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BACKGROUND: Deep vein thrombosis (DVT) is a common and serious risk in elderly patients with knee osteoarthritis (OA), making preoperative detection crucial. Despite this, identifying OA patients at high risk for preoperative DVT and appropriately targeting them for venous ultrasound screening remains a challenge. There is limited research-based evidence on the risk factors for preoperative DVT in elderly patients with end-stage OA. We examined the incidence of and risk factors for preoperative DVT in elderly patients with end-stage OA scheduled for total knee arthroplasty. METHODS: We retrospectively analyzed the demographic data (age, sex, body mass index, current smoking, alcohol consumption, walking status, and Barthel index score), medical history, and laboratory test indices of 1411 patients with end-stage OA aged ≥ 60 years scheduled for total knee arthroplasty from January 2015 to December 2018. Risk factors for preoperative DVT were evaluated by univariate and multivariate logistic analyses. Receiver operating characteristic analysis was performed to determine optimal cut-off values. RESULTS: The incidence of preoperative DVT was 4.5% (63 of 1411 patients). Seven independent risk factors were correlated with preoperative DVT in the multivariate logistic regression: age (odds ratio [OR], 1.073; P = 0.002), D-dimer concentration (OR, 1.173; P = 0.003), hyperlipidemia (OR, 2.038; P = 0.045), atrial fibrillation (OR, 4.004; P = 0.033), chronic renal failure (OR, 6.732; P = 0.008), chronic obstructive pulmonary disease (COPD) (OR, 8.721; P = 0.001), and walking status (wheelchair) (OR, 2.697; P = 0.002). The optimal cut-off values for predicting preoperative DVT were 0.585 µg/mL for the D-dimer concentration (area under the curve [AUC], 0.769; P < 0.001) and 72.5 years for age (AUC, 0.668; P < 0.001). CONCLUSION: Among elderly patients with end-stage OA, venous ultrasonography to rule out DVT risk should be prioritized in those with a high D-dimer concentration (> 0.585 µg/mL), high age (> 72.5 years), hyperlipidemia, atrial fibrillation, chronic renal failure, COPD, and walking status (wheelchair).
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Artroplastia do Joelho , Osteoartrite do Joelho , Trombose Venosa , Humanos , Artroplastia do Joelho/efeitos adversos , Masculino , Estudos Retrospectivos , Feminino , Fatores de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Trombose Venosa/diagnóstico por imagem , Idoso , Incidência , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/epidemiologia , Pessoa de Meia-Idade , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Fatores Etários , Período Pré-OperatórioRESUMO
The motion control system of a lower-limb exoskeleton rehabilitation robot (LLERR) is designed to assist patients in lower-limb rehabilitation exercises. This research designed a motion controller for an LLERR-based on the Twin Delayed Deep Deterministic policy gradient (TD3) algorithm to control the lower-limb exoskeleton for gait training in a staircase environment. Commencing with the establishment of a mathematical model of the LLERR, the dynamics during its movement are systematically described. The TD3 algorithm is employed to plan the motion trajectory of the LLERR's right-foot sole, and the target motion curve of the hip (knee) joint is deduced inversely to ensure adherence to human physiological principles during motion execution. The control strategy of the TD3 algorithm ensures that the movement of each joint of the LLERR is consistent with the target motion trajectory. The experimental results indicate that the trajectory tracking errors of the hip (knee) joints are all within 5°, confirming that the LLERR successfully assists patient in completing lower-limb rehabilitation training in a staircase environment. The primary contribution of this study is to propose a non-linear control strategy tailored for the staircase environment, enabling the planning and control of the lower-limb joint motions facilitated by the LLERR.
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Algoritmos , Exoesqueleto Energizado , Extremidade Inferior , Robótica , Humanos , Extremidade Inferior/fisiologia , Robótica/métodos , Articulação do Quadril/fisiologia , Articulação do Quadril/fisiopatologia , Articulação do Joelho/fisiologia , Marcha/fisiologia , Fenômenos Biomecânicos/fisiologia , Movimento (Física)RESUMO
BACKGROUND: A previous validation study showed a very low sensitivity and higher specificity associated with Hanifin and Rajka criteria (H&R) and the UK Working Party criteria (UKWP) in diagnosing AD vs. the Chinese criteria of atopic dermatitis (AD) for children (CCAD). However, their diagnostic efficacy in adult and elderly Chinese populations remains unknown. OBJECTIVES: To validate the diagnostic efficacy of three sets of AD criteria in adult and elderly Chinese populations in a hospital setting. METHODS: A total of 1034 patients (aged 19-95â years) from five university hospital dermatological clinics were recruited. Medical history, dermatological examination, AD diagnosis and evaluation of AD severity were done by dermatologists. Each patient was investigated by two dermatologist panels, one to establish a clinical diagnosis, and the other to identify and record the major or minor signs of H&R criteria, UKWP criteria and CCAD. Taking clinical diagnosis as the reference, the diagnostic efficacy of three sets of diagnostic criteria was evaluated. The χ2 test or rank sum test were used for between-groups comparisons. RESULTS: CCAD had a higher sensitivity (84.0%), especially among mild and moderate cases of AD (72.7% and 90.3%, respectively), than the H&R (58.0%; P < 0.001) and UKWP criteria (56.0%; P < 0.001) in diagnosing AD. The specificity of CCAD (92.7%) was slightly lower than the H&R (97.3%; P < 0.001) or UKWP criteria (97.4%; P < 0.001). The CCAD had the highest Youden index (0.77), accuracy rate (0.90) and Kappa value (0.76) of the three sets of diagnostic criteria. CONCLUSIONS: Consistent with results in a population of Chinese children, although the H&R and UKWP criteria had a high specificity for diagnosing AD, their low sensitivity limited their use in adult and elderly Chinese patients. Based on the high sensitivity and favourable diagnostic efficacy, the CCAD is proposed for AD diagnosis in adult and elderly Chinese populations, especially for cases of mild and moderate AD.
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Dermatite Atópica , Adulto , Idoso , Humanos , Povo Asiático , Dermatite Atópica/diagnóstico , População do Leste Asiático , Estudos Prospectivos , Adulto Jovem , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
Context: The informatization of the medical system is increasingly closely linked with people's daily life. As people pay more and more attention to the quality of life, it's very necessary to closely integrate the management information and clinical information systems to promote the steady improvement of a hospital's service level. In the process of modernization Chinese hospitals, comprehensive promotion of hospital informatization is very important. Objective: The study intended to examine the role in China of informatization for hospital management, analyze its shortcomings in that role, and explore its role based on an analysis of hospital data, and propose effective measures to continuously improve the level of informatization, promote the steady improvement of hospital management and services, and fully demonstrate the application advantages of information construction. Design: The research team discussed: (1) China's informatization, including hospitals' roles, current informatization, the information community, and medical and information-technology (IT) staff; (2) methods of analysis, including system composition, theoretical basis, definition of the problem as well as data evaluation, collection, processing, mining and model evaluation and knowledge presentation; (3) the procedures the team followed to perform a case study, including types of hospital data and the process framework, and (4) the study's results from informatization based on data analysis, including satisfaction surveys for outpatients, inpatients, and medical staff. Setting: The study took place at Nantong First People's Hospital in Jiangsu Province in Nantong, China. Conclusions: In the process of hospital management, it's imperative to strengthen hospital informatization, which can continuously strengthen a hospital's service capacity, ensure good-quality medical service, further improve the discipline of the database construction, enhance the satisfaction of employees and patients, and achieve a high-quality and benign development for the hospital.
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Hospitais , Qualidade de Vida , Humanos , China , Análise de DadosRESUMO
The treatment of recessive dystrophic epidermolysis bullosa (RDEB) remains challenging. Elevated IgE levels have previously been reported in several RDEB patients. In this prospective, single-centre, open intervention study, elevated IgE levels were seen in 11 out of 12 patients with intense pruritus, and the patients with elevated IgE levels received anti-IgE therapy every 4 weeks for at least three cycles. Compared with the baseline, 10 patients with RDEB had good clinical outcomes with enhanced wound healing, a reduction in Birmingham (epidermolysis bullosa) EB severity score by 15%, a reduction in affected body surface area by 23.3%, amelioration of skin inflammation, and an increase in type VII collagen deposition by 13.1-fold. All the patients had a good tolerance to anti-IgE therapy. Furthermore, patients with higher IgE levels tended to have higher disease severity and more favorable clinical outcomes. Our report also suggested the potential role of IgE in the pathogenesis of inflammatory conditions associated with RDEB. (ChiCTR1900021437).
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Anticorpos Anti-Idiotípicos/uso terapêutico , Epidermólise Bolhosa Distrófica/tratamento farmacológico , Adolescente , Adulto , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Anti-Idiotípicos/efeitos adversos , Autoimunidade , Biópsia , Criança , Colágeno Tipo VII/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças/imunologia , Epidermólise Bolhosa Distrófica/diagnóstico , Epidermólise Bolhosa Distrófica/etiologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Pele/imunologia , Pele/metabolismo , Pele/patologia , Resultado do Tratamento , Cicatrização , Adulto JovemRESUMO
Children with severe atopic dermatitis (AD) can benefit from intravenous immunoglobulin (IVIG) therapy. This study aimed to identify the efficacy and safety of IVIG therapy in children with severe AD. Twenty pediatric AD patients were enrolled in this study. Patients with an Investigator's Global Assessment score of 0 or 1 or a reduction of 2 points after treatment were defined as high-responders (HRs), otherwise, they were defined as low-responders (LRs). Twelve patients (60%) achieved an excellent treatment response after 2 months, while eight (40%) had a low response. The Scoring Atopic Dermatitis index had improved significantly at 2 months post-treatment compared with baseline (p < 0.001). Baseline total serum IgE levels and eosinophil counts were elevated in all subjects and decreased significantly at 2 months post-treatment (p = 0.004 and 0.021, respectively). Baseline IgE levels were significantly higher in the HR group compared with the LR group (p = 0.020). The treatment was well tolerated. Fever was the most common adverse event and occurred in five patients (25%). In conclusion, IVIG could be a safe and effective therapy for children with severe AD and may be more effective in patients with higher IgE levels. Further studies are needed to investigate the different therapeutic responses in patients with different AD phenotypes.
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Dermatite Atópica , Humanos , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Imunoglobulinas Intravenosas/efeitos adversos , Índice de Gravidade de Doença , Contagem de Leucócitos , Imunoglobulina E , Resultado do TratamentoRESUMO
We propose a new, to the best of our knowledge, scheme for the frequency measurement of wideband microwave signals by applying the optical frequency comb (OFC) and channelization technique. Unlike the usual method of using radio-frequency driving signals to generate an OFC, our scheme uses digital driving signals, which makes the comb spacing adjustable and the comb bandwidth wider. In the measurement process, multiple sets of beat signals can be obtained at the same time, and multiple frequency components of the microwave signals can be measured at the same time. The theoretical analysis model of the scheme is established, and the scheme is validated by VPI simulation software. The results show that the range of frequency measurement is 0â¼50GHz, and it can be further expanded by extending the width of the OFC.
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A new, to the best of our knowledge, scheme for the generation of ultra-flat optical frequency combs (OFCs) is proposed, which mainly uses a polarization modulator (PolM) and a first-order Butterworth band-stop filter. The PolM is driven by a digital periodic square-wave signal, and the output of the PolM is an uneven OFC. The function of the Butterworth band-stop filter is to obtain flat and stable OFCs by changing its bandwidth. The comb spacing of the OFCs can be adjusted by changing the period of the square-wave signal. The theoretical model for the scheme is also established. The simulation results show that the generator constructed according to the proposed scheme can produce 64, 128, and 256 comb lines with 200 MHz comb spacing and with spectral flatness lower than 0.3 dB. The comb spacing can be further increased by using the square-wave signal at GHz rates, and the generated OFCs exhibit good frequency tunability.
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BACKGROUND: Eczema is usually the first allergic manifestation to appear in life attributed to gene-environment interactions. IL13, IL4, MS4A2 and ILR4A are four key inflammatory genes associated with atopy. This study aimed to explore gene-environment interactions on eczema in early life among the above four genes and environmental factors in Chinese Han children. METHODS: Five hundred ninety-seven children from a birth cohort who completed two-year follow-up were enrolled and their cord blood was collected. Subjects were genotyped for six polymorphisms in the aforementioned four genes. The children were followed at 6, 12 and 24 months, with epidemiologic information and medical history of eczema collected by questionnaire and eczema assessed by dermatologists. RESULTS: Among the 597 children, 168 were diagnosed with eczema and the others were not after 2 years of follow-up. MS4A2 rs569108 GG genotype (P = 1.68E-02, odds ratio (OR) = 4.66) and antibiotic use (P = 3.75E-4, OR = 2.02) were found independently associated with development of childhood eczema. Children with both antibiotic use and MS4A2 rs569108 GG genotype were more likely to develop eczema than those with only antibiotic use or GG homozygote (OR = 6.24 VS. 2.04 or 4.68). CONCLUSIONS: MS4A2 rs569108 polymorphism and antibiotic use were solely associated with eczema, and they interacted with each other to increase the risk of developing the disease in Chinese Han toddlers. Long-term follow-up along with functional and replication studies are still needed.
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Dermatite Atópica , Eczema , Receptores de IgE/genética , Antibacterianos , Estudos de Coortes , Dermatite Atópica/genética , Eczema/genética , Humanos , Lactente , Polimorfismo Genético , Estudos ProspectivosRESUMO
BACKGROUND: Antibody-mediated rejection (AMR) can cause graft loss and reduces long-term graft survival after kidney transplantation. Human leukocyte antigen (HLA) and/or non-HLA antibodies play a key role in the pathogenesis of AMR by targeting the allograft epithelium via complement activation and complement-independent mechanisms. However, the precise mechanisms of AMR remain unclear and treatment is still limited. METHODS: In this study, we investigated the role of the endothelial-associated transcription factor Sox7 in AMR, using the anti-HLA antibody W6/32, shRNA-mediated Sox7 knockdown, and by manipulating the Notch pathway. We used an in vitro human kidney glomerular endothelial cells (HKGECs) model and an in vivo MHC-mismatched kidney transplantation model. RESULTS: Sox7 expression was upregulated and the Jagged1-Notch1 pathway was activated in HKGECs after W6/32 activation. W6/32 antibodies increased the expression of adhesion molecules (VCAM-1, ICAM-1), inflammatory cytokines (IL-6, TNF-α), and chemokines (CXCL8, CXCL10), and Sox7 knockdown and inhibition of the Notch pathway by DAPT significantly reduced these effects. Jagged1 overexpression rescued the inhibitory effects of Sox7 knockdown. In addition, Sox7 knockdown attenuated acute allograft kidney injury in mice and reduced the expression of adhesion molecules and Jagged1-Notch1 signaling after transplantation. CONCLUSIONS: Our findings suggest that Sox7 plays an important role in mediating HLA I antibody-dependent endothelial cell activation and acute kidney allograft rejection via the Jagged1-Notch1 pathway. Manipulating Sox7 in donor organs may represent a useful treatment for AMR in solid organ transplantation.
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Células Endoteliais/imunologia , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Transplante de Rim/efeitos adversos , Fatores de Transcrição SOXF/metabolismo , Aloenxertos/imunologia , Animais , Células Cultivadas , Humanos , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Receptores Notch/genética , Receptores Notch/metabolismo , Fatores de Transcrição SOXF/genéticaRESUMO
To generate a flat optical frequency comb (OFC), a new scheme based on a dual-parallel Mach-Zehnder modulator and a single recirculation frequency shift loop is proposed and analyzed. Compared with the traditional single loop recirculation frequency shift method, the quantity of comb lines is doubled, and the comb flatness is better when the number of cycles is the same. The theoretical analysis model is established, and the simulation results show that a 111-line OFC with frequency spacing of 10 GHz, flatness of 1.32 dB, and optical signal to noise ratio of 27.4 dB can be obtained by adopting the proposed scheme.
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BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been reported to suppress immune function. However, previous studies on prenatal exposure to PFASs and allergic disorders in offspring provided inconsistent results. We aimed to examine the association between prenatal exposure to PFASs and childhood atopic dermatitis (AD) in offspring up to 24 months of age. METHODS: A prospective birth cohort study involving 1056 pregnant women was conducted in two hospitals in Shanghai from 2012 to 2015. Prenatal information was collected by an interview with the women and from medical records. Fetal umbilical cord blood was collected at birth. Cord blood plasma PFASs were measured. Children were followed at 6, 12 and 24 months and information on the development of AD was recorded. AD was diagnosed by 2 dermatologists independently based on the questionnaires. Multiple logistic regression was used to compute odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between AD and each PFASs, adjusting for potential confounders. RESULTS: A total of 687 children completed a 2-year follow-up visit and had PFASs measurement. AD was diagnosed in 173 (25.2%) children during the first 24 months. In female children, a log-unit increase in perfluorooctanoic acid (PFOA) was associated with a 2.1-fold increase in AD risk (AOR 2.07, 95% CI 1.13-3.80) after adjusting for potential confounders. The corresponding risk was 2.22 (1.07-4.58) for perfluorononanoic acid (PFNA). The highest PFOA quartile was significantly associated with AD (2.52, 1.12-5.68) compared with the lowest quartile. The highest quartile of PFNA, perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS) were associated with AD with AOR (95% CI) being 2.14 (0.97-4.74), 2.14 (1.00-4.57), and 2.30 (1.03-5.15), respectively. Additionally, the second quartile of perfluorododecanoic acid (PFDoA) was associated with a 3.2-fold increase in AD risk (3.24, 1.44-7.27). However, no significant associations were found in male children. CONCLUSIONS: Prenatal exposure to PFOA, PFDA, PFDoA and PFHxS significantly increased the risk of childhood AD in female children during the first 24 months of life. In addition, the associations between AD with prenatal exposure to PFNA were close to statistical significance.
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Ácidos Alcanossulfônicos/sangue , Dermatite Atópica/epidemiologia , Poluentes Ambientais/sangue , Fluorocarbonos/sangue , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , China/epidemiologia , Cidades , Dermatite Atópica/induzido quimicamente , Feminino , Sangue Fetal/química , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos Prospectivos , Adulto JovemRESUMO
Prostate Cancer has become the second leading cause of male cancer-related incidence and mortality in United States. Hyperthermia (HT) is known to serve as a powerful tool in treatment of prostate cancer in clinical. The combination treatment with HT and cisplatin has a synergistic effect to inhibit prostate cancer progression and demonstrates better clinical effectiveness than HT or chemotherapy alone. But molecular mechanisms of this phenomenon have not been illuminated clearly. In this study, we used MTS assay to examine cell viabilities of PC-3, LNCaP, DU-145 and RM-1 cells after treated by HT and cisplatin. Then colony formation of PC-3 and DU-145 cells after treated with HT and cisplatin were photographed. To investigate whether the combination therapy would enhance apoptosis of PC-3 and DU-145 cells, we used Western blot analysis to detect expression level of proteins on apoptosis-regulated signaling pathway in PC-3 and DU-145 cells. Our results showed that the combination treatment decreased cell viabilities and colony formation of prostate cancer cells in a dose-dependent manner and this combination therapy enhanced apoptosis of PC-3 and DU-145 cells via activation of Caspase-3 and cleavage of PARP. We also found that the combination therapy could down-regulate the anti-apoptotic Bcl-2 and IAP family proteins. At last, the combination therapy activated AMPKα-JNK signaling pathway and inhibited Akt-mTOR-p70s6k signaling pathway to promote apoptosis of PC-3 and DU-145 cells. In conclusion, this study clearly elucidated how the combination therapy with HT and cisplatin promoted apoptosis of prostate cancer cells in synergy.
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Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Temperatura Alta , Animais , Antineoplásicos/farmacologia , Western Blotting , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Poli(ADP-Ribose) Polimerase-1/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
UNLABELLED: Dlg5 (Discs large homolog 5), a member of the membrane-associated guanylate kinase adaptor family of scaffolding proteins, has been shown to participate in cancer progression. However, little is known about whether abnormal expression of Dlg5 facilitates bladder cancer metastasis. In the current study we initiated a study analyzing Dlg5 expression and its roles in human bladder cancer metastasis. The expression of Dlg5 is decreased in most bladder cancer tissues compared with adjacent normal tissues, and Dlg5 expression is further downregulated in patients with muscle-invasive tumors. DNA methylation analysis showed a methylation of Dlg5 gene in bladder cancer cell lines and in bladder cancer tumors, especially in muscle-invasive tumors. Hypermethylation of Dlg5 in bladder tumors is tightly correlated with silencing of Dlg5 expression, which is further functionally validated by demethylation analysis in bladder cancer cell lines. Knockdown of Dlg5 increases cancer cell invasion in vitro and promotes cancer metastasis in vivo. Of clinical significance, Kaplan-Meier analysis showed that downregulation of Dlg5 is significantly associated with reduced overall survival in patients with bladder cancer. CONCLUSION: These data suggest that inhibition of Dlg5 by DNA hypermethylation contributes to provoke invasive phenotypes in bladder tumor.
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Metilação de DNA , Proteínas de Membrana/genética , Proteínas Supressoras de Tumor/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Ilhas de CpG/genética , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Regiões Promotoras Genéticas/genética , Interferência de RNA , RNA Interferente Pequeno , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
This study aimed to investigate the effects and molecular mechanism of cyclosporin A (CsA) on cobalt chloride (CoCl2)-induced injury in H9c2 embryonic rat cardiac cells. The results showed that CsA could protect H9c2 cells against CoCl2-induced hypoxic injury. CsA effectively improved cell viability, and decreased LDH leakage, cell apoptosis, MDA concentration, and ROS generation, and increased SOD activity, GSH production, and CAT activity in a dosedependent manner. In addition, CsA treatment blocked the CoCl2-induced increases in ROS production and mitochondrial dysfunction, including a decrease in membrane potential, cytochrome c (cyto-c) release, Bax/Bcl-2 imbalance, as well as the ratios of cl-casp-9/casp-9 and cl-casp-3/casp-3 ratios, via the inhibition of p38 and ERK MAPK signaling pathways. The results also suggested that CsA protected H9c2 cells against CoCl2-induced hypoxic injury, possibly by suppressing the MAPK signaling pathway. Thus, CsA is a potential therapeutic agent for cardiac hypoxic injury.
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Ciclosporina/farmacologia , Hipóxia/prevenção & controle , Imunossupressores/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Cobalto , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) possess immunomodulatory properties on a diverse array of immune cell lineages, including regulatory T and B cells (Tregs and Bregs, respectively). However, their specific effects and mechanisms underlying induction of Bregs remain unclear. The immune regulatory function of MSCs is exerted through both cell-cell contact and the release of soluble factors. The main objective of this study was to examine the role of the SDF-1-CXCR4/CXCR7 axis in the secretory action of MSCs, and potential effects on the immunoregulatory function of these cells. METHODS: MSCs were isolated from mouse bone marrow and characterized according to their multilineage differentiation potential and their surface antigen expression. CD19(+) B cells purified from mice splenocytes were co-cultured with MSCs at various ratios in the presence of LPS and αCD40. After 4 days, intracellular IL-10 production and cell surface CD1d and CD5 expression by CD19(+) B cells were determined using flow cytometry, and the secretion of IL-10, IL-6, IgM, and IgG were assessed with ELISA. MSCs were treated with different concentrations of stromal derived factor-1α (SDF-1α) stimuli or transiently overexpressed with CXCR7. and their cell viability and immune regulatory effects of MSCs on Bregs were assessed. RESULTS: MSCs induced IL-10-producing regulatory B cells and primarily stimulated the CD1d(+)CD5(+)B cell subset of IL-10+Breg cells to express IL-10. IL-10, IL-6, and IgM secretion were additionally induced by MSCs. The CXCR7 pathway was required for MSC viability and the production of paracrine factors under SDF-1α culture condition. Low concentrations of SDF-1α promoted the immunomodulatory effect of MSCs, leading to a further increase in IL-10-producing regulatory B cells and IL-10 secretion. In contrast, high concentrations of SDF-1α inhibited MSCs induction of IL-10(+)Breg cells. Notably, CXCR7 overexpression in MSCs reversed the inhibitory effect of high concentrations of SDF-1α and promoted the immunomodulatory effect of these cells. CONCLUSION: MSCs induce IL-10(+)Breg cells, which contribute to the generation of an immunosuppressive environment. SDF-1α and its receptor, CXCR7 play important roles in the immunomodulatory function of MSCs by regulating their paracrine actions.
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Linfócitos B Reguladores/metabolismo , Quimiocina CXCL12/metabolismo , Células-Tronco Mesenquimais/metabolismo , Receptores CXCR/metabolismo , Animais , Medula Óssea/metabolismo , Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Células Cultivadas , Técnicas de Cocultura , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/fisiologiaRESUMO
To reevaluate the association between the costimulatory molecule cytotoxic T lymphocyte-associated antigen4 (CTLA4) single nucleotide polymorphism (SNP) +49A/G and acute rejection (AR) in renal transplantation, nine studies published before June 2013 were analyzed. Meta-analysis and cumulative meta-analysis (metacum) were performed for each genotype in a random/fixed effect model. The combined odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the strength of the association. In the sensitivity analysis, a single study involved in the meta-analysis was deleted each time to investigate the influence of the individual data sets on the pooled ORs. Meta-analysis regression was used for some influence factors, such as year of publication, total number in each group (AR group and control group), ethnicity, the ratio of GG to GA + AA, the ratio of G to A in CTLA4 +49A/G. Overall, a significant correlation was noted between the CTLA4 SNP (+49A/G) and the risk of AR (for GG vs. AG + AA: OR = 1.35, 95% CI = 1.05-1.73, p = 0.02; for G vs. A: OR = 1.21, 95% CI = 1.03-1.42, p = 0.02), especially in the Asian subgroup (for GG vs. AG + AA: OR = 1.79, 95% CI = 1.15-2.78, p = 0.009; for G vs. A: OR = 1.47, 95% CI = 1.04-2.07, p = 0.03). Of the influence factors, the ratio of GG to GA+AA (p = 0.046) and the ratio of G to A (p = 0.017) were significant factors. In conclusion, our results suggest that CTLA4 +49A/G contribute to the risk of AR following renal transplantation.
Assuntos
Antígeno CTLA-4/genética , Rejeição de Enxerto/genética , Transplante de Rim/efeitos adversos , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: Accumulating evidence supports the hypothesis that HLA antibodies play an important role in early renal allograft injury. However, the effects of HLA antibodies on long-term graft survival are still poorly understood. In this study, we examined the impact of HLA antibodies on graft survival in long-term renal recipients with functional grafts for 10 years. MATERIAL AND METHODS: In this retrospective study, long-term renal recipients were defined as kidney transplant recipients who had normally functioning renal grafts (serum creatinine level <2.0 mg/dl) for 10 years. Posttransplant serum samples from a total of 92 long-term renal allograft recipients on cyclosporine-based triple maintenance drug therapy (121.6 ± 0.886 months) were screened for the specificities of anti-HLA antibodies. The results of HLA antibodies before the transplantation, assessed using the same test method, were compared with those after their transplantations. Moreover, these 92 patients who received cadaveric renal transplant between January 2000 and December 2002 were followed up for about 10 years (range 107-135 months). RESULTS: 27 patients had HLA-I antibodies and 16 patients had HLA-II antibodies before the transplantation, whereas 12 patients had HLA-I antibodies and 18 patients had HLA-II antibodies after the transplantation. Moreover, the types of HLA antibodies were different from those found before the transplantation. In these renal recipients with functioning renal grafts, the estimated glomerular filtration rate was 66.52 ± 14.52 ml/min/1.73 m(2) in the HLA antibody-positive group (n = 23) and 69.09 ± 25.54 ml/min/1.73 m(2) negative in the HLA antibody-negative group (n = 69, p > 0.05). Three patients (3.26%) (3 out of 92) had donor-specific anti-HLA antibodies (DSA). The frequency of DSA in this study was lower than that in the general Chinese Han renal recipient population. CONCLUSIONS: We find that all HLA antibodies in the long-term renal grafts are newly formed after the transplantation. The HLA antibody status has little impact on the renal graft function in the long-term renal recipients.
Assuntos
Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Antígenos HLA/imunologia , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim , Adulto , Idoso , China , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/sangue , Rejeição de Enxerto/fisiopatologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the long-term use of ciclosporin on kidney transplant recipients who survived more than 10 years. METHODS: We reviewed cadaveric kidney transplant patients who had survived 10 years or longer in this study. Patients were divided into five groups based on their ciclosporin concentration at one year: group 1 (> 250 ng/ml), group 2 (200-250 ng/ml), group 3 (150-200 ng/ml), group 4 100-150 ng/ml) and group 5 (< 100 ng/ml). Lab parameters were compared among these groups over time. RESULTS: There were no differences in lab parameters among the five groups. At five years, systolic blood pressures (SBP), TG, CH, DB, TB were significantly higher in groups 3, 4, and 5. Uric acid was also higher but albumin was lower in group 5 compared to those in all other groups. Prevalence of proteinuria in both groups 4 and 5 were lower. At 10 years, SBP in group 3 was lower while both uric acid and ALT in all groups were decreased. CONCLUSION: In patients who survived for more than 10 years after kidney transplantation, serum lipid levels were markedly elevated, indicating the increase of cardiovascular risk factors for patients, which might impact long-term survival benefit.
Assuntos
Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim , Corticosteroides/uso terapêutico , Adulto , Contagem de Células Sanguíneas , Análise Química do Sangue , Ciclosporina/efeitos adversos , Feminino , Seguimentos , Humanos , Rim/fisiologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Electric machines emulators (EMEs) based on hardware-in-the-loop (HIL), which effectively act as emulators to mimic the actual motor behavior of Interior Permanent Magnet (IPM) machines. EME is frequently used to evaluate motor controller and motor control methodologies prior to development. The inverse magnetization motor model, which is used as the basis for real-time simulation in this paper's proposal for an electric machine emulator system based on HIL, uses FEA to create the motor model data. The nonlinear features of the motor may be successfully replicated with this motor model, and the accuracy of the electric machine emulator can be enhanced by using a straightforward and trustworthy motor controller. The real-time simulation tool typhoon HIL is used in the study to develop a hardware-in-the-loop simulation platform for an IPM electric machines emulator.