[The Mechanism of Artesunate Combined with Cytarabine and/or Daunorubicin on the Apoptosis of MV4-11 MLL-rearranged Acute Myeloid Leukemia Cell Line].

OBJECTIVE: To investigate the effect and mechanism of artesunate (ARTS) combined with cytarabine(Ara-C) and/or daunorubicin (DNR) on the proliferation and apoptosis of MV4-11 human mixed-lineage leukemia rearranged（MLL-r） acute myeloid leukemia (AML) cell line. METHODS: CCK-8 assay was used to detect the proliferation effect of individual or in combination of ARTS, DNR, Ara-C on MV4-11 cells. The IC50 of ARTS, DNR and Ara-C was calculated separately. The cell apoptosis and expression of receptors DR4 and DR5 were detected by flow cytometry. Western blot was used to detect the expression of Caspase-3 and Caspase-9 in each groups. RESULTS: The inhibition effect of ARTS, Ara-C and DNR on the proliferation of MV4-11 were all dose-dependently (r=0.99, 0.90 and 0.97, respectively). The IC50 of ARTS, Ara-C and DNR on MV4-11 for 48 hours were 0.31 µg/ml, 1.43 µmol/L and 22.47 nmol/L, respectively. At the dose of ARTS 0.3 µg/ml， Ara-C 1.0 µmol/L and DNR 15 nmol/L, the proliferation rate for 48 hours of the tri-combination treatment was significantly lower than that of the bi-combination treatment, while both were significantly lower than that of the individual treatment (all P＜0.05). In terms of bi-combination treatment, the cells proliferation rate for 48 hours of the ARTS+Ara-C group was significantly lower than that of the ARTS+DNR group, while both were significantly lower than that of the Ara-C+DNR group (all P＜0.05). The cooperativity index (CI) of bi- and tri-combination treatment were all less than 1. After 48 hours of drug action, the cell apoptosis rate of the ARTS+DNR+Ara-C group was significantly higher than that of the Ara-C+DNR group, while both were significantly higher than that of the ARTS+DNR group (all P＜0.05). Meanwhile, the was no statistical difference between the cells apoptotic rate of the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (P>0.05). The expression of DR4 and DR5 also showed no difference between control group and drug group. Compared with the DNR+Ara-C group, the expressions of Caspase-3 were significantly down-regulated in both the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (all P＜0.05). The down-regulation of Caspase-3 expression was the most significantly in the combination group of three drugs, while the Caspase-9 expressions in different groups showed no apparent change. CONCLUSION: The in vitro study showed that tri-combination of ARTS+Ara-C+DNR and bi-combination of ARTS+Ara-C could inhibit the proliferation and promote apoptosis of MV4-11 cell line. The inhibition effect of these two combinations were significantly superior to that of the traditional Ara-C+DNR treatment. The mechanism underlying this finding may be identified by the down regulation of Caspase-3, while no altered expression was observed of Caspase-9, DR4 and DR5.

A flow injection fluorescence "turn-on" sensor for the determination of metformin hydrochloride based on the inner filter effect of nitrogen-doped carbon dots/gold nanoparticles double-probe.

In this paper, an ultrasensitive and rapid "turn-on" fluorescence sensor, integrating flow-injection (FI) with nitrogen-doped carbon dots/gold nanoparticles (N-CDs/AuNPs) double-probe is established for the determination of metformin hydrochloride (MET) in biological fluids. The sensing strategy involves the weak inner filter effect between AuNPs and N-CDs due to aggregation products of MET with AuNPs. Unfortunately, the degree of AuNPs aggregation is difficult to control through manual assays, resulting in intolerable measurement error that limits further applications. However, the proposed method overcomes the above problem, and significantly lowers the consumption of expensive reagents (AuNPs: about 60 µL per test). Under optimal conditions, the fluorescence intensity at 400 nm excitation and 505 nm emission wavelengths display a linear correlation with MET concentration (5-100 µg L-1) and the limit of detection is 2.32 µg L-1 (3.3 S/k). The advantages of the presented method include high sensitivity, rapid speed (60 sample h-1), good accuracy and precision (RSD ≤ 2.1%, n = 11) and low cost. Since MET is the first-line hypoglycemic agent in patients with type II diabetes, this method can preliminarily determine MET content in urine samples, giving satisfactory results.

[Clinical Efficacy of R-EDOCH Protocol in the Treatment of Newly Diagnosed Double Expression Lymphoma].

OBJECTIVE: To investigate the clinical efficacy of R-EDOCH protocol in the treatment of newly diagnosed double expression lymphoma. METHODS: The clinical data of 51 patients with newly diagnosed double expression lymphoma treated by R-EDOCH protocol were retrospectively analyzed in the period from May 2012 to October 2017, then overall remission rate (ORR), disease control rate (DCR), progression-free survival (PFS) rate and total survival (OS) rate were evaluated; moreover the patients were grouped according to IPI score and whether accepting hematopoietic stem cell transplantation(HSCT) and the clinical efficacy was compared. RESULTS: The ORR was 96.08% (49/51) and DCR was 100.00% (51/51) in all patients. Six cases out of 51 patients (11.76%) relapsed and progressed during the followed-up. The followed-up showed that 2 year-PFS rate and OS rate were 84.31% (43/51) and 94.12% (48/51) respectively. The ORR, SD rate, 2 year-PFS rate and OS rate in the patients with IPI 0-2 and 3-5 scores were no statistically different(p>0.05); the 2 year-PFS and OS rates between patients in subgroup of IPI 0-2 and 3-5 scores also were not statistically different (p>0.05), no matter whether the patients received auto-HSCT or not. The comparison of 2 year-PFS and OS rates in auto-HSCT patients and non-auto-HSCT patients showed no statistical difference(p>0.05). CONCLUSION: The R-EDOCH protocol in treatment of newly diagnosed double expression lymphoma possess the good overall clinical efficacy, the combination of R-EDOCH with auto-HSCT displays ascending trend of PFS.

Increased BMR in overweight and obese patients with type 2 diabetes may result from an increased fat-free mass.

The study aimed to determine the relationships between the basal metabolic rate (BMR) and body composition of overweight and obese Chinese adults with type 2 diabetes mellitus (DM). This cross-sectional clinical study enrolled 193 Chinese adults with type 2 DM who were overweight (24 kg/m(2)=BMI≤28 kg/m(2), n=99), or obese (BMI ≥28 kg/m(2), n=94). Ninety-seven adults with normal BMIs, including 50 DM patients and 47 healthy adults, were recruited as a control group. BMR was measured by indirect calorimetry; predicted BMR was calculated according to the Schofield equation; and the relationships between BMR, body composition, and biochemical results were determined by the Pearson correlation. The results showed that obese DM patients had significantly higher BMRs than both overweight patients (P<0.05) and patients with normal BMI did (P<0.05). The measured BMR was significantly lower than the predicted BMR (P<0.05) in all groups. Obese and overweight DM patients had significantly greater weight, waist circumference, hip circumference, BMI, body surface area, body fat percentage, fat mass, and fat-free mass than patients with normal BMI. Except for waist circumference, these body composition measurements were significantly increased in obese DM patients when compared with those in overweight DM patients (P<0.05). Fat-free mass was closely correlated with BMR in both DM patients (r=0.874, P<0.01) and in healthy controls (r=0.902, P<0.01). It was concluded that overweight and obese Chinese adults with type 2 DM had increased BMRs compared with normal-weight controls, which may result from the difference in fat-free mass.

[Pathogenic Genes of A Hereditary Hemorrhagic Telangiectasia Pedigree].

OBJECTIVE: To identify the mutation of ENG and ALK1 genes in a hereditary hemorrhagic telangiectasia pedigree. METHODS: 14 exons of ENG gene and 9 exons of ALK1 gene in 11 menbers of this pedigree 4 generation were amplified by reverse transcription-polymerase chain reaction (RT-PCR), the PCR products were screened by direct sequencing. RESULTS: A nonsense mutation c.447G > A was found in exon 4 of ENG gen of the pedigreee, resulting in change of Trp 149 into Stop, while no gene mutation was found in ALK1 gene. CONCLUSION: The hereditary hemorrhagic telangiectasia in this pedigree is caused by the nonsense mutation c.447G > A in ENG gene.