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1.
J Immunol ; 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688465

RESUMO

SM03, an anti-CD22 recombinant IgG1 mAb, is currently in a phase III clinical trial for the treatment of rheumatoid arthritis (NCT04312815). SM03 showed good safety and efficacy in phase I systemic lupus erythematosus and phase II moderate to severe rheumatoid arthritis clinical trials. We propose the success of SM03 as a therapeutic to systemic autoimmune diseases is through the utilization of a novel mechanism of action unique to SM03. CD22, an inhibitory coreceptor of the BCR, is a potential immunotherapeutic target against autoimmune diseases. SM03 could disturb the CD22 homomultimeric configuration through disrupting cis binding to α2,6-linked sialic acids, induce rapid internalization of CD22 from the cell surface of human B cells, and facilitate trans binding between CD22 to human autologous cells. This in turn increased the activity of the downstream immunomodulatory molecule Src homology region 2 domain-containing phosphatase 1 (SHP-1) and decreased BCR-induced NF-κB activation in human B cells and B cell proliferation. This mechanism of action gives rationale to support the significant amelioration of disease and good safety profile in clinical trials, as by enabling the "self" recognition mechanism of CD22 via trans binding to α2,6 sialic acid ligands on autologous cells, SM03 specifically restores immune tolerance of B cells to host tissues without affecting the normal B cell immune response to pathogens.

2.
Fa Yi Xue Za Zhi ; 38(1): 53-58, 2022 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35725704

RESUMO

OBJECTIVES: To explore the application value of virtual autopsy to obtain key evidence information on drowned corpses and its application value of virtual autopsy in the diagnosis of drowning. METHODS: In this study, 7 corpses were selected as the research objects. The image data of corpses were collected by computed tomography (CT) before conventional autopsy. The characteristics of corpses were observed through image reading, combined with virtual measurement indexes, and compared with 15 non-drowned corpses. RESULTS: The postmortem CT of drowning showed the more fluid in respiratory tract than the non-drowning, and ground-glass opacities in the lung. The statistical volume of fluid in the sinus (maxillary sinus and sphenoid sinus) was (10.24±4.70) mL in drowning cases and (2.02±2.45) mL in non-drowning cases. The average CT value of fluid in the sinus, left atrial blood and gastric contents in drowning cases were (15.91±17.20), (52.57±9.24) and (10.33±12.81) HU, respectively, which were lower than those in non-drowning cases (P<0.05). CONCLUSIONS: The comprehensive consideration of multiple characteristic image manifestations and the virtual measurement indexes are helpful to the forensic pathological diagnosis of drowning. Virtual autopsy can be used as an auxiliary method in the forensic diagnosis of drowning.


Assuntos
Afogamento , Autopsia/métodos , Cadáver , Afogamento/diagnóstico por imagem , Patologia Legal/métodos , Humanos , Tomografia Computadorizada por Raios X/métodos
3.
Medicine (Baltimore) ; 101(2): e28544, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029212

RESUMO

RATIONALE: Postmortem imaging (PMI), including computed tomography (PMCT), postmortem computed tomography angiography (PMCTA), and postmortem magnetic resonance imaging (PMMRI), is rapidly becoming effective and a practical method in forensic medicine. This study aimed to present a specific forensic case in which the PMI approach and its applications were used. PATIENT CONCERNS: A 40-year-old male patient had moderate unilateral nose bleeding constantly 10 times after suffering from a head injury induced by a car accident. After a bilateral massive nose bleeding for the last time, he died from hemorrhagic shock. Traumatic internal carotid artery pseudoaneurysm (TICAP) was suspected in this patient. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: A whole-body scanning was performed using PMCT and PMMRI. Then, PMCTA using left ventricular cardiac puncture was also implemented. A water-soluble contrast agent was injected into the left ventricle and pumped toward the intracranial, followed by a repeated whole-body PMCT scan. The PMCT/PMMRI detected a high-density/signal mass inside the left sphenoid sinus. The PMCTA detected a distinct leakage of the contrast agent into the left sphenoid sinus from an adjacent aneurysm of the C3 section of the left internal carotid artery. Autopsy and histology confirmed a TICAP inside the sphenoid sinus. LESSONS: This case showed that the PMI was of great value for identifying the cause of death in special cases. When vascular lesions are suspected in the body, PMI and especially the PMCTA approach may be an effective detection method.


Assuntos
Falso Aneurisma/diagnóstico por imagem , Autopsia/métodos , Artéria Carótida Interna/diagnóstico por imagem , Meios de Contraste , Adulto , Falso Aneurisma/etiologia , Angiografia por Tomografia Computadorizada , Evolução Fatal , Hemorragia , Humanos , Masculino
4.
Bioengineered ; 12(2): 9452-9462, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34696677

RESUMO

LYAR (Ly-1 antibody reactive) is a transcription factor with a specific DNA-binding domain, which plays a key role in the regulation of embryonic stem cell self-renewal and differentiation. However, the role of LYAR in human cancers remains unclear. This study aimed to analyze the prognostic value of LYAR in cancer. In this study, we evaluated the prognostic value of LYAR in various tumors. We research found that, compared with normal tissues, LYAR levels werehigher in a variety of tumors. LYAR expression level was associated with poor overall survival, progression-free interval, and disease-specific survival. LYAR expression was also related to tumor grade, stage, age, and tumor status. Cell counting kit-8, Transwell, and wound healing assay showed that knocking out LYAR significantly inhibited the proliferation, migration, and invasion of hepatocellular carcinoma cells. In addition, this study found that LYARexpression was significantly positively correlated with MKI67IP, BZW2, and CCT2. Gene set enrichment analysis results showed that samples with high LYAR expression levels were rich in spliceosomes, RNA degradation, pyrimidine metabolism, cell cycle, nucleotide excision repair, and base excision repair.


Assuntos
Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/biossíntese , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/biossíntese , Proteínas Nucleares/biossíntese , Carcinoma Hepatocelular/genética , Proteínas de Ligação a DNA/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética
5.
Diabetol Metab Syndr ; 13(1): 108, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654473

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to play vital roles in diabetic nephropathy (DN). The aim of this study was to explore the function of mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in DN. METHODS: DN cell models were established using high glucose (HG) treatment in human glomerular mesangial cells (HGMC) and human renal glomerular endothelial cells (HRGEC). The expression levels of KCNQ1OT1, microRNA-93-5p (miR-93-5p), and Rho associated coiled-coil containing protein kinase 2 (ROCK2) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. ROCK2 and apoptosis/fibrosis-related protein levels were examined by western blot. The predicted interaction between miR-93-5p and KCNQ1OT1 or ROCK2 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: KCNQ1OT1 was upregulated in DN patients and DN cell models. KCNQ1OT1 knockdown inhibited cell proliferation and fibrosis and induced apoptosis in DN cell models. MiR-93-5p was a direct target of KCNQ1OT1, and miR-93-5p inhibition restored the KCNQ1OT1 knockdown-mediated effects on cell proliferation, fibrosis and apoptosis in DN cell models. In addition, ROCK2 was identified as a target of miR-93-5p, and miR-93-5p overexpression suppressed cell proliferation and fibrosis and accelerated apoptosis by targeting ROCK2 in DN cell models. Moreover, KCNQ1OT1 regulated ROCK2 expression by binding to miR-93-5p. CONCLUSION: KCNQ1OT1 knockdown inhibited cell proliferation and fibrosis and induced apoptosis in DN by regulating miR-93-5p/ROCK2 axis, providing potential value for the treatment of DN.

6.
Am J Forensic Med Pathol ; 42(3): 258-262, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397510

RESUMO

ABSTRACT: Postmortem computed tomography (PMCT), PMCT angiography, and 3-dimensonal (3D) printing technology are increasingly applied to forensic practice. Although their effectiveness is undeniably confirmed, their potential role in practice still needs to be further explored. Here, we report a typical case in which such 4 technologies were applied to a woman found dead with stomach content beneath the head on the pillow in her residence. At first, the cause of death was simply considered as hypertensive cerebral hemorrhage after preliminary examination. However, the initial judgment was questioned by her family for her devoid of hypertension history. As indicated by the targeted PMCT with cerebral angiography, the woman died of pathological cerebral hemorrhage due to arteriovenous malformation, which was still unconvincing enough for the family because in violent death, some cerebral hemorrhage could also be located in the same position. Finally, the family came to be convinced when the close connection between the deformed blood vessels and hematoma was perfectly demonstrated by the application of 3D printing technology. This study proved that it can be an efficient tool for identifying the cause of death when the integration is made of 3D printing technology and PMCT angiography, as a more intuitive evidence of forensic science.


Assuntos
Malformações Arteriovenosas/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Angiografia por Tomografia Computadorizada , Morte Súbita/etiologia , Impressão Tridimensional , Adulto , Angiografia Cerebral , Feminino , Humanos , Ruptura Espontânea/diagnóstico
7.
Medicine (Baltimore) ; 100(29): e26671, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398031

RESUMO

BACKGROUND: Knee osteoarthritis (OA) is a major public health concern causing chronic disability as well as a substantial burden on health care and the economy. However, effective treatments for knee OA were still not available. Numerous clinical studies have suggested that Chinese herbal medicine (CHM) seems to be clinically effective in treating knee OA. Thus, this study aims to evaluate the efficacy and safety of CHM in the treatment of knee OA through a systematic review and network meta-analysis. METHODS: A comprehensive search will be performed in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, VIP Database, Wanfang Database, Chinese Biomedical Database, and 3 clinical trials registration websites, from the database inception to May 2021. Randomized controlled trials meeting the eligible criteria based on the PICOS framework will be included. All studies fulfilling the eligible criteria will be assessed for risk of bias using the Cochrane Collaboration's tool. The primary outcome will be the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index, and total effective rate. The secondary outcome is the incidence of adverse events. Data analysis will be performed using Stata, Addis, and WinBUGS. DISCUSSION: This study will provide a reliable evidence to assess effectiveness and safety of CHM for knee OA, which may provide guidance for clinical practice. SYSTEMATIC REVIEW REGISTRATION: This study protocol has been registered on INPLASY202160060.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Fitoterapia , Projetos de Pesquisa
8.
Int J Clin Pharmacol Ther ; 59(11): 691-704, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34423769

RESUMO

BACKGROUND: The pharmacokinetics, safety, and clinical activity of antibodies targeting CD22 have been evaluated in systemic lupus erythematosus (SLE) and non-Hodgkin lymphoma (NHL) patients, however, there have been no reports for the rheumatoid arthritis (RA) population. SM03 is a novel chimeric IgG1 monoclonal antibody which targets the B-cell-restricted antigen CD22. This is the first study of the anti-CD22 antibody in RA patients. OBJECTIVES: This study was designed to preliminarily evaluate the pharmacokinetics, pharmacodynamics, safety, and clinical activity profiles of the anti-CD22 monoclonal antibody SM03 in Chinese patients with active RA. MATERIALS AND METHODS: This study was an open phase I study in 8 RA patients. Eligible patients received two 600 mg doses of SM03 administered through intravenous infusions given 2 weeks apart and were monitored over an 84-day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety, and clinical responses. RESULTS: After multiple doses of SM03, the maximum serum concentration of SM03 was reached within 2 - 4 hours. Mean elimination half-life was 16 days (range: 13 - 22 days). Half of the patients responded according to ACR and DAS28 assessments, and CD19+ B lymphocyte counts decreased. Upper respiratory tract infections and headaches were the most common adverse events (AEs). No drug-related serious AEs were reported. CONCLUSION: This study is the first to report on the preliminary pharmacokinetics, pharmacodynamics, clinical activity, and safety of SM03 in RA patients. All AEs were mild or moderate in severity. SM03 showed potential efficacy in RA patients.


Assuntos
Artrite Reumatoide , Lúpus Eritematoso Sistêmico , Animais , Anticorpos Monoclonais/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Humanos , Infusões Intravenosas , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Camundongos , Resultado do Tratamento
9.
Eur J Cancer ; 156: 35-45, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34418665

RESUMO

BACKGROUND: The EXTREME regimen (chemotherapy [CT; cisplatin/carboplatin and 5-fluorouracil]) plus cetuximab is a standard-of-care first-line (1L) treatment for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), as supported by international guidelines. The phase III CHANGE-2 trial assessed the efficacy and safety of a modified CT regimen (with a reduced dose of both components) and cetuximab versus CT for the 1L treatment of Chinese patients with R/M SCCHN. METHODS: Patients were randomised to receive up to six cycles of CT plus cetuximab followed by cetuximab maintenance until progressive disease or CT alone. The primary end-point was the progression-free survival (PFS) time assessed by the independent review committee (IRC). RESULTS: Overall, 243 patients were randomised (164 to CT plus cetuximab; 79 to CT). The hazard ratios for PFS by IRC and overall survival (OS) were 0.57 (95% CI: 0.40-0.80; median: 5.5 versus 4.2 months) and 0.69 (95% CI: 0.50-0.93; median: 11.1 versus 8.9 months), respectively, in favour of CT plus cetuximab. The objective response rates (ORR) by IRC were 50.0% and 26.6% with CT plus cetuximab and CT treatment, respectively. Treatment-emergent adverse events of maximum grade 3 or 4 occurred in 61.3% (CT plus cetuximab) and 48.7% (CT) of patients. CONCLUSIONS: CHANGE-2 showed an improved median PFS, median OS and ORR with the addition of cetuximab to a modified platinum/5-fluorouracil regimen, with no new or unexpected safety findings, thereby confirming CT plus cetuximab as an effective and safe 1L treatment for Chinese patients with R/M SCCHN. CLINICAL TRIAL REGISTRATION NUMBER: NCT02383966.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Cetuximab/efeitos adversos , China , Cisplatino/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Fatores de Tempo
10.
Endocr J ; 68(10): 1155-1164, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33980772

RESUMO

Diabetic nephropathy (DN), a frequent diabetes complication, has complex pathogenesis. Circular RNAs (circRNAs) circ_0000712 has been reported to be upregulated in kidney tissues and high glucose (HG)-inducted Mesangial cells (MCs). This study is designed to explore the role and mechanism of circ_0000712 in the HG-inducted MCs injury in DN. Circ_0000712, microRNA-879-5p (miR-879-5p), and SRY-Box Transcription Factor 6 (SOX6) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell apoptosis was examined by flow cytometry assay. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), fibronectin (FN), collagen type I (Col. I), collagen type IV (Col. IV), and SOX6 were assessed by western blot assay. Levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) generation, Lactate Dehydrogenase (LDH) activity, and Superoxide Dismutase (SOD) activity were detected by the corresponding kits. The binding relationship between miR-879-5p and circ_0000712 or SOX6 was predicted by starBase and Targetscan, and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Circ_0000712 and SOX6 were highly expressed, and miR-879-5p was decreased in db/db DN mice and HG-inducted SV40-MES13 cells. Furthermore, circ_0000712 deficiency repressed HG-caused apoptosis, inflammation, oxidative stress, and fibrosis in SV40-MES13 cells. Mechanically, circ_0000712 could regulate SOX6 expression by sponging miR-879-5p. Circ_0000712 knockdown could hinder HG-inducted SV40-MES13 cell injury through targeting the miR-879-5p/SOX6 axis, implying a possible circRNA-targeted therapy for DN.


Assuntos
Apoptose , Nefropatias Diabéticas/metabolismo , Hiperglicemia/metabolismo , Inflamação/metabolismo , Células Mesangiais/metabolismo , RNA Circular/metabolismo , Fatores de Transcrição SOXD/metabolismo , Animais , Colágeno Tipo I/metabolismo , Colágeno Tipo IV/metabolismo , Fibronectinas/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , L-Lactato Desidrogenase/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Circular/genética , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição SOXD/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo
11.
PLoS One ; 16(2): e0244390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33556052

RESUMO

The aim of this study was to identify the influence of specimen geometry and size on the results of aortic uniaxial tensile tests using custom-designed tissue cutters, clamps and molds. Six descending thoracic aortas from pigs were used for rectangular sample tests, in which the circumferential and axial specimens had widths of 6 mm, 8 mm and 10 mm. The other six aortas were used for the dog-bone-shaped sample tests and were punched into circumferential, axial and oblique specimens with widths of 2 mm, 4 mm and 6 mm. We performed uniaxial tensile tests on the specimens and compared the test results. The results showed that mid-sample failure occurred in 85.2% of the dog-bone-shaped specimens and in 11.1% of the rectangular samples, which could be caused by Saint-Venant's principle. Therefore, rectangular specimens were not suitable for aortic uniaxial tensile testing performed until rupture. The results also showed that the size effect of the aorta conformed to Weibull theory, and dog-bone-shaped specimens with a width of 4 mm were the optimal choice for aortic uniaxial tensile testing performed until rupture.


Assuntos
Aorta , Estresse Mecânico , Resistência à Tração , Animais , Fenômenos Biomecânicos , Elasticidade , Suínos
12.
Int J Legal Med ; 135(3): 913-920, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33392657

RESUMO

Forensic scholars are paying more attention to postmortem computed tomography (PMCT) and PMCT angiography (PMCTA), which are gradually becoming effective and practical methods in forensic practice. However, few studies have focused on the application of PMCTA to cardiac ventricular puncture-especially of the right ventricle. In this article, we introduce a pulmonary PMCTA approach by right ventricle cardiac puncture and its potential value in fatalities from pulmonary thromboembolism (PTE). The procedure was performed on 11 males and 6 females. PMCT was performed first; then a biopsy core needle was used for percutaneous puncture of the right ventricle under CT guidance. About 400 mL of contrast media was injected at a rate of 50 mL/8 s, followed by CT scanning. Visualization of the pulmonary artery contrast filling was complete in 9 cadavers, and the pulmonary arteries showed significant filling defects in 8 subjects. Unlike in clinical practice, the phenomenon of postmortem coagulation sometimes occurs in the vascular lumina after death. Therefore, the results of these 8 cases can only suggest or be highly suspicious of death from PTE. Then autopsy and histopathological examination confirmed that 4 of the above 8 patients were diagnosed with PTE; the remaining 4 had postmortem clot including chicken fat clot in the pulmonary artery. Pulmonary PMCTA approach is a simple, convenient, and effective method for the visualization of the pulmonary artery, which can be used as an effective auxiliary tool to identify PTE in forensic practice. It will also provide technical support to further investigate PTE imaging characteristics.


Assuntos
Autopsia , Angiografia por Tomografia Computadorizada/métodos , Ventrículos do Coração , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico , Punções/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Medicina Legal , Humanos , Masculino , Pessoa de Meia-Idade
13.
Cardiovasc Pathol ; 49: 107261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32771878

RESUMO

Cardiac inflammation in Coxsackievirus B3 (CVB3)-induced myocarditis is a consequence of viral-related cardiac injury and immune response. Caspase-associated recruitment domain 9 (CARD9) is a critical adaptor protein involved in transduction of signals from various innate pattern recognition receptors. In this study, the role of CARD9 in acute viral myocarditis was evaluated. CARD9-/- and C57BL/6 mice were infected with CVB3. On day 7 postinfection, myocardial tissue and blood samples were collected and examined. After CARD9 knockout, mRNA and protein levels of transforming growth factor-ß(TGF-ß), interleukin-17A(IL-17A), and CARD domain of B-cell CLL/lymphoma 10(BCL-10) in the myocardium were markedly lower in CARD9-/- mice than in C57BL/6 mice with CVB3-induced viral myocarditis. This trend was similar for the pathological scores for inflammation and serum levels of cytokines interleukin-6(IL-6), interleukin-10(IL-10), interferon -γ(IFN-γ), TGF-ß, and IL-17A. These results suggest that the CARD9-mediated secretion of pro-inflammatory cytokines plays an important role in the immune response to acute viral myocarditis.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Infecções por Coxsackievirus/metabolismo , Enterovirus Humano B/imunologia , Miocardite/metabolismo , Miocárdio/metabolismo , Linfócitos T/metabolismo , Animais , Proteínas Adaptadoras de Sinalização CARD/deficiência , Proteínas Adaptadoras de Sinalização CARD/genética , Infecções por Coxsackievirus/genética , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/virologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocardite/genética , Miocardite/imunologia , Miocardite/virologia , Miocárdio/imunologia , Miocárdio/patologia , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/virologia
14.
Leg Med (Tokyo) ; 45: 101697, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32305675

RESUMO

The finite element (FE) method can potentially help in reconstructing skull fracture biomechanisms, enabling differentiation of the injury patterns caused by traffic accidents. This study aims to (1) reconstruct a motorcycle driver-car accident case using the total human model for safety and FE simulations; and (2) analyze the biomechanisms of fatal ring fractures in the motorcyclist's skull base to determine if the fatal craniocerebral injuries were caused by a fall onto the highway after hitting a pedestrian or by the subsequent impact of a car. We simulated a series of loading scenarios of falls onto the road and impacts by a car, with and without a helmet being used. We reconstructed the injury processes and compared the biomechanics results to the skull tolerance limit. For the scenario of falling with a helmet, the Von-Mises stress around the foramen magnum indicated ring fractures with a slight fracture at the impact site, consistent with that detected in a traditional forensic pathology autopsy. Moreover, we found that a helmet can significantly protect the skull by controlling the increase in stress around the impact site. However, it has very little effect on the skull base, neck, or cervical spine. We determined that the characteristic ring fracture was most probably caused by the fall onto the highway. Thus, the subsequent car accident did not contribute to the motorcyclist's death. Our study demonstrates that the FE model and method can explore injury biomechanisms, assisting in the identification of injury patterns in forensic practices.

15.
ACS Appl Mater Interfaces ; 12(14): 16387-16393, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32180392

RESUMO

Ternary organic solar cells (OSCs) provide a convenient and effective means to further improve the power conversion efficiency (PCE) of binary ones via composition control. However, the role of the third component remains to be explored in specific binary systems. Herein, we report ternary blend solar cells by adding the narrow-band-gap donor PCE10 as the mediator into the PBDB-T:IDTT-T binary blend system. The extended absorption, efficient fluorescence resonance energy transfer, enhanced charge dissociation, and induced tighter molecular packing of the ternary blend films enhance the photovoltaic properties of devices and deliver a champion PCE of 10.73% with an impressively high open-circuit voltage (VOC) of 1.03 V. Good miscibility and similar molecular packing behavior of the components guarantee the desired morphology in the ternary blend films, leading to solar cell devices with over 10% PCEs at a range of compositions. Our results suggest that ternary systems with properly aligned energy levels and overlapping absorption among the components hold great promises to further enhance the performance of corresponding binary ones.

16.
Medicine (Baltimore) ; 99(11): e19182, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176043

RESUMO

RATIONALE: Postmortem forensic imaging technologies provide a noninvasive/minimally invasive approach for imaging of internal organ structures of the human body to detect injuries, diseases, and other morphologic changes. Currently, postmortem forensic imaging methods have been widely used in determination of the cause of death. However, these methods do not allow histologic examinations. Endoscopic autopsy emerged in the 1990s. Thoracoscopy and laparoscopy are mainly used to examine organs and tissues in the thoracic and abdominal cavity. Target tissues are also sampled for histologic examination. By combining postmortem forensic imaging with endoscopic autopsy, comprehensive examination of the corpse, organs, and sampling for histologic examination can be carried out. PATIENT CONCERNS: A 34-year-old woman was witnessed jumping into the river, sinking after struggling in the water. The body was found 24 hours later and confirmed with no vital signs. No preexisting medical conditions were known. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: Postmortem computed tomography, target coronary postmortem computed tomography angiography, and endoscopic autopsy were performed before conventional autopsy. Laparoscopic examination was used to examine the abdominal organs. The diaphragm and pericardium were cut open from the abdominal cavity to allow access to the examination of lungs and heart. Tissue samples were collected from various organs for histologic examination, and a diatom test was carried out on lung samples. Postmortem computed tomography revealed fluid in the paranasal sinuses, airways, stomach, and duodenum; emphysema aquosum; and mosaic pattern of the lung parenchyma. Endoscopic examination additionally detected Paltauf spots. The results were consistent with those of conventional autopsy. Histologic examination revealed pulmonary congestion, pulmonary edema, pulmonary emphysema, pulmonary hemorrhage, and congestion in multiple organs such as the liver, spleen, and kidneys. Diatoms were detected in lung tissues, which were identical in morphology to diatoms in water samples collected from the scene. The cause of death was determined as drowning. CONCLUSION: Combining forensic imaging and endoscopic autopsy for postmortem examination yields a more comprehensive and scientific finding, and the combination is minimally invasive and more acceptable to the family members. This method can be used as an alternative for conventional autopsy under specific circumstances.


Assuntos
Autopsia/métodos , Afogamento/diagnóstico , Adulto , Angiografia por Tomografia Computadorizada , Afogamento/diagnóstico por imagem , Afogamento/patologia , Endoscopia/métodos , Feminino , Patologia Legal/métodos , Humanos , Tomografia Computadorizada por Raios X
17.
Forensic Sci Int ; 303: 109943, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31546165

RESUMO

Crime scene reconstruction plays a significant role in crime solving by helping to determine the course of events. Non-invasive, high-resolution measurement and increased insight are always the goal of forensic crime scene documentation. However, entire crime scenes cannot be effectively reconstructed with traditional methods. In this study, we present a portable system that consists of a laser scanner, two hand-held structured light scanners and a low-cost virtual reality (VR) headset with a mobile power supply to conduct multi-angle and omnidirectional three-dimensional spatial data collection of crime scenes. To demonstrate practical use, a real case has been analysed to verify the feasibility and effectiveness of the system. The system accurately obtains information on decedent injuries, possible injury-inflicting tools and on-site traces. Various types of evidence from the crime scene can be jointly studied by three-dimensional visualization to develop a cohesive story. The data are presented via immersive VR rather than displayed on computer screens. The relationship between evidence chains enables us to achieve a complete crime scene reconstruction, using the specialized knowledge of experts and computer-aided forensic tools to analyse the causes of damage and identify suspects. The use of three- dimensional imaging techniques allows a more insightful survey and several useful analyses, such as accurate measurement, relative blood source location determination and injury-inflicting tool comparison.


Assuntos
Ciências Forenses/métodos , Homicídio , Realidade Virtual , Adulto , Manchas de Sangue , Estudos de Viabilidade , Feminino , Pé/anatomia & histologia , Traumatismos Cranianos Penetrantes/patologia , Humanos , Ferimentos Perfurantes/patologia
18.
Onco Targets Ther ; 12: 2299-2309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30988634

RESUMO

Background: This aim of study was to develop and validate clinical nomograms to predict the survival of patients with medullary thyroid cancer. Patients and methods: Patient data were collected from the Surveillance, Epidemiology, and End Results database between 2004 and 2013. All included patients were randomly assigned into the training and validation sets. Multivariate analysis using Cox proportional hazards regression was performed, and nomograms were constructed. Model performance was evaluated by discrimination and calibration plots. Results: A total of 1,657 patients were retrospectively analyzed. The multivariate Cox model identified age, tumor size, extrathyroidal extension, N stage, and M stage as independent covariates associated with overall survival (OS) and cancer-specific survival (CSS). Nomograms predicting OS and CSS were constructed based on these covariates. The nomograms predicting both OS and CSS exhibited superior discrimination power to that of TNM staging system in the training and validation sets. Calibration plots indicated that both the nomograms in OS and CSS exhibited high correlation to actual observed results. Conclusion: The nomograms established in this study provided an alternative tool for prognostic prediction, which may thereby improve individualized assessment of survival risks and lead to the creation of additional clinical therapies.

19.
J Forensic Leg Med ; 65: 15-21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31029002

RESUMO

In dealing with a scooter-related traffic accident with rider death, it is necessary to identify the driver responsible for the accident. This study aimed to reconstruct the kinematics of a scooter-microvan accident involving three riders and explored the differences in injury risks and characteristics of the scooter driver and passengers. We reconstructed a real accident by using MADYMO multi-body simulation software. Moreover, we designed two-variable simulation experiments to analyze how the velocity and impact angle of the microvan are related to the injuries of the three riders. When the microvan speed is set at 18 km/h and that of the scooter is set at 28.8 km/h, the simulated kinematics correlates well with real accident data, and the impact positions and injury parameters correlate well with the actual injuries. When the impact angle is smaller than 30° and the microvan impact velocity is lower than 40 km/h, the head injury of the driver is more life-threatening than the corresponding injuries of the rear passengers. When the impact angle is 15° and the microvan impact velocity is in the range of 0-20 km/h, the femur fracture risk is higher for the driver than for passengers. As the impact angle increases to 45°, passengers have a higher risk of femur fracture than the driver in the velocity range of 0-10 km/h. This impact velocity range becomes 0-30 km/h at an impact angle of 60° and then 40-70 km/h at an impact angle of 90°. Our study shows that the multibody method can reconstruct accidents and predict the different injury features and risks between the driver and passengers, which is useful in identifying the driver.


Assuntos
Acidentes de Trânsito , Automóveis , Simulação por Computador , Motocicletas , Traumatismo Múltiplo/etiologia , Medição de Risco , Fenômenos Biomecânicos , Lesões Encefálicas Traumáticas/etiologia , China , Análise de Elementos Finitos , Ciências Forenses/métodos , Humanos , Escala de Gravidade do Ferimento
20.
Biosci Rep ; 39(3)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30824563

RESUMO

It is difficult to determinate the cause of death from exposure to fatal hypothermia and hyperthermia in forensic casework. Here, we present a state-of-the-art study that employs Fourier-transform infrared (FTIR) spectroscopy to investigate the hypothalamus tissues of fatal hypothermic, fatal hyperthermic and normothermic rats to determine forensically significant biomarkers related to fatal hypothermia and hyperthermia. Our results revealed that the spectral variations in the lipid, protein, carbohydrate and nucleic acid components are highly different for hypothalamuses after exposure to fatal hypothermic, fatal hyperthermic and normothermic conditions. In comparison with the normothermia group, the fatal hypothermia and hyperthermia groups contained higher total lipid amounts but were lower in unsaturated lipids. Additionally, their cell membranes were found to have less motional freedom. Among these three groups, the fatal hyperthermia group contained the lowest total proteins and carbohydrates and the highest aggregated and dysfunctional proteins, while the fatal hypothermia group contained the highest level of nucleic acids. In conclusion, this study demonstrates that FTIR spectroscopy has the potential to become a reliable method for the biochemical characterization of fatal hypothermia and hyperthermia hypothalamus tissues, and this could be used as a postmortem diagnostic feature in fatal hypothermia and hyperthermia deaths.


Assuntos
Febre/metabolismo , Hipotálamo/metabolismo , Hipotermia/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Animais , Autopsia/veterinária , Biomarcadores/análise , Carboidratos/análise , Febre/diagnóstico , Hipotermia/diagnóstico , Lipídeos/análise , Masculino , Ácidos Nucleicos/análise , Patologia Veterinária/métodos , Proteínas/análise , Ratos Sprague-Dawley
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