Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Connective tissue disease in children is a systemic multi-system damage caused by chronic inflammation of systemic connective tissue and blood vessels.Lung is often the first organ invaded by the disease, and interstitial lesions are an important manifestation of lung damage, with an increasing incidence.Initial clinical manifestations of this disease are often insidious and lack specificity.When its clinical symptoms are detectable, lung lesions often have progressed and the lung tissue structure remodeling has occurred.Therefore, early diagnosis and treatment are crucial to improve its prognosis.In this article, the clinical characteristics, diagnosis and treatment of connective tissue disease-associated interstitial lung disease in children were reviewed, in order to help improve its diagnosis and treatment.

Connective tissue disease in children is a systemic multi-system damage caused by chronic inflammation of systemic connective tissue and blood vessels.Lung is often the first organ invaded by the disease, and interstitial lesions are an important manifestation of lung damage, with an increasing incidence.Initial clinical manifestations of this disease are often insidious and lack specificity.When its clinical symptoms are detectable, lung lesions often have progressed and the lung tissue structure remodeling has occurred.Therefore, early diagnosis and treatment are crucial to improve its prognosis.In this article, the clinical characteristics, diagnosis and treatment of connective tissue disease-associated interstitial lung disease in children were reviewed, in order to help improve its diagnosis and treatment.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

OBJECTIVE: We aimed to analyze the current indoor radon level and estimate the population risk of radon-induced lung cancer in urban areas of China. METHODS: Using the passive monitoring method, a new survey on indoor radon concentrations was conducted in 2,875 dwellings across 31 provincial capital cities in Chinese mainland from 2018 to 2023. The attributable risk of lung cancer induced by indoor radon exposure was estimated based on the risk assessment model. RESULTS: The arithmetic mean (AM) and geometric mean (GM) of indoor radon concentrations were 65 Bq/m³ and 55 Bq/m³, respectively, with 13.6% of measured dwellings exceeding 100 Bq/m³ and 0.6% exceeding 300 Bq/m³. The estimated number of lung cancer deaths induced by indoor radon exposure was 150,795, accounting for 20.30% (95% CI: 20.21%-20.49%) of the lung cancer death toll. CONCLUSION This study provided the most recent data on national indoor radon levels in urban areas and the attributable risk of lung cancer. These results served as an important foundation for further research on the disease burden of indoor radon exposure and radon mitigation efforts.
Radon/analysis* ; China/epidemiology* ; Air Pollution, Indoor/analysis* ; Lung Neoplasms/etiology* ; Humans ; Cities/epidemiology* ; Air Pollutants, Radioactive/adverse effects* ; Neoplasms, Radiation-Induced/etiology* ; Risk Assessment ; Radiation Monitoring

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO_2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO_2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

Objective:To explore the clinical features and risk factors of systemic lupus erythematosus(SLE) concomitant with interstitial lung disease(ILD) in children.Methods:A retrospective analysis was performed.A total of 111 hospitalized children diagnosed with SLE in the Department of Rheumatology and Immunology, Children′s Hospital of Soochow University from February 2016 to November 2018 were selected as the research subjects and divided into the SLE-ILD group(18 cases) and the SLE-non-ILD group(93 cases)according to the lung high-resolution CT manifestations. T-test and Wilcoxon rank sum test were used to compare and analyze the general situation, clinical manifestations and laboratory results.Multivariate Logistic regression was used to analyze the risk factors of SLE-ILD. Results:The prevalence of SLE-ILD was 16.2%(18/111 cases). There were significant differences between the SLE-ILD group and the SLE-non-ILD group in the course of disease [14.00 (12.00-24.25) months vs.1.00(1.00-2.00) months], the incidence of serositis [55.6%(10/18 cases) vs.8.6%(8/93 cases)], post-activity shortness of breath [83.3%(15/18 cases) vs.25.8%(24/93 cases)], nervous system damage [27.8%(5/18 cases) vs.6.5%(6/93 cases)], cardiovascular system damage [38.9%(7/18 cases) vs.9.7%(9/93 cases)], the occu-rrence of increased erythrocyte sedimentation rate [66.7%(12/18 cases) vs.31.2%(29/93 cases)], the decreased C 3[88.9%(16/18 cases) vs.62.4%(58/93 cases)], positive anti neutrophil cytoplasmic antibody (ANCA) [88.9%(16/18 cases) vs.18.3%(17/93 cases)], positive anti-Sm antibody [61.1%(11/18 cases) vs.15.1%(14/93 cases)] and anti ribonucleoprotein antibody (anti RNP antibody)[66.7%(12/18 cases) vs.16.1%(15/93 cases)](all P<0.05). Logistic regression analysis demonstrated that serositis( OR=30.535, 95% CI: 2.167-430.336, P=0.011), shortness of breath after exercise( OR=55.115, 95% CI: 1.117-2 579.852, P=0.041), positive ANCA( OR=65.090, 95% CI: 4.488-944.071, P=0.002) and positive anti-RNP antibody( OR=10.007, 95% CI: 1.362-73.500, P=0.024) were risk factors for SLE-ILD. Conclusions:The longer the course of SLE, the higher the incidence of ILD; serositis, shortness of breath after exercise, positive ANCA and positive anti RNP antibody may be risk factors for SLE-ILD.

Objective::Fish oil (FO) contains omega-3 that inhibits inflammation and blood lipid metabolism, giving it a protective cardiovascular effect. Due to dietary habits, a majority of large-scale clinical trials examining FO and cardiovascular health have been conducted in the Caucasian populations. However, the effects of FO on cardiovascular inflammation indicators and blood lipid metabolism in the Chinese population remain unclear. This study aimed to perform a meta-analysis to elucidate the impact of FO on cardiovascular health in the Chinese population.Methods::Web searches were utilized to locate records of clinical trials related to cardiovascular health and consumption of FO capsules or fish containing omega-3 in several databases, including PubMed, Medline, Embase, Cochrane Library, CNKI, and ClinicalTrial.gov, etc. We obtained lipid metabolism and related proinflammatory markers as the study outcome. We used Review Manager 5.4 and Stata 16 for the statistical analysis. If the I2 ≥ 30%, a random effects model was used, and if the I2 < 30%, a fixed effects model was used. Results::Twenty eligible trials were shortlisted from >1000 records. The meta-analysis revealed that supplementation with eicosapentaenoic acid and docosahexaenoic acid reduced systolic blood pressure by 1.88 mmHg (95% CI: -4.97 to -1.20, P = 0.23), diastolic blood pressure by 0.86 mmHg (95% CI: -1.79 to 0.06, P = 0.07), fasting blood glucose by 0.05 mmol/L (95% CI: -0.16 to 0.06, P = 0.40), and low-density lipoprotein-cholesterol by 0.12 mmol/L (95% CI: -0.23 to -0.01, P = 0.04), when compared to placebo. However, these supplements increased high-density lipoprotein-cholesterol by 0.03 mmol/L (95% CI: 0.01 to 0.05, P < 0.001), when compared to placebo. Dose subgroup analyses examining total cholesterol found that the low-dose group (mean difference = -0.44, 95% CI: -0.55 to -0.34, P < 0.001) demonstrated the best results. Further, results from dose subgroup analyses showed that the all-dose group demonstrated a decrease in tumor necrosis factor (TNF-α) levels among the study subjects, when compared to other groups. Conclusions::Consumption of FO containing omega-3 fatty acids in the Chinese population can improve lipid metabolism and reduce levels of proinflammatory markers. Therefore, it is necessary to vigorously promote the benefits of consuming FO to prevent cardiovascular diseases throughout China.

Objective::Pressure overload-induced myocardial apoptosis is a critical pathologically initiated process leading to heart failure (HF). Growth differentiation factor 15 (GDF15) dramatically increases during cardiac hypertrophy and dysfunction, but its functions and mechanisms are barely known. This study aims to elucidate the role and mechanism of GDF15 in HF.Methods::Between January 2017 and August 2018, 57 patients diagnosed with chronic HF (aged >18 years, with left ventricular ejection fraction (LVEF) ≤35%) and 57 non-HF patients (aged >18 years, LVEF >35%) were prospectively enrolled in this study based on the balance of the baseline characteristics. Other acute or chronic diseases and pregnant/lactating women were excluded. The serum concentrations of GDF15 were detected. Isoproterenol (ISO)-induced HF mouse model was established by pumping with ISO (30 mg/(kg·day)) for 4 weeks, and the GDF15 expression in serum and heart tissue was evaluated in vivo. Primary cardiomyocytes were cultured and treated with ISO to induce cardiomyocytes damage. The apoptosis of cardiomyocytes and the effect of GDF15 on ISO-induced cardiomyocytes injury was evaluated in vitro.Results::After adjusting the baseline characteristic, serum levels of GDF15 were significantly higher in HF subjects than in non-HF patients. Similarly, in the ISO-induced HF mouse model, the significant increase in GDF15 was associated with the process of HF in vivo. Moreover, the elevation of GDF15 occurred prior to heart remodeling in the ISO-induced HF mouse model. Furthermore, using primary cardiomyocytes, we demonstrated that the GDF15 was remarkably enhanced in serum from pathological HF patients and cardiac tissue from the ISO-induced mouse model. Reducing GDF15 exaggerated the ISO-induced cell apoptosis by blocking mitochondrial fusion and increasing oxidative stress. In contrast, the silence of GDF15 aggravated the ISO-induced cardiomyocytes damage. Conclusions::GDF15 acts as a protective factor against cardiomyocyte apoptosis by improving mitochondria fusion during HF. These findings indicate that GDF15 may be a potential therapeutic target for HF.