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15 November 2021, Volume 49 Issue 11 Previous Issue    Next Issue

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The expression of miR-199a in gestational diabetes mellitus and its mechanism in insulin resistance MA Shuang-ling, LI Guo-yun, YANG Ying, LI Ci-mei, ZHOU Fang-fang, ZHANG Xin-ning, WANG Xi 2021, 49 (11):  1121-1125.  doi: 10.11958/20210996 Abstract ( 801 )   PDF (522KB) ( 3001 )   Objective　To investigate the expression of microRNA (miR)-199a in gestational diabetes mellitus (GDM) and the mechanism of silent mating type information regulator 2 homolog 1/forkhead box transcription factor O1 (SIRT1/FOXO1) pathway involved in insulin resistance (IR). Methods　A total of 56 GDM pregnant women were selected as the research objects (GDM group), and 60 normal pregnant women were selected as the control group. Real-time fluorescence quantitative PCR (qPCR) was used to detect the level of miR-199a in placenta. The insulin resistance index (HOMA-IR) was calculated. Pearson method was used to analyze the correlation between miR-199a and HOMA-IR. Human beings chorial trophcytes HTR-8/SVneo cells were cultured in vitro, and IR model was made. The function of miR-199a was verified. Cells were divided into the model group, the miRNA inhibitor NC group, the miR-199a inhibitor group, the miRNA mimic NC group and the miR-199a mimic group. The expression levels of miR-199a were detected by qPCR in each group. The intracellular glucose uptake was measured by anthrone method. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by kit. The protein levels of SIRT1, FOXO1 and acely (Ac)-FOXO1 were detected by Western blot assay. The double luciferase reporter gene assay was used to identify the targeting relationship between miR-199a and SIRT1. Results　Compared with the normal pregnant women, the levels of miR-199a and HOMA-IR in placenta were higher in GDM patients (P＜0.05), and there was a positively correlation between miR-199a level and HOMA-IR (P＜0.05). The combined action of palmitic acid and insulin on cells for 24 h could establish an IR model. Compared with the model group and the miRNA inhibitor NC group, the levels of miR-199a and MDA were decreased in the miR-199a inhibitor group, while the levels of glucose uptake, SOD and SIRT1 protein were increased (P＜0.05). Compared with the model group and the miRNA mimic NC group, the levels of miR-199a, Ac-FOXO1 protein and MDA were increased in the miR-199a mimic group, while the levels of glucose uptake and SIRT1 protein were decreased (P＜0.05). Tarbase database analysis showed that miR-199a and SIRT1 had complementary binding sites, which were verified by double luciferase. Conclusion　The level of miR-199a in placenta is highly expressed in GDM patients. The increased miR-199a can promote FOXO1 acetylation by targeting down-regulation of SIRT1, relulting in IR. Related Articles | Metrics

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The regulatory effects and mechanism of urolithin C on biological behaviors of glioblastoma LIU Cui-lan, LI Jian-jun, ZHAO Di, LI Cheng-long, QIU Chang-yun, LIU Song 2021, 49 (11):  1126-1132.  doi: 10.11958/20210976 Abstract ( 694 )   PDF (1201KB) ( 2931 )   Objective　To investigate the effects of urolithin C (UC) on biological behaviours of glioblastoma (GBM) U251 and U87 MG cells and its regulatory mechanism. Methods　U251 and U87 MG cells were divided into 0, 20, 40, 80, 120 and 160 μmol/L UC treatment groups. The cell proliferation rates in each group at 24, 48 and 72 h were detected by CCK-8 method, respectively. The cells were divided into 0, 40, 80 and 120 μmol/L UC treatment groups. The cell colony formation ability was detected by colony formation assay. The cell migration ability at 24 and 48 h was detected by wound healing assay. The cell invasion ability was detected by Transwell invasion assay at 24 h, and the cell apoptosis and cell cycle were detected by flow cytometry at 24 h. Western blot assay was used to detect the expression levels and phosphorylation levels of AMPK, ERK and p38 MAPK. Results Compared with the 0 μmol/L group, the proliferation rates of U251 cells decreased at 48 h at different concentration UC groups, while the proliferation rate of U87 MG cells at 40 µmol/L and above decreased at 48 h (P＜0.05). Compared with the 0 µmol/L group, the clone formation rate, cell migration and invasion ability decreased in a concentration-dependent manner in the 40, 80 and 120 μmol/L U251 and the U87 MG cell groups (P＜0.05). Compared with the 0 μmol/L group, the apoptosis rates increased in the 120 µmol/L U251 and the U87 MG cell groups, and the cell cycle of U251 and U87 MG cells in the 40, 80 and 120 μmol/L groups were all blocked in the S phase (P＜0.05). Compared with the 0 μmol/L group, the levels of p-AMPK and p-p38 MAPK in U251 and U87 MG cells increased in the 40, 80, and 120 μmol/L groups, and the p-ERK levels in U251 cells increased in the 80 and 120 μmol/L groups, but the p-ERK level of U87 MG cells only increased in the 120 μmol/L group (P＜0.05). Conclusion　A certain concentration of UC can inhibit the proliferation, migration and invasion of GBM cells, induce cell apoptosis and cell cycle arrest, and the mechanism may be related to the regulation of AMPK/ERK/p38 MAPK signaling pathway. Related Articles | Metrics

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The protective effect of SIRT3-FOXO1-mediated autophagy on ischemia-reperfusion injury of H9C2 cells WANG Shang-xu, LIN Xian-he 2021, 49 (11):  1133-1137.  doi: 10.11958/20211124 Abstract ( 930 )   PDF (825KB) ( 2938 )   Objective　To investigate the role of silent mating type information regulator 2 homolog 3 (SIRT3) -forkhead box O1(FOXO1) pathway-mediated autophagy in myocardial ischemia-reperfusion (IR) injury. Methods　SIRT3 overexpression stable strain was constructed by lentivirus infection of H9C2 cells. The cells were divided into four groups: the normal control (NC) group, the ischemia-reperfusion (IR) group, the SIRT3 overexpression +IR (S+IR) group and the SIRT3 overexpression +IR+ SIRT3 inhibitor (S+IR+3-TYP) group. The expressions of SIRT3, Ac-FOXO1, autophagy labeled protein LC3B, Beclin1 and apoptotic proteins Bcl-2 and Bax were detected by Western blot assay. The apoptosis rate was detected by flow cytometry. The level of lactate dehydrogenase (LDH) in the supernatant of cell culture was determined by automatic biochemical analyzer. Results　Compared with the NC group, the expression of SIRT3 was decreased, Ac-FOXO1 was increased, the expressions of autophagy related proteins Beclin1 and LC3B were increased, the expression of anti-apoptotic protein Bcl-2 was decreased, the expression of pro-apoptotic protein Bax was increased, LDH release and cell apoptosis rate were increased in the IR group (P＜0.05). Compared with the IR group, the expression of SIRT3 increased, Beclin1, LC3B and Bcl-2 were increased, the expressions of Ac-FOXO1, pro-apoptotic protein Bax were decreased, LDH release and cell apoptosis rate were decreased in the S+IR group (P＜0.05). After adding SIRT3 inhibitor 3-TYP, there was no significant change in SIRT3 expression compared with that of the S+IR group, but the expression of Ac-FOXO1 was increased, the expressions of Beclin1 and LC3B were decreased, the expression of anti-apoptotic protein Bcl-2 was decreased, the expression of pro-apoptotic protein Bax was increased, LDH release and cell apoptosis rate were increased (P＜0.05). Conclusion　The activation of SIRT3-FOXO1 pathway can increase autophagy level of H9C2 cells, and has a protective effect on myocardial ischemia reperfusion injury. Related Articles | Metrics

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The effect and its mechanism of apigenin on proliferation and apoptosis of HEC-1-B cells CHEN Rong, SHI Yan-hua 2021, 49 (11):  1138-1142.  doi: 10.11958/20210940 Abstract ( 678 )   PDF (649KB) ( 2990 )   Objective　To study the effect of apigenin on proliferation, invasion, migration and apoptosis of endometrial carcinoma cell line HEC-1-B cells and its mechanism. Methods　HEC-1-B cells in logarithmic growth phase were treated with 0, 20, 40 and 80 μmol/L apigenin. CCK-8 method was used to detect the absorbance of cells cultured for 24, 48 and 72 hours. The level of apoptosis was detected by flow cytometry, and the ability of invasion and migration were detected by Transwell assay. Western blot assay was used to detect the expression levels of Bax, Bcl-2, p-PI3K, PI3K, p-AKT and AKT. Results　With the increase of apigenin concentration from 20 to 80 μmol/L, the proliferation of HEC-1-B cells was significantly inhibited, the apoptosis rate increased. Meanwhile, the expression of pro-apoptotic protein Bax increased, and the expression of anti-apoptotic protein Bcl-2 decreased. With the increase of apigenin concentration in 0, 5, 10 and 20 μmol/L, the invasion and migration ability decreased in HEC-1-B cells. Western blot assay showed that 40 μmol/L apigenin could inhibit the expression levels of p-PI3K and p-AKT. Conclusion　Apigenin can inhibit the proliferation, invasion and migration, and promote apoptosis of HEC-1-B cells, which may be related to PI3K/AKT signaling pathway. Related Articles | Metrics

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Effects of quercetin on p53/AMPK/mTOR signaling pathway related to gastric cancer LI Xin, LIN Ming-zhe, ZHAO Jiu-da 2021, 49 (11):  1143-1147.  doi: 10.11958/20211129 Abstract ( 988 )   PDF (589KB) ( 3262 )   Objective　To explore the effect of quercetin (QE) on gastric cancer-related p53/AMPK/mTOR signaling pathway. Methods　Gastric cancer cells were divided into the QE group and the solvent group. DMSO was used as the solvent. QE was formulated into 0.02 (QEA group), 0.04 (QEB group), 0.06 (QEC group), and 0.08 mmol/L (QED group) solutions. The solvent group was added the same amount of solvent without QE. MTT test was used to detect the effect of quercetin on gastric cancer cell proliferation. MDC staining method was used to detect the effect of quercetin on gastric cancer cell autophagy. Double staining method was used to detect the effect of quercetin on gastric cancer cell apoptosis. Real-time polymerase chain reaction test was used to detect the relative expression levels of p53, AMPK and mTOR mRNA in cells. Western blot assay was used to detect the differences in the expression levels of LC3Ⅱ/LC3Ⅰ, P53, AMPK and mTOR in cells. Results　Compared with the solvent group, the autophagy and apoptosis rate of gastric cancer cells were significantly increased in the different QE dose groups (P＜0.05). The expression of LC3Ⅱ/LC3Ⅰ protein in cells was up-regulated in the QE groups, and p53, AMPK mRNA and protein levels were also up-regulated, and the mRNA and protein expression of mTOR were down-regulated (P＜0.05) with a dose-dependent pattern. Conclusion　Quercetin can inhibit the proliferation of gastric cancer cells, induce autophagy and promote apoptosis, which may be related to the p53/AMPK/mTOR signaling pathway. Related Articles | Metrics

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The study of asiaticoside regulating SIRT1-FOXO3-PINK1-Parkin pathway-mediated protective mechanism of mitochondrial autophagy on renal ischemia-reperfusion injury HU Yan, WANG Suo-gang, ZHAI Qiong-yao, WANG Di, ZHU Shi-yu, WANG Guang-ce 2021, 49 (11):  1148-1153.  doi: 10.11958/20210354 Abstract ( 743 )   PDF (1156KB) ( 3465 )   Objective　To investigate the protective effect and mechanism of asiaticoside (AC) on renal ischemia-reperfusion injury (RIRI) by regulating SIRT1-FOXO3-PINK1-Parkin pathway mediated mitochondrial autophagy. Methods　Fifty male SD rats were divided into the sham-operation group (Sham group), the model group, the AC group, the AC+SIRT1 inhibitor (EX-527) group and the EX-527 group by random number table method, with 10 rats in each group. RIRI model was constructed. The AC group was given AC suspension 80 mg/(kg·d) by intragastric administration for 4 weeks before modeling. The AC+EX-527 group was intraperitoneally injected with 1% DMSO solution containing EX-527 (5 mg/kg) 3 days before modeling, and intraperitoneally injected once 20 min before intraoperative reperfusion. The remaining treatments were the same as the AC group. The Ex-527 group was intraperitoneally injected with the same amount of 1% DMSO solution containing EX-527 80 mg/(kg·d). Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were detected 24 h after modeling. Pathological changes and scores of renal tissues were observed by HE staining. Western blot assay was used to detect SIRT1, FOXO3, PINK1, Parkin pathway proteins, autophagy related Beclin1, LC3A/B-Ⅰ, LC3A/B-Ⅱ protein levels. The value of (LC3A/B-Ⅱ)/(LC3A/B-Ⅰ) was calculated. ATP content was detected by ultraviolet spectrophotometry. The changes of mitochondrial membrane potential were detected by JC staining. Results　Compared with the Sham group, the levels of Scr and BUN were increased, pathological damage occurred in renal tissue, expression levels of pathways and autophagy related proteins were increased, ATP content was decreased, and mitochondrial membrane potential level was decreased in the model group (P＜0.05). Compared with the model group, the levels of Scr and BUN were significantly decreased, the pathological damage of kidney tissue was alleviated, the expression levels of pathways and autophagy related proteins increased, ATP content and mitochondrial membrane potential were also increased in the AC group (P＜0.05). Compared with the AC group, the Scr and BUN levels were increased, the histopathological damage was aggravated, the expression levels of pathways and autophagy related proteins were decreased, ATP content was decreased, and the mitochondrial membrane potential level was decreased in the AC+EX-527 group and the EX-527 group (P＜0.05). Conclusion　AC can improve mitochondrial function of renal cells, inhibit apoptosis and protect RIRI by up regulating the expression levels of SIRT1-FOXO3-PINK1-Parkin signaling pathway proteins and promoting mitochondrial autophagy. Related Articles | Metrics

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Effects of rhynchophylline solid lipid nanoparticles on miR-155/p38 MAPK axis in asthmatic mice WANG Meng, Paligu·Maimaitili, LI Hui, LYU Chuan-feng 2021, 49 (11):  1154-1158.  doi: 10.11958/20210729 Abstract ( 736 )   PDF (550KB) ( 2898 )   Objective　To observe the effect of rhynchophylline solid lipid nanoparticles (Rhy-SLN) on the microRNA-155/p38 mitogen activated protein kinase (p38 MAPK) axis in asthmatic mice. Methods　Fifteen BALB/c mice were randomly divided into the normal control group, the model group and the Rhy-SLN group. The mice in Rhy-SLN group were given the Rhy-SLN (50 mg/kg) before each sensitization operation of aluminum hydroxide. The normal control group and the model group were given equal amount of normal saline. After intervention, the number of eosinophils was observed by the smear of alveoli lavage. HE staining was used to observe the pathological changes of lung tissue in mice. The activities of immunoglobulin E (IgE) and interleukin-13 (IL-13) in mice were determined by ELISA. The hydroxyproline level in the lung tissue of mice was detected by hydroxyproline test. Western blot assay was used to detect expression levels of α-SMA, collagenⅠ, p38 MAPK and p-p38 MAPK in lung tissue of mice. The expression of miR-155 in mouse lung tissue was detected by RT-PCR. Results　The number of eosinophils in BALF, the serum level of IgE and IL-13 in BALF of asthmatic mice were decreased in the Rhy-SLN group compared with those of the model group (P＜0.05). Rhy-SLN can reduce the infiltration of inflammatory cells in lung tissue, reduce expression levels of α-SMA, collagen Ⅰ, hydroxyproline and p-p38 MAPK in lung tissue of asthmatic mice (P＜0.05). The expression of miR-155 in lung tissue of mice was up regulated by Rhy-SLN (P＜0.05). Conclusion　Rhy-SLN can relieve asthma in mice, and its mechanism may be related to the regulation of the miR-155/p38 MAPK axis and reduction of airway inflammation. Related Articles | Metrics

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The neuroprotective effect of dexmedetomidine on preeclampsia rats based on NF-κB/ICAM-1 pathway ZHANG Lei, ZHU Yong-yi ZHAO Nian-zhang, LIANG Shao-ling 2021, 49 (11):  1158-1162.  doi: 10.11958/20210847 Abstract ( 757 )   PDF (513KB) ( 2863 )   Objective　To investigate the neuroprotective effect of dexmedetomidine (DEX) on preeclampsia rats, based on the nuclear factor-κB (NF-κB)/intercellular adhesion molecule-1 (ICAM-1) pathway. Methods　SD pregnant rats were randomly divided into the control group, the model group, the low-, middle- and high-dose DEX groups, with 10 rats in each group. Except for the sham operation group, the other groups were intraperitoneally injected with homocysteine (Hcy, 200 mg/kg) daily and subcutaneously injected with monosodium glutamate (MSG, 1 g/kg) on the back every other day to prepare the preeclampsia model. During the 10th day to the 20th day of pregnancy, the low-, middle- and high-dose DEX groups were intraperitoneally injected 7.5, 15.0 and 30.0 μg/kg of DEX for 10 days. Neurological function score was used to evaluate the behavioral defects of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the S100B and ferritin in cerebrospinal fluid, the expression levels of brain tissue inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). TUNEL staining was used to detect the apoptosis of brain tissue. Western blot assay was used to detect the expression levels of NF-κB/ICAM-1 pathway related proteins in brain tissue. Results　Compared with those in the control group, the apoptosis of brain tissue was serious, the neurological function score, S100B and ferritin in cerebrospinal fluid, contents of IL-1β, TNF-α, IL-6 in brain tissue, protein expression levels of p-NF-κB/NF-κB and ICAM-1 were significantly higher in the model group (P＜0.05). Compared with those in the model group, the proportion of apoptotic cells was less in the low-, medium-, and high-dose DEX groups, the neurological function score, S100B and ferritin in cerebrospinal fluid, contents of IL-1β, TNF-α, IL-6 in brain tissue, protein expression levels of p-NF-κB/NF-κB and ICAM-1 were significantly lower (P＜0.05). There was a dose-dependent relationship between the DEX groups. Conclusion　DEX has a therapeutic effect on nerve cells, and its mechanism may be related to the inhibition of the NF-κB/ICAM-1 signal activation, the inflammatory factor release and the apoptosis of brain nerve cells. Related Articles | Metrics

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The effect of lentivirus-mediated NK4 overexpression on the growth of lung adenocarcinoma xenograft tumor in nude mice DAI Ting-ting, XU Ting, YU Xiao-wei 2021, 49 (11):  1163-1168.  doi: 10.11958/20210833 Abstract ( 1010 )   PDF (8342KB) ( 2841 )   Objective　To study the effect of NK4 overexpression mediated by intratumoral injection of lentivirus on the growth, invasion, metastasis and microangiogenesis of lung adenocarcinoma xenografts in nude mice. Methods　A549 cells were implanted into the right flank of BALB/c mice. After modeling, the mice were randomly divided into three groups: the PBS group, the LV-con group and the LV-NK4 group, 5 mice in each group. Mice in the three groups were received intratumoral injections of PBS (25 µL), LV-con (25 μL, 6×108 TU/mL) and LV-NK4 (25 μL, 6×108 TU/mL) respectively, twice at an interval of 3 days. The tumor volumes and weights of xenografts were measured, and the inhibitory rate of tumor was calculated at the end of the experiments. The tumor tissues and lung tissues in each group were observed by hematoxylin-eosin staining. The expressions of c-Met and CD31 were detected by immunohistochemistry, and microvessel density (MVD) was used to detect angiogenesis. The apoptosis of tumor cells in each group was detected by TUNEL. The expression levels of NK4 mRNA and protein in xenograft tumors were detected by real-time PCR and Western blot assay, respectively. Results　The xenograft tumor model of human lung adenocarcinoma was established successfully. The volume of tumor was smaller in the LV-NK4 group than that of the LV-con group and the PBS group (P＜0.05). There was no significant difference between the LV-con group and the PBS group. The tumor weight was significantly decreased in the LV-NK4 group compared with the LV-con group and the PBS group (P＜0.05). The tumour suppression rate was 44.51% in the LV-NK4 group and 10.35% in the LV-con group. The necrosis and apoptosis in tumor tissue of nude mice were significantly more in the LV-NK4 group than those in the LV-con group and the PBS group. The expression of c-Met in tumor tissue was significantly decreased in the LV-NK4 group, and the microangiogenesis was inhibited. There were no obvious lung metastases in the LV-NK4 group while there were obvious metastases in the LV-con group and the PBS group. The expression levels of NK4 mRNA and protein were significantly up-regulated in the LV-NK4 group than those of the other two groups. Conclusion　Lentivirus-mediated NK4 overexpression can inhibit the growth and lung metastasis of lung adenocarcinoma xenograft in nude mice by inhibiting the expression of c-Met protein and the formation of microvessels. Related Articles | Metrics

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Effects of miR-186-5p on vascular endothelial cell injury and FGF2/FGFR1 signaling pathway in rat model of coronary heart disease ZHANG Xiao-lei, XU Guo-ying, WANG Shi-zhen, CHEN Pei, CHEN Shan-shan, ZHANG Kai 2021, 49 (11):  1169-1174.  doi: 10.11958/20211008 Abstract ( 737 )   PDF (605KB) ( 2835 )   Objective　To investigate the effect of microRNA-186-5p (miR-186-5p) on vascular endothelial cell injury and fibroblast growth factor 2 (FGF2)/fibroblast growth factor receptor 1 (FGFR1) signaling pathway in model rats with coronary heart disease (CHD). Methods　A total of 48 male SD rats were divided into the control group, the model group, the miR-186-5p inhibitor group and the miR-186-5p inhibitor NC group (n=12). Except for the control group, rats in the other groups were all constructed CHD models and given corresponding interventions for 4 weeks. The serum levels of left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and endothelin-1 (ET-1) were measured in the four groups of rats. HE staining was used to observe the pathological changes of coronary artery in each group. Western blot assay was used to detect the expression levels of FGF2 and FGFR1 proteins in rat coronary artery. The double luciferase was used to verify the target relationship between miR-186-5p and FGF2. Results　In the control group, the vascular wall of the coronary arteries of rats was uniform without inflammatory cell infiltration. In the model group and the miR-186-5p inhibitor NC group, vascular endothelial cells arranged disorderly and inflammatory cells infiltrated obviously. Compared with the model group, less pathological changes and less inflammatory cell infiltration were found in the miR-186-5p inhibitor group. Compared with the control group, the contents of LVEF, LVFS, HDL-C, NO, the protein expression levels of FGF2 and FGFR1 were significantly decreased in the model group, and the levels of TC, TG, LDL-C, IL-1β, IL-6, TNF-α and ET-1 were significantly increased (P＜0.05). Compared with the model group and the miR-186-5p inhibitor NC group, the contents of LVEF, LVFS, HDL-C, NO, the protein expression levels of FGF2 and FGFR1 were significantly increased, and the levels of TC, TG, LDL-C, IL-1β, IL-6, TNF-α and ET-1 were significantly decreased in the miR-186-5p inhibitor group (P＜0.05). There were no significant differences in the above indicators between the model group and the miR-186-5p inhibitor NC group (P＞0.05). The results of double luciferase assay confirmed that miR-186-5p had a targeted binding site with FGF2. Conclusion　The down-regulation of miR-186-5p can reduce inflammatory reaction and vascular endothelial cell injury in CHD rats, which is related to the activation of FGF2/FGFR1 signaling pathway. Related Articles | Metrics

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Clinicopathological characteristics and prognostic analysis of IgA nephropathy patients with microalbuminuria and renal insufficiency WANG Xin-nian, ZHAI Ya-ling, YAO Xing-chen, SHENG Xiao-xiao, ZHANG Wen-hui, ZHAO Zhan-zheng 2021, 49 (11):  1175-1179.  doi: 10.11958/20211484 Abstract ( 845 )   PDF (462KB) ( 2858 )   Objective　To analyze the clinical data, pathological characteristics and prognosis of IgA nephropathy patients with microalbuminuria and renal insufficiency. Methods　A total of 162 patients with primary IgA nephropathy diagnosed by percutaneous renal biopsy and 24 hour urinary protein quantification (≤0.5 g) were selected. They were divided into the normal renal function group (n=107, the serum creatinine ≤115 μmol/L) and the renal insufficiency group (n=55, the serum creatinine > 115 μmol/L) according to their creatinine values. The clinicopathological data of patients hospitalized with renal puncture biopsy were collected, and the clinical and pathological characteristics and prognosis were analyzed between the two groups. The survival curve was plotted by Kaplan-Meier method to compare the difference in renal survival rate between the two groups. Cox proportional risk model was used to analyze the risk factors of end-point events in IgA nephropathy patients with microalbuminuria. Results　Compared with the normal renal function group, the proportion of male patients and proportion of patients with hypertension, age, albumin, serum creatinine, serum uric acid, triglyceride, neutrophils and potassium levels were higher in the renal insufficiency group, and the levels of hemoglobin and platelets were lower (P＜0.05). Patients in the renal insufficiency group showed more segmental sclerosis synechia (S1) of the glomerulus, higher proportion of renal tubular atrophy or (and) renal interstitial fibrosis (T1/T2) and crescents (C1/C2), and higher proportion of glomerular ischemia sclerosis, glomerular segmental sclerosis, cell/fibrous crescents, and heavier arteriole injury (P＜0.05). The results of survival analysis showed that the cumulative renal survival rate was lower in patients with renal insufficiency than that of patients with normal renal function (Log-rank χ2=24.960，P＜0.01). Multivariate Cox proportional risk model analysis showed that the increased serum creatinine, decreased hemoglobin and small arterial injury were independent risk factors for end-point events in patients with microproteinuria combined with renal insufficiency (P＜0.05). Conclusion　The clinical and pathological changes of microproteinuria combined with renal insufficiency are more severe and the prognosis is worse than those of IgA nephropathy with microproteinuria alone. Related Articles | Metrics

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Expression levels of peripheral blood PCT, HMGB-1 and ICAM-1 in patients with traumatic lung injury and their prognostic value SHI Wei, LI Xing-jing, HE Mu-dan, WANG Peng 2021, 49 (11):  1179-1183.  doi: 10.11958/20211128 Abstract ( 658 )   PDF (512KB) ( 2867 )   Objective　To explore the expression levels of peripheral blood procalcitonin (PCT), high mobility group box-1 protein (HMGB-1) and intercellular adhesion molecule-1 (ICAM-1) in patients with traumatic lung injury and their relationship with prognosis. Methods　A total of 78 patients with traumatic lung injury were enrolled as the observation group, while other 53 patients without lung injury were enrolled as the control group. The scores of Acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ), lung injury and trauma severity were compared between the two groups. The levels of peripheral blood PCT, HMGB-1 and ICAM-1 were detected by enzyme-linked immunosorbent assay (ELISA), and their relationship with scores of APACHEⅡ and lung injury was analyzed. According to the patient's prognosis, patients in the observation group were divided into the good prognosis group and the poor prognosis group. The changes of PCT, HMGB-1 and ICAM-1 were compared between the two groups. Their relationship with poor prognosis was analyzed by receiver operating characteristic (ROC) curves. Results　The scores of APACHEⅡ, lung injury and trauma severity, and levels of peripheral blood PCT, HMGB-1 and ICAM-1 were significantly higher in the observation group than those in the control group (P＜0.05). The levels of peripheral blood PCT, HMGB-1 and ICAM-1 were positively correlated with APACHEⅡ and lung injury scores (P＜0.05). The levels of peripheral blood PCT, HMGB-1 and ICAM-1 were significantly higher in the poor prognosis group than those in the good prognosis group (P＜0.05). The area under the ROC curve (AUC) for poor prognosis of PCT, HMGB-1, ICAM-1 and their combined detection were 0.801 (0.695-0.907), 0.736 (0.618-0.855), 0.821 (0.707-0.936) and 0.938 (0.885-0.991). The sensitivity values were 0.810, 0.762, 0.667 and 0.905, and the specificity values were 0.719, 0.632, 0.860 and 0.842. Conclusion　The levels of peripheral blood PCT, HMGB-1 and ICAM-1 are increased in patients with traumatic lung injury, and the combined detection of the three indexes is of high predictive value for the poor prognosis. Related Articles | Metrics

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Study on related factors and effect relationship of abnormal plasma viscosity in health check-up participants ZHUO Lin, CAI Ting, CHEN Si-ting, WANG Xiu-ying, ZHUO Lang, CUI Jing-qiu 2021, 49 (11):  1184-1188.  doi: 10.11958/20211194 Abstract ( 761 )   PDF (494KB) ( 2820 )   Objective　To investigate the influencing factors of abnormal plasma viscosity (PV) and provide reference for the early prevention of chronic diseases. Methods　A total of 930 participants with abnormal PV (the abnormal group) were selected from the database of health examinees. After matching age, gender and type of work, 2 790 participants with normal PV (the normal group) were selected according to the ratio of normal group to abnormal group = 3∶1. Univariate analysis and conditional Logistic regression analysis were used to screen the related factors of abnormal PV. The aggregation of different levels of PV and related factors were demonstrated by correspondence analysed. The mediating effect verified the mediating role of PV between abnormal metabolic indicators and abnormal renal function. Results　The serum levels of creatinine (SCr), uric acid (UA), fasting plasma glucose (FPG), total cholesterol (TC) and triglyceride (TG) were significantly higher in the abnormal group than those in the normal group, while the estimated glomerular filtration rate (eGFR) was lower (P＜0.01). Conditional Logistic regression analysis showed that the higher SCr, TC and TG were risk factors for abnormal PV (P＜0.05). Correspondence analysis showed that during the gradual increase of PV, TC was the first to appear abnormal, followed by TG, and the increase of SCr appeared last. The mediating effect showed that in the changes of renal function, the mediating effects of PV on TC and TG were 44.0% and 47.1%, respectively. Conclusion　PV shows a positive correlation with SCr, TC and TG. TC and TG have a direct impacts on renal impairment, and PV plays a certain mediating role in TC, TG and renal function injury. Related Articles | Metrics

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The effect of the systemic immune-inflammation index on conversion time of virus nucleic acid turning negative in COVID-19 patients GUO Jing, LI Li, WU Qian, LI Hong-wei, SHI Li-xia, WU Qi 2021, 49 (11):  1188-1192.  doi: 10.11958/20211164 Abstract ( 1390 )   PDF (453KB) ( 2855 )   Objective　To investigate the effect of the systemic immune-inflammation index (SII) on the conversion time of virus nucleic acid turning negative in patients with coronavirus disease 2019 (COVID-19). Methods　A total of 127 patients were selected who were admitted to our hospital from January to March 2020. Clinical data and laboratory results within 24 hours of admission were obtained from the electronic medical record system. Blood routine results were recorded to calculate SII. According to the median SII, the patients were divided into the high SII group (≥393) and the low SII group (<393). The clinical data, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP), interleukin(IL)-6 and albumin (ALB) were compared between the two groups. Cox regression analysis was performed to identify risk factors affecting the negative time of viral nucleic acid. Kaplan-Meier analysis was used to describe the nucleic acid turning negative curve of different groups of patients. Results　The male proportion, NLR, PLR and CRP were higher in the high SII group than those in the low SII group (P＜0.05). Cox multivariate regression analysis showed that severe patients, higher SII and the time from onset to admission > 5 days were independent risk factors affecting the time of nucleic acid negative conversion (P＜0.05). Kaplan-Meier curve showed that the median nucleic acid turning negative time was significantly longer in patients with high SII value, severe disease and time from onset to admission > 5 days than that in patients with low SII value, non-severe disease and time from the onset to admission ≤5 days (P＜0.05). Conclusion　SII is a simple biomarker representing inflammation and the immune response. It can be used as an independent risk factor for prolonged nucleic acid negative conversion time in COVID-19 patients. Related Articles | Metrics

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The study on the relationship between serum Runx2 gene expression and arterial vascular calcification in patients with uremia HU Chun-yan, LIU Lan, ZHANG Dong-xue, ZHANG Yuan, ZHU Rong-fang 2021, 49 (11):  1193-1197.  doi: 10.11958/20211281 Abstract ( 617 )   PDF (559KB) ( 2821 )   Objective　To explore the relationship between serum runt-related transcription factor 2 (Runx2) mRNA expression and arterial calcification in patients with uremia. Methods　A total of 78 uremic patients who underwent autologous arteriovenous fistula plasty and resection and reconstruction in our hospital were selected as the research objects, and blood vessel tissue, serum samples and clinical data of patients were collected. The calcification score were based on silver nitrate results, the patients were divided into the calcified group (n=23) and the non-calcified group (n=55). The expression level of Runx2 in blood vessel tissue was detected by immunohistochemistry, and the expression level of Runx2 mRNA in serum was detected by real-time fluorescence quantitative method. The changes of clinical indicators were compared between the two groups. The factors affecting vascular calcification of each indicator were analyzed by linear regression, and the predictive ability of serum Runx2 mRNA on vascular calcification was evaluated by ROC curve. Results　The results of silver nitrate staining showed that compared with the non-calcified group, the black deposits were significantly increased in the calcified group. The immunohistochemical results showed that the Runx2 score was significantly increased in the calcified group (P＜0.05). Compared with the non-calcified group, the age, dialysis age, blood phosphorus, iPTH and serum Runx2 mRNA expression levels were significantly increased in the calcified group (P＜0.05), and serum albumin and blood calcium were significantly decreased (P＜0.05). Spearman correlation analysis showed that age, dialysis age, blood phosphorus, iPTH, serum Runx2 mRNA, Runx2 score were positively correlated with calcificationscore, and serum albumin and blood calcium were negatively correlated with calcification score (P＜0.05). The results of multiple linear regression analysis showed that the elevated serum Runx2 mRNA expression levels, long dialysis age and hypocalcemia were independent risk factors for arterial vascular calcification in patients with uremia (P＜0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of serum Runx2 mRNA combined with dialysis age and blood calcium to diagnose vascular calcification was 0.934. Conclusion　Serum Runx2 mRNA expression is an independent risk factor for arterial vascular calcification in uremic patients, and which may be a biomarker for the diagnosis and prediction of arterial vascular calcification in uremic patients. Related Articles | Metrics

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Finite element analysis of lingual attachment in the treatment of torsional maxillary premolars YANG Yue, ZHANG Xi-zhong, XIANG Biao, RAN Yu-ting 2021, 49 (11):  1198-1202.  doi: 10.11958/20211119 Abstract ( 615 )   PDF (836KB) ( 2837 )   Objective　To analyze the orthodontic efficiency of buccal and lingual attachments with different sizes by finite element method in order to determine the optimal position and size of the attachments. Methods　Experiment 1: a normal occlusion sample was selected to establish the model. Attachments were divided into five groups: the control group, the buccal horizontal rectangular attachment group, the buccal vertical rectangular attachment group, the lingual horizontal rectangular attachment group and the lingual vertical rectangular attachment group. Except for the control group, the other 4 groups contained 3 subgroups (grouped by rectangular attachment length 3/4/5 mm). The long axis of the maxillary first premolar was set as the rotation central axis, and a 2° clockwise rotation (occlusion view) displacement was applied to carry out simulation operation to observe the stress distribution and displacement changes. In experiment 2, the attachment was modified and divided into 4 groups: the control group, the lingual b (2/3) rectangular attachment group, the lingual b (1/2) rectangular attachment group and the lingual b (1/3) rectangular attachment group. The method was the same as experiment 1. Results　In experiment 1, the periodontal membrane stress, the maximum displacement of the crown and the torsion efficiency of orthodontic force showed the maximum stress with the 3 mm attachment size in the lingual vertical group, and it decreased with the increase of the attachment size units in each group. The vertical group was larger than the horizontal group, and the expression of the torsion degree efficiency was the smallest in the group without the attachment. In the experiment 2, the periodontal membrane stress and the maximum displacement of the crown of the b (2/3) lingual vertical group were the closest to that of the 3 mm lingual vertical group, while the highest expression of torsion efficiency was the 3 mm lingual vertical group, and decreased with the decrease of the size. Conclusion　The 3 mm lingual vertical group shows more beneficial to correct torsional premolars, and the b (2/3) lingual vertical attachment could be used as the improved specification. Related Articles | Metrics

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The predictive value of two-dimensional ultrasonic speckle tracking imaging technology for ventricular arterial coupling in uremic patients WANG Xiao-yan, ZHU Xue-feng, LU Zhao-yang, ZAN Ling-juan, XU Bin, CHEN Xin 2021, 49 (11):  1203-1206.  doi: 10.11958/20203570 Abstract ( 587 )   PDF (714KB) ( 2784 )   Objective　To study the value of two-dimensional speckle tracing imaging (2DSTI) in the evealuation of ventricular-arterial coupling (VAC) in uremic patients. Methods　A total of 96 uremic patients were divided into two groups based on left ventricular ejection fraction (LVEF): the normal LVEF group (LVEF≥0.55, n=48) and the LVEF decline group (LVEF＜0.55, n=48). Forty-five healthy subjects were recruited as the control group. All the patients underwent conventional echocardiography. VAC and myocardial performance index were calculated. Longitudinal strain (LS) of 17 segments was measured using 2DSTI, and the longitudinal strain values of the bottom (LSBA), papillary muscle (LSPM) and apex (LSAP) were calculated. Results　Compared to subjects in the control group and the normal LVEF group, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular mass index (LVMI) were increased, and left ventricular short axis shorting rate (LVFS), LSBA, LSPM and LSAP were decline in the LVEF decline group (P＜0.01). 2DSTI results showed that compared with the control group and the normal LVEF group, Ees decreased and VAC value increased in the LVEF-decline group (P＜0.05). Correlation analysis showed that LSBA, LSPM and LSAP were positively correlated with Ees, LVEF and LVFS (all P＜0.05), and negatively correlated with effective arterial elasticity (Ea), VAC, peripheral vascular resistance index (SVRI), heart rate, blood pressure product (RPP) and LVMI (all P＜0.05). Conclusion　2DSTI can be used to evaluate VAC in uremia patients. Related Articles | Metrics

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Evaluation of the curative effect of 3D printing artificial vertebral body in total vertebral resection of spinal tumor SUN Yue, WANG Hai-rui, LIU Yan-cheng, ZHANG Jing-yu, LI Shuang, HU Yong-cheng 2021, 49 (11):  1207-1211.  doi: 10.11958/20212116 Abstract ( 448 )   PDF (874KB) ( 2870 )   Objective　To analyze the application value of 3D printing artificial vertebral body for spinal cord reconstruction after total vertebrectomy for spinal tumors. Methods　Data of 11 patients in our hospital who used 3D printed artificial vertebrae for reconstruction after total vertebral tumor resection was analyzed. The operation time, intraoperative blood loss, hospital stay, internal fixation stability, and visual analogue rating scale (VAS) score were recorded. The degree of pain before operation, 24 hours after operation, 6 months after operation and the last follow-up were evaluated. The spinal function at the above time points was evaluated according to the evaluation treatment score of the Japanese Orthopaedic Association (JOA). At the last follow-up, the severity of spinal cord injury was analyzed by Frankel classification, and complications were recorded during the follow-up. Results　Patients were followed up for 8 to 15 months, with an average of 11 months. The operation time was (320.21±43.21) min, the amount of bleeding was (1 354.28±101.54) mL, and the hospital stay was (22.21±10.24) d. Ten of the 11 patients had at least 1 grade improvement in Frankel classification at the last follow-up. There was no movement or breakage of the pedicle screw position in all patients, and no dislocation of the prosthesis. The VAS scores showed a decreasing trend before surgery, 24 hours after surgery, and 6 months after surgery (P＜0.01); but there was no significant difference in VAS score between the last follow-up and 6-month after surgery. There were no significant differences in JOA scores before and 24 hours after surgery, and the JOA scores showed a sequential upward trend at other time points (P＜0.01). One patient with giant cell tumor of bone recurred 3 months after operation, and one patient with secondary thyroid cancer to spine died 9 months after opertion. Conclusion　The application of 3D printing artificial vertebral body after total vertebrectomy for spinal tumors has high stability, less complications, high safety and good prognosis. Related Articles | Metrics

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The value of CellCollector® in vivo CTC capture technology for stratification of breast cancer patients WANG Ling-yan, GAO Chun-hui, FENG Xue-yuan, CUI Xin-miao, SUN Jian-yun, HE Xiang-hui 2021, 49 (11):  1211-1215.  doi: 10.11958/20210761 Abstract ( 673 )   PDF (437KB) ( 2823 )   Objective　To explore the possibility of using circulating cancer cells (CTC) captured by CellCollector® technology for screening breast cancer patients with higher risk of metastasis. Methods　Sixty patients with primary breast cancer were enrolled as the breast cancer group, including 16 in stage Ⅰ, 29 in stage Ⅱ, 11 in stage Ⅲ and 4 in stage Ⅳ. Patients were tested for at least one CTC detection through CellCollector® and followed up for 4-19 months. At the same time, 10 healthy female volunteers were enrolled as the control group, and only one CTC test was performed. The CTC positive rates in patients with different age, menopause, TNM stage, molecular typing and Ki-67 expression were analyzed. Results　The baseline CTC detection rate of breast cancer patients was 73.33%. The detection rates of Ⅰ-Ⅳ stage were 43.75%, 82.76%, 81.82% and 100%, respectively. There were significant differences in the detection rates of CTC under different clinical stages ( P＜0.05). There were no significant differences in CTC detection rates in patients with different age, menopause, molecular typing and Ki-67 expression. Among the 24 patients received twice CTC tests, the number of CTC increased in 1 of the 4 patients with disease progression. Of the 20 progression-free patients, the number of CTC increased in 3 patients, and there was no correlation between the dynamic changes of CTC number and disease progression. Conclusion　The detection rate of CellCollector® in vivo CTC is higher in non metastatic breast cancer. It is possible for CTC to screen patients with breast cancer with higher metastatic risk. Related Articles | Metrics

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Research progress on drug sensitivity test and drug resistance mechanism of Mycobacterium abscessus complex GUO Ming-ri, ZHU Yu, SUN Hai-bai 2021, 49 (11):  1216-1222.  doi: 10.11958/20211209 Abstract ( 1110 )   PDF (476KB) ( 2831 )   Mycobacterium abscessus complex (MABC) is one of the most common fast-growing mycobacteria in nontuberculosis mycobacterial diseases. Drug resistance to most of the antituberculosis drugs makes its clinical teratment very difficult. There are great differences in the sensitivity of the three subspecies of MABC to a variety of antibiotics. The accurate typing and identification of the three subspecies in clinical laboratory is of great value for the selection of therapeutic drugs. The tuberculosis branch of Chinese Medicine Association has formulated the guideline for the diagnosis and treatment of nontuberculosis mycobacterial disease (2020 Edition), MABC susceptibility test should be carried out according to the standard of mycobacterium susceptibility test from Clinical and Laboratory Standards Institute (CLSI) of the United States (2018 Edition). It is suggested that multidrug combination therapy should be selected according to the results of drug sensitivity test. In order to provide reference for related research, this paper reviewed the progress of drug sensitivity test of MABC and its resistance mechanism to main therapeutic drugs. Related Articles | Metrics

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Progress in clinical trials of monoclonal antibody therapy for neuromyelitis optica pedigree diseases LIU Ye, MENG De-wang, YANG Gui-li, SUN Li 2021, 49 (11):  1222-1227.  doi: 10.11958/20211261 Abstract ( 1063 )   PDF (493KB) ( 2793 )   Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system mediateNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system mediated by humoral immunity. It is characterized by inflammatory demyelination of the spinal cord and optic nerve, which may lead to paralysis and blindness. In addition to traditional immunosuppressants, more and more new drugs are used in the treatment of NMOSD, such as rituximab and inebilizumab targeting B cells, tocilizumab and satralizumab inhibiting interleukin-6 receptor and eculizumab blocking complement mediated cytotoxicity and secondary inflammation. In recent years, the results of several randomized clinical trials of these monoclonal antibody drugs have been published. This paper will review the research progress of these targeted drugs in the treatment of NMOSD from the aspects of the mechanism of action, efficacy and adverse reactions. Related Articles | Metrics

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Research progress of TRAIL in the treatment of digestive cancer LI Da-huan, XU Liang-bi, LIU Xue-ying, TANG Shan, DENG Chao-nan 2021, 49 (11):  1228-1232.  doi: 10.11958/20210953 Abstract ( 470 )   PDF (372KB) ( 2847 )   Tumour necrosis factor-related apoptosis-inducing ligands (TRAIL) can inhibit tumour proliferation, infiltration and metastasis by specifically recognising tumour cell death receptors and inducing and initiating various apoptotic mechanisms. TRAIL is not sensitive to the treatment of digestive malignancies such as oesophageal, gastric and colorectal cancers. TRAIL can improve its anti-cancer ability by combining some small molecular compounds or by regulating the expression of apoptosis-related proteins. However, its exact mechanism of action is not yet clear. This article reviews the research progress of tumor necrosis factor-related apoptosis-inducing ligand in the treatment of digestive system tumors. Related Articles | Metrics