Predictors of early neurological deterioration in patients with acute ischemic stroke.

Background: The present study aimed to develop a reliable and straightforward Nomogram by integrating various parameters to accurately predict the likelihood of early neurological deterioration (END) in patients with acute ischemic stroke (AIS). Methods: Acute ischemic stroke patients from Shaoxing People's Hospital, Shanghai Yangpu District Shidong Hospital, and Shanghai Fifth People's Hospital were recruited based on specific inclusion and exclusion criteria. The primary outcome was END. Using the LASSO logistic model, a predictive Nomogram was generated. The performance of the Nomogram was evaluated using the ROC curve, the Hosmer-Lemeshow test, and a calibration plot. Additionally, the decision curve analysis was conducted to assess the effectiveness of the Nomogram. Results: It was found that the Nomogram generated in the present study showed strong discriminatory performance in both the training and the internal validation cohorts when their ROC-AUC values were 0.715 (95% CI 0.648-0.782) and 0.725 (95% CI 0.631-0.820), respectively. Similar results were observed in two external validation cohorts when their ROC-AUC values were 0.685 (95% CI 0.541-0.829) and 0.673 (95% CI 0.545-0.800), respectively. In addition, CAD, SBP, neutrophils, TBil, and LDL were found to be positively correlated with the occurrence of END post-stroke, while lymphocytes and UA were negatively correlated. Conclusion: Our study developed a novel Nomogram that includes CAD, SBP, neutrophils, lymphocytes, TBil, UA, and LDL and it demonstrated strong discriminatory performance in identifying AIS patients who are likely to develop END.

Spatial differentiation and influencing factors of effective phosphorus in cultivated soil in the water source area of the mid-route of South-to-North water transfer project.

The long-term application of phosphate fertilizers in agricultural production leads to a large accumulation of phosphorus in the soil. When it exceeds a certain limit, phosphorus will migrate to surrounding water bodies through surface runoff and other mechanisms, potentially causing environmental risks such as eutrophication of water bodies and increasing the risk of water source pollution. This study takes Shiyan City, the water resources area of the mid-route of the South-to-North Diversion Project (MSDP), as the study area. Based on 701 sampling points of topsoil, geostatistics and geodetectors were used to explore the spatial heterogeneity and influencing factors of available phosphorus (AP) in the topsoil of the area. The results show that the effective phosphorus content in the topsoil of the study area ranges from 0.30 to 146.00 mg/kg, with an average value of 14.28 mg/kg, showing strong variability characteristics. Geostatistical analysis shows that among all theoretical models, the exponential model has the best fitting effect, with a lump gold effect of 0.447 and a range of 82,000 m. The soil available phosphorus content shows an increasing trend from the Central Valley lowlands to the surrounding mountainous hills. Among them, elevation is the main controlling factor for the spatial variation of available phosphorus in the topsoil, followed by soil types, planting systems, annual precipitation, and organic matter. The non-linear enhancement or dual-factor enhancement among various environmental factors reveals the diversity and complexity of spatial heterogeneity affecting available phosphorus content in cultivated soil. This study could provide scientific references for maintaining ecological security in the water source area of the MSDP, improving the precise management of AP, and enhancing cultivated land quality.

Highly Sensitive Perovskite Photoplethysmography Sensor for Blood Glucose Sensing Using Machine Learning Techniques.

Accurate non-invasive monitoring of blood glucose (BG) is a challenging issue in the therapy of diabetes. Here near-infrared (NIR) photoplethysmography (PPG) sensor based on a vapor-deposited mixed tin-lead hybrid perovskite photodetector is developed. The device shows a high detectivity of 5.32 × 1012 Jones and a large linear dynamic range (LDR) of 204 dB under NIR light, guaranteeing accurate extraction of eleven features from the PPG signal. By a combination of machine learning, accurate prediction of blood glucose level with mean absolute relative difference (MARD) as small as 2.48% is realized. The self-powered PPG sensor also works for real-time outdoor healthcare monitors using sunlight as a light source. The potential for early diabetes diagnoses by the perovskite PPG sensor is demonstrated.

Characterization of isoniazid resistance and genetic mutations in isoniazid-resistant and rifampicin-susceptible Mycobacterium tuberculosis in China.

Background: Patients with tuberculosis resistant to isoniazid but susceptible to rifampicin (Hr-Rs TB) remain a neglected demographic, despite a high disease burden and poor outcomes of these patients. The aim of this study was to investigate the characteristics of isoniazid-resistance-related mutations in Mycobacterium tuberculosis and resistance rates to drugs included in WHO-recommended regimens for Hr-Rs patients. Methods: Mycobacterium tuberculosis isolates (n = 4922) obtained from national tuberculosis drug-resistance surveillance were subjected to whole-genome sequencing to identify Hr-Rs strains. The minimal inhibitory concentrations (MICs) were established for the Hr-Rs strains to determine the isoniazid resistance levels. We also identified drug-resistance-associated mutations for five drugs (fluoroquinolones, ethambutol, pyrazinamide, streptomycin, and amikacin) in the Hr-Rs strains. Results: Of the 4922 strains, 384 (7.8 %) were Hr-Rs. The subculture of seven strains failed, so 377 (98.2 %) strains underwent phenotypic MIC testing. Among the 384 genotypic Hr-Rs strains, 242 (63.0 %) contained the katG Ser315Thr substitution; 115 (29.9 %) contained the -15C>T in the promoter region of the fabG1 gene; and 16 (4.2 %) contained Ser315Asn in the katG gene. Of the 239 strains with the Ser315Thr substitution, 229 (95.8 %) had MIC ≥ 2 µg/mL, and of the 114 strains with the -15C>T mutation, 103 (90.4 %) had 0.25 µg/mL ≤ MIC ≤ 1 µg/mL. The genotypic resistance rates were 0.8 % (3/384) for pyrazinamide, 2.3 % (9/384) for ethambutol and fluoroquinolones; 39.6 % (152/384) of the strains were resistant to streptomycin, but only 0.5 % (2/384) of the strains were resistant to amikacin. Conclusion: Ser315Thr in katG was the predominant mutation conferring the Hr-Rs phenotype, followed by the fabG1 -15C>T mutation. The combination of rifampicin, pyrazinamide, ethambutol, and levofloxacin should be effective in the treatment of patients with Hr-Rs tuberculosis because the resistance rates for these drugs in China are low.

Artificial intelligence-assisted quantitative CT parameters in predicting the degree of risk of solitary pulmonary nodules.

INTRODUCTION: Artificial intelligence (AI) shows promise for evaluating solitary pulmonary nodules (SPNs) on computed tomography (CT). Accurately determining cancer invasiveness can guide treatment. We aimed to investigate quantitative CT parameters for invasiveness prediction. METHODS: Patients with stage 0-IB NSCLC after surgical resection were retrospectively analysed. Preoperative CTs were evaluated with specialized software for nodule segmentation and CT quantification. Pathology was the reference for invasiveness. Univariate and multivariate logistic regression assessed predictors of high-risk SPN. RESULTS: Three hundred and fifty-five SPN were included. On multivariate analysis, CT value mean and nodule type (ground glass opacity vs. solid) were independent predictors of high-risk SPN. The area under the curve (AUC) was 0.811 for identifying high-risk nodules. CONCLUSIONS: Quantitative CT measures and nodule type correlated with invasiveness. Software-based CT assessment shows potential for noninvasive prediction to guide extent of resection. Further prospective validation is needed, including comparison with benign nodules.

Reamer-scraping and implant-pushing technique for transcrestal sinus floor elevation.

Transcrestal maxillary sinus floor elevation is an effective method to solve the problem of insufficient bone height in the posterior maxillary region. However, current methods, such as osteotome sinus floor elevation, cushioned grind-out technique, Smart Drill technique, etc., require specialized surgical tool boxes. In this article, we introduce a new method of transcrestal maxillary sinus elevation that uses built-in reamers of various implant systems to scrap residual bone at the sinus floor and uses the implant to push the sinus membrane during implant placement. This technique is easy to operate and time saving and has a low rate of sinus membrane perforation. After a one-year follow-up observation of 146 people and 175 implants, the endo-sinus bone gains were 5.00 (4.70, 5.30) mm and 2.10 (1.40, 2.70) mm in the group of 3 mm≤residual bone height (RBH)<5 mm and the group of 5 mm≤RBH<8 mm, respectively, which can meet the clinical requirements of implant stability. This technique is suitable in generalizing dental implantation.

Impairment of oocyte quality caused by gut microbiota dysbiosis in obesity.

Obesity poses risks to oocyte maturation and embryonic development in mice and humans, linked to gut microbiota dysbiosis and altered host metabolomes. However, it is unclear whether symbiotic gut microbes have a pivotal role in oocyte quality. In mouse models of fecal microbiota transplantation, we demonstrated aberrant meiotic apparatus and impaired maternal mRNA in oocytes, which is coincident with the poor developmental competence of embryos. Using metabolomics profiling, we discovered that the cytosine and cytidine metabolism was disturbed, which could account for the fertility defects observed in the high-fat diet (HFD) recipient mice. Additionally, cytosine and cytidine are closely related with gut microbiota dysbiosis, which is accompanied by a notable reduction of abundance of Christensenellaceae R-7 group in the HFD mice. In summary, our findings provided evidence that modifying the gut microbiota may be of value in the treatment of infertile female individuals with obesity.

Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies.

Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP3/28), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation.

Vasculature segmentation in 3D hierarchical phase-contrast tomography images of human kidneys.

Efficient algorithms are needed to segment vasculature in new three-dimensional (3D) medical imaging datasets at scale for a wide range of research and clinical applications. Manual segmentation of vessels in images is time-consuming and expensive. Computational approaches are more scalable but have limitations in accuracy. We organized a global machine learning competition, engaging 1,401 participants, to help develop new deep learning methods for 3D blood vessel segmentation. This paper presents a detailed analysis of the top-performing solutions using manually curated 3D Hierarchical Phase-Contrast Tomography datasets of the human kidney, focusing on the segmentation accuracy and morphological analysis, thereby establishing a benchmark for future studies in blood vessel segmentation within phase-contrast tomography imaging.

Efficacy Analysis of Endoscopic-Assisted Traditional Surgery and Traditional Surgery for Sinonasal Malignant Melanoma.

Object: To analyze the effect of traditional surgery and endoscope-assisted traditional surgery on patients with sinonasal malignant melanoma (SMM), and to explore the effective treatment of SMM. Methods: The clinicopathological data and surgical methods of 47 patients with SMM, diagnosed in the Department of Otorhinolaryngology-Head and Neck Surgery at the Third People's Hospital of Yunnan Province from October 2000 to June 2020, were retrospectively analyzed. Among them, 26 cases were treated with traditional surgery, and 21 cases were treated with endoscope-assisted traditional surgery. The 3 and 5 year local recurrence and survival rates were monitored and compared. Results: The 3 year local recurrence rate was compared between the 2 groups: χ2 = 5.4558, P = .020 (P < .05), the endoscope-assisted traditional surgery group had a lower 3 year local recurrence rate. The 3 year survival rate was compared between the 2 groups: χ2 = 1.0231, P = .312 (P > .05), the difference in 3 year survival was not significant between the 2 groups. The 5 year local recurrence rate was compared between the 2 groups: χ2 = 4.4052, P = .036 (P < .05), the endoscope-assisted traditional surgery group had a lower 5 year local recurrence rate. The 5 year survival rate was compared between the 2 groups: χ2 = 4.3085, P = .038 (P < .05), the endoscope-assisted traditional surgery group had a higher 5 year survival rate. Therefore, there were significant differences in the local recurrence rates at 3 and 5 years, as well as the 5 year survival rate, between endoscope-assisted traditional surgery and traditional surgery in the treatment of SMM. Conclusion: Endoscope-assisted traditional surgery can remove local lesions of SMM more completely, reduce the local recurrence rate, and improve the 5 year survival rate of patients.

Monocyte/lymphocyte ratio as a risk factor of cardiovascular and all-cause mortality in coronary artery disease with low-density lipoprotein cholesterol levels below 1.4 mmol/L: A large longitudinal multicenter study.

BACKGROUND AND AIMS: The monocyte/lymphocyte ratio (MLR), an inflammatory marker, has an unclear relationship with the risk of residual inflammation in patients with coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) below 1.4 mmol/L. This study aimed to assess the association between the MLR and cardiovascular and all-cause mortalities in these patients. METHODS: A total of 2747 patients diagnosed with CAD via coronary angiography (CAG) and presenting with LDL-C levels < 1.4 mmol/L were enrolled in this observational study conducted from January 2007 to December 2020. Patients were categorized into four groups based on the MLR quartiles. We used Kaplan-Meier analysis and Cox regression models to evaluate the relationship between baseline MLR and cardiovascular and all-cause mortalities. RESULTS: Among the 2747 participants followed up for a median duration of 6 years, there were 184 cardiovascular and 462 all-cause deaths. Elevated MLR levels were found to be associated with an increased risk of both cardiovascular and all-cause mortalities according to the Kaplan-Meier analysis. Multivariate Cox regression analysis demonstrated a significant association between higher MLR and an elevated risk of cardiovascular and all-cause mortality. Compared to the older group, with an increase in MLR levels, the younger group showed a higher hazard ratio for cardiovascular death. Similar results were obtained in the single-vessel disease group. CONCLUSIONS: In patients with CAD and LDL-C levels < 1.4 mmol/L, MLR can serve as a risk factor for both cardiovascular and all-cause mortalities owing to the risk of residual inflammation.

Chondrocyte Ferritinophagy as a Molecular Mechanism of Arthritis-A Narrative Review.

Osteoarthritis (OA) is a prevalent joint disease affecting orthopedic patients. Its incidence is steadily increasing, causing great economic hardship for individuals and society as a whole. OA is connected with risk factors such as genetics, obesity, and joint diseases; yet, its pathophysiology is still largely understood. At present, several cell death pathways govern the initiation and advancement of OA. It has been discovered that the onset and progression of OA are strongly associated with pyroptosis, senescence, apoptosis, ferroptosis, and autophagy. Ferroptosis and autophagy have not been well studied in OA, and elucidating their molecular mechanisms in chondrocytes is important for the diagnosis of OA. For this reason, we aim was reviewed recent national and international developments and provided an initial understanding of the molecular pathways underlying autophagy and ferroptosis in OA. We determined the reference period to be the last five years by searching for the keywords "osteoarthritis, mechanical stress, Pizeo1, ferroptosis, autophagy, ferritin autophagy" in the three databases of PUBMED, Web of Science, Google Scholar. We then screened irrelevant literature by reading the abstracts. Ferroptosis is a type of programmed cell death that is dependent on reactive oxygen species and Fe2+. It is primarily caused by processes linked to amino acid metabolism, lipid peroxidation, and iron metabolism. Furthermore, Piezoelectric mechanically sensitive ion channel assembly 1 (PIEZO1), which is triggered by mechanical stress, has been revealed to be intimately associated with ferroptosis events. It was found that mechanical injury triggers changes in the intracellular environment of articular chondrocytes (e.g., elevated levels of oxidative stress and increased inflammation) through PIEZO1, ultimately leading to iron death in chondrocytes. Therefore, we believe that PIEZO1 is a key initiator protein of iron death in chondrocytes. Widely present in eukaryotic cells, autophagy is a lysosome-dependent, evolutionarily conserved catabolic process that carries misfolded proteins, damaged organelles, and other macromolecules to lysosomes for breakdown and recycling. Throughout OA, autophagy is activated to differing degrees, indicating that autophagy may play a role in the development of OA. According to recent research, autophagy is a major factor in the process that leads cells to ferroptosis. Despite the notion of ferritinophagy being put forth, not much research has been done to clarify the connection between ferroptosis and autophagy in OA.

Eupafolin hinders cross-talk between gastric cancer cells and cancer-associated fibroblasts by abrogating the IL18/IL18RAP signaling axis.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are involved in the progression of gastric cancer (GC) as a critical component of the tumor microenvironment (TME), yet specific interventions remain limited. Natural products hold a promising application prospect in the field of anti-tumor in view of their high activity and ease of binding with biological macromolecules. However, the role of natural products in modulating the cross-talk between CAFs and GC cells has not been fully investigated. PURPOSE: The aim of this study was to identify a potential therapeutic target in CAFs and then screen for natural small molecule drugs with anti-tumor activity against this target. METHODS: Integrating bioinformatics analysis of public databases and experimental validation of human samples and cell lines to identify a candidate target in CAFs. Molecular docking and biolayer interferometry technique were utilized for screening potential natural small molecule drugs. The efficacy and underlying mechanisms of the candidates were explored in vitro and in vivo through techniques such as lentiviral infection, cell spheroids culture, immunoprecipitation and cells-derived xenografts. RESULTS: IL18 receptor accessory protein (IL18RAP) was found to be overexpressed in CAFs derived from GC tissues and facilitated the protumor function of CAFs on GC. Based on virtual screening and experimental validation, we identified a natural product, eupafolin, that interfered with IL18 signaling. Phenotyping studies confirmed that the proliferation, spheroids formation and tumorigenesis of GC cells facilitated by CAFs were greatly attenuated by eupafolin both in vitro and in vivo. Mechanistically, eupafolin impeded the formation of IL18 receptor (IL18R) complex by directly binding to IL18RAP, thus blocking IL18-mediated nuclear factor kappa B (NF-κB) activation and reduced the synthesis and secretion of IL6 in CAFs. As a consequence, it inactivated signal transducer and activator of transcription 3 (STAT3) in GC cells. CONCLUSION: This study provides new evidence that IL18 signaling regulates the cross-talk between GC cells and CAFs. And it highlights a novel pharmacological role of eupafolin in inhibiting IL18 signaling, thereby curbing the development of GC via modulating CAFs.

Protective effects of tetramethylpyrazine on myocardial ischemia/reperfusion injury involve NLRP3 inflammasome suppression by autophagy activation.

Tetramethylpyrazine (TMP) belongs to the active ingredients of the traditional Chinese medicine Chuanxiong, which has a certain protective effect in myocardial ischemia-reperfusion (I/R) injury. It can improve postoperative cardiac function and alleviate ventricular remodeling in acute myocardial infarction patients. However, its specific protective mechanism is still unclear. In this study, a certain concentration of TMP was introduced into I/R mice or H9C2 cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment to observe the effects of TMP on cardiomyocyte activity, cytotoxicity, apoptosis, autophagy, pyroptosis, and NLRP3 inflammasome activation. The results displayed that TMP intervention could reduce OGD/R and I/R-induced cardiomyocyte apoptosis, accelerate cellular activity and autophagy levels, and ameliorate myocardial tissue necrosis in I/R mice in a dose-dependent manner. Further, TMP prevented the formation of NLRP3 inflammasomes to suppress pyroptosis by increasing the level of cardiomyocyte autophagy after I/R and OGD/R modelling, the introduction of chloroquine to suppress autophagic activity in vivo and in vitro was further analyzed to confirm whether TMP inhibits NLRP3 inflammasome activation and pyroptosis by increasing autophagy, and we found the inhibitory effect of TMP on NLRP3 inflammasomes and its protective effect against myocardial injury were blocked when autophagy was inhibited with chloroquine. In conclusion, this experiment demonstrated that TMP unusually attenuated I/R injury in mice, and this protective effect was achieved by inhibiting the activation of NLRP3 inflammasomes through enhancing autophagic activity.

Estimation of Linear Functionals in High-Dimensional Linear Models: From Sparsity to Nonsparsity.

High dimensional linear models are commonly used in practice. In many applications, one is interested in linear transformations ß âŠ¤ x of regression coefficients ß ∈ R p , where x is a specific point and is not required to be identically distributed as the training data. One common approach is the plug-in technique which first estimates ß , then plugs the estimator in the linear transformation for prediction. Despite its popularity, estimation of ß can be difficult for high dimensional problems. Commonly used assumptions in the literature include that the signal of coefficients ß is sparse and predictors are weakly correlated. These assumptions, however, may not be easily verified, and can be violated in practice. When ß is non-sparse or predictors are strongly correlated, estimation of ß can be very difficult. In this paper, we propose a novel pointwise estimator for linear transformations of ß . This new estimator greatly relaxes the common assumptions for high dimensional problems, and is adaptive to the degree of sparsity of ß and strength of correlations among the predictors. In particular, ß can be sparse or non-sparse and predictors can be strongly or weakly correlated. The proposed method is simple for implementation. Numerical and theoretical results demonstrate the competitive advantages of the proposed method for a wide range of problems.

Revealing the links between hair metal(loids) and alterations in blood pressure among children in e-waste recycling areas through urinary metabolomics.

Hypertension is prevalent in e-waste recycling areas, and elevated blood pressure in children significantly increases the risk of hypertension in adulthood. However, the associations and toxic pathways between chronic exposure to metal(loids) and elevated blood pressure are rarely investigated. In this study, we measured the levels of 29 hair metal(loids) (chronic exposure biomarkers) and blood pressure in 667 susceptible children from an e-waste recycling area to explore their relationships. Paired urine metabolomics analysis was also performed to interpret potential mechanistic pathways. Results showed that the hypertension prevalence in our recruited children (13.0 %) exceeded the average rate (9.5 %) for Chinese children aged 6-17 years. The top five abundant metal(loids), including lead, strontium, barium, and zinc, demonstrated the most profound associations with elevated systolic blood pressure. Quantile g-computation, weighted quantile sum, and Bayesian kernel machine regression analysis jointly demonstrated a significant association between chronic exposure to metal(loids) mixture and systolic blood pressure. Interestingly, selenium showed significant antagonistic interactions with these four metals, suggesting that supplementing selenium may help children resist the elevated blood pressure induced by metal(loids) exposure. Increased metal(loids) and blood pressure levels were significantly linked to changes in urine metabolomics. Structural equation model indicated that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid were the significant mediators of the associations between metal(loids) and blood pressure, with mediation effects of 77.4 % and 29.0 %, respectively, suggesting that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid may be involved in the development of metal-induced blood pressure elevating effect. Girls were more vulnerable to metal(loids)-induced hormonal imbalance, especially androsterone glucuronide, than boys. Chronic exposure to metal(loids) at e-waste recycling sites may contribute to elevated blood pressure in children through disrupting various metabolism pathways, particularly hormonal balance. Our study provides new insights into potential mechanistic pathways of metal(loids)-induced changes in children's blood pressure.

A Monte Carlo Simulation Dataset of Radiation Field Parameters for a Simple Nuclear Facility Scenario.

Radioactive safety in nuclear facilities is of utmost importance. Prior to workers entering these areas, a 3D radiation field is needed for accurately estimating their exposure. Due to the complex relationship between radiation measurements and radiation fields, implementing neural networks is a promising approach for reconstruction. However, research on direct 3D radiation field reconstruction using neural networks is limited, and there is no standardized open-source dataset for training and evaluation. To address these issues, we created a simplified model of a nuclear facility and utilized the Monte Carlo program MCShield to simulate 3D radiation parameters. MCShield, which is mainly used for shielding calculations, has been verified for accuracy through benchmark tests. In addition, this paper proves the correctness of the MCShield program and the effectiveness of the AIS variance reduction method through calculations on the WinFrith Iron benchmark experiment and the NUREG/CR-6115 benchmark. The results show that the MCShield program as well as the AIS method can be used for dataset calculations.

Association of ACEI/ARB therapy with total and cardiovascular death in coronary artery disease patients with advanced chronic kidney disease: a large multi-center longitudinal study.

INTRODUCTION: Advanced chronic kidney disease (CKD) is common among patients with coronary artery disease (CAD), and angiotensin­converting enzyme inhibitors (ACEI) or angiotensin­receptor blockers (ARB) can improve cardiac and renal function, but whether ACEI/ARB therapy improves long-term prognosis remains unclear among these high-risk patients. Therefore, this research aimed to investigate the relationship between ACEI/ARB therapy and long-term prognosis among CAD patients with advanced CKD. METHODS: CAD patients with advanced CKD were included in five hospitals. Advanced CKD was defined as estimated glomerular filtration rate (eGFR)<30 ml/min per 1.73 m2. Cox regression models and competing risk Fine and Gray models were used to examine the relationship between ACEI/ARB therapy and all-cause and cardiovascular death, respectively. RESULTS: Of 2527 patients, 47.6% population of our cohort was discharged on ACEI/ARB. The overall all-cause and cardiovascular mortality were 38.6% and 24.7%, respectively. Multivariate Cox regression analyses indicated that ACEI/ARB therapy was found to be associated with lower rates of both all-cause mortality (hazard ratio (HR)=0.836, 95% confidence interval (CI): 0.738-0.948, p = 0.005) and cardiovascular mortality (HR = 0.817, 95%CI: 0.699-0.956, p = 0.011). In the propensity-matched cohort, the survival benefit was consistent, and significantly better survival was observed for all-cause mortality (HR = 0.856, 95%CI: 0.752-0.974, p = 0.019) and cardiovascular mortality (HR = 0.830, 95%CI: 0.707-0.974, p = 0.023) among patients treated with ACEI/ARB. CONCLUSION: ACEI/ARB therapy showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up, which manifested that strategies to maintain ACEI/ARB treatment may improve clinical outcomes among these high-risk populations.

What is the current knowledge on the topic? Advanced CKD is highly prevalent and strongly associated with higher mortality risk and worse outcomes among CAD patients, and patients with advanced CKD have often been excluded from randomized controlled trials, creating an evidence gap for these high-risk CAD patients. ACEI/ARB are beneficial for greater survival among CAD patients, but the effect of ACEI/ARB therapy on long-term prognosis is unclear among CAD patients with advanced CKD.What does this study add to our knowledge? ACEI/ARB treatment showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up.How might this change clinical pharmacology or translational science? CAD patients with advanced CKD are not only have worse outcomes but also limited in their choice of therapy strategies. Our study may prompt an important reference for the subsequent improvement of long-term prognosis among these high-risk populations.

Predictive Analysis in Oral Cancer Immunotherapy: Profiling Dual PD-L1-Positive Extracellular Vesicle Subtypes with Step-Wedge Microfluidic Chips.

PD-L1-positive extracellular vesicles (PD-L1+ EVs) play a pivotal role as predictive biomarkers in cancer immunotherapy. These vesicles, originating from immune cells (I-PD-L1+ EVs) and tumor cells (T-PD-L1+ EVs), hold distinct clinical predictive values, emphasizing the importance of deeply differentiating the PD-L1+ EV subtypes for effective liquid biopsy analyses. However, current methods such as ELISA lack the ability to differentiate their cellular sources. In this study, a novel step-wedge microfluidic chip that combines magnetic microsphere separation with single-layer fluorescence counting is developed. This chip integrates magnetic microspheres modified with anti-PD-L1 antibodies and fluorescent nanoparticles targeting EpCAM (tumor cell marker) or CD45 (immunocyte marker), enabling simultaneous quantification and sensitive analysis of PD-L1+ EV subpopulations in oral squamous cell carcinoma (OSCC) patients' saliva without background interference. Analysis results indicate reduced levels of I-PD-L1+ EVs in OSCC patients compared to those in healthy individuals, with varying levels of heterogeneous PD-L1+ EVs observed among different patient groups. During immunotherapy, responders exhibit decreased levels of total PD-L1+ EVs and T-PD-L1+ EVs, accompanied by reduced levels of I-PD-L1+ EVs. Conversely, nonresponders show increased levels of I-PD-L1+ EVs. Utilizing the step-wedge microfluidic chip allows for simultaneous detection of PD-L1+ EV subtypes, facilitating the precise prediction of oral cancer immunotherapy outcomes.

Analysis of the primary factors influencing donor derived cell-free DNA testing in kidney transplantation.

The donor-derived cell-free DNA (ddcfDNA) is found in the plasma and urine of kidney transplant recipients and displays notable potential in diagnosing rejection, specifically antibody-mediated rejection (ABMR). Nonetheless, the quantitative methods of ddcfDNA lacking standardization and diverse detection techniques can impact the test outcomes. Besides, both the fraction and absolute values of ddcfDNA have been reported as valuable markers for rejection diagnosis, but they carry distinct meanings and are special in various pathological conditions. Additionally, ddcfDNA is highly sensitive to kidney transplant injury. The various sampling times and combination with other diseases can indeed impact ddcfDNA detection values. This review comprehensively analyses the various factors affecting ddcfDNA detection in kidney transplantation, including the number of SNPs and sequencing depths. Furthermore, different pathological conditions, distinct sampling time points, and the presence of complex heterologous signals can influence ddcfDNA testing results in kidney transplantation. The review also provides insights into ddcfDNA testing on different platforms along with key considerations.