OBJECTIVETo evaluate and compare the clinical efficacy and safety of recombinant human thrombopoietin(rhTPO) and recombinant human interleukin11(rhIL-11) for the treatment of chemotherapy-induced thrombocytopenia in adult acute myeloid leukaemia patients.

METHODSTotal of 96 adult acute myeloid leukaemia patients were divided into 3 groups according to randomized controlled method: rhTPO group, rhIL-11 group and control group, 32 cases in each group. The patients in rhTPO group and rhIL-11 received rhTPO of 15000 IU/d and rhIL-11 of 1.5 mg/d, respectively after the standard combined chemotherapy within 24 hours, and patients in control group, received nothing drugs to promote thrombocyte recovery. And rhTPO and rhIL-11 should be stopped when the Plt≥100× 10/L. After chemotherapy, the platelet recovery degree, duration of Plt<50× 10/L, ≥50× 10/L and ≥100× 10/L, the count of infusion thrombocytes, and incidence of adverse reactions all were compared.

RESULTSThe duration of Plt<50× 10/L was obviously less than that in control group(P<0.01). The duration of rhIL-11 was less than that in control group, but there was no statistical significance(P>0.05). As compared with that in control group, the Plt count in rhTPO and rhIL-11 groups can faster increase to Plt≥50× 10/L (P<0.01, P<0.05), among them the Plt count in rhTPO group faster increase, but there was no statistical signiticance. As compared with that in control group, the Plt count in rhTPO group and rhIL-11 group can increase to Plt≥100× 10/L (P<0.01), the Plt count in rhTPO group was more obviously increase than that in rhIL-11 group(P<0.05). The count of infusion Plt in rhTPO and rhIL-11 groups was lese than that in control group(P<0.01, P<0.05), and the count of infusion Plt in rhTPO group was less than that in rhIL-11 group(P<0.05). After using rhTPO and rhIL-11, the adverse reactions, such as low fever, induration of injection site, athralgia, nausea and vomiting occured in rhTPO group and rhIL-11 group, but all can be tolerated.

CONCLUSIONBoth rhTPO and rhIL-11 can reduce the duration of thrombocytopenia and the amount of infused thrombocyte, promote platelet recovery in the patients with acute myeloid leukaemia after chemotherapy, to decreae the risk of bleeding, and reduce incidence of adverse reactions, both of them can be tolerated by patients, and rhTPO is more advantage than rhIL-11, worthy of clinical popularization and application.

PURPOSE: Insufficient sensitivity and specificity prevent the use of most existing biomarkers for early detection of breast cancer. Recently, it was reported that serum microRNAs (miRNAs) may be potential biomarkers in many cancer diseases. In this study, we investigated whether serum levels of 5 miRNAs including miR-21, miR-125b, miR-145, miR-155, and miR-365 could discriminate breast cancer patients and healthy controls. METHODS: Serum levels of miRNAs were measured by using quantitative real-time polymerase chain reaction in 99 breast cancer patients and 21 healthy controls. The abundance change of serum miRNAs were also evaluated following surgical resection in 20 breast cancer patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the sensitivity and specificity of miRNAs as diagnostic biomarkers. RESULTS: Serum levels of miR-21 and miR-155 was significantly higher, while miR-365 was significantly lower in breast cancer as compared with healthy controls. The serum levels of miR-21 and miR-155 significantly decreased following surgical resection. Additionally, the serum level of miR-155 at stages I and II was significantly higher compared to stage III. The serum miR-145 level was remarkably higher in progesterone receptor (PR)-positive patients than PR-negative. The positivity of miR-21, miR-155, and miR-365 was high compared to CA 153 and CEA in breast cancer. ROC curve analyses of a combination of miR-21, miR-155, and miR-365 yielded much higher area under curve and enhanced sensitivity and specificity in comparison to each miRNA alone. CONCLUSION: The combination of serum miR-21/miR-155/miR-365 may potentially serve as a sensitive and specific biomarker that enables differentiation of breast cancer from healthy controls.
Area Under Curve ; Biomarkers ; Breast Neoplasms* ; Breast* ; Humans ; MicroRNAs ; Real-Time Polymerase Chain Reaction ; Receptors, Progesterone ; ROC Curve ; Sensitivity and Specificity

To establish a method for the determination of coagulation activity in vitro by using fibrinogen plate method. The extraction route of compound Huanghuai was optimized by selecting thrombin as the reference substance. The comprehensive score of extract yield and the extraction transfer rate of baicalin and rutin was set as the dependent variable, with alcohol concentration, solvent volume and extraction time as the influence factors in central composite design for quadratic fitting, and the extraction process of compound Huanghuai was optimized by using response surface methodology. The results of thrombin concentration and precipitation zone area showed a good linear relationship in 0.4-16 U•mL⁻¹, r=0.997 5. The average recovery rate was 103.8% and the RSD was 4.7 %. The circle of precipitation area of compound Huanghuai combined extract was 38.81 mm², which was bigger than that of fractionated extract. The activity on the daily amount of compound Huanghuai extract was 84.28 U; and the optimum extraction technology was as follows: alcohol concentration 40%, extracted 3 times, the liquid-solid ratio 6∶1, and extraction time 2 h. The predicted value of comprehensive score was 94.26 and the measured value was 88.34, respectively, with a relative deviation of 6.28%. The coagulation activity of the intermediate obtained by optimal extraction process was better. So the method established in this paper was simple, fast and accurate for determination of coagulation activity of compound Huanhuai, which can be also used for the screening of follow-up process and quality control.

OBJECTIVETo analyze the subtype and functional biomarker expression changes of natural kill cells(NK) in peripheral blood of patients with myelodysplastic syndrome(MDS) and normal people, so as to evaluate the relationships between these changes and hematopoietic functions and to explore the role of NK cells in the pathogenesis of MDS.

METHODSThe quantity of NK cells and the expression of biomarkers(NKp30,NKp46,NKG2A) on NK cells were detected by flow cytometry in 35 MDS patients from 2015 to 2016 in our hospital and 34 normal controls. The correlation between these changes and hematopoietic functions, including the percentages of neutrophil(ANC), hemoglobin in peripheral blood and the hematopoietic function in bone marrow(CD34%) were evaluated.

RESULTSThe percentage and quantity of NK cells and CD56NK cells in MDS patients were significantly lower than those in normal controls(P<0.05); the percentage of CD56NK cells was higher than that in controls. The percentage of CD56NK cells in NK cells of MDS patients was significantly lower than that of controls; the percentage of CD56NK cells in NK cells of MDS patients was significantly higher than that of controls. The expression of NKp30 and NKp46 of MDS patients was significantly lower than that of controls. In MDS group, the percentage of NK cells and CD56NK cells of peripheral blood lymphocytes in high risk MDS group was significantly lower than that in low risk MDS group. The percentage of NK and CD56NK cells negatively correlated with that of CD34% in bone marrow, but positively correlated with ANC and Hb. The CD34% in bone marrow negatively correlated with expression of NKp46, but positively correlated with expression of NKG2A.

CONCLUSIONThe decrease of NK number and function may cause the immune surveillance and lead to disease progression.

To evaluate the effect of Chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque. Eight SIV rhesus macaques of the same age were randomly divided into Chinese medicine of invigorating spleen and kidney detoxification group(hereinafter referred to as Chinese medicine group) and anti-virus drug(HAART) group. The traditional Chinese medicine and antiviral therapy were given for 8 weeks, and peripheral blood was collected for detection in every 4 weeks. The results showed that Chinese medicine of invigorating spleen and kidney detoxification could not obviously decrease plasma viral load as HAART, but it can increase CD4 number in peripheral blood, especially the CD4 naive cells, and increase the number of CD4 and CD8 cells, enhance the immune response to pathogens. Therefore, it delayed the occurrence and development of spleen deficiency to a certain extent, indicating that the medicine had immune regulation effect, with considerable clinical value and application prospects.

To establish HPLC-MS/MS method for simultaneous determination of daphnetin, daphnoretin, and daphneticin in rat plasma after oral and intravenous administration of Daphne giraldii extract, and then use them in the calculation of pharmacokinetic parameters. Six sprague-dawley rats received intragastric administration of D. giraldii extract (daphnetin, daphnoretin and daphneticin were 88.40, 3.24 and 4.28 mg•kg⁻¹, respectively). Their drug plasma concentration was determined by LC-MS/MS with schisandrin as an internal standard to draw plasma concentration-time curve. The pharmacokinetic parameters were calculated by Kinetica 4.4. The results showed that the linear range was 5-1 000 μg•L⁻¹ for daphnetin, daphnoretin and daphneticin, and the method ological test showed conformance to the requirements.The intraday and inter-day variable coefficients (RSD) were both less than 15.0%, indicating that both of legitimate precise and accuracy were consistent with the analysis requirements of biological samples. For daphnetin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 4 h, 858.96 μg•L⁻¹, 10 566.4 μg•L⁻¹•h, 5.19 h and 9.43 h, respectively. For daphnoretin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2.92 h, 178.00 μg•L⁻¹, 905.89 μg•L⁻¹•h, 3.50 h and 6.95 h, respectively. For daphneticin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2 h, 36.67 μg•L⁻¹, 355.11 μg•L⁻¹•h, 4.95 h and 8.27 h, respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of daphnetin, daphnoretin and daphneticin.

Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.

OBJECTIVETo compare clinical outcomes of external and posterior malleolar fractures associated with compressive articular surface through posteriorlateral incision and posteriormedial incision.

METHODSFrom January 2012 to January 2015, 52 patients with external and posterior malleolar fractures associated with compressive articular surface were treated by interfix. Among them, 24 patients were treated through posteriourlateral incision, including 16 males and 8 females, aged from 20 to 65 years old with an average of(35.2±6.4);28 patients were treated through posteromedi and posterior lateral incision, including 18 males and 10 females, aged from 22 to 62 years old with an average of(36.4±4.8). Operation time, blood loss, length of incision, times of X-ray exposure and complications between two groups were recorded and compared, AOFAS scores were applied for evaluate clinical outcomes.

RESULTSAll patients were followed up, group A were followed up from 13 to 55 months with an average of (27.5±2.5) months;group B were followed up from 12 to 54 months with an average of (28.5±2.4) months. All fractures were obtained good reduction, and the healing time ranged from 10 to 16 weeks with an average of 12 weeks. Two patients in group B occurred incision infection, and 1 patient occurred screw loosening; while no incision infection occurred in group A, and 1 patient occurred screw loosening. There were statistical significance in operation time, blood loss, times of X-ray exposure and complications between two group;while no significant difference in ankle AOFAS score between two groups.

CONCLUSIONSCompared with reduction through achilles tendon, reduction for external and posterior malleolar fractures combined with compressive articular surface through tibiafibular fractures region has advantages of less blood loss, shorter operation time, less times of X-ray exposure, good recovery of ankle joint function, especially in treating external and posterior malleolar combined with compressive articular surface which could not obtained good reduction through normal pathway.

To study sesquiterpenes with anti-metastasis breast cancer activity from Chloranthus henryi, ten sesquiterpenes ,zedoarofuran (1), chlorajapolide D (2), 4β, 8β-dihydroxy-5α(H)-eudesm-7(11)-en-8, 12-olide (3), curcolonol (4), lasianthuslactone A (5), chlomultin C (6), (1E,4Z)-8-hydroxy-6-oxogermacra-1(10), 4, 7(11) -trieno-12, 8-lactone (7), shizukanolide E (8) , shizukanolide F (9) , 9α-hydroxycurcolonol (10), and five bis-sesquiterpenes, shizukaol B (11), shizukaol C (12) , cycloshizukaol A (13) , sarcandrolide B (14) , henriol A(15), were isolated by using different kinds of column chromatography methods from the ethyl acetate part of Ch.henryi and their structures were identified based on spectroscopic methods. Compounds 2, 8, 9, and 10 were obtained from the genus Chloranthus for the first time. Compounds 2, 5, 8-10, 12,and 14 were obtained from this plant for the first time. Some isolated compounds were subjected to evaluate the anti-metastasis breast cancer activity by using pharmacological methods, and only compounds 4, 11, and 12 were potent active.