Multi-omics analysis of innate and adaptive responses to BCG vaccination reveals epigenetic cell states that predict trained immunity.

Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate immune activation and memory that are indicative of trained immunity. We established personal immune profiles and chromatin accessibility maps over a 90-day time course of BCG vaccination in 323 individuals. Our analysis uncovered genetic and epigenetic predictors of baseline immunity and immune response. BCG vaccination enhanced the innate immune response specifically in individuals with a dormant immune state at baseline, rather than providing a general boost of innate immunity. This study advances our understanding of BCG's heterologous immune-stimulatory effects and trained immunity in humans. Furthermore, it highlights the value of epigenetic cell states for connecting immune function with genotype and the environment.

A multifaceted poverty reduction program has economic and behavioral consequences.

This paper examines the causal impact of poverty reduction interventions on the social preferences of the poor. A multifaceted poverty reduction program in China provides a setting for the use of a fuzzy regression discontinuity design. The design compares households with base-year income just below a preset criterion, who were more likely to receive the program treatment, with households just above the criterion. Five years after the program's launch, we conducted a lab-in-the-field experiment to measure the distributional preferences of household heads. Combining quasi-random variation from program rules with administrative census and experimental data, we find both economic and behavioral consequences of the program: It increased household income by 50% 5 y later, increased consistency with utility maximization by household heads, and increased their efficiency preference while reducing selfishness and leaving equality preference unchanged. Our findings advance scientific understanding of social preferences formation and highlight a broad perspective in evaluating poverty reduction interventions.

3D-SMGE: a pipeline for scaffold-based molecular generation and evaluation.

In the process of drug discovery, one of the key problems is how to improve the biological activity and ADMET properties starting from a specific structure, which is also called structural optimization. Based on a starting scaffold, the use of deep generative model to generate molecules with desired drug-like properties will provide a powerful tool to accelerate the structural optimization process. However, the existing generative models remain challenging in extracting molecular features efficiently in 3D space to generate drug-like 3D molecules. Moreover, most of the existing ADMET prediction models made predictions of different properties through a single model, which can result in reduced prediction accuracy on some datasets. To effectively generate molecules from a specific scaffold and provide basis for the structural optimization, the 3D-SMGE (3-Dimensional Scaffold-based Molecular Generation and Evaluation) work consisting of molecular generation and prediction of ADMET properties is presented. For the molecular generation, we proposed 3D-SMG, a novel deep generative model for the end-to-end design of 3D molecules. In the 3D-SMG model, we designed the cross-aggregated continuous-filter convolution (ca-cfconv), which is used to achieve efficient and low-cost 3D spatial feature extraction while ensuring the invariance of atomic space rotation. 3D-SMG was proved to generate valid, unique and novel molecules with high drug-likeness. Besides, the proposed data-adaptive multi-model ADMET prediction method outperformed or maintained the best evaluation metrics on 24 out of 27 ADMET benchmark datasets. 3D-SMGE is anticipated to emerge as a powerful tool for hit-to-lead structural optimizations and accelerate the drug discovery process.

Exosomes in tumor-stroma crosstalk: Shaping the immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) is a multifaceted disease characterized by a complex interaction between tumor cells and the surrounding microenvironment. Within this intricate landscape, exosomes have emerged as pivotal players in the tumor-stroma crosstalk, influencing the immune microenvironment of CRC. These nano-sized vesicles, secreted by both tumoral and stromal cells, serve as molecular transporters, delivering a heterogeneous mix of biomolecules such as RNAs, proteins, and lipids. In the CRC context, exosomes exert dual roles: they promote tumor growth, metastasis, and immune escape by altering immune cell functions and activating oncogenic signaling pathways and offer potential as biomarkers for early CRC detection and treatment targets. This review delves into the multifunctional roles of exosomes in the CRC immune microenvironment, highlighting their potential implications for future therapeutic strategies and clinical outcomes.

OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3ß/ß-catenin pathway.

BACKGROUND: Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. METHODS: In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. RESULTS: Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3ß and resulted in increased ß-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. CONCLUSIONS: OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.

Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression.

Circular RNAs (circRNAs) play important roles in gastric cancer progression but the regulatory role of circRNAs in controlling macrophage function remains elusive. Exosomes serve as cargo for circRNAs and play a crucial role as mediators in facilitating communication between cancer cells and the tumor microenvironment. In this study, we found that circATP8A1, a previously unreported circular RNA, is highly expressed in both gastric cancer tissues and exosomes derived from plasma. Increased circATP8A1 was associated with advanced TNM stage and worse prognosis in patients with gastric cancer. We showed that  the circATP8A1 knockdown significantly inhibited gastric cancer proliferation and invasion in vitro and in vivo. Functionally, exosome circATP8A1 induced the M2 polarization of macrophages through the STAT6 pathway instead of the STAT3 pathway. Mechanistically, circATP8A1 was shown to activate the STAT6 pathway through competitive binding to miR-1-3p, as confirmed by Fluorescence In Situ Hybridization (FISH), RNA immunoprecipitation, RNA pulldown, and Luciferase reporter assays. The reversal of circATP8A1-induced STAT6 pathway activation and macrophage polarization was observed upon blocking miR-1-3p. Macrophages treated with exosomes from gastric cancer cells overexpressing circATP8A1 were able to promote gastric cancer migration, while knockdown of circATP8A1 reversed these effects in vivo. In summary, exosome-derived circATP8A1 from gastric cancer cells induce macrophages M2 polarization via the circATP8A1/miR-1-3p/STAT6 axis, and tumor progression. Our results highlight circATP8A1 as a potential prognostic biomarker and therapeutic target in gastric cancer.

Force-Encoding DNA Nanomachines for Simultaneous and Direct Detection of Multiple Pathogenic Bacteria in Blood.

Pathogen detection is growing in importance in the early stages of bacterial infection and treatment due to the significant morbidity and mortality associated with bloodstream infections. Although various diagnostic approaches for pathogen detection have been proposed, most of them are time-consuming, with insufficient sensitivity and limited specificity and multiplexing capability for clinical use. Here, we report a force-encoding DNA nanomachine for simultaneous and high-throughput detection of multiple pathogens in blood through force-induced remnant magnetization spectroscopy (FIRMS). The force-encoding DNA nanomachines coupled with DNA walkers enable analytical sensitivity down to a single bacterium via a cascade signal amplification strategy. More importantly, it allows for rapid and specific profiling of various pathogens directly in blood samples, without being affected by factors such as light color and solution properties. We expect that this magnetic sensing platform holds great promise for various applications in biomedical research and clinical diagnostics.

SS-31 inhibits the inflammatory response by increasing ATG5 and promoting autophagy in lipopolysaccharide-stimulated HepG2 cells.

SS-31 is a mitochondria-targeting short peptide. Recent studies have indicated its hepatoprotective effects. In our study, we investigated the impact of SS-31 on LPS-induced autophagy in HepG2 cells. The results obtained from a dual-fluorescence autophagy detection system revealed that SS-31 promotes the formation of autolysosomes and autophagosomes, thereby facilitating autophagic flux to a certain degree. Additionally, both ELISA and qPCR analyses provided further evidence that SS-31 safeguards HepG2 cells against inflammatory responses triggered by LPS through ATG5-dependent autophagy. In summary, our study demonstrates that SS-31 inhibits LPS-stimulated inflammation in HepG2 cells by upregulating ATG5-dependent autophagy.

Lipid Nanocarrier-Based mRNA Therapy: Challenges and Promise for Clinical Transformation.

Due to the outbreak of novel coronavirus pneumonia, messenger RNA (mRNA) technology has attracted heated attention. A specific, safe, and efficient mRNA delivery system is needed. Lipid nanocarriers have become attractive carriers for mRNA delivery due to their high delivery efficiency, few side effects, and easy modification to change their structures and functions. To achieve the desired biological effect, lipid nanocarriers must reach the designated location for effective drug delivery. Therefore, the effects of the composition of lipid nanocarriers on their key properties are briefly reviewed. In addition, the progress of smart drug delivery by changing the composition of lipid nanocarriers is summarized, and the importance of component design and structure is emphasized. Subsequently, this review summarizes the latest progress in lipid nanocarrier-based mRNA technology and provides corresponding strategies for its current challenges, putting forward valuable information for the future design of lipid nanocarriers and mRNA.

High Energy Storage Performance in BiFeO3-Based Lead-Free High-Entropy Ferroelectrics.

Dielectric capacitors are widely used in advanced electrical and electronic systems due to the rapid charge/discharge rates and high power density. High comprehensive energy storage properties are the ultimate ambition in the field of application achievements. Here, the high-entropy strategy is proposed to design and fabricate single-phase homogeneous (Bi0.5Ba0.1Sr0.1Ca0.2Na0.1)(Fe0.5Ti0.3Zr0.1Nb0.1)O3 ceramic, the hierarchical heterostructure including rhombohedral-tetragonal multiphase nanoclusters and locally disordered oxygen octahedral tilt can lead to the increased dielectric relaxation, diffused phase transition, diverse local polarization configurations, grain refinement, ultrasmall polar nanoregions, large random field, delayed polarization saturation and improved breakdown field. Accordingly, a giant Wrec ≈13.3 J cm-3 and a high η ≈78% at 66.4 kV mm-1 can be simultaneously achieved in the lead-free high-entropy BiFeO3-based ceramic, showing an obvious advantage in overall energy-storage properties over BiFeO3-based lead-free ceramics. Moreover, an ultrafast discharge rate (t0.9 = 18 ns) can be achieved at room temperature, concomitant with favorable temperature stability in the range of 20-160 °C, due to the enhanced diffuse phase transition and fast polarization response. This work provides a feasible pathway to design and generate dielectric materials exhibiting high comprehensive energy-storage performance.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

An Atlas of Dietary Intakes and Medication Uses on Risk of Bladder Cancer: A Wide-Angle Mendelian Randomization Analysis.

BACKGROUND: Observational studies suggests that diets and medications affect bladder cancer (BC) development, which are subject to confounding and difficult to make causal inference. Here we aimed to investigate whether those observational associations are causal and determining the potential directions and pathways. METHODS: We used 2-sample Mendelian randomization (MR) analysis to assess associations of dietary intakes, medication uses and molecules with BC risk. Genetic summary data were derived from participants of predominantly European ancestry with rigorous instruments selection, where univariable MR, mediation MR and multivariable MR were performed. RESULTS: The results of univariable MR showed 4 dietary intakes and 4 medication uses having a protective effect on BC, while 4 circulating metabolites, 440 circulating proteins and 2 gut microbes were observed to be causally associated with BC risk. Through mediation MR, we found 572 analytes showing consistent mediating effects between dietary intakes or medication uses and BC risk. Furthermore, 9 out of 16 diet-medication pairs showed significant interactions and alterations on BC when consumed jointly. CONCLUSION: In summary, the findings obtained from the current study have important implications for informing prevention strategies that point to potential lifestyle interventions or medication prescriptions to reduce the risk of developing BC.HighlightsThe current study extends observational literature in showing the importance of diets and medications on bladder cancer prevention.The associations of diets and medications on bladder cancer prevention might be through circulating metabolites, circulating proteins and gut microbiotaOur results provide a new understanding of interactions in certain diet-medication pairs which should be taken into account by both physicians and patients during the development of a treatment strategy.

Automated Ki-67 labeling index assessment in prostate cancer using artificial intelligence and multiplex fluorescence immunohistochemistry.

The Ki-67 labeling index (Ki-67 LI) is a strong prognostic marker in prostate cancer, although its analysis requires cumbersome manual quantification of Ki-67 immunostaining in 200-500 tumor cells. To enable automated Ki-67 LI assessment in routine clinical practice, a framework for automated Ki-67 LI quantification, which comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of multiplex fluorescence immunohistochemistry (mfIHC) staining, was developed and validated in a cohort of 12,475 prostate cancers. The prognostic impact of the Ki-67 LI was tested on a tissue microarray (TMA) containing one 0.6 mm sample per patient. A 'heterogeneity TMA' containing three to six samples from different tumor areas in each patient was used to model Ki-67 analysis of multiple different biopsies, and 30 prostate biopsies were analyzed to compare a 'classical' bright field-based Ki-67 analysis with the mfIHC-based framework. The Ki-67 LI provided strong and independent prognostic information in 11,845 analyzed prostate cancers (p < 0.001 each), and excellent agreement was found between the framework for automated Ki-67 LI assessment and the manual quantification in prostate biopsies from routine clinical practice (intraclass correlation coefficient: 0.94 [95% confidence interval: 0.87-0.97]). The analysis of the heterogeneity TMA revealed that the Ki-67 LI of the sample with the highest Gleason score (area under the curve [AUC]: 0.68) was as prognostic as the mean Ki-67 LI of all six foci (AUC: 0.71 [p = 0.24]). The combined analysis of the Ki-67 LI and Gleason score obtained on identical tissue spots showed that the Ki-67 LI added significant additional prognostic information in case of classical International Society of Urological Pathology grades (AUC: 0.82 [p = 0.002]) and quantitative Gleason score (AUC: 0.83 [p = 0.018]). The Ki-67 LI is a powerful prognostic parameter in prostate cancer that is now applicable in routine clinical practice. In the case of multiple cancer-positive biopsies, the sole automated analysis of the worst biopsy was sufficient. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Prevalence, risk factors, and prognostic value of anxiety and depression in acute myeloid leukemia.

INTRODUCTION: Limited studies report anxiety and depression prevalence and their correlations with prognosis in acute myeloid leukemia (AML). Even worse, their risk factors in AML remained unclear. This study aimed to investigate the prevalence, risk factors, and prognostic value of anxiety and depression in AML patients. METHODS: Totally, 132 de novo AML patients, 60 non-malignant hematological disease patients (as disease controls) and 60 healthy controls were enrolled. Anxiety and depression status were evaluated by Hospital Anxiety and Depression Scale (HADS) in all participants. RESULTS: HADS-anxiety score (8.2±3.2 vs. 6.1±2.9 vs. 4.7±2.8), anxiety rate (48.5% vs. 25.0% vs. 10.0%), HADS-depression score (7.8±3.0 vs. 5.8±3.0 vs. 4.0±2.8) and depression rate (43.2% vs. 23.3% vs. 8.3%) were highest in AML patients, followed by disease controls, and the lowest in healthy controls (all P<0.001). Multivariate logistic regression analysis identified that factors independently associated with anxiety included male (P=0.002, odds ratio (OR)=0.240), smoking (P=0.043, OR=2.474), education duration (P=0.024, OR=0.889) and NCCN high-risk stratification (P=0.008, OR=2.347); while those independently associated with depression were age (P=0.005, OR=1.055), single/divorced/widowed status (P=0.014, OR=3.149), NCCN high-risk stratification (P=0.002, OR=3.077) and WBC (P<0.001, OR=1.062). Additionally, depression was correlated with shorter accumulating event-free survival (P=0.012) and overall survival (P=0.041) in AML patients, whereas anxiety was not. CONCLUSIONS: Anxiety and depression are prevalent, among which depression is associated with poor survival profile, but anxiety is not; moreover, age, male, education, single/divorced/widowed status, smoking, NCCN high-risk stratification and WBC were independent related factors of anxiety and depression in AML patients.

Development and validation of a diagnostic nomogram to evaluate tubular atrophy/interstitial fibrosis of IgA nephropathy.

Background: IgA nephropathy (IgAN) is a cause of chronic kidney disease (CKD). Tubular atrophy/interstitial fibrosis is associated with IgAN prognosis. However, simple tools for predicting pathological lesions of IgAN remain limited. Our objective was to develop a tool for evaluating tubular atrophy/interstitial fibrosis in patients with IgAN. Methods: In this cross-sectional study, 410 biopsy-verified IgAN patients were included. The factors associated with the incident interstitial fibrosis or tubular atrophy in IgAN were confirmed by using logistic regression analysis. A nomogram was developed using logistic regression coefficients to evaluate tubular atrophy or interstitial fibrosis. Receiver operating characteristic curves (ROC) and calibration curves were used to determine the discriminative ability and predictive accuracy of the nomogram. Results: In this study, the IgAN patients with tubular atrophy or interstitial fibrosis were older and had a higher percentage of males, hypertension and urinary protein excretion (UPE), with high levels of serum cystatin C, serum creatinine, high-sensitivity C-reactive protein and serum C4. The eGFRcr-cys equation calculated using serum creatinine, cystatin C and UPE were considered independent influencing factors of tubular atrophy or interstitial fibrosis in patients with IgAN. Furthermore, the nomogram demonstrated good discrimination (AUC: 0.87, 95% CI 0.81 to 0.93) and calibration in the validation cohort. Conclusion: The eGFRcr-cys and UPE are associated with tubular atrophy or interstitial fibrosis in patients with IgAN. Diagnostic nomogram can predict tubular atrophy or interstitial fibrosis in IgAN.

Genome-wide characterization of extrachromosomal circular DNA in gastric cancer and its potential role in carcinogenesis and cancer progression.

Extrachromosomal circular DNAs (eccDNAs) carrying random genomic segments are broadly found across different cancer types, but their molecular functions and impact in gastric cancer (GC) are rarely known. In this study, we aimed to investigate the potential role of eccDNA in GC. Using the Circle-seq strategy, we observed the eccDNA abundance in gastric cancer tissues (GCT) was aberrantly higher than that of normal adjacent tissues (NAT). The high abundance of eccDNAs carrying oncogene-segments in GCT may represent the DNA damage products of amplified oncogenes. Analysis of GCT over-represented eccDNA carrying enhancer (eccEnhancer) based on data from FANTOM5 project combined with TCGA database suggested the GC over-represented eccEnhancers may contribute to development of GC. GC over-represented eccDNAs carrying pre-miRNA (eccMIR) were enriched to multiple cancer-relevant signal pathways by KEGG analysis. We then synthesized the top six GC over-represented eccMIRs and found four of them enabled high expression of miRNAs and down-regulation of miRNA-target genes in MGC803 cells. Furthermore, we observed the inheritance of GC over-represented eccMIRs benefited host cell proliferation and promoted the aggressive features of host cells. Altogether, this study revealed the GC over-represented eccDNAs carrying functional genomic segments were related to the carcinogenesis of GC and presented the capability to facilitate cancer progression, suggesting the cancerous eccDNAs may serve as a dynamic reservoir for genome plasticity and rapid adaptive evolution of cancer. Therefore, blocking the pathways for eccDNAs generation may provide a novel therapeutic strategy for the treatment of gastric cancer.

Association between physical activity and risk of premenstrual syndrome among female college students: a systematic review and meta-analysis.

BACKGROUND: This study aimed to analyze the relationship between physical activity and the risk of premenstrual syndrome among college students. METHODS: Eligible studies were searched from the PubMed, Web of Science, and Embase databases. The link between physical activity and the risk of premenstrual syndrome was evaluated using odds ratio (OR) and 95% confidence interval (CI). The heterogeneity of the included studies was tested and their sources were explored by subgroup analysis. A sensitivity analysis was performed to assess the effect of a single study on the pooled results. The included studies were evaluated for publication bias. Five moderate-quality studies were included in this meta-analysis. RESULTS: Physical activity levels were negatively associated with risk of premenstrual syndrome among college students (OR [95%CI] = 1.46 [1.09, 1.96], P = .011). The pooled results were not influenced after being stratified by the study region and whether multi-factor correction was performed or not. Publication bias was not observed in the included studies. CONCLUSION: A high level of physical activity is dramatically associated with a reduced risk of premenstrual syndrome among female college students.

Variations of sediment organic phosphorus and organic carbon during the outbreak and decline of algal blooms in Lake Taihu, China.

In this study, sediment organic phosphorus (OP) and organic carbon (OC) in Lake Taihu, China, as well as their relationships, were analyzed during the outbreak and decline of algal blooms (ABs) over a five-month field study. The results showed synchronous temporal changes in the sediment OP and OC contents with the development of ABs. In addition, there was a significant positive correlation between the sediment OP and OC (p < 0.01), suggesting simultaneous deposition and consumption during the ABs outbreak. The sediment OP and OC contents decreased significantly at the early and last stages of the ABs outbreak and increased at the peak of the ABs outbreak and during the ABs decline. These temporal variation patterns suggest that the sediment OC and OP contents did not consistently increase during the ABs outbreak, even though algae are an important source of organic matter in sediments. The depletion or enrichment of OC and OP in sediments may also depend on the scale of the ABs outbreak. The obtained results revealed significant differences in the sediment OC and OP contents between the months (p < 0.05). In addition, OP in the sediments was dominated by orthophosphate diester (phospholipids and DNA-P) and orthophosphate monoester during the ABs outbreak and decline, respectively. The active OC contents and proportions in the sediments in the ABs outbreak were significantly lower than those observed in the ABs decline period, demonstrating the significant impacts of the ABs outbreak and decline on the sediment OC and OP in Lake Taihu.

Graphical multispectral radiation temperature inversion algorithm based on deep learning.

Neural networks are the most promising tool to solve the problem that an assumed emissivity model is needed in the field of multispectral radiometric temperature measurement. Existing neural network multispectral radiometric temperature measurement algorithms have been investigating the problems of network selection, network porting, and parameter optimization. The inversion accuracy and adaptability of the algorithms have been unsatisfactory. In view of the great success of deep learning in the field of image processing, this Letter proposes the idea of converting one-dimensional multispectral radiometric temperature data into two-dimensional image data for data processing to improve the accuracy and adaptability of multispectral radiometric temperature measurement by deep learning algorithms. Simulation and experimental validation are carried out. In the simulation, the error is less than 0.71% without noise and 1.80% with 5% random noise, which improves the accuracy by more than 1.55% and 2.66% compared with the classical BP (backpropagation) algorithm, and 0.94% and 0.96% compared with the GIM-LSTM (generalized inverse matrix-long short-term memory) algorithm. In the experiment, the error is less than 0.83%. This indicates that the method has high research value and is expected to lead multispectral radiometric temperature measurement technology to a new level.

Clinicopathological Features and Outcomes of IgA Nephropathy with Serum Antineutrophil Cytoplasmic Autoantibody Positivity.

INTRODUCTION: IgA nephropathy (IgAN) with serum antineutrophil cytoplasmic autoantibody (ANCA) positivity is uncommon. This study analyzed the clinicopathologic features and prognosis of IgAN patients with serum ANCA positivity. METHODS: 2,864 IgAN patients were tested for ANCA by the indirect immunofluorescence assay and chemiluminescence immunoassay. Patients with serum ANCA positivity (n = 85) were identified, and their clinical, pathological, and prognostic characteristics were analyzed. They were compared with ANCA-negative IgAN patients (n = 170) and ANCA-associated systemic vasculitis (AAV) with renal involvement patients (n = 85) selected randomly. RESULTS: 2.97% (85/2,864) of IgAN were ANCA positive, and 4 patients were diagnosed as having crescentic IgAN with ANCA positivity. The clinicopathological characteristics of ANCA-positive IgAN patients were comparable to ANCA-negative IgAN patients, but they had higher antinuclear antibody (ANA)-positive rates, lower levels of renal interstitial inflammation, and fewer immune depositions than ANCA-negative IgAN patients. Compared with AAV patients, ANCA-positive IgAN patients were younger and had fewer extrarenal manifestations, milder renal damage, and more immune complex depositions. The renal outcomes were similar between IgAN patients with and without ANCA positivity. Multivariate Cox analysis revealed that in IgAN patients with ANCA positivity, male, ANA positivity, higher serum creatinine and proteinuria, and more severe renal tubular atrophy/interstitial fibrosis were risk factors for adverse renal outcomes. CONCLUSION: The clinical, pathological features and prognosis of ANCA-positive IgAN patients were similar to those of ANCA-negative IgAN patients except for higher ANA-positive rate, milder renal inflammation, and fewer immune depositions. ANA positivity was an independent risk factor for adverse renal outcomes in ANCA-positive IgAN patients.