ABSTRACT
BackgroundSuper-spreading events were associated with the outbreaks of SARS and MERS, but their association with the outbreak of COVID-19 remains unknown. Here, we report a super-spreading transmission chain of SARS-CoV-2 involving an index patient, seven cancer patients, 40 health care workers and four family members. MethodsWe conducted a retrospective study to identify the index patient and the exposed individuals linked to a chain of transmission associated with COVID-19. We collected and analyzed the data on demographic features, exposure history, clinical presentation, laboratory investigation, radiological examination, and disease outcome of these patients. ResultsWe identified the index patient and another presumptive "super-spreader", who initiated and amplified a super-spreading transmission chain associated with COVID-19, respectively. There were 31 female and 21 male patients in this cohort, and the median age was 37 years (range: 22-79 years). Each of them had an exposure history with the index patient or his close contacts. Approximately 87% (45/52) of the patients had fever or other symptoms, 96% (50/52) had abnormal chest CT-scan findings, 86% of the tested patients (39/45) were positive for SARS-CoV-2 in the nasopharyngeal or throat swab specimen, 85% of the tested patients (29/34) were positive for SARS-CoV-2-specific IgM and/or IgG, 15% of the RT-PCR positive patients were tested negative for the specific IgM and/or IgG at the convalescent phase, and 15% of the RT-PCR negative patients were tested positive for the specific IgM and/or IgG. The severe patients experienced a significant decrease in oximetry saturation, lymphocyte, and platelet counts, along with a significant increase in C-reactive protein, D-dimer, and lactate dehydrogenase. All six fatal cases had comorbidities and five of the seven cancer patients (71%) died within 2-20 days of the disease onset. ConclusionsThe super-spreading events were associated with the outbreak of COVID-19 in Wuhan and its impact on disease transmission warrants further investigation. Cancer patients appeared highly vulnerable to COVID-19. The finding that a significant portion of SARS-CoV-2 infected patients were tested negative for the serum specific IgM and IgG at the convalescent phase should be addressed by additional studies.
ABSTRACT
Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87–199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial–mesenchymal transition (EMT) process of sarcomatous components of GS. We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.
Subject(s)
Humans , Glioblastoma , Gliosarcoma , Prevalence , PrognosisABSTRACT
ObjectiveTo observe the effects of human IL-10 gene transfection on the mRNA and protein expressions of IL-1β and TNF-α in the penumbra area following focal cerebral ischemia-reperfusion injury in rats and to investigate its neuroprotective mechanism. MethodsRats were divided into four groups: normal control group, ischemic control group, empty plasmid group and human IL-10 gene transfected group. The mRNA and protein expressions of IL-1β and TNF-α in the penumbra area were detected by fluorescence real-time quantitative PCR and ELISA respectively. ResultsIn normal control group, ischemic control group, empty plasmid group and human IL-10 gene transfected group, the levels of protein expression of TNF-α in penumbra area were(0.66±0. 04) ,(1.16±0.26),(1. 155±0. 26)ng/g and(0. 84±0. 05)ng/g, and the levels of protein expression of IL-1βin penumbra area were(0.37±0.05), (1.25±0.39), (1.21±0.57) ng/g and(0.62+0.05)ng/g, respectively. Compared with normal control group, the levels of protein expression of TNF-α and 1L-1β were significantly higher in other three groups(all P＜0. 01), and lower in human IL-10 gene transfected group than in ischemic control group and empty plasmid group(all P＜0. 01). In normal control group, ischemic control group, empty plasmid group and human IL-10 gene transfectedgroup, the levels of mRNA expression of TNF-α in penumbra area were 1.00 ±0.53,9.42±1.83,9.69±1.96 and 3.53±1.09, and the levels of mRNA expression of IL-1β in penumbra area were 1.00 ±0.51,27. 81±4.84,23.96 ± 4.90 and 13.55± 4.45, respectively. Compared with normal control group, the levels of mRNA expression of TNF-α and IL-1β were significantly higher in other three groups(all P＜0. 01), and lower in human IL-10 gene transfected group than in ischemic control group and empty plasmid group(all P＜0. 01). ConclusionsThe human IL-10 gene transfection may play an protective effect on cerebral ischemia through inhibiting mRNA and protein expression of IL-1β and TNF-α in the penumbra area following focal cerebral ischemia-reperfusion in rats.