To observe the effects of sera containing Liuwei Dihuang Pill (LDP), a compound traditional Chinese herbal medicine, and its monomer catalpol on transforming growth factor-β1 (TGF-β1)/Smad pathway in HK-2 cells.

Objective:To study whether Noxa mediates cell death induced by etoposide in the human neuroblastoma(NB)cells.Methods:NB cells(TB3 and TB8) were treated with different concentrations of etoposide(0, 0.125, 0.25, 0.5 0.75, 1.0 mg/L), and the cell survival was detected by CCK8 assay.After treated with etoposide, NB cells were collected at different time points, then total RNAs were isolated and RT-qPCR was performed to detect the mRNA expression of Noxa.At the same time, the whole cell lysates were extracted and western blot was performed to detect the protein expression of Noxa.In order to evaluated the effect of Noxa on etoposide-induced cell survival, Noxa siRNA was transfected into NB cells, then CCK8 assay was performed.Results:After treatment with different concentrations of etoposide(0.125 mg/L、0.25 mg/L、0.5 mg/L、0.75 mg/L、1.0 mg/L ), the survival rates of TB3 cells were(73.13±8.45)%, (56.18±10.50)%, (33.90±4.17)%, (26.76±6.67)%, (13.49±0.58)%, respectively(compared with the control group, P<0.01); the survival rates of TB8 cells were(71.06±6.96)%, (37.45±0.68)%, (25.53±3.70)%, (20.28±2.75)%, (10.09±2.52)%, respectively(compared with the control group, P<0.01).The mRNA and protein expression of Noxa in NB cells were both increased in a time-dependent manner after treated with etoposide.The siRNA of Noxa could reduce the expression of Noxa in TB3 and TB8 cells after transfection.Treated with etoposide 0.5 mg/L, cell survival rates of TB3 cells tranfected with control siRNA, Noxa siRNA1, Noxa siRNA2 were(45.12±13.58)%, (72.70±21.34)%, (52.08±20.36)%, respectively; cell survival rates of TB8 were(35.52±0.38)%, (63.94±0.10)%, (50.27±1.62)%, respectively(compared with the control group, P<0.01); Treated with etoposide 1.0 mg/L, cell survival rates of TB3 cells tranfected with control siRNA, Noxa siRNA1, Noxa siRNA2 were(13.26±1.84)%, (51.08±2.41)%, (42.80±1.42)%, respectively(compared with the control group, P<0.05); cell survival rates of TB8 were(22.22±3.39)%, (58.00±11.37)%, (40.55±6.94)%, respectively(compared with the control group, P<0.05). Conclusion:Pro-apoptotic molecular Noxa mediated the Etoposide-induced cell death in NB cells(TB3 and TB8) in time and concentration-dependent manner.

Leukemia inhibitory factor (LIF) plays important roles in varieties of biological processes. This factor is highly conserved in mammalian animals and only one heterozygous LIF mutation was reported to cause the infertility of women. A LIF mutation was generated and the evidences were provided that the mutation of mature LIF at the 29th amino acid totally abolished its functions, including stimulation of STAT activation assayed by Luciferase reporter gene expression and EMSA experiments. In addition, the mutated LIF failed to inhibit the proliferation of M1 cells. The data indicated that the mutation of LIF did not have a dominant negative effect but lost the biological functions, suggesting that the 29th amino acid is critical for maintaining the activities of LIF.

AIM To evaluate the integration method for analysis of voltage-dependent Ca2+-independent transient outward K+ currents (Ito) in pharmacology. METHODSThe inactivation phases of Ito were best fitted by the sum of two or three exponentials equations. The area under the raw current curves (AUC) was obtained by the integration of exponential equations. The AUC normalized to the cell capacitance represented the net K+ charge flow during any depolarized duration and was as the index for comparison. Calcineurin overexpression transgenic (TG) mice showed downregulation of Ito. These data were tested by the integration method. RESULTS AUC obtained from three or two exponentials fittings was calculated as: AUC=A1τ1+A2τ2+A3τ3+A0t-A1τ1e-t/τ1-A2τ2e-t/τ2-A3τ3e-t/τ3 or AUC=A1τ1+A2τ2+A0t-A1τ1e-t/τ1-A2τ2e-t/τ2. The 50% and 90% action potential duration (APD50, APD90) in ventricular myocytes of mice are about 10 ms and 30 ms, respectively. AUC at 10 ms (AUC50, AUC of 50% APD) and 30 ms (AUC90, AUC of 90% APD) in left ventricle cardiomyocytes of wild type (WT) and TG mice were normalized to the cell capacitance. The normalized AUC50 and AUC90 of WT group were significantly more than those of TG group, which was consistent to the prolongation of APD in TG mice and the previous published results(downregulation of components of Ito in TG mice). CONCLUSION The integration method was an ideal way for analysis of transient outward K+ currents in pharmacology.

Background and purpose: Natural killer/T-cell lymphoma (NKTCL) is a scarce subtype of malignant lymphoma, and it has heterogeneous clinical manifestation and treatment effect. Currently, no precise risk stratification is used to guide prognosis. This study aimed to evaluate the prognostic impact of pre-treatment peripheral blood absolute monocyte count (AMC) and platelet-lymphocyte ratio (PLR) in patients with primary nasal NKTCL, and provide more precise information for better risk stratification to select appropriate treatment and improve survival. Methods: Clinical data of 132 patients newly diagnosed with primary nasal NKTCL was collected in the Tianjin Medical University Cancer Institute and Hospital from Jan. 2008 to Dec. 2013. The relationship between AMC and PLR in pre-treatment peripheral blood and 5-year overall survival (OS) and progression-free survival (PFS) of patients was analyzed retrospectively. Independent prognostic factors of patients were determined by univariate analysis and Cox regression analysis. Results: Pre-treatment peripheral blood AMC and PLR play important roles in the prognosis stratification of patients with primary nasal NKTCL. The prognosis in patients of AMC<0.5×109/L were higher than those of AMC≥0.5×109/L, The prognosis in patients of PLR<150 were higher than those of PLR≥150 (P<0.05). Based on the four independent risk factors of staging, ECOG scoring, AMC and PLR, we tried to establish a new prognostic model, dividing all patients into three different risk groups and found that the 5-year OS and PFS of three groups had significant statistical differences. Conclusion: Peripheral blood AMC and PLR were significantly correlated with the prognosis of patients with primary nasal NKTCL. The new prognostic patterns based on the four independent risk factors, such as staging, ECOG scoring, AMC and PLR may be more convenient and more economical than IPI (International Prognostic Index, IPI) and KPI (Korean Prognostic Index, KPI).

OBJECTIVETo evaluate the efficacy of HLA- haploidentical donor hematopoietic transplantation (Haplo- HSCT)for severe aplastic anemia (SAA)by compared with the same period of unrelated donor transplantation (UD- HSCT).

METHODSOf a cohort of 50 SAA patients between September 2012 and July 2014, 26 patients underwent UD- HSCT and 24 patients Haplo- HSCT.

RESULTSOS rate was 91.3% with a median follow-up of 9 (2-26)months. According to transplant type, there was no significant difference between UD- and Haplo-HSCT (96.1%vs 86.0%,P=0.30). 3 of 50 (6%)patients had primary engraft failure. Haplo- HSCT developed higher significantly incidence of Ⅱ- Ⅳ aGVHD (37.5%vs 3.83%,P=0.003)and cGVHD (37.5%vs 15.3%,P=0.030)than UD-HSCT. Haplo-HSCT also had significantly higher incidences of CMV viremia (78.2%vs 46.1%,P=0.005)and EBV viremia (43.1%vs 16.0%,P=0.040), respectively than UD-HSCT. But the incidences of hemorrhagic cystitis were similar between two transplant types (39.1%vs 23.0%,P=0.120).

CONCLUSIONThis study showed favorable outcome of Haplo-HSCT for SAA, which was comparable with UD-HSCT.

Objective To evaluate the application of TeamSTEPPS in training of community osteoporosis management team .Methods The TeamSTEPPS was applied for training of osteoporosis management team, and 1 513 residents aged ≥45 year were screened for osteoporosis in Kangjian community from January 2014 to March 2017.The identified patients with osteopenia and osteoporosis were intervened for one year.Cognitive level of the risk factors and symptoms associated with osteoporosis were assessed by questionnaires before and after the intervention .The bone density was examined at baseline and 6 months, 12 months after intervention.The effect of intervention was evaluated .Results A total of 467 patients (30.87%) with osteopenia and 476 patients (31.46%) with osteoporosis were detected .The cognitive levels of osteoporosis risk factors , including low calcium, vitamin D deficiency, lack of exercise, low weight, women menopause, matrilineal family history, smoking, excessive alcohol drinking and coffee drinking, were higher than those before intervention ( χ2＝62.909,78.742,59.974,50.478,29.512, 34.699,6.500,15.779,6.089,all P＜0.05).The awareness rates of symptoms , including lower back pain or body bone pain, shorter height and hunchback , low energy or nonviolent fracture , were also increased (χ2＝59.942,76.220,16.856,all P＜0.01).After intervention, the bone mineral density levels were increased compared to those before intervention (F＝530.28, P＜0.01 for osteopenia group; F＝339.51, P＜0.01 for osteoporosis group ); meanwhile, the differences were also significant between 6 months, 12 months after intervention and before intervention , between 12 months and 6 months after intervention (t＝-0.452,-0.968,-0.516,all P＜0.01 for osteopenia group; t＝-0.530,-1.045,-0.518, all P＜0.01 for osteoporosis group ).Conclusion The community osteoporosis management team trained by TeamSTEPPS can effectively improve the management levels of osteoporosis among residents in the community.

One hundred and fifty diabetic patients,who received management by community family doctors and hospital consortium (1+1+1) team for at least 1 year,were enrolled from January 2017 to May 2017.After that they continued to receive the management for 1 more year by the team which were trained with TeamSTEPPS (team strategies and tools to enhance performance and patient safety).The management effect before and after TeamSTEPPS training was compared.After the TeamSTEPPS training,the team management ability was improved,so that the compliance of diabetic patients with medical advice,regular examination of blood glucose,regular follow-up assessment,health education,regular exercise and diet control were all better than before,and the differences were statistically significant (all P＜0.01).Fasting blood glucose,postprandial 2 h-blood glucose,glycosylated hemoglobin and LDL-C levels were all lower than before,and the achieved rate of the above indicators were also increased (P＜0.05).It is suggested that application of TeamSTEPPS in team training can effectively enhance the management ability for chronic disease of family doctors and improve compliance and clinical indicators of patients with diabetes under management.

Objective: To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR₁-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR₁-AML. Methods: Between April 2012 and March 2015, consecutive 186 patients with CR₁-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive. Results: ①Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . ② With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95%CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95%CI 50.6%-75.2%) vs 88.9% (95%CI 76.6%-100.0%) , P<0.001], higher relapse[11.4% (95%CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P=0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P=0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P=0.004]. ③Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [HR=4.565 (95%CI 2.918-9.482) , P<0.001], relapse [HR=5.854 (95%CI 1.538-22.288) , P=0.010] and NRM [HR=3.379 (95%CI 1.361-8.391) , P=0.009] after allo-HSCT in CR₁-AML. Conclusion MRD positive pre-conditioning was the only negative impact factor for patients with CR₁-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR₁-AML after allo-HSCT.

Objective: To investigate three different types of donor hematopoietic stem cell transplantation (HSCT) for intermediate and high-risk myelodysplastic syndrome (MDS) . Methods: Between August 2001 and May 2015, 167 consecutive patients with MDS in intermediate and high-risk who underwent allogeneic HSCT were analyzed retrospectively. Results: With the median follow up of 60 (12-177) months, The total 5-year DFS was 67.8% (95%CI 60.0%-75.6%) . Among three different types of donor, 5-year DFS rates were 68.0% (95%CI 54.1%-81.9%) in MSD-HSCT vs 77.4% (95%CI 62.1%-92.7%) in MUD-HSCT vs 64.0% (95% CI 52.4%-75.6%) in Haplo-HSCT (P=0.632) , respectively. Univariate analysis showed that median disease course before HSCT was the influencing factor of DFS (P=0.018) . Five-year relapse and TRM had no correlation with the above-mentioned factor. Conclusions Haplo-HSCT for intermediate and high-risk MDS achieved similar effect produced by MUD or MSD, Haplo-HSCT could be used as an important alternative donor. allo-HSCT must be performed on intermediate and high-risk MDS patients as early as possible after diagnosis.