2.1]undecane core skeleton, and also featured an undescribed oxygen bridge between C-6 and C-14 to construct an unprecedentedly caged tetracyclic system. Alterbrassicenes B-D showed moderate cytotoxic activity against certain human tumor cell lines with IC50 values in the range of 15.87-36.85 μM. Chemical modifications on the A ring of limonin (1) and deoxylimonin (2) afforded 28 structural characterized derivatives, which were firstly subjected to preliminary in vivo analgesic and anti-inflammatory screen by mice model. The most promising candidate, deoxylimonin analog II-B-2 (70 mg/kg) with 3,4-dimethoxyphenylethyl moiety substitued δ-lactam in the A ring, exhibited better analgesic activity than aspirin (200 mg/kg) and stronger anti-inflammatory efficacy than naproxen (150 mg/kg). Further in vivo evaluation confirmed its advantage over limonin and showed dose-response dependent manner, and follow-up research suggested that the anti-inflammatory effect of compound II-B-2 may be attributed to the downregulation of cyclooxygenase 2 expression and the suppression of prostaglandin E2 formation.  https://www.selleckchem.com/products/mz-1.html  BACKGROUND We evaluated programmed death ligand 1 (PD-L1) expression and efficacy of PD-1/PD-L1 inhibitors in patients with pulmonary pleomorphic carcinoma (PC). METHODS We created two cohorts of patients diagnosed with pulmonary PC from 2016 to 2019, PD-L1 expression and programmed death 1 (PD-1)/PD-L1 inhibitor efficacy cohorts. The PD-L1 expression cohort included all patients evaluated for PD-L1 expression, irrespective of PD-1/PD-L1 inhibitor therapy. High PD-L1 expression was defined as ≥50% positive tumour cells (TC) for 22C3, ≥25% for SP263 or ≥10%/5% TC/immune cell (IC) for SP142. The PD-1/PD-L1 efficacy cohort included patients treated with PD-1/PD-L1 inhibitors, irrespective of PD-L1 tests. RESULTS One hundred twenty-five of 175 patients diagnosed with pulmonary PCs were included in the PD-L1 expression cohort. Among them, 112 patients (89.6%) had PD-L1-positive (≥1%) tumours and 100 (80.0%) had tumours with high PD-L1 expression. A total of 49 patients were included in the efficacy cohort 40 received pembrolizumab, 7 nivolumab and 2 atezolizumab. The objective response rate was 49.0%, with a median progression-free survival (PFS) of 7.2 months and a median overall survival of 22.2 months. In the efficacy cohort, high PD-L1 expression (n = 41) was associated with longer PFS (median 7.2 versus 1.5 months, hazard ratio [HR] 0.53 [0.22-1.29], p = 0.16) and overall survival (median 22.2 versus 3.5, HR 0.21 [0.08-0.57], p = 0.001) than low/negative/unknown PD-L1 expression (n = 8). CONCLUSION PD-1/PD-L1 inhibitors show outstanding efficacy for pulmonary PCs, and this is possibly attributable to high PD-L1 expression in these tumours. Perinatal deaths are devastating for families and staff involved. Failure to examine perinatal deaths for substandard care prevents learning and may lead to recurrence of events, as well as prolonged morbidity in bereaved families and hospital staff. Perinatal mortality reviews can identify factors contributing to suboptimal care. An integrative literature review was carried out to study the different types of perinatal mortality reviews currently being done internationally, establishing a comparison and examining promising new developments. We start by outlining issues with the classification of perinatal deaths and the different types of perinatal mortality reviews carried out in high-income countries. We reflect on the challenges that are encountered in the current processes and we then comment on how these may be overcome. Current literature shows that differences in classifications of perinatal deaths continue to impede important international comparisons. National perinatal mortality audits can provide cycle is completed with implementation and re-evaluation of recommended changes in maternity services. BACKGROUND Immune checkpoint inhibitors (ICIs) have been identified as validated medications in non-small cell lung cancer (NSCLC). However, they are often associated with immune-related adverse events (irAEs) including liver dysfunction. Therefore, we conducted a systematic review of the literature and performed a meta-analysis to ascertain overall incidence and risk of immune mediated liver dysfunction in NSCLC patients. METHODS PubMed, the Cochrane Library, Embase and ClinicalTrials.gov (http//clinicaltrials.gov/) were searched from inception to December 2019. Studies regarding all grade (1-5), high grade (3-5) hepatitis and ALT or AST elevation were included. RESULTS A total of 11 clinical trials including 7086 patients were selected for further assessment. The overall incidence of ALT elevation, AST elevation and hepatitis for the application of ICIs was 6.18%, 4.99% and 1.09%, respectively. Compared with chemotherapy group, treatment with ICIs had a significantly higher risk of all grade (RR 7.27, p = 0.001) and high grade (RR 6.70, p = 0.003) hepatitis. When ICIs combined with chemotherapy, the relative risk of all grade hepatitis was higher than monotherapy group (RR 7.89, p = 0.044 vs RR 6.94, p = 0.008). CONCLUSION The application of ICIs could result in a higher incidence and relative risk of all grade immune-induced liver dysfunction. Moreover, immunotherapy combined with chemotherapy may also increase relative risk of all grade hepatic AEs when compared with monotherapy. Prompt recognition and proper administration is required for clinicians to prevent potentially hepatic deterioration. BACKGROUND Asthma is characterized by chronic airway inflammation, and inhaled corticosteroids (ICSs) have been recommended as first-line treatment. However, response to ICS treatment is various, and the prediction of response to ICS is still difficult, especially in individuals with newly diagnosed asthma. OBJECTIVE We aimed to assess the clinical factors and biomarkers associated with response to ICS in newly diagnosed asthma. METHODS A total of 150 patients with newly diagnosed asthma in the allergy clinic of a single tertiary hospital in Korea from January 2014 to January 2019 were included in this study, and they were all naïve to ICS. All patients initially received moderate-dose ICS, and were treated for more than 1 year. We compared the clinical characteristics and parameters between patients with and without acute exacerbation (AE) during the study period. RESULTS In this study, 99 patients had no AE (stable asthma group), and 51 patients presented with more than one AE (unstable asthma group). The blood eosinophil count (635.