1.Methylene blue reduces IL-1β levels by enhancing ERK1/2 and AKT phosphorylation to improve diabetic retinopathy in rats.
Huade MAI ; Shenhong GU ; Biwei FU ; Xinbo JI ; Minghui CHEN ; Juming CHEN ; Yunbo ZHANG ; Yunyun LIN ; Chenghong LIU ; Yanling SONG
Chinese Journal of Cellular and Molecular Immunology 2023;39(5):423-428
Objective To investigate the neuroprotective effect of methylene blue on diabetic retinopathy in rats. Methods Thirty SD rats were randomly divided into blank, control and experimental groups. The control and experimental groups were induced with diabetes by streptozotocin (STZ) intraperitoneal injection. After 6 weeks of successful modeling, the experimental group received intravitreal injection of methylene blue at a dose of [0.2 mg/(kg.d)], while the control group received an equal amount of dimethyl sulfoxide (DMSO) intravitreal injection, both continuously injected for 7 days. ELISA was used to detect the levels of retinal superoxide dismutase (SOD), 8-iso-prostaglandin F2alpha (iPF2α) and interleukin-1β (IL-1β) in rats. Western blot analysis was used to detect the expression of retinal extracellular signal-regulated kinase 1/2 phosphorylation (p-ERK1/2) and phosphorylated protein kinase B (p-AKT), and PAS staining was used to detect retinal morphological changes. Results Compared with the blank group rats, the retinal SOD activity in the control and experimental group rats was significantly reduced. iPF2α, IL-1β and p-ERK1/2 level increased, while p-AKT level decreased. Compared with the control group, the SOD activity of the experimental group rats increased. iPF2α and IL-1β level went down, while p-ERK1/2 and p-AKT level went up significantly. The overall thickness of the retinal layer and the number of retinal ganglion cells were significantly reduced. Conclusion Methylene blue improves diabetic retinopathy in rats by reducing retinal oxidative stress and enhancing ERK1/2 and AKT phosphorylation.
Rats
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Animals
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Diabetic Retinopathy/metabolism*
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Proto-Oncogene Proteins c-akt/metabolism*
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Mitogen-Activated Protein Kinase 3/metabolism*
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Interleukin-1beta/metabolism*
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Methylene Blue/pharmacology*
;
Phosphorylation
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Rats, Sprague-Dawley
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MAP Kinase Signaling System
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Diabetes Mellitus, Experimental/drug therapy*
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Superoxide Dismutase/metabolism*
2.Clinical Efficacy and Safety of Different Doses of Dexamethasone Combined with Bortezomib and Thalidomide for Treating Patients with Multiple Myeloma.
Chang-Sheng LI ; Ye JI ; Wan-Ping ZHANG ; Li-Ping FU
Journal of Experimental Hematology 2018;26(3):836-841
OBJECTIVETo study the clinical efficacy and safety of dexamethasone of different doses combined with bortezomib and thalidomide for treatment of primary multiple myeloma.
METHODSNinety-six patients with multiple myeloma from January 2013 to January 2014 were randomly divided into group A (high-dose dexamethasone + bortezomib + thalidomide, 32 cases), group B (low-dose dexamethasone + bortezomib + thalidomide, 32 cases) and group C (placebo + bortezomib + thalidomide, 32 cases). The clinical efficacy and safety of patients was compared among 3 groups.
RESULTSThe overall remission rate (ORR) in group A and B was significantly higher than that in group C (P<0.05), but the ORR was not significant difference between group A and group B (P>0.05). After treatment, the KPS and RNS score in 3 groups were significantly higher and lower than those before treatment, respectively; the KPS score in group A and B was significantly higher than that in group C (P<0.05), the RNS score in group A and B was significantly lower C (P<0.05). After treatment, the positive expression rates of CD38, CD56 and CD138 as well as small residual lesion (SRL) positive rate in 3 grops were significantly lower than those before treatment, but the positive expression rate of CD19 was significantly higher that before treatment; the positive expression rates of CD38, CD56 and CD138 as well as SRL positive rate in group A and B were significantly lower thant those in group C, while the positive expression rate of CD19 was significantly higher that in group C (P<0.05), but the positive expression rates of CD19, CD38, CD56 and CD138 as well as SRL positive rate were not significantly different between group A and B (P>0.05). The incidence of fatigue, rash, peripheral neuropathy, anlmia, granulocyte deficiance and so on in group B and C was significantly lower than that in group A(P<0.05), but the difference in group B and C was not significant (P>0.05).
CONCLUSIONThe therapeutic efficacy of different doses of dexamethasone combined with bortezomib and thalidomide for patients with multiple myeloma is similar, can obviously enhance remission rate, prolong the survival time, promote life quality, but the incidence of adverse reactions in low dose dexamethason rigemen is significantly reduced, and the safety is better.
Antineoplastic Combined Chemotherapy Protocols ; Bortezomib ; Dexamethasone ; Disease-Free Survival ; Humans ; Multiple Myeloma ; Thalidomide ; Treatment Outcome
3.Relationship between Early Treatment Response and Prognosis in Children with Acute Lymphoblastic Leukemia.
Yu ZHENG ; Yun-Wang CAI ; Qi-Chang FU ; Qiang WANG ; Xun-Qi JI ; Lu-Liang CAI
Journal of Experimental Hematology 2018;26(3):733-737
OBJECTIVETo analyze the relationship between the early treatment response and the pregnosis in children with acute lymphoblastic leukemia(ALL).
METHODSTwo hundred and Seventy-eight ALL children diagnosed and treated in Hainan general hospital from March 2013 to March 2017 were collected. All ALL children received therapy with CCLg-ALL-2008 regimen. The 3 year event-free survival (EFS) rate of ALL children in different groups was analyzed in terms of 4 indexes including sensitivity response to prednison at day 8 (D8-SRP), bone marrow remission at day 15 (D15-BMR) and at day 33 (D33-BMR), and minimal residual disease at day 33 (D33-BMR), and minimal residual disease at day 33(D33-MRD). These 4 indexes and other indexes possibly affecting the prognosis of ALL children were enrolled in Cox regression model for analysis of independent factors affecting the prognosis of ALL children.
RESULTSThe D8-SRP test showed that among 269 ALL children, 240(89.22%) cases displayed prednisone poor response (PPR); the 3-year EFS rate in predrisone good response(PGR) group was significantly higher than that in PPR group(P<0.05). The D15-BMR detection showed that among 262 ALL children, the bone marrow remission(BMR) as M1 was observed in 230 cases (87.79%), M2 in 20 cases (7.63%) and M3 in 9 cases (4.58%); the 3-year EFS rate showed as follows:M1 group >M2 group >M3 group(P<0.05). The D33-BMR detection showed that among 257 ALL children, the BMR as M1 was observed in 227 cases (88.33%), M2 in 21 cses(8.17%) and M3 in 9 caes (3.51%); the 3-year EFS rate in 3 groups showed as follows: M1 group >M2 group >M3 group(P<0.05). The D33-MRD detection showed that among 185 ALL children, MRD<10 was found in 128 cases (69.19%), MRD≥10-10 in 43 cases (23.24%), MRD ≥10 in 14 cases (7.57%); the 3-year EFS rate in 3 groups showed as follows: MRD <10 group > MRD≥ 10-10 group>MRD≥10 group. The Cox regression analysis showed that PPR in D8-SRP test, M2 and M3 in D15 and D33 BMR detection, and MRD≥10 in D33 MRD detection as well as T-ALL typing were independent risk factors affecting the prognosis of ALL children.
CONCLUSIONThe early treatment response can predict the prognosis of ALL children, which is an independent prognostic factor for ALL children.
Child ; Disease-Free Survival ; Humans ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prednisone ; Prognosis
4.Biological Characteristics and Therapeutic Efficacy of 103 Patients with Acute Erythroleukemia.
Yue YIN ; Wen-Qi ZHAN ; Hui-Fang HUANG ; Chen-Qing ZHANG ; Dang-Hui FU ; Shu-Juan XU ; Jian-Da HU ; Xin-Ji CHEN
Journal of Experimental Hematology 2017;25(3):678-682
OBJECTIVETo investigate the biological characteristics and therapeutic efficacyt of acute erythroleukemia (AEL,AML-M6).
METHODSBlood cell count, liver function, lactate dehydrogenase level, coagulation, morphology, immunology, cell genetics and molecular biology were retrospectively analyzed in 103 cases of acute erythroleukemia patients admitted in our department from May 2016 to June 2009. The therapeutic efficacy was observed by means of remission rate, relapse rate, relapse-free survival and overall survival.
RESULTSThe medians of white blood cells, granulocyte, hemoglobin and platelet were 3.04×10/L, 0.67×10/L, 66 g/L, and 45×10/L,respectively. Nucleated red blood cells were found in the peripheral blood smears from 71.1% of AEL patients. None of the patients showed abnormal coagulation function. Flow cytometry analysis indicated that CD13 (93.5%),CD117(89.1%), HLA-DR(87.0%), and CD34 (80.0%) were highly expressed in AEL, and lymphoid antigens of CD4 (42.9%) and CD7(28.9%) were expressed in partial patients. Karyotype analysis in 82 patients showed 52.4% (43/82) normal karyotype, 41.5% (34/82) abnormal karyotype, and 6.1% (5/82) failed tests. In the 34 cases with abnormal karyotype, there were 14(41.2%) cases with simple chromosomal abnomality and 20(58.8%) cases with complex karyotype. The positive rate of fusion gene accounted for 16.7% in 60 patients, and the gene mutations accounted for 77.8% in 27 patients. Among 103 cases of AEL, 81 cases were treated with chemotherapy, but 66 cases can be used for therapeutic analysis, as a results the total complete remission rate derived from 2 courses of treatment was 45.5% (30/66). The relapse rate was 36.7% (11/30), and the median relapse time was 15.5 months (6.2-50 months). The median survival time of 66 patients for therapeutic analysis was 29 months. The median survival time of CR patients was very significantly longer than that of the non-CR patients(P=0.001). The 5 year survival rate of CR patients was 65%, the median time of relapse-free survival (RFS) was 46.2 months and 3-years RFS was 58%.
CONCLUSIONAEL is characterized by the highly expressed CD34 antigen, and complex karyotype. Although AEL has lower CR rate and poor prognosis, CR patients can achieve long-term survival and have good quality of life.
5.Effect of pushing manipulation on Qiaogong acupoint on hemodynamics in cynomolgus monkeys with mild carotid atherosclerotic plaques.
Lei ZHANG ; Ji QI ; Ya-Jun JING ; Bo QIN ; Yi-Kai LI ; Gang LIU ; Xiao-Guang GUO ; Shi-Jie FU
Journal of Southern Medical University 2017;37(12):1592-1596
OBJECTIVETo explore the hemodynamic changes in cynomolgus monkeys with mild carotid atherosclerotic (CAS) plaques after therapy with pushing manipulation on Qiaogong acupoint (MPQ).
METHODSNine cynomolgus monkeys were equally randomized into MPQ group, mild CAS model group and blank control group. Mild CAS models were established in the monkeys in MPQ and model groups, and the monkeys in MPQ group received treatment with MPQ intervention after the modeling. The conditions of the carotid artery and the hemodynamic changes in the 3 groups were evaluated after the treatment.
RESULTSFormation of CAS plaques was detected in monkeys in both MPQ and model groups. The vascular cross?sectional area, plaque cross?sectional area and stenosis rate of the plaques in the two groups all differed significantly from those in the blank control group (P<0.05), but these parameters were similar between MPQ group and the model group (P>0.05). Compared with those in the blank control group, the hemodynamic parameters showed significant changes in MPQ and the model groups (P<0.05) but remained similar between the latter two groups (P>0.05).
CONCLUSIONCAS plaques can cause changes in hemodynamic parameters. Short?term therapy with MPQ does not affect the stability of the plaques or cause adverse effects on hemodynamics in cynomolgus monkeys with mild CAS plaques.
6.Immunophenotypic Analysis of Acute Promyelocytic Leukemia.
Fang CHEN ; Yan-Ping HU ; Xiao-Hui WANG ; Shuang FU ; Yu FU ; Xuan LIU ; Min-Yu ZHANG ; Shao-Kun WANG ; Ji-Hong ZHANG
Journal of Experimental Hematology 2016;24(2):321-325
OBJECTIVETo investigate the immunophenotype of leukemia promyelocytes (LP) in bone marrow of patients with acute promyelocytic leukemia (APL) and to explore their characteristics and significance.
METHODSThe immunophenotypes of leukemia cells in 43 patients with APL were analyzed by means of 4 color immunophenotypes; the cell population in which CD45 strength localized at 10(2) and the SSC strength locatized at 10(2) was defined as R3, the cell population in which CD45 strength localized at 10(3) and the SSC strength localized at 10(2) was defined as R5, moreover the ratio of positive cells >80% was defined as strong positive expression, the ratio of positive cells between 20%-80% was difined as weak positive expression, the ratio of positive cells <20% was difined as negative by gating method of CD45/SSC.
RESULTSThere was a abnormal cell population (R3) in 79.07% cases; the immunophenotypes of R3 was cheracteried by high SSC, weaker expression of CD45, the rate of CD38, CD9 and CD13 all was 100%, moreover their bright expression (>80%) was 86.05%, 90.70% and 86.05%, respectively; the positive expression rate of CD33, CD117 and CD64 was 97.67%, 95.35% and 83.80% respectively, moreover thier bright expression was 84.04%, 69.77% and 30.23% respectively; the CD15 was weakly expressed in 39.53% cases, the CD34 and HLA-DR were weakly expression in 16.28% and 6.98% cases respectively. All the cases did not express CD116. There were 2 cell populations (R3 and R5) in 20.93% cases, the immunophenotypic features of R3 were cosistant with above mentioning, while the immunophenotypes of R5 were lower than those of R3 SSC; the fluorescence intensity of CD45 was higher, but lower than that in normal lymphycytes, the positive rate of CD9, CD13, MPO was 100%, moreover thier fluorescence intensity was high; they did not expressed CD123, CD25, CD22, CD4, CD64 and CD14. Thereby it can be concluded that the typical immunophenotypes is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-) in APL. There was a special immunophenotype in the APL with basophilic granules. Conclusoin: APL has a characteristic immunophenotypic profile, whose typical immunophenotype is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-). The special immunophenotype exists in the APL with basophilic granules. Flow cytometric immunophenotyping may be a useful for rapid recognition of APL and has significant for prognosis.
Antigens, CD ; metabolism ; Cell Count ; Flow Cytometry ; Granulocyte Precursor Cells ; classification ; HLA-DR Antigens ; metabolism ; Humans ; Immunophenotyping ; Leukemia, Promyelocytic, Acute ; classification ; immunology ; Leukocyte Common Antigens ; metabolism ; Prognosis
7.Change and clinical significance of peripheral blood T-lymphocyte functional subsets in acute graft-versus-host disease.
Zhi-Rui YANG ; Hai-Yan ZHU ; Wan-Ming DA ; Chun-Ji GAO ; Li YU ; Li-Ye FU ; Meng LI
Journal of Experimental Hematology 2015;23(1):190-194
OBJECTIVEThis study was aimed to detect the change of T-lymphocyte functional subsets marked by CCR7 and CD45RA in the aGVHD within 100 days after allo-HSCT and to explore its clinical significance.
METHODSThe peripheral blood of 42 patients after allo-HSCT was collected every two weeks since hematopoietic reconstitution. The expression of CD3, CD4, CD8, CCR7 and CD45RA-marked T-lymphocytes was detected by flow cytometry, the relationship between their expression and the prognosis of aGVHD was analyzed.
RESULTSThe percentage and the absolute count of CCR7(+) T lymphocyte were significantly reduced in aGVHD. The percentage of T(naïve), T(CM), T(EM) and the absolute count of T(naïve), T(EM), TTD were sharply reduced in aGVHD, moreover has changed correspondingly with outcome of aGVHD. The percentage of CD3, CD4, CD8-marked T-lymphocyte subsets did not significantly changed.
CONCLUSIONT-lymphocyte functional subsets marked by CCR7 and CD45RA are a valuable indicator to monitor early immune reconstruction for patients with the aGVHD after allo-HSCT.
Acute Disease ; Flow Cytometry ; Graft vs Host Disease ; Humans ; T-Lymphocyte Subsets
8.RNAi-mediated Silencing of CXCR4 Inhibits the Adhesion, Invasion and Tumorigenicity of Acute Monocytic Leukemic Cell Line SHI-1.
Lei FU ; Zhen-Jiang LI ; Gui-Ling YANG ; Ji-Fu ZHENG ; Qing-Zhi SHI ; San-Jun CHEN ; Jian LI
Journal of Experimental Hematology 2015;23(5):1286-1291
OBJECTIVETo investigate the effect of CXCR4 gene on the proliferation, adhesion, invasion and tumorigenicity of a human monocytic leukemic cell line SHI-1.
METHODSThe lentivirus vector silencing the expression of CXCR4 was constructed for infection of SHI-1 cells silencing expression of CXCR4 in SHI-1 cells. The expression of CXCR4, MMP-2 and MMP-9 was detected by real time PCR. The expression of CXCR4 on membrane of SHI-1 cells was detected by flow cytometry. The SHI-1 cell proliferation ability was detected by MTT. The co-culture system of the leukemia cells and bone marrow stromal cells was used to detect the adhesion and migration ability of leukemia cells. SHI-1 cells were inoculated subcutaneously in nude mice to investigate the growth ability in vivo.
RESULTSAfter SHI-1 cells were infected by lentivirus silencing expression of CXCR4, the expression of CXCR4 mRNA in SHI-1 CXCR-4i cells decreased by 76% as compared with expression of SHI-1/NC of negative control virus, the expression of CXCR4 on membrane of SHI-1/CXCR4i obviously downregulated; the expression of MMP-2 and MMP-9 in SHI-1/CXCRi cells also declined by 63% and 62% respectively; the proliferation ability of SHI-1/CXCR4i in vitro did not obviously changed, but the adhesion and trans-matrigel invasion ability significantly decreased, the SHI-1/CXCR4i cells could not form neoplasm subcutaneously in mice, but the SHI-1 and SHI-1/NC cells could form neoplasm subcutaneously in mice, and there was no significant difference in volumn of neoplasm mass.
CONCLUSIONThe silencing expression of CXCR4 can decline the adhesion and migration ability of SHI-1 cells, and can completely suppress the formation of neoplasm subcutaneously, so the CXCR4 may serve as a target for treating leukemia.
Animals ; Cell Adhesion ; Cell Line, Tumor ; Cell Proliferation ; Coculture Techniques ; Humans ; Lentivirus ; Leukemia, Monocytic, Acute ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Mesenchymal Stromal Cells ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; RNA Interference ; RNA, Messenger ; Receptors, CXCR4 ; genetics ; Signal Transduction
9.Surgical Indications of Exploring Optic Canal and Visual Prognostic Factors in Neurosurgical Treatment of Tuberculum Sellae Meningiomas.
Hao-Cheng LIU ; E QIU ; Jia-Liang ZHANG ; Jun KANG ; Yong LI ; Yong LI ; Li-Bin JIANG ; Ji-Di FU
Chinese Medical Journal 2015;128(17):2307-2311
BACKGROUNDTuberculum sellae meningiomas (TSMs) present a special symptom because of the adherence and compression to the optic nerve, optic artery, and the chiasm. A significant number of patients with TSMs appear visual deficits. This study aimed to investigate the surgical indications of exploring the optic canal and visual prognostic factors in the neurosurgical treatment of TSMs.
METHODSTotally 21 patients with TSM, who were operated from September 2007 to August 2011 in the Department of Neurosurgery, Tongren Hospital were enrolled in this study. Results of orbital computed tomography (CT) and magnetic resonance imaging (MRI), visual acuity, Goldmann visual field test, orbital color Doppler flow imaging (CDI) test in these patients were retrospectively analyzed.
RESULTSVisual deficit and optic canal involvement (OCI) were detected in all the 21 patients. Fourteen patients had bone proliferation within the area of the optic canal. After the operation, visual outcomes were improved in 13 patients, unchanged in 7 patients, and deteriorated in 1 patient. All the 21 patients performed orbital CDI test preoperatively, the results showed that if the peak systolic velocity (PSV) of central retinal artery (CRA) value was ≤ 8 cm/s, the visual outcome would be better.
CONCLUSIONSThe surgical indications of exploring optic canal in TSM cases included: (1) The neuroimaging evidences of OCI (CT and/or MRI); (2) PSV of CRA in orbital CDI test was ≤ 8 cm/s; (3) visual acuity was below 0.1; (4) visual field deficit. The PSV of CRA in CDI test could be a prognostic factor for visual outcomes of TSMs.
Adult ; Aged ; Female ; Humans ; Male ; Meningeal Neoplasms ; pathology ; surgery ; Meningioma ; pathology ; surgery ; Middle Aged ; Neurosurgical Procedures ; methods ; Retrospective Studies ; Sella Turcica ; pathology ; surgery ; Skull Base Neoplasms ; pathology ; surgery ; Visual Acuity
10.Clinical and pathological analysis of 41 cases of acute leukemia combined with intracranial hemorrhage.
Jing-Hua LIU ; Fan ZHOU ; Xiao-Lin ZHANG ; Su-Fen ZHANG ; Fu-Lin SONG ; Yan-Qin LIU ; Ji-Gang WANG ; Xi-Mei LI ; Bo TANG
Journal of Experimental Hematology 2013;21(6):1409-1412
This study was aimed to summarize the clinical and pathological features of patients with acute leukemia combined with intracranial hemorrhage. The clinical and pathological data of 41 adult patients diagnosed as acute leukemia in our hospital from 1953 to 1990 year were analyzed retrospectively. The results showed that there were 35 cases of AML, 6 cases of ALL; 9 cases in clinical hematologic remission, 32 cases in non-remission, 3 cases of AL with hypertension, 2 cases of AL with diabetes, 4 cases of AL with sepsis, 19 cases with WBC ≥ 100×10(9)/L; the pathologic examination showed 4 cases of AL accompanied with disseminated intravascular coagulation, 10 cases with prothrombin time INR ≥ 1.5, 26 cases with multifocal intracranial hemorrhage, 7 cases with single intracranial hemorrhage, 8 cases with diffused spotting intracranial hemorrhage; the examination also showed that 84 hemorrhage foci were found in 41 cases of AL, among them 46 foci located under cerebral cortex, 23 foci in cerebellum, 6 in basal ganglia, 5 foci in pons, 2 foci in thalamus, 2 foci in spinal cord. It is concluded that the intracranial hemorrhage is a major cause resulting in death of AL patients which should be think highly, and the diagnosis and treatment should be conducted through comprehensive analysis.
Acute Disease
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Adolescent
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Adult
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Female
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Humans
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Intracranial Hemorrhages
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complications
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pathology
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Leukemia
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complications
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pathology
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Male
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Middle Aged
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Retrospective Studies
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Young Adult

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