Objective To study the clinical monitoring of tacrolimus (FK506) area under the curve (AUC) of concentration-time after the first oral dose in kidney transplant recipients. Methods Sixteen kidney transplant recipients were treated with anti-lymphocyte globulin (ALG) and methyprednisolone (MP) for 3 days after operation.Then FK506 capsules were given orally at the same dose,0.075 mg/kg,on the third day.The pharmacokinetic monitoring of FK506 were conducted as follows.FK506 concentrations were measured by ELISA at 0.5,1.0,1.5,2.0,3.0,5.0,8.0,12.0 hours after the first oral dose. The data of FK506 pharmacokinetics were calculated using 3P87 pharmacokinetic procedures and SPSS 8.0. Results AUC of concentration-time of the first dose ranged from 44.40 ?g?h -1 ?L -1 to 158.01 ?g?h -1 ?L -1 (mean, 92.23?34.97 ?g?h -1 ?L -1 ). The correlation between the first tacrolimus trough concentration (C min ) and AUC had statistic significance ( r=0.650,P

Objective To investigate the incidence,characteristics and risk factors of cognitive impairment in patients with transient ischemic attack(TI A) or minor stroke.Methods Montreal cognitive assessment(MoCA) was carried out in 279 patients with TIA or minor stroke and 150 healthy controls to assess their cognitive function.Results (1) Compared with the healthy controls,the TIA/minor stroke patients scored significantly lower on MoCA total score((23.98±2.55) vs (26.60±0.99),t=12.084,P＜0.01) and subtests including visuoexecutive function((3.68±0.94) vs (4.41±0.64),t=8.483,P＜0.01),digital span ((1.81±0.40) vs (1.95±0.23),t=3.771,P＜0.01),attention((0.84±0.37) vs (0.95±0.23),t=3.357,P＜ 0.01),repetition((1.59±0.62) vs (1.89±0.37),t=5.496,P＜0.01),verbal fluency((0.88±0.33) vs (0.95 ± ±0.23),t=2.286,P＜0.05),abstraction((1.55±0.64) vs (1.91±0.34),t=6.357,P＜0.01) and recall ((2.87±1.13) vs (3.18±0.41),t=3.281,P＜0.01) were significantly decreased.(2) Of 279 TIA/Minor stroke patients,213 (76.3％) suffered from cognitive impairment.The incidence of cognitive impairment was positively correlated with the gender,age,educational level,smoking,course,leukoaraiosis,comorbidities such as hypertension,diabetes mellitus(P＜0.05),and negatively correlated with hyperlipidemia(P＞0.05).Conclusion Extensive impairments of cognitive functions occur along with the incidence of TIA or minor stroke.It is thus suggested that cognitive assessment and interventions may be carried out at an early stage.

Objective:To evaluate the effectiveness and safety of using apatinib in the treatment of refractory triple-negative advanced breast cancer. Methods:Eight cases of advanced triple-negative breast cancer patients confirmed via histopathology, who were previously treated with anthracycline, taxane, gemcitabine, capecitabine, and 500 mg/d apatinib in our hospital from July 2015 to November 2016, were retrospectively analyzed. The time of disease progress, effective rate, clinical benefits, and side effects were observed. Results:Eight patients were administrated with an average of 4 treatment cycles, and the effects were evaluated after 2 weeks. Four patients exhibited partial remission, 3 had a stable disease, and 1 had a progressive disease. The disease control rate was 87.5%, and the median progression free survival was 4.2 months. The main side effects were hand-foot syndrome (3/8), bone marrow arrest (4/8), hypertension (2/8), proteinuria (3/8), hemoptysis (1/8), nausea (2/8), and fatigue (2/8). Most of these side effects were tolerable. Conclusion:Apatinib can effectively and tolerably prolong survival time and improve the quality of life of patients with advanced triple-negative breast cancer.

0.05).However,the effect on decreasing mean yearly incidence of RRTI and duration of each onset in group A was superior to that in group B(P0.05).【Conclusion】JY can reduce the mean yearly incidence of RRTI and duration of each onset in preschool children with RRTI,and its mechanism may be related to the regualtion of cellular immune function by improving the parameters of subgroups of T lymphocytes.

Objective to investigate therapeutic methods and effect of X-knife for on intracranial diseases. Method Recent effect of 44pqtients with cranial diseases by X-knife was observed. Radiological follow-up was performed on 40 cases with mean 5.65 months of followup time. Result 92.5% of tumors were controlled locally, stability and recovery rate was 90.0%. The local control of metastatic tumors of brain was higher, but most patients with metastatic tumors died of primary lesion. New metastatic lesions appeared in patients without panencephalic radiotherapy in 1～5months. Tumors of pineal region were sensitive to X-knife. Conclusion X-knife has a definite effect on intracranial diseases. For patients with tumors of pineal region complicated by serious hydrocephalus, shunting should be conducted before X-knife treatment. For patients with mild or morderate hydrocephalus, X-knife chould be utilized only under correct interventions such as dehydration. The local control rate of intracranial metastatic tumors was high, but survival time postoperation depended on panencephalic radiotherapy or control of primafry lision. For tumors with diameter＞ 3cm, pituitary tumors, brains stem tumors and tumors in cerebellopontine angle region repeated X-knife were suggested, which could improve cure rate and decrease complications.

10.3969/j.issn.1000-8179.2013.12.006

Objective:To investigate the mechanism of histone deacetylase (HDAC) inhibitor in down-regulating the expression of HER-2 in breast cancer cells and to provide an innovative therapeutic option to overcome the disadvantages of anti-HER-2 therapy. Meth-ods:HER-2-positive breast cell lines were treated with HDAC inhibitors. The changes in the gene and protein levels of HER-2 were de-tected by qPCR and Western blot. MiRNA microarray was used to identify the HDAC inhibitors, whereas qPCR was used to verify the miRNA expression. Results:In vitro cell experiments confirmed that the HDAC inhibitors TSA and SAHA can down-regulate the expres-sion of HER-2 in breast cancer cell lines. TSA can down-regulate the expression of HER-2 gene in BT474 and decrease the concentra-tions of 100 nmol by 10.7%and 200 nmol by 38.9%(P<0.05). TSA had no effect on the primary cells. The expression of HER-2 gene of BT474 was down-regulated by 93.9%(P<0.05) in the 5μmol/L group but not in the 1μmol/L group. SAHA significantly affected the pri-mary cells at a concentration of 1μmol/L and reduced the cells at 87.1%at a concentration of 5μmol/L. Seven miRNAs were identified from the miRNA microarray. MiR-762 was used as a basis to identify the changes in miRNA. The miRNA sputum identified by miRNA microarray and qPCR may be associated with the down-regulation of HER-2 by HDAC inhibitors. Conclusion: HDAC inhibitors may down-regulate the expression of HER-2 in breast cancer cells by changing some miRNAs.

Objective To study the calcium metabolism in tacrolimus(FK506)induced rats nephrotoxicity and the preventive effect of calcium channel blocker.Methods Twenty-four Spragueinduced or FK506-induced nephropathy model.Blood creatinine,blood electrolytes,renal tissue histopathology(HE stain)and the change of ultrastructural organization in renal cells by transmission electron microscope were observed.Results The blood creatinine levels of both CsA and FK506 groups [(36.00±2.61)and(34.17±4.54)μmol/L] were significantly higher than those of the FK506+Dilgroup and control group(all P＜0.05).The blood calcium levels of both CsA and FK506 groups (2.00±0.04 and 2.05±0.04 mmol/L) were significantly lower than those of the FK506+Dil group and control group(all P＜0.05).The blood creatinine and calcium levels of FK506+Dil group were not significantly different with those of control group(P＞O.05).Histopathology examination showed cloudy swelling and vacuolization of the renal tubular epithelial cells and intra-cellular mitochondria swelling and vacuolization in the CsA and FK506 groups.However,the pathological changes of the FK506+Dil group were remarkably milder in comparison with the CsA and FK506 groups.Concluum channel blocker,Dil,could prevent the FK506-induced nephrotoxicity.

Objective To study the immune re-constitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies.Methods From June 2011 to May 2015,65 patients with hematological malignancies were analyzed retrospectively.Lymphocyte subsets were determined by flow cytometry (FCM),including total T lymphocytes (CD3+),helper T cells (CD3+ CD4+),cytotoxic T cells (CD3+ CD8+),CD4/CD8 ratio,nature killer (NK) cells (CD3-CD56+),NKT cells (CD3+ CD56+),B lymphocytes (CD19+),naive T cells (CD3+ HLA-DR+),static T cells (CD3+ HLA-DR-),and regulatory T cells (CD4+ CD25high Foxp3+) on the day 14,28 and 42,and on the month 2,3,6,9,12,15,18 and 24 after allo-HSCT.Results The percentage of CD3+ T cells located normal range after hematological recovery,and its absolute number recovered to normal range at + 15 months.The percentage of CD3+ CD4+ T cells recovered to normal range at + 24 months.However,the absolute number of CD3+ CD4+ T cells did not recover to normal range until 24 months after allo-HSCT.The percentage of CD3+ CD8+ T cells was higher than normal range at + 42 day,and its absolute number was greater than normal range at + 3 months.Hence,low CD4/CD8 ratio was observed for a long period.The re-constitution time points of the percentage and absolute number of CD3+ HLA-DR+ T cells were + 3 months and + 24 months respectively.The re-constitution time points of the percentage and absolute number of CD3 + HLA-DR-T cells were + 2 months and + 15 months respectively.The re-constitution time points of the percentage and absolute number of regulatory T cells were + 12 months and + 15 months respectively.The percentage of NKT cells located in normal range after hematological recovery,and its absolute number retumed to normal range at + 12 months.The re-constitution time points of the percentage and absolute number of B cells were + 9 months and + 18 months respectively.The percentage of NK cells located in normal range after hematological recovery,and its absolute number returned nearly to normal range at + 3 months.Conditioning regimen containing ATG,source of stem cells,CD34+ cell number,GVHD,and CMV reactivation were all associated with immune re-constitution after allo-HSCT.Conclusion Different immune cells showed different re-constitution models after allo-HSCT,and the percentage recovered faster than absolute number for a certain kind of immune cells.Studying immune re-constitution and its associated factors may offer beneficial information for insight into transplantation immunology and improve the management of allo-HSCT.

Objective To explore the long-term outcomes and complications of patients with hematological malignancies (HM) after haploidentical donor transplantation (HDT) or siblingidentical donor transplantation (SDT).Methods From June,2011 to July,2016,89 patients with HM receiving allo-HSCT were retrospectively analyzed,including 57 patients undergoing HDT and 32 cases undergoing SDT.Results The median time to achieve neutrophil engraftment was 2 days shorter after HDT than SDT,whereas that of platelet engraftment was 3 days longer after HDT than SDT.The cumulative incidence for 3 to 4 grade acute graft-versus-host disease (GVHD) was not obviously different between HDT and SDT (8.77％ versus 12.5％ respectively;x2 =0.313,P =0.576).The cumulative incidence for chronic GVHD was not significantly different between HDT and SDT (45.6％ versus 37.5％;~ =0.551,P =0.458).Cytomegalovirus (CMV) reactivity was significantly higher in patients after HDT (77.19％) than those after SDT (21.88％) (x2 =25.633,P＜0.001).The occurrence of hemorrhagic cystitis was also obviously higher in patients after HDT (26.32％)than those after SDT (3.85％) (x2 =5.340,P =0.021).The 1-,2-,and 3-year relapse-free survival rate of patients receiving HDT and SDT was 63.9％,55.4％,44.3％ and 71.2％,58.3％,51.8％,respectively (P =0.541).The 1-,2-,and 3-year overall survival rate of patients receiving HDT and SDT was 75.3％,65.3％,52.3％ and 76.9％,62.9％,62.9％,respectively (P =0.777).Conclusion Considering similar incidence of severe GVHD and long-term outcomes,haploidentical donors should be recommended as a potential alternative donor source when an identical donor is lacking for patients with HM.