OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

Objective: To investigate the attention cognitive function and symptom correlations of school aged children with attention deficit hyperactivity disorder (ADHD)using event related potential (ERP) technology, so as to provide references for the early diagnosis of children with ADHD. Methods: A total of 52 school aged children diagnosed with ADHD at the outpatient department of the Third Affiliated Hospital of Zhengzhou University from September 2022 to September 2024 and 50 age /sex matched healthy controls were selected. The ERP experiment adopted the auditory Oddball task to conduct comparative analyses of the amplitude and latency of the mismatch negative(MMN) at the Fz, Cz, and Pz points of the scalp electrode and the P3a component respectively. The symptom assessment scales adopted the Swanson,Nolan,and Pelham-Ⅳ Rating Scale (SNAP-Ⅳ) and the Parent Symptom Questionnaire (PSQ), which were filled out by the parents. Spearman correlation analysis was used to analyze the correlation between ERP components and symptoms in schoolaged children with ADHD. Results: The latency of MMN components in the healthy control group on the Fz lead was (188.30±2.06)ms, and the amplitude was (-15.54±1.35)μV; the latency of the P3a component on the Pz lead was (312.82±7.80)ms, and the amplitude was (3.80±0.18)μV. The latency of MMN components in the ADHD group on the Fz lead was (188.94±1.39)ms, and the amplitude was (-14.78±1.40)μV; the latency of the P3a component on the Pz lead was (317.21±5.65)ms, and the amplitude was (3.70±0.13)μV. Compared with normal children, the MMN of children with ADHD had smaller amplitudes in the Fz and Cz leads, and the P3a had greater latency and smaller amplitudes in the Cz and Pz leads ( t =2.79,2.20；-2.04，-3.25；2.35,3.21， P <0.05). Correlation analysis showed that the latency of MMN in children with ADHD was positively correlated with the inattention score in the SNAP-Ⅳ( r =0.22), and the amplitude of MMN was negatively correlated with the inattention score in the SNAP-Ⅳ and the learning problem score in PSQ ( r = -0.26 , -0.34)( P <0.05). The latency of P3a was positively correlated with the scores of inattention in the SNAP-Ⅳ and the score of learning problems in the PSQ ( r =0.26 ,0.24); the amplitude of P3a was negatively correlated with the scores of attention deficit and hyperactivity/impulsivity in the SNAP-Ⅳ and the scores of learning problems and impulsivity/hyperactivity in the PSQ( r = -0.26 , -0.22, -0.25,-0.32)( P <0.05). Conclusions School aged ADHD children exhibit abnormal MMN/P3a components, indicating attention related cognitive dysfunction. Symptoms such as inattention, learning problems and hyperactivity/impulsivity in children with ADHD are related to abnormal components of MMN and P3a.

Gallbladder cancer is a malignant tumor with an extremely poor prognosis， and radical surgery remains the only potentially curative treatment method for this disease. For stage Tis and T1a gallbladder cancer， cholecystectomy alone can achieve a curative effect； for stage T1b-T2 gallbladder cancer， radical surgery （including resection of the gallbladder， partial hepatectomy， and regional lymphadenectomy） remains the preferred treatment modality； for stage T3-T4 gallbladder cancer， extended radical resection helps to improve the prognosis of some patients， but with a high risk and a high incidence rate of complications， and it is necessary to grasp the indications and conduct surgery by a team with rich experience in pancreatobiliary surgery. There are currently still controversies over the application of minimally invasive surgery in the treatment of gallbladder cancer； however， an increasing number of evidence has shown that minimally invasive surgery for gallbladder cancer is safe and feasible in centers with extensive experience in minimally invasive techniques. This article systematically elaborates on the current status and advances in the surgical treatment of gallbladder cancer based on the authors’ clinical experience and related articles.

BACKGROUND:At present,the treatment of infected bone defects has the problems of long course of disease,poor treatment effect and high cost.The osteogenic effect of personalized bone replacement materials in clinical treatment is limited.Therefore,a 3D-printed bone graft material with both good osteogenic effect and antibacterial effect is urgently needed for clinical treatment. OBJECTIVE:To summarize the research status of 3D-printed scaffolds loaded with antimicrobial agents for the treatment of infected bone defects. METHODS:PubMed,Web of Science,Elsevier,and CNKI databases from January 2010 to June 2022 were searched for related articles.The Chinese search terms were"bone defect,3D printing,scaffold material,antibacterial,animal experiments,in vitro experiments".English search terms were"bone defect,3D printing,scaffold,antibiosis,animal experiment,in vitro".Finally,60 articles were included for review and analysis. RESULTS AND CONCLUSION:The 3D scaffolds made of titanium,magnesium,tantalum and other metals and their alloys have certain osteogenic properties,but do not have antibacterial function.Hydroxyapatite and other bioceramic materials have good biocompatibility and are prone to be degraded,whereas due to the lack of strength,they are usually combined with artificial polymer materials to form composite materials,which respectively mimic the inorganic and organic components in natural bone,and play their respective excellent functions.Antibiotics,silver/copper nanoparticles,antimicrobial peptides,gallium and other antibacterial agents play an antibacterial role by destroying bacterial cell membrane,producing reactive oxygen species to interfere with bacterial DNA replication,inhibiting iron absorption and other mechanisms.As a result,the 3D-printed scaffold has both antibacterial and osteogenic effects.However,there are still some problems such as drug resistance and difficult to control effective concentrations.3D-printed scaffolds are often loaded with antibacterial agents by loading drug-loaded microspheres on scaffolds,preparing antibacterial coating on the scaffold surface,and participating in joint 3D printing with drugs.The loading mode of antibacterial coating prepared on the scaffold surface is the most widely used,and its antibacterial effect is more stable.Nonetheless,the selection of the most suitable loading mode for antibacterial agents needs to be further discussed and summarized.It is a future research prospect to optimize the mechanical properties of composite scaffolds and prepare biomimetic bone scaffolds so that the degradation rate is consistent with the bone reconstruction rate in infected bone defects.The ideal antibacterial agents may play a role through a variety of antibacterial mechanisms,thus being expected to play a good antibacterial effect through low antibacterial concentration,which should be a hot spot of anti-bone infection research.After loading antibacterial agents on the surface of the scaffold,antibacterial agents can"intelligently"react to the local microenvironment,achieving controlled release,and regulating the osteogenesis,vascularization and immune response of the microenvironment,which is the focus of current research.

Objective To explore the research status and hot highlights in the field of Alzheimer's disease nursing,and provide reference and direction for future research.Methods The high-level articles on Alzheimer's disease nursing during 2012 to 2022 were collected from Web of Science core database,were analyzed and visualized by the CiteSpace 5.8.R3C software.Re-sults 956 articles were included in the Web of Science core database.The demand and focus on AD nursing research increased year by year.United States America had the largest number of articles(175 articles),followed by France(43 articles)and Chi-na(31 articles).Minnesota University and Harvard Medical School had the largest number of articles(11 articles).The authors'analysis shows that BRUNO VELLAS,an academician of the French Academy of Sciences,had the largest number of articles.Keyword co-occurrence analysis shows that the research in the past decade mainly focuses on"nursing home","people"and"quality of life","long-term care"and"exercise therapy"may become the key research directions in the future.Conclusion Domestic scholars should improve the social security system of long-term care,promote"people-oriented"humanistic nursing services and develop appropriate sports training programs in the future.

Objective:To study the relationship between the absorptive capacity of inpatients with infectious diseases and the structure of diseases in 65 secondary and tertiary general hospitals in Beijing,and to objectively analyze the current situation of space utilization of inpatients with infectious diseases,so as to provide data support for the formulation of relevant policies.Methods:The variability of spatial absorption capacity indicators for secondary and tertiary general hospitals in 6 urban districts and 10 suburbs were compared separately,and the correlation between the spatial absorption capacity of secondary and tertiary general hospitals and the structure of disease types was visualized and analyzed using quadrant bubble charts.Results:In terms of spatial absorption capacity,there was a statistically significant difference in the proportion of patients from suburban districts treated in the secondary and tertiary general hospitals in 6 urban districts of the Beijing(P=0.003),while there was no statistically significant difference in the proportion of patients from other districts treated in the secondary and tertiary general hospitals in 10 suburbs(P=0.336).The spatial absorption capacity and disease structure of the secondary and tertiary hospitals in 6 urban districts and the tertiary hospitals in 10 suburbs showed significant correlation,while the secondary hospitals in 10 suburbs showed no significant correlation.Conclusion:The tertiary general hospitals in 6 urban districts have superior infectious disease type structure indicators,with significantly stronger spatial absorption capacity and stronger correlation between these two,which plays the function of inpatient service of difficult and severe infectious diseases.Only the district hospitals in the outer suburbs can provide inpatient services for infectious diseases,and the number of cases admitted is large,which meets the needs of inpatient diagnosis and treatment of common infectious diseases in the district.It is necessary to strengthen the investment of infectious disease medical resources and capacity building in 10 suburban districts according to the actual situation.

Objective:The service capacity of infectious diseases department in Beijing secondary and tertiary general hospitals was quantitatively analyzed to provide objective data support for the construction of infectious diseases department.Methods:The scope of infectious diseases was defined by the DRG tool,and the service capacity of medical institutions was described by the Case Mix Index(CMI)and number of DRG groups.The differences in the service capacity of infectious diseases in 67 secondary and tertiary general hospitals in Beijing from 2016 to 2020 were analyzed by data visualization and generalized linear equation,and the disease structure of different hospitals at different levels was compared by selecting representative hospitals.Results:From 2016 to 2020,the mean CMI of tertiary hospitals ranged from 0.94 to 0.97,while that of secondary hospitals ranged from 0.70 to 0.72.From 2016 to 2019,the average number of DRG groups in tertiary hospitals ranged from 26.75 to 27.79,and the average number of DRG groups in secondary hospitals ranged from 15.32 to 15.77,and the average number of DRG groups in secondary and tertiary hospitals showed a significant decline in 2020.CMI and number of DRG groups had statistical significant difference at hospital level(P＜0.001),and number of DRG groups had statistical difference in time dimension(P＜0.001).Conclusion:The infectious disease service capacity of tertiary general hospitals is obviously stronger than that of secondary general hospitals,and the infectious disease medical service capacity of large tertiary hospitals is obviously ahead,while the overall service level of secondary hospitals is low.We should give full play to the advantages of top three hospitals to build a high ground for infectious disease department construction,and combine the spatial distribution of medical resources and demand characteristics to improve the infectious disease service capacity of secondary hospitals.

Objective:To study the relationship between the absorptive capacity of inpatients with infectious diseases and the structure of diseases in 65 secondary and tertiary general hospitals in Beijing,and to objectively analyze the current situation of space utilization of inpatients with infectious diseases,so as to provide data support for the formulation of relevant policies.Methods:The variability of spatial absorption capacity indicators for secondary and tertiary general hospitals in 6 urban districts and 10 suburbs were compared separately,and the correlation between the spatial absorption capacity of secondary and tertiary general hospitals and the structure of disease types was visualized and analyzed using quadrant bubble charts.Results:In terms of spatial absorption capacity,there was a statistically significant difference in the proportion of patients from suburban districts treated in the secondary and tertiary general hospitals in 6 urban districts of the Beijing(P=0.003),while there was no statistically significant difference in the proportion of patients from other districts treated in the secondary and tertiary general hospitals in 10 suburbs(P=0.336).The spatial absorption capacity and disease structure of the secondary and tertiary hospitals in 6 urban districts and the tertiary hospitals in 10 suburbs showed significant correlation,while the secondary hospitals in 10 suburbs showed no significant correlation.Conclusion:The tertiary general hospitals in 6 urban districts have superior infectious disease type structure indicators,with significantly stronger spatial absorption capacity and stronger correlation between these two,which plays the function of inpatient service of difficult and severe infectious diseases.Only the district hospitals in the outer suburbs can provide inpatient services for infectious diseases,and the number of cases admitted is large,which meets the needs of inpatient diagnosis and treatment of common infectious diseases in the district.It is necessary to strengthen the investment of infectious disease medical resources and capacity building in 10 suburban districts according to the actual situation.

Objective:The service capacity of infectious diseases department in Beijing secondary and tertiary general hospitals was quantitatively analyzed to provide objective data support for the construction of infectious diseases department.Methods:The scope of infectious diseases was defined by the DRG tool,and the service capacity of medical institutions was described by the Case Mix Index(CMI)and number of DRG groups.The differences in the service capacity of infectious diseases in 67 secondary and tertiary general hospitals in Beijing from 2016 to 2020 were analyzed by data visualization and generalized linear equation,and the disease structure of different hospitals at different levels was compared by selecting representative hospitals.Results:From 2016 to 2020,the mean CMI of tertiary hospitals ranged from 0.94 to 0.97,while that of secondary hospitals ranged from 0.70 to 0.72.From 2016 to 2019,the average number of DRG groups in tertiary hospitals ranged from 26.75 to 27.79,and the average number of DRG groups in secondary hospitals ranged from 15.32 to 15.77,and the average number of DRG groups in secondary and tertiary hospitals showed a significant decline in 2020.CMI and number of DRG groups had statistical significant difference at hospital level(P＜0.001),and number of DRG groups had statistical difference in time dimension(P＜0.001).Conclusion:The infectious disease service capacity of tertiary general hospitals is obviously stronger than that of secondary general hospitals,and the infectious disease medical service capacity of large tertiary hospitals is obviously ahead,while the overall service level of secondary hospitals is low.We should give full play to the advantages of top three hospitals to build a high ground for infectious disease department construction,and combine the spatial distribution of medical resources and demand characteristics to improve the infectious disease service capacity of secondary hospitals.