1.Influencing factors and network analysis of aggressive behavior among Chinese college students based on propensity score matching
ZENG Rui, ZHAO Mengxiao, HU Mengmeng, LIU Xin, CHANG Hongjuan
Chinese Journal of School Health 2025;46(3):358-363
Objective:
To explore the influencing factors and network structure of aggressive behaviors among college students based on propensity score matching (PSM), so as to provide precise targeted interventions for the prevention and improvement of aggressive behaviors among college students.
Methods:
A total of 2 652 college students were selected by convenient sampling method from three colleges in Wuhan, Hubei Province in June 2023. Questionnaire surveys were carried out by using the Buss-Warren Aggression Questionnaire (BWAQ), Ruminative Responses Scale (RRS), Cognitive Emotion Regulation Questionnaire-Chinese Version (CERQ-C), Family APGAR Index (APGAR) ,Brief Fear of Negative Evaluation Scale (BFNES).By bias score matching (PSM) for 1∶1 matching, univariate and multivariate Logistic regression analysis, and network analysis were conducted on the college students.
Results:
College students with higher levels of ruminant thinking,non adaptive emotional regulation and fear of negative appraisal were more likely to have highly aggressive behaviors( OR =1.14,1.18,1.06),and those with higher adaptive emotional regulation and family care index were more likely to have highly aggressive behaviors ( OR =0.88,0.82)( P < 0.01 ). Network structure was significantly different between the two groups ( M =0.27, P <0.05). The core affective factors of college students with high levels of aggressive behavior were brooding reflective pondering and symptom rumination( EI =3.50, 3.49, 3.48 ),low aggressive behavior college students core affective factors were adaptive emotion regulation growth and non adaptive emotion regulation( EI =4.37, 4.12, 4.08).
Conclusion
Factors affecting Chinese college students aggressive behaviors are of different characteristics on different behaviour types, and targeted interventions should be adopted to reduce aggressive behaviors of college students.
2.2,3,5,4′-tetrahydroxyldiphenylethylene-2-O-glucoside Attenuates Cerebral Ischemia-reperfusion Injury via PINK1/LETM1 Signaling Pathway
Hongyu ZENG ; Kaimei TAN ; Feng QIU ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Chang LEI ; Hongqing ZHAO ; Yuhong WANG ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):145-154
ObjectiveTo investigate the mechanism by which 2,3,5,4'-tetrahydroxyldiphenylethylene-2-O-glucoside (THSG) mitigates cerebral ischemia/reperfusion (CI/R) injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham, model, SAS (40 mg·kg-1), and low-, medium- and high-dose (10, 20, 40 mg·kg-1, respectively) THSG groups, with 10 rats in each group. The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring, and cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 (CCK-8) assay, and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 (PINK1) and leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) in neurons. Transmission electron microscopy (TEM) was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 (TOMM20), autophagy-associated protein p62, microtubule-associated protein light chain 3 (LC3), cysteinyl aspartate-specific proteinase-9 (Caspase-9), B-cell lymphoma 2-associated protein X (Bax), and cytochrome C (Cyt C). ResultsCompared with the sham group, the model group exhibited increased infarct volume (P<0.01) and neurological deficit scores (P<0.01), neuronal structure was disrupted with reduced Nissl bodies. (P<0.01), mitochondrial swelling/fragmentation, decreased PINK1/LETM1 co-localization (P<0.01), upregulated protein levels of LC3Ⅱ/LC3Ⅰ, TOMM20, Caspase-9, Bax, and Cyt C (P<0.01), downregulated protein level of p62 (P<0.05), weakened PC12 viability (P<0.01), and elevated mitochondrial calcium level (P<0.01). Compared with the model group, THSG and SAS groups showed reduced infarct volumes (P<0.05,P<0.01) and neurological deficit scores (P<0.05,P<0.01), mitigated mitochondrial damage, and increased PINK1/LETM1 co-localization (P<0.01). Medium/high-dose THSG and SAS alleviated the neurological damage, increased Nissl bodies (P<0.05,P<0.01), downregulated the protein levels of p62, TOMM20, Caspase-9, Bax, and Cyt C (P<0.05,P<0.01), and elevated the LC3Ⅱ/LC3Ⅰ level (P<0.05,P<0.01). High-dose THSG enhanced PC12 cell viability (P<0.01), increased PINK1/LETM1 co-localization (P<0.01), and reduced mitochondrial calcium (P<0.01). ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway, reducing the mitochondrial calcium overload, and promoting mitophagy.
3.2,3,5,4′-tetrahydroxyldiphenylethylene-2-O-glucoside Attenuates Cerebral Ischemia-reperfusion Injury via PINK1/LETM1 Signaling Pathway
Hongyu ZENG ; Kaimei TAN ; Feng QIU ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Chang LEI ; Hongqing ZHAO ; Yuhong WANG ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):145-154
ObjectiveTo investigate the mechanism by which 2,3,5,4'-tetrahydroxyldiphenylethylene-2-O-glucoside (THSG) mitigates cerebral ischemia/reperfusion (CI/R) injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham, model, SAS (40 mg·kg-1), and low-, medium- and high-dose (10, 20, 40 mg·kg-1, respectively) THSG groups, with 10 rats in each group. The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring, and cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 (CCK-8) assay, and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 (PINK1) and leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) in neurons. Transmission electron microscopy (TEM) was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 (TOMM20), autophagy-associated protein p62, microtubule-associated protein light chain 3 (LC3), cysteinyl aspartate-specific proteinase-9 (Caspase-9), B-cell lymphoma 2-associated protein X (Bax), and cytochrome C (Cyt C). ResultsCompared with the sham group, the model group exhibited increased infarct volume (P<0.01) and neurological deficit scores (P<0.01), neuronal structure was disrupted with reduced Nissl bodies. (P<0.01), mitochondrial swelling/fragmentation, decreased PINK1/LETM1 co-localization (P<0.01), upregulated protein levels of LC3Ⅱ/LC3Ⅰ, TOMM20, Caspase-9, Bax, and Cyt C (P<0.01), downregulated protein level of p62 (P<0.05), weakened PC12 viability (P<0.01), and elevated mitochondrial calcium level (P<0.01). Compared with the model group, THSG and SAS groups showed reduced infarct volumes (P<0.05,P<0.01) and neurological deficit scores (P<0.05,P<0.01), mitigated mitochondrial damage, and increased PINK1/LETM1 co-localization (P<0.01). Medium/high-dose THSG and SAS alleviated the neurological damage, increased Nissl bodies (P<0.05,P<0.01), downregulated the protein levels of p62, TOMM20, Caspase-9, Bax, and Cyt C (P<0.05,P<0.01), and elevated the LC3Ⅱ/LC3Ⅰ level (P<0.05,P<0.01). High-dose THSG enhanced PC12 cell viability (P<0.01), increased PINK1/LETM1 co-localization (P<0.01), and reduced mitochondrial calcium (P<0.01). ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway, reducing the mitochondrial calcium overload, and promoting mitophagy.
4.Effect of tritiated water on the immune system of zebrafish and mechanism analysis
Xiaofang GENG ; Chang LIU ; Yinyin YANG ; Yang ZHANG ; Le ZHAO ; Bingqing ZENG ; Chen WANG ; Pengyu LIN ; Yulong LIU
Chinese Journal of Radiological Health 2025;34(3):354-362
Objective To investigate the effect of tritiated water on the immune system of zebrafish and its potential molecular mechanism. Methods Zebrafish embryos (2.5 to 3 hours post-fertilization [hpf]) were exposed to 3.7 × 104 Bq/mL tritiated water (tritiated water group), and those exposed to E3 culture medium were used as the control group. The mortality rate, hatching rate, deformity rate, heart rate, body length, yolk sac area, neutrophil count in the tail, immune-related gene expression, and immune-related protein expression of zebrafish in the two groups were determined. Then transcriptome technology was used to further analyze the possible mechanism of tritiated water affecting the immune system of zebrafish. Results Compared with the control group, zebrafish at 72 hpf in the tritiated water group had no significant changes in the mortality rate, hatching rate, deformity rate, body length, and yolk sac area((t = 0.9045, 0.5000, 1.0000, 0.7238, 0.0337, P = 0.4169, 0.6433, 0.3739, 0.4785, 0.9735), but had significantly increased heart rate(t = 4.575,P = 0.002). At 4 days post-fertilization (dpf), the neutrophil count in the tail of zebrafish in the tritiated water group was significantly increased(t = 2.563,P = 0.0196), the mRNA expression of TNF-α was significantly decreased(t = 2.891, P = 0.045), the protein expression of nuclear factor-kappa B (NF-κB) was significantly increased(t = 3.848, P = 0.018), and the protein expression of NLRP3 was significantly decreased(t = 14.98, P = 0.001). At 7 dpf, the neutrophil count in the tail and the protein expression levels of NF-κB, NLRP3, and interleukin-1β were significantly decreased(t = 3.772, 7.048, 15.620, 4.423, P = 0.014, 0.002, 0.0001, 0.012). Transcriptome sequencing revealed that differentially expressed genes were mainly enriched in the “neutrophil activation” and “platelet activation pathways” at 4 dpf and in the “neutrophil apoptosis”, “ferroptosis”, and “necroptosis” pathways at 7 dpf. Conclusion Tritiated water exposure induces a temporally dynamic immune response in zebrafish, potentially affecting immune homeostasis by regulating neutrophil activation and apoptosis, as well as the expression of NF-κB and NLRP3.
5.Study on mechanism of naringin in alleviating cerebral ischemia/reperfusion injury based on DRP1/LRRK2/MCU axis.
Kai-Mei TAN ; Hong-Yu ZENG ; Feng QIU ; Yun XIANG ; Zi-Yang ZHOU ; Da-Hua WU ; Chang LEI ; Hong-Qing ZHAO ; Yu-Hong WANG ; Xiu-Li ZHANG
China Journal of Chinese Materia Medica 2025;50(9):2484-2494
This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals
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Rats, Sprague-Dawley
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Reperfusion Injury/genetics*
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Flavanones/administration & dosage*
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Rats
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Dynamins/genetics*
;
Male
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Brain Ischemia/genetics*
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Protein Serine-Threonine Kinases/genetics*
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Signal Transduction/drug effects*
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Humans
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Drugs, Chinese Herbal/administration & dosage*
6.Study on the application of different-length peripheral intravenous catheters in patients undergoing metabolic and bariatric surgery:a randomized clinical trial
Xiaohui YANG ; Chang LIU ; Weihua YU ; Jionghuang CHEN ; Wanting SHENG ; Xiuzhu CAO ; Xufen ZENG ; Xianghong JIN ; Linfang ZHAO
Chinese Journal of Nursing 2024;59(4):401-407
Objective To investigate the appropriate venous access for obese patients undergoing metabolic and bariatric surgery by comparing the clinical outcomes of different lengths of peripheral intravenous catheters.Methods Inpatients who underwent bariatric surgery in a tertiary hospital in Zhejiang from August 2022 to December 2022 were selected as the study population using a fixed-point continuous convenience sampling method.A stratified block randomisation method was used to divide the group into an experimental group 1(mini-midline catheters),an experimental group 2(midline catheters)and a control group(short peripheral intravenous catheters,Short PIVCs).The incidence of catheter-related complications,the rate of extubation due to complications,the duration of catheter retention,the time to first catheter-related complication were compared in the 3 groups.Results A total of 186 patients were included,with 62 patients in each group.The overall incidence of catheter-related complications in experimental group 1,experimental group 2,and control group were 25.81%,8.06%,and 58.06%.The extubation rates due to complications were 19.35%,4.84%,and 41.94%,and the duration of catheter retention was 7.00(6.00,7.00)d,7.00(6.00,7.00)d,6.00(3.00,6.25)d.The differences were statistically different(P<0.05)when comparing the 3 groups.Among them,the differences in the overall incidence of catheter-related complications and the rate of extubation due to complications were statistically significant when comparing experimental group 1 with the control group,experimental group 2 with the control group,and experimental group 1 with experimental group 2(P<0.017);the duration of catheter retention in both experimental group 1 and experimental group 2 were higher than it in the control group,and the differences were statistically different(P<0.017).Conclusion The complication rate of mini-midline catheters and midline catheters is lower than that of short ones,and the indwelling time is consistent with the perioperative period of metabolic and bariatric surgery,which is suitable for use in patients undergoing metabolic and bariatric surgery.
7.Modified Xiaoyaosan Alleviates Depression-like Behaviors by Regulating Activation of Hippocampal Microglia Cells in Rat Model of Juvenile Depression
Jiayi SHI ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Feng QIU ; Chang LEI ; Hongyu ZENG ; Kaimei TAN ; Hongqing ZHAO ; Dong YANG ; Yuhong WANG ; Pengxiao GUO ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):46-56
ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction (Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex) in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control, model, fluoxetine, and low-, medium-, and high-dose (5.36, 10.71, 21.42 g·kg-1, respectively) Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress (CUMS). The sucrose preference test (SPT) was carried out to examine the sucrose preference of rats. Forced swimming test (FST) was carried out to measure the immobility time of rats. The open field test (OFT) was conducted to measure the total distance, the central distance, the number of horizontal crossings, and the frequency of rearing. Morris water maze (MWM) was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase (iNOS, the polarization marker of M1 microglia) and CD206 (the polarization marker of M2 microglia). Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS, CD206, pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] and anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group, the model rats showed a reduction in sucrose preference (P<0.05), an increase in immobility time (P<0.05), decreased motor and exploratory behaviors (P<0.05), and weakened learning and spatial memory (P<0.05). In addition, the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β, IL-6, and TNF-α (P<0.05). Compared with the model group, Baihuan Xiaoyao decoction increased the sucrose preference value (P<0.05), shortened the immobility time (P<0.01), increased the motor and exploratory behaviors (P<0.05), and improved the learning and spatial memory (P<0.01). Furthermore, the decoction down-regulated the positive expression and protein level of iNOS, lowered the levels of TNF-α, IL-1β, and IL-6 (P<0.01), promoted the positive expression of CD206, and elevated the levels of IL-4 and IL-10 (P<0.01) in the hippocampus of the high dose group. Moreover, the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value (P<0.01), shorter immobility time (P<0.01), longer central distance (P<0.01), stronger learning and spatial memory (P<0.01), higher positive expression and protein level of iNOS (P<0.01), lower levels of TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), lower positive expression and mRNA level of iNOS (P<0.05), and higher levels of IL-4 and IL-10 (P<0.05, P<0.01) than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.
8.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
9.Whole genome analysis of a Coxsackievirus A4 strain from Yunnan
Jun-Wei CHEN ; Chang-Zeng FENG ; Zhao-Yang CHU ; Yu-Han LIU ; Ming ZHANG ; Li LI ; Shao-Hui MA
Chinese Journal of Infection Control 2024;23(9):1061-1069
Objective To understand the whole genome sequence characteristics of a Coxsackievirus A4(CVA4)isolated from Yunnan,China in 2022,and explore the phylogenetic characteristics of CVA4.Methods The whole genome sequence of CVA4 isolate 194R3/YN/CHN/2022 was amplified and sequenced,and the phylogenetic tree of CVA4 isolate was constructed by using Mega 7.0,Geneious 9.1.4 and Simplot 3.5.1 softwares.The whole ge-nome sequence characteristics were analyzed.Results The 194R3/YN/CHN/2022 isolate was identified as CVA4,belonging to the C2 gene subtype,which was consistent with the dominant gene subtype in recent years in China.Recombination analysis showed that recombination of CVA4 virus isolate with EVA114 prototype(V13-0285),CVA16 prototype(G-10),and CVA14 prototype(G-14)at the non-structural coding regions of P2 and P3 may have occurred.Conclusion The 194R3/YN/CHN/2022 isolated from Yunnan belongs to the C2 gene subtype,which is the prevalent CVA4 in China,but with certain mutations.
10.Study of lncRNA-miRNA-mRNA ceRNA regulatory network mediated by serum exosomes in coronary heart disease and prediction and experimental validation of potential target herbal medicines
Lu MA ; Lei YANG ; Huang DING ; Wan-Yu LI ; Wei TAN ; Yan-Ling LI ; Yan-Yan ZHANG ; Xiao-Dan LIU ; Zhao-Wen ZENG ; Chang-Qing DENG ; Wei ZHANG
Chinese Pharmacological Bulletin 2024;40(6):1153-1164
Aim To analyze serum exosome sequencing data from patients with coronary heart disease(CHD)and normal subjects by using bioinformatics-related methods to construct a competitive endogenous ln-cRNA-miRNA-mRNA(ceRNA)regulatory network,to mine the predicted potential Chinese medicines,and to perform preliminary validation of the biological processes and core Chinese medicines involved in the ceRNA network.Methods We used exoRbase data-base to obtain the expression matrix of differential genes,combined with the raw letter method to con-struct the ceRNA network,and performed GO analysis and KEGG analysis on the differential mRNAs in the network,and used COREMINE database to predict the biological processes and core target genes involved in the ceRNA network,and to screen the herbal medi-cines with potential therapeutic effects;AVECs oxida-tive damage cell model was constructed in vitro,and the cytoskeleton,tube-forming function,cell prolifera-tion,LDH leakage rate,ROS level and p-AKT,AKT,p-PI3K and AKT protein expression were examined to verify the action pathways and targets of the core Chi-nese medicine Salvia miltiorrhiza for the treatment of coronary heart disease.Results Compared with nor-mal subjects,395 mRNAs,80 miRNAs,60 lncRNA differential genes,and 80 miRNAs were predicted in serum exosomes of coronary heart disease,and the constructed ceRNA sub-network,mainly consisted of 21 lncRNAs,80 miRNAs,and 82 mRNAs;AKT1,VEGFA,IL1B and other genes in the network.The abnormally expressed mRNAs were involved in biologi-cal processes such as oxidative stress and signaling pathways such as PI3 K/Akt,and Dan Shen,Chuanx-iong and Panax notoginseng were most closely related to exosome-mediated biological processes and core genes in coronary heart disease.The active ingredients of tanshinone ⅡA,the core Chinese medicine,could pro-mote vascular endothelial cell proliferation,tube for-mation,skeleton formation and repair,reduce LDH leakage rate and ROS level,and promote the expres-sion of p-AKT and p-PI3K protein.Conclusion There is a complex ceRNA regulatory network trans-duction in coronary artery disease serum exosomes,and traditional Chinese medicine can be used to treat CHD through multi-target intervention,and Dan Shen,Chuanxiong and Panax notoginseng are expected to be candidate sources of traditional Chinese medicine,a-mong which the active ingredient of Dan Shen,tanshi-none ⅡA,activates PI3 K/Akt signaling pathway to play a protective role against oxidative stress-injured cells,and treats CHD.


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