OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Objective:To assess the effect of transversus abdominis plane block (TAPB) with liposomal bupivacaine and general anesthesia on postoperative delirium (POD) in elderly patients with prior novel coronavirus pneumonia (COVID-19).Methods:In this randomized double-blind controlled study, 416 patients of either sex, aged 65-90 yr, weighing 50-90 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, diagnosed as having COVID-19 within 6 months prior to surgery, who underwent laparoscopic colorectal cancer surgery under combination of elective TAPB and combined intravenous-inhalational general anaesthesia at Qingdao Municipal Hospital from June 2023 to December 2024, were selected. The patients were divided into liposomal bupivacaine group ( n=208) and bupivacaine hydrochloride group ( n=208) using the random number table method. After induction of anaesthesia, bilateral TAPB was performed with liposomal bupivacaine injectio 266 mg (40 ml) in liposomal bupivacaine group and with 0.5% bupivacaine hydrochloride 40 ml in bupivacaine hydrochloride group. The primary outcome measure was the occurrence of POD within 7 days after surgery. Secondary outcome measures included severity of POD, pain scores at 24, 48 and 72 h after operation, the rate of postoperative rescue analgesia and consumption of morphine, duration of post-anesthesia care unit stay, and length of hospital stay. The occurrence of complications such as death, reoperation, atelectasis and pneumonia was recorded at 30 days after surgery. Results:Compared with bupivacaine hydrochloride group, the incidence of POD was significantly decreased (21.5% [43/200]versus 12.0% [24/200]), pain scores at 24, 48 and 72 h after operation were decreased, the rate of postoperative rescue analgesia and consumption of morphine were decreased, and the duration of post-anesthesia care unit stay and length of hospital stay were shortened in liposomal bupivacaine group ( P<0.05). There was no significant difference in the severity of POD and the case fatality rate and related complications within 30 days after surgery between the two groups ( P>0.05). Conclusions:Liposomal bupivacaine TAPB combined with general anesthesia can reduce the development of POD in elderly patients with prior COVID-19.

Objective:To evaluate the relationship between preoperative concentrations of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) and postoperative delirium (POD) in patients undergoing total knee/hip arthroplasty.Methods:Six hundred and twenty-five patients of either sex, aged 50-90 yr, weighing 50-80 kg, with American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, with the preoperative Mini-Mental State Examination score > 23, who underwent elective knee/hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital from January 2022 to December 2023, were selected. The CSF specimens 2 ml were withdrawn from the subarachnoid space after successful subarachnoid puncture for determination of the concentrations of sTREM2, Amyloid beta protein (Aβ 42), total tau protein (T-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay. POD was assessed using the Confusion Assessment Method. Patients were divided into POD group and non-POD group based on whether POD occurred. Logistic regression was used to identify the risk and protective factors for POD. The performance of CSF sTREM2 concentration combined with CSF biomarker levels in predicting POD was evaluated using the receiver operating characteristic (ROC) curve and clinical decision curve. The mediating effect of CSF biomarker concentrations in the relationship between CSF sTREM2 concentration and POD was analyzed. Results:Five hundred and nineteen patients were finally included, with 112 patients in POD group and 407 patients in non-POD group. The results of logistic regression analysis showed that the elevated preoperative sTREM2 concentration in CSF was the risk factor for POD after adjusting for multiple confounding factors such as age, sex, body mass index, years of education, Mini-Mental State Examination score, history of smoking, history of drinking, hypertension, diabetes mellitus and coronary heart disease. The area under the ROC curve of the preoperative sTREM2 concentration in CSF in predicting POD was 0.716, and the area under the ROC curve of the preoperative sTREM2 concentration in CSF combined with CSF biomarkers in predicting POD was 0.796. This model had high clinical application value and predictive efficacy. The relationship between the preoperative sTREM2 concentration in CSF and POD was partially mediated by the CSF p-tau concentration (proportion of mediated effect 24.67%) and t-tau protein concentration (proportion of mediated effect 17.33%).Conclusions:The elevated preoperative concentration of sTREM2 in CSF is a risk factor for POD in patients undergoing total knee/hip arthroplasty, and concentrations of t-tau and p-tau in CSF play a mediating role in the relationship between the preoperative CSF sTREM2 concentration and POD.

Objective:To evaluate the association between postoperative delirium (POD) and preoperative frailty in elderly patients undergoing knee or hip arthroplasty.Methods:This nested case-control study utilized medical records from elderly patients who underwent knee or hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital between September 2021 and May 2023. Participants were divided into 2 groups based on clinically diagnosed POD: POD group ( n=53) and non-POD group ( n=256). Univariate analysis was conducted on suspected influencing factors, and logistic regression analysis was utilized to identify the risk factors for POD. Receiver operating characteristic and clinical decision curves were plotted to evaluate the predictive performance of these risk factors for POD. Mediation analysis was performed, and a clinically applicable nomogram was constructed to achieve visual prediction of outcomes. Results:There were statistically significant differences in age, preoperative frailty, body mass index, American Society of Anesthesiologists Physical Status classification, Memorial Delirium Assessment Scale scores, and concentrations of Aβ 42, Aβ 40, phosphorylated tau protein (p-tau protein) and tau protein, Aβ 42/tau ratio and Aβ 42/p-tau ratio in cerebrospinal fluid (CSF) between non-POD group and POD group ( P<0.05). Preoperative frailty was a risk factor for POD ( P<0.05). Mediation analysis revealed that the association between preoperative frailty and POD was mediated by CSF tau protein concentrations. The area under the receiver operating characteristic curve of preoperative frailty and CSF biomarker concentrations in predicting POD was 0.974 ( P<0.05). The clinical decision curve demonstrated that the model combining the preoperative frailty and CSF biomarker concentrations predicted a higher net benefit ( P<0.05). The clinical decision curve showed that the model combining preoperative frailty and CSF biomarker concentrations predicted a higher net benefit. Conclusions:Preoperative frailty is a risk factor for POD in elderly patients undergoing knee or hip arthroplasty, and its combination with CSF biomarker concentrations can effectively predict the occurrence of POD. CSF tau concentration mediates the association between preoperative frailty and development of POD.

Objective:To evaluate the association between the preoperative aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and postoperative delirium (POD) in patients undergoing total knee/hip arthroplasty.Methods:In this nested case-control study, medical records from patients, aged ≥55 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, with Mini-Mental State Examination (MMSE) scale score >24 on preoperative day 1, scheduled for elective total knee/hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital between November 2021 and December 2023, were collected. POD was assessed using the Confusion Assessment Method. Patients were categorized into POD and non-POD groups based on the occurrence of POD. Logistic regression was employed to identify protective and risk factors for POD. The predictive performance of preoperative AST/ALT ratio alone and its combination with cerebrospinal fluid (CSF) biomarker concentrations for POD was evaluated using receiver operating characteristic curves, and the clinical utility of the prediction models was assessed using decision curve analysis. Mediation analysis was conducted to examine the mediation role of CSF biomarkers in the relationship between the preoperative AST/ALT ratio and POD. Restricted cubic splines were used to assess the nonlinear relationship between the preoperative AST/ALT ratio and POD.Results:A total of 460 patients were finally included, with 49 in POD group and 411 in non-POD group. After adjustment for multiple confounding factors including age, sex, educational level, MMSE score, history of hypertension, history of diabetes, history of smoking and history of alcohol use, multivariable logistic regression identified that the higher preoperative AST/ALT ratio, CSF total tau protein (t-tau) and phosphorylated tau protein (p-tau) concentrations were independent risk factors for POD, whereas lower CSF β-amyloid 42 (Aβ 42) concentration, Aβ 42/t-tau ratio and Aβ 42/p-tau ratio served as protective factors ( P<0.05). The area under the receiver operating characteristic curve of the preoperative AST/ALT ratio combined with CSF biomarkers in predicting POD was 0.939 ( P<0.001), demonstrating high clinical efficacy. After adjusting for age, educational level, sex, MMSE score, history of hypertension, history of diabetes, history of smoking, history of alcohol use and body mass index, restricted cubic splines revealed a nonlinear relationship between preoperative AST/ALT levels and the probability of POD, and the probability of POD increased with rising ratios when the preoperative AST/ALT ratio ranged from 1.09 to 1.40 ( Poverall < 0.05, Pnonlinear <0.05). After stratification by sex, the preoperative AST/ALT ratio demonstrated a linear relationship with the probability of POD ( Poverall <0.05, Pnonlinear>0.05). Mediation analysis indicated that the relationship between the preoperative AST/ALT ratio and POD was partially mediated by CSF p-tau concentration (proportion mediated 18.1%), CSF t-tau concentration (proportion mediated 12.0%), and the Aβ 42/t-tau ratio (proportion mediated 15.4%). Conclusions:A higher preoperative AST/ALT ratio is an independent risk factor for POD in total knee/hip arthroplasty patients. The concentrations of CSF t-tau and p-tau and Aβ 42/t-tau ratio have a mediating role in the relationship between the preoperative AST/ALT ratio and POD.

Objective:To evaluate the association between preoperative cardiometabolic multimorbidity (CMM) and postoperative delirium (POD) in elderly patients undergoing knee or hip replacement.Methods:Based on a perioperative neurocognitive dysfunction and biomarker lifestyle cohort, a nested case-control study was conducted using medical records of patients scheduled for elective knee or hip joint replacement at Qingdao Municipal Hospital from January 2022 to November 2023. Patients were divided into POD group ( n=124) and non-POD group ( n=414) based on whether POD occurred. The influencing factors were collected, and intergroup differences were analyzed. Logistic regression was used to identify the risk factors for POD, and sensitivity analysis was conducted to assess the stability of the regression model. A mediation model was employed to examine whether cerebrospinal fluid (CSF) biomarkers mediated the association between CMM and POD. Results:There were statistically significant differences in the rate of CMM, age, years of education, rate of hypertension, rate of diabetes mellitus, rate of coronary heart diseases, rate of stroke, Aβ 42 concentration, t-tau concentration, p-tau concentration, Aβ 42/t-tau ratio, and Aβ 42/p-tau ratio in CSF between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative CMM was a risk factor for POD ( P<0.05). Mediation analysis revealed that the relationship between CMM and POD was partly mediated by Aβ 42 concentrations in CSF. Conclusions:Preoperative CMM is a risk factor for POD in elderly patients undergoing knee or hip replacement, and the CSF Aβ 42 concentration may play a partly mediating role in the association between preoperative CMM and POD.

Objective Immunoglobulin G4-related hypertrophic pachymeningitis （IgG4-RHP） is a rare autoimmune disorder. This study aims to conduct a clinical analysis of seven cases with IgG4-RHP to enhance the understanding of this disease. Methods A retrospective analysis was conducted on seven patients diagnosed with IgG4-RHP. The demographic data， clinical manifestations， laboratory examinations， cerebrospinal fluid analysis， imaging， pathological manifestations， treatments， and efficacy analysis data were collected. Results The patients’ ages ranged from 38 to 67 years， with most being males. Headache （6/7） and cranial nerve palsies （5/7） were the most common clinical symptoms. Notably， one case presented with seizures and another with limb weakness. All patients exhibited elevated serum IgG4 levels （1.48-3.25 g/L）. Imaging studies revealed varying degrees of dural thickening and enhancement located in the global dura， tentorium cerebelli， cavernous sinus， and thoracic spinal dura. A definitive pathological diagnosis was obtained via biopsy （intracranial， nasal sinus， or orbital） in 3 patients. All patients received glucocorticoid therapy， with 5 receiving combined cyclophosphamide due to extensive or severe lesions. At the 6-month follow-up， 2 patients achieved complete response， 4 showed partial response， and 1 showed no response. During long-term follow-up， one patient experienced relapse during steroid tapering， which ended up in response again after immunosuppressive regimen adjustment. Conclusion IgG4-RHP is characterized by significant heterogeneous manifestations， which may involve the spinal cord or induce seizures. Diagnosis requires a combination of serological， radiological， and pathological results. While glucocorticoids with immunosuppressants are the main treatment measures， patients with long disease duration and significant fibrosis may respond poorly， highlighting the importance of early intervention and the exploration of novel therapies for refractory cases.
Diagnosis

Objective:To establish a method for evaluating the material attributes and skeletal performance of 2208 hydroxypropyl methylcellulose(HPMC),to clarify the influence of different material attributes on the skeletal per-formance of HPMC,to compare the differences between the products of different manufacturers,and to analyze the factors affecting the process.Methods:In this study,the material attributes such as powder chemical properties,viscosity,gelation temperature,thermodynamic properties,weight-average molecular weight,methoxy and hydroxypropoxy contents of different manufacturers were firstly investigated.Then,the water absorption,swelling,and dissolution properties of HPMC blank skeleton tablets were determined using the weighing method.Finally,Principal Component Analysis(PCA)and Orthogonal Partial Least-Squares Discrimination Analysis(OPLS-DA)were used to systematically evaluate the material attributes and skeleton performance of HPMC.The systematic evaluation of each material attribute and skeleton performance of HPMC was carried out to elucidate the intrinsic relationship between each material attribute and skeleton performance of HPMC.Results:The results showed that there were obvious differences in the material attributes of HPMC from different manufacturers,such as the proper-ties of powder,viscosity,and weight-average molecular weight,and that there were differences in the corrosion performance,water absorption,and swelling performance of the skeleton tablets prepared from different manufactur-ers,with the most obvious differences between K4Mand K100M.The results of the PCA and OPLS-DA analyses indicated that these 19 variables showed some correlation with each other.Both mathematical models showed better differentiation and classification effects on HPMC samples,and the OPLS-DA model had better classification effects than the PCA model.Conclusion:Based on the PCA and OPLS-DA models,this study conducted systematical research on HPMC,clarified the degree of influence of different material attributes on the skeletal performance of HPMC,and suggested the addition of HPMC particle size and size distribution,and weight-average molecular weight as the quality standards,which provide a basis for the quality control of the related excipients,the screening of formulation prescriptions,and the improvement of performance.

Taking Xiaochaihu Decoction as an example,the application differences of classical prescriptions in modern medical context and Chinese medicine practice are compared and analyzed from the aspects of clinical application scope,understanding of pre-scription connotation,dosage specification,dosage form and decoction method.Strategies to solve the differences in efficacy are pro-posed:integrating the wisdom of classical prescriptions and reshaping the framework of Chinese medicine diagnosis and treatment;transforming the results of modern pharmacology and exploring the principles of classical prescriptions;controlling drug quality stand-ards and exploring new uses and dosages of classical prescriptions;keeping pace with the times in Chinese medicine decoction and strengthening management and control to ensure efficacy.It is believed that combining the essence of Chinese medicine with modern technology can make the application of classical prescriptions maintain traditional characteristics while meeting modern clinical require-ments.This can not only improve the adaptability of classical prescriptions to modern complex diseases,but also provide a reference for the modernization of traditional medicine.

OBJECTIVE:Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease,which seriously affects patients'quality of life.Non-invasive brain stimulation,as a common non-pharmacological treatment,has good efficacy in improving cognitive impairment after Parkinson's disease,but how to choose the optimal stimulation modality of non-invasive brain stimulation in clinical practice is still unclear.This study assessed the effects of different stimulation modalities of non-invasive brain stimulation on cognitive function in patients with Parkinson's disease by means of the network Meta-analysis,which provides an evidence-based basis for the selection of non-invasive brain stimulation modalities in the clinic.METHODS:PubMed,EMbase,Web of Science,Cochrane Library,CNKI,CBM,and WanFang databases were searched for randomized controlled trials on the effects of non-invasive brain stimulation interventions on cognitive function in patients with Parkinson's disease from the inception to August 2024.The control group was treated with conventional therapy(rehabilitation training and conventional medication)or sham stimulation,and the experimental group was treated with non-invasive brain stimulation based on the treatment in the control group.The Cochrane Risk of Bias Assessment Tool for Randomized Controlled Trials RoB 2 was used to evaluate the quality of the included studies.Literature screening and data extraction were performed independently by two researchers and the risk of bias for the included studies was evaluated.Traditional Meta-analysis and network Meta-analysis of short-term cognitive functioning scale scores and long-term cognitive functioning scale scores were performed using RevMan 5.4 and Stata 16.0 software to draw network relationship,diagrams league table and cumulative probability ranking tables.GRADE was used to rate the level of evidence for the outcome indicators.RESULTS:(1)A total of 31 randomized controlled trials were included,of which 8 studies were rated as low-risk,23 studies were rated as medium-risk,and there were no high-risk studies,comprising 1 670 subjects and involving different stimulation modalities for 14 types of non-invasive brain stimulation.(2)Network Meta-analysis showed that compared with conventional treatment,high-frequency repetitive transcranial magnetic stimulation of the first motor cortex(standardized mean difference[SMD]=0.73,95％confidence interval[CI]=0.14-1.32,P＜0.05,the surface under the cumulative ranking curve[SUCRA]=66.2％)was the most effective in improving short-term cognitive functioning in Parkinson's patients,followed by transcranial direct current stimulation of the dorsolateral prefrontal cortex(SMD=0.56,95％CI=0.14-0.98,P＜0.05,SUCRA=54.4％)and high-frequency repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex(SMD=0.52,95％CI=0.11-0.93,P＜0.05,SUCRA=51.4％);and in terms of improvement of long-term cognitive functioning in patients with Parkinson's disease,high-frequency repetitive transcranial magnetic stimulation of the first motor cortex(SMD=1.17,95％CI=0.48-1.85,P＜0.05,SUCRA=91.2％)was the most effective.CONCLUSION:Low-level intensity clinical evidence suggests that high-frequency repetitive transcranial magnetic stimulation of the first motor cortex is the most effective in improving short-term cognitive function in patients with Parkinson's disease,followed by transcranial direct current stimulation of the dorsolateral prefrontal cortex and high-frequency repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex.Also high-frequency repetitive transcranial magnetic stimulation of the first motor cortex is the best stimulation modality in improving long-term cognitive function in patients with Parkinson's disease.