BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

There is a complex biological mechanism in the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(PKB/Akt)/mammalian target of rapamycin(mTOR)signaling pathway,which plays a key role in the development and development of lymphoma.In this review,the relevant literature of PI3K inhibitor research in the past five years summarized and analyzed,and found that the research and development,application,efficacy,and adverse reactions of PI3K inhibitors are the current research hotspots,and the positive results of PI3K inhibitors in clinical trials and basic research have strongly demonstrated the potential of PI3K inhibitors in personalized treatment of lymphoma.In order to maximize the clinical benefits,a variety of strategies need to be explored,including novel drugs with better selectivity and safety,and related combination therapies.

Objective A targeted nanopeptides(VEGF/TIE-2 targeted nanopeptides,VTN)that simultaneously inhibits vascu-lar endothelial growth factor(VEGF)/tyrosine kinase with immunoglobulin-like and EGF-like domains-2(TIE-2)signaling pathways were designed and synthesized,and explore its inhibitory effect on angiogenesis in renal clear cell carcinoma(ccRCC).Methods VTN and non-self-assembling control VTN-C were prepared by solid-phase peptide synthesis technology,and the molecular structures of VTN and VTN-C were analyzed by electrospray ionization mass spectrometry(ESI-MS).The CCK-8 method was used to evaluate the effect of VTN on the cell viability of human umbilical vein endothelial cells(HUVEC).The cell scratch assay,Transwell invasion assay and angiogenesis assay were used to detect the inhibitory effects of VTN on migration,invasion and angiogenesis of HUVEC.Western blot was used to detect the effect of VTN on the phosphorylation of downstream proteins of VEGF and TIE-2 signaling pathways.A 786-O cell mouse model was established,and the effects of VTN on tumor angiogenesis and tumor progression were observed through animal ex-periments.Results ESI-MS showed that the main charge state peaks of both synthesized VTN and VVTN-C pointed to the same molec-ular weight,which was highly consistent with the corresponding theoretical molecular mass.Immunofluorescence showed that VTN co-lo-calized with VEGF and TIE-2.VTN combined with MMP-2 could significantly inhibit the activity of HUVEC(P<0.001).The cell inva-sion rate and scratch closure rate in the VTN group were reduced by(78.30±1.35)%and(37.09±3.49)%compared those in the PBS group,respectively(P<0.001).Angiogenesis experiments showed that VTN could significantly inhibit the angiogenesis of HUVEC(P<0.001).Western blot showed that VTN significantly inhibited the phosphorylation of Akt and ERK(P<0.001).The results from animal experimentsshowed that tumor volume in the VTN group was decreased by(87.16±1.30)%compared with the control group,and the CD31-positive area was reduced(P<0.001).Conclusion VTN significantly blocks ccRCC angiogenesis and delays tumor progression by inhibiting VEGF and TIE-2 signaling pathways and downregulating Akt and ERK phosphorylation.

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.