BackgroundChoriodal neovascularization is an important ocular manifestation of angiogenesis in eyes,which derives from the choroid capillaries.Recent studies have found that complement activation is playing a key role in the laser-induced CNV.Because of the key position of CFB in the alternative pathway,bytargeting CFB and blocking the alternative pathway may provide an approach to observe the role of this alternative pathway in the generation of CNV.Objective This study was to investigate the inhibitory effect of reconstructed complement factor B (CFB)-small interfering ribonucleicacid(siRNA)on choroidal neovascularization (CNV)and its mechanism. Methods Experimental CNV was induced by laser photocoagulation in 96 eyes of 48 clean Brown Norway rats.The rats were randomly divided into 4 groups.25,50 and 75 μg B factor siRNA were injected via caudal vein on 1 day,3,5 days after photocoagulation in different dose groups,and normal saline solution was injected at the same way in experimental control group.Other 12 normal rats were used as blank control group.Fundus fluorescein angiography(FFA) was performed on 3,7,14,21,28 days after injection of CFB-siRNA and CNV was scored.The expressions of vascular endothelial growth factor(VEGF) and factor Ⅷ in choroid were detected by immunochemistry.The expressions of CFB-siRNA,VEGF,transforming growth factor β2( TGF-β2 )proteins in choroid were determined using immunochemistry in 7,14,21,28 days,and the expressions of mRNA of CFB-siRNA,VEGF,TGF-β2 were examined by reverse transcription polymerase chain reaction(RT-PCR). ResultsFFA revealed that the CNV rates in various doses of CFB-siRNA groups were significant lower than those of experimental control group in various time points(P＜0.05),and those in 75 μg B factor siRNA were decreased in comparison with 25 μg B factor siRNA (P＜0.05).Immunochemistry showed that the intensities of the VEGF and factor Ⅶ expression in various doses of CFB-siRNA groups were weaker than the blank control group ( P ＜ 0.05 ).Compared with the control group,the expression of CFB reduced in 7 days,and then approached to the level near the control group.Fourteen to twenty-one days after injection of CFB-siRNA,VEGF and TGF-β2 depressions in different doses of CFB-siRNA groups were lower than blank control group( P＜0.05 ).CFB expression in choroid showed the lower levels in CFB-siRNA injection group compared with blank control group in from 7 through 21 days (P＜0.05).RT-PCR displayed the gradual increase of CFB mRNA and curve-like changes of VEGF and TGF-β2 with time prolong. Conclusions Recombinated CFB-siRNA can effectively inhibit laser-induced CNV by down-regulating the expression of VEGF and factor Ⅷ.Alternative pathway of complement plays an important role in the production of CNV.

OBJECTIVEThe objective of this study was to observe the interventional effect of cod liver oil supplementation on re-vaccination to hepatitis B virus (HBV) among infants and young children.

METHODSAll 7-36 months old infants and young children, who had been vaccinated with obligatory HBV vaccines routinely by the national technical and administrative procedures for HBV vaccination on children of China, were convened among villages in Linyi, Shandong province, from October 2008 to March 2009. After detection of serum anti-HBV, one hundred children with lower serum anti-HBV were picked out for the randomized, double blinded, placebo controlled vitamin A supplementation study. The children in the intervention group (50 subjects) took 0.5 g condensed cod liver oil (containing 25 000 IU vitamin A and 2500 IU vitamin D(2)) every 15 days for six times. The children in the control group (50 subjects) were given corn oil with same volume. All children were re-vaccinated at the 30th and the 60th day of the experiment. The serum samples were collected from each child at the 90th day of the experiment. Retinol concentration in serum samples was analyzed with HPLC method before and after the intervention. The levels of serum anti-HBs were detected by the electro-chemi-luminescence immunoassay (ECLIA).

RESULTSTotal 74 children finished the supplemental experiment and blood collection, 37 subjects in each group, respectively. After intervention, the serum retinol level in the experimental and control group were (404.1 ± 123.1) and (240.8 ± 92.8) µg/L (t = 6.441, P < 0.01), respectively. The serum anti-HBs levels in the experimental and control group were (2737.2 ± 2492.6) and (1199.7 ± 2141.6) U/L (t = 2.846, P < 0.01), respectively. The rate of weak or no-answer case in experimental and control groups was 0.00% (0/37) and 10.81% (4/37) (χ(2) = 4.229, P = 0.040), respectively.

CONCLUSIONThe results showed that vitamin A supplementation might enhance the re-vaccination reaction against HB vaccine in infants and young children.

Child, Preschool ; Cod Liver Oil ; therapeutic use ; Dietary Supplements ; Double-Blind Method ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; blood ; immunology ; Hepatitis B Vaccines ; immunology ; Hepatitis B virus ; immunology ; Humans ; Immunity, Active ; Infant ; Vitamin A ; therapeutic use ; Vitamins ; therapeutic use

OBJECTIVETo study the effects of Liangge San to the expression of CD14 and scaverger receptor(SR) in the kupffer cells of liver and the pathological changes of liver tissue of endotoxemia-mice.

METHODThe model was established with intravenous injection of lipopolysaccharide (LPS) and at the same time different dose Liangge San were given. The expression of CD14 and scaverger receptor were detected with immunohigtochemistry at the 2nd, 4th, 8th hour ofter injury and analyzed with computer image system, and the pathological changes of liver tissue were also observed.

RESULTAt the three different hours, the expression of CD14 and scaverger receptor in macrophages of liver of LPS-injury group showed significant increase and significant decrease respectively, compared with that of the blank-control group (P < 0.01). The expression in dexamethasone group and Liangge San different dose groups were intermediate between those in injury group and those in control group. Compared with expression of LPS-injury group, those of dexamethasone group and Liangge San different dose groups showed significant differences (P < 0.01), especially that of Liangge San high dose group. Liver cells showed vacuole change. Changes of CD14 and SR expression were paralleled with the severity of liver damages of the mice.

CONCLUSIONLiangge San can inhibite the up-regulation of CD14 expression and down-regulation of scaverger receptor expression in a dosage-dependent manner and also alleviate the damages of liver induced by LPS.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Dexamethasone ; pharmacology ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Endotoxemia ; chemically induced ; metabolism ; pathology ; Female ; Kupffer Cells ; metabolism ; pathology ; Lipopolysaccharide Receptors ; metabolism ; Lipopolysaccharides ; Liver ; metabolism ; pathology ; Mice ; Plants, Medicinal ; chemistry ; Receptors, Scavenger ; metabolism

OBJECTIVEThe traditional gracilis musculocutaneous flap is supplied by a branch of deep femoral artery, which enters the muscle in between the upper and middle third of it. So the flap barely reaches the pelvis and perineum region for reconstruction. By exploring the blood supply pattern we tried to rotate the flap Upon at the higher point starting at the obturator foramen in order to let it cover a bigger area.

METHODSanatomical reviewing of the blood supply of the gracilis branches of obturator, medial femoral circumflex and deep femoral arteries. Based on this a new type of longitudinal gracilis musculocutaneous flap supported only by the obturator artery was designed to reach the pelvis, female genitalia, pubic symphysis, inguinal area easily.

RESULTSThe new kind of flap has been applied to 9 patients for deformity repairing and tissue replacement in the pelvic and perineal area. All the flaps survived and achieved satisfactory result with 3 months to 3 years' follow up.

CONCLUSIONSLongitudinal gracilis musculocutaneous flaps supplied by the obturator artery can be used as regular musculocutaneous flap clinically.

Female ; Femoral Artery ; surgery ; Humans ; Muscle, Skeletal ; blood supply ; transplantation ; Surgical Flaps ; blood supply

OBJECTIVETo investigate the protective effects of oxymatrine on chronic heart failure induced by isoproterenol (ISO) and to observe its effects on ADMA metabolism pathway in ISO-induced chronic heart failure in rats.

METHODMale Sprague-Dawley rats were given oxymatrine (100,50 mg kg-1) orally for 14 days. Heart failure was induced in rats by subcutaneous injection of isoproterenol (5 mg kg-1 d-1 ) at the 8th day for 1 week. Serum parameters, haemodynamic parameters, Heart weight, and histopathological variables were analysed. Expression of protein levels were measured by Western blot.

RESULTOxymatrine (100,50 mg kg-1) significantly attenuated serum content of cTn I, improved left ventricle systolic and diastolic function and left ventricular remodeling, reduced the ISO-induced myocardial pathological changes compared with ISO group. In addition, oxymatrine (100,50 mg kg-1) significantly reduced serum level of ADMA (P <0. 01), normalize the reduced dimethylarginine dimethylaminohydrolase 2 (DDAH2) expression (P <0. 01) , but had no effect on the isoproterenol-induced upregulated protein arginine methyltransferases 1 expression.

CONCLUSIONOxymatrine could ameliorate the experimental ventricular remodeling in ISO-induced chronic heart failure in rats and the mechanism involved in reducing serum content of ADMA and increased DDAH2 expression.

Alkaloids ; pharmacology ; therapeutic use ; Amidohydrolases ; metabolism ; Animals ; Arginine ; analogs & derivatives ; blood ; metabolism ; Chronic Disease ; Gene Expression Regulation, Enzymologic ; drug effects ; Heart Failure ; drug therapy ; metabolism ; pathology ; physiopathology ; Hemodynamics ; drug effects ; Isoproterenol ; adverse effects ; Male ; Organ Size ; drug effects ; Quinolizines ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Troponin I ; metabolism

OBJECTIVE: To explore the relationship between beta-actin mRNA degradation in SD rat's brain, heart and kidney and early postmortem interval (PMI) in order to find new markers for estimating early PMI. METHODS: Rats were sacrificed and kept in the place at a temperature of 20 degrees C. The total RNA were extracted from the brain, heart and kidney at different PMI points. Real time RT-PCR was applied to determine beta-actin mRNA levels in total RNA and the results were given in the form of Ct values. Linear relationships between PMI and Ct values were obtained and the functions of linear regression were established. RESULTS: The great decrease of beta-actin mRNA level were observed in the three organs. The degradation rate was obviously higher in 24 hours after death in the heart and kidney. However, there were no significant changes in the brain. The changes of Ct values and PMI showed a good linear relationship. CONCLUSION beta-actin mRNA in rat's brain, heart and kidney degrades obviously after death and can be used for estimating early PMI by its degradation rules.
Actins/metabolism* ; Animals ; Brain/metabolism* ; Forensic Medicine/methods* ; Kidney/metabolism* ; Male ; Myocardium/metabolism* ; Postmortem Changes ; RNA Stability ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction/methods* ; Time Factors

OBJECTIVETo investigate the relationship between DNA homologous recombination (HR) repair genes RAD51-G135C/XRCC3-C241T polymorphisms and development of acute myeloid leukemia (AML) with recurrent chromosome translocation.

METHODSGenomic DNA was extracted from bone marrow cells of 625 de novo AML patients and peripheral blood cells of 806 patient family members and 704 unrelated volunteers. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by PCR-RFLP. Cell lines with genotypes differed from XRCC3-C241T were selected and irradiated in vitro. The CBFβ-MYH11 fusion gene was detected by TaqMan real-time PCR.

RESULTSThe XRCC3-C241T variant (C/T + T/T) showed 6.22-fold and 6.99-fold increase in the risk of developing the AML with inv(16)/t(16;16)/CBFβ-MYH11 as compared with the volunteer and family member controls respectively; the RAD51-G135C homozygote-type (C/C) variant showed 0.87-fold (P = 0.010) and 1.15-fold (P = 0.001) respectively increase in the risk of this subtype AML. In the irradiated group, the CBFβ-MYH11 mRNA level in HL-60 cells was 59.49 times increased than that in KG1a cells. However, the RAD51-G135C and XRCC3-C241T variants had no correlations with the risk of development of t(15;17)/PML-RARα(+)AML, t(8;21)/AML1-ETO(+) AML and 11q23 AML subtypes.

CONCLUSIONThe XRCC3-C241T variant and the RAD51-G135C homozygote-type significantly increase the risk of the development of AML with inv(16)/t(16;16)/CBFβ-MYH11.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Child ; Child, Preschool ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Leukemia, Myeloid, Acute ; etiology ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Polymorphism, Single Nucleotide ; Rad51 Recombinase ; genetics ; Translocation, Genetic ; Young Adult

OBJECTIVETo investigate the high-risk factors for the quality of general movements (GMs), which has a predictive value for brain dysfunction in infants.

METHODSA total of 618 infants in the stage of writhing movements and 539 infants in the stage of fidgety movements were selected separately for the evaluation of GMs. The high-risk factors for the quality of GMs in infants were analyzed by ANOVA, chi-square test, and multivariate logistic regression.

RESULTSMultivariate logistic regression analysis showed that the factors significantly associated with the quality of GMs in the stage of writhing movements were gestational age (OR=0.762, P<0.001), birth weight (OR=0.264, P<0.001), severe asphyxia (OR=2.445, P=0.012), and intrauterine distress (OR=4.865, P<0.001); the factors significantly associated with the quality of GMs in the stage of fidget movements were gestational age (OR=0.786, P=0.003), birth weight (OR=0.217, P<0.001), severe asphyxia (OR=3.765, P=0.001), and hyperbilirubinemia (OR=2.640, P=0.028).

CONCLUSIONSLow gestational age, low birth weight, severe asphyxia, hyperbilirubinemia and intrauterine distress are high-risk factors for abnormal GMs in infants, and early screening and intervention should be performed to reduce the incidence of abnormal nervous system sequelae.

Asphyxia ; complications ; Birth Weight ; Female ; Gestational Age ; Humans ; Infant ; Logistic Models ; Male ; Movement ; Movement Disorders ; etiology ; Risk Factors

OBJECTIVETo study the interaction between polymorphisms of estrogen receptor (ER) gene and puberty on bone mineral density (BMD).

METHODSOne hundred and forty-six boys aged 13-17 years were divided into two groups according to their first spermorrhea. DNA was analyzed for Xba I and Pvu II genotypes by PCR-RFLP. BMD of the total body, forearm and lumbar spine was measured by dual-energy X-ray absorptiometry (DXA). The relationship between polymorphisms of ER gene and BMD in these two groups was analyzed.

RESULTSThe BMD at all sites in the spermorrhea group was significantly higher than that in the un-spermorrhea group. The independent contribution of ER genotypes to BMD at two pubertal stages was analyzed after adjusting co-variables. In the un-spermorrhea group, the BMD at distal 1/10 and 1/3 forearm of those carrying pp genotype was significantly higher than that of the non-carries, whereas in the spermorrhea group BMD in those carrying the same genotype was significantly lower than that in the non-carriers. Similar results were obtained by haplotype analysis. Multiple stepwise regression analysis showed that body weight, age and the first spermorrehea were the dominant determinants for BMD. BMD at forearm might be influenced by interaction between ER genotype and the first spermorrehea.

CONCLUSIONThe polymorphisms of ER gene play a different role in BMD influenced by the first spermorrhea. Chinese boys carrying p or x allele should pay more attention to their bone mass.

Absorptiometry, Photon ; Adolescent ; Base Sequence ; Bone Density ; DNA Primers ; Humans ; Male ; Polymorphism, Genetic ; Puberty ; Receptors, Estrogen ; genetics ; Spermatozoa

BACKGROUNDFamitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).

METHODSThe data of famitinib in treating patients with mRCC from the single-center phases I and II clinical trials were analyzed. Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression, occurrence of intolerable adverse reactions or withdrawal of the informed consent.

RESULTSA total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily, 4 patients at a dose of 27 mg and 1 patient each at a dose of 13 mg, 20 mg and 30 mg, respectively. Twelve (50.0%) patients achieved partial response (PR) and 9 patients achieved stable disease (SD). Progressive disease was found in 3 (12.5%) patients. The disease control rate was 87.5%. The median follow-up time was 17.6 months; the median progression free survival (PFS) was 10.7 (95% CI 7.0-14.4) months; and the estimated median overall survival (OS) time was 33.0 (95% CI 8.7-57.3) months. The adverse drug reactions mainly included hypertension (54.1%), hand-foot skin reactions (45.8%), diarrhea (33.3%), mucositis (29.2%), neutropenia (45.8%), thrombocytopenia (29.2%), hyperlipidemia (41.7%) and proteinuria (41.7%). The incidence rate of grades 3 and 4 adverse events was low, mainly including hypertension 12.5%, hand-foot skin reactions 4.2%, neutropenia 4.2%, thrombocytopenia 4.2%, hyperlipidemia 4.2% and proteinuria 12.5%.

CONCLUSIONSFamitinib has significant anti-tumor activity in mRCC. The common adverse reactions are generally manageable.

Adult ; Aged ; Carcinoma, Renal Cell ; drug therapy ; Female ; Humans ; Indoles ; adverse effects ; therapeutic use ; Kidney Neoplasms ; drug therapy ; Male ; Protein Kinase Inhibitors ; Pyrroles ; adverse effects ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Young Adult