Objective:To evaluate the efficacy and safety of modified FC/ATG pretreatment in the treatment of severe aplastic anemia(SAA).Methods:From June 2012 to June 2020, clinical data of 64 patients with severe aplastic anemia undergoing allogeneic hematopoietic stem cell transplantation with modified FC/ATG(Flu 30 mg·m -2·d -l, -5~-2 d、CTX 50 mg·kg -1·d -1~-2 d、ATG: 2.5 mg·kg -1·d -1, -5~-2 d) pretreatment were retrospectively analyzed.There were MSD-HSCT ( n=29) and Haplo-HSCT ( n=35). Results:One patient died of intracerebral hemorrhage before transplantation and the remainders were completely implanted.During a median follow-up period of 14.5(1-95) months, overall survival (OS) rate of 92.2%.It was significantly higher than OS rate of 67.2% in the treatment of SAA by foreign pretreatment regimens containing low-dose TBI.And pretreatment scheme containing FC+ BU/TBI had an OS of slightly >91.3% in the treatment of SAA.The 3-year OS rates were 85.7% and 93.5% in Haplo-HSCT and MSD-HSCT groups ( P=0.058). The OS rate of SAA Haplo-HSCT/MSD-HSCT group was similar to that of " Beijing Protocol" (BU/CY+ ATG) (89%, 91%). The viral infection rates of EB and CMV were significantly higher in haplo-HSCT group than those in MSD-HSCT group and inter-group difference was statistically significant ( P<0.05). However, univariate analysis showed that two groups had no effect on survival time ( P=0.403, P=0.132). Univariate analysis showed that survival time was significantly associated with the presence of Ⅲ-Ⅳ° aGVHD and the presence of severe complications ( P=0.007, P=0.001). Further multivariate analysis revealed that severe complication was an independent risk factor for survival ( P=0.003). Conclusions:The efficacy of improved FC/ATG pretreatment in the treatment of SAA in MSD-HSCT or Haplo-HSCT is higher than other domestic and international pretreatment schemes in OS rate, safety and effectiveness.Onset of severe complication and association with Ⅲ ~ Ⅳ ° aGVHD are the influencing factors for patient survival.The efficacy of Haplo-HSCT group is similar to that of MSD-HSCT group.It may be employed as an alternative donor for SAA patients without fully congruent donors.

Objective:To compare the effects of two pretreatment schemes on the efficacy, gonad and reproductive function of haploid hematopoietic stem cell transplantation recipients with severe aplastic anemia(SAA).Methods:The data of 73 patients with SAA who underwent haploid hematopoietic stem cell transplantation were analyzed retrospectively.The pretreatment scheme was divided into Fludarabine+ Cyclophosphamide+ Antithymocyte globulin group(FC lowATG group, 45 cases)and Busulfan+ Cyclophosphamide+ Antithymocyte globulin group(Bucy/ATG group, 28 cases). The changes of blood cell implantation time, follicle stimulating hormone(FSH), luteinizing hormone (LH), estradiol and testosterone were compared between the two groups. Results:there was no significant difference in blood cell implantation time between the two groups( P=0.096; P=0.133). The levels of FSH and LH in female recipients in Bucy/ATG group were higher than those in FC lowATG group, and the level of estradiol was lower than that in FC lowATG group.There were significant differences between the groups(all P<0.05). The pregnancy or fertility rate of female recipients in Bucy/ATG group was lower than that in FC lowATG group(all P<0.05). There was no significant difference in FSH, LH, testosterone and fertility between the two groups(all P>0.05). There was no significant difference in 2-year overall survival rate and failure free survival rate between the two groups( P=0.091; P=0.084). Conclusions:FC lowATG may be an effective pretreatment scheme for haploid hematopoietic stem cell transplantation in SAA with less damage to gonad and reproductive function.

Objective: To compare the clinical efficacy and safety of bortezomib, cyclophosphamide, dexamethasone (VCD) regimen and bortezomib dexamethasone (VD) regimen in the treatment of the patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical data of 73 patients with NDMM in Shanxi Dayi Hospital from January 2013 to January 2016 were retrospectively analyzed. According to the chemotherapy regimen, the patients were divided into VCD group (41 cases) and VD group (32 cases). The efficacy and adverse reactions of the two groups were evaluated. Results: The overall response rate of VCD group and VD group was 80.5% (33/41) and 78.1% (25/32) respectively, and the difference was not statistically significant (χ ²= 0.061, P= 0.804); and complete remission (CR) rate was 36.6% (15/41) and 15.6% (5/32) respectively, and the difference was statistically significant (χ ²= 3.970, P= 0.046); the median progression-free survival (PFS) was 27 months and 24 months respectively, and the median overall survival (OS) was 35 months and 33 months respectively, and the differences were not statistically significant (all P > 0.05). Most adverse reactions occurred in grade 1-2, in which peripheral polyneuropathy and thrombocytopenia were the most common. Peripheral neuritis was the most common finding among the adverse reactions of grade 3. The incidence of adverse reactions in both groups was not statistically significant (P > 0.05). Conclusions VCD and VD regimen could be recommended as a better induction therapy for NDMM patients. Compared with VD scheme, VCD scheme has a higher CR rate.

Objective To observe the clinical effects and safety of sodium valproate combined with decitabine for treatment of myelodysplastic syndrome (MDS). Methods Forty-two patients with MDS were enrolled in department of hematology in Shanxi Dayi Hospital from February 2012 to February 2017. According to random number table, the patients were divided into the control group (21 cases) and the experimental group (21 cases). The patients in the control group received decitabine at the dose of 20 mg·m-2·d-1, and intravenous infusion was completed in 2 hours, continuous therapy up to 5 days, 4 weeks as a course; the patients in the experimental group received combined medication, orally given sodium valproate 0.2 g once, 3 times per day. One week later, the dosage was added to 0.4 g once, 3 times per day. Both groups received at least 4 courses of treatment. The treatment was stopped when serious adverse reactions or obvious disease progression occurred. The bone marrow smear was rechecked every 4 weeks after treatment to evaluate the efficacy. The expressions of ASXL1, DNMT3A and TET2 in bone marrow cells were detected by fluorescence quantitative PCR before and after treatment. Results The total treatment response rate of the experimental group and the control group were 76.2 % (16/21) and 57.1 % (12/21) respectively, and there was statistically significant difference (P< 0.05); the total remission rate of the two groups was 47.6 % (10/21) and 38.1 %(8/21) respectively, and there was no significant difference (P> 0.05). All patients had slight adverse reactions, and the adverse reaction rate was 42.9 % (9/21) and 38.1 % (8/21), and there was no significant difference (P>0.05). The content of TET2 mRNA and DNMT3A mRNA after treatment in both groups were decreased compared with the expressions before treatment, and there were significant differences (P<0.05). However, there was no significant difference between the two groups after treatment (P> 0.05); the content of ASXL1 mRNA had no obvious change in the control group and a dramatic decrease in the experimental group compared with that before treatment (P<0.05). Conclusion Sodium valproate combined with decitabine has favorable effects and mild adverse reactions for treatment of MDS, besides, it can influence the expressions of TET2, DNMT3A and ASXL1.

Aim To explore the mechanism of E.coli heat-labile enterotoxin B subunit(LTB)as adjuvant by analysis of cellular proteins interacting with LTB. Methods Whole cell proteins were purified from RAW 264.7 cell after treated with LTB or NaCl 12 h, respectively.The cellular proteins were interacted with LTB and the interacting proteins were purified by pull-down assay and identified by mass spectrography.The LTB interaction proteins were conformed with Western blot and immunofluorescence assay.Results 25 LTB interaction proteins were found,and their interaction network was mapped;four proteins (Jup,Dsp,Ddx5 and Vimentin)were indicated to be related with LTB adjuvant activity;immunofluorescence assay indicated that GM130 interacted with LTB,however,Vimentin had no interaction with LTB in vivo.After treated by LTB,the expression of β-actin was upregulated obvi-ously in RAW 264.7 cell,whereras,Hspd1 did not show any change.Conclusions LTB exerts adjuvant activity through binding to GM1 of immune cells,cau-sing endocytosis and transporting to the Golgi apparatus by vesicles.Then LTB might bind to Jup and affect TCF/LEF activity,regulating the expression of Bcl 2, IL-6,and Runx3.The result is promoted T cell and B cell proliferation,differentiation and activation by se-cretion of cytokines and immunoglobulins.

Protease inhibitors(PIs)are a class of antiviral drugs widely used for the treatment of HIV/AIDS. The status of intellectual property of HIV protease inhibitors lopinavir is briefly reviewed in this paper. Based on the indication of Kaletra® , the follow-up studies and generic development of PIs were discussed. It was concluded that the combination of PIs and anti-bacterial/anti-fungal drugs with CYP450 inhibitory effects would be of great use for AIDS and the infectious complications, in the hope of seeking the secondary innovation of other drugs with expired patents in the fields of drug combination and indication expansion.

OBJECTIVETo investigate the efficacy and toxicity of modified FLAG and CAG on relapsed or refractory acute myeloid leukemia (AML).

METHODSSixty-one patients with relapsed or refractory AML were divided into modified FLAG or CAG group. In modified FLAG group: G-CSF 200 μg·m⁻²·d⁻¹ on days 0-5; fludarabine 30 mg·m⁻²·d⁻¹ on days 1-5; Ara-C 1.0 g·m⁻²·d⁻¹ on days 1-5. In CAG group: Ara-C 10 mg·m⁻²·12 h⁻¹ on days 1-14, aclarubicin 20 mg/d on days 1-4, G-CSF 200 μg·m⁻²·d⁻¹ on days 0 1-14.

RESULTSThe complete response (CR) rate was 43% (12/28) and the partial response (PR) rate 18% (5/28) with the overall response (OR) rate of 61% in modified FLAG group. CR rate was 21% (7/33) and PR rate 15% (5/33) with OR rate of 36% in CAG group. There was significant statistical difference between two groups (P<0.05). The main toxicities of these groups were myelosupression and infection. The infection rate was 68% (19/28) in modified FLAG group (twenty-two patients were treated in the sterile laminar flow ward duing neutropenic period), treatment related mortality (TRM) in modified FLAG group was 7%; The infection rate was 55% (18/33) in CAG group (no patient was treated in the sterile laminar flow ward), TRM in CAG group was 3%. There was no significant statistical difference in two groups (P>0.05).

CONCLUSIONModified FLAG was effective for relapsed or refractory AML. The supportive cares to strengthen infection-controlled measures and shorten the period of bone marrow suppression produced the additional effect. CAG regimen has low adverse reactions and could be individualized to elder or weak patients.

Aclarubicin ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Recurrence

Objective:To study the clinical value and telomerase activity of malignant ascites treated by lifein combination with cisplatin.Methods:48 patients with malignant ascites were divided randomly into two groups.Treatment group of 28 cases were treated with lifein and cisplatin,control group of 20 cases were treated with cisplatin alone.Telomerase activity was detected by semi-TRAP assay before treatment,at the first week,the second week and the third week after treatment,respectively.Results:the effective rates of treatment group(89.3%) was much higher than that of control group (60%),P