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

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

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.

OBJECTIVETo determine the mechanism underlying the therapeutic activities of glycogen synthase kinase 3b (GSK3b) against hepatic ischemia-reperfusion (H-IR) injury by investigating the inhibitive effects of GSK3b on inflammation mediated by Toll-like receptor 4 (TLR4).

METHODSC57BL/6 male mice were subjected to 90 min of warm liver cephalad lobe ischemia, followed by reperfusion for various lengths of time. The mice were divided into three groups: the H-IR untreated model (control group), and the H-IR inflammation-induced models that received an intraperitoneal injection of purified lipopolysaccharide (LPS) endotoxin alone (inflammation group) or with pretreatment of the SB216763 GSK3b-specific inhibitor (intervention group). To create a parallel isolated cell system for detailed investigations of macrophages, marrow-derived stem cells were isolated from femurs of the H-IR control group of mice and used to derive primary macrophages. The cells were then divided into the same three groups as the whole mouse system: control, LPS-induced inflammation model, and inflammation model with SB216763 intervention. Differential expressions of inflammation-related proteins and genes were detected by Western blotting and real-time quantitative PCR, respectively.

RESULTSThe phosphorylation levels of ERK, JNK and p38 MAPK were induced in liver at 1 h after reperfusion, but then steadily decreased and returned to baseline levels by 4 h after reperfusion. In addition, the phosphorylation levels of ERK and JNK were induced in macrophages at 15 min after LPS stimulation, while the phosphorylation level of p38 MAPK was induced at 1 h; SB216763 pretreatment suppressed the LPS-stimulated ERK, JNK and p38 phosphorylation in macrophages. In the mouse model, GSK3b activity was found to promote the gene expression of anti-inflammatory cytokine IL-10 (control: 0.21 ± 0.08, inflammation: 0.83 ± 0.21, intervention: 1.76 ± 0.67; F = 3.16, P = 0.027) but to significantly inhibit the gene expression of pro-inflammatory cytokines IL-12 (control: 0.11 ± 0.05, inflammation: 0.85 ± 0.11, intervention: 0.43 ± 0.10; F = 2.67, P = 0.038), TNF-a, (control: 0.052 ± 0.012, inflammation: 8.11 ± 0.98, intervention: 3.9 ± 0.82; F = 4.13, P = 0.016), IL-6 (control: 0.22 ± 0.08, inflammation: 6.37 ± 0.81, intervention: 2.11 ± 0.63; F = 3.21, P = 0.024), and IL-1b (control: 0.12 ± 0.07, inflammation: 2.51 ± 0.62, and intervention: 1.28 ± 0.33; F = 2.22, P = 0.030).

CONCLUSIONInhibition of GSK3b selectively regulates the expression of anti-inflammatory and pro-inflammatory cytokines in liver Kupffer cells (liver macrophages). This process may be one of the mechanisms underlying the ability of GSK3b to ameliorate hepatic ischemia-reperfusion injury, possibly because inhibition of pro-inflammatory cytokines may indirectly mediate liver cell apoptosis.

Animals ; Cells, Cultured ; Cytokines ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Inflammation ; metabolism ; pathology ; Lipopolysaccharides ; adverse effects ; Liver ; pathology ; Macrophages ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury ; Toll-Like Receptor 4 ; metabolism

OBJECTIVETo construct an apparatus for the oxygen uptake measurement of rats exposed to hypobaric hypoxia at different simulated altitude.

METHODSThe capacity of this apparatus was about 0.01 m3. It included animal experimental cabin, reference cabin, altimeter, altitude vertical velocity indicator, pressure difference inductor and oxygen compensator, low scale manometer, soda lime and calcium chloride, small fan, thermometer, circulating water system and vacuum pump. The oxygen uptake of the rats at 6 000 m, 4 000 m and 1 000 m simulated altitude was measured using this apparatus.

RESULTSThe oxygen uptake of the rats at 50 m, 4 000 m and 6 000 m simulated altitude was (24.4 +/- 2.1), (10.8 +/- 2.0) and (8.8 +/- 1.6) ml O2/(kg x min) respectively (average +/- s, n = 10). The oxygen uptake decreased as altitude increased.

CONCLUSIONThis apparatus can be used to measure the oxygen uptake of the rats at different simulated altitude.

Altitude ; Altitude Sickness ; physiopathology ; Animals ; Computer Simulation ; Equipment and Supplies ; Hypoxia ; physiopathology ; Male ; Oxygen ; metabolism ; Oxygen Consumption ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the role of the key intracellular signaling molecule glycogen synthase kinase-3 beta in the mechanism of liver ischemia reperfusion (IR).

METHODSC57BL/6 mice were subjected to 90 min warm liver cephalad lobe ischemia, followed by various length of reperfusion. Experiment groups included sham control group, liver IRI model group and glycogen synthase kinase-3 beta inhibitor-treated group (SB216763 in DMSO, 25 g/kg, i.p, 2 hour prior to the onset of liver ischemia). The expression of glycogen synthase kinase-3 beta protein was analysed by Western blotting. The serum ALT levels were determined to reflect the function of liver. The affected liver lobes were harvested for histology analysis. The inflammatory gene expression was detected by Quantitative PCR.

RESULTSBy western blot analysis, we found that ischemia itself activated glycogen synthase kinase-3 beta by a significant decrease of its phosphorylation. Glycogen synthase kinase-3 beta inhibitor SB216763-pretreatment ameliorated the liver damages significantly as compared to the controls (sALT: 2046+/-513 U/L vs 5809+/-1689 U/L, P = 0.0153), and suppressed the gene expressions of IL-12, TNFa, IL-1b and IL-6.

CONCLUSIONSThis study demonstrated that the ischemia process modulated liver innate immune activation via a GSK-3-dependent mechanism which favored the development of a pro-inflammation response and lead to liver tissue damages. GSK-3b may be a new therapeutic target to ameliorate liver IRI in transplant patients.

Animals ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Inflammation ; metabolism ; Liver ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury ; metabolism ; pathology

This study was purposed to investigate the effects of 2-deoxy-D-glucose (2-DG) on sensitizing HL-60 cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis and its possible mechanism. The proliferative inhibition of HL-60 cells treated with different concentrations of 2-DG and TRAIL was measured by MTT assay. The cells were treated with 2-DG, TRAIL, and 2-DG combined with TRAIL at the concentration < IC50 value, i.e. 10 mmol/L for 2-DG and 100 ng/ml for TRAIL. Apoptosis was analyzed by flow cytometry with PI staining; the expression of RIP1, GRP78, and PARP was analyzed by Western blot; the activity of caspase-3 was detected by special detection kit. The results showed that the combined treatment of HL-60 cells for 48 h induced an apoptotic rate of (45.1 ± 4.3)%, which was significantly higher than that of treated with 2-DG or TRAIL alone; at the same time, the combined treatment potentiated the expression of GRP78 and caspase-3 activity, and down-regulated the expression of RIP1. It is concluded that 2-DG can sensitize HL-60 cells to TRAIL-induced apoptosis, which may be correlated with excessive endoplasmic reticulum stress response, down-regulation of RIP1, and increase of caspase-3 activity.
Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Deoxyglucose ; pharmacology ; HL-60 Cells ; Heat-Shock Proteins ; metabolism ; Humans ; Nuclear Pore Complex Proteins ; metabolism ; RNA-Binding Proteins ; metabolism ; TNF-Related Apoptosis-Inducing Ligand ; metabolism ; pharmacology