Objective To determine the occurrence rate of liver toxicity and related risk factors after receiving highly active an-tiretroviral-therapy(HAART)by the non-nucleoside reverse transcriptase inhibittor.Methods To observe the changes of liver func-tion indexes before and after antiviral therapy in 102 patients receiving HAART,the incidence rates of the liver toxicity were com-pared between nevirapine(NVP)and efavirenz(EFV)and the risk factors of liver toxicity after treatment were analyzed.Results A-mong 102 patients,73 cases accepted the treatment of NVP,the incidence rate of hepatotoxicity was 35.6%,29 cases accepted the treatment of EFV,the incidence rate of hepatotoxicity was 13.8%,the hepatotoxicity incidence rate had statistically significant difference between the two treatment methods(χ2 =4.761,P =0.029).Co-infected by hepatitis C virus(HCV)and baseline ALT el-evation were the independent risk factors of hepatotoxicity occurrence(P <0.05).Conclusion The patients receiving the treatment of NVP are more likely to have hepatotoxicity than the patients receiving the treatment of EFV.Co-infected by HCV and baseline ALT elevation are the independent risk factors of hepatotoxicity occurrence.

The effects of high-intensity pulsed electromagnetic stimulation (HIPEMS) on proliferation and differentiation of neonatal rat neural stem cells in vitro were investigated. Neural stem cells derived from neonatal rats were exposed to 0.1 Hz, 0.5-10 Tesla (T) [8 groups of B-I, respectively], 5 stimuli of HIPEMF. The sham exposure controls were correspondingly established. Inverted phase contrast microscope was used to observe the cultured cells, MTT assay to detect the viability of the cells as expressed by absorbance (A) value, and flow cytometry to measure differentiation of neural stem cells. The results showed that A values of neural stem cells in both 3.0 T and 4.0 T groups were significantly higher than the other groups 24 to 168 h post HPEMS, indicating a strong promotion of the growth of neural stem cells (P<0.05). The A values of neural stem cells in the 6.0 T, 8.0 T, and 10.0 T groups were lower than the sham exposure control group, indicating a restraint of the growth of neural stem cells. The rate of neuron-specific enolase-positive neurons revealed by flow cytometry in HPEMS groups was the same as that in control group (P>0.05). It was suggested that 0.1 Hz, 5 pulses stimulation of HPEMS within certain scale of intensity (0.5-10.0 T), significantly promoted the growth of neural stem cells with the rational intensity being 4.0 T.

BACKGROUND: The principal deterrent to the success for hematopoietic stem cell transplantation (HSCT) is the complications after transplantation. The complications are associates with the conditioning regimens in the early stage. The highly-effective preparative regimens of proper dose and low-toxicity are the key to the successful HSCT.OBJECTIVE: To evaluate the curative effects and regimen related toxicity (RRT) of high-dose alkylating-agent-based chemotherapy as conditioning regimens for HSCT in the patients with hematological malignancies.DESIGN: Controlled study with observation.SETTING: Department of Hematology, Affiliated Hospital of Xuzhou Medical College.PARTICIPANTS: A total of 45 patients with leukemia and lymphoma hospitalized at Affiliated Hospital of Xuzhou Medical College from July 1997 to February 2006 were enrolled, including 31 males and 14 females. The median age was 31 years (from 7 to 52 years). The median course was 8 months (from 5 to 17 months) until transplantation.METHODS: Totally 45 patients with leukemia and lymphoma approached or got complete remission were treated by bone marrow transplantation and peripheral blood stem cell transplantation with preparative regimens of high-dose alkylating-agent-based chemotherapy. RRT was graded according to Bearman proposal, from grade 0 (no toxicity) to grade Ⅳ (fatal toxicity). The period of hematopoietic reconstitution, the rates of complete remission and relapse and disease-free survival were statistically observed in transplant recipients.MAIN OUTCOME MEASURES: Occurrence of RRT as conditioning regimens.RESULTS: ①Five patients did not show any toxicity. The greatest toxicity of grade Ⅲ was uncommon (13%, 6/45). Most of the cases with RRT were in grade Ⅰ - Ⅱ and severe oases in grade Ⅲ were rare. In grade Ⅰ - Ⅱ, stomatocace and gastrointestinal toxicity were common respectively of 73% (33/45) and 51% (23/45) which were recovered in short time after treatment; Heart toxicity was rare and only in grade Ⅰ, most of which were tachyoardia and changes of ST-T shape. The increase of transaminase was common in the clinical manifestations of liver RRT except two cases of HVOD.There were four oases of HC, in which one was delayed. RRT on kidney, lungs and CNS was uncommon. ②Totally 43 patients engrafted gained hematopoietic reconstitution, 2 patients died of implant failure (4%). Within the median follow-up period of 37 (8-102) months, 10 patients relapsed, 5 patients died of transplantation-related complications and 28 patients were alive in a disease-free situation (62.2%). The cause of death within 100 days after transplantation was ordinal as acute graft-versus-host disease (GVHD), cytomegalovirus (CMV) interstitial pneumonia, disseminated infections,multiple organ failure and early relapses.CONCLUSION: Alkylating-agent-based conditioning regimens may be well tolerated with low toxicities for HSCT in leukemia and lymphoma.

Objective To explore relationship of the anesthetic risks and intraoperative complications.Methods Preoperative anesthetic risks were assessed with Hussman's method from May 2015 to May 2016 in 2 494 surgical patients, including 1 462 males and 1 032 females.Intraoperative data and complications were tracked and recorded.Results Three hundred and thirty-six intraoperative complications occurred, accounting for 13.47% of total patients.The cardiovascular complications were a major intraoperative complications, accounting for 80.7%.2 494 patients were graded respectively into risk grade 1 with 1 540 (61.75%), grade 2 with 660 (26.46%), grade 3 with 202 (8.10%), grade 4 with 80 (3.21%) and grade 5 with 12 (0.48%).The incidence of complications were 112 (7.28%), 82 (12.42%), 82 (40.59%), 50 (62.50%) and 10 (83.33%) respectively.The sensitivity of prediction was 33.33%, 24.40%, 24.40%, 14.88% and 2.78%;the specificity 33.76%, 73.26%, 94.44%, 98.61% and 99.91%;and the accuracy 33.76%, 66.64%, 85.01%, 87.33% and 86.85%, respectively, in patients with risk grade 1, 2, 3, 4 and 5.Conclusion Hussman's method of anesthetic risks well predicts the intraoperative complications.

BACKGROUND: The primary qualification of peripheral blood stem cell transplantation (PBSCT) is the effective mobilization and harvesting of hematopoietic stem cells. The mobilization efficacy is closely related to the selection of high-efficacy low-toxicity regimen, the timing of mobilization and harvesting as well.OBJECTIVE: To investigate the efficacy of mitoxantone (MIT) combined with high-dose arabinosylcytosin (Ara-C),followed by granulocyte colony-stimulating factor (G-CSF) alone or combination of G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) on mobilizing PBSCs in patients with hematological malignancies and solid tumors.DESIGN: Controlled study with observation.SETTTNG: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College.PARTICIPANTS: Forty-two patients with hematological malignancies and solid tumors admitted to Department of Hematology, Xuzhou Medical College from September 1998 to December 2006 were involved in this study. They were diagnosed according to FAB classification criteria and new WHO proposals. The involved patients, 25 male and 17 female, averaged 29 years ranging from 7 to 54 years and weighted (52±18) kg. Among them, 12 were patients with acute myeloblastic leukemia, 6 were patients with acute lymphoblastic leukemia (ALL), 1 was patient with chronic granulocytic leukemia (CGL) at chronic phase, 15 were patients with non-Hodgkin lymphoma (NHL), 4 were patients with Hodgkin lymphoma (HL), 2 was patient with multiple myeloma (MM), 2 were patients with advanced breast cancer. All the patients apprcached to or got complete remission after conventional chemotherapy. No tumor cell infiltration was observed in bone marrow cytological examination. The functions of the main organs such as heart, lung, liver and kidney,and so on, were normal. The patients underwent an average of 8-course chemotherapy before the mobilization. Informed consents of all the patients were obtained.METHODS: MIT was intravenously injected at 10 mg/(m2·d)for 2 to 3 days, then Ara-C was also intravenously injected at 2 g/m2 every 12 hours for 1 to 2 days. When white blood cell (WBC) count recovered from the lowest value, 5 to 7.5 μg/ (kg·d)G-CSF was applied in 20 patients for 3 to 5 days successively. And 5 to 7.5 μg/ (kg·d)G-CSF and 5 to 7 μ g/(kg·d)GM-CSF were applied in another 22 patients at 6:00 in the morning and in the evening, respectively. PBSCs harvesting started when WBC ＞ 2.5×109 L-1, especially when CD34+ cells≥ 1%,WBC was doubly increased. Autologous peripheral blood mononuclear cells (MNCs) were collected with CS3000 plus blood cell separator for detecting the level of CD34+ cells and T lymphocyte subsets. CFU-GM assays were performed in a methyl-cellulose-based clonogenic assay.① MNCs mixed with FITC-labeled CD34+, CD3 and CD8 monoclonal antibodies as well as CD4 PE-labeled CD monoclonal antibody at 4 ℃ for 30 minutes. 5×105 cells were determined, and CD3 and CD34+ levels, CD4/CD8 were determined by flow cytometer.Colony forming unit-granulocyte macrophage (CFU-GM) was determined with methyl cellulose. ② Related adverse reactions were observed after operation. ③ Aiming to different types of diseases,autologous PBSCs were back infused 36 to 48 hours after pre-disposal treatment. MNCs count and trypan-blue drying were done. Levels of CFU-GM and CD34+ cells were determined after unfreezing.MATN OUTCOME MEASURES: ① Changes in CD34+ cells and T lymphocyte subsets before and after mobilization. ② Postoperative related adverse reactions. ③ Back perfusion volume of autologous PBSCs (MNCs count, the number of CFU-GM and CD34+ cells).RESULTS: Forty-two involved patients participated in the final analysis. ① Changes in CD34+ cells and T lymphocyte subsets before and after mobilization: Without using hematopoietic growth factors (HGF), the percentage of CD34+ cells in peripheral blood of the patients was (0.054±0.032)%. After using G-CSF/GM-CSF treatment, it was (1.82±0.76)%,which was obviously increased compared with that of without using HGF (P ＜ 0.001). The CD34+ cells and CFU-GM yields of 22 patients in C-CSF plus GM-CSF combination group [(8.76±3.39)×106/kg, (3.52±1.33)×105/kg, respectively]were significantly higher than those of 20 patients in G-CSF alone group [(6.12±2.11)×106/kg, (2.03±1.07)×105/kg,respectively (P ＜ 0.05)]. There were no obvious changes of T lymphocyte subsets in the patients when using G-CSF/GM-CSF for some days except that CD34+ cells increased gradually (P ＞ 0.05). ② Postoperative related adverse reactions: Ⅱ to Ⅲ degree hair-loss was seen in all the patients. Blood platelets dropped to (54.43±26.14)×109 L-1 at different degrees. Infective fevers (37.8 ℃ to 41.0 ℃) occurred in 21 patients. But they were controlled in short term after antibiotics treatment. All the side effects of G-CSF and GM-CSF were mild and reversible, easily controlled with paracetamol or steroids. Bone pain (mainly in lumbosacral region) occurred in 13 patients when WBC went up quickly. ③ Back perfusion volume of autologous PBSCs: PBSCs were cryopreserved at -80 ℃ without program control for 2.0 to 6.5 months. The cell recovery rate was (88.7±7.4) %. Trypan blue exclusion rate was (92.1±5.5) %. The back perfusion volume of MNCs, CD34+ cells and CFU-GM yields were (5.21±2.44)×108/kg, (6.89±3.55)×106/kg, (2.58±2.33)×105/kg,respectively. ④Circulation blood volume were 10 to 16 L (end-point separation blood volume were all above trebling TBV). Hematopoiesis was well reconstituted in 40 patients received autologous PBSCT.CONCLUSTON: MIT and high-dose Ara-C chemotherapy combined with both G-CSF alone and G-CSF plus GM-CSF can safely and effectively mobilize autologous PBSCs, while G-CSF plus GM-CSF is superior to G-CSF alone.Large-volume leukapheresis is an important method to enhance the productive rate of stem cells and decrease the times of harvesting.

The effects of high-intensity pulsed electromagnetic stimulation (HIPEMS) on proliferation and differentiation of neonatal rat neural stem cells in vitro were investigated. Neural stem cells derived from neonatal rats were exposed to 0.1 Hz,0.5-10 Tesla (T) [8 groups of B-I,respectively],5 stimuli of HIPEMF. The sham exposure controls were correspondingly established. Inverted phase contrast microscope was used to observe the cultured cells,MTT assay to detect the viability of the cells as expressed by absorhance (A) value,and flow cytometry to measure differentiation of neural stem cells. The results showed that A values of neural stem cells in both 3.0 T and 4.0 T groups were significantly higher than the other groups 24 to 168 h post HPEMS,indicating a strong promotion of the growth of neural stem cells (P＜0.05). The A values of neural stem cells in the 6.0 T,8.0 T,and 10.0 T groups were lower than the sham exposure control group,indicating a restraint of the growth of neural stem cells. The rate of neuron-specific enolase-positive neurons revealed by flow cytometry in HPEMS groups was the same as that in control group (P＞0.05). It was suggested that 0.1 Hz,5 pulses stimulation of HPEMS within certain scale of intensity (0.5-10.0 T),significantly promoted the growth of neural stem cells with the rational intensity being 4.0 T.

OBJECTIVETo verify the feasibility and safety of the vascular interventional vascular interventional surgical robot system applied to vascular interventional operation.

METHODSFrom March to September 2013, 10 patients had undergone robot-assisted cerebral angiography. There were 6 male and 4 female patients; aged from 19 to 58 years, with an average age of 38.4 years. The operation were carried out by neurosurgeons and vascular interventional robot. After successfully implanted of femoral artery sheath by hand, the catheter was fixed on the robot, under the guidance of navigation image the surgeon manipulate the master part and control the slave part of robot by sending command through network transmission, finally finished the whole cerebral angiography. The operation time was recorded from placing the sheath into femoral artery to finishing cerebrovascular selective angiography, simultaneously the time of staff under exposure of X ray was recorded, and the position difference between the setted targets and the actual position(positioning accuracy).

RESULTSIt took 25-41 minutes to finish the cerebral angiography, the average time was (31 ± 5) minutes, and the robot-assisted angiography went quickly and smoothly without surgical complications. The remote positioning accuracy was (1.03 ± 0.23) mm. The time of staff under exposure of X ray was 0 minute, the entire experimental process was basically implemented mechanization and automation.

CONCLUSIONThis system basically achieves initial medical purposes, such as reducing the radiation, facilitating interventional procedures on the basis of enhancing the image navigation, shorting the operation time, and improve the quality of operation.

Objective: To explore effects of histone deacetylase inhibitor Belinostat on the immunologic function of dendritic cells (DC) and its possible mechanism. Methods: Cultured mouse bone marrow-derived DC from C57BL/6 mouse in vitro. The experiments were divided into 0, 50, 100 nmol/L Belinostat + immature DC (imDC) group, and 0, 50, 100 nmol/L Belinostat mature DC (mDC). The changes of the ultrastructure of DC were observed by transmission electron microscope (TEM). Immunophenotype and CCR7 expression rate were detected by FCM, and the migration rate was observed by chemotaxis assay. The proliferation of lymphocytes stimulated by different DC was detected by mixed lymphocyte culture reaction. The cytokines in the culture supernatant, including TNF-α, IL-12 and IL-10, were examined by ELISA. RQ-PCR was used to examine the relative expression of mRNA in RelB. Results: Successful cultured and identified the qualified imDC and mDC. Belinostat decreased the expression of CCR7 on imDC [(25.82±7.25)% vs (50.44±5.61)% and (18.71±2.00)% vs (50.44±5.61)%], meanwhile increased the rate on mDC [(71.14±1.96)% vs (64.90±1.47)%]. Chemotaxis assay showed that the migration rate of Belinostat+imDC and Belinostat+mDC group were both decreased, but the difference in imDC was not significant. T lymphocyte proliferation rate stimulated by 100 nmol/L Belinostat+imDC group was lower than imDC group in condition irritation cell∶reaction cell=1∶2 [(227.09±13.49)% vs (309.49±53.69)%]. Belinostat significantly suppressed the secretion of cytokines TNF-α, IL-12 and IL-10 (all P<0.01). The relative expression of mRNA in RelB was slightly decreased in Belinostat+imDC and Belinostat+mDC group (all P<0.05). Conclusion Belinostat could effectly suppress DC maturation and regulate immune tolerance of DC, which may be due to the down-regulation of mRNA level of RelB in DC.

Objective:To investigate the clinical characteristics, efficacy and prognostic influencing factors of IgD multiple myeloma (MM) in the new immunotherapy era.Methods:The clinical data of 29 patients diagnosed with IgD MM in the Affiliated Hospital of Xuzhou Medical University from March 2014 to February 2021 were retrospectively collected. The clinical characteristics, treatment regimens and efficacy, especially the efficacy of new drugs and immunotherapy for the disease were analyzed. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS). Multivariate Cox proportional risk model was used for analysis of prognostic influencing factors.Results:The median age of patients was 58 years. There were 20 cases (69.0%) below 65 years, 12 cases (41.4%) of complicated with stomach function damage, 6 cases (20.7%) of extramedullary invasion. All patients were treated with combined therapy containing proteasome inhibitor bortezomib in the first-line therapy, and the overall response rate was 82.8% (24/29). Among 21 relapsed/refractory patients, 12 patients were treated with the second-line or above treatment regimen chimeric antigen receptor T cell (CAR-T) immunotherapy, including 9 cases achieving very good partial remission (VGPR) or above; 5 patients were treated with the new drug daratozumab, including 1 case achieving complete remission (CR). The median OS time of 29 patients was 48 months (95% CI 17-79 months), the median PFS time after the first-line treatment was 9 months (95% CI 3-15 months), and the median PFS time after the second-line treatment was 11 months (95% CI 1-21 months). Multivariate Cox regression results showed that CAR-T therapy is an independent influencing factor of the prognosis of relapsed/ refractory IgD MM patients ( HR = 0.094, 95% CI 0.019-0.473, P = 0.004). Conclusions:IgD MM patients are characterized with lower onset age, more renal function damage and a high incidence of extramedullary invasion. The first-line therapy containing proteasome inhibitor has a better short-term efficacy, and CAR-T therapy can improve the remission rate and survival rate of relapsed/refractory IgD MM to a certain extent.