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    Cell and Molecular Biology
    Effects of different concentrations of minocycline on the proliferation, autophagy and apoptosis of human glioma cells and its mechanism
    HAN Li-min, YAN Wan-yue, LI Qiao-qiao, LI Ke, LIU Li, ZHAO Hai-long△
    2020, 48 (9):  801-806.  doi: 10.11958/20200238
    Abstract ( 809 )   PDF (1358KB) ( 6277 )  
    AbstractObjective To investigate the effects and mechanism of minocycline at different concentrations on the
    proliferation and apoptosis of human glioma U87 and LN229 cells. Methods (1) U87 and LN229 cells were divided into
    three groups: control group (DMSO treatment), 5 μmol/L minocycline group and 10 μmol/L minocycline group. After 72
    hours of treatment, the level of cell proliferation was detected by MTT method, the expression of autophagy LC3B was
    detected by immunofluorescence labeling and the expressions of autophagy and apoptosis-related proteins were detected by
    Western blot assay. (2) SIRT1-shRNA vector was constructed to observe the effects of different concentrations of
    minocycline on the autophagy of U87 and LN229 cells after knockdown of SIRT1 expression. Results (1) Compared with
    the control group, the MTT results showed that the proliferation of glioma cells was significantly inhibited in 5 μmol/L and 10
    μmol/L minocycline groups, and immunofluorescence staining showed that the development of autophagy labeled protein
    LC3B was increased. Western blot results showed that the level of mTOR was significantly decreased, and the levels of Atg5,
    p-AMPK α and SIRT1 were significantly increased (P0.05). Western blot assay showed that the levels of Bcl-2 and pp70s6k were significantly decreased and the activated Caspase-3 level was significantly increased in 10 μmol/L minocycline group compared with those of control group (P0.05), but there were no significant changes in the levels of Bcl-2 and pp70s6k proteins in 5 μmol/L minocycline group (P0.05). (2) After knocking down the expression of SIRT1, the expression
    levels of mTOR and LC3B were significantly lower in shSIRT1 group than those of control group, while after minocycline
    treatment, the expression of mTOR increased significantly, while the expression level of LC3B only partially recovered.
    Conclusion Minocycline of 5 and 10 μmol/L can effectively inhibit the growth of human glioma U87 and LN229 cells,
    which may be related to the AMPK/SIRT1 pathway induced cell autophagy and p70s6k/Bcl-2 pathway induced apoptosis.

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    Effects and mechanism of apatinib on the proliferation of HCT116 inhibited by p53
    YANG Han-lin, TANG Hong-ting, YANG Juan, LIU Hong-lin, LI Meng-xing, LI Qin-shan, △
    2020, 48 (9):  807-812.  doi: 10.11958/20200157
    Abstract ( 927 )   PDF (716KB) ( 5609 )  
    Abstract: Objective To investigate the inhibition effects of apatinib on human colon cancer cells HCT116 p53+/+and
    HCT116 p53
    -/-, and further explore the molecular mechanisms in vitro. Methods The gradient concentrations of apatinib
    (0, 15,30 and 60 μmol/L) were used to treat HCT116 p53
    +/+ and HCT116 p53-/- for 24 h and 48 h. The inhibitory effects of
    apatinib on the proliferation of two cell lines were detected by CCK-8. Flow cytometry (Annexin V/PI method) was used to
    detect the apoptosis rates of apatinib treated HCT116 p53
    +/+ and HCT116 p53-/-cells. The expression levels of p53, NF-κB
    p65, Caspase-3
    mRNA and protein of apatinib treated HCT116 p53+/+ and HCT116 p53-/-cells were revealed by real-time
    PCR and Western blot assay.
    Results CCK-8 results showed that apatinib could inhibit the viability of HCT116 p53+/+ and
    HCT116 p53
    -/-cells in a dose-dependent manner (P0.01). Flow cytometry results showed that after treatment with
    apatinib, the apoptosis rates of HCT116 p53
    +/+ and HCT116 p53-/-cells were increased (P0.01). Compared with HCT116
    p53
    +/+ , the pro-apoptotic effect of apatinib on HCT116 p53-/- was lower (P0.05). After treatment with apatinib, the
    expression levels of
    p53, NF- κB p65, capsase-3 mRNA and Caspase-3 protein were increased in HCT116 p53+/+ and
    HCT116 p53
    -/-cells (P0.05). After treatment with apatinib, the protein expressions of p53 and NF- κB p65 were downregulated in HCT116 p53+/+ cells, while the protein expression of NF-κB p65 was up-regulated in HCT116 p53-/- cells (P
    0.01). Conclusion Apatinib could inhibit cell proliferation and promote the apoptosis of HCT116 p53+/+ and HCT116
    p53
    -/- cells through p53/NF-κB pathway. Colorectal cancer cells may develop drug resistance to apatinib through HCT116
    p53
    -/- cells.
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    Effects of TRAP1 on proliferation and apoptosis of colorectal cancer cells
    LI Pin-yu, SHENG Wen-jie, ZHANG Yuan-yi, YANG Jian, ZHENG Pei-li, ZHANG Fei-fei
    2020, 48 (9):  813-817.  doi: 10.11958/20193099
    Abstract ( 1090 )   PDF (556KB) ( 6671 )  
    Abstract: Objective To investigate the expression of tumor necrosis factor receptor-associated protein 1 (TRAP1) in colorectal cancer and its effects on proliferation and apoptosis of colorectal cancer cells. Methods The Oncomine database was used to analyze the expressions of TRAP1 in colorectal cancer tissues and normal intestinal mucosal tissues. Western blot assay was used to detect the expressions of TRAP1 in colorectal cancer tissues and their paired paracancerous mucosa tissues, LOVO, HT29, HCT116, RKO, SW480 and NCM460 cells. CCK-8 and plate cloning assay were used to detect the effects of TRAP1 on the proliferation of colorectal cancer cells. Flow cytometry was used to detect the effects of TRAP1 on cell cycle and apotosis. The effects of TRAP1 on cell cycle-associated protein, apoptosis-related protein and PI3K/AKT pathway markers were detected by Western blot assay. Results Bioinformatics analysis showed that TRAP1 was highly expressed in colorectal cancer. Western blot results showed that the protein expression levels of TRAP1 were higher in colorectal cancer cells and tissues than those in normal tissues and cells (P<0.05). Interfering TRAP1 expression with siRNA significantly inhibited cell proliferation and clonality (P<0.05), and cells were arrested in G0/G1 phase, which increased apoptosis (P<0.01). The expression of cell cycle-associated protein CyclinD1 was decreased, the expression of apoptosis-related protein Cleaved-Casp3 was increased and the expressions of p-PI3K and p-AKT were decreased (P<0.05). Conclusion TRAP1 is highly expressed in colorectal cancer. Interfering the expression of TRAP1 can inhibit the proliferation of colorectal cancer cells and promote apoptosis by inhibiting the activation of PI3K/AKT pathway.
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    Effects and mechanism of SIRT5 on the proliferation, apoptosis and migration of colon cancer cells in high glucose environment#br#
    HE Shuai, YUE Shu-fen, ZHOU Lei, QI qi
    2020, 48 (9):  818-823.  doi: 10.11958/20193951
    Abstract ( 815 )   PDF (878KB) ( 5093 )  
    Abstract: Objective To explore the effect of Sirtuin5 (SIRT5) on the proliferation, apoptosis and migration of Lovo cells in high glucose environment and its possible mechanism. Methods Lovo cells with high expression of SIRT5 were cultured in vitro with high glucose medium (4 500 mg/L) and ordinary medium (2 000 mg/L). Lentivirus transfection experiment was performed. SIRT5-RNAi transfected with SIRT5-RNAi lentivirus was used as KD group, blank control group with no intervention was used as MOCK group, and negative control group transfected with control RNAi lentivirus was used as NC group. The cell proliferation was observed by MTT assay, apoptosis rate was determined by flow cytometry, and cell migration rate was measured by scratch test. The expressions of mammalian target of rapamycin (mTOR), hypoxia inducible factor-1α (HIF-1α), M2 pyruvate kinase (PKM2) and hexokinase2 (HK2) were detected by real-time PCR, and their protein expressions were detected by Western blot assay. Results Compared with NC and MOCK, the proliferation decreased at the 3-5 day following SIRT5 silence, the cell apoptosis rate increased and the cell migration rate decreased in KD with high glucose medium (P<0.01). The proliferation decreased at the 5-day following SIRT5 silence (P<0.05), but no significant difference in the cell apoptosis rate between KD and NC groups at the 1-4 day. The expressions of SIRT5, mTOR, HIF-1 α, PKM2, HK2 mRNA and proteins were significantly lower in KD group than those in NC and MOCK groups with high glucose medium (P<0.05). Conclusion SIRT5 promotes the development of colon cancer in high glucose environment, which may be related with the regulating glycolysis by affecting the key glucose metabolism enzymes HK2 and mTOR/HIF-1α/PKM2 signal pathway. 
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    Effects of paeonol on expressions of SP, NK1R and mast cell activation in eczema model mice
    XIAO Wei-mian, ZHA Xu-shan△, WANG You-fa
    2020, 48 (9):  824-828.  doi: 10.11958/20200896
    Abstract ( 796 )   PDF (1026KB) ( 4478 )  
    Abstract: Objective To investigate the effects of paeonol on the expressions of substance P (SP) and neurokinin 1 receptor (NK1R) and mast cell activation in eczema model mice. Methods One hundred healthy and clean grade C57BL mice were selected, and 2,4-dinitrochlorobenzene (DNCB) was applied to the insides of both ears of the mice to sensitize to establish an eczema model. After successful modeling, a random number table method was used to divide model mice into eczema model group, paeonol low (25 mg/kg), medium (50 mg/kg) and high (100 mg/kg) dose groups and positive drug (dexamethasone 0.65 mg/kg) group, 20 mice in each group. The another 20 mice were used as control group (apply the same amount of normal saline on the inner sides of both ears). Each group began to administer the drug after successful modeling.The paeonol low, medium and high dose groups and the positive drug group were intraperitoneally injected with the corresponding dose of drugs, once per day for 14 days. Control group and eczema model group were injected with the same amount of normal saline. The skin damage of eczema was observed and scored with naked eyes in ears of mice. Hematoxylin eosin staining (HE) was used to detect the pathological changes in ears of mice in each group. SP secretion was detected by ELISA method. The expressions of NK1R and Tryptase, a marker of mast cell activity in ear lesions, were detected by immunohistochemistry. Results Compared with the control group, the mice in eczema model group showed redness, keratosis scab, exudation and other damages, hyperkeratosis of epidermis, inflammatory cell infiltration of dermis and other pathological damages. The skin damage degree score, SP content, NK1R and Tryptase expression levels were increased (P<0.05). Compared with eczema model group, mice of the paeonol low, medium and high dose groups and positive drug group showed a reduced pathological damage such as redness, keratinization, inflammatory infiltration in ears, the reduced degree of skin lesion score, SP content, NK1R and Tryptase expression levels (P<0.05). Moreover, each dose group of paeonol was dose-dependent, and there was no significant difference between the high dose paeonol group and the positive drug group (P>0.05). Conclusion Paeonol may inhibit the activation of mast cells and alleviate the symptoms of eczema inflammatory damage by inhibiting the expressions of SP and NK1R in ear lesions of eczema model mice.
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    Experimental Study
    Effects of Pipa Qingfei decoction on auricular inflammation in acne model rats
    XUE Bing, REN Wei-wei, XUE Si-si, YANG Cai-rui, WANG Di, FANG Hui-min, CHENG Xiu-mei△
    2020, 48 (9):  828-833.  doi: 10.11958/20200992
    Abstract ( 842 )   PDF (841KB) ( 5642 )  
    Abstract: Objective To observe the effect of Pipa Qingfei decoction on the expressions of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interferon-gamma (IFN-γ) in the auricle of acne model rats. Methods Forty Wistar rats were randomly divided into three groups: blank group, model group, isotretinoin group and Pipa Qingfei decoction group. In addition to the blank group, the other three groups were injected Propionibacterium acnes (P.acnes, 6×107 cfu/mL) solution into the auricle skin to make the acne model of rats. After the model was established, Pipa Qingfei decoction group was administrated by gavage (11.25 g/kg), isotretinoin group was administrated by gavage (3.125 mg/kg) and the other two groups were administrated by gavage with the same dose of normal saline. After 21 days of continuous administration, the changes of the appearance and shape of the rat ear were observed. The thickness of the auricle was measured. The swelling rate of the rat auricle was calculated, and the pathological changes of the rat auricle were observed by HE staining. The serum levels of TNF-α, IL-1β and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA), and the expressions of TNF-α, IL-1β, IFN-γ and mRNA in rat auricle were detected by Western blot assay and qPCR. Results Compared with the blank group, the auricle was dark red, the hair follicle mouth was rough and dry, the skin surface was uneven, the pathological finding showed that the boundary of epidermis, dermis and subcutaneous tissue wfere fuzzy, the hair follicle epithelium and epidermis granular layer were thickened, the adjacent hair follicles expanded and fused with each other, and a large number of inflammatory cells infiltrated in the model group. Compared with the blank group, the auricle thickness and swelling rate were significantly increased in the model group (P<0.05). The TNF-α and IL-1β contents in serum and auricle tissue were significantly increased, and the IFN-γ content was significantly decreased (P<0.05). Compared with the model group, the thickness and swelling rate of auricle tissue decreased, TNF-α and 1L-1β levels in serum and auricle tissue decreased, and IFN-γ increased in isotretinoin group and loquat Qingfeiyin group (P<0.05). Compared with isotretinoin group, the thickness and swelling rate of auricle decreased, and the content of TNF-α and 1L-1β in serum and auricle tissue decreased in loquat Qingfeiyin group (P<0.05). Conclusion Loquat Qingfeiyin can inhibit the local inflammatory response of acne in rats by down regulating the expressions of TNF-α, 1L-1β and up regulating the expression of IFN-γ.
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    Effects of Jiawei Dachaihu decoction on liver injury and expressions of JNK and Bcl-2 proteins in obstructive jaundice rats#br#
    XIAO Huang-man, SHANG Hai-tao, ZHANG Jing-yu, HAO Cheng-fei, LIU Jun-jian, CHEN Shuai, ZHANG Jing-hong, LI Zhong-lian∆
    2020, 48 (9):  834-838.  doi: 10.11958/20201173
    Abstract ( 750 )   PDF (547KB) ( 4497 )  
    Abstract: Objective To investigate the effects of Jiawei Dachaihu decoction on liver injury and expressions of JNK and Bcl-2 in obstructive jaundice rats. Methods Ninety SD male rats were divided into sham operation group (group S), terrier yellow group (group O) and intervention group (group M) according to random number table method, 30 rats in each group. Group S and group O were gavaged with 10 µL/g of normal saline, group M was gavaged with 10 µL/g of Jiawei Dachaihu decoction with a crude drug amount of 1 g / mL. Each group was sampled at 3 d, 7 d and 10 d after the operation, and 10 rats were randomly taken per group at each point. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total biliary red (TBIL) were detected in the three groups. RT-PCR and Western blot assay were used to detect mRNA and protein expressions of liver tissue JNK and Bcl-2, respectively. Results The serum levels of AST, ALT and TBIL were significantly higher in group O and group M than those in group S, and which were significantly lower in group M than those of group O (P<0.05). The levels of JNK mRNA and protein were significantly higher in group O and group M than those in group S, and which were significantly lower in group M than those in group O (P<0.05). The levels of Bcl-2 mRNA and protein were significantly lower in group O and group M than those of group S (P<0.05), and which were significantly higher in group M than those of group O (P<0.05). Conclusion Jiawei Dachaihu decoction can improve liver injury and promote liver tissue repairing in rats with obstructive jaundice, which may be related to the down-regulation of JNK protein, the increase of the expression level of Bcl-2 protein, the weakening of the stress of endoplasmic reticulum and the inhibition of the apoptosis of liver cells. 
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    Experimental Study
    Study on Yinchenhao decoction regulating bile acid metabolism and intervening the mitochondrial DNA damage in liver cells of rats with obstructive jaundice
    LIU Jun-jian, , LI Zhong-lian△, SHANG Hai-tao
    2020, 48 (9):  839-842.  doi: 10.11958/20200487
    Abstract ( 902 )   PDF (430KB) ( 3953 )  
    Abstract: Objective To investigate the effect of Yinchenhao decoction on mitochondrial DNA (mtDNA) damage of hepatocytes by the regulation of bile acid metabolism in rats with obstructive jaundice. Methods A total of 54 SPF male adult SD rats were selected and divided into 3 groups randomly, including the sham operation group, the model group and the Yinchenhao decoction group. Three days after building the obstruction modeling, the model group was given a gavage of normal saline every day, while the Yinchenhao decoction group was given a gavage of Yinchenhao decoction. The observation time points of each group were the first, third, and eighth day after modeling. Six rats were killed at each rated point to detect the changes of total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), total bile acid (TBA) in blood, TBA in urine and urine volume. The relative amount of mtDNA in hepatocytes was detected by quantitative PCR. Results The content of circulating blood bile acid decreased, and the urine volume and urine bile acid increased in rats treated with Yinchenhao Decoction (P<0.05). The relative amount of mtDNA decreased in the mode group and Yinchenhao decoction group compared with that of the sham operation group. The  relative amount of mtDNA in the Yinchenhao decoction group increased on the 8th day compare with that on the 3rd day. Conclusion Yinchenhao decoction can improve the function of hepatocytes by regulating bile acid metabolism through the liver-kidney axis to reduce liver cell mtDNA damage in rats with obstructive jaundice. 
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    Clinical Study
    The diagnostic value of improved Cornell voltage for hypertensive left ventricular hypertrophy
    MIAO Yu-xia, XU Min△, ZHU Yun, WANG Xing, JIANG Shu, GE Zhi-xiang
    2020, 48 (9):  843-847.  doi: 10.11958/20200057
    Abstract ( 1060 )   PDF (470KB) ( 4415 )  
    Abstract: Objective To explore the diagnostic value of improved Cornell voltage in hypertensive patients with left ventricular hypertrophy (LVH). Methods Data of 381 patients (male 233, female 148) with hypertension were retrospectively analyzed. The different ECG indicators were collected and calculated including improved Cornell voltage (sum of the maximum S-wave or QS amplitudes in 12 leads and R amplitudes of aVL lead), SD (maximum S-wave or QS amplitude in 12 leads), Cornell voltage (sum of the amplitude of S wave of V3 lead and R wave of aVL lead) and Sokolow-Lyon voltage (sum of the amplitude of the S wave of V1 and the amplitude of R wave of V5 or V6). The left ventricular mass index (LVMI) measured by echocardiography was used as the gold standard for diagnosis of LVH. Patients were divided into no-LVH group (n=213, male 143, female 70) and LVH group (n=168, male 90, female 78). The improved Cornell voltage, SD, Cornell voltage and Sokolow-Lyon voltage were compared between the two groups. The diagnostic value of various indexes for LVH was also compared between the two groups. Results Compared with the no-LVH group, the improved Cornell voltage, SD, Cornell voltage and Sokolow-Lyon voltage were significantly higher in the LVH group (P<0.01). In male patients with hypertension, the AUC, cut-off value, sensitivity, and specificity of improved Cornell voltage for the diagnosis of hypertension with LVH were 0.810, 1.60 mV, 86.67% and 67.83%, respectively. The diagnostic efficacy of improved Cornell voltage was better than that of SD, Cornell voltage and Sokolow-Lyon voltage (Z=2.501, 2.616 and 2.650, P<0.05). In female patients with hypertension, the AUC, cut-off value, sensitivity and specificity of improved Cornell voltage for diagnosis of hypertension with LVH were 0.737, 1.45 mV, 70.51% and 68.57%, respectively. The diagnostic efficacy of improved Cornell voltage was better than that of Cornell voltage and Sokolow-Lyon voltage (Z=2.632 and 2.404, P<0.05). Stepwise Logistic regression analysis of binary classification found that improved Cornell voltage and diastolic blood pressure were independent risk factors of LVH(P<0.01). Conclusion The diagnostic value of improved Cornell voltage is better than Cornell voltage and Sokolow-Lyon voltage in hypertensive patients with left ventricular hypertrophy.
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    The role and mechanism of vitamin B2 in gastric cancer
    ZHOU Jian, TANG Chao-liang, HU Wen-jun△, TIAN Tian
    2020, 48 (9):  848-852.  doi: 10.11958/20200017
    Abstract ( 2230 )   PDF (655KB) ( 5434 )  
    Abstract: Objective To investigate the expression and biological effects of vitamin B2 in gastric cancer. Methods Thirty-nine patients with gastric carcinoma (gastric cancer group) and 40 healthy controls (control group) were collected in this study. The serum expressions of vitamin B2 were detected in the two groups. The relationship between the level of vitamin B2 and the clinical pathological characteristics of gastric cancer patients was analyzed. Human gastric cancer MGC-803 cells were cultured and treated with 0 μmol/L, 10 μmol/L, 25 μmol/L, 50 μmol/L and 100 μmol/L vitamin B2 respectively. Glucose, lactic acid and succinate dehydrogenase levels were detected by biochemical kit. The mRNA expressions of  HKⅡ, PKM2 and GLUT1 were detected by qPCR. The cell proliferation was detected by CCK-8. Moreover, the cell apoptosis was detected by flow cytometry. Results Compared with control group, the serum expression of vitamin B2 was significantly decreased in gastric cancer group (207.85 μg/L±39.71 μg/L vs. 246.07 μg/L±45.43 μg/L, P<0.05). The serum expression of vitamin B2 was related with tumor TNM staging and the differentiation degree in patients with gastric cancer (P<0.05). Compared with 0 μmol/L group, glucose consumption and lactate production were significantly decreased, while the content of succinate dehydrogenase was increased in 25 μmol/L, 50 μmol/L and 100 μmol/L groups (P<0.05). Compared with 0 μmol/L group, HKⅡ, PKM2 and GLUT1 mRNA expressions were significantly decreased in 25 μmol/L, 50 μmol/L and 100 μmol/L groups (P<0.05). Compared with the control group, the cell proliferation activities were decreased in turn in vitamin B2, Apatinib and combination groups (P<0.05). Moreover, the combination could further reduce the cell proliferation activity (P<0.05). Compared with the control group, the cell apoptosis rates were increased in turn in vitamin B2, Apatinib and combination groups (P<0.05). Conclusion The serum vitamin B2 levels decrease in patients with gastric cancer. The combination of vitamin B2 and apatinib could improve the anti-tumor effect on gastric cancer. 
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    Clinical Study
    The correlation between serum uric acid level with erectile dysfunction and vascular endothelial injury in male hypertensive patients
    XIA Da-sheng, HE Qiang, WANG Li, MAO Da-qing, XIA Wei, LU Cheng-zhi, LI Chao
    2020, 48 (9):  853-857.  doi: 10.11958/20200310
    Abstract ( 914 )   PDF (440KB) ( 4349 )  
    Abstract: Objective To study the correlation between serum uric acid level with erectile dysfunction (ED) and vascular endothelial injury in male hypertensive patients. Methods A total of 200 newly diagnosed hypertensive patients were included in the study. One hundred male hypertensive patients with ED were defined ED group (31 mild ED patients, 34 moderate ED patients and 35 severe ED patients) and 100 male hypertensive patients without ED who were matched in age were defined non-ED group according to international index of erectile function-5 (IIEF-5). Serum levels of uric acid were measured by uricase reagents. Serum nitric oxide (NO) and Endothelial nitric oxide synthase (eNOS) levels were tested by enzyme-linked immunosorbent assay. The level of plasma EMP was measured by flow cytometry. Results Serum levels of uric acid and EMP were significantly increased in severe ED patients compared with those of moderate ED patients, mild ED patients and non-ED patients. These parameters were significantly increased in moderate ED patients compared with those of mild ED patients and non-ED patients. These parameters  were significantly increased in mild ED patients compared with those of non-ED patients. While serum levels of NO and eNOS were markedly decreased in severe ED patients compared with those of moderate ED patients, mild ED patients and non-ED patients. Serum levels of NO and eNOS were markedly decreased in moderate ED patients  compared with those of mild ED patients and non-ED patients (P<0.05). Serum levels of NO and eNOS were markedly decreased in mild ED patients  compared with those of non-ED patients (P<0.05). There was a negative  correlation between uric acid and NO as well as eNOS, and a positive correlation with EMP (P<0.05) in all hypertensive patients. Uric acid was independently and positively associated with EMP in male hypertensive patients by stepwise multiple regression analysis. Logistic regresson analyses showed that serum uric acid level had independent relation with the occurrence of ED in hypertensive patients (P<0.01). Area under receiver operating characteristic curve of uric acid to predict ED was 0.785 (95%CI: 0.717-0.852, P<0.01). The optimal serum uric acid cut-point for predicting ED was 384.5 µmol/L, with a sensitivity of 90%, a specificity of 69%, a positive predictive value 74.8% and a negative predictive 87.3%. Conclusion Hyperuricemia probably influences the occurrence and development of ED in male hypertension by promoting vascular endothelial injury.
    Key words:hypertension; erectile dysfunction; uric acid; endothelium, vascular;nitric oxide;nitric oxide synthase;endothelial microparticle
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    Combined stimulation of inspiratory and expiratory muscles for pulmonary rehabilitation in stable COPD patients
    LI Bo-jun, ZHAO Xiao-yun△, HU Xiu-juan, ZHANG Li, LI Guan-hua, YANG Xue-jin, LI Yue-chuan
    2020, 48 (9):  857-861.  doi: 10.11958/20200100
    Abstract ( 877 )   PDF (395KB) ( 4587 )  
    Abstract: Objective To study the effect of external diaphragm and abdominal muscle stimulation in patients with stable chronic obstructive pulmonary disease (COPD). Methods Ninety-six COPD patients with stable COPD diagnosed according to gold 2017 standard (FEV1< 50% of the predicted value) were selected as the research objects. Patients were randomly divided into drug treatment group (n=32), diaphragm stimulation group (n=34), diaphragm and abdominal muscle stimulation group (n=30). The drug treatment group received general respiratory exercise, health education and conventional drug therapy.The diaphragm stimulation group received external diaphragm pacemaker intervention while receiving conventional medication.The diaphragm and abdominal muscle stimulation group received the diaphragm and abdominal muscle stimulation at the same time during the drug therapy.The electrical stimulation intensity was 40 Hz, treatment time was 30 minutes and the whole treatment time was 20 days. Data of lung function (FEV1, FVC, MVV, PEF), 6MWD distance and bilateral diaphragm motion were monitored after 20 days. Results After 20 days of treatment, the activity of bilateral diaphragms was higher in the diaphragm and abdominal muscle stimulation group than that in the other two groups (P<0.05).The activity of diaphragms was also higher in the diaphragm stimulation group than that in the drug treatment group (P<0.05). Five lung function indexes of FEV1, FVC,MVV,PEF, and 6MWD were better in the diaphragm and abdominal muscle stimulation group than those in the other two groups (P<0.05), and these five indexes were also better in the diaphragm stimulation group than those in the drug treatment group (P<0.05). Conclusion Combined stimulation of diaphragm and abdominal muscles in vitro can be used as a new method to improve the lung function and quality of life of COPD patients.
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    Predictive value of cervical-brain arterial stiffness in functional outcome of patients with acute ischemic stroke#br#
    HUANG Min, CHEN Ke-yu, YANG Xue-mei
    2020, 48 (9):  862-865.  doi: 10.11958/20200183
    Abstract ( 915 )   PDF (384KB) ( 5745 )  
    Abstract: Objective To investigate the predictive value of cervical-brain arterial stiffness in functional outcomes in patients with acute ischemic stroke. Methods A retrospective analysis was performed on 226 patients admitted to our hospital for acute ischemic stroke from November 2016 to November 2018. The patients were divided into good prognosis groups based on the mRS score 3 months after discharge (mRS score ≤ 2 points, 153 cases) and poor prognosis group (mRS score> 2 points, 73 cases). Ultrasound transcranial Doppler blood flow analyzer was used to measure the carotid-cerebral pulse wave velocity (ccPWV) of patients, and the differences in stroke risk factors, clinical data and stroke types were compared between the two groups. Multivariate Logistic regression analysis were used for influential factors on patients prognosis. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of ccPWV for poor prognosis of acute ischemic stroke. Results The age, the proportion of risk factors (hypertension, diabetes, smoking and coronary heart disease), the National Institute of Health Stroke Scale (NIHSS) and ccPWV were lower in poor prognosis group than those at admission. In the poor prognosis group, the difference was statistically significant (P<0.05). The area under the ROC curve of ccPWV predicting the prognosis of patients with acute ischemic stroke was 0.881, the best cutoff value was 6.79 m/s, the sensitivity was 83.84%, and the specificity was 76.69%. The results of multivariate Logistic regression analysis showed that the NIHSS score was ≥6 points (OR=6.588, 95%CI: 2.197-15.342), ccPWV≥6.79 m/s (OR=2.638, 95%CI: 1.367-5.647), hypertension (OR=2.146, 95%CI: 1.079-3.254), diabetes (OR=2.014, 95%CI: 1.403-5.341), coronary heart disease (OR=5.349, 95%CI: 3.246-18.298), and age≥70 years (OR=2.341, 95%CI: 1.579-6.241) were independent risk factors for poor prognosis in patients with acute ischemic stroke. Conclusion ccPWV≥6.79 m/s indicates poor prognosis in patients with acute ischemic stroke.
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    The effect of hypoxic preconditioning before one-lung ventilation on oxygenation in patients with pulmonary lobectomy#br#
    2020, 48 (9):  866-870.  doi: 10.11958/20200411
    Abstract ( 758 )   PDF (421KB) ( 4077 )  
    Abstract: Objective To investigate the effect of hypoxic preconditioning (HPC) before single-lung ventilation on oxygenation in patients with pulmonary lobectomy. Methods Fifty-eight patients who underwent elective lobectomy in our hospital were selected in this study. Patients were divided into treatment group (group P) and control group (group N) according to the random number table, with 29 cases in each group. After anesthesia-induced intubation and before one-lung ventilation (OLV), hypoxia was used to reduce SpO2 to 0.90 in group P, and then reoxygenation was used to increase SpO2 to 1.00. The ventilation was continued for 3 minutes, and repeated twice. The arterial blood, gas was measured at the end of each treatment, and the hypoxia tolerance time of SpO2 from 1.00 to 0.90 was recorded. Group N was subjected to routine ventilation. Radial arterial and internal jugular vein blood were taken for blood, gas and intrapulmonary shunt rate (Qs/Qt) was measured before and after OLV (T0), OLV 30 min (T1), OLV 60 min (T2) and OLV 90 min (T3). Platelet (PLT) and mean platelet volume (MPV) were measured at T0, T1, T2 and T3. The OLV time, vital signs at each time point during the operation and peak airway pressure (Peak) were also recorded. Results There were no significant differences in OLV time, the average arterial pressure (MAP), SpO2, heart rate (HR), Peak, p(CO2), pH, hemoglobin (Hb) and arterial blood oxygen saturation (SaO2) during operation between the two groups (P>0.05). During the two HPC sessions, the hypoxia tolerance time was extended from (6.9±1.3) min to (7.9±1.1) min (P<0.05), and no serious adverse reactions were observed. After OLV, the levels of p(O2) were significantly lower in the two groups than before OLV, but the levels of p(O2) were significantly lower at each time point in the group N than that in the group P(P<0.05). After OLV, the Qs/Qt values were significantly higher than those before OLV in the two groups, and the Qs/Qt of each time point was higher in the group N than that of the group P (P<0.05). There were no significant differences in PLT and MPV between the two groups (P>0.05). Conclusion Hypoxic pretreatment before one-lung ventilation is safe for patients. It can reduce Qs/Qt in patients during OLV, increase p(O2) and improve the oxygenation of patients undergoing lobectomy. The relationship between its effect and platelet count and function is not clear.
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    The expressions of circled RNA CDR1as and miR-7 in epileptic patients and their relationships with abnormal EEG#br#
    HAN Yong-kai, LI Si-na, ZHANG Ping, LI Jing, WANG Xu-sheng, ZHANG Fan, DU Ai-ling, ZHANG Liu-sha, SONG Jing-gui△
    2020, 48 (9):  871-874.  doi: 10.11958/20201182
    Abstract ( 872 )   PDF (427KB) ( 7029 )  
    Abstract: Objective To investigate the expressions of circular RNA cerebellar degeneration-related protein 1 antisense (CDR1as) and microRNA-7 (miR-7) in the plasma of epileptic patients and their relationships with abnormal EEG. Methods A total of 87 epileptic patients treated and hospitalized in the Second Affiliated Hospital of Xinxiang Medical College from December 2016 to December 2019 were selected as the study objects (observation group). According to the electroencephalograph (EEG) results, patients were divided into normal group (n=6), mild abnormal group (n=18), moderate abnormal group (n=37) and severe abnormal group (n=26). In addition, 90 healthy people in the same period were selected as the control group. The plasma levels of CDR1as and miR-7 were detected by real-time fluorescent quantitative PCR (qPCR). The plasma levels of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA). Pearson's method was used to analyze the correlation between the levels of CDR1as, miR-7 and the levels of IL-2, TNF-α and IL-1β. Results The levels of CDR1as, IL-2, TNF-α and IL-1β were significantly increased in the normal group, mild abnormal group, moderate abnormal group and severe abnormal group (P<0.05), while the level of miR-7 was significantly decreased (P<0.05). There was a positive correlation between the plasma levels of CDR1as and IL-2, TNF - α and IL-1 β in epileptic patients (P < 0.05). There was a negative correlation between the level of miR-7 and IL-2, TNF-α and IL-1β (P<0.05). Conclusion The plasma expressions of CDR1as and miR-7 are higher and lower in epileptic patients, respectively, and they are closely related to the levels of inflammatory factors and the abnormal degree of EEG, which may cause abnormal discharge of brain by influencing the  inflammatory response.
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    The correlation between TyG index and stable coronary artery disease and coronary artery calcified plaque burden#br#
    SI Yue-qiao, FAN Wen-jun, GAO Xiu-xin, HAN Chao, LIU Jing-yi, SUN Wang-le-xian△
    2020, 48 (9):  875-880.  doi: 10.11958/20200623
    Abstract ( 1444 )   PDF (412KB) ( 5064 )  
    Abstract: Objective To explore the correlation between triglyceride glucose (TyG) index with coronary artery disease (CAD) and coronary artery calcified plaque burden. Methods A total of 620 inpatients with suspected stable CAD were consecutively enrolled from September 2015 to June 2017 in the Affiliated Hospital of Chengde Medical College. Patients were divided into CAD group (n=449) and non-CAD group (n=171) according to coronary computed tomographic angiography (CCTA) results. The clinical data and coronary artery calcification score (CACS) of all patients were collected. A binary Logistic regression model was established on the risk factors of CAD and CAC. Results The prevalence of CAD, type 2 diabetes, dyslipidemia and CAC were higher in the high TyG index group than those in the low TyG index group (all P<0.05). TyG index was positively correlated with CACS and classical risk factors of CAD including epicardial adipose tissue enlargement, pericardial adipose tissue enlargement and body mass index, while negatively correlated with serum magnesium (all P<0.05). Conclusion High TyG index is associated with coronary atherosclerosis plaque burden and CAD. The increased TyG index is an independent risk factor for CAD and CAC.
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    Drug Clinical Evaluations
    The efficacy of Kudiezi combined with low molecular weight heparin on preventing deep venous thrombosis after operation of lower limb fracture 
    JIAO Jia-xun, ZHU Xiao-li, SUO Na, JIN Xian-hui△, ZHANG Qing-sheng, CUI Sheng-jie
    2020, 48 (9):  881-885.  doi: 10.11958/20193060
    Abstract ( 840 )   PDF (391KB) ( 4481 )  
    Abstract: Objective To study the efficacy of Kudiezi injection plus low molecular weight heparin (LMWH) on preventing deep venous thrombosis (DVT) in elderly patients with lower limb fracture surgery. Methods Totally 120 senile patients (≥60 years old) with lower limb fracture were randomly divided into control group (CG, n=58) and treatment group (TG, n = 62). CG was received LMWH 12 h after surgery. TG was given Kudiezi injection and LMWH. Data of hemorheology (whole high blood viscosity, whole low blood viscosity and plasma viscosity), D-dimer, coagulation function (prothrombin time, activated partial thromboplastin time) and inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-8) before surgery and 7 days after surgery were compared between CG and TG. Pain scores of 1, 3, 5 and 7 days postoperatively were recorded with numerical rating scale in two groups. Circumference differences of fracture and healthy thigh and shank were measured before surgery and 3 and 7 days after surgery. Incidences of DVT and adverse reactions within 30 days were followed up. Results No significant differences were observed in preoperative indexes between the two groups (P>0.05). Data of hemorheology, D-dimer, coagulation function and inflammatory factors were decreased 7 days after surgery in TG versus CG (P<0.05), and no significant differences in coagulation index were found between the two groups (P>0.05). Pain scores of 3, 5 and 7 days after surgery were decreased in TG compared with those in CG (P<0.01). Differences in circumference of fracture and healthy thigh and shank were lower 7 days after surgery in TG than those in CG (P<0.01). The incidence of DVT was lower in TG (3.23%) than that of CG (13.79%, P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (4.84% and 3.45%, P>0.05). Conclusion Kudiezi injection combined with LMWH can decrease the postoperative levels of hemorheology and inflammatory factors, alleviate pain and swelling of affected extremity, and reduce the incidence of DVT in elderly patients with lower limb fracture.
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    The effects of Zishen Yugui decoction on serum anti-Mullerian hormone, estradiol and follicle stimulating hormone in patients with premature ovarian insufficiency
    CHI Lei, ZHANG Qin△
    2020, 48 (9):  886-890.  doi: 10.11958/20200853
    Abstract ( 750 )   PDF (422KB) ( 3616 )  
    Abstract: Objective To study the impact of Zishen Yugui decoction on serum anti-Müllerian hormone (AMH), estradiol (E2) and follicle stimulating hormone (FSH) in patients with premature ovarian insufficiency (POI). Methods A total of 157 patients with POI were randomized into 3 groups: the Chinese medicine group (51 cases treated with Zishen Yugui decoction), the Femoston group (54 cases treated with Femoston) and the combined treatment group (52 cases treated with both Femoston and Chinese medicine). The total efficiency was analyzed compared between the 3 groups.The serum levels of AMH, E2 and FSH before and after treatment were compared between the three groups.Besides, the situation of menstruation, pregnancy rate, endometrial thickness, ovarian volume, antral follicle count, ovarian peak systolic velocity (PSV) and RI before treatment and 4 weeks after treatment were compared between the 3 groups. Meanwhile, the incidence of adverse reaction was recorded. Results Compared with the Chinese medicine group and the Femoston group, the total efficiency was higher in the combined treatment group (P<0.05).In the 4th and 12th week of treatment, the serum levels of AMH and E2 were higher in the combined treatment group than those of Chinese medicine group and the Femoston group, and the FSH level was lower in the combined treatment group (P<0.05). At 4-week treatment, the menstrual cycle, menstrual period and menstrual volume were longer/more in the combined treatment group than those of Chinese medicine group and the Femoston group (P<0.05), and the pregnancy rate was higher in the combined treatment group (P<0.05). Compared with the Chinese medicine group and the Femoston group, the endometrial thickness and resistance index (RI) were smaller, and the ovarian volume, antral follicle count and ovarian PSV were larger in the combined treatment group (P<0.05). No significant adverse reactions were found in the 3 groups.Conclusion Menstrual disorders, vaginal ultrasound parameters, pregnancy rate, and serum levels of AMH, E2 and FSH can be effectively improved through treatment with Zishen Yugui decoction in patients with POI. The treatment method is safe and reliable.
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    Clinical Study
    Late-onset glutaric aciduria type Ⅱ combined with spinal cord injury with familial hypercholesterolemia: a case report
    XU Gang, ZHAO Peng△, CAI Chun-quan
    2020, 48 (9):  891-893.  doi: 10.11958/20193898
    Abstract ( 1917 )   PDF (1193KB) ( 4668 )  
    Abstract: Glutaric aciduria type Ⅱ is an autosomal recessive disease that affects the metabolism of fatty acids, amino acids and choline, and is an important molecular cause of lipid deposition disease. Children with this disease are rare, and clinicians lack awareness, easy to misdiagnose or miss diagnosis. Late-onset glutaruria type Ⅱ with abdominal pain and spinal cord injury is rarer. This case report describes a retrospective analysis of a child with late-onset glutaric aciduria type Ⅱ and familial hypercholesterolemia with abdominal pain and spinal cord injury. Blood lipid, urine organic acid test and genetic testing early are of great significance for the diagnosis and treatment of children and improve their quality of life. 
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    A case of novel coronavirus pneumonia complicated with obesity
    QIAO Zhi-fei, LIU Chun-yan, LI Fu-long△, LIN Wei-jia, LIU Hua-qing, LIU Hai-chun, WANG Lei
    2020, 48 (9):  894-897.  doi: 10.11958/20200335
    Abstract ( 1026 )   PDF (1495KB) ( 5437 )  
    Abstract: The novel coronavirus pneumonia (COVID-19) has a high critical fatality rate, most of patients are the elderly, and with underlying diseases or obesity. This article reports a successful treatment of a severe COVID-19 patient with obesity, and describes an effective respiratory and circulatory support process, in order to provide the reference for the treatment of obese patients with severe COVID-19.
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    Research progress of Tim-3 regulating the polarization of macrophage in rheumatoid arthritis
    ZHONG Yu-mei, CHEN Yang, LUO Xiao-chao, ZHOU Hai-yan
    2020, 48 (9):  898-902.  doi: 10.11958/20200625
    Abstract ( 859 )   PDF (454KB) ( 5954 )  
    Abstract: Rheumatoid arthritis (RA) is a chronic and refractory disease caused by autoimmune dysfunction. The continuous activation and the status of long-term high response of T cells are important links of its immune response. T cell immunoglobulin and mucin-domain-containing molecule-3 (Tim-3) is a surface molecule expressed on various cell types of immune system, and its signal transduction can enhance or inhibit the immune response of macrophages. A large number of studies have indicated that Tim-3 plays an important role in the immune system, such as regulating the polarization of macrophage, promoting the transduction of various intracellular signal and immune responses and playing a key role in the pathogenesis of RA. Therefore, the paper reviews the relevant research progress on Tim-3 regulating the polarization of macrophage in RA in recent years and provides new ideas for deepening the treatment of RA.
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    Review
    The application of next generation sequencing in the diagnosis and treatment of colorectal cancer#br#
    CHEN Ru-ping, , LIU Rui△
    2020, 48 (9):  903-907.  doi: 10.11958/20193232
    Abstract ( 1139 )   PDF (392KB) ( 6099 )  
    Abstract: The potential application value of next generation sequencing (NGS) technology in the clinical diagnosis and treatment of colorectal cancer (CRC) has become a research hotspot. NGS can be used not only to detect gene mutations in the early CRC screening, but also to guide the selection of targeted drugs, the predicting of the efficacy and the evaluation of the prognosis. This paper reviews the applications of NGS technology in clinical diagnosis and treatment of CRC in recent years.
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    Advances in the study of type 2 innate lymphocytes in allergic diseases
    LIU Li, ZOU Ying-xue△
    2020, 48 (9):  908-912.  doi: 10.11958/20193570
    Abstract ( 1761 )   PDF (396KB) ( 5949 )  
    Abstract:Innate lymphocytes (ILCs) are a unique class of immune effector cells, which has been widely concerned in the past decade, especially the role of type 2 innate lymphocyte (ILC2) in allergic diseases and autoimmune diseases. ILC2 is involved in the formation of mucosal immunity, repairing and remodeling of tissue damage, and plays an important role in fighting infection, regulating inflammation and maintaining immune homeostasis. ILC2 is involved in the inflammatory response of allergic rhinitis, asthma, food allergy and eosinophil esophagitis, which cannot be ignored. This paper reviews the research progress of ILC2 in allergic diseases.
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