Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer's disease diagnosis and differential diagnosis.

Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer's disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD+- or GPR162+-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD+- and GPR162+-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD+- or GPR162+-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD.

[CatSper in sperm hyperactivation and male infertility: Advances in studies].

The CatSper channel is known as one of the most important Ca²âº channels on the cell membrane of mammalian sperm and plays a key role in the motility, hyperactivation and fertilization function of sperm. The CatSper protein, expressed exclusively in the principal piece of the sperm tail, is composed of CatSper1-4 and 5 auxiliary unitsß,γ,δ and ε, and has an essential part in the functional and structural domains of Ca²âºas well as in the spatiotemporal regulation of the P-Tyr protein, sperm hyperactivation, efficient sperm migration in the oviduct, egg penetration, and normal fertility. Recent studies show that functional deficiency of CatSper seriously affects sperm function,and the loss of any one of its 9 subunits may lead to male reproductive dysfunction. This paper outlines recent advances in the studies of the CatSperprotein, focusing on its expression, location, structure, and regulation,as well as itsinfluence on sperm hyperactivation and male reproduction.

[Application of oxytocin antagonists in thaw embryo transfer].

OBJECTIVE: To study the effects of oxytocin antagonists-atosiban on pregnancy outcome after thaw embryo transfer (TET). METHODS: Between Jul. and Dec. 2012, a total of 120 women undergoing TET in Reproductive Medical Center, General Hospital of Tianjin Medical University were randomly allocated into atosiban and control group. They were all transferred 2 or 3 top quality embryos at phase of 7-8 cells . Patients in atosiban group were administered by intravenous administration of atosiban before 30 minutes of embryo transfer with a total administered dose of 37.5 mg. In the control group, no special treatment was given before embryo transfer. All patients in 2 groups underwent progesterone luteal support regularly after embryo transfer, then the clinical rate of pregnancy, implantation and early abortion was compared. RESULTS: The clinical pregnancy rate per cycle and implantation rate per transfer were 60% (36/60) and 30.0% (48/160) in the atosiban group, which were higher than 42% (25/60) and 20.3% (31/153) in the control group (all P < 0.05). Early abortion rate was 6% (2/36) in the atosiban group, which was no statistical difference comapring with control group [16% (4/25), P > 0.05]. CONCLUSION: It was suggested that atosiban treatment before embryo transfer can improve the outcome of pregnancy, and increase clinical pregnancy rate and implantation rate after TET.

Modified super-long down-regulation protocol improves fertilization and pregnancy in patients with poor ovarian responses.

BACKGROUND: The successful end-point of in vitro fertilization (IVF) treatment is for a woman to give live birth. This outcome is based on various factors including adequate number of retrieved eggs. Failure to recruit adequate follicles, from which the eggs are retrieved, is called a "poor response". How to improve the clinical pregnancy rates of poor responders was one of the tough problems for IVF. METHODS: The study involved 51 patients who responded poorly to high dose gonadotropin treatment in their previous cycles at our reproductive center, between April 2010 and February 2012. The previous cycle (group A) received routine long protocol; the subsequent cycle (group B) received modified super-long down-regulation protocol. The primary outcome of the study was the number of oocytes fertilized. The increase in the pregnancy rate was the secondary outcome. Differences between the groups were assessed by using Student's t test and c(2) test where appropriate. RESULTS: The patients' average age was (36.64 ± 3.85) years. The mean duration of ovarian stimulation cycles of the group A patients was longer than those of the group B patients. The total dose of follicle-stimulating hormone (FSH) was significantly lower in the subsequent cycle. The peak value of serum estradiol on human chorionic gonadotrophin (hCG) day was lower in group A as compared with group B. The number of metaphase II oocytes recovered was significantly higher in group B. The cleavage rate in group A was significantly lower than in group B, 49 patients in group B reached embryo transfer stage, while 46 patients in group A reached this stage. Patients in group B received significantly more embryos per transfer as compared with group A. More pregnancies and more clinical pregnancies with fetal heart activity were achieved in group B. CONCLUSIONS: This comparative trial shows that poor responder women undergoing repeated assisted reproduction treatment using modified super-long down-regulation protocol achieve more oocytes, leading to higher fertilization rate, compared to women receiving routine long protocol. Our study also showed that clinical pregnancy rate was significantly improved.

[Influence of EmbryoGlue on the implantation of embryo and pregnancy outcome in vitro fertilization-embryo transfer].

OBJECTIVE: To study the influence of EmbryoGlue on the implantation of embryo and pregnancy outcome in vitro fertilization (IVF)-embryo transfer (ET). METHODS: From August 2010 to January 2011, 243 infertile patients in Reproductive Medical Center of Tianjin Medical University General Hospital who underwent IVF or intracytoplasmic sperm injection (ICSI) were divided into two groups, including 129 cases used EmbryoGlue as the embryo transfer medium in experimental group and 114 cases used G-2 as embryo transfer medium in control group. Pregnancy outcome were compared between two groups. RESULTS: (1) The female age, IVF/ICSI constituent ratio, previous failure cycles and infertile factors of patients did not show statistical difference between experimental group and control group (P > 0.05). (2) The implantation rate of women in experimental group increased significantly compared with the control group [30.4% (85/280) vs. 18.8% (48/255), P < 0.05]; Clinical pregnancy rate increased significantly compared with the control group [48.8% (63/129) vs.34.2%(39/114), P < 0.05]; Multiple pregnancy rate increased significantly compared with the control group [34.9% (22/63) vs. 20.5% (8/39), P < 0.05]; Ectopic pregnancy rate decreased significantly compared with the control group [4.8% (3/63) vs. 17.9% (7/39), P < 0.05]. CONCLUSION: EmbryoGlue can facilitate embryo implantation in IVF-ET and reduce the occurrence of ectopic pregnancy.

[Extracellular signal-regulated protein kinase activation in endometrium with polycystic ovary syndrome and its significance].

OBJECTIVE: to investigate the activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling pathway in the endometrium of women with polycystic ovary syndrome (PCOS) and its effect and significance in the cause of hyperplasia and carcinoma; and investigate the factors which affect the activation of the MAPK/ERK signaling pathway. METHODS: collected 52 patients diagnosed as PCOS who were taken dilation and curettage of uterus as study, while 32 non-PCOS patients matched as control group. Serum hormonal parameters, fasting blood glucose and insulin were measured in all patients. The PCOS patients were sub-group as insulin resistance group and non-insulin resistance group; all the patients were carried out pathology inspection of endometria, and the PCOS patients were sub-group as endometrial hyperplasia and carcinoma group and normal endometrium group based on the outcome of pathology inspection. Western blot were performed to detect the expressions of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2), the activation of ERK1/2. RESULTS: (1) the expression of p-ERK1/2 [(61 ± 13)%] in the endometrium in PCOS group was higher than that in the control [(44 ± 10)%, P < 0.01]. (2) The expression of p-ERK1/2 was significantly increased in group of endometrial hyperplasia and carcinoma [(70 ± 11)%] compared to that in group of normal endometrium [(55 ± 10)%, P < 0.01], while there were significant difference between group of insulin resistance [(63 ± 13)%] and group of non-insulin resistance [(55 ± 7)%, P < 0.01]. (3)Fasting insulin level, insulin area under the curve and body mass index were related to the expression of p-ERK1/2 in endometrium with PCOS, the correlation coefficient were 0.447, 0.456 and 0.381, respectively (all P < 0.01). CONCLUSIONS: the MAPK/ERK signaling pathway in endometrium with PCOS was overactivation, which was related to the endometrial hyperplasia and carcinoma; while the activation of MAPK/ERK signaling pathway were effected by insulin resistance and hyperinsulinemia.

[Influence of embryo transfer depth on in vitro fertilization and embryo transfer outcomes].

OBJECTIVE: To investigate the influence of transfer distance from the fundus on clinical pregnancy rate and implantation rate in in vitro fertilization and embryo transfer. METHODS: A total of 98 patients (108 cycles) undergoing ultrasound-guided embryo transfer were divided into two groups according to the distance between the tip of catheter and the uterine fundus: group A: > or = 5 - < 10 mm, group B: > or = 10 - < or = 15 mm. RESULTS: Clinical pregnancy rate and implantation rate were significantly higher in group B compared with group A [44 % (23/52) vs 25% (14/56), 24% (28/115) vs 14% (17/121), P < 0.05]. The multiple pregnancy rate, ectopic rate and miscarriage rate were similar in the two groups (P > 0.05). CONCLUSION: The depth of the embryo replacement into the uterine cavity may influence pregnancy rate and implantation rate.