Ablation apprentices and their first experience of pulmonary vein isolation procedure on paroxysmal atrial fibrillation with different sheaths.

OBJECTIVES: This study aimed at exploring how using different kinds of sheaths will affect the very first ablation procedure of apprentices. METHODS: 15 patients with paroxysmal atrial fibrillation were randomized to used fixed-curve, conventional steerable or visualized steerable sheath, and received complete isolation of pulmonary veins. All ablations were the very first procedure performed by 15 ablation apprentices. The use of fluoroscopy and catheter stability during the PVI were analyzed. RESULTS: Procedure duration was much longer in the fixed-curve group (116.8 ± 27 vs. 62.2 ± 17 vs. 60.4 ± 17, p < 0.001). X-ray exposure was lowest with visualized sheath (17.6 ± 5 vs. 18.6 ± 6 vs. 5.2 ± 6, p < 0.001). CF SD differed significantly, especially at the anterior aspect of LSPV (7.90 ± 2.90 vs. 5.04 ± 2.18 vs. 4.52 ± 2.40, p < 0.001) and posterior aspect of RSPV (6.84 ± 2.79 vs. 3.42 ± 2.04 vs. 3.50 ± 2.30, p < 0.001) in the fixed-curve group. Impedance drop was significantly smaller in the fixed-curve group at the anterior aspect of LSPV (8.74 ± 3.02 vs. 11.49 ± 5.48 vs. 12.57 ± 5.96, p = 0.005). CONCLUSION: Even for the very first ablation procedure of an ablation apprentice, the use of steerable sheaths will significantly reduce the procedure duration and improve the catheter stability, but only visualized steerable sheath can reduce fluoroscopic time.

Associations of lipids and lipid-modifying drug target genes with atrial fibrillation risk based on genomic data.

BACKGROUND: The causal associations of lipids and the drug target genes with atrial fibrillation (AF) risk remain obscure. We aimed to investigate the causal associations using genetic evidence. METHODS: Mendelian randomization (MR) analyses were conducted using summary-level genome-wide association studies (GWASs) in European and East Asian populations. Lipid profiles (low-density lipoprotein cholesterol, triglyceride, and lipoprotein[a]) and lipid-modifying drug target genes (3-hydroxy-3-methylglutaryl-CoA reductase, proprotein convertase subtilisin/kexin type 9, NPC1-like intracellular cholesterol transporter 1, apolipoprotein C3, angiopoietin-like 3, and lipoprotein[a]) were used as exposures. AF was used as an outcome. The inverse variance weighted method was applied as the primary method. Summary-data-based Mendelian randomization analyses were performed for further validation using expression quantitative trait loci data. Mediation analyses were conducted to explore the indirect effect of coronary heart disease. RESULTS: In the European population, MR analyses demonstrated that elevated levels of lipoprotein(a) increased AF risk. Moreover, analyses focusing on drug targets revealed that the genetically proxied target gene LPA, which simulates the effects of drug intervention by reducing lipoprotein(a), exhibited an association with AF risk. This association was validated in independent datasets. There were no consistent and significant associations observed for other traits when analyzed in different datasets. This finding was also corroborated by Summary-data-based Mendelian randomization analyses between LPA and AF. Mediation analyses revealed that coronary heart disease plays a mediating role in this association. However, in the East Asian population, no statistically significant evidence was observed to support these associations. CONCLUSIONS: This study provided genetic evidence that Lp(a) may be a causal factor for AF and that LPA may represent a promising pharmacological target for preventing AF in the European population.

Procatechuic acid and protocatechuic aldehyde increase survival of Caenorhabditis elegans after fungal infection and inhibit fungal virulence.

Protocatechuic acid (PCA) and protocatechuic aldehyde (PAL) are important phenolic compounds in plants. We here investigated their possible beneficial effect against fungal infection and the underlying mechanism. The model animal of Caenorhabditis elegans was used as host, and Candida albicans was used as fungal pathogen. The nematodes were first infected with C. albicans, and the PCA and PAL treatment were then performed. Post-treatment with 10-100 µM PCA and PAL suppressed toxicity of C. albicans infection in reducing lifespan. Accompanied with this beneficial effect, treatment with 10-100 µM PCA and PAL inhibited C. albicans accumulation in intestinal lumen. In addition, treatment with 10-100 µM PCA and PAL suppressed the increase in expressions of antimicrobial genes caused by C. albicans infection. The beneficial effect of PCA and PAL against C. albicans infection depended on p38 MAPK and insulin signals. Moreover, although treatment with 10-100 µM PCA and PAL could not exhibit noticeable antifungal activity, PCA and PAL treatment obviously suppressed biofilm formation, inhibited hyphal growth, and reduced expressions of virulence genes (ALS3, CaVps34, Vma7, Vac1, and/or HWP1) related to biofilm formation and hyphal growth in C. albicans. Therefore, our data demonstrated the potential of PCA and PAL post-treatment against fungal infection and fungal virulence.

Synergistic effect of chimeric antigen receptor modified with Bcl-2 on enhanced solid tumour targeting.

Engineered T cells expressing chimeric antigen receptors (CARs) have shown remarkable therapeutic effects on haematological malignancies. However, CART cells are less effective on solid tumours mainly due to their weak persistence, which might be caused by activation-induced cell death (AICD). To overcome this limitation, CART cell with the antigen, Epidermal growth factor receptor variant III (EGFRvIII), targeting was modified to carry the anti-apoptotic molecule B cell lymphoma 2 (Bcl-2), and the final construct was named as EGFRvIII·CART-Bcl2 cells. Compared with the EGFRvIII·CART cells, EGFRvIII·CART-Bcl2 cells revealed higher capacities of proliferation, anti-apoptosis and tumour cell killing in vitro. Moreover, EGFRvIII·CART-Bcl2 cells had a longer persistence rate and exerted better anti-tumour effects than EGFRvIII·CART cells in cervical carcinoma xenograft model. Taken together, our findings suggest that incorporating anti-apoptotic molecules into CART cells may enhance its therapeutic effects against solid tumours.

Transgenerational Response of Germline Nuclear Hormone Receptor Genes to Nanoplastics at Predicted Environmental Doses in Caenorhabditis elegans.

Transgenerational nanoplastic toxicity could be detected in Caenorhabditis elegans after exposure at the parental generation (P0-G); however, the underlying mechanisms remain largely unclear. We aimed to examine the role of germline nuclear hormone receptors (NHRs) in controlling the transgenerational toxicity of polystyrene nanoparticles (PS-NPs) based on gene expression screening and functional analysis. Among germline NHR genes, daf-12, nhr-14, and nhr-47 expressions were increased and nhr-12 expression was decreased by PS-NPs (1 and 10 µg/L). Transgenerational alterations in expressions of these four NHR genes were also induced by PS-NPs (1 and 10 µg/L). RNAi of daf-12, nhr-14, and nhr-47 caused resistance, whereas RNAi of nhr-12 conferred susceptibility to transgenerational PS-NP toxicity. After PS-NP exposure, expressions of ins-3, daf-28, and ins-39 encoding insulin ligands, efn-3 encoding Ephrin ligand, and lin-44 encoding Wnt ligand, as well as expressions of their receptor genes (daf-2, vab-1, and/or mig-1), were dysregulated by the RNAi of daf-12, nhr-14, nhr-47, and nhr-12. Therefore, alteration in certain germline NHRs could mediate the induction of transgenerational nanoplastic toxicity by affecting secreted ligands and their receptors in the offspring of exposed organisms.

Overexpressing Bcl-2 enhances murine chimeric antigen receptor T cell therapy against solid tumor.

Chimeric antigen receptor T (CART) cell therapy has demonstrated promising potential in the treatment of hematologic malignancies. However, its application to solid tumors is limited due to the restrictive nature of the tumor microenvironment, resulting in functional failure and poor persistence of CART cells. Overexpression of Bcl-2 in human CART cells (hCART) has been found to significantly enhance their anti-apoptotic effects both in vitro and in vivo. Nevertheless, the evaluation of hCART cells in preclinical studies has predominantly relied on immunodeficient mice xenograft tumor models, making it challenging to assess the impact of hCART cells on normal tissues and the immune system. We established a murine CART (mCART) that overexpresses Bcl-2 and targets the epidermal growth factor receptor variant III (EGFRvIII), named EGFRvIII·mCART-Bcl2. It demonstrated superior proliferation, cytotoxicity, and anti-apoptotic capabilities in vitro. In an immunocompetent mouse model of abdominal metastasis of colorectal cancer, EGFRvIII·mCART-Bcl2 exhibited improved survival of CART in the abdomen, increased tumor clearance, and significantly prolonged overall mouse survival. In summary, our study provides evidence that the introduction of Bcl-2 into mCART cells can enhance their therapeutic efficacy against solid tumors while ensuring safety.

Bioactive components and potential mechanisms of Biqi Capsule in the treatment of osteoarthritis: based on chondroprotective and anti-inflammatory activity.

Cartilage damage and synovial inflammation are vital pathological changes in osteoarthritis (OA). Biqi Capsule, a traditional Chinese medicine formula used for the clinical treatment of arthritis in China, yields advantages in attenuating OA progression. The drawback here is that the bioactive components and pharmacological mechanisms by which Biqi Capsule exerts its anti-inflammatory and chondroprotective effects have yet to be fully clarified. For in vivo studies, a papain-induced OA rat model was established to explore the pharmacological effects and potential mechanisms of Biqi Capsule against OA. Biqi Capsule alleviated articular cartilage degeneration and chondrocyte damage in OA rats and inhibited the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in synovial tissue. Network pharmacology analysis suggested that the primary biological processes regulated by Biqi Capsule are inflammation and oxidative stress, and the critical pathway regulated is the PI3K/AKT signaling pathway. The result of this analysis was later verified on SW1353 cells. The in vitro studies demonstrated that Glycyrrhizic Acid and Liquiritin in Biqi Capsule attenuated H2O2-stimulated SW1353 chondrocyte damage via activation of PI3K/AKT/mTOR pathway. Moreover, Biqi Capsule alleviated inflammatory responses in LPS-stimulated RAW264.7 macrophages via the NF-κB/IL-6 pathway. These observations were suggested to have been facilitated by Brucine, Liquiritin, Salvianolic Acid B, Glycyrrhizic Acid, Cryptotanshinone, and Tanshinone ⅡA. Put together, this study partially clarifies the pharmacological mechanisms and the bioactive components of Biqi capsules against OA and suggests that it is a promising therapeutic option for the treatment of OA. Chemical compounds studied in this article. Strychnine (Pubchem CID:441071); Brucine (Pubchem CID:442021); Liquiritin (Pubchem CID:503737); Salvianolic Acid B (Pubchem CID:6451084); Glycyrrhizic Acid (Pubchem CID:14982); Cryptotanshinone (Pubchem CID:160254); Tanshinone ⅡA (Pubchem CID:164676).

Enhanced ApcMin/+ adenoma formation after epithelial CUL4B deletion by recruitment of myeloid-derived suppressor cells.

Colorectal cancer (CRC) stands as a prevalent malignancy globally. A pivotal event in CRC pathogenesis involves the loss-of-function mutation in the APC gene, leading to the formation of benign polyps. Despite the well-established role of APC, the contribution of CUL4B to CRC initiation in the pre-tumorous stage remains poorly understood. In this investigation, we generated a murine model by crossing ApcMin/+ mice with Cul4bΔIEC mice to achieve specific deletion of Cul4b in the gut epithelium against an ApcMin/+ background. By employing histological methods, RNA-sequencing (RNA-seq), and flow cytometry, we assessed alterations and characterized the immune microenvironment. Our results unveiled that CUL4B deficiency in gut epithelium expedited ApcMin/+ adenoma formation. Notably, CUL4B in adenomas restrained the accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs). In vivo inhibition of MDSCs significantly delayed the growth of CUL4B deleted ApcMin/+ adenomas. Furthermore, the addition of MDSCs to in vitro cultured ApcMin/+; Cul4bΔIEC adenoma organoids mitigated their alterations. Mechanistically, CUL4B directly interacted with the promoter of Csf3, the gene encoding granulocyte-colony stimulating factor (G-CSF) by coordinating with PRC2. Inhibiting CUL4B epigenetically activated the expression of G-CSF, promoting the recruitment of MDSCs. These findings offer novel insights into the tumor suppressor-like roles of CUL4B in regulating ApcMin/+ adenomas, suggesting a potential therapeutic strategy for CRC initiation and progression in the context of activated Wnt signaling.

Rho kinase inhibitor Y-27632 downregulates IL-1ß expression in mice with experimental autoimmune myocarditis.

Autoimmune myocarditis is the limited or diffuse inflammation of the myocardium due to dysfunctional cellular and humoral immunity mechanisms. We constructed mouse models of experimental autoimmune myocarditis (EAM) using peptide MyHC-α614-629. On the day after secondary immunization, the mice were intraperitoneally injected with Rho kinase (ROCK) inhibitor Y-27632. On day 21, the cardiac tissues were harvested and weighed. The hearts of EAM mice were significantly enlarged and whitened. Furthermore, body weight (BW) slowly increased during the treatment period, the heart weight (HW) and the ratio of HW/eventual BW were increased, and inflammatory infiltration and fibrosis were aggravated in the myocardial tissue. Y-27632 treatment improved the aforementioned phenotypic and pathological features of EAM mice. Mechanistic analysis revealed a significant increase in Notch1, Hes1, Jag2, Dil1, Toll-like receptor (Tlr) 2, and interleukin (IL)-1ß expression in the myocardial tissue of EAM mice. Notably, IL-1ß expression was correlated with that of Notch1 and Tlr2. Following Y-27632 treatment, the expression of key target genes of the Notch signaling pathway (Notch1, Hes1, Dil1, and Jag2) and Tlr2 were obviously decreased. Y-27632 treatment also decreased the number of monocytes in the spleen of EAM mice. Thus, ROCK inhibitor Y-27632 exerted a protective effect in EAM mice by downregulating IL-1ß expression. This study aimed to provide a reference point for the future treatment of myocarditis in clinical settings.

Comparison of intestinal toxicity in enhancing intestinal permeability and in causing ROS production of six PPD quinones in Caenorhabditis elegans.

As the derivatives of p-phenylenediamines (PPDs), PPD quinones (PPDQs) have received increasing attention due to their possible exposure risk. We compared the intestinal toxicity of six PPDQs (6-PPDQ, 77PDQ, CPPDQ, DPPDQ, DTPDQ and IPPDQ) in Caenorhabditis elegans. In the range of 0.01-10 µg/L, only 77PDQ (10 µg/L) moderately induced the lethality. All the examined PPDQs at 0.01-10 µg/L did not affect intestinal morphology. Different from this, exposure to 6-PPDQ (1-10 µg/L), 77PDQ (0.1-10 µg/L), CPPDQ (1-10 µg/L), DPPDQ (1-10 µg/L), DTPDQ (1-10 µg/L), and IPPDQ (10 µg/L) enhanced intestinal permeability to different degrees. Meanwhile, exposure to 6-PPDQ (0.1-10 µg/L), 77PDQ (0.01-10 µg/L), CPPDQ (0.1-10 µg/L), DPPDQ (0.1-10 µg/L), DTPDQ (1-10 µg/L), and IPPDQ (1-10 µg/L) resulted in intestinal reactive oxygen species (ROS) production and activation of both SOD-3::GFP and GST-4::GFP. In 6-PPDQ, 77PDQ, CPPDQ, DPPDQ, DTPDQ, and/or IPPDQ exposed nematodes, the ROS production was strengthened by RNAi of genes (acs-22, erm-1, hmp-2, and pkc-3) governing functional state of intestinal barrier. Additionally, expressions of acs-22, erm-1, hmp-2, and pkc-3 were negatively correlated with intestinal ROS production in nematodes exposed to 6-PPDQ, 77PDQ, CPPDQ, DPPDQ, DTPDQ, and/or IPPDQ. Therefore, exposure to different PPDQs differentially induced the intestinal toxicity on nematodes. Our data highlighted potential exposure risk of PPDQs at low concentrations to organisms by inducing intestinal toxicity.

Human emissions of size-resolved fluorescent bioaerosols in control situations.

Human bioaerosols contribute significantly to indoor air quality. This study used a Wideband Integrated Bioaerosol Sensor (WIBS-4A) instrument for real-time measurement of particle size distribution and count to differentiate fluorescent bioaerosols from non-fluorescent aerosols. Through an experiment involving 12 subjects (six men and six women) wearing standard cotton clothing in a 2 m × 2 m × 2 m environmental chamber, we established a quantitative method to obtain the bioaerosol emission rate of a single subject, aiming to explore the effects of masks and sex on bioaerosol emissions from different individuals. The mean emission rates of fluorescent bioaerosols in the particle size ranges of 0.5-2.5 µm and 2.5-10 µm were 3.192±2.11×104 counts/(person·h) and 13.98±9.34×104 counts/(person·h), respectively. A comparison between those wearing and not wearing masks revealed no significant differences in the emissions of fluorescent bioaerosols. This suggests respiratory sources may not significantly impact the emissions of fluorescent bioaerosols from individuals under seated breathing conditions. Significant disparities in the fluorescent bioaerosol emission rates of different biological sexes were observed through independent sample analysis. Males exhibited 41 % and 15 % higher emission rates than females for particle size ranges of 0.5-2.5 µm and 2.5-10 µm, respectively, possibly because of different metabolic rates. A significant correlation between metabolic rates and fluorescent bioaerosols (sig = 0.044 < 0.05) was observed in all the subjects. These findings underscore the individual variations that affect bioaerosol emission rates. The data provided by this study will facilitate further analysis of the on-site measured data and source analysis.

Deep learning-based label-free imaging of lymphatics and aqueous veins in the eye using optical coherence tomography.

We demonstrate an adaptation of deep learning for label-free imaging of the micro-scale lymphatic vessels and aqueous veins in the eye using optical coherence tomography (OCT). The proposed deep learning-based OCT lymphangiography (DL-OCTL) method was trained, validated and tested, using OCT scans (23 volumetric scans comprising 19,736 B-scans) from 11 fresh ex vivo porcine eyes with the corresponding vessel labels generated by a conventional OCT lymphangiography (OCTL) method based on thresholding with attenuation compensation. Compared to conventional OCTL, the DL-OCTL method demonstrates comparable results for imaging lymphatics and aqueous veins in the eye, with an Intersection over Union value of 0.79 ± 0.071 (mean ± standard deviation). In addition, DL-OCTL mitigates the imaging artifacts in conventional OCTL where the OCT signal modelling was corrupted by the tissue heterogeneity, provides ~ 10 times faster processing based on a rough comparison and does not require OCT-related knowledge for correct implementation as in conventional OCTL. With these favorable features, DL-OCTL promises to improve the practicality of OCTL for label-free imaging of lymphatics and aqueous veins for preclinical and clinical imaging applications.

Cancer-Alterome: a literature-mined resource for regulatory events caused by genetic alterations in cancer.

It is vital to investigate the complex mechanisms underlying tumors to better understand cancer and develop effective treatments. Metabolic abnormalities and clinical phenotypes can serve as essential biomarkers for diagnosing this challenging disease. Additionally, genetic alterations provide profound insights into the fundamental aspects of cancer. This study introduces Cancer-Alterome, a literature-mined dataset that focuses on the regulatory events of an organism's biological processes or clinical phenotypes caused by genetic alterations. By proposing and leveraging a text-mining pipeline, we identify 16,681 thousand of regulatory events records encompassing 21K genes, 157K genetic alterations and 154K downstream bio-concepts, extracted from 4,354K pan-cancer literature. The resulting dataset empowers a multifaceted investigation of cancer pathology, enabling the meticulous tracking of relevant literature support. Its potential applications extend to evidence-based medicine and precision medicine, yielding valuable insights for further advancements in cancer research.

A systematic evaluation of computation methods for cell segmentation.

Cell segmentation is a fundamental task in analyzing biomedical images. Many computational methods have been developed for cell segmentation, but their performances are not well understood in various scenarios. We systematically evaluated the performance of 18 segmentation methods to perform cell nuclei and whole cell segmentation using light microscopy and fluorescence staining images. We found that general-purpose methods incorporating the attention mechanism exhibit the best overall performance. We identified various factors influencing segmentation performances, including training data and cell morphology, and evaluated the generalizability of methods across image modalities. We also provide guidelines for choosing the optimal segmentation methods in various real application scenarios. We developed Seggal, an online resource for downloading segmentation models already pre-trained with various tissue and cell types, which substantially reduces the time and effort for training cell segmentation models.

Combined-task deep network based on LassoNet feature selection for predicting the comorbidities of acute coronary syndrome.

Acute coronary syndrome (ACS) is a multifaceted cardiovascular condition frequently accompanied by multiple comorbidities, which can have significant implications for patient outcomes and treatment approaches. Precisely predicting these comorbidities is crucial for providing personalized care and making well-informed clinical decisions. However, there is a shortage of research investigating the identification of risk factors associated with ACS comorbidities and accurately predicting their likelihood of occurrence beyond heart failure. In this study, an approach called Combined-task Deep Network based on LassoNet feature selection (CDNL) is presented for predicting ACS comorbidities, including hypertension, diabetes, hyperlipidemia, and heart failure. In order to identify crucial biomarkers associated with ACS comorbidities, the proposed framework first incorporates LassoNet, which extends Lasso regression to the deep network by adding a skip (residual) layer. Additionally, a correlation score calculation method across tasks is introduced based on measuring the overlap of identified biomarkers and their assigned importance. This method enables the development of an optimal combined-task prediction model for each ACS comorbidity, addressing the challenge of limited representations in traditional multi-task learning. Our evaluation, conducted through a meticulous cross-sectional study at a tertiary hospital in China, involved a dataset of 2941 samples with 42 clinical features. The results demonstrate that CDNL facilitates the identification of significant biomarkers and achieves an average improvement in AUC of 4.93% and 8.58% compared to deep learning multi-layer neural network (DNN) and SVM, respectively. Additionally, it shows an average improvement of 2.64% and 1.92% compared to two state-of-the-art multi-task models.

Synthesis, characterization and discovery of multiple anticancer mechanisms of dibutyltin complexes based on salen-like ligands.

A series of novel dibutyltin complexes based on salen-like ligands (S01-S03) were synthesized and characterized using ultraviolet-visible spectra，infrared spectra, 1H, 13C, and 119Sn nuclear magnetic resonance, high-resolution mass spectrometry, X-ray crystallography, and thermogravimetric analysis. Complex S03 had excellent anticancer activity in vitro (IC50 = 1.5 ± 0.2 µM in CAL-27 cell lines), which highly activated ROS expression levels and induced apoptosis and cell cycle arrest at the G2/M phase. Interestingly, complex S03 induced cancer cell death through multiple mechanisms (mitochondrial pathway, ER-stress pathway, and DNA damage pathway). This study reveals new mechanisms of organotin complexes and provides new insights into the development of organotin metal complexes as anticancer drugs in the future, and compounds with multiple anticancer mechanisms may be a new strategy for delaying or overcoming drug resistance to chemotherapy and target therapy.

TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.

The association between chronic sinonasal inflammation and nasopharyngeal carcinoma - A systematic review and meta-analysis.

PURPOSE: There has been mounting evidence that inflammation is a key risk factor towards the development of certain cancers. Past studies have shown associations between nasopharyngeal carcinoma (NPC) and sinonasal tract inflammation. We aim to conduct a review and meta-analysis on the association between NPC and chronic sinus inflammation. MATERIALS AND METHODS: We conducted a meta-analysis, searching 4 international databases from 1 January 1973 to 28 March 2022 for studies reporting on sinonasal inflammation and NPC in adult patients (>18 years old). We included cohort, case-control or cross-sectional studies. These studies must examine the association between a prior history of sinonasal inflammation and the risk of developing NPC. The outcome is the incidence of NPC in patients who had prior sinonasal inflammation. RESULTS: 8 studies (8245 NPC; 1,036,087 non-NPC) were included. The overall odds ratio (OR) of patients having NPC after reporting sinonasal inflammation was 1.81 (95 % CI 1.73-1.89). Of note, chronic rhinosinusitis (CRS) (OR of 1.78 (95 %-CI: 1.68-1.90)) was more closely associated with an increased risk of NPC, as compared to allergic rhinitis (AR) (OR of 1.60 (95 %-CI: 1.52-1.68)). CONCLUSION: Chronic sinonasal inflammation is significantly associated with NPC in this systemic review and meta-analysis. The true cause-effect relationship and the potential effects of targeted screening need to be explored thoroughly with large scale prospective studies.

The neutrophil percentage-to-albumin ratio is associated with all-cause mortality in patients with chronic heart failure.

BACKGROUND: In this study, we evaluated the predictive utility of neutrophil percentage-to-albumin ratio (NPAR) for all-cause mortality in patients with chronic heart failure (CHF). METHODS: Patients diagnosed as CHF enrolled in this retrospective cohort study were from Beijing Chaoyang Hospital, capital medical university. Admission NPAR was calculated as neutrophil percentage divided by serum albumin. The endpoints of this study were defined as 90-day, 1-year and 2-year all-cause mortality. Multivariable Cox proportional hazard regression model was performed to confirm the association between NPAR and all-cause mortality. Receiver operating characteristics (ROC) curves were used to evaluate the ability for NPAR to predict all-cause mortality. RESULTS: The 90-day (P = 0.009), 1-year (P < 0.001) and 2-year (P < 0.001) all-cause mortality in 622 patients with CHF were increased as admission NPAR increased. Multivariable Cox regression analysis found the higher NPAR value was still independently associated with increased risk of 90-day (Group III versus Group I: HR, 95% CI: 2.21, 1.01-4.86, P trend = 0.038), 1-year (Group III versus Group I: HR, 95% CI:2.13, 1.30-3.49, P trend = 0.003), and 2-year all-cause mortality (Group III versus Group I: HR, 95% CI:2.06, 1.37-3.09, P trend = 0.001), after adjustments for several confounders. ROC curves revealed that NPAR had a better ability to predict all-cause mortality in patients with CHF, than either albumin or the neutrophil percentage alone. CONCLUSIONS: NPAR was independently correlated with 90-day, 1-year, and 2-year all-cause mortality in patients with CHF.