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.

Pathogenic microorganisms are direct causative agents of zoonotic infectious diseases,po-sing severe threats to the livestock industry by inducing massive animal mortality,economic losses in livestock products,and significant risks to human health.The CRISPR/Cas system has been widely adopted in nucleic acid detection of pathogenic microorganisms due to its unique trans-cleavage activity.By leveraging the superior optical properties of nanomaterials,researchers have integrated them with CRISPR/Cas systems to develop numerous visual biosensors,which not only significantly enhance signal output but also substantially reduce detection time and cost.This re-view focuses on five nanomaterials-graphene oxide(GO),gold nanoparticles(AuNPs),MoS2 nanosheets,metal-organic frameworks(MOFs),and quantum dots(QDs)—that have been exten-sively integrated with CRISPR/Cas systems in recent years.We systematically summarize their distinct physical characteristics and specific applications in CRISPR/Cas-based pathogen detection,followed by a concise comparison of the advantages and limitations of different methodologies.Fi-nally,we discuss the prospects for nanomaterials in CRISPR/Cas detection systems,aiming to pro-vide a valuable reference for advancing molecular diagnostics of pathogenic microorganisms.

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.

Pathogenic microorganisms are direct causative agents of zoonotic infectious diseases,po-sing severe threats to the livestock industry by inducing massive animal mortality,economic losses in livestock products,and significant risks to human health.The CRISPR/Cas system has been widely adopted in nucleic acid detection of pathogenic microorganisms due to its unique trans-cleavage activity.By leveraging the superior optical properties of nanomaterials,researchers have integrated them with CRISPR/Cas systems to develop numerous visual biosensors,which not only significantly enhance signal output but also substantially reduce detection time and cost.This re-view focuses on five nanomaterials-graphene oxide(GO),gold nanoparticles(AuNPs),MoS2 nanosheets,metal-organic frameworks(MOFs),and quantum dots(QDs)—that have been exten-sively integrated with CRISPR/Cas systems in recent years.We systematically summarize their distinct physical characteristics and specific applications in CRISPR/Cas-based pathogen detection,followed by a concise comparison of the advantages and limitations of different methodologies.Fi-nally,we discuss the prospects for nanomaterials in CRISPR/Cas detection systems,aiming to pro-vide a valuable reference for advancing molecular diagnostics of pathogenic microorganisms.

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.

Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer, its effectiveness in patients without BRCA mutations remains poorly investigated. This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context. Using real-world data from 11 high-volume tertiary care centers in China, a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer. The primary objective was 1-year progression-free survival rate. Safety was also evaluated. Fifty patients with a median age of 54 years were included, and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency (HRD). The 1-year PFS rate was 75.2% (95% CI, 63.4 to 89.2), and the median PFS was 21.0 months (95% CI, 13.8 to 28.2). All the patients received olaparib at a starting dose of 300 mg twice daily, and none experienced serious adverse events (AEs). Eight (16%) patients had dose adjustment, but none discontinued olaparib treatment due to AEs. We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.
Humans ; Female ; Phthalazines/adverse effects* ; Piperazines/administration & dosage* ; Middle Aged ; Ovarian Neoplasms/genetics* ; Retrospective Studies ; Adult ; Aged ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage* ; China ; Maintenance Chemotherapy ; BRCA2 Protein/genetics* ; Antineoplastic Agents/adverse effects* ; Progression-Free Survival ; BRCA1 Protein/genetics*

A case of secondary Burkitt lymphoma of prostate was reported. A 39-year-old patient was admitted to the hospital with no apparent cause for impaired urination with frequent/urgent urination. CT scan of the whole abdomen showed irregular soft tissue mass of the prostate, involving the bladder and rectum, and mild obstructive hydronephrosis of the renal pelvis and ureter. Biopsy of the prostatic mass was performed, and the pathological findings were consistent with Burkitt lymphoma. PET-CT examination showed multiple lesions and lymph node enlargement throughout the body, secondary prostate lymphoma was diagnosed. After diagnosis, the patient was treated with R-DA-EPOCH chemotherapy and followed up for 9 months. Prostate lymphoma is rare and needs to be combined with clinical manifestations and laboratory tests to determine whether it is primary or secondary, but also to distinguish from prostate diseases such as prostatitis and poorly differentiated prostate cancer.

Objective:To investigate the efficacy and safety of tirofiban versus argatroban in the treatment of acute ischemic stroke. Methods:This study was a retrospective cohort study. Sixty-eight patients with acute ischemic stroke who were continuously admitted to Department of Neurology of The Third People's Hospital of Hubei Province from August 2022 to September 2023 were divided into tirofiban group ( n = 33) and argatroban group ( n = 35) according to the treatment regimen. Both groups were treated according to their respective treatment protocols for 7 days. Clinical outcomes were assessed based on the modified Rankin Scale (mRS) scores. The excellent clinical outcome (mRS score 0-1 points), good clinical outcome (mRS score 0-2 points), symptomatic intracranial hemorrhage, and mortality rates were compared between the two groups at 90 days post-treatment. Results:In the tirofiban group, the proportion of excellent clinical outcomes was 30.3% (10/33), which was significantly lower than the 65.7% (23/35) in the argatroban group (χ2 = 8.53, P = 0.003). However, the difference in the proportion of good clinical outcomes between the two groups was not statistically significant [54.5% (18/33) vs. 74.3% (26/35), χ2 = 2.90, P = 0.089]. There were no statistically significant differences between the two groups regarding symptomatic intracranial hemorrhage and mortality rates (both P > 0.05). Conclusion:For patients with acute ischemic stroke, the use of tirofiban or argatroban is effective and safe. Patients treated with argatroban are more likely to achieve excellent clinical outcomes; however, larger randomized controlled trials are needed for further confirmation.

Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.