Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To evaluate the safety and efficacy of transplanting beard to scalp using follicular unit extraction(FUE).Methods:Data obtained from hirsute patients with extensive alopecia who underwent hair transplantation between March 2017 and April 2014 at Nanfang Hospital were analyzed. Individual beard hair follicular units (FUs) were harvested under tumescence along the direction of beard growth, using a hollow acute punch with an inner diameter of 0.6-0.7 mm driven with a motor machine. The angle between the punch and the skin is adjusted according to the angle of the beard. The depth of the punch is usually between 2-4 mm and just breaks through the dermis of the skin. The rotation speed of punch is 2 500-3 000 r/min. The harvested FUs were implanted to the bald area. The total amount of FUs harvested and the rate of FUs transection were recorded for each patient. Follow-up examinations were scheduled at 3 days, 10 days, 1 month, 3 months and 9 months postoperatively to check for complications, wound healing and hair growth using portrait photograph and trichoscopy.Results:A total of 58 patients male patients with advanced androgenetic alopecia (AGA) (Norwood-Hamilton Ⅴ-Ⅵ) were included in this study. The average harvested FUs was 2 012±631 and the transection rate for beard FUs was(3.4±0.7)%. The incidence of donor folliculitis was 10.3%(6/58). Folliculitis was cured within 1-3 weeks after treatment. Although all the donor areas were healed normally, 62.1% (36/58) of the patients had remaining mild white spots under the trichoscopy. There was no visible hypopigmented scars observed in the bare areas post-operation. The satisfaction scores of both doctors and patients and the third party were 4.78, 4.40 and 4.76, respectively.Conclusions:Transplanting beard FUs to bald scalp using FUE is a safe and effective for severe androgenetic alopecia with abundant beard.

Objective:To evaluate the safety and efficacy of transplanting beard to scalp using follicular unit extraction(FUE).Methods:Data obtained from hirsute patients with extensive alopecia who underwent hair transplantation between March 2017 and April 2014 at Nanfang Hospital were analyzed. Individual beard hair follicular units (FUs) were harvested under tumescence along the direction of beard growth, using a hollow acute punch with an inner diameter of 0.6-0.7 mm driven with a motor machine. The angle between the punch and the skin is adjusted according to the angle of the beard. The depth of the punch is usually between 2-4 mm and just breaks through the dermis of the skin. The rotation speed of punch is 2 500-3 000 r/min. The harvested FUs were implanted to the bald area. The total amount of FUs harvested and the rate of FUs transection were recorded for each patient. Follow-up examinations were scheduled at 3 days, 10 days, 1 month, 3 months and 9 months postoperatively to check for complications, wound healing and hair growth using portrait photograph and trichoscopy.Results:A total of 58 patients male patients with advanced androgenetic alopecia (AGA) (Norwood-Hamilton Ⅴ-Ⅵ) were included in this study. The average harvested FUs was 2 012±631 and the transection rate for beard FUs was(3.4±0.7)%. The incidence of donor folliculitis was 10.3%(6/58). Folliculitis was cured within 1-3 weeks after treatment. Although all the donor areas were healed normally, 62.1% (36/58) of the patients had remaining mild white spots under the trichoscopy. There was no visible hypopigmented scars observed in the bare areas post-operation. The satisfaction scores of both doctors and patients and the third party were 4.78, 4.40 and 4.76, respectively.Conclusions:Transplanting beard FUs to bald scalp using FUE is a safe and effective for severe androgenetic alopecia with abundant beard.

Objective: To investigate the safety of rivaroxaban by detecting prothrombin time (PT). Methods: 105 patients with thrombosis from May 2018 to February 2019 in Tianjin Medical University General Hospital were selected and followed up. 23 patients with hemorrhage were in the bleeding group and 82 others were in the non-bleeding group. PT was detected by IL ACL TOP 700 blood coagulation instrument and its supporting reagents. Data were expressed as M(P 25 ，P 75 ). Mann-Whitney U test was used for data comparison between the bleeding and non-bleeding groups. Kruskal-Wallis H test was used for age data comparison among multiple groups. The diagnostic performance of PT was evaluated by a receiver operating characteristic curve (ROC). Results:: In the bleeding group, PT changed significantly between before and after treatment of rivaroxaban. On the 1st and 3rd days after treatment, PT peak was significantly higher than the day′s trough level, and on the 3rd day, both the peak value and the trough value were all significantly higher than the levels on the 1st day. There was no significant difference in peak PT between the patients in the non-bleeding group and the bleeding group on the 1st day (P＞0.05), while the trough PT level in the bleeding group was significantly higher than that in the non-bleeding group (P＜0.001). On the 3rd day, the levels of peak and trough PT in the bleeding group were significantly higher than those in non-bleeding (P＜0.001). The diagnostic performance of the trough PT predicting bleeding risk on the day 1 and 3 after treatment was superior to the peak PT level, while the effects of the trough PT predicted on the 1st was similar to the 3rd days. In terms of assessing the risk of bleeding, the trough PT level should be superior to the peak PT, and the 3rd day should be better than the 1st day. Conclusion PT could effectively evaluate the bleeding risk of rivaroxaban after sufficient performance verification, and provide a reliable basis for clinical rational use for drug.

Objective To observe the cerebral protective effect of mild hypothermia by semiconductor cooling device on the liver surface in rabbits after cardiac arrest (CA). Methods Eighteen healthy male New Zealand white rabbits were randomly and equally divided into CA control group, ice saline group and semiconductor group. CA was induced by rapid intravenous injection of potassium chloride. Five minutes after onset of CA, CPR was initiated. Compared to the control group, which was not treated by hypothermia intervention after CPR, the ice saline group was treated by 4 ℃ ice saline infusion and the semiconductor group was treated by the semiconductor refrigeration piece device cooling on the liver surface for hypothermia intervention after CPR. We recorded the changes of temperature (tympanic temperature and anus temperature), heart rate (HR), mean arterial pressure (MAP) of rabbits in each group, neurological deficit scores (NDS) at 24, 48, 72 hours after the return of spontaneous circulation (ROSC) and the changes of serum neuron specific enolase (NSE) by enzyme linked immunosorbent assay (ELISA). Pathological changes of the hippocampus tissue, liver tissue and skin tissue were obtained by HE staining. Results There was no significant difference in ROSC time in each group. Two rabbits died at 55 hours and 67 hours after ROSC respectively in the control group. The remaining rabbits survived to 72 hours after challenge. There was no significant difference in the overall survival time in groups. Two hypothermia intervention groups had significantly lower level of serum NSE at 24 hours after ROSC and lower DNS scores at 24, 48, 72 hours after ROSC than control group. And the level of serum NSE after 24 hours of ROSC in the semiconductor group were significantly lower than the ice saline group (μg/L: 6.916±1.161 vs. 8.615±1.430, P < 0.05). DNS scores at 24, 48, 72 hours after ROSC in the semiconductor group were all significantly lower than the ice saline group (scores: 1.33±0.52 vs. 2.00±0.01, 1.01±0.41 vs. 2.00±0.01, 0.92±0.40 vs. 2.10±0.52 respectively, all P < 0.05). Two hypothermia intervention groups had more minor damage of neuronal cell in hippocampus than the control group. And the semiconductor group had more minor damage than the ice saline group. There were no obvious hepatic and subcutaneous tissue injury through which the semiconductor induced hypothermia was performed at corresponding liver surface skin. Conclusion The hypothermia by semiconductor cooling device on the liver surface is a new safe way of protecting brain tissue after CA, which has better cerebral protective effect than ice saline infusion.