Design and synthesis optimization of novel diimide indoles derivatives for ameliorating acute lung injury through modulation of NF-κB signaling pathway.

Acute lung injury (ALI) is a common respiratory disease caused by local or systemic inflammatory reaction. Based on the natural 7-chain diaryl anti-inflammatory framework, a series of diimide indoles derivatives were designed by combining curcumin and indole in this study. The synthesis of diimide compounds was extended using dichloromethane (DCM) as solvent and 1,1'-carbonyldiimidazole (CDI) and sodium hydride (NaH) as double activators, and a total of 40 diimide-indole derivatives were obtained. The results of in vitro anti-inflammatory activity showed that most compounds could inhibit the production of interleukin-6 (IL-6) better than curcumin and indomethacin. Among the compounds, the IC50 of compound 11f on IL-6 reached 1.05 µM with no obvious cytotoxic side effects. Mechanistically, compound 11f could block the expression of NF-κB P65 phosphorylation, and nuclear translocation of P65. The acute toxicity tests in-vivo also showed no obvious toxicity in mice after the intragastric administration of 1000 mg/kg. In addition, the compound 11f could significantly inhibit the LPS-induced inflammatory response in mice and reduce the number of neutrophils and wet/dry lung weight ratio, thereby alleviating ALI. These results indicated that the novel diimide indoles were promising anti-inflammatory agents for the treatment of ALI.

Empirical antibiotics for acute cholecystitis-what generation of antibiotics is an appropriate choice? A prospective, randomized controlled study.

BACKGROUND: In cases of acute cholecystitis (AC), empirical antibiotics are used to prevent infectious morbidities following cholecystectomy. However, there are still no exact guidelines on which antibiotics to use. METHODS: We enrolled 300 patients who had been admitted for cholecystectomy because of grade I or II AC. We randomly allocated them to one of two groups empirically: the first group was to be given first-generation cephalosporins (group I, 150 patients) and the second group was to be given second-generation cephalosporins (group II, 150 patients). We analyzed the clinical outcomes and the incidence of postoperative infectious morbidities. RESULTS: The incidence rate of overall infectious morbidities (18 cases, 12% in group I; 17 cases, 11.3% in group II; P = .859) showed no difference between the two groups. The incidence rate of sepsis (only one case, 0.7% in group II, P = 1.000) or surgical site infection (nine cases, 6% in group I and eight cases, 5.3% in group II, P = 1.000) were also similar in both groups. CONCLUSIONS: The empirical use of first-generation cephalosporins for mild-to-moderate AC without gallbladder perforation was not inferior to using second-generation cephalosporin for prophylaxis against postoperative infection. Our results could allow for a tailored treatment strategy of empirical antibiotics according to the severity of the cholecystitis.

Morphologic Evaluation of Ductus Diverticulum Using Multi - Detector Computed Tomography: Comparison with Traumatic Pseudoaneurysm of the Aortic Isthmus.

OBJECTIVES: To evaluate morphologic variations at the aortic isthmus with particular attention to ductus diverticulum, a mimicker of traumatic pseudoaneurysm, and to describe differences using Computed Tomography (CT) images. PATIENTS AND METHODS: From December 2013 to December 2014, patients who underwent a chest CT examination after blunt trauma at our emergency department were included. Aortic isthmus morphologies were evaluated using multiplanar reconstruction (MPR) and maximum intensity projection (MIP) images as follows. Type I -concave contour, type II -convexity without a discrete bulge, or type III -a discrete focal bulge (defined as ductus diverticulum). RESULTS: After excluding 11 cases of traumatic pseudoaneurysm of the aortic isthmus, a total of 432 trauma patients (mean age = 47.1 ± 19.1 years, number of males = 318) were evaluated for aortic isthmus morphology, and classified as follows; type I (n = 240, 55.6%), type II (n = 157, 36.3%), and type III (n = 35, 8.1%). As compared with traumatic pseudoaneurysm (n = 11), ductus diverticulum had a smaller vertical diameter (5.5 ± 1.3 mm vs. 11.2 ± 2.7 mm, P < 0.001), a broader base (14.9 ± 4.1 mm vs. 8.8 ± 4.5 mm, P < 0.001), a smoother margin (97.1% vs. 27.3%, P < 0.001), and formed obtuse angle with the aortic wall. Furthermore, ductus diverticulum was not associated with the presence of a dissection flap or hemomediastinum. CONCLUSION: Ductus diverticulum, a mimicker of traumatic pseudoaneurysm of the aortic isthmus, is a frequently observed anatomic variant during CT examinations. Familiarity with its CT imaging findings could avoid it being confused with traumatic pseudoaneurysm in blunt trauma patients.

Robust multi-site MR data processing: iterative optimization of bias correction, tissue classification, and registration.

A robust multi-modal tool, for automated registration, bias correction, and tissue classification, has been implemented for large-scale heterogeneous multi-site longitudinal MR data analysis. This work focused on improving the an iterative optimization framework between bias-correction, registration, and tissue classification inspired from previous work. The primary contributions are robustness improvements from incorporation of following four elements: (1) utilize multi-modal and repeated scans, (2) incorporate high-deformable registration, (3) use extended set of tissue definitions, and (4) use of multi-modal aware intensity-context priors. The benefits of these enhancements were investigated by a series of experiments with both simulated brain data set (BrainWeb) and by applying to highly-heterogeneous data from a 32 site imaging study with quality assessments through the expert visual inspection. The implementation of this tool is tailored for, but not limited to, large-scale data processing with great data variation with a flexible interface. In this paper, we describe enhancements to a joint registration, bias correction, and the tissue classification, that improve the generalizability and robustness for processing multi-modal longitudinal MR scans collected at multi-sites. The tool was evaluated by using both simulated and simulated and human subject MRI images. With these enhancements, the results showed improved robustness for large-scale heterogeneous MRI processing.