1.The chelator BPCBG decorporates uranium and protects against uranium-induced kidney injury in rats
Dan WANG ; Yizhong BAO ; Yuxing HU ; Aihong XU ; Honghong CHEN
Chinese Journal of Radiological Medicine and Protection 2012;32(4):337-341
Objective To explore the dose- and time-responses of BPCBG on the decorporation of uranium and its protective effects for uranium-induced kidney injury in rats. Methods Sprague-Dawley (SD) male rats were randomly divided into 4 -7 groups:normal control group,uranium poisoning group,different doses of BPCBG groups and DTPA-CaNa3 group. Rats in chelating agents-treated groups were either injected intramuscularly with 60,120 and 600 μmol/kg of BPCBG or 120 and 600 μmol/kg of DTPA-CaNa3 immediately after intraperitoneal injection of uranyl acetate dihydrate,or injected with 120 μmol/kg of BPCBG 0.5,2 h before or 0,0.5,1 and 2 h after injection of uranium. Uranium poisoning group rats were injected with normal saline after intraperitoneal injection of uranyl acetate dihydrate,and the normal control group rats were merely injected with normal saline. The uranium content in urine,kidney and femurs were detected 24 h after chelator injections by ICP-MS method.After injecting a dose of 500 μg uranyl acetate dihydrate,rats were injected with 600 μmol/kg of BPCBG or 1200 μmol/kg of DTPA-CaNa3. Histopathological changes in the kidney and serum creatinine and urea nitrogen were examined 48 h after chelator administration.Results Prompt injections of BPCBG resulted in 37% -61% ( t =2.22,4.43,5.80,P < 0.05 ) increase in 24 h-urinary uranium excretion,and significantly decreased the levels of uranium in kidney and bone by 59% -69% (t=3.33,5-59,4-53,P<0.01) and 14% -58% (t =2.15,8.70,9.10,P < 0.05 ) respectively in a dose-dependent manner. BPCRG injection obviously reduced the severity of the uranium-induced histological alterations in the kidney,which was in parallel with the amelioration noted in serum indicators,serum creatinine and urea nitrogen,of uranium nephrotoxicity.Advanced 0.5 h or delayed 0.5 and 1 h administrations of BPCBG were effective in 24 h-urinary uranium excretion ( advanced 0.5 h:t =4.34,delayed 0.5 h:t =3.35,P < 0.05 ),decreasing accumulation of kidney uranium ( t =5.75,7.74,5.87,P < 0.05 ) and accumulation of hone uranium (t =6.43,5.222,2.60,P <0.05),but the efficacy decreased with the interval time between uranium and BPCBG injection. Although DTPA-CaNa3 markedly reduced uranium retention in kidney (120,600 μmol/kg,t =2.28,3.35,P < 0.05 ),its efficacy in uranium removal was significantly lower than that of BPCBG,and it had no protective effects against uranium-induced nephrotoxicity.Conclusions BPCBG can effectively decorporate uranium from rats and protect against uranium-induced kidney injury of rats.
2.Characteristics and impact factors of ocular damage effects induced by transitional near-infrared laser:a review
Jiarui WANG ; Dan BAO ; Zaifu YANG ; Xiangjun HU
Military Medical Sciences 2015;(9):717-720,724
The transitional near-infrared (NIR) laser was defined as ranging from 1.3μm to 1.4μm, within which the most sensitive tissue to laser damage changed from the retina to the cornea.The ocular damage effect has attracted much attention due to the increased varieties and output power of laser in this spectrum region in recent years.Compared with visible and mid-and-far infrared wavelengths, the ocular damage effect induced by transitional NIR wavelengths has many peculiarities and impact factors due to the bulk absorptionby ocular media.This paper reviews the existing ocular damage threshold data and analyzes the characteristics, impact factors and unresolved issues relating to ocular effects induced by laser radiation over the transition zone.
3.Mechanism of inflammatory responses and histopathological changes in Staphylococcus aureus induced bloodstream infections in mice
Dan WU ; Shusheng ZHOU ; Shijing HU ; Bao LIU
Chinese Journal of Immunology 2016;32(4):556-562
Objective:To establish mice models of Staphylococcus aureus bloodstream infections so as to investigate the inflammatory responses and histopathological changes in bloodstream infections (BSIs) mice.Methods:C57BL/6 mice were inoculated with S.aureus intravenously or intraperitoneally to induce BSIs.Survival rate , weight loss and murine sepsis scores ( MSS ) were ob-served.Blood samples and tissue homogenates were plated on agar to determine bacterial burden .Inflammatory proteins ( CRP,PCT) and cytokines ( IL-1β, IL-6 and TNF-α) were determined by ELISA kits.Histopathologic changes were also assessed by pathological inflammation scores(PIS),macroscopic and microscopic examination.Results: About 70% survival rate was observed in 4.5×108 CFU/ml S.aureus induced BSIs mice.Body weight decreased and sepsis scores increased significantly since 24 h post-infection in BSIs mice,and more prominent in IV group.The counts of WBC began to significantly increase at 3 h post-infection,while CRP and PCT levels peaked at 48 hours in IV and IP groups ( 60.80 ±5.63 vs 40.58 ±7.54 for CRP;6.796 ±1.16 vs 2.740 ±0.36 for PCT ) . Moreover,the levels of IL-1β,IL-6 and TNF-αin serum and tissue homogenates ( liver,lungs,and kidneys ) were significantly elevated in BSIs mice.Pathological changes in tissues (liver,lungs and kidneys) and higher pathological inflammation scores (PIS) were also observed in BSIs mice.Conclusion:Our study represents an effective approach for S.aureus BSIs model to mimic human sepsis.Our results demonstrated that inflammation protein (PCT,CRP) and cytokines(IL-6,IL-1βand TNF-α) play an important role in the in-flammatory response and histopathological changes during BSIs caused by S .aureus.
4.Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitro.
Yizhong BAO ; Dan WANG ; Yuxing HU ; Aihong XU ; Meizhen SUN ; Honghong CHEN
Acta Pharmaceutica Sinica 2011;46(11):1308-13
This study is to assess the efficacy of BPCBG on the decorporation of uranium (VI) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage. BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2. Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS. After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) oxidation. DTPA-CaNa3 was used as control. It was found that BPCBG at dosages of 60, 120, and 600 micromol kg(-1) resulted in 37%-61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%-31% and 86%-42% of uranium-treated group, respectively. After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%-60% of the intracellular uranium was removed by 10-250 micromol L(-1) of BPCBG. Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS. Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG and it could not protect uranium-induced cell damage. It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3. It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage. BPCBG is worth further investigation.
5.Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitro.
Yi-zhong BAO ; Dan WANG ; Yu-xing HU ; Ai-hong XU ; Mei-zhen SUN ; Hong-hong CHEN
Acta Pharmaceutica Sinica 2011;46(11):1308-1313
This study is to assess the efficacy of BPCBG on the decorporation of uranium (VI) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage. BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2. Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS. After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) oxidation. DTPA-CaNa3 was used as control. It was found that BPCBG at dosages of 60, 120, and 600 micromol kg(-1) resulted in 37%-61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%-31% and 86%-42% of uranium-treated group, respectively. After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%-60% of the intracellular uranium was removed by 10-250 micromol L(-1) of BPCBG. Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS. Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG and it could not protect uranium-induced cell damage. It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3. It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage. BPCBG is worth further investigation.
Animals
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Cell Line
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Cell Survival
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drug effects
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Chelating Agents
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administration & dosage
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chemistry
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pharmacology
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Dose-Response Relationship, Drug
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Epithelial Cells
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cytology
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metabolism
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Humans
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Kidney
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metabolism
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Kidney Tubules, Proximal
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cytology
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Male
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Micronucleus Tests
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Molecular Structure
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Organometallic Compounds
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toxicity
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species
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metabolism
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Uranium
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metabolism
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urine
6.Survival and prognostic factors in resected satellite-nodule T4 non-small cell lung cancer.
Kai MA ; Tian-you WANG ; Bao-liang HE ; Dong CHANG ; Xiao-dan HU ; Zhi-yi YIN ; Hua JIANG ; Yong CUI ; Zhi GAO ; Min GONG
Chinese Journal of Surgery 2009;47(2):120-122
OBJECTIVETo study the survival and prognostic implication in surgically resected satellite-nodule T4 (T4 satellite) non-small cell lung cancer (NSCLC).
METHODSFrom January 1995 to March 2005, the complete resection was performed to 42 patients with NSCLC who were postoperatively identified as pathologic-stage T4 satellite. Survival and associations between clinicopathological parameters and prognosis were analyzed. Thirty-two patients with pathologic stage local-invasion T4 (T4 invasion) NSCLC who underwent resection at the same time were also analyzed.
RESULTSThe 1-, 3- and 5-year survival was 76.2%, 57.1% and 46.0% for patients with T4 satellite, while 62.3%, 31.5% and 20.0% for patients with T4 invasion. There was a significant higher survival in T4 satellite group when compared to that in T4 invasion group (P < 0.05). Furthermore, patients with T4 satellite N0M0 got a better survival than those with T4 satellite N1-2M0, T4 invasion N0M0 and T4 invasion N1 -2M0 (P < 0.05). For patients with T4 satellite, univariate analysis showed that histology, main tumor size, lymph node status and adjuvant chemotherapy were linked with survival, while main tumor size, lymph node status and adjuvant chemotherapy served as the independent prognostic factors with multivariate analysis.
CONCLUSIONSPatients with completely resected T4 satellite NSCLC have a better prognosis than those with T4 invasion. Main tumor size over 3 cm, lymph node metastasis or no adjuvant chemotherapy means an unfavorable prognosis.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; pathology ; surgery ; Female ; Humans ; Lung Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; Prognosis ; Retrospective Studies ; Survival Analysis
7.Construction of a recombinant adeno-associated virus hybrid vectors with the HBV capsid for gene therapy of liver diseases.
Ming-man ZHANG ; Xing-hua GOU ; De-hua LI ; Chun-bao GUO ; Dan TANG ; Quan KANG ; Lei HAN ; Lan-ying ZHAO ; Hai-yang HU
Chinese Journal of Hepatology 2009;17(9):707-708
Capsid
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Cell Line
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Dependovirus
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genetics
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Genetic Therapy
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Genetic Vectors
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genetics
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Hepatitis B virus
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genetics
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Humans
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Liver Diseases
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therapy
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Plasmids
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Recombination, Genetic
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Transfection
8.Clinical Analysis of Gene Mutation and Vascular Events in Patients with BCR/ABL Negative Myeloproliferative Neoplasms.
Journal of Experimental Hematology 2022;30(3):813-818
OBJECTIVE:
To explore the relationship between clinical features, peripheral blood cell count, coagulation function, gene mutation and hemorrhagic events and thrombotic events in essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis(PMF) patients.
METHODS:
Clinical data of 78 patients with ET, PV, and PMF who were admitted to the Second Affiliated Hospital of Chongqing Medical University between September 2019 and August 2020 were retrospectively analyzed. Information about sex, age, gene mutation, peripheral blood cell count, coagulation function, and hemorrhagic and thrombotic events was included, and the influence of these data on the occurrence of hemorrhagic and thrombotic events was estimated.
RESULTS:
Among the 78 patients with myeloproliferative neoplasms, there were 47 cases of ET, 15 cases of PV, and 16 cases of PMF.A total of 10 patients (12.82%) experienced hemorrhagic events and 27 (34.62%) experienced thrombotic events. Male,patients aged ≥ 60 years, and patients with a JAK2V617F mutation were more likely to experience thrombotic events (P<0.05). Patients with thrombotic events had higher platelet (PLT) counts and fibrinogen (FIB) levels than patients without hemorrhagic-thrombotic events (P<0.05).White blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (HGB) level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and international normalized ratio (INR) showed no statistical difference between patients with thrombotic events and patients without hemorrhagic-thrombotic events (P>0.05). There was also no significant difference in the above-mentioned indexes between patients with hemorrhagic events and patients without hemorrhagic-thrombotic events (P>0.05). Among JAK2V617F positive myeloproliferative neoplasm patients, male patients were more likely to have thrombotic events (P<0.05), and patients with thrombotic events had higher platelet counts than those without hemorrhagic-thrombotic events (P<0.05). There was no significant difference in age, white blood cell count, red blood cell count, hemoglobin level, PT, APTT, FIB, TT or INR between patients with thrombotic events and patients without hemorrhagic-thrombotic events (P>0.05).
CONCLUSION
Sex, age, JAK2V617F mutation and platelet count have a certain value for predicting thrombosis in patients with myeloproliferative neoplasms.
Hemoglobins/genetics*
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Hemorrhage
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Humans
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Janus Kinase 2/genetics*
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Male
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Mutation
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Myeloproliferative Disorders/genetics*
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Polycythemia Vera/genetics*
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Retrospective Studies
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Thrombocythemia, Essential
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Thrombosis
9.Immunotherapy effect of dendritic cells pulsed by lysate of tumor cell Ar-He cryoablation on rat models of intracraniai gliomas
Dao-Qing SU ; Guo-Hui LU ; Li-Juan HU ; Bao-An WANG ; Ming LI ; Xiao-Zheng HE ; Xiao-Dan JIANG ; Yi-Quan KE ; Shi-Zhong ZHANG
Chinese Journal of Neuromedicine 2012;11(4):342-346
Objective To investigate the role of C6 glioma cells mediated by rapid freezing and thawing ofAr-He cryoablation in the maturation of marrow-derived dendritic cells (BM-DCs) in Wistar rats,and the anti-tumor effect of these DCs on rat models of intracranial gliomas. Methods C6 glioma cells were routinely cultured in vitro; rapid freezing and thawing of Ar-He cryoablation was employed in C6 glioma cells of the experimental group, and C6 glioma cells of the negative control group were only performed insertion of the probe; blank control group (using rapid freezing and thawing of Ar-He cryoablation on the same amount of PBS) was also employed.Bone marrow-derived mononuclear cells (MNCs) were first prepared from tibia and femur bones of Wistar rats. These cells were cultured with such cytokines as recombinant granulocyte-macrophage colony-stimulating factor (rmGM-CSF),recombinant interleukin-4 (rmIL-4) and tumor necrosis factor-alpha (TNFα) to induce their maturation; BM-DCs were pulsed with or without tumor cell lysate obtained by rapid freezing and thawing of Ar-Hecryoablation at a ratio of (DC:tumor cells =1:3) 7 d after that.Morphological observation of BM-DCs was performed by light microscopy and the expression of DCs costimulatory molecules CD80 and CD86 were measured by flow cytometry 48 h after the addiction; the IL-12 level in the supematant of DCs was detected by ELISA. In order to determine whether or not vaccination with C6 TP DCs can induce the therapeutic potential in the established glioma-bearing models, the C6 cells cultured in vitro were stereotaxically implanted into the left caudate nucleus of Wistar rat brain; glioma-bearing rats were injected with vaccination with DCs,cells from the blank control group and negative control group on the 3rd and 10th d. Survival time was observed and determined using the method of Kaplan-Meier and Log-Rank analysis. Results DCs from rats' bone marrow cells cultured with cytokines and pulsed with tumor lysates showed the characters of typical mature DCs.Morphologically,these cells were large with oval or irregularly shaped nuclei and with many small dendrites. Phenotypically, they expressed high levels of CD80 and CD86 antigens (71.8 1%± 1.10% and 74.66%± 1.48% in experimental group,49.49%±1.08% and 51.20%±2.06% in negative control group, and 48.47%±1.09% and 49.53%±1.89% in blank control group); significant difference was noted between each 2 groups (P<0.05).Functionally,the IL-12level in the supernatant of DCs showed obvious increment in the experimental group (245.99 ±3.20pg/mL) as compared with that in the negative control group (138.68±3.20 pg/mL) and blank control group (135.16±2.88 pg/mL,P<0.05).These cells gained the capacity of mediating immunotherapy against intracranial gliomas in rats:the median survival in the experimental group (33 d) was significantly higher than that in the negative control and blank control groups (22 and 24 d, respectively, P<0.05).Conclusion C6 glioma cells mediated by rapid freezing and thawing of Ar-He cryoablation can induce maturation of BM-DCs in Wistar rats; these BM-DCs pulsed with tumor lysates, as new therapeutic vaccines,can mediate immunotherapy against intracranial gliomas in rats.
10.Construction and identification of a vector inserted with gene of T7 RNA Polymerase
Hong-Hui SHEN ; Bing-Ke BAI ; Hao-Dong LIU ; Sheng-Dong LUO ; Yan HU ; Jun HOU ; Zhi-Fie WANG ; Wei KONG ; Yi-Dan BAO ; Pan-Yong MAO
Chinese Journal of Experimental and Clinical Virology 2011;25(2):146-148
Objective To develop a system to rescue virus by intracellular expression of T7 RNA Polymerase. Methods The gene of T7 RNA Polymerase was amplified and cloned to VR1012 by molecular biological technology. The expression plasmid VR-1a was then identified. VR-1a and EV71 infectious plasmid were co-transfected in Veto cell. CPE was observed and viral gene viral antigen were detected.Results The gene of T7 RNA Polymerase was successfully cloned into vector VR1012. Vere cell developed to CPE after being transfected VR-1a and EV71 infectious plasmid. EV71 gene was amplified by RT-PCR from the culture. EV71 antigen was also detected by ELISA. Conclusion The method can be used to rescue virus. It could apply to immunologic research of EV71 DNA vaccine.