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.
Aging ; Autophagy ; Drug Discovery ; Humans ; Lysosomes ; metabolism ; Neurodegenerative Diseases ; Phagosomes ; metabolism ; Protein Folding

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.

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.

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.

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.

Objective To evaluate the arc renal parenchyma incision of pelvis within renal sinus and renal posterior lib for the removal of complex staghorn renal calculi.Methods Arc renal parenchyma incision of pelvis within renal sinus and renal posterior lib was performed to remove stones in 86 cases (97 sides) with complex staghorn renal calculi.Among the 86 cases,42 had stones on the right side;33,on the left side;11,on bilateral sides.Seventeen cases had concomitantly calculi in the ureter,and 54 had calculi in upper and mid calyx or multiple renal calculi.As for comorbidity,11 cases had hypertensions;4,diabetes; and 5,hepatitis B.Twenty-five cases had renal insufficiency,with BUN of 12.3 -76.0mmol/L and Cr of 231 -1721?mol/L.The procedure was performed as follows:the kidney was dissected free and the pelvis within renal sinus was isolated.Two rows of bottom style sutures were made on the renal parenchyma with 2-0 plain catgut along mid-lower 1/3 of the dorsal surface of kidney free of vessels from the renal posterior lib to the plane of lower major calyx.The renal parenchyma was opened.Then,the incision was developed from the plane of lower through the middle major calyx to the plane of upper major calyx.The renal parenchyma and mid-low calyx along the incision were opened,suturing while incising,so that all the stones could be easily removed with hook.Results The calculi were completely removed in all 86 cases (97 sides).The opera- tive time was 105-187min ( mean,129min).The intraoperative blood loss was 120-460 ml ( mean,220 ml).Forty-three cases needed intraoperative blood transfusion of 120 -200 ml (mean,140 ml).One month after operation,KUB+IVU and ultrasonic findings were normal with improved hydronephrosis,no intrarenal stricture and no residual calculi.Conclusions This procedure has the advantages of less bleeding,slight impairment of renal function,simple handling,clear operative field,high clearance rate,therefore is indica- ted for the removal of complex staghorn calculi.

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.