Placental pathologies include placental insufficiency,infection,meconium stained,abnormal planting and placental vascular anastomosis,et al.All those can lead to fetal and neonatal hypoxia ischemia or premature birth,which can cause brain damage.

Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.

ObjectiveTo explore the effects and possible mechanisms of VCR combined with low dose cyclophosphamide(CTX) intermittently to treat severe systemic lupus erythematosus(SLE).It is assumed that this might be a new combination therapy for SLE and expected to improve the overall prognosis and outcome of SLE.MethodsMurine chronic graft-versus-host disease(cGVHD) model were developed for study.They were randomly divided into the control group,vincristine (VCR) pulse therapy group,CTX pulse therapy group,CTX every other day(EOD) group,VCR+CTX combination group.One way ANOVA and repeated measure variance analysis were used for statistical analysis.Results① Six weeks after cGVHD models were set up,the average 24-hour urine protein quantification was(5.02±0.88) mg,anti-dsDNA antibody was positive,and Ⅳ LN pathology could be observed histologically in the model murine.So cGVHD models were successfully developed.② Significantly difference in decreasing of 24-hour urine protein quantification was found in the CTX EOD group,VCR+CTX combination group and other groups (P＜0.01).Significant decrease in Cr,ALT,anti-dsDNA,was found in the CTX EOD group,VCR+CTX combination group,CTX pulse therapy group and other groups(P＜0.05).Decrease in urine MCP-1 and TGF-β1 could be detected,and statistical significant difference in these parameters could be found in the CTX EOD group,CTX pulse therapy group,VCR+CTX combination group and other groups (P＜0.01).MCP-1 and TGF-β1'expression in model kidney were reduced in the CTX EOD group,VCR+CTX combination group and had statistical significant difference in the CTX EOD group,VCR+CTX combination group,VCR pulse therapy group,and CTX pulse therapy group.③ VCRand CTX combination treatment was effectivein 24-hour urine protein quantification,blood Cr,ALT,anti-dsDNA and urine MCP-1,as well as urine TGF-β1 (P＜0.05).Conclusion ① The combination of VCR and CTX is synergistic in decreasing 24-hour urine protein quantification,Cr,and the expression of MCP-1,TGF-β1.② The adverse effect of VCR+CTX combination group is similar to VCR pulse therapy group and CTX pulse therapy group.

Dextrocardia ; diagnosis ; Female ; Heart Septal Defects, Atrial ; diagnosis ; Heart Ventricles ; abnormalities ; Humans ; Infant, Newborn ; Truncus Arteriosus, Persistent ; diagnosis

Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.
Aging ; Autophagy ; Drug Discovery ; Humans ; Lysosomes ; metabolism ; Neurodegenerative Diseases ; Phagosomes ; metabolism ; Protein Folding

Objective To establish the HPLC fingerprint of amino acids compounds from Buzhong Yiqi Pill.Methods A pre-column derivatization HPLC method was adopted with praline as a reference.Separation was performed on a AccQ? TagTM C18(3.9? 150 mm)analytical column with mobile phase consisting of 0.15 mol/L sodium acetate buffer solution and 60 % acetonitrile,gradient elution with the flow rate of 1.0 mL/min.The column temperature was at 37 ℃.The Fluorescence detecting wavelength was set at 250 nm(excitation wavelength)and 395 nm(emission wavelength),the analysis time was 35 min.Results Twelve common peaks on the HPLC fingerprints of Buzhong Yiqi Pill were presented.The similarity was determined by the correlation coefficient,included angle cosine coefficient and evaluation software of chromatogram fingerprint similarity.The results showed the similarity for 10 bathes of samples was in 0.97～ 1.00.Conclusion Good fingerprints were obtained,which can be used for the quality control of Buzhong Yiqi Pill.

TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.

Aim To investigate whether capacitative Ca~(2+) entry involved in excitation-contraction coupling in rat distal colon smooth muscle.Methods Changes of isolated organ's tension were monitored with force-displacement transducer and Powerlab 4/25T recording system.Results Thapsigargin(10 nmol?L~(-1)～1 ?mol?L~(-1))produced slowly developing sustained contractions in isolated distal colon smooth muscle strips of rats.The timed contractile responses to thapsigargin(10 n mol?L~(1)-1 ?mol?L~(-1)) were significantly different.The contractile response to Ca~(2+) reintroduction following incubation of strips in a Ca~(2+)-free Krebs in the presense of thapsigargin was significantly higher than in its absence(99%?28% vs 70%?8%).Contractile responses to Ca~(2+)reintroduction following depletion of sarcoplasmic reticulum Ca~(2+) stores with thapsigargin were attenuated by La~(3+),while unaffected by verapamil.Conclusion Contractile responses to Ca~(2+)reintroduction following depletion of sarcoplasmic reticulum Ca~(2+)stores with thapsigargin,are mediated by capacitative Ca~(2+)entry.The results suggested that CCE provided activator Ca~(2+)for the contraction and participated in excitation-contraction process in rat distal colon smooth muscle.

BACKGROUND:Hidden blood loss is one of most important complications after total knee arthroplasty, but the mechanism and influential factors are not yet clear. OBJECTIVE:To analyze the relative influential factors for hidden blood loss in primary unilateral total knee arthroplasty. METHODS:Data of 235 patients who had undergone primary unilateral total knee arthroplasty from April to September 2014 were retrospectively studied. There were 38 males and 197 females aged from 48 to 82 years old with a mean age of 66 years. The Gross formula was used to calculate the amount of hidden blood loss. The effects of gender, age, height, body weight, body mass index, anesthesia method, administration of tranexamic acid, postoperative anticoagulation method, typeof prosthesis, tourniquet time and pre-operative coagulation function on the postoperative hidden blood loss and total blood loss after total knee arthroplasty were analyzed. RESULTS AND CONCLUSION:(1) Significant differences in hidden blood loss and total blood loss after total knee arthroplasty were detected between male and female patients (P< 0.01). Significant differences in hidden blood loss and total blood loss were found between tranexamic acid and non-tranexamic acid groups (P< 0.05,P< 0.01).(2) Multivariate linear regression analysis showed that preoperative hemoglobin level and heightwere important factors influencing the blood loss after arthroplasty. Hidden blood loss and total blood loss were not correlated with age, body mass index, anesthesia method, postoperative anticoagulation method, type of prosthesis, tourniquet time and preoperative coagulation function. (3) Results indicate that gender and administration of tranexamic acid affect hidden blood loss and total blood loss after total knee arthroplasty. However, age, body mass index, anesthesia method, postoperative anticoagulation method, type of prosthesis, tourniquet time and preoperative coagulation function do not greatly affect hidden blood loss.

Objective To investigate the effects of caffeine citrate and aminophylline in treatment of primary apnea of premature infants and its related complications. Methods A total of 152 preterm infants who were diagnosed primary apnea within 10 days after birth were randomly divided into caffeine citrate group(n=77) and aminophylline group(n =75). The changes in the time of the apnea disappeared after treating,needing oxygen,non-invasive and invasive mechanical ventilation,and the incidence of bronchopul-monary dysplasia ( BPD ) , necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus (PDA),intercranial hemorrhage(ICH)were compared between the two groups. Results The time of the apnea disappeared after treating[(47. 4 ± 5. 3) h],needing oxygen[(20. 5 ± 7. 6) d],non-invasive mechani-cal ventilation[(8. 7 ± 4. 2) d] and invasive mechanical ventilation[(1. 0 ± 1. 3) d] in the caffeine citrate group were significantly lower than those in the aminophylline group [ ( 54. 8 ± 6. 2 ) h, ( 24. 4 ± 8. 5 ) d, (10.4±5.3)d,(10.4±5.3)d,respectively](P<0.05).TheincidenceofBPD[16.9%(13/77)],PDA [13. 0%(10/77)] and ICH[16. 9%(13/77)] in the caffeine citrate group were significantly lower than those in the aminophylline group[33.3%(25/75),26.7%(20/75),22.7%(17/75),respectively](P <0. 05),but there were no differences between the two group about the incidence of necrotizing enterocolitis [caffeine group 7. 8%(6/77),aminophylline group 9. 3%(7/75)] and retinopathy of prematurity[caffeine group 6. 5%(5/77),aminophylline group 9. 3%(7/75)](P>0. 05). Conclusion The caffeine citrate has a better efficacy in the treating primary apnea of preterm infants than aminophylline. It can also decrease the incidence of BPD,PDA and ICH in premature infants.