Traditional Chinese medicine (Xiaoai Jiedu Decoction) as an adjuvant treatment for prevention new colorectal adenomatous polyp occurrence in post-polypectomy: Study protocol for a randomized controlled trial.

BACKGROUND: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy. METHODS/DESIGN: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy. TRIAL REGISTRATION: NCT03616444.

TNFR/TNF-α signaling pathway regulates apoptosis of alveolar macrophages in coal workers' pneumoconiosis.

We explored the role of TNFR/TNF-α signalingin apoptosis among alveolar macrophages (AM) and its relevance to the development of coal workers' pneumoconiosis (CWP). Purified alveolar macrophages (AMs) were prepared from bronchoalveolar lavage fluid harvested from 366 CWP patients and 120 healthy subjects enrolled inthe study. The purified AMs were then divided into control, SOD, anti-TNFR, TNFR and NFkB inhibitor groups and analyzed for apoptosis usingflow cytometry (sub-diploid peak) and western blotting (Bcl-2, Caspase-3 and Caspase-8 expression). We found thatAM apoptosis washigher amongCWP patients than thehealthycontrols. Expression ofBcl-2, Caspase-3 and Caspase-8 was higher inAMs from CWP patientsthan in those from the controlsand correlated with increased AM apoptosis. Univariate and multivariate analyses suggested that CWP grade, initial exposure time, exposure time inyears, and CWP onset agewereall associated with altered levels of Bcl-2, Caspase-3 and Caspase-8. Inhibition of TNFR/TNF-α signaling usinganti-TNFR antibody, SOD or NFkB inhibitionreduced AM apoptosisand decreased Bcl-2, Caspase-3 and Caspase-8 expression. These data suggestinhibition of a TNFR/TNF-α signaling pathway is a potentiallyeffective means ofalleviating CWP by inhibiting AM apoptosis.

1, 25(OH)2D3-induced interaction of vitamin D receptor with p50 subunit of NF-κB suppresses the interaction between KLF5 and p50, contributing to inhibition of LPS-induced macrophage proliferation.

KLF5 and nuclear factor κB (NF-κB) regulate cell proliferation and inflammation. Vitamin D signaling through vitamin D receptor (VDR) exerts anti-proliferative and anti-inflammatory actions. However, an actual relationship between KLF5, NF-κB and VDR in the inflammation and proliferation of macrophages is still unclear. Here, we showed that LPS and proinflammatory cytokines stimulate KLF5 gene expression in macrophages, and that 1, 25(OH)2D3 suppresses LPS-induced KLF5 expression and cell proliferation via upregulation of VDR expression. Mechanistic studies suggested that KLF5 interacts with p50 subunit of NF-κB to cooperatively induce the expressions of positive cell cycle regulators cyclin B1 and Cdk1/Cdc2 in LPS-treated macrophages. Further studies revealed that 1, 25(OH)2D3-induced interaction of VDR with p50 decreases LPS-induced interaction of KLF5 with p50. Collectively, we identify a novel regulatory pathway in which 1, 25(OH)2D3 induces VDR expression and promotes VDR interaction with p50 subunit of NF-κB, which in turn attenuates the association of KLF5 with p50 subunit of NF-κB and thus exerts anti-inflammatory and anti-proliferative effects on macrophages.

Fast and Online Determination of Five Avermectin Residues in Foodstuffs of Plant and Animal Origin Using Reusable Polymeric Monolithic Extractor Coupled with LC-MS/MS.

A hydrophobic monolith (10 mm × 2.1 mm i.d.) was developed as a reusable online solid-phase extraction (SPE) sorbent coupled with LC-MS/MS for the rapid determination of five avermectin residues in foodstuffs of both plant and animal origin. The online SPE was achieved using a 10 mmol/L ammonium acetate solution as the loading solvent, and acetonitrile (MeCN) was selected for the washing step. After being transferred from the monolith into a C18 analytical column using MeCN, the analytes were analyzed by LC-MS/MS using MeCN/0.1% NH4OH (10:90, v/v) as the mobile phase. The detection limit was 2 µg/kg for five avermectins, and the recoveries in fresh pear, chili seed, bovine muscle, and milk ranged from 71.8% to 101.3% with relative standard deviations of less than 8.94%. The online SPE and determination were achieved within 15 min, and the monolithic extractor was reusable for more than 500 experiments.

Heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice.

The present study was designed to investigate whether administration of CoPPIX, an HO-1 inducer, could significantly inhibit TNF-alpha and Hmgb1 expression and thus attenuate the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Acute lung injury was induced successfully by intratracheal administration of LPS (0.5 mg/kg) in male BALB/c mice. CoPPIX or ZnPPIX (an HO-1 inhibitor) was administered to mice 24 h prior to LPS exposure. It was found that CoPPIX (5, 10 mg/kg, i.p.) caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and EBA leakage at 24 h after LPS challenge. Furthermore, the histopathologic findings indicated that alveolitis with leukocyte infiltration in the alveolar space was less severe in the CoPPIX-treated mice than in the mice treated with LPS alone. In addition, CoPPIX was also believed to have down-regulated the expression of LPS-induced proinflammatory cytokines, including early proinflammatory cytokine TNF-a, and late proinflammatory cytokine Hmgb1. In contrast, no obvious difference was observed between the ZnPPIX group and the LPS group. These findings demonstrate the significant protection of CoPPIX against LPS-induced ALI, and the effect mechanism of CoPPIX was associated with decreasing the expression of TNF-a and Hmgb1.