The Pharmacokinetics and Pharmacodynamics of A Novel Recombinant Activated Human Factor VII, GEN-0828, in Hemophilia B Mice.

GEN-0828, a proposed clinical candidate for hemophilia and trauma hemorrhage treatment, is a novel recombinant activated human factor VII (rFVIIa). The purpose of this paper is to compare the pharmacokinetics and pharmacodynamics of GEN-0828 in hemophilia B mice with those of NovoSeven®, the only marketed rFVIIa product worldwide., GEN-0828 and NovoSeven® showed similar affinity bioactivity to recombinant tissue factor (rTF) in vitro. Pharmacodynamics data indicated a generally similar hemostatic efficacy (ED50) of GEN-0828 (10.91 KIU·kg-1) and NovoSeven® (18.91 KIU·kg-1) at the doses studied in hemophilia B mice, while GEN-0828 represented a lower initial effective dosage compared with that of NovoSeven® in terms of both blood loss and APTT. GEN-0828 exhibited linear pharmacokinetic profiles in hemophilia B mice at the 30-338 KIU·kg-1 dose range, the comparative pharmacokinetic study with NovoSeven® indicated better characteristics than NovoSeven® in terms of the appropriate higher maximal concentration (Cmax) and area under the plasma concentration-time curve (AUClast) and longer mean residence time (MRT). In conclusion, GEN-0828 was a promising new type of rFVIIa compound with favourable pharmacokinetic and pharmacodynamic profiles.

Clinical evaluation of a multitarget fecal immunochemical test-sDNA test for colorectal cancer screening in a high-risk population: a prospective, multicenter clinical study.

Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals defined as having positive risk-adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT-sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT-sDNA test was 91.9% (95% CI, 86.8-95.3), compared with 62.4% (95% CI, 54.9-69.3) for FIT (P < 0.001). The sensitivity for detecting advanced precancerous neoplasia was 63.5% (95% CI, 58.3-68.3) for FIT-sDNA test, compared with 30.9% (95% CI, 26.3-35.6) for FIT (P < 0.001). Multitarget FIT-sDNA test detected more colorectal advanced neoplasia than FIT. Overall, these findings indicated that in areas with limited colonoscopy resources, FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening.

An effective perineal procedure for the management of full-thickness rectal prolapse.

AIMS: To evaluate the clinical and functional outcome of transanal purse-string sutures for rectal mucosa and submucosa plus perianal suture (TAS-PAS) for the management of full-thickness rectal prolapse. METHODS: The clinical data of 62 patients with full-thickness rectal prolapse treated with TAS-PAS between March 2000 and March 2008 were analyzed retrospectively. RESULTS: No patient died. Satisfaction with surgery was high in 50 cases (80.6%), moderate in 9 cases (14.5%), and low in 3 cases (4.84%). Prolapse relapse rate was 4.84%. Anal continence improved in 82.6% of patients, constipation improved in 69.2%, and anal tenesmus in 86.7%. No surgery-associated constipation occurred. The mean operative time was 52 min (range 40-80). Mean hospital stay was 4 days (range 3-7). Mean patient follow-up was 17 months (range 4-36). CONCLUSIONS: From our data, TAS-PAS for the management of full-thickness rectal prolapse showed encouraging results with little complications and an acceptable relapse rate. This procedure induces only mild trauma and is easy to perform making it worthy of further practice and investigation.

[Association of soluble human leukocyte antigen DQB1 with recurrent spontaneous abortion].

OBJECTIVE: To investigate the relationship between the recurrent spontaneous abortion and soluble human leukocyte antigen (HLA) DQB1 gene polymorphism. METHODS: Sixty one cases with recurrent spontaneous abortion were included in study group. Of them, 31 were anticardiolipin antibody (ACA) positive, while 30 were negative. Twenty eight cases were with early abortion, 22 were with late abortion, and 11 were with both early and late abortions. Thirty six women without abnormal pregnancy history were recruited as control group. HLA-DQB1 genotyping was carried out by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of DQB1*0201allele in the study group (16.4%, 20/122) was higher than that in the control group (8.3%, 6/72), but the difference was not statistically significant (P > 0.05). The frequency of 57 site with non Asp in the study group was significantly higher than that in the control group (P < 0.05). The frequencies of both DQB1*0201 and *0303 were significantly different among early abortion, late abortion and both early and late abortion groups (P < 0.05 and P < 0.05). The frequency of DQB1*0201 was significantly higher in the early abortion group than that in the late abortion group (P < 0.01). The frequency of DQB1*0303 was significantly increased in the late abortion group when compared to that in the early group (P < 0.01). The frequency of DQB1*0303 was found to be significantly higher in patients with ACA positive than that in ACA negative group (P < 0.05). CONCLUSION: The 57 site with non Asp may be a gene related to recurrent spontaneous abortions. DQB1*0201 may be correlated to the early abortion, while DQB1*0303 correlated to the late abortion and abortion with ACA positive.