Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency / 中国当代儿科杂志

Phosphomannomutase 2 deficiency is the most common form of N-glycosylation disorders and is also known as phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG). It is an autosomal recessive disease with multi-system involvements and is caused by mutations in the PMM2 gene (OMIM: 601785), with varying severities in individuals. At present, there is still no specific therapy for PMM2-CDG, and early identification, early diagnosis, and early treatment can effectively prolong the life span of pediatric patients. This article reviews the advances in the diagnosis and treatment of PMM2-CDG.

Case report of congenital disorder of glycosylation type Ia combined with dilated cardiomyopathy / 中华实用儿科临床杂志

Clinical data and follow-up of a case of congenital disorder of glycosylation type Ia (CDG-Ia) combined with dilated cardiomyopathy admitted to the Department of Cardiology, Children′s Hospital of Nanjing Medical University were analyzed retrospectively.The 5-year-old female patient was admitted in December 2016 due to recu-rrent shortness of breath for 2 months.Clinical symptoms and signs included repeated attacks of shortness of breath, physical retardation, malnutrition, binocular esotropia, multiple episodes of hypoglycemia, hepatosplenomegaly, hypotonia and other multi-system damages.Cardiac echocardiography suggested the feature of dilated cardiomyopathy, including the significant enlargement of the left ventricle, and decreased systolic function.Genetic testing revealed a compound heterozygous mutation in the PMM2 gene, and as a result, the patient was diagnosed as CDG-Ia.The patient′s condition improved after symptomatic treatments such as Cedilanid, Dopamine, Dobutamine, Furosemide, as well as support treatments like myocardium nutrition, blood sugar maintenance, liver protection, etc.After discharge, the patient was given oral Digoxin, Betaloc, Captopril and diuretics, and hypoglycemia-controlling agents.The patient was followed up every 3-6 months.After more than 2 years of follow-up, the heart function and heart enlargement gradually returned to normal.During the Corona Virus Disease 2019 outbreak, self-withdrawal continued for 2 months.Re-examinations showed decreased cardiac function and enlarged left ventricle again.Medications were resumed again, and the patient was followed up closely.This case report suggested that CDG-Ia may be associated with dilated cardiomyopathy, and the cardiac phenotype may be improved by symptomatic supportive treatment.

Antiviral activity of shikonin ester derivative PMM-034 against enterovirus 71 in vitro

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

O Programa Mais Médicos, a infraestrutura das Unidades Básicas de Saúde e o Índice de Desenvolvimento Humano Municipal / The Mais Médicos (More Doctors) Program, the infrastructure of Primary Health Units and the Municipal Human Development Index

Resumo O presente trabalho tem como objeto central o estudo do contexto em que atuam os profissionais do Programa Mais Médicos. Para isto, a pesquisa utiliza a escala de infraestrutura das UBSs, desenvolvida recentemente por Soares Neto e colegas para aprofundar o conhecimento das relações entre a infraestrutura das UBSs e o IDHM dos municípios que receberam médicos do PMM. Utilizando estatísticas exploratórias e inferenciais, o artigo mostra que das UBSs que receberam médicos do PMM, 65,2% têm infraestrutura de média qualidade e apenas 5,8% delas têm infraestrutura de baixa qualidade. A correlação de 0,50 entre o indicador de infraestrutura e o IDHM aponta para uma tendência moderada de que municípios com baixos IDHMs tenham UBSs mais precárias. Por meio de uma análise de regressão linear múltipla, pode-se inferir que o fator que mais contribui para o aumento do indicador de infraestrutura das UBSs é a renda média municipal. Por outro lado, o fator que afeta negativamente a infraestrutura das UBSs é estar localizada na região Norte ou Nordeste.

Abstract The main objective of this article was to examine the context in which professionals working within the Mais Médicos (More Doctors) Program operate. This study used the infrastructure scale of primary health units (PHUs), which was recently developed by Soares Neto and colleagues to provide more information regarding the relationship between the infrastructure of PHUs and the Municipal Human Development Index (MHDI) of municipalities that received Mais Médicos Program doctors. Using exploratory and inferential statistics, the article shows that 65.2% of the PHUs that received Mais Médicos Program doctors had medium-quality infrastructure and only 5.8% of them had low-quality infrastructure. The correlation of 0.50 between the infrastructure indicator and the MHDI points to a moderate tendency for municipalities with low MHDIs to have more precarious PHUs. Using multiple linear regression analysis it can be inferred that the main factor that contributed to the increase in the infrastructure indicator of the PHUs was the average municipal income. On the other hand, the factor that negatively affected the infrastructure of the PHUs was being located in the north or northeast regions.