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BACKGROUND: Neuroendocrine tumors (NET) are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body. Acromegaly, a rare and slowly progressive disorder, usually results from a growth hormone (GH)-secreting pituitary adenoma. CASE SUMMARY: We herein describe a 38-year-old patient who was initially diagnosed with diabetes. During colonoscopy, two bulges were identified and subsequently removed through endoscopic submucosal dissection. Following the surgical intervention, the excised tissue samples were examined and confirmed to be grade 2 NET. 18F-ALF-NOTATATE positron emission tomography-computed tomography (PET/CT) and 68Ga-DOTANOC PET/CT revealed metastases in the peri-intestinal lymph nodes, prompting laparoscopic low anterior resection with total mesorectal excision. The patient later returned to the hospital because of hyperglycemia and was found to have facial changes, namely a larger nose, thicker lips, and mandibular prognathism. Laboratory tests and magnetic resonance imaging (MRI) suggested a GH-secreting pituitary adenoma. The pituitary adenoma shrunk after treatment with octreotide and was neuroendoscopically resected via a trans-sphenoidal approach. Whole-exome sequencing analysis revealed no genetic abnormalities. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: 18F-ALF-NOTATE PET/CT and MRI with pathological analysis can effectively diagnose rare cases of pituitary adenomas complicated with rectal NET.
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Adenoma , Tumores Neuroendocrinos , Neoplasias Hipofisarias , Neoplasias del Recto , Humanos , Adulto , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Neoplasias del Recto/cirugíaRESUMEN
Satoh-Miura reaction is an important method for extending π-systems by forging multi-substituted benzene rings via double aryl C-H activation and annulation with alkynes. However, the development of highly enantioselective Satoh-Miura reaction remains rather challenging. Herein, we report an asymmetric Satoh-Miura reaction between 1-aryl benzo[h]isoquinolines and internal alkynes enabled by a SCpRh-catalyst. Judiciously choosing the counteranion of the Rh-catalyst is crucial for the desired reactivity over the competitive formation of azoniahelicenes. Detailed mechanistic studies support the proposal of counteranion-directed switching of reaction pathways in Rh-catalyzed asymmetric C-H activation.
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OBJECTIVE: To explore the changes of â « antithrombin (Fâ «a-AT), thrombospondin-1 (TSP-1), and lupus anticoagulant (LA) ratio in the peripheral blood factor of patients with systemic lupus erythematosus (SLE) and the clinical value of combined diagnosis of thrombotic events. METHODS: A total of 133 SLE patients treated in Xingtai People's Hospital were selected and divided into simple SLE group (105 cases) and SLE complicated with thrombosis group (28 cases) according to whether thrombotic events occurred, and 102 cases of healthy people in the same period were selected as control. The clinical data of the 3 groups, the level of peripheral blood Fâ «a-AT, TSP-1, and LA ratio were compared, the relationship between each peripheral blood index and SLE disease activity index (SLEDAI) score were analyzed. The influencing factors of thrombotic events in SLE patients were analyzed, and the value of each peripheral blood index in the diagnosis of SLE complicated with thrombotic events were evaluated. RESULTS: The proportion of the patients with age ≥60 year, hypertension, and smoking history in SLE complicated with thrombosis group was higher than those in simple SLE group and control group (Pï¼0.05). The SLEDAI score, peripheral blood Fâ «a-AT, TSP-1, LA ratio levels of the patients in SLE complicated with thrombosis group were significantly higher than those in simple SLE group and control group, and the simple SLE group was significantly higher than the control group (Pï¼0.05). Fâ «a-AT, TSP-1, LA ratio in peripheral blood of SLE patients were positively correlated with SLEDAI score (r=0.663, 0.578 and 0.625). Age, blood pressure, smoking history, peripheral blood Fâ «a-AT, TSP-1, LA ratio were the important influencing factors of thrombotic events in SLE patients (Pï¼0.05). The AUC diagnosed by the Fâ «a-AT, TSP-1, and LA ratio in peripheral blood was 0.881, the 95% CI was 0.813-0.931, the sensitivity was 82.14%, and the specificity was 91.43%, which was superior to each index alone (Pï¼0.05). CONCLUSION: Peripheral blood Fâ «a-AT, TSP-1, LA ratio level changes in SLE patients are significantly related to disease activity, and the combined diagnosis of thrombotic events is more reliable.
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Lupus Eritematoso Sistémico , Trombosis , Humanos , Lupus Eritematoso Sistémico/complicaciones , Factores de Riesgo , Trombosis/etiología , Trombospondina 1RESUMEN
A rhodium-catalyzed asymmetric oxidative C-H/C-H cross-coupling reaction between 1-aryl isoquinolines and indolizines is disclosed. With a matched pair of SCpRh complex and chiral carboxylic acid, enantioselective two-fold C-H/C-H cross-coupling reactions between 1-aryl isoquinolines and indolizines provide a variety of axially chiral bi(hetero)aryls in excellent yields and enantioselectivity (up to 96% yield and 98% ee). Mechanistic studies suggest that both C-H cleavages are likely reversible.
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To investigate effects of agomelatine and mirtazapine on sleep disturbances in patients with major depressive disorder. A total of 30 depressed patients with sleep disturbances, 27 of which completed the study, took agomelatine or mirtazapine for 8 weeks. Subjective scales were administered, and polysomnography was performed at baseline and at the end of week 1 and 8. Functional magnetic resonance imaging was performed at baseline and at the end of week 8. Compared with baseline, scores on the Hamilton Depression Scale, Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Sleep Dysfunction Rating Scale, and Insomnia Severity Index after 8 weeks of treatment significantly decreased in both groups, with no significant differences between groups, accompanied by significant increases in total sleep time, sleep efficiency, and rapid eye movement (REM) sleep and significant decrease in wake after sleep onset. Mirtazapine treatment increased N3 sleep at week 1 compared with agomelatine treatment, but this difference disappeared at week 8. The increases in the percentage and duration of N3 sleep were positively correlated with increases in connectivity between right dorsal lateral prefrontal cortex (dlPFC) and right precuneus and between left posterior cingulate cortex and right precuneus in both groups, respectively. Functional connectivity (FC) between right dlPFC and left precuneus in mirtazapine group was higher compared with agomelatine group after 8 weeks of treatment. These findings indicated that both agomelatine and mirtazapine improved sleep in depressed patients, and the effect of mirtazapine was greater than agomelatine with regard to rapidly increasing N3 sleep and gradually improving FC in the brain.
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Trastorno Depresivo Mayor , Acetamidas , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Método Doble Ciego , Humanos , Mirtazapina , Sueño , Resultado del TratamientoRESUMEN
BACKGROUND: Hypertensive cerebral hemorrhage (HCH) is a potentially life-threatening neurological condition with an extremely high morbidity and mortality. In recent years, neuroendoscopy has been used to treat intracerebral hemorrhage (ICH). However, the choice of neuroendoscopic surgery versus craniotomy for patients with intracerebral hemorrhages is controversial. AIM: We conducted this meta-analysis to assess the efficacy of neuroendoscopic surgery compared with craniotomy in patients with supratentorial hypertensive ICH. METHODS: A systematic electronic search was conducted of online electronic databases: PubMed, Embase, and the Cochrane Library updated on December 2017. The meta-analysis only included randomized controlled studies. RESULTS: Three randomized controlled trials met our inclusion criteria. The pooled analysis of death showed that neuroendoscopic surgery decreased the rate of death when compared with craniotomy (RR = 0.58, 95% CI 0.26-1.29; p = .18). The pooled result of complications indicated that neuroendoscopic surgery has a tendency toward lower complications (RR = 0.37, 95% CI 0.28-0.49; p < .001). CONCLUSIONS: Our results suggested that neuroendoscopic surgery has lower complications, but no superior advantages in morbidity rates. Since the advantage of neuroendoscopic surgery has been performed in some area, the continuation of multi-center comparative investigation with craniotomy may be necessary. Moreover, some efforts need to be taken in selecting appropriate patients with different treatments.
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Craneotomía , Hemorragia Intracraneal Hipertensiva/cirugía , Neuroendoscopía , Complicaciones Posoperatorias , Craneotomía/efectos adversos , Craneotomía/métodos , Humanos , Neuroendoscopía/efectos adversos , Neuroendoscopía/métodos , Evaluación de Procesos y Resultados en Atención de Salud , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. METHODS: We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. RESULTS: Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140-3.124), severe agitation (OR 1.846, 95%CL 1.266-2.693), unemployment or retirement (OR 1.614, 95%CL 1.189-2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032-2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436-0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240-0.902) were less likely to be associated with antipsychotic polypharmacy. CONCLUSION: The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy.
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Antipsicóticos/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Esquizofrenia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Agresión/efectos de los fármacos , China , Quimioterapia Combinada , Femenino , Humanos , Pacientes Internos/psicología , Pacientes Internos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , PolifarmaciaRESUMEN
A cationic Ag(i) coordination polymer with 1D nanoporous channels (ca. 1.22 nm diameter) shows the selective and complete removal of carcinogenic dye Acid Red 26 from aqueous solution upon the size-exclusion and charge-matching effect.
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Background: Morinda officinalis oligosaccharides have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test in mice. However, the mechanisms that underlie the antidepressant-like effects of Morinda officinalis oligosaccharides are unclear. Methods: Chronic unpredictable stress and forced swim test were used to explore the antidepressant-like effects of Morinda officinalis oligosaccharides and resilience to stress in rats. The phosphoinositide-3 kinase inhibitor LY294002 was microinjected in the medial prefrontal cortex to explore the role of glycogen synthase kinase-3ß in the antidepressant-like effects of Morinda officinalis oligosaccharides. The expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase 3ß, ß-catenin, and synaptic proteins was determined in the medial prefrontal cortex and the orbitofrontal cortex by western blot. Results: We found that Morinda officinalis oligosaccharides effectively ameliorated chronic unpredictable stress-induced depression-like behaviors in the sucrose preference test and forced swim test. The Morinda officinalis oligosaccharides also significantly rescued chronic unpredictable stress-induced abnormalities in the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway and synaptic protein deficits in the medial prefrontal cortex but not orbitofrontal cortex. The activation of glycogen synthase kinase-3ß by the phosphoinositide-3 kinase inhibitor LY294002 abolished the antidepressant-like effects of Morinda officinalis oligosaccharides in the forced swim test. Naïve rats that were treated with Morinda officinalis oligosaccharides exhibited resilience to chronic unpredictable stress, accompanied by increases in the expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase-3ß, and ß-catenin in the medial prefrontal cortex. Conclusion: Our findings indicate that the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway in the medial prefrontal cortex may underlie the antidepressant-like effect of Morinda officinalis oligosaccharides and resilience to stress.
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Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Oligosacáridos/farmacología , Corteza Prefrontal/efectos de los fármacos , beta Catenina/metabolismo , Animales , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Modelos Animales de Enfermedad , Masculino , Morinda , Corteza Prefrontal/metabolismo , Ratas Sprague-Dawley , Resiliencia Psicológica/efectos de los fármacos , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismoRESUMEN
PURPOSE: Conjunctivochalasis (CCh) is an age-related inflammatory ocular surface disease manifesting redundant, loose conjunctiva folds. The pathogenic role of Pentraxin 3 (PTX3) in controlling upregulation of matrix metalloproteinase 1 (MMP-1) and MMP-3 in CCh remains undefined. METHODS: Cytolocation of PTX3 and apoptosis were compared by immunostaining and terminal deoxyribonucleotidyl transferase-mediated FITC-linked dUTP nick-end DNA labeling (TUNEL) assay between normal and CCh specimens containing the conjunctiva and the Tenon. Second to third cultures of normal and CCh fibroblasts were treated with or without Aprotinin, Batimastat, or N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), followed by transfection with or without PTX3 siRNA, and TNF-α or IL-1ß. Cell lysates and culture media were collected to assess apoptosis measured by the Cell Death Detection ELISA and expression of PTX3, MMP-1, and MMP-3 transcripts and proteins by quantitative RT-PCR and Western blot, respectively. RESULTS: PTX3 immunostaining was negative in normal specimens, but strongly positive in the subconjunctival stroma of CCh specimens. More apoptotic cells were found in CCh samples than in normal specimens. Expression of PTX3 transcripts and protein was not constitutive in resting normal fibroblasts but was in resting CCh fibroblasts and was upregulated by IL-1ß in both cell lysates and culture media of both fibroblasts. PTX3 siRNA further upregulated MMP-1 and MMP-3 transcripts in resting normal fibroblasts, but synergistically with IL-1ß upregulated the expression of MMP-1 and MMP-3 transcripts only in CCh fibroblasts, with activation of MMP-1 more so than MMP-3. PTX3 siRNA knockdown also promoted cell death characterized by apoptosis and necrosis, and such cell death could be rescued by inhibitors against serine proteinase, MMP1, or MMP3. CONCLUSIONS: Perturbation of PTX3 expression might partake in apoptosis and pathogenesis of CCh by upregulating expression of MMP-1 and MMP-3, and activation of MMP-1 and MMP-3.
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Proteínas de Fase Aguda/fisiología , Apoptosis , Proteína C-Reactiva/fisiología , Enfermedades de la Conjuntiva/enzimología , Enfermedades de la Conjuntiva/patología , Metaloproteinasa 1 de la Matriz/metabolismo , Componente Amiloide P Sérico/fisiología , Anciano , Anciano de 80 o más Años , Aprotinina/farmacología , Western Blotting , Células Cultivadas , Activación Enzimática , Ensayo de Inmunoadsorción Enzimática , Fibroblastos/enzimología , Fibroblastos/patología , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Ácidos Hidroxámicos/farmacología , Etiquetado Corte-Fin in Situ , Persona de Mediana Edad , Fenilalanina/análogos & derivados , Fenilalanina/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Sulfonamidas/farmacología , Cápsula de Tenon/enzimología , Cápsula de Tenon/patología , Tiofenos/farmacología , TransfecciónRESUMEN
PURPOSE: To investigate the role of anti-inflammatory TSG-6 in controlling MMP-1 and MMP-3, which have been shown to be upregulated in conjunctivochalasis (CCh). METHODS: Immunostaining of TSG-6 was compared between normal and CCh conjunctiva and Tenon's capsule. Second cultures of normal and CCh fibroblasts were transfected with or without TSG-6 siRNA and then with or without the addition of TNF-α or IL-1ß. Cell lysates and culture media were collected to assess apoptosis with the use of ELISA and the expression of TSG-6, MMP-1, and MMP-3 transcripts and proteins with the use of qRT-PCR and Western blot analysis, respectively. RESULTS: TSG-6 expression was constitutive in the in vivo normal conjunctival epithelium. Significantly more TSG-6-positive cells than normal specimens were noted in CCh subconjunctival tissue and Tenon's capsule. TSG-6 was constitutively expressed intracellularly by both resting normal and CCh fibroblasts but was secreted extracellularly only by resting CCh fibroblasts. Intracellular and extracellular TSG-6 proteins were markedly upregulated by TNF-α or IL-1ß in normal and CCh fibroblasts. Active MMP-1 was found in CCh fibroblasts intracellularly and extracellularly, whereas only proMMP-1 was found intracellularly in normal fibroblasts. Knockdown by TSG-6 siRNA upregulated more MMP-1 than MMP-3 transcripts in normal and CCh fibroblasts. TSG-6 siRNA led to extracellular MMP-1 expression by normal fibroblasts such as CCh fibroblasts. This activation of MMP-1 was further enhanced by IL-1ß. Cell apoptosis was higher in CCh fibroblasts and further aggravated by TSG-6 siRNA knockdown. CONCLUSIONS: TSG-6 exerts an anti-inflammatory function by counteracting the transcription of MMP-1 and MMP-3 and the activation of MMP-1. Dysfunction of TSG-6 might play a role in the pathogenesis of CCh.
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Antiinflamatorios/farmacología , Moléculas de Adhesión Celular/fisiología , Enfermedades de la Conjuntiva/enzimología , Metaloproteinasa 1 de la Matriz/metabolismo , Activación Transcripcional/fisiología , Antiinflamatorios/metabolismo , Apoptosis , Western Blotting , Moléculas de Adhesión Celular/metabolismo , Células Cultivadas , Enfermedades de la Conjuntiva/metabolismo , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Interleucina-1beta/farmacología , Masculino , Metaloproteinasa 3 de la Matriz/metabolismo , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Necrosis Tumoral alfa/farmacología , Regulación hacia ArribaRESUMEN
BACKGROUND: The relationship between melanosis coli (MC) and aquaporin 8 (AQP8) has not yet been elucidated. The aim of this research was to investigate the relationship between the expression of AQP8 and the pathological mechanism of MC. METHODS: Expression of AQP8 was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) in 37 MC colon tissues and 13 control colon tissues. Global gene expression analysis was also used to identify differently expressed genes. Its relationship with MC was analyzed by SPSS 11.5 statistical software. RESULTS: The positive rate of AQP8 expression detected by immunohistochemistry in the MC group was 24.3% (9/37), significantly lower than the 69.2% (9/13) in the control group (P < 0.05). The relative expression level of AQP8 in MC group was 0.639 ± 0.160, lower than 0.921 ± 0.148 of controls (P < 0.05). Global gene expression analysis showed that AQP8 mRNA expression was downregulated in MC patients. CONCLUSIONS: The decreased AQP8 expression in MC patients indicates that chronic use of laxatives containing anthraquinone may cause reduced water absorption. The expression of AQP8 may be related to MC.
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Acuaporinas/análisis , Enfermedades del Colon/etiología , Melanosis/etiología , Adulto , Anciano , Acuaporinas/genética , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To analyze the clinical characteristics of concomitant vertigo in patients with sudden deafness (SD). METHODS: Ninety-six cases of SD were reviewed retrospectively from January 2005 to July 2009. SD and benign paroxysmal positional vertigo (BPPV) were diagnosed according to the guides of China Medical Association. The characteristics of vestibular function and the order of the onset of cochlear and vestibular symptoms were analyzed. RESULTS: Of all 96 cases, 23 (24.0%) cases presented with BPPV; 58 (60.4%) cases took the form of unilateral vestibular hypofunction and 15 (15.6%) cases had normal vestibular function. Time interval between cochlear and vestibular symptoms was as follows: 46 patients could tell the exact time of onset of cochlear and vestibular symptoms, of which 6 (13.0%) cases occurred simultaneously; 4 (8.7%) cases presented vertigo within 1 hour after onset of cochlear symptom hypofunction; 21 (45.7%) cases showed time interval between 1 hour and 24 hours; and 13 (28.3%) cases presented vertigo at several days (less than 10 days) after cochlear symptoms. And only in 2 (4.3%) cases did vertigo occur before cochlear symptoms. CONCLUSIONS: Concomitant vertigo in idiopathic SD took the forms of normal or abnormal vestibular function, some of which were BPPV. Occurrence of vertigo was after cochlear symptoms.
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Pérdida Auditiva Súbita/complicaciones , Pérdida Auditiva Súbita/diagnóstico , Vértigo/complicaciones , Vértigo/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To investigate the incidence of complications of canalith repositioning procedure (CRP) for benign paroxysmal positional vertigo (BPPV) in order to recognize and intervene the complication. METHODS: Totally 430 cases of BPPV were treated by CRP between Jan., 2005 and Nov., 2007. The patients with complication were retreated with CRP according to the new canals otolith falling into. RESULTS: There were 313 patients with posterior canal BPPV, among which 5 had complications during CRP for posterior canal BPPV and 3 for horizontal canal BPPV. And 1 patient transformed from cupulolithiasis to canalithiasis during Semont CRP, which made CRP possible. Three patients had horizontal BPPV during CRP for posterior canal BPPV. Horizontal BPPV emerged during CRP for anterior canal BPPV in 1 patient. CRP for the posterior BPPV had more patients with complication than that of CRP for the anterior BPPV, but the percentage was on the contrary, and they were 1.9% (8/313) and 28.6% (2/7) respectively. The rate of complication during CRP was 3.3% (14/430) and all of them recovered well with CRP. CONCLUSIONS: There are possibility for canal otolith transferred from one canal to another. Careful observation of nystagmus and reevaluation of the patients with BPPV in case of unsuccessful treatments are crucial to determine the complications.
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Membrana Otolítica , Canales Semicirculares , Vértigo/diagnóstico , Vértigo/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Skeletal muscles have the potential to regenerate by activation of quiescent satellite cells, however, the molecular signature that governs satellite cells during muscle regeneration is not well defined. Myosin light chains (Myls) are sarcomere-related proteins as traditional regulator of muscle contraction. In this report, we studied the possible role of Myl in the proliferation of skeletal muscle-derived myoblasts. Compared to diaphragm-derived myoblasts, the extraocular muscle-derived myoblasts with lower levels of Myl proliferated faster, maintained a longer proliferation phase, and formed more final myotubes. It was found that blockading Myl with anti-Myl antibody or knockdown of Myll by siRNA targeted against Myll could enhance the myoblast proliferation and delay the differentiation of myoblasts. Our results suggested that Myl, likely Myll, can negatively affect myoblast proliferation by facilitating myoblast withdrawal from cell cycle and differentiation.
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Proliferación Celular , Diafragma/citología , Mioblastos/fisiología , Cadenas Ligeras de Miosina/fisiología , Músculos Oculomotores/citología , Regeneración/fisiología , Animales , Western Blotting , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Angiogenesis is crucial for solid tumor growth. By secreting angiogenic factors, tumor cells induce angiogenesis. However, targeting these angiogenic factors for cancer therapy is not always successful, suggesting that other factors may be involved in tumor angiogenesis. This work shows that 25 protein spots were differentially expressed by two-dimensional gel electrophoretic analysis when HepG2 cells induced endothelial cell differentiation to tube in vitro, and most of them were upregulated. Twenty-one proteins were identified with MALDI-TOF-MS, and the other four were identified by LTQ-MS/MS. Keratins were identified as one class of these upregulated proteins. Further study indicated that the expression of keratin 17 in cultured endothelial cells is likely microenvironment regulated, because its expression can be induced by HepG2 cells and bFGF as well as serum in culture media. Increased expression of keratins in endothelial cells, such as keratin 17, may contribute to the angiogenesis induced by HepG2 cells.
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Queratina-17/aislamiento & purificación , Queratina-17/fisiología , Neoplasias/irrigación sanguínea , Neovascularización Patológica/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Células Endoteliales/metabolismo , Humanos , Queratina-17/genética , Queratina-17/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neovascularización Patológica/genética , Proteómica/métodosRESUMEN
Evidence has shown that Notch signaling modulates CD4(+)CD25(+) regulatory T-cells (Tregs). As transcription factor Foxp3 acts as a master molecule governing the development and function of Tregs, we investigated whether Notch signaling might directly regulate Foxp3 expression. Here, we provide evidence that Notch signaling can modulate the FOXP3 promoter through RBP-J- and Hes1-dependent mechanisms. A conserved RBP-J-binding site and N-box sites were identified within the FOXP3 promoter. We show that the Notch intracellular domain (NIC), the active form of Notch receptors, activates a reporter driven by the FOXP3 promoter. Dissection of the FOXP3 promoter revealed bipartite effects of the RBP-J-binding site and the N-boxes: the RBP-J-binding site positively, while the N-boxes negatively regulated the FOXP3 promoter activity. Moreover, in freshly isolated Tregs, NIC-RBP-J complex is bound to the FOXP3 promoter in Tregs. Our results suggest that Notch signaling might be involved in the development and function of Tregs through regulating Foxp3 expression.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción Forkhead , Regulación de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Regiones Promotoras Genéticas , Receptores Notch/metabolismo , Transducción de Señal/fisiología , Animales , Secuencia de Bases , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/metabolismo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Genes Reporteros , Células HeLa , Proteínas de Homeodominio/genética , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/genética , Células Jurkat , Ratones , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Receptores Notch/genética , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/metabolismo , Factor de Transcripción HES-1RESUMEN
The extraocular muscle (EOM) suffers much less injury from Duchenne muscular dystrophy (DMD) than other skeletal muscles such as diaphragm and gastrocnemius. The present study was undertaken to test the hypothesis that differential expression of regulatory proteins between the EOM and other skeletal muscles is responsible for the observed difference in the sensitivity to DMD-associated damage. Protein expression in the tissue samples obtained from EOM, diaphragm or gastrocnemius of C57BL/6 mice was analyzed by two-dimensional gel electrophoresis and mass spectrometry. There were 35 proteins that were identified to be differentially expressed among different skeletal muscle tissues. Among the 35 proteins, a fast skeletal muscle isoform myosin light chain 1 (MLC1f) protein was further studied in relation to muscle cell proliferation. The EOM-derived myoblasts had much lower levels of MLC1f and higher rate of cell proliferation in contrast to the myoblasts derived from diaphragm or gastrocnemius, which displayed a higher expression of MLC1f along with a slow proliferation. Deletion of MLC1f using siRNA targeting MLC1f resulted in an increased rate of cell proliferation in the myoblasts. Cell cycle analysis revealed that MLC1f inhibited the transition of the cell cycle from the G1 to the S phase. Therefore, the present study demonstrates that MLC1f may negatively regulate proliferation of myoblasts through inhibition of the transition from the G1 to the S phase of the cell cycle. Low levels of MLC1f in myoblasts of EOM may ensure cell proliferation and enhance the repair process for EOM under the DMD disease condition, thus making EOM suffer less injury from DMD.