In recent decades, the mortality and morbidity of diabetes have increased such that it is becoming a major worldwide public health problem. Intensive blood glucose control could significantly raise the patients life and their survival quality nevertheless it develops hypoglycaemia. Repeated hypoglycemia leads to glucose conterregulate deficiencyand hamper reaching glucose target goals. Astragalus, a traditional Chinese herb used in diabetic therapy for thousands years, has also proven its glucose counterregulationeffect on preventing hypoglycemia. Here, we summarize its glycemic regulation mechanism in different extracts. It is projected that the efficacy and safety of astragalus extracts will be proven in clinical trials and animal experiments in future, and this herb extract might be known as a new class of anti-diabetic drug without hypolycemia danger.

Objective:To investigate the association of XPD rs13181 (codon751A/C, Lys751Gln), rs238406 (codon156C/A, Arg156Arg), XPC rs2279017 (i11C/A), and XRCC4 rs3734091 (codon247T/C, Ala247Ser) polymorphisms with colorectal cancer (CRC) susceptibility. Methods:A total of 338 patients with CRC who were treated at the Beijing Cancer Hospital from April 2013 to January 2016 (case group) and 315 healthy controls (control group) were genotyped using TaqMan technology. Results:The genotype GT and G alleles of XPD rs13181 increased the risk of CRC (GT>TT, adjusted OR=1.69, 95%CI=1.15-2.47, P=0.007;G>T, adjusted OR=1.77, 95%CI=1.19-2.64, P=0.005). The genotype GT and T alleles of XRCC4 rs3734091 increased the susceptibility of CRC (GT>GG, adjusted OR=9.02, 95%CI=5.61-14.50, P<0.001;T>G, adjusted OR=4.06, 95%CI=2.49-6.61, P<0.001). Analyses of XPD rs13181 and rs238406 indicated that the haplotype GT significantly decreased the risk of CRC (adjusted OR=0.39, 95%CI=0.18-0.85, P=0.018). Moreover, the combinations of the XPC rs2279017 G allele and the XRCC4 rs3734091 T allele (adjusted OR=28.43, 95%CI=6.85-117.95, P<0.001) and the XPD rs13181 G allele and the XRCC4 rs3734091 T allele (adjusted OR=10.24, 95%CI=4.69-22.35, P<0.001) exhibited significantly increased CRC risk. Conclusion:The polymorphisms of XPD rs13181 and XRCC4 rs3734091 increased the risk of CRC.

OBJECTIVE:To prospectively study the effects of trimetazidine on myocardial remodeling and oxidative stress in patients with hypertensive heart disease (HHD),in order to provide reference for clinical treatment of HHD.METHODS:Eighty-two HHD patients were selected from our hospital during Jan.2014-Jul.2016,and they were divided into control group and observation group by sortition randomization method,with 41 cases in each group.Control group received routine HHD chemical drug (antihypertensive drugs,lipid-lowering drugs,hypoglycemic agents and antiplatelet drugs,etc.) therapy.Observation group was additionally given trimetazidine 20 mg,tid,on the basis of control group.Both groups were treated for 3 months.Before treatment and after 3 months of treatment,SBP,DBP,New York Heart Association (NYHA) cardiac function grade,LVEF,LVESD,LVEDD,LVMI and the levels of GSH-Px,SOD,MDA and ROS were compared between 2 group.The occurrence of ADR was observed in 2 groups.RESULTS:Before treatment,there was no statistical significance in each index between 2 groups (P＞0.05).After 3 months of treatment,SBP and DBP of 2 groups were decreased significantly compared to before treatment (P＜0.01);there was no statistical significance between 2 groups (P＞0.05).There was no statistical significance in NYHA cardiac function grade compared to before treatment or between 2 groups (P＞0.05).LVESD,LVEDD and LVMI of observation group were decreased significantly compared to before treatment (P＜0.05);LVEF was increased significantly compared to before treatment (P＜0.05);LVEDD and LVMI of observation group were significantly lower than control group (P＜0.05).Compared to before treatment,SOD level of control group was decreased significantly,while the levels of GSH-Px and SOD in observation group were increased significantly;MDA and ROS of observation group were significantly lower than those of control group,with statistical significance (P＜0.05).No obvious ADR was found in 2 groups.CONCLUSIONS:Trimetazidine can improve cayocardial remodeling and reduce oxidative stress level of HHD patients with good safety.

The central nervous system (CNS) plays a key regulatory role in glucose homeostasis. In particular, the brain is important in initiating and coordinating protective counterregulatory responses when blood glucose levels fall. This may due to the metabolic dependency of the CNS on glucose, and protection of food supply to the brain. In healthy subjects, blood glucose is normally maintained within a relatively narrow range. Hypoglycemia in diabetic patients can increase the risk of complications, such as heart disease and diabetic peripheral neuropathy. The clinical research finds that the use of traditional Chinese medicine (TCM) has a positive effect on the treatment of hypoglycemia. Here the authors reviewed the current understanding of sensing and counterregulatory responses to hypoglycemia, and discuss combining traditional Chinese and Western medicine and the theory of iatrogenic hypoglycemia in diabetes treatment. Furthermore, the authors clarify the feasibility of treating hypoglycemia on the basis of TCM theory and CNS and have an insight on its clinical practice.

OBJECTIVE: To explore the genetic basis of cerebral palsy (CP). METHODS: A pair of twins with cerebral palsy and different phenotypes were subjected to whole genome sequencing, and other 8 children with CP were subjected to whole exome sequencing. Genetic variations were screened by a self-designed filtration process in order to explore the CP-related biological pathways and genes. RESULTS: Three biological pathways related to CP were identified, which included axon guiding, transmission across chemical synapses and protein-protein interactions at synapses, and 25 susceptibility genes for CP were identified. CONCLUSION The molecular mechanism of CP has been explored, which may provide clues for development of new treatment for CP.
Cerebral Palsy ; genetics ; Child ; Genetic Testing ; Humans ; Phenotype ; Whole Exome Sequencing ; Whole Genome Sequencing

Objective To investigate the characteristics and feasibility of genipin-crosslinked amniotic membrane(AM) as bio-scaffold.Methods Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from fresh umbilical cord and cultured by adherent method.The expressions of PE-CD34,PE-CD45,PE-CD90,FITC-105 and FITC-Oct-4,the markers of hUCMSCs,were detected by flow cytometry.Alizarin red and oil red O staining were performed to identify the cells after adipogenesis and osteogenesis induction on the third-generation cells.Human AMs were treated at 37 ℃ and 45 ℃ by 0.5％ and 1％ genipin solution for 24,36 and 48 hours respectively,and the mechanical properties of AM in each group were measured and compared.The hUCMSCs were divided into only hUCMSCs culture group,fresh AM group,crosslinked AM group,gelatin group and crosslinked AM+gelatin group,and the cells were cultured in the corresponding medium.The content of hydroxyproline among the groups was detected with hydroxyproline kit,and proliferation of the cells (absorbance) was assayed by MTT method to evaluate the biological compatibility of crosslinked AM.Results The maximum tensile displacement of the crosslinked-AM by 0.5％ and 1％ genipin was (8.31±0.43)mm and (4.49±0.37)mm respectively,and those after crosslinked with 0.5％ genipin under the 37 ℃ and 45 ℃ for 24 hours was (9.89±1.09)mm and (5.39±0.59)mm,respectively,showing a significant difference between them (t =6.389,P＜0.05).The maximum tensile displacement of the crosslinked-AM was gradually decreased as the lapse of crosslinking time,and an insignificant difference was found among 24,36 and 48 hours after 0.5％ genipin treatment under the 37 ℃ (P＞0.05).The loading force of the crosslinked-AM was significantly higher in the 1％ genipin treated group than that in the 0.5％ genipin treated group (P＜0.05),and the loading force of the AM was significantly increased in 45 ℃,0.5％ genipin,24 hours crosslinked group compared with the 37 ℃,0.5％ genipin,24 hours crosslinked group (t =5.528,P＜0.05).The content of hydroxyproline in the AM was (1.28±0.36),(2.03 ±0.49) and (2.11 ±0.10) mg/g in the 1％ genipin crosslinked AM group,0.5％ genipin crosslinked AM group and fresh AM group,respectively,and the content of hydroxyproline in the AM in the 1％ genipin group was significantly lower than that in the 0.5％ genipin group in the fresh AM group (both at P＜0.05).The proliferative values of the hUCMSCs were significantly lower in the only hUCMSCs culture group,fresh AM group and gelatin group were significantly reduced in comparison with the crosslinked AM group and crosslinked AM+gelatin group (all at P＜0.05).There was no significant difference in the proliferative values of the hUCMSCs between crosslinked AM group and crosslinked AM+gelatin group (P＞0.05).Conclusions Different crosslinked temprature,crosslinking period and concentration of genipin impact the mechanical properties of AM.Crosslinked AM with genipin is feasible as a carrier scaffold of artificial cornea because of less tissue toxicity and better plasticity.

Objective To assess the effect and underlying molecular events of caffeic acid phenethyl ester (CAPE) on rat hepatic stellate HSC-T6 cells. Methods HSC-T6 cells were grown and treated with different concentrations of CAPE (5, 10, or 15 μmol/L), transfected with or without LC3-GFP plasmid, and then treated with or without an autophagy inducer rapamycin or the autophagy inhibitor 3-methyladenine (3-MA). The changed cell viability and morphology were assessed by using cell viability MTT assay and Transmission electron microscope, respectively. The expression of LC3 protein in HSC-T6 cells was detected by immunofluorescence assay, the autophagy-related genes expression of ATG5, ATG7, ATG12, Beclin1 and LC3 were detected by qRT-PCR, and the expression of ATG7, Beclin1, LC3I/Ⅱ, p-AKT/AKT, p-mTOR protein was detected by Western-blot. Comparison between multiple groups was analyzed by one-way ANOVA with Dunnett t -test. Results Compared with the control, CAPE treatment significantly reduced cell viability but induced formation of lipid droplets and roulette-shaped autophagosomes. Compared with the control (13.34%±2.59), LC3 protein was significantly induced in HSC-T6 cells after CAPE treatment (5 μmol/L, 23.68%±3.76, t =-5.553, P < 0.001; 10 μmol/L, 43.47%±3.83, t =-15.958, P < 0.001; 15 μM, 57.25%±2.78, t =-28.334, P < 0.001), while levels of ATG5, ATG7, ATG12, Beclin 1, and LC3 mRNAs were all significantly increased in 10 μm and 15 μm CAPE treated cells vs the control (all P < 0.05). After LC3 overexpression in HSC-T6 cells, LC3 protein was induced vs the vector control (79.01%±6.69% vs 67.06%±6.74%, t =-3.083, P =0.012), while rapamycin treatment further increased LC3 expression (86.88%±5.42%, t =-2.239, P =0.049); however, 3-MA treatment significantly decreased LC3 expression in cells (71.22%±4.29%, t =-2.404, P =0.037). In addition, levels of ATG7, Beclin1, and LC3 Ⅰ/Ⅱ proteins were increased, whereas levels of AKT/p-AKT and p-mTOR were decreased in the CAPE and rapamycin groups vs controls. However, the 3-MA treatment had an opposite result, indicating that 3-MA reversed CAPE-induced effects in HSC-T6 cells. Conclusion Caffeic acid phenethyl ester may induce autophagy to reduce cell viability in hepatic stellate cells by inhibition of the AKT/mTOR signaling.

Objective : To study the protective effect of polydatin on lipopolysaccharide-induced injury of human umbilical vein vascular endothelial cells (HUVECs) through the protein Janus kinase 2 (JAK2) / signal transducers and activators of transcription 3 ( STAT3) signaling pathway． Methods : HUVECs were cultured in vitro，and 500 ng / ml LPS induced their injury and set as a model group ; based on the model group，endothelial cells were intervened with different concentrations ( 10，20，and 40 μmol / L ) of polydatin for 24 h，and set as polydatin low concentration group，polydatin medium concentration group，and polydatin high concentration group，respectively ; a control group was set as another group．CCK-8，monocyte-endothelial cell adhesion，scratch and Transwell assays were used to detect cell viability，adhesion，migration and invasive ability ; ELISA was used to detect interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels in the cell supernatant ; Western blot was used to detect the expression of proteins related to the JAK2 / STAT3 signaling pathway levels of JAK2 / STAT3 signaling pathway relat- ed proteins. Results : Compared with the control group，the model group showed decreased cell survival ( P < 0. 01) ，increased cell adhesion，migration and invasion (P＜0. 001，P ＜0. 05，P ＜0. 01) ，increased levels of IL-6 and TNF-α in the cell supernatant (P＜0. 001) ，and increased levels of phosphorylation of JAK2 and STAT3 pro- teins in the cells (P＜0. 05) ．Compared with the model group，LPS damage to cells was attenuated after polydatin intervention，cell survival was increased in polydatin low －，medium － and high － concentration groups ( P < 0. 05) ，cell adhesion，migration，and invasion decreased (P＜0. 05，P＜0. 05，P＜0. 001) ，IL-6 and TNF-α levels in cell supernatants decreased (P＜0. 05) ，and the levels of cellular JAK2 and STAT3 protein phosphorylation lev- els decreased (P＜0. 05) ． Conclusion Polydatin seems to reduce the inflammatory injury of human umbilical vein endothelial cells induced by LPS，reducing the secretion of inflammatory factors，and inhibiting the ability of cell ad- hesion，migration and invasion，which may be related to the down-regulation of JAK2 / STAT3 signal pathway by polydatin.

Objective : To investigate the effects of glycated low density lipoprotein (Gly⁃LDL) on the growth of human umbilical vein endothelial cells (HUVECs) and the expression of toll like receptor 4 (TLR4) and hypoxia inducible factor⁃1α (HIF⁃1α), and to explore its possible mechanism . Methods : HUVECs were cultured in vitro and divided into control group, positive control group[50 mg/L normal low density lipoprotein(n⁃LDL)], low concentration, medium concentration and high concentration Gly⁃LDL(50, 75, 100 mg/L) groups . Respectively, the effects of different concentrations of Gly⁃LDL on survival rate of HUVECs were detected by CCK⁃8; The motility of HUVECs under different treatments were detected by wound healing assays; The level of inflammatory cytokine, such as tumor inducing factor⁃α(TNF⁃α), interleukin⁃6(IL⁃6), intercellular adhesion molecule⁃1(ICAM⁃1) and vascular cell adhesion molecule⁃1(VCAM⁃1) were detected by ELISA; The mRNA levels of TLR4, HIF⁃1α, TNF⁃α and IL⁃6 were detected by qRT⁃PCR; Protein expressions of TLR4, HIF⁃1α, TNF⁃α and IL⁃6 were detected by Western blot; Respectively, si⁃RNA of TLR4 and HIF⁃1α was used to intervene the effects of Gly⁃LDL on HUVECs . The experiment was divided into control group, model group (Gly⁃LDL 100 mg/L), si⁃TLR4 group (Gly⁃LDL 100 mg/L + si⁃TLR4), TLR4 unloading group( Gly⁃LDL 100 mg/L + si⁃NC1), si⁃HIF⁃1α group ( Gly⁃LDL 100 mg/L + si⁃HIF⁃1α) and HIF⁃1α unloading group ( Gly⁃LDL 100 mg/L + si⁃NC2) . Protein expressions of TLR4 and HIF⁃1α were detected by Western blot to verify the interaction between TLR4 and HIF⁃1α . Results: The survival rate and migration rate of HUVECs were inhibited in Gly⁃LDL(50 mg/L, 75 mg/L, 100 mg/L) group (P < 0. 01), the inflammatory cytokines, such as TNF⁃α, IL⁃6, ICAM⁃1,VCAM⁃1 increased by Gly⁃LDL function on HUVECs(P < 0. 001), and the mRNA and protein levels of TLR4, HIF⁃1α, TNF⁃α and IL⁃6 increased by Gly⁃LDL in a dose dependent manner. After TLR4 was knocked out, the proteins expression of TLR4 and HIF⁃1α were down⁃regulated compared with model group(P < 0. 05),but after HIF⁃1α was knockout, only the protein expression of HIF⁃1α was down⁃regulated compared with model group( P < 0. 01),while the protein expression of TLR4 was up⁃regulated under the influence of Gly⁃LDL. Conclusion Gly⁃LDL may inhibit the proliferation and migration of HUVECs by up⁃regulating TLR4/HIF⁃1α inflammatory signaling pathway, and promote the expression of inflamma⁃tory cytokines, leading to vascular endothelial injury .