2.Experimental study on the therapeutic effectiveness of defibrase in rat focal cerebral ischemia reperfusion model
Xiao-ling WU ; Ling YIN ; Ru-xun HUANG
Chinese Journal of Rehabilitation Theory and Practice 2002;8(7):418-420
ObjectiveTo investigate the therapeutic effectiveness of defibrase in treating penumbra and reperfusion.MethodsIntraluminal suture method was used to develope reversible middle cerebral artery occlusion(MCAO). Rats were subjected to MCAO 3 hours followed by reperfusion for 3, 6, 24, 72 hours, and to MCAO 6 hours followed by reperfusion for 3, 6, 24 hours. The treatment groups rats were injected intravenously defibrase at 0.5 hour before reperfusion. Meanwhile, the control group received normal saline. Clinically Neurological Deficits Scale were evaluated every day. Infarction volume was measured by using 2,3,5-triphenyltetrazolium chloride staining. Pathologic change were examined microscopically in HE stained sections.ResultsThere were significant difference at treatment groups of reperfusion 3 hours after MCAO.Infarction volume and Clinically Neurological Deficits Scale was significant reduced as control group (P<0.05). There were no significant differences at treatment groups of reperfusion 6 hours after MCAO (P>0.05). Cerebral hemorrhage wasn't increased in defibrase treatment group.ConclusionsDefibrase was effective on Clinically Neurological Deficits of rats in reperfusion 3 hours after MCAO.
3.Advances in photodynamic therapy based on tumor hypoxia
Xiao-jie YIN ; Xiao-qian WANG ; Feng-ling ZHANG
Acta Pharmaceutica Sinica 2020;55(11):2618-2627
Photodynamic therapy (PDT) has attracted wide attention due to its unique advantages such as minimal invasiveness, high efficiency and high selectivity, and its ability to induce anti-tumor immune response. However, the treatment process is heavily dependent on the oxygen content of the treatment site, and the widespread oxygen deficiency in malignant tumors severely limits its efficacy. In addition, PDT-mediated oxygen depletion exacerbates tumor hypoxia, which further reduces its therapeutic effect. In recent years, many researches have been devoted to overcoming this problem. This paper summarized various strategies based on tumor hypoxic PDT in recent years, discussing the advantages and disadvantages of these strategies, and analyzing the main challenges and future directions of PDT in the treatment of tumors, so as to provide references for the in-depth study of photodynamic therapy of tumors.
4.Analysis of the curative effect of extensive pterional approach combined with cutting of the zygomatic arch for the resection of large sphenoid ridge meningioma
Ling XU ; Shunwu XIAO ; Xuejun ZHANG ; Chunyue YOU ; Yin DAI
Chinese Journal of Clinical Oncology 2017;44(16):822-825
Objective: To explore the application of extensive pterional approach combined with cutting of the zygomatic arch for the resection of large sphenoid ridge meningioma. Methods: Thirty-three patients with large sphenoid ridge meningioma underwent operation using the extensive pterional approach combined with cutting of the zygomatic arch. Twenty patients with large sphenoid ridge meningioma received operation with the traditional pterional approach as the control. The resection rate, operative time, intraoperative blood loss, and postoperative complications were compared between the groups. Results: Two groups of patients underwent craniotomy under microscope. The Simpon grade I resection and grade Ⅱ resection rate was 93.9% in the cutting of the zygomatic arch approach group and 60.0% in the control group (P<0.01). The operative time was (325.2±121.3) min in the cutting of the zygomatic arch approach group, which was significantly shorter than that in the control group with (406.4±182.9) min (P<0.05). The intraoperative blood loss was (502.5±101.8) mL and (697.7±115.4) mL in the two groups (P<0.05). In addition, postoperative complication rate was 15.2% and 45.0% in the cutting the zygomatic arch approach group and the control group, respectively (P<0.05). No death was reported in both groups. Conclusion: Extensive pterional approach combined with cutting of the zygomatic arch can fully expose the anatomical structures of the skull base and the sellar region to eliminate the influence of temporal muscle in the exposure of the surgical area. The operative field is exposed to reduce the stretch injury to only the frontotemporal brain tissue, which might be helpful for the complete resection of large sphenoid ridge meningioma, and is more conducive to neurovascular anatomy and relevant functional protection.
5.Correlation of visual acuity and metamorphopsia with foveal morphology before and after vitrectomy with internal limiting membrane peeling in idiopathic macular epiretinal membrane eyes
Miao ZENG ; Xiao CHEN ; Ling HONG ; Yin YAN ; Zhijian HUANG
Chinese Journal of Ocular Fundus Diseases 2017;33(4):378-382
Objective To analyze the correlation of visual acuity and metamorphopsia with foveal morphology before and after vitrectomy with internal limiting membrane peeling (ILMP) in idiopathic macular epiretinal membrane (IMEM) eyes.Methods This is a retrospective case series of 47 IMEM patients (49 eyes).All the patients underwent 25G pars plana vitrectomy with IMEM removal and ILMP.The best corrected visual acuity (BCVA) was measured using the international standard visual acuity chart,and the results were converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity.The severity of metamorphopsia was measured using M-charts.The central macular thickness (CMT),inner nuclear layer thickness (INT),inner retinal layer thickness (IRT),outer retinal layer thickness (ORT),the status of ellipsoid zone (EZ) were assessed with spectral-domain optical coherence tomography at baseline and each month postoperatively.The differences in BCVA,CMT,INT,IRT,ORT and status of EZ before and after surgery were analyzed,so did the correlations between these indexes at the same time.Results Compared with baseline,the postoperative BCVA was significantly increased (F=6.133,P<0.001),but the M value,CMT,INT,IRT,ORT were significantly decreased (F=12.481,10.565,15.739,6.046,10.569;P<0.001);the integrity of EZ was improved significantly (x2=12.309,P<0.001).Preoperative BCVA was positively related to the CMT (r=0.720) and ORT (r=0.720,0.887;P<0.05),while negatively related to preoperative integrity of EZ (r=-0.295,P<0.05).The postoperative BCVA was positively related to the preoperative BCVA and postoperative CMT,ORT (r=0.774,0.754,0.842;P<0.05),while negatively related to postoperative integrity of EZ (r=-0.676,P<0.05).The preoperative M value was positively related to the preoperative CMT,INT,IRT,and ORT (r=0.931,0.668,0.840,0.637;P< 0.05).The postoperative M value was positively related to the preoperative M value and postoperative CMT,INT,IRT,and ORT (r=0.723,0.722,0.767,0.825,0.387;P<0.05).Conclusions Vitrectomy with ILMP for IMEM can improve the visual acuity,metamorphopsia and foveal morphology.Both visual acuity and metamorphopsia correlate with foveal morphology.
6.Experimental study of the therapeutic effectiveness of defibrase on treating acute cerebral ischemia and the effectiveness in different administrated ways
Xiao-ling WU ; Ling YIN ; Wei DU ; Luning WANG ; Ke ZHU
Chinese Journal of Rehabilitation Theory and Practice 2002;8(9):520-522
ObjectiveTo investigate the intensity of degrading plasma fibrinogen(FIB) and the therapeutic effectiveness of defibrase on treating cerebral ischemia by different administrated ways. MethodsIntraluminal suture method was used to develop reversible middle cerebral artery occlusion (MACO). 154 healthy male Wistar rats were randomized into 2 groups. The rats in intravenous treatment group were injected defibrase intravenously at 0.5,3,6,9,12hours after MACO,while the rats in coeliac treatment group were injected defibrase by abdominocentesis. Meanwhile the control group received normal saline. All rats were killed at 24 hours after MCAO. The thrombus in middle cerebral artery (MCA) and cerebral infarction were examined microscopically in HE stained sections. Infarction volume was measured by using 2,3,5-triphenyltetrazolium chloride staining. 24 rats were selected randomly and injected defibrase by intravenous injection and abdominocentesis. Plasma FIB was measured before and after injection 1,3,6,12,24h by intravenous haemospasia. ResultsPlasma FIB was significantly reduced in intravenous treatment group, and it was lowerest in 3h after intravenous treatment.Clinical Neurological Deficits Scale and infarction volume was significantly reduced in intravenous treatment group than saline control group and coeliac treatment group.There was improvement in Clinical Neurological Deficits Scale in coeliac treatment group compared with that of saline control group, but there was no statistically significant differences at infarction volume.Clinical Neurological Deficits Scale and infarction volume was statistically significant differences in intravenous treatment group at 0.5,3 hours after MCAO. There were no statistically significant differences in intravenous treatment group at 6, 9,12 hours after MCAO.Conclusions Defibrase can reduce the infarction volume in cerebral ischemia early stage.
7.Experimental studies on the protective effect of defibrase againstreperfusion injury after cerebral ischemia
Ru-Xun HUANG ; Xiao-Hua XIAO ; Mei YIN ; Ling LI ; Hua LI ; Zheng-Pei SU ;
Chinese Journal of Clinical Pharmacology and Therapeutics 2000;0(03):-
Aim To ascertain whether defibrase has the protective effect against reperfusion injury after cerebral ischemia.Methods 70 renovascular hypertensive rats(RHR) were randomly divided into defibrase group, control group and sham-operated group.Reversible middle cerebral artery occlusion(MCAO) models were produced by the modified. Longa's method,and reperfusion was begun 2 hours after occlusion.Rats in the defibrase group were given defibrase 10 U?kg-1 body weight via femonal intraveneous injection, and in the control group with the same amount of saline. The brain pieces were processed by TTC and HE staining and the infarct size,brain microvessels damage and secondary bleeding were compared between the two groups. Results The volume of infarction in the defibrase group was obviously smaller than in the control group, the damage of brain microvessels was less severe, and the bleeding lesions under optical microscope were less than in the control group. Conclusion Defibrase has protective effect against reperfusion injury post cerebral ischemia.
8.Effect of pigment epithelium derived factor on NO and the expression of caspase-3 in retinal tissues of model rats with optic nerve crush injury
Xiao-Xiao, YAN ; Hai-Bo, JIA ; Xiao-Ling, YIN ; Cui, CUI ; Wei-Xing, PU ; Nan, HUO ; Jun-Bo, ZHAO
International Eye Science 2017;17(6):1047-1050
AIM: To analyze the effect of pigment epithelium derived factor (PEDF) on nitrogen monoxide (NO) and expression of cysteine-containing, aspartate-specific proteases-3 (caspase-3) in retinal tissues of model rats with optic nerve crush injury.METHODS: A total of 60 SD rats were randomly divided into the blank control group, model group and PEDF group, with 20 rats in each group.Except the blank control group, the optic nerve crush injury rat models were established in the other groups, and left eyeballs were taken as samples.After successfully modeling, the model group were treated with intravitreal injection of 5μL of balanced salt solution while PEDF group were treated with intravitreal injection of 5μL of PEDF (0.2μg/μL).Two weeks later, the retinal tissues were collected, and changes of shape were observed under microscope after HE staining.The changes of NO level were measured by colorimetry assay, the expression of caspase-3 mRNA and caspase-3 protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western-blot.RESULTS: HE staining showed that retinal tissues of the blank control group arranged neatly and clearly.Retinal ganglion cells (RGCs) arranged in a monolayer, and cells were oval, uniform in size and distribution, the cell nuclei were clear, closely arranged, with clear boundaries.The retinal tissues of the model group were sparse in shape, RGCs showed vacuolar changes, the overall number of cells was reduced, and cell nuclei of residual RGCs showed pyknosis and uneven staining.RGCs in PEDF group were with slightly edema and arranged closely, and the degree of injury was significantly milder than that in the model group.Levels of Caspase-3 mRNA and protein and NO levels in the three groups showed the model group > PEDF group > blank control group (all P < 0.05).CONCLUSION: The application of PEDF can down regulate the expression of Caspase-3 and NO in rates with optic nerve injury and reduce RGCs injury.
9.Design, synthesis and biological evaluation of novel 3-(2-oxo-2-substituted acetamido)benzamides as PARP-1 inhibitors.
Yu-wen YIN ; Ming JI ; Ran CAO ; Xiao-guang CHEN ; Bai-ling XU
Acta Pharmaceutica Sinica 2015;50(6):738-745
Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents
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Benzamides
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chemistry
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DNA Repair
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Drug Design
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Humans
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Molecular Docking Simulation
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Poly(ADP-ribose) Polymerase Inhibitors
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chemical synthesis
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chemistry
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Poly(ADP-ribose) Polymerases
10.The influence of CTP-OD1-HA and CTP-OD2-HA fusion peptides or combine with imatinib on proliferation of K562 cells
Heng XIAO ; Yanbin REN ; Zhiming YANG ; Shujie ZHOU ; Lei YIN ; Zhimei QIN ; Ling XU ; Shouxia LI
International Journal of Laboratory Medicine 2017;38(14):1876-1878
Objective To study the influence of CTP-OD1-HA and CTP-OD2-HA fusion peptides and combined with imatinib on proliferation of K562 cells.Methods K562 cells were treated with CTP-OD1-HA and CTP-OD2-HA peptides or together with imatinib.The proliferation of cells were detected and compared by MTT and clone formation methods.Results MTT examination demonstrated that CTP-OD1-HA and CTP-OD2-HA peptides could inhibit the proliferation of K562 cells,and the effect was more obvious when acted along with imatinib;Clone formation showed that CTP-OD1-HA and CTP-OD2-HA peptides suppressed the continuous colony forming ability of K562 cells.Conclusion CTP-OD1-HA and CTP-OD2-HA could specially inhibit the proliferation of K562 cells,and increase the sensitivity of imatinib.