1.Mdivi-1 improves cognitive dysfunction in immature SD rats induced by hypoxia combined with propofol by inhibiting excessive mitophagy
Yao XU ; Shun YANG ; Fei YANG ; Ying YANG ; Huanjie YUN ; Ahmad TAUSEEF ; Shengfen TU
Journal of Army Medical University 2025;47(21):2621-2629
Objective To investigate the protective effect of mitochondrial division inhibitor 1(Mdivi-1),a mitophagy inhibitor,on cognitive dysfunction in immature SD rats induced by hypoxia combined with propofol.Methods A total of 72 neonatal SD rats(half male and half female,aged 7 d,weighing 16.14±3.08 g)were randomly divided into 4 groups(n=18):blank control group(CON),Mdivi-1+blank control group(MCON),propofol+hypoxia group(PH),and Mdivi-1+propofol+hypoxia group(MPH).The MCON group and MPH group were pretreated with 2.4 mg/kg Mdivi-1 in 30 min in advance,and subsequently,50 mg/kg propofol was respectively given to the PH group and the MPH group.Immediately after the intraperitoneal injections were completed,the corresponding rats were transferred into a constant temperature chamber containing 18%O2.Then the rats were continuously monitored until resuming the reversing reflex and then transferred to a normoxic environment.The hypoxic treatment was carried out once per day for 7 consecutive days.Transcriptome sequencing was used to screen for differential expressed genes(DEGs),and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis was employed to conduct functional analysis.Morris water maze test was applied to exam spatial learning and memory abilities.HE staining was used to observe the morphological changes of neurons in the hippocampal CA1 region.Morphological changes of mitochondria in hippocampal neurons were observed by transmission electron microscopy(TEM).Western blotting was utilized to detect the expression of Parkin Rbr E3 ubiquitin protein ligase(Parkin)and PTEN-induced putative kinase 1(PINK1)in the hippocampal tissues.Results KEGG analysis results indicated that the mitophagy pathway was more significantly enriched in the PH group when compared with the CON group.Morris water maze test revealed that the PH group exhibited obviously prolonged escape latency(P<0.05),reduced frequency of crossing the platform(P<0.05),and shortened residence time in the target quadrant(P<0.01)when compared with the CON group and the MPH group.HE staining demonstrated that the cells in the PH group were in disordered arrangement,with great loss in cell count in some areas,and widened intercellular spaces.Although the cell arrangement in the MPH group also showed a sparse state,but the condition was milder than that in the PH group,with slightly widened intercellular space.In the CON group and the MCON group,the cells exhibited round in shape,good morphological structure,relatively clear contours,and uniform cell nuclei.TEM revealed that in the hippocampal neurons of the PH group,the mitochondria were swollen and deformed,and mitochondrial cristae were disordered,dissolved and disappeared.In the MPH group,only some mitochondria were swollen and the cristae were reduced.However,the mitochondrial morphology of the CON and MCON groups was relatively complete,and the matrix was uniform.Western blot analysis showed that the expression levels of Parkin and PINK1 in the hippocampus were up-regulated in the PH group than the CON group(P<0.05),and reduced in the MPH group than the PH group(P<0.05).Conclusion Mdivi-1 may reduce hippocampal neuron damage by inhibiting excessive mitophagy and then improve cognitive dysfunction in immature SD rats induced by hypoxia combined with propofol.
2.Correlation between uterine artery blood flow parameters detected by ultrasound examination during early pregnancy and pregnancy outcomes
Chinese Journal of Primary Medicine and Pharmacy 2023;30(10):1545-1549
Objective:To investigate the relationship between uterine artery blood flow parameters detected by ultrasound examination during early pregnancy and pregnancy outcomes in pregnant women who had a history of recurrent spontaneous abortion.Methods:A total of 100 pregnant women with a history of recurrent spontaneous abortion who were at 6-10 weeks of gestation and received treatment in Zhuji Maternal and Child Health Hospital from June 2020 to June 2022 were included in the study group. Using a case-control study method, 100 normal pregnant women who were at 6-10 weeks of gestation who concurrently underwent physical examination were selected and included in the control group. Both groups of pregnant women were tested for uterine artery blood flow parameters using color Doppler ultrasound diagnostic equipment, including peak systolic/diastolic velocity (S/D), resistance index (RI), and pulsatility index (PI). The occurrence of early miscarriage was monitored in both groups. The value of uterine artery blood flow parameters in the prediction of adverse pregnancy outcomes and the correlation between uterine artery blood flow parameters and adverse pregnancy outcomes were analyzed. Multivariate logistic regression was performed to analyze the relationship between uterine artery blood flow parameters and adverse pregnancy outcomes.Results:S/D, RI, and PI in the study group were (3.87 ± 0.43), (0.93 ± 0.16), and (1.73 ± 0.41), respectively, which were significantly higher than (2.54 ± 0.37), (0.64 ± 0.14), and (1.24 ± 0.35) in the control group ( t = 23.44, 13.64, 9.09, all P < 0.05). The early abortion rate in the study group was 57.0% (57/100), which was significantly higher than 2.0% (2/100) in the control group ( χ2 = 72.73, P < 0.05). The receiver operating characteristic curve analysis showed that S/D sensitivity and specificity in the prediction of adverse pregnancy outcomes were 79.1% and 70.2%, respectively, RI sensitivity and specificity were 88.4% and 84.2%, respectively, and PI sensitivity and specificity were 65.1% and 75.4%, respectively. Pearson analysis results showed that S/D, RI, and PI were positively linearly correlated with adverse pregnancy outcomes ( r = 0.587, 0.648, 0.613, all P < 0.05). Conclusion:Uterine artery blood flow parameters S/D, RI, and PI are abnormally high in pregnant women with a history of recurrent spontaneous abortion in the early stage of pregnancy. These parameters are closely associated with adverse pregnancy outcomes and are the independent risk factors of adverse pregnancy outcomes.
3.Application of chromosome painting technique to analysis of structural aberration of human chromosomes
Huanjie YANG ; Yan SONG ; Quanzhang LIU ; Yu LI ; Songbin FU ; Guiyin ZHANG ; Pu LI
Chinese Journal of Medical Genetics 2001;18(2):135-138
Objective This study was aimed at using chromosome painting technique to detect translocation, especially microtranslocations, on chromosomes in comparison with G-banding analysis. Methods Chromosome painting technique was applied to analysis of metaphase chromosomes of patients for detecting translocations with biotin-labeled chromosomes X, Y, 14q, 10 specific probes. Results Fluorescence in situ hybridization FISH signals were shown clearly in slides even in specimen stored at room temperature for 10 years and at -80℃. Translocations were located precisely. Conclusion Microtranslocations, which are hard to analyze by G-banding, can be detected exactly using chromosome painting technique with G-band karyotype on metaphase chromosome.

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