Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis.

The heterogeneous cellular microenvironment of human airway chronic inflammatory diseases, including chronic rhinosinusitis (CRS) and asthma, is still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on the nasal mucosa of healthy individuals and patients with three subtypes of CRS and identified disease-specific cell subsets and molecules that specifically contribute to the pathogenesis of CRS subtypes. As such, ALOX15+ macrophages contributed to the type 2 immunity-driven pathogenesis of one subtype of CRS, eosinophilic CRS with nasal polyps (eCRSwNP), by secreting chemokines that recruited eosinophils, monocytes and T helper 2 (TH2) cells. An inhibitor of ALOX15 reduced the release of proinflammatory chemokines in human macrophages and inhibited the overactivation of type 2 immunity in a mouse model of eosinophilic rhinosinusitis. Our findings advance the understanding of the heterogeneous immune microenvironment and the pathogenesis of CRS subtypes and identify potential therapeutic approaches for the treatment of CRS and potentially other type 2 immunity-mediated diseases.

Development and validation of a nomogram for predicting overall survival in patients with sinonasal mucosal melanoma.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a relatively rare malignant tumour with a poor prognosis. This study was designed to identify prognostic factors and establish a nomogram model to predict the overall survival (OS) of patients with SNMM. METHODS: A total of 459 patients with SNMM were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort. Univariate and multivariate Cox regression analyses were used to screen for independent factors associated with patient prognosis and develop the nomogram model. In addition, external validation was performed to evaluate the effectiveness of the nomogram with a cohort of 34 patients with SNMM from Peking Union Medical College Hospital. RESULTS: The median OS in the cohort from the SEER database was 28 months. The 1-year, 3-year and 5-year OS rates were 69.8%, 40.4%, and 30.0%, respectively. Multivariate Cox regression analysis indicated that age, T stage, N stage, surgery and radiotherapy were independent variables associated with OS. The areas under the receiver operating characteristic curves (AUCs) of the nomograms for predicting 1-, 3- and 5-year OS were 0.78, 0.71 and 0.71, respectively, in the training cohort. In the validation cohort, the area under the curve (AUC) of the nomogram for predicting 1-, 3- and 5-year OS were 0.90, 0.75 and 0.78, respectively. Patients were classified into low- and high-risk groups based on the total score of the nomogram. Patients in the low-risk group had a significantly better survival prognosis than patients in the high-risk group in both the training cohort (P < 0.0001) and the validation cohort (P = 0.0016). CONCLUSION: We established and validated a novel nomogram model to predict the OS of SNMM patients stratified by age, T stage, N stage, surgery and radiotherapy. This predictive tool is of potential importance in the realms of patient counselling and clinical decision-making.

Seismic evidence of effects of water on melt transport in the Lau back-arc mantle.

Processes of melt generation and transport beneath back-arc spreading centres are controlled by two endmember mechanisms: decompression melting similar to that at mid-ocean ridges and flux melting resembling that beneath arcs. The Lau Basin, with an abundance of spreading ridges at different distances from the subduction zone, provides an opportunity to distinguish the effects of these two different melting processes on magma production and crust formation. Here we present constraints on the three-dimensional distribution of partial melt inferred from seismic velocities obtained from Rayleigh wave tomography using land and ocean-bottom seismographs. Low seismic velocities beneath the Central Lau Spreading Centre and the northern Eastern Lau Spreading Centre extend deeper and westwards into the back-arc, suggesting that these spreading centres are fed by melting along upwelling zones from the west, and helping to explain geochemical differences with the Valu Fa Ridge to the south, which has no distinct deep low-seismic-velocity anomalies. A region of low S-wave velocity, interpreted as resulting from high melt content, is imaged in the mantle wedge beneath the Central Lau Spreading Centre and the northeastern Lau Basin, even where no active spreading centre currently exists. This low-seismic-velocity anomaly becomes weaker with distance southward along the Eastern Lau Spreading Centre and the Valu Fa Ridge, in contrast to the inferred increase in magmatic productivity. We propose that the anomaly variations result from changes in the efficiency of melt extraction, with the decrease in melt to the south correlating with increased fractional melting and higher water content in the magma. Water released from the slab may greatly reduce the melt viscosity or increase grain size, or both, thereby facilitating melt transport.

Acoustic spatial patterns recognition based on convolutional neural network and acoustic visualization.

In this work, a convolutional neural network (CNN) is applied to recognize acoustic spatial patterns with the aid of acoustic visualization. The acoustic spatial patterns are obtained by the singular value decomposition of an acoustic radiation operator built with the boundary integral equation. It is to explore the powerful capability of the CNN in the image processing by analogously rendering the measured acoustic spatial patterns into images. Due to practical limitations, a higher resolution of an acoustic image is achieved by interpolating the pressure on a coarse grid. Steady-state analysis of acoustic problems is a complex domain problem. The acoustic fields are then supplied into a CNN scheme as two-channel data which are real and imaginary components of the pressure. Random noises and incident waves with varying energy are added to the measured data to simulate influences from uncorrelated and correlated noises, respectively. It is demonstrated that once the CNN scheme is built and trained with adequate data, which is numerically synthesized, the patterns can be more accurately and robustly recognized by comparing it with the cross-correlation based methods. The hierarchical feature representative as well as nonlinear perception makes the proposed method a promising approach for fault diagnosis and condition monitoring based on spatial acoustic measurements.

The Value of Neutrophil-to-Lymphocyte Ratio in Predicting Mortality After Transjugular Intrahepatic Portosystemic Shunt Placement.

Background and Aims: The objective of this study was to investigate the effect of neutrophil-to-lymphocyte ratio (NLR) on the survival of cirrhotic patients with esophagogastric variceal bleeding (EGVB) treated with transjugular intrahepatic portosystemic shunt (TIPS). Methods: A total of 293 patients treated with TIPS were included. The receiver operator characteristic curve (ROC) was used to calculate the optimal cut-off values of parameters such as NLR. The Kaplan-Meier curve and Cox proportional risk model were used to evaluate the effects of NLR and other variables on 2-year all-cause mortality. Results: The area under the ROC for NLR was 0.634, with an optimal cutoff value of 4.9. Two-year mortality rates for patients with high (≥4.9) and low (<4.9) NLR were 22.1% and 9.3%, respectively (Log rank test: P = 0.002). After correcting for confounders, multivariate analysis demonstrated that NLR ≥ 4.9 (HR = 2.741, 95% CI 1.467-5.121, P = 0.002), age ≥ 63 (HR = 3.403, 95% CI 1.835-6.310, P < 0.001), and gender (male) (HR = 2.842, 95% CI 1.366-5.912, P = 0.001) were independent risk factors for the mortality outcome. Considering the stratification of early and selective TIPS treatment, high NLR still significantly increased the risk of mortality for patients (Log rank test: P = 0.007, HR = 2.317, 95% CI 1.232-4.356). Conclusion: NLR can help to predict survival in EGVB patients after TIPS, and the type of TIPS should also be considered in practical applications.

Associations between liver function parameters and poor clinical outcomes in peritoneal dialysis patients.

Patients with end-stage renal disease (ESRD) have significantly lower survival rates compared with the general population of the same age. Peritoneal dialysis (PD) is an effective treatment for patients with ESRD, but the clinical outcome of PD patients is still not promising. The survival of PD patients is associated with various clinical factors, and exploring some valid risk predictors may be beneficial for this population. In this review, by integrating the latest research, we summarized the association of some common and novel liver function parameters (ALT, AST, ALP, GGT, serum bilirubin, pre-albumin, albumin, albumin-globulin ratio [AGR], serum ferritin, and hyaluronic acid) with clinical outcomes in PD patients. It may contribute to a better understanding of potential risk factors and help to develop strategies to prevent the disease progression.

Daucosterol Alleviates Alcohol-Induced Hepatic Injury and Inflammation through P38/NF-κB/NLRP3 Inflammasome Pathway.

Alcoholic liver disease (ALD) is caused by chronic excessive alcohol consumption, which leads to inflammation, oxidative stress, lipid accumulation, liver fibrosis/cirrhosis, and even liver cancer. However, there are currently no effective drugs for ALD. Herein, we report that a natural phytosterol Daucosterol (DAU) can effectively protect against liver injury caused by alcohol, which plays anti-inflammatory and antioxidative roles in many chronic inflammatory diseases. Our results demonstrate that DAU ameliorates liver inflammation induced by alcohol through p38/nuclear factor kappa B (NF-κB)/NOD-like receptor protein-3 (NLRP3) inflammasome pathway. Briefly, DAU decreases NF-κB nuclear translocation and inhibits NLRP3 activation by decreasing p38 phosphorylation. At the same time, DAU also protects against hepatic oxidative stress and lipid accumulation. In conclusion, our research provides a new clue about the protective effects of naturally active substances on ALD.

Sinonasal NUT carcinoma: A retrospective case series from a single institution.

Purpose: Nuclear protein in testis (NUT) carcinoma is a rare, aggressive tumor defined by the presence of NUT gene rearrangement. The aim of this study was to describe the clinical, radiologic, and biological features of sinonasal NUT carcinoma. Methods: We retrospectively investigated NUT expression with clinicopathologic features in 145 cases with sinonasal malignancies diagnosed from January 2017 to December 2021 and reviewed the reported cases. Results: Three (3/145, 2.07%) cases showed strong nuclear expression for NUT immunohistochemical, including one male and two females with ages from 37 to 57 years (mean, 45.33 years). All three cases involved the nasal cavity and sinuses; one of them involved the orbit and intracranial area. Histologically, all subjects showed poorly differentiated, small round cell morphology with distinct nuclei. All patients received surgery and chemoradiotherapy. One patient died of the disease 13 months after diagnosis, and two survived 12 and 15 months, respectively, without evidence of tumor recurrence. 51 cases of sinonasal NUT carcinoma (mean age 40.96 years) have been described to date. Among them, 28 are male, and 23 are female. Most cases expressed p63, AE1/AE3, as well as p40. Conclusion: NUT carcinoma is a rare and aggressive disease with a poor prognosis. It is crucial to perform NUT rearrangement-related tests for differential diagnosis of poorly differentiated/undifferentiated tumors in the nasal cavity and sinuses.

Adverse Events for Monoclonal Antibodies in Patients with Allergic Rhinitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

(1) Background: Allergic rhinitis (AR) is a common disease in otolaryngology and novel biological therapies are required for clinical needs. To assess the tolerability of monoclonal antibodies, justifying their clinical applications, we presented a comprehensive safety profile of biologics in AR; (2) Methods: A systematic literature search was conducted following PRISMA guidelines for randomized clinical trials comparing monoclonal antibodies and placebo in AR. PubMed, Web of Science, Medline, and Cochrane were searched up until 9 January 2023. Among 3590 records in total, 12 studies with more than 2600 patients were included. Quality was assessed for all studies using Cochrane risk-of-bias tool for randomized trials, and subgrouped meta-analysis was performed; (3) Results: We accomplished an up-to-date literature overview and analysis on adverse events of monoclonal antibodies in AR. Total, common, severe, discontinuation-causing, and serious adverse events failed to reach statistical significance. Country was an essential factor for heterogeneity, and urticaria was the adverse event at highest risk (RR 2.81, 95% CI 0.79-9.95); (4) Conclusions: Monoclonal antibodies are considered well tolerated and relatively safe in patients with AR. The regions of patients and hypersensitive adverse reactions such as urticaria require a special caution in biological treatments in AR.

A novel method for three-dimensional analysis of endoscopic spatial relationships of pterygopalatine fossa structures and associated regions.

BACKGROUND: The spatial orientation rules of the important skull base structures are essential for performing endoscopic surgery. However, there is no satisfactory three-dimensional (3-D) anatomy study available to the surgeon at present. The aims of this study are to construct a new method to learn the spatial orientation of anatomical features under endoscopy and to help the surgeon establish a 3-D image of skull base structures in his mind. METHODS: A modified MicronTracker navigation system was used to measure the pitch angle, direction angle and distance from the reference points to various anatomical landmarks of the pterygopalatine fossa and related structures (PPFRS) at the skull base in 10 fresh cadavers (20 sides). RESULTS: The location data of the positions of the major landmarks were acquired and a digital model of the anatomical structures of the PPFRS was built, which can be moved, whirled or demonstrated easily. CONCLUSION: It is practical to measure the positions of the anatomical structures of the PPFRS with a modified binocular vision-based MicronTracker navigation system. It is a valuable exploration tool to help the surgeon establish the orientation of surgical landmarks in his mind by the 3-D parameters and model.