This study was designed to investigate inhibitory effects and possible mechanisms of snake venom tripeptide (pENW) on platelet adhesion in order to promote the development of a novel anti-platelet therapy. To study the inhibitory effects of pENW on platelet adhesion, washed platelets pre-incubated with pENW (116.5-466.2 μmol x L(-1)) were used to test the ability of platelet adhesion to fibrinogen. Effect of pENW on fibrin clot retraction was also tested. Effect of pENW on platelets viability was tested by MTT assay. Effect of pENW on reactive-oxygen species (ROS) levels of platelet was studied by flow cytometry assay. Calcium mobilization in Fura-2/AM-loaded platelets was monitored with a spectrofluorimeter. Cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), thromboxane A2 (determined as its metabolite thromboxane B2) were measured using enzyme immunoassay kits. Akt, ERK and p38 phosphorylation were tested by Western blot. The results showed that pENW inhibited platelet adhesion and fibrin clot retraction in a concentration-dependent manner without cytotoxicity. Intracellular cGMP and cAMP in both resting and thrombin-activated platelets were increased by pENW. In addition, pENW attenuated intracellular Ca2+ mobilization and TXA2 production in platelets stimulated by thrombin. As shown by Western blot assay, Akt, ERK and p38 phosphorylation in thrombin-induced platelet were attenuated by pENW. However, inhibitory effects of pENW had nothing to do with ROS. Thus, pENW exhibited a significant inhibition on platelet adhesion to fibrinogen, which means pENW could block the first step of thrombosis as while as retard the more stable clot formation. The mechanisms of pENW on inhibition platelet adhesion might be related to instant regulations, such as protein kinases.
Blood Platelets ; drug effects ; Blotting, Western ; Calcium ; metabolism ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Flow Cytometry ; Phosphorylation ; Platelet Aggregation ; drug effects ; Reactive Oxygen Species ; metabolism ; Snake Venoms ; chemistry ; Thromboxane A2 ; metabolism ; Thromboxane B2 ; metabolism

Humans ; Tachycardia, Ventricular ; genetics

Objective To evaluate the practical value of the method of contrast enhanced ultrasoundguided reduced-fine needle aspiration (CEUS-FNA) in decreasing the complications of prostate nodule puncture.Methods Nine hundred patients with suspected prostate cancer(PCa) who underwent traditional 10-point blind transperineal prostate nodule puncture(n =548) or CEUS-FNA(n =352) were collected retrospectively and classfied into normal group or CEUS group,respectively.The ratio of prostate cancer diagnosis,number of punctur and compliations were observed in both groups.Results Altogether 362 PCa were diagnosed from 900 patients.Among these cases the diagnosis ratio of normal group was 38.0％ (208/548) and that of CEUS group was 43.8 ％ (154/352).There was no significant difference in diagnosis ratio between two groups (x2 =2.992,P =0.084).The puncture number of normal group were more than that of CEUS group(P ＜0.01).There were 134 cases occurred infection and other complications in tradition group and 56 cases in CEUS group.The complication rate in normal group was higher than that in CEUS group (24.5 ％ vs 15.9 ％),with significant differences between the two groups (x2 =9.393,P =0.002).Conclusions CEUS-FNA could reduce puncture number,but not decrease the PCa diagnsis rate.And also that could reduce the complication rate of prostate puncture.

Objective To investigate the relationship between cervical intraepithelial neoplasia (CIN) and high-risk (HR)HPV infection among late pregnant women.Methods From Aug.2007 to Feb.2010,168 women at 13 to 32 gestational weeks undergoing prenatal examination in Beijing Obstetrics and Gynecology Hospital went through three stage cervical disease screening,including 21 women with cervicitis and 147 women with C1N (42 women with CIN Ⅲ,37 women with CIN Ⅱ and 68 women with CIN Ⅰ ).Hybrid capture assay version Ⅱ ( HC- Ⅱ ) test was used to measure HR-HPV DNA load,and the logarithmic transtormation (log10) was performed.All 168 women were followed up to postpartum 3 -6 months.HR-HPV infections rates of cervicitis and different CIN,the rate of HR-HPV infection turned naturally negative at postpartum of 3 to 6 months,and HR-HPV load at pregnancy and 3 -6 months postpartum were observed.Results ( 1 ) HR-HPV infection rate:CIN Ⅲ,Ⅱ,Ⅰ and cervicitis pregnant women's HR-HPV positive infection rates were 98％ (41/42),86％ ( 32/37 ),76％ ( 52/68 ) and 62％( 13/21 ) respectively,which reached statistical difference (P =0.002).(2) HR-HPV naturally negative:the rate of pregnant women with different levels of CIN who turned HR-HPV naturally negative within 3 -6 months of postpartum were CIN Ⅲ 5％ (2/41),CIN Ⅱ 47％ (15/32),CIN Ⅰ 52 ％ (27/52) and cervicitis 10/13,which also reached statistical difference among those four groups (P =0.000).(3) HR-HPV load:pregnant women with different grade of CIN and cervicitis HR-HPV DNA load were CIN Ⅲ 2.02 ng/L(1.53,2.67 ng/L),CIN Ⅱ 1.94 ng/L ( 0.75,2.75 ng/L),CIN Ⅰ 2.04 ng/L (0.08,2.95 ng/L) and cervicitis 1.98 ng/L( -0.07,2.47 ng/L).There was no significantly different HPV load in women with cervicitis and different CIN (P =0.719).At 3 -6 months postpartum,HR-HPV load was CIN Ⅲ1.55 ng/L(0.90,2.10 ng/L),which was significantly higher than the amount of CIN Ⅱ 0.09 ng/L(-0.69,1.74 ng/L),CIN Ⅰ 0.48 ng/L( -0.56,2.2 ng/L) and cervicitis -0.46 ng/L ( -0.78,1.40 ng/L,P =0.036).Conclusions With the increasing of CIN grade,the rate of HR-HPV infection in pregnant women was increased,however,the rate of HR-HPV turning negative naturally at 3 -6 months postpartum decreased.With different CIN grade during pregnancy,HR-HPV DNA load did not change significantly,but HR-HPV DNA load increased at 3 -6 months of postpartum.HR-HPV DNA loads with the same grade of CIN and cervicitis during pregnancy higher than that of postpartum among pregnant women.

Objective To investigate the value and safety of biopsy guided by colposcopy in diagnosis of cervical diseases in pregnant women.Methods From Aug.2007 to Feb.2009.17 828 pregnant women who receive antenatal examination underwent cervical cytological screening thinprep cytology test(TCT)in Beijing Obstetrics and Gynecology Hospital.If abnormal cytological results were found,those preguant women were administered by eolposcopic examination and biopsy after they signed informed consent.Results (1)TCT:the abnormal TCT results of 1502 preguant women(8.425%,1502/17 828) were found in 17 828 cases.(2)Colposeopie examination:two hundred and four pregnant women underwent colposcopic examination.The rate of satisfied colposcopic imaging wag 92.6%(189/204),colposcopic examination identified 125 cages with cervical inflammation or cervical intraepithelial neoplasia (CIN)Ⅰ,25 cases with CIN Ⅱ and 54 cases with CIN Ⅲ or microinvasive squamous carcinoma (MIVC) of squamous cervical carcinoma(SCC).(3)The results of biopsy guided by colposcopy:among 204 cases,it was found 33 cases with cervical inflammation or wart,95 cases with CIN Ⅰ,28 CIN Ⅱ,36 cases with CIN Ⅲ and 12 cases with MIVC. (4) The rate of concordance: compared with biopsy pathologic examination, colposcopy examination found 113 cases with cervical inflammation and CIN Ⅰ , the rate of concordance was 90. 4%(113/125). And 54 cases with CIN Ⅲ or SCC diagnosed by colposcopy examination, however biopsy pathologic examination confirm 23 cases with CIN % and 10 cases with SCC at stage Ⅰ a, the concordance rate was 61% (33/54). (5) Complication: eight (3.9%, 8/204) pregnant women underwent cervical wound suturing due to continuous bleeding after colposcopy exam or biopsy. No other complications were recorded. Conclusions It is necessary that TCT should be performed in pregnant women without cytological screening within one year. Colposcopic examination and biopsy were indicated if pregnant woman with abnormal cytological result were found. Pregnant women with cervicitis or CIN Ⅰ diagnosed by colposcopy should be followed up. If pregnant woman was suspected with CIN Ⅱ or advanced disease, biopsy guided by colposcopy should be performed.

Objective To evaluate the maternal and fetal outcomes of planned delay in treatment for cervical microinvasive squamous cancer during pregnancy.Methods A prospective study of pregnant women was done from August 1,2007 to May 31,2010.Pregnant women who had not been carried out cervical cytological screening within one year were got thin-prep cytology test (TCT) screening at their initial prenatal visit.Patients with abnormal cytological results were performed colposcopic examination and directed biopsy.Women with cervical microinvasive cancer were followed up every 8 to 12 weeks.If lesion progression were suspected,compared with previous image,repeated biopsy directed by colposcopy should be performed.Once worsening invasive cancer was confirmed,the pregnancy should be terminated timely.All patients should be reevaluated 6 to 12 weeks postpartum with repeated colposcopic examination and biopsy.All mothers were performed cold knife conization (CKC) at 6 to 12 weeks postpartum.Results We totally diagnosed 17 cases cervical microinvasive squamous carcinoma during pregnancy.The positive rate is 6.2/10 000 (17/27 230).After informed consent,15 pregnant women decided to delay treatment until fetal maturation.The mean gestational age of initial diagnosis was (19.3 ± 5.9) weeks.The women were followed up 2 to 4 times during pregnancy.Only 1 patient was verified lesion progression by directed biopsy at 34 weeks and delivered by cesarean section.The progression rate during pregnancy was 1/15.The mean delivered time was (37.1 ± 1.8) weeks (ranged from 34 to 40 weeks).The mean diagnosis-to-delivery interval was (18.4 ± 5.2) weeks.All patients were delivered by cesarean section and all newborns had good outcomes.Finally we confirmed 1 case with cervical cancer stage Ⅰ a2,11 cases with stage Ⅰ al,3 cases with cervical intraepithelial neoplasia (CIN) Ⅲ by pathological diagnosis after CKC during 6 to 12 weeks postpartum.All cases were disease free after follow-up ranged from 22 to 48 months.Conclusions It is necessary to perform TCT screening for pregnant women who have not been carried out cervical cytology screening within 1 year.If cervical microinvasive squamous cancer were suspected during pregnancy,in order to achieve fetal maturity it is acceptable for the women who desired pregnancy to delay treatment under closely monitoring until postpartum.

This study reports the outcomes of a collaborative program between dialysis clinics and a referral hospital, which consisted of clinical monitoring and supplementary routine surveillance, for improving the quality of vascular access care. Methods: This retrospective observational study was performed at five dialysis clinics as part of a 2-year collaborative program (2019–2020) in conjunction with a hospital-based dialysis access management center. A total of 392 hemodialysis patients (arteriovenous fistula [AVF], n = 339 and arteriovenous graft [AVG], n = 53) were included. Outcome measures included the prognosis of vascular access, clinic satisfaction, and referral rate to the hospital. Results: Increased vascular access flow was observed and critical flow events decreased from the first to the second year (AVF: 18.3% vs. 12.7%, p < 0.001; AVG: 26.2% vs. 20.1%, p = 0.30). There were fewer percutaneous transluminal angioplasty events in the AVG group (0.77 per person-year vs. 0.51 per person-year, p = 0.005). New AVF or AVG creation events also remained low. All dialysis clinics were satisfied with the program. The overall referral rate from the participating clinics increased (65.7% vs. 72.0%) during the study period independently of the physical distance between the dialysis clinic and the hospital. Conclusion: The collaboration between dialysis clinics and a referral hospital for improving the quality of vascular access care was successful in this study, and the model can be used by other clinics and hospitals looking to improve care coordination in dialysis patients.

Animals ; Binding Sites ; Capsid ; chemistry ; immunology ; metabolism ; Escherichia coli ; genetics ; metabolism ; Gene Expression ; HIV-1 ; chemistry ; immunology ; Humans ; Mice ; Myxovirus Resistance Proteins ; chemistry ; immunology ; metabolism ; Protein Binding ; Protein Multimerization ; Protein Structure, Tertiary ; Recombinant Proteins ; chemistry ; immunology ; metabolism

Nasal polyp (NP) is a common chronic inflammatory disease of the nasal cavity and sinuses.Although some authors have suggested that NP is related to inflammatory factors such as interleukin (IL)-1β,IL-5,IL-8,granulocyte-macrophage colony-stimulating factor (GM-CSF),tumor necrosis factor (TNF)-α,and IL-17,the mechanisms underlying the pathogenesis and progression of NP remain obscure.This study investigated the expression and distribution of IL-17 and syndecan-1 in NP,and explored the roles of these two molecules in the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) and non-Eos CRSwNP.Real-time PCR and immunohistochemistry were used to detect the expression of IL-17 and syndecan-1 in samples [NP,unciform process (UP) from patients with CRS,and middle turbinate (MT) from healthy controls undergoing pituitary tumor surgery].The results showed that the expression levels of IL-17 and syndecan-1 were upregulated in both NP and UP tissues,but both factors were higher in NP tissues than in UP tissues.There was no significant difference in IL-17 levels between the Eos CRSwNP and non-Eos CRSwNP samples,and syndecan-1 levels were increased in the non-Eos CRSwNP tissues as compared with those in Eos CRSwNP tissues.In all of the groups,there was a close correlation between the expression of IL-17 and syndecan-1 in nasal mucosa epithelial cells,glandular epithelial cells,and inflammatory cells,suggesting that IL-17 and syndecan-1 may play a role,and interact with each other,in the pathogenesis ofnon-Eos CRSwNP.

Objective To explore the protective effect of insulin-like growth factor 1 (IGF-1) on apoptosis of dopaminergic neurons induced by L-dopa via JAK/STAT signaling pathway. Methods PC12 cells were induced to differentiate into dopaminergic neurons with 100 μg/L β-NGF; MTT assay was employed to identify the changes in the viability of PC12 cells following L-dopa treatment at 0, 10,20, 50, 100, 150 and 200 μmol/L, and the different concentrations of IGF-1 at 0, 10, 25, 50 and 100 nmol/L with the same concentration of L-dopa (150 μmol/L); Western blotting was used to detect the levels of P-JAK2/P-STAT3 in PC12 cells treated with PBS (controls), L-dopa, L-dopa+IGF-1 and L-dopa+IGF-1+AG490 for 24 h, and then the apoptosis rate was assessed by flow cytometry and Hchest33258 staining. Results Western blotting showed that the expressions of P-JAK2 and P-STAT3 were detected in the L-dopa+IGF-1 and L-dopa+IGF-1+AG490 treatment groups but not in the control group or L-dopa treatment group; the expression of P-STAT3 in the L-dopa+IGF-1+AG490 treatment group was obviously lower than that in the L-dopa+IGF-1 treatment group (P<0.05). Hchest33258 staining indicated that L-dopa treatment group had the most obvious karyopyknosis and karyorrhexis,much more apoptotic bodies than the L-dopa+IGF-1 and L-dopa+IGF-1+AG490 treatment groups. Flow cytometry showed that the apoptosis rate was significantly different among the 4 groups (F=180.991,P=0.000): as compared with the control group, the other 3 groups had a higher apoptosis rate (P<0.05);L-dopa treatment group (38.13 ±2.54 %) enjoyed the highest level, followed by L-dopa+IGF-1 +AG490treatment group (25.60±1.30 %) and L-dopa+IGF-1 treatment group (20.17±1.54 %). Conclusion L-dopa has toxic effect on PC12 cells; IGF-1 could protect the PC12 cells from the neurotoxic effect of L-dopa and JAK2/STAT3 signaling pathway is activated in this procedure.