: ]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL). METHODS: The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups. RESULTS: There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P＞0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037，0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770). CONCLUSION For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.
Anthracyclines ; Antineoplastic Combined Chemotherapy Protocols ; Humans ; Leukemia, Promyelocytic, Acute ; Remission Induction ; Retrospective Studies ; Treatment Outcome ; Tretinoin

OBJECTIVE: To explore the role of Ca-NFAT signaling pathway in Ph-ALL drug resistance mediated by bone marrow stromal cells. METHODS: The transcription level of NFAT mRNA in Sup-B15 cells and Ph ALL primary cells was detected by polymerase chain reaction. The expression of P-glycoprotein in Sup-B15 cells was detected by flow cytometry. The change of NFAT protein in Sup-B15 cells was detected by Western blot. AnnexinV/7-AAD was used to label cells. Flow cytometry was used to detect cell apoptosis; Fluo 3-AM dye was used to label cells, and flow cytometry used to detect changes of Ca concentration in leukemia cells. RESULTS NFAT expression could be detected in both Sup-B15 and Ph ALL primary cells; P-glycoprotein could not be detected by flow cytometry; CAS could significantly inhibit NFAT protein expression in clinically applied drug concentrations (2.5, 5 μmol/L); Clinically applied concentration of CAS (2.5, 5 μmol / L) has no significant effect on the apoptosis of Sup-B15 cells, while higher concentration of CAS (10 μmol / L) could induce apoptosis of Sup-B15 cells. Bone marrow stromal cells OP9 could, decrease the sensitivity of Sup-B15 cells and Ph ALL primary cells to imatinib (IM); After co-culture with bone were marrow stromal cells, the Ca concentration in Sup-B15 cells was enhanced, the levels of NFAT protein and nullear protein in sup-B15 cells also were enhanced. The addition of CAS in co-culture system could inlibit the Ca-NFAT signaling pathway, reduce the protective effect of OP9 on Sup-B15 cells.Conclution:The Ca-NFAT sigualing pathway, contributes to the survival of Ph ALL cells. Bone marrow stromal cells can mediate the resistance of Ph ALL cells to IM by activating Ca-NFAT signaling pathway.
Bone Marrow Cells ; Cell Line, Tumor ; Humans ; Imatinib Mesylate ; Mesenchymal Stem Cells ; NFATC Transcription Factors ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Signal Transduction

BACKGROUND: Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy. METHODS: A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis. RESULTS: The κ values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P < 0.001). CONCLUSIONS The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS1 equations and the CKD-EPI and BIS1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.
Aged, 80 and over ; Asian Continental Ancestry Group ; Creatinine ; blood ; Cystatin C ; blood ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Male ; Renal Insufficiency, Chronic ; blood ; physiopathology ; Uric Acid ; blood

OBJECTIVE: To investigate the relationship of cytogenetic features, clinical characteristics and prognosis in patients with myelodysplastic syndrome. METHODS: The clinical characteristics and prognosis of 236 patients with MDS admitted to the Affiliated Hospital of Xuzhou Medical University from January 2013 to September 2017 were analyzed retrospectively, the follow-up observation and correlation analysis were performed. RESULTS: There were 33 cases of refractory cytopenia with unilateral dysplasia (RCUD), 8 cases of refractory anemia with ring-shaped iron granulocytes (RARS), 70 cases of refractory cytopenia with multiple dysplasia (RCMD), 23 cases of refractory anemia (RA), 46 cases of refractory anemia with excessive blasts (RAEB-1), 48 cases of (RAEB-2), MDS-U 2 cases, simple del(5q) 6 cases. The detection analysis showed that the chromosome abnormality rate and complex chromosome abnormality rate in RAEB group (RAEB-1 + RAEB-2) and in non-RAEB group (RARS+RCMD+RCUD+RA) were 48.94% vs 43.94%, and 18.09% vs 12.69%, respectively, which were no statistically different. The grouping according to IPSS-R and IPSS showed that the chromosome abnormality rate gradually increased along with enhancement of risk stratifi-cation (P<0.05). The cytogenetic characteristics analysis showed that a total of 108 cases had chromosomal abnormalities, the detection rate was 45.76%, Out of 108 cases, 36 cases had complicated karyotypes, accounted for 15.25% of all patients. The types of chromosomal abnormalities mainly include numbers, structural abnormalities and mixed abnormalities. The chromosome abnormality with the highest detection rate was +8, accounted for 30.56% (33/100) of patients with chromosome abnormalities; followed by -7/7q-, del(5q), del(20q), etc. -7/7q-chromosome abnormalities accounted for 29.63% of all karyotypic abnormalities (including -7/7q-chromosome abnormalities alone and other chromosome abnormalities). The median age of the patients with MDS was 61 (13-88) years old, and the male-female ratio was 1.36∶1. Analysis of blood cell characteristics showed that the three lines were reduced or increased to varying degrees. The median WBC count was 2.8 (0.3-267.1)×10/L, the median Hb level was 69 (20-156) g/L, and the median Plt count was 55 (2-1733)×10/L. The 1 year OS rate in 32 cases of chromosome 7 abnormality and 128 cases of normal chromosome was 25% and 44.53%, respectively, the difference was statistically significant (χ=4.05, P<0.05) . CONCLUSION Chromosome karyotype is an independent factor affecting the prognosis of patients with MDS. It is important for the diagnosis, treatment and prognosis evalnation of patients with MDS. The overall prognosis of patients with abnormal chromosome 7 is poor. .
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Cytogenetics ; Female ; Humans ; Karyotyping ; Male ; Middle Aged ; Myelodysplastic Syndromes ; Prognosis ; Retrospective Studies ; Young Adult

A highly sensitive and selective bioluminescent probe for hydrazine (BPH) was designed, synthesized and evaluated for detection of hydrazine in vitro and in vivo. BPH was designed to include a specific recognition group (acetyl) of hydrazine at an appropriate modification site of the optical reporter hydroxyluciferin (D-luciferin), which showed excellent performance both in selectivity and sensitivity to hydrazine. The results showed that the bioluminescent probe BPH developed in this study is an innovative and widely applicable tool for detecting hydrazine in complex natural environment or in animals.

Objective: To observe the effect of Shenghuitang on learning and memory and expressions of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and cyclooxygenase-2(COX-2) in hippocampus of chronic sleep deprived mice, in order to explore the possible mechanism of Shenghuitang in improving learning and memory ability. Method: Mice were randomly divided into sleep deprivation group, blank group, melatonin group(7.8×10^-4 g·kg^-1·d^-1), high, middle and low-dose Shenghuitang groups(54,27,13.5 g·kg^-1·d^-1). The model of chronic sleep deprivation in mice was established using the "multi-platform water environment method". 28 d sleep deprivation and intragastric administration were provided. Morris water maze was used to detect the learning and memory ability of mice in each group. Real time-PCR was used to detect mRNA expressions of IL-6, TNF-α and COX-2 in the hippocampus of each group. Result: The results of Morris water maze test showed that compared with the blank group, the total time spent on finding the platform and the total swimming distance of the model group were significantly prolonged (P<0.01), while the number of crossing platforms and the target quadrant were significantly reduced (P<0.01). The time for the original platform was significantly increased (P<0.01). Compared with the model group, the total time spent on finding the platform and the total swimming distance decreased significantly in each drug-administered group (P<0.05,P<0.01) reduced, whereas the number of times for crossing the platform and the target quadrant increased significantly (P<0.05,P<0.01). The time for the first arrival of the original platform was significantly reduced (P<0.05,P<0.01). The results of RT-PCR showed that mRNA expressions of IL-6, TNF-α, and COX-2 were increased in the model group compared with the blank group. Compared with the model group, mRNA expressions of IL-6, TNF-α, and COX-2 were decreased in the treated group. COX-2 mRNA expression was down-regulated. Conclusion: Shenghuitang may improve the learning and memory ability of mice by decreasing mRNA expressions of IL-6, TNF-α and COX-2 in hippocampus.

Objective: To observe effect of Mori Folium-containing serum on glucose consumption and cell activity of fat cell line 3T3-L1 insulin resistance (IR) model, in order to screen out the optimal concentration of drug-containing serum, detect effect of Mori Folium on the content of inflammatory factors, and explore the possible mechanism. Method: 3T3-L1 preadipocytes in logarithmic growth phase were selected, and induced with 10 mg·L^-1 insulin (Ins), 0.25 mmol·L^-1 dexamethasone (DEX) and 0.5 mmol·L^-1 3-isobutyl-methylxanthine(IBMX) for 48 h and then with 10 mg·L^-1 Ins for 48 h. After the cells were differentiated into mature adipocytes, they were induced with 1 μmol·L^-1 DEX for 96 h to establish IR model. Glucose content in the supernatant of cells was detected by glucose oxidase after serum containing Mori Folium cultured for 12,24,36, 72 h. Methyl-thiazdyl-tetrazolium(MTT) was used to detect the effect of serum containing Mori Folium on IR cells activity. The content of tumor necrosis factor-α(TNF-α) was determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the effects of inflammatory factors on the expressions of insulin signaling pathway proteins insulin receptor (InsR), insulin receptor substrate (IRS), p-IRS1 and glucose transporter 4 (GLUT4) were determined by Western blot. Result: Serum containing Mori Folium could significantly increase the glucose consumption rate and cell activity of IR cells (P<0.01), reduce the content of TNF-α (P<0.01), and regulate the expression of insulin signaling pathway proteins (P<0.05,P<0.01). Conclusion: Mori Folium can significantly improve IR status of 3T3-L1 cells, and its mechanism may be related to inhibiting TNF-α and promoting the expressions of insulin signaling pathway proteins.

Objective:To investigate the effect of Shenghuitang on learning and memory, biological clock gene[brain and muscle arnt-like 1 (Bmal1)] in hypothalamus and interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in hippocampus of APP/PS1 double transgenic dementia model mice, in order to explore the possible mechanism of Shenghuitang to improve learning and memory and sleep disorders. Method:The experimental mice were randomly divided into model group, blank control group, melatonin group, high-dose Shenghuitang group and low-dose Shenghuitang group. Autonomic activity analysis system was used to detect the autonomic activities of mice in each group. Morris water maze was used to detect the learning ability and spatial memory ability of each group. quantitative real-time fluorescence polymerase chain reaction(Real-time PCR) was used to detect the expression of Bmal1 mRNA in the hypothalamic area of mice. Western blot was used to detect the expression of Bmal1 protein in each group. The content of inflammatory factors IL-6 and TNF-α in hippocampus of mice was detected by enzyme-linked immunosorbent assay(ELISA). The correlation between inflammatory factors IL-6, TNF-α and Bmal1 gene was analyzed by pearson analysis. Result:The results of voluntary activities showed that compared with the control group, the number of activities and activity distance of the model group were significantly decreased (P<0.01). Compared with the model group, the number of activities and activity distance of the mice in each drug group increased significantly (P<0.05, P<0.01), there was no significant difference in the low dose group of Shenghuitang. Morris water maze results showed that compared with the control group, the platform latency and swimming total distance were significantly prolonged in the model group (P<0.01), and the number of crossing platforms and target quadrant time was significantly reduced (P<0.01). The original platform time increased significantly (P<0.05). Compared with the model group, the platform latency and total swimming distance were significantly decreased in each group (P<0.05, P<0.01), and the number of crossing platforms and target quadrant time increased significantly(P<0.05, P<0.01), the time to the original platform was significantly reduced (P<0.05, P<0.01). Real-time PCR results showed that the expression of Bmal1 mRNA was up-regulated in the model group compared with the control group. Compared with the model group, the mRNA expression of Bmal1 gene was down-regulated in each group. Western blot results showed that compared with the control group, the expression of Bmal1 protein in the model group was significantly increased (P<0.01). Compared with the model group, Bmal1 protein expression was significantly decreased in each group(P<0.01). The results of ELISA showed that the levels of IL-6 and TNF-α in the model group were significantly higher than those in the control group (P<0.01). Compared with the model group, the levels of IL-6 and TNF-α in the drug group were significantly lower(P<0.01). Pearson analysis showed that IL-6, TNF-α and Bmal1 were correlated and negatively correlated. Conclusion:Shenghuitang may reduce the levels of inflammatory factors IL-6 and TNF-α in hippocampus by up-regulating the expression of Bmal1 gene in hypothalamic region, thus improving Alzheimer' s disease(AD) and circadian rhythm disorders.

Objective:To explore the hepatoprotective effect and its mechanism of the geraniin on mice with acute liver injury induced by D-galactosamine (D-GalN). Method:A total of 60 Kunming mice were randomly divided into normal group, model group, Silymarin group (positive group 180 mg·kg^-1), and low, medium and high-dose geraniin groups (50, 100, 200 mg·kg^-1). All the mice were given with saline or corresponding dose of drugs (10 mL·kg^-1) by gavage once a day for 10 d. After 2 h of the last administration, except the normal group, the mice of other groups were injected intraperitoneally with D-GalN (500 mg·kg^-1) to induce the acute liver injury. After 16 h, the eye balls of mice were removed to take blood, and all mice were put to death to collect samples of liver. Activity or content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in liver were determined by biochemical method. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-interferon (IFN-γ) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA), and expressions of Toll-like receptor-4(TLR-4) and nuclear factor(NF)-κB proteins were detected by Western blot. Liver histopathological changes were observed by hematoxylin-eosin (HE) staining. Result:Compared with the normal group, the serum levels of ALT, AST, ALP, TBIL and liver MDA in the model group were significantly increased (P<0.05, P<0.01). Compared with the model group, geraniin can reduce activities or contents of ALT, AST, ALP, TBIL in serum and MDA in liver of mice (P<0.05, P<0.01), but increase activities of T-SOD and GSH-Px in liver (P<0.05,P<0.01), while inhibiting the contents of TNF-α, IL-1β, IL-6, IFN-γ and the expressions of TLR-4 and NF-κB proteins in serum (P<0.05,P<0.01). HE staining showed that acute liver injury of mice was alleviated obviously by geraniin. Conclusion:Geraniin has an obvious protective effective on acute liver injuries induced by D-GalN in mice. Its mechanism may be correlated with oxidative stress, inflammation and TLR-4/NF-κB signaling pathway.

Objective To observe the skin irritation and anaphylaxis of the liquid bandage to facilitate its safety evaluation. Methods In case of skin irritation test,some New Zealand rabbits were divided into an unaffected skin group and an affected skin group, and had their skin observed for erythema, edema and etc after undergoing 1-d and 7-d administration respectively;in case of anaphylaxis,the guinea pigs went through drug sensitization respectively at the 1st,7th and 14th days and experienced re-sensitization 14 days after,and the symptoms of anaphylaxis were observed such as erythema and edema. Results The liquid bandage had no irritation to the unaffected and affected skin of New Zealand rabbit by single or multiple administration with the irritation mean value being lower than 0.5.There were no anaphylaxis symptoms such as erthema and edema found in the guinea pig by the liquid bandage.Conclusion The liquid bandage proves its skin safety by non-irritation to the unaffected and affected skin of New Zealand rabbit and non-anaphylaxis to the guinea pig.