Functional Multivariable Logistic Regression With an Application to HIV Viral Suppression Prediction.

Motivated by improving the prediction of the human immunodeficiency virus (HIV) suppression status using electronic health records (EHR) data, we propose a functional multivariable logistic regression model, which accounts for the longitudinal binary process and continuous process simultaneously. Specifically, the longitudinal measurements for either binary or continuous variables are modeled by functional principal components analysis, and their corresponding functional principal component scores are used to build a logistic regression model for prediction. The longitudinal binary data are linked to underlying Gaussian processes. The estimation is done using penalized spline for the longitudinal continuous and binary data. Group-lasso is used to select longitudinal processes, and the multivariate functional principal components analysis is proposed to revise functional principal component scores with the correlation. The method is evaluated via comprehensive simulation studies and then applied to predict viral suppression using EHR data for people living with HIV in South Carolina.

Diffusing on Two Levels and Optimizing for Multiple Properties: A Novel Approach to Generating Molecules with Desirable Properties.

In the past decade, Artificial Intelligence (AI) driven drug design and discovery has been a hot research topic in the AI area, where an important branch is molecule generation by generative models, from GAN-based models and VAE-based models to the latest diffusion-based models. However, most existing models pursue mainly the basic properties like validity and uniqueness of the generated molecules, a few go further to explicitly optimize one single important molecular property (e.g., QED or PlogP), which makes most generated molecules little usefulness in practice. In this paper, we present a novel approach to generating molecules with desirable properties, which expands the diffusion model framework with multiple innovative designs. The novelty is two-fold. On the one hand, considering that the structures of molecules are complex and diverse, and molecular properties are usually determined by some substructures (e.g., pharmacophores), we propose to perform diffusion on two structural levels: molecules and molecular fragments respectively, with which a mixed Gaussian distribution is obtained for the reverse diffusion process. To get desirable molecular fragments, we develop a novel electronic effect based fragmentation method. On the other hand, we introduce two ways to explicitly optimize multiple molecular properties under the diffusion model framework. First, as potential drug molecules must be chemically valid, we optimize molecular validity by an energy-guidance function. Second, since potential drug molecules should be desirable in various properties, we employ a multi-objective mechanism to optimize multiple molecular properties simultaneously. Extensive experiments with two benchmark datasets QM9 and ZINC250k show that the molecules generated by our proposed method have better validity, uniqueness, novelty, Fr´echet ChemNet Distance (FCD), QED, and PlogP than those generated by current SOTA models. The Code of D2L-OMP is available at https://github.com/bz99bz/D2L-OMP.

A study on the correlation between physical fitness index and executive function in Chinese adolescents.

OBJECTIVE: To explore the relationship between physical fitness index and executive function in Chinese adolescents, and to provide a reference for improving the development of executive function in Chinese adolescents. METHODS: From September to December 2023, 5336 adolescents aged 13 to 18 years were selected by stratified whole cluster random sampling method in six regions of China for physical fitness and executive function tests. The relationship between adolescent physical fitness index and executive function was analyzed using t-test, ANOVA, Pearson's correlation, and logistic regression. RESULTS: The correlation coefficients between adolescents' physical fitness index and inhibitory control reaction time were all 0.00094, p > 0.05; the correlation coefficients between adolescents' physical fitness index and working memory (1-back, 2-back) reaction time were -0.13 and -0.093, respectively, p < .05; the correlation coefficients between adolescents' physical fitness index and cognitive flexibility reaction time were -0.17 and -0.18, p < .05. Logistic regression analyses showed that 1-back, 2-back, and cognitive flexibility were significantly and positively correlated with physical fitness index in Models 1, 2, and 3 (all p values less than.01). The coefficients of inhibitory control were not significant in all three models (p > .05), and there was no significant relationship with physical fitness index. CONCLUSION: The physical fitness index of Chinese adolescents has a significant positive correlation with working memory and cognitive flexibility, but not with inhibitory control, i.e. the higher the physical fitness index, the better the working memory and cognitive flexibility.

Differences in physiology and behavior between male winner and loser mice in the tube test.

Social hierarchy is a crucial element for survival, reproduction, fitness, and the maintenance of a stable social group in social animals. This study aimed to investigate the physiological indicators, nociception, unfamiliar female mice preference, spatial learning memory, and contextual fear memory of male mice with different social status in the same cage. Our findings revealed significant differences in the trunk temperature and contextual fear memory between winner and loser mice. However, there were no major discrepancies in body weight, random and fasting blood glucose levels, whisker number, frontal and perianal temperature, spleen size, mechanical and thermal pain thresholds, preference for unfamiliar female mice, and spatial memory. In conclusion, social status can affect mice in multiple ways, and, therefore, its influence should be considered when conducting studies using these animals.

Interplay among attention, appraisal, and memory bias in provisional posttraumatic stress disorder: Exploring the combined cognitive biases hypothesis.

OBJECTIVE: Both theoretical and empirical studies suggest that negative cognitive biases significantly influence the onset and persistence of posttraumatic stress disorder (PTSD) symptoms. However, the interplay among these cognitive biases and their conjoint contribution to the long-term trajectory of posttraumatic stress symptoms remains underexplored. This study delves into the interplay among attention, appraisal, and memory biases within a provisional PTSD population and evaluates the predictive effects of two integrative models (weakest link, additive approach) on posttraumatic stress symptoms reported 2 months later. METHOD: Sixty Chinese participants (Mage = 20.17, SDage = 2.11) with provisional PTSD undertook the scrambled sentences test (appraisal bias) with their eye movements recorded (attention bias) and then the free recall task (memory bias). Posttraumatic stress symptom was assessed at baseline and 2-month follow-up. RESULTS: Selective attention bias toward negative words was positively associated with the negative appraisal of scrambled sentences, which subsequently showed a strong association with negative memory bias. Regarding the progression of posttraumatic stress symptoms, the additive approach was found to be a more reliable predictor of self-reported posttraumatic stress symptoms at 2 months than the weak link approach. CONCLUSIONS: This study provides initial evidence supporting the combined cognitive biases hypothesis in provisional PTSD. It also underscores potential avenues to enhance cognitive bias modification techniques. Replication of these findings in broader clinical samples is essential. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neuropeptide ACP is required for fat body lipid metabolism homeostasis in locusts.

Fat body metabolism plays crucial roles in each aspect of insect life traits. Although neuropeptides have been documented to be one of the major neuroendocrinal regulators involved in fat body metabolism, the detailed regulatory mechanism is poorly explored. Here, we conducted comparative metabolome and transcriptome analyses of fat body between wide type (WT) and adipokinetic hormone/corazonin-related peptide (ACP) loss of function mutants of the migratory locust, Locusta migratoria. We found that knockout of ACP resulted in significantly reduced fat body triacylglycerol content but enhanced abundance of phospholipids, particularly phosphatidylcholine and phosphatidylethanolamine. Additionally, the expression levels of genes involved in triacylglycerol and phospholipid synthesis and degradation were significantly altered in the fat body of ACP mutants. Moreover, female ACP mutants displayed much higher fecundity compared to WT females. These findings highlight the important role of neuropeptide ACP in fat body lipid metabolism homeostasis in locusts.

Radiographic Progression-Free Survival and Clinical Progression-Free Survival as Potential Surrogates for Overall Survival in Men With Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: Despite major increases in the longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC), most men still die of prostate cancer. Phase III trials assessing new therapies in mHSPC with overall survival (OS) as the primary end point will take approximately a decade to complete. We investigated whether radiographic progression-free survival (rPFS) and clinical PFS (cPFS) are valid surrogates for OS in men with mHSPC and could potentially be used to expedite future phase III clinical trials. METHODS: We obtained individual patient data (IPD) from 9 eligible randomized trials comparing treatment regimens (different androgen deprivation therapy [ADT] strategies or ADT plus docetaxel in the control or research arms) in mHSPC. rPFS was defined as the time from random assignment to radiographic progression or death from any cause whichever occurred first; cPFS was defined as the time from random assignment to the date of radiographic progression, symptoms, initiation of new treatment, or death, whichever occurred first. We implemented a two-stage meta-analytic validation model where conditions of patient-level and trial-level surrogacy had to be met. We then computed the surrogate threshold effect (STE). RESULTS: IPD from 6,390 patients randomly assigned from 1994 to 2012 from 13 units were pooled for a stratified analysis. The median OS, rPFS, and cPFS were 4.3 (95% CI, 4.2 to 4.5), 2.4 (95% CI, 2.3 to 2.5), and 2.3 years (95% CI, 2.2 to 2.4), respectively. The STEs were 0.80 and 0.81 for rPFS and cPFS end points, respectively. CONCLUSION: Both rPFS and cPFS appear to be promising surrogate end points for OS. The STE of 0.80 or higher makes it viable for either rPFS or cPFS to be used as the primary end point that is surrogate for OS in phase III mHSPC trials with testosterone suppression alone as the backbone therapy and would expedite trial conduct.

The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.

PURPOSE: HOXB13 is an androgen receptor (AR) coregulator specifically expressed in cells of prostatic lineage. We sought to associate circulating tumor cell (CTC) HOXB13 expression with outcomes in men with mCRPC treated with abiraterone or enzalutamide. EXPERIMENTAL DESIGN: We conducted a retrospective analysis of the multicenter prospective PROPHECY trial of mCRPC men (NCT02269982, n = 118) treated with abiraterone/enzalutamide. CTC detection and HOXB13 complementary DNA (cDNA) expression was measured using a modified Adnatest, grouping patients into 3 categories: CTC 0 (undetectable); CTC+ HOXB13 CTC low (<4 copies); or CTC+ HOXB13 CTC high. The HOXB13 threshold was determined by maximally selected rank statistics for prognostic associations with overall survival (OS) and progression-free survival (PFS). RESULTS: We included 102 men with sufficient CTC HOXB13 cDNA, identifying 25%, 31%, and 44% of patients who were CTC 0, CTC+ HOXB13 low, and CTC+ HOXB13 high, respectively. Median OS were 25.7, 27.8, and 12.1 months whereas the median PFS were 9.0, 7.7, and 3.8 months, respectively. In subgroup analysis among men with CellSearch CTCs ≥5 copies/mL and adjusting for prior abi/enza treatment and Halabi clinical risk score, the multivariate HR for HOXB13 CTC detection was 2.39 (95% CI, 1.06-5.40) for OS and 2.78 (95% CI, 1.38-5.59) for PFS, respectively. Low HOXB13 CTC detection was associated with lower CTC PSA, PSMA, AR-FL, and AR-V7 detection, and more liver/lung metastases (41% vs. 25%). CONCLUSIONS: Higher CTC HOXB13 expression is associated with AR-dependent biomarkers in CTCs and is adversely prognostic in the context of potent AR inhibition in men with mCRPC.

Simultaneous improvement of polarization and bandgap by finite solid solution engineering.

A narrow-bandgap-induced potential field always results in decreased photovoltaic performance. Here, a finite solid solution was designed to explore the simultaneous improvement of the polarization property and bandgap obtained from the critical effect in which BiMnO3 (BM) enters the Na0.5Bi0.5TiO3 (NBT) crystal lattice, resulting in a strong lattice expansion; by contrast, the incorporation of Mn without a d-orbital weakened the orbital hybridization accompanied by Jahn-Teller (J-T) distortion to reduce the optical bandgap. A narrow bandgap of 2.90 eV and polarization of 65.9 µC cm-2 were achieved by finite solid solution engineering. The open-circuit voltage and the short-circuit current with a BM doping component of 0.04 reached as high as 1.1 V and 0.0132 mA cm-2, respectively. This work provides an optimized strategy for the mutual benefit of the polarization and bandgap by finite solid solution engineering.

Protocol for a scoping review of the role of siblings in supporting middle-aged and older people with early-acquired severe mental illness.

INTRODUCTION: For older individuals who developed severe mental illness (SMI) during late adolescence or early adulthood (referred to as early-acquired SMI), the combination of ageing and SMI presents persistent health and psychosocial challenges. This group, with a higher likelihood of being unmarried or experiencing marriage dissolution, often lacks social and economic resources to address the difficulties they face in later life. In recent years, there has been a growing interest in understanding the role of siblings in supporting the ageing process of individuals with early-acquired SMI. However, to date, no reviews have investigated the role of siblings in assisting their middle-aged and older brothers or sisters with SMI as they age within community settings. Our scoping review aims to explore and synthesise the existing literature on sibling support for individuals with early-acquired SMI, with the goal of informing further advancements in research, practice and policy. METHODS AND ANALYSIS: The methodological framework developed by Arksey and O'Malley will inform this scoping review. Four groups of search keywords, derived from four related concepts (sibling, SMI, support and ageing), will be employed. Additionally, a group of keywords related to unrelated life stages and diseases will be used to exclude irrelevant articles. A search will be carried out across major online databases, namely PubMed, Scopus, PsycINFO, Ovid MEDLINE, ProQuest and Google Scholar to identify the articles between 2000 and 2023. English-language studies meeting specific eligibility criteria will be identified following a review of titles and abstracts and will then undergo a full-text review. The data from the selected articles will be extracted using a customised data-charting framework and content analysis will be conducted. ETHICS AND DISSEMINATION: There are no requirements for ethical approval. The findings of this review will be shared through professional connections, academic conferences and scholarly journals.

Site Engineering of Covalent Organic Frameworks for Regulating Peroxymonosulfate Activation to Generate Singlet Oxygen with 100 % Selectivity.

Singlet oxygen (1 O2 ) is an excellent reactive oxygen species (ROSs) for the selective conversion of organic matter, especially in advanced oxidation processes (AOPs). However, due to the huge dilemma in synthesizing single-site type catalysts, the control and regulation of 1 O2 generation in AOPs is still challenging and the underlying mechanism remains largely obscure. Here, taking advantage of the well-defined and flexibly tunable sites of covalent organic frameworks (COFs), we report the first achievement in precisely regulating ROSs generation in peroxymonosulfate (PMS)-based AOPs by site engineering of COFs. Remarkably, COFs with bipyridine units (BPY-COFs) facilitate PMS activation via a nonradical pathway with 100 % 1 O2 , whereas biphenyl-based COFs (BPD-COFs) with almost identical structures activate PMS to produce radicals (⋅OH and SO4 .- ). The BPY-COFs/PMS system delivers boosted performance for selective degradation of target pollutants from water, which is ca. 9.4 times that of its BPD-COFs counterpart, surpassing most reported PMS-based AOPs systems. Mechanism analysis indicated that highly electronegative pyridine-N atoms on BPY-COFs provide extra sites to adsorb the terminal H atoms of PMS, resulting in simultaneous adsorption of O and H atoms of PMS on one pyridine ring, which facilitates the cleavage of its S-O bond to generate 1 O2 .

Admission on weekends does not increase mortality after hip fracture: a meta-analysis of 1.4 million patients.

BACKGROUND: The "weekend" effect resulting in increased complication rates in patients admitted on weekends has been noted in many diseases. OBJECTIVE: This systematic review and meta-analysis aimed to collate adjusted data from published studies to assess if admission on weekends as compared to weekdays increases mortality rates in hip fracture patients. METHODS: Databases of PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched up to 31st December 2022 for studies comparing mortality between weekend versus weekday admission of hip fracture patients. Adjusted hazard ratios (HR) were pooled. RESULTS: Fourteen studies including 1,487,986 patients were analyzed. Most studies were from Europe and North America. Results showed no difference in mortality rates of hip fracture patients admitted on weekends versus weekdays (HR: 1.00 95% 0.96, 1.04 I2 = 75%). There was no publication bias and results did not change on the leave-one-out analysis. Subgroup analysis based on sample size and treatment did not change outcomes. CONCLUSION: This meta-analysis has shown no apparent weekend effect in cases of hip fractures. Patients admitted on weekends had similar mortality rates as compared to those admitted on weekdays. Current data has high heterogeneity and is mostly from developed countries.

[Gene clone and functional identification of sterol glycosyltransferases from Paris polyphylla var. yunnanensis].

In this study, the authors cloned a glycosyltransferase gene PpUGT2 from Paris polyphylla var. yunnanensis with the ORF length of 1 773 bp and encoding 590 amino acids. The phylogenetic tree revealed that PpUGT2 belonged to the UGT80A subfamily and was named as UGT80A49 by the UDP-glycosyltransferase(UGT) Nomenclature Committee. The expression vector pET28a-PpUGT2 was constructed, and enzyme catalytic reaction in vitro was conducted via inducing protein expression and extraction. With UDP-glucose as sugar donor and diosgenin and pennogenin as substrates, the protein was found with the ability to catalyze the C-3 hydroxyl ß-glycosylation of diosgenin and pennogenin. To further explore its catalytic characteristic, 15 substrates including steroids and triterpenes were selected and PpUGT2 showed its activity towards the C-17 position of sterol testosterone with UDP-glucose as sugar donor. Homology modelling and molecule docking of PpUGT2 with substrates predicted the key residues interacting with ligands. The re-levant residues of PpUGT2-ligand binding model were scanned to calculate the corresponding mutants, and the optimized mutants were obtained according to the changes in binding affinity of the ligand with protein and the surrounding residues within 5.0 Å of ligands, which had reference value for design of the mutants. This study laid a foundation for further exploring the biosynthetic pathway of polyphyllin as well as the structure of sterol glycosyltransferases.

Evolution between ferroelectric photovoltaic effect and resistance switching behavior engineered by the polarization field and barrier characteristics.

The bandgap and polarization field play a key role in the ferroelectric photovoltaic effect. However, narrow bandgap induced electrical conductivity always brings out a depression of the photovoltaic performances. Based on the mechanisms of the photovoltaic effect and resistance switching behaviors in ferroelectric materials, this work realizes an evolution between the two effects by engineering the polarization field and barrier characteristics, which addresses the trade-off issues between the bandgap and polarization for ferroelectric photovoltaic effect. SrCoOx (SC, 2.5≤x≤3) with multivalent transition is introduced into Na0.5Bi0.5TiO3 (NBT) matrix material to engineered the polarization field and barrier characteristics. (1-x)NBT-xSC (x=0.03, 0.05, 0.07) solid solution films present an evolution of ferroelectric photovoltaic effect to grow out of nothing again to the disappearance of the photovoltaic effect and the appearance of resistance switching behavior. The 0.95NBT-0.05SC film achieve the open-circuit voltage of 0.81 V and the short-circuit current of 23.52 µA/cm2, and the 0.93NBT-0.07SC film obtains the resistive switching behavior with switch ratio of 100. This work provides a practicable strategy to achieve the fascinating evolution between photovoltaic effect and resistive switching.

Impact of HIV on COVID-19 Outcomes: A Propensity Score Matching Analysis with Varying Age Differences.

To exploratorily test (1) the impact of HIV and aging process among PLWH on COVID-19 outcomes; and (2) whether the effects of HIV on COVID-19 outcomes differed by immunity level. The data used in this study was retrieved from the COVID-19 positive cohort in National COVID Cohort Collaborative (N3C). Multivariable logistic regression models were conducted on populations that were matched using either exact matching or propensity score matching (PSM) with varying age difference between PLWH and non-PLWH to examine the impact of HIV and aging process on all-cause mortality and hospitalization among COVID-19 patients. Subgroup analyses by CD4 counts and viral load (VL) levels were conducted using similar approaches. Among the 2,422,864 adults with a COVID-19 diagnosis, 15,188 were PLWH. PLWH had a significantly higher odds of death compared to non-PLWH until age difference reached 6 years or more, while PLWH were still at an elevated risk of hospitalization across all matched cohorts. The odds of both severe outcomes were persistently higher among PLWH with CD4 < 200 cells/mm3. VL ≥ 200 copies/ml was only associated with higher hospitalization, regardless of the predefined age differences. Age advancement in HIV might significantly contribute to the higher risk of COVID-19 mortality and HIV infection may still impact COVID-19 hospitalization independent of the age advancement in HIV.

Facile access to chiral γ-butyrolactones via rhodium-catalysed asymmetric hydrogenation of γ-butenolides and γ-hydroxybutenolides.

The highly efficient Rh/ZhaoPhos-catalysed asymmetric hydrogenation of γ-butenolides and γ-hydroxybutenolides was successfully developed. This protocol provides an efficient and practical approach to the synthesis of various chiral γ-butyrolactones, which are synthetically valuable building blocks of diverse natural products and therapeutic substances, with excellent results (up to >99% conversion and 99% ee). Further follow-up transformations have been revealed to accomplish creative and efficient synthetic routes for several enantiomerically enriched drugs via this catalytic methodology.

Association of BRCA2 Gene Functional Polymorphisms with Nonsyndromic Cleft Lip With or Without Cleft Palate in a Chinese Population.

Background: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a complex congenital disease affected by genetic and environmental factors however, the specific pathogenic alleles and regulatory mechanisms remain unclear in many cases. Here, we aimed to study the association between eight potentially functional single nucleotide polymorphisms (SNPs) of the BRCA2 and MGMT genes and NSCL/P in a Chinese population through a case-control study. Materials and Methods: To investigate the relationship between potentially functional SNPs of the BRCA2 and MGMT genes and NSCL/P, we selected 200 affected patients and 200 unrelated normal controls in a Chinese population. The BRCA2 gene SNPs (rs11571836, rs144848, rs7334543, rs15869, rs766173 and rs206118) and MGMT gene SNPs (rs12917 and rs7896488) were genotyped using the SNaPshot technique and the resulting data were subjected to statistical and bioinformatic analyses. Results: Our study identified for the first time that alleles of the BRCA2 are associated with NSCL/P in a Chinese population and that the s11571836 G allele was protective against NSCL/P. Under four genetic models, rs11571836 had a significant correlation with NSCL/P. Preliminary bioinformatic analyses revealed four potential miRNA matching sites (miR-1244, miR-1323, miR-562, and miR-633) associated with the rs11571836 which is located in the 3' untranslated region of BRCA2. Conclusions: These results support the role of polymorphisms of BRCA2 gene in affecting susceptibility to NSCL/P and its progression, but further research is necessary to elucidate the mechanism by which the BRCA2 gene polymorphisms affect the penetrance of NSCL/P.

Cordycepin buffers anisomycin-induced fear memory deficit by restoring hippocampal BDNF.

The process of memory consolidation involves the synthesis of new proteins, and interfering with protein synthesis through anisomycin can impair memory. Memory deficits due to aging and sleep disorders may also result from a reduction in protein synthesis. Rescuing memory deficits caused by protein synthesis deficiency is therefore an important issue that needs to be addressed. Our study focused on the effects of cordycepin on fear memory deficits induced by anisomycin using contextual fear conditioning. We observed that cordycepin was able to attenuate these deficits and restore BDNF levels in the hippocampus. The behavioral effects of cordycepin were dependent on the BDNF/TrkB pathway, as demonstrated by the use of ANA-12. Cordycepin had no significant impact on locomotor activity, anxiety or fear memory. Our findings provide the first evidence that cordycepin can prevent anisomycin-induced memory deficits by regulating BDNF expression in the hippocampus.

Juvenile idiopathic arthritis presenting as diffuse alveolar hemorrhage at onset: A case series.

OBJECTIVE: The etiology of diffuse alveolar hemorrhage (DAH) in childhood is often unknown, and it may be an early manifestation of rheumatic disease. Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in children, but DAH as an onset manifestation of JIA is rare. This study summarizes the clinical characteristics of patients with JIA presenting as DAH. METHODS: We retrospectively analyzed the age of onset, clinical manifestations, imaging features, treatments, and prognosis of five cases of JIA presenting as DAH. RESULTS: Themedian age at DAH onset was 6 months (range, 2 months-3 years). Pallor was the most common manifestation of onset (5/5). Other symptoms included cough (2/5), tachypnea (2/5), hemoptysis (1/5), cyanosis (1/5), and fatigue (1/5). Imaging showed ground-glass opacity (GGO) (5/5), subpleural or intrapulmonary honeycombing (4/5), consolidation (3/5), interlobular septal thickening (2/5), and nodules (1/5). Anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were positive in five children (5/5), and antinuclear antibody (ANA) was positive in four children (4/5). ANA in three children and ACPA/RF in one child were positive before the onset of joint symptoms. The median age at the onset of joint symptoms was 3 years and 9 months (2 years and 6 months-8 years). Joint symptoms were mainly characterized by joint swelling, pain, and difficulty walking, and the most commonly affected joints were the knees, ankles, and wrists. After the diagnosis of DAH, the five patients were treated with glucocorticoids. Alveolar hemorrhage was effectively controlled in three cases, but the other two patients still had anemia and poor improvements in chest imaging. After joint symptoms, the patients were treated with glucocorticoids combined with diclofenac, disease-modifying antirheumatic drugs, and biological agents. Alveolar hemorrhage was in remission, and joint symptoms were relieved in the five cases. CONCLUSION: DAH can be the first clinical manifestation of JIA, and joint involvement occurs 1-5 years later. Children with DAH who are positive for RF, ACPA, and/or ANA and have GGO accompanied by honeycombing on imaging should be concerned about their joint involvement in future.