Rates and Impact of Serious Adverse Events after Endovascular Thrombectomy among Large Vessel Occlusion Stroke Patients.

Objective Complications or serious adverse events (SAEs) are common in the treatment of patients with large vessel occlusion stroke. There has been limited study of the impact of SAEs for patients after endovascular thrombectomy (EVT). The goal of this study was to characterize the rates and clinical impact of SAEs following EVT. Methods A post-hoc analysis was performed using pooled databases of the 'DEVT' and 'RESCUE BT' trials. SAEs were designated as symptomatic intracranial hemorrhage, brain herniation or craniectomy, respiratory failure, circulatory failure, pneumonia, deep venous thrombosis, and systemic bleeding. The primary endpoint was functional independence (modified Rankin Scale score 0-2 within 90 days). Logistic regression analysis was used to determine the predictors and associations between SAEs and outcomes. Results Of 1182 enrolled patients, 402 (34%) had a procedural complication, 745 (63%) had 1404 SAEs occurrences with 4.65% in-hospital mortality. The three most frequent SAEs were pneumonia (620, 52.5%), systemic bleeding (174, 14.7%) and respiratory failure (173, 14.6%). Pneumonia, systemic bleeding or deep venous thrombosis were less life-threatening. Patients with advanced age (adjusted odds ratio, 1.28 [95% confidence interval, 1.14-1.43]), higher NIHSS (1.09 [1.06-1.11]), occlusion site (middle cerebral artery-M1 vs. intracranial cerebral artery [ICA]: 0.75 [0.53-1.04]; M2 vs. ICA: 1.30 [0.80-2.12]), longer procedure time (1.01 [1.00-1.01]) and unsuccessful vessel recanalization (1.79 [1.06-2.94]) were more likely to experience SAEs. Compared with no SAE, patients with SAEs had lower odds of functional independence (0.46 [0.40-0.54]). Conclusions Overall, SAEs diagnosed following thrombectomy in patients with stroke were common (more than 60%) and associated with functional dependence. Patients with advanced age, higher NIHSS, longer procedure time and failed recanalization were more likely to experience SAEs. There was no statistical difference in the risk of SAEs among patient with M1 and M2 occluded compared with those ICA occluded. An understanding of the prevalence and predictors of SAEs could alert clinicians to the estimated risk of an SAE for a patient after EVT.

Resection of Tumors at the Root of the Tongue and Free Flap Reconstruction: Midline Split With Bilateral Lingual Artery Preservation.

The removal of tumors at the root of the tongue can be challenging due to anatomic constraints (deep location of the root of the tongue, obstruction by the mandible), leading to poor surgical visibility. Clear visibility of the surgical field is crucial for complete excision to reduce recurrence, hence the need to choose an appropriate surgical approach based on the tumor's location and size. In this report, the authors describe a case where a midline mandibulotomy and temporary midline glossectomy were utilized to expose and resect a tumor at the root of the tongue. This approach allowed for the complete removal of the tumor while preserving the anterior tongue tissue and bilateral lingual arteries. The defect was then reconstructed using an anterolateral thigh flap. The patient showed good postoperative recovery with significant improvement in swallowing and speech functions. The authors emphasize that the surgical treatment of squamous cell carcinoma (SCC) at the root of the tongue should strive to ensure radical tumor removal while preserving surrounding healthy tissues and critical anatomic structures, particularly the lingual arteries, to facilitate better postoperative recovery for patients.

Prediction of non-muscle invasive bladder cancer recurrence using deep learning of pathology image.

We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752-0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer-Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

First-principles modeling of H2CO3 molecular adsorption on CaSiO3(001) surface for application in the sequestration and utilization of CO2.

This work employed density functional theory (DFT) to further study the adsorption of H2CO3, HCO3-, and CO32- on the CaSiO3(001) surface, which could provide additional insights into the mechanism of carbonation on the CaSiO3 surface. It was concluded that the carbonation of CO2 promoted carbon sequestration, whereby the aqueous carbonation route increased the reaction rate substantially compared to direct gas-solid carbonation. H2CO3 is more conducive to CO2 sequestration, which can be attributed to the interaction of H atoms with the surface. Further, H2CO3 can be converted into HCO3- or CO32- on the CaO-terminated (001) surface, whereas only HCO3- was formed on the SiO-terminated (001) surface. All the adsorption energies of H2CO3 were negative, suggesting that H2CO3 adsorption was energetically stable and spontaneous. The most likely adsorption model of HCO3-, having negative adsorption energy, was the one adsorbed on the SiO-terminated (001) surface, in which HCO3- is transformed into CO32-. The other adsorption models of HCO3- and all the adsorption models of CO32- have positive adsorption energies. Considering the adsorption process of H2CO3, HCO3- and CO32- adsorption reactions may occur successively to some extent depending on the environment.

Water temperature and salt ions respectively drive the community assembly of bacterial generalists and specialists in diverse plateau lakes.

Plateau lakes (e.g., freshwater and saltwater lakes) are formed through intricate processes and harbor diverse microorganisms that mediate aquatic ecosystem functions. The adaptive mechanisms of lake microbiota to environmental changes and the ecological impacts of such changes on microbial community assembly are still poorly understood in plateau regions. This study investigated the structure and assembly of planktonic bacterial communities in 24 lakes across the Qinghai-Tibetan and Inner Mongolia Plateaus, with particular focus on habitat generalists, opportunists, and specialists. High-throughput sequencing of the 16S ribosomal RNA genes revealed that bacterial generalists had a lower species number (2196) but higher alpha diversity than the specialist and opportunist counterparts. Taxonomic dissimilarity and phylogenetic diversity analyses unraveled less pronounced difference in the community composition of bacterial generalists compared to the specialist and opportunist counterparts. Geographical scale (14.4 %) and water quality (12.6 %) emerged as major ecological variables structuring bacterial communities. Selection by water temperature and related variables, including mean annual temperature, elevation, longitude, and latitude, mainly shaped the assembly of bacterial generalists. Ecological drift coupled with selection by salt ions and related variables, including total phosphorus, chlorophyll a, and salinity, predominantly drove the assembly of bacterial specialists and opportunists. This study uncovers distinct bacterial responses to interacting ecological variables in diverse plateau lakes and the ecological processes structuring bacterial communities across various lake habitats under anthropogenic disturbance or climate change.

Occurrence, spatial distribution, and ecological risk of benzotriazole UV stabilizers (BUVs) in sediments from Bohai sea of China.

Benzotriazoles are a class of ultraviolet absorbents which absorb UV ranging from 280 to 400 nm and are widely used in personal care products and industrial production. Their residues in environmental matrices have received great concern in recent years, but most studies have focused on pollution in water and few have examined BUVs in marine sediments. In this study, we investigated the occurrence, potential sources, and ecological risk of 15 types of BUVs in the sediments of Bohai Sea in China for the first time. The total concentrations of the 15 BUVs ranged from 0.139 to 4.125 ng/g dw with a median concentration of 0.340 ng/g. UV-327 and UV-360 were predominant among the BUV congeners, accounting for 22.6% and 17.7% of the total concentration of Σ15BUVs, respectively. The detection frequencies of the BUV congeners generally exceeded 95%, reflecting the wide use and persistence of these chemicals. The concentrations of the BUV congeners in this study were one order of magnitude lower than those in other areas. Moreover, the distributions of BUVs presented a decreasing gradient from nearshore to offshore, indicating that coastal input was the main influencing factor. Two potential primary sources, plastic manufacturing and domestic wastewater, were identified via principle component analysis. The ecological risks of BUVs to aquatic organisms in the sediments were evaluated using the risk quotient (RQ) method. Generally, the risk to aquatic organisms from exposure to BUVs in Bohai Sea could be considered low at the measured concentrations. While our study provides important new insight into the ecological risks of BUVs in the estuary, further research on the pollution levels and toxicity risks of BUVs in Bohai Sea should be conducted to better understand the ecological effect of these pollutants.

Enhanced interleukin-16-CD4 signaling in CD3 T cell mediates neuropathic pain via activating astrocytes in female mice.

Immune cells and interleukins play a crucial role in female-specific pain signaling. Interleukin 16 (IL-16) is a cytokine primarily associated with CD4+ T cell function. While previous studies have demonstrated the important role of spinal CD4+ T cells in neuropathic pain, the specific contribution of IL-16 to neuropathic pain remains unclear. In this study, by using a spinal nerve ligation (SNL)-induced neuropathic pain mice model, we found that SNL induced an increase in IL-16 mRNA levels, which persisted for a longer duration in female mice compared to male mice. Immunofluorescence analysis further confirmed enhanced IL-16- and CD4-positive signals in the spinal dorsal horn following SNL surgery in female mice. Knockdown of spinal IL-16 by siRNA or inhibition of CD4 by FGF22-IN-1, a CD4 inhibitor, attenuated established mechanical and thermal pain hypersensitivity induced by SNL. Furthermore, female mice injected with IL-16 intrathecally exhibited significant spontaneous pain, mechanical and thermal hyperalgesia, all of which could be alleviated by FGF22-IN-1 or a CD3 antibody. Additionally, IL-16 induced astrocyte activation but not microglial activation in the spinal dorsal horn of female mice. Meanwhile, astrocyte activation could be suppressed by the CD3 antibody. These results provide compelling evidence that IL-16 promotes astrocyte activation via CD4 on CD3+ T cells, which is critical for maintaining neuropathic pain in female mice.

Lower indoor spatial frequency increases the risk of myopia in children.

BACKGROUND/AIMS: Animal models have shown that the absence of high-frequency visual information can precipitate the onset of myopia, but this relationship remains unclear in humans. This study aims to explore the association between the spatial frequency content of the visual environment and myopia in children. METHODS: Images from the rooms of children and their frequently visited outdoor areas were taken by their parents and collected by the researcher through questionnaires. The spatial frequency was quantified using Matlab. Cycloplegic refraction was used to measure the spherical equivalent (SE), and IOL Master was used to measure axial length (AL) and corneal radius (CR). AL/CR ratio was calculated. RESULTS: The study included 566 children with an average age of (8.04±1.47) years, of which 270 were girls (47.7%), and the average SE was (0.70±1.21) D. Image analysis revealed that indoor spatial frequency slope was lower than that of the outdoor environment (-1.43±0.18 vs -1.11±0.23, p<0.001). There were 79 myopic individuals (14.0%). Images from indoor content of myopic children had a lower spatial frequency slope than non-myopic children (-1.47±0.16 vs 1.43±0.18, p=0.03) while there was no significant difference in outdoor spatial frequency slope. Regression analysis indicated that the indoor spatial frequency slope was positively associated with SE value (ß=0.60, p=0.02) and inversely related to myopia (OR=0.24, p<0.05). CONCLUSION: The spatial frequency of the outdoor environment is significantly higher than that of the indoor environment. Indoor spatial frequency is related to children's refractive status, with lower indoor spatial frequency being associated with a higher degree of myopia.

Schisandrol B inhibits calcification of aortic valve by targeting p53 related inflammatory and senescence.

Calcific aortic valve disease (CAVD) primarily involves osteogenic differentiation in human aortic valve interstitial cells (hVICs). Schisandrol B (SolB), a natural bioactive constituent, has known therapeutic effects on inflammatory and fibrotic disorders. However, its impact on valve calcification has not been reported. We investigated the effect of SolB on osteogenic differentiation of hVICs. Transcriptome sequencing was used to analyze potential molecular pathways affected by SolB treatment. The study also included an in vivo murine model using aortic valve wire injury surgery to observe SolB's effect on valve calcification. SolB inhibited the osteogenic differentiation of hVICs, reversing the increase in calcified nodule formation and osteogenic proteins. In the murine model, SolB significantly decreased the peak velocity of the aortic valve post-injury and reduced valve fibrosis and calcification. Transcriptome sequencing identified the p53 signaling pathway as a key molecular target of SolB, demonstrating its role as a molecular glue in the mouse double minute 2 (MDM2)-p53 interaction, thereby promoting p53 ubiquitination and degradation, which further inhibited p53-related inflammatory and senescence response. These results highlighted therapeutic potential of SolB for CAVD via inhibiting p53 signaling pathway and revealed a new molecular mechanism of SolB which provided a new insight of theraputic mechanism for CAVD.

Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma.

Patients with high ALDH1A3-expressing glioblastoma (ALDH1A3hi GBM) show limited benefit from postoperative chemoradiotherapy. Understanding the mechanisms underlying such resistance in these patients is crucial for the development of new treatments. Here, we show that the interaction between ALDH1A3 and PKM2 enhances the latter's tetramerization and promotes lactate accumulation in glioblastoma stem cells (GSCs). By scanning the lactylated proteome in lactate-accumulating GSCs, we show that XRCC1 undergoes lactylation at lysine 247 (K247). Lactylated XRCC1 shows a stronger affinity for importin α, allowing for greater nuclear transposition of XRCC1 and enhanced DNA repair. Through high-throughput screening of a small-molecule library, we show that D34-919 potently disrupts the ALDH1A3-PKM2 interaction, preventing the ALDH1A3-mediated enhancement of PKM2 tetramerization. In vitro and in vivo treatment with D34-919 enhanced chemoradiotherapy-induced apoptosis of GBM cells. Together, our findings show that ALDH1A3-mediated PKM2 tetramerization is a potential therapeutic target to improve the response to chemoradiotherapy in ALDH1A3hi GBM.

Global Research Trends in Postoperative Delirium and Its Risk Factors: A Bibliometric and Visual Analysis.

PURPOSE: Postoperative delirium (POD) is one of the most frequent complications after surgery which is closely associated with many adverse outcomes, including high mortality and low quality of life. This study aims to carry out a bibliometric analysis of POD and its risk factors from 2012 to 2022 to reveal the research status and hot spots. DESIGN: This study is a bibliometric and visualized analysis. METHODS: Relevant publications between 2012 and 2022 were extracted from the Web of Science Core Collection database. CiteSpace software (v6.1. R2, Drexel University), VOSviewer software (v1.6.18, Leiden University), and the Online Analysis Platform of Literature Metrology were used to analyze research attributes. These publications were used to analyze research attributes, including countries, journals, institutions, authors, keywords, and burst detection, to predict trends and hot spots. FINDINGS: We included a total of 1,324 related documents from 2012 to 2022. The literature on POD has increased significantly since 2016. The United States and Harvard University were the leading literature publishing country (436/1324, 32.9%) and institution (112/1324, 8.5%). Anesthesia and Analgesia was the most frequently published journal. Keywords analysis with VOSviewer revealed that the keywords could be divided into five clusters, including anesthesia techniques, cardiac surgery, risk factors, intraoperative anesthesia monitoring, and postoperative cognitive dysfunction. We included a total of 198 POD risk factors documents, and the literature on POD risk factors increased. The People's Republic of China and Harvard University were the leading literature publishing country (53/198, 26.8%) and institution (12/198, 6.1%). Elderly, hip surgery, frailty, postoperative pain, cardiac surgery, dementia, and depression are keywords that are risk factors for POD. CONCLUSIONS: The number of literature on POD in the field of anesthesia has increased significantly. Risk factors and anesthesia techniques are still key areas of research. Encephalogram, the use of sedatives, and perioperative nursing may be the new research focus. Older adults, hip fractures, cardiac surgery, liver transplants, dementia, and depression are hot words in the field of POD risk factors.

Are Art-Based Interventions Effective in Improving Psychological Well-Being Among Informal Caregivers of Cancer Patients? A Systematic Review.

Objectives: To systematically synthesize the current evidence on the effects of art-based interventions on improving anxiety, depression, stress, sleep, and well-being of cancer caregivers. Design: A systematic review. Methods: We searched PubMed, EMBASE, Web of Science, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trials databases from their inception up to April 2024. Studies exploring the effects of art-based interventions on the psychological symptoms of cancer caregivers were included. We did not restrict the publication to the particular study designs, including randomized controlled trials, quasiexperimental studies, and qualitative studies. Results: Fifteen studies of 607 participants were identified in this systematic review. Overall, the existing studies provided preliminary evidence to suggest that art-based interventions may benefit cancer caregivers in improving anxiety, depression, stress, caregiver burden, and quality of life. However, the relatively low quality of the current evidence limits the efficacy of these findings. Conclusions: According to the existing evidence, the therapeutic benefits of using art-based interventions for improving the psychological well-being of cancer caregivers are uncertain. More high-quality and well-designed studies are still required to confirm the psychological effectiveness of art-based interventions for cancer caregivers in the future.

Increased viral tolerance mediates by antiviral RNA interference in bat cells.

Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigate the antiviral RNA interference pathway in bat cells and discover that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs upon Sindbis virus infection that are missing in human cells. Disruption of Dicer function results in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors, such as retinoic acid-inducible gene I, with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.

Ameliorating the detrimental effects of chromium in wheat by silicon nanoparticles and its enriched biochar.

Increased anthropogenic activities over the last decades have led to a gradual increase in chromium (Cr) content in the soil, which, due to its high mobility in soil, makes Cr accumulation in plants a serious threat to the health of animals and humans. The present study investigated the ameliorative effect of foliar-applied Si nanoparticles (SiF) and soil-applied SiNPs enriched biochar (SiBc) on the growth of wheat in Cr-polluted soil (CPS). Two levels of CPS were prepared, including 12.5 % and 25 % by adding Cr-polluted wastewater in the soil as soil 1 (S1) and soil 2 (S2), respectively for the pot experiment with a duration of 40 days. Cr stress significantly reduced wheat growth, however, combined application of SiF and SiBc improved root and shoot biomass production under Cr stress by (i) reducing Cr accumulation, (ii) increasing activities of antioxidant enzymes (ascorbate peroxidase and catalase), and (iii) increasing protein and total phenolic contents in both root and shoot respectively. Nonetheless, separate applications of SiF and SiBc effectively reduced Cr toxicity in shoot and root respectively, indicating a tissue-specific regulation of wheat growth under Cr. Later, the Langmuir and Freundlich adsorption isotherm analysis showed a maximum soil Cr adsorption capacity ∼ Q(max) of 40.6 mg g-1 and 59 mg g-1 at S1 and S2 respectively, while the life cycle impact assessment showed scores of -1 mg kg-1 and -211 mg kg-1 for Cr in agricultural soil and - 0.184 and - 38.7 for human health at S1 and S2 respectively in response to combined SiF + SiBC application, thus indicating the environment implication of Si nanoparticles and its biochar in ameliorating Cr toxicity in different environmental perspectives.

Cdc14 phosphatases use an intramolecular pseudosubstrate motif to stimulate and regulate catalysis.

Cdc14 phosphatases are related structurally and mechanistically to protein tyrosine phosphatases (PTP) but evolved a unique specificity for phosphoSer-Pro-X-Lys/Arg sites primarily deposited by cyclin-dependent kinases. This specialization is widely conserved in eukaryotes. The evolutionary reconfiguration of the Cdc14 active site to selectively accommodate phosphoSer-Pro likely required modification to the canonical PTP catalytic cycle. While studying Saccharomyces cerevisiae Cdc14 we discovered a short sequence in the disordered C-terminus, distal to the catalytic domain, that mimics an optimal substrate. Kinetic analyses demonstrated this pseudosubstrate binds the active site and strongly stimulates rate-limiting phosphoenzyme hydrolysis, and we named it "substrate-like catalytic enhancer" (SLiCE). The SLiCE motif is found in all Dikarya fungal Cdc14 orthologs and contains an invariant glutamine, which we propose is positioned via substrate-like contacts to assist orientation of the hydrolytic water, similar to a conserved active site glutamine in other PTPs that Cdc14 lacks. AlphaFold2 predictions revealed vertebrate Cdc14 orthologs contain a conserved C-terminal alpha helix bound to the active site. Although apparently unrelated to the fungal sequence, this motif also makes substrate-like contacts and has an invariant glutamine in the catalytic pocket. Altering these residues in human Cdc14A and Cdc14B demonstrated that it functions by the same mechanism as the fungal motif. However, the fungal and vertebrate SLiCE motifs were not functionally interchangeable, illuminating potential active site differences during catalysis. Finally, we show that the fungal SLiCE motif is a target for phosphoregulation of Cdc14 activity. Our study uncovered evolution of an unusual stimulatory pseudosubstrate motif in Cdc14 phosphatases.

Rbm24/Notch1 signaling regulates adult neurogenesis in the subventricular zone and mediates Parkinson-associated olfactory dysfunction.

Rationale: Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson's disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated. Methods: We generated an RNA binding motif protein 24 (Rbm24) knockout model to investigate its impact on adult neurogenesis in the SVZ, employing immunofluorescence, immunoblot, electrophysiology, RNA-sequencing, and in vitro experiments. Further investigations utilized a PD mouse model, along with genetic and pharmacological manipulations, to elucidate Rbm24 involvement in PD pathology. Results: Rbm24, a multifaceted post-transcriptional regulator of cellular homeostasis, exhibited broad expression in the SVZ from development to aging. Deletion of Rbm24 significantly impaired NSPC proliferation in the adult SVZ, ultimately resulting in collapsed neurogenesis in the olfactory bulb. Notably, Rbm24 played a specific role in maintaining Notch1 mRNA stability in adult NSPCs. The Rbm24/Notch1 signaling axis was significantly downregulated in the SVZ of PD mice. Remarkably, overexpression of Rbm24 rescued disruption of adult neurogenesis and olfactory dysfunction in PD mice, and these effects were hindered by DAPT, a potent inhibitor of Notch1. Conclusions: Our findings highlight the critical role of the Rbm24/Notch1 signaling axis in regulating adult SVZ neurogenesis under physiological and pathological circumstances. This provides valuable insights into the dynamic regulation of NSPC homeostasis and offers a potential targeted intervention for PD and related neurological disorders.

Co-delivery of Siape1 and Melatonin by 125I-loaded PSMA-targeted Nanoparticles for the Treatment of Prostate Cancer.

BACKGROUND: Both apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) inhibition and melatonin suppress prostate cancer (PCa) growth. OBJECTIVE: This study evaluated the therapeutic efficiency of self-assembled and prostate-specific membrane antigen (PSMA)-targeted nanocarrier loading 125I radioactive particles and encapsulating siRNA targeting APE1 (siAPE1) and melatonin for PCa. METHODS: The linear polyarginine R12 polypeptide was prepared using Fmoc-Arg-Pbf-OH. The PSMA-targeted polymer was synthesized by conjugating azide-modified R12 peptide to PSMA monoclonal antibody (mAb). Before experiments, the PSMA-R12 nanocarrier was installed with melatonin and siAPE1, which were subsequently labeled by 125I radioactive particles. In vitro biocompatibility and cytotoxicity of nanocomposites were examined in LNCaP cells and in vivo biodistribution and pharmacokinetics were determined using PCa tumor-bearing mice. RESULTS: PSMA-R12 nanocarrier was ~120 nm in size and was increased to ~150 nm by melatonin encapsulation. PSMA-R12 nanoparticles had efficient loading capacities of siAPE1, melatonin, and 125I particles. The co-delivery of melatonin and siAPE1 by PSMA-R12-125I showed synergistic effects on suppressing LNCaP cell proliferation and Bcl-2 expression and promoting cell apoptosis and caspase-3 expression. Pharmacokinetics analysis showed that Mel@PSMA-R12-125I particles had high uptake activity in the liver, spleen, kidney, intestine, and tumor, and were accumulated in the tumor sites within the first 8 h p.i., but was rapidly cleared from all the tested organs at 24 h p.i. Administration of nanoparticles to PCa tumors in vivo showed that Mel@PSMA-R12- 125I/siAPE1 had high efficiency in suppressing PCa tumor growth. CONCLUSION: The PSMA-targeted nanocarrier encapsulating siAPE1 and melatonin is a promising therapeutic strategy for PCa and can provide a theoretical basis for patent applications.

Intraoperative hypotension associated with postoperative acute kidney injury in hypertension patients undergoing non-cardiac surgery: a retrospective cohort study.

Background: Acute kidney injury (AKI) is a common surgical complication and is associated with intraoperative hypotension. However, the total duration and magnitude of intraoperative hypotension associated with AKI remains unknown. In this study, the causal relationship between the intraoperative arterial pressure and postoperative AKI was investigated among chronic hypertension patients undergoing non-cardiac surgery. Methods: A retrospective cohort study of 6552 hypertension patients undergoing non-cardiac surgery (2011 to 2019) was conducted. The primary outcome was AKI as diagnosed with the Kidney Disease-Improving Global Outcomes criteria and the primary exposure was intraoperative hypotension. Patients' baseline demographics, pre- and post-operative data were harvested and then analyzed with multivariable logistic regression to assess the exposure-outcome relationship. Results: Among 6552 hypertension patients, 579 (8.84%) had postoperative AKI after non-cardiac surgery. The proportions of patients admitted to ICU (3.97 vs. 1.24%, p < 0.001) and experiencing all-cause death (2.76 vs. 0.80%, p < 0.001) were higher in the patients with postoperative AKI. Moreover, the patients with postoperative AKI had longer hospital stays (13.50 vs. 12.00 days, p < 0.001). Intraoperative mean arterial pressure (MAP) < 60 mmHg for >20 min was an independent risk factor of postoperative AKI. Furthermore, MAP <60 mmHg for >10 min was also an independent risk factor of postoperative AKI in patients whose MAP was measured invasively in the subgroup analysis. Conclusions: Our work suggested that MAP < 60 mmHg for >10 min measured invasively or 20 min measured non-invasively during non-cardiac surgery may be the threshold of postoperative AKI development in hypertension patients. This work may serve as a perioperative management guide for chronic hypertension patients. Trial registration: clinical trial number: ChiCTR2100050209 (8/22/2021). http://www.chictr.org.cn/showproj.aspx?proj=132277.

Long-term outcomes following hepatectomy in patients with lean non-alcoholic fatty liver disease-associated hepatocellular carcinoma versus overweight and obese counterparts: A multicenter analysis.

BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) as a significant etiology for hepatocellular carcinoma (HCC), lean NAFLD-HCC has emerged as a specific distinct subtype. This study sought to investigate long-term outcomes following curative-intent hepatectomy for early-stage NAFLD-HCC among lean patients compared with overweight and obese individuals. METHODS: A multicenter retrospective analysis was used to assess early-stage NAFLD-HCC patients undergoing curative-intent hepatectomy between 2009 and 2022. Patients were stratified by preoperative body mass index (BMI) into the lean (<23.0 kg/m2), overweight (23.0-27.4 kg/m2) and obese (≥27.5 kg/m2) groups. Study endpoints were overall survival (OS) and recurrence-free survival (RFS), which were compared among groups. RESULTS: Among 309 patients with NAFLD-HCC, 66 (21.3 %), 176 (57.0 %), and 67 (21.7 %) were lean, overweight, and obese, respectively. The three groups were similar relative to most liver, tumor, and surgery-related variables. Compared with overweight patients (71.3 % and 55.6 %), the lean individuals had a worse 5-year OS and RFS (55.4 % and 35.1 %, P = 0.017 and 0.002, respectively), which were comparable to obese patients (48.5 % and 38.2 %, P = 0.939 and 0.442, respectively). After adjustment for confounding factors, multivariable Cox-regression analysis identified that lean bodyweight was independently associated with decreased OS (hazard ratio: 1.69; 95 % confidence interval: 1.06-2.71; P = 0.029) and RFS (hazard ratio: 1.72; 95 % confidence interval: 1.17-2.52; P = 0.006) following curative-intent hepatectomy for early-stage NAFLD-HCC. CONCLUSIONS: Compared with overweight patients, individuals with lean NAFLD-HCC had inferior long-term oncological survival after hepatectomy for early-stage NAFLD-HCC. These data highlight the need for examination of the distinct carcinogenic pathways of lean NAFLD-HCC and its potential consequences in HCC recurrence.

An artificial intelligence-enabled electrocardiogram algorithm for the prediction of left atrial low-voltage areas in persistent atrial fibrillation.

OBJECTIVES: We aimed to construct an artificial intelligence-enabled electrocardiogram (ECG) algorithm that can accurately predict the presence of left atrial low-voltage areas (LVAs) in patients with persistent atrial fibrillation. METHODS: The study included 587 patients with persistent atrial fibrillation who underwent catheter ablation procedures between March 2012 and December 2023 and 942 scanned images of 12-lead ECGs obtained before the ablation procedures were performed. Artificial intelligence-based algorithms were used to construct models for predicting the presence of LVAs. The DR-FLASH and APPLE clinical scores for LVA prediction were calculated. We used a receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis to evaluate model performance. RESULTS: The data obtained from the participants were split into training (n = 469), validation (n = 58), and test sets (n = 60). LVAs were detected in 53.7% of all participants. Using ECG alone, the deep learning algorithm achieved an area under the ROC curve (AUROC) of 0.752, outperforming both the DR-FLASH score (AUROC = 0.610) and the APPLE score (AUROC = 0.510). The random forest classification model, which integrated a probabilistic deep learning model and clinical features, showed a maximum AUROC of 0.759. Moreover, the ECG-based deep learning algorithm for predicting extensive LVAs achieved an AUROC of 0.775, with a sensitivity of 0.816 and a specificity of 0.896. The random forest classification model for predicting extensive LVAs achieved an AUROC of 0.897, with a sensitivity of 0.862, and a specificity of 0.935. CONCLUSION: The deep learning model based exclusively on ECG data and the machine learning model that combined a probabilistic deep learning model and clinical features both predicted the presence of LVAs with a higher degree of accuracy than the DR-FLASH and the APPLE risk scores.