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15 April 2021, Volume 49 Issue 4 Previous Issue    Next Issue
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Cell and Molecular Biology
Experimental Study
Clinical Study
Applied Essay
Drug Clinical Evaluations
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Cell and Molecular Biology

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Cytotoxic effects of spiruline platensis polysaccharides on acute T lymphocyte leukemia LI Yan, ZHANG Jing-nan, ZHANG Jin, SHI Wen-hua, YE Shu-mei, DENG Xiu-ling, HU Rui-ping, XUE Hui-ting 2021, 49 (4):  337-341.  doi: 10.11958/20202591 Abstract ( 886 )   PDF (432KB) ( 4723 )   Objective　To investigate the cytotoxic effect of spirulina platensis polysaccharides (SPP) on acute T lymphocyte leukemia Jurkat cells. Methods　SPP was obtained by water extraction and ethanol precipitation. The effect of SPP on cell proliferation was determined by MTT assay. Caspase-3 was tested by Western blot assay. Furthermore, the cell surface expression of CD45 and CD71, and the expression levels of p-ERK, p-JNK, t-ERK and t-JNK were also evaluated. Results　SPP inhibited Jurkat cell proliferation in a dose-dependent manner (1 g/L, 2 g/L and 5 g/L), the inhibitory rates were 53.286%±3.112%, 80.075%±4.240% and 86.430%±4.614%, respectively. The expression levels of cleaved caspase-3 were higher in 2 g/L and 5 g/L SPP groups than those in the control group, and that in 5 g/L SPP group was higher than that in 1 g/L SPP group (P＜0.05). The expression levels of CD45 were higher in 1 g/L and 2 g/L SPP groups than those in the control group (P＜0.05), while there was no significant difference in the expression level of CD71 between the two groups. The expression levels of CD45 were higher in 5 g/L SPP group than those in control group, 1 g/L SPP group and 2 g/L SPP group. The expression level of CD71 was lower in 5 g/L SPP group than that in control group (P＜0.05), and there was no significant difference in the expression level of CD71 between 1 g/L and 2 g/L SPP groups. The expression levels of p-ERK were increased significantly in turn in the control group, 1 g/L, 2 g/L and 5 g/L SPP groups. There were no significant differences in expression levels of t-ERK, p-JNK and t-JNK between groups. Conclusion　SPP could inhibit Jurkat cell growth and induce cell death, which might through affecting CD45 and CD71 expression on cell surface, then activating ERK and finally activating caspase-3 to induce cell apoptosis. Related Articles | Metrics

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The regulation role of abnormal expression of Survivin on metastasis and TGF-β/Smad pathway of prostate cancer XU Zi-han, PENG Yun, DONG Shi-qiang, HOU Ding-kun, WANG Hai-tao 2021, 49 (4):  342-348.  doi: 10.11958/20201912 Abstract ( 846 )   PDF (1165KB) ( 4333 )   Objective　To investigate the role and mechanism of abnormal expression of Survivin in the metastasis of prostate cancer (PCa). Methods　(1) The difference of Survivin mRNA expression between normal prostate tissue and PCa tissue was analyzed by TCGA database, and the lymph node metastasis, Gleason grade and prognosis were analyzed. (2) Immunohistochemical staining was used to detect the expression of Survivin protein in 15 cases of benign prostatic hyperplasia (BPH) biopsies and 60 cases of PCa biopsies, and the differences of Survivin protein expressions were compared between different clinical features of the patients. (3) The expression levels of Survivin in routine culture of human benign prostatic hyperplasia cell line BPH and human PCa cell lines LNCaP, Du-145 and PC-3 were detected by Western blot  assay. LNCaP cells were used to construct Survivin stable overexpression group (Survivin-OE) and corresponding control group (Vector). At the same time, Survivin stable knockdown group (Survivin-KD) and corresponding control group (NC) were constructed in PC-3 cells. CCK-8 proliferation assay and Transwell assay were used to detect the changes of cell invasion and proliferation after knocking-down and overexpressing Survivin. Western blot assay was used to detect the expression of Survivin, E-cadherin, N-cadherin and proteins related to TGF-β/Smad pathway such as phosphorylated Smad2/3, TGF-β1 and Smad4 in two kinds of cells. Results　(1) The results of TCGA database analysis showed that Survivin was abnormally high in prostate adenocarcinoma, and the expression levels of Survivin were higher in patients with lymph node metastasis than those in patients without lymph node metastasis (P＜0.01). The expression levels of Survivin increased with the increase of Gleason score (P＜0.01), and the progression-free survival time was significantly shorter in PCa patients with high expression of Survivin than that of patients with low expression of Survivin (P＜0.01). (2) Immunohistochemistry confirmed that the high expression ratio of Survivin protein was significantly higher in PCa samples than that in BPH tissues (60.0% vs. 26.7%, χ2=5.357, P＜0.05). The proportion of high expression of Survivin was significantly increased in patients with clinical stage T3+T4, local lymph node metastasis and distant metastasis (P＜0.05). (3) In vitro experiment results showed that Survivin levels were higher in LNCaP, DU-145 and PC-3 cells than those in BPH (P＜0.05). The overexpression of Survivin increased the proliferation and invasion ability in LNCaP cells. The expression of epithelial marker E-cadherin decreased, the expression of interstitial marker N-cadherin increased, and the expression levels of pSmad2/3, TGF-β1 and Smad4 increased after overexpressing Survivin. However, the underexpression of Survivin decreased the proliferation and invasion ability in PC-3 cells. The expression of epithelial marker E-cadherin increased, the expression of interstitial marker N-cadherin decreased and the expression levels of pSmad2/3, TGF-β1 and Smad4 decreased after knocking-down Survivin. Conclusion　Survivin is abnormally highly expressed in prostate adenocarcinoma, which can promote EMT progress to improve tumor metastasis and invasion by regulating TGF-β/Smad pathway in prostate cancer. Related Articles | Metrics

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Effects of TSA on the apoptosis of HT-22 cells in mouse hippocampal neurons under different concentrations of glucose XU Wen, XU Yong-jie, LIU Xin-lei, SHEN Jie, ZHU Ke-jing, LIN Hai-rong, LI Xing, PAN Wei 2021, 49 (4):  349-353.  doi: 10.11958/20202807 Abstract ( 951 )   PDF (846KB) ( 4734 )   Objective　To explore the effect of trichostatin A (TSA) on the apoptosis of mouse hippocampal neuron cell line HT-22 cells under different sugar concentrations. Methods　The mouse hippocampal neuron HT-22 cells in high glucose medium (glucose concentration 55 mmol/L) and normal medium (grape concentration 25 mmol/L) were cultured. The cells in high glucose medium and normal medium were divided into control group (NC group) and inhibitor group (TSA group). Cells were treated with 1 mmol/L TSA for 1, 4 and 8 h, or 0.4 mmol/L TSA for 1, 4, 8, 12, 14, 16, 20 and 24 h. The cell viability was detected by the CCK8 method after treatment. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) enzyme activities were detected by ELISA. Cell apoptosis was detected by flow cytometry. The expression levels of B lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax) and cysteine protease 3 (Caspase-3) were detected by Western blot assay. Results　The 0.4 mmol/L of TSA and 20 hours were the optimal condition for culturing HT-22 cells after testing. ELISA results showed that after treatment with TSA, HDAC significantly decreased and HAT increased significantly (P＜0.05). Flow cytometry results showed that after TSA inhibiting for 20 h, the apoptosis rate increased significantly. While TSA was added to cells under high glucose conditions, the apoptosis rate increased more. After 20 hours of TSA treatment, Bcl-2 expression was significantly down-regulated, while Caspase-3 was significantly up-regulated (P＜0.05). Conclusion　TSA may increase the level of histone acetylation by inhibiting HDAC, which could lead to the apoptosis of mouse neuronal cells HT-22. Related Articles | Metrics

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Experimental study of lncRNA FOXCUT regulating Notch pathway to inhibit proliferation and invasion of colon cancer cells SHE Ming-hao, LIU Han-song, YANG Wen-hui, YU Yang, ZHANG Lei 2021, 49 (4):  354-358.  doi: 10.11958/20202872 Abstract ( 929 )   PDF (658KB) ( 4512 )   Objective　To study the effect of long non-coding RNA (lncRNA) FOXC1 promoter upstream transcript (FOXCUT) on the proliferation and invasion of colon cancer cell (HCT116) and its mechanism. Methods　 HCT116 cells transfected with FOXCUT siRNA were used as FOXCUT siRNA group. The transfection-negative interfering RNA was used as the negative control group (FOXCUT siRNA-NC group), and the untransfected group was used as the normal control group (NC group). The qPCR method was used to determine the FOXCUT interference effect and to detect the mRNA expression levels of FOXCUT in colon cancer and adjacent tissues, human colon cancer (SW480, SW620, HCT116, HT29) and human normal colon epithelial cells (NCM460). The effects of silencing FOXCUT on the proliferation and the invasion of HCT116 cells were detected by Cell Counting Kit-8 (CCK-8), colony forming assay and Transwell assay. qPCR was used to detect the mRNA expressions of Notch1 and Hes1 in HCT116 cells after FOXCUT silencing, and Western blot assay was used to detect the protein expressions of Notch1 and Hes1 in HCT116 cells. Results　Compared with adjacent tissues, the expression level of FOXCUT mRNA increased significantly in colon cancer tissues (P＜0.01). Compared with NCM460 cells, the FOXCUT mRNA expression levels increased significantly in colon cancer cell lines SW480, SW620, HCT116, and HT29 (P＜0.05), and the expression level was the highest in HCT116 cells. Compared with the FOXCUT siRNA-NC group, the FOXCUT mRNA expression levels were significantly reduced in HCT116 cells of the FOXCUT siRNA group (P＜0.01). There was no significant difference in the FOXCUT mRNA expression level in the HCT116 cells between the NC group and FOXCUT siRNA-NC group (P＞0.05). The silencing FOXCUT could significantly inhibit the proliferation and invasion of HCT116 cells (P＜0.05), and inhibit the mRNA and protein expressions of Notch1 and Hes1 in HCT116 cells (P＜0.01). Conclusion　Silencing FOXCUT can inhibit the proliferation and invasion of HCT116 cells, which may be related to the inhibition of Notch pathway. Related Articles | Metrics

Experimental Study

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The effect of G6PD inhibitor on the proliferation of mouse airway Club cells GENG Bei, LI Kuan, , WU Qi, △, LI Shuang-yan, CHEN Huai-yong, , 2021, 49 (4):  359-363.  doi: 10.11958/20203446 Abstract ( 901 )   PDF (563KB) ( 4889 )   Objective　To evaluate the effect of 6-AN, an inhibitor of G6PD, on the proliferation of mouse airway Club cells. Methods　The C57BL/6 mice were randomly divided into control group and asthma group. The asthma group were induced to develop asthma by intraperitoneal injection and then nebulized aspiration of OVA. Samples of lung tissues were harvested for immunostaining after successful modeling. The fraction of Ki67+CCSP+ cells in total CCSP+ cells of lung tissues were quantified. Mouse airway Club cells were isolated from lungs by fluorescent activated cell sorting. Real-time PCR was conducted to analyze mRNA expression of glucose-6-phosphate dehydrogenase X-linked (G6pdx) in mouse airway Club cells. Organoid culture model was used to culture Club cells with 6-AN (0, 10 μmol/L). Organoid cultures were imaged with inverted microscopy at day 8 after seeding. The number of colonies and colony size were analyzed. Results　Compared to the control mice, the fraction of Ki67+CCSP+ over CCSP+ cells was higher in the asthma group (P＜0.01). The G6pdx mRNA expression was elevated in Club cells isolated from asthma group relative to the control group (P＜0.01). The number of colonies and average colony size were significantly decreased in 10 μmol/L 6-AN treatment groups compared with those of 0 μmol/L group (P＜0.01). Conclusion　The 6-AN, an inhibitor of G6PD can inhibit the proliferation of mouse airway      Club cells. Related Articles | Metrics

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The protective effect of anisodamine on acute renal injury induced by rhabdomyolysis in rats AN Li-ping, WANG Wei, YANG Hong-xia, AN Ran, YU Kun, WU Guang-li, LI Yun-feng 2021, 49 (4):  364-370.  doi: 10.11958/20202268 Abstract ( 854 )   PDF (1058KB) ( 4399 )   Objective　To observe the effect of anisodamine on the expressions of lysosome associated membrane protein-2 and cathepsin B in acute renal tubular epithelial cells induced by inrhabdomyolysis in rats and explore the mechanism. Methods　Sixty-three male Sprague-Dawley rats were randomly divided into control group, model group and administration group. The rat model of acute kidney injury induced by rhabdomyolysis was established by glycerol intramuscular injection in the model group and the administration group, while the administration group was given anisodamine by intraperitoneal injection (1 mg/kg) before the initial glycerol injection. At different time points after glycerol injection, HE staining was used to observe the pathological changes of kidney tissues. The renal function indicators including serum urea nitrogen (BUN), serum creatinine (Scr), creatine kinase (CK) and serum myoglobin (Mb) were measured. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in kidney tissues were detected. After acute kidney injury was induced by intramuscular injection of glycerol for 24 h, the expressions of LAMP2, Cathepsin B and Megalin in kidney tissues were detected by immunohistochemistry and Western blot assay. Results　HE staining indicated that the rats in the model group had obvious kidney injury. However, anisodamine significantly ameliorated kidney injury. The serum BUN levels of 12 h and 24 h, Scr of 24 h and 48 h, CK of 6 h, and Mb of 24 h were significantly higher in model group than those of the control group (P＜0.05). In contrast, all of these markers at the corresponding time points were significantly ower in anisodamine administration group than those of the model group (P＜0.05). In comparison to the model group, the MDA content was significantly decreased at 6 h and 12 h in the administration group (P＜0.05), while SOD activity was significantly increased (P＜0.05). In addition, the results of immunohistochemistry and Western blot assay showed that the expression levels of LAMP2, Cathepsin B and Megalin at 24 h were significantly higher in the model group than those of the control group and the administration group. However, the expression levels of these proteins in the administration group were significantly lower than those in the model group (P＜0.05). Conclusion　Anisodamine could perform a protective role to kidney by reducing the production of Mb, down-regulating the expressions of LAMP2 and Cathepsin B in renal tissues and restraining oxidative stress. Related Articles | Metrics

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The protective effect and mechanism of Xyloketal B on seizure-induced brain damage in developing rats#br# CHEN Fen-fang, HU Qing-peng 2021, 49 (4):  371-377.  doi: 10.11958/20202542 Abstract ( 571 )   PDF (1400KB) ( 4177 )   Objective　To explore the protective effect of marine natural product Xyloketal B (Xyl-B) on brain damage after seizure in developing rats and its regulation on oxidative stress pathway. Methods　Forty SD rats on the 20th day were randomly divided into 4 groups, control group, KA group, KA+Xyl-B (25 mg/kg) group and KA+Xyl-B (50 mg/kg) group. The rat seizure model was constructed through intraperitoneal injection of kainic acid. The control group was injected with saline only. In KA+Xyl-B group, Xyl-B was administered intraperitoneally 2 hours before KA induced seizure. Rats were sacrificed 24 hours after seizure, hippocampal tissue was separated. The number of mature neurons and activated astrocytes were detected by immunofluorescence. The mRNA and protein expression levels of Keap1, Nrf2, HO-1, NQO1, caspase3, Bcl-2 and IL6 were detected by qPCR and Western blot assay, respectively. Results　The immunofluorescence results showed that the number of neurons decreased significantly and the activated astrocytes increased significantly in the KA group compared with those of the control group. Xyloketal B treatment can increase the number of mature neurons and  the activated astrocytes. Compared with the control group, the mRNA and protein expression levels of Keap1 increased significantly, while the expression levels of Nrf2, HO-1 and NQO1 were significantly reduced. Xyloketal B treatment could reverse the mRNA and protein levels after KA-induced seizure. The mRNA and protein expression levels of caspase3 and IL-6 increased significantly, Bcl-2 decreased significantly in the KA group (P＜0.05). Xyloketal B treatment (50 mg/kg) can inhibit the expression levels of caspase3 and IL-6 and increase the expression of Bcl-2, which showed a better therapeutic effect than those of Xyl-B (25 mg/kg). Conclusion　Xyloketal B can activate the Nrf2 anti-oxidative stress pathway, inhibit the activation of astrocytes, inflammatory response and the expression of apoptosis protein, increase anti-apoptosis protein and surviving neurons, and thus play a protective role against brain damage after seizure. Related Articles | Metrics

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The experimental study on astragaloside Ⅳ regulating mitochondrial autophagy to reduce myocardial toxicity induced by 5-Fu in aging rats LI Yuan-yang, , ZHOU Xiang-zhong, LEI Xiang-hong, ZHANG Yu-fan, , XU Yue, , WEI Li-ping△ 2021, 49 (4):  378-384.  doi: 10.11958/20202229 Abstract ( 846 )   PDF (1216KB) ( 4417 )   Objective　To investigate the effect and mechanism of astragaloside Ⅳ (AS-Ⅳ) regulating autophagy to reduce 5-fluorouracil (5-Fu) induced myocardial toxicity based on PINK1/Parkin signaling pathway in the rats. Methods　Thirty-six male SD rats aged 18 months were divided into control group, model group and AS-Ⅳ group by random number table method, with 12 rats in each group. The rat model was administered the intraperitoneal injection of 30 mg/kg 5-Fu every other day for 7 times. The intervention group was administered the intragastrical 20 mg/kg AS-Ⅳ diluent every day for 14 times. The serum levels of troponin I (cTnI), creatine kinase isoenzyme (CK-MB), myocardial mitochondrial ATP and membrane potential were measured. HE and Masson staining were used to evaluate the pathological changes of myocardium. The expression of microtubule-associated protein (LC3Ⅱ) was evaluated by immunofluorescence. The ultrastructure of mitochondria was observed under electron microscope. The protein expressions of PINK1/Parkin pathway (key molecules PINK1, Parkin, Beclin1, LAMP and LC3) were detected by Western blot assay. Results　Compared with the model group, AS-Ⅳ could slow down the weight loss (P＜0.05), reduce the secretion of myocardial enzyme cTnI and CK-MB (P＜0.05) and inhibit the decrease of mitochondrial ATP levels (P＜0.05). Compared with control group, the myocardial fibers were disorderly arranged and a large number of blue collagen fibers were deposited in the model group. After the intervention of AS-Ⅳ, the collagen volume fraction decreased in the model group (P＜0.05). Electron microscopy and LC3Ⅱ fluorescence labeling showed that after AS-Ⅳ intervention, the degree of mitochondrial damage was reduced and the expression of LC3Ⅱ was decreased (P＜0.05). Western blot results indicated that Beclin1, PINK1, Parkin, LAMP and LC3Ⅱ/Ⅰ expression levels were significantly reduced (P＜0.05). Conclusion　The 5-Fu induces myocardial mitochondrial injury and excessive cardiac mitochondrial autophagy, and AS-Ⅳ alleviates it by regulating autophagy 5-Fu myocardial toxicity.  Related Articles | Metrics

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CD137-CD137L signaling promotes angiogenesis in atherosclerosis plaque of mice through activating TNF receptor associated factor 6 WENG Jia-yi, YIN Yun-jie, MA Xue-xing, LI Yuan, CHEN Lu, HE Hong-tao, XU Gui-dong, SUN Kang-yun 2021, 49 (4):  384-389.  doi: 10.11958/20202041 Abstract ( 712 )   PDF (599KB) ( 4318 )   Objective　To explore whether CD137-CD137L signaling pathway can promote angiogenesis in atherosclerosis plaque via activating TNF receptor associated factor 6 (TRAF6). Methods　Endothelial cells (bEnd.3) and the aortic rings from male mice were divided into the following groups: control group (with 10 μg/L TNF-α in culture medium), IgG isotype control group (with 10 μg/L TNF-α+5 mg/L IgG2b in culture medium) and CD137 activated group (with 10 μg/L TNF-α+5 mg/L CD137 antibody in culture medium). Small interfering RNA (siRNA) oligonucleotide was used for TRAF6 gene knockdown in MBVEC and the aortic rings, which were divided into two groups: control siRNA group (control siRNA transfected) and TRAF6 siRNA group (TRAF6 siRNA transfected). Western blot assay was used to determine protein expressions of TRAF6, Smad1/5 and VEGF. Transwell assay was used to observe the migration ability of endothelial cells. Matrigel tube formation was used to test the tube formation ability of endothelial cells and the mouse aortic rings. Angiogenesis assay were used for detecting the aortic ring microangiogenesis. Results　The expression levels of mRNA and protein of TRAF6 and VEGF were significantly higher in CD137 activated group than those in IgG isotype control group and  control group (both in the endothelial cells and aortic rings, P＜0.05). The expression levels of mRNA and protein of TRAF6 and Smad1/5 were significantly lower in TRAF6 siRNA group than those in control siRNA group in endothelial cells and aortic rings. Migration cell number was remarkably lower in TRAF6 siRNA group than that in control siRNA group. Values of the formation of the tube lengthand branch number were both significantly lower in TRAF6 siRNA group than those in control siRNA group. The numbers of microvessels outgrowth were dramatically reduced in aortic rings in control siRNA group (P＜0.05). Conclusion　CD137-CD137L signaling pathway can promote angiogenesis in atherosclerosis plaque by activating TRAF6. Related Articles | Metrics

Clinical Study

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Changes of serum nociceptin/orphanin FQ and lipoprotein‐associated phospholipase A2 levels in diabetic patients with silent myocardial ischemia XIE Meng-li, SU Jing, LI Jing, HAN Yi 2021, 49 (4):  390-395.  doi: 10.11958/20203430 Abstract ( 889 )   PDF (469KB) ( 4495 )   Objective　To observe the changes of serum endogenous nociceptin/orphanin FQ (N/OFQ) and serum lipoprotein-associated phospholipase A2 (Lp-PLA2) levels in diabetic patients with silent myocardial ischemia (SMI), and to explore its significance. Methods　A total of 120 diabetes patients underwent coronary angiography were included in this study. Patients were divided into simple type 2 diabetes group (D group, n=60) and type 2 diabetes with SMI group (DS group, n=60). Clinical data of both groups were collected. The levels of fasting blood glucose (FBG), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum N/OFQ and Lp-PLA2 were detected. The differences of serum N/OFQ and Lp-PLA2 levels were compared between the two groups. The risk factors of type 2 diabetes with SMI and the correlation between     N/OFQ, Lp-PLA2 and various indicators were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the predictive values of N/OFQ and Lp-PLA2 for type 2 diabetes with SMI. Results　The diabetes course, FBG, TG, LDL-C, serum N/OFQ and Lp-PLA2 levels were significantly higher in DS group than those in D group, and the HDL-C level was significantly lower in DS group than that in D group (P＜0.01). Multiple Logistic regression analysis showed that the increased serum levels of FBG, TG, LDL- C, N/OFQ and Lp-PLA2 were the risk factors of diabetic patients with SMI (P＜0.05). The serum levels of N/OFQ and Lp-PLA2 were positively correlated with FBG, LDL-C, and Gensini score in DS group. The diabetes course, HbA1c and serum N/OFQ levels were positively correlated. There was no significant correlation between diabetes course, HbA1c and serum Lp-PLA2 levels. The serum N/OFQ and Lp-PLA2 levels were positively correlated. ROC curve analysis results showed that the areas under the curves of N/OFQ, Lp-PLA2 and combined predictors predicting the occurrence of diabetes with SMI were 0.949, 0.899 and 0.956 (P＜0.01). Conclusion　The serum levels of    N/OFQ and Lp-PLA2 are higher in patients with diabetes and SMI. N/OFQ and Lp-PLA2 are closely related to the occurrence of diabetes and SMI. Related Articles | Metrics

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The relationship between smoking and the severity of coronary lesions in male patients≤45 years old with premature myocardial infarction YANG Ya-nan, GAO Jing, LI Xiao-wei, MA Jing, XIAO Jian-yong, GAO Ming-dong, LIU Yin 2021, 49 (4):  396-400.  doi: 10.11958/20202917 Abstract ( 732 )   PDF (625KB) ( 4302 )   Objective　To explore the relationship between smoking and the severity of coronary lesions in male patients ≤45 years old with premature myocardial infarction (PMI). Methods　Two hundred and eighty three male patients ≤45 years old with initial acute myocardial infarction (AMI) and underwent coronary angiography were included in the study. Patients were divided into two groups according to smoking status. The clinical baseline data were compared between the two groups, and binary Logistic regression model was used to analyze the correlation between smoking and SYNTAX score and the severity of coronary lesions. Results　A total of 283 cases were enrolled, and 232 patients (82.0%) were smokers. The leukocyte count, triglyceride (TG), very low density lipoprotein cholesterol (VLDL-C) and lipoprotein(a) were significantly higher in the smoking group than those in the non-smoking group (P＜0.05). SYNTAX score was significantly higher in the smoking group than that in the non-smoking group (P＜0.05). In patients with coronary single-vessel lesion and patients with multi-vessel lesions, the proportion of severe stenosis was significantly higher in smoking group than that in non-smoking group (P＜0.05). Logistic regression analysis showed that after adjusting confounding factors, patients in the smoking group faced a higher risk of a mid-high SYNTAX score (≥23, OR=3.000, 95%CI: 1.152-7.811) and coronary multi-vessel severe stenosis (OR=2.275, 95%CI: 1.098-4.713). Conclusion　Smoking is related with the severity of coronary lesions in male patients ≤45 years old with PMI, which significantly increases the risk of the mid-high SYNTAX score and coronary multi-vessel severe stenosis.  Related Articles | Metrics

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The correlation analysis of inter-arm difference in systolic blood pressure and #br# ankle-brachial index#br# LI Lu, WANG Jian-li, WANG Dan, ZHAO Xiu-juan, WANG Na, WU Shou-ling, CHEN Shuo-hua△ 2021, 49 (4):  401-405.  doi: 10.11958/20202531 Abstract ( 529 )   PDF (393KB) ( 3951 )   Objective　To investigate the relationship between systolic pressure difference between arms (sIAD) and ankle-brachial index (ABI). Methods　A cross-sectional study was conducted to select the subjects who participated in the 2010 and 2018 annual physical examination of Kailuan Group and completed the measurement of arteriosclerosis. Epidemiological data were collected by questionnaire, and total cholesterol, triglyceride, fasting blood glucose, high density lipoprotein cholesterol and low density lipoprotein cholesterol were detected on the day of physical examination. Both arm systolic blood pressure values and ankle-brachial index (ABI) were collected using the Omron arteriosclerosis detector. Multiple linear regression analysis was used to analyze the relationship between the sIAD and ABI in the total population, different gender and different age groups. Results　A total of 48 976 patients were included in the statistical analysis. In the general population, different gender groups (male group and female group), people of different ages (＜60 years old group and ≥60 years old group), and adjustment for age, gender, systolic blood pressure, body mass index (BMI), fasting glucose, three acyl glycerin, total cholesterol, smoking, drinking, exercise, sIAD and ABI values were negatively correlated (P＜0.05). It was found that ABI decreased by 0.006 for every 1 mmHg increase in sIAD in the total population. ABI decreased by 0.006 and 0.005 for every 1 mmHg increase in sIAD in different gender groups (male and female). ABI decreased by 0.006 and 0.005 (＜60 years old group and ≥60 years old group) for every 1 mmHg increase in sIAD in different age groups. Conclusion　sIAD is negatively associated with ABI, and the increased sIAD is a risk factor for ABI decline. Related Articles | Metrics

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Relationship between FOSL2 DNA methylation level and insulin resistance and islet β cell secretion function in type 2 diabetes mellitus of Xinjiang Uygur nationality HOU Ze-xin, LI Si-yuan, CAO Guo-lei, HU Ying, WANG Tong-yao, LI Jun 2021, 49 (4):  406-409.  doi: 10.11958/20202810 Abstract ( 1015 )   PDF (361KB) ( 4362 )   Objective　To investigate the relationship between FOSL2 DNA methylation level and insulin resistance and islet β cell secretion function in type 2 diabetes mellitus of Xinjiang Uygur nationality. Methods　A total of 100 Uygur patients in the department of endocrinology and metabolism were selected as normal control group (NC group, n=50) and type 2 diabetes group (T2DM group, n=50). Biochemical indicators such as fasting plasma glucose (FPG), triglyceride (TG) and fasting serum insulin (FINS) were measured. DNA methylation level of FOSL2 was detected by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The homeostatic model assessment index of insulin resistance (HOMA-IR) was evaluated by steady-state model. The correlation between indicators was analyzed by Spearman method, and influencing factors of insulin resistance and the secretory function of pancreatic β cells were analyzed by multiple stepwise linear regression. Results　Compared with NC group, body mass index (BMI), FPG, glycosylated hemoglobin (HbA1c), low density lipoprotein cholesterol (LDL-C), TG, total cholesterol (TC), FINS and HOMA-IR increased and high density lipoprotein cholesterol (HDL-C), homeostatic model pancreatic β cell function (HOMA-β), homeostasis model insulin sensitivity index (HOMA-ISI) decreased in T2DM group. The methylation levels of 8 cytosine-phosphor-guanine (CpG) units were increased in the T2DM group. The results of correlation analysis showed that methylation levels of 6 CpG units in FOSL2 DNA were positively correlated with HOMA-IR and negatively correlated with HOMA-ISI. The methylation levels of 4 CpG units were positively correlated with BMI and negatively correlated with HOMA-β. The results of regression analysis showed that the increased methylation level of CpG 12.13.14 was the influencing factor for the decrease of HOMA-ISI, HOMA-β and the increase of HOMA-IR. The increased methylation level of CpG 15.16.17 was the influencing factor for the increase of BMI. Conclusion　FOSL2 may be involved in insulin resistance and pancreatic β cell secretion defect in Uyghur T2DM through the elevated DNA methylation level, thus leading to the occurrence and development of T2DM. Related Articles | Metrics

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The relationship between changes of peripheral blood inflammatory markers and cognitive function in elderly patients with stroke sequelae and periodontitis FU Xiao-yan, WANG Xiao-li 2021, 49 (4):  410-414.  doi: 10.11958/20203134 Abstract ( 744 )   PDF (381KB) ( 4129 )   Objective　To explore the changes of peripheral blood inflammatory markers in elderly patients with stroke sequelae and periodontitis and the correlation with their cognitive function. Methods　A total of 68 elderly patients with chronic stroke and periodontitis were selected. All of the patients received standard treatment for periodontitis. According to whether periodontitis persisted after 6 months of treatment, the patients were divided into periodontitis present group (n=33) and cure group (n=35). The serum levels of C-reactive protein (CRP), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), MMSE score and ADAS-cog score before and after treatment were compared between the two groups. The correlation between the variation values of CRP, IL-10, TNF-α and the variation values of MMSE score, ADAS-cog score before and after treatment were explored by Spearman correlation analysis. The influencing factors of the variation values of MMSE score, ADAS-cog score before and after treatment were explored by multiple linear regression analysis. Results　After 6 months of treatment, the levels of CRP, IL-10 and TNF-α were significantly higher in the periodontitis present group than those in the cure group (P＜0.05). Compared with before treatment, after 6 months of treatment, the levels of CRP, IL-10 and TNF-α were significantly increased in the periodontitis present group, while CRP was significantly decreased in the cure group (P＜0.05). After 6 months of treatment, MMSE score and ADAS-cog score were significantly lower in the periodontitis present group than those in cure group (P＜0.05). Compared with before treatment, after 6 months of treatment, MMSE score and ADAS-cog score were significantly decreased in the periodontitis present group (P＜0.05). Spearman correlation analysis showed that the variation values of CRP, IL-10, TNF-α were negatively correlated with the variation values of MMSE score and ADAS-cog score. Multivariate linear regression analysis showed that persistent periodontitis was the independent influencing factor for the variation values of MMSE score and ADAS cog score before and after treatment (P＜0.05). Conclusion　Periodontitis is associated with the further decline of the cognitive function in elderly patients with stroke sequelae, which possibly through the effects of systemic inflammation. Related Articles | Metrics

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The effect of oral dydrogesterone on frozen-thawed embryo transfer in hormone replacement cycle#br# NI Jin-lian, PENG Xuan 2021, 49 (4):  415-418.  doi: 10.11958/20202778 Abstract ( 1498 )   PDF (383KB) ( 4248 )   Objective　 To investigate the effect of oral dydrogesterone alone on endometrial transformation and luteal support in hormone replacement cycles of frozen thawed embryo transfer (FET). Methods　 Two hundred patients under the age of 35 years who underwent FET for the first time after whole embryo freezing for various reasons were randomly selected and divided into control group and observation group with 100 cases for each group. All enrolled patients underwent endometrial preparation with hormone replacement cycles, and endometrial transformation was performed when the endometrial thickness was ≥ 8 mm and serum estradiol (E2) ≥ 549 pmol/L. The observation group received dydrogesterone   20 mg/time, twice/d orally only. The control group received dydrogesterone (10 mg/time, twice/d) orally + vaginal plug by placing progesterone vaginal sustained-release gel 90 mg/d. The cleavage stage embryo transfer was performed 3 d after the conversion of endo-metrium and 5 d after the blastocyst transfer in the 2 groups of patients. From the day of transplantation until 14 days after transplantation, the observation group continued to take oral dydrogesterone tablets 40 mg/d alone, and the control group continued with oral dydrogesterone 20 mg/d + vaginal plugs placed with progesterone vaginal sustained release gel 90 mg/d for luteal support. If the patient was pregnant, luteal support was maintained until 60 days after transplantation. The implantation rate, clinical pregnancy rate, early pregnancy loss rate, satisfaction with medication, adverse drug reactions and cost of medication were compared between the 2 groups. Results　 The implantation rates of patients in control and observation groups were 50.98% (78/153) and 49.34% (75/152), clinical pregnancy rates were 67.00% (67/100) and 65.00% (65/100), and early pregnancy abortion rates were 8.96% (6/67) and 9.23% (6/65), respectively, with no significant differences between the 2 groups. The medication satisfaction was significantly higher in observation group than that of the control group, and the medication cost was significantly lower in observation group than that of the control group (P < 0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups. Conclusion　 In FET with hormone replacement cycle, endometrial transformation and luteal support with oral dydrogesterone alone are safe and effective, which is worthy of clinical promotion and application. Related Articles | Metrics

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Changes of serum platelet reactive protein-1 level and its clinical significance in patients with knee osteoarthritis  WANG Wei-wei, YIN Xiang-yun, SHAO Yi-ming, SUN Jian-sheng, LIAN Hong-kai△ 2021, 49 (4):  419-423.  doi: 10.11958/20203444 Abstract ( 982 )   PDF (422KB) ( 4152 )   Objective　To explore the serum expression of thrombospondin-1 (TSP-1) and clinical significance in patients with knee osteoarthritis. Methods　A total of 186 patients with knee osteoarthritis were selected. According to KL classification, the patients were divided into KL 0 group (n= 44), KLⅠgroup (n= 52), KLⅡgroup (n=39), KL Ⅲ group (n= 28) and KL Ⅳ group (n=23). The control group were included 170 healthy people in our hospital. The serum level of TSP-1 was detected by enzyme-linked immunosorbent assay (ELISA), and the correlation between TSP-1 and the severity and clinical indicators of osteoarthritis was analyzed. The subject performance characteristic curve (ROC) was drawn to obtain the optimal threshold value of TSP-1 to predict osteoarthritis. Results　The serum level of TSP-1 was significantly higher in osteoarthritis group than that in control group (P＜0.05). Compared with patients of KL 0 group, the serum TSP-1 levels were significantly higher in KLⅠ, KL Ⅱ, KL Ⅲ and KL Ⅳ groups (P＜0.05). Compared with patients of KLⅠgroup, the serum TSP-1 levels were significantly higher in patients of KL Ⅲ and KL Ⅳ groups (P＜0.05). Compared with patients of KLⅡ and KLⅢgroups, the serum TSP-1 levels were significantly higher in patients of KLⅣgroup (P＜0.05). The serum TSP-1 level was positively correlated with erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-13 (MMP-13) and transforming growth factor-β1 (TGF-β1) levels. The ROC results showed that the optimal threshold of serum TSP-1 for the diagnosis of osteoarthritis was 250.9 μg/L (sensitivity=81.1%, specificity=81.9%). Conclusion　The serum level of TSP-1 is abnormally high in patients with osteoarthritis, which is closely related to the severity of osteoarthritis. Related Articles | Metrics

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The effect of caffeine citrate on prevention of retinopathy of prematurity LU Zhen-qi, GAO Ping-ming, LIU Li-jun 2021, 49 (4):  423-426.  doi: 10.11958/20200578 Abstract ( 735 )   PDF (389KB) ( 4448 )   Objective　To investigate the effect of caffeine citrate on the prevention of retinopathy in prematurity (ROP). Methods　A total of 148 premature infants (gestational age from 24 to 32 weeks) admitted to Foshan Maternity and Child Healthcare Hospital Affiliated to Southern Medical University were included and randomly divided into study group (71 cases) and control group (77 cases). Both groups were given regular treatment of premature infants. At the same time，the study group was given caffeine citrate 20 mg/kg intravenous drip (time > 30 min). After 24-h interval, 5 mg/(kg·d) was given intravenously as maintenance dose. If apnea still occurred during the course of treatment, 10 mg/(kg·d) maintenance dose was given, and physical stimulation, oxygen therapy and respiratory support were given to promote the recovery of spontaneous breathing until the gestational age was corrected to 37 weeks or they discharged from hospital. The serum levels of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) were detected by enzyme-linked immunosorbent assay (ELISA) at the first week after birth and 36 weeks of corrected gestational age. Fundus screening was started at 4 weeks after birth or 32 weeks of corrected gestational age, and the incidence of ROP was counted. Results　At the first week after birth, the levels of IGF-1 and VEGF were significantly higher in the study group than those in the control group (P＜0.05). At 36 weeks of corrected gestational age, the serum levels of IGF-1 and VEGF were significantly increased in the control group, while the serum levels of IGF-1 and VEGF had no significant changes in the study group. The serum levels of IGF-1 and VEGF were lower in the study group than those in the control group (P＜0.05). Compared with the control group, the total incidence rate of ROP [11.3% (8/71) vs. 46.8% (36/77)] and the incidence rate of severe ROP [Ⅲ-Ⅴ period, 1.4% (1/71) vs. 13.0% (10/77)] were significantly lower in the study group (P＜0.05). Conclusion　Caffeine citrate has a positive effect on the prevention of ROP and can reduce the incidence rate of severe ROP. Related Articles | Metrics

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A preliminary comparative study of PET/CT and PET/MR in the diagnosis of intracranial tumors WANG Jia, XU Yuan-fan, GONG Jian, LI De-peng, ZHANG Xiao-hong 2021, 49 (4):  427-431.  doi: 10.11958/20202825 Abstract ( 850 )   PDF (565KB) ( 4304 )   Objective　To compare the differences between PET/CT and integrated PET/MR in the diagnosis of intracranial tumors, and the effects on clinical  therapy strategy. Methods　Thirty-two patients with intracranial tumors detected by sequentially 18F-FDG PET/CT imaging and PET/MR intracranial imaging on the same day were enrolled. Pearson correlation analysis, Bland-Altman analysis and t test were used to compare the maximum standard uptake value (SUVmax) and target area/back ground ratio (T/B) of PET/CT and PET/MR. With reference to the pathological and follow-up results, the χ2 test was used to compare the differences in detection rates of PET/CT and PET/MR. Results　A total of 78 lesions (32 patients) were confirmed by pathology or clinical follow-up including 10 glioma, 11 lymphoma, 55 metastases, 1 meningiomas and 1 pituitary tumor. All lesions were benign. PET/MR found 31 more lesions compared with PET/CT, and there was a significant difference between them (χ2=40.266，P＜0.01). In the 78 lesions, the 18F-FDG uptake of 40 lesions were significantly higher than intracranial parenchyma, with good agreement in SUVmax-MR and SUVmax-CT (r=0.799，P＜0.05). For other 38 lesions with comparable or lower uptake of intracranial parenchymal, PET/MR detected 28 more lesions than PET/CT, and the detection rate was statistically significant (χ2=44.335, P＜0.01). There were 36 lesions with obvious edema found in both examinations (χ2=2.060，P＞0.05), although 3 only found edema with no clear lesions in PET/CT. Among the 42 lesions without edema, 29 more lesions were found in PET/MR, which was significant compared with that of PET/CT (χ2=44.290， P＜0.01). For 62 lesions with Dmax＜3.0 cm, 31 more lesions were detected by PET/MR than PET/CT (χ2=41.338, P＜0.01). Conclusion　The detection rate of integrated PET / MR is significantly higher than that of PET/CT. Sequentially 18F-FDG PET/CT imaging and PET/MR intracranial imaging can obviously make up the deficiency of detection rate of PET/CT for intracranial lesions, guiding clinical selection of treatment options. Related Articles | Metrics

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The comparison of efficacy between rivaroxaban and low molecular weight heparin in the treatment of central venous access device associated upper extremity deep vein thrombosis WANG Ning, GUO Zhen-jiang, ZHANG Yuan-yuan, GUO Wei, CUI Zhao-bo 2021, 49 (4):  432-435.  doi: 10.11958/20202912 Abstract ( 1334 )   PDF (404KB) ( 4266 )   Objective　To compare the therapeutic effects of rivaroxaban and low molecular heparin (LMWH) on malignant tumor complicated with central venous access device (CVAD) related upper extremity deep vein thrombosis (UEDVT). Methods　A total of 84 malignant tumor patients with CVAD related UEDVT in Harrsion International Peace Hospital were randomly divided into LMWH group (42 cases) and rivaroxaban group (42 cases). The catheter dysfunction rate, recurrent venous thromboembolism, D-dimer level and bleeding events were compared between the two groups in 90 days of follow-up. Results　There were no significant differences in the basic data between the two groups before treatment (all P＞0.05). There was no significant difference in the catheter dysfunction rate between the two groups (11.9% vs. 4.8%, χ2＝0.623, P＞0.05). Kaplan-Meier survival analysis suggested that there was no significant difference in the cumulative recurrence rate between the two groups (5.2% vs. 2.9%, Log-rank χ2=0.249, P＞0.05). There were no significant differences in d-dimer levels between the two groups before and after treatment at 1, 4, and 12 weeks (all P＞0.05). There was no significant difference in cumulative incidence of bleeding events between the two groups (7.1% vs. 12.1%, Log-rank χ2=0.574, P＞0.05). Conclusion　Rivaroxaban and LMWH have similar efficacy and safety in the treatment of malignant tumors with CVAD-related UEDVT. LMWH has poor compliance with subcutaneous injection, and rivaroxaban is easy to take orally, which can be used as the first choice. Related Articles | Metrics

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The clinical efficacy and safety of anlotinib combined with irinotecan as the second-line therapy in patients with small cell lung cancer LYU Yi-hua, ZHAO Zi-long, HUANG Ge-hong, BA Ya-er, DU Wei, GAO Hui, ZHANG Mei-yun 2021, 49 (4):  436-440.  doi: 10.11958/20202963 Abstract ( 3471 )   PDF (445KB) ( 4654 )   Objective　To observe the clinical efficacy and safety of anlotinib combined with irinotecan in the second-line treatment of small cell lung cancer (SCLC). Methods　A total of 82 SCLC patients who failed at the first-line treatment were selected as the research objects, and they were randomly divided into control group (41 cases) and study group (41 cases) according to the random number table method. The control group was treated with irinotecan, and the study group was treated with anlotinib on the basis of the control group for six courses. The disease control rate (DCR), objective remission rate (ORR), overall survival time (OS), progression free survival time (PFS) and adverse reactions were observed. The serum vascular endothelial growth factor (VEGF), pleiotropic protein (PTN) and soluble death receptor 5 (sDR5) levels were detected by enzyme-linked immunosorbent assay (ELISA) before and after treatment. Results　The ORR (53.66% vs. 31.71%, χ2=4.038) and DCR (87.80% vs. 68.29%, χ2=4.556) were significantly higher in the study group than those of the control group (P＜0.05). The median PFS in the study group was longer than that in the control group (5 months vs. 3 months, Log-rank χ2=7.752, P＜0.01), and the median OS difference was not statistically significant (9 months vs. 7 months, Log-rank χ2=3.701, P＞0.05). After treatment, the serum levels of VEGF, PTN and sDR5 were significantly lower than those of before treatment in the two groups (P＜0.05), and the levels of VEGF, PTN and sDR5 were significantly lower in the study group than those of in the control group (P＜0.05). During the treatment, there were no significant differences in the incidence of blood system, digestive system and fatigue of grade Ⅲ and above adverse reactions between the two groups (P＞0.05). Conclusion　Anlotinib combined with irinotecan as the second-line treatment for SCLC has good curative effect, can effectively reduce the serum expressions of VEGF, PTN and sDR5, and has good safety. Related Articles | Metrics

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Research progress of relaxin in atrial fibrillation LI Rui-ling, ZHAO Zhi-qiang△ 2021, 49 (4):  441-444.  doi: 10.11958/20201643 Abstract ( 600 )   PDF (368KB) ( 4263 )   Atrial fibrillation (AF) is a common persistent arrhythmia. Its mechanism is still unclear, involving electrical remodeling, structural remodeling, inflammatory response, oxidative stress and many other aspects. Recent studies on relaxin (RLX) have shown that relaxin plays an important role in the cardiovascular system. This paper summarizes the potential role of RLX in AF and its related mechanisms, which provides a new way for the prevention and treatment of AF. Related Articles | Metrics

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Research progress of cognitive dysfunction and hippocampal changes induced by ketamine abuse#br# PENG Jin-zhi, LI Xiao-dong, WANG Qian-xing 2021, 49 (4):  444-448.  doi: 10.11958/20203082 Abstract ( 615 )   PDF (400KB) ( 4701 )   As a dissociative anesthetic, ketamine is widely used in clinical surgery anesthesia. Because of its hallucinogenic effect, ketamine has been abused in different degrees aroud the world. Ketamine abuse increases the burden of family and social expenditure because it can cause many aspects of cognitive dysfunction. In view of the crucial role of hippocampus in cognitive activities, this paper reviews the relationship between cognitive dysfunction caused by ketamine abuse with the structural and functional changes of hippocampus. The aim is to provide new ideas and strategies for the prevention and treatment of cognitive dysfunction caused by ketamine abuse. Related Articles | Metrics