Clinical characteristics and prognosis of patients with severe pneumonia with Pneumocystis jirovecii colonization: A multicenter, retrospective study.

BACKGROUND: For decades, the incidence and clinical characteristics of Pneumocystis jirovecii (P. jirovecii) colonization in patients with severe pneumonia was remained unclear. RESEARCH QUESTION: What are the clinical features and outcomes associated with P. jirovecii colonization in individuals diagnosed with severe pneumonia? STUDY DESIGN AND METHODS: In this multicenter, retrospective, matched study, severe pneumonia patients who underwent bronchoalveolar lavage clinical metagenomics from 2019 to 2023 in the ICUs of 17 medical centers were enrolled. Patients were diagnosed based on clinical metagenomics, pulmonary CT scans, and clinical presentations. Clinical data were collected retrospectively, and according to propensity score matching and Cox multivariate regression analysis, the prognosis of patients with P. jirovecii colonization was compared to that of P. jirovecii-negative patients. RESULTS: 40% of P. jirovecii positive patients are considered to have P. jirovecii colonization. P. jirovecii colonization group had a higher proportion of patients with immunosuppression and a lower lymphocyte count compared to P. jirovecii-negative group. More frequent detection of cytomegalovirus, Epstein-Barr virus, human herpesvirus-6B, human herpesvirus-7, and torque teno virus in the lungs was associated with P. jirovecii colonization than with P. jirovecii negativity. By constructing two cohorts through propensity score matching, we incorporated codetected microorganisms and clinical features into a Cox proportional hazards model and revealed that P. jirovecii colonization was an independent risk factor for mortality in severe pneumonia patients. According to sensitivity analyses, which included or excluded codetected microorganisms, as well as patients not receiving TMP-SMX treatment, similar conclusions were reached. INTERPRETATION: Immunosuppression and a reduced lymphocyte count were identified as risk factors for P. jirovecii colonization in non-PCP patients. More frequent detection of various viruses was observed in P. jirovecii colonization patients, and P. jirovecii colonization was associated with an increased 28-day mortality in patients with severe pneumonia.

SNORD3A Regulates STING Transcription to Promote Ferroptosis in Acute Kidney Injury.

Acute kidney injury (AKI) signifies a sudden and prolonged decline in kidney function characterized by tubular cell death and interstitial inflammation. Small nucleolar RNAs (snoRNAs) play pivotal roles in oxidative stress and inflammation, and may play an important role in the AKI process, which remains elusive. an elevated expression of Snord3a is revealed in renal tubules in response to AKI and demonstrates that Snord3a deficiency alleviates renal injury in AKI mouse models. Notably, the deficiency of Snord3a exhibits a mitigating effect on the stimulator of interferon genes (STING)-associated ferroptosis phenotypes and the progression of tubular injury. Mechanistically, Snord3a is shown to regulate the STING signaling axis via promoting STING gene transcription; administration of Snord3a antisense oligonucleotides establishes a significant therapeutic advantage in AKI mouse models. Together, the findings elucidate the transcription regulation mechanism of STING and the crucial roles of the Snord3a-STING axis in ferroptosis during AKI, underscoring Snord3a as a potential prognostic and therapeutic target for AKI.

Insight into the generation of toxic by-products during UV/H2O2 degradation of carbamazepine: Mechanisms, N-transformation and toxicity.

Carbamazepine (CBZ) is a widely used anticonvulsant drug that has been detected in aquatic environments. This study investigated the toxicity of its by-products (CBZ-BPs), which may surpass CBZ. Unlike the previous studies, this study offered a more systematic approach to identifying toxic BPs and inferring degradation pathways. Furthermore, quadrupole time-of-flight (QTOF) and density functional theory (DFT) calculations were employed to analyze CBZ-BP structures and degradation pathways. Evaluation of total organic carbon (TOC) and total nitrogen (TN) mineralization rates, revealed carbon (C) greater susceptibility to mineralization compared with nitrogen (N). Furthermore, three rules were established for CBZ decarbonization and N removal during degradation, observing the transformation of aromatic compounds into aliphatic hydrocarbons and stable N-containing organic matter over time. Five potentially highly toxic BPs were screened from 14 identified BPs, with toxicity predictions guiding the selection of commercial standards for quantification and true toxicity testing. Additionally, BP207 emerged as the most toxic, supported by the predictive toxicity accumulation model (PTAM). Notably, highly toxic BPs feature an acridine structure, indicating its significant contribution to toxicity. These findings offered valuable insights into the degradation mechanisms of emerging contaminants and the biosafety of aquatic environments during deep oxidation.

Time-resolved map of serum metabolome profiling in D-galactose-induced aging rats with exercise intervention.

Exercise, an intervention with wide-ranging effects on the whole body, has been shown to delay aging. Due to aging and exercise as modulator of metabolism, a picture of how exercise delayed D-galactose (D-gal)-induced aging in a time-resolved manner was presented in this paper. The mapping of molecular changes in response to exercise has become increasingly accessible with the development of omics techniques. To explore the dynamic changes during exercise, the serum of rats and D-gal-induced aging rats before, during, and after exercise was analyzed by untargeted metabolomics. The variation of metabolites was monitored to reveal the specific response to D-gal-induced senescence and exercise in multiple pathways, especially the basal amino acid metabolism, including glycine serine and threonine metabolism, cysteine and methionine metabolism, and tryptophan metabolism. The homeostasis was disturbed by D-gal and maintained by exercise. The paper was expected to provide a theoretical basis for the study of anti-aging exercise.

The correlation of interstitial change with renal prognosis in patients with myeloperoxidase-ANCA-associated glomerulonephritis: a single-center retrospective analysis.

OBJECTS: We aim to explore the correlation between active/chronic tubulointerstitial injury and renal survival, and to compare their predictive value in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). METHOD: A total of 225 patients with MPO-AAGN diagnosed between February 2004 and December 2020 were included. Survival and univariate/multivariate Cox regression analyses were used to analyze the prognostic value of interstitial inflammation and interstitial fibrosis/tubular atrophy (IF/TA). RESULTS: Of the 225 patients, 73 (32.4%) patients developed end-stage renal disease (ESRD) requiring maintenance dialysis. Interstitial inflammation>50% and IF/TA>50% were important predictors for ESRD in MPO-AAGN in multivariate Cox regression analysis adjusted by age, gender, estimated glomerular filtration rate (eGFR)≤15 ml/min/1.73m2, and normal glomeruli% (classified by <25%, 25-50%, >50%). Furthermore, we conducted stratified Cox regression analysis and found different results in the subgroups of eGFR>15 ml/min/1.73m2 and eGFR≤15 ml/min/1.73m2. Interstitial inflammation>50% and IF/TA>50% were significant risk factors for ESRD in the subgroup of eGFR>15 ml/min/1.73m2, but not or less significant in the subgroup of eGFR≤15 ml/min/1.73m2. Similarly, the survival analysis according to interstitial inflammation>50%/≤50% and IF/TA>50%/≤50% showed significant differences in the subgroup of eGFR>15 ml/min/1.73m2, but not or less significant in the subgroup of eGFR≤15 ml/min/1.73m2. CONCLUSIONS: Interstitial inflammation>50% and IF/TA>50% were prognostic factors for renal survival in MPO-AAGN. In particular, interstitial inflammation and IF/TA had a better predictive ability in the subgroup of eGFR>15 ml/min/1.73m2. Key Points • Interstitial inflammation>50% and IF/TA>50% can help to predict renal survival in MPO-AAGN. • Both interstitial inflammation and IF/TA had a better predictive ability in the subgroup of eGFR>15 ml/min/1.73m2 than those in the subgroup of eGFR≤15 ml/min/1.73m2.

Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents.

Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

Visualization analysis of exercise intervention on Alzheimer disease based on bibliometrics: Trends, hotspots and topics.

BACKGROUND: As the challenges of an aging society continue to escalate, Alzheimer disease (AD) has emerged as a significant health, social, and public concern, garnering substantial attention. Exercise, as a safe, effective, and cost-efficient approach with the potential to mitigate brain aging, has garnered considerable interest. Nevertheless, there has been a limited research investigating the current trends, hotspots, and topics of exercise on AD. METHODS: The literature spanning from 2013 to 2022 was obtained from the Web of Science database, and CiteSpace VI was employed to conduct an analysis encompassing fundamental data, keywords, and co-citation analysis. RESULTS: A total of 9372 publications were included in the analysis. The annual number of publications has exhibited a gradual increase. The United States and China made significant contributions, with England showing higher citation rates and greater academic influence. The Journal of Alzheimers Disease, Neurosciences Neurology, Liu-Ambrose, Teresa represents the most published journal, discipline, and author, respectively. The research trends can be summarized as exploring functional changes and potential mechanisms related to exercise impact on AD. The hotspots in the research include the intersection of AD and diabetes mellitus, as well as the underlying effects induced by exercise. The topics of interest revolve around the application of emerging technologies in the context of exercise and AD. CONCLUSION: This bibliometric analysis has identified relevant trends, hotspots, and topics within the exercise intervention on AD. It offers a comprehensive overview that can equip researchers with valuable insights for future exploration and assist scholars in charting research trajectories in related domains.

Effects of 4 weeks of whole-body vibration training on energy expenditure during deep squats of male well-trained students.

From the perspective of energy expenditure, this study investigated the effects of whole-body vibration training on the energy metabolism of deep squats with different weights. Twenty-two healthy male college students with sports experiences were selected and randomly assigned to perform resistance exercise vibration (REV) or resistance exercise (RE) with varying loads two times per week for 4 weeks. Oxygen uptake and heart rate were measured before, during, and after exercises using a gas analyzer, and energy expenditure was calculated. The results showed the following: 1) the oxygen uptake and energy expenditure of the REV group were significantly higher than those of the RE group during and 30 min after exercise (p < 0.01), respectively, and the excess post-exercise oxygen consumption (EPOC) was also significantly higher than that of the RE group (p < 0.01). 2) Changes in the oxygen uptake and energy expenditure were stable with increasing exercise in both vibration and non-vibration conditions. There was no difference in energy expenditure per unit of body mass versus additional energy per kilogram of body weight (p > 0.05). 3) No significant differences in changing exercise intensity were observed in the REV group compared to those in the RE group during the adjacent incremental load phases of △ (40%-0%) and △ (80%-40%) of load during and 30 min after exercise (p > 0.05). Our results suggest that 1) vibration training can increase energy expenditure during low-intensity training and excess post-exercise oxygen consumption, and improve the exercise intensity. 2) The effects on energy expenditure were the same for both weight-bearing and non-weight-bearing deep squats, up to 40% of body mass.

Bioinformatics Analysis and Experimental Verification of Exercise for Aging Mice in Different Brain Regions Based on Transcriptome Sequencing.

PURPOSE: Physical exercise mitigates the effects of aging and cognitive decline. However, the precise neurobiological mechanisms underlying this phenomenon remain unclear. The primary aim of this study was to investigate the protective effect of exercise on age-related memory deficits in the prefrontal cortex (PFC) and hippocampus using bioinformatic analysis and biochemical verification. METHODS: Young and aging mice were subjected to natural feeding or treadmill exercise (12 m/min, 8 weeks). Cognitive function was accessed using the Barnes maze and novel object recognition. Bioinformatic analysis was performed to identify co-expressed genes in different groups and brain regions. The selected genes and pathways were validated using RT-qPCR. RESULTS: Regular exercise significantly ameliorated age-related cognitive deficits. Four up-regulated targets (Ifi27l2a, Irf7, Oas1b, Ifit1) and one down-regulation (Septin2) were reversed by exercise, demonstrating the underlying mechanisms of cognitive functions induced by aging with exercise in the hippocampus and PFC. The Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that the NOD-like receptor signaling pathway was inhibited in the neuroinflammation effects of exercise in aging mice in both brain regions. CONCLUSION: Exercise enhances age-related learning and memory deficits. This beneficial effect may be attributed to the changes in five up/down-regulated genes and the NOD-like receptor signaling pathway in both the hippocampus and PFC. These findings establish the modulation of neuroinflammation as a pivotal molecular mechanism supporting exercise intervention in the brain aging process.

Visual perception and linguistic abilities, not quantitative knowledge, count in geometric knowledge of kindergarten children.

Geometric knowledge is one of the important mathematical skills acquired by children at a young age and is a major area of future mathematical learning; however, there is no direct research on the factors influencing kindergarteners' early geometric knowledge. The pathways model to mathematics was modified to examine the cognitive mechanisms underlying geometric knowledge in Chinese kindergarten children aged 5-7 (n = 99). Quantitative knowledge, visual-spatial processing, and linguistic abilities were stepped into hierarchical multiple regression models. The results revealed that after age, sex, and nonverbal intelligence were statistically controlled, visual perception, phonological awareness, and rapid automatized naming in linguistic abilities significantly predicted the variation in geometric knowledge. For quantitative knowledge, neither dot comparison nor number comparison test could be a significant precursor of geometry skills. The findings indicate that visual perception and linguistic abilities, not quantitative knowledge, account for the geometric knowledge of kindergarten children.

Incidence and clinical features of HHV-7 detection in lower respiratory tract in patients with severe pneumonia: a multicenter, retrospective study.

PURPOSE: The significance of detecting human herpesvirus 7 (HHV-7) in the lower respiratory tract of patients with severe pneumonia is unclear. This study aims to evaluate the clinical characteristics and prognosis of detecting HHV-7 in the lower respiratory tract of patients with severe pneumonia. METHODS: Patients with severe pneumonia requiring invasive mechanical ventilation and underwent commercial metagenomic next-generation sequencing (mNGS) testing of bronchoalveolar lavage fluid from January 2019 to March 2023 were enrolled in 12 medical centers. Clinical data of patients were collected retrospectively, and propensity score matching was used for subgroup analysis and mortality assessment. RESULTS: In a total number of 721 patients, 45 cases (6.24%) were identified with HHV-7 positive in lower respiratory tract. HHV-7 positive patients were younger (59.2 vs 64.4, p = 0.032) and had a higher rate of co-detection with Cytomegalovirus (42.2% vs 20.7%, p = 0.001) and Epstein-Barr virus (35.6% vs 18.2%, p = 0.008). After propensity score matching for gender, age, SOFA score at ICU admission, and days from ICU admission to mNGS assay, there was no statistically significant difference in the 28-day mortality rate between HHV-7 positive and negative patients (46.2% vs 36.0%, p = 0.395). Multivariate Cox regression analysis adjusting for gender, age, and SOFA score showed that HHV-7 positive was not an independent risk factor for 28-day mortality (HR 1.783, 95%CI 0.936-3.400, p = 0.079). CONCLUSION: HHV-7 was detected in the lungs of 6.24% of patients with severe pneumonia. The presence of HHV-7 in patients with severe pneumonia requiring invasive mechanical ventilation is associated with a younger age and co-detected of Cytomegalovirus and Epstein-Barr virus. While HHV-7 positivity was not found to be an independent risk factor for mortality in this cohort, this result may have been influenced by the relatively small sample size of the study.

SARS-CoV-2 induces cardiomyocyte apoptosis and inflammation but can be ameliorated by ACE inhibitor Captopril.

Although the clinical manifestation of COVID-19 is mainly respiratory symptoms, approximately 20% of patients suffer from cardiac complications. COVID-19 patients with cardiovascular disease have higher severity of myocardial injury and poor outcomes. The underlying mechanism of myocardial injury caused by SARS-CoV-2 infection remains unclear. Using a non-transgenic mouse model infected with Beta variant (B.1.351), we found that the viral RNA could be detected in lungs and hearts of infected mice. Pathological analysis showed thinner ventricular wall, disorganized and ruptured myocardial fiber, mild inflammatory infiltration, and mild epicardia or interstitial fibrosis in hearts of infected mice. We also found that SARS-CoV-2 could infect cardiomyocytes and produce infectious progeny viruses in human pluripotent stem cell-derived cardiomyocyte-like cells (hPSC-CMs). SARS-CoV-2 infection caused apoptosis, reduction of mitochondrial integrity and quantity, and cessation of beating in hPSC-CMs. In order to dissect the mechanism of myocardial injury caused by SARS-CoV-2 infection, we employed transcriptome sequencing of hPSC-CMs at different time points after viral infection. Transcriptome analysis showed robust induction of inflammatory cytokines and chemokines, up-regulation of MHC class I molecules, activation of apoptosis signaling and cell cycle arresting. These may cause aggravate inflammation, immune cell infiltration, and cell death. Furthermore, we found that Captopril (hypotensive drugs targeting ACE) treatment could alleviate SARS-CoV-2 induced inflammatory response and apoptosis in cardiomyocytes via inactivating TNF signaling pathways, suggesting Captopril may be beneficial for reducing COVID-19 associated cardiomyopathy. These findings preliminarily explain the molecular mechanism of pathological cardiac injury caused by SARS-CoV-2 infection, providing new perspectives for the discovery of antiviral therapeutics.

Case Report: Parvovirus B19 infection complicated by hemophagocytic lymphohistiocytosis in a heart-lung transplant patient.

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.

The predictive value of Berden's classification versus renal risk score for renal survival of Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

OBJECTIVES: This study aims to compare the prognostic values of two histopathological classification, Berden's classification versus renal risk score (RRS) by Brix et al. for predicting renal survival in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (MPO-AAGN). METHODS: The medical records of 225 patients with MPO-AAGN diagnosed in our centre between February 2004 and December 2020 were retrospectively analysed. The predictive model of Berden's classification or RRS was established by Cox regression, respectively. The above two models were compared on aspects of discrimination, calibration, and decision curve analysis for predicting the 0.5-, 1-, 3-, and 5-year renal survival. RESULTS: After a median follow up of 38.99 months, 32.44% of patients developed end-stage renal disease (ESRD). In the Kaplan-Meier analysis, there were significant differences in renal survival among groups according to Berden's classification or RRS (both log-rank p<0.001). According to time-dependent receiver operating characteristic (ROC) curve analysis, the model based on RRS showed better discrimination ability than the model based on Berden's classification for predicting 0.5-, 1-, and 3-year renal survival. For calibration analysis, the model based on RRS showed worse calibration than the model based on Berden's classification for predicting 1- and 3-year renal survival. According to the decision curve analysis, the clinical decisions based on RRS could achieve more clinical benefits than those based on Berden's classification in predicting 0.5-, 1-, and 3-year renal survival. CONCLUSIONS: The model based on RRS has better predictive value for renal survival than Berden's classification in aspect of discrimination and clinical decision from 0.5- to 3-year renal survival.

Efficacy and acceptability of supervised group exercise for mild to moderate major depressive disorder: A feasibility study.

BACKGROUND: Exercise can efficiently reduce the symptoms of major depression disorder (MDD). This study aims to examine the efficacy and acceptability of supervised group exercise intervention among patients in an acute phase of mild to moderate MDD. METHODS: We enrolled patients in the psychiatric clinic of Beijing Anding Hospital affiliated to Capital Medical University in a prospective, single-arm objective performance criteria (OPC) trial. A total of 40 adults aged 18-50 who had a diagnosis of an episode of depression and the 17-item Hamilton Rating Scale for Depression (HRSD-17) score of 7-20 were recruited. Supervised exercise group intervention was applied on participants with a new episode of mild to moderate depression 3 times a week for 8 weeks without any other treatment. Every exercise session should meet the standard of moderate intensity, defined as approximately equal to 50 %-80 % of the maximal heart rate for 150 min every week. The primary end point was the clinical response at week 8, defined as a 50 % reduction in the baseline HRSD-17 score. Meanwhile, the secondary end points included the acceptability of the supervised group exercise intervention for both patients and investigators, remission rate (defined as an HRSD-17 score of 7 or less), the change of Patient Health Questionnaire (PHQ-9) and the Quality of Life, Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). RESULTS: Among the 46 screened patients, 40 were enrolled. Of them, 4 people dropped out, while 36 received all the planned sessions of the supervised group exercise therapy and completed the week-8 assessment. At week 8, the response rate was 89 % (95 % confidence interval [CI] 74 % to 97 %) and the remission rate was 83 % (95%CI 67 % to 94 %). The overall acceptance of the supervised group exercise based on the VAS score (range 0-10) was 9.19 ± 1.27 for patients and 9.67 ± 0.62 for investigators. The least-squares mean (±SE) change from baseline at week 8 was-9.99 in the PHQ-9 score and 25.15 in the Q-LES-Q-SF score. No serious adverse events were reported during this trial. The percentage of any adverse event was 5 %. CONCLUSION: Supervised group exercise intervention is effective in patients with acute mild to moderate MDD and has good acceptance rate among both patients and investigators.

Pharmacokinetics and bioequivalence studies of fluvoxamine maleate tablets in healthy Chinese subjects.

Fluvoxamine is a selective serotonin reuptake inhibitor commonly used for various types of depression. The purpose of this study was to evaluate the pharmacokinetics and bioequivalence of fluvoxamine maleate tablets orally on an empty stomach and after a meal in healthy adult Chinese subjects and to preliminarily evaluate their safety. A single-center, randomized, open-label, two-drug, two-period, crossover, single-dose trial protocol was designed. Sixty healthy Chinese participants were enrolled and randomly classified into fasting (n = 30) and fed groups (n = 30). Each week, subjects took fluvoxamine maleate tablets 50 mg orally once as a test preparation or as a reference preparation on an empty stomach/after meals. To evaluate the bioequivalence of test and reference tables, the concentration of fluvoxamine maleate in the plasma of the subjects at different time points after administration was detected by liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters including the maximum plasma drug concentration (Cmax ), the time to reach maximum concentration (Tmax ), the area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t ) and the area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞ ) were calculated. Our data revealed that the 90% confidence intervals of the geometric mean ratio of the test or reference drugs for the Cmax , AUC0-t and AUC0-∞ fell within the acceptance range for bioequivalence (92.30-102.77%). The absorption, measured by AUC, did not show a significant difference between the two groups. There were no suspected serious adverse reactions or serious adverse events over the entire trial. Our results demonstrated that the test and reference tablets were bioequivalent under fasting and fed conditions.

Validation of the Antineutrophil Cytoplasmic Antibody Renal Risk Score and Modification of the Score in a Chinese Cohort With a Majority of Myeloperoxidase-Positive Patients.

OBJECTIVE: We aimed to validate and modify the renal risk score for antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) in a Chinese cohort with a majority of myeloperoxidase (MPO)-positive patients. METHODS: A total of 285 patients with biopsy-proven AAGN in our center were retrospectively included. Patients were randomly assigned to the development set (n = 201) and the validation set (n = 84). We calculated the renal risk score and analyzed the clinicopathological characteristics and follow-up data. The nomogram was constructed based on the independent prognostic factors identified by the multivariable Cox regression and then compared with the renal risk score. RESULTS: Over a median follow-up period of 41.3 (range 20.0-63.8) months, 84 (29.5%) patients reached end-stage kidney disease (ESKD). In the development set, hypertension (hazard ratio [HR] 2.16, 95% CI 1.08-4.32, P = 0.03), high serum creatinine (HR 1.002, 95% CI 1.001-1.003, P < 0.001), high daily urine protein (HR 1.34, 95% CI 1.15-1.57, P < 0.001), high glomerular sclerosis (HR 13.98, 95% CI 3.50-55.92, P < 0.001), and interstitial fibrosis > 50% (HR 4.18, 95% CI 1.90-9.19, P < 0.001) were independent risk factors for ESKD, and these indicators were included in the nomogram. The C-indices of the nomogram model in the development set, validation set, and all-data set were 0.838 (range 0.785-0.891), 0.794 (range 0.774-0.814), and 0.822 (range 0.775-0.869), respectively, which were higher than those of the renal risk score model, 0.801 (range 0.748-0.854), 0.746 (range 0.654-0.838) and 0.783 (range 0.736-0.830), respectively. The net reclassification improvement and the integrated discrimination improvement further illustrated the higher predictive ability of the nomogram. CONCLUSION: We present a nomogram as a practical tool to predict renal outcomes in Chinese patients with MPO-ANCA glomerulonephritis.