ABSTRACT
Objective:Nivolumab is one of the most common programmed death 1 (PD-1) inhibitors used as an immune checkpoint inhibitor (ICI). It brings significant therapeutic effects but often accompanied by serious drug toxicity. The pulmonary toxicities of nivolumab are not clear. This study aims to systematically explore the nivolumab-associated pulmonary toxicities and provide reference for clinical treatment. Methods:Data were extracted from US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 1, 2016 to September 30, 2019. Two types of disproportionality analysis, information component (IC) and reporting odds ratio (ROR), were applied in nivolumab-associated pulmonary adverse events (AEs) signal detection. Results:A total of 28 489 309 records were extracted from FAERS database and 8 181 records were associated with nivolumab. Analysis was conducted in 179 AEs and 86 signals were detected. Notably, potent signals were detected in radiation pneumonitis (IC025: 3.99, ROR025: 17.25), pneumonitis (IC025: 3.34, ROR025: 10.64) and bronchial fistula (IC025: 2.94, ROR025: 8.78). Nivolumab-associated pulmonary toxicities were more frequently reported in dyspnoea (IC025: 0.50, ROR025: 1.44), pneumonia (IC025: 0.08, ROR025: 1.07) and pneumonitis (IC025: 3.34, ROR025: 10.64). Results of IC and ROR methods were similar to each other. Most pulmonary toxicities were observed in patients with non-small cell lung cancer (N=3 711, 32.13%), malignant melanoma (N=1 658, 14.36%) and renal cell carcinoma (N=731, 6.33%). Conclusion:Significant pulmonary toxicities were detected in patients treated with nivolumab. Thus, it is highly important for clinicians to be vigilant about nivolumab-associated pulmonary AEs and be prepared to take immediate action for patient safety.
ABSTRACT
In this study the chemical constituents of the higher polar sustances from Desmodium caudatum were investigated.The compounds were isolated by using column chromatographies over silicagel, polyamide, ODS, Sephadex LH-20, and preparative HPLC. The structures of these compounds were identified on the basis of NMR and MS spectra. Thirteen compounds were obtained and their structures were identified as vanillin(1), loliolide(2), indole-3-carboxaldehyde(3), salicylic acid(4), swertisin(5), saccharumoside C(6), isosinensin (7), kaempferol 3-O-β-D-glucopyranoside-7-O-α-L-rhamnopyranoside (8), isovitexin (9), vitexin (10), nothofagin(11), resveratroloside (12), and 2"-α-rhamnopyranosyl-7-O-methylvitexin (13). Except for compound 5, the remaining compounds were isolated from D. caudatum for the first time. Compounds 2, 3, 6-8, 11-13 were separated from the genus Desmodium for the first time.
Subject(s)
Apigenin , Chemistry , Drugs, Chinese Herbal , Chemistry , Fabaceae , Chemistry , Molecular Structure , Saponins , Chemistry , Spectrometry, Mass, Electrospray IonizationABSTRACT
<p><b>OBJECTIVE</b>To study the chemical constituents of Elephantopus tomentosus.</p><p><b>METHOD</b>The compounds were isolated by repeated HP20 macro porous adsorption resin column combined with Sephadex LH-20, ODS and silica gel chromatographies. The structures were identified on the basis of extensive spectroscopic data analysis and by comparison of their spectral data reported.</p><p><b>RESULT</b>Eighteen compounds were identified as 2-deethoxy-2beta-hydroxyphantomolin (1), 2beta-hydroxy-2-deethoxy-8-O-deacylphantomolin-8-O-tiglinate (2), 2beta-methoxy-2-deethoxyphantomolin (3), 2beta-methoxy-2-deethoxy-8-O-deacylphantomolin-8-O-tiglinate (4), molephantin (5), molephantinin (6), tricin (7), luteolin (8), quercetin (9), 3beta-friedelinol (10), 3beta-hydroxyolean-12-en-28-oic acid (11), 3, 5-di-O-caffeoyl quinic acid (12), 3,4-di-O-caffeoyl quinic acid (13), syringaresinol-4-beta-D-glucopyranoside (14), xylogranatinin (15), byzantionoside B (16), 2'-hydroxycinnamaldehyde (17), and caffeic acid ethyl ester (18).</p><p><b>CONCLUSION</b>Compounds 9, 11, 14-18 were separated from Elephantopus for the first time.</p>
Subject(s)
Asteraceae , Chemistry , Drugs, Chinese Herbal , Chemistry , Mass Spectrometry , Molecular StructureABSTRACT
<p><b>OBJECTIVE</b>To construct chimerical DNA vaccine plasmid of human papillomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity.</p><p><b>METHODS</b>Molecular cloning techniques were used to construct recombinant plasmid pcDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection.IL-2 and gamma-INF secreted by immunized spleens lymphocyte and HPV 11 L1 or E7 specific antibodies were assayed by ELISA method. Spleens lymphocyte proliferation was measured by MTT assay.</p><p><b>RESULTS</b>The chimerical DNA plasmid of pcDNA3 L1-E7 was constructed correctly. Specific anti-HPV11 E7 and L1 antibodies, specific lymphocyte proliferation and secretions of IL-2 and gamma-INF were detected in vaccinated mice.</p><p><b>CONCLUSION</b>Specific immune response, including cellular immunity and humoral immunity, could been detected in mice vaccinated with chimerical DNA vaccine of pcDNA3 L1-E7.</p>
Subject(s)
Animals , Female , Humans , Mice , Antibodies, Viral , Blood , Allergy and Immunology , Base Sequence , Genetic Engineering , Human papillomavirus 11 , Genetics , Allergy and Immunology , Mice, Inbred BALB C , Molecular Sequence Data , Papillomavirus Infections , Blood , Allergy and Immunology , Virology , Papillomavirus Vaccines , Genetics , Allergy and Immunology , Random Allocation , Vaccines, DNA , Genetics , Allergy and ImmunologyABSTRACT
<p><b>BACKGROUND</b>Several studies have shown that coronary stenting reduces the frequency of clinical and angiographic restenosis in patients with mild to moderate renal insufficiency. However, less is known about the long-term benefits of stent use in this population. This study was aimed to determine the impact of coronary stenting on extended (5 years) long-term outcomes of patients with chronic renal insufficiency.</p><p><b>METHODS</b>The study included 602 consecutive patients who underwent successful percutaneous coronary intervention with stenting. Renal insufficiency was defined as an estimated glomerular filtration rate < 60 ml x min(-1) x 1.73 m(-2). The major adverse cardiac events were compared for patients with (n = 160) and without (n = 442) renal insufficiency.</p><p><b>RESULTS</b>After the third year of follow-up, nonfatal myocardial infarction and revascularization rates were significantly increased in patients with renal insufficiency compared with those without renal dysfunction (16.9% vs 7.7%, P = 0.001; 29.4% vs 15.8%, P < 0.001). In patients who had recurrent cardiovascular events, a significantly higher rate of de novo stenosis revascularization was found in patients with renal insufficiency than without renal insufficiency (57.7% vs 22.7%, P < 0.001), while there was no significant difference in target lesion revascularization between the groups (51.9% vs 43.6%, P = 0.323). Multivariate analysis demonstrated an independent impact of the presence of renal insufficiency on the major adverse cardiac events (hazard ratio: 1.488, 95% confidence interval: 1.051 - 2.106, P = 0.025) and de novo stenosis (hazard ratio: 5.505, 95% confidence interval: 2.151 - 14.090, P < 0.001).</p><p><b>CONCLUSIONS</b>The late major adverse cardiac events, after successful coronary stenting, is increased in patients with an estimated glomerular filtration rate < 60 ml x min(-1) x 1.73 m(-2). This might be associated with increased risk of de novo stenosis in this population.</p>