1.Activation of paraptosis and autophagy in rat retina following acute retinal ischemia-reperfusion injury
Ting WEI ; Shan GAO ; Qiao-Chu CHENG ; Li-Jun CUI ; Qian-Yan KANG
Recent Advances in Ophthalmology 2018;38(6):501-505
Objective To investigate whether paraptosis and autophagy have an effect on acute retinal ischemia-reperfusion injury (RIRI) in an experimental rat model that recapitulates features of acute hypertensive glaucoma and to explore the possible underlying mechanisms.Methods A total of 30 adult male Sprague-Dawley rats were randomly divided into RIRI group and control group.The acute RIRI model was induced with normal saline in the right eye of rats from the RIRI group by anterior chamber perfusion,while the rats in the control group left untreated.On day 1,day 3,day 7,day 28 after RIRI model establishment,the changes in morphology of retinal ganglion cells (RGCs) were observed by transmission electron microscopy (TEM),and the expression of microtubule-associated protein 1 light chain 3 (LC3) was measured by immumofluorescence methods.Results When compared with the control group,the number of cytoplasmic vacuoles predominantly derived from the progressive swelling of mitochondria and/or endoplasmic reticulum (ER) in RGCs were increased in the RIRI group from day 1 to day 28 by TEM.And ultra-structural analyses showed the double-or multiple-membrane autophagosomes were markedly accumulated in the cytoplasm of RGCs following acute RIRI.The average number of autophagic vacuoles in the cytoplasm of RGCs was 0.79 per 50 μm2 in the control group,and the average number of autophagosomes reached to a maximum on day 7 after acute RIRI at 2.29 per 50 μm2,which was statistically significant compared with the control group (P < 0.05).Compared to the control group,LC3 expression in the cytoplasm of RGCs was up-regulated on day 1 after acute RIRI,which sustained throughout the experimental period.The percentage of LC3 positive cells in the retinal ganglion cell layer was 15.90% in the control group,and the data was 46.95% and 52.30% on day 1 and day 28 after RIRI,respectively,both which were statistically significant compared with the normal control group (both P < 0.05).Conclusion Both paraptosis and autophagy participate in death of RGCs after acute RIRI.Programmed cell death in different cells,either coexistence of multiple-cell death form or a single-cell death form,participates in the pathogenesis of acute RIRI.
2.Aike mixture has good anti-inflammatory and analgesic effects on mice.
Min-jian ZHANG ; Ke-dan CHU ; Xin-ling CHENG ; Xu-dong PAN ; Wan-jun CHENG ; Kai-yuan YU ; Yu-hong TAN ; Jin-zhi LIU ; Ya-lei SHI ; Sheng ZHENG ; Qiao-bin LIU
National Journal of Andrology 2007;13(5):471-473
OBJECTIVETo study the anti-inflammatory and analgesic actions of Aike Mixture (AKM).
METHODSA total of 100 male mice were randomly assigned into 5 groups: a normal control group, a drug control group (a hydrocortisone subgroup and an atropine subgroup), a high-dose AKM group, a mid-dose AKM group and a low-dose AKM group. Xylene was spread on the left ear of the experimental mice to induce inflammation, and 1% acetic acid solution injected into the abdominal cavity to produce pain so as to cause the body bend. Different doses of AKM were given and their actions observed.
RESULTSAKM had obvious anti-inflammatory effect on the xylene-induced ear tumefaction and inhibited the pain-caused body bend in the AKM groups, with significant difference from the normal control (P < 0.01).
CONCLUSIONAKM has good anti-inflammatory and analgesic effects, which is of clinical significance in the treatment of chronic prostatitis.
Animals ; Chronic Disease ; Disease Models, Animal ; Drug Combinations ; Male ; Mice ; Mice, Inbred ICR ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; therapeutic use ; Phytotherapy ; Prostatitis ; drug therapy ; Saponins ; pharmacology ; therapeutic use
3.Mutation Spectrum of FANCJ Gene in Adult Acute Myeloid Leukemia.
Song-Bai LIU ; Xiao-Ling CHU ; Rong HAN ; Jia-Hui DU ; Qiao-Cheng QIU ; Sheng-Li XUE
Journal of Experimental Hematology 2019;27(2):348-353
OBJECTIVE:
To detect and analyze the mutation status of FANCJ gene in adult AML patients, so as to provide the basis for studying the mechanism of FANCJ driven AML and guiding the preventim and treatment of deseese.
METHODS:
The cDNAs were extracted and transeripted from bone marrow cells and normal skin cells in 222 newly diagnosed AML patients. The primers were designed for FANCJ gene coding region, the mutations of FANCJ gene coding region in AML patients as well as the mutations of FANCJ gene in mucous membrane epethelia in patients were detected by PCR and sanger seguencing; the evolutionary conservation of FANCJ mutation in different organisms was analyzed by NCBI Blast online bioinformaties software.
RESULTS:
The sequencing analysis showed that the mutations of FANCJ gene happened in 11 sites of FANCJ gene coding region, which were as followed: exon5:c.G430A:p.A144T, exon6:c.A587G:pN196S, exon9:c.C1255T:p.R419W, exon10:c.G1442A:p.G481D, exon11:c.C1609G:p.L537V, exon16:c.C2360T:p.P787L, exon17:c.C2440T:p.R814C, exon19:c.C2608T:pH870Y, exon19:c.A2686G:p.I896V, exon19:c.C2830G:p.Q944E, exon20:c.G3412A:p.D1138N. Among them, the repeatability existed in mutations of A144T, N196S, R814C, I896V and Q944E. Beside, the mutation sites of A144, R419, G381, L537, P787, H870, Q944 and D1138 were highly conserved in different organisms.
CONCLUSION
Among 222 adult AML patients, the mutations of FANCJ gene have been found in 26 patients, moreover, the mutation sites are relatively conserved in different organisms, and possess important fanction. The results of this study provide the basis for exploring the mexhanism of FANCJ gene driven AML and for guiding the prevantion and treatment of AML.
Adult
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DNA Primers
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Humans
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Leukemia, Myeloid, Acute
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Mutation
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Polymerase Chain Reaction
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Prognosis
4.68Ga-PSMA ligand PET/CT integrating indocyanine green-guided salvage lymph node dissection for lymph node metastasis after radical prostatectomy.
Teng-Cheng LI ; Yu WANG ; Chu-Tian XIAO ; Ming-Zhao LI ; Xiao-Peng LIU ; Wen-Tao HUANG ; Liao-Yuan LI ; Ke LI ; Jin-Ming DI ; Xing-Qiao WEN ; Xin GAO
Asian Journal of Andrology 2022;24(1):97-101
To efficiently remove all recurrent lymph nodes (rLNs) and minimize complications, we developed a combination approach that consisted of 68Gallium prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET)/computed tomography (CT) and integrated indocyanine green (ICG)-guided salvage lymph node dissection (sLND) for rLNs after radical prostatectomy (RP). Nineteen patients were enrolled to receive such treatment. 68Ga-PSMA ligand PET/CT was used to identify rLNs, and 5 mg of ICG was injected into the space between the rectum and bladder before surgery. Fluorescent laparoscopy was used to perform sLND. While extensive LN dissection was performed at level I, another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal, and laparoscopy was introduced to intensively target stained LNs along levels I and II, specifically around suspicious LNs, with 68Ga-PSMA ligand PET/CT. Next, both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV. In total, pathological analysis confirmed that 42 nodes were rLNs. Among 145 positive LNs stained with ICG, 24 suspicious LNs identified with 68Ga-PSMA ligand PET/CT were included. The sensitivity and specificity of 68Ga-PSMA ligand PET/CT for detecting rLNs were 42.9% and 96.6%, respectively. For ICG, the sensitivity was 92.8% and the specificity was 39.1%. At a median follow-up of 15 (interquartile range [IQR]: 6-31) months, 15 patients experienced complete biochemical remission (BR, prostate-specific antigen [PSA] <0.2 ng ml-1), and 4 patients had a decline in the PSA level, but it remained >0.2 ng ml-1. Therefore, 68Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.
Gallium Isotopes
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Gallium Radioisotopes
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Humans
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Indocyanine Green
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Ligands
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Lymph Node Excision
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Lymphatic Metastasis/diagnostic imaging*
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Male
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Neoplasm Recurrence, Local/surgery*
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Positron Emission Tomography Computed Tomography
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Prostate
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Prostatectomy
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Prostatic Neoplasms/surgery*
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Salvage Therapy
5.The prognostic value of cloned genetic mutations detected by second-generation sequencing in RUNX1-RUNX1T1 positive acute myeloid leukemia patients receiving intensive consolidation therapy.
Jing Qiu YU ; Sheng Li XUE ; Zheng LI ; Jun WANG ; Chao WANG ; Xiao Ling CHU ; Rong HAN ; Tao TAO ; Qiao Cheng QIU ; De Pei WU
Chinese Journal of Hematology 2020;41(3):210-215
Objective: To investigate the prognostic value of clonal gene mutations detected by second-generation sequencing in patients with positive RUNX1-RUNX1T1 acute myeloid leukemia (AML) who received high-dose chemotherapy or autologous transplantation (intensive consolidation therapy) in the first complete remission (CR(1)) state. Methods: 79 AML patients with positive RUNX1-RUNX1T1 who received intensive consolidation therapy in CR(1) state from July 2011 to August 2017 were analyzed retrospectively. Kaplan-Meier curve and Cox regression model were used to figure out the effect of leukocyte counts at onset and gene mutations for prognosis. Results: C-KIT, FLT3, CEBPA and DNMT3A gene mutations were found in 25 (31.6%) , 6 (7.6%) , 7 (8.9%) and 1 (1.3%) patient among the population. Mutations in C-KIT exon17 and C-KIT exon8 were detected in 19 (24.1%) and 5 (6.3%) cases, respectively, and mutations of FLT3-ITD were confirmed in 5 (6.3%) cases. The higher leukocyte counts presented at onset of leukemia, the shorter overall survival (OS) was seen in these patients (P=0.03) . Patients with C-KIT exon17 mutation had significantly shorter OS (P=0.01) and disease free survival (DFS) (P=0.006) compared with those without gene mutations, and patients with FLT3-ITD gene mutation got the inferior OS (P=0.048) and DFS (P=0.071) . Conclusion: In AML patients with positive RUNX1-RUNX1T1 receiving intensive consolidation therapy, the white blood cell counts at onset of leukemia, C-KIT mutations in exon 17, and FLT3-ITD gene mutations suggest poor prognosis, which would contribute to elaborate risk stratification, personalized treatment and predict prognosis for these patients.
Consolidation Chemotherapy
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Core Binding Factor Alpha 2 Subunit/genetics*
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Humans
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Leukemia, Myeloid, Acute/genetics*
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Mutation
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Prognosis
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RUNX1 Translocation Partner 1 Protein/genetics*
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Retrospective Studies
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fms-Like Tyrosine Kinase 3