Comparison of long-term quality of life and their predictors in survivors between paediatric and adult nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.

BACKGROUND: To compare the differences in long-term quality of life (QoL) between survivors of paediatric and adult patients with nasopharyngeal carcinoma (NPC) and assess the clinical factors that predict long-term QoL. METHODS: We enrolled 420 long-term NPC survivors who were alive for at least 8 years after treatment, including 195 paediatric and 225 adult patients diagnosed and treated with intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Centre (SYSUCC) between 2011 and 2015. Data on clinical factors and EORTC QLQ-C30 were collected from all participants. The QoL of paediatric and adult NPC survivors was compared. RESULTS: The paediatric group had significantly better outcomes in global health status (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027), physical function (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P < 0.001), role function (paediatric: 97.0 ± 9.2; adult: 90.5 ± 15.2; P < 0.001), social function (paediatric: 96.0 ± 8.9; adult: 93.5 ± 11.8; P = 0.038), insomnia (paediatric: 1.9 ± 7.8; adult: 13.1 ± 22.3; P < 0.001), constipation (paediatric: 1.3 ± 7.5; adult: 8.0 ± 17.4; P < 0.001), diarrhea (paediatric: 0.7 ± 4.6; adult: 2.8 ± 9.3; P = 0.010), and financial difficulties (paediatric: 1.9 ± 7.8; adult: 11.0 ± 19.8; P < 0.001), but poorer cognitive function (paediatric: 88.3 ± 9.9; adult: 93.8 ± 12.6; P < 0.001) than the adult group. Pretreatment clinical factors, including T stage, N stage, and pre-treatment EBV (Epstein-Barr Virus) DNA, showed a strong association with QoL. However, the factors that affected the QoL outcomes differed between the two groups. In survivors of paediatric cancer, global health status/QoL was strongly correlated with T stage (P < 0.001) and clinical stage (P = 0.018), whereas it was strongly correlated with pre-treatment EBV DNA (P = 0.008) in adults. CONCLUSION: Paediatric survivors of NPC have a significantly better QoL than adult NPC survivors. Moreover, pre-treatment T stage, N stage, and EBV DNA significantly influenced the overall health status of the survivors. These results highlight the need to tailor care to both age groups to promote better long-term health outcomes.

Joint modeling of longitudinal health-related quality of life during concurrent chemoradiotherapy period and long-term survival among patients with advanced nasopharyngeal carcinoma.

BACKGROUND: To investigate the prognosis of longitudinal health-related quality of life (HRQOL) during concurrent chemoradiotherapy (CCRT) on survival outcomes in patients with advanced nasopharyngeal carcinoma (NPC). METHODS: During 2012-2014, 145 adult NPC patients with stage II-IVb NPC were investigated weekly using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORCT QLQ-C30) during their CCRT period. The effects of longitudinal trends of HRQOL on survival outcomes were estimated using joint modeling, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were reported as a 10-point increase in HRQOL scores. RESULTS: After a median follow-up of 83.4 months, the multivariable models showed significant associations of longitudinal increasing scores in fatigue and appetite loss during the CCRT period with distant metastasis-free survival: 10-point increases in scores of fatigue and appetite loss domains during CCRT period were significantly associated with 75% (HR: 1.75, 95% CI: 1.01, 3.02; p = 0.047) and 59% (HR: 1.59, 95% CI: 1.09, 2.59; p = 0.018) increase in the risk of distant metastasis, respectively. The prognostic effects of the longitudinal HRQOL trend on overall survival and progress-free survival were statistically non-significant. CONCLUSION: Increases in fatigue and appetite loss of HRQOL during the CCRT period are significantly associated with high risks of distant metastasis in advanced NPC patients. Nutritional support and psychological intervention are warranted for NPC patients during the treatment period.

Management considerations and treatment outcomes for newly diagnosed prostate cancer in advanced age patients (≥80 years): real-world data from a single urological center over a 10-year period.

Background: There is ongoing debate regarding prostate cancer (PCa) screening in advanced age males, leading to treatment decisions often based on tumor staging and life expectancy. A critical gap in clinical evidence and tailored guidelines for the advanced age with PCa persists. This study aims to compare survival outcomes of various treatment approaches in this demographic. Methods: We analyzed data from a large urological center for advanced age patients suspected of having PCa between 2012 and 2022. We collected clinical and pathological characteristics and evaluated treatment modalities, including palliative therapy and definitive therapy. Propensity score matching (PSM) analysis was implemented to reduce bias between treatment modalities. Kaplan-Meier and multivariate Cox proportional hazard regression analyses were conducted to evaluate progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: Out of 4,333 suspected patients, 376 individuals aged 80 years and older underwent prostate biopsy. The overall detection rate of PCa was 78.7%, with a high prevalence of high-grade tumors [International Society of Urological Pathology (ISUP) grade ≥2]. Most patients (86.5%) received palliative therapy, while 13.5% underwent definitive therapy. Patients in the definitive therapy group had lower prostate-specific antigen (PSA) values, lower tumor stage, and Charlson Comorbidity Index (CCI), longer life expectancy, and a higher Geriatric 8 (G8) score compared to the palliative therapy group. The median OS for the entire cohort was 72.0 months, with 70.0 months for palliative therapy and 96.0 months for definitive therapy. Multivariable analyses identified lymphatic and bone metastasis, as well as definitive therapy, as independent prognostic factors for PFS, CSS, and OS. Conclusions: Advanced age patients, although a small group, have distinct characteristics, including higher PSA levels, positive biopsy rates, and pathological grading and staging. In medically fit elderly patients, especially those with localized PCa and a life expectancy of ≥5 years, definitive therapy could improve survival outcomes.

Evaluation of tracheal diameter and angles in fetuses with double aortic arch using prenatal ultrasound: implications for postnatal management.

Objective: This study aims to analyze the value of prenatal ultrasound in the screening, diagnosis, and treatment of double aortic arch (DAA) malformations. Methods: A retrospective analysis was conducted on 31 fetal cases with double aortic arch anomalies over a 12-year period from June 1, 2011 to June 1, 2023. The assessment included combined measurements of fetal tracheal internal diameter Z-score and DAA pinch angle, along with ultrasonographic findings, associated anomalies, genetic abnormalities, postnatal CTA images, and long-term postnatal outcomes. Results: Of the 31 fetal double aortic arch cases, 15 were right aortic arch dominant, 2 were left aortic arch dominant, and 14 had a balanced double arch. Genetic testing was performed on 19 cases, revealing abnormalities in 2 cases, including one Turner syndrome, and one carrier of ichthyosis gene with heterozygous deletion. Out of the total cases, 29 were delivered, and 2 cases were terminated. Prenatal diagnosis accurately identified 29 cases (29/31, 93.5%), which was confirmed by postnatal pathological anatomy, echocardiography, surgery or CTA. Fetal tracheal internal diameter Z-scores were significantly smaller in the symptomatic group than in the asymptomatic group (-1.27 ± 0.49 vs -0.68 ± 0.60, P = 0.018). The area under the curve was 0.776 (95% confidence interval, 0.593-0.960) using a tracheal internal diameter z-score cutoff of -0.73 with a sensitivity of 90% and specificity of 64.7%. The double arch pinch angle was significantly smaller in the symptomatic group than in the asymptomatic group [52.50° (38.25° to 59.00°) vs 60.00° (53.50° to 70.50°), P = 0.035]. The area under the curve was 0.744 (95% confidence interval, 0.554-0.935), and the sensitivity for determining the presence or absence of symptoms was 90% when the cutoff value was 62.5°, with a specificity of 47.1%. Fifteen cases opted for surgery with favorable surgical outcome. Conclusion: Prenatal echocardiography demonstrates good diagnostic efficacy for fetal double aortic arch. It is also essential to detect the presence of other underlying intra- and extracardiac malformations and genetic abnormalities. There is a significant difference in prenatal tracheal internal diameter Z-scores and double arch pinch angle between asymptomatic and symptomatic DAA infants. Symptomatic infants require early surgery, while asymptomatic infants should be monitored.

Effect of differences in proximal neck angles on biomechanics of abdominal aortic aneurysm based on fluid dynamics.

BACKGROUND: This study aimed to analyze the effect of proximal neck angulation on the biomechanical indices of abdominal aortic aneurysms (AAA) and to investigate its impact on the risk of AAA rupture. METHODS: CT angiography (CTA) data of patients with AAA from January 2015 to January 2022 were collected. Patients were divided into three groups based on the angle of the proximal neck: Group A (âˆ ß ≤ 30°), Group B (30°<âˆ ß ≤ 60°), and Group C (âˆ ß > 60°). Biomechanical indices related to the rupture risk of AAA were analyzed using computational fluid dynamics modeling (CFD-Post) based on the collected data. RESULTS: Group A showed slight turbulence in the AAA lumen with a mixed laminar flow pattern. Group B had a regular low-speed eddy line characterized by cross-flow dominated by lumen blood flow and turbulence. In Group C, a few turbulent lines appeared at the proximal neck, accompanied by eddy currents in the lumen expansion area following the AAA shape. Significant differences were found in peak wall stress, shear stress, and the maximum blood flow velocity impact among the three groups. The maximum blood flow velocity at the angle of the proximal neck impact indicated the influence of the proximal neck angle on the blood flow state in the lumen. CONCLUSION: As the angle of the proximal neck increased, it caused stronger eddy currents and turbulent blood flow due to a high-speed area near the neck. The region with the largest diameter in the abdominal aortic aneurysm was prone to the highest stress, indicating a higher risk of rupture. The corner of the proximal neck experienced the greatest shear stress, potentially leading to endothelial injury and further enlargement of the aneurysm.

Carbonate Ester-Based Sodium Metal Battery with High-Capacity Retention at -50 °C Enabled by Weak Solvents and Electrodeposited Anode.

Sodium metal batteries (SMBs) have received increasing attention due to the abundant sodium resources and high energy density, but suffered from the sluggish interfacial kinetic and unstable plating/stripping of sodium anode at low temperature, especially when matched with ester electrolytes. Here, we develop a stable ultra-low-temperature SMBs with high-capacity retention at -50 °C in a weak solvated carbonate ester-based electrolyte, combined with an electrodeposited Na (Cu/Na) anode. The Cu/Na anode with electrochemically activated "deposited sodium" and stable inorganic-rich solid electrolyte interphase (SEI) is favor for the fast Na+ migration, therefore accelerating the interfacial kinetic process. As a result, the Cu/Na||NaCrO2 battery exhibited the highest capacity retention (compared to room-temperature capacity) in carbonate ester-based SMBs (98.05 % at -25 °C, 91.3 % at -40 °C, 87.9 % at -50 °C, respectively). The cyclic stability of 350 cycles at -25 °C with a high energy efficiency of 96.15 % and 70 cycles at -50 °C can be achieved. Even in chill atmospheric environment with the fluctuant temperature, the battery can still operate over one month. This work provides a new opportunity for the development of low-temperature carbonate ester-based SMBs.

Enantiopure trigonal bipyramidal coordination cages templated by in situ self-organized D2h-symmetric anions.

The control of a molecule's geometry, chirality, and physical properties has long been a challenging pursuit. Our study introduces a dependable method for assembling D3-symmetric trigonal bipyramidal coordination cages. Specifically, D2h-symmetric anions, like oxalate and chloranilic anions, self-organize around a metal ion to form chiral-at-metal anionic complexes, which template the formation of D3-symmetric trigonal bipyramidal coordination cages. The chirality of the trigonal bipyramid is determined by the point chirality of chiral amines used in forming the ligands. Additionally, these cages exhibit chiral selectivity for the included chiral-at-metal anionic template. Our method is broadly applicable to various ligand systems, enabling the construction of larger cages when larger D2h-symmetric anions, like chloranilic anions, are employed. Furthermore, we successfully produce enantiopure trigonal bipyramidal cages with anthracene-containing backbones using this approach, which would be otherwise infeasible. These cages exhibit circularly polarized luminescence, which is modulable through the reversible photo-oxygenation of the anthracenes.

Retinal image registration method for myopia development.

OBJECTIVE: The development of myopia is usually accompanied by changes in retinal vessels, optic disc, optic cup, fovea, and other retinal structures as well as the length of the ocular axis. And the accurate registration of retinal images is very important for the extraction and analysis of retinal structural changes. However, the registration of retinal images with myopia development faces a series of challenges, due to the unique curved surface of the retina, as well as the changes in fundus curvature caused by ocular axis elongation. Therefore, our goal is to improve the registration accuracy of the retinal images with myopia development. METHOD: In this study, we propose a 3D spatial model for the pair of retinal images with myopia development. In this model, we introduce a novel myopia development model that simulates the changes in the length of ocular axis and fundus curvature due to the development of myopia. We also consider the distortion model of the fundus camera during the imaging process. Based on the 3D spatial model, we further implement a registration framework, which utilizes corresponding points in the pair of retinal images to achieve registration in the way of 3D pose estimation. RESULTS: The proposed method is quantitatively evaluated on the publicly available dataset without myopia development and our Fundus Image Myopia Development (FIMD) dataset. The proposed method is shown to perform more accurate and stable registration than state-of-the-art methods, especially for retinal images with myopia development. SIGNIFICANCE: To the best of our knowledge, this is the first retinal image registration method for the study of myopia development. This method significantly improves the registration accuracy of retinal images which have myopia development. The FIMD dataset we constructed has been made publicly available to promote the study in related fields.

Efficacy of tacrolimus monotherapy in primary membranous nephropathy.

Objective: The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC). Methods: This was tested in a prospective monocentric observational trial of 70 patients with PMN, of whom 34 received TAC (0.05-0.075 mg/kg/day) or 36 received TAC (0.05-0.075 mg/kg/day) and GC (0.3-0.5 mg/kg/day of prednisone). Results: At 3, 6, 9, and 12 months of treatment, the effective rates in the TAC group and the TAC + GC group were similar (P > 0.05). The urinary protein quantification was reduced in patients under both therapeutic protocols, and the differences in the proteinuria quantification at 3, 6, 9, and 12 months of treatment were not statistically significant between the two groups (P > 0.05). The overall incidence of adverse reactions in the TAC group was lower than that in the TAC + GC group (23.5% < 36.1%), and the difference was statistically significant (P < 0.05). Conclusion: TAC monotherapy for PMN could effectively reduce urinary protein quantification and increase serum albumin levels. Compared with TAC + GC, TAC monotherapy for PMN had no difference in efficacy and fewer incidences of adverse reactions.

Conversion-type anode chemistry with interfacial compatibility toward Ah-level near-neutral high-voltage zinc ion batteries.

High-voltage aqueous zinc ion batteries (AZIBs) with a high-safety near-neutral electrolyte is of great significance for practical sustainable application; however, they suffer from anode and electrode/electrolyte interfacial incompatibility. Herein, a conversion-type anode chemistry with a low anodic potential, which is guided by the Gibbs free energy change of conversion reaction, was designed for high-voltage near-neutral AZIBs. A reversible conversion reaction between ZnC2O4·2H2O particles and three-dimensional Zn metal networks well-matched in CH3COOLi-based electrolyte was revealed. This mechanism can be universally validated in the battery systems with sodium or iodine ions. More importantly, a cathodic crowded micellar electrolyte with a water confinement effect was proposed in which lies the core for the stability and reversibility of the cathode under an operating platform voltage beyond 2.0 V, obtaining a capacity retention of 95% after 100 cycles. Remarkably, the scientific and technological challenges from the coin cell to Ah-scale battery, sluggish kinetics of the solid-solid electrode reaction, capacity excitation under high loading of active material, and preparation complexities associated with large-area quasi-solid electrolytes, were explored, successfully achieving an 88% capacity retention under high loading of more than 20 mg cm-2 and particularly a practical 1.1 Ah-level pouch cell. This work provides a path for designing low-cost, eco-friendly and high-voltage aqueous batteries.

Integrated analysis of microbiome and host transcriptome unveils correlations between lung microbiota and host immunity in bronchoalveolar lavage fluid of pneumocystis pneumonia patients.

OBJECTIVE: The lung microbiota of patients with pulmonary diseases is disrupted and impacts the immunity. The microbiological and immune landscape of the lungs in patients with pneumocystis pneumonia (PCP) remains poorly understood. METHODS: Multi-omics analysis and machine learning were performed on bronchoalveolar lavage fluid to explore interaction between the lung microbiota and host immunity in PCP. Then we constructed a diagnostic model using differential genes with LASSO regression and validated by qPCR. The immune infiltration analysis was performed to explore the landscape of lung immunity in patients with PCP. RESULTS: Patients with PCP showed a low alpha diversity of lung microbiota, accompanied by the elevated abundance of Firmicutes, and the differential expressed genes (DEGs) analysis displayed a downregulation of MAPK signaling. The MAPK10, TGFB1, and EFNA3 indicated a potential to predict PCP (AUC = 0.86). The lung immune landscape in PCP showed the lower levels of naïve CD4+ T cells and activated dendritic cells. The correlation analysis of the MAPK signaling pathway-related DEGs and the differential microorganisms at the level of phylum showed that the Firmicutes was negatively correlated with these DEGs. CONCLUSION: We profiled the characteristics of lung microbiota and immune landscape in PCP, which may contribute to elucidating the mechanism of PCP.

Crosstalk between human immunodeficiency virus infection and salivary bacterial function in men who have sex with men.

Background: Engaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to salivary microbiota, which, combined with an individual's positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect. Methods: Based on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4+ T lymphocyte counts ≥ 500, 200-499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM. Results: The core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts. Conclusion: As HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.

Bioassay-Guided and DeepSAT-Driven Precise Mining of Monoterpenoid Coumarin Derivatives with Antifeedant Effects from the Leaves of Ailanthus altissima.

Demand for the exploration of botanical pesticides continues to increase due to the detrimental effects of synthetic chemicals on human health and the environment and the development of resistance by pests. Under the guidance of a bioactivity-guided approach and HSQC-based DeepSAT, 16 coumarin derivatives were discovered from the leaves of Ailanthus altissima (Mill.) Swingle, including seven undescribed monoterpenoid coumarins, three undescribed monoterpenoid phenylpropanoids, and two new coumarin derivatives. The structure and configurations of these compounds were established and validated via extensive spectroscopic analysis, acetonide analysis, and quantum chemical calculations. Biologically, 5 exhibited significant antifeedant activity toward the Plutella xylostella. Moreover, tyrosinase being closely related to the growth and development of larva, the inhibitory potentials of 5 against tyrosinase was evaluated in vitro and in silico. The bioactivity evaluation results highlight the prospect of 5 as a novel category of botanical insecticide.

Potential clinical value of fibrinogen-like protein 1 as a serum biomarker for the identification of diabetic cardiomyopathy.

Diabetic individuals with diabetic cardiomyopathy (DbCM) present with abnormal myocardial structure and function. DbCM cannot be accurately diagnosed due to the lack of suitable diagnostic biomarkers. In this study, 171 eligible participants were divided into a healthy control (HC), type 2 diabetes mellitus (T2DM) patients without DbCM (T2DM), or DbCM group. Serum fibrinogen-like protein 1 (FGL-1) and other biochemical parameters were determined for all participants. Serum FGL-1 levels were significantly higher in patients with DbCM compared with those in the T2DM group and HCs. Serum FGL-1 levels were negatively correlated with left ventricular fractional shortening and left ventricular ejection fraction (LVEF) and positively correlated with left ventricular mass index in patients with DbCM after adjusting for age, sex and body mass index. Interaction of serum FGL-1 and triglyceride levels on LVEF was noted in patients with DbCM. A composite marker including serum FGL-1 and triglycerides could differentiate patients with DbCM from those with T2DM and HCs with an area under the curve of 0.773 and 0.789, respectively. Composite marker levels were negatively correlated with N-terminal B-type natriuretic peptide levels in patients with DbCM. Circulating FGL-1 may therefore be a valuable index reflecting cardiac functions in DbCM and to diagnose DbCM.

A Cages-on-Cluster Structure Constructed by Post-Clustering Covalent Modifications and Guest-Enabled Stimuli-Responsive Luminescence.

A gold(I)-cluster-based twin-cage has been constructed by post-clustering covalent modification of a hexa-aldehyde cluster precursor with triaminotriethylamines. The cages-on-cluster structure has double cavities and four binding sites, which show site-discriminative binding for silver(I) and copper(I) guests. The guests in the tripodal hats affect the luminescence of the cluster: the tetra-silver(I) host-guest complex is weakly red-emissive, while the bis-copper(I)-bis-silver(I) one is non-emissive but is a stimuli-responsive supramolecule. The copper(I) ion inside the tri-imine cavity is oxidation sensitive, which enables the release of the bright emissive precursor cluster triggered by H2O2 solution. The hybridization of a cluster with cavities to construct a cluster-based cage presents an innovative concept for functional cluster design, and the post-clustering covalent modification opens up new avenues for finely tuning the properties of clusters.

Dichotomous roles of ADAR1 in liver hepatocellular carcinoma and kidney renal cell carcinoma: Unraveling the complex tumor microenvironment and prognostic significance.

BACKGROUND: Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-editing enzyme that significantly impacts cancer progression and various biological processes. The expression of ADAR1 mRNA has been examined in multiple cancer types using The Cancer Genome Atlas (TCGA) dataset, revealing distinct patterns in kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and liver hepatocellular carcinoma (LIHC) compared to normal controls. However, the reasons for these differential expressions remain unclear. METHODS: In this study, we performed RT-PCR and western blotting (WB) to validate ADAR1 expression patterns in clinical tissue samples. Survival analysis and immune microenvironment analysis (including immune score and stromal score) were conducted using TCGA data to determine the specific cell types associated with ADAR1, as well as the key genes in those cell types. The relationship between ADAR1 and specific cell types' key genes was verified by immunohistochemistry (IHC), using clinical liver and kidney cancer samples. RESULTS: Our validation analysis revealed that ADAR1 expression was downregulated in KICH, KIRC, and KIRP, while upregulated in LIHC compared to normal tissues. Notably, a significant correlation was found between ADAR1 mRNA expression and patient prognosis, particularly in KIRC, KIRP, and LIHC. Interestingly, we observed a positive correlation between ADAR1 expression and stromal scores in KIRC, whereas a negative correlation was observed in LIHC. Cell type analysis highlighted distinct relationships between ADAR1 expression and the two stromal cell types, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs), and further determined the signature gene claudin-5 (CLDN5), in KIRC and LIHC. Moreover, ADAR1 was inversely related with CLDN5 in KIRC (n = 26) and LIHC (n = 30) samples, verified via IHC. CONCLUSIONS: ADAR1 plays contrasting roles in LIHC and KIRC, associated with the enrichment of BECs and LECs within tumors. This study sheds light on the significant roles of stromal cells within the complex tumor microenvironment (TME) and provides new insights for future research in tumor immunotherapy and precision medicine.

Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis.

Pathogens detected by metagenomic next-generation sequencing (mNGS) and the laboratory blood culture flask method were compared to understand the advantages and clinical significance of mNGS assays in the etiological diagnosis of peritoneal dialysis-associated peritonitis (PDAP). The study involved a total of 37 patients from the hospital's peritoneal dialysis centre, six of whom were patients with non-peritoneal dialysis-associated peritonitis. Peritoneal dialysis samples were collected from the 37 patients, who were divided into two groups. One group's samples were cultured using conventional blood culture flasks, and the other samples underwent pathogen testing using mNGS. The results showed that the positive rate of mNGS was 96.77%, while that of the blood culture flask method was 70.97% (p < 0.05). A total of 29 pathogens were detected by mNGS, namely 24 bacteria, one fungus, and four viruses. A total of 10 pathogens were detected using the bacterial blood culture method, namely nine bacteria and one fungus. The final judgment of the PDAP's causative pathogenic microorganism was made by combining the clinical condition, response to therapy, and the whole-genome sequencing findings. For mNGS, the sensitivity was 96.77%, the specificity was 83.33%, the positive predictive value was 96.77%, and the negative predictive value was 83.33%. For the blood culture flask method, the sensitivity was 70.97%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 0%. In conclusion, mNGS had a shorter detection time for diagnosing peritoneal dialysis-related peritonitis pathogens, with a higher positive rate than traditional bacterial cultures, providing significant advantages in diagnosing rare pathogens.

Novel insights into the protective effects of leonurine against acute kidney injury: Inhibition of ER stress-associated ferroptosis via regulating ATF4/CHOP/ACSL4 pathway.

Acute kidney injury (AKI) is a common and serious global health problem with high risks of mortality and the development of chronic kidney diseases. Leonurine is a unique bioactive component from Leonurus japonicus Houtt. and exerts antioxidant, antiapoptotic or anti-inflammatory properties. This study aimed to explore the benefits of leonurine on AKI and the possible mechanisms involved, with a particular foc on the regulation of ferroptosis and endoplasmic reticulum (ER) stress. Our results showed that leonurine exhibited prominent protective effects against AKI, as evidenced by the amelioration of histopathological alterations and reduction of renal dysfunction. In addition, leonurine significantly suppressed ferroptosis in AKI both in vivo and in vitro by effectively restoring ultrastructural abnormalities in mitochondria, decreasing ASCL4 and 4-HNE levels, scavenging reactive oxygen species (ROS), as well as increasing GPX4 and GSH levels. In parallel, leonurine also markedly mitigated ER stress via down-regulating PERK, eIF-2α, ATF4, CHOP and CHAC1. Further studies suggested that ER stress was closely involved in erastin-induced ferroptosis, and leonurine protected tubular epithelial cells in vitro by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway. Mechanistically, ATF4 silencing in vitro regulated CHOP and ACSL4 expressions, ultimately weakening both ER stress and ferroptosis. Notably, analyses of single-cell RNA sequencing data revealed that ATF4, CHOP and ASCL4 in renal tubular cells were all abnormally upregulated in patients with AKI compared to healthy controls, suggesting their contributions to the pathogenesis of AKI. Altogether, these findings suggest that leonurine alleviates AKI by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway, thus providing novel mechanisms for AKI treatment.

Clinical evaluation of droplet digital pcr for suspected ascites infection in patients with liver cirrhosis.

BACKGROUND: Droplet digital PCR (ddPCR) is increasingly used in diagnosing clinical pathogens, but its effectiveness in cirrhosis patients with suspected ascites infection remains uncertain. METHODS: The diagnostic performance of ddPCR was assessed in 305 ascites samples, utilizing culture and clinical composite standards. The quantitative value and potential clinical impact of ddPCR were further analyzed in patients with spontaneous bacterial peritonitis. RESULTS: With culture standards, ddPCR demonstrated a sensitivity of 86.5% and specificity of 83.2% for bacterial or fungal detection. After adjustment of clinical composite criteria, specificity increased to 96.4%. Better diagnostic performance for all types of targeted pathogens, particularly fungi, was observed with ddPCR compared to culture, and more polymicrobial infections were detected (30.4% versus 5.7%, p < 0.001). Pathogen loads detected by ddPCR correlated with white blood cell count in ascites and blood, as well as polymorphonuclear cell (PMN) count in ascites, reflecting infection status rapidly. A positive clinical impact of 55.8% (43/77) was observed for ddPCR, which was more significant among patients with PMN count ≤ 250/mm3 in terms of medication adjustment and new diagnosis. ddPCR results for fungal detection were confirmed by clinical symptoms and other microbiological tests, which could guide antifungal therapy and reduce the risk of short-term mortality. CONCLUSIONS: ddPCR, with appropriate panel design, has advantages in pathogen detection and clinical management of ascites infection, especially for patients with fungal and polymicrobial infections. Patients with atypical spontaneous bacterial peritonitis benefited more from ddPCR.