BACKGROUND:Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory-particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons. METHODS:We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT. RESULTS:Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death. CONCLUSION:The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons. TRIAL REGISTRATION:ClinicalTrials.gov , NCT02879526.

Objectives: Patients with myelodysplastic syndrome (MDS) currently get therapy in accordance with their prognosis scores. The newest MDS risk-stratified score, the IPSS-M, isn't still being extensively used in clinical practice and is based on clinical and molecular data. Comparing the IPSS-M score to the current IPSS-R score will enable us to assess the clinical relevance of the IPSS-M score, especially for low-risk MDS patients. Methods: In order to determine the IPSS-R and IPSS-M scores, we gathered clinical, cytogenetic, and molecular information from 210 MDS patients who were diagnosed between 2016 and 2023 and followed up until April 2023. Harrell's c index and Kaplan-Meier survival analysis were used to examine the impact of the two scores on overall survival (OS).The lower-risk group included patients with IPSS-R≤3.5 and IPSS-M≤0, whereas the higher-risk group included the remaining patients. Analysis was done on the differences in gene mutations between the two risk groups based on the two scoring standards, as well as the impact of IPSS-M reclassification on the choice of therapeutic treatments. Results: At least one genetic mutation was identified in 77.1% of patients. The genes ASXL1 (21.4%), TET2 (19.0%), TP53 (14.8%), and DNMT3A (13.3%) have the highest frequency of mutations. According to IPSS-R score, the higher-risk group's TP53 gene mutation rate was significantly higher than that of the lower-risk group; According to IPSS-M score, the higher-risk group had more instances of TP53 and ASXL1 gene mutations than the lower-risk group did, while the lower-risk group had a relatively higher incidence of SF3B1 gene mutations than the higher-risk group did. The difference in survival between IPSS-M groups was more prominent than that between IPSS-R groups under Kaplan-Meier survival analysis, which was used to assess the prognostic prediction power of IPSS-R and IPSS-M. When t 50 months, the Harrell's c index of OS predicted by IPSS-M exceeded that of IPSS-R (IPSS-R vs IPSS-M c-index: 0.710vs0.747, 0.692vs0.707, 0.705vs0.726, 0.752vs0.759, 0.743vs0.773, t=10, 20, 30, 40, 50 months), demonstrating that IPSS-M enhanced the outcome prediction.87 patients (41.4%) were re-stratified by IPSS-M, with 65 (30.9%) being upgraded and 22 (10.5%) being degraded. 64 patients (30.5%) who had changes in their IPSS-M scores qualified for reduced therapy, whereas 48 (22.9%) qualified for intensive treatment, including 32 patients who were reclassified as being in the lower risk category based on their IPSS-R scores. Conclusions: The research shows that IPSS-M offers a more thorough prognostic evaluation than IPSS-R. Certain patients' treatment modalities may need to be changed as a result of modifying IPSS-M in clinical settings, especially those who were previously classified as low-risk.

Background: Immunotherapy with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors has been widely used in the treatment of solid tumors and Hodgkin lymphoma, demonstrating powerful efficacy and good safety. However, there is no systematic review and meta-analysis to fully investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treating non-Hodgkin lymphoma (NHL). Methods: We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and abstracts of conference proceedings of annual meetings up to January 23, 2022, to identify eligible clinical trials. To evaluate the efficacy of PD-1/PD-L1 inhibitors, objective response rate (ORR), complete response rate (CRR), 1-year overall survival rate, and 1-year progression-free survival rate were analyzed. For safety analysis, we calculated rates of any grade and grade ≥3 treatment-related adverse events. Results: Overall 22 studies and 1150 participants were enrolled in this meta-analysis. The pooled ORR, CRR, 1-year overall survival, and 1-year progression-free survival rates were 0.43 (95% confidence interval [CI], 0.33–0.54), 0.21 (95% CI, 0.13–0.31), 0.72 (95% CI, 0.58–0.89), and 0.42 (95% CI, 0.29–0.62), respectively. The ORR and CRR in the combination immunochemotherapy subgroup (0.65 and 0.41) were higher than those in the monotherapy (0.27 and 0.09) and combination chemotherapy (0.39 and 0.19) subgroups. This study was registered with PROSPERO (#CRD 42022316805). Conclusion: Given that there were limited clinical trials and relatively few relevant studies, we conducted this meta-analysis to fully elucidate the efficacy and safety of PD-1/PD-L1 inhibitors in NHL. Our results suggested that PD-1/PD-L1 inhibitors improved outcomes of responses as well as survival rates in NHL patients with tolerable adverse events. More well-designed randomized clinical trials are still needed to further confirm our findings.

Objective:To investigate the diagnosis and treatment of intravascular large B-cell lymphoma (IVLBCL).Methods:The clinical data of 1 patient with adrenal IVLBCL in Zhongda Hospital Southeast University in May 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was an elderly male with recurrent fever of unknown cause at initial stage, and was finally diagnosed as adrenal IVLBCL based on the results of laboratory, imaging and adrenal biopsy at different stages. After multiple courses of R-COP in combination with Bruton tyrosine kinase (BTK) inhibitor, the patient achieved complete remission.Conclusions:IVLBCL is rare and it lacks specific clinical symptoms. PET-CT and pathological biopsy can help in the diagnosis of it. R-COP combined with BTK inhibitor is effective in the treatment of biphenotype IVLBCL.

T细胞免疫球蛋白黏蛋白分子3(TIM3)是TIM家族免疫调节蛋白的成员,因与自身免疫及肿瘤免疫反应的调节相关而备受关注.TIM3在肿瘤微环境中主要通过抑制辅助性T细胞、诱导CD8+T细胞衰竭、促进骨髓来源的抑制性细胞(MDSCs)扩增等途径发挥免疫抑制作用.作者就TIM3的生物学特征、TIM3与髓系肿瘤及淋巴系统肿瘤关系、TIM3抑制剂在肿瘤治疗中作用的相关研究进展进行综述,以期为血液系统肿瘤患者带来更多的治疗方案.

Increasing drug efflux pumps (P-gp) on the cell membrane due to the overexpression of MDR1 gene in tumor cells is the main mechanism of multidrug resistance of cancer cells. P-gp belongs to the ATP-binding cassette family and functions as a transmembrane efflux pump that translocates chemotherapy drugs from an intracellular to an extracellular domain; thus, it is impossible to achieve efficient drug accumulation in tumor cells. Tetrandrine (TTD) has been shown in both in vitro and in animal experiments to reverse MDR by reducing the expression of MDR1 mRNA and P-gp. However, the effect of administration of TTD one week before chemotherapy is not ideal in the current clinical trials. In view of the previous in vitro and animal experiments have confirmed the effect of TTD in reversing the drug resistance of leukemia, this study returned to the cell experiment, selected K562 and K562/ADM cell lines as the research object, through different ADM combined with TTD administration sequences, to detect the inhibitory effect of different administration sequences on cell proliferation and whether it affected the intracellular ADM concentration, P- gp ATPase activity, MDR1 mRNA and P-gp expression levels, comparing the effect of TTD combined with ADM different administration sequences on the reversal of MDR in K562/ADM cells. We found that TTD can significantly antagonize P-gp-mediated ADM resistance by competitively binding P-gp and down-regulating P-gp expression and we, therefore, conclude that the co-administration of TTD, as a drug resistance reversal agent with ADM may be a better administration in the clinic.

Acute myeloid leukemia (AML) is a common malignancy of the blood system, and most patients are so ill that they often die if they are untreated in time. In recent years, with the improvement of chemotherapy drugs and methods, the complete remission rate has been significantly improved, but the long-term survival rate still has great room for improvement. This review summarized the influencing factors related to the long-term survival of AML patients through reading and sorting out multiple pieces of literature.

Background: Prophylactic transfusion of platelets provides a good protection for the implementation of invasive procedures and the prevention of bleeding events during chemotherapy and hematopoietic stem cell transplantation in patients who are suffering from hematological diseases. The issues that what is the optimal dose of platelet transfusion and how to monitor platelet transfusion efficiency are important due to the short storage time of platelet products, rising clinical demands, and decreasing donors. It is worthy that there are amount of studies have been conducted in the past to explore factors that may affect the clinical efficacy of platelet transfusion and characteristics of patients under these different transfusion effects. While, previous studies failed to exactly address the problems of clinical needs for platelet transfusion. Methods: The aim of our study is to develop a model to evaluate the efficacy of platelet transfusion and the statistic method of machine learning algorithm (ML) was involved. The differences between this algorithm and traditional methods are that the former one can continuously be learning from the data and form a self-training model, therefore ML is more accurate than traditional artificial models and generally independent of the model and parameters themselves. We further take the multi-layer fully connected layer neural network model (MLNN) into our consideration because it simulates the multi-layer interconnection of human nervous systems, which is suitable for processing inaccurate and fuzzy information. In our study, the establishment of a neural network model was used to make a multiple-dimension analysis between factors affecting platelet transfusion efficacy and platelet count added value correction index (aCCI), and explore the correlation among these influencing factors as well. Results: The study utilized the data relative to 1840 platelet transfusions performed in 460 patients with hematological diseases. The participants ranged in age from 16 to 92, and the median age was 59.5. There were 199 females and 261 men. The whole data was divided to 2 parts, 2/3 of them were analyzed as a training set and the others were used for validating. We selected 30 factors (including patient-related factors and transfusion product-related characteristics) that may affect the efficacy of platelet transfusion except the storage time of platelet (all data < 2 days), and established a model for predicting platelet transfusion efficacy based on the volume of platelet transfusion. After the model was established, it was tested for goodness of fit, and the results showed that the LOSS value tended to be stable. Conclusions: The establishment of this model may not only be used for predicting the platelet count after platelet transfusions in patients and the amount of platelets that need to be transfused, but also provide supports for the solution of related problems. Disclosures No relevant conflicts of interest to declare.

目的:探讨急性白血病(AL)患者P-糖蛋白(P-gp)、CD34表达与患者化疗预后的相关性.方法:收集2015年1月至2017年12月东南大学附属中大医院血液科和常州市第一人民医院血液科AL患者的实验室检测指标和临床资料39份.按照FBA标准及白血病免疫学分型诊断为急性淋巴细胞白血病(ALL)和急性髓细胞性白血病(AML)两大类.根据39例AL患者骨髓细胞中P-gp和CD34表达的流式细胞术检测结果,以患者P-gp表达≤2％(或＞2％)和CD34表达≤30％(或＞30％)分组,探讨急性白血病细胞P-gp和CD34表达与患者化疗预后的相关性.结果:P-gp≤2％组患者化疗后完全缓解率高于P-gp ＞2％组,且两组之间差异有统计学意义(P＜0.05);CD34表达≤30％组患者化疗后完全缓解率高于CD34表达＞30％组,但两组差异无统计学意义(P＞0.05).结论:P-gp表达检测对AL患者的化疗后完全缓解率评估有较大意义,但尚不能认为CD34表达检测对AL患者的化疗后完全缓解率评估有较大意义.

Objective To analyze the efficacy and safety of tetrandrine in the adjuvant treatment of relapsed/refractory acute leukemia (except M3).Methods A total of 58 patients with relapsed/refractory acute leukemia (except M3) admitted to six tertiary hospitals in Jiangsu Province from January 2015 to December 2017 were included in this study.The tetrandrine-adjuvant standard chemotherapy regimen and standard chemotherapy regimen were given to treatment and control groups respectively.There were 17 and 41 patients in treatment and control groups.The treatment group was given tetrandrine for 5 days before the use of standard chemotherapy.The dose of tetrandrine was 4 mg ·kg-1 ·d-1,and patients had continuous oral administration of 5 days.After that,the patients in the treatment group started chemotherapy immediately.On the other side,the control group received standard chemotherapy without any other multidrug reversal medicine.Then the clinical efficacy and safety outcomes in both groups were analyzed.Results In the treatment group,5,3,and 9 cases achieved complete remission (CR),partial remission (PR),and nonremission (NR) respectively,and the total effective (CR+PR) rate was 47.06 ％ (8/17);in the control group,14,10,and 17 cases achieved CR,PR,and NR,and the total effective rate was 58.54 ％ (24/41).There was no significant difference in the total effective rate between the two groups (x2 =0.64,P =0.424).There was no significant difference in the efficacy between the two groups of patients with different genders (P ＞ 0.05).When the disease duration was 6-11 months,the difference of efficacy between the two groups was statistically significant (P =0.041).There was no significant difference in the proportion of myeloid leukemia cells,white blood cell count,platelet count,red blood cell count,and hemoglobin between the two groups before and after treatment (all P ＞ 0.05).There was no significant difference in clinical safety indicators (urine,faecal routine,liver and kidney function,and electrocardiogram) between the two groups (all P ＞ 0.05).Conclusions Tetrandrine is more effective in patients with relapsed/refractory acute leukemia (except M3) with shorter duration of disease.Compared with chemotherapy alone,the clinical efficacy of adding tetrandrine in chemotherapy cannot be considered superior to the former.

Objective: To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment. Methods: Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed. Results: The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) . Conclusions: Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.

As more and more clinical trials about chimeric antigen receptor T cells (CAR-T) have been carried out successfully, the CAR-T are getting well-known. Thanks for genetic engineering, CAR-T has the tumor special antigen expressed on the surface. CAR-T therapy is the adoptive immunotheraphy for rapidly advancing tumors. This technology has made a great progress in both blood malignancies and solid tumor. However, CAR-T also meet many difficulties in the way of development. This review discusses the clinical application, challenges and developing trend of CAR-T.

Acinetobacter baumannii (Ab) bacteraemia in patients with haematological malignancies is fatal but rarely reported. We explored the clinical characteristics, drug resistances and prognostic factors in these patients. This multicentre, retrospective study was conducted at the department of haematology wards of 18 tertiary hospitals in China from January 2014 to June 2015. The total clinical isolates from every source were collected from patients with haematological malignancy. Haematological malignancy patients diagnosed with Ab bacteraemia were analysed. During the study period, 40 patients with Ab bacteraemia were identified, accounting for 2.9% (40/1358) of bacteraemia cases, of which 25 (62.5%) had acute leukaemia (AL) and 27 (67.5%) had neutropaenia. Compared with non-neutropaenic patients, neutropaenic patients showed higher Acute Physiology and Chronic Health Evaluation (APACHE) scores and 30-day mortality rates (p < 0.05). The in vitro antibiotic susceptibility of Ab to colistin was highest, at 100%, followed by that of tigecycline (91.30%) and amikacin (75.86%). Compared with the patients who had carbapenem-susceptible Ab infections, patients infected with carbapenem-resistant Ab (CRAB) had significantly longer hospital stays and were more likely to have had exposure to carbapenem before bacteraemia (p < 0.05). The 30-day mortality rate was 32.5%. CRAB, neutropaenia, higher APACHE score, Pitt bacteraemia score and inappropriate initial antimicrobial therapy were significantly associated with 30-day mortality. Multivariable analysis showed that APACHE score and CRAB were independent predictors of 30-day mortality. Haematologic patients with AL and febrile neutropaenia were at high risk of Ab bacteraemia. More attention should be paid to CRAB, which is an independent risk factor for mortality in haematological malignancy patients with Ab bacteraemia.

PURPOSE:Develop and evaluate an electrochemical method to identify healthy individuals, malignant hematopathic patients and solid tumor patients by detecting the leukocytes in whole-blood.METHODS:A total of 114 individual blood samples obtained from our affiliated hospital in China (June 2015- August 2015) were divided into three groups: healthy individuals (n = 35), hematologic malignancies (n = 41) and solid tumors (n = 38). An electrochemical workstation system was used to measure differential pulse voltammetry due to the different electrochemical behaviors of leukocytes in blood samples. Then, one-way analysis of variance (ANOVA) was applied to analyze the scanning curves and to compare the peak potential and peak current.RESULTS:The scanning curve demonstrated the specific electrochemical behaviors of the blank potassium ferricyanide solution and that mixed with blood samples in different groups. Significant differences in mean peak potentials of mixture and shifts (ΔEp (mV)) were observed of the three groups (P< = 0.001). 106.00±9.00 and 3.14±7.48 for Group healthy individuals, 120.90±11.18 and 18.10±8.81 for Group hematologic malignancies, 136.84±11.53 and 32.89±10.50 for Group solid tumors, respectively. In contrast, there were no significant differences in the peak currents and shifts.CONCLUSIONS:The newly developed method to apply the electrochemical workstation system to identify hematologic malignancies and solid tumors with good sensitivity and specificity might be effective, suggesting a potential utility in clinical application.

Abstract Text: Objective: The mortality rate of refractory/relapsed acute myeloid leukemia (AML) is very high with poor prognostic. Three are still no standard treatments for these patients nowadays. Our research compared the treatment effect between patients with chemotherapy and transplantation. Method: A retrospective research of 45 patients with refractory/relapsed AML was performed in our center. We analyzed the clinical features including gender, age, classification of AML, performance status (PS), complete remission (CR) duration, cytogenetic and molecular abnormities. Survival analyses were made by using the Kaplan Meier method and took the Log - rank test. Results: The mean survival time of the 45 patients with refractory/relapsed AML was (36.25¡À8.40) months and the median follow up was (9¡À2.58) months. The one year and two years overall survival rate was (40.6¡À7.5)% and (23.7¡À7.0)%. Univariate analysis results demonstrated that age¡Ý60 years and failing to undergo HSCT after relapse had poor influence on OS. Conclusion: Performance of HSCT after relapse can improve the prognosis through the single center study. HSCT is still the effective salvage therapy for patients with refractory/relapsed AML. Our research is benefit for individual therapy and can be applied to improve the survival.

To increase the encapsulation of hydrophilic antitumor agent daunorubicin (DNR) and multidrug resistance reversal agent tetrandrine (Tet) in the drug delivery system of nano-particles (NPs), a functional copolymer NP composed of poly(lactic-co-glycolic acid) (PLGA), poly-l-lysine (PLL), and polyethylene glycol (PEG) was synthesized and then loaded with DNR and Tet simultaneously to construct DNR/Tet-PLGA-PLL-PEG-NPs using a modified double-emulsion solvent evaporation/diffusion method. And to increase the targeted antitumor effect, DNR/Tet-PLGA-PLL-PEG-NPs were further modified with transferrin (Tf) due to its specific binding to Tf receptors (TfR), which is highly expressed on the surface of tumor cells. In this study, the influence of the diversity of formulation parameters was investigated systematically, such as drug loading, mean particle size, molecular weight, the concentration of PLGA-PLL-PEG-Tf, volume ratio of acetone to dichloromethane, the concentration of polyvinyl alcohol (PVA) in the external aqueous phase, the volume ratio of the internal aqueous phase to the external aqueous phase, and the type of surfactants in the internal aqueous phase. Meanwhile, its possible effect on cell viability was evaluated. Our results showed that the regular spherical DNR/Tet-PLGA-PLL-PEG-Tf-NPs with a smooth surface, a relatively low polydispersity index, and a diameter of 213.0 +/- 12.0 nm could be produced. The encapsulation efficiency was 70.23%+/- 1.91% for DNR and 86.5%+/- 0.70% for Tet, the moderate drug loading was 3.63%+/- 0.15% for DNR and 4.27%+/- 0.13% for Tet. Notably, the accumulated release of DNR and Tet could be sustained over 1 week, and the Tf content was 2.18%+/- 0.04%. In cell viability tests, DNR/Tet-PLGA-PLL-PEG-Tf-NPs could inhibit the proliferation of K562/ADR cells in a dose-dependent manner, and the half maximal inhibitory concentration value (total drug) of DNR/Tet-PLGA-PLL-PEG-Tf-NPs was lower than that of DNR, a mixture of DNR and Tet, and DNR/Tet-PLGA-PLL-PEG-NPs. These results clearly indicate that the PLGA-PLL-PEG formulation is a potential drug delivery system for hydrophilic and hydrophobic drugs, and that Tf modification may increase its targeting properties.

OBJECTIVE:To study the incidence, risk factors and outcome of invasive fungal infection(IFI) in the recipients with allogeneic hematopoietic cell transplantation(HSCT).METHODS:79 cases received HSCT in our hospital from January 2005 to November 2014 with complete data were analyzed retrospectively according to the diagnostic criteria of IFI. the clinical features, risk factors and outcome of IFI were investigated and analysed.RESULTS:17 cases of IFI were diagnosed, among them 13 cases were defined in clinic and 4 cases were possible. The median time of IFI occurence was 112 days(9-1931 d). The recurrence-free survival rate in non-infection and infection groups were 61.2% and 35.2% respectively. By single-factor analysis, the matching, II and IV degree of aGVHD were the risk factors of IFI, and the sex, protopathy, glucocorticoid used before infection were the risk factors of the death outcome. Multivariate analysis may indicated that the matching, II-IV degree of aGVHD and glucocorticoid used before infection were associated with IFI and outcome.CONCLUSION:The patients received HSCT and having many risk factors are more likely predisposed to IFI. A greater dose of glucocorticoid used before infection is more likely to results in death, morever avoiding the risk factors may reduce the incidence of IFI, and the retrospecion of immunosupperssor dose used within 30 days before infection may improve prognosis.

Background: MCM7 is one of the subunits of the MCM2-7 complex that are essential for DNA replication licensing and control of cell cycle progression. It also participates in mRNA transcription and DNA damage regulation. It is found that MCM7 was highly expressed in many cancer cells including Leukemia. Thus, lentivirus-mediated siRNA targeting MCM7 was used to suppress its endogenous expression in K562 cells and develop a novel therapeutic strategy for leukemia. Method: Lentivirus-mediated siRNA targeting MCM7 were designed and infected K562 cells. Down-regulation of MCM7 mRNA and protein expression in K562 cells were determined by Real-time PCR and Western blot analysis. The proliferation of the transfected K562 cells was assessed by CCK8 assay. Cell cycle progression and apoptosis were calculated by flow cytometry. The related protein levels of the transfected K562 cells were detected by Western blot. The stably transfected K562 cells were injected into nude mice. The transplanted tumors were measured and weighed, then Western blot and Immunocytochemistry were used to evaluated the expression of the proteins for mechanism. Results: The mRNA and protein expression of MCM7 in the stably transfected K562 cells decreased with the percentage of 92.3±1.88 and 91.18%±0.93 respectively. Compared with control and negative control groups, the proliferative rate of K562 cells was significantly reduced after LV-MCM7-RNAi infection. The cell cycle progression of K562 cells was blocked, with a massive increase in the percentage of cells in the G0/G1 phase and decrease in S phase. The apoptosis rate of the transfected K562 cells was significantly higher. PLK1 and pPLK1 protein were down-regulated in response to MCM7 inhibition; P53 and bax protein were up-regulated simultaneously. In vivo, the tumor size and weight dramatically decreased in the MCM7-RNAi group than in negative control group. PLK1, pPLK1 proteins in transplanted tumors were down- regulated and P53,bax were up-regulated correspondingly. Conclusions: Lentivirus-mediated MCM7 shRNA has effectively down regulated the expression of MCM7 gene on mRNA and protein levels. Moreover, the silence of MCM7 has led to the significant decrease in proliferation, blocking the cell cycle progression of K562 cells in vitro. Simultaneity, the apoptosis of the leukemia cell was enhanced. Both of the functions above cause the inhibition of the tumor growth in nude mice. Overall, these results suggest that the proliferation and cell cycle of K562 cells could be regulated by silencing MCM7 gene which is a promising gene therapeutic method to treat gastric cancer. Disclosures No relevant conflicts of interest to declare.

Objective: This study aims to investigate the potential benefit of combination therapy with magnetic nanoparticles of Fe3O4 (Fe3O4-MNP) and gambogic acid (GA) on SMMC-7721 cells.Methods: The inhibition of proliferation of SMMC-7721 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was calculated and analyzed by flow cytometry, and the expressions of the apoptosis-related protein were detected by Western blot.Results: GA enhanced the cytotoxicity of SMMC-7721 cells in a dose-dependent manner. The Fe3O4-MNP itself had no obviously inhibitory effect, but it could enhance the effect of GA on proliferation of SMMC-7721 cells. The apoptotic rate of SMMC-7721 cells induced by combination of GA with Fe3O4-MNP was higher than that by GA alone. The expression levels of caspase-3 and caspase-8 after co-treatment of GA and Fe3O4-MNP were higher than that exposed to either GA or Fe3O4-MNP alone, while the levels of bcl-2 were downregulated.Conclusion: Fe3O4-MNP can promote GA-induced apoptosis of SMMC-7721 cells, which may be related to the downregulation of Bcl-2 and upregulation of caspase-3.

Chronic graft-versus-host disease (cGVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is also one of the major causes of patients' death following transplantation. Recently, extracorporeal photochemotherapy (ECP) has shown a considerable efficacy in cGVHD treatment, which is based on the infusion of autologous peripheral blood mononuclear cells collected by aphesis, incubated with the photoactivable drug 8-methoxypsoralen (8-MOP) and UV-A irradiation. The therapeutic effect of ECP is mainly achieved by the induction of cell apoptosis, influencing the function of dendritic cells and the induction of immune tolerance. ECP has many advantages in the treatment of cGVHD, such as no increasing the risk of infection in patients, unaffecting the graft-versus-leukemia effect, nearly no side effect and so on. Many medical centers have done a lot of research on the treatment of cGVHD in both children and adults by using ECP and achieved good results. CD19(+) CD21(-) B lymphocytes, serum BAFF and serum TNFα can be used to measure and early evaluate the efficacy of ECP treatment. The effect of ECP is associated with many factors, and certain complications may occur during the treatment. At present, the application of ECP treatment is limited by the unclear mechanisms, varying treatment cycles in different studies, and small number of patients in clinical research. In the near future, with deeper basic research, increasing the case number and standard clinical treatment, ECP will have a more extensive application prospects. This review focuses mainly on the clinical advances of ECP in the treatment of cGVHD.