GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma / 医学前沿

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.

Current situation of emergency medical service system for patients with acute myocardial infarction in Hebei Province and its influence on treatment and prognosis / 中华急诊医学杂志

Objective:To investigate the current situation of emergency medical service (EMS) system and its effect on treatment of the acute stage and short- and long-term prognosis in patients with acute myocardial infarction in Hebei province.Methods:Totally 2 961 patients with acute myocardial infarction who were admitted to major tertiary and some representative secondary hospitals in Hebei province from January 2016 to December 2016 were collected. According to the pattern of arriving hospital, all the patients were divided into the EMS group and self-transport group. The general conditions, time from onset to treatment, treatment methods, in-hospital mortality rate and 3-year mortality rate were compared between the two groups.Results:Of the included 2 961 patients, 33.13% of them were transported through EMS and 66.87% of them by private transport. Patients with a history of hypertension and ST-segment elevation myocardial infarction were more likely to choose EMS, and the difference was statistically significant ( P<0.05). Moreover, patients in the EMS group were more likely to go to tertiary hospitals for treatment (88.58% vs 85.76%, P=0.033). The time from onset to treatment of the EMS group was significantly shorter than that of the self-transport group (160 min vs 185 min, P<0.01), and the proportion of patients in the EMS group from onset-to-door time in <3 h and 3-6 h was higher than that of the self-transport group (55.76% vs 49.14%, 21.41% vs 19.09%, P<0.01). Compared with the self-transport group, the EMS group has a higher rate of reperfusion therapy (67.48% vs 61.67%, P=0.002). Patients in the EMS group had a higher in-hospital mortality rate in the acute stage (7.03% vs 4.44%, P=0.003), but its 3-year mortality rate was lower than that of the self-transport group (17.31% vs 20.77%, P<0.05). Conclusions:EMS can shorten symptom-onset-to-arrival time, increase the rate of reperfusion therapy and improve long-term prognosis of patients with acute myocardial infarction.

Connectivity between visual brain regions and whole brain among children diagnosed with autism spectrum disorder / 中国学校卫生

Objective@#To explore the functional connectivity between the visual brain regions and whole brain in children with autism spectrum disorder (ASD) at resting state, and to further analyze the correlation with their clinical manifestations.@*Methods@#The functional magnetic resonance imaging (fMRI) data of 34 boys with ASD enrolled from ASD designated rehabilitation institutions and 29 healthy boys enrolled from several kindergartens in Heilongjiang were collected. Based on the resting-state functional connectivity magnetic resonance imaging (rs-fc MRI) analysis, the BA17 of the primary visual brain region and the BA18/19 of the higher visual brain region were taken as the regions of interest (ROI) to calculate the functional connectivity level between the visual brain regions and whole brain, and the differences between the two groups were compared. Multiple developmental scales were used to evaluate the behavior of ASD children, and Pearson correlation analysis was used to explore the relationship between functional connection strength and autistic behavior.@*Results@#The ASD group had decreased positive connectivity between BA17 and the right fusiform gyrus (FFG), and was negatively correlated with social interaction of ADI-R and the total scores of CARS (r=-0.41, -0.48, P<0.05); ASD group had decreased positive connectivity between BA17 and the left FFG, there was a negative correlation with social motivation of SRS (r=-0.43, P<0.05); ASD group had decreased positive connectivity between BA17 and the left posterior cingulate gyrus (PCG). Children with ASD had decreased positive connectivity between BA18/19 and left calcarine fissure and surrounding cortex (CAL), which was positively correlated with attention conversion of AQ, total scores of CARS (r=0.43, 0.40, P<0.05), and the children with ASD had deceased positive connectivity between BA18/19 and right precuneus (PCUN).@*Conclusion@#In resting state, the functional connectivity of primary and higher visual brain regions and whole brain of ASD children is different from that in healthy children, and there is a significant correlation between abnormal level and autistic behaviors.

Study on the Effect and Its Mechanism of Dihydroartemisinin on the Metabolism of Amino Acids in Hepatoma Cells / 中国药房

OBJECTIVE：To investigate the effects of dihydroartemisinin （DHA）on the metabolism of amino acid metabolites in human hepatocellular carcinoma cells Huh 7 and BEL- 7402，and to provide theoretic basis for clarifying the mechanism of DHA regulating the metabolism of hepatocellular carcinoma cells. METHODS ：CCK-8 method was taken to detect the effect of different concentrations of DHA （12.5，25，50，100 µmol/L）treating for 24，48，72 h on the two kinds of cells. Two kinds of cells were divided into control group and administration group （DHA，25 µmol/L），and then cultured with drug-free or drug-containing medium for 24 h，operated in parallel for three times. After derivatization of cell samples in each group ，GC-MS method was used to detect the content of amino acid metabolites ，combined with SIMCA-P software analysis and compound library comparison ，the differential metabolites in two kinds of cells were screened out. The pathway enrichment analysis of differential metabolism was conducted with Metaboanalyst 4.0 software. RESULTS ：Compared with control group ，the contents of glutamine ，glutathione， phenylalanine，fumaric acid and taurine were trending down in Huh 7 or BEL- 7402 cells. There were 28 and 29 differential metabolites obtained from the above two kinds of cells ，and 10 of them were common differential metabolites ，including glutamine，glutathione，taurine，fumaric acid ，phenylalanine，etc. The differential metabolites were enriched in 8 and 6 pathways respectively. The common enrichment pathways were amino acid-tRNA biosynthesis ，aspartate-alanine-glutamate metabolism ， nitrogen metabolism ，phenylalanine metabolism and pentose phosphate pathway ，etc. CONCLUSIONS ：DHA can significantly reduce the activities of Huh 7 cells and BEL- 7402 cells，and the contents of glutamine ，glutamic acid ，glutathione and phenylalanine，etc. It may regulate the growth of the two kinds of cells by influencing the mechanism of aspartic acid- alanine-glutamate metabolic pathway ，etc.

Study on the effect of curculigoside on osteoporosis / 中华口腔医学杂志

Objective@#To investigate the regulation of curculigoside on osteogenic differentiation of MG63 and the protective effect on osteoporosis model mice.@*Methods@#The effects of curculigoside on the survival rate of dexamethasone or H2O2 treated MG63 were detected by methyl thiazolyl tetrazolium (MTT). The specimens were divided into six groups: blank control group, blank administration group, model group (dexamethasone or H2O2 treatment group), low dose group (dexamethasone or H2O2+1.0 μmol/L curculigoside), medium dose group (dexamethasone or H2O2+2.5 μmol/L curculigoside) and high dose group (dexamethasone or H2O2+5.0 μmol/L curculigoside), the sample size of each group was 10. Western blotting was used to detect the expression of osteogenic differentiation-related proteins [type Ⅰ collagen, integrin β1, osteoblast-specific transcription factor (Osterix), osteocalcin and osteopontin] in MG63 cells after 1, 7 and 14 days incubated with 0, 1.0, 2.5 and 5.0 μmol/L of curculigoside. The sample size for each group at each time point was six. The experimental mice were divided into 4 groups: blank group, model group (dexamethasone treatment group), curculigoside low-dose group (dexamethasone+5 mg/kg curculigoside) and high-dose group (dexamethasone+45 mg/kg curculigoside), twenty each. After treatment, the tibia of the mice in each group were subjected to sacral HE staining. The number of osteoclasts was counted, and the levels of oxidative related factors in serum were determined by enzyme-linked immunosorbent assay (ELISA).@*Results@#The MTT results showed that compared with the blank control group [(100±3.7)%], the cell survival rate decreased to (44.1±5.7)% after treatment with dexamethasone, and the survival rate increased to (79.7±3.8)% after treatment with 5.0 μmol/L of curculigoside. The cell survival rate decreased to (59.1±4.7)% after H2O2 treatment, and the survival rate increased to (80.8±3.5)% after treatment with 2.5 μmol/L of curculigoside. The results of Western blotting showed that the expression of type Ⅰ collagen and integrin β1 in MG63 cells was significantly increased after 1.0, 2.5 and 5.0 μmol/L of curculigoside for 1, 7 and 14 days compared with 0 μmol/L of curculigo side for the same period. After increasing (P<0.05), the expression of Osterix and osteocalcin was significantly increased after 1 day of incubation (P<0.05). However, compared with 0 μmol/L curculigoside treatment, the expression of osteopontin in MG63 cells was not significantly different after incubation with 1.0, 2.5, 5.0 μmol/L of curculigoside for 7 and 14 days (P>0.05). Compared with the blank group, the number of tibia osteoclasts in the osteoporosis model group increased. In the low-dose and high-dose groups of curculigoside, the tibia cortex was more continuous and the number of osteoclasts decreased. Compared with the blank group, the activity of oxygen in the osteoporosis model group was significantly increased (P<0.05), and superoxide dimutase and catalase were significantly decreased (P<0.05).@*Conclusions@#Curculigoside promotes the differentiation of MG63 cells by increasing the expression of osteoblast differentiation-related proteins, and has a certain therapeutic effect on dexamethasone-induced osteoporosis mice.

Morphological characteristics of expressions of DKK1 in different periods of tooth development in postnatal mice and their significances / 吉林大学学报(医学版)

Objective:To study the expression characteristics of Dickkopf1 (DKK1) in different time and space during tooth development of the postnatal mice, and to provide the theoretical basis for clarifying the mechanism of Wnt signaling pathway in regulating the tooth development.Methods:The postnatal Kunming mice at days 0.5, 6.5, 12.5, 18.5, 24.5, and 30.5 respectively after birth were selected and divided into various groups by time,three in each group.The mice in each group were sacrificed and the paraffin sections of mandibular bone including the first molar were prepared at the thickness of 5 μm, followed by HE staining and immunohistochemical staining in order to detect the expressions of DKK1 in tooth tissue and periodontal tissue.Results:At 0.5 d after birth, the mandibular first molar tooth germ was in the bell stage.At 6.5 d the enamel development of mandibular first molar was almost completed, and the epithelium root sheath extended to the root direction.At 12.5 d the dentin development of crown was completed, with the root formatted about 1/3. At 18.5 d the root had formatted about 2/3.At 24.5 d the root had reached the full length.At 30.5 d the apical foramen was narrow, and the root development was basically completed.There was no DKK1 expression at 0.5 d, but it expressed in the odontoblasts and predentin at 6.5 d. From days 12.5 to 30.5,the expressions of DKK1 were positive in periodontal ligament, alveolar bone, and cellular cementum as odontoblasts, which were gradually increased with the prolongation of time.However, no expression of DKK1 was detected in the pulp.Conclusion:DKK1 shows regular expressions at different tooth developmental stages after birth, suggesting its potential role in the growth of dentin and periodontal tissues.

Controllable Abdominal Breath in treatment of Migraine / 中国心理卫生杂志

Objective:To study the effect of controllable abdominal breath in treatment of migraine.Method:20 patients(10 male,10 female,aged 20-30 years)with migraine according to international diagnostic standard published 1990 were randomly divided into study group and control group.The study group received training of controllable abdominal breath.All subjects were followed for 3 months.Changes of symptoms and hemorhelogy were recorded.Result:Study group improved in both symptom and index of hemorheology after treatment,and the results were better than that of control.Conclusion:Controllable abdominal breath is effective in treatment of migraine.