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BACKGROUND: Progressive axon degeneration is a common pathological feature of neurodegenerative diseases. Cdc42 is a member of the Rho GTPase family that participates in axonogenesis. GSK-3ß is a serine/threonine kinase highly implicated in neuronal development and neurodegeneration. This study aimed to examine whether cdc42 promotes axonogenesis by regulating GSK-3ß activity. METHODS: Hippocampal neurons were isolated from neonatal Sprague-Dawley rats and transfected with designated plasmid vectors to alter the activities of cdc42 and GSK-3ß. LiCl treatment was used to inhibit the GSK-3ß activity in primary neurons. GSK-3ß activity was determined by an enzyme activity assay kit. Immunofluorescence staining was used to detect axons stained with anti-Tau-1 antibody and dendrites stained with anti-MAP2 antibody. RESULTS: Transfection with an active cdc42 mutant (cdc42F28L) decreased the activity of GSK-3ß and induced axonogenesis in primary rat hippocampal neurons, while transfection with a negative cdc42 mutant (cdc42N17) resulted an opposite effect. Moreover, transfection with plasmid vectors carrying wild-type GSK-3ß or a constitutively active GSK3ß mutant (GSK-3ß S9A) increased the activity of GSK-3ß and attenuated axonogenesis of primary hippocampal neurons with excessive cdc42 activity, whereas inhibition of GSK-3ß by LiCl abolished the inhibitory effect of the negative cdc42 mutant on axonogenesis. CONCLUSIONS: This study suggests that cdc42 induces axonogenesis of primary rat hippocampal neurons via inhibiting GSK-3ß activity. These findings support further investigation into the mechanisms of cdc42/GSK-3ß-mediated axonogenesis.
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Hipocampo , Neuronas , Proteína de Unión al GTP cdc42 , Animales , Glucógeno Sintasa Quinasa 3 beta , Hipocampo/citología , Neuronas/fisiología , Fosforilación , Proteínas Serina-Treonina Quinasas , Ratas , Ratas Sprague-Dawley , Serina/farmacología , Proteína de Unión al GTP cdc42/fisiologíaRESUMEN
Background: Ascites is a common clinical finding caused by many different diseases, so we developed a technique termed single orifice percutaneous endoscopic surgery (SOPES) which can access peritoneal cavity through the contralateral McBurney's point or umbilicus to seek the underlying causes. In this study, we describe the initial clinical experience of SOPES and compare the application of two accesses. Methods: This is a retrospective study performed between 2007 and 2018. Patients with ascites of unknown origin who underwent these two kinds of SOPES were included. Main outcomes were measured by diagnostic accuracy, complication rate, procedure time, time till stitches removal, length of hospital stay, and hospital cost. Results: 148 patients successfully undergone SOPES via the contralateral McBurney's point (IM group, n = 70) or the umbilicus (UM group, n = 78). 63 patients in the IM group and 71 patients in the UM group reached clear diagnosis (90.0% vs. 91.0%, p = 0.831). The overall complication rate was 5.4%, while the UM group was higher than the IM group (10.3% vs. 0%, p = 0.017). All complications were resolved after medical treatment, and no mortality resulted from this procedure. The procedure time and the time until stitches removal in the UM group were longer than that in the IM group. There were no significant differences in length of hospital stay and hospital cost between the two groups. Conclusions: SOPES, which combines the strength of minimally invasive single orifice incision and flexible angles of examination and instrumentation, is a newly developed flexible endoscopic surgical modality that provides new important clinical valuable in evaluation of ascites of unknown origin. Moreover, SOPES via the contralateral McBurney's point was safer than the umbilicus approach.
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SARS-CoV-2 infection causes a wide spectrum of clinical manifestations in humans, and olfactory dysfunction is one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism by which SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein, we demonstrate that intranasal inoculation with SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not the olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 (hACE2) mice. The sustentacular cells and Bowman's gland cells in the OE were identified as the major target cells of SARS-CoV-2 before invasion into olfactory sensory neurons (OSNs). Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration and directly impairs the uniformity of the OE structure. Combined transcriptomic and quantitative proteomic analyses revealed the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates olfactory dysfunction in COVID-19 patients and provides critical clues for understanding the physiological basis for extrapulmonary manifestations of COVID-19.
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Background US has proven valuable in the diagnosis of subpleural pulmonary lesions (SPLs); however, existing US indicators have limitations. Purpose To propose and validate a revised contrast-enhanced (CE) US indicator for differential diagnosis of benign and malignant SPLs and to compare its performance with existing CE US diagnostic criteria. Materials and Methods This prospective study (Chinese clinical trial registry, ChiCTR1800019828) enrolled patients with SPLs between May 2019 and August 2020. They were divided into a developmental cohort (DC) and a validation cohort (VC). In the DC, the optimal indicator was selected from five CE US indicators. In the VC, the selected indicator was compared with existing CE US diagnostic criteria using the area under the receiver operating characteristic curve (AUC). Pathologic analysis, microbial evidence, and clinical follow-up were used as reference standards for all SPLs. Results A total of 902 participants (DC, 424 participants; VC, 478 participants) with SPLs (mean age, 56 years ± 17; 593 men) were evaluated. The arrival time (AT) difference ratio proved to be the optimal indicator to distinguish benign from malignant SPLs. In the overall (regardless of lesion size), large (vertical diameter >3 cm), and small (vertical diameter ≤3 cm) lesion groups, the cutoff values of the AT difference ratio were 43%, 42%, and 50% and the AUCs obtained from the VC were 0.91 (95% CI: 0.88, 0.93), 0.97 (95% CI: 0.94, 0.98), and 0.77 (95% CI: 0.71, 0.83) respectively, which were higher than those of lesion-lung AT difference greater than 2.5 seconds (0.81 [P < .001], 0.85 [P < .001], and 0.7 [P = .005], respectively), lesion AT greater than 7.5 seconds (0.65 [P < .001], 0.64 [P < .001], and 0.63 [P < .001], respectively), and lesion AT greater than 10 seconds (0.67 [P < .001], 0.68 [P < .001], and 0.64 [P < .001] respectively). Conclusion The US contrast agent arrival time difference ratio enables better differentiation of benign and malignant subpleural lesions when compared with existing diagnostic criteria. Online supplemental material is available for this article. Published under a CC BY 4.0 license.
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Medios de Contraste/farmacocinética , Aumento de la Imagen/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Ultrasonografía/métodos , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
OBJECTIVE: To develop and prospective validate an ultrasound (US) prediction model to differentiate between benign and malignant subpleural pulmonary lesions (SPLs). METHODS: This study was conducted retrospectively from July 2017 to December 2018 (development cohort [DC], n = 592) and prospectively from January to April 2019 (validation cohort [VC], n = 220). A total of 18 parameters of B-mode US and contrast-enhanced US (CEUS) were acquired. Based on the DC, a model was developed using binary logistic regression. Then its discrimination and calibration were verified internally in the DC and externally in the VC, and its diagnostic performance was compared with those of the existing US diagnostic criteria in the two cohorts. The reference criteria were from the comprehensive diagnosis of clinical-radiological-pathological made by two senior respiratory physicians. RESULTS: The model was eventually constructed with 6 parameters: the angle between lesion border and thoracic wall, basic intensity, lung-lesion arrival time difference, ratio of arrival time difference, vascular sign, and non-enhancing region type. In both internal and external validation, the model provided excellent discrimination of benign and malignant SPLs (C-statistic: 0.974 and 0.980 respectively), which is higher than that of "lesion-lung AT difference ≥ 2.5 s" (C-statistic: 0.842 and 0.777 respectively, P <0.001) and "AT ≥ 10 s" (C-statistic: 0.688 and 0.641 respectively, P <0.001) and the calibration curves of the model showed good agreement between actual and predictive malignancy probabilities. As for the diagnosis performance, the sensitivity and specificity of the model [sensitivity: 94.82% (DC) and 92.86% (VC); specificity: 92.42% (DC) and 92.59% (VC)] were higher than those of "lesion-lung AT difference ≥ 2.5 s" [sensitivity: 88.11% (DC) and 80.36% (VC); specificity: 80.30% (DC) and 75.00% (VC)] and "AT ≥ 10 s" [sensitivity: 64.94% (DC) and 61.61% (VC); specificity: 72.73% (DC) and 66.67% (VC)]. CONCLUSION: The prediction model integrating multiple parameters of B-mode US and CEUS can accurately predict the malignancy probability, so as to effectively differentiate between benign and malignant SPLs, and has better diagnostic performance than the existing US diagnostic criteria. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR1800019828.
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The establishment of polarity is an essential process in early neuronal development. Cdc42, a GTPase of the Rho family, is a key regulator of cytoskeletal dynamics and neuronal polarity. However, the mechanisms underlying the action of cdc42 in regulating axonogenesis have not been elucidated. Here, we expressed wild-type cdc42, a constitutively active cdc42 mutant (cdc42F28L) and a dominant negative cdc42 mutant (cdc42N17), respectively, in the primary hippocampal neurons to alter the activity of cdc42. We found that cdc42 activities were paralleled with the capacities to promote axonogenesis in the cultured neurons. Cdc42 also enhanced microtubule stability in the cultured neurons. Pharmacologically stabilizing microtubules significantly abrogated the defective axonogenesis induced by cdc42 inhibition. Moreover, cdc42 promoted the dephosphorylation of collapsing response mediator protein-2 (CRMP-2) at Thr514 by increasing GSK-3ß phosphorylation at Ser9 in the cultured neurons. These findings suggest that cdc42 may facilitate axonogenesis by promoting microtubule stabilization in rat primary hippocampal neurons.
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Axones/metabolismo , Hipocampo/metabolismo , Microtúbulos/metabolismo , Neuronas/metabolismo , Proteína de Unión al GTP cdc42/metabolismo , Animales , Axones/patología , Polaridad Celular/fisiología , Células Cultivadas , Dendritas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neurogénesis/fisiología , Fosforilación/fisiología , Ratas Sprague-DawleyRESUMEN
We aimed to explore the value of contrast-enhanced ultrasound (CEUS) of the pleural cavity in locating catheters and identifying fibrous septa and to compare CEUS with multiple existing methods. We included 304 participants whose pleural effusion could not continue to be drained and compared the catheter-localization capabilities of empirical diagnosis, B-mode ultrasound with normal saline and CEUS, with computed tomography as the reference standard. CEUS performed the best (accuracy, 100%; sensitivity, 100%; specificity, 100%), followed by B-mode ultrasound with normal saline (accuracy, 77.78%; sensitivity, 62.5%; specificity, 100%), and finally empirical diagnosis (accuracy, 54.17%; sensitivity, 66.67%; specificity, 33.33%). The capabilities of CEUS and computed tomography to identify fibrous septa were evaluated, with B-mode ultrasound as the reference, and CEUS (accuracy, 100%; sensitivity, 100%; specificity, 100%) was superior to computed tomography (accuracy, 82.41%; sensitivity, 26.09%; specificity, 97.65%). Overall, CEUS can accurately locate catheters and identify fibrous septa, with performance superior to existing methods.
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Medios de Contraste , Cavidad Pleural/diagnóstico por imagen , Adulto , Anciano , Catéteres , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ultrasonografía/métodosRESUMEN
OBJECTIVE: This study aimed to analyze the differential metabolites and their metabolic pathways from the serum of patients with hepatitis B cirrhosis, with two typical patterns of Gan Dan Shi Re (GDSR) and Gan Shen Yin Xu (GSYX) based on the theory of traditional Chinese medicine (TCM). It also investigated the variation in the internal material basis for the two types of patterns and provided an objective basis for classifying TCM patterns using metabolomic techniques. METHODS: The serum samples taken from 111 qualified patients (40 GDSR cases, 41 GSYX cases, and 30 Latent Pattern (LP) cases with no obvious pattern characters) and 60 healthy volunteers were tested to identify the differential substances relevant to hepatitis B cirrhosis and the two typical TCM patterns under the gas chromatography-time-of-flight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. RESULTS: After excluding the influence of LP groups, six common substances were found in GDSR and GSYX patterns, which were mainly involved in the metabolic pathways of glycine, serine, threonine, and phenylalanine. Eight specific metabolites involved in the metabolic pathways of linoleic, glycine, threonine, and serine existed in the two patterns. CONCLUSIONS: The data points on the metabolic spectrum were found to be well distributed among the differential substances between the two typical TCM patterns of patients with hepatitis B cirrhosis using metabolomic techniques. The differential expression of these substances between GDSR and GSYX patterns provided an important objective basis for the scientific nature of TCM pattern classification at the metabolic level.
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BACKGROUND: The study aimed to estimate the value of embryonal natural orifice transluminal endoscopic surgery (ENOTES) in treating severe acute pancreatitis (SAP) complicated with abdominal compartment syndrome (ACS). METHODS: The patients, who were randomized into an ENOTES group and an operative group, underwent ENOTES and laparotomy, respectively. The results and complications of the two groups were compared. RESULTS: Enterocinesia was observed earlier in the ENOTES group than in the operative group. Acute Physiology and Chronic Health Evaluation II (APACHE II) score of patients in the ENOTES group was lower than that of the operative group on the 1st, 3rd and 5th post-operative day (P<0.05). The cure rate was 96.87% in the ENOTES group, which was statistically different from 78.12% in the operative group (P<0.05). There were significant differences in complications and mortality between the two groups (P<0.01). CONCLUSION: Compared with surgical decompression, ENOTES associated with flexible endoscope therapy is an effective and minimal invasive procedure with less complications.
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@#BACKGROUND: The study aimed to estimate the value of embryonal natural orifice transluminal endoscopic surgery (ENOTES) in treating severe acute pancreatitis (SAP) complicated with abdominal compartment syndrome (ACS). METHODS: The patients, who were randomized into an ENOTES group and an operative group, underwent ENOTES and laparotomy, respectively. The results and complications of the two groups were compared. RESULTS: Enterocinesia was observed earlier in the ENOTES group than in the operative group. Acute Physiology and Chronic Health Evaluation II (APACHE II) score of patients in the ENOTES group was lower than that of the operative group on the 1st, 3rd and 5th post-operative day (P<0.05). The cure rate was 96.87% in the ENOTES group, which was statistically different from 78.12% in the operative group (P<0.05). There were significant differences in complications and mortality between the two groups (P<0.01). CONCLUSION: Compared with surgical decompression, ENOTES associated with flexible endoscope therapy is an effective and minimal invasive procedure with less complications.
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BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has been established in animal models and human studies. OBJECTIVE: The aim of this study was to assess the feasibility and efficacy of applying transgastric NOTES to diagnose patients with ascites of unknown origin. DESIGN: Prospective study. SETTING: Two university and teaching hospitals. PATIENTS: Patients with ascites of unknown origin. INTERVENTIONS: Diagnostic transgastric NOTES. MAIN OUTCOME MEASUREMENTS: Characteristic of ascites cases, conditions of the abdominal cavity, diagnostic accuracy, adverse events, and follow-up time. RESULTS: Transgastric NOTES was performed successfully in 78 patients with ascites of unknown origin, and 72 cases (92.3%) were clearly diagnosed. They included malignant tumors (39 cases), tuberculous peritonitis (28 cases), chronic hepatic inflammation (3 cases), necrotizing lymphadenitis (1 case), and eosinophilic serositis of the small intestine (1 case). In addition, there were 6 nondiagnostic cases, and no severe adverse events were found. LIMITATIONS: Nonrandomized control analysis. CONCLUSION: Transgastric NOTES in combination with biopsy can elucidate the causes of ascites of unknown origin in the majority of cases. Therefore, it is a feasible and effective approach to access the peritoneal cavity and also a valuable modality to detect the cause of diseases with ascites of unknown origin.
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Ascitis/diagnóstico , Hepatitis Crónica/diagnóstico , Cirugía Endoscópica por Orificios Naturales/métodos , Neoplasias/diagnóstico , Peritonitis Tuberculosa/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ascitis/etiología , Niño , Estudios Transversales , Estudios de Factibilidad , Femenino , Hepatitis Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Peritonitis Tuberculosa/complicaciones , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: To investigate the protective effect of Qihuang Mingmu capsule (QHMM) on retina of diabetic mice and its impact on VEGF expression. METHOD: Forty KK/Upj-Ay mice were randomly divided into the model group and high, middle and low dose QHMM (8.32, 4.16, 2.08 g x kg(-1)) groups. Additional 10 C57BL/6 mice were selected as the control group. Mice were orally administered for three months. Their general appearance, fasting blood-glucose (FBG) and glycosylated hemoglobin (HbA1c) were observed. Pathological changes of retina were observed by light microscope and electron microscope. The expressions of vascular endothelial growth factor (VEGF), growth factor receptors-1 (Flt-1) and growth factor receptors-2 (Flk-1) were examined by Real-time PCR (qPCR) and Western blot. RESULT: QHMM could ameliorate the symptoms of diabetic mice to varying degrees, decrease FBG and HbA1c, alleviate pathological lesions of retina and decrease the expressions of VEGF, Flt-1, Flk-1 mRNA and protein. CONCLUSION: QHMM has the protective effect on diabetic retinopathy of mice by inhibiting the expressions of VEGF, Flt-1 and Flk-1 and intervening VEGF-VEGFR signal transduction pathway.
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Retinopatía Diabética/prevención & control , Medicamentos Herbarios Chinos/administración & dosificación , Sustancias Protectoras/administración & dosificación , Enfermedades de la Retina/prevención & control , Factor A de Crecimiento Endotelial Vascular/genética , Animales , Cápsulas/administración & dosificación , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/genética , Retinopatía Diabética/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/genética , Enfermedades de la Retina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To evaluate the value of peritoneoscopy via natural orifice transluminal endoscopic surgery (NOTES) in the diagnosis of patients with peritoneal carcinomatosis. METHODS: A total of 32 patients with peritoneal carcinomatosis were diagnosed by histological examination of biopsies at our hospital from April 2007 to October 2010. Their data of clinical manifestations, gastroscopy, colonoscopy, abdominal ultrasonography, abdominal computed tomography, magnetic resonance imaging, ascitic cytology and transgastric peritoneoscopy via NOTES were analyzed retrospectively. RESULTS: Among them, gastrointestinal cancers were diagnosed by digestive endoscopy in 9 cases (28.1%). And ovarian lesions in 8 cases (25.0%), pancreatic cancer in 2 cases (6.3%), primary liver cancer in 2 cases (6.3%) and bile duct carcinoma in 1 case (3.1%) were suspected according to imaging examinations. No peritoneal carcinomatosis was found by digestive endoscopy or imaging examinations. Ascitic cytology was positive in 6 cases (18.8%). Peritoneal carcinomatosis was diagnosed by transgastric peritoneoscopy via NOTES with histological examination of biopsies in all patients. Their findings of transgastric peritoneoscopy via NOTES were divided into 5 types, i.e., mass type (n = 3, 9.4%), nodular type (n = 5, 15.6%), ulcerative type (n = 1, 3.1%), omentum-embracing type (n = 1, 3.1%) and mixture type (n = 22, 68.8%). CONCLUSION: Transgastric peritoneoscopy via NOTES with histological examination of biopsies has important value in the pathologic diagnosis and the endoscopic typing of peritoneal carcinomatosis.
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Laparoscopía/métodos , Neoplasias Peritoneales/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/diagnóstico , Neoplasias Peritoneales/secundario , Neoplasias Retroperitoneales/diagnóstico , Neoplasias Retroperitoneales/secundario , Estudios Retrospectivos , Adulto JovenRESUMEN
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) the etiology of which has not yet been fully clarified. Cytokine interleukin-10 (IL-10) plays a central role in downregulating inflammatory cascade in UC and is likely a candidate for therapeutic intervention. However, its intravenous administration is costly and inconvenient. Therefore, we established a novel IL-10 delivery system by transforming a hIL-10-containing plasmid into B. longum (BL-hIL-10) and investigated its effects on 5% dextran sulfate sodium (DSS)-induced ulcerative colitis in mice and the possible underlying mechanism. Our results show that (1) hIL-10 was expressed and secreted into the culture supernatant of BL-hIL-10 after L-arabinose induction in vitro as examined by Western blot, enzyme-linked immunosorbent assay (ELISA) and RT-PCR; (2) addition of BL-hIL-10 culture supernatant had no cytotoxic effect and morphological alteration, but significantly inhibited the enhancement of proinflammatory cytokines by lipopolysaccharide (LPS) in THP-1 cells; (3) oral administration of BL-hIL-10 alleviated colitis syndrome of the model mice, attenuated colitis-activated NF-κB pathway measured by DNA-binding assay and colitis-elevated expression of proinflammatory cytokines examined with CCK cytotoxic kits, and upregulated CD4+CD25+Foxp3+ Treg in blood and mesenteric lymph nodes measured by flow cytometry. In conclusion, BL-hIL-10 as a novel oral hIL-10 delivery system has been successfully established and oral administration of BL-hIL-10 alleviated inflammatory damage of colonic tissue in the model mice by blocking the colitis-activated NF-κB pathway and upregulating CD4+CD25+Foxp3+ Treg in blood and mesenteric lymph nodes in mice.
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Bifidobacterium/metabolismo , Colitis/tratamiento farmacológico , Sulfato de Dextran/toxicidad , Portadores de Fármacos , Interleucina-10/administración & dosificación , Interleucina-10/metabolismo , Administración Oral , Animales , Bifidobacterium/genética , Western Blotting , Colitis/inducido químicamente , Colitis/metabolismo , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos BALB C , Monocitos/efectos de los fármacos , Monocitos/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Peroxidasa/metabolismo , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismoRESUMEN
OBJECTIVE: To observe the changes of vascular endothelial functions and general neuro-endocrine-immunity (NEI) network under the state of qi-deficiency syndrome induced by excessive idleness and to approach their internal relevance and illuminate initially the pathophysiological mechanism of vascular lesion induced by excessive idleness. METHODS: A total of 100 male Wistar rats were randomly divided into the control group and the qi-deficiency syndrome model group, 50 rats in each group. The qi-deficiency syndrome model was established by feeding the animals with hyper-alimentation diet in combination with restricting movement for 10 weeks. Changes of common chemical signal molecules related to NEI and vascular endothelial functions were measured by the end of the experiment. Furthermore, their internal relevance was analyzed by the method of canonical correlation analysis. RESULTS: The vascular endothelial structure and function were obviously injured in the model group. Compared with the control group, the chemical signal molecules, such as 5-hydroxytryptamine (5-HT), corticosterone (CORT), triiodothyronine (T3), tetraiodothyronine (T4), angiotensin II (Ang II), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in peripheral blood of the model group (n=43) were changed significantly (P<0.05 or P<0.01). Canonical correlation analysis showed that vascular endothelial dysfunction was correlated to the changes of these signal molecules in the NEI network. CONCLUSIONS: Comfort-based lifestyle induced not only vascular endothelial dysfunction but also an imbalance of the NEI network. Vascular endothelial dysfunction and the imbalanced NEI network interacted with each other, and an imbalance of the NEI network may be the pathophysiologic basis for the genesis and development of vascular endothelial dysfunction, even diseases of the blood vessel.
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Enfermedades Cardiovasculares/etiología , Endotelio Vascular/fisiopatología , Sistema Inmunológico/fisiología , Neuroinmunomodulación/fisiología , Sistemas Neurosecretores/fisiología , Conducta Sedentaria , Animales , Aorta/metabolismo , Aorta/patología , Aorta/fisiopatología , Aorta/ultraestructura , Biomarcadores/análisis , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Enfermedades Cardiovasculares/fisiopatología , Modelos Animales de Enfermedad , Endotelinas/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Sistema Inmunológico/metabolismo , Sistema Inmunológico/patología , Masculino , Sistemas Neurosecretores/metabolismo , Sistemas Neurosecretores/patología , Óxido Nítrico/metabolismo , Qi , Ratas , Ratas Wistar , Síndrome , Deficiencia Yin/etiología , Deficiencia Yin/metabolismo , Deficiencia Yin/patología , Deficiencia Yin/fisiopatologíaRESUMEN
OBJECTIVE: To study the effects of Tongxinluo ultramicro-pulverization (TXLU) on experimental myocardial infarction and platelet aggregation of rats, investigate its mechanisms on ischemia heart disease and offer a reference to clinical usage. METHOD: Rats were separated randomly into 7 groups: sham, model, diltiazem (0.15 mg x kg(-1)), TXL(1.2 g x kg(-1)), TXLU (1.2, 0.6, 0.3 g x kg(-1)). The experimental myocardial infarction was induced with ligating the left anterior descending branch of the coronary of rats. The infarction size was determined after myocardium tissue was stained with 2,3,5-triphenyltetrazolium chloride (TTC). And the serum of rats was separated to analyze CK, LDH, SOD, MDA. Another 60 rats were separated randomly into 6 groups: control, aspirin (0.15 mg x kg(-1)), TXL (1.2 g x kg(-1)), TXLU (1.2 ,0.6,0.3 g x kg(-1)). The rat platelet aggregation was induced with adenosine diphosphate (ADP) and collagen to observe the inhibitory effects of TXLU. RESULT: TXLU could relieve the myocardial infarction size and weight stained with TTC significantly, the myocardial infarction size of the three groups of TXLU were (2.7 +/- 2.1)%, (3.4 +/- 1.2)%, (2.8 +/- 1.8)%, compared with model group (8.9 +/- 5.9)%, P < 0.05 or P < 0.01. The myocardial infarction weight of the three groups of TXLU were (8.4 +/- 3.5)%, (8.7 +/- 4.1)%, (9.7 +/- 4.1)%, compared with model group (l2.2 +/- 3.6)% P < 0.05 or P < 0. 01. And the content of MDA and the activities of CK and LDH in rats subjected with ligation of coronary artery were inhibited obviously too, compared with model group P < 0.05 or P < 0.01, then the activity of SOD increased. TXLU could inhibit the maximum percentage of rats platelet aggregation induced with ADP and collagen, the maximum percentage of platelet aggregation induced with ADP were (26.9 +/- 9.2)%, (24.4 +/- 13.4)%, (30.6 +/- 12.2)%, compared with control group (44.3 +/- 15. 7)% P < 0.05 or P < 0.01; The maximum percentage of platelet aggregation induced with collagen were (33.8 +/- 6.9)%, (32.1 +/- 8.3)%, (41.5 +/- 7.8)%, compared with control group (49.2 +/- 15.9)%, P < 0.05 or P < 0.01. CONCLUSION: The experiment results indicated that TXLU could protect myocardial tissue of rats from ischemic injury and the mechanism may be related with antioxidation and inhibiting platelet aggregation, and the results also suggested TXLU could lower clinical dosage.
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Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China/métodos , Infarto del Miocardio/tratamiento farmacológico , Adenosina Difosfato/farmacología , Animales , Aspirina/farmacología , Diltiazem/farmacología , Medicamentos Herbarios Chinos/farmacología , Femenino , Masculino , Infarto del Miocardio/sangre , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/patología , Agregación Plaquetaria/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Sales de Tetrazolio/farmacologíaRESUMEN
AIM: To explore the influence of DNA of bifidobacteriua adolescence on PKC and NK-kappaB of murine macrophages. METHODS: The fluorescent intensity of PKCalpha, PKCbetaI, PKCbetaII, PKCgamma, PKCepsilon and PKCzeta in murine peritoneal macrophages was detected by using laser confocal microscope. The density of NK-kappaB(+) macrophages was detected by immunocytochemical staining. RESULTS: The average fluorescent intensity of PKCalpha and PKCbetaII produced by mouse peritoneal macrophages in bifidobacterium DNA injection group was markedly higher than that in control group(P<0.01). There was no statistically significant difference of average fluorescent intensity of PKCbetaI, PKCgamma, PKCepsilon and PKCzeta between the two groups (P>0.05). The density of NK-kappaB(+) macrophages in bifidobacterium DNA injection group was markedly higher than that in control group (P<0.01). CONCLUSION: DNA of bifidobacteria adolescence could activate macrophages by promoting the activity of PKCalpha, PKCbetaII and NF-kappaB.
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Bifidobacterium/genética , ADN Bacteriano/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , FN-kappa B/metabolismo , Proteína Quinasa C/metabolismo , Animales , ADN Bacteriano/administración & dosificación , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Confocal , Proteína Quinasa C-alfa/metabolismo , Proteína Quinasa C-epsilon/metabolismoRESUMEN
AIM:To compare the features of gastroesophageal reflux disease between elderly and younger patients.METHODS:Twenty-four hour pH-monitoring and endoscopy were performed for the 66 elderly patients with typical gastroesophageal reflux symptoms, and the results were compared with 112 symptomatic younger patients.RESULTS:The results of 24-h pH-monitoring and endoscopy showed that the elderly patients had pathological reflux and reflux esophagitis more frequently than the younger patients. Percentage time with pH < 4 in elderly patients with reflux esophagitis was 32.5% in 24 hours, as compared with 12.9%in the younger patients with reflux esophagitis (P < 0.05). The elderly patients with reflux esophagitis have longer periods of acid reflux in both upright and supine-positions than the younger patients. Endoscopy showed that 20.8% of elderly patients had grade III/IV esophagitis, whereas only 3.4% of younger patients had grade III/IV esophagitis (P <0.002). Percentages of grades I/IIesophagitis in the two groups were 12.5% and 26.5%, respectively (P <0.002).CONCLUSION: Elderly patients, as compared with younger patients, have more severe gastroesophageal reflux and esophageal lesions. The incompetence of lower esophageal sphincter and the presence of hiatal hernia may be important factors leading to the difference in incidence and severity of reflux esoph agitis between elderly and younger patients.
RESUMEN
AIM:To assess the relationship between gastric acid output (GAO) and both pattern of gastroesophageal reflux (GER) and esophageal lesions,and to evaluate the role of GAO and other potential pathogenetic factors in the development of esophagitis.METHODS:Gastric acid secretory testing and 24h intraesophageal pH monitoring were performed in 31 patients with esophagitis and concomitant duodenal ulcer (E+DU) and compared with those of 72 patients with esophagitis (E) alone.RESULTS: The GAO in patients with E+DU was significantly higher than in patients with E (P <0.05). There was no significant difference between the two groups of patients as to endoscopicl findings and parameters of GER (P >0.05). A multiple regression analysis with stepwise deletion showed that the pre-sence of hiatal hernia (HH), GER in upright position and age appeared to correlate significantly with the presence of esophagitis.CONCLUSION:No parallel relationship between GAO and severity of GER or esophageal lesions exists in patients with E+DU, and that GAO is not a major pathogenetic factor in GER disease.