STAT3-EphA7 axis contributes to the progression of esophageal squamous cell carcinoma.

BACKGROUND: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear. MATERIALS AND METHODS: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals. RESULTS: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000∼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells. CONCLUSION: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.

Early prediction of persistent organ failure by serum apolipoprotein A-I and high-density lipoprotein cholesterol in patients with acute pancreatitis.

BACKGROUND: Early identification of acute pancreatitis (AP) patients at high-risk of developing persistent organ failure (persistent OF) is a vital clinical goal. This research intends to assess the ability of apolipoprotein A-I (APO A-I) and high-density lipoprotein cholesterol (HDL-C) to predict persistent OF. METHODS: Between January 2011 and September 2016, a total of 102 adult AP patients with organ failure, local complications or deterioration of former comorbidities disease during hospitalization were included in this study retrospectively. Serum lipids were tested and computed the correlation with clinical outcomes or scoring systems. The AUCs to predict persistent OF were also calculated and compared with each other. RESULTS: Serum APO A-I and HDL-C levels were negatively associated with scoring systems. Meanwhile, serum lipids were negatively correlated with poor clinical outcomes. The AUCs of APO A-I, HDL-C, the combination of APO A-I and BISAP, or the combination of APO A-I and MCTSI to predict persistent OF among Moderately severe acute pancreatitis (MSAP) and Severe acute pancreatitis (SAP) patients were 0.886, 0.811, 0.912, and 0.900 or among those with organ failure were 0.915, 0.859, 0.933, and 0.933, respectively. CONCLUSIONS: The concentrations of APO A-I, HDL-C, and the combinations of APO A-I and scoring systems have high predictive value to predict persistent OF.

Co-circulation of Hantaan, Kenkeme, and Khabarovsk Hantaviruses in Bolshoy Ussuriysky Island, China.

Hemorrhagic fever with renal syndrome (HFRS) was first recognized in far eastern Asia in the 1930s, and has been highly prevalent in this region ever since. To reveal the molecular epidemiology of hantaviruses in this region, a total of 374 small mammals (eight species of rodents and one species of shrew) were captured in the Chinese part of the Bolshoy Ussuriysky Island (Heilongjiang Province). Hantavirus sequences were recovered from three striped field mice (Apodemus agrarius), 11 Maximowicz's voles (Microtus maximowiczii), and one flat-skulled shrew (Sorex roboratus). Genetic and phylogenetic analysis revealed the presence of three viruses: Hantaan virus (HTNV), Khabarovsk virus (KHAV), and Kenkeme virus (KKMV). HTNV sequences recovered from A. agrarius were closely related to those identified in Apodemus mice from the surrounding areas, while a new lineage of KHAV was present in M. maximowiczii. Additionally, while the viral sequences recovered from one flat-skulled shrew were most closely related to KKMV, their divergence to the prototype strain suggests that they represent a new viral subtype. Overall, these results suggest that Bolshoy Ussuriysky Island harbors considerable hantavirus diversity.

[The genetic features of drug resistance to group A streptococcus and macrolides antibiotics among pediatric patients in Beijing 2012].

OBJECTIVE: To investigate the genetic features of drug resistance to group A streptococcus(GAS) and macrolides antibiotics among pediatric patients in Beijing 2012. METHODS: A total of 199 strains of GAS were collected from 36 hospitals in Beijing between May and July, 2012. All strains were isolated from oropharyngeal swabs. The minimum inhibitory concentrations (MICs) of ten antibiotics (penicillin, ampicillin, erythromycin, clindamycin, tetracycline, levofloxacin, tigecycline, vancomycin, linezolid and streptogramin) were detected by VITEK-2 compact with GPS-67 test kit. The genes encoding macrolides resistance (ermA, ermB and mefA ) were amplified and tested by PCR. The macrolides resistant phenotype of group A streptococcus was detected by double disc test (D-test). RESULTS: Among 199 strains of GAS collected in this study, 101(50.8%) were from suburbs and the other 98(49.2%) were from urban areas. 111(55.8%) strains were collected from scarlet fever patients while the other 88(44.2%) were from oropharyngeal infection cases. All the strains were sensitive to penicillin and ampicillin, and the percentage of resistance to erythromycin, clindamycin and tetracycline were 96.5% (192/199), 95.5% (190/199) and 92.0% (183/199), respectively. All strains were susceptible to levofloxacin, tigecycline, vancomycin, linezolid and streptogramin. The rates of resistance to erythromycin, clindamycin and tetracycline were different in different districts, however, the difference in it between ages and clinical diagnosis did not show statistical significance (P > 0.05) . The detected rate of drug resistance gene ermB was 98.5% (196/199). The gene ermA was only detected out in 5 strains and the gene mefA was not detected out. 199 strains showed A macrolides resistant phenotype cMLS, while the phenotype iMLS was not found in this study. CONCLUSION: This study demonstrates the high level of clindamycin resistance in group A streptococcus collected from children in Beijing, 2012. The macrolides resistance of group A streptococcus was highly prevalent in Beijing, and the dominant phenotype was cMLS mediated by gene ermB.

[Application of EARS in early-warning of influenza pandemic in Beijing].

OBJECTIVE: To illustrate the efficiency of cumulative sum (CUSUM) in pre-warning of the influenza peak in Beijing. METHODS: CUSUM was used to analyze the data of influenza like illness (ILI), and the results of the influenza laboratory surveillance was regarded as the gold standard to judge the approaching of the influenza peak. RESULTS: The surveillance was launched in 421 hospitals in Beijing during the 2009 to 2010 influenza season, while the influenza laboratory surveillance was launched by 7 collaborative laboratories. From Jun. 2009 to Apr. 2010, the average ILI percentage in the 421 hospitals was 2.56%. In the study, 19 262 pharyngeal swab samples were collected from the ILI cases in 11 hospitals and 5 045 of them were tested positive for the influenza virus, with the novel swine-origin influenza A H1N1 virus dominating. After analyzing of the ILI surveillance data with CUSUM, it was found that the ILI surveillance in Beijing could make a satisfactory early warning for the approaching of the influenza peak referring to the gold standard based on the influenza laboratory results. CONCLUSION: It could give the prediction and early warning for the influenza peak efficiently and precisely, by using CUSUM to analyze the influenza surveillance data of Beijing.

[Study on types of M protein gene in group A streptococcus isolated from children in Beijing, 2011].

OBJECTIVE: To explore the distribution characteristics of the types of M protein gene (emm) in group A streptococcus (GAS) isolated from children in Beijing in the year 2011. METHODS: During May to July in 2011, a total of 3315 patients who were diagnosed scarlet fever or pharyngeal infection by doctors in pediatric outpatient and emergency units of 36 hospitals, were selected as subjects. Their throat swab samples were collected and isolated the strains of GAS. Gene emm was then amplified and sequenced by PCR method, and the differences in types of gene emm between different populations and diseases were compared. RESULTS: A total of 633 strains of GAS were isolated from the 3315 throat swab samples, 610 strains out of which were gene emm positive and were recruited in the study. Out of the 610 recruited strains, 448 (73.4%) were isolated from scarlet fever patients, the other 162 (26.6%) were isolated from pharyngeal infection patients; 397 (65.1%) were from urban, the other 213 (34.9%) were from suburb; 240 (39.4%) were from patients aging between 1 - 5 years old, the other 369(60.6%) were from patients aging 6 - 18 years old. A total of 8 types of gene emm (scarlet fever: 6 types, pharyngeal infection: 4 types) and 21 subtypes of gene emn (scarlet fever: 16 subtypes, pharyngeal infection: 10 subtypes) were identified. Three new subtypes were found in the study, naming emm1.63, emm12.62 and st5144.20. Among them, emm1.63 was found both in scarlet fever and pharyngeal infection patients, while emm12.62 and st5144. 20 were only found in pharyngeal infection patients. Among all the types of gene-emm, emm12 accounted for the highest percentage as 80.5% (491/610) and then followed by emm1 (18.0% (110/610)). Among all the subtypes, the dominant subtype was emm12.00, accounting for 69.0% (421/610), following by emm1.00 (16.9% (103/610)) and emm12.19 (6.1% (37/610)). All the above types and subtypes of gene emm were the most prevalent strains in scarlet fever patients and pharyngeal infection patients. Significant differences in the distribution of prevalent strains were observed among various aging patients and regions. The constituent ratios of emm1, emm1.00 and emm12.19 were higher in patients from suburb (emm1: 22.1% (47/213), emm1.00: 19.2% (40/213), emm12.19: 8.0% (17/213)) than those in urban areas (emm1: 15.9% (63/397), emm1.00: 15.6% (62/397), emm12.19: 5.0% (20/397)). The difference showed statistical significance (P < 0.05). The constituent ratio of emm1.00 was higher among patients aging 6-18 years old (19.2% (71/369)) than those aging 1 - 5 years old (13.3% (32/240)). The difference also showed statistical significance (χ(2) = 8.45, P < 0.05). CONCLUSION: Among the types of gene emm in GAS isolated from children in Beijing in year 2011, the most prevalent two were emm12 and emm1, and the most prevalent emm subtypes were emm12.00, emm1.00 and emm12.19. A significant difference in their distribution between various aging patients and isolated places can be obviously found.

[Quantitative evaluation on the effectiveness of prevention and control measures against pandemic influenza A (H1N1) in Beijing, 2009].

OBJECTIVE: To quantitatively evaluate the effectiveness of prevention and control measures against pandemic influenza A (H1N1) in Beijing, 2009 and to provide evidence for developing and adjusting strategies for prevention and control of the disease. METHODS: Considering the seasonality and the number of vaccination on pandemic influenza A (H1N1), data regarding pandemic influenza A (H1N1) in Beijing were collected and analyzed. Based on the dynamics of infectious disease transmission, a quantitative model for evaluation of prevention and control measures was developed. RESULTS: Both latency and infectious periods of pandemic influenza A (H1N1) were estimated to be 1.82 days and 2.08 days, respectively. The effective reproduction numbers of the three periods were 1.13, 1.65 and 0.96, respectively. Thanks to the implementation of a series of measures to prevent and control pandemic influenza A (H1N1), the cumulative number of laboratory-confirmed cases of pandemic influenza A (H1N1) was reduced, making it much smaller than what would have been under the natural situation. Specifically, the program on pandemic (H1N1) 2009 vaccination reduced the cumulative number of laboratory-confirmed cases by 24.08% and postponed the peak time. CONCLUSION: Measures that had been taken during this period, had greatly contributed to the successful prevention and control of pandemic influenza A (H1N1). The 2009 Pandemic (H1N1) vaccination was confirmed to have contributed to the decrease of cumulative number of laboratory-confirmed cases and postponed the peak arrival time.

[Investigation on the source of the first human of avian influenza A (H5N1) case in Beijing].

OBJECTIVE: To investigate the source of the first human case of avian influenza A (H5N1) infection in Beijing. METHODS: Interviewing the relatives of the case and other key persons, collecting and detecting samples of related biological, epidemiological and environmental data of the case were conducted. Later, the infection source was thoroughly investigated. RESULTS: The case ever contacted a slaughtered duck 5 days prior to the onset of illness, and the duck was bought from a stall of a wet market in Yanjiao area of Hebei province. Ten environmental samples were collected in this stall and the neighboring stall of the market. Another 6 samples were tested positive for H5N1 virus by PCR method, with 5 virus strains isolated. The whole-genome sequencing indicated that the amino acid homology between the H5N1 virus strains from the environment and the virus isolated from the case reached 99.8% - 100%. CONCLUSION: From both epidemiological and virological evidence, it was proved that the first human case of avian influenza A (H5N1) infection in Beijing was infected by a duck that carrying H5N1 virus the case contacted 5 days proceeding the onset of illness.