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BACKGROUND AND PURPOSE: Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro-immune communication. Neuronal mechanism-based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro-immune mechanism. EXPERIMENTAL APPROACH: Pharmacological intervention, immunofluorescence, RNA-sequencing, genetic modification and immunoassay were performed to dissect the neuro-immune basis of itch and inflammation in atopic dermatitis-like mouse model and in patients. KEY RESULTS: Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)-induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX-314, a charged NaV blocker that enters through pathologically activated large-pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV 1.8-expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1-positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model. CONCLUSION AND IMPLICATIONS: NaV 1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti-inflammatory and anti-pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis.
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Dermatitis Atópica , Ratones , Animales , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Prurito/tratamiento farmacológico , Piel/patología , Inflamación/patología , Células Receptoras SensorialesRESUMEN
Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.
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Femenino , Humanos , Persona de Mediana Edad , Carcinoma Hepatocelular/diagnóstico por imagen , Ictericia Obstructiva/etiología , Neoplasias Hepáticas/diagnóstico por imagen , Conducto Hepático Común/patología , Trombosis/complicaciones , Hemorragia/complicacionesRESUMEN
Aberrant differentiation of keratinocytes has been demonstrated to be associated with a number of skin diseases. A growing number of studies have showed that long noncoding RNAs (lncRNAs) have an important part in gene regulation, however, the role of lncRNAs in keratinocyte differentiation remains to be largely unknown. In the present study, we demonstrated that lncRNA-H19 act as an endogenous 'sponge', which binds directly to miR-130b-3p and therefore inhibits its activity on Dsg1. MiR-130b-3p was illustrated to inhibit keratinocyte differentiation by targeting Dsg1. H19 regulates Dsg1 expression and the consequent keratinocyte differentiation through miR-130b-3p. Our study casts light on a novel regulatory model of keratinocyte differentiation, which may provide new therapeutic targets of skin diseases.
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Queratinocitos/fisiología , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Diferenciación Celular/fisiología , Niño , Desmogleína 1/genética , Desmogleína 1/metabolismo , Regulación de la Expresión Génica , Genes Supresores de Tumor , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , MicroARNs/antagonistas & inhibidores , TransfecciónRESUMEN
To sort out the existing problems within the published 35 evidence-based acupuncture-moxibustion clinical practice guidelines (group standards) in Chinese: the development methods and the development process are not clear and strict enough; the evidence evaluation system fails to fully reflect the characteristics of acupuncture and moxibustion. Therefore,
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Acupuntura , Terapia por Acupuntura , China , Práctica Clínica Basada en la Evidencia , MoxibustiónRESUMEN
BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory cutaneous diseases. Thymic stromal lymphopoietin (TSLP) has been demonstrated to be an important immunologic factor in the pathogenesis of AD. The production of TSLP can be induced by a high level of intracellular calcium concentration and activation of the receptor-interacting protein 2/caspase-1/NF-κB pathway. Andrographolide (ANDRO), a natural bicyclic diterpenoid lactone, has been found to exert anti-inflammatory effects in gastrointestinal inflammatory disorders through suppressing the NF-κB pathway. OBJECTIVE: To explore the effect of ANDRO on the production of TSLP in human mast cells and AD mice model. METHODS: We utilized enzyme-linked immunosorbent assay, real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, and immunofluorescence staining assay to investigate the effects of ANDRO on AD. RESULTS: ANDRO ameliorated the increase in the intracellular calcium, protein, and messenger RNA levels of TSLP induced by phorbol myristate acetate/calcium ionophore A23187, through the blocking of the receptor-interacting protein 2/caspase-1/NF-κB pathway in human mast cell line 1 cells. ANDRO, via oral or local administration, also attenuated clinical symptoms in 2,4-dinitrofluorobenzene-induced AD mice model and suppressed the levels of TSLP in lesional skin. CONCLUSION: Taken together, ANDRO may be a potential therapeutic agent for AD through suppressing the expression of TSLP.
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Calcimicina/farmacología , Citocinas/antagonistas & inhibidores , Dermatitis Atópica/tratamiento farmacológico , Diterpenos/farmacología , Mastocitos/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/patología , Dinitrofluorobenceno , Modelos Animales de Enfermedad , Diterpenos/química , Relación Dosis-Respuesta a Droga , Humanos , Mastocitos/metabolismo , Mastocitos/patología , Ratones , Conformación Molecular , Relación Estructura-Actividad , Células Tumorales Cultivadas , Linfopoyetina del Estroma TímicoRESUMEN
OBJECTIVE@#To carry out the methodological quality evaluation and content analysis of the evidence-based clinical practice guidelines for acupuncture-moxibustion in China, and to provide reference for the development and updating of future guidelines.@*METHODS@#With Appraisal of Guidelines for Research and EvaluationⅡ(AGREEⅡ), 20 evidence-based clinical practice guidelines for acupuncture and moxibustion in China were evaluated from six aspects: scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability and editorial independence. In addition, the contents of 20 guidelines were systematically analyzed, and the characteristics of guidelines were summarized from the aspects of disease selection, operation technology type and safety.@*RESULTS@#The scores of six domains were scope and purpose (91.1%), stakeholder involvement (68.5%), rigour of development (68.6%), clarity of presentation (90.3%), applicability (34.5%) and editorial independence (16.7%). The recommendations of the 20 acupuncture guidelines covered common clinical problems such as diagnosis, treatment and precautions, which were in line with the clinical characteristics of acupuncture and moxibustion in terms of content structure.@*CONCLUSION@#The methodology of the evidence-based clinical practice guidelines for acupuncture and moxibustion in China conformed to the requirements of AGREEⅡ on the quality evaluation, and the overall quality was moderate, but the aspects of applicability and editorial independence were still needed to be improved. The contents of recommendations in 20 guidelines were specific and clear, in line with the characteristics of acupuncture and moxibustion, presenting clinical reference value. In the future, in the process of guideline development, the method of developing acupuncture and moxibustion guidelines should be constantly improved to improve the quality of the guidelines; in the meantime, more attention should be paid to the generalization and clinical applicability evaluation.
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Humanos , Terapia por Acupuntura , China , Medicina Basada en la Evidencia , Práctica Clínica Basada en la Evidencia , MoxibustiónRESUMEN
Objective To study the status and environment-related risk factors for falls among older adults in the urban community,and to provide evidences for the development of specific interventions.Methods A total of 993 older adults aged ≥60 years old from 2 communities in Cixi City were selected by stratified cluster sampling. Face-to-face interview and field investigation were carried out to collect participants' basic information,the situation and environment-related risk factors for falls occurred to them from November 2012 to October 2013.Results The overall incidence of falls was 14.90%,and it was significantly higher in wowen (17.19%) than in men(12.47%)(P<0.05). There were 109 participants reported to have fall-related injury with an incidence of 10.98%(109/993). Moreover,the incidence of fall-related injury for women(13.87%) was significantly higher than that for men(7.69%)(P<0.05). Among them, 35.14% falls occurred in home,the washroom(93.62%)and drawing room(85.02%) had higher proportion of having falling-related environmental risk factors. The multivariate logistic analysis showed that uneven carpet in aisle (OR=3. 542,95% CI:1.235-10.161)and having clutters beside the bed (OR=8.611,95% CI:2.051-36.574) were two main environmental risk factors for elder falls in home.Conclusion The incidence of falls of older adult in Cixi was 14.90%. Uneven carpet in aisle and having clutters beside the bed were two main environmental risk factors for falls among the elderly at home.
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Objective To analysis the awareness of community doctors on the knowledge of osteoporosis and to provide suggestions for conducting pertinent training for community doctors.Methods The design of questionnaire was based on the Osteoporosis Knowledge Questionnaire (OKT)and the Guideline of Diagnosis and Treatment of Osteoporosis in 2011.A total of 170 community doctors were investigated.Results The score of community doctors about osteoporosis was 29. There was 83.80% of community doctors who knew osteoporosis related knowledge well.However,there was 15.49% of community doctors'knowledge about osteoporosis that was not good enough.The most of community doctors got full score in the part of prevention knowledge with 52.82%.The most of community doctors failed in the part of treatment knowledge with 12.68%.The score of osteoporosis knowledge in different gender and title had no statistical significance (P >0.05). Conclusion It is necessary to strengthen community doctors's awareness about osteoporosis.
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<p><b>OBJECTIVE</b>To screen and identify serum biomarkers for childhood hepatoblastoma (HB).</p><p><b>METHODS</b>The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins.</p><p><b>RESULTS</b>After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group.</p><p><b>CONCLUSIONS</b>Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.</p>
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Preescolar , Femenino , Humanos , Lactante , Masculino , Apolipoproteína A-I , Sangre , Genética , Biomarcadores , Sangre , Detección Precoz del Cáncer , Hepatoblastoma , Sangre , Diagnóstico , Neoplasias Hepáticas , Sangre , Diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
AIM: To observe the application of Suresight handheld auto- refractometer in measuring diopter of infants in Community Health Service Center. METHODS:Totally 836 cases ( 1 672 eyes ) from June 2013 to December 2013 were examined diopter of infants by Suresight handheld auto-refractometer in Community Health Service Center. RESULTS: Within 1 672 eyes of 836 infants were examined, 202 eyes were diagnosed ametropia, 38 eyes were suspicious, 240 eyes were transferred to the department of ophthalmology, the referral rate was 14.35%; 172 eyes were diagnosed ametropia, and the diagnosis rate of the referral patients was 71. 67%. Among 172 eyes, 46 eyes were provided with corrected glasses, accounting for 2. 75% of the number of screening, and 126 eyes were given intensive monitoring, accounting for 7.54% of the number of screening. CONCLUSION: Application of Suresight handheld auto-refractometer in refraction screening for infants in Community Health Service Center is convenient and effective. With two - way referral between community health service center and department of ophthalmology can monitor and intervene vision development of infants much earlier.
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<p><b>OBJECTIVE</b>To investigate the role of heme oxygenase and carbon monoxide (HO/CO) in the development of spontaneous pain and hyperalgesia of rats induced by formalin injection.</p><p><b>METHODS</b>Zinc protoporphyrin Znpp (the inhibitor of HO) was intrathecally injected to the rats with formalin inflammatory pain. Hemin (the agonist of HO) was intrathecally injected to the normal rats. The weighted pain scores were used to evaluate the degree of pain response. Thermal withdrawal latency and mechanical withdrawal threshold were observed to assess the degree of thermal hyperalgesia and mechanical allodynia.</p><p><b>RESULTS</b>After the intrathecal injection of Znpp, the weighted pain score obviously reduced in a dose-dependent manner compared with the rats with formalin inflammatory pain. Intrathecal injection of Znpp had no obvious effect on thermal withdrawal latency and mechanical withdrawal threshold in injected feet compared with formalin group. But there was a prolongation in a dose-dependent manner in non injected feet. Intrathecal injection of Hemin to normal rats could shorten the thermal withdrawal latency and reduce the mechanical withdrawal threshold on both sides of hindpaws.</p><p><b>CONCLUSION</b>Intrathecal injection of the HO inhibitor produced prominent inhibition to pain related behavior and thermal and mechanical hyperalgesia induced by formalin injection. Intrathecal injection of HO inductor could induce thermal and mechanical hyperalgesia in normal rats. The results indicated that HO/CO took part in the processes of spinal cord nociceptive information transmission and the development of thermal and mechanical hyperalgesia.</p>
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Animales , Masculino , Ratas , Monóxido de Carbono , Formaldehído , Hemo Oxigenasa (Desciclizante) , Hemina , Hiperalgesia , Nocicepción , Nociceptores , Fisiología , Dolor , Protoporfirinas , Ratas Sprague-DawleyRESUMEN
<p><b>AIM</b>To investigate whether formalin inflammatory pain can induce hippocampal neuronal apoptosis of rats or not.</p><p><b>METHODS</b>Rats were subcutaneously injected with 0.2 ml 0.5% formalin into the ventral surface of right hind paw to induce periphery inflammatory pain. The flinches of rats were counted to observe their painful reaction. Flow cytometry was used to assay the ratio of apoptosis of hippocampal neurons. The immunohistochemistry was used to observe the expression of p53 protein in hippocampal subregions.</p><p><b>RESULTS</b>Compared with control group, the apoptotic ratio of hippocampal neurons was significantly increased in rats with inflammatory pain, and formalin inflammatory pain induced upregulation of p53 protein expression in all hippocampal subregions. Both the apoptotic ratio and the p53 protein expression peaked on the third day after the formalin injection. The twice injection of formalin into the hind paws of rats resulted in an enhancement of painful reaction and increase in apoptotic ratio of hippocampal neurons compared with the rats of injection formalin once group.</p><p><b>CONCLUSION</b>Formalin inflammatory pain can induce the hippocampal neuronal apoptosis in rats with a certain time course. Neuronal apoptosis is relevant to the intensity of pain. The up-regulation of p53 protein expression may implicate in the induction of hippocampal neuronal apoptosis in rats with inflammatory pain.</p>
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Animales , Masculino , Ratas , Apoptosis , Formaldehído , Hipocampo , Patología , Inflamación , Neuronas , Patología , Dolor , Distribución Aleatoria , Ratas Sprague-Dawley , Proteína p53 Supresora de Tumor , MetabolismoRESUMEN
<p><b>AIM</b>To study the effect of different intervals between occlusions of vertebral arteries and bilateral common carotid arteries on the Pulsinelli 4-vessel occlusion global cerebral ischemic model, and the features of ischemia of the brainstem and hippocampus induced by occulusion of bilateral common carotid arteries under the condition of occlusion of unilateral vertebral artery.</p><p><b>METHODS</b>Eighty four adult male Wistar rats were divided into 4 groups randomly: control group, bilateral vertebral artery occluding group, global brain ischemic insult group, and unilateral vertebral artery occluding plus bilateral common carotid arteries occluding group. In the global brain ischemic insult group, rats were further divided into 24 h, 48 h, and 72 h interval subgroups according to the interval between the occlusion of the vertebral arteries and bilateral common carotid arteries. The responses including enlarging of pupils and the light reflex during the brain ischemia were observed. The duration of right reflex disappearing, the general state, and the delayed neuronal death (DND) of pyramidal neurons in the CA1 hippocampus of the rats after the brain ischemia were also observed.</p><p><b>RESULTS</b>Among the global brain ischemic insult group, both the responses and DND were more severe in 72 h interval subgroup than those in 24 h and 48 h interval subgroups. There was no significant difference between 24 h and 48 h interval subgroups. When the bilateral common carotid arteries were occluded under the condition of occlusion of unilateral vertebral artery, severe DND was observed in the CA1 hippocampus ipsilateral to the occluding vertebral artery, but no significant DND was observed in the contralateral CA1 hippocampus.</p><p><b>CONCLUSION</b>The results suggested that the prior occlusion of the bilateral vertebral arteries during producing Pulsinelli 4-vessel occlusion global cerebral ischemic model might be a cerebral ischemic preconditioning that could protect to some extent pyramidal neurons of the hippocampus against severe ischemic insult induced by occlusion of bilateral common carotid arteries within 48 h. Moreover, There is ipsilateral predominance of blood perfusion from one side of vertebral artery to the brainstem and hippocampus, although there was Willis artery circle in rats.</p>
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Animales , Masculino , Ratas , Isquemia Encefálica , Hipocampo , Precondicionamiento Isquémico , Métodos , Ratas Wistar , Arteria Vertebral , PatologíaRESUMEN
<p><b>OBJECTIVE</b>To explore the correlation between homozygous deletions and mutation of p16 gene and the carcinogenesis and progression of squamous cell carcinoma of buccal mucosa.</p><p><b>METHODS</b>Thirty buccal cancers, 10 leukoplakias and 8 buccal mucosas were involved. DNA was extracted from the tissues. PCR was used to analyses homozygous deletion of p16 gene. PCR-SSCP-DNA sequencing was performed to detect the point mutation of p16 gene. Immunohistochemical techniques were used to detect the expression of P16 protein.</p><p><b>RESULTS</b>Gene deletions and point mutations were not found in leukoplakia and normal buccal mucosa. Gene deletions were found in 7 samples out of 30 cases of squamous cell carcinoma of buccal mucosa (23.3%), while point mutations were found in 5 samples out of 30 cases of squamous cell carcinoma of buccal mucosa (16.7%). Sequencing analysis showed that 5 cases point mutations were missense mutations, occurred on exon 2. Three cases occurred in the same point, codon 99 (GAT --> AAT). The result of immunohistochemical stains showed that 11 out of 12 cases gene inactivation did not expressed P16 protein.</p><p><b>CONCLUSION</b>Homozygous deletion and point mutation of p16 were the main pattern of gene inactivation in squamous cell carcinoma of buccal mucosa. There was a closely correlation between p16 gene inactivation and the carcinogenesis of squamous cell carcinoma of buccal mucosa.</p>
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Humanos , Carcinoma de Células Escamosas , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Eliminación de Gen , Genes p16 , Mucosa Bucal , Mutación , Mutación PuntualRESUMEN
<p><b>OBJECTIVE</b>To study the regulation of Fc receptor expression by immune complexes (ICs) on neutrophils and U937 cells.</p><p><b>METHODS</b>IgA ICs, IgG1 ICs, IgG2 ICs, IgG3 ICs, IgG4 ICs, and IgM ICs were incubated with neutrophils or U937 cells for 1 h. Then their surface Fc receptors were stained by anti-Fc gammaR I, anti-Fc gammaR II , anti-Fc gammaR III, and anti-Fc alphaR I monoclonal antibodies and analyzed by fluorescent activated cell sorting (FACS).</p><p><b>RESULTS</b>IgG1 ICs and IgG3 ICs up-regulated Fc gammaR II and Fc gammaR III on U937 cells, Fc gammaR I and Fc alphaR I on neutrophils. Almost all ICs down-regulated Fc gammaR II on neutrophils.</p><p><b>CONCLUSIONS</b>ICs can regulate Fc receptor expression on neutrophils and U937 cells, among which IgG1 ICs and IgG3 ICs are most effective.</p>
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Humanos , Anticuerpos Antiidiotipos , Alergia e Inmunología , Anticuerpos Monoclonales , Farmacología , Complejo Antígeno-Anticuerpo , Alergia e Inmunología , Metabolismo , Antígenos CD , Alergia e Inmunología , Inmunoglobulina A , Clasificación , Alergia e Inmunología , Inmunoglobulina G , Química , Clasificación , Alergia e Inmunología , Metabolismo , Neutrófilos , Metabolismo , Receptores Fc , Genética , Receptores de IgG , Alergia e Inmunología , Células U937 , Alergia e InmunologíaRESUMEN
Objective To evaluate the effects of TENS on metatarsus plantar flexion and inversion in stroke patients,and to explore its mechanism.Methods Thirty-two stroke patients with gastrocnemius spasticity were randomly divided into a control group (n=16) and a TENS group (n=16).All patients were treated with foot sup- ports,neurodevelopmental and manipulation therapies.In addition,the TENS group received TENS on the anterior tibialis,peroneus longus and brevis muscles.All patients were assessed in terms of their Chinese stroke scale(CSS) and H reflex scores before and after therapy.Results Compared with those in the control group,the H reflex scores in the TENS group were obviously decreased,while H reflex latency was prolonged and H/M was reduced. Gait in the TENS group was evidently improved.Conclusion TENS is an effective therapy to decrease gastrocnemi- us spasticity and to improve the gait of stroke patients.