1.Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma.
Meng ZHANG ; Pan WU ; Yan Long DUAN ; Ling JIN ; Jing YANG ; Shuang HUANG ; Ying LIU ; Bo HU ; Xiao Wen ZHAI ; Hong Sheng WANG ; Yang FU ; Fu LI ; Xiao Mei YANG ; An Sheng LIU ; Shuang QIN ; Xiao Jun YUAN ; Yu Shuang DONG ; Wei LIU ; Jian Wen ZHOU ; Le Ping ZHANG ; Yue Ping JIA ; Jian WANG ; Li Jun QU ; Yun Peng DAI ; Guo Tao GUAN ; Li Rong SUN ; Jian JIANG ; Rong LIU ; Run Ming JIN ; Zhu Jun WANG ; Xi Ge WANG ; Bao Xi ZHANG ; Kai Lan CHEN ; Shu Quan ZHUANG ; Jing ZHANG ; Chun Ju ZHOU ; Zi Fen GAO ; Min Cui ZHENG ; Yonghong ZHANG
Chinese Journal of Pediatrics 2022;60(10):1011-1018
Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Burkitt Lymphoma/drug therapy*
;
Child
;
Disease-Free Survival
;
Female
;
Humans
;
Lactate Dehydrogenases
;
Lymphoma, B-Cell/drug therapy*
;
Male
;
Prognosis
;
Retrospective Studies
;
Rituximab/therapeutic use*
;
Treatment Outcome
2.In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy.
Tian-Zi WEI ; Hao WANG ; Xue-Qing WU ; Yi LU ; Sheng-Hui GUAN ; Feng-Quan DONG ; Chen-le DONG ; Gu-Li ZHU ; Yu-Zhou BAO ; Jian ZHANG ; Guan-Yu WANG ; Hai-Ying LI
Chinese journal of integrative medicine 2020;26(9):663-669
OBJECTIVE:
To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening.
METHODS:
The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper.
RESULTS:
It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score.
CONCLUSIONS
A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.
China
;
Computer Simulation
;
Coronavirus Infections
;
diagnosis
;
drug therapy
;
Drug Repositioning
;
methods
;
Drugs, Chinese Herbal
;
pharmacology
;
Glycoproteins
;
drug effects
;
metabolism
;
Humans
;
Imaging, Three-Dimensional
;
Mass Screening
;
methods
;
Molecular Docking Simulation
;
methods
;
Pandemics
;
Peptidyl-Dipeptidase A
;
drug effects
;
Pneumonia, Viral
;
diagnosis
;
drug therapy
;
Protein Binding
;
United States
;
United States Food and Drug Administration
3.Influence of multi-stage psychological intervention on long-term prognosis of CHD patients undergoing revascularization
Jing YANG ; ying Cheng BAO ; Quan ZHOU ; qin Yu GUAN
Chinese Journal of cardiovascular Rehabilitation Medicine 2017;26(6):593-596
Objective:To explore influence of multi-stage psychological intervention on long-term prognosis of patients with coronary heart disease(CHD)undergoing revascularization therapy.Methods:A total of 160 CHD patients, who suffered from depression after revascularization in our hospital,were selected.According to random number ta-ble,they were randomly and equally divided into routine psychological nursing group and multi-stage psychological nursing group,both groups were followed up for two years.Scores of self-rating anxiety scale(SAS),self-rating de-pression scale(SDS),Gensini score and incidence rate of main adverse cardiovascular events(MACE)were com-pared between two groups at enrollment and two years after enrollment.Results:Compared with enrollment,two years later,all scores significantly reduced in two groups(P=0.001 all);compared with routine psychological nurs-ing group,there were significant reductions in scores of SAS[(65.74 ± 3.95)scores vs.(61.13 ± 3.87)scores],SDS [(70.14 ± 5.69)scores vs.(65.59 ± 5.70)scores]and Gensini[(40.33 ± 4.30)scores vs.(35.14 ± 3.61)scores]in multi-stage psychological nursing group,P=0.001 all;Incidence rate of MACE in multi-stage psychological nursing group was significantly lower than that of routine psychological nursing group(13.75% vs.31.25%,P=0.008). Conclusion:Multi-stage psychological intervention can significantly relieve anxiety and depression state,reduce inci-dence of major adverse cardiovascular events in patients with coronary heart disease after revascularization.
4.Expression and clinical significance of miR-21 in diffuse large B cell lymphoma.
Chun-Hong LI ; Rong FU ; Yi-Hao WANG ; Wen-Jing SONG ; Er-Bao RUAN ; Wen QU ; Hua-Quan WANG ; Guo-Jin WANG ; Jia SONG ; Xiao-Ming WANG ; Yu-Hong WU ; Li-Min XING ; Hong LIU ; Li-Juan LI ; Jing GUAN ; Zong-Hong SHAO
Journal of Experimental Hematology 2014;22(2):339-343
This study was aimed to investigate the expression of microRNA-21 and its correlation with PTEN in diffuse large B cell lymphoma (DLBCL) paraffin-embedded tissues, and evaluate its potential relevance with clinical characteristics. The expression levels of miR-21 in 26 primary DLBCL and 10 normal lymph node tissue specimens were examined by real-time polymerase chain reaction. The expression of PTEN was detected by immunohistochemical staining. The results indicated that the expression of miR-21 was significantly higher in tumor tissues [6.586(1.10,38.22)] than that in normal tissues [0.791 (0.35,2.87)] (P < 0.05). Among 26 patients with DLBCL the expression of PTEN protein was positive in 6 patients (23%), and was negative in 20 patients (77%). In patients with DLBCL, the expression level of miR-21 was negatively correlated with the level of PTEN protein. The high expression of miR-21 was positively correlated with the level of serum LDH. The expression level of miR-21 in patients with Ann Arbor III-IV stage was obviously higher than that of patients with Ann Arbor I-II stage, but did not correlate with the subtype of patients in clinic (P > 0.05). It is concluded that the expression of miR-21 is high in DLBCL and its overexpression may be related with poor prognosis of DLCBL. These findings suggest that PTEN is possibly one of the targets of miR-21 in DLBCL.
Adult
;
Aged
;
Aged, 80 and over
;
Female
;
Humans
;
Lymphoma, Large B-Cell, Diffuse
;
metabolism
;
pathology
;
Male
;
MicroRNAs
;
metabolism
;
Middle Aged
;
PTEN Phosphohydrolase
;
metabolism
;
Real-Time Polymerase Chain Reaction
5.Neuroprotective effects of the effective components group of xiaoshuantongluo against oxygen-glucose deprivation in primary cultured rat cortical neurons.
Xin-Mei XIE ; Xiao-Bin PANG ; Yan ZHAO ; Bao-Quan WANG ; Ruo-Yun CHEN ; Guan-Hua DU
Acta Pharmaceutica Sinica 2014;49(8):1130-1135
This study is to investigate the effect of the effective components group of Xiaoshuantongluo (XECG) on neuronal injury induced by oxygen-glucose deprivation (OGD) in primary cortical cultures isolated from SD rat cortex at day 3 and the possible mechanism. Cells were divided into control group, OGD model group and XECG group (1, 3 and 10 mg x L(-1)). The cell viability was assessed with MTT assay and the LDH release rate was measured by enzyme label kit. The cell apoptosis was analyzed using Hoechst staining. RT-PCR was applied to detect the mRNA levels of JAK2 and STAT3. Western blotting was used to detect the expressions of Bcl-2, Bax, p-JAK2 and p-STAT3 proteins. Results showed that XECG resulted in an obvious resistance to oxygen-glucose deprivation-induced cell apoptosis and decrement of cell viability, decrease the cell LDH release rate. XECG could adjust the expression of Bcl-2 and Bax proteins and increase Bcl-2/Bax ratio, up-regulate the expression of p-JAK2 and p-STAT3. In conclusion, XECG could protect against the neuronal injury cells exposed to OGD, which may be relevant to the promotion of JAK2/STAT3 signaling pathway, and impact the expression of Bax and Bcl-2.
Animals
;
Apoptosis
;
Cell Survival
;
Cells, Cultured
;
Drugs, Chinese Herbal
;
pharmacology
;
Glucose
;
Janus Kinase 2
;
metabolism
;
Neurons
;
drug effects
;
metabolism
;
Neuroprotective Agents
;
pharmacology
;
Oxygen
;
Proto-Oncogene Proteins c-bcl-2
;
metabolism
;
Rats
;
STAT3 Transcription Factor
;
metabolism
;
Signal Transduction
;
bcl-2-Associated X Protein
;
metabolism
6.Quantity and function of T follicular helper cells in the bone marrow of patients with immune thrombocytopenia.
Yang ZHANG ; Wen QU ; Er-Bao RUAN ; Rong FU ; Guo-Jin WANG ; Hong LIU ; Xiao-Ming WANG ; Yu-Hong WU ; Jia SONG ; Li-Min XING ; Jing GUAN ; Li-Juan LI ; Hua-Quan WANG ; Zong-Hong SHAO
Journal of Experimental Hematology 2014;22(3):758-761
This study was purposed to detect the quantity and function of bone marrow (BM) T follicular helper (Tfh) cells of patients with immune thrombocytopenia, and to explore the role of Tfh cells in the pathogenesis of ITP. Twenty-one newly diagnosed ITP patients, twenty ITP patients in recovery stage and eighteen normal controls were enrolled in this study. The percentages of Tfh cells, Tfh-related molecules ICOS, CD40L, IL-21 in BM were detected by flow cytometry (FCM), and the mRNA expression of BCL-6 in BMMNC was determined by semi-quantitive RT-PCR. Correlation of Tfh cell level with the disease severity of ITP patients was analysed. The results showed that the ratio of CD4(+)CXCR5(+)/CD4(+) cells in newly diagnosed ITP patients [(5.532 ± 2.599)%] was significantly higher than that in ITP patients with recovery stage [(4.064 ± 2.026)%] and controls [(4.048 ± 1.413)%] (P < 0.05). The ratio of CD4(+)CXCR5(+)ICOS(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(14.586 ± 8.561)%] was higher than that in recovery stage ITP patients [(12.884 ± 10.161)%] and controls [(7.487 ± 5.176)%]. The differences be-tween newly diagnosed ITP patients and controls were statistically significant (P < 0.05). The ratio of CD4(+)CXCR5(+) CD40L(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(15.309 ± 10.756)%] and in ITP patients with recovery stage [(18.242 ± 12.243)%] were significantly higher than that in controls [(8.618 ± 5.719) %] (P < 0.05). The ratio of intracytoplasm CD4(+) CXCR5(+) IL-21(+)/CD4(+)CXCR5(+) cells in newly diagnosed ITP patients [(58.560 ± 26.285)%] and in ITP patients with recovery stage [(57.035 ± 30.936)%] were significantly higher than that in controls [(36.289 ± 24.868)%] (P < 0.05). The relative expression levels of BCL-6 mRNA in BMMNC of three groups were (1.407 ± 0.264), (1.149 ± 0.217) and (0.846 ± 0.157), respectively. The differences between 3 groups were significant(P < 0.05). It is concluded that the quantity and function of Tfh cells in ITP patients increase, which may play an important role in the pathogenesis of ITP.
Adolescent
;
Adult
;
Aged
;
Bone Marrow
;
immunology
;
Bone Marrow Cells
;
cytology
;
Case-Control Studies
;
Child
;
Female
;
Flow Cytometry
;
Humans
;
Lymphocyte Count
;
Male
;
Middle Aged
;
T-Lymphocytes, Helper-Inducer
;
cytology
;
immunology
;
Thrombocytopenia
;
immunology
;
Young Adult
7.Impacts on analgesia and detumescence in ankle sprain treated with acupuncture at Xiaojie point combined with tendon-regulation manipulation.
Wei-Bin DU ; Guan-Ai BAO ; Ren-Fu QUAN
Chinese Acupuncture & Moxibustion 2014;34(7):647-650
OBJECTIVETo compare the efficacy difference of analgesia and detumescence on ankle sprain among acupuncture at Xiaojie point combined with tendon regulation manipulation, acupuncture at Xiaojie point and tendon regulation manipulation.
METHODSSixty cases of ankle sprain were randomized into a combined therapy group, a Xiaojie point group and a tendon-regulation manipulation group, 20 cases in each one. The combined therapy of acupuncture at Xiaojie point and tendon regulation manipulation, the acupuncture at Xiaojie point and the simple application of tendon-regulation manipulation were applied respectively in the three groups, once a day, 3 treatments were required. The symptom score such as pain, ecchymosis, swelling and motor dysfunction and the total score were observed before and after treatment in the three groups. The different values of pain and swelling scores were compared before and after treatment in the three groups. The efficacy was compared among the groups.
RESULTSThe total effective rate was 100.0% (20/20) in each group. But the curative rate was 85.0% (17/20) in the combined group, 65.0% (13/20) in the Xiaojie point tion manipulation group. After treatment, the symptom scores of pain, ecchymosis, swelling and motor dysfunction and the total score were all improved as compared with those before treatment in the three groups (P < 0.01, P < 0.05). The pain score in either the combined therapy group or Xiaojie point group was lower than that in the tendon-regulation manipulation group after treatment (0.20 -/+ 0.41, 0.15 +/- 0.37 vs 0.60 +/- 0.50, both P < 0.05). Swelling score in the Xiaojie point group was different significantly from that in the tendon-regulation manipulation 0.49 vs 06.4 vs. 20+0.41, P < 0.05). The different value of pain score in either the combined therapy group or Xiaojie point group was higher than that in the tendon-regulation manipulation group before group after treatment (0.65 bined therapy group or Xiaojie point group was higher than that in the tendon-regulation manipulation group before and after treatment (2.35 +/- 0.59, 2.45 +/- 0.51 vs 2.00 +/- 0.46, both P < 0.05). The different value of swelling score in the tendon-regulation manipulation group was higher than that in the Xiaojie point group before and after treatment (2.30 +/- 0.57 vs 1.60 +/- 0.60, P < 0.05).
CONCLUSIONAcupuncture at Xiaojie point combined with tendon-regulation manipulation achieve an apparent effect of analgesia and detumescence on ankle sprain.
Acupuncture Analgesia ; Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Ankle Injuries ; physiopathology ; therapy ; Combined Modality Therapy ; Female ; Humans ; Male ; Tendons ; physiopathology ; Therapy, Soft Tissue ; Young Adult
8.Expression of microRNA-223 in lymphocytic leukemia cells and its action mechanism.
Zhen NAN ; Yong LIANG ; Rong FU ; Hui LIU ; Er-Bao RUAN ; Xiao-Ming WANG ; Guo-Jin WANG ; Wen QU ; Hong LIU ; Yu-Hong WU ; Jia SONG ; Li-Min XING ; Jing GUAN ; Li-Juan LI ; Hua-Quan WANG ; Zong-Hong SHAO
Journal of Experimental Hematology 2013;21(3):556-561
This study was aimed to investigate the expression level and mechanism of microRNA-223 and LMO2 in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) cells and the mechanism. MicroRNA-223 mimics was transfected to increase the expression of MicroRNA-223 in the lymphocytes sorted by ficoll separation from the bone marrow mononuclear cells (BMMNC) of ALL and CLL patients. MicroRNA-223 inhibitor was transfected to decrease the expression of the MicroRNA-223 in the lymphocytes of normal controls. Then the expression of the MicroRNA-223 and LMO2 in transfected lymphocytes before and after cultivating for 72 hours were detected by RT-PCR, the apoptosis and cell cycle of these cells were measured by flow cytometery. The results indicated that before the transfection, the expression of MicroRNA-223 in ALL and CLL cells was (433.11 ± 144.88), which was significantly lower than that in the normal lymphocyte (949.59 ± 267.39); the expression of LMO2 was (807.10 ± 238.41), which was significantly higher than that in the normal lymphocytes (455.32 ± 176.83) (P < 0.05); after the transfection, the expression of MicroRNA-223 was (571.86 ± 142.00) in ALL and CLL cells, which was significantly higher than that before transfection (P < 0.05), but the expression of LMO2 was significantly lower than that before transfection (651.97 ± 230.12) (P < 0.05); in the normal control the expression of MicroRNA-223 obviously decreased (646.32 ± 172.93) (P < 0.05), the expression of LMO2 was significantly increased (541.27 ± 158.86.2) (P < 0.05). After transfection, the cell cycle G1/G2 phase and apoptosis changed in ALL and CLL cells. Before transfection the cell ratio in cell cycle G1/G2 phase was (94.75 ± 3.15)%, the cell ratio in S phase was (5.14 ± 3.12)%; after transfection the cell ratio in cell cycle G1/G2 phase was (97.03 ± 2.08)% and obviously increased (P < 0.05), the cell ratio in S phase was (2.97 ± 2.08)% and significantly decreased (P < 0.05). Before transfection the apoptosis rate was (54.47 ± 8.72)%, and obviously was higher than that after transfection (60.48 ± 8.81)%. And in the normal control, the cell ratio in G1/G2 phase was significantly higher than that after transfection [(96.73 ± 2.26)%, (94.55 ± 2.77)%, P < 0.05)], and the cell ratio in S phase was significantly increased [(3.25 ± 2.26)%, (5.45 ± 2.77)% (P < 0.05)]. The apoptotic rate in the ALL and CLL patients was significantly higher than that after the transfection [(54.47 ± 8.72)% vs (60.48 ± 8.81)%, respectively (P < 0.05)]. The apoptotic rate in the normal control was significantly lower than that after the transfection [(59.02 ± 10.20)%, (51.96 ± 10.20)%, respectively (P < 0.05)]. It is concluded that the expression of MicroRNA-223 decreases, and the expression of LMO2 increases in lymphocytic leukemia cells which leads to the lymphocytes over-proliferation and abnormal apoptosis, thus may be one of pathogenesis in lymphocytic leukemia.
Adaptor Proteins, Signal Transducing
;
genetics
;
metabolism
;
Adolescent
;
Adult
;
Aged
;
Apoptosis
;
Case-Control Studies
;
Cell Cycle
;
Cell Line, Tumor
;
Cell Proliferation
;
Female
;
Humans
;
LIM Domain Proteins
;
genetics
;
metabolism
;
Leukemia, Lymphocytic, Chronic, B-Cell
;
genetics
;
metabolism
;
Male
;
MicroRNAs
;
genetics
;
metabolism
;
Middle Aged
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma
;
genetics
;
metabolism
;
Proto-Oncogene Proteins
;
genetics
;
metabolism
;
Transfection
;
Young Adult
9.Increased circulating of myeloid-derived suppressor cells in myelodysplastic syndrome.
Hui-juan JIANG ; Rong FU ; Hua-quan WANG ; Li-juan LI ; Wen QU ; Yong LIANG ; Guo-jin WANG ; Xiao-ming WANG ; Yu-Hong WU ; Hong LIU ; Jia SONG ; Jing GUAN ; Li-Min XING ; Er-Bao RUAN ; Zong-Hong SHAO
Chinese Medical Journal 2013;126(13):2582-2584
Adult
;
Aged
;
Aged, 80 and over
;
Bone Marrow Cells
;
physiology
;
Female
;
Humans
;
Immune Evasion
;
Male
;
Middle Aged
;
Myelodysplastic Syndromes
;
etiology
;
immunology
10.The mechanisms underlying bone marrow damage by iron overload in pancytopenic patients with positive BMMNC-Coombs test.
Lei HUANG ; Rong FU ; Li-juan LI ; Hui LIU ; Yi-hao WANG ; Hong-lei WANG ; Tian ZHANG ; Kai DING ; Shao-xue DING ; Er-bao RUAN ; Wen QU ; Jing GUAN ; Guo-jin WANG ; Jia SONG ; Hua-quan WANG ; Yu-hong WU ; Li-min XING ; Hong LIU ; Xiao-ming WANG ; Zong-hong SHAO
Chinese Journal of Hematology 2013;34(5):430-434
OBJECTIVETo investigate the mechanisms underlying bone marrow damage by iron overload in pancytopenic patients with positive BMMNC-Coombs test (IRP).
METHODSTwenty-one iron overloading, 26 non-iron overloading IRP patients and 10 normal controls were enrolled in this study. The expressions of ROS, Bcl-2, Caspase-3 and apoptosis of BMMNC were analyzed by flow cytometry (FCM). Antioxidants were added to iron overloading IRP BMMNC, and then the changes of indices above were detected by FCM. The number and apoptosis of T lymphocytes of IRP patients were also detected.
RESULTSROS and apoptosis of BMMNC, myelocytes, erythrocytes and stem cells of iron overloading IRP patients were significantly higher than that of non-iron overloading IRP ones and normal controls (P < 0.05). The expressions of Bcl-2 on BMMNC, erythrocytes and stem cells of iron overloading IRP patients were significantly lower than those of non-iron overloading IRP ones (P < 0.05). The levels of Caspase-3 on myelocytes, erythrocytes and stem cells of iron overloading IRP patients were significantly higher than those of non-iron overloading IRP ones and normal controls (P < 0.05). After treatment with antioxidants, the expressions of ROS, Caspase-3 and apoptosis of iron overloading IRP BMMNC significantly decreased, but opposite for Bcl-2. The percentages of CD4(+) lymphocytes [ ( 40.86 ± 8.74)%] and CD4(+)/CD8(+) (1.44 ± 0.36) in PB of iron overloading IRP patients were significantly higher than that of non-iron overloading IRP ones [(35.96 ± 7.03)% and 1.14 ± 0.37] and normal controls [(28.00 ± 6.73)% and 0.79 ± 0.21], respectively (P < 0.05), as opposite for CD8(+) lymphocytes (P < 0.05). The apoptosis of CD8(+) lymphocytes [(27.35 ± 10.76)%] and the ratio of CD8(+) apoptosis/CD4(+) apoptosis (2.51 ± 0.81) in BM of iron overloading IRP patients were significantly higher than those of non-iron overloading IRP ones [(15.47 ± 8.99)%] and normal controls (1.39 ± 0.47), respectively (P < 0.05). The apoptosis of erythrocytes and stem cells coated with auto-antibodies in BM of iron overloading IRP patients were significantly higher than those of non-iron overloading IRP and normal controls.
CONCLUSIONMechanisms underlying bone marrow damage by iron overload might be through the follows: ①The increased ROS induced by excessive iron deposition affected the expressions of Caspase-3 and Bcl-2, which caused more BMMNC apoptosis; ②The abnormal number and ratio of T lymphocytes caused by iron overload aggravated the abnormality of immunity of IRP; ③Iron overload may increase the damage to erythrocytes and stem cells coated with auto-antibodies.
Adolescent ; Adult ; Aged ; Bone Marrow ; pathology ; Case-Control Studies ; Caspase 3 ; metabolism ; Coombs Test ; Female ; Humans ; Iron Overload ; Male ; Middle Aged ; Pancytopenia ; immunology ; pathology ; physiopathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Reactive Oxygen Species ; metabolism ; Young Adult

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