The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

Regio- and diastereoselective synthesis of diverse spirocyclic indenes by cyclization with indene-dienes as two carbon building blocks.

We report a base-promoted cyclization with indene-dienes as two carbon building blocks toward diverse spirocyclic indene scaffolds including hexacyclic spiroindenes bearing benzo pyran motifs and pentacyclic spiroindenes containing oxindole units in high yields with excellent diastereoselectivities.

A regioselective [3 + 2] cycloaddition reaction of 2-benzylidene-1-indenones with functional olefins to access indanone-fused 2D/3D skeletons.

The regioselective [3 + 2] cycloaddition reaction of 2-benzylidene-1-indenones with functional olefins was established with DABCO as a base under mild conditions. Using this approach, a series of diversely substituted indanone-fused cyclopentane polycycles with highly crowded multiple substituents were synthesized in high yields.

Construction of an Axially Chiral Fluorene Nitrile-Based Framework via Benzannulation of Indene Diene with Benzoylacetonitrile.

The methodology for the synthesis of fluorene-based atropisomers was developed via the strategy of aromatic ring formation. By this strategy, an efficient benzannulation of indene-based diene with benzoylacetonitrile divergently promoted by DABCO and a chiral organocatalyst was established, and various atropisomeric fluorene-based skeletons were generated in good yields, which not only provide a new strategy for the construction of atropisomeric biaryls but also offer a new member to the atropisomeric family.