AIM: To investigate the expression of vitamin D3 up-regulated protein 1 (VDUP1) in peripheral eosinophils of asthma patients and its relation with eosinophil activation.METHODS: 10 normal volunteers and 31 mild to moderate asthma patients were selected. Symptom severity, pulmonary function index, induced sputum eosinophil counts were recorded. Then, gene and protein expressions of VDUP1 and ?-actin were evaluated by RT-PCR and Western blotting, respectively. In addition, eosinophils were incubated with IL-5, both VDUP1 and ?-actin were amplified by RT-PCR. The eosinophil cationic protein (ECP) of supernatant and serum were also detected by ELISA assay. RESULTS: There was a significant decrease in expression of VDUP1 in asthma attack patients without treatment compared with normal volunteers and patients in remission. In contrast, no significant difference between the patients in remission and normal volunteers was observed. In patients with asthma attacks, a negative relationship between expression intensity of VDUP1 and EOS% in induced sputum and serum ECP concentration was also observed. The expression of VDUP1 in eosinophils was decreased by IL-5 stimulation, simultaneously, the ECP in supernatant was increased. CONCLUSION: The expression of VDUP1 in eosinophils decreases in asthma patients, and is negatively associated with serum ECP and induced sputum EOS%. EOS activation by IL-5 may be related to VDUP1 pathway.

OBJECTIVETo study the effect of Qingre Yulin Decoction (QYD) on male infertility caused by accessory gland infection (AGI) with randomized controlled trial (RCT).

METHODSSixty infertility outpatients were equally divided into two groups randomly, the QYD group treated with modified QYD and the control group with antibiotic plus vitamin E, both for 3 months with another 6 months' follow-up. Pregnant rates, routine test of sperm and expressed prostatic secretion (EPS) were determined.

RESULTSThe healed rate was 26.7% (8 cases), the markedly effective rate was 43.3% (13 cases), the effective rate was 16.7% (5 cases), and the total effective rate was 86.7% in the QYD group, while in the control group it was 6.7% (2), 30.0% (9), 40.0% (12) and 76.7% respectively, showing higher healed rate and total effective rate in the former than those in the latter. Sperm quality of infertility patients with AGI decreased obviously, manifesting short ened average liquefaction time, reduced concentration, survival rate and vitality of sperm. These abnormal changes were improved after treatment in both groups, and the efficacy was better in the QYD group than that in the control group.

CONCLUSIONInfertility patients with AGI were manifested as oligospermatism and asthenospermia, which may not be the definite outcome of AGI. QYD is able to improve sperm quality, especially sperm vitality in infertility patients with AGI and therefore increase pregnant rate of their wives.

Adult ; Bacterial Infections ; complications ; Drugs, Chinese Herbal ; therapeutic use ; Epididymitis ; complications ; Female ; Humans ; Infertility, Male ; drug therapy ; etiology ; Male ; Phytotherapy ; Prostate ; drug effects ; pathology ; secretion ; Prostatitis ; complications ; Sperm Motility ; drug effects ; Treatment Outcome

12E7 Antigen ; Antigens, CD ; metabolism ; Bone Neoplasms ; metabolism ; pathology ; surgery ; Cell Adhesion Molecules ; metabolism ; Chondrosarcoma, Mesenchymal ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Hemangiopericytoma ; pathology ; Humans ; Lung Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Pneumonectomy ; methods

2 in some patients with the loss of high and medium sized vWF multimers in plasma.Eight patients with vWD were identified, wherein two were characterized as type 1,4 as type 2A and 2 as type 3 respectively.Conclusion The panel of tests is suitable for diagnosis and classification of vWD.

OBJECTIVETo study the intervention of Morindae officinalis extract in human sperm membrane, and to study the treatment of male infertility and asthenoospermia by M. officinalis.

METHODTo select sperm with normal physiological function using the Percoll gradient centrifugation for the normal sperm model. Then separating the sperm suspension into the normal, model, and control group (Vitamin C group), and the large, medium and small dose of M. officinalis. The ROS was made from hypoxanthine-xanzine xanzine (HX-XO), and ROS, different concentrations (0.125, 0.25, 0.5 mg x mL(-1) of the extract were hatched with sperm in the oxygen environment, the sperm membrane Lipid peroxide injury were analyzed, and the function of sperm membrane were analyzed by sperm Hypoosmoticswelling (HOS) and compared with the controlled group.

RESULTIn the same conditions, all the small, medium and large extracts of M. officinalis (0.125, 0.25, 0.5 g x mL(-1)) improved SOD vitality of sperm suspension, reduced the content of MDA, intervened in the injury of sperm membrane by ROS to some extent and protected some function of sperm membrane. The 0.125 mg x mL(-1) extract had no obvious difference (P > 0.05) with Vitamin C in it, but the (0.25, 0.5 mg x mL(-1)) concentration of the extract is significantly better than control Vitamin-C (P < 0.01, P < 0.001). Furthermore, there was a dependence on the dosage, the large dose (0.5 mg x mL(-1)) of M. officinalis especially protected the function of sperm membrane.

CONCLUSIONThe extract from M. officinalis can significantly intervene in lipin peroxidation in sperm membrane by guarding against oxidation, and protect the structure and function of sperm membrane, that is one of the mechanisms for treating male's infertility and asthenoospermia with M. officinalis.

Adult ; Cell Membrane ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Humans ; Lipid Peroxidation ; drug effects ; Male ; Malondialdehyde ; metabolism ; Morinda ; chemistry ; Plants, Medicinal ; chemistry ; Protective Agents ; pharmacology ; Reactive Oxygen Species ; Spermatozoa ; drug effects ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the oxidation damage of active oxygen (ROS) to human sperm acrosome and ultrastructure, and study the function mechanism about Cuscuta japonica treating male's infertility and asthenoospermia.

METHODBy using the Percoll gradient centrifugation, the sperm with normal physiological function were selected for the normal sperm model, and the sperm suspension were divided into the normal group, the model group, the positive control group (Vitamin C group), and the lugh, the median and the low dose gvoups of C. japonica. The ROS made from hypoxanthine-xanzine xanzine(HX-XO) and different content (0.125, 0.25, 0.5 g x mL(-1)) of extract were incubated with sperm in the oxygen environment. The acrosomic integrity rate were calculated and the sperm acrosome and ultrastructure were observed.

RESULTThe content (0.125, 0.5 g x mL(-1)) of extract had no obvious difference as compared with Vitamin C (0.25 mg x mL(-1)) in protecting the acrosome and ultrastructure, but the content (0.25 mg x mL(-1)) of extract was significantly better than Vit C (P < 0.001).

CONCLUSIONThe suitable content of extract from C. japonica can significantly protect the sperm membrane, the acosomic structure and the mitochondrion function from the damage caused by ROS.

Acrosome ; drug effects ; ultrastructure ; Adult ; Cuscuta ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Humans ; Male ; Mitochondria ; drug effects ; ultrastructure ; Plants, Medicinal ; chemistry ; Reactive Oxygen Species ; Spermatozoa ; drug effects ; ultrastructure

OBJECTIVETo explore 6-mercaptopurine (6-MP) treatment-related adverse reactions in children with acute lymphoblastic leukemia (ALL), and to assess the association between the polymorphisms of thiopurine methyltransferase (TPMT) gene and these 6-MP related toxicities.

METHODSTotal RNA was extracted from bone marrow samples of 46 children with ALL and was then reversed to cDNA. TPMT(*)1S and (*)3C were screened by denaturing gradient gel electrophoresis (DGGE) combining with DNA sequencing. Drug toxicities were classified according to national cancer institute-common toxicity criteria version 3.0 (NCI CTC 3.0). The relationship between TPMT gene polymorphisms and the adverse reactions of 6-MP treatment was analyzed.

RESULTSDuring the maintenance treatment period, 22% (10/46) of children discontinued 6-MP treatment because of serious adverse reactions. Two children with TPMT(*)3C genotypes presented severe adverse reactions, including 1 child with homozygotic mutation who had 6-MP dose-related myelosuppression and hepatotoxicity. The main side effects of 6-MP were myelosuppression, hepatotoxicity and gastrointestinal reaction. And there were no significant differences between TPMT(*)1S genotypes and severe myelosuppression or hepatotoxicity caused by 6-MP (P>0.05).

CONCLUSIONSTPMT(*)3C may correlate with severe adverse reactions caused by 6-MP.

Child ; Child, Preschool ; Female ; Humans ; Male ; Mercaptopurine ; adverse effects ; Methyltransferases ; genetics ; Polymorphism, Genetic ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics

Objective To understand the forming cause of the Oncomelania hupensis snail-existent non-endemic areas of schistosomiasis(SENEAS),and to verify the conclusion of previous studies,so as to provide the evidence for schistosomiasis monitoring in such areas in Nantong City,Jiangsu Province. Methods The controlled field tests were carried out to observe the O. hupensis snails artificially infected by schistosome miracidia in SENEAS. The influence of the soil from SENEAS and the en-demic areas on O. hupensis snails artificially infected by miracidia were observed. Results All the experimental snails could be infected by schistosome miracidia except the smooth-shell snails from Tangyuan Village in the controlled field test environment of SENEAS or the endemic areas. The infection rates of the smooth-shell snails were lower than those of the ribbed-shell snails , but there were no statistically significant differences. The mortality rates of the smooth-shell snails were higher than those of the ribbed-shell snails,which were statistically significant (χ2Xindian = 135.118,χ2Shuangdian = 122.836,χ2Baipu =154.436,χ2Dingyan =138.288,χ2Control=151.923,all P<0.01). There were no significant differences in the infection rates of snails between each test group of the soil from SENEAS and the endemic areas(χ2Rugao=0.071,χ2Rudong=0.216,both P>0.05). Also there was no signifi-cant difference between each test group and the control group without soil(χ2=7.148,P>0.05). Conclusion It is likely to form the spread of schistosomiasis in SENEAS in Nantong City with sufficient amount of infection source of schistosomiasis im-ported. It is still necessary to implement the surveillance of schistosomiasis and O. hupensis snails in Nantong City.

AIM:To investigate the mechanism of angiotensinⅡ(AngⅡ)/angiotensinⅡ type 1 receptor (AT1R)pathway activating protein phosphatase 2A(PP2A)which leads to down-regulation endothelial nitric oxide syn-thase(eNOS)phosphorylation level in mesenteric arteries of rats.METHODS: METHODS: The mesenteric arteries of adult male SD rats(weighing 160~180 g;n=90)were isolated under aseptic conditions.Firstly,to determine the effect of angiotensinⅡdown-regulated eNOS(Ser1177)phosphorylation level,the mesenteric arteries were randomly divided into normal control(control)group and AngⅡgroup.The mesenteric arteries in AngⅡgroup were incubated with AngⅡat 1×10 -7mol/L,1×10 -6mol/L and 1×10 -5mol/L for 6 h,12 h and 24 h,respectively.Secondly,to investigate the mo-lecular mechanism by which angiotensinⅡ activated PP2A leading to down-regulation eNOS(Ser1177)phosphorylation level,the mesenteric arteries were randomly divided into control group, AngⅡ group and candesartan(CAN; a specific AT1R blocker)+AngⅡgroup.The mesenteric arteries were pretreated with 1×10 -5mol /L CAN for 1 h,then incubated with 1×10 -7mol/L AngⅡfor 12 h in CAN+AngⅡgroup.The protein levels of eNOS,p-eNOS(Ser1177),PP2Ac,p-PP2Ac(Tyr307)and protein phosphatase 2A inhibitor 2(IPP2A2 )in the arteries were determined by Western blot.The ac-tivity of PP2A in the arteries was detected by PP2A activity kit.RESULTS:Compared with the control group,the protein level of p-eNOS(Ser1177)in the mesenteric arteries was decreased after incubated with AngⅡfor 6 h,12 h and 24 h(P<0.05).The decreasing tendency of p-eNOS(Ser1177)showed concentration-dependently,especially in 12 h and 24 h groups.The expression of eNOS protein showed no significant difference in each group.Compared with the control group, the mesenteric arteries of the rats were incubated with AngⅡ at 1×10-7mol/L for 12 h in vitro, the protein levels of p-eNOS(Ser1177)were down-regulated(P<0.05); pretreatment with CAN significantly increased the protein level of p-eNOS(Ser1177)(P<0.05);the protein levels of eNOS showed no significant difference in each group.Compared with the control group,the protein levels of p-PP2Ac(Tyr307)and IPP2A2 were decreased after the mesenteric arteries were trea-ted with AngⅡat 1×10 -7mol/L for 12 h(P<0.05).Candesartan pretreatment restored the protein levels of p-PP2Ac (Tyr307)and IPP2A2 (P<0.05),however the expression of PP2Ac protein showed no significant difference in each group. Compared with the control group,the activity of PP2A was increased in the mesenteric arteries incubated with AngⅡat 1× 10-7mol/L for 12 h(P<0.05).Candesarten pretreatment inhibited the activity of PP 2A significantly(P<0.05).CON-CLUSION:AngⅡincreases PP2A activity via AT1R pathway,thus leading to down-regulation eNOS(Ser1177)phospho-rylation level in mesenteric arteries.The molecular mechanism of PP2A activation may be associated with decreasing the protein levels of p-PP2Ac(Tyr307)and IPP2A2.

OBJECTIVETo study the molecular mechanisms of protein C (PC) deficiency caused by PC gene mutations of C64W, F139V and K150 deletion (K150d).

METHODSWild-type and mutant PC cDNA expression plasmids (PCwt, PC C64W, PC F139V, PC K150d) were constructed and transfected into COS-7 cells or CHO cells respectively for in vitro expression study and immunofluorescent assay. Fluorescent real-time PCR was used to detect the expression of PC mRNA, protein degradation inhibition and endo-beta-N-acetylglucosaminidase H (Endo H) digestion experiments to explain the mutant protein degradation pathway and its localizations inside the cells.

RESULTSPC C64W was not secreted from the cells and was gradually degraded inside the cells. There was partial secretion of PC F139V, most of the protein molecule was not secreted and degraded intracellularly. Mutant PC K150d was secreted normally from the cells. Fluorescent realtime PCR analysis of total mRNA from transfected cells showed no reduction of the mutant PC mRNA expression compared with that of wild-type PC mRNA. Protein degradation inhibition experiments showed that mutants PC C64W and PC F139V were degraded intracellularly through the proteasome pathway. Endo H digestion experiments and immunofluorescence results suggested that mutant PC molecules were located mainly in pre-Golgi apparatus.

CONCLUSIONSImpaired secretion and degradation intracellularly of the mutants might be the molecular mechanisms of PC deficiency caused by C64W and F139V mutations. K150 deletion mutation might not affect the secretion of the mutant.

Animals ; CHO Cells ; COS Cells ; Cercopithecus aethiops ; Cricetinae ; Cricetulus ; Humans ; Mutation ; Plasmids ; genetics ; Protein C ; genetics ; Protein C Deficiency ; genetics ; Transfection