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OBJECTIVE: Bell's palsy, also referred to as clinical manifestations of unilateral facial nerve palsy, encompasses downward angling of the corners of the mouth, the absence of forehead creases, and unilateral incomplete eyelid closure. The incidence of Bell's palsy has increased progressively in recent years, but the underlying mechanism of its occurrence remains unknown; therefore, it is essential to investigate both the cause and treatment of Bell's palsy. Member 2 of the Subfamily V Transient Receptor Potential Cation Channel is a mechanically and thermally sensitive ion channel that plays a crucial role in neural growth and development. Using a novel modeling technique, we endeavored to develop an animal model of Bell's palsy and determine whether TRPV2 expression is altered throughout the course of a facial nerve injury. MATERIALS AND METHODS: The rats were categorized into 3 groups, and their facial nerve function was assessed using RT-qPCR, WB, and pathologic testing, respectively, after undergoing unilateral cold air stimulation for 1, 3, and 7 days. TRPV2 expression was identified using these techniques. RESULTS: In response to cold stimulation, rats exhibited facial nerve paralysis symptoms, demyelinating lesions in the facial nerve, and increased TRPV2 expression. CONCLUSIONS: Extended cold stimulation of the facial nerve in rats may lead to an imbalance in facial nerve homeostasis and increased TRPV2 expression. These findings will contribute to the understanding of the potential mechanism by which cold stimulation affects the facial nerve. Moreover, this finding implies that TRPV2 could possibly function as an additional diagnostic marker or therapeutic target in the context of Bell's palsy.
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OBJECTIVE: This study aimed to use network pharmacology to investigate the molecular mechanisms and potential targets of naringenin (NR) for nonalcoholic fatty liver disease (NAFLD) treatment to offer new drug development ideas. METHODS: The structure and compound information of NR were obtained from PubChem and the traditional Chinese medicine system pharmacology database and analysis platform. The traditional Chinese medicine system pharmacology database and analysis platform Database, Comparative Toxicogenomics Database and Encyclopedia of Traditional Chinese Medicine Database were then used to predict the related targets of NR. Online mendelian inheritance in man, Disgenet, Gene cards, The therapeutic target database and Drug bank were used to screen NAFLD targets, and the intersection analysis was performed with the targets of NR active components to obtain the targets of NR in the treatment of NAFLD. The protein-protein interaction network of therapeutic targets was constructed by protein-protein interaction networks functional enrichment analysis 11.0, and gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis of therapeutic targets was performed by Metascape platform. RESULTS: In this study, 171 NR targets and 1748 potential targets of NAFLD were screened, and 89 crossover targets and 16 core targets were screened and finally obtained. A total of 176 GO items were obtained by GO enrichment analysis (Pâ <â .05), including 389 biological process, 6 cell composition and 30 molecular function. A total of 137 signaling pathways were obtained by Kyoto encyclopedia of genes and genomes pathway enrichment and screening (Pâ <â .05). The core targets of NR in the treatment of NAFLD are TP53, CASP3, PRKCA, AKT1, RELA, PPARG, NCOA2, CYP1A1, ESR1, MAPK3, STAT3, JAK1, MAPK1, TNF, PPARA and PRKCB. Enrichment analysis showed that NR mainly involved in biological processes such as cellular response to nitrogen compound, regulation of miRNA transcription and negative regulation of miRNA-mediated gene silencing. It regulates Hepatitis B, Lipid and atherosclerosis, cytomegalovirus infection, Hepatitis C, AGE-RAGE signaling pathway in diabetic patients complications and other ways play a role in the treatment of NAFLD. CONCLUSIONS: The therapeutic effect of NR on NAFLD has the characteristics of multi-targets and multi-pathways, which provides a preliminary theoretical basis for clinical trials and the development of new drugs.
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Medicamentos de Ervas Chinesas , Flavanonas , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Farmacologia em Rede , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Medicina Tradicional ChinesaRESUMO
Bell's palsy is the most common form of facial nerve palsy. This study aimed to explore the pathogenesis of Bell's palsy by investigating the effect of cold-stimulated adipocyte supernatant on adhesion molecule expression in Schwann cell line. Schwann cells were cultured in regular or adipocyte-conditioned medium and analyzed using RNA sequencing. The mRNA expression of Schwann cell adhesion molecules melanoma cell adhesion molecule (MCAM), protocadherin 9 (PCDH9), and intercellular cell adhesion molecule 1 (ICAM1) was determined using real-time reverse-transcription polymerase chain reaction. Differentially expressed genes were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted. Compared with Schwann cells in 37 °C, the expression of MCAM, PCDH9, and ICAM1 was downregulated in Schwann cells treated with cold-stimulated adipocyte supernatant compared with Schwann cells in 37 °C. Adipocytes subjected to cold exposure may weaken the adhesion capacity of Schwann cells and disrupt the local homeostasis of Schwann cell-axon interactions by affecting the expression of MCAM, PCDH9, and ICAM1, ultimately leading to the development of demyelinating lesions.
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OBJECTIVE: Epidemiological and clinical studies have shown that sharp changes in the ambient temperature are associated with the occurrence and development of Bell's palsy. However, the specific pathogenesis of peripheral facial paralysis remains nebulous. This study investigated the effect of cold stress on transient receptor potential cation channel subfamily V member 2 (TRPV2) secretion by Schwann cells and its role in Bell's palsy. MATERIALS AND METHODS: Schwann cell morphology was observed using transmission electron microscopy (TEM). Cell proliferation, apoptosis and cell cycle were analysed using CCK8 and flow cytometry. ELISA, Reverse transcription-quantitative PCR, western blotting and immunocytochemical fluorescence staining were used to detect the effects of cold stress on TRPV2, neural cell adhesion molecule (NCAM) and nerve growth factor (NGF) expression in Schwann cells. RESULTS: Cold stress resulted in a widening of the intercellular space, and the particles on the membrane showed different degrees of loss. Cold stress may cause Schwann cells to enter a cold dormant state. ELISA, RT-qPCR, western blotting and immunocytochemical fluorescences staining indicated that cold stress inhibited the expression of TRPV2, NCAM, and NGF. CONCLUSIONS: Drastic temperature difference between cold and heat can downregulate TRPV2 and the secretome of Schwann cells. The imbalance of Schwann cell homeostasis under such stress may contribute to nerve signalling dysfunction leading to the development of facial paralysis.
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Paralisia de Bell , Resposta ao Choque Frio , Paralisia Facial , Canais de Cátion TRPV , Paralisia de Bell/diagnóstico , Paralisia de Bell/etiologia , Regulação para Baixo , Paralisia Facial/complicações , Fator de Crescimento Neural , Moléculas de Adesão de Célula Nervosa , Células de Schwann , Canais de Cátion TRPV/genéticaRESUMO
INTRODUCTION: The use of mechanical ventilators in the intensive care unit (ICU) is often associated with higher risk of respiratory tract infections, including ventilator-associated pneumonia (VAP). Concomitant bacterial-viral infection was reported to worsen patient's clinical condition. This study evaluated the rate of concomitant bacterial-viral infections in patients with VAP and analyzed their clinical outcomes. METHODOLOGY: In this retrospective observational study 107 patients diagnosed with VAP and admitted in ICU with mechanical ventilator support between April 2018 and May 2019 in the Department of Respiratory Medicine, Dachang Hospital, Shanghai, China were included. 27 most commonly involved lower respiratory tract infection (LRTI) pathogens (bacteria and virus) and seven genetic markers of antibiotic resistance were detected and analyzed using Biofire® FilmArray® Pneumonia Panel plus (bioMérieux SA, Paris, France). RESULTS: Of the 107 patients, 45 (42.1%) patients had bacterial infection alone (bacterial group), 26 (24.3%) had virus infection alone (viral group) and 24 (22.4%) patients had concomitant bacterial-viral infection (mixed group). Sixty-nine (64.5%) and 50 (46.7%) patient samples were positive for bacterial (bacterial and mixed groups) and viral (viral and mixed groups) detection, respectively. Streptococcus pneumonia (11.2%) and Influenza A (17, 15.9%), were the predominantly identified bacterial and viral species. The blaCTX-M (21.5%) was the predominant resistance gene detected. Twenty-four (22.4%) patients were positive for concomitant bacterial-viral infection; Staphylococcus aureus and Influenza A were the most common bacterial-viral combination identified. CONCLUSIONS: Concomitant bacterial-viral infection was higher compared to previously published studies and the increased duration of mechanical ventilation was associated with increased disease severity.
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Influenza Humana , Pneumonia Bacteriana , Pneumonia Associada à Ventilação Mecânica , Infecções Respiratórias , Bactérias/genética , China/epidemiologia , Marcadores Genéticos , Humanos , Unidades de Terapia Intensiva , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/epidemiologia , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Respiração Artificial/efeitos adversos , Infecções Respiratórias/etiologiaRESUMO
The flame retardancy of layered double hydroxides (LDHs) correlates with their structure and dispersion in a polymeric matrix. To improve the flame retardant effectiveness of Mg-Al LDH in polyethylene (PE), 2-carboxy ethyl (phenyl) phosphinic acid (CEPPA) was adopted as a flame retardant modifier to prepare CEPPA-intercalated LDH (CLDH) by the regeneration method, which was then exfoliated in PE by melt blending in the form of a masterbatch prepared from solution mixing. By compounding CLDH with intumescent flame retardant (IFR) composed of ammonium polyphosphate (APP) and pentaerythritol (PER), the thermal degradation and combustion behaviors of the flame retardant PE-based composites were investigated to reveal the flame retardant mechanism between CLDH and IFR in PE. The reactions between CLDH and IFR were revealed to make a predominant contribution to the compact and fully developed char of PE/IFR/CLDH, which enhanced the flame retardancy of the composites.
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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a global pandemic, and its incidence is increasing year by year. At present, there are no definite curative drugs for the treatment of NAFLD in modern medicine. Surprisingly, complementary and alternative therapies play an important role and have special advantages. In this study, we will adopt Bayesian network meta-analysis (NMA) to evaluate the efficiency and safety of complementary therapy and alternative therapies for NAFLD. METHODS: We will collect randomized controlled trials (RCTs) related to the treatment of NAFLD in PubMed, Cochrane Library, CNKI, and other databases. Two reviewers will screen the literature and extract data in line with the inclusion and exclusion criteria, and then assess the risk of bias according to Cochrane risk of bias assessment tool. The Bayesian NMA will be performed by Stata16.0 and WinBUGS1.4.3. RESULTS: Our study will compare and rank the efficacy and safety of diverse complementary and alternative therapies for NAFLD. CONCLUSION: This study can provide credible evidence for the efficacy and safety of complementary therapies and alternative therapies in the treatment of NAFLD. We expect to assist clinicians and patients to choose the optimal therapeutic regimen. PROTOCOL REGISTRATION NUMBER: INPLASY2020120136.
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Terapias Complementares/métodos , Hepatopatia Gordurosa não Alcoólica/terapia , Teorema de Bayes , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Resultado do TratamentoRESUMO
BACKGROUND: Primary trigeminal neuralgia (PTN) is a type of peripheral neuralgia that seriously affects people's lives. In recent years, complementary therapies and alternative therapies have played a significant role in treating PTN. However, there is a lack of comparison among all the complementary and alternative therapies at present. Thus, the aim of this study is to discuss the efficacy and safety of diverse complementary and alternative therapies by Bayesian network meta-analysis (NMA). METHODS: We will retrieve the Chinese and English databases to gather related randomized controlled trials (RCTs) of complementary and alternative therapies for treating PTN. The deadline is November 2020. Two independent researchers will be in charge of screening qualified literature, extracting data, and independently evaluating bias risks involved in the research. Pairwise meta-analysis and Bayesian network meta-analysis will be performed to assess all evidence. Then, we will use STATA16.0 as well as WinBUGS1.4.3 software for data analysis. Besides, the quality of NMA evidence will be classified by grading of recommendations assessment development and evaluation (GRADE). RESULTS: This study will compare and rank the efficacy and safety of different complementary and alternative therapies in treating primary trigeminal neuralgia. CONCLUSION: Complementary and alternative therapies play an essential role in treating primary trigeminal neuralgia. We expect our study will furnish meaningful evidence support for clinicians and patients. PROTOCOL REGISTRATION NUMBER: INPLASY2020120026. ETHICAL APPROVAL: Since the study is based on published or registered RCTs, ethical approval and patient informed consent are abandoned.
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Protocolos Clínicos , Terapias Complementares/normas , Neuralgia do Trigêmeo/terapia , Teorema de Bayes , Terapias Complementares/métodos , HumanosRESUMO
BACKGROUND: Gastric cancer is one of the most common malignant tumors, which seriously affect peoples quality of life and threaten people's health. Precancerous lesions of gastric cancer (PLGC) are a critical stage in the occurrence and development of gastric cancer. Early effective intervention is an important means to prevent and control gastric cancer. In this study, we will evaluate the efficacy and safety of complementary and alternative therapies in the treatment of PLGC by Bayesian network meta-analysis (NMA). METHODS: We will search PubMed, Cochrane Library, CNKI and other databases to gather randomized controlled trials (RCTs) on the treatment of PLGC with complementary and alternative therapies. Two reviewers will screen the literature and extract the data according to the inclusion and exclusion criteria, and then assess the quality and bias risk according to Cochrane's Risk of Bias Assessment Tool. Bayesian network meta-analysis will be conducted by Stata16.0 and WinBUGS1.4.3. RESULTS: This study will compare and rank the efficacy and safety of different complementary and alternative therapies for PLGC. CONCLUSION: This study can provide reliable evidence for the efficacy and safety of complementary and alternative therapies in treatment of PLGC. We expect to provide scientific and rigorous evidence support for clinicians and patients, and then assist them to choose the optimum treatment. PROTOCOL REGISTRATION NUMBER: INPLASY2020120077.
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Terapias Complementares/métodos , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/terapia , Teorema de Bayes , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
In this study, the molecular mechanism of astragaloside â £(AS-â £) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-â £ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-â £ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-â £ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-â £ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-â £ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-â £ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-â £ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-â £.
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Medicamentos de Ervas Chinesas , Fosfatidilinositol 3-Quinases , Animais , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Células PC12 , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Saponinas , Transdução de Sinais , TriterpenosRESUMO
A polymer ceramic precursor material-polycarbosilane (PCS)-was used as a synergistic additive with magnesium hydroxide (MH) in flame-retardant ethylene-vinyl acetate copolymer (EVA) composites via the melt-blending method. The flame-retardant properties of EVA/MH/PCS were evaluated by the limiting oxygen index (LOI) and a cone calorimeter (CONE). The results revealed a dramatic synergistic effect between PCS and MH, showing a 114% increase in the LOI value and a 46% decrease in the peak heat release rate (pHRR) with the addition of 2 wt.% PCS to the EVA/MH composite. Further study of the residual char by scanning electron microscopy (SEM) proved that a cohesive and compact char formed due to the ceramization of PCS and close packing of spherical magnesium oxide particles. Thermogravimetric analysis coupled with Fourier-transform infrared spectrometry (TG-FTIR) and pyrolysis-gas chromatography coupled with mass spectrometry (Py-GC/MS) were applied to investigate the flame-retardant mechanism of EVA/MH/PCS. The synergistic effect between PCS and MH exerted an impact on the thermal degradation products of EVA/MH/PCS, and acetic products were inhibited in the gas phase.
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The robot-assisted insertion surgery plays a crucial role in biopsy and therapy. This study focuses on determining the optimum puncture pattern for robot-assisted insertion, aiming at the matching problem of needle insertion parameters, thereby to reduce the pain for patients and to improve the reachability to the lesion point. First, a 6-degrees of freedom (DOFs) Computed Tomography (CT)-guided surgical robotic system for minimally invasive percutaneous lung is developed and used to perform puncture experiments. The effects of four main insertion factors on the robotic puncture are verified by designing the orthogonal test, where the inserting object is the artificial skin-like specimen with high transparent property and a digital image processing method is used to analyze the needle tip deflection. Next, the various phases of puncture process are divided and analyzed in detail in view of the tissue deformation and puncture force. Then, short discussion on the comparison of puncture force with different effect factors for the same beveled needle is presented. The same pattern can be observed for all of the cases. Finally, based on the experimental data, the formulations of the puncture force and needle deflection which depends on Gauge size, insertion velocity, insertion angle, and insertion depth are developed using the multiple regression method, which can be used to get an optimum puncture pattern under the constrains of minimum peak force and minimum needle tip deflection. The developed models have the effectiveness and applicability on determining the optimum puncture pattern for one puncture event, and which can also provide insights useful for the setting of insertion parameters in clinical practice.
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Procedimentos Cirúrgicos Robóticos , Robótica , Biópsia , Humanos , Agulhas , PunçõesRESUMO
The success of using immune checkpoint inhibitors to treat cancers implies that inhibiting an immunosuppressive cytokine, such as TGF-ß2, could be a strategy to develop novel adjuvants for microbial vaccines. To develop nucleic acid based TGF-ß2 inhibitors, we designed three antisense oligonucleotides, designated as TIO1, TIO2, and TIO3, targeting the conserve regions identical in human and mouse TGF-ß2 mRNA 3'-untranslated region. In cultured immune cells, TIO3 and TIO1 significantly reduced the TGF-ß2 mRNA expression and protein production. In mice, the TIO3 and TIO1, when formulated in various microbial vaccines, significantly enhanced the antibody response to the vaccines, and the TIO3-adjuvanted influenza virus vaccine induced effective protection against the influenza virus challenge. In the immunized mice, TIO3 formulated in microbial vaccines dramatically reduced surface-bound TGF-ß2 expression on CD4+ T cells and CD19+ B cells in the lymph node (LN) cells and spleen cells; up-regulated the expression of CD40, CD80, CD86, and MHC II molecules on CD19+ B cells and CD11c+ dendritic cells; and promoted IFN-γ production in CD4+ T cells and CD8+ T cells in the LN cells. Overall, TIO3 or TIO1 could be used as a novel type of adjuvant for facilitating the microbial vaccines to elicit more vigorous and persistent antibody response by interfering with TGF-ß2 expression.
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Adjuvantes Imunológicos/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Oligonucleotídeos/farmacologia , Fator de Crescimento Transformador beta2/antagonistas & inibidores , Vacinação , Vacinas/farmacologia , Adjuvantes Imunológicos/genética , Animais , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/imunologia , Cães , Humanos , Células Madin Darby de Rim Canino , Camundongos , Oligonucleotídeos/genética , Células RAW 264.7 , Fator de Crescimento Transformador beta2/genética , Fator de Crescimento Transformador beta2/imunologia , Células U937 , Vacinas/genética , Vacinas/imunologiaRESUMO
Background: The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. Methods: We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. Findings: We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53â617 patients visiting fever clinics, 1004 (1·9%) were considered as suspected cases, with 188 (0·4% of all patients, 18·7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4·16, 95% CI 2·74-6·33; p<0·0001), fatigue (OR 1·56, 1·01-2·41; p=0·043), white blood cell count less than 4â×â109 per L (OR 2·44, 1·28-4·64; p=0·0066), lymphocyte count less than 0·8â×â109 per L (OR 1·82, 1·00-3·31; p=0·049), ground glass opacity (OR 1·95, 1·32-2·89; p=0·0009), and having both lungs affected (OR 1·54, 1·04-2·28; p=0·032) were independent risk factors for confirmed COVID-19. Interpretation: The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease. Funding: National Natural Science Foundation of China.
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COVID-19/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/etiologia , COVID-19/patologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Febre/etiologia , Humanos , Lactente , Recém-Nascido , Contagem de Leucócitos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Robot-assisted puncture has gradually attracted more attention and practical clinical application. The lesion positioning and the needle positioning are the basis to ensure the accuracy of puncture and the key techniques in insertion operation. METHODS: A lesion positioning method is established which is realized only by the robot-CT system without using external positioning system, and an omnidirectional needle positioning method is also developed and realized by using VRCM, in order to make the puncture needle always keep pointing to the lesion point. A CT-guided surgical robotic system used for minimally invasive percutaneous lung is designed and the physical prototype is manufactured, to perform in-vitro experiments, thereby to validate the effectiveness of the lesion positioning method and the feasibility of omnidirectional needle positioning method. RESULTS: The accuracy of established lesion positioning method based on three non-collinear markers is within 3 mm, which is similar to that of the least squares method based on the five non-coplanar markers, but the positioning efficiency can be improved by about 40%, and the non-collinearity of markers is easier to be satisfied than non-coplanarity in practical applications. The average calculation error of the established positioning method is 0.997 mm. Moreover, the omnidirectional positioning of the puncture needle under the designed surgical robot is feasible. CONCLUSIONS: The designed surgical robot has good control accuracy and it can satisfy the requirements for use. The established lesion positioning method can provide a good precision basis for robot-assisted puncture surgery. The suitable insertion point and insertion posture can be determined by the developed omnidirectional needle positioning method. This study can provide theoretical reference for further study of path planning or autonomous positioning.
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Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Agulhas , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Biópsia , Desenho de Equipamento , Humanos , Técnicas In Vitro , Procedimentos Cirúrgicos Minimamente Invasivos , Modelos Teóricos , Movimento (Física) , Reprodutibilidade dos Testes , Procedimentos Cirúrgicos Robóticos/instrumentação , Estresse Mecânico , Cirurgia Assistida por Computador/instrumentaçãoRESUMO
Lung resident mesenchymal stem cells (LR-MSCs) contribute to the progression of idiopathic pulmonary fibrosis (IPF). We aimed to investigate the molecular mechanism underlying LR-MSCs regulation upon transforming growth factor (TGF)-ß1 stimulation. We induced fibrogenic differentiation of LR-MSCs isolated from mice by TGF-ß1. Several stem cell markers were detected by flow cytometric analysis. Protein expression level was tested by Western blotting and mRNA level was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, proliferation and apoptosis were measured. TGF-ß1 promoted fibrogenic differentiation of LR-MSCs and upregulated ß-catenin and p-glycogen synthase kinase-3ß, suggesting the activation of Wnt signaling. MicroRNA (MiR)-124-3p was significantly upregulated in TGF-ß1 treated LR-MSCs compared to untreated cells. Intriguingly, silence of miR-124 reversed the TGF-ß1-induced changes in cell viability and proliferation, and also led to a decrease of cell apoptosis. Additionally, in miR-124 silenced cells, α-smooth muscle actin, collagen I and fibronectin were downregulated compared to control cells. We ultimately identified a new target of miR-124, AXIN1, which was repressed by miR-124. In conclusion, miR-124 regulates AXIN1 to activate Wnt signaling and therefore plays a crucial role in the TGF-ß1-induced fibrogenic differentiation.
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Diferenciação Celular/genética , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Miofibroblastos/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Via de Sinalização Wnt/genética , Animais , Proteína Axina/genética , Proteína Axina/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Pulmão/citologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Miofibroblastos/citologia , Miofibroblastos/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
BACKGROUND: The diverse medicinal properties of herbal compounds make them suitable candidates to treat multifactorial conditions such as pulmonary fibrosis. We investigated the effects and mechanisms of compound Chuanxiong Kangxian granules (CCKG) on a bleomycin (BLM)-induced pulmonary fibrosis model in rats. METHODS AND RESULTS: Following an intratracheal instillation of BLM, Sprague Dawley rats were intragastrically administrated with different doses of CCKG solution or hydrocortisone for 28 d, while control and BLM-treated rats were administered with saline solution. The effects of CCKG treatment on pulmonary injury were evaluated with lung wet/dry weight ratios, histopathology and levels of hydroxyproline. Oxidative stress was evaluated by detecting serum levels of glutathione and total superoxide dismutase. Inflammation was assessed by measuring levels of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in bronchoalveolar lavage fluid. Immunohistochemistry and western blotting was used to analyze protein expressions of matrix metalloproteinase-2, 9, α-smooth muscle actin and transforming growth factor-ß1 in lung tissue. The results indicate that CCKG treatment can ameliorate BLM-induced pulmonary fibrosis and attenuate BLM-induced oxidative stress and inflammation. CONCLUSIONS: We found that CCKG-mediated suppression of fibroproliferation and may contribute to the anti-fibrotic effect by inhibiting oxidative stress and inflammatory responses. Our study indicates a therapeutic potential for CCKG in the treatment of pulmonary fibrosis.
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Bleomicina/toxicidade , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Animais , Medicamentos de Ervas Chinesas/farmacologia , Interleucina-1beta/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Fibrose Pulmonar/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. METHODS: A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. RESULTS: We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (pï¼0.001) and total cholesterol (TC) (pï¼0.001) were found in HSs in the genotype GG/GC carriers, but not the genotype CC carriers (pï¼0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08-1.25; pï¼0.0001, random-effect method). CONCLUSION: Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese.
RESUMO
The goal of this study was to investigate the contribution of NOS1AP-promoter DNA methylation to the risk of intracranial aneurysm (IA) and brain arteriovenous malformation (BAVM) in a Han Chinese population. A total of 48 patients with IAs, 22 patients with BAVMs, and 26 control individuals were enrolled in the study. DNA methylation was tested using bisulfite pyrosequencing technology. We detected significantly higher DNA methylation levels in BAVM patients than in IA patients based on the multiple testing correction (CpG4-5 methylation: 5.86±1.04% vs. 4.37±2.64%, P=0.006). In women, CpG4-5 methylation levels were much lower in IA patients (3.64±1.97%) than in BAVM patients (6.11±1.20%, P<0.0001). However, in men, CpG1-3 methylation levels were much higher in the controls (6.92±0.78%) than in BAVM patients (5.99±0.70%, P=0.008). Additionally, there was a gender-based difference in CpG1 methylation within the controls (men vs. women: 5.75±0.50% vs. 4.99±0.53%, P=0.003) and BAVM patients (men vs. women: 4.70±0.74% vs. 5.50±0.87%, P=0.026). A subgroup analysis revealed significantly higher CpG3 methylation in patients who smoked than in those who did not (P=0.041). Our results suggested that gender modulated the interaction between NOS1AP promoter DNA methylation in IA and BAVM patients. Our results also confirmed that regular tobacco smoking was associated with increased NOS1AP methylation in humans. Additional studies with larger sample sizes are required to replicate and extend these findings.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Metilação de DNA , Aneurisma Intracraniano/genética , Malformações Arteriovenosas Intracranianas/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Although asthma symptoms can be temporarily controlled, it is recommended to use effective low-risk, non-drug strategies to constitute a significant advance in asthma management. Acupuncture has been traditionally used to treat asthma; however, the evidence for the efficacy of this treatment is still lacking. Previous clinical trials of acupuncture in treating asthma were limited by methodological defects; therefore, high-quality research is required. METHODS/DESIGN: This trial is designed as a multi-center, randomized, double-blind, parallel-group controlled trial. Patients with mild to moderate asthma will be randomly allocated to either a verum acupuncture plus as-needed salbutamol aerosol and/or prednisone tablets group or a sham acupuncture plus as-needed salbutamol aerosol and/or prednisone tablets group. Acupoints used in the verum acupuncture group are GV14 (Da Zhui), BL12 (Feng Men), BL13 (Fei Shu) and acupoints used in the sham acupuncture group are DU08 (Jin Suo), BL18 (Gan Shu), BL19 (Dan Shu). After a baseline period of 1 week, the patients in both groups will receive verum/sham acupuncture once every other day with a total of 20 treatment sessions in 6 weeks and a 3-month follow-up. The primary outcome will be measured by using the asthma control test and the secondary outcomes will be measured by using the percentage of symptom-free days, the average dosage of salbutamol aerosol and/or prednisone tablets, lung functions, daily asthma symptom scores, asthma quality of life questionnaire, and so on. DISCUSSION: This trial will assess the effect of acupuncture on asthma and aims to provide reliable clinical evidence for the efficacy of acupuncture in treating asthma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01931696 , registered on 26 August 2013.