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.