The choice of biopsy method is critical in diagnosing prostate cancer (PCa). This retrospective cohort study compared systematic biopsy (SB) or cognitive fusion-targeted biopsy combined with SB (CB) in detecting PCa and clinically significant prostate cancer (csPCa). Data from 2572 men who underwent either SB or CB in Fudan University Shanghai Cancer Center (Shanghai, China) between January 2019 and December 2023 were analyzed. Propensity score matching (PSM) was used to balance baseline characteristics, and detection rates were compared before and after PSM. Subgroup analyses based on prostate-specific antigen (PSA) levels and Prostate Imaging-Reporting and Data System (PI-RADS) scores were performed. Primary and secondary outcomes were the detection rates of PCa and csPCa, respectively. Of 2572 men, 1778 were included in the PSM analysis. Before PSM, CB had higher detection rates for both PCa (62.9% vs 52.4%, odds ratio [OR]: 1.54, P < 0.001) and csPCa (54.9% vs 43.3%, OR: 1.60, P < 0.001) compared to SB. After PSM, CB remained superior in detecting PCa (63.1% vs 47.9%, OR: 1.86, P < 0.001) and csPCa (55.0% vs 38.2%, OR: 1.98, P < 0.001). In patients with PSA 4-12 ng ml -1 (>4 ng ml -1 and ≤12 ng ml -1 , which is also applicable to the following text), CB detected more PCa (59.8% vs 40.7%, OR: 2.17, P < 0.001) and csPCa (48.1% vs 27.7%, OR: 2.42, P < 0.001). CB also showed superior csPCa detection in those with PI-RADS 3 lesions (32.1% vs 18.0%, OR: 2.15, P = 0.038). Overall, CB significantly improves PCa and csPCa detection, especially in patients with PSA 4-12 ng ml -1 or PI-RADS 3 lesions.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Propensity Score ; Retrospective Studies ; Middle Aged ; Aged ; Image-Guided Biopsy/methods* ; Prostate-Specific Antigen/blood* ; Prostate/diagnostic imaging*

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

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.

AIM To investigate the effects of Polygonum cuspidatum and polydatin on lipid deposition in adipose tissue of high-fat diet-induced obese mice.METHODS Forty male C57BL/6J mice were randomly assigned to either a control group(10 mice)fed standard chow or a diet-induced obesity(DIO)group(30 mice)fed a high-fat diet for 8 weeks.The successful mouse models were randomly assigned to the model group,the polydatin group(250 mg/kg)and the P.cuspidatum group(4.5 g/kg),with 8 mice in each group,to resume their high-fat diet during the following 8 weeks corresponding drug administration by gavage.Weekly body weight measurements were recorded for all mice.Serum TG,TC and LDL levels were quantified post-treatment.Histopathological assessment of adipose tissue was performed using HE staining.The mRNA expressions of AMPK,SREBP-1c and FAS in adipose tissue were analyzed by RT-qPCR.The protein expressions of p-AMPK,SREBP-1c and FAS in adipose tissue was detected by Western blot.RESULTS Compared to the control group,the model group displayed significantly higher body weight,inguinal fat weight and epididymal fat weight(P＜0.05);elevated serum TG,TC and LDL levels(P＜0.05);markedly enlarged volumes of inguinal and epididymal adipocytes(P＜0.01);reduced p-AMPK protein expression in inguinal adipose tissue(P＜0.01);and upregulated mRNA and protein expressions of SREBP-1c and FAS(P＜0.05,P＜0.01).Compared to the model group,both the P.cuspidatum group and polygonin group exhibited significantly reduced body weight and inguinal fat weight(P＜0.05);decreased serum TG and TC levels(P＜0.05);reduced inguinal adipocyte size(P＜0.01);elevated p-AMPK protein expression in inguinal adipose tissue(P＜0.01);and downregulated mRNA and protein expressions of SREBP-1c and FAS(P＜0.05,P＜0.01).CONCLUSION P.cuspidatum and polydatin significantly increases p-AMPK expression while decreasing SREBP-1c and FAS levels in adipose tissue.This regulatory effect likely contributes to reduction of body weight in obese mice through suppression of lipogenesis.

Objective:To investigate the sleep characteristics and executive function development in children aged 6-12 years with attention deficit hyperactivity disorder(ADHD),and to examine the relationship between them.Methods:A total of 112 children diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ),and 45 age-and gender-matched typically developing children were recruited.Sleep characteristics were assessed with the Chinese version of Children's Sleep Habits Questionnaire(CSHQ)and ActiGraph GT9X Link Three-axis acceleration body dynamometert.Core ADHD symptoms and multi-ple dimensions of executive function were evaluated withthe Swanson,Nolan,and Pelham scale,Fourth Edition(SNAP-Ⅳ)assessment scale,Stroop Color-Word Test(SCWT),Rey-Osterrieth Complex Figure Test(ROCFT),and Trail Making Test(TMT).Results:Compared with controls,children with ADHD showed significantly higher total CSHQ scores,sleep resistance,sleep anxiety,and sleep maintenance time(P＜0.05),and had significantly lower sleep efficiencies measured by ActiGraph GT9X Link(P＜0.05).In the SCWT,children with ADHD re-quired more time in the word interference and color interference tests(P＜0.05).In the ROCFT,the scores of im-mediate details,delayed details,immediate structure,and delayed structure were lower in the children with ADHD(P＜0.05).In the TMT,the number of errors in the digit connection and the time and number of errors in the digit-letter connection were higher in the children with ADHD(P＜0.05).The total CSHQ scores of ADHD children were negatively correlated with the working memory scores and positively correlated with the core symptom scores.Conclusion:Children with ADHD exhibit notable sleep disturbance and underdeveloped executive func-tion.the sleep problems,as measured by CSHQ are associated significantly with deficits in executive function.