Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Improving cadmium mobilization by phosphate-solubilizing bacteria via regulating organic acids metabolism with potassium.

Organic acids secreted by phosphorus-solubilizing bacteria (PSB) is one of the main biological metabolites with cadmium (Cd) mobilization capacity in the conversion of insoluble precipitate forms to bioavailable forms in contaminated soil. However, the fluctuating concentrations of nutrient elements caused by agricultural activities may result in the substantial variances of carbohydrate metabolism of microorganisms involved in Cd remediation, it is therefore essential to study how metabolic strategies, especially for organic acids, affected by the environmentally friendly fertilizers, such as potassium (K). In this study, adding K+ (KCl) concentrations from 0.0 to 100.0 mg/L in medium clearly accelerated Cd mobilization from 15.9 to 35.9 mg/L via inducing the secretion of tartaric acid, 3-hydroxybutyrate, fumaric and succinic acids, increased by 10.0-, 7.5-, 4.3- and 4.1-fold changes, respectively. Current data revealed that the significant differences of metabolic pathways and genes expressions with the varied K+ concentrations included: ⅰ) K+ induces a substantial up-regulation in metabolic pathway of pyruvic acid to oxaloacetate and tartaric acids; ⅱ) the varied expression of genes involved in encoding enzymes of tricarboxylic acid cycle result in the up-regulated fumaric acid, succinic acid and 3-hydroxybutyrate; ⅲ) the expression of genes related enzyme cysteine and glutamate metabolism processes promoted with the increasing bioavailable Cd concentrations. Besides, P-type ATPase activity increased with K+ levels, indicating that H+ efflux and medium acidification were strengthened. In general, an appropriate enhancement of K based fertilizer is an effective manner for soil Cd remediation via the regulation of organic acids metabolism and H+ secretion of PSB.