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15 November 2022, Volume 50 Issue 11 Previous Issue    Next Issue
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Cell and Molecular Biology
Experimental Research
Clinical Research
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Cell and Molecular Biology

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Molecular mechanism study of melanoma cell proliferation regulated by miR-101-3p-E2F2 targeting pathway LI Wenwen, ZHU Zhixin, HAN Limin, JIAO Yanlin, WENG Zongqin, ZHAO Hailong 2022, 50 (11):  1121-1127.  doi: 10.11958/20212787 Abstract ( 1041 )   HTML ( 22 )   PDF (1370KB) ( 1849 )   Objective To explore effect and mechanism of miR-101-3p targeting E2F transcription factor 2 (E2F2) in regulating the melanoma cell proliferation. Methods GEPIA, OSskcm databases were used to analyze the expression of E2F2 in melanoma and evaluate the value of transcription factor E2F2 in the prognosis of melanoma. The expression of E2F2 in melanoma cells MV3 was inhibited by shRNA, and the cell cycle changes were detected by PI staining flow cytometry. The expression levels of CyclinE and Cyclin-dependent kinase 2 (CDK2) were detected by Western blot assay. The expression level of autophagy-associated protein LC3B was detected by immunofluorescence, and the growth changes of melanoma in vivo were observed by tumor-bearing experiments in nude mice. The expression level of miR-101-3p in MV3 cells was detected by real-time fluorescence quantitative PCR, the expression level of E2F2 was detected by qPCR and Western blot assay, and the proliferation level of MV3 cells was detected by MTT and BrdU methods. Results Melanoma patients with increased E2F2 expression had worse prognosis (P<0.05). Compared with the shGFP group, the proportion of cells in G0/G1 phase increased significantly in the shE2F2 group (P<0.05), the expression levels of CyclinE and CDK2 decreased significantly, the fluorescence signal of autophagy-associated protein LC3B decreased significantly (P<0.05), and the weight of melanoma formation in vivo decreased significantly (P<0.05). The expression level of miR-101-3p in MV3 cells increased significantly after treated with miR-101-3p mimics (P<0.05), and the mRNA and protein expression of E2F2 were significantly lower than those in the NC mimics treatment group (P<0.05). Meanwhile, MTT results showed that the vitality of MV3 cells decreased significantly in the miR-101-3p mimics group (P<0.05). BrdU labeling test results showed that the BrdU positive signal decreased significantly in the miR-101-3p mimics group (P<0.05). Conclusion miR-101-3p targets to E2F2 and inhibits its expression, and then reduces the proliferation level of melanoma cells. Figures and Tables | References | Related Articles | Metrics

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The expression and significance of GPR19 gene in prostate cancer LIU Shuaibing, YAN Mo, WANG Kaibin, YANG Kuo, WANG Yuzhuo 2022, 50 (11):  1128-1133.  doi: 10.11958/20220419 Abstract ( 766 )   HTML ( 10 )   PDF (1263KB) ( 1741 )   Objective To analyze the expression of G protein-coupled receptor 19 (GPR19) in prostate cancer (PCa), and explore the mechanism of GPR19 in prostate cancer. Methods TCGA and Oncomine online databases were used to analyze the expression level and clinicopathological information of GPR19 in PCa. Expression levels of GPR19 mRNA and protein in PCa cell lines were detected by qPCR and Western blot assay, and the key molecules in related pathways were verified. EdU assay was used to verify the effect of GPR19 knockdown on tumor cell proliferation. Results Database analysis showed that GPR19 gene expression was increased in PCa samples. GPR19 gene expression was related to patient's age, disease-free survival rate, Gleason score and TNM stage. Univariate Cox analysis showed that Gleason score, TNM stage and GPR19 expression were the influencing factors of progression-free survival in PCa patients. qPCR and Western blot assay showed that GPR19 was expressed higher in PCa cell lines than that of normal prostate epithelial cell line, RWPE-1. EdU experiments verified that the proliferation ability of PCa cells was reduced after GPR19 knockdown. Pathway enrichment analysis showed that GPR19 was involved in cell cycle regulation of PCa. It was confirmed that knockdown of GPR19 reduced the expression of cyclin dependent kinase 1 (CDK1), a key molecule at the G2M signaling checkpoint in PCa cells. Pathway correlation analysis showed that GPR19 had the highest correlation with CDKN3 gene. Conclusion The expression of GPR19 is increased in PCa and related to a variety of clinical information, which affects tumor cell proliferation through the G2M signaling checkpoint. GPR19 is expected to be a potential therapeutic target for PCa. Figures and Tables | References | Related Articles | Metrics

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Study on the mechanism of circMTO1 regulating Wnt/β-catenin to inhibit proliferation and metastasis of breast cancer cell SU Yajing, WU Huanliang, JING Bo, WU Canzhang 2022, 50 (11):  1134-1138.  doi: 10.11958/20220183 Abstract ( 607 )   HTML ( 7 )   PDF (855KB) ( 1755 )   Objective To study the effect of a circRNA derived from MTO1 gene (circMTO1) on the proliferation and metastasis of breast cancer and its possible mechanism. Methods A total of 102 patients with invasive breast cancer were included in this study. Breast cancer cell lines MDA-MB-231, HCC-70, MCF-7 and human normal breast cell line MCF-10A were selected, and fluorescence quantitative PCR (qPCR) was used to detect the expression level of circMTO1 in breast cancer tissues and cell lines. The circMTO1 overexpression and circMTO1 knockdown plasmids were respectively constructed to transfect breast cancer cell lines, and which were divided into the NC group, the oe-circMTO1 group and the sh-circMTO1 group. The transfection effect was tested by qPCR. The MTS experiment was used to detect the cell proliferation ability of each group, and the Transwell experiment was used to detect the cell metastasis ability of each group. TOP/FOP luciferase assay was used to detect the activity of Wnt/β-catenin signaling pathway in each group of cells, and Western blotting was used to detect the expression of key proteins Wnt3a,β-catenin, cMyc, Cyclin D1 and matrix metalloproteinase 7 (MMP7) in Wnt/β-catenin signaling pathway. Results Compared with adjacent tissues and human normal breast cell lines, the relative expression of circMTO1 was significantly decreased in breast cancer tissues and breast cancer cell lines (P<0.05). The relative expression level of circMTO1 was lower in breast cancer patients with lymph node metastasis and TNM stage Ⅲ (P<0.05). Compared with the NC group, the relative expression of circMTO1 was significantly increased in the oe-circMTO1 group, the cell proliferation and metastasis ability and the activity of the Wnt/β-catenin signaling pathway were weakened, and the protein expressions of Wnt3a, β-catenin, cMyc, Cyclin D1 and MMP7 were also decreased (P<0.05). In the sh-circMTO1 group, the relative expression of circMTO1 was decreased, the proliferation and metastasis ability of cells and the activity of Wnt/β-catenin signaling pathway were enhanced, and the protein expression levels of Wnt3a, β-catenin, cMyc, Cyclin D1 and MMP7 were increased (P<0.05). Conclusion circMTO1 is down-expressed in breast cancer cells. circMTO1 inhibits the proliferation and metastasis of breast cancer cells by inhibiting Wnt/β-catenin. Figures and Tables | References | Related Articles | Metrics

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PM2.5 aggravates the inflammatory response of Raw264.7 macrophages by disrupting autophagic flow through TLR4 HUANG Qiuyang, WANG Wei, LUO Shu, ZHENG Wenwu, FENG Jian, YE Qiang, ZHENG Shuzhan 2022, 50 (11):  1139-1145.  doi: 10.11958/20220086 Abstract ( 724 )   HTML ( 6 )   PDF (1218KB) ( 1801 )   Objective To explore the effect and mechanism of PM2.5 on the autophagy and inflammatory response of Raw264.7 macrophages. Methods CCK-8 was used to detect the effect of PM2.5 on the viability of Raw264.7 cells, and transmission electron microscopy was used to observe the autophagy structure. The autophagic flux was observed by fluorescence microscope after Ad-mCherry-GFP-LC3B transfection to explore the effect of PM2.5 on macrophage activity and autophagy. Then the blank control group, the PM2.5 group, the rapamycin (Rap, autophagy inducer) group, the hydroxychloroquine (HCQ, autophagy inhibitor) group, the PM2.5+HCQ group and PM2.5+TAK-242 [Toll-like receptor 4 (TLR4) inhibitor] group were set. Western blot method was used to detect levels of autophagy-related proteins, including microtubule-associated light chain protein 3 ratio (LC3Ⅱ/Ⅰ), p62, cathepsin B (CTSB), lysosomal membrane protein 2 (LAMP2) and inflammation-related proteins TLR4 and nucleotide binding Domain-like receptor protein 3 (NLRP3)]. ELISA method was used to detect the levels of inflammatory factors, including interleukin (IL)-1β, IL-18 and IL-10. Results The activity of Raw264.7 macrophages decreased with the increase of PM2.5 concentration and the prolonged action time. Transmission electron microscopy showed that there were more autophagic vacuoles and double-membrane autophagosomes in the PM2.5 group, while autophagic lysosomes were rare, and under the fluorescence microscope, the ratio of yellow fluorescent dots to red fluorescent dots was higher in the PM2.5 group than that in the control group and the Rap group (P<0.05). Compared with the blank control group, the expressions levels of NLRP3, LC3Ⅱ/Ⅰ, p62, CTSB, IL-1β and IL-18 were up-regulated in the PM2.5 group, and the expressions of LAMP2 and IL-10 were down-regulated (P<0.05). While HCQ inhibited autophagy, it promoted the expression of NLRP3, IL-1β and IL-18, and inhibited the expression of IL-10 (P<0.05). Compared with the blank control group, the PM2.5 group and the HCQ group, NLRP3, IL-1β and IL-18 were significantly up-regulated and IL-10 was significantly down-regulated in the PM2.5+HCQ group (P<0.05). In addition, the expression of TLR4 was high in the PM2.5 group. Expressions of NLRP3, LC3Ⅱ/Ⅰ, p62, CTSB, IL-1β and IL-18 were down-regulated after TLR4 was inhibited by TAK-242, and expressions of LAMP2 and IL-10 were up-regulated (P<0.05). Conclusion PM2.5 reduces macrophage activity in a time- and concentration-dependent manner. PM2.5 induces autophagy in Raw264.7 macrophages, but blocks autophagic flow and aggravates the inflammatory response of macrophages, which may be mediated by TLR4. Figures and Tables | References | Related Articles | Metrics

Experimental Research

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The effect of electroacupuncture at "Neiguan" and "Zusanli" points on inhibiting mTOR signaling pathway in alleviating cerebral ischemic injury in rats ZHANG You, JIN Ziyan, YIN Yalong, WU Xingui 2022, 50 (11):  1146-1152.  doi: 10.11958/20220727 Abstract ( 578 )   HTML ( 4 )   PDF (1290KB) ( 1735 )   Objective To investigate the effects of electroacupuncture (EA) stimulation at “Zusanli” and “Neiguan” points on cerebral ischemia and the mTOR signaling pathway in rats. Methods A total of 75 rats were divided into the sham group, the middle cerebral artery occlusion (MCAO) model 3-d group, the EA intervention 3-d group, the MCAO model 7-d group, and the EA intervention 7-d group by random number table method, with 15 rats in each group. Except for the sham group, the permanent MCAO rat model was constructed using the Longa thread embolization method. The EA intervention group was treated at "Neiguan" and "Zusanli" points for 20 min daily after surgery. The neurological deficits were scored at the corresponding time points in each group. 2,3,5-triphenyltetrazolium (TTC) staining was used to analyze the cerebral infarct volume. HE and Nissler staining were used to assess the post-ischemic pathological changes. Western blot assay was used to detect the expression levels of mammalian target of rapamycin (mTOR) pathway-related factors protein kinase B (AKT), p-mTOR and t-mTOR protein in cerebral cortex on the infarct side. Real-time fluorescence quantitative PCR was used to detect the expression levels of LC3B, Beclin-1 and B lymphocytoma-2-associated protein X (Bax) mRNA in cerebral cortex on the infarct side. Results Compared with the sham group, neurological deficit scores at all time points increased in the MCAO group (P<0.05), large necrotic and inflammatory infiltrates in cortical areas, massive neuronal necrosis, disturbed cell arrangement and significantly reduced intact neurons (P<0.05). There were significantly decreased LC3B and Beclin-1 mRNA expression (P<0.05), and Bax mRNA expression was significantly increased in the MCAO model 7-d group (P<0.05). The phosphorylation level of mTOR (p-mTOR/t-mTOR) was significantly higher in the MCAO model 7-d group than that in the MCAO model 3-d group (P<0.05). Compared with the MCAO group, the neurological deficit score was significantly reduced in the EA intervention 7-d group, and the percentage of brain infarct volume was significantly reduced in the EA intervention 3-d group and 7-d group (P<0.05). The necrotic foci were significantly reduced in cortical area, the inflammatory infiltration was improved, the cell arrangement was inregular and the number of intact neurons was significantly increased (P<0.05). Compared with the MCAO model 7-d group, LC3B and Beclin-1 mRNA expression levels were significantly increased (P<0.05), and Bax mRNA, p-mTOR/t-mTOR expression levels were significantly decreased (P<0.05) in the EA intervention 7-d group (P<0.05). There was no significant difference in AKT protein expression between the different groups. Conclusion EA stimulation at “Zusanli” and “Neiguan” points has a neuroprotective effect on cerebral ischemic injury and induces autophagy and inhibits apoptotic responses, which may be related to the inhibition of mTOR signaling pathway activation. Figures and Tables | References | Related Articles | Metrics

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Mechanism of miR-196b-5p in alleviating secondary edema and astrocyte activation after spinal cord injury in rats KONG Jundong, LI Jian, ZHANG Qiangqiang, LI Gang, CAI Jiajun, FAN Zhongkai 2022, 50 (11):  1153-1157.  doi: 10.11958/20220282 Abstract ( 486 )   HTML ( 3 )   PDF (1104KB) ( 1806 )   Objective To explore the mechanism of miR-196b-5p in promoting tissue repair and neuronal axon regeneration by targeting AQP4 after spinal cord injury (SCI) in rats. Methods The targeting relationship between miR-196b-5p and AQP4 was detected by Dual-Luciferase reporter assay. Changes of miR-196b-5p and AQP4 at 1 d, 2 d, 3 d, 5 d and 7 d after SCI were detected by real time quantitative polymerase reaction (RT-qPCR). The relative expression levels of miR-196b-5p and AQP4 mRNA were detected by RT-qPCR in the Sham group, the SCI group, the miR-196b-5p overexpression (miRNA) group and the miR-196b-5p negative control (NC) group, respectively. The relative expression levels of AQP4, GFAP, PCNA and GAP-43 protein in spinal cord were detect by Western blot assay. Dry-wet weight method and hematoxylin eosin (HE) staining were used to detect water content and size of spinal cord cavity. Results Dual-Luciferase reporter assay showed that AQP4 was the target gene of miR-196b-5p. Compared with the Sham group, the expression of miR-196b-5p decreased at each time point after SCI, while the expression of AQP4 mRNA increased, peaked at 2 days and then decreased gradually (P<0.05). The relative expression levels of AQP4 mRNA, AQP4 protein, GFAP protein, PCNA protein, GAP-43 protein and spinal cord water content increased in the SCI group, the miRNA group and the NC group compared with those of the Sham group (P<0.05), while the relative expression levels of miR-196b-5p decreased in the SCI group and the NC group (P<0.05). The relative expression levels of AQP4 mRNA, AQP4 protein, GFAP protein, PCNA protein and spinal cord water content were lower in the miRNA group than those of the SCI group and the NC group. the area of spinal cord cavity decreased (P<0.05), while the relative expression levels of miR-196b-5p and GAP-43 protein increased (P<0.05). Conclusion miR-196b-5p can inhibit SCI induced secondary edema, astrocyte activation glial scar formation and ultimately promote axon regeneration and spinal cord repair by targeting AQP4. Figures and Tables | References | Related Articles | Metrics

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The analysis and verification of osteoporosis associated hub genes and prediction of miRNA interactions ZHANG Yimeng, ZHANG Yuxin, TIAN Faming 2022, 50 (11):  1158-1164.  doi: 10.11958/20220418 Abstract ( 827 )   HTML ( 3 )   PDF (1855KB) ( 1702 )   Objective To screen hub genes and miRNA interaction in aging osteoporosis. Methods The GSE35956 gene chip data set was downloaded from GEO database, and the differentially expressed genes (Degs) in bone marrow mesenchymal stem cells were screened by R language in patients with osteoporosis. GO enrichment and KEGG pathway were analyzed in Degs using DAVID database. String database and Cytoscape software were used to analyze the protein interaction network and screen hub genes. The mirnas interacting with hub genes were predicted by Targetscan database, and the predicted mirnas were enriched by funrich database. Bone marrow mesenchymal stem cells from 3 to 4 month-old (the young group) and 18 to 20 month-old (the old group) in C57BL/6 mice were extracted and cultured. The expression levels of miRNA in bone marrow mesenchymal stem cells were verified by qPCR technique in the young and the old groups. Results A total of 982 up-regulated Degs and 99 down-regulated degs were identified in patients with osteoporosis. Degs were mainly enriched in plasma membrane adhesion molecule-mediated homologous cell adhesion and calcium ion binding, and were mainly involved in neuroactive ligand-receptor interaction signaling pathways. PPI interaction network analysis identified eight core genes: leptin (LEP), lymphocyte-specific protein tyrosine kinase (LCK), WT1 transcription factor (WT1), SRY-box transcription factor 10 (SOX10), integrin subunit beta 2 (ITGB2), albumin (ALB), cholecystokinin (CCK) and bone morphogenetic protein 7（BMP7). The interaction between 105 miRNA and 6 core genes was predicted by Trargetscan. qPCR results showed that BMP7, CCK, ITGB2 and SOX10 genes in bone marrow mesenchymal stem cells were significantly up-regulated in the old group compared with those of the young group. It is consistent with the results of bioinformatics analysis. Conclusion The expression levels of the selected core genes are related to the differentiation degree of bone marrow mesenchymal stem cells in aged mice. The identified miRNA may be a diagnostic marker and a therapeutic target for aging osteoporosis. Figures and Tables | References | Related Articles | Metrics

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Effects of tripterygium hypoflaucum (Levl.) hutch polysaccharide on the AMPK/mTOR signal pathway in mice with exercise-induced fatigue DU Wei, WU Silan, YANG Xue, CHEN Hui, YE Lan 2022, 50 (11):  1165-1170.  doi: 10.11958/20220320 Abstract ( 447 )   HTML ( 4 )   PDF (766KB) ( 1785 )   Objective To study the effect and possible mechanism of polysaccharide from tripterygium hypoflaucum (Levl.) hutch on exercise-induced fatigue in mice. Methods Twenty-four ICR mice were randomly divided into the static control group, the fatigue control group, the fatigue + monosaccharide group and the fatigue + tripterygium hypoflaucum (Levl.) hutch polysaccharide group, with 6 mice in each group. The fatigue + tripterygium hypoflaucum (Levl.) hutch polysaccharide group was given 20 g/L aqueous solution of tripterygium hypoflaucum (Levl.) hutch polysaccharide, the fatigue + monosaccharide group was given 20 g/L aqueous solution of monosaccharide mixture, and the static control group and the fatigue control group were given purified water. Each group was given intervention 20 mL/kg by gavage once a day for 14 days. The body mass, food intake, water consumption and other general conditions of mice were observed during administration. On the 6th day and the 13th day of administration, mice were evaluated by rotary rod fatigue tester, and on the 14th day of administration, the exhaustive swimming experiment was carried out. After exhaustive swimming, the serum levels of triglyceride (TG) and blood glucose (GLU) were detected. The pathological changes of left gastrocnemius muscle were observed by HE staining and Periodic Acid-Schiff staining (PAS). The expression levels of AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and glucose transporter 4 (GLUT-4) mRNA were observed by real-time fluorescence quantitative PCR (qPCR). Results After treatment for 13 days, compared with the static control group, the body mass was decreased in the fatigue + tripterygium hypoflaucum (Levl.) hutch polysaccharide group (P<0.05). There were no significant differences in body mass, food intake and water consumption at other time points between the four groups (P>0.05). Compared with the fatigue control group, there was no significant increase in the rotating rod lasting time after treatment for 6 days in the fatigue + tripterygium hypoflaucum (Levl.) hutch polysaccharide group (P>0.05), but it increased significantly on the 13th day of administration (P<0.05). The exhaustive swimming time significant increased after treatment for 14 days in the fatigue + tripterygium hypoflaucum (Levl.) hutch polysaccharide group (P<0.05). HE staining showed no obvious abnormality, PAS staining showed that the gastrocnemius muscle was slightly darker in the fatigue control group and the fatigue + monosaccharide group, while the colour was the deepest in the fatigue+tripterygium hypoflaucum (Levl.) hutch polysaccharide group. Compared with the fatigue control group, there was no significant difference in TG, the GLU decreased in the fatigue + tripterygium hypoflaucum (Levl.) hutch polysaccharide group (P<0.05), while the expression levels of AMPK, mTOR and GLUT-4 mRNA were significantly increased (P<0.05). Conclusion The tripterygium hypoflaucum (Levl.) hutch polysaccharide has the effect of anti-exercise-induced fatigue in mice, and its mechanism may be related to the glucose metabolism regulated by AMPK/mTOR signal pathway. Figures and Tables | References | Related Articles | Metrics

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Study on the cardioprotective mechanism of sacubitril and valsartan in post-myocardial infarction heart failure of rats PANG Zhihua, ZHAO Wei, TIAN Liuyang, REN Ying, LI Dong, YAO Zhuhua 2022, 50 (11):  1171-1176.  doi: 10.11958/20220298 Abstract ( 637 )   HTML ( 6 )   PDF (1359KB) ( 1884 )   Objective To investigate the mechanism of cardioprotective effect of sacubitril/valsartan (ARNI) on heart failure rats after myocardial infarction. Methods A total of 60 adult male rats were randomly divided into the control group, the model group and the ARNI group. The model of heart failure was established by the ligation of of anterior descending branch of left coronary artery, while in the control group, threaded was inserted without ligation. The other two groups were given normal saline and ARNI (68 mg/kg) by gavage after ligation. After 3 months, echocardiography was completed to measure left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular end diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF). Hematoxylin and eosin (HE) staining and Masson staining were used to determine the myocardial structure and fibrosis. Enzyme linked immunosorbent assay (ELISA) was used to detect related indicators of inflammation and oxidative stress. Western blot assay was used to detect the expression levels of Bcl-2, Bax, Caspase3, Fas and FasL proteins. Results Compared with the control group, values of LVEDD, LVESD, LVEDV, IL-2, IL-6, TNF-α, Bax, Caspase-3, Fas and FasL were increased, but LVEF, LVFS, SOD, GST, IL-10 and Bcl-2 were decreased in the model group. Myocardial cell necrosis obviously increased, collagen production and fibrosis intensified in the model group. The application of ARNI reduced left ventricular remodeling and increased LVEF and LVFS, decreased inflammation and fibrosis, and decreased expression levels of IL-2, IL-6, TNF-α, Fas and FasL, and increased the expression levels of GST, IL-4, IL-10 and Bcl-2 (P<0.05). Conclusion Sacubitril/valsartan can reduce myocardial cell apoptosis, reduce oxidative stress, inflammatory response and fibrosis by down-regulating Bax, Fas and FasL proteins, and reducing left ventricular remodeling to preserve LVEF. Figures and Tables | References | Related Articles | Metrics

Clinical Research

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Association of the expression of Ki67 with the prognosis of liver transplantation in patients with hepatocellular carcinoma CHEN Chiyi, ZHANG Weiqi, XIE Yan, JIANG Wentao 2022, 50 (11):  1177-1181.  doi: 10.11958/20220912 Abstract ( 1081 )   HTML ( 4 )   PDF (911KB) ( 1874 )   Objective To explore the relationship between the expression of Ki67 in hepatocellular carcinoma (HCC) tissues and the prognosis of liver transplantation (LT) in patients with HCC. Methods The clinical data and results of immunohistochemical staining of 178 patients with HCC who underwent orthotopic liver transplantation between July 2014 and June 2018 were collected. According to the median expression level of Ki67 in tumor tissues, patients were divided into the Ki67 high expression group and the Ki67 low expression group. The clinical parameters were compared between the two groups. Kaplan-Meier methods was used to plot survival curves to compare the prognosis of the two groups of patients. Univariate and multivariate Cox regression were used to analyze risk factors affecting the prognosis of patients after LT. Results Among the 178 patients in this study, 85 were in the Ki67 high expression group and 93 were in the Ki67 low expression group. The overall survival (78.7%, 52.6%, 39.5%) and recurrence-free survival (47.9%, 34.7%, 32.0%) were significantly lower in patients in the Ki67 high expression group than those in the Ki67 low expression group (86.5%, 76.3%, 76.3%; 84.4%,77.5%,72.4%), Log-rank χ2 were 9.016 and 28.467, respectively (P<0.01). Cox multivariate analysis showed that the high expression of Ki67 was an independent risk factor affecting recurrence-free survival (HR=3.653, 95%CI: 1.997-6.683, P<0.01). The incidence of microvascular invasion, poor tumor differentiation and preoperative serum alpha-fetoprotein level were higher in the Ki67 high expression group than those in the Ki67 low expression group (P<0.05). Conclusion The expression of Ki67 is related to the prognosis of HCC patients after LT. Ki67 can be used as a potential indicator to predict the prognosis of HCC patients after LT. Figures and Tables | References | Related Articles | Metrics

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The relationship between secreted frizzled-related protein 5 and abnormal postpartum glucose metabolism in patients with gestational diabetes mellitus YANG Guanlan, ZHENG Dan, YANG Guanjiao, LIU Yan 2022, 50 (11):  1182-1185.  doi: 10.11958/20220140 Abstract ( 475 )   HTML ( 8 )   PDF (754KB) ( 1969 )   Objective To analyze the relationship between secreted frizzled-related protein 5 (SFRP5) and abnormal postpartum glucose metabolism in patients with gestational diabetes mellitus (GDM). Methods A total of 238 GDM patients were selected. All patients underwent outpatient reexamination at 12 weeks postpartum, and were divided into the normal glucose metabolism group and the abnormal glucose metabolism group according to their glucose metabolism. The relevant clinical data of all patients were collected, and the serum level of SFRP5 was detected by enzyme-linked immunosorbent assay. Logistic regression equation was used to analyze the risk factors of abnormal postpartum glucose metabolism in patients with GDM. Receiver operating characteristic curves (ROC) were used to analyze the predictive value of relevant indicators for postpartum glucose metabolism abnormalities in patients with GDM. Results Of the 238 GDM patients, 192 patients were in the normal glucose metabolism group and 46 patients were in the abnormal glucose metabolism group at 12 weeks postpartum. The pre-pregnancy body mass index (BMI) and the glucose tolerance test (OGTT) 1 h blood glucose were higher in the abnormal glucose metabolism group than those in the normal glucose metabolism group, and the serum SFRP5 level was lower than that in the normal glucose metabolism group (P<0.05). Multivariate Logistic regression analysis showed that high pre-pregnancy BMI (OR=1.844, 95%CI: 1.099-3.094) was a risk factor for postpartum abnormal glucose metabolism in GDM patients, while high serum SFRP5 level (OR=0.794, 95%CI: 0.645-0.977) was a protective factor for postpartum abnormal glucose metabolism in GDM patients (P<0.05). ROC analysis showed that the areas under the curve of progestational body mass index and serum SFRP5 in predicting postpartum glucose metabolism abnormalities in patients with GDM were 0.727 (95%CI: 0.656-0.799) and 0.715 (95%CI: 0.625-0.806), respectively. The predictive value could be further improved after the combination of the two, and the area under the curve of ROC was 0.809 (95%CI: 0.739-0.878). Conclusion Serum SFRP5 level is closely related to abnormal postpartum glucose metabolism in GDM patients, and its combined application with pre-pregnancy body mass index has certain predictive value for postpartum abnormal glucose metabolism. Figures and Tables | References | Related Articles | Metrics

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Effect of ALB-dNLR score on the prognosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention FAN Wenjun, LIU Yixiang, LIU Jingyi, ZHANG Ying, SI Yueqiao, SHI Fei, SUN Lixian 2022, 50 (11):  1186-1191.  doi: 10.11958/20220405 Abstract ( 574 )   HTML ( 5 )   PDF (1005KB) ( 1807 )   Objective To investigate the predictive values of ALB-dNLR score on long-term prognosis of patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods A total of 1 744 patients with ACS after PCI were consecutively enrolled. The clinical and laboratory data of all the subjects were collected. After discharge, patients were followed up by outpatient visit and telephone call. Major adverse cardiovascular events (MACE) were recorded. The receiver operating characteristic (ROC) curve was used to determine the best cutoff value of each inflammatory markers for predicting MACE. The correlation between ALB and dNLR and other inflammatory markers was analyzed. Kaplan-Meier curve and Cox regression models were used to determine the influencing factors of MACE. Results A total of 1 539 patients with ACS after PCI were enrolled in our study. The median follow-up time was 1 141 days, including 60 patients in the MACE group and 1 479 patients in the non-MACE group. The neutrophil count, dNLR, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), systemic immune-inflammation index (SII), creatine kinase MB isoenzyme and creatinine levels were higher in the MACE group than those in the non-MACE group, and the lymphocyte count and ALB level were lower. The area under the ROC curve of ALB, dNLR, ALB-dNLR, NLR, PLR, MLR and SII were 0.619, 0.600, 0.645, 0.619, 0.576, 0.587 and 0.611 (all P<0.05). ALB was negatively correlated with dNLR, NLR, PLR, MLR and SII, while dNLR was positively correlated with NLR, PLR, MLR and SII (all P<0.05). ALB≤40.72 g/L, dNLR≥2.30 and ALB-dNLR score were found to be independent risk indicators for MACE in ACS patients after PCI (P<0.05). Conclusion ALB-dNLR score is an independent predictor of MACE in ACS patients after PCI, which is expected to be a new prognostic index. Figures and Tables | References | Related Articles | Metrics

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Study on the influencing factors of basal insulin combined with oral medication in the treatment of type 2 diabetes with poor glycemic control ZHANG Shujie, ZHANG Ruiqing, ZHENG Xianling, ZHANG Kai 2022, 50 (11):  1192-1195.  doi: 10.11958/20220091 Abstract ( 571 )   HTML ( 5 )   PDF (694KB) ( 1778 )   Objective To investigate the influencing factors of basal insulin combined with oral medication in type 2 diabetic patients with poor glycemic control. Methods A total of 208 patients with type 2 diabetes mellitus with poor blood glucose control were selected from the Department of Endocrinology of Handan Central Hospital. Patients were treated with multiple daily injections of insulin (MDI) after admission. After achieving and maintaining the blood glucose control target for 1 week, the islet function was evaluated and the therapy was shifted to basal insulin-supported OAD (S) therapy (BOT). Patients were classified as the achieving group, if fasting plasma glucose (FPG) and 2 h postprandial plasma glucose (2 hPG) reached the control target after 2 week. Others would be classified as the underachieving group. Patients in the achieving group who maintained their target at least 3 months were deemed to be responded to the BOT. Patients who failed to achieve the target were transferred to the underachieving group and received the MDI program. The baseline data of the two groups were compared, including duration of diabetes, body mass index (BMI), FC-P and 2 hC-P. The dosage of basal insulin and preprandial insulin during intensive insulin therapy were compared between the two groups. The influencing factors of BOT program in type 2 diabetes patients with poor blood glucose control were analyzed. Results Compared with the underachieving group, the achieving group had shorter duration of diabetes [6.50 (1.00, 10.00) years vs. 10.00 (3.25, 15.00) years，P<0.01], and higher BMI, FC-P, 2 hC-P and basal insulin dosage before conversion (P<0.05). Multivariate Logistic regression analysis showed that BOT program might not be successful in patients with long course of diabetes (OR=0.930, 95%CI: 0.876-0.987, P=0.017), while high levels of BMI (OR=1.145, 1.003-1.308, P=0.045), 2 hC-P (OR=2.866, 1.938-4.239, P<0.01) and basal insulin dosage (OR=1.254, 1.119-1.406, P<0.01) could promote the success of BOT program. Conclusion The duration of diabetes, BMI, 2 hC-P and the dosage of basal insulin are main factors influencing the conversion of type 2 diabetic patients with poor glycemic control to basal insulin combined with oral medication after intensive insulin therapy. Figures and Tables | References | Related Articles | Metrics

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Influence of seasonal meteorological factors on blood pressure fluctuation in elderly patients with essential hypertension BI Weixuan, ZHANG Yu, WANG Zhongyan, DONG Qi, CUI Hongyan, WANG Lin, LI Xin 2022, 50 (11):  1196-1200.  doi: 10.11958/20220213 Abstract ( 552 )   HTML ( 3 )   PDF (703KB) ( 1861 )   Objective To analyze the influence of temperature changes in different seasons on blood pressure fluctuation in very old patients with essential hypertension. Methods Elderly inpatients with essential hypertension were included in this study. The general data of 24-hour ambulatory blood pressure, plasma homocysteine (Hcy) level and meteorological data of the day obtained by wearing ambulatory sphygmomanometer were collected. Blood pressure values and fluctuations of blood pressure in different sexes and different seasons were compared. Effects of temperature and Hcy on blood pressure in essential hypertensive patients were discussed. Results The 24 h mean systolic blood pressure (24 hSBP), the 24 h standard deviation of systolic blood pressure (24 hSSD) and the 24 h pulse pressure index (24 hPPI) were higher in males than those of females, and the proportion of stroke history was higher in males than that in females. The results of seasonal grouping showed that 24 hSBP was the highest in winter, followed by spring and autumn, and the lowest in summer. The 24 hSSD and 24 hPPI were higher in winter than those in other seasons. In the hypothermia group, 24 hSSD was higher in the type H hypertension group, and it was positively correlated with Hcy. The daily average temperature in spring, summer and autumn was negatively correlated with 24 hSBP. The 24 hSBP decreased by 0.641 mmHg when the daily mean temperature increased by 1 ℃. Conclusion The blood pressure of very old patients with essential hypertension fluctuates seasonally. Patients with H hypertension are more sensitive to cold. Figures and Tables | References | Related Articles | Metrics

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Predictive value of serum sTREM1 combined with ABCD-3I score for short-term ischemic stroke in patients with transient ischemic attack YU Miao, CHEN Wei, SUN Yang, LI Bin, NIU Yuguang 2022, 50 (11):  1201-1204.  doi: 10.11958/20220632 Abstract ( 477 )   HTML ( 3 )   PDF (719KB) ( 1775 )   Objective To investigate the predictive value of serum soluble triggering receptors expressed on myeloid cells 1 (sTREM1) combined with ABCD-3I score in the prediction of recent acute ischemic stroke (AIS) in patients with transient ischaemic attack (TIA). Methods A total of 288 TIA patients were selected, and they were divided into the low-risk group (102 cases), the intermediate-risk group (131 cases) and the high-risk group (55 cases) according to their ABCD-3I scores. In addition, the patients were sub-divided into the AIS group (41 cases) and the non-AIS group (247 cases) according to whether AIS occurred after 90 days. The clinical data such as age, sex and basic diseases were collected, and the serum sTREM1 level was detected by enzyme-linked immunosorbent assay. Results The age, proportion of diabetes, proportion of hypertension, low-density lipoprotein cholesterol (LDL-C) level, sTREM1 level and AIS ratio were significantly higher in the high-risk group than those in the intermediate-risk group and the low-risk group (P<0.05). The sTREM1 level was significantly higher in the intermediate-risk group than that in the low-risk group (P<0.05). The age, proportion of hypertension, LDL-C level, ABCD-3I score and sTREM1 level were significantly higher in the AIS group than those in the non-AIS group (P<0.05). Multivariate Logistic regression model analysis showed that both higher ABCD-3I score and higher sTREM1 level were risk factors for recent AIS in TIA patients (P<0.05). The area under the curve of ABCD-3I score and sTREM1 level in predicting AIS in TIA patients were 0.795 (95%CI: 0.723-0.867) and 0.755 (95%CI: 0.672-0.839) respectively, and the area under the curve increased to 0.881 (95%CI: 0.830-0.932) after the combination of ABCD-3I score and sTREM1 level. Conclusion Serum sTREM1 combined with ABCD-3I score has a high predictive value for recent AIS in TIA patients, and which has certain clinical application value. Figures and Tables | References | Related Articles | Metrics

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The expression of serum PU.1 and IL-4 in children with acute upper respiratory tract infectious diseases and their clinical diagnostic values GUO Chaojin, XUAN Yan 2022, 50 (11):  1205-1208.  doi: 10.11958/20212783 Abstract ( 847 )   HTML ( 1 )   PDF (719KB) ( 1755 )   Objective To analyze the expression levels of serum transcription factor PU.1 and interleukin-4 (IL-4) in children with acute upper respiratory tract infectious diseases and explore their clinical diagnostic values. Methods A total of 78 children with acute upper respiratory tract infection treated in our hospital were selected as the disease group, and 78 healthy children with physical examination during the same period were selected as the normal control group. Fluorescence quantitative method and enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of serum transcription factors PU.1 and IL-4 in children respectively. The receiver operating characteristic (ROC) curve was used to analyze its clinical diagnostic value. Multivariate Logistic regression was used to analyze the independent risk factors affecting the occurrence of acute upper respiratory tract infectious diseases. Results The serum levels of interleukin-6 (IL-6), C reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor alpha (TNF-α), IL-4 and the relative expression of PU.1 were significantly higher in the disease group than those in the normal control group (P<0.05). The areas under the ROC curve of serum IL-4 level and the relative expression of PU.1 and their combined detection for diagnosing the upper respiratory tract infectious diseases in children were 0.752, 0.855 and 0.984, respectively, the corresponding sensitivities were 58.97%, 78.21%, 94.87%, respectively, and the specificities were 83.33%, 78.21% and 97.44%, respectively. A multivariate Logistic regression analysis was performed, and the results showed that higher serum IL-4, PU.1, IL-6, CRP and TNF-α expression levels were independent risk factors affecting the occurrence of upper respiratory tract infectious diseases (P<0.05). Conclusion The serum levels of PU.1 and IL-4 in children with acute upper respiratory tract infectious diseases are relatively high, which have certain diagnostic value. Figures and Tables | References | Related Articles | Metrics

Drug Clinical Evaluations

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Postoperative analgesic effect of intravenous flurbiprofen axetil combined with nalbuphine in patients undergoing orbital decompression CHEN Yiren, ZHENG Yajing, CHEN Ying 2022, 50 (11):  1209-1212.  doi: 10.11958/20220383 Abstract ( 526 )   HTML ( 2 )   PDF (681KB) ( 1786 )   Objective To evaluate the postoperative analgesic effect of intravenous flurbiprofen axetil combined with nalbuphine in patients undergoing orbital decompression. Methods A total of 120 patients who planned to undergo orbital decompression in our hospital were included. Patients were randomly divided into the flurbiprofen group (F group), the nalbuphine group (N group) and the flurbiprofen combined nalbuphine group (F+N group) with 40 patients in each group. All patients were given analgesic drugs intravenously immediately after the operation. Patients in the F group were intravenously injected 100 mg flurbiprofen axetil, patients in the N group were intravenously injected with nalbuphine 0.1 mg/kg and patients in the F+N group were intravenously injected with flurbiprofen axetil 100 mg and nalbuphine 0.1 mg/kg. The Numerical Rating Scale (NRS) and Ramsay sedation score were used to evaluate pain and sedation of patients in the three groups immediately after returning to ward (T0), 2 h (T2) and 12 h (T12) after surgery. Adverse reactions including the incidence of hypotension, nausea, vomiting, shivering, respiratory depression and pruritus were recorded within 24 hours of operation. Results A total of 116 patients were eventually enrolled, including 38 patients in the F group, 38 patients in the N group and 40 patients in the F+N group, respectively. NRS scores at T0 and T2 were significantly lower in the F+N group than those in the F group and the N group (P<0.05). There was no significant difference in NRS score at T12 between the three groups (P>0.05). There were no significant differences in Ramsay sedation scores at T0, T2 and T12 between the 3 groups (P>0.05). In terms of adverse reactions, there were no significant differences in the incidence of hypotension, nausea, vomiting, shivering, respiratory depression and pruritus between the three groups (P>0.05). Conclusion Intraoperative intravenous flurbiprofen axetil combined with nalbuphine can provide better postoperative analgesic effect and higher safety for patients undergoing orbital decompression. Figures and Tables | References | Related Articles | Metrics

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Dose-response study of sugammadex sodium on reversing neuromuscular block of rocuronium in patients with abnormal liver function FAN Fangfei, DENG Li 2022, 50 (11):  1213-1216.  doi: 10.11958/20212847 Abstract ( 616 )   HTML ( 3 )   PDF (777KB) ( 1830 )   Objective To investigate the dose-effect relationship of sugammadex sodium on reversing neuromuscular block of rocuronium in patients with liver dysfunction. Methods Eighty patients who underwent elective partial hepatectomy were selected. According to the Child-Pugh classification, patients were divided into the experimental group (Child-Pugh class A) and the control group (normal liver function), with 40 cases in each group. Sugammadex sodium was intravenously injected immediately after the operation at the time of 1-2 times of single-stimulated muscle twitch count (PTC) after tonic stimulation. Dixon sequential method was used to adjust the dosage of sugammadex sodium in both groups, and the first patient was intravenously injected with the initial dose of sugammadex sodium 4 mg/kg, with a dose gradient of 0.5 mg/kg. The ED95 of sugammadex sodium was calculated. Results The intraoperative dose of rocuronium bromide was significantly lower in the experimental group than that in the control group (P<0.05). The maximum dosage of sugammadex sodium was 5.5 mg/kg in the experimental group, and the maximum dosage of sugammadex was 4.5 mg/kg in the control group. The Probit model formula of the control group was Probit(P)=-10.891+3.009×dose, and the Probit model formula of the experimental group was Probit(P)=-8.095+1.864×dose. The ED95 of sugammadex sodium for reversing rocuronium bromide neuromuscular block was 4.167 mg/kg in patients of the control group (95%CI: 3.824-4.509 mg/kg). The ED95 of sugammadex sodium for reversing neuromuscular blockade in patients of the experimental group was 5.224 mg/kg (95%CI: 4.577-5.872 mg/kg). Conclusion Compared with patients with normal liver function, patients with abnormal liver function require a larger dose of sugammadex to reverse the neuromuscular blockade of rocuronium bromide, with an ED95 of 5.224 mg/kg. Figures and Tables | References | Related Articles | Metrics

Review

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Research progress related to the mechanism of mesenchymal stem cell-mediated mitochondrial transfer and its application in cancer treatment SUN Wenmei, WANG Jiaping, ZHANG Weihu, XIAO Peilin 2022, 50 (11):  1217-1221.  doi: 10.11958/20220498 Abstract ( 465 )   HTML ( 3 )   PDF (898KB) ( 2040 )   The tumor microenvironment that contains mesenchymal stem cells (MSCs) plays a significant role in cancer recurrence, drug resistance and metastasis. MSCs can transfer their own mitochondria to tumor cells, enhance mitochondrial oxidative phosphorylation and promote cancer progression. Factors that interfere with mitochondrial transfer have positive effects on cancer. This paper elaborates on the mechanisms associated with the mitochondrial transfer and its related application in cancer treatment, aiming to provide novel strategies and ideas for cancer treatment. Figures and Tables | References | Related Articles | Metrics

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Research progress on etiology and clinical characteristics of ICM-induced hypothyroidism HAN Chuyi, ZHANG Jingxia, CONG Hongliang 2022, 50 (11):  1222-1226.  doi: 10.11958/20220392 Abstract ( 568 )   HTML ( 2 )   PDF (762KB) ( 1796 )   Iodinated contrast media (ICM) administration may induce hypothyroidism (IIHypo). Recent studies have found that ICM can specifically inhibit thyroid iodide uptake by iodide independently of free iodide through a mechanism different from the conventional Wolff-Chaikoff effect. At present, issues regarding the incidence of IIHypo, related risk factors and indications for monitoring ICM-induced events have not been fully determined. Recognizing of potential risk factors for IIHypo and timely assessment of iodine-induced events within the time window of iodine exposure have important clinical significance for optimizing the diagnosis and management procedures of ICM-induced thyroid dysfunction. Figures and Tables | References | Related Articles | Metrics

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Research progress on early neurological deterioration after vascular recanalization in acute ischemic stroke LIU Jie, XIA Pan, PAN Chunhua, LI Hang, WANG Zeying 2022, 50 (11):  1227-1232.  doi: 10.11958/20220310 Abstract ( 574 )   HTML ( 4 )   PDF (700KB) ( 1750 )   Recanalization therapy has become an effective treatment for acute ischemic stroke (AIS), but due to the influence of various factors such as bleeding transformation, poor reperfusion and vascular reocclusion, some AIS patients will experience early neurological deterioration (END) after recanalization therapy, which is mainly manifested as disease progression and aggravated neurological impairment, seriously affecting the prognosis of patients. At present, there is no uniform name and diagnostic criteria for END, and results of studies on END after recanalization therapy are also different. This article reviews the pathogenesis, risk factors and predictors of END after recanalization therapy. References | Related Articles | Metrics