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    Recommendations and Consensus
    Beijing-Tianjin-Hebei expert consensus on the surgical treatment of extracranial segmental carotid atherosclerotic disease
    Neurosurgery Branch of Tianjin Medical Association
    2024, 52 (3):  225-230.  doi: 10.11958/20231157
    Abstract ( 278 )   HTML ( 10 )   PDF (806KB) ( 338 )  

    Extracranial segmental carotid atherosclerotic disease is the most common type of cerebrovascular disease, and surgical treatment is an important means to reduce disability and mortality of patients. The Neurosurgery Branch of Tianjin Medical Association led the organization of Beijing-Tianjin-Hebei experts to develop this consensus by combining the clinical practice in China in recent years and relevant evidence-based medical evidence at home and abroad. The consensus summarizes the screening of the risk group of extracranial segmental carotid atherosclerotic disease, risk factor control, surgical treatment options, and perioperative management, aiming to provide evidence-based normative guidance for the clinical treatment of carotid atherosclerotic disease in China.

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    Cell and Molecular Biology
    The effect of lncRNA FEZF1-AS1 targeting regulation of miR-200c-3p on biological behaviors of human lung fibroblasts
    MAN Jun, GAO Yanyan, SONG Longfei, GAO Fusheng
    2024, 52 (3):  231-236.  doi: 10.11958/20230719
    Abstract ( 278 )   HTML ( 5 )   PDF (1601KB) ( 149 )  

    Objective To investigate the effect of FEZ family zinc finger 1-antisense RNA 1 (LncRNA FEZF1-AS1) targeting regulation of miR-200c-3p expression on biological behaviors of human lung fibroblasts (HLF). Methods Transforming growth factor β1 (TGF-β1) was used to induce the transformation of HLF into myofibroblasts, which were divided into the Blank group and the model group (HLF+TGF-β1 group). According to different transfection plasmid, cells were divided into the Blank group, the TGF-β1+Si LncRNA FEZF1-AS1 NC group and the TGF-β1+Si LncRNA FEZF1-AS1 group. The protein expressions of α-SMA, Collagen Ⅰ and Vimentin were detected by Western blot assay. The expressions of LncRNA FEZF1-AS1 and miR-200c-3p were detected by quantitative real-time PCR (qRT-PCR). Cell proliferation ability was detected by CCK-8 method, migration ability was detected by cell scratch experiment and invasion ability was detected by Transwell assay. The targeting relationship between FEZF1-AS1 and miR-200c-3p was detected by dual-luciferase reporter assay. Results Compared with the Blank group, protein expressions of α-SMA, Collagen Ⅰ, Vimentin and the expression of LncRNA FEZF1-AS1 were increased in the HLF+TGF-β1 group (P<0.05), and the expression of miR-200c-3p was decreased (P<0.05). Compared with the TGF-β1+Si LncRNA FEZF1-AS1 NC group, cell proliferation, migration, invasion ability, LncRNA FEZF1-AS1 expression, protein expressions of α-SMA, Collagen Ⅰ and Vimentin were decreased in the TGF-β1+Si LncRNA FEZF1-AS1 group (P<0.05), and the expression of miR-200c-3p was increased (P<0.05). There were binding sites between miR-200c-3p and FEZF1-AS1 gene sequence. Conclusion LncRNA FEZF1-AS1 promotes the formation and progression of idiopathic pulmonary interstitial fibrosis by inhibiting miR-200c-3p.

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    circ_HIPK3 regulates function and morphology of Aβ induced hippocampal neurons by targeting miR-381-3p/ZNF217 axis
    LI Wei, CHEN Liang, LYU Changying
    2024, 52 (3):  237-244.  doi: 10.11958/20231013
    Abstract ( 241 )   HTML ( 1 )   PDF (1426KB) ( 506 )  

    Objective To analyze the influence of cyclic RNA homologous domain interacting protein kinase 3 (circ_HIPK3) on function and morphology of myloid β-protein (Aβ) induced hippocampal neurons by targeting miR-381-3p/zinc finger protein 217 (ZNF217) axis. Methods Hippocampal neurons of neonatal rats were prepared and divided into the control group, the Aβ group, the si NC1 group, the si HIPK3 group, the si HIPK3+inhibitor NC group, the si HIPK3+miR-381-3p inhibitor group, the si HIPK3+miR-381-3p inhibitor+si NC2 group and the si HIPK3+miR-381-3p inhibitor+si ZNF217 group. Except the control group, all the other groups were modeled by 40 μmol/L Aβ1~42. qRT-PCR was used to determine the circ of hippocampal neurons circ_HIPK3, miR-381-3p and ZNF217 mRNA levels. Cell morphology was observed by transmission electron microscope, and the survival rate of hippocampal neurons was measured by CCK-8 method. Hochesst 33342 method was used to measure apoptosis of hippocampal neurons. The intracellular Ca2+ fluorescence intensity of hippocampal neurons was detected by flow cytometry. The expression levels of P-Tau, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3 and ZNF217 proteins in hippocampal neurons were measured by Western blot assay. Double luciferase reporter genes were used to analyze the targeting relationship between miR-381-3p and circ_HIPK3, ZNF217. Results In the control group, the structure of hippocampal neurons was normal, the morphology of nucleus was normal, and there were no pathological changes in mitochondria and endoplasmic reticulum. In the Aβ group, hippocampal neurons showed degenerative changes, abnormal nuclear morphology, membrane invagination, a large number of mitochondria swelling and a large number of lipid droplets vacuoles in cytoplasm. Compared with the Aβ group, the hippocampal neuronal structure was partially restored in the si HIPK3 group. Compared with the si HIPK3 group, the hippocampal neuronal structure was severely damaged in the si HIPK3+miR-381-3p inhibitor group. Compared with the si HIPK3+miR-381-3p inhibitor group, the damage of hippocampal neurons in the si HIPK3+miR-381-3p inhibitor+si ZNF217 group was reduced. Compared with the control group, the circ_HIPK3, ZNF217 mRNA and ZNF217 protein levels, apoptosis rate, Ca2+ fluorescence intensity, P-Tau, Bax, Caspase-3 protein expression of hippocampal neurons were increased in the Aβ group, and the miR-381-3p level, survival rate and Bcl-2 protein expression decreased (P<0.05). Compared with the Aβ group, the circ_HIPK3, ZNF217 mRNA and ZNF217 protein levels, apoptosis rate, Ca2+ fluorescence intensity, P-Tau, Bax and Caspase-3 protein expression of hippocampal neurons were decreased in the si HIPK3 group, and miR-381-3p level, survival rate and Bcl-2 protein expression increased (P<0.05). Compared with the si HIPK3 group, the circ_HIPK3, ZNF217 mRNA and ZNF217 protein levels, apoptosis rate, Ca2+ fluorescence intensity, P-Tau, Bax and Caspase-3 protein expression of hippocampal neurons in the si HIPK3+miR-381-3p inhibitor group were increased, and the miR-381-3p level, survival rate and Bcl-2 protein expression decreased (P<0.05). Compared with the si HIPK3+miR-381-3p inhibitor group, the ZNF217 mRNA and ZNF217 protein levels, apoptosis rate, Ca2+ fluorescence intensity, P-Tau, Bax and Caspase-3 protein expression of hippocampal neurons in the si HIPK3+miR-381-3p inhibitor+si ZNF217 group were decreased, and the survival rate and Bcl-2 protein expression increased (P<0.05). miR-381-3p targeted and combined with HIPK3 and ZNF217. Conclusion circ_HIPK3 silencing may ameliorate Aβ-induced damage of hippocampal neuronal structure and function by regulating miR-381-3p/ZNF217 axis.

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    Expression of MMP-9 in patients with chronic rhinosinusitis and its correlation with epithelial-mesenchymal transition
    SONG Xi, GE Yilin, LI Yin, SONG Hui, CHENG Jiaming
    2024, 52 (3):  245-249.  doi: 10.11958/20231439
    Abstract ( 208 )   HTML ( 3 )   PDF (2779KB) ( 93 )  

    Objective To investigate the mechanism of matrix metalloproteinase (MMP)-9 involved in epithelial mesenchymal transformation (EMT) in chronic sinusitis (CRS). Methods The expression of MMP-9 from polypoid middle turbinate tissue was detected by immunohistochemical staining qPCR and Western blot assay in 42 patients with CRS and 8 patients underwent septoplasty. Primary human nasal epithelial cells HNEpc were cultured in vitro and divided into the control group, the TGF-β1 group (5 μg/L TGF-β1 intervention) and the TGF-β1+si-MMP-9 group (transfected with si-MMP-9 and 5 μg/L TGF-β1 intervention). The expression of MMP-9 was detected by cell immunofluorescence staining. Expression levels of TGF-β1, MMP-9 and EMT-related proteins E-cadherin, vimentin and α-SMA were detected by Western blot assay. Results (1) The positive expression rate of MMP-9 was significantly higher in the nasal mucosa of CRS with nasal polyps (CRSwNP) group (54.5%, 12/22) than that of the CRS without polyps (25.0%, 5/20) group and the control group (12.8%, 1/8). The relative expression levels of MMP-9 mRNA and protein in nasal mucosa were higher in the CRSwNP group than those in the CRSsNP group and the control group (P<0.05). (2) Compared with the control group, the expressions levels of TGF-β1, MMP-9, vimentin and α-SMA were increased in the TGF-β1 group, while the expression of E-cadherin was decreased (P<0.05). Compared with the TGF-β1 group, expression levels of TGF-β1, MMP-9, vimentin and α-SMA were decreased in the TGF-β1+si-MMP-9 group, and the expression of E-cadherin was increased (P<0.05). Conclusion The expression of MMP-9 is increased in CRS patients, which may be involved in the development of CRS through the regulation of EMT.

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    Molecular mechanisms of Ca2+-induced pyroptosis and adhesion changes of HK-2 cells in the formation of calcium-containing kidney stones
    XIANG Jinjie, LYU Maoxin, WANG Mengyue, ZHANG Kun, LI Hao
    2024, 52 (3):  250-255.  doi: 10.11958/20231036
    Abstract ( 206 )   HTML ( 4 )   PDF (2287KB) ( 105 )  

    Objective To investigate the possible role and mechanism of activation of pyroptosis classical pathway and alterations in cell adhesion in calcium-containing kidney stones after the action of high concentration of Ca2+ on HK-2 cells. Methods HK-2 cells were cultured in the presence of different concentrations of CaCl2 (0, 0.1, 0.5, 1.0, 2.0, 4.0 and 8.0 g/L) for 24 hours, and cell counting Kit-8 (CCK-8) and flow cytometry were used to determine the optimal treatment concentration. Subsequently, the ultrastructure of renal tubular epithelial cells under high Ca2+ condition was observed by transmission electron microscopy after Ca2+ treatment. DCFH-DA staining was used to detect intracellular reactive oxygen species production, and quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were performed to examine the expression of pyroptosis-related proteins NLRP3, Caspase-1, gasdermin D (GSDMD), adhesive molecules osteopontin (OPN) and CD44 at mRNA and protein levels after high concentration Ca2+ treatment. The expression levels of pyroptosis-related inflammatory factors interleukin (IL)-1β, IL-18 and adhesive molecule monocyte chemotactic protein-1 (MCP-1) were detected by enzyme-linked immunosorbent assay (ELISA) after high Ca2+ stimulation. Results Ca2+ showed cytotoxicity for HK-2 cell growth and can promote apoptosis. The higher the Ca2+ concentration, the more toxicity and apoptosis rate for HK-2 cell growth. High concentration of Ca2+ can promote pyroptosis-like morphological changes in HK-2 cells, including loss of cell membrane integrity, release of contents and numerous intracellular vacuoles. Compared with the control group, the expression levels of ROS were sequentially increased in the 1.0 g/L CaCl2 group and the 2.0 g/L CaCl2 group, and the expression levels of pyroptosis-related genes NLRP3, Caspase-1, GSDMD, and the pyroptosis-associated inflammatory factors IL-1β and IL-18, as well as the adhesion molecules OPN, CD44 and MCP-1 were significantly increased (P<0.05). Conclusion High Ca2+ treatment can cause oxidative stress damage in HK-2 cells to produce ROS, which activates NLRP3 inflammasome, leads to the activation of the classical pathway of pyroptosis and increase the adhesion of cells, and ultimately leads to the formation of kidney stones.

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    Experimental Research
    Mechanism of quercetin alleviating postherpetic neuralgia in rats by inhibiting MIP-1α/CCR1/CCR5 signaling pathway
    TIAN Jiayu, FENG Dan, HU Han, ZHANG Shuli, TONG Shengxiong, LI Shaojun
    2024, 52 (3):  256-260.  doi: 10.11958/20221587
    Abstract ( 250 )   HTML ( 3 )   PDF (1212KB) ( 103 )  

    Objective To investigate the impact of quercetin (Que) on postherpetic neuralgia (PHN) and chemokine ligand 3 (CCL3, namely MIP-1α)/C-C chemokine receptor 1 (CCR1)/C-C chemokine receptor 5 (CCR5) signaling pathway in rats. Methods Sixty rats were divided into the control group (Con), the PHN group (model group), the L-Que (30 mg/kg) group, the M-Que (60 mg/kg) group, the H-Que (120 mg/kg) group and the H-Que+pathway activator MIP-1α (120 mg/kg Que+0.4 μg/kg recombinant MIP-1α) group. The mechanical paw withdrawal threshold (PWT) and thermal pain threshold (TWL) of rats were detected in each group. The kit was used to detect adenosine, Adenine ribonucleotide (AMP), adenosine diphosphate (ADP) and tumor necrosis factor in spinal dorsal horn samples- α (TNF-α), and interleukin-1 β (IL-1 β) levels in spinal dorsal horn samples. HE staining was applied to observe the pathological sections of spinal dorsal horn. Immunofluorescence staining was used to detect the activation of microglia in spinal dorsal horn. Western blot assay was applied to detect MIP-1α/CCR1/CCR5 signaling pathway protein expression. Results In the PHN group, the dorsal horn of the spinal cord was ruptured, the arrangement of nerve bundles was disordered, and inflammatory cell infiltration, edema, and slight atrophy of neurons appeared. Compared with the Con group, the PWT value, adenosine, AMP and ADP levels were obviously decreased in the PHN group (P<0.05), and TWL value, TNF-α, IL-1β levels, the number of Iba1-positive microglia, MIP-1α, CCR1 and CCR5 protein levels were obviously increased (P<0.05). After treatment with Que, the disordered arrangement of nerve bundles was improved, the infiltration of inflammatory cells was reduced, and the phenomenon of neuronal atrophy disappeared. Compared with the PHN group, the PWT value, adenosine, AMP and ADP levels were obviously increased in the L-Que group, the M-Que group and the H-Que group (P<0.05). TWL value, TNF-α and IL-1β levels, the number of Iba1-positive microglia, and MIP-1α, CCR1 and CCR5 protein levels were obviously decreased (P<0.05). The effect of Que was dose dependent. Compared with the H-Que group, PWT value, adenosine, AMP and ADP levels were obviously decreased in the H-Que+MIP-1α group (P<0.05), and TWL value, TNF-α, IL-1β levels, the number of Iba1 positive microglia, MIP-1α, CCR1 and CCR5 protein levels were obviously increased (P<0.05). Conclusion Que may reduce the inflammatory response in rats by inhibiting the MIP-1α/CCR1/CCR5 signaling pathway, thereby reducing PHN.

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    Hydrogen-rich saline treated neuropathic pain in rats by increasing autophagy
    HE Ying, ZHANG Guanghua, TIAN Lidong, YU Yonghao
    2024, 52 (3):  261-265.  doi: 10.11958/20230698
    Abstract ( 243 )   HTML ( 2 )   PDF (875KB) ( 157 )  

    Objective To evaluate the role of autophagy in the treatment of neuropathic pain (NP) with hydrogen-rich saline. Methods Forty adult male Sprague-Dawley rats with successful intubation were randomly divided into 5 groups (n=8) using a random number table: the sham operation group (group S), the neuropathic pain group (group C), the hydrogen-rich saline group (group H), the autophagy inhibitor group (group M) and the hydrogen-rich saline + autophagy inhibitor group (group HM). There were 8 rats in each group. The NP model was established by chronic constriction of the sciatic nerve (CCI) in rats. The autophagy inhibitor 3-methyladenine (3-MA) was intraperitoneally injected with 30μg/kg in the group M and the group HM. The hydrogen-rich saline (0.6 mmol/L) was intraperitoneally injected with 10 mL/kg in the group H and the group HM. The other groups were intraperitoneally injected with the same amount of normal saline twice a day for 7 consecutive days. Paw withdrawal threshold to mechanical stimulation (MWT) and paw withdrawal latency to thermal stimulation (TWL) were measured at 1 day before and 1, 3, 5, 7 and 14 days after modeling (T0-T5). After the last measurement of pain threshold, the L4-L6 segment of spinal cord was removed for determination of the expression of autophagy-related proteins microtubule-associated protein light chain 3 (LC3) Ⅱ, Beclin-1 and p62 proteins by Western blot assay. The expression levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in spinal cord tissue were detected. Results Compared with the group S, MWT and TWL were decreased in the group C at T2-5, the expression levels of LC3 Ⅱ, Beclin-1 and p62 were increased, SOD activity was decreased, and MDA content was increased at T5 (P<0.05). Compared with the group C, MWT and TWL were increased in the group H at T2-5, LC3 Ⅱ and Beclin-1 protein expression levels were increased, p62 protein expression levels were decreased, SOD activity was increased, and MDA content was decreased at T5 (P<0.05). MWT and TWL were decreased in the group M at T2-5, LC3 Ⅱ and Beclin-1 protein expression levels were decreased, p62 protein expression levels were increased, SOD activity was decreased, and MDA content was increased at T5 (P<0.05). Compared with the group M, MWT and TWL were increased in the group HM at T2-5, LC3 Ⅱ and Beclin-1 protein expression levels were increased, p62 protein expression levels were decreased, SOD activity was increased, and MDA content was decreased at T5 (P<0.05). Conclusion Hydrogen-rich saline can alleviate neuropathic pain and inhibit oxidative stress in spinal cord in rats, and the mechanism may be related to the increase of autophagy.

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    Huangqi Yanghe Decoction regulates PI3K/AKT/NF-κB signaling pathway to promote wound healing in diabetes foot ulcer rats
    BAO Yaling, LEI Hui, MA Jun, Zhao Xinmei
    2024, 52 (3):  266-272.  doi: 10.11958/20230561
    Abstract ( 210 )   HTML ( 3 )   PDF (1246KB) ( 98 )  

    Objective To explore the effect of Huangqi Yanghe Decoction on wound healing of diabetic foot ulcer (DFU) rats based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor-κB (NF-κB) signal pathway. Methods DFU rat model was constructed, and 48 rats successfully modeled were randomly divided into the model group, the Huangqi Yanghe Decoction low (8.5 g/kg) group, the Huangqi Yanghe Decoction high (17 g/kg) dose group and the Huangqi Yanghe Decoction high dose (17 g/kg)+LY294002 (PI3K/AKT pathway inhibitor, 0.3 mg/kg) group. There were 12 rats in each group. Another 12 rats were selected as the control group. Rats in each group were given corresponding drug intervention for 4 weeks. After the 14th and 28th day-administration, the general state and wound changes of rats were observed, and the wound healing rate was calculated. The fasting blood glucose (FBG) level of rats was measured, and the percutaneous partial pressure of oxygen (TcpO2) of tissue around the wound was detected. Serum levels of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α), C-reactive protein (CRP) and interleukin (IL)-6 were determined by enzyme linked immunosorbent assay. Histopathological changes of the wound were observed by hematoxylin-eosin staining. Immunohistochemical staining was used to measure the microvascular density of rat wound tissue. The protein expression levels of PI3K, phosphorylated PI3K (p-PI3K), AKT, phosphorylated AKT (p-AKT), NF-κB p65, phosphorylated NF-κB p65 (p-NF-κB p65) and NF-κB inhibitory protein α (IκB-α) in rat wound tissue were determined by Western blot assay. Results Rats in the control group had smooth hair color, normal diet, drinking water and excretion, more active, wound healing fast, less inflammatory reaction in wound tissue, and there were more new blood vessels. Fibroblasts and collagen matrix were abundant in granulation tissue. In the model group, the fur color of rats was dull and matte, and the activity was reduced. The symptoms of polydipsia, polyphagia and polyuria were appeared in the model group, the wound color was dark, and edema and ulcer appeared in the surrounding tissue, a large number of inflammatory cells infiltrated in the wound tissue, accompanied by tissue necrosis and exudation, fewer neovascularization and fibroblasts were observed. Wound healing rate, TcpO2 in wound surrounding tissue, serum VEGF, HIF-1α, microvascular density, p-PI3K, p-AKT and IκB-α protein expression levels in wound tissue were decreased, and FBG, serum CRP, IL-6, p-NF-κB p65 protein expression in wound tissue were increased (P<0.05). Compared with the model group, the state of rats was gradually improved in the Huangqi Yanghe Decoction low and high dose groups, and the lesion degree of wound tissue was reduced successively, wound healing rate, TcpO2 in wound surrounding tissue, serum VEGF, HIF-1α, microvascular density, p-PI3K, p-AKT and IκB-α protein expression levels in wound tissue were increased in turn (P<0.05). The FBG, serum CRP, IL-6 and p-NF-κB p65 protein expression in wound tissue were decreased in turn (P<0.05). LY294002 could partially reverse the therapeutic effect of high-dose Huangqi Yanghe Decoction on DFU rats (P<0.05). Conclusion Huangqi Yanghe Decoction can regulate PI3K/AKT/NF-κB pathway, inhibit inflammatory response in DFU rats, promote angiogenesis and thus promote wound healing.

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    Effect of Yiqi Huoxue Tongluo Decoction on miR-126a-5p and VEGF signaling pathway in cervical spondylotic myelopathy model rats
    LIU Dan, TANG Zhanying, LI Pan, YUAN Weina, LI Fangfang, CHEN Qian, HU Zhijun
    2024, 52 (3):  273-277.  doi: 10.11958/20230607
    Abstract ( 240 )   HTML ( 2 )   PDF (860KB) ( 77 )  

    Objective To investigate the effect of Yiqi Huoxue Tongluo Decoction on microRNA-126a-5p (miR-126a-5p) and vascular endothelial growth factor (VEGF) signaling pathway in cervical spondylotic myelopathy model rats. Methods Thirty healthy male SD rats were divided into the sham operation group, the model group and the traditional Chinese medicine (TCM) group by random number table method. Cervical spondylotic myelopathy models were prepared in the model group and the TCM group. The TCM group was given intragastric administration of Yiqi Huoxue Tongluo Decoction, while the sham operation group and the model group were given intragastric administration of normal saline for 12 weeks. After intervention, the threshold of mechanical stimulation and retraction time of thermal stimulation in each group were measured by behavior tests. Rats were sacrificed to collect intervertebral disc tissue for hematoxylin-eosin (HE) staining and observe the number of vascular buds in intervertebral disc. Rat intervertebral disc annulus fibrosus cells were subjected to terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The miR-126a-5p and VEGF mRNA of rat intervertebral disc tissue were detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). The expression of VEGF protein of rat intervertebral disc tissue was detected by Western blot assay. Results Compared with the sham operation group, the number of vascular buds in intervertebral disc was decreased in the model group and the TCM group. The cell destruction of intervertebral disc annulus was obvious in rats, and apoptosis was high and cell density decreased. Mechanical stimulation threshold decreased, and mechanical stimulation threshold decreased. The level of miR-126a-5p was decreased, and the expression levels of VEGF mRNA and protein were increased. Compared with the model group, the number of vascular buds in intervertebral disc was increased in the TCM group. The destruction of intervertebral disc annulus cells was alleviated in rats. The apoptosis of annulus fibrosus cells in intervertebral disc decreased and cell density increased. The threshold of mechanical stimulation increased, and the retraction time of thermal stimulation was prolonged. The level of miR-126a-5p increased, and the expression levels of VEGF mRNA and protein decreased (P<0.05). Conclusion The mechanism of Yiqi Huoxue Tongluo Decoction in the treatment of cervical spondylotic myelopathy may be related to the up-regulation of miR-126a-5p expression and the down-regulation of VEGF expression.

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    The mechanism of Wumei pill on ulcerative colitis in mice based on Nrf2/ARE antioxidant stress pathway
    CHEN Jing, WEI Yunjiao, LUO Chao, HUANG Lihua, CHEN Cheng, DUAN Shasha
    2024, 52 (3):  278-254.  doi: 10.11958/20230533
    Abstract ( 240 )   HTML ( 2 )   PDF (1481KB) ( 392 )  

    Objective To explore the mechanism of Wumei pill on ulcerative colitis (UC) in mice based on the anti oxidative stress pathway of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE). Methods Seventy SPF male C57BL/6 mice were randomly divided into the control group, the UC group, the mesalazine group (MES group, 0.82 g/kg MES), the low dose Wumei pill group (WMW-L group, 5 g/kg crude drug), the middle dose Wumei pill group (WMW-M group, 10 g/kg crude drug), the high dose Wumei pill group (WMW-H group, 20 g/kg crude drug) and the high dose Wumei pills+Nrf2 inhibitor ML-385 group (WMW-H+ML-385 group, Wumei pills crude drug 20 g/kg+20 mg/kg ML-385), with 10 rats in each group. The disease activity index (DAI) score and colonic mucosa injury score were performed in mice after the last administration. Pathological changes of colonic mucosa in mice were observed by HE staining. The levels of interleukin (IL) -1β, tumor necrosis factor-α (TNF-α) and IL-6 in serum and colon tissue of mice were measured by enzyme-linked immunosorbent assay (ELISA). The content of malondialdehyde (MDA) in serum and colon tissue of mice was determined by thiobarbituric acid colorimetry (TBA). The activity of superoxide dismutase (SOD) in serum and colon tissue of mice was measured by xanthine oxidase method. The activity of glutathione peroxidase (GSH-px) in serum and colon tissue of mice was determined by direct method with dithiodinitrobenzoic acid (DTNB). The positive expression of Nrf2 in colon tissue of mice was observed by immunohistochemistry. The expression of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO1) proteins in colon tissue of mice were detected by Western blot assay. Results Compared with the control group, the DAI score, colonic mucosa injury score, colonic histopathology score, levels of IL-1β, TNF-α, IL-6 and MDA in serum and colonic tissue, and expression levels of Nrf2, HO-1 and NQO1 protein in colonic tissue of mice were increased in the UC group, levels of SOD and GSH-px in serum and colon tissue decreased (P<0.05), the colon mucosa of mice was seriously damaged. Compared with the UC group, changes of corresponding indexes were contrary to the above in the MES group, the WMW-M group and the WMW-H group. However, the expression levels of Nrf2, HO-1 and NQO1 proteins in colon tissue were increased (P<0.05), and the damage of colon mucosa in mice was alleviated. Changes of the above indexes were dose-dependent in the WMW-L group, the WMW-M group and the WMW-H group. There were no significant differences in the above indexes between the WMW-H group and the MES group. ML-385 attenuated the improvement effect of high dose Wumei pill on colon mucosa injury. Conclusion Wumei pill may alleviate the colon mucosal damage of UC mice by activating Nrf2/ARE antioxidant stress pathway.

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    Protective effect of asiatic acid on brain injury after experimental subarachnoidhemorrhage in rats
    WU Xiaoxiao, HU Yukun, WU Jiang
    2024, 52 (3):  285-289.  doi: 10.11958/20231956
    Abstract ( 185 )   HTML ( 2 )   PDF (2175KB) ( 102 )  

    Objective To explore the neuroprotective effect of asiatic acid (AA) on brain damage after experimental subarachnoid hemorrhage (SAH) in rats. Methods A total of 108 adult SD rats were divided into the sham1 group, the SAH+vehicle group and the SAH+AA group, with 36 rats in each group. The 42 rats were divided into the sham2 group, 3, 6, 12, 24, 48 and 72 h after SAH groups, with 6 rats in each group. Except the sham group, SAH model was established by unilateral external carotid artery puncture method in other groups. After modeling, the SAH+AA group was given AA solution (30 mg/kg) by gavage. Neurobehavioral changes were assessed by foot fault test and modified Garcia score. Western blot assay was used to detect the protein level of glutathione peroxidase 4 (GPX4) in brain tissue. ELISA was used to detect the concentrations of glutathione (GSH) and malondialdehyde (MDA). Fluoro Jade B (FJB) staining was used to detect the neuronal death. Results Compared with the sham1 group, the SAH+vehicle group showed a significant increase in the proportion of empty steps and a significant decrease in the modified Garcia score, a significant decrease in GPX4 protein levels, a significant increase in MDA concentration (P<0.05), a decrease in GSH concentration (P<0.01) and a significant increase in the number of dead neurons (P<0.05). Compared with the SAH+vehicle group, a significant decrease in the proportion of empty steps, a significant increase in the modified Garcia score, a significant increase in GPX4 protein level, a significant decrease in MDA concentration, a significant increase in GSH concentration (P<0.05) and a significant decrease in the number of dead neurons in the SAH+AA group (P<0.05). Conclusion AA may reduce brain injury after SAH in rats by inhibiting lipid peroxidation.

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    Clinical Research
    Comparison of clinical outcomes in patients with 4b acute myocardial infarction caused by early and late stent thrombosis
    LI Xiaowei, GAO Jing, LIU Yin, GAO Mingdong, XIAO Jianyong
    2024, 52 (3):  290-296.  doi: 10.11958/20230488
    Abstract ( 230 )   HTML ( 8 )   PDF (923KB) ( 108 )  

    Objective To observe and compare in-hospital and 1-year survival and prognosis of patients with 4b acute myocardial infarction (AMI) caused by early and late stent thrombosis (ST). Methods A total of 302 patients with 4b acute myocardial infarction caused by ST were enrolled in this study from January 2015 to February 2018. ST patients were confirmed by coronary angiography. These patients were divided into two groups: the early ST group (n=26) and the late ST group (n=276) according to the time of ST occurrence. Endpoint events during hospitalization and one year of follow up were compared between the two groups of patients. The primary endpoint events included cardiac death and recurrent AMI. The secondary endpoint events included target lesion revascularization (TLR), re-stent thrombosis, heart failure and stroke. The incidence of no endpoint events was compared between two groups of patients by Kaplan and Meier survival analysis. Cox regression analysis was used to analyze risk factors for endpoint events in patients with type 4b AMI. Results There was no significant difference in the incidence of the primary endpoint events during hospitalization between the two groups (7.7% vs. 3.3%,P=0.243). The incidence of heart failure was higher in the early ST group than that of the late ST group (11.5% vs.1.4%, P=0.016). There was no significant difference in the incidence rates of other secondary endpoint events between the two groups (P>0.05). After a mean follow-up of 1 year, the incidence rates of primary endpoint events and the secondary eendpoint events were higher in the early ST group (20.0% vs. 5.9%,P<0.05 and 36.0% vs. 11.5%,P<0.01)than that of the late ST group. Kaplan and Meier survival analysis showed that the 1-year cumulative incidences of non-primary (P=0.022) and non-secondary events (P<0.001) were lower in the early ST group than those of the late ST group. Cox regression analysis showed that hypertension and history of coronary artery bypass grafting were independent risk factors for primary endpoint events in patients with 4b AMI, and intraoperative implantation of intraaortic balloon pump (IABP) and shortening the time from stent thrombosis to balloon dilation (ST to B) were independent protective factor. Conclusion Early ST patients have similar in-hospital outcomes and poor long-term prognosis compared with late ST induced 4b type AMI patients. Intraoperative implantation of IABP and shortening of ST to B time may improve the prognosis of 4b type AMI patients.

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    The relationship between plasma sCD163/sTWEAK ratio and prognosis in patients with spontaneous acute cerebral hemorrhage
    ZHANG Wenchao, YANG Xuehui, YIN Tao, WANG Ruijian, ZHANG Mengmeng
    2024, 52 (3):  297-301.  doi: 10.11958/20231437
    Abstract ( 277 )   HTML ( 4 )   PDF (846KB) ( 102 )  

    Objective To investigate the relationship between the ratio of soluble hemoglobin scavenger receptor 163 protein (sCD163)/soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) in plasma and prognosis in patients with spontaneous acute cerebral hemorrhage (ACH). Methods From August 2020 to August 2022, 90 patients with ACH admitted to the Department of Neurosurgery, Harison International Peace Hospital, Hengshui City were regarded as the research group. According to the Glasgow outcome scale, patients with ACH were separated into the poor prognosis group (n=38) and the good prognosis group (n=52). Another 45 healthy examinee who underwent physical examination were used as the control group. Enzyme linked immunosorbent assay (ELISA) was applied to detect plasma sCD163 and sTWEAK levels, and the sCD163/sTWEAK ratio was calculated. Pearson method was applied to analyze the correlation between plasma sCD163, sTWEAK levels, sCD163/sTWEAK ratio and clinical data. Logistic regression was applied to analyze influencing factors of poor prognosis in patients with ACH. Receiver operating characteristic (ROC) was applied to analyze the predictive value of sCD163/sTWEAK ratio for poor prognosis of patients with ACH. Results The plasma levels of sCD163, sTWEAK and sCD163/sTWEAK ratio were obviously higher in the research group than those in the control group (P<0.05). The plasma levels of sCD163, sTWEAK and sCD163/sTWEAK ratio were obviously lower in the good prognosis group than those in the poor prognosis group (P<0.05). Hematoma volume, National Institutes of Health Stroke Scale (NIHSS) scores, hypertension and subtentorial hemorrhage were lower in the good prognosis group than those in the poor prognosis group, and low density lipoprotein cholesterol (LDL-C) was higher in the good prognosis group than that in the poor prognosis group (P<0.05). Correlation analysis showed that plasma sCD163, and sTWEAK levels and the sCD163/sTWEAK ratio were positively correlated with bleeding site, hematoma volume, NIHSS score, white blood cell count, platelet count and neutrophil/lymphocyte ratio (NLR) (P<0.05). Results of Logistic regression analysis showed that sCD163, sTWEAK, sCD163/sTWEAK ratio, hematoma volume, bleeding site and NIHSS score were influencing factors for poor prognosis in patients with ACH (P<0.05). Results of receiver operating characteristic showed that the AUC of sCD163/sTWEAK ratio in evaluating poor prognosis of patients with ACH was 0.850, and the sensitivity and specificity were 86.84% and 69.23%. Conclusion The sCD163/sTWEAK ratio has a high level in the plasma of patients with ACH, which is associated with poor prognosis and has important value in predicting the prognosis of patients with ACH.

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    Study on analgesic effect of anterior quadratus lumborum block at lateral supra-arcuate ligament and transversus abdominis plane block in analgesia in patients undergoing laparoscopic partial hepatectomy
    JIANG Lingling, LI Yun, SHENG Kui, ZHANG Lili, HU Yang, ZHANG Ye
    2024, 52 (3):  302-305.  doi: 10.11958/20230884
    Abstract ( 285 )   HTML ( 6 )   PDF (841KB) ( 98 )  

    Objective To observe the effect of ultrasound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament (QLB-LSAL) and transversus abdominis plane block (TAPB) on analgesia and recovery quality after laparoscopic partial hepatectomy (LPH). Methods Fifty-eight patients underwent elective LPH were selected and divided into the quadratus lumborum group or the transversus abdominis group randomly, with 29 patients in each group. The quadratus lumborum group received bilateral QLB-LSAL, and the transversus abdominis group received bilateral subcostal TAPB block before surgery. Both groups received 20 mL of 0.33% ropivacaine on each side. All patients used patient-controlled intravenous analgesia (PCIA) postoperatively. The numeric rating scale (NRS) scores for rest and movement were recorded at 2, 4, 6, 12, 24 and 48 hours postoperatively, as well as the Quality of Recovery-15 (QoR-15) scores at 1 day preoperatively, 1 and 3 days postoperatively. The perioperative anesthetic agent consumption, PCIA pressing frequency, remedial analgesia use in 48 h, postoperative nausea and vomiting (PONV) incidence and time of first out-of-bed mobilization were also recorded. Results Compared with the transversus abdominis group, the quadratus lumborum group had lower movement NRS scores at 2, 4, 6, 12, 24 and 48 hours postoperatively, and lower rest NRS scores at 2, 4, 6, 12 and 24 hours postoperatively (P<0.05). The quadratus lumborum group had higher QoR-15 scores at 1 and 3 days postoperatively (P<0.05). Patients in the quadratus lumborum group had reduced perioperative remifentanil and sufentanil consumption, postoperative 48-hour rescue analgesia use, PCIA pressing frequency, PONV incidence and time of first out-of-bed mobilization (P<0.05). Conclusion QLB-LSAL block provides superior analgesic effects and recovery quality compared to TAPB block after LPH.

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    The predictive value of MP hypertension monitoring system combined with PLGF and PI for preeclampsia
    ZHANG Liran, ZHAO Yanhua
    2024, 52 (3):  306-310.  doi: 10.11958/20231021
    Abstract ( 247 )   HTML ( 5 )   PDF (860KB) ( 101 )  

    Objective To establish a clinical prediction model for preeclampsia by monitoring risk rating of MP gestation and levels of placental growth factor (PLGF) combined with uterine artery pulsatility index (PI) measured during examination of fetal nuchal translucency (NT). Methods Twenty-four patients with preeclampsia who met the inclusion criteria were selected as the case group, and 95 healthy pregnant women during the same period were randomly selected as the control group. Serum concentrations of PLGF, uterine artery PI values measured by quantitative immunofluorescence assay at 11-14 weeks of gestation, risk ratings for MP hypertension monitoring at 11-20 weeks of gestation, and other relevant data, BMI, age, gestation, mode of delivery, neonatal birth weight and Apgar score were collected in the two groups. Results Results of univariate regression analysis showed that BMI, age, high risk of PI, MP and PLGF<12 were influencing factors for adverse outcomes. Results of multivariate regression analysis showed that high PI, medium high risk in MP and PLGF<12 were independent risk factors for adverse outcomes. The prediction model of PE established was logit (P) = -15.767 + 0.020 × PI + 0.072 × MP risk (medium-high risk = 1, low risk = 0) + 0.181 × PLGF classification (<12 = 1, ≥12 = 0), with an AUC area of 0.883, specificity of 0.816 and sensitivity of 0.846. Conclusion The combination of PI, MP risk and PLGF to establish a clinical predictive model for preeclampsia has certain value, and its combined predictive value is higher than that of single application.

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    Correlation between neutrophil-to-lymphocyte ratio and disease activity in Behcet’s disease
    YUAN Changfen, XU Ying, GUO Yunfan, WU Yuntao, WANG Xiuyan, ZHANG Jingyi
    2024, 52 (3):  311-314.  doi: 10.11958/20230872
    Abstract ( 226 )   HTML ( 2 )   PDF (805KB) ( 204 )  

    Objective To explore the correlation between neutrophil-to-lymphocyte ratio (NLR) and Behcet’s disease (BD) activity. Methods A total of 103 BD patients were divided into the low activity group (0-4, 61 cases) and the high activity group (5-11, 42 cases) according to electronic medical record-based disease activity index (EMRAI) score. The white blood cell (WBC), neutrophil (NEU), lymphocyte (LY), platelet (PLT), red blood cell (RBC), hemoglobin (Hb), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IgG, IgA, IgM, complement C3 and C4 were detected. NLR and platelet-to-lymphocyte ratio (PLR) were calculated. The correlation between NLR, PLR and ESR, CRP, EMRAI were analyzed. Logistic regression was used to analyze the influencing factors of BD disease activity. Receiver operating characteristic (ROC) curve was drawn to evaluate the effectiveness of NLR in judging BD disease activity. Results WBC, NEU, PLT, ESR, CRP, NLR, PLR, complement C3 and C4 in patients were higher in the high activity group than those in the low activity group (P<0.05), and there were no significant differences in other indexes (P>0.05). NLR was positively correlated with ESR, CRP and EMRAI in the whole group, while PLR was positively correlated with ESR, CRP and EMRAI in the whole group (P<0.05). Logistic regression analysis showed that high NLR was a risk factor for BD disease activity (OR=1.511, 95%CI: 1.080-2.113, P<0.05). ROC curve analysis showed that the area under the curve (AUC) of NLR in evaluating BD disease activity was 0.706 (95%CI: 0.603-0.809). Conclusion NLR is effective in judging the disease activity of BD patients, and can be used as a biological index to evaluate the disease activity of BD.

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    Frst-line treatment of Zorifertinib in EGFR-mutant NSCLC with CNS metastases: a report of two cases
    XU Dan, LIU Xia, ZHONG Diansheng
    2024, 52 (3):  315-318.  doi: 10.11958/20231793
    Abstract ( 236 )   HTML ( 1 )   PDF (1173KB) ( 82 )  

    Objective To investigate the efficacy of Zorifertinib in first-line treatment of patients with untreated epidermal growth factor receptor (EGFR) mutation in non-small-cell lung cancer (NSCLC) with central nervous system (CNS) metastases. Methods Two patients received Zorifertinib as first-line treatment. The response of tumor treatment was evaluated by response evaluation criteria in solid tumors version 1.1 (RECEST v1.1) and RANO criteria for brain metastases (RANO-BM). Results Case 1 had EGFR exon 19del mutation and multiple brain metastases at baseline. After 51.4 months of treatment with Zorifertinib, case 1 still maintained partial response (PR) in lung lesions and complete response (CR) in intracranial lesions. Case 2 had EGFR exon 19del mutation and a single brain metastasis at baseline. Case 2 achieved PR in lung lesions and CR in intracranial lesions during the treatment with Zorifertinib. After 13.7 months, lung disease progression (PD) and new single brain metastases occurred. The comprehensive evaluation was PD. Case 1 had three-grade treatment-related adverse events (TRAEs), including dry skin, and other TRAEs were rash, abnormal liver function and diarrhea. The TRAEs were generally controllable. Conclusion Zorifertinib has a good effect on controlling intracranial and extracranial lesions in patients with EGFR-mutated NSCLC with CNS metastases. The efficacy of Zorifertinib is consistent with the EVEREST study. Zorifertinib can be one of the first-line initial treatment options.

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    Applied Research
    Study on the value of screening cytokines in pleural effusion by liquid array technology in the diagnosis of tuberculous pleurisy
    DU Fengjiao, DU Boping, JIA Hongyan, XING Aiying, LI Zihui, ZHU Chuanzhi, LI Hua
    2024, 52 (3):  319-323.  doi: 10.11958/20230793
    Abstract ( 222 )   HTML ( 3 )   PDF (855KB) ( 88 )  

    Objective To screen the specific cytokines of tuberculous pleural effusion (plTB) by using liquid array technique to establish a diagnostic model and discuss its application value. Methods A total of 86 patients with plTB (plTB group) were included, including 41 patients in the confirmed plTB group and 45 patients in the clinically diagnosed plTB group. There were 42 other patients with pleural effusion in the control group. Seventeen cytokines in pleural effusion were analyzed by liquid array technology. Interleukin (IL) -1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, gamma-interferon-induced protein 10 (IP-10), IL-15, IL-17F, IL-27, tumor necrosis factor (TNF) -α, monocyte chemotactic protein-1 (MCP-1), the expression levels of macrophage inflammatory protein-3a (MIP-3α), macrophage colony-stimulating factor (M-CSF) and β-interferon (IFN-β) were detected. Difference factors between the confirmed plTB group and the control group were screened, and the receiver operating characteristic (ROC) curve was drawn in the confirmed plTB patients. IP-10, IL-27 and MCP-1 with AUC > 0.850 and specificity > 80% were combined to diagnose plTB, and were compared with adenylate deaminase (ADA) and T-SPOT.TB in pleural effusion to evaluate the diagnostic efficacy. Results The levels of IL-2, IP-10, IL-27, TNF-α and MCP-1 were higher in the confirmed plTB group than those in the control group (P<0.05). The sensitivity and specificity of IP-10, IL-27 and MCP-1 in the diagnosis of plTB were 87.8% and 81.0%. The sensitivity of three-factor combined diagnosis in 45 patients with plTB was still as high as 86.7%, and there was no significant difference in sensitivity compared with that in the diagnosed plTB group (P>0.05). In the plTB group, the sensitivity of IP-10, IL-27 and MCP-1 combined detection was 87.2%,which was higher than that of T-SPOT.TB (81.4%) and ADA (54.7%). Conclusion The application of liquid array technology to the joint detection of pleural effusion IP-10, IL-27 and MCP-1 can provide help for the diagnosis of plTB.

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    Technical Specifications
    Technical operating points of polysomnography-assisted drug-induced sleep endoscopic positive airway pressure titration
    LIU Dan, WAN Nansheng, WANG Jie, JU Renhua, XIE Wei, TIAN Yu, FENG Jing
    2024, 52 (3):  324-326.  doi: 10.11958/20231612
    Abstract ( 204 )   HTML ( 3 )   PDF (758KB) ( 181 )  

    Recognizing upper airway obstruction and stenosis is critical to determine the subsequent treatment options in patients with obstructive sleep apnea (OSA). Drug-induced sleep endoscopy (DISE) is a 3D visual evaluation technology for the anatomical structure of the upper respiratory tract of OSA patients during "sleeping" state after being anesthetized. The dynamic situation of upper respiratory tract obstruction and collapse can be observed safely and quickly through endoscopy, which provides important reference for formulating surgical methods and positive airway pressure (PAP) intervention treatments. With the assistance of polysomnography (PSG), DISE plays an important role in optimizing individualized treatment plans for OSA. The present article introduces the technical operating points of PSG-assisted drug-induced sleep endoscopic positive airway pressure titration.

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    Review
    Research progress in the prevention of contrast-related acute kidney injury
    FAN Hui, MA Yu, LI Ximing
    2024, 52 (3):  327-330.  doi: 10.11958/20230617
    Abstract ( 221 )   HTML ( 8 )   PDF (900KB) ( 105 )  

    Contrast-associated acute kidney injury (CA-AKI) is an important complication caused by the use of contrast medium (CM) in diagnostic or interventional surgery. At present, it has become one of the major causes of acute renal insufficiency in hospitalized patients. Choosing a relatively low toxic CM and reducing the exposure time and dose of CM can prevent CA-AKI occurrence to some extent. Drugs such as statins and postoperative hydration can reduce the risk of CA-AKI. In addition, nanomedicine has shown a benefit in animal models. This paper reviews the current prevention and treatment of CA-AKI to lay the foundation for further study of new interventions and provide a theoretical basis for clinical treatment.

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    Research progress of RNA m6A methylation in post-stroke cognitive impairment
    XIAO Yuqian, SUN Kexin, WAN Jun, CHEN Shuying, CHEN Limin, WANG Yan, BAI Yanjie
    2024, 52 (3):  331-336.  doi: 10.11958/20230780
    Abstract ( 248 )   HTML ( 9 )   PDF (887KB) ( 101 )  

    Post-stroke cognitive impairment (PSCI) is mainly manifested as learning and memory disorders. Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation. Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI, it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI. This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation, which will provide reference for researchers in this field.

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