OBJECTIVEHigh altitue pulmonary edema (HAPE) impacts seriously people's health at high altitude. Screening of susceptibility genes for HAPE will be used for the evaluation and protection of susceptible people.

METHODSWe performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 23 HAPE patients and 17 healthy controls. GO and Pathway analysis softwares were used to analyze and draw gene network.

RESULTSThirty-nine SNPs were found to be significantly different between case and control groups (P < 10(-4)). GO and Pathway analysis of 27 genes around the 39 SNPs indicated that these genes mainly participate in the regulating of cell proliferation, regulation of nitrogen compound metabolic process and G-protein coupled receptor protein signaling pathway and so on.

CONCLUSIONIt suggests that these SNPs and genes found in this study may be associated with the susceptibility of HAPE.

Adult ; Altitude Sickness ; genetics ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Hypertension, Pulmonary ; genetics ; Polymorphism, Single Nucleotide ; Young Adult

The applicator therapy is a unique method to treat infant diarrhea in traditional Chinese medicines and widely applied in clinical practice. Currently, many researchers have proved the rationality of the therapy based on the traditional Chinese medicine mechanism and on the data from clinical practice, but its action mechanism is uncertain at present. In this study, with the assistance of pediatric practitioners, the automated ribosomal intergenic-spacer analysis (ARISA) was adopted to study the effect of the adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants, in which Dingguier umbilical paste served as the adjuvant therapy in oral traditional Chinese medicines and fecal samples of infants with different diarrhea symptoms were collected and used as the study materials. The results showed that the adjuvant therapy had a significant effect on the shift of intestinal flora, which was associated with the decrease in the similarity difference to the normal control group and the increase in the number of operational taxonomic units (OTUs) shared with the normal control group. Additionally, adjuvant therapy with Dingguier umbilical paste also showed long action duration and increased OTUs number. These results indicated that Dingguier umbilical paste has the effect in restoring the micro-ecosystem of unbalanced intestinal bacteria. Intestinal flora may be one of major targets for the applicator therapy for the infant diarrhea, but not for the single oral traditional Chinese medicine for infant diarrhea.
Adjuvants, Pharmaceutic ; therapeutic use ; Diarrhea ; drug therapy ; microbiology ; Feces ; microbiology ; Female ; Humans ; Infant ; Intestines ; drug effects ; microbiology ; Male ; Medicine, Chinese Traditional ; methods ; Ointments ; Treatment Outcome ; Umbilicus

Recombinant adenoviral vectors have been widely applied for the basic research and clinical trials of gene therapy. However, the inability of adenovirus to infect hematopoietic cells which lack the specific adenovirus receptors-coxsackie virus and adenovirus receptor (CAR) represents an important limitation in therapeutic applications. This limitation may be overcome by several approaches including modification of adenovirus vector and improvement of the susceptibility of hematopoietic cells. The current progresses in this field were summarized.
Adenoviridae ; genetics ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Genetic Therapy ; Hematopoietic Stem Cells ; metabolism ; Humans ; Receptors, Virus ; genetics ; Transfection

Background: Thoracolumbar junction (TLJ) is the transitional area between the lower thoracic spine and the upper lumbar spine. Vertebral compression fractures and proximal junctional kyphosis following spine surgery often occur in this area. Therefore, the study of development and mechanisms of thoracolumbar junctional degeneration is important for planning surgical management. This study aimed to review radiological parameters of thoracolumbar junctional degenerative kyphosis (TLJDK) in patients with lumbar degenerative kyphosis and to analyze compensatory mechanisms of sagittal balance. Methods: From January 2016 to March 2017, patients with lumbar degenerative kyphosis were enrolled in this radiographic study. Patients were divided into two groups according to thoracolumbar junctional angle (TLJA): the non?TLJDK (NTLJDK) group (TLJA <10°) and the TLJDK group (TLJA≥10°). Complete spinopelvic radiographic parameters were analyzed and compared between two groups. Pearson or Spearman correlation coefficients and independent two?sample t?test or Mann?Whitney U?test were used. Results: Atotal of 77 patients with symptomatic sagittal imbalance due to lumbar degenerative kyphosis were enrolled in this study. There were 34 patients in NTLJDK group (TLJA <10°) and 43 patients in TLJDK group (TLJA ≥10°). The median angle of lumbar lordosis (LL) in the NTLJDK or TLJDK groups was 23.40° (18.50°, 29.48°) or 19.50° (13.30°, 24.55°), respectively. The median TLJAs in all patients and both groups were ?11.20° (?14.60°, ?4.80°), ?3.70° (?7.53°, ?1.73°), and ?14.30° (?17.45°, ?13.00°), respectively. In the NTLJDK group, LLwas correlated with thoracic kyphosis (TK; r = ?0.400, P = 0.019), sacral slope (SS; r = 0.681, P < 0.001), and C7?sagittal vertical axis (r = ?0.402, P = 0.018). In the TLJDK group, LL was correlated with TK (r = ?0.345, P = 0.024), SS (r = 0.595, P < 0.001), and pelvic tilt (r = ?0.363, P = 0.017). There were significant differences in LL, TLJA, TK, SS, and pelvic incidence (PI) between two groups. Conclusions:Although TLJDK is common in patients with lumbar degenerative kyphosis, it might be generated by special characteristics of morphology and biomechanics of the TLJ. To maintain sagittal balance, pelvis back tilt might be more important in patients with TLJDK, whereas thoracic curve changes might be more important in patients without TLJDK.

Altitude ; Heart Rate ; Humans ; Oxygen ; Oxygen Consumption

Objective To investigate the therapeutic effect of interleukin-2(IL-2)on experimental autoimmune encephalomyelitis(EAE)mice.Methods After establishment of the EAE(experimental autoimmune encephalomyelitis) mouse models with MOG35-55 polypeptides,the mice were grouped according to the neurological function score and divided into control group,EAE group and low dose IL-2 treatment group.A double blind method was used to evaluate the neuro-logical impairment in mice.On the 29th day,pathological experiments were carried out in the mice's brain and spinal cord, hematoxylin-eosin staining was used to evaluate the scoring of inflammatory cell infiltration and luxol fast blue staining was used to evaluate the scoring of demyelinating.The proportion of regulatory T cells(Treg)and NK cells(natural killer cell, NK)was detected by flow cytometry,and the immunohistochemical method was used to detect the expressions of glial fibril -lary acidic protein(GFAP)and myelin basic protein(MBP)in the spinal cord.Results Compared with the EAE group, the neurological function score, the inflammatory cell infiltration score and the demyelinating score of the low dose IL-2 treatment group were reduced.The proportion of Treg cells in the low dose IL-2 treatment group was significantly higher than that in the EAE group,and the proportion of NK cells in the low dose IL-2 treatment group was slightly higher than that in the EAE group The expression of GFAP and MBP was detected by immunohistochemistry.The expression level of GFAP in low dose IL-2 treatment group was significantly lower than that in the EAE group,while the expression level of MBP was higher than that in the EAE group.Conclusion Low dose IL-2 has significant therapeutic effect on EAE mice.

The aim of this research was to understand the influence of rhG-CSF on the sphingosine kinase (SphK) activity of monocytes. The peripheral blood monocytes were collected from 6 peripheral blood progenitor cell donors on the fifth day of mobilization with rhG-CSF and from 5 blood donors' buffy coats. The mRNA expressions of monocyte G-CSF receptor and SphK were tested with RT-PCR. The changes of SphK activity of monocytes were assayed after being treated with rhG-CSF. The results showed that the two kinds monocytes collected from both blood donors and peripheral blood progenitor cell donors mobilized with rhG-CSF expressed mRNA of G-CSF receptor and SphK. The SphK activity of monocytes collected from blood donors was not changed significantly after being treated with rhG-CSF (P > 0.05). The SphK activity of monocytes collected from peripheral blood progenitor cell donors transiently increased by (39.6 - 87.2)% after being treated by means of rhG-CSF (P < 0.05) without obviously dose-dependent effect. It is concluded that the SphK activity of monocytes collected from peripheral blood progenitor cell donors can be activated by rhG-CSF.
Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; Humans ; Monocytes ; cytology ; enzymology ; Phosphotransferases (Alcohol Group Acceptor) ; drug effects ; metabolism ; Receptors, Granulocyte Colony-Stimulating Factor ; biosynthesis ; genetics ; Recombinant Proteins

The study was purposed to investigate the effect of extract of Agkistrodon Halys venom on proliferation and apoptosis of K562 cells. The inhibition of K562 cell proliferation was measured by MTT assay; The morphologic changes of K562 cells was observed by microscopy; the apoptosis of K562 cells was measured by flow cytometry; the activity of extracellular signal-regulated kinase (ERK) in K562 cells was detected by Western blot. The results showed that when K562 cells were treated with 0, 1, 10, 20 microg/ml of the extraction for 48 hours, the apoptosis rates were 2.1%, 21.3%, 49.7%, 70.1%, respectively. The proliferation of K562 cells was obviously inhibited in dose-dependent manner. Typical morphologic changes significantly appeared in the extract-treated K562 cells. The extract obviously inhibited the activity of ERK in K562 cells. It is concluded that the extract of Agkistrodon Halys' venom can inhibit the proliferation of K562 cells and induce apoptosis of K562 cells.
Agkistrodon ; Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Complex Mixtures ; pharmacology ; Crotalid Venoms ; chemistry ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; K562 Cells

AIMTo elucidate the effect of sphingosine kinase (SPK) on the hepatocyte growth factor (HGF)-induced migration of endothelial cells.

METHODSWe constructed recombinant adenoviral vectors, which contain SPK gene and its mutant respectively. These adenoviral vectors were packaged and amplified in 293 cells. And intracellular SPK activity was assayed via measurement of [32]P radioisotope labeled S1P; the effect of SPK activation on HGF-induced migration of endothelial cell was observed by Transwell technique.

RESULTSAdenoviral mediated expression of SPK gene increased in ECV 304 cells intracellular SPK activity, which in turn enhanced the HGF-induced migration. Whereas these activities were blocked by the dominant negative SPK gene.

CONCLUSIONThese findings show that SPK activation plays important roles in the regulation of HGF-induced migration of endothelial cells.

Adenoviridae ; metabolism ; Cell Line ; Cell Movement ; drug effects ; Endothelial Cells ; cytology ; Hepatocyte Growth Factor ; pharmacology ; Humans ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; metabolism ; Signal Transduction

AIMTo establish the methods for determining the activity of sphingosine kinase(SPK) and the content of sphingosine 1-phosphate (S1P) in biological samples.

METHODSThe ECV304 cells were transfected with pcDNA3 vector encoding Flag-labeled SPK gene. The expression of SPK was measured by Western blot assay and the activity of SPK was determined by enzymatic reaction, isotope incorporation and thin-layer chromatography methods. The S1P in biological samples was extracted, digested by alkaline phosphatase and then catalyzed by SPK. The S1P contents were determined according to the amounts of products.

RESULTSSPK gene transfection could enhance the expression and activity of SPK in cells markedly, and the cellular S1P was also increased obviously. HGF stimulation could increase the activity of SPK and cellular S1P in ECV304 cells.

CONCLUSIONMethods for determining the activity of SPK and the content of SPK in biological samples were established.

Cell Line ; Cytophotometry ; Humans ; Isotope Labeling ; Lysophospholipids ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; metabolism ; Sphingosine ; analogs & derivatives ; metabolism