National Center for Clinical Laboratories

Pulmonary alveolar proteinosis (PAP) with concurrent anti-neutrophil cytoplasmic antibody (ANCA) positivity represents an exceptionally rare clinical phenomenon, the pathogenesis and management implications of which remain poorly understood. A 49-year-old woman was referred to our institution for evaluation of progressive respiratory symptoms. Two months prior to admission, she developed an intermittent cough productive of whitish sputum, followed by exertional dyspnea limiting ambulation to 400–500 m on level ground. Initial investigations revealed hypoxemic respiratory failure (PaO₂/FiO₂ 277 mmHg) and the characteristic “crazy-paving” pattern on chest computed tomography. Bronchoalveolar lavage yielded milky-white fluid with periodic acid-Schiff (PAS)-positive material, confirming the diagnosis of PAP. Notably, immunological evaluation demonstrated positive myeloperoxidase (MPO)-ANCA (20.03 RU/mL) (reference < 5 RU/mL), with perinuclear ANCA (p-ANCA) positive at a titer of 1:10 by indirect immunofluorescence, and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies, establishing a rare coexistence of autoimmune PAP with ANCA positivity. A comprehensive vasculitis workup—including serial urinalysis with microscopy, and otorhinolaryngological evaluation—revealed no evidence of subclinical vasculitis. The patient underwent successful bilateral whole lung lavage without the need for immunosuppressive therapy. At 3-month follow-up, p-ANCA remained positive (1:10) with MPO-ANCA at 14.15 RU/mL (reference < 5 RU/mL), while urinalysis and renal function remained within normal limits. At 12-month follow-up, the patient reported no dyspnea during daily activities and maintained oxygen saturation above 95% without supplemental oxygen. This case illustrates the rare association between autoimmune PAP and ANCA positivity, underscoring the importance of comprehensive immunological evaluation and individualized therapeutic approaches. Long-term surveillance is imperative, as vasculitic manifestations may emerge years after the initial PAP diagnosis.

Genomic loci and genome‐independent DNA exhibit heterogeneous dynamics related to physiological function. Live‐cell imaging of non‐repetitive sequences is essential but limited by low signal‐to‐noise ratio (SNR), restricting accurate identification and dynamic tracking. Here, the development of a BRIGHT (bivalent near‐infrared nanobody‐mediated cascade illumination of genomic loci for high‐SNR tracking) system for non‐repetitive sequence live imaging is reported. BRIGHT employs dCas9‐n×ALFA to target genomic loci and realizes high SNR by triggering cascade‐dependent illumination via bivalent binding and antigen‐dependent illumination of a bivalent near‐infrared fluorescent nanobody targeting ALFA tags (Bi‐NIR‐FbALFA). BRIGHT achieves ≈6.26‐fold and ≈6.76‐fold higher SNR than SunTag and PP7‐PCP in telomere labeling, and enables non‐repetitive DNA imaging with SNR up to 284.84. Furthermore, BRIGHT tracks chromatin dynamics comparably to previous tools, links dynamics and nuclear positioning to transcriptional activity, and detects the distribution and dynamic heterogeneity of extrachromosomal circular DNA (eccDNA). Overall, BRIGHT dramatically improves the SNR of non‐repetitive sequence imaging and offers an innovative tool for studying genomic dynamics and gene regulation.

[This corrects the article DOI: 10.1016/j.heliyon.2023.e14980.].

Heart failure with preserved ejection fraction (HFpEF) is a widespread public health issue worldwide. Despite recent advances in pharmacologic treatments and the introduction of new diagnostic approaches, HFpEF remains underdiagnosed and under-recognized in clinical practice. Traditional Chinese medicine (TCM) may offer a potentially effective treatment for HFpEF. Nevertheless, few clinical trials employ rigorous research methodologies to evaluate the efficacy and safety of TCM in treating HFpEF. Consequently, we propose to assess the hypothesis that patients with HFpEF may benefit from Fuzheng Yangxin Granule (FZYX) and evaluate its safety in a rigorously designed clinical trial. This multicenter, double-blind, randomized controlled trial will be conducted across seven tertiary hospitals in China. We will enroll 150 participants aged 18-80 years with confirmed HFpEF (Qi-Yin deficiency and blood stasis syndrome) meeting inclusion criteria. Participants will be randomly assigned (1:1) to the FZYX group or the placebo group, ​with both groups receiving standardized Western medical therapy according to the National Heart Failure Guideline 2023. The 12-week intervention phase will be followed by 40-week safety follow-up. The primary outcome will be maximal peak oxygen uptake (peak VO2). Secondary outcomes will include composite endpoint events, all-cause mortality, 6-minute walking distance (6MWD), New York Heart Association (NYHA) functional class, serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiographic variables, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, TCM syndrome scores, and the FRAIL scale. The objective of this study is to evaluate the efficacy and safety of FZYX in treating HFpEF (Qi-Yin deficiency and blood stasis syndrome), thereby providing a high-quality, reliable evidence-based foundation for clinical practice. China Clinical Trial Registry (ChiCTR2400087293), Registered on July 24, 2024.

Hematological parameters are among the most accessible and routinely performed clinical tests. Recent studies have gradually revealed their potential for risk prediction. This study aimed to assess the association between hematological parameters and major adverse cardiovascular events (MACEs) in patients with coronary artery disease. This prospective study included 2,970 Chinese participants who underwent coronary angiography, with hematological and biochemical indicators measured at baseline. MACEs, comprising myocardial infarction, stroke, revascularization, and all-cause mortality, were recorded during follow-up. Univariate and multivariate analyses were conducted to evaluate the relationship between the hematological parameters and MACEs. Over a median follow-up period of 79 months, 474 MACEs were documented. Kaplan-Meier analysis indicated that the participants with lower levels of RBC, PLT, PCT, LYMPH% and BASO%, as well as higher RDW-CV, RDW-SD, MONO% and NEUT%, exhibited reduced survival probability. Multivariate Cox regression analysis identified elevated RDW-CV as a significant risk factor for MACE (T3 HR, 1.292; 95% CI, 1.013-1.647; P=0.039), while lower BASO% demonstrated a protective effect (T3 HR, 0.750, 95 % CI: 0.591-0.953; P=0.018). LYMPH% also showed a significant association with MACEs. Additionally, nonlinear correlations were observed between PLT and PCT and MACEs. In conclusion, RDW-CV, BASO%, PLT, PCT and LYMPH% were closely associated with MACEs and may serve as potential predictors for cardiovascular risk in patients with coronary artery disease.

Although existing cytopathological examination is considered essential for the diagnosis of malignant serous effusions, its accuracy is pretty low. Tumor specific protein 70 (SP70), which is highly expressed on human tumor cell membrane, was identified in our previous study. This study aimed to explore whether SP70 targeted tumor cell isolation technology with immunomagnetic beads can improve the accuracy of cytopathological examination. Cytopathological analysis with SP70 targeted tumor cell isolation technology was used in this study. In total, 255 cases were enrolled. Serous effusions were analyzed by both existing cytopathological examination and the new cytopathological analysis concurrently. The sensitivities of existing cytopathological examination and the new cytopathological analysis were 51.26 % and 85.43 %, respectively, while the specificities were 100 % for both. This new cytopathological analysis demonstrated a higher interobserver agreement with malignant diagnosis than the existing cytopathological examination (kappa coefficient: 0.720 vs. 0.316, p<0.001). In addition, it achieved superior diagnostic efficacy for malignancy differentiation compared to existing cytopathological examination (AUC: 0.927 vs. 0.756, p<0.001). The follow-up results showed that 74 malignant cases with final clinical diagnosis were positive only with the new cytopathological analysis. Among these cases, there were 58 negative and 16 atypical by the existing cytopathological examination. In these malignant cases, 74.3 % (55/74) had been confirmed to have serosa metastasis based on radiographic evidence, and 73.7 % (28/38) harbored tumor hotspot mutations. As illustrated in this work, cytopathological analysis with SP70 targeted tumor cell isolation technology can improve the accuracy of existing cytopathological examination prominently.