MedNexus
2022年 · 第05卷第01期
MedNexus
Targeted sequencing and whole exome sequencing are the most common approaches used to detect causative variants in Mendelian diseases; however, using DNA-based sequencing techniques, the current molecular diagnostic yield is at best 50%. In recent years, RNA sequencing has been shown to be able to provide a genetic diagnosis in patients whose conditions were previously unable to be identified by DNA analysis. RNA sequencing can reveal expression outliers, aberrant splicing events, allele-specific expression, and new pathogenic variants, and as such can complement and expand on the traditional genomic methods used to diagnose Mendelian diseases. Therefore, RNA sequencing is expected to become a routine method for genetic diagnosis in the future. This article reviews the applications and challenges of RNA sequencing in the genetic diagnosis of Mendelian diseases.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the digestive system and are not sensitive to traditional chemotherapy. Therefore, historically, surgical resection was the only effective therapy. However, the emergence of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of GISTs, because they target c-Kit and PDGF receptor-α (PDGFRA), which are important in GIST development and progression. As research into c-Kit and PDGFRA continues, an increasing number of different TKIs are being used in the clinical setting. This review aims to discuss the current state of chemotherapy for the treatment of GISTs with different genotypes.
The coronavirus disease 2019 (COVID-19) pandemic has been an unmitigated disaster for society and the economy worldwide. However, much remains unknown about the pathogenesis of, treatment methods for, and preventive measures against COVID-19. Single-cell sequencing is a novel sequencing technology whose use has recently become prevalent in various life-science fields. This high-resolution technology is being used to analyze the COVID-19 pandemic at a single-cell level. In this review, we summarize the application of single-cell sequencing technology to the field of COVID-19-related research, including the biology of severe acute respiratory syndrome coronavirus 2, clinical concerns associated with COVID-19, neutralizing antibody screening, and vaccine development. We also address challenges to, and improvements in, existing single-cell research related to COVID-19.
Observational studies have reported malnutrition and vitamin deficiency in patients with schizophrenia (SZ), which can lead to serious metabolic syndromes and decrease anti-psychiatric drug outcomes. Whereas, vitamin intake along with psychiatric medication can enhance the medication outcomes. However, it is still unknown if SZ induces vitamin deficiency. Herein, we conduct the Mendelian randomization analysis to explore the causal relationship between schizophrenia and vitamins supplementation.
We retrieved the genome-wide summary statistical data for schizophrenia from recent SZ GWAS data (43,175 cases and 65,166 controls) and vitamins supplementation GWAS data from Neale’s GWAS datasets (more than 337,000 samples from the European population) and performed a two-sample Mendelian randomization analysis to determine the causal association of SZ with vitamin supplementation, in addition, we conduct the sensitivity analysis to obtain reliable results and remove confounding bias.
SZ have causal relationships with vitamins A, B, C, D, and E (SZ/vitamin A: β = 0.002, se= 0.001, 95% confidence interval (CI): 0.001 to 0.004, P= 1.41E-05, heterogeneity P= 0.4486; SZ/vitamin B: β= 0.004, se= 0.001, 95% CI: 0.002-0.005, P= 7.0E-05, heterogeneity P= 0.2217; SZ/vitamin C: β= 0.004, se= 0.001, 95% CI: 0.002-0.007, P= 0.001, heterogeneity P= 0.1349; SZ/vitamin D: β= 0.003, se= 0.001, 95% CI: 0.002-0.005, P= 0.001, heterogeneity P= 0.433; SZ/vitamin E: β= 0.003, se= 0.001, 95% CI: 0.002-0.005, P= 5.0E-05, heterogeneity P= 0.1382).
Our findings suggest that vitamin levels and supplementation should be carefully controlled in patients with SZ, which in turn may enhance the therapeutic effects of antipsychotic drug treatments.
The coronavirus disease 2019 (COVID-19) epidemic resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has still spread globally. The occurrence of the Delta variant, which is more infectious and spreads faster than earlier forms of the virus that causes COVID-19, makes infection prevention more challenging. Therefore, this study aimed to gain a comprehensive insight into the transmission routes of SARS-CoV-2 for curbing the propagation of SARS-CoV-2 in human populations.
We studied a prospective cohort of 576 patients admitted consecutively to the First Affiliated Hospital of Guangzhou Medical University from January 21 to June 8, 2020. These patients were chosen based on their similar clinical phenotypes or imaging findings. There were 21 (3.6%) laboratory-confirmed COVID-19 patients (16 severe and 5 mild cases) and 555 non-COVID-19 patients. The antibody response and routes and duration of viral shedding were systematically evaluated in serial clinical specimens. Moreover, SARS-CoV-2 RNA was also detected in a mouth rinse, urine, and tear samples. This study was approved by the Medical Ethical Committee of The First Affiliated Hospital of Guangzhou Medical University (approval No. 2020-77).
SARS-CoV-2 mainly existed in sputum, nasal and throat swabs, and feces samples. Virus latency was longer in sputum and feces samples than in nasopharyngeal samples. IgG antibody response in respiratory samples was related to disease severity. Although droplets and aerosols are the major transmission routes for COVID-19, covert routes of transmission from asymptomatic patients, contaminated surfaces, and wastewater are also of interest.
Our findings provide a solid foundation for developing prophylactic measures against SARS-CoV-2.
Rubicon is an inhibitory interacting protein of the autophagy-related protein Uvrag. We previously showed that Rubicon deficiency promotes autophagic flux in vivo and that autophagy can degrade lipid droplets. This study aimed to investigate the effects of Rubicon deficiency on fasting-induced hepatic steatosis.
Two-month-old wild-type (WT) and Rubicon-deficient mice were subjected to feeding or fasting for 24 hours to induce hepatic steatosis. The distribution of liver lipid droplets was revealed by oil red O staining. Hepatic and plasma triglyceride, non-esterified fatty acid (NEFA), and cholesterol levels were detected using commercially available kits. Real-time reverse transcriptasepolymerase chain reaction was performed to analyze the mRNA expression of genes related to lipid metabolism in the liver. Western blot was conducted to assess autophagy-related protein levels in the liver. The animal experiments were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University, China.
We showed that under fasting conditions, Rubicon-deficient mice had more lipid droplets in the liver than WT controls. Consistent with these results, the hepatic triglyceride, NEFA, and cholesterol levels in fasted Rubicon-deficient mice were significantly higher than those of fasted WT controls. The levels of SREBP-1, a key regulator of lipid synthesis, were significantly lower in livers from fasted WT mice than those of fed WT mice. However, the decrease in SREBP-1 in fasted mice was attenuated by Rubicon deficiency. Western blot analysis demonstrated that the fasting-induced increase in autophagic flux was amplified by Rubicon deficiency. Finally, we showed that Rubicon deficiency in mice led to elevated plasma triglyceride and NEFA acid levels under fasting conditions.
Rubicon deficiency exacerbates fasting-induced hepatic steatosis in mice.
Human immunodeficiency virus (HIV) p24 antigen and antibody and herpes simplex virus 2 IgM are seromarkers indicating infection with HIV and herpes simplex virus-2 (HSV-2), respectively, whereas tumor necrosis factor α is an inflammatory biomarker that can be triggered by infections. Female children of single parents are faced with many socio-economic challenges that make them vulnerable to sexual influences and prone to sexually transmitted infections. The goal of this work was to determine HIV p24 antigen/antibody, HSV-2 IgM and tumor necrosis factor-α plasma levels in adult female children living in single-parent households.
In this case-control observational study, 100 adult female children living with a single parent (50 living with a single mother and 50 living with a single father; age: 18-22 years) and 100 age-matched women living with both parents were recruited to serve as the test and control groups, respectively. All subjects were negative for acid-fast bacilli, plasmodium, hepatitis C virus, and hepatitis B virus. Human tumor necrosis factor α, HSV-2 IgM, antibody to hepatitis C virus, hepatitis B surface antigen and human immunodeficiency virus p24 antigen and antibody (HIV p24 Ag/Ab) levels were determined by ELISA, while the detection of acid-fast bacilli in sputum and Plasmodium in blood was carried out by optical microscopy. This work was carried out in the Owo/Ose Federal Constituency in Ondo State that shares boundaries with Edo State. The study protocol was approved by the Research and Ethical Committee of the Department of Medical Laboratory Science, Achievers University, Owo, Nigeria (AUO/MLS/2020/127) on August 27, 2020.
HIV p24 Ag/Ab was detected in 0 adult female children living with a single mother, 1 (2%) adult female child living with a single father and 1 (1 %) adult female child living with both parents. HSV-2 IgM was detected in 9 (18%) adult female children living with a single mother, 13 (26%) adult female children living with a single father, and 5 (10%) adult female children living with both parents.
This work shows that adult female children of single parents are vulnerable to sexual influences, and thereby more prone to HSV-2 and possibly HIV, especially adult female children of single fathers.
There is an error in the title of the published paper "PA1426regulatesPseudomonas aeruginosaquorum sensing and virulence: an in vitro study" (DOI: 10.1097/JBR.0000000000000088) because of a mistake in description and also oversight during final proof checking.[
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