Olfactomedin 1 Deficiency Leads to Defective Olfaction and Impaired Female Fertility.

Olfactomedin 1 (OLFM1) is a glycoprotein highly expressed in the brain. Olfm1(-/-) female mice were previously reported to have reduced fertility. Previous microarray analysis revealed Olfm1 among the most highly upregulated genes in the uterine luminal epithelium upon embryo implantation, which was confirmed by in situ hybridization. We hypothesized that Olfm1 deficiency led to defective embryo implantation and thus impaired fertility. Indeed, Olfm1(-/-) females had defective embryo implantation. However, Olfm1(-/-) females rarely mated and those that mated rarely became pregnant. Ovarian histology indicated the absence of corpora lutea in Olfm1(-/-) females, indicating defective ovulation. Superovulation using equine chorionic gonadotropin-human chorionic gonadotropin rescued mating, ovulation, and pregnancy, and equine chorionic gonadotropin alone rescued ovulation in Olfm1(-/-) females. Olfm1(-/-) females had a 13% reduction of hypothalamic GnRH neurons but comparable basal serum LH levels and GnRH-induced LH levels compared with wild-type controls. These results indicated no obvious local defects in the female reproductive system and a functional hypothalamic-pituitary-gonadal axis. Olfm1(-/-) females were unresponsive to the effects of male bedding stimulation on pubertal development and estrous cycle. There were 41% fewer cFos-positive cells in the mitral cell layer of accessory olfactory bulb upon male urine stimulation for 90 minutes. OLFM1 was expressed in the main and accessory olfactory systems including main olfactory epithelium, vomeronasal organ, main olfactory bulb, and accessory olfactory bulb, with the highest expression detected in the axon bundles of olfactory sensory neurons. These data demonstrate that defective fertility in Olfm1(-/-) females is most likely a secondary effect of defective olfaction.

[Effect of Naoshuantong capsule on change of SSQOL index in patients with ischemic stroke in six mouths follow-up].

To evaluate the effect of Naoshuantong capsule on the life quality of patients with ischemic stroke in six months of follow-up studies, and observe the adverse events. The results would provide reference for the secondary prevention on the recovery stage of ischemic stroke. 696 patients from 12 Class III Grade I hospitals nationwide were divided into 2 groups by central randomization system. The study group, 344 cases, were treated with Naoshuantong capsule plus Aspirin, and the control group, 352 cases, were treated with Aspirin. The patients were treated for 6 months. At the end of treatment, SS-QOL used for evaluating the quality of life was observed. The safety index was defined by adverse observation event. The incidence of adverse events and laboratory tests results were observed before and after treatment at the same time. The results indicated that compared to the control group, the treatment group had significant statistical difference in the impact of effort, self-care ability and the the work or labor ability of patients (P < 0.05). No serious adverse events were observed. Naoshuantong capsule showed some superiority to Asprin on improving the quality of life on patients with ischemic stroke, and it could be used in secondary prevention on the recovery stage of ischemic stroke. Naoshuantong capsule is safe and effective in the treatment of convalescence ischemic stroke.

Postweaning dietary genistein exposure advances puberty without significantly affecting early pregnancy in C57BL/6J female mice.

An epidemiological study indicates higher plasma level of genistein in girls with earlier puberty. This study tests the hypothesis in C57BL/6J mice that postweaning (peripubertal) dietary genistein exposure could result in earlier puberty in females assessed by vaginal opening, estrous cyclicity, corpus luteum and mammary gland development. Newly weaned female mice were fed with 0, 5, 100, or 500 ppm genistein diets. Decreased age at vaginal opening, increased length on estrus stage, and accelerated mammary gland development were detected in 100 and 500 ppm genistein-treated groups. Increased presence of corpus luteum was found in 5 ppm genistein-treated group at 6 weeks old only. Increased expression of epithelial-specific genes but not that of ERα or ERß was detected in 500 ppm genistein-treated mammary glands at 5 weeks old. No significant adverse effect on embryo implantation was observed. These data demonstrate causal effect of dietary genistein on earlier puberty in female mice.

[Post-marketed re-evaluation of fleabane injection and Dengzhan Shengmai capsule study on treatment in patients with ischemic stroke].

OBJECTIVE: To verify the efficacy and safety of post-marketed fleabane injection combined with Dengzhan Shengmai capsules in the treatment of ischemic stroke (IS). METHOD: A multicentre, prospective, practical, randomized controlled study was carried out to compare the efficacy and safety of Dengzhan group (n = 343) and western medicine group (n = 335), appling "clinical study central stochastic system". The treatment of Dengzhan group is using fleabane injection in acute stage and Dengzhan Shengmai capsules in convalescence. The primary indexes of effect evaluation are the important outcome events in 360 days' follow-up, including mortality, recurrence, disability and quality of life to reflect the effect of clinical study. The indexes of safety evaluation involve laboratory examination results and incidence of adverse events. RESULT: After 360 days' follow-up, 4 people died of IS in Dengzhan group, and the mortality rate of which is 1.17%, while 16 died in Western medicine group (WM group), and the mortality rate is 4.78%, suggesting that the mortality rate of Dengzhan group is significantly lower than WM group (P<0.05). Eleven cases recurred in Dengzhan group, and the recurrence rate of which is 3.21%, while 12 recurred in WM group, and the recurrence rate is 3.59%, indicating that the recurrence rate of Dengzhan group is slightly lower than WM group. The disability rate of Dengzhan group is 39.53%, among which the rate of severely disabled cases are 1.49%, while the disability rate of WM group is 40.13%, among which the rate of severely disabled cases are 3.13%, suggesting that the disability rate of Dengzhan group is lower and the severity of disability is also lighter than WM group. In the field of quality of life, the activity ability and the upper limb function store of stroke patients in Dengzhan group improved far much better than WM group (P<0.05). Analysis of safety suggested that, adverse events occurred in 11 cases in Dengzhan group, among which 4 cases is related with the drug treatment, the incidence of adverse events of which is 1.17%, and the main manifestations involve fever and chilling, rash, nausea, dizziness, palpitation, etc. which were all appeared after the treatment of fleabane injection, and disappeared 1 to 2 days after drug withdrawal. 13 cases occurred abnormal liver function and 2 cases abnormal kidney function in Dengzhan group. According to the judgment of clinical physicians, 3 case of ALT abnormality is possibly related to the treatment, the others are all unrelated with the treatment. CONCLUSION: Fleabane injection and Dengzhan Shengmai capsules are all safe and effective TCM in the treatment of ischemic stroke.

[Post-marketing re-evaluation of Kudiezi injection study on early treatment in patients with ischemic stroke].

OBJECTIVE: To study the effect and safety of Kudiezi injection on patients with acute ischemic stroke. METHOD: Seven hundreds patients were divided into two groups by central randomization system. The study group, 346 cases, was treated with kudiezi injection plus traditional Chinese medicine (TCM) synthesis rehabilitation project, and the control group, 354 cases, was treated with synthetic rehabilitation project. The patients were treated for 10 to 21 days. Before treatment and at the 7th, 14th and 21th day of treatment, the indexes include NIHSS used for evaluating the neurological deficit degree and the motor function score (Fugl-Meyer) for evaluating motor function were observed. The safety index is defined by adverse observation event and laboratory test. The incidence of adverse events and laboratory tests results were observed before and after treatment at the same time. RESULT: Application of generalized estimating equation model, we found that as the treatment time, NIHSS score and FMI score of the two groups showed a trend of improvement. And at the 14th days and 21th days of treatment, compared to the control group the treatment group showed significant statistical difference on the impact of NIHSS and FMI (P<0.05). No serious adverse events were observed. CONCLUSION: Kudiezi injection plus TCM rehabilitation project of ischemic stroke showed some superiority to western medicine rehabilitation program on improving the neurological deficit and motor function. Kudiezi injection is safe and effective in the treatment of acute ischemic stroke.

[Studies on triterpenoid saponins in Hemsleya chensnsis].

OBJECTIVE: To study the triterpenoid saponins in Hemsleya chensnsis. METHOD: The chemical constituents were isolated and purified by various chromatographic methods and their structures were elucidated on the basis of spectral analysis. RESULT: Seven known triterpenoid saponins were isolated from the root of H. chensnsis and were identified as 3-O-beta-D-glucuropyranosyl-oleanol-icacid (1), 3-O-beta-D-glucopyra-noside-oleanolicacid-28-O-beta-D-glucopyranoside (2), 3-O-(6'-methylester)-beta-D-glucuropyranosyl olea- nolic acid-28-O-alpha-L-arabinopyranoside (3), 3-O-(6'-methylester)-beta-D- glucuropyranosyl- oleanolic acid-28-O-beta-D-mannupyranoside (4), 3-O-(6'-ethyl ester)-beta-D-glucuropyranosyl oleanolic acid-28-O-beta-D- glucopyranoside (5), 3-O-alpha-L-arabinopyranoside-(1-->3) -beta-D-glucuropyranosyl- oleanolic acid-28-O-beta-D-glucopyranoside (6), 3-O-beta-D-glucu-ropyranosyl-oleanolic acid-28-O-beta-D-glucopyra-noside-(1-->6)-beta-D-glucopyranoside (7). CONCLUSION: Compounds 1-7 were isolated from this plant for the first time.