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【Objective】 To evaluate the clinical efficacy and prognostic factors in multiple myeloma (MM) patients treated with autologous hematopoietic stem cell transplantation (auto-HSCT). 【Methods】 The clinical data of 155 MM patients newly diagnosed and suitable for transplantation in our hospital from 2014 to 2021 were retrospectively analyzed. They were divided into auto-HSCT group and non-auto-HSCT group according to the treatment mode. The clinical efficacy, overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Furthermore, the prognostic factors of auto-HSCT group were analyzed. 【Results】 ① There were 51 patients in auto-HSCT group and 104 patients in non-auto-HSCT group. There was no statistical difference in baseline characteristics except age between the two groups. ② Hematopoietic reconstruction was achieved in all patients in auto-HSCT group, and no transplantation-related mortality was found. ③ The clinical efficacy of pre-and post-transplantation was compared in auto-HSCT group. sCR/CR rate was significantly increased after transplantation (P=0.041). The effective remission rate (≥VGPR) was also higher (P=0.05). As for the best efficacy, sCR/CR rate and effective remission rate were both significantly higher in auto-HSCT group than in non-auto-HSCT group (P=0.001). ④ In auto-HSCT group, by the end of follow-up, the median OS was not reached, the median PFS was 30.5 months, and 3-year OS and PFS was 87% and 40.3%, respectively. In non-auto-HSCT group, the median OS was 61 months, the median PFS was 21 months, and 3-year OS and PFS was 65.3% and 33.1%, respectively. It indicated that OS was significantly prolonged in auto-HSCT group (P=0.004). PFS was also prolonged but without significant difference (P=0.065). ⑤ Analysis of prognostic factors in auto-HSCT group showed that decreased PLT (P=0.038) and increased serum-adjusted calcium (P=0.017) were independent risk factors for OS, decreased PLT (P=0.005), female (P=0.018) and disease status of PR or worse before transplantation (P=0.012) were independent risk factors for PFS. 【Conclusion】 Auto-HSCT can improve the remission rate, prolong OS in MM patients, and possibly prolong PFS. Increased serum-corrected calcium and decreased PLT are independent prognostic factors for OS in patients treated with auto-HSCT. Decreased PLT, female, and disease status of PR or worse before transplantation are independent prognostic factors for PFS.
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【Objective】 To clarify the composition of essential oil extracted from Chimonanthus praecox flowers in Shiyan area and to explore its anti-inflammatory effects to provide support for further development of the resources of Chimonanthus praecox flowers. 【Methods】 SD rats were randomly divided into blank control group, model group, positive control group (aspirin 200 mg/kg), and low-, medium- and high-dose essential oil groups (0.1, 0.3 and 0.8g/kg). The blank control group and the model group were treated with distilled water by intragastric administration. The positive control group was treated with aspirin by intragastric administration. The low, medium, and high doses of the essential oil extracted from Chimonanthus praecox flowers were given 10, 30 and 80 mL/L at 10 mL/kg once a day. On day 5 of the experiment, 30 minutes after intragastric administration, 0.1 mL of Freund’s complete adjuvant was injected subcutaneously into the right foot plantar of each group of rats, and the blank control group was subcutaneously injected with 0.1 mL of normal saline. We observed and measured the toe’s volume of the rats before and 1, 2, 3, 5, 24, 48, and 72 h after injection by using drainage method. We then calculated the toe’s swelling rate in each group of rats at each time point, and used ELISA kit to measure the content of inflammatory factors in swollen foot tissue. 【Results】 In the medium- and high-dose essential oil groups, we observed significant inhibitory effects on the toe’s swelling rate in rats at 1, 2, 3, 5, 24, and 48 h after inflammation with Freund’s complete adjuvant (P<0.05). The essential oil extracted from Chimonanthus praecox flowers could significantly decrease the contents of TNF-α and IL-1β in the swollen foot tissue, and its anti-inflammatory effect was dose-dependent. 【Conclusion】 The essential oil extracted from Chimonanthus praecox flowers has obvious inhibitory effects on the rate of the toe’s swelling induced by Freund’s complete adjuvant. The anti-inflammatory effect may be related to the inhibition of TNF-α and IL-1β, but its anti-inflammatory effect is weaker than that of aspirin.
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Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.
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Objective To investigate the protective effects of 3-n-butylphthalide (dl-NBP) on the cognitive dysfunction of chronic cerebral ischemic rats and its mechanism.Methods Old chronic cerebral ischemic rats (15 months) were modelized with ligating bilateral common carotid arteries for three months.Model rats were divided into four groups:sham,model,NBP 30 and 120 mg · kg-1 groups.The former and the latter two groups were administered vegetable oil and NBP for 45 days,respectively.Then,the cognitive function was measured in rats with Morris water maze.Meanwhile,the activities of superoxide dismutase (SOD),choline acetyltransferase (ChAT),true choline esterase (TChE),and the malondialdehyde (MDA) levels in brain cortex and hippocampus were detected with biochemical methods.Results During the five days of Morris water maze,the change of escape latency was from (57.7±3.8) s to (30.5±17.1) s in low dose of NBP group,and from (58.4±1.8) s to (28.9±11.3) s in high dose of NBP group as compared with no change from 60s to 60s in model group.Significant differences were found in escape latency between NBP's and model groups(P＜0.05 or 0.01).In spatial exploratory test,the time percentages spent in the platformquadrant were increased obviously in low and high doses of NBP [(26.0±6.9) ％ and (27.3±5.3) ％,respectively,P＜0.05],compared with that of model group.The SOD activity was obviously reduced in cortices of high dose of NBP group [(112.3 ± 7.6) U/mg protein] compared with that (134.6 ± 13.9) U/mg protein of model group (P＜0.01).The MDA contents were significantly reduced in cortices of low and high doses of NBP (2.39±0.31) nmol/mg protein and (1.56±0.19) nmol/mg protein,compared with that of model group (P＜0.01).The MDA contents in hippocampi of low and high doses of NBP [(0.71±0.10) nmol/mg protein and (0.83±0.05) nmol/mg protein] were also decreased significantly,compared with that of model group (P＜0.01).The ChAT level in cortex of high dose of NBP was increased significantly [(1615 ± 100) U/g protein,P＜0.05].The ChAT level in hippocampi of two doses of NBP also increased significantly [(1746±204) U/g protein and (1697± 117) U/g protein,P＜0.05].Conclusions NBP may improve cognition damage of chronic cerebral ischemic rats by ameliorating oxidative stress lesion and enhancing the activity of cholinergic nerve in brain tissue.
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Objective To investigate the expression level and clinical significance of WT1 gene in acute luekemia (AL) patients.Methods WT1 gene level was detected by real time quantitative-polymerase chain reaction in acute myelogenous leukemia (AML) and in acute lymphocytic leukemia (ALL) patients.Then the expression levels of WT1 gene in different subtypes of AML were compared,and the correlation between gene expression and disease courses and prognosis were observed.Moreover,the relationship between disease courses and WT1 expression in patiens after receiving haemopoietic stem cell transplantation were analyzed.Results Among 66 cases,WT1 expression positive rate was 87.5 ％ (14/16) in AML and 76.0 ％ (38/50) in ALL.In AML,the expression level in M3 showed the lowest than that in any other subtypes (compared with M1,M2,M4,M5,P value was 0.040,0.007,0.006 and 0.01,respectively).The expression level of WT1 was closely correlated with leukemia disease courses.The expression level in complete remission (CR) group showed a significant lower expression level than that in non-remission group (P =0.018) and relapse group (P =0.003),and the re-increase of WT1 expression level could predict relapse as early as 1.5 months.Moreover,WT1 expression also showed an close relationship with prognosis of patients receiving haemopoietic stem cell transplantation.Patients whose WT1 was undetectable had a better prognosis than those with persistent expression,and increase again after becoming undetectable.Conclusion WT1 has a high expression level in AL,which can represent minimal residual disease.The expression level in M3 was lowest than that in different AML subtypes,and its expression level has a close correlation with clinical disease course and prognosis of AL.
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ObjectiveTo perform pharmacology problem-based learning (PBL) and evaluate its effects.MethodsPBL was performed for the clinical medicine class of grade 2007 and the satisfactory degree of students to teaching effects was observed with questionnaire. Results The students thought that PBL teaching had substantial contents and proper schedule and increased learning interest. Students' participating degree, mutual communication and controlling discussion procedure were fine,which reached the expected learning objective. ConclusionsThe effects of PBL teaching were excellent and most of our students could accept it.
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Objective To study the clinic effect and safety of MEAD chemotherapy regimen for adult patients with relapsed or refractory acute lymphocyte leukemia. Methods Between July 2006 and July 2009,twenty-two adult patients with relapsed or refractory acute lymphocyte leukemia received MEAD regimen (mitoxantrone 6 mg/d dl-3 iv drip,cytarabine 100 mg/d dl-5 iv drip,etoposide 100 mg/d dl-5 iv drip,dexmethasone 10 mg/d dl-8 iv drip). Results The complete remission (CR) rate of adult patients with relapsed or refractory acute lymphocyte leukemia was 31.8 %,the partial remission(PR) rate was 22.7 % and the overall response (OR) rate 54.5 %. The cumulitive CR rate was 50.0 %,and the PR rate 40.9 % after two times MEAD chemotherapy regimen. The main adverse effect was different level of myelosuppression,and other toxicity of vital organ was mild. Conclusion MEAD regimen is effective and can be tolerated for adult patients with relapsed or refractory acute lymphocyte leukemia,and its side effect is mild.
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The functional experimental teaching reform plays a very important role in raising the teaching resources,consummating the experimental teaching management system,enhancing the student to practice the ability and so on and has obtained the good effect.But it also faces some problems waiting urgently to be solved and further perfected,to which this article has made the analysis and the discussion from the management science angle.The goal lies in deepening the educational reform in functional experiment unceasingly to provide the model.
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Human acute premyeloid leukemia cell cDNA expression library was constructed to screen acute premyeloid leukemia tumor antigen. Total RNA and purified mRNA were extracted from human premyeloid cell line NB4. First and second strands of cDNA were synthesized by reverse transcription. After blunting, the cDNA fragments were ligated with EcoR I adapters. Then the cDNAs were digested with Xho I, and less than 400 bp cDNA fragment was removed by Sephacryl-S400 spin column, the remaining were ligated with lambdaZAP vector. The recombinants were packaged in vitro, and a small portion of packaged phage was used to infect E. coli XL1-Blue-MRF' for titration. The recombinants were examined by color selection. In order to evaluate the size of cDNA inserts and the diversity of library, the pBK-CMV phagemid was excised from the ZAP express vector by using ExAssist helper phage with XLOLR strain, and then the pBK-CMV phagemid was digested by Xho I and EcoR I. The results showed that the NB4 cell line cDNA library consisting of 1.65 x 10(6) recombinant bacteriophages was constructed with the recombinant ratio of 99.6%. The average length of the recombinant exogenous inserts was about 1.7 kb. It was concluded that the constructed cDNA library are deserved to screen target clones.
Subject(s)
Bacteriophages/genetics , DNA, Complementary/biosynthesis , DNA, Neoplasm/biosynthesis , DNA, Recombinant/biosynthesis , Gene Library , Genetic Vectors , Leukemia, Promyelocytic, Acute/genetics , Leukemia, Promyelocytic, Acute/metabolism , Leukemia, Promyelocytic, Acute/pathology , RNA-Directed DNA Polymerase/metabolism , Transcription, Genetic/geneticsABSTRACT
Human acute premyeloid leukemia cell cDNA expression library was constructed to screen acute premyeloid leukemia tumor antigen. Total RNA and purified mRNA were extracted from human premyeloid cell line NB4. First and second strands of cDNA were synthesized by reverse transcription. After blunting, the cDNA fragments were ligated with EcoR I adapters. Then the cDNAs were digested with Xho I, and less than 400 bp cDNA fragment was removed by Sephacryl-S400 spin column, the remaining were ligated with lambdaZAP vector. The recombinants were packaged in vitro, and a small portion of packaged phage was used to infect E. coli XL1-Blue-MRF' for titration. The recombinants were examined by color selection. In order to evaluate the size of cDNA inserts and the diversity of library, the pBK-CMV phagemid was excised from the ZAP express vector by using ExAssist helper phage with XLOLR strain, and then the pBK-CMV phagemid was digested by Xho I and EcoR I. The results showed that the NB4 cell line cDNA library consisting of 1.65 x 10(6) recombinant bacteriophages was constructed with the recombinant ratio of 99.6%. The average length of the recombinant exogenous inserts was about 1.7 kb. It was concluded that the constructed cDNA library are deserved to screen target clones.
Subject(s)
Humans , Bacteriophages , Genetics , DNA, Complementary , DNA, Neoplasm , DNA, Recombinant , Gene Library , Genetic Vectors , Leukemia, Promyelocytic, Acute , Genetics , Metabolism , Pathology , RNA-Directed DNA Polymerase , Metabolism , Transcription, Genetic , GeneticsABSTRACT
Objective: To evaluate the effect of the active specific immunotherapy with leukemia vaccine in the malignant hematopoietic diseases. Methods: We established the animal models by inoculating C57BL/6 rats with FBL-3 erythroleukemia cells and prepared three types of tumor vaccine, which were administered on the rats respectively. The MTT colorimetric assay was adopted 2 and 4 weeks later to test the cytotoxicity of macrophage (MΦ) and that of cytotoxic T lymphocyte(CTL) derived from the rats injected with tumor vaccines, and compared the results with the control group. Results: With the growth of erythroleulemia cells in the rats, the cellular immunity was seriously depressed, and the inhibition of specific cellular immunity was later than that of non-specific cellular immunity. The tumor vaccine made from inactivated tumor cells, IFA and cytokines (rGM-CSF, rIL-2 and rIL-6), promote the cellular immunity of tumor burden rats, especially the specific cellular immunity more efficiently than that of tumor vaccine made from inactivated tumor cells and IFA, but the third vaccine made from inactivated tumor cells alone has no effect. Conclusion: The tumor vaccine made from inactivated tumor cells with addition of IFA and cytokines (rGM-CSF, rIL-2 and rIL-6) provides a promising future in the active specific immunotherapy against hematopoietic tumor.
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Objective:To evaluate the cytotoxicity of macrophage of C57BL/6 mice treated with the prepared leukemia vaccine.Methods:Established the leukemia burden mice and prepared three types of leukemia vaccine,which were administered on the mice respectively.The MTT colormetric method was adopted 2 and 4 weeks later to measure the cytotxicity of M? derived from the mice accept immunotherapy or prevention,and compared with control group.Results:(1)With the growth of leukemia cells in the mice,the cytotoxicity of M? was seriously depressed;(2)The administration of tumor vaccine prepared from inactivated tumor cells,IFA and cytokines,such as rGM CSF,rIL 2 and rIL 6,promote the cellular immunity of tumor burden mice,more effciently than tumor vaccine made from either inactivated tumor cells and IFA or inactive tumor cells themselves along.Conclusion:The tumor vaccine simply prepared with inactive tumor cells,IFA and cytokines can active the non specific cellular immunity that represented as M?,for example non specific cytotoxicity,antigen present,immune surveillance and so on,these can build a base for active the T lymphocyte the next.The tumor vaccine provides a promising future in the therapy against hematopietic tumor.
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Objective: To observe the promoting blood circulation by removing blood stasis of Lubai Capsule(LBC)(Rhizoma Phragmitis, Radix Paeoniae Alba, Radix Saposhnikoviae, Flos Schizonepetae, etc.). Methods: Acute blood stasis rat models were established with swimming in iced water and sc adrenalin in order to observe the effect of LBC on blood rheology. Mesenteric microcirculatory disturbance rat models were also established with adrenalin in order to observe the effect of LBC. Clotting time was measured in vitro with prothrombin time(PT) and kaolin partial thromboplastin time(KPTT) kit in order to observe its effects. Results: LBC could decrease the whole blood and plasma viscosity, fibrinogen, erythrocyte sedimentation and aggregation ratio of blood platelets of rats, ease the sticky condition of blood stasis rat models and prevent from forming thrombus. It could also inhibit the constraction and slowing of blood flow of thin artery, the reducing of open capillaries and change of fluid condition caused by adrenalin and improve these phenomena. PT and KPTT could be increased obviously. Conclusion: LBC can significantly promote blood circulation by removing blood stasis, because of improving blood rheology and mesenteric microcirculatory disturbance and inhibit endogenous and exogenous coagulation system.