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.

Free radicals and oxidative stress play key roles in cerebral ischemic pathogenesis and represent pharmacological targets for treatment. Edaravone (Edv), one of antioxidant agents that have been used in acute ischemic stroke in both clinical settings and animal experiments, exerts neuroprotective effect on ischemic injured brains. This review is aimed to elaborate the latest molecular mechanisms of the neuroprotection of Edv on cerebral ischemia and provide reasonable evidence in its clinical application. It is found that Edv has neuroprotective influence on cerebral ischemia, which is closely related to the facets of scavenging reactive oxygen species (ROS), hydroxyl radical (ċOH) and reactive nitrogen species (RNS). And it is a good antioxidant agent that can be safely used in the treatment of cerebral ischemia and chronic neurodegenerative disorders as well as other ischemia/reperfusion (I/R)-related diseases. The combination of Edv with thrombolytic therapy also can be applied in clinical settings and will be greatly beneficial to patients with stroke.

Departmental sources Background: Leptin is an adipokine related to overweight and cardiovascular diseases. However, the leptin expression level in epicardial adipose tissue (EAT) of humans and its association with coronary atherosclerosis has never been investigated. Material/Methods: Patients receiving cardiac surgery were divided into a coronary artery disease group (CAD group) and a non-CAD group (NCAD group). Blood samples from coronary vein, biopsies of subcutaneous adipose tissue (SAT), and EAT were acquired during the surgery. Serum leptin level and leptin level in EAT and SAT were tested with ELISA, quantitative PCR, and immunohistochemistry and were compared between the CAD group and NCAD group, as well as between stenosis and non-stenosis subgroups. Logistic regression analysis was performed to explore the risk factors for coronary artery stenosis. Results: No statistically significant differences were found in demographic and clinical data between groups (all P>0.05). Serum leptin concentration and leptin expression in EAT and SAT of the CAD group were much higher in than in the NCAD group (all P<0.05). In subgroup analysis, there was no difference in serum leptin and expression in SAT of stenosis and non-stenosis patients (All P>0.05). The leptin expression level in EAT of stenosis patients was significantly higher than in non-stenosis patients (P=0.0431). By multivariate logistic regression analysis, we demonstrated that leptin expression level in EAT was an independent risk factor for coronary artery stenosis [OR=1.09, 95%CI (1.01±1.18), P=0.031]. Conclusions: Leptin expression in EAT and SAT were both increased for CAD patients. Leptin expression in EAT was an independent risk factor for coronary atherosclerosis in the adjacent artery, while leptin in SAT was not associated.

b 2 -Adrenoceptor agonists, the most effective bronchodilator, have long been widely used in symptomatic therapy of asthma. A variety of b 2 -adrenoceptor agonists are currently available, such as salbutamol, terbutaline, salmeterol, formoterol and procaterol. The majority of b 2 -adrenoceptor agonists possess chiral center(s) (asymmetric carbon atom) in their structures; therefore, they exist as pair(s) of enantiomers.1) Based on the conformational stereochemistry and pharmacokinetic parameters, enantiomers can vary greatly in their pharmacological effects on target tissue(s).2) Except for levalbuterol, most available b 2 -adrenoceptor agonists are a racemic mixture of equimolar (R)-and (S)-enantiomer. Against this background, separation of enantiomers is a practice increasing in popularity, since a single optical isomer may represent a safer and more efficacious alternative than its corresponding racemate.3) 2-(4-Amino-3-chloro-5-trifluomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride (SPFF) is synthesized and exploited by the drug synthesis laboratory of Shenyang Pharmaceutical University as a novel b 2 -adrenoceptor agonist. Gan et al. 4) has found that bronchodilator effects of racemic SPFF on isolated guinea pig trachea strips with or without precontraction of bronchoconstrictors (histamine and acetylcholine) were more potent than isoprenaline. Moreover, it was confirmed that the bronchodilator effect of racemic SPFF was due to the activation of b 2 -adrenoceptor because this effect was easily antagonized by a specific b 2 -adrenoceptor antagonist, ICI-118551 (pA 2 ϭ8.90Ϯ0.01). Furthermore, the positive chronotropic effect of SPFF on isolatd guinea pig left atria (pD 2 ϭ5.41Ϯ0.38) was much weaker than that of isoprenaline (pD 2 ϭ8.75Ϯ0.24). A radioligand binding experiment using guinea pig lung and cardiac ventricle as b 2 and b 1 adrenoceptor sources, respectively, also demonstrated that racemic SPFF possesses high affinity and selectivity to b 2 -adrenoceptor. The protective effect of racemic SPFF on bronchospasm induced by bronchoconstrictor aerosol in guinea pig in vivo was 6 times more potent than that of sulbutamol, and the Konzett and Rösler experiment performed in anesthetized rabbits showed that racemic SPFF exerted action of longer duration than sulbutamol did. In the present study we compared the pharmacological effects of racemic SPFF with its individual enantiomers on bronchodilating action and potency in guinea pigs. MATERIALS AND METHODS Chemicals and Drugs

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