Objective:To investigate the efficacy of zicronapine on different animal models of schizophrenia and its affinity for dopamine D1 and D2 receptors in vitro.Methods:A total of 324 male SPF ICR mice, 72 male SPF Wistar rats, and 10 male and female each SPF SD rats were included in the study. (1) One hundred ICR mice were divided into 10 groups: Blank group (solvent+normal saline, Veh+NS), model group (Veh+APO 1 mg/kg), risperidone (0.03, 0.10, 0.30, 1.00 mg/kg, gavage)+APO group, and zicronapine (0.3, 1.0, 3.0, 10.0 mg/kg, gavage)+APO group; The effect of zicronapine on the climbing behavior of mice was observed. (2) Eighty-four ICR mice were divided into 10 groups: Blank group (Veh+NS), model group (Veh+MK-801 0.3 mg/kg), risperidone (0.01, 0.03, 0.10, 0.30 mg/kg, gavage)+MK-801 group, and zicronapine (0.3, 1.0, 3.0, 10.0 mg/kg, gavage)+MK-801 group; 8-10 rats were allocated in each group to observe the effect of zicronapine on MK-801-induced hyperactivity behavior in mice. (3) Seventy mice were divided into 7 groups: Blank group (Veh), risperidone 0.3, 1.0 and 3.0 mg/kg groups (gavage), and zicronapine15, 27 and 45 mg/kg groups (gavage), with 10 mice in each group. The maintaining immobilized time of rats was observed at 30 min, 60 min and 90 min after administration. (4) A total of 72 Wistar rats were selected for CAR training, and the successfully trained rats were divided into 7 groups: blank group, zicronapine20, 40 and 60 mg/kg groups, risperidone 0.2, 0.4 and 0.8 mg/kg groups, with 5 to 6 rats in each group. The effects of zicronapine on avoidance response times of rats were investigated. (5)Seventy ICR mice were divided into blank group (Veh+NS), model group (Veh+PCP) and risperidone 0.05 mg/kg+PCP group. The effects of zicronapine (0.5, 1.0, 2.0 mg/kg)+PCP groups on novel object recognition disorder in mice were investigated. (6) The affinity of zicronapine to D 1, D 2, 5-HT 2A, 5-HT 6 and 5-HT 2C was investigated by radiolig and receptor binding assay. One-way analysis of variance was used for measurement data, and non-parametric U test was used for count data. Results:(1) Compared with the model group, 3.0 and 10.0 mg/kg of zicronapine significantly inhibited APO-induced climbing behavior in mice ( Z=-3.43, -4.07; P<0.01), and its ED 50 was 4.31 mg/kg. Risperidone at doses of 0.10, 0.30 and 1.00 mg/kg significantly inhibited the climbing behavior of mice ( Z=-1.83, -2.48, -4.26; P<0.05 or P<0.01) and the ED 50 was 0.19 mg/kg. (2) Compared to the model group, zicronapine 3.0 and 10.0 mg/kg significantly inhibited MK-801-induced hyperactivity behavior in mice ( t=-7.18, 3.90; P<0.01), and the ED 50 was 2.63 mg/kg. Risperidone 0.01, 0.03, 0.10 and 0.30 mg/kg significantly inhibited hyperactivity behavior in mice ( t=-3.02, 4.98, -6.08, 7.10; all P<0.01), and the ED 50 was 0.011 mg/kg. (3) The ED 50 of zicronapine and risperidone were 35.36 mg/kg and 1.25 mg/kg, respectively. (4) Both zicronapine and risperidone could inhibit the number of avoidance responses in a dose-dependent manner. Zicronapine dose at 40 and 60 mg/kg significantly inhibited the number of conditioned avoidance responses in rats ( t=11.84, 13.07; P<0.01), and the ED 50 was 34.36 mg/kg. Risperidone of 0.8 mg/kg could significantly inhibit the number of conditioned avoidance responses in rats ( t=13.50, P<0.01), and the ED 50 was 0.60 mg/kg. (5) Compared to the model group, zicronapine 0.5 and 1.0 mg/kg could significantly improve the discrimination index of PCP-induced new object recognition disorder model mice ( t=-3.67, -2.12; P<0.05 and P<0.01) to improve cognitive ability. However, risperidone 0.05 mg/kg had no significant effect on the discrimination index of PCP-induced new object recognition disorder model mice. (6) Zilonapine had high affinity for D 1 (K i=3.21 nmol/L) and 5-HT 2A (K i=13.11 nmol/L) receptors, but weak affinity for D 2 (K i=563.20 nmol/L) receptors. In addition, chilonapine also had high affinity for 5-HT 6 (K i=21.49 nmol/L) and 5-HT 2C (K i=48.90 nmol/L). Risperidone had high affinity for 5-HT 2A , 5-HT 2C and D 2 receptors with K i of 2.37, 18.79 and 4.82 nmol/L, respectively. Risperidone had weak affinity for D 1 and 5-HT6 receptors. Conclusions:Zicronapine has good efficacy in multiple animal models with positive symptoms of schizophrenia and can improve the cognition of mice. Its in vivo efficacy may be related to dopamine D 1 and D 2 receptors and 5-HT 2A and 5-HT 6 receptors.

Objective:To investigate the efficacy of zicronapine on different animal models of schizophrenia and its affinity for dopamine D1 and D2 receptors in vitro.Methods:A total of 324 male SPF ICR mice, 72 male SPF Wistar rats, and 10 male and female each SPF SD rats were included in the study. (1) One hundred ICR mice were divided into 10 groups: Blank group (solvent+normal saline, Veh+NS), model group (Veh+APO 1 mg/kg), risperidone (0.03, 0.10, 0.30, 1.00 mg/kg, gavage)+APO group, and zicronapine (0.3, 1.0, 3.0, 10.0 mg/kg, gavage)+APO group; The effect of zicronapine on the climbing behavior of mice was observed. (2) Eighty-four ICR mice were divided into 10 groups: Blank group (Veh+NS), model group (Veh+MK-801 0.3 mg/kg), risperidone (0.01, 0.03, 0.10, 0.30 mg/kg, gavage)+MK-801 group, and zicronapine (0.3, 1.0, 3.0, 10.0 mg/kg, gavage)+MK-801 group; 8-10 rats were allocated in each group to observe the effect of zicronapine on MK-801-induced hyperactivity behavior in mice. (3) Seventy mice were divided into 7 groups: Blank group (Veh), risperidone 0.3, 1.0 and 3.0 mg/kg groups (gavage), and zicronapine15, 27 and 45 mg/kg groups (gavage), with 10 mice in each group. The maintaining immobilized time of rats was observed at 30 min, 60 min and 90 min after administration. (4) A total of 72 Wistar rats were selected for CAR training, and the successfully trained rats were divided into 7 groups: blank group, zicronapine20, 40 and 60 mg/kg groups, risperidone 0.2, 0.4 and 0.8 mg/kg groups, with 5 to 6 rats in each group. The effects of zicronapine on avoidance response times of rats were investigated. (5)Seventy ICR mice were divided into blank group (Veh+NS), model group (Veh+PCP) and risperidone 0.05 mg/kg+PCP group. The effects of zicronapine (0.5, 1.0, 2.0 mg/kg)+PCP groups on novel object recognition disorder in mice were investigated. (6) The affinity of zicronapine to D 1, D 2, 5-HT 2A, 5-HT 6 and 5-HT 2C was investigated by radiolig and receptor binding assay. One-way analysis of variance was used for measurement data, and non-parametric U test was used for count data. Results:(1) Compared with the model group, 3.0 and 10.0 mg/kg of zicronapine significantly inhibited APO-induced climbing behavior in mice ( Z=-3.43, -4.07; P<0.01), and its ED 50 was 4.31 mg/kg. Risperidone at doses of 0.10, 0.30 and 1.00 mg/kg significantly inhibited the climbing behavior of mice ( Z=-1.83, -2.48, -4.26; P<0.05 or P<0.01) and the ED 50 was 0.19 mg/kg. (2) Compared to the model group, zicronapine 3.0 and 10.0 mg/kg significantly inhibited MK-801-induced hyperactivity behavior in mice ( t=-7.18, 3.90; P<0.01), and the ED 50 was 2.63 mg/kg. Risperidone 0.01, 0.03, 0.10 and 0.30 mg/kg significantly inhibited hyperactivity behavior in mice ( t=-3.02, 4.98, -6.08, 7.10; all P<0.01), and the ED 50 was 0.011 mg/kg. (3) The ED 50 of zicronapine and risperidone were 35.36 mg/kg and 1.25 mg/kg, respectively. (4) Both zicronapine and risperidone could inhibit the number of avoidance responses in a dose-dependent manner. Zicronapine dose at 40 and 60 mg/kg significantly inhibited the number of conditioned avoidance responses in rats ( t=11.84, 13.07; P<0.01), and the ED 50 was 34.36 mg/kg. Risperidone of 0.8 mg/kg could significantly inhibit the number of conditioned avoidance responses in rats ( t=13.50, P<0.01), and the ED 50 was 0.60 mg/kg. (5) Compared to the model group, zicronapine 0.5 and 1.0 mg/kg could significantly improve the discrimination index of PCP-induced new object recognition disorder model mice ( t=-3.67, -2.12; P<0.05 and P<0.01) to improve cognitive ability. However, risperidone 0.05 mg/kg had no significant effect on the discrimination index of PCP-induced new object recognition disorder model mice. (6) Zilonapine had high affinity for D 1 (K i=3.21 nmol/L) and 5-HT 2A (K i=13.11 nmol/L) receptors, but weak affinity for D 2 (K i=563.20 nmol/L) receptors. In addition, chilonapine also had high affinity for 5-HT 6 (K i=21.49 nmol/L) and 5-HT 2C (K i=48.90 nmol/L). Risperidone had high affinity for 5-HT 2A , 5-HT 2C and D 2 receptors with K i of 2.37, 18.79 and 4.82 nmol/L, respectively. Risperidone had weak affinity for D 1 and 5-HT6 receptors. Conclusions:Zicronapine has good efficacy in multiple animal models with positive symptoms of schizophrenia and can improve the cognition of mice. Its in vivo efficacy may be related to dopamine D 1 and D 2 receptors and 5-HT 2A and 5-HT 6 receptors.

Objective:Breast cancer has been the first cancer among women with the incidence increasing gradually. In September 2016, the Breast Cancer Cohort Study in Chinese Women (BCCS-CW) was initiated, aiming to establish a standardized and sharable breast cancer-specific cohort by integrating the existing cohort resource and improving the quality of follow-up. The BCCS-CW may provide a research basis and platform for the precision prevention and treatment of breast cancer in etiology identification, prevention, early diagnosis, treatment, and prognosis prediction.Methods:We conducted a population-based perspective cohort by questionnaire interview, anthropometry, biological specimens, breast ultrasound and mammography. The cohort was followed by using regional health surveillance and ad hoc survey.Results:Finally, BCCS-CW included 112 118 women, in which 55 419 women completed the standardized investigation and blood specimens were collected from 54 304 women. The mean age of participants was 51.7 years old, 62.7% were overweight or obese, and 48.9% were menopausal.Conclusion:The BCCS-CW will provide population-based cohort resource and research platform for the precise prevention and treatment of breast cancer in Chinese women.