Objective To investigate early reduction of the dose of immunosuppressive drug after allogeneic peripheral blood stem cell transplantation(allo-PBSCT)for patients with refractory or relapsed leukemia.Methods Between Janaury 2004 and December 2006,15 patients with relapsed or refractory leukemia in Department of Hematology,the First Affiliated Hospital,Sun Yat-Sen University and Institute of Hematology & Blood Diseases Hospital,CAMS & PUMC,received allo-PBSCT from their relatives,12 from HLA-identical siblings.The preparative regimens included BuCy and TBICy with or without cytarabine.Cyclosporine A(CsA)or tacrolimus was used for graft-versus-host disease(GVHD)prophylaxis,with rapid decreasing starting on day 30 of post transplant if no GVHD appeared in receipts of matched sibling tranplantation.Results(1)Faster engraftment was achieved in all patients.Grade Ⅰ~Ⅱ acute GVHD appeared in 5 patients.Chronic GVHD occured in 7 of 11 evaluable patients.(2)Of 9 patients with an lower CsA or tacrolimus dosage,only 1 developed grade Ⅰ acute GVHD,4 chronic GVHD,2 extramedullary relapse.(3)After a median follow-up of 328 days,8 patients has leukemia-free-survival(LFS),4 relapsed,and only 1 had transplantation-related mortality(TRM)in the first 3 months post-transplant.The estimated LFS at 1 year and 2 years was 51% and 25%,respectively.Conclusion Patients with advanced leukemia might benefit from allo-PBSCT with significant lower treatment failure incidence.Dose reductions of CsA and tacrolimus in early transplant might enhance graft-versus-leukemia effect,and improve long-term LFS.

Objective To systematically evaluate the effects of metformin on serum vitamin B12,folic acid and homocysteine (Hcy) levels in the patients with type 2 diabetes mellitus (T2DM).Methods The databases of Cochrane Library,EMbase,PubMed,CBM,CNKI,VIP and Wanfang were retrieved by computer to collect the randomized controlled trials (RCTs) on the association between metformin and serum vitamin B12 level in T2DM patients.Two researchers independently screened the literatures,assessed the risk of bias of included RCTs and extracted the data.The RevMan5.3 software was used for conducting the meta analysis.Results A total of 5 RCTs were included.The Meta-analysis results showed that serum vitamin B12 level in the metformin group was significantly decreased compared with the placebo group (MD=-55.86,95 ％ CI(-86.89,-24.84),P =0.000 4);the subgroup analysis showed that serum vitamin B12 level was negatively correlated with the duration of diabetes,metformin use time and dose.The serum Hcy level in the metformin group was increased compared with the placebo group (MD=2.44,95 ％ CI(1.41,3.46),P＜0.01);the serum folic acid level had no statistical differences between the two groups [MD=-2.39,95 ％CI (-4.93,0.15),P=0.06];the incidence rate of adverse reactions in the metformin group was higher than that in the placebo group[RR=2.0,95 ％ CI(1.32,3.03),P =0.001].Conclusion Metformin treatment may lead to decrease of serum vitamin B12 level and increase of Hcy level while has no obvious influence on the folic acid level in T2DM patients,but has higher incidence rate of adverse reactions.

Objective To compare the clinical efficacy and complications of allogeneic peripheral blood stern cell transplantation (Allo-PBSCT) and immunosuppressive therapy (IST) for severe aplastic anemia(SAA). Methods Twenty-five patients with SAA underwent allogeneic HLA-matched sibling donor PBSCT(n = 12) and IST (n = 13). PBSCT group received conditioning regimen of cyclophosphamido(Cy) in combination with antithymocyte globulin(ATG). IST group received ATG followed by cyclosporine A (CsA).The short-term and long-term effects and complications were investigated. Results The mean time of recovery in the absolute neutrophil count (ANC), platelet and hemoglobin (Hb) in PBSCT group [(13.5±2.3), (23.5±4.1), (82.7±6.1)d, respectively]was shorter than those in IST group [(32.6±3.5), (73.8±6.2), (296.4±12.5)d, respectively]and there were statistical differences between two groups(P<0.05). But the one-year treatment effect between two groups showed no difference (P>0.05). There were no statistical differences in 3-year survival and overall survival rate between two groups (P>0.05). However, statistical difference was observed in overall relapse rate (P<0.05). The common complication in two groups was virus infection including cytomegalovirus (CMV) and varicella zoster virus (VZV), but there was no statistical difference in the incidence of virus infection between them (P>0.05). Conclusions Both allo-PBSCT and IST are effective methods for treating patients with SAA. PBSCT is considered preferentially in clinic, because of its advantages in faster hematopoietic engraftment, lower relapse rate and no increased complication.

Objective: To compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) . Methods: Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively. Results: ①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3^rd month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) . Conclusion HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.

Objective:To analyze the results of quality detection of different brands of spectrum therapy apparatuses in complex environment,so as to improve the reliability of that in clinical use and to provide reference for medical institutions in selecting spectrum therapy apparatus that suits to different environments.Methods:A total of 4 different brands of spectrum therapy apparatuses(brand A,B,C,D)were selected,and the environments of cold,hot,wet and heat,and salt fog area were respectively simulated.The detection tests of low temperature storage,high temperature storage,wet and heat storage,and salt fog were conducted on the spectrum therapy apparatuses.According to the national standard"Environmental requirements and test methods for medical electrical equipment"and"Laboratory environmental test methods for military materiel Part 11:salt fog test",the results of quality tests of appearance function and temperature control of the spectrum therapy apparatuses after the test were analyzed.Results:In the test of appearance function,the appearance functions of brand A,brand B and brand C were normal in the tests of low temperature storage,high temperature storage,wet and heat storage,and salt fog,and brand D only showed obvious surface corrosion after salt fog test.In the test of temperature control,the errors of the temperature non-uniformity of the 4 spectral therapy apparatuses were less than 10%after the tests of low temperature storage,high temperature storage,wet and heat storage,and salt fog.The error ranges of brand B and brand D were between-10%and+10%due to the marked values of the surface temperatures of radiation devices of them were known,while those of brand A and C could not be analyzed due to the marked values of them were not known.Conclusion:The analysis on the quality detection of spectrum therapy apparatuses in the complex environment can improve the reliability of that in clinical use,and can choose the suitable brand and model for medical institutions at differently environmental regions,so as to ensure the clinical treatment effect of them.

Objective:To explore the calibration method of quality detection of spectrum therapy instrument in low pressure environment,so as to ensure its safety and stability in clinical use.Methods:Aimed at the 4 types of vertical spectrum therapy instrument,the calibration of quality test were carried out in normal environment and the simulated low pressure environment for 5 different altitudes that included 1.0,2.5,3.5,4.5 and 5.5 km.The detection of appearance function,unevenness of surface temperature and surface error,as well as the repetition of measurement of spectrum therapy instrument among different low pressure environment were compared.Results:In the low pressure environments of 5 different altitudes,the performance parameters of 3 types of spectrum therapy instruments were better,and the error of temperature unevenness was less than 10％.The performance of one type of spectrum therapy instrument was poor,and the error of temperature unevenness was between 10％and 20％.For the error of surface temperature of radiator,one type of spectrum therapy instrument was＜10％,and one type of that was＞15％,and two types of that cannot be assessed because there was not specific value.In normal environment,each detection indicator of 4 spectrum therapy instruments were normal.In this trial,the repetition of the result of only 1 type of spectrum therapy instrument was relatively larger,which was between 1.5％and 2.4％,and the repetition of other types was smaller.Conclusion:The calibration and detection methods of quality test of spectrum therapy instrument was explored in this article,which can ensure the clinical therapeutic effect,safety and stability.It is helpful to reduce the risk of that in clinical use.

Schizophrenia(SZ)is a serious mental illness,and traditional diagnostic methods are prone to missed and misdiagnosis.Using machine learning(ML)algorithms can extract SZ relative features from functional MRI(fMRI)data,hence being helpful for diagnosing and predicting treatment response of SZ.The research progresses of ML based on fMRI for diagnosis and treatment of SZ were reviewed in this article.

A corresponding calibration method was proposed for the key performance parameters of the endoscopic liquid expansion pump,such as the pressure indication error,the flow rate indication error and the flow rate repeatability.4 different brands of endoscopic liquid expansion pumps in clinical use in the hospital were selected for calibration,and the feasibility of the calibration method was evaluated.In the pressure and flow range of the endoscope liquid expansion pump,3 calibration points of high,medium and low were selected,and each flow point was calibrated 3 times.The calibration results showed that the maximum error of pressure indication was 4.3%,the maximum error of flow indication was 9.3%,and the maximum repeatability of flow indication value was 0.8%,all of which met the technical requirements for the maximum allowable error of"Medical Endoscopes.Endoscope Functional Supply Units.Irrigation Pump"(YY/T 0864-2011)and"Calibration Specification for Syringe Pumps and Infusion Pumps"(JJF 1259-2018).The calibration method for endoscopic liquid expansion pump can improve the metrological traceability system of this type of equipment,ensure the accuracy and reliability of equipment values,improve product quality,and ensure medical safety.

Objective:To examine the survival and influential factors of an integrated approach of novel agents, autologous hematopoietic stem cell (auto-HSCT) , and maintenance therapy in patients with multiple myeloma (MM) patients from a single center over the past 15 years.Methods:In our center, 300 MM patients who received an integrated strategy of new agents, auto-HSCT, and maintenance therapy over 15 years were retrospectively and prospectively analyzed.Results:The complete remission rates (CR) and ≥very good partial remission rates (VGPR) following induction therapy, transplantation, and maintenance therapy were respectively 35.3% and 55.2% , 72.4% and 80.0% , 89.2% , and 93.4% . When compared to patients receiving double-drug induction, the ≥VGPR and ORR of patients receiving triple-drug induction were improved. No difference existed in CR, ≥VGPR, and ORR between the PAD (bortezomib + liposome doxorubicin+ dexamethasone) and RAD (lenalidomide + liposome doxorubicin + dexamethasone) regimens, but the benefits speed differed. The negative rate of flow minimal residual disease following induction, transplantation, and maintenance was 18.8% (54 cases) , 41.4% (109 cases) , and 58.7% (142 cases) , respectively. The median time to progress (TTP) was 78.7 months and the median overall survival (OS) was 109 months. The median TTP for RISS-Ⅰ-Ⅲ patients were 111.8 months, 77.4 months, and 30.6 months, and the median OS was 118.8 months, 91.4 months, and 48.5 months, respectively. At various points during treatment, the TTP and OS of patients obtaining CR and MRD negative were longer than those of patients who did not obtain CR and MRD negative. TTP was noticeably shorter in high-risk cytogenetic patients compared to standard-risk patients even when CR was acquired during induction. There was no difference in TTP between patients with high-risk cytogenetics and those with standard-risk cytogenetics if MRD negative was acquired during induction. According to a multivariate analysis, the R-ISS stage was a poor predictor of TTP and OS at various treatment intervals. Therapeutic effectiveness was a newly independent prognostic factor following treatment.Conclusion:A median survival of almost 10 years is possible for MM patients who receive an integrated strategy of induction regimens followed by auto-HSCT and maintenance therapy, which significantly improves prognosis. However, this approach did not significantly benefit high-risk cytogenetic MM patients.

Objective:To investigate the efficacy and safety of house dust mite (HDM) allergen subcutaneous specific immunotherapy (SCIT) in patients with allergic rhinitis (AR) with single dust mite allergy and multiple allergen allergy.Methods:A retrospective study was conducted. A total of 372 patients with allergic rhinitis induced by house dust mite were diagnosed in the allergy clinic of General Hospital of North Theater Command from January 2013 to January 2018.They were treated with house dust mite allergen preparation for standardized SCIT for 3 years or more, and had complete follow-up data. The age ranged from 5 to 55 years, the median age was 13 years, and the average age was (19.4±14.7) years; 216 males and 156 females. According to their age, they were divided into the older group (age >14 years) and younger group (age ≤ 14 years). According to the number of allergens, they were divided into single group (only HDM group allergic to house dust mites) and multi recombination (including 2 or more allergens including house dust mites). The multi recombination was further divided into HDM+1 group, HDM+2 group, HDM+3 group, HDM+4 and above group. Before treatment (T0), 1 year (T1) and 3 years (T2) after SCIT treatment, the patients in each group established files, analyzed and compared the average total nasal symptoms score (TNSS), total non nasal symptoms score (TNNSS), visual analogue scale (VAS), total medicine score (TMS) and rhinoconjunctivitis quality of life questionnaire (RQLQ), and evaluated the clinical efficacy of the treatment and the comparison of various scores in the efficacy of SCIT with different allergens and ages. Record the occurrence of local and systemic adverse reactions of all patients during treatment, and evaluate the safety of SCIT. All scores are measurement data that do not conform to normal distribution. Mann-Whitney U and Kruskai-Wallis test of independent samples are used for inter group comparison, and Bonferroni correction is used for further pairwise comparison; Chi square test and continuity correction method were used for the comparison between count data groups such as the incidence of adverse reactions and the effective rate of TNSS, and a-division method was used for further pairwise comparison. Results:After SCIT treatment, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in T1 and T2 were significantly lower than those in T0, and the scores in T2 were significantly lower than those in T1 ( Z=-11.168, -4.786, -6.639, -13.012, -10.652 in T0 vs T1; Z=-13.527, -8.746, -13.397, -14.477, -11.833 in T0 vs T2; Z=-4.721, -4.607, -10.020, -7.180, -5.721 in T1 vs T2; P<0.05). In T1 and T2, compared with the older group, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in younger group were lower, and the differences of various indexes were statistically significant(the median scores of T1: Myounger=3.0, 1.0, 2.0, 4.0, 2.6, Molder=5.0, 2.0, 3.0, 5.0, 3.2; the median scores of T2: Myounger=3.0, 1.0, 0, 2.0, 1.3, Molder=4.0, 1.0, 1.5, 3.0, 2.3; ZT1=-4.525, -5.830, -4.061, -3.608, -2.785; ZT2=-3.847, -4.055, -2.820, -2.998, -3.418; P<0.05). In T1 and T2, the scores of TNSS, VAS and RQLQ in a single group after SCIT treatment were lower than those in multiple recombination(the median scores of T1: Msingle=4.0, 4.0, 2.6, Mmultiple=5.0, 5.0, 3.2; the median scores of T2: Msingle=3.0, 2.0, 1.4, Mmultiple=4.0, 3.0, 2.1), and the difference was statistically significant ( ZT1=-3.002, -2.092, -1.977; ZT2=-3.354, -2.469, -2.116; P<0.05). There was no significant difference in TMS (the median score during T1 period: Msingle=2.0, Mmultiple=3.0, ZT1=-1.130; the median score during T2 period: Msingle=1.0, Mmultiple=1.0, ZT2=-1.544; P>0.05). Further comparison within the group showed that there was no significant difference in the improvement rate of TNSS during T2 period among HDM group, HDM+1 group, HDM+2 group and HDM+3 group (HDM vs HDM+1 group χ 2=0.277, HDM vs HDM+2 group χ 2=0.78, HDM vs HDM+3 group χ 2=0.075, HDM+1 vs HDM+2 group χ 2=0.057, HDM+1 vs HDM+3 group χ 2=0.019, HDM+2 vs HDM+3 group χ 2=0.003; P>0.005), the improvement rates were 92.5%, 90.3%, 89.1% and 89.5%. Respectively in HDM group,HDM+1 group, HDM+2 group, HDM+3 group, compared with HDM+4 and above group, the difference was statistically significant (χ 2=26.144, 13.254, 15.144, 8.808; P<0.005). The improvement rate of TNSS in HDM+4 and above group was 60.9%. 122 patients had local adverse reactions during the treatment of SCIT, accounting for 32.8%. The local adverse reactions were 759 injections (15 336 injections in total), accounting for 4.95%. Most of them were swelling, dizziness, induration and pruritus at the injection site, which could be relieved by oral antihistamines or within 2 hours. There were 2 cases of local urticaria, once for each case. The symptoms were relieved within 1 week after oral antihistamine. No serious systemic adverse reactions occurred. Conclusion:Standardized SCIT may be a safe and effective treatment for AR patients, and the type of allergen may be one of the important factors affecting the efficacy of SCIT. The efficacy of SCIT was significant in AR patients with three or less allergens other than house dust mite.