BACKGROUND Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and mortality of the disease. The discovery of serum microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for tumor diagnosis. In this study, we investigated the serum miRNA profile in ESCC patients to develop a novel diagnostic ESCC biomarker. METHODS Serum samples were taken from 290 ESCC patients and 140 age- and sex-matched controls. Solexa sequencing technology was used for an initial screen of miRNAs in serum samples from 141 patients and 40 controls. A hydrolysis probe–based stem–loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification phases to confirm the concentrations of selected miRNAs in serum samples from 149 patients and 100 controls. RESULTS The Solexa sequencing results demonstrated marked upregulation of 25 serum miRNAs in ESCC patients compared with controls. RT-qPCR analysis identified a profile of 7 serum miRNAs (miR-10a, miR-22, miR-100, miR-148b, miR-223, miR-133a, and miR-127-3p) as ESCC biomarkers. The area under the ROC curve for the selected miRNAs ranged from 0.817 to 0.949, significantly higher than for carcinoembryonic antigen (0.549; P < 0.0005). More importantly, this panel of 7 miRNAs clearly distinguished stage I/II ESCC patients from controls. CONCLUSIONS This panel of 7 serum miRNAs holds promise as a novel blood-based biomarker for the diagnosis of ESCC.

Background: Etiology surveillance of Hand Foot and Mouth disease (HFMD) in Beijing showed that Coxsackievirus A6 (CVA6) became the major pathogen of HFMD in 2013 and 2015. In order to understand the epidemiological characteristics and clinical manifestations of CVA6-associated HFMD, a comparison study among CVA6-, EV71- (Enterovirus 71), and CVA16- (Coxsackievirus A16) associated HFMD was performed.Methods: Epidemiological characteristics and clinical manifestations among CVA6-, EV71- and CVA16-associated mild or severe cases were compared from 2013 to 2015. VP1 gene of CVA6 and EV71 from mild cases, severe cases were sequenced, aligned, and compared with strains from 2009 to 2015 in Beijing and strains available in GenBank. Phylogenetic tree was constructed by neighbor-joining method.Results: CVA6 became the predominant causative agent of HFMD and accounted for 35.4 and 36.9% of total positive cases in 2013 and 2015, respectively. From 2013 to 2015, a total of 305 severe cases and 7 fatal cases were reported. CVA6 and EV71 were responsible for 57.5% of the severe cases. Five out six samples from fatal cases were identified as EV71. High fever, onychomadesis, and decrustation were the typical symptoms of CVA6-associated mild HFMD. CVA6-associated severe cases were characterized by high fever with shorter duration and twitch compared with EV71-associated severe cases which were characterized by poor mental condition, abnormal pupil, and vomiting. Poor mental condition, lung wet rales, abnormal pupil, and tachycardia were the most common clinical features of fatal cases. The percentage of lymphocyte in CVA6-associated cases was significantly lower than that of EV71. High percentage of lymphocyte and low percentage of neutrophils were the typical characteristics of fatal cases. VP1 sequences between CVA6- or EV71-associated mild and severe cases were highly homologous.Conclusion: CVA6 became one of the major pathogens of HFMD in 2013 and 2015 in Beijing. Epidemiological characteristics, clinical manifestations of CVA6-, EV71- and CVA16-associated cases in this study enriched the definition of HFMD caused by different pathogens and shed light to accurate diagnosis, appropriate treatment and effective prevention of HFMD.

Patients with swimming pool-acquired human adenovirus (HAdV) infections usually manifest characteristic clinical features that include fever, pharyngitis, and conjunctival inflammation, syndromically referred to as pharyngoconjunctival fever (PCF). HAdV types 3, 4, and 7 are most commonly associated with PCF. This article reports an outbreak of PCF that involved 55 students and staff at a university in Beijing, China. Fifty patients had used the same swimming pool 2 weeks before the onset of symptoms. HAdV type 4 was identified from patient eye and throat swabs and concentrated swimming pool water samples. Partial hexon gene sequences obtained from the water samples were 100% identical to the sequences obtained from the swab samples, which clustered with HAdV-4 within species E. Swimming pool water contaminated with HAdV-4 was the most likely source of infection, although one instance of likely person-to-person transmission was noted.

BackgroundCoxsackievirus A6 (CVA6) is one of the major agents to cause hand, foot and mouth disease (HFMD) outbreaks globally. The objective of this study is to investigate the epidemiologic and clinical manifestations of CVA6 outbreak, and thus guide the diagnosis and treatment of the disease, as well as disease prevention.MethodsAn HFMD outbreak in a kindergarten was reported to Shijingshan District Center for Disease Control and Prevention (SCDC) on November 2, 2015 in Beijing, China. Epidemiological investigation was conducted. We performed a nine-week follow-up study to collect and analyze the clinical manifestations of HFMD cases.ResultsThe outbreak yield 56 (15.7%) clinical diagnosed HFMD cases out of 357 registered children in the kindergarten with the mean age of 3.5 years old. This outbreak lasted for three days and ceased after initiating infectious disease controlling procedures, including periodical suspension of the kindergarten activities, environmental disinfection, and family health education. Fifty-one cases were followed for nine weeks. The positive rate of clinical manifestations of rash, fever, desquamation, pigmentation and onychomadesis were 100.0%, 84.3%, 68.6%, 17.6% and 43.1%, respectively. Children developed desquamation within the first 4 weeks after disease onset and developed onychomadesis between the 3th and 8th week after disease onset. Children with desquamation had 9.3 (95%CI: 1.836–47.437) times higher odds of developing onychomadesis compared to those without this manifestation. Ten out of 14 collected samples were CVA6 positive, and five positive samples shared a high degree of similarity in the VP1 nucleotide and amino acid sequences (99.9–100.0% and 100%).ConclusionThis HFMD outbreak was caused by CVA6, featured with delayed symptoms. Emerging CVA6-associated HFMD and its delayed symptoms should be paid more attention to reduce outbreaks and provide more information to doctors and parents.Electronic supplementary materialThe online version of this article (10.1186/s12887-018-1253-1) contains supplementary material, which is available to authorized users.

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Introduction: Enterovirus A71(EV-A71)-associated hand, foot, and mouth disease (HFMD) has been reported worldwide, and poses a particularly heavy burden on patients, families, and society in China. Three Chinese companies have licensed inactivated EV-A71 vaccines, all of which have demonstrated good efficacy for preventing EV-A71-associated disease in clinical trials. However, real-world performance of EV-A71 vaccine has not been evaluated. Methods: We used a test-negative design case-control study to estimate vaccine effectiveness (VE) against medically attended EV-A71-associated HFMD. Subjects were children 5 years of age and under who had been in health facilities participating in the HFMD case and virologic surveillance platforms in Beijing. Enterovirus infections were laboratory confirmed, and EV-A71 vaccination status was extracted from electronic immunization records. Children testing positive for EV-A71 were cases; controls were children testing negative for EV-A71 infection. Logistic regression was used to estimate VE. We assessed sensitivity of VE estimates to control group inclusion criteria by repeating the regression analyses with two alternative control groups. Results: A total of 2,184 HFMD patients aged 5 years and under were enrolled in the study; 24 were severe, and 2,160 were mild. For severe cases, two-dose VE estimate was 100% (95% CI: −68.1%, 100%). For mild cases, 1-dose and 2-dose adjusted VE estimates were 69.8% and 83.7%, respectively. Two-dose VE estimates varied by less than 4 percentage points regardless of control group definition. Conclusions: Our findings suggested the vaccines performed well in the real world for children 5 years of age and under in Beijing, China.

Among 417 COVID-19 patients in Shenzhen, demographic characteristics, clinical manifestations and baseline laboratory tests showed significant differences between mild-moderate cohort and severe-critical cohort.Based on these differences, a convenient mathematical model was established to predict the illness severity of COVID-19. The model includes four parameters: age, BMI, CD4 + lymphocytes and IL-6 levels. The AUC of the model is 0.911.The high risk factors for developing to severe COVID-19 are: age R 55 years, BMI > 27 kg / m 2 , IL-6 R 20 pg / ml, CD4 + T cell % 400 count / m L.Among 249 discharged COVID-19 patients, those who recovered after 20 days had a lower count of platelet, a higher level of estimated glomerular filtration rate, and higher level of interleukin-6 and myoglobin than those who recovered within 20 days.

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