zhiping li
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Background
Inactivating mutations of the protein kinase A regulatory subunit 1 alpha (PRKAR1A) gene have been reported in familial cardiac myxoma. However, the role of PRKAR1A mutation in sporadic cardiac myxoma remains unknown.
MethodsTargeted next-generation sequencing (NGS) was performed to identify mutations with the PRKAR1A gene in seven cases of sporadic cardiac myxomas. Sanger sequencing of DNA from cardiac myxoma specimens and matched peripheral blood samples was performed to verify the identified mutations.
ResultsTargeted NGS of myxoma DNA revealed 232 single nucleotide variants in 141 genes and 38 insertion-deletion mutations in 13 genes. Six PRKAR1A mutations were identified in four of the seven cardiac myxoma cases, and thus, the PRKAR1A inactivating mutation rate was 57.2% (4/7, 95% CI=0.44-0.58, P<0.05). The PRKAR1A variants identified by Sanger sequencing analysis were consistent with those from the NGS analysis for the four myxoma specimens. All of the pathogenic PRKAR1A mutations led to premature termination of PRKAR1A, except for one synonymous mutation. Moreover, none of the nonsense and missense mutations found in the myxoma specimens were found in the matched peripheral blood samples.
ConclusionPathogenic mutations of the PRKAR1A gene were identified in tumor specimens from four cases of sporadic cardiac myxoma, and the absence of these mutations in peripheral blood samples demonstrated that they were somatic mutations.
Keywords: Cardiac myxoma, PRKAR1A gene, Somatic mutation, Sporadic -
Context
Since December 2019, the coronavirus disease 2019 (COVID-19) has broken out in Wuhan, Hubei Province, China. Due to the highly pathogenic and infectious characteristics, COVID-19 spread across China and later globally and became a severe pandemic. To date, there have been no efficacious specialized drugs to treat COVID-19. The China-issued Diagnosis and Treatment of Pneumonia Caused by Novel Coronavirus (Trial version 6) added the chloroquine phosphate to the antiviral treatment protocol for infected adults.
Evidence AcquisitionIn this review, government documents and authoritative guidelines on COVID-19 were collected from the official website of organizations related to health and medicine. Research articles related to chloroquine and its application for COVID-19 treatment were searched and acquired from the PubMed platform. Facts and data related to the use of chloroquine were summarized in several parts.
ResultsRecently, there has been an increase in research on the use of chloroquine for the treatment of COVID-19. This drug is utilized as an antimalarial and antiviral medication. There are some concerns and cautions on the clinical application of chloroquine, about which clinicians should be informed during this global pandemic. The present review summarized data on the mechanism of action, drug-drug interaction (DDI), and adverse drug reaction (ADR) of chloroquine and pharmaceutical care for special patients in order to provide a reference for the rational use of this drug in COVID-19 patients.
ConclusionCurrently, there is mixed evidence on the efficacy of chloroquine in the treatment of COVID-19. Potential DDIs and ADRs, as well as pharmaceutical care, for special patients should be considered in fighting against the pandemic.
Keywords: Adverse drug reactions, Chloroquine, COVID-19 -
BackgroundTreatment of steroid-resistant nephrotic syndrome (SRNS) remains a huge challenge in pediatric patients. Immunosuppressive agents including cyclosporine A (CsA), tacrolimus (TAC) and mycophenolate mofetil (MMF) are recommended for the management of children with SRNS. The aim of this study was to compare the efficacy of CsA, TAC and MMF in children with SRNS and provide guidance for clinical practice.MethodsThis is a retrospective analysis of the records of 70 children with SRNS recruited from a children hospital over a period of seven years. They were treated with CsA, TAC and MMF as initial immunosuppressive therapy in addition to steroids. Complete or partial remission was considered a good response.ResultsFive (41.7%) of 12 children who were on CsA therapy achieved remission at 6 months and 5 (41.7%) at 12 months. Nine (19.1%) of 47 patients treated with TAC achieved remission at 6 months, 20 (42.6%) at 12 months and 6 (12.8%) within or over 24 months. The remission achieved at 6 months and 12 months was 4 (36.4%) and 2 (18.2%) respectively in MMF group. The relapse rates in children who had achieved remission were 30.0%, 45.7% and 50.0% in CsA, TAC and MMF group respectively.ConclusionsBased on similar baseline characteristics, CsA and TAC as initial therapy for SRNS have a better remission and relapse rates whereas MMF shows a rapid remission effect.Keywords: Steroid-Resistant Nephrotic Syndrome, Immunosuppressive Agent, Remission, Relapse, Children
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BackgroundPatent ductus arteriosus (PDA) is a common congenital heart defect in premature infants. Intravenous injection of ibuprofen is used for PDA treatment, but its optimum dose, efficacy, and safety are unclear.ObjectivesThis meta-analysis aimed to access randomized controlled trials that compared high- or low-dose ibuprofen with a standard dose of ibuprofen for closure of PDA in preterm infants.MethodsThe standard search methods of the Cochrane neonatal review group were used to screen ibuprofen versus indomethacin trials. All groups that used ibuprofen in those trials were filtered out. The high-dose group was defined as those using an average dose of ibuprofen greater than or equal to 10 mg/kg in the first three days.ResultsWe identified 14 studies of good methodological quality comparing ibuprofen to indomethacin trials among neonates. Results showed that high-dose ibuprofen could remarkably raise the closure rate (relative risk = 0.90, 95% CI = [0.81, 1.00], P = 0.04). No significant differences were found in adverse effects, bleeding disorders, or oliguria. The closure rate in neonates with PDA increased with the ibuprofen dosage (R2 = 0.9990). The loading dose produced a significant closure rate compared with the low-dose group (relative risk = 1.91, 95% CI = [1.25, 2.92], P = 0.003), with no increase in toxic side effects.ConclusionsLoading dose is a necessary strategy for infants with PDA. A high dose of ibuprofen for PDA closure was more effective than a normal dose of ibuprofen. The side effects in both treatment groups were not significantly different. Given the small sample size and risk of bias in all trials, the tolerability and safety of the dose regimen should be assessed in a large population before considering the use of these doses for PDA.Keywords: Ibuprofen, Indomethacin, Patent Ductus Arteriosus, Premature Infant
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This study reports hepatitis B serologic test results among foreign-born Asian Americans. In 2013 - 2014, a sample of foreign-born Asian American adults, (≥ 18 years of age) were drawn from community-based organizations in the Baltimore-Washington Metropolitan Area. Hepatitis B screening tests were administered, including tests for HBsAg, anti-HBs, and anti-HBc. Among total of 600 people who completed screening, 33 (5.5%) tested positive for HBsAg, indicating chronic hepatitis B virus (HBV) infection.
About 44% (n = 263) tested positive for anti-HBc, indicating a previous exposure to HBV. Asian Americans from Vietnam (53.2%) had the highest exposure to HBV, followed by Asian Americans from Korea (43.4%) and China (34.8%) (PKeywords: Hepatitis B Virus Infection_Exposure_Asian Americans
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