OBJECTIVETo investigate the intracellular trafficking pathway of fusion protein epidermal growth factor-adenovirus early region 4 open reading frame 4 protein (EGF-E4orf4) internalized via epidermal growth factor (EGF) receptor and its affectivity on extracellular signal-regulated kinase (ERK) phosphorylation.

METHODSMDA-MB-231 and BGC823 cells were incubated with fluorescein isothiocyanate-EGF-E4orf4 or EGF at different time points. The specific molecular mark of early endosome or late lysosome was labeled by indirect immunofluorescence, and then colocalization staining was observed using confocal laser microscopy. The levels of ERK phosphorylation were detected by Western blot.

RESULTSThe fluorescent signal of fusion protein EGF-E4orf4 accumulated within the cells and congregated to the perinuclear region. A nucleus localization of the fusion protein was only at MDA-MB-231 cell. Colocalization of EGF-E4orf4 with early endosome/late lysosome was observed. EGF-E4orf4 stimulated ERK phosphorylation, which was most obvious 10 minutes after stimulation, and then gradually attenuated, which was similar to EGF stimulation but with a less decrease.

CONCLUSIONSInternalized EGF-E4orf4 can be slowly degraded via endosome-lysosome pathway. The action features of EGF-E4orf4 are remarkably different between MDA-MB-231 and BGC823 cells, which may help explain the differences in its anti-tumor potency and in the special selectivity toward different tumor cells.

Adenovirus E4 Proteins ; pharmacokinetics ; Cell Line, Tumor ; Epidermal Growth Factor ; pharmacokinetics ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Phosphorylation ; drug effects ; Protein Transport ; Recombinant Fusion Proteins ; pharmacokinetics ; Viral Proteins ; pharmacokinetics

In order to learn about the genetic characteristic of human enterovirus type71 (HEV71) isolated from cases of Hand, Foot and Mouth Disease (HFMD) in Yunnan Province from 2009 to 2010. 50 isolates form HFMD cases were performed entire VP1 coding region amplification by reverse transcription-polymerase chain reaction and sequencing the nucleotide sequences; then the phylogenetic tree was constructed. The complete nucleotide sequences of region VP1 of the 50 strains were all 891nt length coding 297 amino acids. The result of molecular identification of the 50 strains is HEV71. Phylogenetic analysis indicated that 48 EV71 isolates belonged to subgenotype C4a and 2 EV71 isolates belonged to genotype A. From 2009 to 2010, the pathogen of HFMD cases were EV71 strains in Yunnan province, which were co-evolved with isolates from other provinces in mainland of China. There was no significant difference found in the whole sequence of VP1 gene of the strains isolated from different regions or under different diseases occurred, but the spread of genetype A appared in Yunnan Province in 2009.
Capsid Proteins ; genetics ; Child, Preschool ; China ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; pathogenicity ; Female ; Genotyping Techniques ; Hand, Foot and Mouth Disease ; virology ; Humans ; Male ; Phylogeny ; Sequence Analysis, DNA

BACKGROUNDAnomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare but potentially life-threatening congenital heart defect. A retrospective analysis was carried out to elucidate the surgical outcomes of ALCAPA in infants and children using follow-up echocardiography.

METHODSFrom September 2008 to March 2017, 26 children diagnosed with ALCAPA underwent left coronary re-implantation. All surviving patients received echocardiography during follow-up.

RESULTSThe mortality rate after the operation was 11.5%. Before repair, twenty patients (76.9%) presented with left ventricular (LV) dysfunction. The mean Z-score of the preoperative LV end-diastolic diameter was 4.42 ± 2.09. Mitral regurgitation (MR) was present in all patients. Two patients (7.7%), both with mitral valve prolapse, underwent mitral valve repair at the time of ALCAPA repair. Two children required postoperative extracorporeal membrane oxygenation. LV function normalized at a median time of 5.3 months (range: 0.5-36.0 months). The Z-score of the LV end-diastolic diameter decreased simultaneously. The degree of MR gradually decreased in all surviving patients. All patients had patency of the proximal left coronary artery confirmed by echocardiography at the most recent follow-up. Six patients (26.1%) showed supravalvar pulmonary stenosis and seven patients (30.4%) showed right pulmonary stenosis during follow-up.

CONCLUSIONSCoronary re-implantation was effective for rebuilding a dual coronary system in patients with ALCAPA and resulted in progressive improved LV function and reduced functional MR. Echocardiography was valuable for evaluating the outcomes. LV function, the degree of MR, and possible complications could be detected with follow-up echocardiography.

OBJECTIVETo investigate the clinical features of unexpected sudden death (SUD) clustered in families in Yunnan province.

METHODSThis retrospective study analyzed the clinical features of SUD occurred between July to September 2005 in 7 families in Yunnan province.

RESULTSAll 16 SUD patients shared common clinical features such as fatigue and repeated syncope and one group of SUD patients (n = 8 from 4 families) presented with the gastric intestinal tract manifestations including nausea, vomiting, abdominal pain and diarrhea with suspected dietary history and abnormal laboratory enzyme findings (GOT/GPT, CK/CKMB, LDH/LDH1 etc.). In SUD patients without gastric intestinal tract manifestations (n = 8 from 3 families), there were no clear symptoms before death and repeated ventricular tachycardia and ventricular fibrillation were recorded in one survivor. There was no clear evidence for the involvements of hereditary and infectious factors for observed SUD.

CONCLUSIONThe reason for the unexpected sudden death clustered in 7 families in Yunnan remains unclear. Repeated syncope and fatigue served as the common clinical features in the presence or absence of gastric intestinal tract manifestations in all SUD cases. Further studies are needed to clarify the pathology and detailed clinical manifestations of SUD occurred in this area.

Adolescent ; Adult ; Bias ; Cause of Death ; Child ; China ; epidemiology ; Death, Sudden ; epidemiology ; Family ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Objective: To understand the spatial characteristics of echinococcosis and associated factors in the pastoral area of Qinghai province, and provide evidence for the effective prevention and control of echinococcosis. Methods: The number of echinococcosis cases in the pastoral areas of Qinghai in 2019 was collected to perform spatial epidemiological analysis. The thematic map of the distribution of echinococcosis cases was generated with software ArcGIS 10.8 for visual analysis and spatial autocorrelation analysis. The spatial autocorrelation and spatial scanning analysis were performed to estimate the clustering of echinococcosis with software SaTScan 9.5. Software GeoDa 1.14 and ArcGIS 10.8 were used to establish spatial lag model and geographical weighted regression model to analyze the related factors of echinococcosis epidemic. Results: In 2019, the echinococcosis surveillance covered 64 741 people in the pastoral area of Qinghai, and 829 echinococcosis cases were found, with a prevalence rate of 1.28%. The distribution of the cases had spatial correlation (Moran's I=0.41, P<0.001). The most possible clustering areas indicated by spatial scanning analysis included Banma, Jiuzhi, Dari and Gande counties of Guoluo Tibetan Autonomous Prefecture (LLR=460.77, RR=9.20, P<0.001). The prevalence of echinococcosis in the pastoral areas was positively associated with the total annual precipitation (β=0.13, P=0.036), and negatively associated with population density (β=-1.36, P=0.019) and doctors/nurse ratio (β=-25.60, P=0.026). Conclusions: The distribution of echinococcosis cases in the pastoral areas of Qinghai in 2019 had spatial correlation, and the prevalence was affected by total annual precipitation, population density, and doctors/nurse ratio.
China/epidemiology* ; Cluster Analysis ; Echinococcosis/epidemiology* ; Epidemics ; Humans ; Prevalence ; Spatial Analysis

This work was launched to explore the effect of habitat and growth year on the secondary metabolites contents of cultivated Polygala tenuifolia. The samples of cultivated P. tenuifolia were analyzed by ultra-high performance liquid chromatography(UPLC)-quadrupole time-of-flight mass spectrometry(Q-TOF MS), and the obtained data were analyzed using multiple statistical analysis and cluster analysis. The results showed that compared with growth year, habitat is a main influencing factor which affected the secondary metabolites contents of P. tenuifolia. The contents of sucrose esters and oligosacchride multi-esters are greatly dependent on the habitat (the sample-AG with high levels of components of tenuifoliside B and tenuifoliside C, and the sample-FY with high levels of 3,6'-disinapoyl sucrose, tenuifoliose S, tenuifoliose L, and tenuifoliose V). There is no obvious effect of habitat and growth year on xanthone. The contents of triterpene saponins are greatly dependent on the growth year, and the content of parts of triterpene saponins increased as time goes on.The result indicated that the effect of habitat and growth year on different types of secondary metabolites is not completely equivalent. This study will contribute to the breeding of P. tenuifolia and amendment of current commodity criteria.