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.

BACKGROUND:At present,the surgical treatment of atlantoaxial dislocation mainly adopts the posterior atlantoaxial screw-rod internal fixation system for lifting and reduction.During the operation,the curvature of the connecting rod is often increased to increase the drop between the atlantoaxial vertebrae to improve the reduction effect,but it increases the difficulty and risk of surgery.The axis pivot screw directly increases the reduction drop between the atlantoaxial vertebrae,but the extent to which it increases the reduction capacity is unclear.OBJECTIVE:To test the reduction ability of axis pivot screw and compare it with ordinary screw.METHODS:Six fresh human craniocervical specimens were used in study.The joint capsules of two lateral mass joints and atlanto-odontoid joint and transverse ligament were removed to make an atlantoaxial instability model.Three kinds of internal fixation were performed successively on both sides of the axis of each specimen:uniaxial axis pivot screws(group A),multi-axial axis pivot screws(group B)and ordinary screws(group C).Flexible ultra-thin film pressure sensors were placed in the anterior atlanto-odontoid space.Two connecting rods with the same curvature were placed to simulate the lifting and reduction,and the pressure of the anterior atlanto-odontoid space was obtained.Comparative analysis was conducted among the three groups.RESULTS AND CONCLUSION:(1)The anterior atlanto-odontoid space pressure of groups A-C was(97.59±8.58),(60.43±5.09),and(22.74±0.81)N,respectively.There were significant differences among the three groups(F=251.603,P=0.000).The pairwise comparison among the three groups showed significant differences(P=0.000).(2)The axis pivot screw applied to the posterior atlantoaxial screw-rod internal fixation system can improve the reduction capacity compared with the common cervical posterior screw,and the uniaxial axis pivot screw has more reduction capacity than the multi-axis uniaxial axis pivot screw to improve the posterior atlantoaxial screw-rod internal fixation system.

Objective To analyze the clinical significance of subjective visual vertical (SVV) tests at different head deflection angles in assessing utricle function in patients with benign paroxysmal positional vertigo (BPPV). Methods A total of 61 BPPV patients who were treated at the Hearing Impairment and Vertigo Diagnosis and Treatment Center of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August 2022 to May 2023 were retrospectively included, and 29 healthy adults were selected as controls. SVV tests were performed on all research subjects at different head deflection angles: upright head (0°), left head 45° (L45°), right head 45° (R45°). The test results between the two groups were compared. Results SVV absolute value at R45° in BPPV group was lower than that in the control group (P＝0.003); there was no significant difference in SVV values at 0° and L45° between the two groups. There was no statistical difference in SVV values at different head deflection angles between the control group and the left BPPV group. SVV absolute value at R45° in right BPPV group was lower than that in the control group (P＜0.001); there was no statistical difference in SVV values at 0° and L45° between the two groups. Conclusions SVV test can provide subjective information about the utricle, and SVV tests at different head deflection angles can fine-tune evaluate the function of the utricle in BPPV patients.

Objective:To analyze the revision strategies for failed atlantoaxial dislocation (AAD) surgery.Methods:A retrospective analysis was conducted on 145 patients who underwent revision surgery for AAD at the General Hospital of Southern Theatre Command of PLA between September 2009 and December 2023. The cohort included 74 males and 71 females, with a mean age of 43±16 years (range, 6-72 years). The initial surgical approaches were: anterior 31 cases, posterior 114 cases. Based on imaging assessments of immediate postoperative reduction and fusion status prior to revision, the cases of failure were classified into reduction-nonfusion type (22 cases), nonreduction-fusion type (31 cases), and nonreduction-nonfusion type (92 cases). Among the nonreduction-nonfusion cases, 39 had initial surgery with internal fixation for reduction, while 53 had initial surgery with simple decompression (posterior arch resection, foramen magnum decompression) without reduction. In the nonreduction-fusion cases, 8 cases had spot fusion and 23 had extensive fusion. Japanese Orthopaedic Association (JOA) scores were compared before and after revision, and complication rates were observed.Results:All patients successfully underwent surgery. The revision approaches included: anterior (anterior fixation and fusion 52 cases, anterior implant removal combined anterior fixation and fusion 4 cases, transoral odontoidectomies 16 cases, anterior implant removal combined transoral odontoidectomy 2 cases), posterior (posterior fixation and fusion 2 cases, posterior implant removal combined posterior fixation and fusion 22 cases), and combined anterior-posterior (posterior implant removal combined anterior fixation and fusion 18 cases, anterior implant removal combined posterior fixation and fusion 25 cases, posterior implant removal combined transoral odontoidectomy 5 cases). Operative time was 254.20±107.63 min (range, 90-660 min), and blood loss was 218.83±172.17 ml (range, 20-800 ml). Except for 3 patients who died due to postoperative complications, all patients were followed up for a duration of 12±11 months (range, 3-60 months). Six patients who failed to achieve bony fusion after the initial revision surgery underwent a second revision due to poor reduction (1 case), infection (1 case), suboptimal implant position (3 cases), and graft nonunion (1 case). All three patients with bony fusion after the initial revision surgery underwent a second revision due to poor reduction. Following the second revision surgery, none of the 9 patients exhibited graft nonunion or spinal cord compression. The 136 successful initial revision cases had a final follow-up JOA score of 14.75±2.00, significantly higher than the preoperative score of 11.93±2.92 ( t=-18.869, P<0.001). Conclusions:Revision surgery for AAD should take into account the immediate postoperative reduction status and fusion status prior to revision. An appropriate revision strategy should be selected to achieve satisfactory reduction and bony fusion.

BACKGROUND:At present,the surgical treatment of atlantoaxial dislocation mainly adopts the posterior atlantoaxial screw-rod internal fixation system for lifting and reduction.During the operation,the curvature of the connecting rod is often increased to increase the drop between the atlantoaxial vertebrae to improve the reduction effect,but it increases the difficulty and risk of surgery.The axis pivot screw directly increases the reduction drop between the atlantoaxial vertebrae,but the extent to which it increases the reduction capacity is unclear.OBJECTIVE:To test the reduction ability of axis pivot screw and compare it with ordinary screw.METHODS:Six fresh human craniocervical specimens were used in study.The joint capsules of two lateral mass joints and atlanto-odontoid joint and transverse ligament were removed to make an atlantoaxial instability model.Three kinds of internal fixation were performed successively on both sides of the axis of each specimen:uniaxial axis pivot screws(group A),multi-axial axis pivot screws(group B)and ordinary screws(group C).Flexible ultra-thin film pressure sensors were placed in the anterior atlanto-odontoid space.Two connecting rods with the same curvature were placed to simulate the lifting and reduction,and the pressure of the anterior atlanto-odontoid space was obtained.Comparative analysis was conducted among the three groups.RESULTS AND CONCLUSION:(1)The anterior atlanto-odontoid space pressure of groups A-C was(97.59±8.58),(60.43±5.09),and(22.74±0.81)N,respectively.There were significant differences among the three groups(F=251.603,P=0.000).The pairwise comparison among the three groups showed significant differences(P=0.000).(2)The axis pivot screw applied to the posterior atlantoaxial screw-rod internal fixation system can improve the reduction capacity compared with the common cervical posterior screw,and the uniaxial axis pivot screw has more reduction capacity than the multi-axis uniaxial axis pivot screw to improve the posterior atlantoaxial screw-rod internal fixation system.

Objective:To analyze the revision strategies for failed atlantoaxial dislocation (AAD) surgery.Methods:A retrospective analysis was conducted on 145 patients who underwent revision surgery for AAD at the General Hospital of Southern Theatre Command of PLA between September 2009 and December 2023. The cohort included 74 males and 71 females, with a mean age of 43±16 years (range, 6-72 years). The initial surgical approaches were: anterior 31 cases, posterior 114 cases. Based on imaging assessments of immediate postoperative reduction and fusion status prior to revision, the cases of failure were classified into reduction-nonfusion type (22 cases), nonreduction-fusion type (31 cases), and nonreduction-nonfusion type (92 cases). Among the nonreduction-nonfusion cases, 39 had initial surgery with internal fixation for reduction, while 53 had initial surgery with simple decompression (posterior arch resection, foramen magnum decompression) without reduction. In the nonreduction-fusion cases, 8 cases had spot fusion and 23 had extensive fusion. Japanese Orthopaedic Association (JOA) scores were compared before and after revision, and complication rates were observed.Results:All patients successfully underwent surgery. The revision approaches included: anterior (anterior fixation and fusion 52 cases, anterior implant removal combined anterior fixation and fusion 4 cases, transoral odontoidectomies 16 cases, anterior implant removal combined transoral odontoidectomy 2 cases), posterior (posterior fixation and fusion 2 cases, posterior implant removal combined posterior fixation and fusion 22 cases), and combined anterior-posterior (posterior implant removal combined anterior fixation and fusion 18 cases, anterior implant removal combined posterior fixation and fusion 25 cases, posterior implant removal combined transoral odontoidectomy 5 cases). Operative time was 254.20±107.63 min (range, 90-660 min), and blood loss was 218.83±172.17 ml (range, 20-800 ml). Except for 3 patients who died due to postoperative complications, all patients were followed up for a duration of 12±11 months (range, 3-60 months). Six patients who failed to achieve bony fusion after the initial revision surgery underwent a second revision due to poor reduction (1 case), infection (1 case), suboptimal implant position (3 cases), and graft nonunion (1 case). All three patients with bony fusion after the initial revision surgery underwent a second revision due to poor reduction. Following the second revision surgery, none of the 9 patients exhibited graft nonunion or spinal cord compression. The 136 successful initial revision cases had a final follow-up JOA score of 14.75±2.00, significantly higher than the preoperative score of 11.93±2.92 ( t=-18.869, P<0.001). Conclusions:Revision surgery for AAD should take into account the immediate postoperative reduction status and fusion status prior to revision. An appropriate revision strategy should be selected to achieve satisfactory reduction and bony fusion.

Objective: To compare the clinical outcomes of transoral anterior Jefferson-fracture reduction plate (JeRP) and posterior screw rod (PSR) surgery for unstable atlas fractures via C1-ring osteosynthesis. Methods: From June 2009 to June 2022, 49 consecutive patients with unstable atlas fractures were treated by transoral anterior JeRP fixation (JeRP group) or PSR fixation (PSR group) and followed up at General Hospital of Southern Theatre Command of PLA; 30 males and 19 females were included. The visual analogue scale (VAS) score, Neck Disability Index (NDI), distance to anterior arch fracture (DAAF), distance to posterior arch fracture (DPAF), lateral mass displacement (LMD), Redlund-Johnell value, postoperative complications, and fracture healing rate were retrospectively collected and statistically analyzed. Results: Compared with that in the PSR group, the bleeding volume in the JeRP group was lower, and the length of hospital stay was longer. The VAS scores and NDIs of both groups were significantly improved after surgery. The postoperative DAAF and DPAF were significantly smaller after surgery in both groups. Compared with the significantly shorter DPAF in the PSR group, the JeRP group had a smaller DAAF, shorter LMDs and larger Redlund-Johnell value postoperatively and at the final follow-up. The fracture healing rate at 3 months after surgery was significantly greater in the JeRP group (p < 0.05). Conclusion Both C1-ring osteosynthesis procedures for treating unstable atlas fractures yield satisfactory clinical outcomes. Transoral anterior JeRP fixation is more effective than PSR fixation for holistic fracture reduction and short-term fracture healing, but the hospital stay is longer.

Objective: To compare the clinical outcomes of transoral anterior Jefferson-fracture reduction plate (JeRP) and posterior screw rod (PSR) surgery for unstable atlas fractures via C1-ring osteosynthesis. Methods: From June 2009 to June 2022, 49 consecutive patients with unstable atlas fractures were treated by transoral anterior JeRP fixation (JeRP group) or PSR fixation (PSR group) and followed up at General Hospital of Southern Theatre Command of PLA; 30 males and 19 females were included. The visual analogue scale (VAS) score, Neck Disability Index (NDI), distance to anterior arch fracture (DAAF), distance to posterior arch fracture (DPAF), lateral mass displacement (LMD), Redlund-Johnell value, postoperative complications, and fracture healing rate were retrospectively collected and statistically analyzed. Results: Compared with that in the PSR group, the bleeding volume in the JeRP group was lower, and the length of hospital stay was longer. The VAS scores and NDIs of both groups were significantly improved after surgery. The postoperative DAAF and DPAF were significantly smaller after surgery in both groups. Compared with the significantly shorter DPAF in the PSR group, the JeRP group had a smaller DAAF, shorter LMDs and larger Redlund-Johnell value postoperatively and at the final follow-up. The fracture healing rate at 3 months after surgery was significantly greater in the JeRP group (p < 0.05). Conclusion Both C1-ring osteosynthesis procedures for treating unstable atlas fractures yield satisfactory clinical outcomes. Transoral anterior JeRP fixation is more effective than PSR fixation for holistic fracture reduction and short-term fracture healing, but the hospital stay is longer.

Objective: To compare the clinical outcomes of transoral anterior Jefferson-fracture reduction plate (JeRP) and posterior screw rod (PSR) surgery for unstable atlas fractures via C1-ring osteosynthesis. Methods: From June 2009 to June 2022, 49 consecutive patients with unstable atlas fractures were treated by transoral anterior JeRP fixation (JeRP group) or PSR fixation (PSR group) and followed up at General Hospital of Southern Theatre Command of PLA; 30 males and 19 females were included. The visual analogue scale (VAS) score, Neck Disability Index (NDI), distance to anterior arch fracture (DAAF), distance to posterior arch fracture (DPAF), lateral mass displacement (LMD), Redlund-Johnell value, postoperative complications, and fracture healing rate were retrospectively collected and statistically analyzed. Results: Compared with that in the PSR group, the bleeding volume in the JeRP group was lower, and the length of hospital stay was longer. The VAS scores and NDIs of both groups were significantly improved after surgery. The postoperative DAAF and DPAF were significantly smaller after surgery in both groups. Compared with the significantly shorter DPAF in the PSR group, the JeRP group had a smaller DAAF, shorter LMDs and larger Redlund-Johnell value postoperatively and at the final follow-up. The fracture healing rate at 3 months after surgery was significantly greater in the JeRP group (p < 0.05). Conclusion Both C1-ring osteosynthesis procedures for treating unstable atlas fractures yield satisfactory clinical outcomes. Transoral anterior JeRP fixation is more effective than PSR fixation for holistic fracture reduction and short-term fracture healing, but the hospital stay is longer.

Objective: To compare the clinical outcomes of transoral anterior Jefferson-fracture reduction plate (JeRP) and posterior screw rod (PSR) surgery for unstable atlas fractures via C1-ring osteosynthesis. Methods: From June 2009 to June 2022, 49 consecutive patients with unstable atlas fractures were treated by transoral anterior JeRP fixation (JeRP group) or PSR fixation (PSR group) and followed up at General Hospital of Southern Theatre Command of PLA; 30 males and 19 females were included. The visual analogue scale (VAS) score, Neck Disability Index (NDI), distance to anterior arch fracture (DAAF), distance to posterior arch fracture (DPAF), lateral mass displacement (LMD), Redlund-Johnell value, postoperative complications, and fracture healing rate were retrospectively collected and statistically analyzed. Results: Compared with that in the PSR group, the bleeding volume in the JeRP group was lower, and the length of hospital stay was longer. The VAS scores and NDIs of both groups were significantly improved after surgery. The postoperative DAAF and DPAF were significantly smaller after surgery in both groups. Compared with the significantly shorter DPAF in the PSR group, the JeRP group had a smaller DAAF, shorter LMDs and larger Redlund-Johnell value postoperatively and at the final follow-up. The fracture healing rate at 3 months after surgery was significantly greater in the JeRP group (p < 0.05). Conclusion Both C1-ring osteosynthesis procedures for treating unstable atlas fractures yield satisfactory clinical outcomes. Transoral anterior JeRP fixation is more effective than PSR fixation for holistic fracture reduction and short-term fracture healing, but the hospital stay is longer.