 42.86% (72/168) of patients with ARLD were comorbid with sarcopenia. The overall survival in patients with ARLD was 77.38% at 24 months. The survival rate of patients with sarcopenia was lower than that of patients without sarcopenia (66.67% vs. 85.42%, p = 0.004). Multiple Cox regression analysis showed that sarcopenia, abstinence, and baseline creatinine level were independent prognostic factors of 24-month survival with hazard ratios (95% confidence intervals) of 2.022 (1.025-3.991), 0.275 (0.122-0.617), and 1.018 (1.008-1.027), respectively. The cut-off value of the L3-SMI for predicting 24-month survival was 40.0 cm2/m2 for male patients with ARLD. Conclusion: Sarcopenia is an independent mortality risk factor in male patients with ARLD in mainland China. Early diagnosis and intervention of sarcopenia are important for optimizing the management of patients with ARLD.
RESUMO
BACKGROUND: The Model for End-stage Liver Disease (MELD) 3.0 yields high prognostic performance for patients with end-stage liver disease (ESLD). However, its prognostic performance for patients with alcohol-related liver disease (ARLD) has limited results. The aim of this study was to perform such an evaluation among Chinese patients. METHODS: Patients hospitalized with ARLD in one institution between 2015 and 2018 were retrospectively included and followed up for 12 months. The original MELD, MELD-Na, MELD 3.0, and modified Maddrey discriminant function (MDF) scores were calculated for each patient at baseline. Their prognostic performances for 1-year survival were assessed. Time-dependent receiver operating characteristic curves were constructed, and AUCs were calculated for each scoring system. RESULTS: Among the 576 patients included in our analysis, 209 patients had alcoholic hepatitis (AH). By the 1-year follow-up, 14.8% (84/567) of all the patients and 23.4% (49/209) of those with AH had died. Overall, patients who had died had higher MELD, MELD-Na, MELD 3.0, and MDF scores (all p < 0.001) than those who had not. The same was true in the AH subgroup (MELD: p < 0.001, MELD-Na: p < 0.001, MELD 3.0: p = 0.007, MDF: p = 0.017). The AUC of the MELD 3.0 for prediction of 1-year survival among patients with ARLD was 0.682, lower than that of the original MELD (0.728, p < 0.001) and MELD-Na (0.735, p < 0.001). Moreover, in the AH subgroup, the AUC for the prediction of 1-year survival was lower than that in the MELD-Na subgroup (0.634 vs. 0.708, p < 0.001). CONCLUSIONS: The MELD 3.0 was not superior to the original MELD or the MELD-Na in predicting the mortality of patients with ARLD.