Objective:To evaluate the association between preoperative serum β 2-microglobulin (β 2MG) concentrations and postoperative delirium (POD) in elderly patients. Methods:The study selected patients who underwent knee or hip arthroplasty under spinal-epidural anesthesia on an elective basis at Qingdao Municipal Hospital from May 2021 to November 2022. The patients were divided into a POD group and a non-POD group based on the occurrence of POD. The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. The study collected baseline data from two groups of patients and analyzed the differences between them. Logistic regression was used to identify the risk factors for POD. The stability of the regression model was tested using sensitivity analysis. The mediation model was used to examine whether cerebrospinal fluid (CSF) biomarkers mediated the relationship between β 2MG and POD. The receiver operating characteristic curve was drawn and the area under the curve was calculated to evaluate the accuracy of preoperative β 2MG concentrations and CSF biomarker concentration in predicting POD. Results:There were 57 cases in POD group and 449 cases in non-POD group. The results of logistic regression analysis showed that the increased β 2MG and CSF total tau protein (t-tau) concentrations were risk factors for POD, and the increased CSF β-amyloid 42 concentration was a protective factor for POD after adjustment for multiple confounders such as age, gender, education, Mini-Mental State Examination, history of hypertension and infusion volume ( P<0.05). The results of mediation analysis showed that the serum β 2MG′s effect on POD was partly mediated by t-tau (18.1%). The results of the receiver operating characteristic curve showed that the area under the curve of the β 2MG concentration combined with the CSF biomarker concentration was 0.742. Conclusions:Elevated preoperative serum β 2MG concentration is a risk factor for POD in elderly patients, and the relationship may be partly mediated by CSF t-tau.

Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

Objective To analyze the current state,research hotspots,and development trends of electroencephalography(EEG)applied in the field of autism spectrum disorder(ASD). Methods Relevant literature from the Web of Science core collection database from January,2014 to January,2024 were retrieved and analyzed using CiteSpace 6.2.R4. Results A total of 1 509 articles were included,with an increasing trend in publication volume over the years.The United States ranked highest in both publication volume and node centrality.The primary journals in this field were concentrated in clinical medicine,immunology and psychology.Keyword co-occurrence and clustering indicated that research primarily focused on the correlation between core symptoms of ASD and EEG indicators,differential diagnosis of ASD and its comorbidities,brain functional connectivity,and assessment of rehabilitation efficacy.Keywords bursted in the past three years mainly included artificial intelligence and machine learning. Conclusion The researches in EEG technology in the field of ASD is generally increasing.Future researches may focus on exploring the brain network mechanisms of ASD using EEG combined with multimodal neuroimaging,and machine learning technologies.

Background and purpose:Silent information regulator proteins(sirtuins,SIRT)are a class Ⅲ histone deacetylases with nicotinamide adenine dinucleotide(NAD+)as coenzyme.YME1 like 1 ATPase(YME1L1)is essential for the maintenance of mitochondrial morphology,function and plasticity.Optic atrophy 1(OPA1)mainly mediates mitochondrial fusion.The aim of this study was to explore the expression of SIRT3 in the endocrine resistance of breast cancer,the relationship between SIRT3 and YME1L1 and OPA1,and the mechanism of SIRT3 in the endocrine resistance of breast cancer.Methods:4-hydroxytamoxifen was used to induce tamoxifen-resistant MCF-7/TAM cells.cell counting kit-8(CCK-8)was used to detect cell proliferation and verify drug resistance.The mitochondrial morphology was observed by transmission electron microscopy(TEM)and immunofluorescence staining.The expressions of SIRT3 and OPA1 were detected by real-time fluorescent quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.JC-1 staining was used to detect mitochondrial membrane potential,and dihydroethidium(DHE)staining was used to detect reactive oxygen species(ROS)to verify mitochondrial function.SIRT3 was knocked down in drug-resistant cells by RNA interference,and SIRT3 and YME1L1 wild type(WT),simulated acetylation state mutant(MUT K237Q),and simulated deacetylation state mutant(MUT K237R)were overexpressed in parental cells by overexpression plasmid.Immunoprecipitation assay(IP)and immunofluorescence(IF)were used to verify the interaction between SIRT3 and YME1L1.Results:RTFQ-PCR and Western blot results showed that SIRT3 gene expression and protein level was significantly higher in drug-resistant cells than in parental cells.Overexpression of SIRT3 in parental cells decreased the sensitivity of breast cancer cells to tamoxifen.Knockdown of SIRT3 in drug-resistant cells enhanced the sensitivity of drug-resistant cells to tamoxifen.DHE staining showed that the ROS level was lower in tamoxifen resistant cells than in parental cells at the same concentration.Transmission electron microscopy and fluorescence staining showed that the mitochondria of the drug-resistant cells were elongated compared with the parental cells.Western blot results showed that the expression level of L-OPA1 protein was higher in drug-resistant cells than in parental cells.Overexpression of SIRT3 in the parental cells resulted in enhanced mitochondrial function and longer mitochondrial morphology compared with the control cells.Western blot showed that the expression of L-OPA1 was upregulated.When SIRT3 was knocked down in drug-resistant cells,the opposite result was obtained.We further verified how SIRT3 regulated OPA1 protein,affected the morphology and function of mitochondria,and promoted drug resistance of breast cancer.Overexpression of YME1L1(wild-type and mutant plasmids)in parental cells showed that overexpression of YME1L1 in the simulated deacetylation state resulted in similar results as overexpression of SIRT3,and overexpression of YME1L1 in the acetylated state resulted in similar results as knockdown of SIRT3.IP assay confirmed the interaction between SIRT3 and YME1L1 in breast cancer cells.The acetylation level of YME1L1 was different at different SIRT3 expression levels.IF assay showed that YME1L1 was co-localized with SIRT3 in MCF-7 cells.Conclusion:SIRT3 is highly expressed in tamoxifen-resistant breast cancer cells.SIRT3 upregulates L-OPA1 expression by deacetylating YME1L1,thereby promoting mitochondrial fusion and enhancing mitochondrial function,and promotes tamoxifen resistance in breast cancer.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.

The goal of Medical Immunology is to enable students to pay attention to integration of immunology theory with clini-cal practice,be familiar with professional English,consciously pay attention to cutting-edge knowledge,and can learn independently and lifelong.However,existing teaching models lack explanation of clinical disease related events,and arrangement of experimental content and projects is seriously disconnected from clinical practice,scientific research on solving clinical problems is clearly insuffi-cient.We established a"B to B"cycle model for immunology teaching by starting from clinical practical problems(Bedside),return to basic research(Bench),and then solve clinical problem(Bedside),which will comprehensively cultivate senior medical profession-als with clinical competence,scientific research thinking ability,innovative spirit,and international perspective.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) cine sequences in determining the range of tumor motion in radiotherapy, providing a basis for the precise delineation of the target volume in motion for radiation therapy.Methods:A modified chest motion phantom was placed in a MRI scanner, and a water-filled sphere was used to simulate a tumor. True fast imaging with steady precession (TrueFISP) MRI cine sequences from Siemens were used to capture the two-dimensional motion images of the simulated tumor. The phantom experiments were divided into three modes: head-foot motion mode, rotation motion mode, and actual respiratory waveform mode. In the head-foot motion mode, respiratory motion period (3, 4, 5, 6, 7 and 8 s), amplitude (5, 10 and 15 mm), and respiratory waveform of the simulated tumor (sin and cos4) were set, resulting in a total of 36 motion combinations. In the rotation motion mode, a cos4 waveform was used for respiration, with respiratory periods of 3, 4, 5, 6, 7 and 8 s, head-foot motion set amplitudes of 5, 10 and 15 mm, and anterior-posterior (AP) and left-right (LR) motion set amplitudes in three combinations ([2.5, 2.5] mm, [2.5, 5.0] mm, [5.0, 5.0] mm), resulting in a total of 54 motion combinations. In the actual respiratory waveform mode, respiratory waveforms of 5 randomly selected patients from Affiliated Cancer Hospital of Zhengzhou University were obtained. Under each motion combination, TrueFISP cine images (30 frames, with an acquisition time of 11 s per frame) were obtained. The code was used to automatically identify the two-dimensional coordinates of the center of the simulated tumor in each image, and sin and cos4 functions were separately employed to fit the tumor position in the motion direction, thereby obtaining the fitted motion period and amplitude. The difference between the maximum and minimum values of the tumor's center coordinates in the head-to-foot direction is taken as the range of movement, referred to as the calculated amplitude. For the actual respiratory waveform, the distance between the measured maximum and minimum positions is used to calculate the amplitude.Results:In the head-foot motion mode, the fitted amplitudes of both sin and cos4 waveforms deviated from the set amplitudes by 0-0.51 mm, with relative deviations of 0%-4.2%. The deviation range between the calculated amplitudes and the set amplitudes of the two waveforms were 0.08-0.94 mm, with relative deviations of 1.1%-6.3%. In the rotation motion mode, the fitted amplitudes deviated from the set amplitudes by 0-0.61 mm, with relative deviations of 0%-6.2%. And the deviation range between the calculated amplitudes and the set amplitudes were 0.16-0.94 mm, with relative deviations of 0%-6.3%. In the actual respiratory waveform motion mode, the deviation range between the calculated amplitudes and the set amplitudes were 0.10-0.48 mm, with relative deviations of 2.2%-8.6%.Conclusion:TrueFISP cine sequences show minimal deviations in determining the range of tumor head-foot motion and effectively captures the tumor's movement state, thereby providing important support for the precise definition of the tumor movement target area during radiotherapy .

Objective:To evaluate the relationship between physical activity (PA) and postoperative delirium (POD) in elderly patients undergoing knee or hip arthroplasty.Methods:The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. Medical records from elderly patients undergoing elective knee or hip arthroplasty under spinal-epidural anesthesia at Qingdao Municipal Hospital from August 2022 to August 2023 were collected. The patients were divided into a POD group ( n=89) and a non-POD group ( n=221) based on the occurrence of POD. Peripheral blood samples were collected before surgery, and the cerebrospinal fluid (CSF) 2 ml was extracted after successful puncture under spinal-epidural anesthesia for determination of the concentrations of amyloid-β 42 (Aβ 42), total tau protein (t-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay. Logistic regression was used to analyze the influencing factors of POD, and the mediation analysis was conducted to examine the mediating role of CSF biomarker in the relationship between PA and POD. Results:Logistic regression analysis showed that the increased concentration of CSF biomarkers Aβ 42 ( OR=0.997, P=0.006), elevated ratio of Aβ 42/t-tau ( OR=0.642, P=0.003), elevated ratio of Aβ 42/p-tau ratio ( OR=0.872, P=0.001) and PA ( OR=0.374, P=0.001) were protective factors for POD, while the elevated concentrations of t-tau ( OR=1.006, P=0.001) and p-tau ( OR=1.030, P=0.011) were risk factors for POD after adjusting for multi-confounders such as hypertension, diabetes, history of drinking, years of education and Mini-Mental State Examination score. The results of the mediation analysis showed that Aβ 42 (20%), t-tau (16%), Aβ 42/t-tau (23%) and Aβ 42/p-tau (28%) played mediating roles in the relationship between PA and POD. Conclusions:PA is a protective factor for POD in elderly patients undergoing knee or hip arthroplasty and CSF biomarkers may play a mediating role in the relationship between PA and POD.

Objective:To evaluate the relationship between the preoperative sleep quality and postoperative delirium (POD) in elderly patients.Methods:Three hundred and eighty-nine patients of either sex, aged 65-90 yr, with American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, who underwent elective knee/hip arthroplasty under combined spinal-epidural anesthesia in Qingdao Municipal Hospital from May 2022 to October 2023, were selected. The Pittsburgh Sleep Quality Index scale was applied at 1 day before surgery to assess the sleep quality within 1 month before surgery. The cerebrospinal fluid (CSF) specimens 2 ml were withdrawn from the subarachnoid space before anesthesia for determination of the concentrations of biomarkers (β-amyloid), total tau protein [t-tau], and phosphorylated tau protein [p-tau]) by enzyme-linked immunosorbent assay. Patients were divided into POD group and non-POD group based on whether delirium occurred within 7 days after surgery. Logistic regression was used to identify the risk factors for POD, and the sensitivity analysis was used to test the stability of the regression models. The mediation model was used to examine whether CSF biomarkers mediated the link between sleep quality and POD. The accuracy of preoperative sleep quality and CSF biomarker concentrations in predicting the occurrence of POD was evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve.Results:Two hundred and seventy-nine patients were finally included, with 33 patients in POD group and 246 patients in non-POD group. The results of logistic regression analysis showed that shorter sleep duration, use of hypnotics, daytime dysfunction within 1 month before surgery, elevated t-tau concentrations in CSF, and elevated p-tau concentrations in CSF were risk factors for POD after adjusting for multiple confounding factors such as age, sex, body mass index, years of education, Mini-Mental State Examination score, and VAS score. The results of mediating effect showed that the effect of use of hypnotics and daytime dysfunction within 1 month before surgery on POD was partially mediated by p-tau concentrations in CSF (>10%). The area under the curve of combination of daytime dysfunction, sleep duration, use of hypnotics within 1 month before surgery, and CSF biomarker concentrations in predicting POD was 0.979.Conclusions:Shortened sleep duration, use of hypnotic, and daytime dysfunction with 1 month before surgery are risk factors for POD in elderly patients, and the association between use of hypnotics and daytime dysfunction and POD is partially mediated by p-tau in CSF.

Restricted repetitive behaviors (RRBs) are the most characteristic behaviors of autism spectrum disorder. The clinical diagnosis and treatment of RRBs are extremely difficult resulting from its complex and variable etiology, highly heterogeneous clinical manifestations influenced by multiple factors (sleep quality, gastrointestinal health, age and gender), lack of precise diagnostic criteria and low effectiveness of current clinical interventions. This article mainly reviews the recent related studies on RRBs and discusses the challenges and progress in clinical diagnosis and treatment of RRBs so as to provide new ideas for future clinical diagnosis and treatment.