YuPingFeng (YPF) upregulates caveolin-1 (CAV1) to alleviate pulmonary fibrosis through the TGF-ß1/Smad2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) is considered a valuable asset in China's medical tradition. YPF is a classic prescription that has been derived from the "Jiu Yuan Fang" formula and consists of three herbs: Huangqi (Astragalus membranaceus Bunge), Baizhu (Atractylodes rubra Dekker), and Fangfeng (Saposhnikovia divaricata (Turcz.) Schischk). This prescription is widely acclaimed for its exceptional pharmacological properties, including potent antioxidant effects, hormone regulation, and immune modulation effects. AIM OF THE STUDY: Previous research provides evidence suggesting that YPF may have therapeutic effects on pulmonary fibrosis. Further exploration is essential to confirm its effectiveness and elucidate the fundamental processes. MATERIALS AND METHODS: First, the active components and target genes of YPF were extracted from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Next, the GSE53845 dataset, which contains information on pulmonary fibrosis, was downloaded from the GEO database. Network informatics methods was then be utilized to identify target genes associated with pulmonary fibrosis. A YPF-based network of protein-protein interactions was constructed to pinpoint possible target genes for pulmonary fibrosis treatment. Additionally, an in vitro model of pulmonary fibrosis induced by bleomycin (BLM) was established to further investigate and validate the possible mechanisms underlying the effectiveness of YPF. RESULTS: In this study, a total of 24 active ingredients of YPF, along with 178 target genes associated with the treatment, were identified. Additionally, 615 target genes related to pulmonary fibrosis were identified. Functional enrichment analysis revealed that 18 candidate genes (CGs) exhibited significant responses to tumor necrosis factor, NF-kB survival signaling, and positive regulation of apoptosis processes. Among these CGs, CAV1, VCAM1, and TP63 were identified as key target genes. Furthermore, cell experiments confirmed that the expression of CAV1 protein and RNA expression was increased in pulmonary fibrosis, but significantly decreased after treatment with YPF. Additionally, the expression of pSmad2, α-SMA, TGF-ß1, and TNF-α was also decreased following YPF treatment. CONCLUSIONS: Network pharmacology analysis revealed that YPF exhibits significant potential as a therapeutic intervention for pulmonary fibrosis by targeting various compounds and pathways. This study emphasizes that the efficacy of YPF in treating pulmonary fibrosis may be attributed to its ability to up-regulate CAV1 expression and inhibiting pulmonary fibrosis via modulation of the TGF-ß1/Smad2 signaling pathway. These findings underscore the promising role of YPF and its ability to potentially alleviate pulmonary fibrosis.

Short-acting beta-2 agonist prescription patterns and clinical outcomes in Chinese patients with asthma: an observational study in mainland China for the SABINA programme.

OBJECTIVES: The SABINA CHINA study aimed to determine prescription data for asthma medication with a focus on SABA and ICS in a representative population of patients with asthma in China. METHODS: SABINA China was a multicentre, observational, cross-sectional study with data collected retrospectively from a convenience sample of 25 tertiary centres across China. Patients (age ⩾ 12 years) with ⩾3 consultations/year were enrolled. Data were collected on clinical characteristics, asthma severity, and symptom control (as per GINA 2017), treatment and history of severe exacerbations over the past year. SABA over-prescription was defined as ⩾3 SABA canisters/year. Descriptive statistics are presented. RESULTS: Between March and August 2020, 498 patients were included in the outcome analysis. Mean (SD) age was 48.7 (15.0) years, 57.9% were female and 91% had moderate-to-severe asthma (n = 453). Overall, 12.5% (n = 62) and 26.4% (n = 131) of patients had uncontrolled and partly controlled asthma, respectively. SABA add-on was prescribed to 20.3% (n = 101) of patients; one patient with moderate-to-severe asthma was prescribed SABA-alone. SABA over-prescription in the overall population was 4.0% (n = 20; all with moderate-to-severe asthma) and 19.8% (20/101) among those prescribed SABA add-on. In the mild asthma group, 50% (n = 22) were prescribed ICS/LABA and 43.2% (n = 19) were prescribed LTRA. Among those with moderate-to-severe asthma, 97.4% (n = 441) were prescribed ICS/LABA and 55.0% (n = 249) were prescribed LTRA. Approximately 30% of patients (n = 149) experienced ⩾1% and 6.6% (n = 33) ⩾3 severe exacerbations in the preceding year; mean annual number of severe exacerbation/patient was 0.6 (1.2). Among those prescribed SABA add-on, ICS/LABA and LTRA (non-mutually exclusive groups due to overlapping prescriptions), 54.5%, 29.9%, and 35.3% had ⩾1 severe exacerbations, respectively. CONCLUSION: Among patients with predominantly moderate-to-severe asthma managed in tertiary care and were prescribed SABA, 1 in 5 received ⩾3 canisters/year. Fewer patients who received ICS/LABA prescriptions experienced annual exacerbations than those prescribed SABA add-on.

A Retrospective and Multicenter Study on COVID-19 in Inner Mongolia: Evaluating the Influence of Sampling Locations on Nucleic Acid Test and the Dynamics of Clinical and Prognostic Indexes.

COVID-19 is spreading widely, and the pandemic is seriously threatening public health throughout the world. A comprehensive study on the optimal sampling types and timing for an efficient SARS-CoV-2 test has not been reported. We collected clinical information and the values of 55 biochemical indices for 237 COVID-19 patients, with 37 matched non-COVID-19 pneumonia patients and 131 healthy people in Inner Mongolia as control. In addition, the results of dynamic detection of SARS-CoV-2 using oropharynx swab, pharynx swab, and feces were collected from 197 COVID-19 patients. SARS-CoV-2 RNA positive in feces specimen was present in approximately one-third of COVID-19 patients. The positive detection rate of SARS-CoV-2 RNA in feces was significantly higher than both in the oropharynx and nasopharynx swab (P < 0.05) in the late period of the disease, which is not the case in the early period of the disease. There were statistically significant differences in the levels of blood LDH, CRP, platelet count, neutrophilic granulocyte count, white blood cell number, and lymphocyte count between COVID-19 and non-COVID-19 pneumonia patients. Finally, we developed and compared five machine-learning models to predict the prognosis of COVID-19 patients based on biochemical indices at disease onset and demographic characteristics. The best model achieved an area under the curve of 0.853 in the 10-fold cross-validation.

High-flow nasal cannula versus conventional oxygen therapy in acute COPD exacerbation with mild hypercapnia: a multicenter randomized controlled trial.

BACKGROUND: High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain. METHODS: This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90. RESULTS: Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0-13.0] vs. 8.0 [interquartile range, 7.0-11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613-$3782] vs. $2005 [interquartile range, $1439-$2968]). There were no significant differences in other secondary outcomes between groups. CONCLUSIONS: In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups. TRIAL REGISTRATION: NCT03003559 . Registered on December 28, 2016.

Clinical characteristics of patients with chronic obstructive pulmonary disease assessed using GOLD 2016 and GOLD 2018 classifications: a cross-sectional study in China.

BACKGROUND: In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) removed spirometry as a criterion for classifying GOLD risk groups (A-D, low-high risk). METHODS: In this cross-sectional observational study in China, we used the GOLD 2016 (spirometry included) and 2018 (spirometry eliminated) criteria for classifying GOLD risk groups to describe: the proportion of patients with chronic obstructive pulmonary disease (COPD) in each GOLD risk group; disease severity; demographics and comorbidities. Patients aged ≥40 years with a clinical COPD diagnosis for ≥1 year were included. During a single study visit, patients completed the COPD assessment test, modified Medical Research Council (mMRC) dyspnea scale assessment, and spirometry tests. Demographics, medical history, and treatment data were recorded. RESULTS: In total, 838 patients were included. Most patients were male (86.4%), ≥65 years old (58.6%), and current or former smokers (78.5%). By GOLD 2016, the highest proportion of patients were Group D (42.8%), followed by B (28.2%). By GOLD 2018, the highest proportion of patients were Group B (57.3%), followed by A (25.5%). A total of 296 patients (35.3%) were reclassified, either from Group C to Group A or from Group D to Group B. Overall, 36.2% of patients were receiving treatment concordant with GOLD 2016 recommendations; 34.1% were not receiving any inhaled medication. CONCLUSIONS: The distribution of COPD severity shifted from a high-risk category (by GOLD 2016) to a low-risk category (by GOLD 2018). The high proportion of patients not receiving maintenance medication reflects a high level of under-treatment of the disease.

Evaluating the diagnostic accuracy of a ctDNA methylation classifier for incidental lung nodules: protocol for a prospective, observational, and multicenter clinical trial of 10,560 cases.

BACKGROUND: Lung nodules are a diagnostic challenge. Current clinical management of lung nodule patients is inefficient and therefore causes patient misclassification, which increases healthcare expenses. However, a precise and robust lung nodule classifier to minimize discomfort for patients and healthcare costs is still lacking. The aim of the present protocol is to evaluate the effectiveness of using a liquid biopsy classifier to diagnose nodules compared to physician estimates and whether the classifier can reduce the number of unnecessary biopsies in benign cases. METHODS: A prospective cohort of 10,560 patients enrolled at 23 clinical centers in China with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by LDCT or CT will be included. After signed consent forms, the participants' pulmonary nodules will be assessed using three evaluation tools: (I) physician cancer probability estimates (II) validated lung nodule risk models, including Mayo Clinic and Veteran's Affairs models (III) ctDNA methylation classifier previously established. Each patient will undergo LDCT/CT follow-ups for 2 to 3 years and their information and one blood sample will be collected at baseline, 3, 6, 12, 24 and 36 months. The primary study outcomes will be the diagnostic accuracy of the methylation classifier in the cohort. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) will be used to compare the diagnostic value of each testing tool in differentiating benign and malignant pulmonary nodules. DISCUSSION: We are conducting an observational study to explore the accuracy of using a ctDNA methylation classifier for incidental lung nodules diagnosis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03651986.

Different expression about induced sputum cell sorting in the two main types of chronic obstructive pulmonary disease.

BACKGROUND: The difference in expression of sputum cells types between the two main types of chronic obstructive pulmonary disease (COPD) is largely unknown. This study aims to investigate the difference and then wants to depend on sputum cells sorting to direct the treatment of COPD. METHODS: A total of 218 patients with stable COPD (FEV1 < 80%) were selected. Stable COPD patients (n = 218) were classified as eosinophilic (A phenotype) or noneosinophilic (B phenotype); sometimes, the subjects were separated into cough group (C phenotype) and dyspnea group (D phenotype). Cross-sectional analysis was conducted comparing demographics and clinical characteristics. Receiver-operating characteristic curve was used to assess predictive ability of sputum eosinophils for D phenotype. RESULTS: The A phenotype showed a higher correlation with the patients complaining of presenting with dyspnea on exertion, the dyspnea group (D phenotype). The B phenotype showed a higher prevalence of those who cough and product sputum, this was cough group (C phenotype). Sputum eosinophil and macrophages counts were significantly higher in patients with dyspnea (n = 95) compared to those with cough (P < .05), and neutrophils were significantly lower in patients with dyspnea (n = 95) compared to those with cough (P < .05). Percentage sputum eosinophil count was predictive of dyspnea (D phenotype) COPD with area under curve (AUC) of 0.831 (95% confidence interval (CI) 0.77-0.89; P ≤ .001). Neutrophils were also predictive of dyspnea (D phenotype) COPD with AUC of 0.276 (95% CI 0.204-0.347; P ≤ .001). CONCLUSION: These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different sputum cell sorting.