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Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC50 value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.
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Objective:To investigate the effects of letrozole combined with human menopausal gonadotropin (HMG) on pregnancy rate and prognosis in patients with refractory polycystic ovary syndrome (PCOS).Methods:A total of 102 patients with refractory PCOS who received treatment in Jinhua Hongyue Women's and Children's Hospital between May 2019 and May 2020 were included in this study. They were randomly assigned to observation and control groups ( n = 51/group). All patients received the same treatment in the early period. During later ovulation induction period, patients in the control group were administered HMG and those in the observation group were given letrozole combined with HMG. Before treatment and 3 months after treatment, sex hormones [follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2), testosterone (T)], arterial hemodynamic indicators around the follicle [end diastolic velocity (EDV), peak systolic velocity (PSV), pulsation index (PI)], endometrial thickness and classification were compared between the two groups. The ovulation rate and pregnancy rate as well as pregnancy outcomes at 6 months of follow-up were recorded in each group. Results:After 3 months of treatment, FSH, LH, E 2 and T levels in each group were significantly decreased compared with those before treatment (all P < 0.05). FSH, LH, E 2 and T levels in the observation group were (1.85 ± 0.45) U/L, (9.86 ± 1.47) U/L, (81.25 ± 10.47) pmol/L, (1.75 ± 0.26) nmol/L, respectively, which were significantly lower than those in the control group [(3.12 ± 1.47) U/L, (12.58 ± 2.14) U/L, (109.25 ± 27.14) pmol/L, (3.58 ± 0.76) nmol/L, t = 5.90, 7.48, 6.87, 16.27, all P < 0.05). EDV in each group was significantly decreased after 3 months of treatment compared with that before treatment (both P < 0.05). After treatment, EDV in the observation group was significantly lower than that in the control group [(3.12 ± 1.42) cm/s vs. (5.14 ± 1.89) cm/s, t = 21.14, P < 0.001]. PSV in each group was significantly increased after treatment compared with that before treatment (both P < 0.05). After treatment, PSV in the observation group was significantly higher than that in the control group [(13.36 ± 2.01) cm/s vs. (10.24 ± 2.47) cm/s, t = 4.21, P < 0.001]. In each group, PI measured after treatment was not significantly different from that measured before treatment (both P > 0.05). After treatment, endometrial thickness in the observation group was significantly higher than that in the control group [(9.09 ± 1.58) mm vs. (8.41 ± 1.42) mm, t = 2.28, P < 0.05]. Ovulation rate in the observation group was significantly higher than that in the control group [88.24% (45/51) vs. 70.59% (36/51), χ2 = 4.85, P < 0.05]. There were no significant differences in endometrial type, biochemical pregnancy, clinical pregnancy rate, abortion rate, and premature delivery rate between the two groups (all P > 0.05). Conclusion:Letrozole combined with HMG has an ideal effect on refractory PCOS. It can improve the levels of sex hormones, restore the hemodynamic status in ovarian stroma and increase ovulation rate.
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Objective To investigate the effect of ovulation induction of letrozole and clomiphene on the treatment of polycystic ovary syndrome.Methods From February 2014 to February 2014 80 cases with polycystic ovary syndrome in Hangzhou maternity hospitalas the research object were divided into two groups: the control group and the observation group.The control group were treated with clomiphene;the observation group were treated with letrozole.The clinical effect in the two groups were compared.Results The total effective rate was 95.0% in the observation group, which was higher than 67.5% in the control group, the difference was statistically significant(P<0.05).The thickness of endometrium in the observation group was(9.10±1.32)mm and(5.38±0.61)mm in the control group at the HCG injection day, the difference between the two groups was statistically significant (P<0.05).Conclusion Letrozole can be used in the treatment of polycystic ovary syndrome, can get high quality treatment effect, worthy of promotion.
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Objective To observe the clinical effect of Guizhi Fuling pill in the treatment of interstitial tubal pregnancy.Methods80 cases with interstitial tubal pregnancy in Hangzhou obstetrics and gynecology hospital from August 2015 to December.2016 were randomly divided into the observation group and the control group, 40 cases in each group.The control group were given methotrexate and mifepristone, at this basis, the observation group were given Guizhi Fuling pill.The effect was analyzed in the two groups.Results①β-HCG negative time in the observation group were significantly shorter than that in the control group(P<0.05).②Adverse reactions rate in the observation group was significantly lower than that in the control group(P<0.05).ConclusionIt can shorten the treatment time, reduce the adverse reaction which Guizhi Fuling pill was used in the adjuvant treatment of interstitial tubal pregnancy.
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Objective To investigate the clinical efficacy and safety of six-hole moxibustion box therapy for stable chronic obstructive pulmonary diseases(COPD).Methods Sixty patients with thoracic facet joint disorder were randomly allocated to treatment and control groups, 30 cases each. The control group inhaled tiotropium bromide inhalation powder spray and the treatment group received six-hole moxibustion box therapy in addition. The COPD Assessment Test (CAT) score and the dyspnea score were recorded and peripheral blood oxygen saturation was measured in the two groups before and after treatment. The adverse reactions were monitored in the two groups. Results There were statistically significant pre-/post-treatment differences in the CAT score and the dyspnea score in the two groups (P<0.05). There were statistically significant post-treatment differences in the CAT score and the dyspnea score between the treatment and control groups (P<0.05). There were statistically significant differences in pre-/post- treatment CAT score difference value and dyspnea score difference value between the two groups (P<0.05). There was a statistically significant pre-/post-treatment difference in peripheral blood oxygen saturation in the treatment group (P<0.05). There was a statistically significant post-treatment difference in peripheral blood oxygen saturation between the two groups (P<0.05).Conclusion Six-hole moxibustion box therapy plus tiotropium bromide inhalation powder spray is safe and effective in treating stable COPD.