Targeting PRKDC activates the efficacy of antitumor immunity while sensitizing to chemotherapy and targeted therapy in liver hepatocellular carcinoma.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) ranks among the malignancies with the highest mortality rates, primarily due to chemoresistance culminating in treatment failure. Despite its impact, predictive models addressing disease progression, tumor microenvironment, and drug sensitivity remain elusive for LIHC patients. Recognizing the significant influence of various programmed cell death (PCD) modes on tumor evolution, this study investigates PCD genes to elucidate their implications on the prognosis and immune landscape of LIHC. METHODS: To develop the classification and model, we employed a total of 17 genes associated with PCD patterns. To collect data, we acquired gene expression profiles, somatic mutation information, copy number variation data, and corresponding clinical data from the TCGA database, specifically from LIHC patients. Moreover, we obtained spatial transcriptome data and additional bulk datasets from the Gene Expression Omnibus (GEO) database to conduct further analysis. Various experiments were conducted to validate the role of the PCD gene PRKDC in proliferation, migration, invasion, EMT, cell cycle, therapeutic sensitivity, and antitumor immunity. RESULTS: A novel LIHC classification based on these genes divided patients into two clusters, C1 and C2. The C2 cluster exhibited characteristics indicative of poor prognosis and an immune-activated microenvironment. This group showed greater response potential to immune checkpoint inhibitors, displaying higher levels of certain immune signatures and receptors. A programmed cell death index (PCDI) was constructed using 17 selected PCD genes. This index could effectively predict patient prognosis, with higher PCDI indicating poorer survival rates and a more pro-tumor microenvironment. Immune landscapes revealed varying interactions with PCDI, suggesting therapeutic targets and insights into treatment resistance. Moreover, experiments results suggested that PRKDC can augment the invasive nature and growth of malignant cells and it can serve as a potential target for therapy, offering hope for ameliorating the prognosis of LIHC patients. CONCLUSIONS: The study uncovers the insights of programmed cell death in the prognosis and potential therapeutic interventions. And we found that PRKDC can serve as a target for enhancing the efficacy of antitumor immunity while sensitizing chemotherapy and targeted therapy in liver hepatocellular carcinoma.

An Aggregation-Induced Fluorescence Probe for Detection H2S and Its Application in Cell Imaging.

Monitoring hydrogen sulfide (H2S) in living organisms is very important because H2S acts as a regulator in many physiological and pathological processes. Upregulation of endogenous H2S concentration has been shown to be closely related to the occurrence and development of tumors, atherosclerosis, neurodegenerative diseases and diabetes. Herin, a novel fluorescent probe HND with aggregation-induced emission was designed. Impressively, HND exhibited a high selectivity, fast response (1 min) and low detection limit (0.61 µM) for H2S in PBS buffer (10 mM, pH = 7.42). Moreover, the reaction mechanism between HND and H2S was conducted by Job's plot, HR-MS, and DFT. In particular, HND was successfully employed to detect H2S in HeLa cells.

Cell Cycle-Related Centromere Protein F Deficiency Suppresses Ovarian Cancer Cell Growth by Inducing Ferroptosis.

OBJECTIVES: This study aimed to investigate the involvement of the cell cycle-related protein centromere protein F (CENPF) in the development of ovarian cancer (OC) and explored its relationship with ferroptosis. DESIGN: The databases were analysed to identify differential expression of cell cycle-related proteins between individuals with OC and normal individuals. Immunohistochemistry and statistical analysis were conducted on ovarian tissues obtained from 40 patients with epithelial OC and 20 normal individuals. In vitro experiments were performed using SKOV3 and HEY epithelial OC cell lines. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mRNA microarray dataset, consisting of GSE14001, GSE54388, GSE40595, and GSE14407, was downloaded from the Gene Expression Omnibus (GEO) database to investigate the genes associated with cell cycle regulation in OC cells. CENPF was selected as the subject of study through differential analysis.Assessed the expression of CENPF in both OC patients and normal ovarian tissues using immunohistochemistry. Lentivirus infection was employed to downregulate CENPF expression, and subsequent experiments including Cell Counting Kit-8 assay, cell cycle analysis, transwell assay, and wound-healing assay were conducted to investigate the effects of CENPF on proliferation, invasion, migration, and cell cycle regulation in OC cells. The reactive oxygen species (ROS) and the malondialdehyde (MDA) assays were performed to assess the involvement of CENPF in cellular redox reactions. Western blot analysis was conducted to examine the expression levels of ferroptosis-related proteins (GPX4, SLC7A11, DMT1, and protein 53 [p53]). RESULTS: By querying and integrating cell cycle-related genes from the GEO database, in silico analyses using The Cancer Genome Atlas database combined with immunohistochemical studies, we discovered that CENPF is upregulated in OC tissues and is related to survival. Downregulation of CENPF inhibited biological function of OC cells, increased intracellular ROS and MDA levels, and downregulated the GPX4 protein and the SLC7A11/xCT protein, but upregulated the DMT1 protein and the tumour p53 expression to induce ferroptosis. LIMITATIONS: This study did not investigate ferroptosis-related studies following CENPF overexpression, and the findings have not been validated in animal studies. CONCLUSIONS: Our findings demonstrated that the deficiency of CENPF played a crucial anti-oncogenic role in the progression of OC through the mechanism of ferroptosis.

Potential value of serum prealbumin and serum albumin in the identification of postoperative delirium in patients undergoing knee/hip replacement: an observational study and internal validation study.

Background: Postoperative delirium (POD) is a common postoperative neurological complication that can lead to a variety of postoperative complications. At present, the pathogenesis of POD is unclear. This study aims to explore the relationship between serum prealbumin and serum albumin and POD and whether serum prealbumin and serum albumin influence POD through POD core pathology. Objective: We enrolled 500 Chinese Han patients between September 2020 to January 2023. We analyzed the risk and protective factors of POD using the multivariate logistic regression. We also assessed the predictive power of serum prealbumin, serum albumin, and both in combination with CSF POD biomarkers. We used Stata MP16.0. to examine whether the association between serum prealbumin and serum albumin and POD was mediated by CSF POD biomarkers, and conducted an internal validation study to verify the accuracy of the combination of serum prealbumin + serum albumin + CSF POD biomarkers for predicting POD. The model was visualized using ROC curve and decision curve analysis (DCA). DynNom and Shiny packages were used to create an online calculator. Ten patients who had POD occurring from February 2023 to October 2023 were selected for internal verification. Results: Finally, a total of 364 patients were included in our study. Levels of serum prealbumin, serum albumin in the POD group were lower than those in the NPOD group. The lever of serum prealbumin, serum albumin were protective factors for POD. The relationship between serum prealbumin, serum albumin and POD was partially mediated by T-tau (12.28%) and P-tau (20.61%). The model combining serum prealbumin and serum albumin and POD biomarkers exhibited a relatively better discriminatory ability to predict POD. DCA also showed that the combination of serum prealbumin and serum albumin and POD biomarkers brought high predictive benefits to patients. The dynamic online calculator can accurately predict the occurrence of POD in the internal validation study. Conclusion: Preoperative low serum prealbumin and serum albumin levels were the preoperative risk factors for POD, which is partly mediated by T-tau and P-tau. The model combining serum prealbumin and serum albumin and CSF POD biomarkers can accurately predict the occurrence of POD. Clinical trial registration: http://www.clinicaltrials.gov, identifier ChiCTR2000033439.

Integrated network pharmacology and cellular assay reveal the biological mechanisms of Limonium sinense (Girard) Kuntze against Breast cancer.

BACKGROUND: Limonium Sinense (Girard) Kuntze (L. sinense) has been widely used for the treatment of anaemia, bleeding, cancer, and other disorders in Chinese folk medicine. The aim of this study is to predict the therapeutic effects of L. sinense and investigate the potential mechanisms using integrated network pharmacology methods and in vitro cellular experiments. METHODS: The active ingredients of L. sinense were collected from published literature, and the potential targets related to L. sinense were obtained from public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and DisGeNET enrichment analyses were performed to explore the underlying mechanisms. Molecular docking, cellular experiments, RNA-sequencing (RNA-seq) and Gene Expression Omnibus (GEO) datasets were employed to further evaluate the findings. RESULTS: A total of 15 active ingredients of L. sinense and their corresponding 389 targets were obtained. KEGG enrichment analysis revealed that the biological effects of L. sinense were primarily associated with "Pathways in cancer". DisGeNET enrichment analysis highlighted the potential role of L. sinense in the treatment of breast cancer. Apigenin within L. sinense showed promising potential against cancer. Cellular experiments demonstrated that the L. sinense ethanol extract (LSE) exhibited a significant growth inhibitory effect on multiple breast cancer cell lines in both 2D and 3D cultures. RNA-seq analysis revealed a potential impact of LSE on breast cancer. Additionally, analysis of GEO datasets verified the significant enrichment of breast cancer and several cancer-related pathways upon treatment with Apigenin in human breast cancer cells. CONCLUSION: This study predicts the biological activities of L. sinense and demonstrates the inhibitory effect of LSE on breast cancer cells, highlighting the potential application of L. sinense in cancer treatment.

Daytime dysfunction may be associated with postoperative delirium in patients undergoing total hip/knee replacement: The PNDABLE study.

PURPOSE: Postoperative delirium (POD) is a usual complication after total hip/knee replacement, which may be affected by sleep characteristics. However, up to now, preoperative sleep characteristics have not been evaluated as risk factors of POD. The relationship between self-reported sleep characteristics and POD in patients has been investigated in this study. PATIENTS AND METHODS: We recruited 495 cognitively intact individuals in the final analysis from the Perioperative Neurocognitive Disorder and Biomarker Lifestyle study. Sleep characteristics were tested by the Pittsburgh Sleep Quality Index (PSQI). Mini-mental state examination was applied to assess preoperative mental status of patients. Postoperatively, we used confusion assessment method and memorial delirium assessment scale to evaluate the incidence of POD and POD severity, respectively. The cerebrospinal fluid (CSF) levels of T-tau, P-tau, Aß40, and Aß42 were detected by enzyme-linked immune-sorbent assay before the operation. Logistic regression, multiple linear regression, and mediation effects were performed to analyze the relationship between self-reported sleep characteristics and POD. RESULTS: POD was detected in 11.31% (56/495) of the patients, with logistic regression analysis showing that daytime dysfunction, P-tau, and T-tau were risk factors of POD, and Aß42 was a protective factor of POD. Multiple linear regression analysis confirmed that daytime dysfunction was positively correlated with P-tau in patients with POD. Meanwhile, compared to the patients with no postoperative delirium, the CSF levels of P- and T-tau were higher in patients with POD. Furthermore, mediation analysis showed that it was probable that daytime dysfunction mediated POD through P-tau (proportion: 12.90%) partially. CONCLUSION: Daytime dysfunction is a risk factor of POD preoperatively. To sum up, CSF P-tau protein might partially mediate the influence of daytime dysfunction on POD. CLINICAL TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (ChiCTR2000033439).

Relationship between preoperative neutrophil-to-lymphocyte ratio and postoperative delirium: The PNDABLE and the PNDRFAP cohort studies.

OBJECTIVES: In this study, the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and Alzheimer-related biomarkers in cerebrospinal fluid (CSF) was investigated to determine whether high NLR is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy. METHODS: We selected 1000 patients from the perioperative neurocognitive disorder risk factor and prognosis (PNDRFAP) database and 999 patients from the perioperative neurocognitive disorder and biomarker lifestyle (PNDABLE) database. Patients in the PNDABLE database have been measured for Alzheimer-related biomarkers in CSF (Aß40 , Aß42 , P-tau, and tau protein). Mini-mental state examination was used to assess the preoperative mental status of patients. POD was diagnosed using the confusion assessment method and assessed for severity using the memorial delirium assessment scale. Logistic regression analysis was utilized to explore the association of preoperative NLR with POD. What's more, we also performed sensitivity analysis by adding corrected confounders, and the results were almost unchanged. Spearman's rank correlation was used to determine the associations between NLR and Alzheimer-related biomarkers. Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Finally, we use decision curves and the nomogram model to evaluate the efficacy of preoperative NLR in predicting POD; we also performed external validation using data from Qilu Hospital. RESULT: Logistic regression results showed that an elevated preoperative NLR was a risk factor for the development of POD in patients (PNDRFAP: OR = 1.067, 95% CI 1.020-1.116; PNDABLE: OR = 1.182, 95% CI 1.048-1.335, p < .05). Spearman's rank correlation analysis showed a positive but weak correlation between NLR and P-tau/T-tau (R = .065). The mediating effect results indicate that NLR likely mediates the occurrence of POD through elevated tau protein levels (proportion: 47.47%). The results of the box plots showed statistically significant NLR and CSF biomarkers between the POD and non-POD (NPOD) groups (p < .05), with higher NLR, P-tau, and T-tau in the POD group than in the NPOD group. In contrast, the NPOD group had higher Aß42 levels compared to the POD group. In addition, we used R package to plot the decision curve and nomogram both suggesting a good predictive effect of preoperative NLR on the occurrence of POD. CONCLUSION: Elevated preoperative NLR levels may be a risk factor for POD and likely mediate the development of POD through elevated P-tau/T-tau levels.

Alcohol consumption may be associated with postoperative delirium in the elderly: the PNDABLE study.

OBJECTIVES: This study aimed to reveal the relationship between alcohol consumption and Postoperative delirium (POD) in the elderly. METHODS: We selected 252 patients from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE ) study. Patients in the PNDABLE database have been measured for Alzheimer-related biomarkers in CSF (Aß40, Aß42, P-tau, and tau protein). Mini-Mental State Examination (MMSE) was used to assess the preoperative mental status of patients. POD was diagnosed using the Confusion Assessment Method (CAM) and assessed for severity using the Memorial Delirium Assessment Scale (MDAS). Logistic regression analysis was utilized to explore the association of alcohol consumption with POD. Linear regression analysis was used to study the relationship between alcohol consumption and CSF biomarkers. Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of alcohol consumption and CSF biomarkers in predicting POD.  RESULT: The incidence of POD was 17.5%. Logistic regression showed that alcohol consumption (OR = 1.016, 95%CI 1.009-1.024, P < 0.001) is a risk factor for POD. What's more, Aß42 is a protective factor for POD (OR = 0.993, 95%CI 0.989-0.997, P < 0.05), and P-Tau was a risk factor for POD (OR = 1.093, 95%CI 1.022-1.168, P < 0.05). Linear regression analysis revealed that alcohol consumption was negatively associated with CSF Aß42 (ß = -0.638, P < 0.001) in POD patients. Mediation analyses showed that alcohol consumption is likely to partially mediate POD through Aß42 (proportion:14.21%). ROC curve showed that alcohol consumption (AUC = 0.904; P < 0.001) exhibited a relatively better discriminatory ability in POD prediction compared to Aß42 (AUC = 0.798; P < 0.001). The calibration curve indicated a good nomogram prediction (P = 0.797). CONCLUSION: Alcohol consumption is a risk factor for POD (particularly for those with > 24 g a day on average) in the elderly, and contributes to POD through the mediation of Aß42.

Selection and Validation of Reference Genes in Different Tissues of Okra (Abelmoschus esculentus L.) under Different Abiotic Stresses.

Okra (Abelmoschus esculentus L.) is a particular vegetable with both edible and medicinal values. However, the expression pattern of the okra reference genes in response to abiotic stress has not been explored. In the present study, 18 potential reference genes were selected from okra in various tissues and abiotic stress conditions, and their expression levels were detected by Real-Time quantitative PCR (RT-qPCR). Their expression stabilities were calculated by four algorithms (geNorm, NormFinder, BestKeeper, and RefFinder). Under cold stress, the most stable genes included GAPC1 and CYP (leaf), CYP and ACT7 (root), HIS6 and GAPC1 (stem), and HIS6 and 60s (different tissues). Under salt stress, EF-1α and UBQ (leaf), EF-1α and UBQ (root), TUA4 and Eif (stem), and HIS6 and Eif (different tissues) were the most stable genes. Under drought stress, UBQ and Eif in the leaf, HIS6 and Eif in the root, TUA4 and HIS6 in the stem, and UBQ and Eif in different tissues were most stably expressed in okra. In addition, complete sequencing results by RefFinder showed that HIS6 and ACT7 in the leaf, HIS6 and Eif in the root, UBC5B and 60s in the stem, and HIS6 and Eif in different tissues, were most the suitable reference genes for okra. Furthermore, AeMYB1R1 transcription factor was used to verify the reliability of RT-qPCR values. In summary, this study was carried out to demonstrate the potential reference genes of okra under abiotic stress, aiming to provide a molecular basis for functional gene analysis and regulatory mechanism research of okra.

Low-valent copper on molybdenum triggers molecular oxygen activation to selectively generate singlet oxygen for advanced oxidation processes.

Singlet oxygen (1O2), which is difficult to generate, plays an important role in chemosynthesis, biomedicine and environment. Molecular oxygen (O2) is a green oxidant to produce 1O2 cost-effectively. However, O2 activation is difficult due to its spin-forbidden nature. Moreover, the main products of O2 activation are basically hydrogen peroxide (H2O2) and hydroxyl radical (•OH), but rarely 1O2. Herein, we innovatively realize the selective generation of 1O2 via O2 activation by a facile molybdenum (Mo)/Cu2+ system. In this system, Mo firstly reduces Cu2+ in solution to low-valence Cu0/Cu+ on its surface. Cu0/Cu+ activates O2 to generate superoxide radical (O2•-). Importantly, O2•- can be captured immediately and oxidized to 1O2 by surface-bound Mo6+ rather than reduced to H2O2. As a result, the Mo/Cu2+ system can selectively produce 1O2. Under air and O2 conditions, the degradation efficiency of ibuprofen by Mo/Cu2+ system is 67.2 % and 76.6 %, respectively. The degradation efficiencies of bisphenol A, rhodamine B and furfuryl alcohol are 77.1 %, 87.7 % and 91.1 %, respectively. The dosages of Mo and Cu2+ are 0.4 g/L and 3 mM, respectively, and the reaction time is 2 h. Interestingly, the activity of Mo decreased by only 4.2 % after 4 cycles. Therefore, this study provides a green pathway to selectively generate 1O2 for advanced oxidation processes.

Spontaneous Formation of Low Valence Copper on Red Phosphorus to Effectively Activate Molecular Oxygen for Advanced Oxidation Process.

Efficient spontaneous molecular oxygen (O2) activation is an important technology in advanced oxidation processes. Its activation under ambient conditions without using solar energy or electricity is a very interesting topic. Low valence copper (LVC) exhibits theoretical ultrahigh activity toward O2. However, LVC is difficult to prepare and suffers from poor stability. Here, we first report a novel method for the fabrication of LVC material (P-Cu) via the spontaneous reaction of red phosphorus (P) and Cu2+. Red P, a material with excellent electron donating ability and can directly reduce Cu2+ in solution to LVC via forming Cu-P bonds. With the aid of the Cu-P bond, LVC maintains an electron-rich state and can rapidly activate O2 to produce ·OH. By using air, the ·OH yield reaches a high value of 423 µmol g-1 h-1, which is higher than traditional photocatalytic and Fenton-like systems. Moreover, the property of P-Cu is superior to that of classical nano-zero-valent copper. This work first reports the concept of spontaneous formation of LVC and develops a novel avenue for efficient O2 activation under ambient conditions.

Integrated analysis reveals effects of bioactive ingredients from Limonium Sinense (Girard) Kuntze on hypoxia-inducible factor (HIF) activation.

Limonium Sinense (Girard) Kuntze is a traditional Chinese medicinal herb, showing blood replenishment, anti-tumour, anti-hepatitis, and immunomodulation activities amongst others. However, the mechanism of its pharmacological activities remains largely unknown. Here, we investigated the effects of bioactive ingredients from Limonium Sinense using an integrated approach. Water extracts from Limonium Sinense (LSW) showed a strong growth inhibitory effect on multiple cells in both 2D and 3D cultures. Global transcriptomic profiling and further connectivity map (CMap) analysis identified several similarly acting therapeutic candidates, including Tubulin inhibitors and hypoxia-inducible factor (HIF) modulators. The effect of LSW on the cell cycle was verified with flow cytometry showing a G2/M phase arrest. Integrated analysis suggested a role for gallic acid in mediating HIF activation. Taken together, this study provides novel insights into the bioactive ingredients in Limonium Sinense, highlighting the rich natural resource and therapeutic values of herbal plants.

The relationship between mild cognitive impairment and postoperative delirium undergoing total knee arthroplasty: The PNDABLE study.

Background: Patients undergoing surgery are at a higher risk of developing postoperative delirium (POD) as a result of anesthesia and surgical procedures. This study examined the association between POD and mild cognitive impairment (MCI) and whether MCI influences POD through the core pathology of POD. Methods: We enrolled Chinese Han patients undergoing unilateral total knee arthroplasty (aged 50-90, weighing 50-80 kg, and using ASAI-II), combined with epidural anesthesia between October 2020 and June 2021. All the participants were assessed using Winblad's criteria for diagnosing MCI on pre-operation and using the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment Scale (MDAS) postoperative 1-7 days (or before discharge) for diagnosing POD by an anesthesiologist. Cerebrospinal fluid (CSF) biomarkers of POD were measured by enzyme-linked immunosorbent assay (ELISA). To examine the mechanism by which POD pathologies affect cognition, causal mediation analyses were performed. Results: POD incidence was 20.2%, including 32.5% in the MCI group and 12.4% in the non-mild cognitive impairment (NMCI) group. The MCI and CSF levels of T-tau and P-tau were risk factors, and the CSF levels of Aß42, Aß42/ T-tau, and Aß42/ P-tau were protective factors in POD (p < 0.05). Part of the effects of MCI on cognition can be attributed to amyloid pathology and tau. Conclusion: MCI may be a reasonably good prognostic factor in POD development. Overall, amyloid pathology and tau protein might partially mediate the influence of MCI on POD. Clinical trial registration: www.clinicaltrials.gov, identifier: ChiCTR2000033439.

Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells.

This study was intended to establish the predictive target of Shikonin (SK) against ovarian cancer using network pharmacology and to clarify the potential mechanism of SK in promoting apoptosis in ovarian cancer. Cell Counting Kit-8 assay, plate clone assays, LDH assay, flow cytometric analysis of Annexin V-fluorescein isothiocyanate/propidium iodide staining, and western blotting were used to assess the effect of SK on apoptosis of ovarian cancer cell lines (SKOV3 and A2780). Pharmacodynamic targets were used to predict the targets of SK and ovarian cancer. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses were used to analyze the biological functions and signal pathways of these targets. SK promoted apoptosis in ovarian epithelioid adenocarcinoma cells. SK-ovarian cancer pharmacodynamic target analysis screened 17 related genes. GO and KEGG analyses showed that SK affected the estrogen signaling pathway. SK inhibited the expression of GPER in SKOV3 and A2780 cells and downregulated the expression of EGFR, p-EGFR, PI3K, and p-AKT in a concentration-dependent manner. The apoptosis-promoting effect of SK was enhanced by GPER-specific agonist G1 and inhibited by the specific inhibitor G15. The expression of EGFR, p-EGFR, PI3K, and p-AKT was decreased by G1 and reversed by G15. SK also inhibited tumor growth in the SKOV3 xenograft model, and it acted synergistically with G1. However, the effect can be attenuated by G15 in vivo. In summary, SK may affect the apoptosis of ovarian cancer cells through GPER/EGFR/PI3K/AKT, and GPER may be a key target of SK in ovarian cancer cell apoptosis.

Potential value of preoperative fasting blood glucose levels in the identification of postoperative delirium in non-diabetic older patients undergoing total hip replacement: The perioperative neurocognitive disorder and biomarker lifestyle study.

Background: Postoperative delirium (POD) is a common complication after total hip replacement. This study aims to explore the relationship between preoperative fasting blood glucose (FBG) levels and POD in non-diabetic older patients undergoing total hip replacement. Materials and methods: This study included a total of 625 patients undergoing elective total hip replacement under combined spinal and epidural anesthesia from the PNDABLE study. The relationship between POD and preoperative FBG was analyzed by using the logistic regression model. The associations of FBG with individual cerebrospinal fluid (CSF) biomarkers were detected by using the multivariable linear regression model controlling for age, gender, and education level. The mediation effects were explored by mediation analyses with 5,000 bootstrap iterations, while sensitivity analysis was used to test the reliability and stability of the results. The receiver operating characteristic (ROC) curve and the nomogram model were applied to evaluate the efficacy of FBG and POD-related CSF biomarkers in predicting POD. POD assessment was performed two times daily by a trained anesthesiologist at 9:00-10:00 am and 2:00-3:00 pm on postoperative days 1-7 or before the patients were discharged from the hospital. POD was defined by the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Enzyme-linked immunosorbent assay (ELISA) was used to measure CSF Aß40, Aß42, T-tau, and P-tau levels. Results: POD was detected in 10.2% (60/588) of the patients. Logistic regression analysis showed that after adjusting for age and education level, the increased levels of FBG (OR 1.427, 95% CI 1.117-1.824, P = 0.004), CSF P-tau (OR 1.039, 95% CI 1.019-1.060, P < 0.001), and CSF T-tau (OR 1.013, 95% CI 1.009-1.018, P < 0.001) were risk factors for POD, and the increased level of CSF Aß42 (OR 0.996, 95% CI 0.994-0.998, P = 0.001) was a protective factor for POD. Multivariable linear regression models showed that when adjusting for age, gender, and education level, in the POD group, higher preoperative FBG levels were negatively correlated with the CSF Aß42 level (ß = -0.290, P = 0.028) and positively correlated with CSF P-tau (ß = 0.384, P = 0.004) and T-tau (ß = 0.447, P < 0.001). In the non-POD group, a higher preoperative FBG was not related to CSF biomarkers. Mediated effect analysis showed that CSF T-tau (proportion = 17.1%) had an apparent mediation effect on the relationship between FBG and POD. Sensitivity analysis revealed that the results from the logistic regression and multivariable linear regression models were consistent with previous results. Conclusion: Increased preoperative FBG was a risk factor for POD in older patients without T2DM, and T-tau might mediate the relationship between FBG and POD.

Potential Value of Serum Uric Acid in the Identification of Postoperative Delirium in Geriatric Patients Undergoing Knee Replacement.

Objectives: The relationship between preoperative serum uric acid (SUA) and cerebrospinal fluid (CSF) Alzheimer-related biomarkers were investigated to determine whether high SUA is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy. Methods: The participants were selected from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study and the Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study. The logistic regression equation was used to analyze the risk factors and protective factors of POD. The interaction term (SUA × Sex) was introduced into the linear model to explore the potential modification effects of sex on the identified correlations. We analyzed the mediating effects of Alzheimer-related biomarkers. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of SUA and Alzheimer-related biomarkers in predicting POD. Results: Patients with POD had elevated SUA level (PNDRFAP: p = 0.002, PNDABLE: p < 0.001). Preoperative SUA level was positively correlated with CSF phosphorylated tau (P-tau) (p = 0.027) and ß-amyloid42 (Aß42)/P-tau (p = 0.023). Interaction analysis did not find any modification effect of sex. The relationship between SUA and POD was partially mediated by CSF P-tau (15.3%). ROC curve showed that the model combining SUA and Alzheimer-related biomarkers had better performance in predicting POD [area under the curve (AUC) = 0.880; p < 0.001], and the predictive model is accurate. Conclusions: High SUA may enhance CSF P-tau level, thus increasing the risk of POD, and the model combining SUA and Alzheimer-related biomarkers can accurately predict the occurrence of POD.

The Relationship Between Cardiovascular Disease Risk Score and Postoperative Delirium: The PNDABLE Study.

Objective: We aimed to investigate the relationship between Framingham Heart Study general cardiovascular disease risk score (FHS-CVD risk score) and postoperative delirium (POD) among patients who had unilateral total knee arthroplasty performed under epidural anesthesia. Furthermore, we examined whether such a hypothesized relationship was mediated by the cerebrospinal fluid (CSF) biomarkers. Methods: A total of 750 participants were included in the current study. And the data were drawn from the database obtained from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study. The preoperative cognitive function of participants was measured by using Mini-Mental State Examination (MMSE). The incidence of POD was assessed using the Confusion Assessment Method (CAM). The POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). The POD CSF biomarkers included in the current study were: Aß42, T-tau, P-tau, Aß42/T-tau, and Aß42/P-tau. The level of the CSF biomarkers was measured using the enzyme-linked immune-sorbent assay (ELISA) in the PNDABLE study. Linear regression analysis was performed to examine the relationship between the FHS-CVD risk score and the POD CSF biomarkers. Logistic regression was used to analyze the relationship between FHS-CVD risk score, POD CSF biomarkers, and POD incidence. The proposed mediating effect of CSF biomarkers was evaluated using Mediation Analysis with 10,000 bootstrapped iterations. The receiver operating characteristic (ROC) curve is chosen as the evaluation metric for assessing the efficacy of the FHS-CVD risk score in predicting POD. Results: In the PNDABLE study, the overall incidence of POD was 22.9% with 37.2% in the higher vascular risk group and 7.9% in the lower vascular risk group. Multiple linear regression models showed that a higher preoperative FHS-CVD risk score was positively correlated with CSF T-tau (ß = 0.218, P = 0.015) and P-tau level (ß = 0.309, P < 0.001) in the higher vascular risk group. After adjusting for age (40-90 years), gender, education, MMSE, smoking history, drinking history, hypertension, diabetes, and the presence of CHD (cardiovascular heart disease), the results of the logistic regression analysis demonstrated the effect of Aß42 (OR = 0.994, 95% CI 0.992-0.996, P < 0.001), Aß42/T-tau (OR = 0.353, 95% CI 0.254-0.491, P < 0.001), and Aß42/P-tau (OR = 0.744, 95% CI 0.684-0.809, P < 0.001) in protecting patients against POD. However, the FHS-CVD risk score (OR = 1.142, 95% CI 1.017-1.282, P = 0.025) and the remaining two biomarkers: T-tau (OR = 1.005, 95% CI 1.004-1.007, P < 0.001) and P-tau (OR = 1.045, 95%CI 1.029-1.062, P < 0.001) were identified as the risk factors. Mediation analyses revealed that the association between FHS-CVD risk score and POD was partially mediated by T-tau (proportion: 31.6%) and P-tau (proportion: 23.6%). The predictive power of the FHS-CVD risk score was validated by the ROC curve with an AUC of 0.7364. Conclusion: Higher vascular risk score is one of the preoperative risk factors for POD, which is partly mediated by CSF biomarker tau protein. Clinical Trial Registration: [www.clinicaltrials.gov], identifier [ChiCTR2000033439].

The Relationship Between Suboptimal Social Networks and Postoperative Delirium: The PNDABLE Study.

Background: Although it has been proven that social networks are related to cognition, studies are conducted to characterize the correlation between social networks and postoperative delirium (POD). Objective: We investigated whether suboptimal social networks are a risk factor for POD, and to verify whether different levels of intimacy in the same social relationship can affect the concentration of cerebrospinal fluid (CSF) biomarkers, such as amyloid-ß (Aß42), total tau (T-tau), and phosphorylated tau (P-tau), and the mediating role of CSF biomarkers between social network and POD in middle-aged and elderly Han people. Methods: Our study recruited 743 participants from The Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study. Confusion Assessment Method (CAM) was used to evaluate the incidence of POD and its severity was measured using the Memorial Delirium Assessment Scale (MDAS). The social networks were measured using self-reported questionnaires about social ties. Mann-Whitney U test, Logistic Regression and Independent-samples test were used for Statistical Analysis. Results: The incidence of POD was 20.7%. Mann-Whitney U test showed that the total score of the social network was associated with POD (P < 0.001). Independent-samples test showed that different levels of intimacy in the same social relationship were significantly associated with CSF POD biomarkers, and mediation analyses revealed that the association between suboptimal social networks and POD was partially mediated by T-tau (proportion: 20%), P-tau (proportion: 33%), Aß42/T-tau (proportion: 14%), and Aß42/P-tau (proportion: 15%). Conclusion: Having suboptimal social networks is a risk factor for POD in middle-aged and elderly Han people. CSF POD biomarkers can mediate the correlation between suboptimal social networks and POD, which is mainly mediated by tau protein. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2000033439.

The Quality of Life of Patients with Colorectal Cancer and a Stoma in China: A Quantitative Cross-sectional Study.

OBJECTIVE: To explore quality of life (QOL) in patients with colorectal cancer and a stoma and factors associated with their QOL. METHODS: A quantitative cross-sectional study was carried out in the stoma and wound care clinic of a cancer hospital in China. Participants were recruited from clinic patients. Investigators collected demographic data and clinical information; QOL was measured using a Chinese version of the stoma-QOL scale. RESULTS: In total, 359 participants took part; 161 (44.8%) had an ileostomy, whereas the others had a colostomy, and about half of the participants (46.5%) had a permanent stoma. The mean age was 57.86 ± 11.92 years. The QOL scores of most participants were poor, with a median value of 49.44. Participants whose stoma was cared for by others had a significantly lower QOL score than those who cared for their own stomas (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.05-2.38; P = .029). Participants with a temporary stoma had a lower QOL score than those with a permanent stoma (OR, 2.08; 95% CI, 1.275-3.40; P = .004). Further, participants with a complication had a lower QOL score than those without (OR, 1.62; 95% CI, 1.07-2.43; P = .022). CONCLUSIONS: These findings suggest a need for well-developed interventions to improve the QOL of these patients. This study provides valuable insights to inform the development of future clinical practice and research in this area in China and beyond.

New fluorescent chemosensors based on mononuclear copper complex for highly selective and sensitive detection of phosphate anion in aqueous solution and living cells.

Three new probes, named, [Cu(L1)2]Cl2 (C1), [Cu(L2)2]Cl2 (C2) and [Cu(L3)2]Cl2 (C3) were synthesized and well characterized. The probes C1, C2 and C3 were successfully achieved for the efficient detection of PO43- as turn-on fluorescence chemosensors in DMSO/H2O (v:v = 2:8, Tris-HCl pH = 7.20). The limit of detection (LOD) of probes C1, C2 or C3 for PO43- could be as low as 0.029 µM, 0.048 µM, 0.079 µM, respectively, which were effectively applied for the determination of the PO43- concentration in environmental water of swimming pool. What's more, the binding constant between probes C1, C2, C3 and PO43- are estimated to be 3.11 × 107 M-1 (R2 = 0.9992), 1.84 × 107 M-1 (R2 = 0.9956), 1.93 × 107 M-1 (R2 = 0.9976), respectively. The proposed mechanism for the "on-off-on" fluorescence response was confirmed by ESI-MS and fluorescence spectrum. Moreover, the membrane-permeable probe C1 was successfully demonstrated in monitoring of PO43- in cultured HepG2 cells.