[Clinical safety studies based on 30 026 post-marketing cases of Shenqi Fuzheng injection by intensive hospital monitoring nested NCCS].

This study adopted a large sample, multicenter, registered hospital centralized monitoring nested prospective case-control study design. From the real world clinical application of Shenqi Fuzheng injection, monitored 30 026 cases of patients with the use of Shenqi Fuzheng injection. A total of 51 adverse drug reaction (ADR) cases was monitored, including 1 case of severe adverse reactions. ADR incidence rate was 1.7 per 1,000. Blood samples were collected from patients with allergic reactions and their matched controls. Related biological indicators of allergic reactions were unified detected and analysed in order to explore the mechanism of allergic reaction and promote the clinical safety.

Correlation between the Human Development Index and the Incidence and Mortality of Non-Hodgkin Lymphoma.

OBJECTIVE: This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma (NHL). METHODS: We compared the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and the ASMR to ASIR ratio (MIR) at national and regional levels and studied the correlation between the MIR and the human development index (HDI) in 2012 and 2018. RESULTS: The highest ASIR was in North America in 2012 and in Australia in 2018, and the lowest ASIR was in Central and South Asia in both 2012 and 2018. The highest ASMR was in North Africa in both 2012 and 2018, and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018. The lowest MIR was in Australia in both 2012 and 2018, and the highest MIR was in Western Africa in both 2012 and 2018. HDI was strongly negatively correlated with MIR (r: -0.8810, P<0.0001, 2012; r: -0.8895, P<0.0001, 2018). Compared to the 2012 data, the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018. CONCLUSION: The MIR is negatively correlated with HDI. Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia.

OBJECTIVE: Methotrexate (MTX) can be safely administered to most patients but may cause severe toxicity in others. This study aimed to summarize the characteristics of high-dose methotrexate (HD-MTX) chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities. METHODS: We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol (clinical trial number: ChiCTR-IPR-14005706) and analyzed the data of actual MTX dosage, MTX concentration, toxicity, and prognosis. We compared data between the dose-adjustment Program 1 (fixed 20% reduction in dose) and the dose-adjustment Program 2 (dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h), which were applied if the MTX clearance was delayed in the previous cycle. RESULTS: The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1 (P<0.001). No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2 (P<0.001). No significant correlations were observed between the MTX dose, dose-adjustment programs, or MTX concentrations and relapse-free survival. CONCLUSION: Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

Huai Qi Huang-induced Apoptosis via Down-regulating PRKCH and Inhibiting RAF/MEK/ERK Pathway in Ph+ Leukemia Cells.

Imatinib mesylate (IM) is the first-line treatment for Philadelphia (Ph) chromosomal positive leukemia by inhibiting phosphorylation of substrates via binding to the ABL kinase domain. Because of the drug resistance, side effects and the high cost of IM, it is necessary to find anti-cancer drugs with relatively low toxicity and cost, and enhanced efficacy, such as traditional Chinese medicines (TCMs). As one of TCMs, Huai Qi Huang (HQH) was chosen to treat BV173 and K562 cells. Various concentrations of HQH were added to cells for 24-72 h. Co-treatment of HQH and trametinib, an MEK inhibitor, was used to verify the synergistic effects on cell viability and apoptosis. Knockdown and overexpression of mitogen-activated protein kinase kinase 4 (MEK4) were implemented to demonstrate the role of MEK in cell apoptosis. Cell viability and apoptosis were measured by cell counting kit-8 assay (CCK8) and flow cytometry, respectively. Western blotting and real-time quantitative PCR (RT-qPCR) were used to assess protein and mRNA expression levels, respectively. The results showed that HQH inhibited survival and promoted apoptosis of BV173 and K562 cells in a dose-dependent manner, accompanied with down-regulation of PRKCH mRNA as well as CRAF, MEK4, phospho-ERK (pERK) and BCL2 proteins, and up-regulation of cleaved caspase3 protein. Co-treatment of HQH and trametinib had a synergistic effect on inhibiting survival and promoting apoptosis. MEK4 knockdown increased apoptosis, and had a synergistic effect with HQH. In contrast, MEK4 overexpression decreased apoptosis, and had the opposite effect with HQH. Collectively, the results of this study may identify a therapeutic mechanism of HQH on promoting apoptosis, and provide a potential option for treatment of Ph+ leukemia.