Tianjin Medical Journal

The mechanism of Notch3 regulating Hes2 to reverse epithelial-mesenchymal transition in triple-negative breast cancer

TIAN Yuan, MOU Yajun, YANG Wenxiu, DOU Xiaowei

2022, 50 (8): 785-790. doi: 10.11958/20220306

Abstract ( 693 )

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Objective To explore the molecular mechanism of Notch3 reversing epithelial-mesenchymal transition (EMT) and inhibiting tumor metastasis in triple negative breast cancer (TNBC). Methods The Notch3 overexpression plasmid (pcDNA3.1-Notch3-GFP) and its negative control plasmid (pcDNA3.1-NC-GFP), the small molecule interference plasmid for Hes2 knockdown (si-Hes2-GFP) and its negative control plasmid (si-NC-GFP) were transfected into TNBC MDA-MB-231 cells. Cells were divided into the control group (no transfection was performed), the pc-NC group (transfection pcDNA3.1-NC-GFP), the Notch3 overexpression group (pc-Notch3 group, transfection pcDNA3.1-Notch3-GFP), the Notch3 overexpression+si-NC group (pc-Notch3+si-NC group, co-transfected pcDNA3.1-Notch3-GFP and si-NC-GFP), and the Notch3 overexpression+Hes2 knockdown group (pc-Notch3+si-Hes2 group, co-transfected pcDNA3.1-Notch3-GFP and si-Hes2-GFP). Real-time quantitative PCR and Western blot assay were performed to measure mRNA and protein expression levels of Notch3 and Hes2 in cells to verify the transfection efficiency. The cell counting kit-8 assay was performed to measure cell proliferation activity. Scratch healing assay and Transwell chamber assay were performed to measure cell migration and invasion abilities. Western blot assay was performed to measure EMT-related proteins (E-cadherin and Vimentin) in cells. Results Compared with the control group and the pc-NC group, the Notch3, Hes2 mRNA and protein, E-cadherin protein levels were significantly increased in the pc-Notch3 group and the pc-Notch3+si-NC group, and the proliferation activity, mobility, number of transmembrane cells and Vimentin protein levels were significantly decreased (P<0.05). Compared with the pc-Notch3 group and the pc-Notch3+si-NC group, the Hes2 mRNA and protein levels and E-cadherin protein were significantly decreased in the pc-Notch3+si-Hes2 group, and the proliferation activity, mobility, number of transmembrane cells and Vimentin protein levels were significantly increased (P<0.05). Conclusion Notch3 may reverse the EMT of TNBC and inhibit tumor metastasis by up-regulating Hes2.

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Mechanism of FUNDC1 affacting apoptosis of H9c2 cardiomyocytes with high glucose injury by regulating mitochondrial fission

ZHENG Junyi, ZHANG Yingying, LIU Yuanyuan, CHEN Mengying, GUO Xukun

2022, 50 (8): 791-795. doi: 10.11958/20220348

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Objective To investigate the mechanism of FUNDC1 affecting high glucose injured H9c2 cardiomyocyte apoptosis by regulating mitochondrial fission. Methods H9c2 cardiomyocytes were cultured in vitro, and the high glucose-induced injury model of cells was established. After cell transfection or AMPK activation by AICAR, the cells were divided into the control (CTRL) group, the high glucose injury (HG) group, the HG with transfected shRNA-NC (HG+shRNA-NC) group, the HG with transfected FUNDC1 shRNA (HG+shRNA-FUNDC1) group and the HG with AICAR (HG+AICAR) group. MTT method was used to detect the cell survival rate. The level of released LDH was measured with microplate reader. The structure of mitochondria was observed by laser confocal microscope. The proteins expression levels of mitochondrial dynamin-related protein1 (DRP1), fission protein 1 (FIS1), Bcl-2 associated X protein (Bax), B-lymphocytoma-2 (Bcl-2), cleaved cysteine-containing aspartate-spicific protease 3 (Cleaved Caspase-3), FUNDC1 and GAPDH were detected by Western blot assay. Results Compared with the CTRL group, the cell survival rate decreased, and the protein levels of DRP1-cyto and Bcl-2 were also decreased, the release of LDH and the protein expression levels of DRP1-mito, FIS1, Bax and Cleaved Caspase-3 increased in the HG group (P<0.05). Compared with the HG group, knocking down FUNDC1 increased the cell survival rate and the protein levels of DRP1-cyto and Bcl-2, decreased the release of LDH and the protein expression levels of DRP1-mito, FIS1, Bax and Cleaved Caspase-3 (P<0.05). There was no difference in each index between the HG group and the HG+shRNA-NC group (P>0.05). The mitochondria were mainly linear structure in the CTRL group, and the mitochondria were mainly pucta structure in the HG group and the HG+shRNA-NC group. Compared with the HG group, the mitochondrial linear structure increased and the puncta structure decreased in the HG+shRNA-FUNDC1 group. Compared with the CTRL group, the protein expression level of FUNDC1 increased in the HG group (P<0.05). Compared with the HG group, the protein level of FUNDC1 significantly decreased in the HG+AICAR group (P<0.05). Conclusion FUNDC1 affects H9c2 cardiomyocyte apoptosis induced by high glucose through regulating mitochondrial fission, and AMPK signaling pathway is involved in this process.

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Study on the mechanism of CDCA8 promoting the occurrence of prostate cancer by regulating proliferation

REN Zhixing, YANG Guanghua

2022, 50 (8): 796-801. doi: 10.11958/20212744

Abstract ( 717 )

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Objective To explore the expression and mechanism of cell division cycle associated protein 8 (CDCA8) in the occurrence of prostate cancer (PCa). Methods The difference of CDCA8 mRNA expression levels between normal prostate tissue and PCa tissue was analyzed by bioinformatics method. The disease-free survival (DFS) associated with CDCA8 expression in PCa patients was analyzed using RNA sequencing data from cancer Genome Atlas (TCGA) database. Immunohistochemical method was used to detect the expression of CDCA8 in 56 pairs of PCa tissues and adjacent tissues after radical prostatectomy. Patients were divided into the CDCA8 high expression group (n=31) and the CDCA8 low expression group (n=25) according to staining results. The potential correlation between clinical characteristics and CDCA8 expression level was further analyzed. The CDCA8 gene was silenced by siRNA, and the expression level of CDCA8 mRNA was detected by qPCR. The proliferation of PCa cells was detected by clonal formation assay, and the changes of CDCA8, Ki67, proliferating cell nuclear antigen (PCNA) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway proteins were detected by Western blot assay. Results In TCGA database, CDCA8 mRNA level was significantly higher in PCa tissues than that in normal tissues, and patients with high expression of CDCA8 mRNA had a worse prognosis (P<0.01). The staining index of expression level of CDCA8 protein was significantly higher in PCa tissue than that in para-cancer tissue, and the expression level was positively correlated with total prostate-specific antigen (tPSA), Gleason score, T stage and surgical margin (P<0.01). The proportion of patients with tPSA≥10 μg/L, T3 stage and positive postoperative resection margin was significantly higher in the high CDCA8 expression group than that in the low CDCA8 expression group (P<0.05). After CDCA8 gene was silenced, the proliferation of PCa cells was decreased, and the protein expression levels of Ki67, PCNA, p-PI3K and p-AKT were down-regulated (P<0.01). Conclusion CDCA8 promotes the occurrence of prostate cancer by regulating proliferation, and its mechanism may be related to PI3K/AKT signaling pathway.

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The effect and underlying mechanism of hippocampal specific knockdown of RNA methyltransferase Pcif1 on spatial learning and memory

SUN Zuhao, SUO Xinjun, XIA Xianyou, ZHAO Shuang, DOU Yan, YU Chunshui

2022, 50 (8): 802-809. doi: 10.11958/20220477

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Objective To investigate the effect and underlying molecular mechanism of RNA methyltransferase Pcif1 on hippocampus-dependent spatial learning and memory. Methods A total of twenty-seven 8-week-old male C57BL/6J Nifdc mice were selected for animal experiments. Animals were randomly divided into 3 groups (9 animals per group): the Pcif1 knockdown group (1 μL adeno-associated virus packaged shRNA targeting Pcif1 was stereotactic injected into mouse hippocampi), the sham-operation group (1 μL contrast adeno-associated virus was stereotactic injected into mouse hippocampi) and the wild-type group (none treatment). After treatment for 3 weeks, Morris water maze (MWM) was used to test the spatial learning and memory of mice, and Western blot assay was performed to detect the expression of related proteins in hippocampal tissues. HT22 cell line, a mouse hippocampal neuronal cell line, was selected for in vitro experiment. Cells were divided into two groups: the HT22-shPcif1 group (cellular Pcfi1 was knocked down by lentivirus packaged shRNA targeting Pcif1) and the HT22-Ctrl group (cells infected by contrast lentivirus). The whole-transcriptome sequencing (RNA-seq), cell-count-kit-8 (CCK8) assay, cell scratching assay and flow cytometry were used to study the mechanism of Pcif1 knockdown on learning and memory of mice. Results Comparing to the wild type group and the sham-operation group, spatial learning and memory were promoted in the Pcif1 knockdown group, and anti-apoptosis protein Bcl-2 in hippocampi was upregulated. Comparing to HT22-Ctrl cells, differentially expressed genes of HT22-shPcif1 cells were enriched in pathways of cell apoptosis, migration and proliferation. The cell migration of HT22-shPcif1 cells was enhanced. The cell proliferation of HT22-shPcif1 cells was enhanced under 400 μmol/L H₂O₂, and the cell apoptosis under 400 μmol/L H₂O₂ was reduced. Conclusion The selective knockdown of hippocampal Pcif1 facilitates spatial learning and memory of mice, and its mechanisms may be related to the upregulation of anti-apoptosis proteins and the enhancement of cell migration and proliferation.

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Effects of renal denervation on the vascular endothelial cell autophagy and NLRP3 activation in type 2 diabetic rats

WANG Yong, NIU Weihua, LU Chengzhi, XU Mengping, XU Jianqiang, HE Qiang, XU Xuesheng

2022, 50 (8): 810-816. doi: 10.11958/20212359

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Objective To explore the effects of renal denervation (RDN) on the autophagy of vascular endothelial cells and NLRP3 inflammatory complexes in type 2 diabetic mellitus (T2DM) rats. Methods T2DM rat model was established by high-fat diet (HFD) combined with low-dose streptozotocin (STZ) intraperitoneal injection. Rats were randomly divided into four groups: the control group (CON, n=6), the diabetic group (T2DM, n=6), the bilateral sham surgery group (Sham, n=6) and the bilateral RDN group (RDN, n=6). Changes in all indicators were recorded at baseline, before and after RDN and 4 weeks after RDN, respectively. In vitro vascular ring tension test was used to evaluate vascular relaxation function. Western blot assay was used to detect the aorta endothelial cell autophagy of Beclin1, LC3 and p62, and the expression of NLRP3 protein and cysteine aspartate protease 1 (Caspase-1) and endothelial nitric oxide synthase (eNOS) protein. Results Compared with the control group, the endothelium diastolic function of the thoracic aorta was significantly decreased in the T2DM group, the expression of autophagy-related proteins Beclin1 and LC3 were decreased, the expression of p62 was increased. The expression levels of NLRP3, Caspase-1 and IL-1β protein were higher in the T2DM group than those of the control group (P<0.05), the level of eNOS protein was decreased (P<0.05). Compared with the T2DM group and the Sham group, the endothelium diastolic function was significantly improved in the RDN group, and the expression levels of Beclin1 and LC3 were increased, the expression of p62 was decreased. The protein expression levels of NLRP3, Caspase-1 and IL-1β were decreased, the level of eNOS increased (P<0.05). Conclusion The vascular endothelial dysfunction in T2DM rats may be associated with the decreased autophagy level and overexpression of NLRP3 inflammatory complex protein. RDN can enhance the autophagy in vascular endothelial cells, decrease the expression of NLRP3 inflammatory complex protein and improve vascular endothelial dysfunction.

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Neuroprotective effects of dexmedetomidine on intracerebral hemorrhage of rats by Nrf2-GPX4 mediated iron death pathway

LI Qiuchang, YAN Shunchang, MENG Yazhen, GU Yunxia, NING Qiaoming, LI Na, WANG Zhihua

2022, 50 (8): 817-821. doi: 10.11958/20212825

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Objective To explore the mechanism of Nrf2-GPX4-mediated iron death pathway in the neuroprotective effect of dexmedetomidine (Dex) on intracerebral hemorrhage (ICH) in rats. Methods A total of 100 rats were randomly divided into the sham group, the ICH group (model group), the Dex-L group (Dex 50 μg/kg), the Dex-H group (Dex 100 μg/kg) and the Dex-H+ML385 group (Nrf2 inhibitor ML385, 30 mg/kg), with 20 rats in each group. Except for the sham group, ICH model was established by autologous blood injection in the other groups. In the Dex-L group, the Dex-H group and the Dex-H+ML385 group, the corresponding Dex or ML385 was injected intraperitoneally 30 minutes before operation, and the sham group and the ICH group were injected with the same amount of normal saline. Zea Longa 5 scoring method was used to evaluate rat nerve function damage. The contents of glutathione (GSH), malondialdehyde (MDA) and iron ions in brain tissue around the hematoma were detected by the kit. The brain water content around the hematoma was measured. HE staining, Nissl staining and Prussian blue staining were used to observe the pathology, nerve cell damage and iron deposition around the hematoma. Western blot assay was used to detect the expression levels of GPX4, cystine/glutamate antiporter system light chain (xCT) and Nrf2 in brain tissue. Results Compared with the sham group, the neurological deficit score, MDA, iron content, brain water content, brain tissue pathological damage and iron deposition were significantly increased in the ICH group, while the GSH content, nerve cell number, GPX4, xCT and Nrf2 expression levels were significantly decreased in the ICH group (P<0.05). Compared with the ICH group, the neurological deficit score, MDA, iron content, brain water content, brain tissue pathological damage and iron deposition were significantly reduced in turn in the Dex-L group and the Dex-H group, and the GSH content, nerve cell number, GPX4, xCT and Nrf2 expression levels were significantly increased (P<0.05). ML385 reversed improvements in neurological function, iron deposition and brain damage caused by Dex-H. Conclusion Dexmedetomidine inhibits iron death by activating the Nrf2-GPX4 pathway, thereby exerting a neuroprotective effect on ICH rats.

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The effect of cardiomyocytes derived from human dental-origin iPSCs on cardiac repair in murine model of acute myocardial infarction

TAN Xiaobing, WANG Ruxian, LYU Meirong, SUN Xianfeng, LYU Naying, DAI Qingyuan

2022, 50 (8): 822-826. doi: 10.11958/20220106

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Objective To investigate the effect of myocardial cells differentiated from human SCAP-induced pluripotent stem cells (iPSCs) on the myocardial function of acute myocardial infarction (AMI) mice. Methods Human stem cells from apical papilla (SCAP) was reprogrammed to iPSCs with Sendai reprogramming kit and passed using single colony subcloning under feeder-free condition. Specific myocardial differentiation medium was utilized to induce iPSCs. Nine BALB/C male mice were divided into the normal group (no intervention), the AMI group (AMI modeling) and the experimental group (AMI modeling + iPSCs-CMs injection) using random number table method. AMI mice model was established by coronary artery ligation. The derived cardiomyocytes (CMs) were injected into peri-infarct region of mice, and myocardial function was accessed by echocardiography. Results The derived iPSCs exhibited morphology resembling with embryonic stem cells (ESCs) and formed three-germ layers in nude mice. The CMs were able to beat independently and expressed specific markers, α-actinin and TNNT-2. The success of AMI model was confirmed by immediate electrocardiogram after operation. Compared with the normal group, LVFS and LVEF decreased significantly in the AMI group, and LVFS and LVEF were significantly higher in the experimental group than those in the AMI group (P<0.05). Conclusion Local injection of human odontogenic iPSCs differentiated cardiomyocytes can significantly improve the cardiac function and promote myocardial repair in AMI mice.

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Experimental study of huxintongluo decoction on rabbit atherosclerosis by intervening CETP mediated lipid metabolism

WANG Hua, HE Xiong

2022, 50 (8): 827-831. doi: 10.11958/20212849

Abstract ( 537 )

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Objective To study the effect and mechanism of huxintongluo decoction on rabbit atherosclerosis (AS) by regulating cholesterol lipid transporter protein (CETP). Methods Forty male New Zealand rabbits were divided into the blank control group, the AS model group, the simvastatin group [0.33 mg/(kg·d)] and the huxintongluo group [0.34 g/(kg·d)] according to random number table method, with 10 rabbits in each group. The blank control group was fed ordinary diet for 22 weeks. The other three groups were fed with high fat diet for 14 weeks, and then different drug intervention was performed in groups for 8 weeks. Serum levels of high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), total cholesterol (TC) and triglyceride (TG) were detected before the experiment, 14 and 22 weeks after administration. The animals were sacrificed at the end of the 22-week, the thoracic aorta was separated, and the pathological changes were observed by hematoxyl-eosin (HE) staining. The expression levels of ABCA1, apoA-I and LCAT in liver tissues were detected by fluorescence quantitative PCR and Western blot assay. Results There were no significant differences in serum levels of TC, TG, HDL-C and LDL-C before the experiment between the four groups (P>0.05). At week 14 of experiment, compared with the blank control group, serum levels of TC, TG and HDL-C were significantly increased in the other three groups, while the serum level of LDL-C was significantly decreased (P<0.05). At week 22 of experiment, compared with the AS model group, serum levels of TC, TG and LDL-C were significantly decreased in the other three groups, while serum level of HDL-C was significantly increased (P<0.05). Compared with the blank control group, the serum level of CETP increased in the AS model group. Compared with the AS model group, the serum level of CETP decreased in the simvastatin group and the huxintongluo group. Compared with the blank control group, ABCA1, apoA-I and LCAT mRNA and protein levels in liver tissues were decreased in the AS model group. Compared with the AS model group, mRNA and protein levels of ABCA1, apoA-I and LCAT were increased in the simvastatin group and the Huxintongluo group (P<0.05). Conclusion Huxintongluo decoction can activate ABCA1/apoA-I/LCAT pathway by reducing CETP level, ultimately improve HDL-C level and improve atherosclerosis in rabbits.

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Changes of serum H₂S in patients with osteoporosis and its clinical significance

TAN Bo, HU Jiang, LU Bing, YUAN Jiabin, WEI Dan, ZHU Zongdong, LIAO Feng, TANG Xiaoming

2022, 50 (8): 832-835. doi: 10.11958/20212020

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Objective To investigate changes and clinical significance of serum hydrogen sulfide (H₂S) in patients with osteoporosis. Methods A total of 128 patients with osteoporosis admitted to our hospital were used as the osteoporosis group, and another 110 patients with low back pain in our hospital during the same period were selected as the control group. The Asian Osteoporosis Self-screening Tool (OSTA) was used to screen for osteoporosis risk by measuring bone mineral density in the lumbar spine (L_1-4) and bilateral femoral neck with dual energy X-ray spectrometer. Five mL of fasting venous blood was collected from all patients after admission. Serum H₂S, alkaline phosphatase (ALP), bone specific alkaline phosphatase (BALP), serum phosphorus, serum calcium, parathyroid hormone (iPTH), CTX, N-terminal propeptide of type 1 procollagen (P1NP), cross-linking C-terminal peptide of urinary 1 collagen (P1CP) and special sequence of carboxy-terminal peptide of type Ⅰ collagen (β-CTX) were detected. Pearson correlation analysis was conducted to analyze the correlation between serum H₂S and bone metabolic markers in patients with osteoporosis. Results Compared with the control group, the bone mineral density of lumbar vertebra and femoral neck decreased, the serum H₂S concentration decreased, the serum ALP, BALP, serum osteocalcin, P1NP, P1CP and iPTH concentration decreased, and the β-CTX level increased in the osteoporosis group (P<0.05). Serum H₂S was positively correlated with ALP, BALP, serum osteocalcin, P1NP, P1CP and iPTH in patients with osteoporosis, but negatively correlated with β-CTX (P<0.05). Conclusion The serum level of H₂S is significantly decreased in patients with osteoporosis. The detection of H₂S is helpful to evaluate the bone metabolism in patients.

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Effects of seasonal and temperature changes on blood glucose levels in patients with acute cerebral infarction

WEI Miaomiao, XIA Xiaoshuang, WANG Lin, LI Xin

2022, 50 (8): 836-839. doi: 10.11958/20212829

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Objective To investigate the effects of seasonal and temperature changes on blood glucose levels in patients with acute cerebral infarction. Methods The meteorological data of 1 260 cases with acute cerebral infarction were retrospectively analyzed. The baseline clinical data and blood test results were collected. The correlation between blood glucose levels in patients with acute cerebral infarction and seasonal and temperature changes were analyzed. Results The blood pressure, body mass index, baseline National Institutes of Health Stroke Scale score, total cholesterol and fasting plasma glucose (FPG) of patients with acute cerebral infarction were significantly higher in winter than those in summer (P<0.05). When the glycated hemoglobin A1c (HbA1c) level was ≥7%, the above indicators in spring were higher than those in other seasons (P<0.05). FPG levels peaked in January and bottomed in July, while HbA1c levels peaked in February and bottomed in August. Glucose levels showed a tendency to increase with the decrease of temperature. There was a lag effect of temperature on HbA1c. Spearman correlation test was performed on temperature and glucose levels. It was found that FPG levels were negatively correlated with monthly mean daily temperature, monthly minimum daily temperature and monthly maximum daily temperature (r_s=-0.690, -0.637, -0.764, respectively, all P<0.05). HbA1c levels were negatively correlated with monthly mean daily temperature, monthly minimum daily temperature and monthly maximum daily temperature with a two-month lag (r_s=-0.729, -0.750, -0.743, respectively, all P<0.05). Conclusion The blood glucose level of patients with acute cerebral infarction complicated with diabetes is higher in winter than that in other seasons. The monthly mean daily temperature, monthly minimum temperature and monthly maximum temperature are negatively correlated with blood glucose level.

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Risk factors for vascular dementia in patients with nonvalvular atrial fibrillation: a case-control study

HE Hongmei, SUN Jian, WANG Huanhuan, MA Shujing, ZHANG Haiyan, ZOU Yu'an, XUE Qian, SONG Aixia

2022, 50 (8): 840-843. doi: 10.11958/20212846

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Objective To investigate the risk factors of vascular dementia in patients with nonvalvular atrial fibrillation, and to evaluate the relationship between different anticoagulants and vascular dementia in patients with atrial fibrillation. Methods A case-control study was conducted in 66 patients with nonvalvular atrial fibrillation and vascular dementia (the case group). The control group included 132 patients with nonvalvular atrial fibrillation and without vascular dementia. Data of age, sex, body mass index (BMI), education level, smoking and other general conditions including disease history of diabetes, hypertension, angina pectoris, chronic obstructive pulmonary disease (COPD), hyperthyroidism, hypothyroidism, myocardial infarction, dyslipidemia and anticoagulant drug use were compared between the two groups. Results There were no significant differences in age, gender, incidence of obesity and average education years between the two groups (P>0.05). The proportion of smoking and utilization rate of warfarin was significantly higher in the case group than that in the control group (P<0.05). The incidence of hypertension, diabetes, angina pectoris and dyslipidemia were significantly higher in the case group than those in the control group (P<0.05). Logistic regression analysis showed that the risk of vascular dementia was lower in patients taking rivaroxaban anticoagulant therapy than that in patients taking warfarin (OR=0.480, 95%CI: 0.244-0.944). Diabetes mellitus (OR=2.117, 95%CI: 1.080-4.149), hypertension (OR=2.224, 95%CI: 1.109-4.461), smoking (OR=2.269, 95%CI: 1.148-4.488), dyslipidemia (OR=2.045, 95%CI: 1.037-4.032) and history of angina pectoris (OR=2.336, 95%CI: 1.165-4.682) were risk factors for vascular dementia in patients with nonvalvular atrial fibrillation (P<0.05). Conclusion Compared with warfarin, rivaroxaban anticoagulant therapy is a protective factor for vascular dementia in patients with nonvalvular atrial fibrillation, while diabetes, hypertension, smoking, dyslipidemia and history of angina are risk factors for vascular dementia in patients with nonvalvular atrial fibrillation.

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Risk factors and establishment of nomogram model for cardiac insufficiency combined with arteriosclerosis obliterans

ZHANG Xiaoshan, LIU Ming, ZHANG Yudong, JI Bo

2022, 50 (8): 844-848. doi: 10.11958/20220020

Abstract ( 676 )

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Objective To investigate the risk factors of arteriosclerosis obliterans (ASO) in patients with cardiac insufficiency, and to construct and verify the nomogram risk prediction model. Methods A total of 319 patients with cardiac insufficiency were selected. According to whether there was lower extremity arterial stenosis or occlusion in the lower extremity, patients were divided into the ASO positive group (n=161) and the ASO negative group (n=158). Gender, age, history of smoking, history of drinking, history of hypertension, New York heart association (NYHA) cardiac function grade, triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), homocysteine (HCY), glycosylated hemoglobin (HbA1c), N-terminal pro-brain natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT), ankle-brachial index (ABI) and left ventricular ejection fraction (LVEF) were collected after admission. Logistic regression was used to analyze the risk factors of ASO in patients with cardiac insufficiency, so as to establish and verify the nomogram risk prediction model. Results Compared with the ASO negative group, the ASO positive group had higher male ratio, high proportion of hypertension, higher smoking rate, high proportion of NYHA cardiac function grade Ⅱ-Ⅲ, higher levels of HbA1c, TG, TC, LDL-C and HCY, and lower ABI (P<0.05). Logistic regression analysis showed that male,hypertension, smoking, NYHA cardiac function grade Ⅱ-Ⅲ,higher levels of TG, TC, LDL-C, and HCY were independent risk factors for ASO in patients with cardiac insufficiency. The nomogram risk prediction model constructed on this basis was verified by Bootstrap internal verification. The Hosmer-Lemeshow test showed that the model had good goodness of fit (χ²=0.602,P>0.05). The C-index of the model was 0.856 (95%CI: 0.815-0.896). Spearman correlation analysis showed that LVEF was positively correlated with ABI (r_s=0.228,P<0.01). NYHA cardiac function grade, NT-proBNP and hs-cTnT were negatively correlated with ABI (r_s=-0.296, -0.303 and -0.268, P<0.01). Conclusion Male, hypertension, smoking, NYHA cardiac function grade Ⅱ-Ⅲ, higher levels of TG, TC, LDL-C and HCY are independent risk factors for ASO in patients with cardiac insufficiency. The established nomogram prediction model could effectively assess the risk of ASO in patients with cardiac insufficiency.

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Effects of different administration timing of butorphanol on oxidative stress and inflammatory response of ischemia-reperfusion injury induced by orthopaedic tourniquet

PENG Yaqi, WANG Dan, ZHAO Lixia, YUAN Dajiang

2022, 50 (8): 849-852. doi: 10.11958/20212741

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Objective To investigate the effects of different administration timing of butorphanol on oxidative stress and inflammatory response of ischemia-reperfusion injury induced by orthopaedic tourniquet. Methods Ninety patients undergoing elective orthopedic lower limb surgery were randomly divided into the butorphanol pretreatment group (group Y), the butorphanol post-treatment group (group H) and the control group (group C), with 30 patients in each group. Subarachnoid block were used in the three groups of patients. Patients in group Y received a slow bolus of 0.02 mg/kg butorphanol intravenously 5 min before tourniquet inflation. A slow bolus of 0.02 mg/kg butorphanol was administered intravenously to patients in group H 5 min before the tourniquet was deflation. Patients in group C were not specifically addressed. Mean arterial pressure (MAP), heart rate (HR), saturation of pulse oximetry (SpO₂) values were compared before loading medication (T₀), 30 min after tourniquet inflation (T₁), 60 min after tourniquet inflation (T₂), and 5 min after tourniquet deflation (T₃). Serum tumor necrosis factor -α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured at T₀ and T₃. Results There were no significant differences in HR, MAP and SpO₂ at each time point between the three groups. There were no significant differences in HR and SpO₂ at each time point between groups. Compared with T₀, MAP was significantly increased at T₂ in the group H and the group C, decreased significantly at T₃ in group Y (P<0.05). Compared with T₀, serum levels of MDA and TNF-α increased at T₃in the three groups of patients, and the serum level of SOD decreased (P<0.05). At T₃, serum levels of MDA and TNF-α were significantly lower in the group Y and the group H than those in the group C, and the serum level of SOD was significantly higher than that in the group C (P<0.05). However, there were no significant differences in the serum concentrations of MDA, SOD and TNF-α between the group Y and the group H. Conclusion Butorphanol pretreatment and post-treatment can effectively reduce the ischemia-reperfusion injury caused by tourniquet, which may be related to the inhibition of oxidative stress and inflammatory response.

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Correlation between ultrasonographic features and molecular subtypes of early mass-type breast invasive ductal carcinoma

ZHANG Yu, LIU Liangsheng, MA Wenjuan, HAN Min, ZHU Ying, LU Hong

2022, 50 (8): 853-858. doi: 10.11958/20220230

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Objective To investigate the diagnostic value of ultrasonic signs to molecular typing of early mass-type breast invasive ductal carcinoma by analyzing the correlation between ultrasonographic features and molecular types of early mass-type breast invasive ductal carcinoma. Methods A total of 298 patients with stage Ⅰ-Ⅱ breast cancer who were diagnosed by ultrasonography as mass-type lesions before operation and were confirmed as breast invasive ductal carcinoma by surgical pathology were retrospective included. The differences of ultrasonographic features and molecular subtypes were compared and analyzed. The influencing factors of Luminal type, HER-2 overexpression type and triple-negative type were analyzed by Logistic regression. Results Among 298 patients, 26 cases were Luminal A type, 178 cases were Luminal B type, 54 cases were HER-2 overexpression type and 40 cases were triple negative type. There were significant differences in age of onset, tumor diameter, margin, morphology, internal calcification and posterior echo between patients with different molecular types (P<0.05). There were no significant differences in axillary lymph node metastasis, growth direction, echo and blood flow signal (P>0.05). Irregular shape (OR=1.206, 95%CI: 1.039-1.400, P<0.05) and rough edge (OR=1.490, 95%CI: 1.224-1.814, P<0.05) were independent risk factors for Luminal type. The enhancement in posterior echo was the independent protective factor for Luminal type (OR=0.674, 95%CI: 0.603-0.752, P<0.05). Rough edge was the independent protective factor for HER-2 overexpression type (OR=0.688, 95%CI: 0.564-0.838, P<0.05). Irregular shape (OR=0.820, 95%CI: 0.728-0.923, P<0.05), attenuation in posterior echo (OR=0.714, 95%CI: 0.644-0.792, P<0.05), no change in posterior echo (OR=0.723, 95%CI: 0.662-0.791, P<0.05) and mixed echo in posterior echo (OR=0.790, 95%CI: 0.638-0.978, P<0.05) were independent protective factors for triple-negative type. Conclusion The ultrasonographic features can provide a basis for molecular typing of early mass-type breast invasive ductal carcinoma, which has certain clinical significance.

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The diagnostic values of WMR, MLR and their combination in the severity of coronary artery disease

LIU Yixiang, FAN Wenjun, DING Zhenjiang, ZHANG Ying, SHI Fei, LIU Jingyi, SUN Lixian

2022, 50 (8): 859-862. doi: 10.11958/20220181

Abstract ( 751 )

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Objective To explore the association of the number of white blood cell to mean platelet volume ratio (WMR), monocyte to lymphocyte ratio (MLR) and their combination on the diagnostic value for coronary artery disease (CAD) and the severity of coronary artery stenosis. Methods A total of 2 728 inpatients were divided into the CAD group (n=1 884) and the non-CAD group (n=844) according to coronary angiography (CAG)．The clinical and laboratory data of all the subjects were collected. The cutoff values of these inflammatory markers to diagnose CAD were calculated using receiver operating characteristic (ROC) curves. Multivariate Logistic regression model for the risk factors of CAD was established. The correlation between WMR, MLR and the severity of CAD was analyzed. Results The proportion of male, age≥65 years, smoking, hypertension, diabetes, dyslipidemia, ischemic stroke, WMR≥0.77 and MLR≥0.27 levels were significantly higher in the CAD group than those in the non-CAD group (P<0.05). The areas under the ROC curves of the WMR, MLR and WMR+MLR were 0.639 (95%CI: 0.618-0.661), 0.621 (95%CI: 0.598-0.644) and 0.677 (95%CI: 0.656-0.698), respectively (P<0.05). The elevated WMR and MLR were independent risk factors for CAD (P<0.05). WMR and MLR were positively correlated with Gensini score (P<0.05). Conclusion The combined elevation of WMR and MLR is an independent risk factor for CAD, which is expected to be a novel inflammatory marker to help diagnose CAD.

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Construction and validation of the nomogram predictive model for recurrence risk after primary meningioma resection

JI Hui, ZHOU Linling, YU Lan, JIANG Wei

2022, 50 (8): 863-867. doi: 10.11958/20211806

Abstract ( 580 )

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Objective To construct a nomogram predictive model for recurrence risk in patients with primary meningioma resection and verified externally. Methods A total of 328 patients with meningiomas confirmed pathologically were included in the model group. The nomogram predictive model of recurrence risk after primary resection was constructed and internally verified. In addition, another 62 patients with meningiomas diagnosed in the same way were included as the verification group, and the model was externally verified. The two groups were sub-divided into the recurrence group and the non-recurrence group. Results The postoperative recurrence was 41 (12.5%) in the model group. Compared with the non-recurrence group, the proportion of men was more, preoperative Karnofsky Performance Scale (KPS) score was lower, the maximum diameter of tumor (>42 mm) was larger in the recurrence group. MRI showed more irregular shape of tumor, peritumoral vessels, uneven reinforcement, regular or irregular tumor-cortical interface, brain invasion, higher peritumoral edema (EI>4) and tumor basal diameter (>42 mm) increase in the recurrence group. Simpson resection grade (Ⅱ-Ⅳ) and pathological grade (Ⅱ-Ⅲ) were increased. Ki-67 index≥5% was more in the recurrence group (P<0.05). Multivariate Logistic regression analysis showed that uneven reinforcement, brain invasion, Simpson resection grade (Ⅱ-Ⅳ) and pathological grade (Ⅱ-Ⅲ) were the independent risk factors of postoperative recurrence in the model group. The nomogram predictive model was internally verified by Bootstrap, and H-L test showed (χ²=6.958, P=0.421). The calibration curve fitted well. The area under the curve (AUC) was 0.856 (95%CI: 0.767-0.901). External verification showed that the AUC value was 0.833 (95%CI: 0.779-0.896). Conclusion The prediction model based on the the construction of nomogram can earlily guide clinicians to identify patients with high risk of recurrence early and take targeted interventive strategies, which has good clinical application value.

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The study on the TNF-α/hs-CRP double-labeled time-resolved fluorescence immunoassay for early screening and diagnosis of sepsis

LI Yunpeng, HAO Peiyuan, CAO Xueming, YAN Zhaoyue, WANG Enfeng, HUANG Shuman, DAI Rongqin

2022, 50 (8): 868-872. doi: 10.11958/20220176

Abstract ( 530 )

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Objective To investigate the value of double-labeled time-resolved fluorescence immunoassay (TRFIA) for quantitatively detecting serum levels of tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP). Methods Anti-TNF-α and hs-CRP monoclonal antibodies were coated on the 96-well plate, meanwhile prepared the europium (Eu³⁺) and samarium (Sm³⁺)-detection antibody conjugates, and then established the double-antibody sandwich TRFIA method and assembly into a kit, and finally evaluated the detection performance of this kit, such as sensitivity, linear range, spike recovery rate. Results A new method for detecting serum TNF-α and hs-CRP levels by TRFIA was successfully established and assembled into a kit. The linear range of the prepared TRFIA kit for TNF-α was 0-100 ng/L, sensitivity was 0.05 ng/L, the linear range for hs-CRP was 0-100 mg/L, sensitivity was 0.02 mg/L. The spiked recovery rate of TNF-α was between 92.00% and 107.00%, and that of hs-CRP was between 95.00% and 106.82%. There was no obvious cross-reaction with the symptom detection indexes. The TNF-α CV of intra-assay was between 4.57% and 9.24%. The inter-assay was between 5.13% and 9.27%. The hs-CRP CV of intra-assay was between 5.12% and 7.69%, and the inter-assay was 6.07%-10.00%. Additionally, the kit can be stored stably at 4 ℃ for half a year and at 37 ℃ for 7 days. The detection threshold of TNF-α was 0.44 ng/L, and the detection threshold of hs-CRP was 1.41 mg/L. The test results of the kit were consistent with the clinical situation, and the coincidence rate reached 100%. Conclusion The double-labeled TRFIA method can quantitatively detect TNF-α and hs-CRP levels, which has the advantages of high sensitivity, high specificity, convenience and fast. This TRFIA kit provides a new detection method for the early screening, efficacy evaluation and prognostic assessment of clinical samples of sepsis.

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Effects of camrelizumab combined with chemotherapy on serum miR-21 and soluble E-cadherin in patients with advanced esophageal cancer

HU Jiahai, XUE Song, CHEN Quan

2022, 50 (8): 873-877. doi: 10.11958/20220150

Abstract ( 616 )

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Objective To investigate the effect of camrelizumab combined with chemotherapy on serum miR-21 and soluble E-cadherin (sE-Cad) in patients with advanced esophageal cancer. Methods A total of 110 patients with advanced esophageal cancer were divided into the combination group (57 cases) and the chemotherapy group (53 cases) according to different therapeutic regimens. Patients in the chemotherapy group were treated with paclitaxel (260 mg/m²) and cisplatin (30 mg/m²) for chemotherapy, while those in the combination group were additionally treated with camrelizumab (200 mg every time, once every 2 weeks) on this basis. The overall curative effect was evaluated after 4-6 cycles of treatment. The serum levels of tumor markers and sE-Cad were detected by enzyme linked immunosorbent assay, and the serum level of miR-21 was detected by real-time fluorescence quantitative polymerase chain reaction. The incidence of adverse reactions during treatment was recorded. Results After treatment, the objective response rate (ORR) and disease control rate (DCR) were higher in the combination group than those in the chemotherapy group (70.18% vs. 45.28% and 91.23% vs. 77.36%, P<0.05). The serum levels of carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), squamous cell carcinoma-related antigens (SCC), miR-21 and sE-Cad were significantly lower in the combination group than those in the chemotherapy group (P<0.05). During treatment, the incidence of reactive capillary endothelial proliferation was higher in the combination group than that of the chemotherapy group (P<0.01). Conclusion Camrelizumab combined with chemotherapy has good short-term efficacy in the treatment of advanced esophageal cancer, which can effectively reduce levels of tumor markers, down-regulate serum miR-21 and sE-Cad.

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Effects of different doses of dexamethasone on iliac fascia block of ropivacaine under ultrasound guidance

WANG Dan, ZHAO Lixia, PENG Yaqi, YUAN Dajiang

2022, 50 (8): 878-882. doi: 10.11958/20212860

Abstract ( 511 )

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Objective To investigate the blocking effects of different doses of dexamethasone combined with ropivacaine in iliac fascia space block (FICB) after total hip replacement (THA). Methods A total of 83 patients with THA were divided into the observation group 1 (n=27), the observation group 2 (n=28) and the control group (n=28) according to the random number table. All patients were performed FICB guided by ultrasound. The observation group 1, the observation group 2 and the control group were given 0.25% ropivacaine 100 mg combined with dexamethasone 5 mg, 10 mg and 0 mg, respectively. The duration of surgery and visual analog scale (VAS) scores at rest and exercise at 4, 8, 12, 24, 36 and 48 hours after local anesthetic injection were recorded. Quadriceps muscle strength scores at 8, 12, 24, 36, 48 hours after injection, analgesic pump pressing times and remedial analgesia times within 48 hours after injection were recorded. Results There were no significant differences in operation duration, VAS scores at 4, 8 and 48 hours between the three groups. At 12, 24 and 36 hours, the VAS scores during rest and exercise were significantly lower in the observation group 1 and the observation group 2 than those of the control group (P<0.05), and there were no significant differences in VAS scores during rest and exercise between the observation group 1 and the observation group 2. There were no significant differences in muscle strength grade 1-5 score composition at 8, 12, 24, 36 and 48 hours between the three groups. The ratio of 2 or more times of analgesic pump pressing and 1 or more times of remedial analgesia within 48 hours after operation were significantly lower in the observation group 1 and the observation group 2 compared with those of the control group (P<0.05), but there were no significant differences between the observation group 1 and the observation group 2. Conclusion The FICB analgesic effect of ropivacaine can be enhanced by dexamethasone 5 mg and 10 mg, but the inhibitory effect of quadriceps muscle strength is not increased.

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Efficacy and safety analysis of tofacitinib and yisaipu combined with methotrexate in the treatment of refractory rheumatoid arthritis

LUO Huan, ZHANG Xia, FENG Yarao, ZHAO Yue, REN Zhanfen, YANG Jinliang, ZHENG Xuejun

2022, 50 (8): 883-887. doi: 10.11958/20212650

Abstract ( 2086 )

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Objective To explore the effect and safety of tofacitinib and tumor necrosis factor-α receptor antagonist (yisaipu) combined with methotrexate in the treatment of refractory rheumatoid arthritis (RRA). Methods According to random number table method, 60 patients with RRA were divided into the group A, the group B and the group C, 20 cases in each group. The group A was treated with citrate tofacitinib (5 mg) and methotrexate (10 mg), the group B was treated with yisaipu (25 mg), and the group C was treated with yisaipu (25 mg) and methotrexate (10 mg). The clinical curative effects, clinical symptoms, disease activity indexes, inflammatory factors and adverse reactions were compared between different groups. Results After treatment, the clinical effective rate was significantly higher in the group A than that in the group B (P<0.05). However, there were no significant differences in indexes of clinical curative effect between the group A and the group C, and between the group B and the group C (P>0.05). After treatment, joint tenderness, joint swelling, levels of erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), serum interleukin (IL)-6, IL-1β and IL-17 were significantly decreased compared with before treatment in the three groups (P>0.05). The number of joint tenderness and joint swelling, morning stiffness time, levels of ESR, RF, CRP, IL-6, IL-1β and IL-17 were lower in the group A than those in the group B and the group C. The morning stiffness time, levels of ESR, RF, CRP, IL-6, IL-1β and IL-17 were lower in the group C than those in the group B (P<0.05). There was no significant difference in the incidence of adverse reactions during treatment between the three groups (P>0.05). Conclusion Tofacitinib combined with methotrexate has significant efficacy in the treatment of RRA, which is superior to yisaipu alone or yisaipu combined with methotrexate in clinical symptom improvement, disease activity index control and inflammatory factor level inhibition, with good safety.

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The research progress on the mechanism of Wnt/β-catenin signaling pathway involved in multiple myeloma

XU Jiawei, GUO Yihui, SONG Hui, CHENG Weimin

2022, 50 (8): 888-891. doi: 10.11958/20220179

Abstract ( 428 )

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Multiple myeloma (MM) is a hematological tumor characterized by malignant proliferation of bone marrow plasma cells, and its mechanism of occurrence is closely related to the abnormalities of related signaling pathways. Wnt/β-catenin signaling pathway is involved in the regulation of cell proliferation, differentiation, apoptosis and other biological processes, and it is associated with cell carcinomatosis. In MM, abnormally expressed non-coding RNAs, transcription factors, proteases and secreted proteins can activate the Wnt/β-catenin signaling pathway, thus accelerating the occurrence and development of MM. Therefore, Wnt/β-catenin signaling pathway plays an important role in the pathogenesis of MM. This paper collates and summarizes the research progress of relevant non-coding RNAs, transcription factors, proteases and secretory proteins in MM that affect the Wnt/β-catenin signaling pathway, in order to provide reference for related research.

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Research progress on effects of sevoflurane on apoptosis related signal pathways of hippocampal neurons

XIE Yunfan, LIU Mi, TIAN Yi

2022, 50 (8): 892-896. doi: 10.11958/20212285

Abstract ( 564 )

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Sevoflurane is a widely used inhalation anesthetic, and there is growing concern about its effects on cognitive function. Sevoflurane can cause neurotoxicity, resulting in neuronal damage, apoptosis and cognitive dysfunction. Neuronal apoptotic pathways include the endogenous apoptotic pathway, the exogenous apoptotic pathway and the endoplasmic reticulum pathway. Apoptosis-related signaling pathways, such as phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK), play an important role in these pathways. This paper reviews the recent literature in this field and provides a review of the possible signaling pathways involved in sevoflurane-induced apoptosis in hippocampal neuronal cells.

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