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.

Dopamine,a neurotransmitter ubiquitous in the body fluids,blood,and urine of mammals and humans,is responsible for regulating their functions and metabolism.The dopamine system is involved in the neurobiological mechanisms of narcolepsy in animals and humans.However,researchers have drawn different or even opposite conclusions when measuring the dopamine level in the cerebrospinal fluid of narcolepsy pa-tients.Studies have confirmed that the occurrence of narcolepsy is related to the irreversible loss of orexins.The autoimmune reaction caused by the interactions of environmental factors with genetic factors destroys the hypotha-lamic orexin neurons and reduces orexin secretion,thereby lowering the level of arousal.We introduce the re-search progress and current status of dopamine and clinical characterization of narcolepsy by reviewing more than 40 articles published from 1982 to 2023,aiming to provide a reference for studying the relationship between the dopamine level and clinical characterization of narcolepsy and searching for the biomarkers of type 2 narcolepsy.

Separation/conversion disorders in functional coma with pseudocataplexy are rare.On De-cember 9,2021,a young female patient with separation/conversion disorders was treated in the Department of Neurology in the First Affiliated Hospital of Shandong First Medical University.The main symptoms were episodic consciousness disorders,sudden fainting,and urinary incontinence.Complete laboratory tests and cranial mag-netic resonance imaging showed no obvious abnormalities.Standard multi-channel sleep monitoring and multiple sleep latency tests were performed.The patient was unable to wake up during nap and underwent stimulation tests.There was no response to orbital pressure,loud calls,or tapping,while the α rhythm in all electroenceph-alogram leads and the increased muscular tone in the mandibular electromyography indicated a period of wakeful-ness.The results of 24-hour sleep monitoring suggested that the patient had sufficient sleep at night and thus was easy to wake up in the morning.The results of daytime unrestricted sleep and wake-up test showed that the patient took one nap in the morning and one nap in the afternoon.When the lead indicated the transition from N3 to N2 sleep,a wake-up test was performed on the patient.At this time,the patient reacted to the surrounding environ-ment and answered questions correctly.Because the level of orexin in the cerebrospinal fluid was over 110 pg/mL,episodic sleep disorder was excluded and the case was diagnosed as functional coma accompanied by pseudocata-plexy.The patient did not present obvious symptom remission after taking oral medication,and thus medication withdrawl was recommended.Meanwhile,the patient was introduced to adjust the daily routine and mood.The follow-up was conducted six months later,and the patient reported that she did not experience similar symptoms after adjusting lifestyle.Up to now,no similar symptoms have appeared in multiple follow-up visits for three years.Functional coma with pseudocataplexy is prone to misdiagnosis and needs to be distinguished from true co-ma and episodic sleep disorders.

The prediction of compound-protein interaction (CPI) is a critical technological tool for discovering lead compounds and drug repurposing during the process of drug development.In recent years, deep learning has been widely used in CPI research, which has accelerated the development of CPI prediction in drug discovery.This review focuses on feature-based CPI prediction models.First, we described the datasets, as well as typical feature representation methods commonly used for compounds and proteins in CPI prediction.Based on the critical problems in modeling, we discussed models for CPI prediction from two perspectives: multimodal features and attention mechanisms.Then, the performance of 12 selected models was evaluated on 3 benchmark datasets for both classification and regression tasks.Finally, the review summarizes the existing challenges in this field and prospects for future directions.We believe that this investigation will provide some reference and insight for further research on CPI prediction.

Objective:To summarize experience and effect of the stylized operation step in the neck endoscopic thyroidectomy for papillary thyroid microcarcinoma (PTMC).Methods:The clinical data of 51 patients who underwent transthoracic breast approach scarless neck endoscopic thyroidectomy (SET) from January 2018 to September 2019 in Tungwah Hospital Affiliated to Sun Yat-sen University were retrospectively analyzed. The operative procedure used stylized operation steps: establishment of operating space, three-step method thyroidectomy, central lymph node dissection (CLND), close operating space.Results:Among 51 patients, 25 cases underwent unilateral thyroidectomy plus isthmic resection, 26 cases underwent total/near-total thyroidectomy, and 16 cases underwent preventive CLND. The recurrent laryngeal nerve (RLN) was exposed in all 51 cases, the external branches of the superior laryngeal nerve (EBSLN) was exposed in 35 cases, no procedure was converted into open neck incision thyroidectomy. Forty-two cases were followed up, 2 cases had postoperative hoarseness and unilateral recurrent laryngeal nerve paralysis, which were recovered 55 and 75 d after operation respectively. There was no bucking, voice blunt or permanent low calcium. One patient had abnormal sensation of neck skin after operation, and recovered gradually 3 months after operation.Conclusions:The stylized operation step in the SET can increase safety of surgery.

OBJECTIVE: To investigate the level of formaldehyde in the air of anatomical laboratories and to explore the effect of different prevention measures on reducing the level of formaldehyde. METHODS: The level of formaldehyde in two morphological laboratories of a medical college of a university were measured with a comprehensive atmospheric sampler at different physical ventilation time,different time after spraying biological enzymes and different masks. RESULTS: The level of formaldehyde decreased with the increase of ventilation time in front,middle and back of the laboratory( P < 0. 05).The level of formaldehyde at 30 and 60 minutes after spraying bio-enzymes in three parts of the laboratory was lower than that at 0 minute in the same part of the laboratory( P < 0. 05),and lower than that in the bio-enzymes non-spraying laboratory at the same part and same time point( P < 0. 05). At 0,30 and 60 minutes ventilation time points,the level of formaldehyde in the activated carbon mask group was lower than that in the normal sampling group,the non-woven mask group and the defatted gauze mask group at the same time point( P < 0. 05). CONCLUSION: Both physical ventilation and bio-enzyme degradation can reduce indoor formaldehyde pollution. Active carbon mask can achieve good protection effect.

Objective To retrospectively review the clinical characteristics and antimicrobial resistance profile of nosocomial bloodstream infections caused by Klebsiella pneumoniae in surgical patients for better use of antimicrobial agents.Methods The clinical data of the surgical patients who were diagnosed with K.pneumoniae-associated bloodstream infections in Tung Wah Hospital from January 2013 to June 2015 were reviewed and analyzed retrospectively.The diagnosis of bloodstream infections was based on national diagnostic criteria.The pathogens were routinely isolated and identified.Antimicrobial susceptibility testing was carried out by using Kirby-Bauer method.The data were analyzed by WHONET 5.6 software.Results A total of 78 surgical patients were identified with nosocomial bloodstream infections due to K.pneumoniae during this period,including primary bloodstream infections (12.8％,10/78) and secondary bloodstream infections (87.2％,68/78).These infections were mainly associated with surgical and invasive procedures.Nearly 40％ of the K.pneumoniae isolates were resistant to ceftriaxone,cefuroxime and piperacillin.ESBLs were produced in 43.6％ (34/78) of the K.pneumoniae isolates.The ESBLs-producing strains showed significantly higher resistance rates to various antibiotics than non-ESBLs-producing strains.Piperacillin-tazobactam,amikacin,imipenem,and meropenem still have good antibacterial activity against these K.pneumoniae isolates.However,imipenem-resistant strains are emerging.Conclusions Most of the bloodstream infections caused by K.pneumoniae were secondary to infections in other body sites in surgical patients.Hospital infection control measures should be strengthened.Meanwhile,the clinicians should take full advantages of microbiological laboratory to profile the pathogens and their susceptibility patterns,which is crucial for rational use of antibiotics.

ObjectiveTo discuss the more aesthetic and minimally invasive surgical approach of endoscopic thyroidectomy.Methods50 cases of endoscopic thyroidectomy via breast areola-axillary approach were retrospectively analyzed.Among these cases,12 received unilateral partial lobectomy,30 received unilateral total lobectomy and 8 received bilateral partial lobectomy.Results Endoscopic thyroidectomy was completed in all the patients.The intraoperative blood loss was ( 12.77 ± 20.12 ) ml.The operation time was (67.00 ± 21.28 )min.The postoperative hospital stay was (3.77 ± 0.50)days.Hoarseness occurred in 2 cases.All the 50 cases were followed up from 1 to 6 months and no other complication occurred.ConclusionEndoscopic thyroidectomy via breast areola-axillary approach is more aesthetic and minimally invasive; however,the operator needs an adaptive process for a better surgical view angle.