RESUMO
OBJECTIVE: To investigate the clinical characteristics, epidemiological characteristics, and transmissibility of coronavirus disease 2019 (COVID-19) in a family cluster outbreak transmitted by a 3-month-old confirmed positive infant. METHODS: Field-based epidemiological methods were used to investigate cases and their close contacts. Real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) was used to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for all collected specimens. Serum SARS-CoV-2 IgM and IgG antibodies were detected by Chemiluminescence and Gold immnnochromatography (GICA). RESULTS: The outbreak was a family cluster with an attack rate of 80% (4/5). The first case in this family was a 3-month-old infant. The transmission chain was confirmed from infant to adults (her father, mother and grandmother). Fecal tests for SARS-CoV-2 RNA remained positive for 37 days after the infant was discharged. The infant's grandmother was confirmed to be positive 2 days after the infant was discharged from hospital. Patients A (3-month-old female), B (patient A's father), C (patient A's grandmother), and D (patient A's mother) had positive serum IgG and negative IgM, but patients A's grandfather serum IgG and IgM were negative. CONCLUSION: SARS-CoV-2 has strong transmissibility within family settings and presence of viral RNA in stool raises concern for possible fecal-oral transmission. Hospital follow-up and close contact tracing are necessary for those diagnosed with COVID-19.
RESUMO
Multidrug resistance (MDR) is a major challenge to the clinical treatment of esophageal cancer. The stress response gene activating transcription factor 4 (ATF4) is involved in homeostasis and cellular protection. However, relatively little is known about the expression and function of ATF4 in esophageal squamous cell carcinoma (ESCC) MDR. In this study, we investigate the potential role and mechanisms of ATF4 in ESCC MDR. We demonstrated that overexpression of ATF4 promotes the MDR phenotype in ESCC cells, while depletion of ATF4 in the MDR ESCC cell line induces drug re-sensitization. We also demonstrated that ATF4 transactivates STAT3 expression by directly binding to the signal transducers and activators of transcription 3 (STAT3) promoter, resulting in MDR in ESCC cells. Significantly, inhibition of STAT3 by small interfering RNA (siRNA) or a selective inhibitor (JSI-124) reintroduces therapeutic sensitivity. In addition, increased Bcl-2, survivin, and MRP1 expression levels were observed in ATF4-overexpressing cells. In conclusion, ATF4 may promote MDR in ESCC cells through the up-regulation of STAT3 expression, and thus is an attractive therapeutic target to combat therapeutic resistance in ESCC.
