The Relative Risk and Incidence of Immune Checkpoint Inhibitors Related Pneumonitis in Patients With Advanced Cancer: A Meta-Analysis

Background: Recently, immune checkpoint inhibitors (ICIs) have been proved one of the most promising anti-cancer therapy, series clinical trials have confirmed their efficacy. But they are also associated with distinctive set of toxic effects, which are recognized as immune-related adverse events. Among those immune-related adverse events, pneumonitis is rare, but it is often clinically serious and potentially life-threatening. Although many clinical trial results of PD-1/PD-L1 inhibitors had been reported incidence of pneumonitis, the knowledge based on the individual cohort data from each clinical trial is limited. So we conducted a meta-analysis of trials of PD-1/PD-L1 inhibitors in patients with advanced cancer and compared relative risk and incidence among different tumor types and therapeutic regimens. Such an analysis may provide important knowledge of this rare but clinically significant and potentially serious immune-related adverse event.Methods: Electronic databases were used to search eligible literatures, include randomized controlled trials (RCTs) comparing immune checkpoint inhibitors vs. standard therapies. All-grade (1–4) or high-grade (3–4) pneumonitis events were extracted. The summary relative risk, summary incidence, and 95% confidence intervals were calculated.Results: The incidence of all-grade and high-grade pneumonitis in non-small cell lung cancer (NSCLC) was significantly higher compared with other tumor types, such as Melanoma, urothelial carcinoma (UC), head and neck squamous cell carcinoma (HNSCC) (3.1% vs. 2.0%; p = 0.02, 1.4% vs. 0.6%; p = 0.03). The risk of all-grade pneumonitis was obtained from all patients in both experimental arm and control arm. Treatment with immune checkpoint inhibitors targeting PD-1/PD-L1 did significantly increase the risk of all-grade and high-grade pneumonitis compared with controls (fixed effects, RR: 4.70; 95% CI: 2.81–7.85; p < 0.00001, RR: 3.33; 95% CI: 1.68–6.59; p = 0.0006).Conclusion: The incidence of immune checkpoint inhibitors related pneumonitis was higher in NSCLC than other tumor types. Patients treated with immune checkpoint inhibitor in experiment arms are more likely to experience any grade pneumonitis than control arms. These findings suggest that clinician need to draw more attention on this rare but serious adverse event

Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways

Excitotoxicity induced by excessive N-methyl-D-aspartate (NMDA) receptor activation underlies the pathology of ischemic injury. Adiponectin (APN) is an adipocyte-derived protein hormone that modulates a number of metabolic processes. APN exerts a wide range of biological functions in the central nervous system. However, the role of APN and its receptors in cerebral ischemia/reperfusion (I/R)-induced injury and the related mechanisms remain to be clarified. Here, we found that APN and APN receptor agonist AdipoRon (APR) were protective against excitotoxicity induced by oxygen and glucose deprivation/reperfusion (OGD/R) and NMDA in primary neurons. Adiponectin receptor 1 (AdipoR1) knockdown reversed the protection conferred by either APN or APR. Moreover, the protective effects offered by both APN and APR were compromised by compound C, an inhibitor of amp-activated protein kinase (AMPK) phosphorylation. Both APN and APR protected the dissipation of the ΔΨm caused by OGD/R. They also up-regulated the PGC-1α expression, which was reversed by compound C. Furthermore, both APN and APR ameliorated but APN knockout aggravated the infarct volume and neurological deficient induced by transient middle cerebral artery occlusion (tMCAO) in vivo. Taken together, these findings show that APN and APR protect against ischemic injury in vitro and in vivo. The protective mechanism is mainly related to AdipoR1-dependent AMPK phosphorylation and PGC-1α up-regulation

Structure and Photoluminescent Properties of ZnO Encapsulated in Mesoporous Silica SBA-15 Fabricated by Two-Solvent Strategy

The two-solvent method was employed to prepare ZnO encapsulated in mesoporous silica (ZnO/SBA-15). The prepared ZnO/SBA-15 samples have been studied by X-ray diffraction, transmission electron microscope, X-ray photoelectron spectroscopy, nitrogen adsorption–desorption isotherm, and photoluminescence spectroscopy. The ZnO/SBA-15 nanocomposite has the ordered hexagonal mesostructure of SBA-15. ZnO clusters of a high loading are distributed in the channels of SBA-15. Photoluminescence spectra show the UV emission band around 368 nm, the violet emission around 420 nm, and the blue emission around 457 nm. The UV emission is attributed to band-edge emission of ZnO. The violet emission results from the oxygen vacancies on the ZnO–SiO2interface traps. The blue emission is from the oxygen vacancies or interstitial zinc ions of ZnO. The UV emission and blue emission show a blue-shift phenomenon due to quantum-confinement-induced energy gap enhancement of ZnO clusters. The ZnO clusters encapsulated in SBA-15 can be used as light-emitting diodes and ultraviolet nanolasers

Dispersion characteristics of guided waves in functionally graded anisotropic micro/nano-plates based on the modified couple stress theory

International audienceIn this paper, the acoustic wave motion characteristics of Lamb and SH waves in functionally graded (FG) anisotropic micro/nano-plates are studied based on the modified couple stress theory. A higher efficient computational approach, the extended Legendre orthogonal polynomial method (LOPM) is utilized to deduce solving process. This polynomial method does not need to solve the FG micro/nano-plates hierarchically, which provides a more realistic analysis model for FG micro/nano-plates and has high computational efficiency. Simultaneously, the solutions based on the global matrix method (GMM) are also deduced to verify the correctness of the polynomial method. Furthermore, the effects of size and material gradient are studied in detail. Numerical results show that the size effect causes wrinkles in Lamb wave dispersion curves, and the material gradient characteristic changes the amplitude and range of wrinkles. For SH waves, the length scale parameter L x increases the cutoff frequency but does not change the overall trend of the dispersion curve; on the contrary, L z does not change the cutoff frequency but causes the dispersion curve to show an upward trend

Aromatic compounds from an aqueous extract of “ban lan gen” and their antiviral activities

A pair of new diphenyl glycerol ether enantiomers (−)-1 and (+)-1 and two new methyl benzamidobenzoates 2 and 3, named (−)-(R)- and (+)-(S)-isatindigotrioic acid [(−)-1 and (+)-1] and isatindigoticamides A (2) and B (3), respectively, were isolated from an aqueous decoction of the roots of Isatis indigotica (ban lan gen). Their structures were elucidated by spectroscopic data analysis including 2D NMR experiments. The absolute configurations of (−)-1 and (+)-1 were assigned based on the CD exciton chirality method. Compounds 2 and 3 exhibited antiviral activities against HSV-1 with IC50 values of 4.87 and 25.87 μmol/L, respectively. Compound 2 was also found active against Coxsackie virus B3 and LPS-induced NO production

Sesquiterpene glycosides from the roots of Codonopsis pilosula

Three new sesquiterpene glycosides, named codonopsesquilosides A−C (1−3), were isolated from an aqueous extract of the dried roots of Codonopsis pilosula. Their structures including absolute configurations were determined by spectroscopic and chemical methods. These glycosides are categorized as C15 carotenoid (1), gymnomitrane (2), and eudesmane (3) types of sesquiterpenoids, respectively. Compound 1 is the first diglycoside of C15 carotenoids to be reported. Compound 2 represents the second reported example of gymnomitrane-type sesquiterpenoids from higher plants. The absolute configurations were supported by comparison of the experimental circular dichroism (CD) spectra with the calculated electronic CD (ECD) spectra of 1−3, their aglycones, and model compounds based on quantum-mechanical time-dependent density functional theory. The influences of the glycosyls on the calculated ECD spectra of the glycosidic sesquiterpenoids, as well as some nomenclature and descriptive problems with gymnomitrane-type sesquiterpenoids are discussed

Correction Method for the Bending Characteristics of Aero Ball Joints under High Temperature and High Pressure

The aero ball joint is pivotal in aircraft duct systems due to its favorable properties, including displacement compensation and flexibility. In the stress assessment of air ducts, ball joints are usually simplified by using “Joints” connections to reduce the convergence problems caused by non-linearity, which requires a high degree of accuracy in the characteristic parameters of the ball joint. Accordingly, this paper builds a high temperature and pressure fatigue test platform to investigate the bending characteristics of the ball joint at different temperatures and pressures and points out the limitations of the current method. Then, a method combining finite element analysis (FEA) and the BP neural network is proposed to obtain the characteristic parameters of the ball joint. The results showed that the bending process of the ball joint tended to have two typically different stiffness properties, which were high rigidity and low rigidity. The bending characteristics were strongly influenced by pressure, but less influenced by temperature. The existing test platform increased the force reaction at the contact areas of the ball joint, resulting in errors in the measurement of characteristic parameters. The BP neural network prediction method could effectively alter the ball joint properties and reduce errors

Acetylenes and fatty acids from Codonopsis pilosula

Four new acetylenes (1–4) and one new unsaturated ω-hydroxy fatty acid (5), together with 5 known analogues, were isolated from an aqueous extract of Codonopsis pilosula roots. Their structures were determined by spectroscopic and chemical methods. The new acetylenes are categorized as an unusual cyclotetradecatrienynone (1), tetradecenynetriol (2), and rare octenynoic acids (3 and 4), respectively, and 3 and 4 are possibly derived from oxidative metabolic degradation of 1 and/or 2. The absolute configuration of 1 was assigned by comparison of the experimental circular dichroism (CD) spectrum with the calculated electronic circular dichroism (ECD) spectra of stereoisomers based on the quantum-mechanical time-dependent density functional theory, while the configuration of 2 was assigned by using modified Mosher׳s method based on the MPA determination rule of ΔδRS values for diols

Sulfur-enriched alkaloids from the root of Isatis indigotica

Five new sulfur-enriched alkaloids isatithioetherins A–E (1–5), and two pairs of scalemic enantiomers (+)- and (−)-isatithiopyrin B (6a and 6b) and isoepigoitrin and isogoitrin (7a and 7b), along with the known scalemic enantiomers epigoitrin and goitrin (8a and 8b), were isolated and characterized from an aqueous extract of the Isatis indigotica roots. Their structures were determined by extensive spectroscopic data analysis, including 2D NMR and theoretical calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory (TDDFT). Compounds 1–5 represent a novel group of sulfur-enriched alkaloids, biogenetically originating from stereoselective assemblies of epigoitrin-derived units. Isolation and structure characterization of 6a and 6b support the postulated biosynthetic pathways for the diastereomers 9a and 9b via a rare thio-Diels–Alder reaction. Compounds 2 and 4 showed antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2, IC50 0.60 and 1.92 μmol/L) and the herpes simplex virus 1 (HSV-1, IC50 3.70 and 2.87 μmol/L), and 2 also inhibited Coxsackie virus B3 (IC50 0.71 μmol/L). KEY WORDS: Cruciferae, Isatis indigotica, Sulfur-containing alkaloids, Isatithioetherins A–E, Isatithiopyrins A and B, Isoepigoitrin, Isogoitrin, Antiviral activit

4-Hydroxybenzyl-substituted amino acid derivatives from Gastrodia elata

Seven new 4-hydroxybenzyl-substituted amino acid derivatives (1−7), together with 11 known compounds, were isolated from an aqueous extract of the rhizomes of Gastrodia elata Blume. Their structures were determined by spectroscopic and chemical methods. Compounds 1−3 are pyroglutamate derivatives containing 4-hydroxybenzyl units at the N atom and 4−7 are the first examples of natural products with the 4-hydroxybenzyl unit linked via a thioether bond to 2-hydroxy-3-mercaptopropanoic acid (4−6) and 2-hydroxy-4-mercaptobutanoic acid (7), which would be biogenetically derived from cysteine and homocysteine, respectively. The structures of 1 and 2 were verified by synthesis, while the absolute configurations of 4, 5 and 7 were assigned using Mosher’s method based on the MPA determination rule of ΔδRS values. The known compound 4-(hydroxymethyl)-5-nitrobenzene-1,2-diol (8) exhibited activity against Fe2+-cysteine induced rat liver microsomal lipid peroxidation with IC50 values of 9.99×10−6 mol/L