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1.
J Gene Med ; 26(1): e3646, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38100138

RESUMO

BACKGROUND: Immune cell homeostasis plays a crucial role in cancer research and therapeutic response. While chemotherapy and immunotherapy hold promise in treating osteosarcoma (OS), identifying patients who are likely to respond would significantly improve clinical practices. Necroptosis, a fundamental mechanism mediating chemotherapy and immunotherapy efficacy, offers valuable insights. In this context, subtypes based on necroptosis-related genes have been established to predict the response of OS patients to immunotherapy and chemotherapy. METHODS: We conducted a high-throughput screening test to identify necroptosis-associated genes that regulate the development of osteosarcoma. Subsequently, the ConsensusClusterPlus package was employed to classify OS patients into subtypes, enabling comparisons of prognosis and clinical information between these subtypes. Patients from the TARGET-OS and GSE21257 datasets were stratified into high-risk and low-risk groups, and their prognoses were compared. Additionally, we assessed the accuracy of the Risk Scoring Model in predicting prognosis, identified independent prognostic factors and explored potential chemotherapeutic agents and immunotherapy drugs. RESULTS: Through the intersection of expression profiles from the TARGET-OS and GSE21257 datasets, we have identified a total of 92 genes associated with necroptosis. Based on differences in the expression of these genes, patients were divided into three subtypes, and we investigated the differences in tumor-infiltrating immune cells, immune-related pathways, and prognosis among these subtypes. Our nomogram effectively differentiated subtypes with distinct responses to chemotherapy and immunotherapy. The established signature demonstrated superior prediction ability compared with single clinical indicators. CONCLUSIONS: This pioneering study unveils the prognostic role of necroptosis-related genes in OS patients, providing a promising alternative for prognostic prediction in clinical disease management. Moreover, our findings highlight the significance of immune cell homeostasis in cancer research and therapeutic response, underscoring its relevance in advancing current treatment strategies.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Criança , Humanos , Apoptose/genética , Osteossarcoma/genética , Osteossarcoma/terapia , Imunoterapia , Diferenciação Celular , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia
2.
BMC Musculoskelet Disord ; 25(1): 81, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245679

RESUMO

BACKGROUND: Symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) present significant challenges for military pilots, which may result in grounding if not effectively managed. Surgical treatment for LDH and LIS may offer a pathway to return to flight duty (RTFD), but recent data on this crucial topic is lacking. This study seeks to address this gap by investigating the RTFD outcomes among Chinese military pilots who have undergone lumbar spine surgery for symptomatic LDH and LIS. METHODS: A retrospective review was conducted on active-duty military pilots who underwent isolated decompressive or fusion procedures at an authorized military medical center from March 1, 2007, to March 1, 2023. The analysis utilized descriptive statistics to examine demographic, occupational, surgical, and outcome data, with a particular focus on preoperative flight status, recommended clearance by spine surgeons, and actual RTFD outcomes and time. RESULTS: Among the identified cases of active-duty military pilots with LDH or LIS treated by lumbar surgery (n = 24), 70.8% (17 of 24) consistently maintained RTFD status without encountering surgical complications or medical issues during the follow-up period. Of the seven pilots who did not RTFD, one retired within a year of surgery, two had anterior cruciate ligament injuries, three had residual radicular symptoms, and one had chronic low back pain. Excluding pilots who retired and did not RTFD for reasons unrelated to their lumbar conditions, the RTFD rate stood at 81.0% (17 of 21). The median time for recommended clearance by spine surgeons was 143.0 days (inter-quartile range, 116.5-196.0), while the median duration for actual RTFD attainment was 221.0 days (inter-quartile range, 182.0-300.0). The median follow-up post-lumbar surgery was 1.7 years (inter-quartile range, 0.4-2.9). CONCLUSION: Most military pilots diagnosed with symptomatic LDH and LIS can continue their careers and regain active-duty flight status following lumbar spine surgery, as reflected by the high RTFD rate. Lumbar spine surgery can successfully alleviate the physical constraints associated with spinal conditions, facilitating the return of military pilots to their demanding profession.


Assuntos
Deslocamento do Disco Intervertebral , Militares , Fusão Vertebral , Espondilolistese , Humanos , Deslocamento do Disco Intervertebral/epidemiologia , Deslocamento do Disco Intervertebral/cirurgia , Espondilolistese/epidemiologia , Espondilolistese/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Vértebras Lombares/cirurgia , China/epidemiologia , Fusão Vertebral/métodos
3.
Environ Toxicol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622876

RESUMO

Osteosarcoma (OS), known for its high recurrence and metastasis rates, poses a significant challenge in oncology. Our research investigates the role of programmed cell death (PCD) genes in OS and develops a prognostic model using advanced bioinformatics. We analyzed single-cell sequencing data from the Gene Expression Omnibus (GEO) database to identify subpopulations, distinguish malignant from non-malignant cells, assess cell cycle phases, and map PCD gene distribution. Additionally, we applied consistency clustering to bulk sequencing data from GEO and TARGET (Therapeutically Applicable Research to Generate Effective Treatments) databases, facilitating survival analysis across clusters with the Kaplan-Meier method. We calculated PCD scores for each cluster using the Single-sample Gene Set Enrichment Analysis (ssGSEA), which enabled a detailed examination of PCD-related gene expression and pathway scores. Our study also explored drug sensitivity differences and conducted comprehensive immune cell infiltration analyses using various algorithms. We identified differentially expressed genes, leading to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses that provided insights into relevant biological processes and pathways. The prognostic model, based on five pivotal genes (BAMBI, TMCC2, NOX4, DKK1, and CBS), was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and validated in the TARGET-OS and GSE16091 datasets, showing significant predictive accuracy. This research enhances our understanding of PCD in OS and supports the development of effective treatments.

4.
Cardiovasc Diabetol ; 22(1): 146, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349787

RESUMO

The occurrence and development of coronary heart disease (CHD) are closely linked to fluctuations in blood glucose levels. While the efficacy of intensified treatment guided by HbA1c levels remains uncertain for individuals with diabetes and CHD, this review summarizes the findings and conclusions regarding HbA1c in the context of CHD. Our review showed a curvilinear correlation between regulated level of HbA1c and therapeutic effectiveness of intensified glycemic control among patients with type 2 diabetes and coronary heart disease. It is necessary to optimize the dynamic monitoring indicators of HbA1c, combine genetic profiles, haptoglobin phenotypes for example and select more suitable hypoglycemic drugs to establish more appropriate glucose-controlling guideline for patients with CHD at different stage of diabetes.


Assuntos
Doença das Coronárias , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas , Glicemia , Controle Glicêmico , Hipoglicemiantes/efeitos adversos , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética
5.
BMC Infect Dis ; 23(1): 837, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38012554

RESUMO

INTRODUCTION: The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis. METHODS: PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022. RESULTS: Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14-2.48, P-value < 0.001) in either prospective (SMD = 2.38, 95% CI = 1.40-3.35, P-value < 0.001) or retrospective studies (SMD = 0.87, 95% CI = 0.63-1.12, P-value < 0.001) with a pooled sensitivity of 79% (95% CI = 62-90%), and a pooled specificity of 91% (95% CI = 73-97%). Also, we found that NLR is higher in neonates with sepsis compared to those who were suspected of sepsis but eventually had negative blood cultures (SMD =1.99, 95% CI = 0.76-3.22, P-value = 0.002) with a pooled sensitivity of 0.79% (95% CI = 0.69-0.86%), and a pooled specificity of 73% (95% CI = 54-85%). In addition, neonates with sepsis had elevated levels of NLR compared to other ICU admitted neonates (SMD = 0.73, 95% CI = 0.63-0.84, P < 0.001). The pooled sensitivity was 0.65 (95% CI, 0.55-0.80), and the pooled specificity was 0.80 (95% CI, 0.68-0.88). CONCLUSION: Our findings support NLR as a promising biomarker that can be readily integrated into clinical settings to aid in diagnosing neonatal sepsis. As evidenced by our results, restoring balance to the innate and adaptive immune system may serve as attractive therapeutic targets. Theoretically, a reduction in NLR values could be used to measure therapeutic efficacy, reflecting the restoration of balance within these systems.


Assuntos
Sepse Neonatal , Sepse , Recém-Nascido , Humanos , Neutrófilos , Sepse Neonatal/diagnóstico , Estudos Retrospectivos , Estudos Prospectivos , Linfócitos , Biomarcadores , Sepse/diagnóstico
6.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(5): 533-538, 2023 Sep 30.
Artigo em Zh | MEDLINE | ID: mdl-37753893

RESUMO

With the characteristics of fast prototyping and personalized manufacturing, 3D-printing (three-dimensional printing) is an emerging technology with promising applications for orthopedic medical devices. It can complete the process of medical devices with complex shape which can not be completed by conventional fabrication process. At present, a variety of orthopedic medical devices manufactured by 3D printing technology, has been approved for marketing, and their use has been proved to be beneficial. 3D bioprinting in this area has also made a few breakthroughs. However, many challenges still remain to be addressed as well. In this study, the research status, as well as the development of the 3D-printing technology in the field of orthopedic medical devices is elaborated.


Assuntos
Bioimpressão , Impressão Tridimensional , Comércio , Pesquisa
7.
Mediators Inflamm ; 2022: 8939449, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110098

RESUMO

The activation of cardiac fibroblasts (CFs) after myocardial infarction (MI) is essential for post-MI infarct healing, during which the regulation of transforming growth factor beta1 (TGF-ß1) signaling is predominant. We have demonstrated that TGF-ß1-mediated upregulation of LBH contributes to post-MI CF activation via modulating αB-crystallin (CRYAB), after being upregulated by TGF-ß1. In this study, the effect of LBH-CRYAB signaling on the cardiac microenvironment via exosome communication and the corresponding mechanisms were investigated. The upregulation of LBH and CRYAB was verified in both cardiomyocytes (CMs) and CFs in hypoxic, post-MI peri-infarct tissues. CM-derived exosomes were isolated and identified, and LBH distribution was elevated in exosomes derived from LBH-upregulated CMs under hypoxia. Treatment with LBH+ exosomes promoted cellular proliferation, differentiation, and epithelial-mesenchymal transition-like processes in CFs. Additionally, in primary LBHKO CFs, western blotting showed that LBH knockout partially inhibited TGF-ß1-induced CF activation, while LBH-CRYAB signaling affected TGF-ß1 expression and secretion through a positive feedback loop. The administration of a Smad3 phosphorylation inhibitor to LBHKO CFs under TGF-ß1 stimulation indicated that Smad3 phosphorylation partially accounted for TGF-ß1-induced LBH upregulation. In conclusion, LBH upregulation in CMs in post-MI peri-infarct areas correlated with a hypoxic cardiac microenvironment and led to elevated exosomal LBH levels, promoting the activation of recipient CFs, which brings new insights into the studies and therapeutic strategies of post-MI cardiac repair.


Assuntos
Cristalinas , Exossomos , Infarto do Miocárdio , Animais , Cristalinas/metabolismo , Cristalinas/farmacologia , Exossomos/metabolismo , Fibroblastos/metabolismo , Hipóxia/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
8.
J Appl Toxicol ; 42(9): 1467-1476, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35187677

RESUMO

Intervertebral disc degeneration (IDD) is a common and chronic inflammatory disorder. α-Mangostin exhibits a novel biological function against inflammation in various inflammatory diseases. Here, we aimed to explore the role of α-mangostin in IDD using an in vitro cell model. Human nucleus pulposus cells (NPCs) were exposed to lipopolysaccharide (LPS) to induce inflammatory injury. Cell viability of NPCs was determined by CCK-8 assay. ELISA was performed to examine the production of interleukin (IL)-1ß and IL-18. Apoptotic cell death in NPCs was detected by TUNEL staining. The expression levels of apoptotic-associated proteins were detected by western blotting. Nuclear factor-kappa B (NF-κB) activation was examined by determining the expression levels of p-p65, p65, and nuclear p65. Results showed that treatment with α-mangostin improved the viability of LPS-treated NPCs. α-Mangostin treatment also inhibited the LPS-induced increase in expression levels of NLRP3, ASC and pro-caspase-1, as well as the production of IL-1ß and IL-18 in NPCs. Moreover, treatment with α-mangostin or NLRP3 inhibitor (MCC950) significantly decreased apoptotic cell death in NPCs, as compared with treatment with LPS. In addition, the expression levels of cleaved caspase-3 and Bax were decreased, while Bcl-2 expression was increased in α-mangostin- or MCC950-treated NPCs. Treatment with α-mangostin also suppressed LPS-induced increase of p-p65/p65 and nuclear p65 levels. Moreover, inhibition of NF-κB by PDTC aggravated the inhibitory effects of α-mangostin on NLRP3 inflammasome activation and apoptosis in LPS-induced NPCs. These findings suggested that α-mangostin exerted a protective effect on NLRP3 inflammasome-mediated apoptosis in LPS-induced NPCs through regulating NF-κB signaling.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Núcleo Pulposo/metabolismo , Xantonas
9.
Mol Cell Biochem ; 476(7): 2685-2701, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33666830

RESUMO

Cardiac fibrosis is an important pathological change after myocardial infarction (MI). Its progression is essential for post-MI infarct healing, during which transforming growth factor beta1 (TGF-ß1) plays a critical role. Limb-bud and Heart (LBH), a newly discovered target gene of TGF-ß1, was shown to promote normal cardiogenesis. αB-crystallin (CRYAB), an LBH-interacting protein, was demonstrated to be involved in TGF-ß1-induced fibrosis. The roles and molecular mechanisms of LBH and CRYAB during cardiac fibrosis remain largely unexplored. In this study, we investigated the alterations of LBH and CRYAB expression in mouse cardiac tissue after MI. LBH and CRYAB were upregulated in activated cardiac fibroblasts (CFs), while in vitro TGF-ß1 stimulation induced the upregulation of LBH, CRYAB, and fibrogenic genes in primary CFs of neonatal rats. The results of the ectopic expression of LBH proved that LBH accelerated CF proliferation under hypoxia, mediated the expression of CRYAB and fibrogenic genes, and promoted epithelial-mesenchymal transition (EMT)-like processes in rat CFs, while subsequent CRYAB silencing reversed the effects induced by elevated LBH expression. We also verified the protein-protein interaction (PPI) between LBH and CRYAB in fibroblasts. In summary, our work demonstrated that LBH promotes the proliferation of CFs, mediates TGF-ß1-induced fibroblast-to-myofibroblast transition and EMT-like processes through CRYAB upregulation, jointly functioning in post-MI infarct healing. These findings suggest that LBH could be a promising potential target for the study of cardiac repair and cardiac fibrosis.


Assuntos
Transição Epitelial-Mesenquimal , Regulação da Expressão Gênica , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Miofibroblastos/metabolismo , Fatores de Transcrição/metabolismo , Animais , Fibrose , Infarto do Miocárdio/patologia , Miofibroblastos/patologia , Ratos , Ratos Sprague-Dawley
10.
J Pediatr Orthop ; 40(10): e990-e993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33045161

RESUMO

BACKGROUND: The COVID-19 pandemic has substantially altered the typical process around performing surgery to ensure protection of health care workers, patients, and their families. One safety precaution has been the implementation of universal preoperative screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study examines the results of universal screening on children undergoing orthopaedic surgery. METHODS: This is a retrospective cohort study evaluating the incidence and symptomatology of COVID-19 in all patients presenting for orthopaedic surgery at 3 pediatric tertiary care children's hospitals during the COVID-19 pandemic (March to June 2020). All patients underwent universal screening with a nasopharyngeal swab to detect presence of SARS-CoV-2. Bivariate and multivariate logistic regression analysis was performed to identify risk factors for positive COVID-19 screening. RESULTS: In total, 1198 patients underwent preoperative screening across all 3 institutions and 7 (0.58%) had detection of SARS-CoV-2. The majority of patients (1/7, 86%) were asymptomatic. Patients that tested positive were significantly more likely to be Hispanic (P=0.046) and had greater number of medical comorbidities (P=0.013), as scored on the American Society of Anesthesiologists (ASA) physical status score. A known COVID-19 positive contact was found to be a significant risk factor in the multivariate analysis (P=0.004). CONCLUSIONS: Early results of universal preoperative screening for COVID-19 demonstrates a low incidence and high rate of asymptomatic patients. Health care professionals, especially those at higher risk for the virus, should be aware of the challenges related to screening based solely on symptoms or travel history and consider universal screening for patients undergoing elective surgery. LEVEL OF EVIDENCE: Level II.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus , Programas de Triagem Diagnóstica , Controle de Infecções , Procedimentos Ortopédicos/métodos , Pandemias , Pneumonia Viral , Cuidados Pré-Operatórios/métodos , COVID-19 , Teste para COVID-19 , Criança , Técnicas de Laboratório Clínico/métodos , Busca de Comunicante , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Etnicidade , Feminino , Humanos , Incidência , Controle de Infecções/métodos , Controle de Infecções/estatística & dados numéricos , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Estudos Retrospectivos , SARS-CoV-2 , Estados Unidos
11.
Ann Emerg Med ; 73(3): 248-254, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30287122

RESUMO

STUDY OBJECTIVE: Patient handoffs at shift change in the emergency department (ED) are a well-known risk point for patient safety. Numerous methods have been implemented and studied to improve the quality of handoffs to mitigate this risk. However, few have investigated processes designed to decrease the number of handoffs. Our objective is to evaluate a novel attending physician staffing model in an academic pediatric ED that was designed to decrease patient handoffs. METHODS: A multidisciplinary team met in August 2012 to redesign the attending physician staffing model. The team sought to decrease patient handoffs, optimize provider efficiency, and balance workload without increasing total attending physician hours. The original model required multiple handoffs at shift change. This was replaced with overlapping "waterfall" shifts. This was a retrospective quality improvement study of a process change that evaluated the percentage of intradepartmental handoffs before and after implementation of a new novel attending physician staffing model. In addition, surveys were conducted among attending physicians and charge nurses to inquire about perceived impacts of the change. RESULTS: A total of 43,835 patient encounters were analyzed. Immediately after implementation of the new model, there was a 25% reduction in the proportion of encounters with patient handoffs, from 7.9% to 5.9%. A survey of physicians and charge nurses demonstrated improved perceptions of patient safety, ED flow, and job satisfaction. CONCLUSION: This new emergency physician staffing model with overlapping shifts decreased the proportion of patient handoffs. This innovative system can be implemented and scaled to suit EDs that have more than single-physician coverage.


Assuntos
Serviço Hospitalar de Emergência/organização & administração , Transferência da Responsabilidade pelo Paciente/organização & administração , Segurança do Paciente/normas , Admissão e Escalonamento de Pessoal/organização & administração , Criança , Hospitais de Ensino , Humanos , Tempo de Internação/estatística & dados numéricos , Pediatria , Melhoria de Qualidade , Estudos Retrospectivos , Gestão de Riscos , Inquéritos e Questionários
13.
Minim Invasive Ther Allied Technol ; 26(3): 168-176, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28084155

RESUMO

AIM: The aim of this study is to assess the long-term clinical and radiological outcomes between minimally invasive (MIS) and conventional transforaminal lumbar interbody fusion (TLIF) in treating one-segment lumbar disc herniation (LDH). MATERIAL AND METHODS: One-hundred and six patients treated by MIS-TLIF (50 cases) or conventional TLIF (56 cases) were included. Perioperative results were evaluated. Clinical outcomes were compared preoperatively and postoperatively. Radiologic parameters were based on a comparison of preoperative and three-year postoperative lumbar lordosis, segmental lordosis, sacral slope, the cross-sectional area of the paraspinal muscle and fusion rates. RESULTS: MIS TILF had significantly less blood, shorter operation time, mean return to work time and lower intramuscular pressure compared with the conventional group during the operation. VAS scores for lower back pain and ODI in MIS-TLIF were significantly decreased. The mean cross-sectional area of the paraspinal muscle was significantly decreased after surgery in the conventional TLIF group and no significant intragroup differences were established in the MIS-TLIF group. No significant differences were found in fusion rate, lumbar lordosis, segmental lordosis and sacral slope. CONCLUSIONS: Both MIS and conventional TLIF were beneficial for patients with LDH. However, MIS-TLIF manifests a great improvement in perioperative outcomes, low back pain, disability and preventing paraspinal muscle atrophy during the follow-up period observation.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fusão Vertebral/métodos , Perda Sanguínea Cirúrgica , Avaliação da Deficiência , Feminino , Humanos , Lordose/epidemiologia , Dor Lombar/epidemiologia , Vértebras Lombares/cirurgia , Masculino , Duração da Cirurgia , Estudos Prospectivos , Retorno ao Trabalho/estatística & dados numéricos , Resultado do Tratamento
14.
Malar J ; 13: 215, 2014 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-24893777

RESUMO

BACKGROUND: When rhesus monkeys (Macaca mulatta) are used to test malaria vaccines, animals are often challenged by the intravenous injection of sporozoites. However, natural exposure to malaria comes via mosquito bite, and antibodies can neutralize sporozoites as they traverse the skin. Thus, intravenous injection may not fairly assess humoral immunity from anti-sporozoite malaria vaccines. To better assess malaria vaccines in rhesus, a method to challenge large numbers of monkeys by mosquito bite was developed. METHODS: Several species and strains of mosquitoes were tested for their ability to produce Plasmodium knowlesi sporozoites. Donor monkey parasitaemia effects on oocyst and sporozoite numbers and mosquito mortality were documented. Methylparaben added to mosquito feed was tested to improve mosquito survival. To determine the number of bites needed to infect a monkey, animals were exposed to various numbers of P. knowlesi-infected mosquitoes. Finally, P. knowlesi-infected mosquitoes were used to challenge 17 monkeys in a malaria vaccine trial, and the effect of number of infectious bites on monkey parasitaemia was documented. RESULTS: Anopheles dirus, Anopheles crascens, and Anopheles dirus X (a cross between the two species) produced large numbers of P. knowlesi sporozoites. Mosquito survival to day 14, when sporozoites fill the salivary glands, averaged only 32% when donor monkeys had a parasitaemia above 2%. However, when donor monkey parasitaemia was below 2%, mosquitoes survived twice as well and contained ample sporozoites in their salivary glands. Adding methylparaben to sugar solutions did not improve survival of infected mosquitoes. Plasmodium knowlesi was very infectious, with all monkeys developing blood stage infections if one or more infected mosquitoes successfully fed. There was also a dose-response, with monkeys that received higher numbers of infected mosquito bites developing malaria sooner. CONCLUSIONS: Anopheles dirus, An. crascens and a cross between these two species all were excellent vectors for P. knowlesi. High donor monkey parasitaemia was associated with poor mosquito survival. A single infected mosquito bite is likely sufficient to infect a monkey with P. knowlesi. It is possible to efficiently challenge large groups of monkeys by mosquito bite, which will be useful for P. knowlesi vaccine studies.


Assuntos
Anopheles/fisiologia , Anopheles/parasitologia , Malária/transmissão , Plasmodium knowlesi/crescimento & desenvolvimento , Animais , Feminino , Macaca mulatta , Vacinas Antimaláricas/administração & dosagem , Masculino , Análise de Sobrevida
15.
Nat Rev Cancer ; 5(2): 102-12, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15685195

RESUMO

Bleomycins are a family of glycopeptide antibiotics that have potent antitumour activity against a range of lymphomas, head and neck cancers and germ-cell tumours. The therapeutic efficacy of the bleomycins is limited by development of lung fibrosis. The cytotoxic and mutagenic effects of the bleomycins are thought to be related to their ability to mediate both single-stranded and double-stranded DNA damage, which requires the presence of specific cofactors (a transition metal, oxygen and a one-electron reductant). Progress in understanding the mechanisms involved in the therapeutic efficacy of the bleomycins and the unwanted toxicity and elucidation of the biosynthetic pathway of the bleomycins sets the stage for developing a more potent, less toxic therapeutic agent.


Assuntos
Antibacterianos/farmacologia , Bleomicina/farmacologia , Animais , Transporte Biológico , DNA/química , Dano ao DNA , Reparo do DNA , DNA de Cadeia Simples/genética , Fibrose , Células HeLa , Humanos , Pulmão/patologia , Modelos Biológicos , Modelos Químicos , Modelos Genéticos , Modelos Moleculares , Mutagênicos , Mutação , Neoplasias/metabolismo
16.
BMC Musculoskelet Disord ; 15: 370, 2014 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-25377946

RESUMO

BACKGROUND: Osteoarthritis (OA) is a major health problem in the increasingly elderly population. Therefore, it is crucial to prevent and treat OA at an early stage. The present study investigated whether pamidronate disodium (PAM), a bone-loss inhibitor, can significantly prevent or reverse the progression of early anterior cruciate ligament transection (ACLT)-induced OA. Whether therapeutic intervention is associated with regulation of the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), metalloproteinase-9 (MMP-9) or Toll-like receptor-4 (TLR-4) in cartilage and/or subchondral bone was also investigated. METHODS: 60 New Zealand rabbits were randomized into four groups: Sham-operated (n = 20); ACLT (n = 20); short-term treatment with PAM (PAM-S, n = 10) and long-term treatment with PAM (PAM-L, n = 10). For cartilage and subchondral bone testing, rabbits from Sham and ACLT groups were harvested at 2, 4, 6, and 14 weeks. Rabbits were given PAM from the 4th week after ACLT operation in PAM-S and PAM-L group, and were harvested at 6 and 14 weeks, respectively. Trabecular characteristics and cartilage changes were detected using Micro-CT, safranin O and rapid green staining, respectively. Immunohistochemical staining for OPG and RANKL were also performed. OPG, RANKL, MMP-9 and TLR-4 expression was evaluated by western blot analysis. RESULTS: Micro-CT and histology analyses indicated that PAM treatment for 2 or 10 weeks could completely prevent or reverse osteoarthritic subchondral bone loss and cartilage surface erosion. Immunohistochemistry and western blot analysis indicated that expression of OPG and RANKL increased, although RANKL expression increased more significantly than that of OPG. Therefore the ratio of OPG to RANKL was lower in the ACLT group. However, the ratio of OPG to RANKL in the PAM group was significantly higher than that in the ACLT group. Additionally, expression of MMP-9 and TLR-4 were upregulated in the ACLT group and downregulated in the PAM treated groups. CONCLUSIONS: PAM can significantly inhibit and even reverse early osteoarthritic subchondral bone loss, thus alleviating the process of cartilaginous degeneration. The mechanisms involved may be associated with the upregulation of OPG expression, and downregulation of RANKL, MMP-9 and TLR-4 expression.


Assuntos
Cartilagem Articular/metabolismo , Difosfonatos/uso terapêutico , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoprotegerina/biossíntese , Ligante RANK/biossíntese , Animais , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Difosfonatos/farmacologia , Regulação da Expressão Gênica , Pamidronato , Coelhos , Distribuição Aleatória , Resultado do Tratamento
17.
Comput Methods Programs Biomed ; 251: 108211, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744058

RESUMO

Mammography screening is instrumental in the early detection and diagnosis of breast cancer by identifying masses in mammograms. With the rapid development of deep learning, numerous deep learning-based object detection algorithms have been explored for mass detection studies. However, these methods often yield a high false positive rate per image (FPPI) while achieving a high true positive rate (TPR). To maintain a higher TPR while also ensuring lower FPPI, we improved the Probability Anchor Assignment (PAA) algorithm to enhance the detection capability for mammographic characteristics with our previous work. We considered three dimensions: the backbone network, feature fusion module, and dense detection heads. The final experiment showed the effectiveness of the proposed method, and the TPR/FPPI values of the final improved PAA algorithm were 0.96/0.56 on the INbreast datasets. Compared to other methods, our method stands distinguished with its effectiveness in addressing the imbalance between positive and negative classes in cases of single lesion detection.


Assuntos
Algoritmos , Neoplasias da Mama , Mamografia , Humanos , Mamografia/métodos , Neoplasias da Mama/diagnóstico por imagem , Feminino , Aprendizado Profundo , Detecção Precoce de Câncer/métodos , Reações Falso-Positivas , Probabilidade , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Mama/diagnóstico por imagem , Bases de Dados Factuais
18.
Huan Jing Ke Xue ; 44(7): 3695-3704, 2023 Jul 08.
Artigo em Zh | MEDLINE | ID: mdl-37438269

RESUMO

Meteorological conditions play an important role in seasonal ozone variations. In order to understand the meteorological formation mechanisms of ozone pollution in Guangdong Province in winter, the moderate ozone pollution process in Guangdong Province from January 3-6, 2022 was selected for comparison with that in autumn (high pollution season) of 2015 to 2021. The research was based on ground and vertical sounding data and reanalysis data of air quality and meteorological elements. Eight cities exceeded the standard during the pollution process, among which Zhaoqing showed moderate pollution (219 µg·m-3) on January 4th. The average O3-8h concentration in Guangdong Province was 123 µg·m-3, which was 21% higher than that in historical autumn. However, its scope of pollution was less than the historical pollution processes in autumn. Lower wind speed, longer sunshine hours, and airflow reflux effect under local circulation were the most important ground-level meteorological conditions for the ozone pollution process, whereas lower temperature might be an important reason for its small scope of pollution. Vertical detection analysis showed that the combined effect of low-level temperature inversion layer, stronger downdraft, and lower wind speed kept the NO2 concentrations at a high level, and further induced a higher increment of ozone concentration in the morning (34.2 µg·m-3 higher than that in the non-pollution period). The downward transport of ozone in the residual layer aggravated the ozone pollution on January 4th. The accumulation of ozone and its precursors was an important factor of the aggravation of ozone pollution the following day. Airflow trajectory analysis revealed that the ground-level ozone was affected by horizontal transport and vertical mixing of pollutants. Potential sources at 10 m were mainly distributed in the coastal areas from Fujian to Guangdong, and the scope of potential sources was concentrated in Guangdong as the height increased. Airflow backward trajectories at different heights during the ozone process passed over the areas of potential sources in Guangdong, which indicated that the local emissions in Guangdong had a greater impact on the ozone pollution process.

19.
ACS Omega ; 8(1): 529-538, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36643549

RESUMO

ZnS@In2S3 core-shell structures with high photocatalytic activity have been delicately designed and synthesized. The unique structure and synergistic effects of the composites have an important influence on the improvement of photocatalytic activity. The photocatalytic activity has been studied by photodegrading individual eosin B (EB) and the mixture solution consisting of eosin B and rhodamine B (EB-RhB) in the presence of hydrogen peroxide (H2O2) under simulated sunlight irradiation. The results show that all of the photocatalysts with different contents of In2S3 exhibit enhanced catalytic activity compared to pure ZnS for the degradation of EB and EB-RhB solution. When the theoretical molar ratio of ZnS to In2S3 was 1:0.5, the composite presents the highest photocatalytic efficiency, which could eliminate more than 98% of EB and 94% of EB-RhB. At the same time, after five cycles of photocatalytic tests, the photocatalytic efficiency could be about 96% for the degradation of the EB solution, and relatively high photocatalytic activity could also be obtained for the degradation of the EB-RhB mixed solution. This work has proposed a facile synthetic process to realize the controlled preparation of core-shell ZnS@In2S3 composites with effectively modulated structures and compositions, and the composites have also proved to be high-efficiency photocatalysts for the disposal of complicated pollutants.

20.
Environ Sci Pollut Res Int ; 30(6): 15842-15860, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36175725

RESUMO

Understanding households' attitudes and willingness to pay (WTP) for clean heating can provide a scientific basis for decision-makers to assess the potential to develop clean heating, choose heating methods, and formulate subsidy standards in the region. In this paper, the double-bounded dichotomous contingent valuation method-modified by the spike model-was used to better estimate the actual WTP of households through a sample survey of 456 households in rural areas of Yongcheng City, China, in 2021. The factors influencing attitudes and WTP were examined to reveal mechanisms of accepting clean heating. The results showed that 94.96% of households were willing to pay for clean heating. The annual WTP was 1071 yuan per household, more than eight times the current heating cost. Factors that affect clean heating attitudes do not necessarily affect the WTP. Specifically, gender, length of time spent living at home, and family income had significant influences on WTP, whereas the educational level, adaptive perceptions in relation to environmental perceptions, and the recognition variables for gender equality in energy consumption had a significant impact on attitudes. It is worth noting that elderly people and females were identified as vulnerable groups in the implementation of clean heating.


Assuntos
Atitude , Calefação , Feminino , Humanos , Idoso , Características da Família , Renda , China
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