Tianjin Medical Journal

Effects of substance P on the secretory function and the expression of endogenous VEGF, bFGF and PDGF in radiation-injured skin fibroblasts

LIN Haipeng, DANG Xuhong, ZUO Yahui

2022, 50 (10): 1009-1013. doi: 10.11958/20220599

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Objective To explore the the effects of neuropeptide substance P (SP) on the secretory function and the expression of endogenous vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) in skin fibroblasts after radiation injured. Methods HFF-1 cells in logarithmic growth phase were divided into 10 experimental groups according to the irradiation dose: the 0 Gy, 2 Gy, 6 Gy, 12 Gy, 18 Gy, 0 Gy+SP, 2 Gy+SP, 6 Gy+SP, 12 Gy+SP and 18 Gy+SP. Exogenous SP intervention was performed before irradiation with 0 Gy+SP, 2 Gy+SP, 6 Gy+SP, 12 Gy+SP and 18 Gy+SP. The enzyme linked immunosorbent assay (ELISA) was used to detect the expression levels of typeⅠcollagen (Col-Ⅰ), type Ⅲ collagen (Col-Ⅲ), calcitonin gene related peptide (CGRP) in cell culture medium and Col-Ⅰ, Col-Ⅲ, CGRP, VEGF, bFGF and PDGF in cell lysate 24 h after irradiation. Quantificational real-time polymerase chain reaction (qPCR) was used to detect the expression levels of VEGF, bFGF and PDGF mRNA. Results Compared with the 0 Gy experimental group, Col-Ⅰ, Col-Ⅰ/Col-Ⅲ in culture medium and CGRP and VEGF proteins in cell lysate were increased in the irradiated groups, bFGF and PDGF mRNA were increased in the irradiated groups (6 Gy, 12 Gy and 18 Gy). The Col-Ⅰ was highly expressed in the culture medium and cell lysate of the 6 Gy group. The Col-Ⅰ, Col-Ⅲ, Col-Ⅰ/Col-Ⅲ and CGRP were highly expressed in the culture medium and cell lysate of the 18 Gy group. The bFGF was highly expressed at protein and mRNA levels in irradiated groups (12 Gy and 18 Gy). When SP intervention was given before irradiation, the CGRP expression was consistently high in the culture medium and lysate of the 0 Gy+SP group than that of the corresponding group without intervention. The Col-Ⅰ and Col-Ⅰ/Col-Ⅲ were consistently low expressed in the culture medium and lysate of the intervention groups (2 Gy+SP, 6 Gy+SP) and (2 Gy+SP, 6 Gy+SP and 18 Gy+SP), respectively. VEGF and PDGF were highly expressed at protein and mRNA levels in the intervention groups (2 Gy+SP, 12 Gy+SP and 18 Gy+SP) and (12 Gy+SP, 18 Gy+SP), respectively. Conclusion Exogenous SP could regulate the expression and secretion of Col-Ⅰ and Col-Ⅲ, decrease the ratio of Col-Ⅰ/Col-Ⅲ and promote the high expression of VEGF and PDGF in radiation injured skin fibroblasts, so as to coordinate the stress response of fibroblasts to electron beam irradiation.

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Effects of hypoxia exposure on proliferation and apoptosis of mouse spleen lymphocytes

GUO Yujing, HU Ying, LONG Qifu, XU Yuzhen, LI Jidong, YONG Sheng

2022, 50 (10): 1014-1019. doi: 10.11958/20220649

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Objective To investigate the relationship between lymphocyte number reduction, cell proliferation and apoptosis induced by hypoxia exposure. Methods Lymphocytes were isolated from spleen of C57BL/6 mice and cultured in hypoxia (1%O₂) and normoxia (21%O₂) for 12, 24 and 48 h, respectively. T and B lymphocytes were assessed by flow cytometry. Proliferation and apoptosis of lymphocytes were detected by CFSE and AnnexinⅤ-FITC/PI method, respectively. The morphology of lymphocytes was observed by scanning electron microscope. The mRNA and protein expression levels of apoptosis-related factor bcl-2 homologous antagonist killer protein (Bak), murine B-cell lymphoma/leukemia-2 (bcl-2) and cysteine aspartate protease-3 (caspase-3) were detected by real-time quantitative reverse transcription PCR (qPCR) and Western blot assay. Results Hypoxic exposure for 12, 24 and 48 h can reduce the number of T and B lymphocytes, inhibit the proliferation of lymphocytes and promote cell apoptosis. Scanning electron microscopy showed that at the same time, the characteristic morphological changes of apoptosis appeared earlier in the hypoxic group. After 12, 24 and 48 h hypoxia exposure, the mRNA and protein expression levels of Bak and caspase-3 in lymphocytes were up-regulated, while the mRNA and protein expression levels of bcl-2 were down-regulated. Conclusion Hypoxic exposure mediates the decline of lymphocyte numbers by inhibiting lymphocyte proliferation and promoting apoptosis.

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Effects of high glucose on the proliferation and migration of mesangial cells and extracellular matrix formation by regulating the CAV-1/EGF through miR-192

WU Weixi, LIU Shuaihui, ZHOU Saijun, LIU Hongyan, ZHANG Rui, YU Pei

2022, 50 (10): 1020-1025. doi: 10.11958/20220268

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Objective To investigate the effect of miR-192 on proliferation, migration and extracellular matrix of mesangial cells under high glucose condition. Methods Human mesangial cells were cultured in vitro for 24 h and divided into six groups: the normal glucose concentration (NG, 5.6 mmol/L glucose) group, the high glucose concentration (HG, 25 mmol/L glucose) group, the normal glucose concentration+miR-192 mimics (NG+mimics) group, the high glucose concentration+miR-192 mimics (HG+ mimics) group, the normal glucose concentration+miR-192 inhibitor (NG+inhibitor) group and the high glucose concentration+miR-192 inhibitor (HG+inhibitor) group. After 24 h of intervention, cell viability was detected by CCK-8 assay, the cell migration ability was detected by Scratch healing test, and expression levels of miR-192, caveolin 1 (CAV-1), epidermal growth factor (EGF), collagen type 1 (COLⅠ) and fibronectin (FN) mRNA and related proteins were detected by qPCR and Western blot assay. Results Compared with the NG group, the proliferation and migration rates were increased, the expression levels of EGF, FN and COLⅠmRNA and protein were increased, and the expression of CAV-1 mRNA and protein decreased in the HG group (all P<0.05). When miR-192 inhibitor was added to the NG group and the HG group, the cell proliferation and migration were decreased, the expression of EGF, FN and COLⅠ mRNA and protein were decreased, while the expression levels of CAV-1 mRNA and protein were increased (all P<0.05). Changes were more significant in the HG group after the addition of miR-192 inhibitor. After adding miR-192 mimics to the NG group and the HG group, the cell proliferation and migration increased, expression levels of EGF, FN and COLⅠ mRNA and protein increased, and the expression of CAV-1 decreased (all P<0.05). Conclusion High glucose increases the proliferation and migration of glomerular mesangial cells through miR-192-CAV-1-EGF pathway, leading to the formation of extracellular matrix and participating in the occurrence and development of diabetic nephropathy.

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Endotoxin exacerbates liver injury by down-regulating HNF4α expression

TANG Yongjing, CHEN Yunfen, LIAO Yue, CHENG Qijiao, ZHANG Guijuan, WANG Yun, HE Yihuai

2022, 50 (10): 1026-1030. doi: 10.11958/20212081

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Objective To investigate the mechanism of endotoxemia down-regulating the expression of hepatocyte nuclear factor 4α (HNF4α) and mediating the progression of liver injury. Methods A total of 144 BALB/c mice were divided into the following experiments using the digital table method. (1) carbon tetrachloride (CCl₄) induced acute liver injury in mice: the control group, the 0.5 mL/kg, the 1.0 mL/kg and the 2.0 mL/kg groups; (2) screening doses of lipopolysaccharide (LPS) intervention in mice: the control group, the 0.1 mg/kg, the 0.5 mg/kg and the 2.5 mg/kg LPS groups; (3) LPS intervention in CCl₄ (1.0 mL/kg)-induced acute liver injury model mice: the control group, the CCl₄ group, the 0.1 mg/kg LPS + CCl₄ group and the 0.5 mg/kg LPS + CCl₄ group. There were 12 mice in each dose group. Mice were sacrificed after 24 hours induction, and blood samples of mice were collected to detect serum alanine aminotransferase (ALT) by enzyme rate method, and total bilirubin (TBil) level by diazo method. The protein contents of HNF4α and Cleaved caspase-3 in liver tissue were detected by Western blot assay. TUNEL assay was used to detect the apoptosis of hepatocytes. Results The serum levels of ALT, TBil, and liver tissue HNF4α and Cleaved caspase-3 protein expression levels were higher in the 0.5, 1.0 and 2.0 mL/kg CCl₄ groups than those in the control group in a dose-dependent manner. The serum levels of ALT and TBil, and liver tissue Cleaved caspase-3 protein were higher in the 2.5 mg/kg LPS group than that in the control group and the 0.1 and 0.5 mg/kg LPS groups. The expression level of HNF4α protein in liver tissue was lower in the 2.5 mg/kg LPS group than that in the control group and the 0.1, 0.5 mg/kg LPS group (P<0.05). Serum levels of ALT and TBil, liver tissue HNF4α and Cleaved caspase-3 protein expression levels and hepatocyte apoptosis index were higher in the CCl₄ group and the 0.1 and 0.5 mg/kg LPS + CCl₄ groups than those in the control group (P<0.05). The serum ALT, TBil, liver tissue Cleaved caspase-3 protein expression level and hepatocyte apoptosis index were higher in the 0.1, 0.5 mg/kg LPS+CCl₄ groups than those of CCl₄ group. The protein expression level of HNF4α was lower than that of the CCl₄ group (P<0.05). Conclusion Endotoxemia increases hepatocyte apoptosis by downregulating the expression of HNF4α, which may be one of the machanisms mediating the progression of liver injury.

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Exploration on the regulation mechanism of Bupi Qiangli compound in immune system balance of EAMG rats based on HPTT axis

WANG Qiang, KUANG Shixiang, LI Ruozhao, LOU Jinbo, QIAN Yijia, YONG Bo, LIU Yunquan

2022, 50 (10): 1031-1036. doi: 10.11958/20220260

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Objective To investigate the mechanism of Bupi Qiangli compound in regulating immune system balance in experimental autoimmune myasthenia gravis (EAMG) rats based on the hypothalamic-pituitary-thyroid-thymus (HPTT) axis. Methods A total of 120 Lewis rats were randomly divided into the control group, the model group, the Bupi Qiangli compound groups (low-dose, medium-dose and high-dose groups, 4.75, 7.12 and 9.49 g/kg) and western medicine group (prednisone, 5.4 mg/kg), with 20 rats in each group. Behavioral changes (body weight, Lennon score) were observed during the experiment. After the experiment, histopathological changes of thymus were assessed by HE staining. The serum contents of acetylcholine receptor antibody (AchR-Ab), tumor necrosis factor-β (TNF-β), interleukin-4 (IL-4) and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the expression of CD4⁺CD25⁺Foxp3⁺Treg cells in rat thymus. At the same time, HPTT axis function damage index [triiodothyronine (T3), thyroxine (T4), TSH, thyroid stimulating hormone (TSH), thyroid stimulating hormone releasing hormone (TRH), hypothalamic T3 receptor (T3R) and norepineadrenalin (NE)] levels were detected. Results After modeling, compared with the control group, the body quality of each modeling group decreased and the Lennon score increased. After administration, body weights were increased in the Bupi Qiangli compound low-dose, medium-dose and high-dose groups and western medicine group than those of the model group, while values of Lennon score were decreased (P<0.05). HE staining showed degeneration and necrosis of lymphocytes in cortical area, disappearance of thymic bodies in medullary area, and decreased cell number in the model group. The number of cells in thymus cortical area and medulla area of rats were significantly increased in the low, medium and high dose groups of Bupi Qiangli compound and western medicine groups. Compared with the control group, the proportion of CD4⁺CD25⁺ Treg and CD4⁺CD25⁺Foxp3⁺ Treg in thymus were decreased in the model group, and the proportion of CD4⁺CD25^-Foxp3⁺ Treg and CD4⁺CD25⁺Foxp3⁺ Treg were increased (P<0.05). The serum levels of AchR-Ab, TNF-β, IL-4, IL-10, TSH and TRH were significantly increased, while the levels of T3R and NE were significantly decreased (P<0.05). Compared with the model group, the proportion of CD4⁺CD25⁺ Treg and CD4⁺CD25⁺Foxp3⁺ Treg were significantly increased in the Bupi Qiangli compound medium-dose and high-dose groups and western medicine group, while the proportion of CD4⁺CD25^-Foxp3⁺ Treg and CD4⁺CD25⁺Foxp3⁺ Treg decreased. Serum AchR-Ab, TNF-β, IL-4, IL-10, TSH and TRH levels were significantly decreased (P<0.05). T3R and NE levels were increased. Conclusion Bupi Qiangli compound can improve the autoimmune balance of EAMG rats by regulating HPTT axis and related factors.

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Effects of pirfenidone on myocardial fibrosis in rats by regulating TGF-β/Smad pathway through miRNA-425-5p

ZOU Lin, ZHANG Xin, LI Li

2022, 50 (10): 1037-1042. doi: 10.11958/20212788

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Objective To investigate the effects of pirfenidone (PFD) on myocardial fibrosis in rats with myocardial infarction by regulating miRNA-425-5p and transforming growth factor (TGF)-β/Smad pathways. Methods Sixty male SD rats were divided into three groups: the sham operation group (no coronary artery ligation), the myocardial infarction model group (coronary artery was ligated) and the PFD group (coronary artery ligation + PFD 0.3 g /kg by gavage). Cardiac function of rats in each group was evaluated by cardiac Doppler ultrasonography 4 weeks after modeling. The levels of interleukin-6 (IL-6), type Ⅰ collagen α2 (COL1α2) and type Ⅲ collagen α1 (COL3α1) were detected by ELISA. Masson staining was used to evaluate the degree of myocardial fibrosis in rats. Image-pro Plus 6.0 was used to analyze myocardial collagen volume fraction in each group. The protein expression levels of TGF-β1, Smad2 and Smad3 in myocardial tissue were detected by Western blot assay. The expression level of miRNA-425-5p in myocardial tissue was detected by quantitative real-time PCR (qPCR). Meanwhile, cardiac fibroblasts from suckling rats were isolated and cultured in vitro and divided into 3 groups: the control group (without any substance), the miRNA-425-5p mimic group (the control group was transfected with miRNA-425-5p mimic), the PFD group (the control group was added with PFD at the final concentration of 1.5 g/L). The mRNA expression levels of miRNA-425-5p and TGF-β1 in each group were detected by qPCR. Results Compared with the sham operation group, cardiac LVESd and LVEDd were increased in the model group, LVEF and FS% decreased (P<0.05). Masson staining and quantitative analysis showed that myocardial fibrosis was aggravated. The serum levels of IL-6, COL3α1 and COL1α2 were significantly increased (P<0.05). The protein expression levels of TGF-β1, Smad2 and Smad3 were significantly increased, and the expression of miRNA-425-5p was significantly decreased (P<0.05). Compared with the model group, LVESd and LVEDd were decreased in the PFD group, while LVEF and FS% were increased (P<0.05). Masson staining and quantitative analysis showed that the degree of myocardial fibrosis was alleviated, and serum levels of inflammatory factors IL-6, COL3α1 and COL1α2 were significantly decreased (P<0.05). The protein expression levels of TGF-β1, Smad2 and Smad3 in myocardial tissue were significantly decreased, while miRNA-425-5p was significantly increased (P<0.05). In vitro cell assay results showed that compared with the control group, the miRNA-425-5p expression level increased in the miRNA-425-5p mimic group, while TGF-β1 mRNA expression level decreased (P<0.05). Compared with the control group, the expression level of miRNA-425-5p was increased, and the expression level of TGF-β1 mRNA was decreased in the PFD group (P<0.05). Conclusion Pirfenidone can regulate TGF-β/Smad signaling pathway by regulating miRNA-425-5p expression level, alleviate myocardial fibrosis and improve cardiac function in rats with heart failure after myocardial infarction.

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Study on the mechanism of resveratrol reversing temozolomide resistance in glioma cells by regulating Wnt/β-catenin pathway through BRD4

LI Zhenjiang, SUN Dechao, KONG Chenxu, GENG Yadong, XU Chenyang, DING Bingqian

2022, 50 (10): 1043-1049. doi: 10.11958/20220566

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Objective To explore whether the effect of resveratrol in reversing temozolomide (TMZ) resistance in glioma cells was related to the regulation of bromodomain-containing protein 4 (BRD4) and Wnt/β-catenin pathways. Methods Human glioma TMZ low-sensitivity cell line (U138), high-sensitivity cell line (U251) and drug-resistant cell line (T98G) were obtained, and Western blot assay was performed to detect the protein expressions of BRD4, Wnt3a, β-catenin and TMZ drug resistance protein (MGMT). T98G cell line was taken and divided into the control group 1 (adding 100 μmoL/L TMZ), the RES1 group (adding 50 μmoL/L RES) and RES+TMZ group (adding 100 μmoL/L TMZ and 50 μmoL/L RES). Cell proliferation and apoptosis were measured by CCK-8 method and flow cytometry. Protein expressions of BRD4, Wnt3a, β-catenin and MGMT were measured by Western blot assay. In order to analyze the effect of BRD4 overexpression on TMZ resistance, on the basis of adding 100 μmoL/L TMZ, T98G cells were transfected with BRD4 overexpression plasmid (pcDNA BRD4) or added 50 μmoL/L RES, and cells were divided into the pcDNA NC group, the pcDNA BRD4 group, the RES2 group and the RES+pcDNA BRD4 group. In order to verify the regulatory effect of BRD4 on Wnt3a/β-catenin pathway, on the basis of adding 100 μmoL/L TMZ, BRD4 inhibitor JQ1 and the Wnt3a/β-catenin pathway activator LiCl were added, and cells were divided into the control 2 groups, the JQ1 group and the JQ1+LiCl group. T98G cells were inoculated into the left scapular region of nude mice, and treated with RES, TMZ and/or JQ1. Protein expressions of Ki67, BRD4, MGMT and Wnt3a/β-catenin in tumor were measured. Results Compared with the high-susceptibility strain (U251), the expressions of BRD4, Wnt3a, β-catenin and MGMT increased in sequence in the low-susceptibility strain (U138) and the drug-resistant strain (T98G) (P<0.05). Compared with the control group 1, RES intervention could inhibit the expression and proliferation of BRD4, Wnt3a/β-catenin and MGMT proteins in T98G cells, promote apoptosis and reverse cell drug resistance (P<0.05). PcDNA BRD4 could reverse the anti-proliferative and pro-apoptotic effects of RES. BRD4 inhibitor JQ1 could inhibit the expression and proliferation of BRD4, Wnt3a/β-catenin and MGMT proteins in T98G cells, and promote apoptosis (P<0.05). LiCl could reverse the anti-proliferative and pro-apoptotic effects of JQ1. RES alone or in combination with JQ1 could activate the inhibitory effect of TMZ on Wnt3a/β-catenin pathway, MGMT expression and cell proliferation in tumors (P<0.05). Conclusion RES can reverse TMZ resistance of glioma T98G cells by downregulating BRD4 and thereby inhibiting the activation of Wnt3a/β-catenin pathway.

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The role of palmitoylated NOD₂ in animal model of hemorrhagic shock

GU Zi, TANG Yong, ZHOU Chengji, ZHENG Qiang

2022, 50 (10): 1050-1055. doi: 10.11958/20212779

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Objective To investigate the effect and mechanism of nucleotide binding oligomerization domain 2 (NOD₂) on lung injury during hemorrhagic shock and ischemia-reperfusion. Methods Ten NOD₂ knockout SD rats were set as the control group after the preparation of hemorrhagic shock model (normal saline was given at the initial stage of resuscitation). Thirty ordinary SD rats were randomly divided into three groups: the blank group (normal saline was given at the initial stage of resuscitation), the palmitoyl modification enzyme (PAT) antibody group (PAT antibody was given at the beginning of resuscitation) and the NOD₂ antibody group (NOD₂ antibody was given at the beginning of resuscitation), with 10 rats in each group. After 24 hours of resuscitation, blood samples were collected, and lung tissues were collected. Blood gas analysis was performed at the beginning of the experiment, at the beginning of shock and 2 hours after reperfusion. Plasma tumor necrosis factor (TNF)-α, interleukin (IL) -1β, IL-6, malondialdehyde (MDA) and myeloperoxidase (MPO) in lung tissue were detected. High mobility group B (HMGB1), palmitoylated transfer protein (ZDHHC5) and NOD₂ were detected by Western blot assay. The pathological sections of lung tissue were observed under fluorescence microscope and light microscope. Results The oxygen partial pressure [p(O₂)] at 240 min was significantly lower in the blank group than that in the other three groups (P<0.05). The lactate levels at 30 min and 240 min were significantly higher in the blank group than those in the other three groups (P<0.05). TNF- α, IL-1β, IL-6, MDA and MPO levels were the highest in the blank group (P<0.05),and which was lower in the control group than that of the anti-PAT group and the anti-NOD₂ group. The expression levels of HMGB1, NOD₂ and ZDHHC5 were the highest in the blank group (P<0.05), and the expression levels of HMGB1 and NOD₂ were lower in the control group than those in the anti-PAT group and anti-NOD₂ group (P<0.05). The immunofluorescence expression of palmitoylated NOD₂ was significantly higher in the blank group than that in the control group, anti-PTA group and anti-NOD₂ group. Compared with the control group, the alveolar endothelium and alveolar tissue were significantly damaged and the inflammatory cell infiltration was obvious in the blank group, anti-PTA group and anti-NOD₂ group. Conclusion In hemorrhagic shock and ischemia-reperfusion animal models, NOD₂ produces palmitoylated NOD₂ under the regulation of ZDHHC5, thereby promoting the release of TNF-α, IL-1β, IL-6, MDA and MPO, resulting in lung inju

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The response of mouse pancreas to gradient cholecystokinin

WU Ping, HU Lijuan, XU Xiaoqing, LI Qiuju, YAO Chuanshan, WANG Feng

2022, 50 (10): 1056-1060. doi: 10.11958/20220309

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Objective To investigate the effect of cholecystokinin (CCK) on pancreas and occurrence of pancreatic cancer, and to explore the anticancer effect of a component of green tea, epigallocatechin galate (EGCG). Methods Growing mice were randomly divided into 4 groups, and mice were given water containing soybean trypsin inhibitor (STI) 0 g/L (n=11), 2 g/L (n=11), 4 g/L (n=10) and 8 g/L (n=11), respectively. After 2 weeks, mice were sacrificed and the wet weight of pancreas was recorded. Plasma CCK level was detected by enzyme-linked immunosorbent assay (ELISA). The contents of protein, DNA, trypsin and lipase in pancreatic tissue were determined. The percentage of proliferating cell nuclear antigen (PCNA) positive cells in pancreatic tissue was detected by immunohistochemical staining. The carcinogenesis model was established by embedding dimethyl benzoanthracene (DMBA) in pancreas. Fifteen mice were randomly divided into the normal control group, the DMBA embedding group, the DMBA+2 g/L STI group, the DMBA+8 g/L STI group and the DMBA+8 g/L STI+EGCG group. After 6 weeks, the mice were sacrificed and the pancreas was taken for histological analysis. Results CCK level was higher in the 2 g/L STI group than that in the 0 g/L STI group, and which was higher in the 8 g/L STI group than that in the 0, 2 and 4 g/L STI group (P<0.05). The wet weight of pancreas was higher in the 2 g/L STI group and the 4 g/L STI group than that in the 0 g/L STI group, and which was higher in the 8 g/L STI group than that in the 0 g/L STI group and the 2 g/L STI group (P<0.05). The contents of pancreatic protein and DNA were higher in the 2 g/L STI group and 4 g/L STI group than those in the 0 g/L STI group, and which were higher in the 8 g/L STI group than those in the 0 g/L STI group, 2 g/L STI group and 4 g/L STI group (P<0.05). The content of trypsin increased successively in the 0 g/L STI group, the 2 g/L STI group, the 4 g/L STI group and the 8 g/L STI group. The lipase content was significantly higher in the 2 g/L STI group, the 4 g/L STI group and the 8 g/L STI group than that in the 0 g/L STI group (P < 0.05). The proportion of PCNA-positive cells in pancreatic tissue of mice increased successively in the 0 g/L STI group, 2 g/L STI group, the 4 g/L STI group and the 8 g/L STI group (P < 0.05). The degree of pancreatic cancer prelesion was aggravated with the increase of STI dose in drinking water, and EGCG can alleviate this lesion. Conclusion STI can induce gradient cholecystokininemia, stimulate pancreatic hyperplasia, trypsin production and pancreatic cancer, while EGCG can alleviate pancreatic precancerous lesions.

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Study on the correlation between glycosylated hemoglobin and carotid intima-media thickness

LI Xuemin, LI Weidong, SHI Wentao, WEI Fengjiang

2022, 50 (10): 1061-1065. doi: 10.11958/20220321

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Objective To study the correlation between glycosylated hemoglobin (HbA1c) level and carotid intima-media thickness (CIMT) thickening in general physical examination population. Methods A total of 9 881 cases with general physical examination were selected as the research object, including 7 091 males and 2 790 females. CIMT was measured by vascular color Doppler ultrasound. According to whether there was CIMT thickening, the cases were divided into the thickening group (4 513 cases) and the normal group (5 368 cases). The general data and laboratory data of the two groups were collected and compared. Logistic regression was used to analyze the risk factors of CIMT thickening in the general population and different genders. Receiver operating characteristic curve (ROC) was used to evaluate the predictive effect of the HbA1c level on CIMT thickening. Results Compared to the normal group, male proportion, age, body mass index (BMI), systolic blood pressure (SBP), direct bilirubin (DBIL), globulin (GLB), blood urea nitrogen (BUN), blood creatinine (Scr), blood glucose (GLU), HbA1c, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels were increased in the thickening group. The glomerular filtration rate (eGFR), alanine aminotransferase (ALT), albumin (ALB) and high density lipoprotein cholesterol (HDL-C) were decreased (P<0.05). Logistic regression analysis showed that in the total population, advanced age, male, ALB, GLU and LDL-C increased, and HbA1c≥5.7% was risk factors for CIMT thickening, while increased GLB and HDL-C were protective factors for CIMT thickening. In males, advanced age, increased ALB and LDL-C, and HbA1c≥5.7% were risk factors for CIMT thickening, while increased ALT, GLB and HDL-C were protective factors for CIMT thickening. In females, increased SBP and TC and HbA1c≥5.6% were risk factors for CIMT thickening, while increased BMI, eGFR, ALB, Scr and HDL-C were protective factors for CIMT thickening. ROC curve analysis showed that the optimal cut-off value of HbA1c in predicting CIMT thickening was 5.65% in the total population, males and females, and HbA1c has better predictive efficiency for CIMT thickening in females. Conclusion The elevated HbA1c levels are a risk factor for CIMT thickening in the general population, and HbA1c has a greater effect on CIMT thickening in the females.

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Comparison of treatment effects and complications of three kinds of gastrointestinal reconstruction procedures after radical gastrectomy

CHEN Hui, ZHU Xiaoming, LUO Zhenling, SHEN Jiahui, GU Qunhao, ZHOU Jia

2022, 50 (10): 1066-1071. doi: 10.11958/20220615

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Objective To compare the treatment effects and complications of three reconstruction procedures in patients after radical gastrectomy. Methods A total of 194 patients with radical gastrectomy were selected and divided into the U-RY group (Uncut Roux-en-Y anastomosis, 69 cases), the B Ⅰ group (Billroth-Ⅰ modified delta-shaped anastomosis, 65 cases) and the B Ⅱ+Braun group (Billroth-Ⅱ+Braun anastomosis, 60 cases) according to the gastrointestinal reconstruction methods. The basic data of the three groups were matched by propensity score matching. The surgical status, postoperative recovery status, intestinal barrier function [diamine oxidase (DAO), D-lactic acid, endotoxin (ETX)], inflammatory stress indicators [interleukin-6 (IL-6), interleukin-10 (IL-10), 8-iso-prostaglandin F2α (8-iso-PGF2α), heme oxygenase-1 (HO-1)] and complications were compared between the three groups. Results Before propensity score matching, gender and age were not evenly distributed in the three groups (P<0.05). After matching, 147 cases of 194 patients were successfully matched, with 49 cases in each group. There were no significant differences in general data between the three groups (P>0.05). The surgical time increased successively in the B Ⅰ group, the B Ⅱ+Braun group and the U-RY group (P<0.05). The intraoperative blood loss, postoperative bowel sound recovery time, first exhaust time, extubation time, eating time, first defecation time and hospital stay were less or shorter in the B Ⅰ group than those in the B Ⅱ+Braun group and the U-RY group (P<0.05), but there were no significant differences in the above indicators between the B Ⅱ+Braun group and the U-RY group (P>0.05). At 3 d after surgery, the levels of DAO, D-lactic acid and ETX were significantly lower in the B Ⅰ group than those of the U-RY group and the B Ⅱ+Braun group, while the levels of IL-6, IL-10, 8-iso-PGF2α and HO-1 were higher compared with those in the U-RY group and the B Ⅱ+Braun group (P<0.05). There were no significant differences in the above indicators between the U-RY group and the B Ⅱ+Braun group (P>0.05). There were no significant differences in incidence rates of complications between the three groups (P>0.05). Conclusion Billroth-Ⅰ modified delta-shaped anastomosis has the advantages of shorter surgical duration, less blood loss, faster recovery and smaller effect on the intestinal barrier compared to Billroth-Ⅱ+Braun anastomosis and Uncut Roux-en-Y anastomosis, but the latter two are more suitable for more indications and have milder inflammatory stimulation, and Uncut Roux-en-Y anastomosis can reduce postoperative reflux.

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A randomized controlled trial of minimally invasive surgery for hypertensive lobar hemorrhage

LI Qianfeng, DUAN Faliang, MIN Qiang, LUO Ming, WANG Chunyan, LUO Zhihua

2022, 50 (10): 1072-1076. doi: 10.11958/20220338

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Objective To compare the therapeutic efficacy of three types of minimally invasive procedures on hypertensive lobar hemorrhage. Methods According to the different preoperative hematoma volume, 120 patients with hypertensive lobar hemorrhage were divided into the large hematoma group and the small hematoma group, with 60 patients in each group. According to the random envelope method, each group was subdivided into the small bone window group (small bone window craniotomy assisted by neuronavigation for hematoma removal), the drilling group (hematoma cavity drainage assisted by neuronavigation) and the endoscopic group (neuroendoscopic hematoma removal assisted by neuronavigation), with 20 patients in each group. The following data of patients in each group were compared, including basic data, intraoperative data (operation time, intraoperative blood loss), postoperative data, hematoma clearance rates at 6 h, 3 d and 7 d after operation, Glasgow coma index score (GCS) at 6 h, 3 d and 7 d after operation, postoperative complications (tracheotomy, intracranial infection, recurrent bleeding), drainage tube retention time and drug injection time, prognosis data, Glasgow prognosis score (GOS) at 3 months after operation. Results There were no significant differences in age, preoperative hematoma volume, bleeding location, onset to operation time and preoperative GCS score between the large hematoma group and the small hematoma group (P>0.05). In the large hematoma group and the small hematoma group, compared with the small bone window group and the endoscopic group, the drilling group had the shortest operation time, the least intraoperative blood loss, and the hematoma clearance rate was reduced at 6 h and 3 d after surgery, and the drainage tube retention time was prolonged (P<0.05). There were no significant differences in complications between the three groups. In the large hematoma group, the GCS score was higher at 6 h after surgery in the endoscopic group than that of the drilling group, and the GCS score was higher at 3 d and 7 d after surgery in the endoscopic group than that of the small bone window group and the drilling group (P<0.05). In the large hematoma group, the average injection time was longer in the drilling group than that of the small hematoma group (P<0.05). In the large hematoma group, the favorable prognostic rate was higher in the endoscopic group than that of the small bone window group and the drilling group (P<0.05), while there was no significant difference in the favorable prognostic rate between the three subgroups of the small hematoma group (P>0.05). Conclusion Hematoma cavity catheterization and drainage can shorten the operation time and reduce the intraoperative blood loss. Both neuroendoscopy and small bone window craniotomy have higher hematoma clearance rates.

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Expression and clinical significance of serum miR-27b-3p and miR-342-3p in patients with type 2 diabetic nephropathy

HAN Jing, GU Jinyi, NIE Junxu, ZHANG Yanping, ZHAO Linghua

2022, 50 (10): 1077-1082. doi: 10.11958/20220434

Abstract ( 555 )

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Objective To investigate the serum expression characteristics of miR-27b-3p and miR-342-3p in type 2 diabetic nephropathy (DN) patients and the diagnostic value for DN. Methods A total of 157 patients with DN were selected and divided into the normal albuminuria group (NA group, n=49), the microalbuminuria group (MA group, n=41) and the macroalbuminuria group (DN group, n=67) according to the ratio of albumin to creatinine (UACR) of urine specimens. Clinical data and the expression of serum miR-27b-3p and miR-342-3p, renal function and urinary fibrosis indicators were detected by real-time quantitative polymerase chain reaction. Blood urea nitrogen (BUN) and blood creatinine (Scr), were detected by automatic biochemical analyzer. Urine type Ⅳ collagen (Ⅳ-C), laminin (LN) and type Ⅲprocollagen peptide (PCⅢ) were detected by double-antibody sandwich enzyme-linked immunosorbent assay. The factors influencing the pathogenesis of DN and the diagnostic value of miR-27b-3p and miR-342-3p for DN were analyzed. Results Compared with the NA group, the levels of HbA1c, UACR, urinary Ⅳ-C, urinary LN and urinary PCⅢ were increased, while the expresson levels of miR-27b-3p and miR-342-3p were decreased in the DN group and the MA group (P<0.05). Levels of BUN and Scr were increased in the DN group (P<0.05), and eGFR level decreased (P<0.05). The higher level of urinary PCⅢ was a risk factor for DN, while the higher levels of miR-27b-3p, miR-342-3p and eGFR were protective factors of DN (P<0.05). The expressions levels of miR-27b-3p and miR-342-3p were positively correlated with eGFR (r = 0.647, 0.661, P<0.05) and negatively correlated with urinary PCⅢ (r=-0.739, P<0.05). The area under the curve for diagnosing DN by combining eGFR, urinary PCⅢ, miR-27b-3p and miR-342-3p was higher than that of eGFR, urinary PCⅢ, miR-27b-3p, miR-342-3p alone (Z=5.631, 5.794, 6.715, 4.577, P<0.05). Conclusion The decreased expressions of serum miR-27b-3p and miR-342-3p are associated with decreased renal function and DN occurrence in patients with type 2 diabetes, which can be used as biological indicators for the auxiliary diagnosis of DN.

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Clinical characteristics of persons infected with imported SARS-CoV-2 Omicron variant in Tianjin

FENG Liting, WANG Xing, LI Li, WU Qi

2022, 50 (10): 1083-1087. doi: 10.11958/20220196

Abstract ( 992 )

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Objective To investigate the epidemiological, clinical and imaging characteristics of SARS-CoV-2 infection caused by Omicron variant. Methods The clinical and imaging data of 52 cases infected with imported Omicron variant were retrospectively reviewed. According to the chest CT findings, the cases were divided into 2 groups: the unaltered group (n=26) and abnormal group (n=26). The characteristics of clinical manifestations and laboratory indicators were compared between the two groups. According to the progress of chest CT during hospitalization, patients in the abnormal group were divided into two subgroups: the improved subgroup (n=13) and the progress subgroup (n=13). The clinical and imaging characteristics were compared between the two subgroups. Results In the 52 cases, males accounted for 71.2%. The average age was 29.5 (24.0, 42.5), and the average age was older in the abnormal group (P<0.05). Vaccination rate was 90.4%, with the main symptoms of cough (50%), dry sore throat (48.1%) and fever (44.2%). There were no significant differences in vaccination rate, symptoms, the level of leukocytes, C-reactive proteins, calcitonogen, interleukin-6, D-dimers and T lymphocytes between the two groups. Among 52 cases, chest CT abnormalities accounted for 50%, among which the most common CT sighs were ground-glass opacity (GGO, 88.5%), consolidation shadow (50.0%) and pleural thickening (30.8%). The progressive group was more likely to have consolidation changes and multiple lobar involvement. Conclusion Cough, throat discomfort and fever are the most common symptoms. The most common chest imaging finding is GGO, which can be used to the early diagnosis and assessment of the disease.

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The serum expression level and clinical significance of Apelin13 and FKBP5 in patients with Alzheimer's disease

YAN Chunxiao, LI Peiyue, ZHENG Qimi, ZOU Xiao, LI Jianbo

2022, 50 (10): 1088-1092. doi: 10.11958/20220022

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Objective To investigate the serum expression level and clinical significance of Apelin13 and FK506 binding protein 51 (FKBP5) in patients with Alzheimer's disease (AD). Methods A total of 93 AD patients were selected (the AD group), and 90 healthy subjects of the same age for physical examination were selected as the control group. The serum levels of Apelin13 and FKBP5 mRNA were compared between the groups. The correlation between Apelin13, FKBP5 mRNA and Mini-mental State Examination (MMSE) score was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of Apelin13 and FKBP5 mRNA for severe cognitive impairment in AD patients. Results The serum level of Apelin13 and MMSE scores were significantly lower in the AD group than those in the control group, while the level of FKBP5 mRNA was significantly higher in the AD group than that in the control group (P<0.01). The serum levels of Apelin13 decreased sequentially in patients with mild, moderate and severe AD, while levels of FKBP5 mRNA increased sequentially (all P<0.05). Binary Logistic regression analysis showed that higher MMSE score and Apelin13 were protective factors for AD, while higher FKBP5 mRNA was a risk factor for the development of AD (all P<0.05). MMSE score was negatively correlated with the serum level of FKBP5 mRNA and positively correlated with the level of Apelin13 in AD patients (all P<0.05). ROC curve showed that the AUC value [0.884 (0.808-0.961)] of Apelin13 combined with FKBP5 mRNA was significantly higher than that of Apelin13 or FKBP5 mRNA [0.776 (0.673-0.879) or 0.801 (0.699-0.902)], and the sensitivity and specificity of combined diagnosis were 81.25 and 86.89, respectively (all P<0.05). Conclusion The serum level of Apelin13 is decreased in AD patients, while FKBP5 mRNA is increased. Apelin13 combined with FKBP5 mRNA has good diagnostic efficacy for severe cognitive impairment in AD patients.

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The value of CT features in differentiating moderately and highly differentiated invasive adenocarcinoma in pure ground glass nodule

ZHANG Lixia, LIU Haixia, ZHANG Xuetao, CAO Zhen, WANG Guidong

2022, 50 (10): 1093-1097. doi: 10.11958/20220292

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Objective To investigate the value of CT signs in differentiating pure ground glass nodule (pGGN) between moderately differentiated and highly differentiated invasive adenocarcinoma (IAC). Methods The clinical data of 83 patients with IAC and imaging data of 84 pGGNs were retrospectively collected. According to the pathological results, patients were divided into the highly differentiated group (46 lesions of lepidic dominant type, 45 patients) and the moderately differentiated group (38 lesions of acinar or papillary dominant type, 38 patients). The clinical data and CT features of pGGN were compared between the two groups, and the factors influencing the differentiation degree and diagnostic value in patients were analyzed. Results There were significant differences in maximum diameter, mean CT value, burrs, abnormal vascular signs and abnormal bronchus signs between the moderately differentiated group and the highly differentiated group (P<0.05). Multivariate Logistic regression analysis showed that the higher mean CT value and abnormal vascular signs were important influencing factors in the prediction of moderately differentiated IAC, and the odds ratios (95% confidence interval) were 1.042 (1.022-1.062) and 5.869 (1.105-31.161) respectively. ROC curve analysis showed that in the combined diagnosis of mean CT value and abnormal vascular signs, the area under the curve of moderately differentiated IAC was 0.903 (0.842-0.964), the efficiency was 0.870, the sensitivity was 0.789. The diagnostic efficacy and sensitivity were higher than the mean CT value, but the diagnostic specificity of average CT value was higher. Conclusion The combined diagnosis of mean CT value and abnormal vascular signs has high predictive value for moderately differentiated IAC with pGGN on CT.

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Effects of different monitoring points on coronary CT angiography image quality under the bolus-tracking method

HUANG Wenxuan, CHEN Weibin, ZHANG Bolun, ZHANG Huiying

2022, 50 (10): 1098-1102. doi: 10.11958/20220216

Abstract ( 608 )

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Objective To evaluate the effect of different monitoring points on the image quality of coronary CT angiography (CCTA) under the bolus-tracking method. Methods A total of 128 prospective patients undergoing CCTA examination were randomly divided into 4 different monitoring points groups: the left atrium (LA) group, the left ventricle (LV) group, the ascending aorta (AA) group and the descending aorta (DA) group. Each group contained 32 patients. The ROI threshold was 130 HU, the contrast agent was iomeprol (contain iodine 400 g/L), and the injection rate was 4 mL/s and the dosage was 40 mL. The differences in subjective and objective image evaluation indicators and radiation dose parameters were compared between the 4 groups. Results There were significant differences in CT values of aortic root and left main of coronary artery between the 4 groups (P<0.05). The CT values of aortic root and left main were higher in the LA group than those of the other three groups. There were no significant differences in CT values of proximal left anterior descending artery, proximal left circumflex artery and the mid of right coronary artery in the 4 groups (P>0.05). The differences in image noise and right coronary contrast-to-noise ratio (CNR) were statistically significant between the 4 groups (all P<0.05). The image noise in the LA group was 21.00±4.11, which was lower than other three groups. There were no significant differences in aortic signal-to-noise ratio (SNR) and CNR, left main and right coronary artery SNR between the 4 groups (P>0.05). There were no significant differences in subjective image quality score and radiation dose-related parameters between the 4 groups (P>0.05). Conclusion In CCTA scan using contrast agent bolus tracking method, positioning the monitoring point in left atrium can obtain better image quality, which is an ideal monitoring point for CCTA examination.

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Genetic and pathogenic characteristics of SARS-CoV-2 variants

WANG Yuliang, LONG Yiyin, CHEN Xiaobo

2022, 50 (10): 1103-1109. doi: 10.11958/20220509

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Coronavirus disease 2019 (COVID-19) can evolve rapidly via genetic mutation. At present, SARS-CoV-2 variants have been categorized as of concern variants (B.1.1.7, B.1.351, P.1, B.1.617.2 and B.1.1.529), variants of interest (B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526, B.1.617.1, C.37 and B.1.621) and variants under monitoring. These variants have had a significant impact on with significant impact on transmissibility of virus, morbidity, reinfection and mortality in the population. Compared to other variants, Omicron new variant has characteristics such as strong infectivity, immune escape, causing a high risk of infection surges. This review outlines genetic characteristics of SARS-CoV-2 variants, the epidemiological, gene mutation and clinical characteristics of new variant Omicron of SARS-CoV-2, the collection method and detective method of SARS-CoV-2 specimen, vaccination and treatment for COVID-19, in order to provide guidance for the prevention and treatment of SARS-CoV-2.

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The research progress and function of SARS-CoV-2 accessory protein ORF8

FU Ya'nan, ZENG Feng, RAO Jingjing, HUANG Yanping, LIU Zhixin, LIU Long

2022, 50 (10): 1110-1114. doi: 10.11958/20220531

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a genome similar to that of the SARS-CoV, which has been circulating since 2002 and encodes multiple viral proteins. The accessory protein ORF8 has low sequence homology with SARS-CoV ORF8, and has characteristics of rapid evolution and mutation. It has functions of inhibiting type I interferon and down-regulating the expression of major histocompatibility complex I (MHC I). This paper reviews the structure and function of accessory protein ORF8 and the diagnostic and therapeutic prospects for COVID-19.

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Research progress on the role of Gal-3 in Alzheimer’s disease

WAN Qi, XIE Ye, WANG Rong, LUO Yan, ZENG Junwei

2022, 50 (10): 1115-1120. doi: 10.11958/20220639

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Galectin-3 (Gal-3), widely expressed in central nervous system, is a member of the galectin family. Gal-3 can bind a variety of molecules and play a role by regulating downstream signals. Recent advances have suggested that changes in Gal-3 expression in brain tissues, serum and cerebrospinal fluid of patients with Alzheimer's disease (AD) are closely related to the severity of AD. Therefore, GAL-3 is expected to be an important biomarker for the diagnosis and detection of drug efficacy in AD. In this review, we present an updated overview of the current understanding of Gal-3 involvement in AD, which may provide useful references for the clinical diagnosis and treatment of AD in the future.

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