The efficacy and safety of eltrombopag in treating TKI-induced thrombocytopenia in patients with chronic myeloid leukemia.

ABSTRACTThrombocytopenia is one of the most common hematological adverse reactions in chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKI) therapy, causing life-threatening bleeding cases. However, there are fewer therapeutic drugs for TKI-induced thrombocytopenia. Eltrombopag is a non-peptide thrombopoietin receptor agonist used for the treatment of immune thrombocytopenia， aplastic anemia, and hepatitis C-associated thrombocytopenia. Nevertheless, studies of eltrombopag for TKI-induced thrombocytopenia are still lacking. This study retrospectively analyzed the clinical and test data of 21 CML patients with TKI-related thrombocytopenia. The results demonstrated that the median baseline value of thrombocytopenia in the 21 CML patients was 15.57 × 109/L [2-28 × 109/L]. Following treatment with eltrombopag, 16 patients had a significant increase in their platelet levels. The peak median for platelet increase in effective responders was 145.12 × 109/L (51-460 × 109/L). However, 5 patients failed to respond to eltrombopag. Moreover, 4 of the 21 patients enrolled had adverse reactions, including reversible liver function impairment, palpitation, headache, insomnia, and loss of appetite. Nonetheless, no cases of disease progression, thrombotic events, or myelofibrosis were observed. Hence, eltrombopag may be a useful adjunctive therapy for relieving TKI-related thrombocytopenia in patients with CML.

HS-SPME/GC×GC-TOFMS-Based Flavoromics and Antimicrobial Properties of the Aroma Components of Zanthoxylum motuoense.

Zanthoxylum motuoense Huang, native to Tibet, China, is a newly discovered Chinese prickly ash, which, recently, has increasingly attracted the attention of researchers. In order to understand its volatile oil compositions and flavor characteristics, and to explore the flavor difference between Z. motuoense and the common Chinese prickly ash sold in the market, we analyzed the essential oils of Z. motuoense pericarp (MEO) using HS-SPME/GC×GC-TOFMS coupled with multivariate data and flavoromics analyses. The common commercial Chinese prickly ash in Asia, Zanthoxylum bungeanum (BEO), was used as a reference. A total of 212 aroma compounds from the 2 species were identified, among which alcohols, terpenoids, esters, aldehydes, and ketones were the major compounds. The predominant components detected from MEO were citronellal, (+)-citronellal, and ß-phellandrene. Six components-citronellal, (E,Z)-3,6-nonadien-1-ol, allyl methallyl ether, isopulegol, 3,7-dimethyl-6-octen-1-ol acetate, and 3,7-dimethyl-(R)-6-octen-1-ol-could be used as the potential biomarkers of MEO. The flavoromics analysis showed that MEO and BEO were significantly different in aroma note types. Furthermore, the content differences of several numb taste components in two kinds of prickly ash were quantitatively analyzed using RP-HPLC. The antimicrobial activities of MEO and BEO against four bacterial strains and nine plant pathogenic fungi were determined in vitro. The results indicated that MEO had significantly higher inhibitory activities against most microbial strains than BEO. This study has revealed the fundamental data in respect of the volatile compound properties and antimicrobial activity of Z. motuoense, offering basic information on valuable natural sources that can be utilized in the condiment, perfume, and antimicrobial sectors.

Oreocharioside A-G, new acylated C-glycosylflavones from Oreocharis auricula (Gesneriaceae).

Seven new acylated C-glycosylflavones, oreocharioside A-G, together with two known compounds were isolated from the whole plant of Oreocharis auricula. Their structures were characterized by the comprehensive analysis of their NMR, IR, UV, CD spectra and HRESIMS data. All the new compounds were evaluated for the antioxidant and anti-inflammatory activities. The results showed that compounds 1 and 2 had significant DPPH and ABTS radical scavenging activities, with the IC50 values of 0.32-3.20 µg/mL. Compounds 2 and 3 exhibited the higher potency among all the new compounds in reducing TNF-α production.

Evaluating the genesis and dominant processes of groundwater salinization by using hydrochemistry and multiple isotopes in a mining city.

The increasing salinization of groundwater renders it challenging to maintain the water quality. Moreover, knowledge regarding the characteristics and mechanism of groundwater salinization in mining areas remains limited. This study represents the first attempt of combining the hydrochemical, isotope (δD, δ18O, δ37Cl, and 87Sr/86Sr) and multivariate statistical analysis methods to explore the origin, control, and influence of fluoride enrichment in mining cities. The TDS content of groundwater ranged from 275.9 mg/L to 2452.0 mg/L, and 54% of the groundwater samples were classified as class IV water according to China's groundwater quality standards (GB/T 14848-2017), indicating a decline in the water quality of the study area. The results of the groundwater ion ratio and isotope discrimination analysis showed that dissolution and evaporation involving water-rock interactions and halite were the main driving processes for groundwater salinization in the study area. In addition to the hydrogeological and climatic conditions, mine drainage inputs exacerbated the increasing salinity of the groundwater in local areas. The mineral dissolution, cation exchange, and evaporation promoted the F- enrichment, while excessive evaporation and salinity inhibited the F- enrichment. Gangue accumulation and infiltration likely led to considerable F- enrichment in individual groundwater regions. Extensive changes in the groundwater salinity indicated differences in the geochemical processes that controlled the groundwater salinization. Given the particularity of the study area, the enrichment of salinization and fluoride triggered by mining activities cannot be ignored.

SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo.

Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent.

Video-assisted thoracoscopic pneumonectomy: the anterior approach.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy is now a well-accepted way to perform a minimally invasive lobectomy. VATS lobectomy is different from the conventional surgery. Different incisions, instruments and camera positions have also been described in the past two decades. There are no fixed patterns in VATS lobectomy. We here describe our method for fissure-based VATS lobectomy using an anterior approach. The aim of this paper is to show our technique for VATS lobectomy and our experience and outcomes obtained. METHODS: A 57-year-old man, who was admitted to the Affiliated Hospital of the Guangdong Medical College, had coughing up blood tinged sputum, right chest pain for one month. Thoracic CT imaging revealed a 22 mm × 22 mm × 20 mm, T1bN1M0 lesion in the right lower lobe. The patient for clinical stage II non-small cell lung cancer underwent VATS lobectomy by using an anterior approach on January 2013. RESULTS: Total volume of chest tube drainage after operation was 450 mL, intraoperative blood loss was 80 mL, operation time was 105.8 min, chest tube duration was three days, length of postoperative hospital stay was eight days. Follow-up no recurrence and metastasis for six months. CONCLUSIONS: The main advantages of the anterior approach in our experience are easy to deal with the absence or incomplete fissure by the "tunneling" approach. In addition, the mediastinal node packets are clearly seen, allowing thorough lymphadenectomy. Therefore, VATS lobectomy by the anterior approach is a safe, feasible procedure.