1.Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.
Wanyu TANG ; Zhixue MA ; Bang LI ; Zhexiang YU ; Xiaobao ZHAO ; Huicui YANG ; Jian HU ; Sheng TIAN ; Linghan GU ; Jiaojiao CHEN ; Xing ZOU ; Qi WANG ; Fan CHEN ; Guangying LI ; Chaonan ZHENG ; Shuliu GAO ; Wenjing LIU ; Yue LI ; Wenhua ZHENG ; Mingmei WANG ; Na YE ; Xuechu ZHEN
Acta Pharmaceutica Sinica B 2025;15(10):5346-5365
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.
2.Triangular Wave tACS Improves Working Memory Performance by Enhancing Brain Activity in the Early Stage of Encoding.
Jianxu ZHANG ; Jian OUYANG ; Tiantian LIU ; Xinyue WANG ; Binbin GAO ; Jinyan ZHANG ; Manli LUO ; Anshun KANG ; Zilong YAN ; Li WANG ; Guangying PEI ; Shintaro FUNAHASHI ; Jinglong WU ; Jian ZHANG ; Tianyi YAN
Neuroscience Bulletin 2025;41(7):1213-1228
Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans
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Memory, Short-Term/physiology*
;
Male
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Female
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Young Adult
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Transcranial Direct Current Stimulation/methods*
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Brain/physiology*
;
Adult
;
Electroencephalography
;
Single-Blind Method
3.Study on the Existing State and Optimization Approach for Executing Orthopedic Case Simulation in a Pediatric Specialty Hospital Using CHS-DRG
Xiaoyan GUO ; Guangying GAO ; Ning XU ; Nianying ZHANG ; Na ZHANG ; Chudi YOU ; Jiashuai TIAN
Chinese Health Economics 2024;43(11):21-26
Objective:To guide cost control and the development of orthopedic specialty services in actual payment by thoroughly analyzing the functioning of DRG simulation in the pediatric orthopedic department of the Capital Institute of Pediatrics.Methods:A total of 736 patients from the orthopedic ward of the Capital Institute of Pediatrics were included as study subjects.The four-quadrant grouping method was employed to examine the profitability status of each diagnosis group in detail.A logistic regression model explored the key factors influencing profitability.Results:Congenital illnesses and traumas account for most pediatric orthopedic cases.Benefit groups(2 groups,4.8%),disadvantageous groups(15 groups,35.7%),key groups(8 groups,19.0%),and potential groups(17 groups,40.5%)are found using the Boston Matrix analysis.The profit group depends on the benefit groups(IF19,IH15)for 67.7%of its total revenue.No matter how profitable they are,medical consumables comprise a sizable portion(43%-45%).According to regression analysis,hospital profitability is highly impacted by age,consumable ratio,examination cost ratio,surgery cost ratio,and other cost ratios(P<0.05).The consumable ratio is the most significant negative predictor(β=-2.238).Conclusion:Hospitals need to optimize their cost structure and increase the probability of profitability through refined management of consumables,the four-quadrant analysis method,strengthened cost accounting,and differentiated resource allocation.
4.Study on the Existing State and Optimization Approach for Executing Orthopedic Case Simulation in a Pediatric Specialty Hospital Using CHS-DRG
Xiaoyan GUO ; Guangying GAO ; Ning XU ; Nianying ZHANG ; Na ZHANG ; Chudi YOU ; Jiashuai TIAN
Chinese Health Economics 2024;43(11):21-26
Objective:To guide cost control and the development of orthopedic specialty services in actual payment by thoroughly analyzing the functioning of DRG simulation in the pediatric orthopedic department of the Capital Institute of Pediatrics.Methods:A total of 736 patients from the orthopedic ward of the Capital Institute of Pediatrics were included as study subjects.The four-quadrant grouping method was employed to examine the profitability status of each diagnosis group in detail.A logistic regression model explored the key factors influencing profitability.Results:Congenital illnesses and traumas account for most pediatric orthopedic cases.Benefit groups(2 groups,4.8%),disadvantageous groups(15 groups,35.7%),key groups(8 groups,19.0%),and potential groups(17 groups,40.5%)are found using the Boston Matrix analysis.The profit group depends on the benefit groups(IF19,IH15)for 67.7%of its total revenue.No matter how profitable they are,medical consumables comprise a sizable portion(43%-45%).According to regression analysis,hospital profitability is highly impacted by age,consumable ratio,examination cost ratio,surgery cost ratio,and other cost ratios(P<0.05).The consumable ratio is the most significant negative predictor(β=-2.238).Conclusion:Hospitals need to optimize their cost structure and increase the probability of profitability through refined management of consumables,the four-quadrant analysis method,strengthened cost accounting,and differentiated resource allocation.
5.Interrupted Time Series Study on the Service Efficiency and Cost Structure of Appendectomy in Children
Chunxia NA ; Dongzi WANG ; Zhihui LIU ; Guangying GAO
Chinese Health Economics 2024;43(2):37-40
Objective:To analyze the changes in service efficiency and cost structure before and after implementing multidisci-plinary treatment in the GD19(appendectomy with perforation,suppuration,gangrene,etc.)and GD29(appendectomy)groups of pedi-atric specialty medical institutions.Methods:The case data of GD19 and GD29 groups of medical insurance patients in sample hospi-tals in Beijing from 2021 to 2022 were collected.Mann Whitney U test was used to analyze the changes of medical expenses and effi-ciency indicators,and intermittent time series model was established to analyze the change trend.Results:Compared to 2021,the av-erage hospitalization expenses of GD19 group in 2022 decreased by 2 462.00 yuan year-on-year,and that of GD29 group decreased by 2 042.60 yuan year-on-year(P<0.05).Among them,the cost of medicines,consumables,examinations and tests and treatment have all decreased.In the month when the management measures were implemented,the average consumption cost of GD19 group de-creased by 920.00 yuan(P<0.05),and the average consumption cost of GD29 group decreased by 632.50 yuan.The average length of stay in GD29 group decreased from 3.74 days to 2.78 days(P<0.05).Conclusion:After the implementation of management mea-sures,the cost of drug consumables in GD19 group and GD29 group was controlled,the cost level was reduced,and the operation effi-ciency was improved.It is suggested to adhere to the management measures of selection of key DRG groups and multidisciplinary con-sultation,mobilize the management enthusiasm of clinical departments,and strengthen the demonstration and optimization of pediatric DRG grouping and payment scheme.
6.Research on the Operation Efficiency of Basic Medical Insurance for Urban Workers and Its Influencing Factors in China from 2020 to 2021
Liliang ZHANG ; Jiashuai TIAN ; Jingyi ZHANG ; Shanshan DAI ; Xinyu CAI ; Guangying GAO
Chinese Health Economics 2024;43(3):10-15
Objective:Efficiency is a key factor in the sustainable operation of the medical insurance system.By measuring the current efficiency of the urban employee basic medical insurance system in 31 provinces in China from 2020 to 2021,it discovers possible problems,and provides reference suggestions for improving the efficiency of the system.Methods:Using the super efficiency SBM model based on unexpected output and the Malmquist index to measure the static and dynamic efficiency of employee medical in-surance in 31 provinces in China,and using Tobit regression analysis to analyze its influencing factors.Results:The overall compre-hensive efficiency of the national employee medical insurance operation is 0.826 in 2020 and 0.827 in 2021 respectively.The efficien-cy of employee medical insurance operation in the eastern region is significantly higher than that in the central and westem regions.Over 60%of provinces have inefficient operation of employee medical insurance.The overall total factor productivity of employee medical insurance operation is showing a downward trend,and the decline in technological progress is the main limiting factor.The level of economic development has a significant promotion effect on the efficiency of employee medical insurance operation,and the degree of population aging has a significant inhibitory effect on it.Conclusion:The efficiency of employee medical insurance opera-tion in China still needs to be improved,and there is a significant efficiency gap among different regions.Therefore,investment and attention should be increased in the central and western regions to bridge regional gaps and promote the equity development of medi-cal insurance.Therefore,the reform efforts should be continuously intensified to achieve technological progress.In addition,attention should also be paid to the driving role of economic development in the efficiency of employee medical insurance operation and the for-mulation of positive policies on population aging.
7.Study on the Existing State and Optimization Approach for Executing Orthopedic Case Simulation in a Pediatric Specialty Hospital Using CHS-DRG
Xiaoyan GUO ; Guangying GAO ; Ning XU ; Nianying ZHANG ; Na ZHANG ; Chudi YOU ; Jiashuai TIAN
Chinese Health Economics 2024;43(11):21-26
Objective:To guide cost control and the development of orthopedic specialty services in actual payment by thoroughly analyzing the functioning of DRG simulation in the pediatric orthopedic department of the Capital Institute of Pediatrics.Methods:A total of 736 patients from the orthopedic ward of the Capital Institute of Pediatrics were included as study subjects.The four-quadrant grouping method was employed to examine the profitability status of each diagnosis group in detail.A logistic regression model explored the key factors influencing profitability.Results:Congenital illnesses and traumas account for most pediatric orthopedic cases.Benefit groups(2 groups,4.8%),disadvantageous groups(15 groups,35.7%),key groups(8 groups,19.0%),and potential groups(17 groups,40.5%)are found using the Boston Matrix analysis.The profit group depends on the benefit groups(IF19,IH15)for 67.7%of its total revenue.No matter how profitable they are,medical consumables comprise a sizable portion(43%-45%).According to regression analysis,hospital profitability is highly impacted by age,consumable ratio,examination cost ratio,surgery cost ratio,and other cost ratios(P<0.05).The consumable ratio is the most significant negative predictor(β=-2.238).Conclusion:Hospitals need to optimize their cost structure and increase the probability of profitability through refined management of consumables,the four-quadrant analysis method,strengthened cost accounting,and differentiated resource allocation.
8.Study on the Existing State and Optimization Approach for Executing Orthopedic Case Simulation in a Pediatric Specialty Hospital Using CHS-DRG
Xiaoyan GUO ; Guangying GAO ; Ning XU ; Nianying ZHANG ; Na ZHANG ; Chudi YOU ; Jiashuai TIAN
Chinese Health Economics 2024;43(11):21-26
Objective:To guide cost control and the development of orthopedic specialty services in actual payment by thoroughly analyzing the functioning of DRG simulation in the pediatric orthopedic department of the Capital Institute of Pediatrics.Methods:A total of 736 patients from the orthopedic ward of the Capital Institute of Pediatrics were included as study subjects.The four-quadrant grouping method was employed to examine the profitability status of each diagnosis group in detail.A logistic regression model explored the key factors influencing profitability.Results:Congenital illnesses and traumas account for most pediatric orthopedic cases.Benefit groups(2 groups,4.8%),disadvantageous groups(15 groups,35.7%),key groups(8 groups,19.0%),and potential groups(17 groups,40.5%)are found using the Boston Matrix analysis.The profit group depends on the benefit groups(IF19,IH15)for 67.7%of its total revenue.No matter how profitable they are,medical consumables comprise a sizable portion(43%-45%).According to regression analysis,hospital profitability is highly impacted by age,consumable ratio,examination cost ratio,surgery cost ratio,and other cost ratios(P<0.05).The consumable ratio is the most significant negative predictor(β=-2.238).Conclusion:Hospitals need to optimize their cost structure and increase the probability of profitability through refined management of consumables,the four-quadrant analysis method,strengthened cost accounting,and differentiated resource allocation.
9.Study on the Existing State and Optimization Approach for Executing Orthopedic Case Simulation in a Pediatric Specialty Hospital Using CHS-DRG
Xiaoyan GUO ; Guangying GAO ; Ning XU ; Nianying ZHANG ; Na ZHANG ; Chudi YOU ; Jiashuai TIAN
Chinese Health Economics 2024;43(11):21-26
Objective:To guide cost control and the development of orthopedic specialty services in actual payment by thoroughly analyzing the functioning of DRG simulation in the pediatric orthopedic department of the Capital Institute of Pediatrics.Methods:A total of 736 patients from the orthopedic ward of the Capital Institute of Pediatrics were included as study subjects.The four-quadrant grouping method was employed to examine the profitability status of each diagnosis group in detail.A logistic regression model explored the key factors influencing profitability.Results:Congenital illnesses and traumas account for most pediatric orthopedic cases.Benefit groups(2 groups,4.8%),disadvantageous groups(15 groups,35.7%),key groups(8 groups,19.0%),and potential groups(17 groups,40.5%)are found using the Boston Matrix analysis.The profit group depends on the benefit groups(IF19,IH15)for 67.7%of its total revenue.No matter how profitable they are,medical consumables comprise a sizable portion(43%-45%).According to regression analysis,hospital profitability is highly impacted by age,consumable ratio,examination cost ratio,surgery cost ratio,and other cost ratios(P<0.05).The consumable ratio is the most significant negative predictor(β=-2.238).Conclusion:Hospitals need to optimize their cost structure and increase the probability of profitability through refined management of consumables,the four-quadrant analysis method,strengthened cost accounting,and differentiated resource allocation.
10.Study on the Existing State and Optimization Approach for Executing Orthopedic Case Simulation in a Pediatric Specialty Hospital Using CHS-DRG
Xiaoyan GUO ; Guangying GAO ; Ning XU ; Nianying ZHANG ; Na ZHANG ; Chudi YOU ; Jiashuai TIAN
Chinese Health Economics 2024;43(11):21-26
Objective:To guide cost control and the development of orthopedic specialty services in actual payment by thoroughly analyzing the functioning of DRG simulation in the pediatric orthopedic department of the Capital Institute of Pediatrics.Methods:A total of 736 patients from the orthopedic ward of the Capital Institute of Pediatrics were included as study subjects.The four-quadrant grouping method was employed to examine the profitability status of each diagnosis group in detail.A logistic regression model explored the key factors influencing profitability.Results:Congenital illnesses and traumas account for most pediatric orthopedic cases.Benefit groups(2 groups,4.8%),disadvantageous groups(15 groups,35.7%),key groups(8 groups,19.0%),and potential groups(17 groups,40.5%)are found using the Boston Matrix analysis.The profit group depends on the benefit groups(IF19,IH15)for 67.7%of its total revenue.No matter how profitable they are,medical consumables comprise a sizable portion(43%-45%).According to regression analysis,hospital profitability is highly impacted by age,consumable ratio,examination cost ratio,surgery cost ratio,and other cost ratios(P<0.05).The consumable ratio is the most significant negative predictor(β=-2.238).Conclusion:Hospitals need to optimize their cost structure and increase the probability of profitability through refined management of consumables,the four-quadrant analysis method,strengthened cost accounting,and differentiated resource allocation.

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