Factors associated with rapid progression in fibrotic interstitial lung disease.

Background: Early identification of fibrotic interstitial lung disease (F-ILD) patients with high risk of progression will help initiate early therapeutic intervention and potential improvement of outcomes. This study was designed to assess the predictors of progression in patients with F-ILD. Methods: Patients with F-ILD in Shanghai Pulmonary Hospital between January 1, 2019 and July 31, 2021 were retrospectively analyzed. The patients enrolled were divided into progressive group and non-progressive group according to the specified criteria. Baseline characteristics were collected and a multivariate regression was conducted to identify independent predictors of progression. Results: Of the 177 F-ILD cases, 87 were enrolled in the progressive group and 90 were in the non-progressive group. The cohort included 11 types of F-ILD, primarily were connective tissue disease-associated interstitial lung disease (CTD-ILD) (43, 24.3 %), idiopathic pulmonary fibrosis (IPF) (39, 22.0 %), interstitial pneumonia with autoimmune features (IPAF) (32, 18.1 %), and unclassifiable (23, 13.0 %). The highest proportion of progression was seen in nonspecific interstitial pneumonia (NSIP) subgroup (66.7 %), followed by IPF (59.0 %) and HP (57.1 %). After adjusting for gender and age, a course of disease longer than 9.5 months (OR: 2.633; 95 % CI: 1.190-5.826, P = 0.017), lymphocyte in peripheral blood more than 2.24 (109/L) (OR: 2.670; 95 % CI: 1.095-6.510, P = 0.031), and emphysema in high-resolution computed tomography (HRCT) (OR: 2.387; 95 % CI: 1.017-5.640, P = 0.046) were independent predictors of progression in F-ILD patients. Conclusions: This study suggested that in patients with F-ILD, long course of disease, elevated blood lymphocyte and emphysema on HRCT were independent predictors of progression, which may suggest utility in early therapeutic intervention.

Pulmonary Function in Pulmonary Sarcoidosis.

The pulmonary function test (PFT) has been widely used in sarcoidosis. It may vary due to the severity, extent, and the presence of complications of the disease. Although the PFT of most sarcoidosis patients is normal, there are still 10-30% of cases who may experience a decrease in the PFT, with a progressive involvement of lungs. Restrictive ventilatory impairment due to parenchymal involvement has been commonly reported, and an obstructive pattern can also be present related to airway involvement. The PFT may influence treatment decisions. A diffusing capacity for carbon monoxide (DLCO) < 60% as well as a forced vital capacity (FVC) < 70% portends clinically significant pulmonary sarcoidosis pathology and warrants treatment. During follow-up, a 5% decline in FVC from baseline or a 10% decline in DLCO has been considered significant and reflects the disease progression. FVC has been recommended as the favored objective endpoint for monitoring the response to therapy, and an improvement in predicted FVC percentage of more than 5% is considered effective.

Prognosis of early-stage lung adenocarcinoma in young patients.

Lung adenocarcinoma (LUAD) is a familiar lung cancer with a poor prognosis. This study was meant to determine whether there are differences in survival between younger and older patients with early-stage LUAD because of the rise in the incidence of LUAD in young individuals over the previous few decades. We analysed the clinical, therapeutic and prognostic features of a cohort (2012-2013) of 831 consecutive patients with stage I/II LUAD who underwent curative surgical resection at Shanghai Pulmonary Hospital. Propensity score matching (PSM) was performed for age, sex, tumour size, tumour stage and therapy in a 2:1 ratio between the two groups without taking gender, illness stage at operation or decisive treatment into account. Following PSM analysis to create a 2:1 match for comparison, the final survival study included 163 patients with early-stage LUAD <50 years and 326 patients ≥50 years. Surprisingly, younger patients were overwhelmingly female (65.6%) and never smokers (85.9%). There were no statistical differences between the two groups in terms of the overall survival rate (P = 0.067) or time to advancement (P = 0.76). In conclusion, no significant differences stood out between older and younger patients with stage I/II LUAD regarding overall and disease-free survival rates. Younger patients with early-stage LUAD were more likely to be female and never smokers, which suggests that risk factors other than active smoking may be responsible for lung carcinogenesis in these patients.

Chemical conversion of human lung fibroblasts into neuronal cells.

It has been previously reported that human embryonic fibroblasts and mouse embryonic fibroblasts can be converted into neuronal cells using chemical agents, along with forced expression specific transcriptional factors. However, the materials required for reprogramming in these approaches presents major technical difficulties and safety concerns. The current study investigated whether a cocktail of small molecules can convert human lung fibroblast cells into neurons. The small molecules valproic acid, CHIR99021, DMH1, Repsox, forskolin, Y­27632 and SP600125 (VCHRFYS) were used to induce MRC­5 cells into neuronal cells in vitro. Neuronal markers were analyzed by immunofluorescence staining. The gene profiles were analyzed by reverse transcription­quantitative polymerase chain reaction. MRC­5 is a human lung fibroblast cell line derived from normal lung tissue of a 14­week­old male fetus. The results of the current study demonstrated that MRC­5 fibroblasts can be directly converted into neuronal cells using a cocktail of seven small molecules (VCHRFYS), with a yield of ~90% Tuj1­positive cells after 7 days of induction. Following a further maturation period, these chemically-induced neurons possessed neuronal morphology and expressed multiple neuron­specific genes. In conclusion, a cocktail of small molecules that can convert fibroblasts MRC­5 cells into functional neurons without the exogenous genetic factors was identified, which has the potential to be useful in neurological disease therapy.

Antigen detection based on background fluorescence quenching immunochromatographic assay.

Gold immunochromatographic assay (GICA) has been around for quite a while, but it is qualitative in the vast majority of applications. A fast, simple and quantitative GICA is in call for better medicine. In the current study, we have established a novel, quantitative GICA based on fluorescence quenching and nitrocellulose membrane background signals, called background fluorescence quenching immunochromatographic assay (bFQICA). Using model analyte alpha-fetoprotein (AFP), the present study assessed the performance of bFQICA in numerous assay aspects. With serial dilutions of the international AFP standard, standard curves for the calculation of AFP concentration were successfully established. At 10 and 100ngmL(-1) of the international AFP standard, the assay variability was defined with a coefficient of variance at 10.4% and 15.2%, respectively. For samples with extended range of AFP levels, bFQICA was able to detect AFP at as low as 1ngmL(-1). Fluorescence in bFQICA strips stayed constant over months. A good correlation between the results from bFQICA and from a well-established Roche electrochemiluminescence immunoassay was observed in 27 serum samples (r=0.98, p<0.001). In conclusion, our study has demonstrated distinctive features of bFQICA over conventional GICA, including utilization of a unique fluorescence ratio between nitrocellulose membrane background and specific signals (F1/F2) to ensure accurate measurements, combined qualitative and quantitative capabilities, and exceptionally high sensitivity for detection of very low levels of antigens. All of these features could make bFQICA attractive as a model for antigen-antibody complex based GICA, and could promote bFQICA to a broad range of applications for investigation of a variety of diseases.