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BACKGROUND: Recent studies found white coats to be reservoirs for bacteria and medical students did not conform to proper hygiene measures when using these white coats. We investigated the knowledge, attitude, and practice (KAP) of medical students toward white coat use in clinical settings (LAUNDERKAP). METHODS: A validated, online-based survey was disseminated to 670 students from four Malaysian medical schools via random sampling. Scores were classified into good, moderate, or poor knowledge and practice, and positive, neutral, or negative attitude. Mann-Whitney U and Kruskal-Wallis tests were used to analyze the relationship between demographic variables and knowledge, attitude, and practice scores. RESULTS: A total of 492/670 students responded (response rate: 73.4%). A majority showed negative attitudes (n = 246, 50%), poor knowledge (n = 294, 59.8%), and moderate practice (n = 239, 48.6%). Senior and clinical year students had more negative attitudes. Male students had higher knowledge, while students from private medical schools and preclinical years had better practice. There was a significant relationship between attitude and practice (r = 0.224, P < .01), as well as knowledge and practice (r = 0.111, P < .05). CONCLUSIONS: The results demonstrate the need for more education to improve medical students' infection control practices. Our results can also guide decision-making among administrators on the role of white coats as part of medical student attire.
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Estudiantes de Medicina , Humanos , Masculino , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Higiene , Proyectos de Investigación , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To explore whether the paraventricular nucleus (PVN) participates in regulation of the anti-myocardial ischemia-reperfusion injury (MIRI) effect of electroacupuncture (EA) and whether this is achieved through the PVN-interposed nucleus (IN) neural pathway. METHODS: The modeling method of myocardial ischemia reperfusion injury was achieved by ligating the left anterior descending coronary artery in Sprague-Dawley rats. We used the Powerlab multi-channel physiological recorder system to record electro-cardiograms and analyze the changes in ST segment displacement; 2,3,5-Triphenyltetrazolium chloride staining was used to observe the percentage of myocardial infarction areas. Detecting cardiac troponin I (cTnI), lactate dehydrogenase (LDH) in serum was done with an enzyme-linked immunosorbent assay kit. Morphological changes in the myocardium were detected in each group with hematoxylin-eosin staining of paraffin sections. Detection of c-fos protein expression in the PVN of the hypothalamus was done with the immune-ofluorescence method. The Plexon multi-channel acquisition system recorded PVN neuron discharges and local field potentials in each group of rats. Offline Sorter software was used for cluster analysis. Neuro Explorer software was used to perform autocorrelation, raster and frequency characteristics and spectral energy analysis of neuron signals in each group. RESULTS: Compared with the MIRI model group, the areas of myocardial infarction in the EA group were significantly reduced; the expression of cTnI, LDH in serum was decreased significantly. The firing frequency of pyramidal cells in the PVN was significantly increased and the spectrum energy map showed energy was reduced, c-fos expression in PVN was reduced, this indicated that neuronal activity in the PVN participates in the effect of EA improving myocardial injury. In addition, we used the kainic acid method to lesion the IN and observed that the effect of EA was weakened. For example, the area of myocardial infarction of lesion IN + EA group in rats was significantly increased compared with that resulting from EA group, the expression of cTnI, LDH in serum was significantly increased, the firing frequency of pyramidal cells in the PVN was significantly reduced. A spectral energy diagram shows that the energy after damage was higher than that of EA group. At the same time, the expression of c-fos in the PVN increased again. CONCLUSION: Our results indicated that the PVN-IN nerve pathway may participate as an effective pathway of EA to improve the effect of myocardial injury.
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Electroacupuntura , Infarto del Miocardio , Isquemia Miocárdica , Daño por Reperfusión Miocárdica , Puntos de Acupuntura , Animales , Humanos , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/terapia , Vías Nerviosas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: Although the gut microbiota (GM) are associated with various diseases, their role in gestational diabetes mellitus (GDM) remains uncharacterized. Further study is urgently needed to expose the real relationship between GM and GDM. METHODS: We performed a prospective study in 33 pregnant Chinese individuals [15, GDM; 18, normal glucose tolerance (NGT)] to observe the fecal microbiota by 16S rRNA gene amplicon sequencing at 24-28 weeks of gestational age after a standard 75 g oral glucose tolerance test. Linear regression analysis was employed to assess the relationships between the GM and GDM clinical parameters. RESULTS: Sequencing showed no difference in the microbiota alpha diversity but a significant difference in the beta diversity between the GDM and NGT groups, with the relative abundances of Ruminococcus bromii, Clostridium colinum, and Streptococcus infantis being higher in the GDM group (P < 0.05). The quantitative PCR results validated the putative bacterial markers of R. bromii and S. infantis. Moreover, a strong positive correlation was found between S. infantis and blood glucose levels after adjusting for body mass index (P < 0.05). CONCLUSION: Three abnormally expressed intestinal bacteria (R. bromii, C. colinum, and S. infantis) were identified in GDM patients. S. infantis may confer an increased risk of GDM. Hence, the GM may serve as a potential therapeutic target for GDM.
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Diabetes Gestacional , Microbioma Gastrointestinal/genética , Adulto , Índice de Masa Corporal , China/epidemiología , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Diabetes Gestacional/microbiología , Heces/microbiología , Femenino , Edad Gestacional , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Embarazo , Resultado del Embarazo/epidemiología , ARN Ribosómico 16S/genética , Medición de Riesgo , Factores de Riesgo , Análisis de Secuencia de ARN/métodosRESUMEN
Autoinflammatory diseases (AIDs) are a group of disorders characterized by dysfunction of innate immunity which caused by gene mutations leading to coded proteins changes, finally causing uncontrolled systemic inflammation. AIDs are a group of rare rheumatic and inflammatory diseases. Here, Chinese Rheumatology Association summarized manifestations of the main AIDs, and to standardize the methods for diagnosis of AIDs.
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Enfermedades Autoinmunes , Enfermedades Autoinflamatorias Hereditarias , Reumatología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/genética , Humanos , Inmunidad Innata , Inflamación/diagnóstico , MutaciónRESUMEN
Cisplatin chemotherapy is standard care for many cancers but is toxic to the kidneys. How this toxicity occurs is uncertain. In this study, we identified apurinic/apyrimidinic endonuclease 2 (APE2) as a critical molecule upregulated in the proximal tubule cells (PTC) following cisplatin-induced nuclear DNA and mitochondrial DNA damage in cisplatin-treated C57B6J mice. The APE2 transgenic mouse phenotype recapitulated the pathophysiological features of C-AKI (acute kidney injury, AKI) in the absence of cisplatin treatment. APE2 pulldown-MS analysis revealed that APE2 binds myosin heavy-Chain 9 (MYH9) protein in mitochondria after cisplatin treatment. Human MYH9-related disorder is caused by mutations in MYH9 that eventually lead to nephritis, macrothrombocytopenia, and deafness, a constellation of symptoms similar to the toxicity profile of cisplatin. Moreover, cisplatin-induced C-AKI was attenuated in APE2-knockout mice. Taken together, these findings suggest that cisplatin promotes AKI development by upregulating APE2, which leads to subsequent MYH9 dysfunction in PTC mitochondria due to an unrelated role of APE2 in DNA damage repair. This postulated mechanism and the availability of an engineered transgenic mouse model based on the mechanism of C-AKI provides an opportunity to identify novel targets for prophylactic treatment of this serious disease. SIGNIFICANCE: These results reveal and highlight an unexpected role of APE2 via its interaction with MYH9 and suggest that APE2 has the potential to prevent acute kidney injury in patients with cisplatin-treated cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/3/713/F1.large.jpg.
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Lesión Renal Aguda/inducido químicamente , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Endonucleasas/metabolismo , Túbulos Renales Proximales/efectos de los fármacos , Enzimas Multifuncionales/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Lesión Renal Aguda/prevención & control , Animales , Carboplatino/efectos adversos , Daño del ADN , ADN Mitocondrial/efectos de los fármacos , ADN-(Sitio Apurínico o Apirimidínico) Liasa/efectos de los fármacos , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Endonucleasas/efectos de los fármacos , Endonucleasas/genética , Pérdida Auditiva Sensorineural/inducido químicamente , Humanos , Túbulos Renales Proximales/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Enfermedades Mitocondriales/genética , Enzimas Multifuncionales/efectos de los fármacos , Enzimas Multifuncionales/genética , Mutación , Cadenas Pesadas de Miosina/genética , Nefritis/inducido químicamente , Oxaliplatino/efectos adversos , Fenotipo , Trombocitopenia/inducido químicamente , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Throughout the 5000-year history of China, more than 300 epidemics were recorded. Traditional Chinese herbal medicine (TCM) has been used effectively to combat each of these epidemics' infections, and saved many lives. To date, there are hundreds of herbal TCM formulae developed for the purpose of prevention and treatment during epidemic infections. When COVID-19 ravaged the Wuhan district in China in early January 2020, without a deep understanding about the nature of COVID-19, patients admitted to the TCM Hospital in Wuhan were immediately treated with TCM and reported later with >90% efficacy. APPROACH: We conducted conduct a systematic survey of various TCM herbal preparations used in Wuhan and to review their efficacy, according to the published clinical data; and, secondly, to find the most popular herbs used in these preparations and look into the opportunity of future research in the isolation and identification of bioactive natural products for fighting COVID-19. RESULTS: Although bioactive natural products in these herbal preparations may have direct antiviral activities, TCM employed for fighting epidemic infections was primarily based on the TCM theory of restoring the balance of the human immune system, thereby defeating the viral infection indirectly. In addition, certain TCM teachings relevant to the meridian system deserve better attention. For instance, many TCM herbal preparations target the lung meridian, which connects the lung and large intestine. This interconnection between the lung, including the upper respiratory system, and the intestine, may explain why certain TCM formulae showed excellent relief of lung congestion and diarrhea, two characteristics of COVID-19 infection. CONCLUSION: There is good reason for us to learn from ancient wisdom and accumulated clinical experience, in combination with cutting edge science and technologies, to fight with the devastating COVID-19 pandemic now and emerging new coronaviruses in the future.
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Antivirales/farmacología , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Plantas Medicinales/química , Antivirales/química , COVID-19/inmunología , China , Ensayos Clínicos como Asunto , Medicamentos Herbarios Chinos/química , Humanos , Medicina Tradicional China , SARS-CoV-2RESUMEN
High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B-cell lymphoma (Tr-iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr-iNHL meeting prespecified transplant eligibility criteria [age <75, LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) intensity front-line chemotherapy] were retrospectively identified. Non-diffuse large B-cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal-zone lymphoma and six (2%) other subtypes. Forty-nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity-score-matched cohort of 98 patients based on age, stage and high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL-DH) was generated. After a median follow-up of 3·7 (range 0·1-18·3) years, ASCT was associated with significantly superior progression-free survival [hazard ratio (HR) 0·51, 0·27-0·98; P = 0·043] with a trend towards inferior overall survival (OS; HR 2·36;0·87-6·42; P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non-ASCT cohort - 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR); 10 chimeric antigen receptor-modified T-cell (CAR-T) therapy with 6 (60%) ongoing CR; 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr-iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR-T.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Reordenamiento Génico , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B de la Zona Marginal , Linfoma Folicular , Proteínas de Neoplasias/genética , Tomografía de Emisión de Positrones , Adulto , Anciano , Autoinjertos , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B de la Zona Marginal/diagnóstico por imagen , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/mortalidad , Linfoma de Células B de la Zona Marginal/terapia , Linfoma Folicular/diagnóstico por imagen , Linfoma Folicular/genética , Linfoma Folicular/mortalidad , Linfoma Folicular/terapia , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Rituximab/administración & dosificación , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
Hyperuricemia/gout is a common metabolic disease in China, which is a serious threat to people's health. In clinical practice, the standardization of prevention and diagnosis and the rate of treat-to-target need to be improved. There is still a lack of education for the patients about the understanding of clinical guidelines, the disease knowledge and the importance of cooperating with doctors to carry out diagnosis and treatment. From the most concerned issues of the patients, we established the hyperuricemia/gout patient practice guideline working group with multidisciplinary physicians and patients. Seventeen opinions, as the hyperuricemia/gout patient practice guidelines, are proposed in accordance with the relevant principles of the "WHO guidelines development manual" , and with the international normative process, aiming to improve the patients compliance, improve the level of health management of the disease.
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Gota , Hiperuricemia , China , Gota/diagnóstico , Gota/terapia , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/terapia , Guías de Práctica Clínica como AsuntoRESUMEN
Dioxins, polybrominated diphenyl ethers, and benzo(a)pyrene are common organic pollutants in food. They have been of concern to academics and government administrations due to high residue and persistence, easy accumulation and strong harmful effects. The National Research Council of the United States of America published Toxicity Testing in the 21st Century: A Vision and Strategy in 2007, which proposed a new concept of toxicity testing that toxicity testing should take full consideration of population exposure data and base on in vitro tests, human cell lines, toxicity pathways and high-throughput screening. Meanwhile, systems biology, bioinformatics and rapid assay technologies will be used to better understand toxicity pathways-the cellular response pathways that can lead to adverse health effects when sufficient perturbing induced by chemicals exposure. The new toxicity testing strategy has changed the traditional testing pattern and has brought a wide impact on the international relevant fields. The European Union, the World Health Organization, and the United States Environmental Protection Agency, the Food and Drug Administration, and the National Center for Toxicological Research have organized relevant discussions and exploratory studies to address the new toxicity testing concept and how to evaluate and utilize the results of traditional toxicity test researches. Compared to the discussion, 'whether to do it', ten years ago, the question, 'how to do it', has become the concern of the current discussion. Therefore, how to respond to the concept of toxicity testing and how to effectively utilize and excavate traditional toxicity test data have been the focus of multi-disciplines and interdisciplinary academia such as toxicology, food hygiene and environmental science. Therefore, this article provides an overview of the exposure levels of dioxin, polybrominated diphenyl ethers and benzo[a]pyrene, which are typical persistent organic pollutants in food in China and the current research status of toxic pathways based on whole animal experiments. The exposure level, toxic effect and toxicity mechanism of three contaminants are analyzed and summarized in order to provide basis for future results based on the 21st century toxicity test compared with traditional tests and data mining analysis of these two kinds of data. Meanwhile, it also lays the foundation for the establishment of a toxicity testing framework based on exposure characteristics, toxic pathways, and biomarkers.
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Contaminantes Ambientales , Contaminación de Alimentos , Dibenzodioxinas Policloradas , Animales , China , Contaminantes Ambientales/análisis , Contaminantes Ambientales/toxicidad , Humanos , Compuestos Orgánicos/análisis , Compuestos Orgánicos/toxicidad , Dibenzodioxinas Policloradas/análisis , Dibenzodioxinas Policloradas/toxicidad , Investigación , Pruebas de ToxicidadRESUMEN
Objective: To evaluate the efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in treating moderate and severe hypertension in comparison with normal dose (10 mg) of sublingual nifedipine dripping pills. Methods: This study was designed as a randomized, double-blind, positive drug parallel controlled, multi-center, non-inferiority clinical trial. Patients with moderate and severe hypertension were enrolled by 14 clinical trial centers, randomly divided into the trial group (sublingual 5 mg nifedipine dripping pills) and the control group (sublingual 10 mg nifedipine dripping pills). The changes in blood pressure were monitored continuously within 2 hours after the initial administration, repeated the dose in 20 minutes interval after the initial administration for up to additional 3 doses (maximum 4 doses) if the antihypertensive efficacy was not satisfactory. The efficacy of antihypertensive therapy between the two groups was evaluated by repeated administration rates and blood pressure changes at 60 minutes post the initial administration, and the safety of treatment was evaluated by recording adverse event rate of the two groups. Results: The anti-hypertensive effective rates at 60 minutes after sublingual administration were 83.5% (202/242) and 86.7% (208/240) respectively between the trial group and control group (χ(2)=1.307, P=0.253) . On the aspect of antihypertensive effectiveness at 60 minutes after single dose of sublingual administration, the anti-hypertension effective rates of the trial group and the control group were 85.6% (154/180) and 87.2% (164/188) respectively (χ(2)=0.221, P=0.639). Prevalence of the repeated administration was also similar between the two groups (25.6%(62/242) in the trial group and 21.7% (52/240) in the control group, χ(2)=1.043, P=0.307). On the safety aspect, there was no adverse events/reactions in the trial group, but there were 15 cases of adverse events/reactions occurred in control group (6.25%, χ(2)=15.611, P<0.001). Conclusions: In the treatment of moderate to severe hypertension, the antihypertensive efficacy of low dose nifedipine dripping pills is similar to that of conventional dosage, and the safety profile of low dose nifedipine dripping pills is better than that of the conventional dose.
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Antihipertensivos , Hipertensión , Nifedipino , Administración Sublingual , Antihipertensivos/administración & dosificación , Presión Sanguínea , Método Doble Ciego , Humanos , Hipertensión/tratamiento farmacológico , Nifedipino/administración & dosificaciónRESUMEN
EuTiO3, a magnetic semiconductor with a simple band structure, is one of the ideal systems to control the anomalous Hall effect (AHE) by tuning the Fermi level. The electrons in the conduction bands of La-doped EuTiO3 are subject to the spin-orbit interaction and Zeeman field from the spontaneous magnetization, which generates rich structures in the electron band such as Weyl nodes. This unique property makes EuTiO3 a relatively simple multiband system with its Berry curvature being controlled by electron doping and magnetic field. We report a nonmonotonic magnetic field dependence of the anomalous Hall resistivity, which is ascribed to the change of electronic bands induced by the Zeeman splitting during the magnetization process. The anomalous Hall resistivity measurement in high-mobility films grown by gas source molecular beam epitaxy shows additional terms in the AHE during the magnetization process, which is not proportional to the magnetization. Our theoretical calculation indicates that the change of Zeeman field in the process of canting the magnetic moments causes the type II Weyl nodes in the conduction band to move, resulting in a peculiar magnetic field dependence of the AHE; this is revealed by the high-quality films with a long scattering lifetime of conduction electrons.
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Persistent chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of HBV-related diseases. The molecular mechanisms that underlie HBV infection and associated carcinogenesis are not fully understood. The aim of this study was to explore the role of ENO1 in HBV replication processes. Here, we examined ENO1 expression levels in HBV-infected and non-HBV-infected liver tissues and cells by Western blot analysis, real-time PCR and immunohistochemistry. In addition, HBsAg and HBeAg in the media of transfected HepG2.2.15 cells were detected using an electrochemical luminescence analyser within 48 hours after ENO1-specific siRNA transfection. The expression levels of HBV DNA, type I interferon and 5 downstream IFN-stimulated genes in HepG2.2.15 cells were examined using real-time PCR. We found ENO1 expression was upregulated in the HBV-infected liver tissues and cells. Silencing of ENO1 resulted in a significant reduction in HBV replication, and this siRNA-mediated reaction also caused the upregulation of expression of type I interferon and downstream IFN-stimulated genes. Therefore, we come to the conclusion ENO1 is involved in HBV replication. It is therefore likely that HBV replication is enhanced following suppression of the IFN signalling pathway. However, the mechanisms that underpin ENO1-mediated modulation of the IFN signalling pathway remain to be elucidated.
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Virus de la Hepatitis B/fisiología , Interacciones Huésped-Patógeno , Evasión Inmune , Interferón Tipo I/antagonistas & inhibidores , Fosfopiruvato Hidratasa/metabolismo , Transducción de Señal , Replicación Viral , Adulto , Western Blotting , Femenino , Perfilación de la Expresión Génica , Células Hep G2 , Hepatocitos/enzimología , Hepatocitos/virología , Humanos , Inmunohistoquímica , Hígado/enzimología , Hígado/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
NUT (nuclear protein of the testis) midline carcinoma (NMC) is a rare, poorly differentiated neoplasm with dismal prognosis. Though NMC are often metastatic by the time of presentation, cutaneous metastases have not been well described in the literature. We report a case of NMC in a patient who presented with grouped well-demarcated tender non-ulcerated erythematous nodules on the right mid-back. The lesions were initially diagnosed and treated as herpes zoster. Following failure to improve with antiviral therapy, imaging and skin biopsy revealed that the lesions were in fact cutaneous NUT carcinoma. Although NMC is an uncommon diagnosis, clinicians should be aware that affected patients can develop skin involvement to avoid unnecessary and harmful treatments.
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Previous studies have indicated that schizophrenia is linked to abnormal lipid metabolism. Free fatty acids (FFAs) in peripheral blood can reflect the status of lipid metabolism in human body. The purpose of this study was to scan the FFA pattern and elucidate the characteristics of lipid metabolic abnormality in schizophrenia patients. One hundred and ten patients with schizophrenia (SCZs) and 109 healthy controls (HCs) were included in the study and divided into a discovery set and a validation set. Forty-seven serum FFAs were detected by UPLC-QTOF-MS and 39 of them were absolutely quantified by establishing standard curves. Monounsaturated fatty acids (MUFAs) and ω-6 polyunsaturated fatty acids (ω-6 PUFAs) were significantly increased in SCZs compared with HCs. Desaturation from saturated fatty acids to MUFAs and ß-oxidation were enhanced, as estimated by the ratios of products to precursors. These results suggest that lipolysis and ß-oxidation are upregulated in SCZ, presumably resulting from insufficient brain energy supply.
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Ácidos Grasos no Esterificados/sangre , Metabolismo de los Lípidos , Esquizofrenia/sangre , Adulto , Femenino , Humanos , Masculino , MetabolómicaRESUMEN
Objective The objective is to perform a comprehensive review of the literature up to 2015 on the genetics and precision medicine relevant to otitis media. Data Sources PubMed database of the National Library of Medicine. Review Methods Two subpanels were formed comprising experts in the genetics and precision medicine of otitis media. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a merged draft was created. The entire panel met at the 18th International Symposium on Recent Advances in Otitis Media in June 2015 and discussed the review and refined the content. A final draft was made, circulated, and approved by the panel members. Conclusion Many genes relevant to otitis media have been identified in the last 4 years in advancing our knowledge regarding the predisposition of the middle ear mucosa to commensals and pathogens. Advances include mutant animal models and clinical studies. Many signaling pathways are involved in the predisposition of otitis media. Implications for Practice New knowledge on the genetic background relevant to otitis media forms a basis of novel potential interventions, including potential new ways to treat otitis media.
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Otitis Media/genética , Medicina de Precisión , Animales , Congresos como Asunto , Ligamiento Genético , Humanos , MutaciónRESUMEN
Curcumin (Cur) is a strong natural antioxidant, who can prevent multiple diseases such as anti-cancer, anti-inflammatory, have a resistance to alzheimer's disease and various malignant diseases. But it has poor oral bioavailability due to its poor aqueous solubility, as well as instability. While its novel derivatives (CB and FE), showed better anti-tumor activity, better anti-oxidant activity and better stability than the original drug (Cur). The aim of this study was to study the intestinal transport of Cur, CB and FE using an in vitro Caco-2 cell monolayer model. The results showed that Cur had a lower permeability coefficient (1.13×10-6±0.11×10-6cm/s) for apical-to-basolated (AP-BL) transport at 25µM, while the transport rate for AP to BL flux of CB (3.18×10-6±0.31×10-6cm/s) and FE (5.28×10-6±0.83×10-6cm/s) were significantly greater than that of Cur. The efflux ratio (ER) value at the concentration of 25µM was 1.31 for Cur, 1.26 for CB and 1.33 for FE, suggesting there was no active efflux involved in the translocation across the Caco-2 cell monolayers for the three compounds. Furthermore, the transport flux of CB and FE was in a concentration dependent manner, suggesting the intestinal transport mechanism in them was passive transport. In summary, the results demonstrated that both the intestinal permeability of CB and FE across Caco-2 cell monolayers was significantly improved compare to Cur. Thus they might show a higher oral bioavailability in vivo, and show the potential application in clinic or nutraceutical.
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Permeabilidad de la Membrana Celular/fisiología , Curcumina/química , Curcumina/metabolismo , Absorción Intestinal/fisiología , Antineoplásicos/química , Antineoplásicos/metabolismo , Transporte Biológico/fisiología , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , HumanosRESUMEN
Usher syndrome (USH) is the most common cause of inherited deaf-blindness, manifested as USH1, USH2 and USH3 clinical types. The protein products of USH2 causative and modifier genes, USH2A, ADGRV1, WHRN and PDZD7, interact to assemble a multiprotein complex at the ankle link region of the mechanosensitive stereociliary bundle in hair cells. Defects in this complex cause stereociliary bundle disorganization and hearing loss. The four USH2 proteins also interact in vitro with USH1 proteins including myosin VIIa, USH1G (SANS), CIB2 and harmonin. However, it is unclear whether the interactions between USH1 and USH2 proteins occur in vivo and whether USH1 proteins play a role in USH2 complex assembly in hair cells. In this study, we identified a novel interaction between myosin VIIa and PDZD7 by FLAG pull-down assay. We further investigated the role of the above-mentioned four USH1 proteins in the cochlear USH2 complex assembly using USH1 mutant mice. We showed that only myosin VIIa is indispensable for USH2 complex assembly at ankle links, indicating the potential transport and/or anchoring role of myosin VIIa for USH2 proteins in hair cells. However, myosin VIIa is not required for USH2 complex assembly in photoreceptors. We further showed that, while PDZ protein harmonin is not involved, its paralogous USH2 proteins, PDZD7 and whirlin, function synergistically in USH2 complex assembly in cochlear hair cells. In summary, our studies provide novel insight into the functional relationship between USH1 and USH2 proteins in the cochlea and the retina as well as the disease mechanisms underlying USH1 and USH2.
Asunto(s)
Proteínas Portadoras/genética , Proteínas de la Matriz Extracelular/genética , Miosinas/genética , Síndromes de Usher/genética , Animales , Proteínas Portadoras/química , Proteínas de Ciclo Celular , Proteínas del Citoesqueleto , Proteínas de la Matriz Extracelular/química , Células Ciliadas Auditivas/patología , Humanos , Ratones , Complejos Multiproteicos/química , Complejos Multiproteicos/genética , Miosina VIIa , Miosinas/química , Dominios PDZ/genética , Retina/metabolismo , Retina/patología , Estereocilios/genética , Estereocilios/metabolismo , Estereocilios/patología , Síndromes de Usher/patologíaRESUMEN
Pyogenic liver abscess (PLA) is a potentially life-threatening disease in many parts of the world, especially in Asia. The aim of this study was to quantify the proportion of common pathogens in patients with PLA in China, using a meta-analysis method based on systematic review of published studies. Several electronic databases were searched to identify the studies reporting the pathogens of PLA. We performed a meta-analysis to calculate the pooled proportion of pathogens and subgroup analysis among the included studies using R 3.1.1 software. In total, 183 studies were included in our final analysis, Klebsiella spp (54 %), Escherichia spp (29 %), Enterobacter spp (9 %), Proteus spp (6 %) and Pseudomonas spp (5 %) comprised the major gram-negative bacteria. Gram-positive bacteria mainly included Staphylococcus spp (13 %), Streptococcus spp (8 %) and Enterococcus spp (7 %). The distribution of pathogens in PLA patients were different in different economic regions in China. The proportion of Klebsiella spp had an upward tendency in recent years compared to other pathogens. In addition, the proportion of common pathogens in PLA patients with diabetes mellitus (DM) were carried out indicating that the dominant pathogens were Klebsiella spp (66 %), Escherichia spp (21 %) and Enterobacter spp (11 %). This meta-analysis showed that the main pathogens of PLA were Klebsiella spp, Escherichia spp, Staphylococcus spp, and Enterobacter spp in China. To ensure a precise estimate of the epidemiology of the pathogens, further large-scale or even a population-based study is needed.