Controversias Diagnósticas en la Clasificación Internacional de las Cefaleas, III Edición / Diagnostic controversies on the International Classifica tion of Headaches Disorders, III Edition

Resumen La revisión consideró los puntos de conflicto que pue dan llevar a confusión en el uso diario de la clasificación internacional de las cefaleas (ICHD-III). Se evaluaron tanto las controversias al momento de confeccionar los criterios como las superposiciones producidas tras su utilización en la práctica diaria, argumentado a través de bibliografía científica. Como puntos relevantes, la anamnesis de un paciente con cefalea debe indicar la intensidad del dolor como así también la duración del episodio doloroso y si su localización es estrictamente unilateral. Estos puntos podrán ser de ayuda en los casos de dolor moderado que no cumplan en forma absoluta los criterios para ninguna de las cefaleas primarias, dilema frecuente en la práctica diaria.

Abstract The review considered points of conflict that may lead to confusion in the daily use of the International Classification of Headache Disorders (ICHD-III). Both the controversies at the time of preparing the criteria and the overlaps produced after their use in daily practice were evaluated, argued through scientific bib liography. As relevant points, the anamnesis of a patient with headache should indicate the intensity of the pain as well as the duration of the painful episode and if its location is strictly unilateral. These points may be help ful in cases of moderate pain that do not fully meet the criteria for any of the primary headaches, a frequent dilemma in daily practice.

Recent applications and chiral separation development based on stationary phases in open tubular capillary electrochromatography(2019-2022) / 药物分析学报

Capillary electrochromatography(CEC)plays a significant role in chiral separation via the double sepa-ration principle,partition coefficient difference between the two phases,and electroosmotic flow-driven separation.Given the distinct properties of the inner wall stationary phase(SP),the separation ability of each SP differs from one another.Particularly,it provides large room for promising applications of open tubular capillary electrochromatography(OT-CEC).We divided the OT-CEC SPs developed over the past four years into six types:ionic liquids,nanoparticle materials,microporous materials,biomaterials,non-nanopolymers,and others,to mainly introduce their characteristics in chiral drug separation.There also added a few classic SPs that occurred within ten years as supplements to enrich the features of each SP.Additionally,we discuss their applications in metabolomics,food,cosmetics,environment,and biology as analytes in addition to chiral drugs.OT-CEC plays an increasingly significant role in chiral separation and may promote the development of capillary electrophoresis(CE)combined with other instruments in recent years,such as CE with mass spectrometry(CE/MS)and CE with ultraviolet light detector(CE/UV).

Quantitative estimation of enzymatic released specific oligosaccharides from Hericium erinaceus polysaccharides using CE-LIF / 药物分析学报

Polysaccharides exhibit multiple pharmacological activities which are closely related to their structural features.Therefore,quantitatively quality control of polysaccharides based on their chemical charac-teristics is important for their application in biomedical and functional food sciences.However,poly-saccharides are mixed macromolecular compounds that are difficult to isolate and lack standards,making them challenging to quantify directly.In this study,we proposed an improved saccharide mapping method based on the release of specific oligosaccharides for the assessment of Hericium eri-naceus polysaccharides from laboratory cultured and different regions of China.Briefly,a polysaccharide from H.erinaceus was digested by β-(1-3)-glucanase,and the released specific oligosaccharides were labeled with 8-aminopyrene-1,3,6-trisulfonic-acid(APTS)and separated by using micellar electrokinetic chromatography(MEKC)coupled with laser induced fluorescence(LIF),and quantitatively estimated.MEKC presented higher resolution compared to polysaccharide analysis using carbohydrate gel elec-trophoresis(PACE),and provided great peak capacity between oligosaccharides with polymerization degree of 2(DP2)and polymerization degree of 6(DP6)in a dextran ladder separation.The results of high performance size exclusion chromatography coupled with multi-angle laser light scattering and refractive index detector(HPSEC-MALLS-RI)showed that 12 h was sufficient for complete digestion of polysaccharides from H.erinaceus.Laminaritriose(DP3)was used as an internal standard for quantifi-cation of all the oligosaccharides.The calibration curve for DP3 showed a good linear regression(R2＞0.9988).The limit of detection(LOD)and limit of quantification(LOQ)values were 0.05 μg/mL and 0.2 μg/mL,respectively.The recovery for DP3 was 87.32(±0.03)％in the three independent injections.To sum up,this proposed method is helpful for improving the quality control of polysaccharides from H.erinaceus as well as other materials.

Prevalência de enteroparasitas em crianças atendidas pelas unidades básicas de saúde do município de Fortaleza, Ceará / Prevalence of enteroparasites in children attending basic health units in the municipality of Fortaleza, Ceará / Prevalencia de enteroparasitosis en niños atendidos en unidades básicas de salud del municipio de Fortaleza, Ceará

As Enteroparasitoses são um problema socioeconômico de países subdesenvolvidos que atingem principalmente crianças, sendo um grupo de maior propensão a exposição a ambientes contaminados. Diante disso, o objetivo desse estudo foi verificar a prevalência de enteroparasitoses em crianças atendidas pelas unidades básicas de saúde de Fortaleza, Ceará, a fim de contribuir para o desenvolvimento de medidas preventivas e terapêuticas mais eficazes para o controle dessas infecções e na saúde da população. Para isso, foram utilizadas para a análise 76 amostras fecais de crianças de 1 a 15 anos, atendidas pelas unidades básicas de saúde do município, adotando a técnica de sedimentação espontânea em água, conforme descrita por Hoffman, Pons e Janer (1934). A prevalência geral de enteroparasitas, parasitas e protozoários, foi de 51,3% na população estudada. Dentre os parasitas encontrados, os protozoários mais frequentes foram: Blastocystis hominis (55,1%) seguido de Giardia lamblia (12,2%) e Entamoeba coli (12,2%). Já os parasitas helmintos, houve ocorrência de Ascaris lumbricoides (6%) e Enterobius vermicularis (2%). Com base nos resultados obtidos, pode-se concluir que a população de crianças estudada apresentou uma alta taxa de infecção por enteroparasitas, com predomínio de protozoários intestinais. Esses achados reforçam a importância da implementação de medidas preventivas e melhoria das condições higiênico-sanitárias para o controle dessas infecções e na promoção da saúde da população.

Enteroparasitoses are a socioeconomic problem in underdeveloped countries that mainly affect children, a group with a higher propensity to be exposed to contaminated environments. Therefore, the aim of this study was to verify the prevalence of enteroparasitoses in children attending basic health units in Fortaleza, Ceará, in order to contribute to the development of more effective preventive and therapeutic measures for the control of these infections and the health of the population. For this purpose, 76 fecal samples from children from 1 to 15 years old, attended in basic health units of the city were used for analysis, adopting the technique of spontaneous sedimentation in water, as described by Hoffman, Pons and Janer (1934). The overall prevalence of enteroparasites, parasites and protozoa, was 51.3% in the studied population. Among the parasites found, the most frequent protozoans were: Blastocystis hominis (55.1%) followed by Giardia lamblia (12.2%) and Entamoeba coli (12.2%). As for the helminth parasites, there were Ascaris lumbricoides (6%) and Enterobius vermicularis (2%). Based on the results obtained, it can be concluded that the population of children studied presented a high rate of infection by enteroparasites, with a predominance of intestinal protozoa. These findings reinforce the importance of implementing preventive measures and improving the hygienic-sanitary conditions for the control of these infections and in promoting the health of the population.

Las enteroparasitosis son un problema socioeconómico en los países subdesarrollados que afecta principalmente a los niños, grupo con mayor propensión a estar expuesto a ambientes contaminados. Por lo tanto, el objetivo de este estudio fue verificar la prevalencia de enteroparasitosis en niños que asisten a unidades básicas de salud en Fortaleza, Ceará, con el fin de contribuir al desarrollo de medidas preventivas y terapéuticas más eficaces para el control de estas infecciones y la salud de la población. Para ello, se utilizaron para el análisis 76 muestras fecales de niños de 1 a 15 años, atendidos en unidades básicas de salud de la ciudad, adoptando la técnica de sedimentación espontánea en agua, descrita por Hoffman, Pons y Janer (1934). La prevalencia global de enteroparásitos, parásitos y protozoos, fue de 51,3% en la población estudiada. Entre los parásitos encontrados, los protozoos más frecuentes fueron: Blastocystis hominis (55,1%), seguido de Giardia lamblia (12,2%) y Entamoeba coli (12,2%). En cuanto a los helmintos parásitos, había Ascaris lumbricoides (6%) y Enterobius vermicularis (2%). En base a los resultados obtenidos, se puede concluir que la población infantil estudiada presenta una elevada tasa de infección por enteroparásitos, con predominio de protozoos intestinales. Estos hallazgos refuerzan la importancia de implementar medidas preventivas y mejorar las condiciones higiénico-sanitarias para el control de estas infecciones y en la promoción de la salud de la población.

La Paz entre judíos y cristianos. El aporte de Juan Pablo II, a la paz interreligiosa en el siglo xx / Peace between Jews and Christians. John Paul II's Contribution to Interreligious Peace in the 20th Century

Resumen Juan Pablo II no sólo expresó sus ideas políticas y sociales a través de Encíclicas y discursos, sino también a través de la diplomacia y diversas acciones cargadas de simbolismo. Acciones que tuvieron por objetivo mostrar como ejemplo a los pertenecientes de ambas religiones, la paz subyacente entre sus líderes religio sos. De lo anterior, aunque muchos datos biográficos y logros han sido tenidos en cuenta por los biógrafos de Wojtyla, el acercamiento generado entre cristia nos y judíos es quizás uno de los puntos menos profundizados en las reflexiones históricas sobre la labor de Wojtyla.

Abstract Not only did John Paul II express his political and social ideas through Encycli cals and speeches, but also through diplomacy and various actions loaded with symbolism. These actions were aimed at showing as an example to the mem bers of both religions, the underlying peace between their religious leaders. From the above, although many biographical data and achievements have been taken into account by Wojtyla's biographers, the rapprochement generated be tween Christians and Jews is perhaps one of the least deepened points in the historical reflections on Wojtyla's work.

Causa rara de parada cardíaca: um caso de extensa dissecção espontânea da artéria coronária esquerda / A rare cause of cardiac arrest: a case of an extensive left coronary artery spontaneous dissection

Um homem de 28 anos com história pregressa de abuso de drogas foi encaminhado para coronariografia de emergência após parada cardíaca. O eletrocardiograma pós-ressuscitação mostrou elevação do segmento ST em V1-V4. A angiografia mostrou dissecção espontânea da artéria coronária, multiarterial e em diversos segmentos. Devido à instabilidade clínica, o paciente foi submetido à intervenção coronária percutânea da artéria descendente anterior. A prevalência da dissecção espontânea da artéria coronária como causa de síndrome coronariana aguda em homens é infrequente. No entanto, nos casos suspeitos, ela deve ser excluída. A parada cardiorrespiratória é um quadro incomum na dissecção espontânea da artéria coronária, e a intervenção coronária percutânea como modalidade terapêutica ainda é uma questão em debate.

A 28-year-old male with a previous history of drug abuse was sent to an emergent coronary angiography, after a cardiac arrest, with a post-resuscitation eletrocardiogram showing ST- segment elevation from V1-V4. Angiography showed multivessel and multisegment spontaneous coronary artery dissection. Due to clinical instability, patient underwent left anterior descending artery percutaneous coronary intervention. Prevalence of spontaneous coronary artery dissection as the cause of acute coronary syndrome is anecdotal in men. Yet, in the right scenarios as in this case, it must be ruled out. Cardiorespiratory arrest is an uncommon presentation of spontaneous coronary artery dissection and percutaneous coronary intervention in spontaneous coronary artery dissection is still a matter of debate.

Review of international experience about the adjustment procedure of essential medicine list / 中国药房

In order to further consolidate the national essential medicine system and establish and improve the selection and adjustment mechanism of the national essential medicine list ，the Department of Drug Policy and Essential Medicine of the National Health Commission of the People ’s Republic of China recently has issued the Measures for the Administration of the National Essential Medicine List （Revised Draft ）. Under the background that China is in a critical period of improving the management procedures for the adjustment of the essential medicines list ，how to better design the adjustment procedure ，clarify the operation process and material requirements of each link ，ensure social participation and improve work transparency are important problems to be solved. By consulting the official websites of World Health Organization （WHO）and some typical countries with essential medicine system as well as related foreign literature ，the advanced practices of WHO and some typical countries in the adjustment procedures of the essential medicine list were summarized from 6 stages，such as start-up stage ，the material collection and summary stage ，the evaluation stage ，result publicity stage ，relief stage and application and promotion stage. It is suggested that China can learn from the relevant successful international experience ，scientifically set the adjustment cycle ，establish a normalized feedback mechanism with multi-agent participation ，design a standardized material collection process and a scientific and efficient evaluation process ，and improve the transparency and social identity of the publicity of the selection results of essential medicines ， so as to build a more scientific and perfect adjustment procedure of essential medicine list.

Investigation of two types of portable γ spectrometer applicability for measurement of thyroid 131I activity and internal doses to radiation workers / 中华放射医学与防护杂志

Objective:To investigate the differences in applicability of both the portable high-purity germanium (HPGe) γ spectrometer and the portable lanthanum bromide (LaBr) γ spectrometer for measuring thyroid 131I activity and internal exposure monitoring for radiation workers. Method:Both DETECTIVE-DX100-KT portable HPGe γ spectrometer and InSpector 1000 portable LaBr γ spectrometer were used to measure the 131I content in thyroid of radiation workers for comparison of the measuring result, minimum detectable activity (MDA) and corresponding annual committed effective doses between two types of spectrometers. Results:The detection rate of 131I in thyroid of radiation workers was 67.7% for HPGe γ spectrometer and 26.2% for LaBr γ spectrometer, respectively. The MDA was 12.26-14.74 Bq (measuring time: 3-5 min) for HPGe γ spectrometer and 56.56-80.37 Bq for LaBr γ spectrometer (measuring time: 2-4 min). The annual committed effective dose corresponding to MDA was 0.07-0.08 mSv (3-5 min) for HPGe and 0.31-0.45 mSv (2-4 min) for LaBr, respectively, in the case of using chronic continuous intake mode and 7 d monitoring period. Conclusions:The minimum detectable activity (MDA) of the two types of portable spectrometers could meet the requirements specified in GBZ 129-2016 Specifications for individual monitoring of occupational internal exposure for thyroid monitoring equipment. The two types of spectrometers could be used for routine monitoring of internal contamination. The difference between the monitoring result of LaBr γ and HPGe γ spectrometers might be due to such factors as large uncertainty in short measuring time and low activity concentrations, incomplete identical of distance between probe and neck, probe angle setting, different response of equipment to the environment, background deduction method.

Estudo do efeito de estatinas e antiplaquetários na evolução do infarto agudo do miocárdio: uma abordagem metabolômica multiplataform / Effect of statins and antiplatelets in the evolution of acute myocardium infarction: a multiplatform metabolomics approach

O infarto agudo do miocárdio (IAM) é a maior causa de mortalidade no mundo. A oclusão coronária determina a necrose completa de cardiomiócitos (células musculares cardíacas) durante as primeiras horas do IAM. Porém, mesmo após a perda de massa de miocárdio viável cessar, a região infartada pode se expandir ou contrair no decorrer das primeiras semanas, afetando o prognóstico dos pacientes. Alguns tratamentos podem auxiliar na recuperação e melhoria do prognóstico desses pacientes, como o uso de estatinas e antiplaquetários, que quando utilizados em conjunto, proporcionam efeitos sinérgicos. O presente estudo investigou e comparou, através da óptica da metabolômica global multiplataforma, tratamentos concomitantes de estatinas (sinvastatina ou rosuvastatina) e antiplaquetários bloqueadores do receptor de ADP (clopidogrel ou ticagrelor), em pacientes que sofreram IAM. Foram coletadas amostras de plasma e urina de cerca 40 pacientes tratados com clopidrogrel e sinvastatina ou ticagrelor e rosuvastatina no Hospital São Paulo em diferentes períodos (basal, 1 mês e 6 meses após IAM). Amostras de plasma (basal e 1 mês) foram analisadas por RPLC-MS nos modos de ionização positivo e negativo, GC-MS e CEMS. Amostras de urina (basal, 1 mês e 6 meses) foram analisadas por RPLC-MS no modo de ionização positivo e HILIC-MS nos modos de ionização positivo e negativo. A abordagem metabolomica global multiplataforma evidenciou alterações no metabolismo de diferentes vias pelos dois tratamentos. Os dois tratamentos proporcionaram um efeito pronunciado no metabolismo de diferentes lipídios, como glicerolipídios, esfingolipídios, glicerofosfolipídios e ácidos graxos, sendo que a combinação rosuvastatina e ticagrelor resultou num efeito mais acentuado. Já o tratamento com clopidogrel e sinvastatina alterou de maneira mais pronunciada o metabolismo de aminoácidos ramificados e de acilcarnitinas de cadeia curta. Observou-se ainda a alteração de possíveis biomarcadores relatados na literatura como associados a problemas cardiovasculares, como hipoxantina, ácido 2-hidroxibutírico, algumas espécies de ceramidas, fosfatidilcolinas e acilcarnitinas de cadeia curta

cute myocardium infarction (AMI) is the main mortality cause in the world. The coronary occlusion determines the complete necrosis of cardiomyocytes (cardiac muscle cells) during the first hours of AMI. However, even after the loss of viable myocardial mass ceases, the infarcted area may still expand or contract during the first weeks after AMI, affecting the patient prognosis. Some treatments may assist patient recovery and improve prognostic, such as statins and antiplatelets which, when combined, provide synergic effects. This study investigated and compared, by untargeted multiplatform metabolomics, simultaneous treatments of statins (simvastatin or rosuvastatin) and ADP receptor antagonist antiplatelets (clopidogrel or ticagrelor) in patients that suffered AMI. Plasma and urine samples from around 40 patients treated with clopidogrel and simvastatin or ticagrelor and rosuvastatin were collected in Hospital Sao Paulo at different time points (basal, 1 month, 6 months after AMI). Plasma samples (basal and 1 month) were analyzed by RPLC-MS in positive and negative ionization modes, GC-MS and CE-MS. Urine samples (basal, 1 month, 6 months) were analyzed by RPLC-MS in positive ionization mode and by HILIC-MS in positive and negative ionization modes. The untargeted multiplatform metabolomics approach has shown that different metabolic pathways have been altered by the two treatments. Both treatments had a profound impact on the metabolism of different lipids, such as glycerolipids, sphingolipids, glycerophospholipids, and fatty acids. However, the combined treatment using rosuvastatin and ticagrelor impacted the most the lipid pathways. On the other hand, clopidogrel and simvastatin treatment affected more intensily the branched chain amino acids and short chain acylcarnitines metabolisms. Reported biomarkers in the literature related to cardiovascular diseases were also observed in this study, such as hypoxanthine, 2-hydroxybutyric acid, some species of ceramides, phosphatidylcholines and short chain acylcarnitines

Identification of pregnant women with DFR genotype and discussion of prenatal examination strategy / 中国输血杂志

【Objective】 To identify three cases of pregnant women with the D variant phenotype using serological and molecular tests, and discuss the strategy of prenatal examination. 【Methods】 The peripheral blood samples from three pregnant women with the D variant phenotype were collected. RhD variant phenotype was determined using routine serological methods with two different kinds of monoclonal anti-D. The serological characteristic for the epitope of D antigen was further analyzed using the commercial panel anti-D reagents (D-Screen, Diagast). The hybrid RHD-CE-D allele was analyzed by the Multiplex Ligation-dependent Probe Amplification (MLPA) assay and polymerase chain reaction with sequence specific primers (PCR-SSP) method. Further Sanger sequencing of RHD gene exons was also performed. 【Results】 DFR phenotype was primarily determined by serological characteristic for the epitope of D antigen. RHD*DFR2/01N.01(n=2) and RHD*DFR1/1227A(n=1) genotypes were identified by the MLPA assay, PCR-SSP and Sanger sequencing. 【Conclusion】 Two pregnant women with RHD*DFR2/01N.01 genotype should be treated as D negative patients clinically, while the pregnant woman with RHD*DFR1/1227A genotype can be treated as Asia type DEL to avoid unnecessary antibody screening and anti-D prophylaxis.

Plano nacional de vacinação contra a COVID-19: uso de inteligência artificial espacial para superação de desafios / National COVID-19 vaccination plan: using artificial spatial intelligence to overcome challenges in Brazil

Resumo O objetivo deste artigo é analisar o uso da inteligência artificial espacial no contexto da imunização contra COVID-19 para a seleção adequada dos recursos necessários. Trata-se de estudo ecológico de caráter transversal baseado em uma abordagem espaço-temporal utilizando dados secundários, em Unidades Básicas de Saúde do Brasil. Foram adotados quatro passos analíticos para atribuir um volume de população por unidade básica, aplicando algoritmos de inteligência artificial a imagens de satélite. Em paralelo, as condições de acesso à internet móvel e o mapeamento de tendências espaço-temporais de casos graves de COVID-19 foram utilizados para caracterizar cada município do país. Cerca de 18% da população idosa brasileira está a mais de 4 quilômetros de distância de uma sala de vacina. No total, 4.790 municípios apresentaram tendência de agudização de casos de Síndrome Respiratória Aguda Grave. As regiões Norte e Nordeste apresentaram o maior número de Unidades Básicas de Saúde com mais de 5 quilômetros de distância de antenas de celular. O Plano nacional de vacinação requer o uso de estratégias inovadoras para contornar os desafios do país. O uso de metodologias baseadas em inteligência artificial espacial pode contribuir para melhoria do planejamento das ações de resposta à COVID-19.

Abstract This article explores the use of spatial artificial intelligence to estimate the resources needed to implement Brazil's COVID-19 immu nization campaign. Using secondary data, we conducted a cross-sectional ecological study adop ting a time-series design. The unit of analysis was Brazil's primary care centers (PCCs). A four-step analysis was performed to estimate the popula tion in PCC catchment areas using artificial in telligence algorithms and satellite imagery. We also assessed internet access in each PCC and con ducted a space-time cluster analysis of trends in cases of SARS linked to COVID-19 at municipal level. Around 18% of Brazil's elderly population live more than 4 kilometer from a vaccination point. A total of 4,790 municipalities showed an upward trend in SARS cases. The number of PCCs located more than 5 kilometer from cell towers was largest in the North and Northeast regions. Innovative stra tegies are needed to address the challenges posed by the implementation of the country's National COVID-19 Vaccination Plan. The use of spatial artificial intelligence-based methodologies can help improve the country's COVID-19 response.

Diseño y validación de un ensayo de minisecuenciación múltiple para detectar polimorfismos asociados con Síndrome Metabólico / Design and validation of a multiple minisequencing assay to detect polymorphisms associated with Metabolic Syndrome

Resumen Introducción: Es importante identificar los polimorfismos de interés clínico en patologías complejas como el Síndrome Metabólico. Por esto, las metodologías para su evaluación deben estar diseñadas y validadas correctamente, esto permite optimizar recursos y tiempo en la genotipificación y detección correcta de los alelos presentes en los individuos. Objetivo: Diseñar y validar una PCR múltiple, seguida de detección por minisecuenciación, para la genotipificación de ocho polimorfismos de nucleótido simple ubicados en el gen del Receptor Beta 3-Adrenérgico (rs4994 y rs4998), gen de la Apolipoproteina A5 (rs3135506 y rs2075291), gen de la Adiponectina (rs1501299 y rs2241766) y gen del Receptor Activador de la Proliferación de los Peroxisomas tipo gamma (rs1801282 y rs1800571), asociados con el síndrome metabólico. Materiales y métodos: Se diseñaron 24 cebadores para la amplificación y detección de ocho polimorfismos de nucleótido sencillo ubicados en cuatro genes candidatos a estar asociados con el síndrome metabólico, usando el software Primer3®. Dieciséis fueron diseñados para amplificar los polimorfismos y ocho para detectarlos por minisecuenciación. Las estructuras secundarias entre los cebadores se verificaron con el software Autodimer. Los polimorfismos se amplificaron simultáneamente y los fragmentos amplificados se acoplaron a las sondas diseñadas para detectar por minisecuenciación el alelo presente, por medio de bases marcadas con fluorocromos. Finalmente, los alelos fueron detectados por electroforesis capilar en un analizador genético ABI 310 y se interpretaron con el software GeneMapper®. La validación del multiplex se realizó genotipando 20 muestras de individuos, cada uno de ellos autorizó este procedimiento por medio del consentimiento informado. Resultados: Se obtuvieron los perfiles genéticos de los 20 controles genotipados, a partir de la amplificación múltiple, seguida de minisecuenciación, diseñada y validada para detectar los ocho polimorfismos. Conclusión: Se diseñó y validó un ensayo para la detección simultánea de los polimorfismos, ubicados en cuatro genes asociados con el Síndrome metabólico. Los cuales pueden ser empleados como referencia para futuros estudios poblacionales.

Abstract Introduction: It is important to identify the polymorphisms of clinical interest in complex pathologies such as Metabolic Syndrome. Therefore, the methodologies for its evaluation must be designed and validated correctly, this permits optimization of resources and time in genotyping and correct detection of the alleles present in individuals. Objective: To design and validate a multiplex PCR, followed by detection by minisequencing, for the genotyping of eight single nucleotide polymorphisms located in the Beta 3-Adrenergic Receptor gene (rs4994 and rs4998), Apolipoprotein A5 gene (rs3135506 and rs2075291), Adiponectin gene (rs1501299 and rs2241766) and gamma-type Peroxisome Proliferation Activating Receptor gene (rs1801282 and rs1800571), associated with metabolic syndrome. Materials and methods: Twenty-four primers were designed for the amplification and detection of eight single nucleotide polymorphisms located in four candidate genes to be associated with the metabolic syndrome, using the Primer3® software. Sixteen were designed to amplify the polymorphisms and eight to detect them by minisequencing. The secondary structures between the primers were verified with Autodimer software. The polymorphisms were simultaneously amplified, and the amplified fragments were coupled to probes designed to minisequence the present allele using fluorochrome-labeled bases. Finally, the alleles were detected by capillary electrophoresis using an ABI 310 genetic analyzer and analyzed with the GeneMapper® software. The validation of the multiplex was performed by genotyping 20 individual samples, each of them authorized this procedure through informed consent. Results: The genetic profiles of the 20 genotyped controls were obtained, from multiple amplification, followed by minisequencing, designed and validated to detect the eight polymorphisms. Conclusion: An essay was designed and validated for the simultaneous detection of polymorphisms, located in four genes associated with metabolic syndrome, and can used as a reference for future population studies.

Insight into chemical basis of traditional Chinese medicine based on the state-of-the-art techniques of liquid chromatography-mass spectrometry

Traditional Chinese medicine (TCM) has been an indispensable source of drugs for curing various human diseases. However, the inherent chemical diversity and complexity of TCM restricted the safety and efficacy of its usage. Over the past few decades, the combination of liquid chromatography with mass spectrometry has contributed greatly to the TCM qualitative analysis. And novel approaches have been continuously introduced to improve the analytical performance, including both the data acquisition methods to generate a large and informative dataset, and the data post-processing tools to extract the structure-related MS information. Furthermore, the fast-developing computer techniques and big data analytics have markedly enriched the data processing tools, bringing benefits of high efficiency and accuracy. To provide an up-to-date review of the latest techniques on the TCM qualitative analysis, multiple data-independent acquisition methods and data-dependent acquisition methods (precursor ion list, dynamic exclusion, mass tag, precursor ion scan, neutral loss scan, and multiple reaction monitoring) and post-processing techniques (mass defect filtering, diagnostic ion filtering, neutral loss filtering, mass spectral trees similarity filter, molecular networking, statistical analysis, database matching, etc.) were summarized and categorized. Applications of each technique and integrated analytical strategies were highlighted, discussion and future perspectives were proposed as well.

Spectrum-effect relationship of the blood-activating efficacy of Notoginseng Radix et Rhizoma / 中国中药杂志

This study aims to establish the high-performance liquid chromatography(HPLC) fingerprints of different batches of Notoginseng Radix et Rhizoma, determine their pharmacodynamic indexes of promoting blood circulation, and explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the efficacy of promoting blood circulation. Firstly, the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma were established. Then, the pharmacodynamic indexes were determined after the capillary coagulation experiment and the cerebral ischemia-reperfusion in rats, including capillary coagulation time, percentage of cerebral ischemic area, cerebral water loss rate, and brain-body index. Afterward, the partial least-squares method was used to explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the pharmacodynamic indexes. The results showed that this study successfully established the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma, found 23 common peaks, and identified 12 of them, all of which were saponins. The method was proved stable and reliable. Both the capillary coagulation experiment and the middle cerebral artery occlusion(MCAO)-induced cerebral ischemia-reperfusion experiment on rats revealed that there were obvious differences in the pharmacodynamic indexes of different batches of Notoginseng Radix et Rhizoma. The relationships between 23 common components of Notoginseng Radix et Rhizoma in different batches and the pharmacodynamic indexes were discussed by means of spectrum-effect correlation analysis, of which 17 components had positive effects while 6 components had negative effects on the pharmacodynamic indexes. This study provides a certain reference basis for the clinical rational use and quality control of Notoginseng Radix et Rhizoma.

Factores en el pronóstico de mortalidad en pacientes con hemorragia intracerebral espontánea / Prognostic factors of mortality rate in patients with spontaneous intracerebral hemorrhage

RESUMEN Introducción: la hemorragia intracerebral espontánea se considera, entre todos los ictus, el efecto más devastador, la mortalidad mensual estimada, oscila entre el 35 y el 52 %. Objetivo: determinar los factores que influyen en la mortalidad, a los 30 días, en pacientes con hemorragia intracerebral espontánea. Métodos: se realizó un estudio observacional analítico transversal en el Hospital Dr. Carlos Juan Finlay, en un periodo de tres años. El universo lo constituyeron 75 pacientes. Se estudiaron variables demográficas, clínicas y tomográficas. Se aplicaron estadígrafos descriptivos: frecuencia absoluta y relativa, media y desviación típica; y estadígrafos inferenciales: regresión logística mediante el Odds Ratio con intervalo de confianza del 95 %, para una significación positiva al ser p<0,05. Resultados: el grupo etario de 48 a 75 años predominó con 45 pacientes (60 %), el sexo masculino con 44 pacientes (58,7 %) y 33 de la raza blanca (44 %). Predominó la hipertensión arterial como principal antecedente con 61 pacientes para un 81,3 %. Se obtuvieron resultados significativamente positivos para la edad mayor de 80 años (p=0,001); el estado grave según la escala de coma de Glasgow (p=0,005); la presencia de extensión ventricular (p=0,001) y el tratamiento con anticoagulantes orales (p=0,023). Conclusiones: la hemorragia intracerebral se presenta con valores considerables de mortalidad. Las personas mayores de 80 años, con tratamiento con anticoagulantes orales presentan mayor riesgo de mortalidad. La extensión ventricular y bajo puntaje en la escala de coma de Glasgow, empeoran el pronóstico.

ABSTRACT Introduction: spontaneous intracerebral hemorrhage (ICH) is considered, among all strokes, the one having the most devastating effect, the estimated mortality rate per month ranges between 35 and 52 %. Objective: to determine the factors that influence 30-day mortality rate in patients with Spontaneous Intracerebral Hemorrhage. Methods: a cross-sectional, analytical, observational study conducted at Dr. Carlos Juan Finlay Military Hospital over a period of 3 years (2017 to 2019). The target group comprised 75 patients. Demographic, clinical and tomographic variables were studied. Descriptive statistics was applied: absolute and relative frequency, arithmetic mean and standard deviation; along with inferential statistics: logistic regression using the Odds Ratio with a 95 % confidence interval, for a positive significance on p <0.05. Results: the age group from 48 to 75 years prevailed with 45 patients (60 %), male sex 44 patients (58. 7%), and white race 33 (44 %). Hypertension predominated as the main antecedent in 61 patients (81. 3 %). Significantly positive results were obtained for ages over 80 (p = 0,001); the severe state according to Glasgow Coma Scale (p = 0,005); the presence of ventricular extension (p = 0,001) and treatment with oral anticoagulants (p = 0.023). Conclusions: intracerebral hemorrhage is evidence for extensive mortality rates. People over 80 years old, treated with oral anticoagulants have a higher risk of death due to this entity. Ventricular extension and a low score on the Glasgow Coma Scale worsen the prognosis.

Role of Magnetic Resonance Venogram as a Tool in Planning for Various Neurosurgical Operations

Objectives and methodology: Exact localization of superficial cortical veins is very important in planning for avoiding venousinjuries. Cod liver oil capsules were placed on anterior and posterior ends of medial and lateral border of the tumor at scalpaccording to location of tumor and thus tumor boundaries were marked. Then 3DCEMRV and 2DTOF images were taken andthen superficial cortical vein studied in marked area for comparison between both modalities of MRV and planning of surgeryfor avoiding venous injury.Results: Most of the cases were in age group 16-60 years (89%). Most common clinical manifestation was headache (86.2%)and meningioma (58.2%) was found to be most common pathology. Clear depiction and morphology of superficial corticalvein was observed in 58 cases (100%) in 3DCEMRV as compared to 2DTOF 24 cases (41.3%) P <0.001S. Clear depictionand morphology of superior sagittal sinus was observed in 58 cases (100%) in 3DCEMRV as compared to 2DTOF 33 cases(60.3%) P <0.001S. In post operative CT Head, we found 6 (10.3%) cases of venous infarction. 7 patients (12%) developedmotor weakness post operatively. In 3 cases, post operative MRV were done and found no venous injury.Conclusion: This study showed that preoperative marking of tumor area and associated venous anatomy with the help of codliver oil capsule and MRV was very helpful in planning the surgery and to avoid injury of the vein. 3DCEMRV was found to bebetter modality than 2DTOF for delineation of veins.

Incidence of cystoid macular edema following routine cataract surgery using NSAIDs alone or with corticosteroids / Incidência de edema macular cistóide após cirurgia de catarata de rotina com a utilização de AINEs isoladamente ou com corticosteroides

ABSTRACT Purpose: To evaluate the rate of cystoid macular edema development among cataract surgery patients on four different therapeutic regimens. Methods: The present study is a retrospective analysis of 5,380 eyes following uncomplicated phacoemulsification at Wake Forest University. The study period went from July 2007 to December 2012. Patients received one of four regimens, as follows: postoperative generic ketorolac 0.4% and prednisolone 1%, postoperative name-brand ketorolac 0.45% and prednisolone 1%, postoperative bromfenac 0.09% and prednisolone 1%, preoperative and postoperative bromfenac 0.09% alone. A statistical analysis was performed to assess the differences in rate of cystoid macular edema development among the four different therapeutic regimens. The diagnosis of cystoid macular edema required worsening of vision and evidence of increased macular thickness on optical coherence tomography. Results: The overall rate of cystoid macular edema was 0.82%. Treatment by postoperative generic ketorolac 0.45% and prednisolone 1% demonstrated the highest rate of cystoid macular edema development (2.20% of the cases). Postoperative name-brand ketorolac 0.45% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.90% of the cases). Postoperative administration of bromfenac 0.09% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.44% of the cases). Preoperative and postoperative bromfenac 0.09% alone resulted in the lowest rate of cystoid macular edema development (0.09% of the cases). The rate of cystoid macular edema was significantly lower when bromfenac was used alone vs. either regimen where ketorolac and prednisolone were used (OR 0.043, 95% CI 0.002 to 0.312; p<0.001). Conclusions: Post-cataract surgery cystoid macular edema developed less frequently following topical non-steroidal anti-inflammatory drugs regimen compared to the other therapies evaluated. Bromfenac, without corticosteroids, achieved lower rates of cystoid macular edema vs. various combinations of non-ste­roidal anti-inflammatory drugs with corticosteroids.

RESUMO Objetivo: Avaliar a taxa de desenvolvimento do edema macular cistóide em pacientes submetidos à cirurgia de catarata em quatro esquemas terapêuticos diferentes. Métodos: O presente estudo é uma análise retrospectiva de 5.380 olhos após facoemulsificação não complicada na Wake Forest University. O período do estudo foi entre julho de 2007 e dezembro de 2012. Os pacientes receberam um dos quatro esquemas: cetorolaco genérico pós-operatório 0,4% e prednisolona 1%, cetorolaco 0,45% pós-operatório e prednisolona 1%, bromfenac 0,09% e a prednisolona 1% pós-operatório, bromfenaco 0,09% no pré-operatório e isoladamente no pós-operatório. Uma análise estatística foi realizada para avaliar as diferenças na taxa de desenvolvimento do edema macular cistóide entre os quatro diferentes regimes terapêuticos. O diagnóstico de edema macular cistóide exigiu uma piora da visão e uma evidência de aumento da espessura macular na tomografia de coerência óptica. Resultados: A taxa global de edema macular cistóide foi de 0,82%. O tratamento com cetorolaco genérico pós-operatório 0,45% e prednisolona 1% demonstrou a maior taxa de desenvolvimento de edema macular cistóide (2,20% dos casos). O cetorolaco 0,45% e a prednisolona 1% no pós-operatório exibiram taxas intermediárias de desenvolvimento de edema macular cistóide (0,90% dos casos). A administração de bromofenac 0,09% e de prednisolona 1% no pós-operatório apresentou taxas interme­diárias de desenvolvimento de edema macular cistóide (0,44% dos casos). O bromfenac 0,09% no pré e pós-operatório isoladamente resultou na menor taxa de desenvolvimento de edema macular cistóide (0,09% dos casos). A taxa de edema macular cistóide foi significativamente menor quando o bromfenac foi utilizado isoladamente em relação ao esquema onde cetorolaco e a prednisolona foram usados (OR 0,043, 95% CI 0,002 a 0,312; p<0,001). Conclusões: O edema macular cistóide pós-cirurgia de catarata desenvolveu-se com menor frequência após o tratamento tópico de medicamentos anti-inflamatórios não esteroidais, comparado às outras terapias avaliadas. Bromfenac, sem corticosteróides, alcançou taxas mais baixas de edema macular cistóide vs. Várias combinações em comparação com as várias combinações de drogas anti-inflamatórias não esteroidais com corticosteróides.

Design, synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure-activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFR simultaneously . Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.

GSH-responsive SN38 dimer-loaded shape-transformable nanoparticles with iRGD for enhancing chemo-photodynamic therapy

Accurate tumor targeting, deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine. To achieve these requirements, a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer (d-SN38)-loaded nanoparticles (d-SN38@NPs/iRGD). Upon intravenous injection, d-SN38@NPs with high drug loading efficiency (33.92 ± 1.33%) could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD. The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy. The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm, which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor.

Construction of PC9 cell lines stably transfectedwith human LncRNAMIR31HG gene and its effects on cell proliferation and migration / 吉林大学学报(医学版)

Objective: To detect the effect of over expressed human MIR31HG gene on the proliferation and m grat on of PC9 ce Is, and to clarify the mechan sm of oncogene MIR31 HG Methods: The ful length sequence of ong non coding RNA (LncRNA) MIR31HG was amp fed by RT PGR and cloned nto the pcDNA3 1 ( ) eukaryot c expression vector. The PG9 cells were transfected w th the pcDNA3 1 MIR31HG overexpress on vector and control vector pcDNA3 1. The construction of MIR31HG overexpress on vector was detected by enzymatic digest on identification. The stab e cell 1 nes w th overexpress on of MIR31HG (PC9 pcDNA3 1 MIR31HG∗ stab e transfection group) and control ce 1 1 nes (PC9 pcDNA3 1, empty vector group) were established by G418 drug screen ng. and the express on evel of MIR31 HG gene n stably transfected cell ine was detected by RT PGR CCK 8 method and scratch heal ng assay were used to detect the proliferation act vities and m gration ab 1 ties of PC9 eel s. Results: The agarose gel e ectrophoresis resu ts showed that the spec f c gene fragment of MIR31HG was obta ned by amplif cation successfu ly. The gene fragments of target gene and vector were produced by double enzyme digest on of MIR31HG eukaryotic expression vector. The RT PGR resu ts showed that the MIR31HG RNA expression leve in the cells n stable transfect on group was sign ficantly h gher than that in empty vector group (P< 0 05). The results of CGK 8 test showed that the pro iferat on act vities of the eels in stable transfection group were s gnif cant y higher than those in empty vector group at 24, 36 and 48 h after culture ( P<0 01). The results of scratch healing assay showed that the scratch heal ng rate of ce Is n stable transfect on group was sign ficantly h gher than that in empty vector group at 48 h after culture ( P<0 05). Conclusion: The eukaryotic overexpression vector and the PG9 eel line stably transfected w th human LncRNA MIR31 HG gene are constructed successfully, and M1R31 HG overexpression can promote the pro iferat on and m grat on of ung cancer PG9 cells.