Daily Respiratory Research Analysis

Early screening, diagnosis, and treatment of lung cancer are pivotal in clinical practice since the tumor stage remains the most dominant factor that affects patient survival. Previous initiatives have tried to develop new tools for decision-making of lung cancer. In this study, we proposed the China Protocol, a complete workflow of lung cancer tailored to the Chinese population, which is implemented by steps including early screening by evaluation of risk factors and three-dimensional thin-layer image reconstruction technique for low-dose computed tomography (Tre-LDCT), accurate diagnosis via artificial intelligence (AI) and novel biomarkers, and individualized treatment through non-invasive molecule visualization strategies. The application of this protocol has improved the early diagnosis and 5-year survival rates of lung cancer in China. The proportion of early-stage (stage I) lung cancer has increased from 46.3% to 65.6%, along with a 5-year survival rate of 90.4%. Moreover, especially for stage IA1 lung cancer, the diagnosis rate has improved from 16% to 27.9%; meanwhile, the 5-year survival rate of this group achieved 97.5%. Thus, here we defined stage IA1 lung cancer, which cohort benefits significantly from early diagnosis and treatment, as the "ultra-early stage lung cancer", aiming to provide an intuitive description for more precise management and survival improvement. In the future, we will promote our findings to multicenter remote areas through medical alliances and mobile health services with the desire to move forward the diagnosis and treatment of lung cancer.

BACKGROUND: Wildfire activity in the United States has increased substantially in recent decades. Smoke fine particulate matter (PM 2.5 ), a primary wildfire emission, can remain in the air for months after a wildfire begins, yet large-scale evidence of its health effects remains limited. METHODS: We obtained hospitalization records for the residents of 15 states between 2006 and 2016 from the State Inpatient Databases. We used existing daily smoke PM 2.5 estimations at 10-km 2 grid cells across the contiguous United States and aggregated them to ZIP codes to match the spatial resolution of hospitalization records. We extended the traditional case-crossover design, a self-controlled design originally developed for studying acute effects, to examine associations between 3-month average exposure to smoke PM 2.5 and hospitalization risks for a comprehensive range of cardiovascular (ischemic heart disease, cerebrovascular disease, heart failure, arrhythmia, hypertension, and other cardiovascular diseases) and respiratory diseases (acute respiratory infections, pneumonia, chronic obstructive pulmonary disease, asthma, and other respiratory diseases). RESULTS: We found that 3-month exposure to smoke PM 2.5 was associated or marginally associated with increased hospitalization risks for most cardiorespiratory diseases. Hypertension showed the greatest susceptibility, with the highest hospitalization risk associated with 0.1 µg/m 3 increase in 3-month smoke PM 2.5 exposure (relative risk: 1.0051; 95% confidence interval = 1.0035, 1.0067). Results for single-month lagged exposures suggested that estimated effects persisted up to 3 months after exposure. Subgroup analyses estimated larger effects in neighborhoods with higher deprivation level or more vegetation, as well as among ever-smokers. CONCLUSIONS: Our findings provided unique insights into medium-term cardiorespiratory effects of smoke PM 2.5 , which can persist for months, even after a wildfire has ended.

UNLABELLED: Respiratory syncytial virus (RSV) entry into host cells is facilitated by viral fusion, wherein the metastable RSV fusion (F) protein undergoes a conformational change from a prefusion state to a highly stable postfusion structure. The prefusion F elicits a more robust human antibody response than its postfusion F and is a primary target for RSV vaccine development. However, the inherent instability of the prefusion F trimer and its low protein expression level in host cells are a significant challenge for developing a high-potency RSV vaccine. Here, we report that the introduction of four hydrophobic residue substitutions in the RSV F protein resulted in a highly stable prefusion F trimer (pre-F-IFLP). This engineered variant exhibits enhanced expression and stability compared to DS-Cav1, with improved thermal stability, increased resistance to acid and base, and extended storage life. Furthermore, pre-F-IFLP induced neutralizing antibody responses 72-fold higher than those elicited by DS-Cav1 following a second booster immunization and fully protected mice against RSV infection. IMPORTANCE: In this study, we demonstrate that introducing four hydrophobic residue substitutions into the RSV F protein leads to the generation of a highly stable prefusion F trimer (pre-F-IFLP) with improved expression levels in cultured cells and superior stability compared to DS-Cav1, the first-generation prefusion F-stabilized RSV vaccine. Furthermore, pre-F-IFLP induced significantly higher neutralizing antibody responses than DS-Cav1 following both the first and second booster immunizations and conferred complete protection against RSV infection in a mouse model. These findings present an alternative approach for stabilizing the trimeric prefusion F protein, enhancing its expression, and significantly improving its protective efficacy for the prevention of RSV infection