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 body temperature and duration of mechanical ventilation in the intensive care unit (ICU) among patients after coronary artery bypass grafting (CABG).Methods:Clinical data from patients, aged >18 yr, undergoing primary isolated CABG, between 2008 and 2019, were extracted from the Medical Information Mart for Intensive Care Ⅳ version 2.0 database. Participants were stratified into 3 groups based on the mean body temperature in ICU: hypothermia group (<36.0 ℃), normothermia group (36.0 ℃ ≤ temperature <37.3 ℃), and hyperthermia group (≥37.3 ℃). Multivariable linear regression and linear curve fitting were performed to assess the association between body temperature and duration of mechanical ventilation.Results:A total of 4, 588 patients were finally included in the statistical analysis, including 133 cases in hypothermia group, 4, 177 cases in normothermia group and 278 cases in hyperthermia group. The duration of mechanical ventilation was significantly prolonged in both hypothermia and hyperthermia groups compared with normothermia group ( P<0.05). The results of multivariable linear regression demonstrated that each 1 ℃ increase in body temperature was associated with a 2.43 h reduction in the duration of mechanical ventilation in hypothermia group ( P<0.001), and each 1 ℃ temperature elevation corresponded to a non-significant reduction of 0.12 h in hyperthermia group ( P=0.851). The results of linear curve fitting revealed a U-shaped relationship between body temperature and duration of mechanical ventilation, and an inflection point was identified at 36.71 ℃, with duration of mechanical ventilation prolonged with temperatures either below or above this threshold ( P<0.05). Conclusions:Hypothermia during ICU stay following CABG may lead to prolonged mechanical ventilation in patients.

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 To investigate the status of oral frailty(OF)in patients who underwent chemotherapy for lung cancer,identify key factors influencing OF,and develop a risk prediction model.Methods Using convenience sampling,431 lung cancer inpatient were recruited from three Tier-IIIA hospitals in Jiangsu Province between September and November 2024 as the training cohort.The patients were divided into OF and non-OF groups.Relevant data were compared between the two groups.Multifactorial logistic regression analysis was performed to determine factors that associated with OF,and a risk prediction model was created accordingly.Receiver operating characteristic(ROC)curve analysis was used to predict model performance.In December 2024,additional 185 patients from one other Tier-IIIA hospitals were recruited to validate the developed model.Results The prevalence of OF among lung-cancer patients undergoing chemotherapy was 58.93%.Following listed items were identified as the risk factors of OF(all P<0.05):older in age(OR=3.420),poor education(OR=0.030),brain metastasis(OR=7.880),high nutritional risk screening 2002 score(OR=1.550),elevated C-reactive protein(OR=1.100),and elevated lactate dehydrogenase(OR=1.010).ROC area under the curve(AUC)of the model was 0.860(95%CI:0.830-0.900)in modelling cohort and 0.840(95%CI:0.780-0.900)in validation cohort.Hosmer-Lemeshow goodness-of-fit test yielded χ 2=4.870,P=0.770 for the training set and χ 2=2.770,P=0.950 for the validation set.Conclusion The risk prediction model for OF developed in this study demonstrates a good predictive performance and can facilitate early identification of high-risk patients,thereby providing a scientific basis for clinical interventions.

Background and purpose:Epithelial ovarian cancer(EOC)has a poor prognosis and is prone to developing resistance to platinum-based chemotherapy.Exosomes are currently believed to be involved in platinum resistance in ovarian cancer.This study explored the role and mechanism of exosomes on platinum resistance of ovarian cancer.Methods:Through ultracentrifugation,exosomes were isolated and analyzed using electron microscopy,particle size studies,and Western blot for detailed exosome analysis.We detected the expression levels of exosomal proteins and related signaling pathways.Exosomal protein expression profile was analyzed by proteomics.Key differential proteins were screened by intersecting with existing drug resistance datasets.Furthermore,patients diagnosed with EOC via pathological analysis at the Fudan University Shanghai Cancer Center from August 2023 to August 2024,who underwent surgery and fulfilled the eligibility requirements,were gathered to examine the link between the expression of interferon-stimulated gene 15(ISG15)in serum exosomes and resistance to platinum medication.The expression levels of related proteins in serum exosomes were quantitatively detected by enzyme-linked immunosorbent assay(ELISA).Receiver operating characteristic(ROC)curve was plotted to explore the predictive value of serum exosomal protein in ovarian cancer resistance.Results:Exosomes derived from platinum-sensitive and drug-resistant ovarian cancer cells were extracted and proteomic analysis was further performed.We identified 9 differential proteins associated with platinum-resistance and found the key molecule interferon-stimulated gene 15(ISG15).Compared with sensitive cells,the expression of ISG15 in exosomes of drug-resistant ovarian cancer cells was significantly upregulated.Exosome tracer tests showed that exosomes were successfully taken up by ovarian cancer receptor cells.After coculture with drug-resistant exosomes,the expression level of ISG15 in ovarian cancer receptor cells was increased.Knockdown ISG15 in EOC cells decreased the expression of ISG15 in exosomes,and incubation of ISG15-knockdown exosomes decreased the cell viability on the condition of platinum drugs,indicating that ISG15 in exosomes regulated platinum resistance of ovarian cancer cells.Moreover,ISG15 could regulate the expression of multidrug resistance protein 1(MDR1)through phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-kappa-light-chain-enchancer of activated B cells(NF-κB)signaling pathway.This study included a total of 87 patients.Clinical serum samples also showed that the expression of ISG15 in exosomes was higher in platinum-resistant ovarian cancer patients than in sensitive ovarian cancer patients.Using serum exosomal ISG15 as an indicator to distinguish between sensitivity and resistance,the area under ROC curve was 0.779(P＜0.05),cutoffvalue was 27.35ng/mL,sensitivity was 70.2%,and specificity was 76.4%.Conclusion:ISG15 in exosomes can regulate the expression of MDR1 in ovarian cancer cells through PI3K/AKT/NF-κB signaling pathway,and promote platinum resistance in ovarian cancer cells.

ObjectiveTo establish the specific chromatogram and quantitative analysis of multi-components by single-marker（QAMS） based on linear calibration using two reference substances（LCTRS）， explore the consistency between Hedyotis Herba dispensing granules and standard decoction， and evaluate the quality of the dispensing granules. MethodsHigh performance liquid chromatography（HPLC） specific chromatogram was established based on 15 batches of Hedyotis Herba standard decoction and 10 batches of the dispensing granules， and LCTRS was used to locate chromatographic peaks. The actual retention times of 7 characteristic peaks in the specific chromatogram was measured on 24 different types of C₁₈ columns， taking deacetyl asperulosidic acid and asperulosidic acid as the dual standard compounds， the retention times of the other 5 characteristic peaks were predicted and validated. Based on this， QAMS was developed to determine the contents of four components（deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid， and p-coumaric acid）. Then， the relative correction factors of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester and p-coumaric acid were calculated using the reference peak of asperulosidic acid in the dual standard compounds， and each component was quantified accordingly. Finally， the consistency between the dispensing granules and standard decoction was assessed by taking extract rate of the standard decoction， consistency of the specific chromatograms， contents and transfer rates of the indicator components as indexes， and the quality of the dispensing granules was evaluated. ResultsThere were 7 common peaks in the characteristic chromatogram of samples of Hedyotis Herba standard decoction and the dispensing granules， and four of them were identified by reference standards， namely deacetyl asperulosidic acid（peak 1）， deacetyl asperulosidic acid methyl ester（peak 3）， asperulosidic acid（peak 6） and p-coumaric acid（peak 7）. The similarity between the dispensing granules and the standard decoction was >0.9. The absolute deviation in the predicted retention time for each component by LCTRS was lower than that of the relative retention time method. The extract rate of the 15 batches of Hedyotis Herba standard decoction ranged from 7.89% to 14.60%， the contents of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid and p-coumaric acid were 6.62-19.70， 3.83-17.99， 1.57-6.69， 1.62-4.52 mg·g^-1， and the transfer rates of these components from decoction pieces to the standard decoction were 22.89%-39.60%， 34.03%-62.24%， 24.25%-43.70%， and 40.58%-73.71%， respectively. The extract rate， index component contents and transfer rates from decoction pieces to the three batches of Hedyotis Herba dispensing granules（P1-P3）， produced by manufacturer A， were similar to those of the standard decoction prepared from the same batch of decoction pieces， and all fell within the specified range. The contents of the 4 indicator components in 7 batches of the dispensing granules（P4-P10） from manufacturers B-E were all within the range of the content converted from the standard decoction based on the quantity of the dispensing granules. ConclusionThe established specific chromatogram and QAMS based on LCTRS are reasonable and reliable. Based on the evaluation indicators of standard decoction yield， consistency of specific chromatograms， contents and transfer rates of the four index components， the 10 batches of Hedyotis Herba dispensing granules from various manufacturers have exhibited good consistency with the standard decoction， indicating that the current production process is relatively reasonable.

Objective:To investigate the role of resveratrol(RES)in improving airway inflammation in children with asthma by regulating miR-125b-5p/PRDM1 axis and its molecular mechanism.Methods:Rat model of asthma was induced by ovalbumin(OVA).The rats were randomly divided into sham group(sham),asthma group(model),10 μmol/L RES(RES-L)group,50 μmol/L RES(RES-H)group,50 μmol/L miR-125b-5p antagomir(miR-125b-5p antagomir)group and miR-125b-5p antagomir+50 μmol/L RES(miR-125b-5p antagomir+RES)group.The number of inflammatory cells in bronchoalveolar lavage fluid(BALF)was detected.HE staining and Masson three-color staining were used to observe pathological changes of lung tissue.Levels of inflammatory factors in lung homogenates were detected by ELISA.Serum from asthmatic children and healthy children was collected for analysis.Expressions of miR-125b-5p and PRDM1 in lung tissues of asthmatic and healthy children and different groups of rats were detected by RT-qPCR.Targeted binding relationship between miR-125b-5p and PRDM1 was detected by double luciferase assay.Results:HE staining showed that the airway epithelium in asthma group had a variety of inflammatory cell infiltration,while pathological changes in RES group were reduced.Masson staining showed that the area of airway collagen deposition was reduced in RES group compared with asth-ma group.The number of inflammatory cells in BALF in asthma group was higher than that in RES group.RES treatment significantly reduced airway wall and smooth muscle thickness.ELISA results showed that lung tissue in the asthma group had increased levels of IL-1β,IL-10 and TNF-α,while decreased level of IL-12,the RES group showed the opposite trend.Level of miR-125b-5p in lung tissue of asthmatic rats was significantly increased,while level of PRDM1 was decreased,and RES treatment could reverse this result.In addi-tion,treatment with miR-125b-5p antagomir alleviated airway inflammation and airway remodeling in asthmic rats.Dual luciferase assay confirmed the targeting binding relationship between miR-125b-5p and PRDM1.Compared with healthy children,serum levels of IL-1β,IL-10 and TNF-α were increased,while IL-12 level was decreased in children with asthma.Conclusion:RES inhibits the re-lease of inflammatory cytokines through HMGB1/TLR4/NF-κB pathway,alleviating asthma-induced airway inflammation and airway remodeling.