1.The effect on succinate dehydrogenase of mitochondria in myocardium and liver in sepsis rats treated with edaravone
Xinjun MIAO ; Honghui CHEN ; Yuxi CHEN ; Zhili CHEN ; Rongkai YOU
Journal of Chinese Physician 2010;12(10):1301-1303
Objective To observe the effect on succinate dehydrogenase (SDH) of mitochondria in myocardium and liver in sepsis rats treated with edaravone. Methods 30 Sprague-Dawley rats were divided into 3 groups: sham operated group ( group A ), controlled operated group ( group B ), treated group with edaravone (group C). The model of sepsis rats was made by the way of caecum ligated and punctured and 20mg/kg lactate levofloxacin was subcutaneously injected (sci) 15min before and 3h after operation in three group. 5mg/kg edaravone were sci 15min before and 3h after operation in group C. Liver and myocardium were taken from all of them 18h after operation. The activities of SDH in myocardial and hepatic mitochondria were detected, pathological change of mitochondria in liver and myocardium were observed. Results The activities of SDH in myocardial and hepatic mitochondria in group B [ (0. 21 ± 0. 07 ) U/mgprot, (0. 23± 0. 08 ) U/mgprot ] were significantly decreased compared with group A [ ( 0. 33 ± 0. 10 ) U/mgprot, ( 0. 38±0. 12)U/mgprot]. The activities of those in group C[ (0.31 ±0. 08) U/mgprot, (0. 36 ±0. 11)U/mgprot] were significantly increased than group B. Myocardial and hepatic mitochondria swelling and endocytoplasmic reticulum expanding were found in group B by electron microscope, while it showed normal in group C. Conclusion Hepatic and myocardial mitochondrial structure were destroyed and activities of SDH were decreased in sepsis rats. They could be effectively protected by edaravone.
2.The effect of Kaolin and propranolol on expression level of matrix metalloproteinase-9 in lung of paraquat intoxicated mice
Xianke QIU ; Zhangping LI ; Xinjun MIAO ; Yuxi CHEN ; Yong LI ; Zhili CHEN
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2015;22(5):478-481
Objective To explore the effect of Kaolin combined with propranolol on matrix metalloproteinase-9 (MMP-9) in lungs of paraquate (PQ) intoxicated mice and the mechanism of protection for lung injury. Methods Fifty-four ICR mice were randomly divided into three groups, 18 mice in each group: namely control group, PQ intoxicated group and treatment group. The PQ intoxicated model was replicated by intra-gastric administration (ig) of PQ 100 mg/kg; after intoxication, 48 g/kg Kaolin combined with 3.2 mg/kg propranolol intra-gastric administration was immediately given to the treatment group, while in the control group, the same volume of normal saline ig was applied. All the mice were sacrificed at 6, 12 and 24 hours after disposal, and the lung was harvested to test the protein expression level of MMP-9 by Western Blot, and the lung tissue pathological changes were observed.Results There was no statistical significance in the protein expression levels of MMP-9 among the control group, PQ intoxicated group and treatment group at 6 hours after disposal (grey value: 0.655±0.045, 0.656±0.045, 0.641±0.036). The protein expression levels of MMP-9 in PQ intoxicated group were increased significantly compared with those in the control group at 12 hours and 24 hours after disposal (12 hours: 0.824±0.039 vs. 0.634±0.038, 24 hours: 0.742±0.039 vs. 0.658±0.041, bothP < 0.05), while the levels of treatment group were significantly lower than those in the intoxicated group (12 hours: 0.760±0.050 vs. 0.824±0.039, 24 hours: 0.686±0.041 vs. 0.742±0.039, bothP < 0.05). In PQ intoxicated group, early capillary dilation and congestion in lung tissue, a large number of inflammatory cells infiltration with mainly neutrophils in alveolar cavity and a small number of red blood cells exudation were seen at 12 hours; at 24 hours, capillary dilation at alveolar walls, congestion, swelling of endothelial cells, small flakes or large patches of inflammatory cell infiltration with mainly neutrophils in lungs were found. In the treatment group, the lung inflammatory cells infiltration, alveolar capillary dilatation, congestion, swelling of the endothelial cells, etc were also visible, but the degree of severity was significantly milder than those in the intoxicated group.Conclusion The interference of Kaolin combined with propranolol can significantly decrease the protein expression level of MMP-9 in lung tissue of acute paraquat poisoned mice that is possibly one of the mechanisms for prevention and treatment of lung injury in paraquat poisoning.
3.Ultrasonic quantitative analysis of the flexion cornal hip in the normal infant
Lili MIAO ; Qinghua LIU ; Xiaofang LIU ; Xincun ZHANG ; Yuxi YAN ; Huanping PANG
Chinese Journal of Ultrasonography 2017;26(8):703-707
Objective To study the influencing factors and clinical significance of ultrasonic quantitative analysis of the hip-flexion coronal section in the normal infants.Methods Totally 100 normal infants were enrolled.Angle α,angle β and FHC on different positions(mild-flexion and flexion of the hip) were mearured.And angle β on different points(the labrum central and the acetabular tips) were measured.The variation of the measurement index between different positions were analyzed.Results ①There was no significant difference in angle α between the neutral position and hip-flexion position (P >0.05).② FHC decreased in the hip-flexion position,and there was significant difference compared with the neutral position (P <0.05).③βc were greater than βt in the two positions (P <0.05);βc and βt were all greater in hip-flexion position than those in neutral position,the difference was statistically significant (P <0.05).Conclusions The results obtained from angle α is stable under the coronal flexion view of the normal infants,and does not vary with changing position.The change of the angle β and FHC with the hip flexion could be used to evaluate the stability of the hip.Measured angle β on the labrum tip has good repeatability.So this point should be selected to measure the angle β.
4.Peptide-drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope?
Chen FU ; Lifeng YU ; Yuxi MIAO ; Xinli LIU ; Zhaojin YU ; Minjie WEI
Acta Pharmaceutica Sinica B 2023;13(2):498-516
Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.
5.Unexpected antibody screening of thalassemia children in Yunnan Province and the blood transfusion strategies
Rui CHEN ; Running HE ; Changsheng LIU ; Yangling HE ; Mengxing LV ; Zhiguo ZHANG ; Kexuan QU
Chinese Journal of Blood Transfusion 2022;35(6):636-639
【Objective】 To study the yielding rate and distribution of unexpected antibodies in blood transfusion children with thalassemia in Yunnan province, and to explore the blood transfusion strategies. 【Methods】 From January 2016 to December 2021, 298 children with thalassemia, who received blood transfusion treatment in Kunming, Xishuangbanna, Wenshan, Dehong, Yuxi and Baoshan hospitals across Yunnan Province, were selected. The unexpected antibodies of blood plasma were screened by microcolumn gel card. The samples with positive antibodies were identified for alloantibody specificity. 【Results】 Unexpected antibodies were yielded in 67 out of 298(22.48%) transfused children with thalassemia. The positive rates of unexpected antibodies in boys and girls were 16.55%(24/145) and 28.10%(43/153), respectively. The positive rates of unexpected antibodies in Han, Dai, Zhuang, Yi, Bulang, Jinuo and Miao people were 14.06%(18/128), 30.80%(32/104), 35.71%(10/28), 36.36%(8/22), 50.00%(4/8), 60.00%(3/5)and 66.67%(2/3), respectively, with statistically significant differences between each other. The positive rate of unexpected antibodies in ethnic minorities was higher than that in Han. The positive rates of unexpected antibodies in children who received the first transfusion at birth-one year old, 1~3 years old, 3~6 years old and above 6 years old were 12.50%(3/24), 10.14%(7/69), 24.54%(40/163)and 40.48%(17/42), respectively. The positive rates of unexpected antibodies in children with first transfusion after 3 years old were significantly higher than those before 3 years old. The positive rates of unexpected antibodies in children with one transfusion, 1~3, 3~10, 10~20 and more than 20 transfusions were 4.76%(1/21), 12.07%(7/58), 23.71%(23/97), 28.16%(29/103)and 36.84%(7/19), respectively, with statistically significant differences between each other. The number of blood transfusions was positively correlated with the unexpected antibody yielding. The yielding rate of unexpected antibodies in children with α thalassemia, βthalassemia, δ+ βthalassemia and untyped thalassemia was 7.50%(3/40), 17.62%(34/193), 53.70%(29/54)and 9.09%(1/11), respectively(P<0.05). The yielding rate of unexpected antibodies in transfused children with δ+ βthalassemia was the highest. And 57 unexpected antibodies of Rh blood group system were yielded, 6 anti-M antibodies, 2 anti-N antibodies and 2 undetermined. 【Conclusion】 The positive rate of unexpected antibodies in transfused children with thalassemia in Yunnan province is high. Routine antibody screening should be carried out for transfusion children with thalassemia, and blood units, compatible with ABO, Rh and MNS typing results, should be selected to ensure the safety and effectiveness of clinical blood use.