RESUMEN
Wound healing is a complicated obstacle, especially for chronic wounds. Mesenchymal stem cell-derived exosomes may be a promising cell-free approach for treating skin wound healing. Exosomes can accelerate wound healing by attenuating inflammation, promoting angiogenesis, cell proliferation, extracellular matrix production and remodeling. However, many issues, such as off-target effects and high degradation of exosomes in wound sites need to be addressed before applying into clinical therapy. Therefore, the bioengineering technology has been introduced to modify exosomes with greater stability and specific therapeutic property. To prolong the function time and the local concentration of exosomes in the wound bed, the use of biomaterials to load exosomes emerges as a promising strategy. In this review, we summarize the biogenesis and characteristics of exosomes, the role of exosomes in wound healing, and the therapeutic applications of modified-exosomes in wound healing. The challenges and prospects of exosomes in wound healing are also discussed.
RESUMEN
Our previous research found that fecal microbiota transplantation (FMT) and inulin synergistically affected the intestinal barrier and immune system function in chicks. However, does it promote the early immunity of the poultry gut-associated lymphoid tissue (GALT)? How does it regulate the immunity? We evaluated immune-related indicators in the serum, cecal tonsil, and intestine to determine whether FMT synergistic inulin had a stronger impact on gut health and which gene expression regulation was affected. The results showed that FMT synergistic inulin increased TGF-ß secretion and intestinal goblet cell number and MUC2 expression on day 14. Expression of BAFFR, PAX5, CXCL12, and IL-2 on day 7 and expression of CXCR4 and IL-2 on day 14 in the cecal tonsils significantly increased. The transcriptome indicated that CD28 and CTLA4 were important regulatory factors in intestinal immunity. Correlation analysis showed that differential genes were related to the immunity and development of the gut and cecal tonsil. FMT synergistic inulin promoted the development of GALT, which improved the early-stage immunity of the intestine by regulating CD28 and CTLA4. This provided new measures for replacing antibiotic use and reducing the use of therapeutic drugs while laying a technical foundation for achieving anti-antibiotic production of poultry products.
Asunto(s)
Pollos , Trasplante de Microbiota Fecal , Inulina , Animales , Inulina/farmacología , Pollos/microbiología , Pollos/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Intestinos/inmunología , Intestinos/microbiología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Ciego/microbiologíaRESUMEN
The late stage of embryo development is a crucial period of metabolic changes, with rapid organ development requiring a substantial supply of nutrients. During this phase, maternal nutritional levels play a vital role in the growth, development, and metabolism of the offspring. In this study, we added 2 doses of ß-carotene (ßc) (120 mg/kg and 240 mg/kg) to the daily diet of Hailan Brown laying hens to investigate the impact of maternal nutritional enrichment on embryo development. Maternal nutrition supplementation significantly increased the expression of chicken embryo liver index, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF) in serum. At the same time, the expression of GH/growth hormone receptor (GHR), IGF-1 mRNA, and Proliferating Cell Nuclear Antigen (PCNA) protein in the liver was upregulated, indicating that maternal nutrition intervention may promote chicken embryo liver development through the GH-IGF-1 axis. Transcriptome sequencing results showed that differential genes in liver after maternal nutritional supplementation with ß-carotene were enriched in pathways related to cell proliferation and metabolism. Consequently, we postulated that maternal ß-carotene supplementation might operate via the GH-IGF-1 axis to regulate the expression of genes involved in growth and development, thereby promoting liver development. These results contribute to formulating more effective poultry feeding strategies to promote offspring growth and development.
Asunto(s)
Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Pollos , Dieta , Suplementos Dietéticos , Desarrollo Embrionario , Hormona del Crecimiento , Animales , Pollos/crecimiento & desarrollo , Suplementos Dietéticos/análisis , Femenino , Alimentación Animal/análisis , Dieta/veterinaria , Hormona del Crecimiento/metabolismo , Embrión de Pollo , Desarrollo Embrionario/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , beta Caroteno/administración & dosificación , beta Caroteno/farmacología , Fenómenos Fisiologicos Nutricionales Maternos , Péptidos Similares a la InsulinaRESUMEN
This experiment was conducted to evaluate the growth performance, growth regulating factors, and liver morphology of chicks hatched from egg-laying breeding hens dietary supplemented with additives (ß-carotene). Hy-line breeding hens were allocated into three groups with three replicates/group. The dietary treatments were as follows: basal diet as a control (Con), basal diet supplemented with 120 (ßc-L) or 240 (ßc-H) mg/kg of ß-carotene diet. After 6 weeks, the eggs were collected and incubated. The hatched chicks were fed the same diet. The results showed that chicks in the ßc-L group increased in body weight at 21 days (p < 0.01). At 42 days, chicks in the ßc-H group showed a significant increase in tibia length (p < 0.05). The liver index increased in the ßc-L and ßc-H groups at 7 days (p < 0.05). Serum HGF (7, 14, 21, and 42 days) and leptin (14 days) were significantly increased in the group supplemented with ßc. Hepatic GHR (14 days), IGF-1R (14 days), and LEPR (21 days) mRNA expression were significantly increased. In addition, there was an increase in PCNA-positive cells in the liver of chicks in the ßc group. In conclusion, the addition of ß-carotene to the diet of laying breeder hens was more advantageous in terms of growth performance and liver development of the offspring.
Asunto(s)
Pollos , beta Caroteno , Animales , Femenino , Pollos/genética , beta Caroteno/farmacología , beta Caroteno/metabolismo , Dieta/veterinaria , Suplementos Dietéticos , Alimentación Animal/análisis , HígadoRESUMEN
BACKGROUND: Nutrition drives immunity and health in animals, and maternal immunity benefits offspring. In our previous study, a nutritional intervention strategy was found to promote the immunity of hens, which subsequently improved immunity and growth in offspring chicks. Maternal effects clearly exist, but how are mothers' immune advantages transferred to their offspring, and how do they benefit them? RESULTS: Here, we traced the beneficial effects back to the process of egg formation in the reproductive system, and we focused on the embryonic intestinal transcriptome and development, as well as on maternal microbial transfer in offspring. We found that maternal nutritional intervention benefits maternal immunity, egg hatching, and offspring growth. The results of protein and gene quantitative assays showed that the transfer of immune factors into egg whites and yolks depends on maternal levels. Histological observations indicated that the promotion of offspring intestinal development begins in the embryonic period. Microbiota analyses suggested that maternal microbes transfer to the embryonic gut from the magnum to the egg white. Transcriptome analyses revealed that offspring embryonic intestinal transcriptome shifts are related to development and immunity. Moreover, correlation analyses showed that the embryonic gut microbiota is correlated with the intestinal transcriptome and development. CONCLUSIONS: This study suggests that maternal immunity positively influences offspring intestinal immunity establishment and intestinal development beginning in the embryonic period. Adaptive maternal effects might be accomplished via the transfer of relatively large amounts of maternal immune factors and by shaping of the reproductive system microbiota by strong maternal immunity. Moreover, reproductive system microbes may be useful resources for the promotion of animal health. Video Abstract.
Asunto(s)
Pollos , Microbioma Gastrointestinal , Animales , Femenino , Humanos , Herencia Materna , Desarrollo Infantil , Perfilación de la Expresión GénicaRESUMEN
Convolutional Neural Network (CNN) plays a vital role in the development of computer vision applications. The depth neural network composed of U-shaped structures and jump connections is widely used in various medical image tasks. Recently, based on the self-attention mechanism, the Transformer structure has made great progress and tends to replace CNN, and it has great advantages in understanding global information. In this paper, the ConvWin Transformer structure is proposed, which refers to the W-MSA structure in Swin and combines with the convolution. It can not only accelerate the convergence speed, but also enrich the information exchange between patches and improve the understanding of local information. Then, it is integrated with UNet, a U-shaped architecture commonly used in medical image segmentation, to form a structure called ConvWin-UNet. Meanwhile, this paper improves the patch expanding layer to perform the upsampling operation. The experimental results on the Hubmap datasets and synapse multi-organ segmentation dataset indicate that the proposed ConvWin-UNet structure achieves excellent results. Partial code and models of this work are available at https://github.com/xmFeng-hdu/ConvWin-UNet.
Asunto(s)
Suministros de Energía Eléctrica , Redes Neurales de la Computación , Sinapsis , Procesamiento de Imagen Asistido por ComputadorRESUMEN
OBJECTIVES: This study aims to explore the status quo of health literacy and quality of life in elderly patients with chronic periodontitis and determine their correlation to understand the influencing factors of health literacy and quality of life. METHODS: A total of 150 elderly patients with chronic periodontitis were investigated using the general information questionnaire, Oral Health Literacy-Adult Questionnaire, and Oral Health Impact Profile for Chronic Periodontitis. RESULTS: The total scores of health literacy and quality of life of elderly patients with chronic periodontitis were 6.59±4.11 and 29.25±9.42, respectively. The total score of health literacy was negatively correlated with the total score of quality of life (r=-0.234, P<0.01). Regression analysis showed that age, place of residence, education level, and disease understanding were the influencing factors of health literacy. Family history, smoking, and education level were the influencing factors of quality of life. CONCLUSIONS: The health literacy level of elderly patients with chronic periodontitis is insufficient, and their quality of life needs to be improved. Improving the health literacy of patients is an effective way to improve their quality of life. Nursing staff must formulate corresponding health education strategies to improve the health literacy of patients and improve their quality of life.
Asunto(s)
Periodontitis Crónica , Alfabetización en Salud , Adulto , Humanos , Anciano , Calidad de Vida , Salud Bucal , Encuestas y CuestionariosRESUMEN
Ankylosing spondylitis (AS) is a refractory autoimmune disease, whose typical pathology is the development of inflammation to ossification and ankylosis. Histone deacetylase 1 (HDAC1) is considered to be a key factor involved in inflammatory gene transduction, but its role in AS remains unclear. The purpose of this study was to explore the role and possible mechanism of HDAC1 in AS based on the Wnt-Smad pathway. Fibroblasts were isolated from hip synovial tissues of AS patients, adeno-associated virus (AAV) was used to regulate the expression of HDAC1, DKK-1 and SIS3 was used to inhibit Wnt and Smad, respectively. The expressions of Wnt-Smad pathway-related proteins were analyzed by WB, and the TRP ion channel proteins were analyzed by immunofluorescence and WB. The proliferation of AS fibroblasts was detected by CCK-8, the expression of inflammatory cytokines was detected by ELISA, and the effects of HDAC1 on osteogenic differentiation of AS fibroblasts were investigated by alkaline phosphatase (ALP) activity, intracellular calcium concentration, mineralization and osteogenic proteins expressions. Results showed that HDAC1 significantly affected the protein expressions of the Wnt-Smad pathway in AS fibroblasts, and Wnt inhibitor DKK-1 and Smad3 inhibitor SIS3 could significantly reverse the effect of HDAC1 on the Wnt-Smad pathway. In addition, HDAC1 significantly activated the TRP ion channel and promoted the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts. DKK-1 or SIS3 treatment significantly inhibit the effect of HDAC-1 on AS fibroblasts, suggesting that the Wnt-Smad pathway is involved in the regulation of AS by HDAC1. In conclusion, HDAC1 promotes the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts through the Wnt-Smad pathway.
Asunto(s)
Histona Desacetilasa 1 , Proteínas Smad , Espondilitis Anquilosante , Vía de Señalización Wnt , Fibroblastos , Histona Desacetilasa 1/genética , Histona Desacetilasa 1/metabolismo , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Osteogénesis , Proteínas Smad/genética , Proteínas Smad/metabolismo , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/metabolismo , Espondilitis Anquilosante/patologíaRESUMEN
This study aimed to reveal the cross association of the Wnt-Smad pathway in AS fibroblasts. Fibroblasts from hip synovial tissue were isolated, and the expressions of Wnt and Smad pathway proteins were detected by western blot analysis. DKK-1 and SIS3 were used to inhibit Wnt and Smad, respectively. The proliferation and apoptosis of AS fibroblasts were detected by CCK-8 and flow cytometry, respectively. And the effects of DKK-1 and/or SIS3 on osteogenic differentiation of AS fibroblasts were investigated by alkaline phosphatase (ALP) activity, intracellular calcium concentration, mineralization and osteogenic proteins expressions. Results showed that AS fibroblasts had stronger osteogenic differentiation ability, accompanied by activation of Wnt and Smad pathways. In AS fibroblasts, inhibition of Wnt by DKK-1 could affect the Smad pathway, while inhibition of Smad by SIS3 affect the Wnt pathway, DKK-1 and SIS3 showed a synergistic effect on the regulation of Wnt and Smad. In addition, DKK-1 and SIS3 also showed synergistic positive effects in inhibiting the proliferation and osteogenic differentiation of AS fibroblasts. In conclusion, there was an interaction between Wnt and Smad pathways in AS fibroblasts. DKK-1 and SIS3 can synergistically and negatively regulate the osteogenic differentiation of AS fibroblasts, showing positive effects on AS.
Asunto(s)
Osteogénesis , Espondilitis Anquilosante , Diferenciación Celular , Células Cultivadas , Fibroblastos/metabolismo , Humanos , Proteínas Smad/metabolismo , Espondilitis Anquilosante/metabolismo , Vía de Señalización WntRESUMEN
AIM: The aim of this study is to evaluate the association between Klebsiella pneumoniae infection and ankylosing spondylitis (AS). METHOD: Five electronic databases, PubMed, Embase, Medline, Web of Science, and Scopes, were searched until September 29, 2021. Cohort and case-control studies that assessed the association between K. pneumoniae infection and AS were included. Pooled odds ratio (OR) was selected to show the effect size. Subgroup analysis (active or inactive AS) and 2 forms of sensitivity analysis were conducted. All statistical analyses were conducted by using STATA 12.0. RESULTS: There were 25 case-control studies finally included, including 8 studies concerning presence of K. pneumoniae in feces, and 17 studies concerning serum antibody (immunoglobulin [Ig]G, IgM, IgA) against K. pneumoniae. The results suggested that when compared with healthy people, presence of K. pneumoniae in feces was associated with AS (OR: 5.65; 95% CI: 1.68-19.00). Similarly, when compared with healthy people, higher positive rates of IgA (OR: 6.28; 95% CI: 3.32-11.91) and IgG (OR: 5.22; 95% CI: 1.36-19.99) were observed. Subgroup analyses suggested that association between K. pneumoniae and AS appears stronger in active AS. CONCLUSION: When compared with healthy people, a significantly higher positive rate of K. pneumoniae in feces, serum IgA and IgG were observed in patients with AS, suggesting that K. pneumoniae probably plays a crucial role in the occurrence of AS. The findings in this study need further prospective investigations for confirmation.
Asunto(s)
Klebsiella pneumoniae , Espondilitis Anquilosante , Anticuerpos Antibacterianos/análisis , Humanos , Inmunoglobulina A , Inmunoglobulina G , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/epidemiologíaRESUMEN
BACKGROUND: Osteosarcoma is a multiple malignant tumor in adolescents. MicroRNAs (MiRNAs) have been found to express abnormally in OS tissues and are considered as potential targets for OS prognosis and treatment. METHODS: MiR-96-5p and SYK expression in clinical samples, osteoblast and OS cell lines were detected. The changes of cell proliferation, apoptosis, adhesion and metastasis of OS cells were detected by CCK-8, BrdU, caspase-3 activity and transwell assay. Dual luciferase report analysis and RNA pull-down were used to confirm binding relation of miR-96-5p and SYK. RESULTS: MiR-96-5p was increased in OS tissue and cells. Moreover, miR-96-5p inhibits proliferation, adhesion and migration of HOS and Saos-2 cells, and promotes cell apoptosis. SYK has been identified to be targeted by miR-96-5p. Overexpressed SYK inhibits the suppressive impact of miR-96-5 on OS cells. CONCLUSION: MiR-96-5p may function as an effective target in OS treatment.
Asunto(s)
Neoplasias Óseas/metabolismo , MicroARNs/metabolismo , Osteosarcoma/metabolismo , Quinasa Syk/metabolismo , Adolescente , Neoplasias Óseas/patología , Adhesión Celular , Proliferación Celular , Niño , Preescolar , Humanos , MicroARNs/genética , Osteosarcoma/patología , Quinasa Syk/genética , Células Tumorales CultivadasRESUMEN
PURPOSE: To analyze the correlation between immediate postoperative coronal imbalance and the matching degree of the correction rates of the main curve and compensatory curves in the surgical treatment of severe adult idiopathic scoliosis. METHODS: Patients were categorized into three types based on the preoperative coronal balance status (type A = balance, type B = shifted to cave side and type C = shifted to convex side), and each type was further divided into two subgroups based on the postoperative coronal balance status (balance and imbalance). Different coronal parameters before and after operations were calculated and compared. RESULTS: The rate of postoperative CIB was highest in type C patients (53.8%) and lowest in type A patients (31.5%). To avoid postoperative CIB, the value of the postoperative CRmain should fall within the range of 1.001 × CRcomp ± 2.84% in type A patients, 1.112 × CRcomp + 3.3% ± 5.02% in type B patients and 0.907 × CRcomp - 2.5% ± 4.38% in type C patients. CONCLUSION: Mismatch between the correction rates of the main curve and compensation curves is a critical cause of immediate postoperative CIB. The relatively equal correction of the main curve and compensatory curves is essential for type A patients to achieve postoperative coronal balance, while the correction rate of the main curve should be higher than the compensatory curves in type B patients and vice versa in type C patients. Three formulas for the three different types were developed to provide helpful guidance information for surgical planning.
Asunto(s)
Escoliosis , Fusión Vertebral , Adulto , Humanos , Vértebras Lumbares , Estudios Retrospectivos , Escoliosis/cirugía , Vértebras Torácicas , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the prevalence of brain MRI abnormalities in people with epilepsy in rural China and to compare it with that of individuals in the United Kingdom. METHODS: Brain MRI scans were obtained in people with epilepsy who participated in a rural community-based program in China between July 2010 and December 2012. Individual epileptogenic lesion types were reviewed and their associations with seizure control examined. The MRI findings were compared with 2 previous similar studies in the United Kingdom. RESULTS: Among the 597 individuals (58% male, median age 38 years) with MRI scans analyzed, 488 (82%) had active epilepsy. The MRI was abnormal in 389 individuals (65%), with potentially epileptogenic lesion in 224 (38%) and nonspecific abnormalities in 165 (28%), and 108 (18%) were potentially resectable. The potentially epileptogenic lesions were less frequently detected in children (<18 years old, 12 of 68, 18%) than in adults (212 of 529, 40%; p < 0.001). In people with potentially epileptogenic lesions, 67% (150 of 224) had failed ≥2 antiseizure medications. They had higher risk of uncontrolled epilepsy than those with normal MRI (risk ratio [RR] 1.25; p < 0.001) and those with nonspecific abnormality (RR 1.15; p = 0.002) after adjustment for age and sex. The diagnostic yield of MRI was similar to that reported in community- and hospital-based studies in the United Kingdom. CONCLUSIONS: More than one-third of people with chronic epilepsy in rural China have potentially epileptogenic lesions identifiable on brain MRI, with two-thirds fulfilling the definition of pharmacoresistance. These findings highlight the magnitude of the unmet needs for epilepsy surgery in China.
Asunto(s)
Encefalomalacia/epidemiología , Epilepsia/epidemiología , Gliosis/epidemiología , Malformaciones del Sistema Nervioso/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/epidemiología , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/epidemiología , Niño , Preescolar , China/epidemiología , Epilepsia Refractaria , Encefalomalacia/diagnóstico por imagen , Epilepsia/diagnóstico por imagen , Femenino , Gliosis/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Malformaciones del Sistema Nervioso/diagnóstico por imagen , Prevalencia , Población Rural , Esclerosis , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/patología , Reino Unido/epidemiología , Adulto JovenRESUMEN
PURPOSE: We evaluated the oral health and dental status of people with epilepsy, and their relationship to seizure frequency, in a community cohort in rural China. METHODS: A cross-sectional study of people with epilepsy was carried out in areas in Henan, Shanxi and Ningxia provinces of China. All participants underwent a specially designed "Oral health and Dental status Questionnaire". Univariate and multivariate analyses were used to explore the relationships between seizure frequency and oral health and dental status. RESULTS: A total of 875 people participated. Almost two thirds (65.8%) reported brushing their teeth at least once a day but 634 (73.0%) brushed their teeth for less than 3 min each time. Only 80 (9.1%) had visited a dental clinic in the previous year. Multivariate logistic regression analysis showed that having 1-4 seizures/month (OR 0.60, 95%CI 0.40-0.90) or >4 seizures/month (OR 0.38, 95%CI 0.22-0.66) was associated with decreased odds of brushing teeth at least once a day, and higher seizure frequency was associated with increased odds of dental injury due to seizures (OR 2.07, 95%CI 1.22-3.50 for <1 seizure/month; OR 2.12, 95%CI 1.25-3.58 for 1-4 seizures/month; OR 3.09, 95%CI 1.57-6.07 for >4 seizures/month). CONCLUSION: Seizure frequency was significantly associated with seizure-related dental injury, and with the lack of good oral health practice. Improvement in the oral health of people with epilepsy in resource-poor areas should be encouraged.
Asunto(s)
Epilepsia/epidemiología , Epilepsia/fisiopatología , Salud Bucal , Población Rural , Enfermedades Dentales/epidemiología , Adulto , China/epidemiología , Estudios de Cohortes , Estudios Transversales , Caries Dental , Ecosistema , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
OBJECTIVE: This study evaluated the relationship between blood concentration of phenobarbital (PB) and its efficacy as well as adverse events in people with epilepsy in rural China. METHODS: People with epilepsy being treated with PB monotherapy were recruited and followed up for averagely 2.5â¯years. Data of clinical characteristics were collected using a standardized questionnaire by face-to-face interviews both at baseline and follow-up. Plasma concentration of PB was detected by the high-performance liquid chromatography. RESULTS: Data on treatment response and PB blood concentration was obtained from 225 subjects. Among them, 119 (52.9%) were recognized as effective cases and 106 (47.1%) as ineffective cases. In the effective group, the blood concentration of 95% subjects ranged from 1.22⯵g/ml to 41.36⯵g/ml with a median at 13.18⯵g/ml (IQRâ¯=â¯8.32-20.19⯵g/ml). The PB concentration of 95% of the subjects in the ineffective group ranged from 2.73⯵g/ml to 70.16⯵g/ml with a median at 19.80⯵g/ml (IQRâ¯=â¯11.30-30.40⯵g/ml), which was significantly higher than that of the effective group (pâ¯<â¯0.001). Multivariate logistic regression analysis showed that PB concentration ≥26.38⯵g/ml was related to a 4.5-fold (95% confidence interval [CI], 1.85-11.08) higher risk of inefficacy. A receiver operation characteristic curve was performed to determine the cutoff value of concentration for PB efficacy at 19.02⯵g/ml. SIGNIFICANCE: Blood concentration may be an important indicator for clinical decision making when PB monotherapy cannot achieve a good efficacy and more attention should be paid on it in clinical practice especially in resource-poor settings.
Asunto(s)
Anticonvulsivantes/sangre , Epilepsia/sangre , Epilepsia/tratamiento farmacológico , Fenobarbital/sangre , Población Rural , Adulto , Anticonvulsivantes/uso terapéutico , China/epidemiología , Epilepsia/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Fenobarbital/uso terapéutico , Estudios Prospectivos , Población Rural/tendencias , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the correlation of tumor necrosis factor α (TNF-α) polymorphisms with upper gastrointestinal bleeding (UGIB) induced by enteric-coated aspirin in coronary heart disease (CHD) patients. METHODS: In total, 154 CHD patients taking enteric-coated aspirin were enrolled in this study. Patients were divided into the UGIB group (n = 57) and non-UGIB group (n = 97) based on the presence or absence of signs of UGIB, respectively. TNF-α polymorphism (-857C > T, -863C > A, and -1031T > C) genotyping was performed using polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP). RESULTS: Patients who had the CC genotype and C allele of -1031T > C exhibited a significantly increase risk of UGIB after receiving enteric-coated aspirin (CC vs. TT: odds (OR) (95% confidence interval (CI)): 7.568 (1.527-37.49), P = 0.005; C vs. T: OR (95% CI): 1.852 (1.036-3.312), P = 0.036). Patients who had CA and CA + AA genotypes and the A allele of -863C > A also exhibited an increased risk of aspirin-induced UGIB (CA vs. CC: OR (95% CI): 2.415 (1.143-5.101), P = 0.019: CA + AA vs. CC: OR (95% CI): 2.218 (1.123-4.381), P = 0.021; A vs. C: OR (95% CI): 1.788 (1.039-3.078), P = 0.035). However, the TNF-α -857 C > T polymorphism was unrelated to the induction of UGIB by enteric-coated aspirin in CHD patients (P > 0.05). In addition, the haplotypes of CCC (-1031T > C, -863C > A, and -857C > T) markedly reduced the risk of aspirin-induced UGIB in CHD patients. CONCLUSION: TNF-α -863A and -1031C increased the risk of UGIB induction by enteric-coated aspirin in CHD patients, whereas TNF-α -857C > T was not correlated with the UGIB risk.
Asunto(s)
Aspirina/efectos adversos , Enfermedad Coronaria/tratamiento farmacológico , Hemorragia Gastrointestinal/inducido químicamente , Factor de Necrosis Tumoral alfa/genética , Anciano , Alelos , Aspirina/uso terapéutico , Femenino , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To investigate the molecular mechanism underlying inflammation-related ectopic new bone formation in ankylosing spondylitis (AS). METHODS: Spinal tissues and sera were collected from patients with AS and healthy volunteers and examined for the expression of Wnt proteins. An in vitro cell culture system mimicking the local inflammatory microenvironment of bone-forming sites was established to study the relationship between inflammation and Wnt expression, the regulatory mechanism of inflammation-induced Wnt expression, and the role of Wnt signaling in new bone formation. Modified collagen-induced arthritis (CIA) and proteoglycan-induced spondylitis (PGIS) animal models were used to confirm the key findings in vivo. RESULTS: The levels of osteoinductive Wnt proteins were increased in sera and spinal ligament tissues from patients with AS. Constitutive low-intensity tumor necrosis factor (TNF) stimulation, but not short-term or high-intensity TNF stimulation, induced persistent expression of osteoinductive Wnt proteins and subsequent bone formation through NF-κB (p65) and JNK/activator protein 1 (c-Jun) signaling pathways. Furthermore, inhibition of either the Wnt/ß-catenin or Wnt/protein kinase Cδ (PKCδ) pathway significantly suppressed new bone formation. The increased expression of Wnt proteins was confirmed in both the modified CIA and PGIS models. A kyphotic and ankylosing phenotype of the spine was seen during long-term observation in the modified CIA model. Inhibition of either the Wnt/ß-catenin or Wnt/PKCδ signaling pathway significantly reduced the incidence and severity of this phenotype. CONCLUSION: Inflammation intensity-dependent expression of osteoinductive Wnt proteins is a key link between inflammation and ectopic new bone formation in AS. Activation of both the canonical Wnt/ß-catenin and noncanonical Wnt/PKCδ pathways is required for inflammation-induced new bone formation.
Asunto(s)
Inflamación/metabolismo , Osteogénesis/fisiología , Espondilitis Anquilosante/metabolismo , Proteínas Wnt/fisiología , Vía de Señalización Wnt/fisiología , Animales , Humanos , Proteoglicanos/metabolismo , Columna Vertebral/metabolismo , Espondilitis Anquilosante/inducido químicamente , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , beta Catenina/metabolismoRESUMEN
OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is associated with the high premature mortality observed among people with epilepsy. It is, however, considered a rare event in China, probably because of lack of awareness and limitation of studies in the country. We aimed to provide some initial estimation of the burden of SUDEP in China. METHODS: We established a large Chinese community-based cohort of people with epilepsy between January 2010 and December 2011. For any participant who died during follow-up, detailed information on cause of death was obtained using a specifically designed Verbal Autopsy Questionnaire. All cases were reviewed by a multidisciplinary expert panel and reinvestigated if necessary. Sudden unexpected death in epilepsy incidence rates were estimated and case details provided. RESULTS: The cohort consisted of 1562 people and during a median 5years follow-up, 72 deaths were reported. The all-causes death incidence was 11.23 (95% CI 8.86-14.07) per 1000 person-years. Fifteen died suddenly and unexpectedly in a reasonable state of health in the week preceding death. We recorded detailed information of these 15 deaths. Thirteen were considered to be probable SUDEP and two possible SUDEP. The incidence of probable SUDEP was 2.03 (95% CI 1.13-3.38) per 1000 person-years, and the incidence of all suspected (probable and possible) SUDEP was 2.34 (95% CI 1.36-3.77) per 1000 person-years. SIGNIFICANCE: The incidence of SUDEP was relatively high among Chinese people with epilepsy when compared with that in previous community-based studies from high-income countries. The burden of SUDEP in China requires further assessments.
Asunto(s)
Pueblo Asiatico , Muerte Súbita/epidemiología , Epilepsia/mortalidad , Mortalidad Prematura , Adolescente , Adulto , Anciano , China/epidemiología , Estudios de Cohortes , Muerte Súbita/etiología , Epilepsia/complicaciones , Epilepsia/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
STUDY DESIGN: A retrospective and radiological study of degenerative spinal diseases. OBJECTIVE: To explore the changes in spinopelvic sagittal alignment after lumbar instrumentation and fusion of degenerative spinal diseases. SUMMARY OF BACKGROUND DATA: Efforts have been paid to clarify the ideal postoperative sagittal profile for degenerative spinal diseases. However, little has been published about the actual changes of sagittal alignment after lumbar lordosis reconstruction. METHODS: Radiographical analysis of 83 patients with spinal degeneration was performed by measuring sagittal parameters before and after operations. Comparative studies of sagittal parameters between short (1 level) and long (≥ 2 level) instrumentation and fusion were performed. Different variances (Δ) of these sagittal parameters before and after operations were calculated and compared. Correlative study and linear regression were performed to establish the relationship between variances. RESULTS: No significant changes were shown in the short-fusion group postoperatively. In the long-fusion group, postoperative lumbar lordosis (LL) and sacral slope (SS) were significantly increased; pelvic tilt (PT), sagittal vertical axis (SVA), pelvic incidence minus lumbar lordosis, and PT/SS were significantly decreased. Different variances of ΔLL, ΔSS, ΔPT, ΔSVA, Δ(pelvic incidence - LL), and ΔPT/SS were significantly greater in the long-fusion group than the short-fusion group. Close correlations were mainly shown among ΔLL, ΔPT, and ΔSVA. Linear regression equations could be developed (ΔPT = -0.185 × ΔLL - 7.299 and ΔSVA = -0.152ΔLL - 1.145). CONCLUSION: In degenerative spinal diseases, long instrumentation and fusion (≥ 2 levels) provides more efficient LL reconstruction. PT, SS, and SVA improve corresponding to LL in a linear regression model. Linear regression equations could be developed and used to predict PT and SVA change after long instrumentation and fusion for LL reconstruction.