Analysis of factors affecting intraoperative hemorrhage during percutaneous nephrolithotomy and establishment of nomogram model.

Intraoperative hemorrhage is an important factor affecting intraoperative safety and postoperative patient recovery in percutaneous nephrolithotomy (PCNL). This study aimed to identify the factors that influence intraoperative hemorrhage during PCNL and develop a predictive nomogram model based on these factors.A total of 118 patients who underwent PCNL at the Department of Urology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2021 to September 2023 was included in this study. The patients were divided into a hemorrhage group (58 cases) and a control group (60 cases) based on the decrease in hemoglobin levels after surgery. The clinical data of all patients were collected, and both univariate analysis and multivariate logistic regression analysis were conducted to identify the independent risk factors for intraoperative hemorrhage during PCNL. The independent risk factors were used to construct a nomogram model using R software. Additionally, receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) were utilized to evaluate the model.Multivariate logistic regression analysis revealed that diabetes, long operation time and low psoas muscle mass index (PMI) were independent risk factors for intraoperative hemorrhage during PCNL (P < 0.05). A nomogram model was developed incorporating these factors, and the areas under the ROC curve (AUCs) in the training set and validation set were 0.740 (95% CI: 0.637-0.843) and 0.742 (95% CI: 0.554-0.931), respectively. The calibration curve and Hosmer-Lemeshow test (P = 0.719) of the model proved that the model was well fitted and calibrated. The results of the DCA showed that the model had high value for clinical application.Diabetes, long operation time and low PMI were found to be independent risk factors for intraoperative hemorrhage during PCNL. The nomogram model based on these factors can be used to predict the risk of intraoperative hemorrhage, which is beneficial for perioperative intervention in high-risk groups to improve the safety of surgery and reduce the incidence of postoperative complications.

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis.

Ferroptosis is a specific type of programmed cell death characterized by iron-dependent lipid peroxidation. Understanding the involvement of ferroptosis in calcium oxalate (CaOx) stone formation may reveal potential targets for this condition. The publicly available dataset GSE73680 was used to identify 61 differentially expressed ferroptosis-related genes (DEFERGs) between normal kidney tissues and Randall's plaques (RPs) from patients with nephrolithiasis through employing weighted gene co-expression network analysis (WGCNA). The findings were validated through in vitro and in vivo experiments using CaOx nephrolithiasis rat models induced by 1% ethylene glycol administration and HK-2 cell models treated with 1 mM oxalate. Through WGCNA and the machine learning algorithm, we identified LAMP2 and MDM4 as the hub DEFERGs. Subsequently, nephrolithiasis samples were classified into cluster 1 and cluster 2 based on the expression of the hub DEFERGs. Validation experiments demonstrated decreased expression of LAMP2 and MDM4 in CaOx nephrolithiasis animal models and cells. Treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, partially reversed oxidative stress and lipid peroxidation in CaOx nephrolithiasis models. Moreover, Fer-1 also reversed the expression changes of LAMP2 and MDM4 in CaOx nephrolithiasis models. Our findings suggest that ferroptosis may be involved in the formation of CaOx kidney stones through the regulation of LAMP2 and MDM4.

Single-Cell Transcriptome Analysis Identified Core Genes and Transcription Factors in Mesenchymal Cell Differentiation during Liver Cirrhosis.

BACKGROUND: Mesenchymal cells, including hepatic stellate cells (HSCs), fibroblasts (FBs), myofibroblasts (MFBs), and vascular smooth muscle cells (VSMCs), are the main cells that affect liver fibrosis and play crucial roles in maintaining tissue homeostasis. The dynamic evolution of mesenchymal cells is very important but remains to be explored for researching the reversible mechanism of hepatic fibrosis and its evolution mechanism of hepatic fibrosis to cirrhosis. METHODS: Here, we analysed the transcriptomes of more than 50,000 human single cells from three cirrhotic and three healthy liver tissue samples and the mouse hepatic mesenchymal cells of two healthy and two fibrotic livers to reconstruct the evolutionary trajectory of hepatic mesenchymal cells from a healthy to a cirrhotic state, and a subsequent integrative analysis of bulk RNA sequencing (RNA-seq) data of HSCs from quiescent to active (using transforming growth factor ß1 (TGF-ß1) to stimulate LX-2) to inactive states. RESULTS: We identified core genes and transcription factors (TFs) involved in mesenchymal cell differentiation. In healthy human and mouse livers, the expression of NR1H4 and members of the ZEB families (ZEB1 and ZEB2) changed significantly with the differentiation of FB into HSC and VSMC. In cirrhotic human livers, VSMCs transformed into HSCs with downregulation of MYH11, ACTA2, and JUNB and upregulation of PDGFRB, RGS5, IGFBP5, CD36, A2M, SOX5, and MEF2C. Following HSCs differentiation into MFBs with the upregulation of COL1A1, TIMP1, and NR1H4, a small number of MFBs reverted to inactivated HSCs (iHSCs). The differentiation trajectory of mouse hepatic mesenchymal cells was similar to that in humans; however, the evolution trajectory and proportion of cell subpopulations that reverted from MFBs to iHSCs suggest that the mouse model may not accurately reflect disease progression and outcome in humans. CONCLUSIONS: Our analysis elucidates primary genes and TFs involved in mesenchymal cell differentiation during liver fibrosis using scRNA-seq data, and demonstrated the core genes and TFs in process of HSC activation to MFB and MFB reversal to iHSC using bulk RNA-seq data of human fibrosis induced by TGF-ß1. Furthermore, our findings suggest promising targets for the treatment of liver fibrosis and provide valuable insights into the molecular mechanisms underlying its onset and progression.

ZCHSound: Open-Source ZJU Paediatric Heart Sound Database With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) is a common birth defect in children. Intelligent auscultation algorithms have been proven to reduce the subjectivity of diagnoses and alleviate the workload of doctors. However, the development of this algorithm has been limited by the lack of reliable, standardized, and publicly available pediatric heart sound databases. Therefore, the objective of this research is to develop a large-scale, high-standard, high-quality, and accurately labeled pediatric congenital heart disease (CHD) heart sound database, and perform classification tasks to evaluate its performance, filling this important research gap. METHOD: From 2020 to 2022, we collaborated with experienced cardiac surgeons from Zhejiang University Children's Hospital to collect heart sound signals from 1259 participants using electronic stethoscopes. To ensure accurate disease diagnosis, the cardiac ultrasound images for each participant were acquired by an experienced ultrasonographer, and the final diagnosis was confirmed through the consensus of two cardiac experts or cardiac surgeons. To establish the benchmark of ZCHSound, we extracted 84 time-frequency features from the heart sounds and evaluated the performance of the classification task using machine learning models. Additionally, we evaluated the importance scores of the 84 features in distinguishing between normal and pathological heart sounds in children using SHapley Additive exPlanations (SHAP) values. RESULTS: The ZCHSound database contains heart sound data from 1259 participants, with all data divided into two datasets: one is a high-quality, filtered clean heart sound dataset, and the other is a low-quality, noisy heart sound dataset. In the evaluation of the high-quality dataset, our random forest ensemble model achieved an F1 score of 90.3% in the classification task of normal and pathological heart sounds. Moreover, the SHAP analysis results demonstrate that frequency-domain features have a more significant impact on the model output compared to time-domain features. Features related to the cardiac diastolic period have a greater influence on the model's classification results compared to those related to the systolic period. CONCLUSION: This study has successfully established a large-scale, high-quality, rigorously standardized pediatric CHD sound database with precise disease diagnosis. This database not only provides important learning resources for clinical doctors in auscultation knowledge but also offers valuable data support for algorithm engineers in developing intelligent auscultation algorithms. Our data can be accessed and downloaded by the public at http://zchsound.ncrcch.org.cn/.

Pipeline Embolization Device for intracranial aneurysms presenting with mass effect: a large Chinese cohort.

BACKGROUND: Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding, relieves symptoms and improve the quality of life for patients. This study aimed to assess the safety and efficacy of Pipeline Embolization Device (PED, Covidien/Medtronic, Irvine, CA) treatment for intracranial aneurysms presenting with mass effect in real-world settings. METHODS: We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation. The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up (3-36 months). We conducted multivariate analysis to identify factors associated with mass effect relief. Subgroup analyses by aneurysm location, size and form were also performed. RESULTS: This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0% (162/218). The postoperative mass effect deterioration rate was 9.6% (21/218). During a median follow-up period of 8.4 months, the mass effect relief rate was 71.6% (156/218). Notably, immediate aneurysm occlusion following treatment was significantly associated with mass effect relief (OR 0.392, 95% CI, 0.170 to 0.907, p=0.029). Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms, while dense embolism impeded symptom relief in aneurysms<10 mm and saccular aneurysms. CONCLUSIONS: Our data confirmed the efficacy of PED in relieving mass effect. The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms. TRIAL REGISTRATION NUMBER: NCT03831672.

Characterization of the microplastic photoaging under the action of typical salt ions of biological nitrogen removal processes.

Microplastics (MPs) are one of the most prevalent and diverse contaminants, and wastewater treatment plants are significant MP aggregators. Controlling the pollution caused by microplastics requires an understanding of how they age. The properties of the MPs photoaging process under the influence of salt ions typical of biological nitrogen elimination processes were disclosed in this work. The aging process of polyvinyl chloride microplastics (PVC-MPs) was greatly slowed down by greater HCO3- and NO2- concentrations, according to a comparison of the carbonyl index changes that occurred during photoaging. The carbonyl index had a negative correlation with the thermal stability of the photo-aged PVC-MPs, and aging accelerated the elimination of chlorine from the water. The samples were aged by UV radiation after 36 h at 40 °C, and the amount of chlorine eliminated was 10.13 times greater than that of the original MPs samples. It was discovered that the leachate concentration of aged MPs dramatically increased with decreasing particle size and was positively connected with the level of aging by comparing the concentration of leachate for two particle sizes (1 mm and 100 m). Photoaging caused MPs to become rougher, which in turn improved the NO3--N, NH4+-N, and NO2--N adsorption by PVC-MPs.

Unveiling the crucial role of iron mineral phase transformation in antimony(V) elimination from natural water.

Antimony (Sb) in natural water has long-term effects on both the ecological environment and human health. Iron mineral phase transformation (IMPT) is a prominent process for removing Sb(V) from natural water. However, the importance of IMPT in eliminating Sb remains uncertain. This study examined the various Sb-Fe binding mechanisms found in different IMPT pathways in natural water, shedding light on the underlying mechanisms. The study revealed that the presence of goethite (Goe), hematite (Hem), and magnetite (Mag) significantly affected the concentration of Sb(V) in natural water. Elevated pH levels facilitated higher Fe content in iron solids but impeded the process of removing Sb(V). To further our understanding, polluted natural water samples were collected from various locations surrounding Sb smelter sites. Results confirmed that converting ferrihydrite (Fhy) to Goe significantly reduced Sb levels (<5 µg/L) in natural water. The emergence of secondary iron phases resulted in greater electrostatic attraction and stabilized surface complexes, which was the most likely cause of the decline of Sb concentration in natural water. The comprehensive findings offer new insights into the factors governing IMPT as well as the Sb(V) behavior control.

Secreted protein acidic and rich in cysteine (SPARC) induces apoptosis of human brain vascular smooth muscle cells through regulating HK2 in intracranial aneurysm.

Background: Vascular smooth muscle cell (VSMC) dysfunction is one of the crucial pathologic processes in the development of intracranial aneurysm (IA). Secreted protein acidic and rich in cysteine (SPARC), a multifunctional glycoprotein, is overexpressed in many tumor, but its underlying mechanism in vascular disease has not been elucidated. The aim of this study is to evaluate the potential function of SPARC in IA generation and regulation of mitochondrial function in VSMC. Methods: Human brain vascular smooth muscle cells were treated with recombinant SPARC to detect apoptosis-related markers. The downstream targets affecting mitochondrial dysfunction after SPARC treatment were explored by transcriptome sequencing and bioinformatics analysis, and verified using by immunohistochemistry and western blot. Further in vitro experiments verified the role of downstream targets in regulating VSMC mitochondrial function. Results: Secreted protein acidic and rich in cysteine (SPARC) expression was associated with the risk of IA rupture. SPARC induces mitochondrial pathway apoptosis in human brain VSMC. We screened 40 differentially expressed genes related to mitochondrial function after SPARC treatment. Hexokinase 2 (HK2) was identified as a downstream target of mitochondrial pathway apoptosis in VSMC induced by SPARC. In addition, immunohistochemical results confirmed that the difference between SPARC and HK2 expression is located mainly in the smooth muscle layer of IA. Overexpression of HK2 reversed the SPARC-induced increase in apoptosis and mitochondrial damage in VSMC. Conclusion: Secreted protein acidic and rich in cysteine (SPARC) regulated mitochondrial function in VSMC and induced apoptosis through HK2, which plays an important role in the formation and rupture of IA. Targeting SPARC may be a novel strategy to delay the development of intracranial aneurysms.

Lower incidence of diabetes mellitus in patients with aneurysmal subarachnoid hemorrhage: a large case-control study with propensity score matching.

Background and purpose: Diabetes mellitus (DM) is a well-established cardiovascular risk factor for atherosclerotic disease; however, its effect on the risk of rupture of intracranial aneurysms remains controversial. Herein, we aimed to perform a case-control study to investigate the relationship between DM and aneurysmal subarachnoid hemorrhage (aSAH). Methods: We retrospectively reviewed the data of patients with ruptured or unruptured aneurysms who were treated between 2013 and 2023. Univariate and multivariate analyses were performed. Propensity score matching (PSM) analysis was conducted to evaluate the relationship between DM and risk of aSAH. Results: A total of 4,787 patients with 5,768 intracranial aneurysms were included. Among them, 2,957 (61.8%) were females, 1765 (36.9%) had ruptured aneurysms, and 531 (11.1%) presented with DM. Female sex, current drinking, and hypercholesterolemia were associated with a higher risk of aSAH, whereas old age, former smoking, and DM were associated with a lower risk of aSAH in multivariate analysis (p < 0.05). The incidence of DM (13.4%, 406/3022) in the unruptured group was higher than that in the ruptured group (7.1%, 125/1765) (odds ratio, 0.55; 95% confidence interval, 0.444-0.680) (p < 0.001). After propensity score matching, 530 patients with DM were successfully matched, and DM was still associated with a lower risk of aSAH (odds ratio, 0.24; 95% confidence interval, 0.185-0.313) (p < 0.001). Conclusion: Patients with aSAH have a lower incidence of DM, however, this case-cohort study could not establish a causal relationship. A prospective and large study with long-term follow-up is warranted to establish a causal relationship.

Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis.

BACKGROUND: Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs remain unclear. In this study, using bioinformatics analysis, we identified the potential pyroptosis-related genes (PRGs) and performed their inflammatory response mechanisms in IAs. METHODS: The mRNA expression matrix of the IA tissue was obtained from the Gene Expression Omnibus database, and 51 PRGs were obtained from previous articles collected from PubMed. The differentially expressed PRGs (DEPRGs) were performed using R software. Subsequently, we performed enrichment analysis, constructed a protein-protein interaction network, performed weighted gene coexpression network analysis (WGCNA) and external validation using another dataset, and identified a correlation between hub genes and immune cell infiltration. Finally, the expression and tissue distribution of these hub genes in IA tissues were detected using Western blotting and immunohistochemical (IHC) staining. RESULTS: In total, 12 DEPRGs associated with IA were identified in our analysis, which included 11 up-regulated and one down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEPRGs were mostly enriched in the NOD-like receptor signaling pathway, interleukin-1 beta production, and the inflammasome complex. Three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module, and external validation revealed statistically significant differences between the expression of these hub genes in the ruptured and unruptured aneurysm groups (p < 0.05). Furthermore, all AUC values were > 0.75. Immune cell infiltration analysis suggested that the hub genes are related to CD8 T cell, macrophages and mast cells. Finally, IHC staining revealed that the protein levels of these hub genes were higher in ruptured and unruptured IA tissues than in normal tissues (p < 0.05). CONCLUSION: The results of bioinformatics analysis showed that pyroptosis is closely related to the formation and rupture of IA, and identified three potential hub genes involved in the pyroptosis and infiltration ofcells. Our findings may improve the understanding of the mechanisms underlying pyroptosis in IA.

Circulating Flow-Electric-Field-Configuration-Enhanced Cadmium Cementation from Sulfate Systems and Its Optimization Mechanism.

In this work, a novel flow-electric field coupling configuration was designed and implemented for enhancing Zn-Cd cementation. A series of tests was conducted to explore the optimization of the Zn-Cd cementation process and its mechanism. Firstly, the various characteristics of the sponge cadmium at various locations in the device were compared, and it was concluded that the optimum purity of the sponge cadmium obtained from the anode was up to 94.1%. The generation and stripping of the cadmium sponge was revealed for the first time by cross-sectional electron microscopy. The four stages of the apparent reaction in the system were analyzed in relation to the pH, cadmium concentration and cadmium sponge flaking at each flow rate. It was proved that the separation of cadmium sponge mainly occurred in the third phase. Secondly, by comparing the morphology and specific surface area of the cadmium sponge at different flow rates, the optimum flow field velocity was identified as 30 mL/s. At this point, the specific surface area reached a maximum of 1.151 m2/g. Six flow field configurations were compared and preferred. The results demonstrated that the LCAH (Low-Cathode-Anode-High) modulation resulted in a sparser structure of the cadmium sponge, which was more easily exfoliated from the zinc anode surface by fluid impact. This was considered to be the most beneficial flow field configuration for improving the cadmium cementation rate and reducing the cost of the reaction. Moreover, the reaction steps of the system were analyzed. Its rate-limiting step was initially empirically identified as the diffusion step and proven by calculating the activation energy of 12.6 kJ/mol. It was confirmed that the diffusion process under different flow field configurations followed the first-order kinetic principle. In addition, the system's reaction phases were compared. Calculations confirmed that the diffusion process under various flow field configurations followed first-order kinetics. The diffusion coefficient of LACH proved to be the highest in the comparative tests, and the evident experimental results supported this conclusion.

Microsurgical revascularization of a symptomatic proximal vertebral artery: pilot experiences from a single center.

Background: Vertebral artery stenosis and occlusion (VASO) is a high-risk factor for posterior circulation stroke. Post-stent restenosis and drug tolerance have facilitated the exploration of microsurgical vascular reconstruction. This study aims to evaluate the safety and efficacy of microsurgical reconstruction of the proximal VA. Methods: Twenty-nine patients (25 men, aged 63.2 years) who had symptoms of posterior circulation ischemia underwent microsurgical revascularization for proximal VASO were retrospectively included in this study. Procedural complications and clinical and angiographic outcomes were reviewed. Results: Twelve, three, and five patients underwent VA endarterectomy, artery transposition, or both, respectively; seven patients underwent vertebral endarterectomy plus stent implantation; and two patients failed surgery because of the difficult exposure of the VA and the occurrence of vascular dissection. The perioperative period-related complications included seven cases of Horner's syndrome, five cases of hoarseness, and one case of chylothorax. No cases of perioperative stroke or death were reported. The mean follow-up period was 28.4 (8-62 months). Most patients improved clinically; however, the vertebrobasilar ischemia symptoms did not decrease significantly in two patients during the follow-up. Moreover, follow-up imaging was performed in all the patients, and no signs of anastomotic stenosis were reported. Conclusion: Microsurgical reconstruction is an alternative option that can effectively treat refractory proximal VASO disease and in-stent stenosis, with a high rate of postoperative vascular recirculation. Prospective cohort studies with larger sample sizes must be conducted to validate the above conclusions.

Development of a novel mesh model to define a new index "amount of stone" to evaluate calculus and predicting the lithotripsy time.

OBJECTIVE: Develop a mesh model to define a new "index amount of stone" to evaluate calculus and predict lithotripsy time. METHODS: The stones were divided into target units with diameter of 5 mm by the mesh from x, y and z directions, and the cross-sectional areas between units were calculated as amount of stone as a new index to evaluate calculus. Design a prospective study with 112 cases of percutaneous nephrolithotomy to verify the reliability of this index, and to compare the accuracy of the quantity, volume and maximum diameter of stones in predicting the time of lithotripsy. RESULTS: Amount of stone (Q) is reliable. The lithotripsy time was significantly correlated with the amount of stone, volume and maximum diameter of the stone (p < 0.01). The three regression equations were valid. The linear fit in the amount group was larger than that in the volume group, and further larger than that in the maximum diameter group, with R2 values of 0.716, 0.661 and 0.471, respectively. CONCLUSIONS: It is more accurate and convenient to use amount of stone to evaluate calculus, which can be used to predict the lithotripsy time.

Treatment of Intracranial Vertebral Artery Dissecting Aneurysms Using Pipeline Embolization Devices : A Multicenter Cohort Study.

PURPOSE: Intracranial vertebral artery dissecting aneurysm (IVADA) is a rare type of aneurysm with high morbidity and mortality. Recently, the application of pipeline embolization devices (PEDs) has been extended to IVADAs. Here, we aim to investigate the safety and effectiveness of PEDs for IVADAs. METHOD: We retrospectively reviewed the PLUS database to identify patients who had IVADAs and were treated with PEDs from 2014 to 2019 at 14 centers across China. Data including patient and aneurysm characteristics, procedure details, angiographic and clinical results, relationship with the ipsilateral posterior inferior cerebellar artery (PICA), and patency of the PICA following PED coverage were analyzed. RESULTS: In this study 52 consecutive patients with 52 IVADAs were included. The mean age was 52.33 years and 82.7% were male. With a median follow-up of 10.5 months, the complete occlusion rate was 93.8% (45/48) and no recurrence or in-stent stenosis was detected. The total postoperative complication rate and mortality were 11.5% and 1.9%, respectively. Complications occurred in 9.6% (5/52) of patients within 30 days after the operation, including ischemic stroke in 3 and hemorrhagic stroke in 2. Another patient suffered an ischemic stroke at follow-up, 78.8% (41/52) PICAs were covered by PEDs, 1 case (2.4%) had a functional disability due to PICA occlusion, while 39.0% (16/41) had reduced flow during follow-up but hardly caused any obvious neurological deficits. Patients with IVADA involving PICA had a trend towards more complications (66.7% vs. 51.1%; P = 1). CONCLUSION: Treating IVADAs with PEDs may be a safe and effective option, with favorable clinical and angiographic outcomes; however, complications associated with this treatment should not be ignored. REGISTRATION: http://www. CLINICALTRIALS: gov . Unique identifier: NCT03831672.

Learning curve in pipeline embolization device: results from the pipeline embolization device in China post-market multicentre registry study.

BACKGROUND: Intracranial aneurysms pose a significant health issue, affecting 3-5% of the adult population. The pipeline embolization device (PED) has emerged as a promising treatment for these lesions. This study aimed to investigate the impact of operator experience on complication and poor outcome rates, as well as the learning curve for PED. METHODS: A total of 217 patients were consecutively enroled from four eligible centres and divided into three groups based on the number of procedures performed: group 1 (first 10 procedures), group 2 (11-20 procedures), and group 3(>20 procedures). Major complications include operation-related ischaemic or haemorrhagic events and mass effect deterioration. Poor outcome was defined as a modified Rankin Scale score greater than 2 at discharge. Cumulative summation (CUSUM) analysis was generated to assess the learning curve according to major complications and poor outcome. RESULTS: The study found that major complications and poor outcomes occurred in 5.1% and 2.3% of cases, respectively. The rate of major complications decreased from 10.0% in group 1 to 2.9% in group 3 ( P =0.053), while the rate of poor outcomes decreased from 7.5% in group 1 to 0.7% in group 3 ( P =0.015). Multivariable regression analysis adjusted for covariates showed that operator experience was associated with a lower rate of poor outcomes ( P =0.034). CUSUM analysis demonstrated that the learning curve for avoiding major complications and poor outcomes required 27 (mean=13) and 40 (mean=20) cases, respectively. CONCLUSIONS: These findings suggest that PED treatment requires a learning curve of 40 cases to achieve reproducibility regarding complications and functional results. Additionally, major complications and poor outcomes significantly decreases after the first 20 procedures. CUSUM analysis can serve as a useful tool for monitoring and assessing surgical performance.

Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis.

Atherosclerosis (AS)-induced cardiovascular disease is a leading cause of death worldwide. To date, there is still a lack of effective approaches for AS intervention. Cardamonin (CAD) is a bioactive food component, but its effect on AS is unknown. In this work, CAD was investigated for its effect on AS using low-density lipoprotein receptor knockout mice and tumor necrosis factor-alpha (TNF-α)-stimulated endothelial cells (ECs). After a 12-week intervention, CAD was found to significantly prevent AS formation in the aortic root and aortic tree, reduce the necrotic core area, and inhibit aortic inflammation and oxidative stress. Moreover, CAD quenched TNF-α-provoked inflammation and oxidative stress in ECs. RNA-sequencing identified nuclear factor erythroid-2 related factor 2 (NFE2L2, NRF2)/heme oxidase 1 (HO1) signaling to be drastically activated by CAD. CAD is a known activator of the aryl hydrocarbon receptor (AHR) which is a transcription factor of the NFE2L2 gene. Surprisingly, AHR was not required for CAD's action on the activation of NRF2/HO1 signaling since AHR gene silencing did not reverse this effect. Furthermore, a molecular docking assay showed a strong binding potential of CAD to the Kelch domain of the Kelch-like ECH-associated protein 1 (KEAP1) which sequesters NRF2 in the cytoplasm. Both CAD and the Kelch domain inhibitor Ki696 promoted NRF2 nuclear translocation, whereas the combination of CAD and Ki696 did not yield a greater effect compared with either CAD or Ki696, confirming the interaction of CAD with the Kelch domain. This work provides an experimental basis for CAD as a novel and effective bioactive food component in future AS interventions.

Could statin improve outcomes after pipeline embolization for intracranial aneurysms in a real-world setting?

Background: Several pharmacological pathways have revealed statin to have a positive role in patients with for intracranial aneurysms. However, prior studies regarding the association between statin use and patients' outcomes after pipeline embolization device (PED) treatment were not completely supportive. Objectives: To investigate whether statin medication following PED treatment would improve the outcomes of intracranial aneurysm patients in a real-world setting. Design: A retrospective multicenter cohort study. Methods: Patients were selected from the PLUS registry study conducted from November 2014 to October 2019 across 14 centers in China. The population was divided into two groups: those who received statin medication after the PED treatment and those who did not receive statin medication after PED treatment. Study outcomes included angiographic evaluation of aneurysm occlusion, parent arteries stenosis, ischemic and hemorrhage complications, all-cause mortality, neurologic mortality, and functional outcome. Results: 1087 patients with 1168 intracranial aneurysms were eligible; 232 patients were in the statin user group and the other 855 were in the non-statin user group. For the statin user group versus the non-statin user group, no significant difference was found for the primary outcomes of complete occlusion of aneurysm (82.4% versus 84.2%; p = 0.697). Of the secondary outcomes, none had a significant difference including stenosis of parent arteries ≥ 50% (1.4% versus 2.3%; p = 0.739), total subarachnoid hemorrhage (0.9% versus 2.5%; p = 0.215), all-cause mortality (0.0% versus 1.9%; p = 0.204), neurologic mortality (0.0% versus 1.6%; p = 0.280), excellent (95.5% versus 97.2%; p = 0.877), and favorable (98.9% versus 98.4%; p = 0.933) functional outcomes. The total ischemic complication rate (9.0% versus 7.1%; p = 0.401) was higher but not significant in the statin user group. The propensity score-matched cohort showed similar results. Results of binary multivariable logistic regression analysis and propensity score-matched analysis both showed that statin usage was not independently associated with an increased rate of complete occlusion or any other secondary outcomes. Subgroup analysis found the same result in patients who did not use statin before the procedure. Conclusion: Among patients with intracranial aneurysms, statin use after the PED treatment was not significantly associated with better angiographic and clinical outcomes. Well-designed studies are needed to further confirm this finding.

LncRNA BCLET variant confers bladder cancer susceptibility through alternative splicing of MSANTD2 exon 1.

BACKGROUND: Alternative splicing (AS)-related single nucleotide polymorphisms (SNPs) are associated with risk of cancers, but the potential mechanism has not been fully elucidated. METHODS: Two-stage case-control studies comprising 1630 cases and 2504 controls were conducted to investigate the association between the AS-SNPs and bladder cancer susceptibility. A series of assays were used to evaluate the functional effect of AS-SNPs on bladder cancer risk. RESULTS: We observed that SNP rs558814 A>G located in lncRNA BCLET (Bladder Cancer Low-Expressed Transcript, ENSG00000245498) can decrease the risk of bladder cancer (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.76-0.92, p = 3.26 × 10-4 ). Additionally, the G allele of rs558814 had transcriptional regulatory effects and facilitated the expression of BCLET transcripts, including BCLET-long and BCLET-short. We also found decreased BCLET expression in bladder cancer tissues and cells, and BCLET transcript upregulation substantially inhibited tumor growth of both bladder cancer cells and xenograft models. Mechanistically, BCLET recognized and regulated AS of MSANTD2 to participate in bladder carcinogenesis, preferentially promoting the production of MSANTD2-004. CONCLUSIONS: SNP rs558814 was associated with the expression of BCLET, which mainly increased the expression of MSANTD2-004 through AS of MSANTD2.

Preparation of Heavy Metal Trapping Flocculant Polyacrylamide-Glutathione and Its Application for Cadmium Removal from Water.

In this study, a heavy metal trapping gel with multiple ligand groups was prepared for the first time using response surface methodology. The gel was produced by condensing and grafting glutathione as a grafting monomer onto the main polyacrylamide chain, based on the Mannich reaction mechanism with formaldehyde. FTIR, SEM, TG-DSC, and zeta potentials were used to characterize the gel. The results demonstrated that the gel was morphologically folded and porous, with a net-like structure, which enhanced its net trapping and sweeping abilities, and that glutathione was used to provide sulfhydryl groups to boost the metal trapping ability of polyacrylamide. Coagulation experiments showed that the highest efficiency of the removal of Cd ions from water samples was achieved when the concentration of polyacrylamide-glutathione was 84.48 mgL-1, the concentration of Cd was 10.0 mgL-1, the initial turbidity was 10.40 NTU, and the initial pH was 9.0. Furthermore, the presence of two cations, Cu and Zn, had an inhibitory effect on the removal of Cd ions. In addition, analysis of the zeta potential revealed the flocculation of polyacrylamide-glutathione. The flocculation mechanism of glutathione is mainly chelation, adsorption bridging, and netting sweeping.

Reconstructive endovascular treatment for basilar artery trunk aneurysms: complications and clinical and angiography outcomes.

BACKGROUND: Basilar artery trunk aneurysms (BTAs) are rare intracranial aneurysms. We aim to investigate the procedural complications and clinical and angiographic outcomes of BTAs treated with reconstructive endovascular treatment (EVT). METHODS: We retrospectively reviewed the data of 111 patients with BTAs who underwent reconstructive EVT during 2013-2022. The factors associated with procedural complications and clinical and angiographic outcomes were analyzed. RESULTS: The study included 81 men and 30 women (median age 60 years). Overall, 26 (23.4%) cases presented with subarachnoid hemorrhage and 85 (76.6%) presented with unruptured aneurysms. Periprocedural ischemic and hemorrhagic complications occurred in 29 (26.1%) and 4 (3.6%) cases, respectively. The rate of favorable clinical outcomes was 83.8% (92/111) and the mortality rate was 14.4% (16/111). Angiographic follow-up data were available for 77/95 (81.1%) survivors; 57 (74.0%) and 20 (26%) aneurysms exhibited complete and incomplete obliteration, respectively. Old age, high Hunt and Hess grades (IV-V), hemorrhagic complications, and increased aneurysm size were independent risk factors for unfavorable clinical outcomes (p<0.05). Increased aneurysm size and incomplete aneurysm occlusion on immediate angiography were independent risk factors for incomplete occlusion during follow-up (p<0.05). CONCLUSION: Reconstructive EVTs are a feasible and effective treatment for BTAs but are associated with a high risk of ischemic and hemorrhagic complications and a high mortality rate. Larger aneurysms may predict unfavorable clinical outcomes and aneurysm recurrence during follow-up. Hemorrhagic complications may predict unfavorable clinical outcomes, whereas immediate complete aneurysm occlusion may predict total occlusion during follow-up.