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15 November 2024, Volume 52 Issue 11 Previous Issue    Next Issue
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Cell and Molecular Biology
Experimental Research
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Cell and Molecular Biology

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The effect of LINC00173 regulating autophagy of PCOS granulosa cells based on PI3K/Akt/mTOR signaling pathway ZHAO Yuanyuan, WU Xiaohua 2024, 52 (11):  1121-1126.  doi: 10.11958/20240511 Abstract ( 287 )   HTML ( 11 )   PDF (1212KB) ( 51 )   Objective To investigate the effect and mechanism of long non-coding RNA 00173 (LINC00173) on autophagy of granulosa cells (GCs) in polycystic ovary syndrome (PCOS). Methods A total of 40 PCOS patients and 40 patients (non-PCOS) treated with tubal factors who underwent in vitro fertilization-embryo transfer (IVF-ET) were selected. The expression levels of LINC00173 in GCs of PCOS were detected by qPCR. Human ovarian granulosa cells KGN were selected as the experimental subject. The cells were divided into the Vector group, the pcLINC00173 group, the siNC group and the siLINC00173 group based on their over-expression or interference with LINC00173. Dansylcadaverine (MDC) staining was employed to assess the impact of LINC00173 on autophagy of KGN cells. Western blot assay was conducted to investigate the effect of LINC00173 on autophagy and the PI3K/Akt/mTOR signaling pathway in KGN cells, focusing on expression levels of key pathway-related proteins including LC3B-Ⅱ/Ⅰ, p62, p-PI3K, p-Akt, p-mTOR, PI3K, Akt and mTOR. The effects of LY294002 on the expression of LC3B-Ⅱ/Ⅰ and p62 proteins were detected in the siNC group, the siLINC00173 group, the siLINC00173+DMSO group and the siLINC00173+LY294002 group. Results LINC00173 was significantly upregulated in GCs of PCOS patients (P<0.05). The overexpression of LINC00173 in KGN cells resulted in the presence of autophagosomes and autophagolysosomes in cytoplasm (P<0.05). Compared with the vector group, there was an increased expression of autophagy-related proteins LC3B-Ⅱ/Ⅰ and a decreased expression in p62 in the pcLINC00173 group (P<0.05). Additionally, there was a decreased expression of PI3K/Akt/mTOR signaling pathway-related proteins p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR. Conversely, in the siLINC00173 group, the expression of LC3B-Ⅱ/Ⅰ decreased while p62 expression increased compared to the siNC group (P<0.05), along with alterations in PI3K/Akt/mTOR signaling pathway-related proteins. Compared to the siLINC00173+DMSO group or the siLINC00173 group, PI3K/Akt/mTOR signaling pathway inhibitor LY294002 was found to alleviate the inhibitory effect of siLINC00173 on LC3B-Ⅱ/Ⅰ protein expression in KGN cells in the siLINC00173 group (P<0.05) and to reduce the impact of siLINC00173 on up-regulation of p62 protein expression (P<0.05). Conclusion Results reveal thatLINC00173 can induce autophagy activation in PCOS GCs, and the mechanism of the action may be related to the inhibition of PI3K/Akt/mTOR signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Effects of imperatorin derivatives on the activity and drug resistance protein of alveolar type Ⅱ epithelial cells in COPD YU Zhihong, WANG Xiaoqin 2024, 52 (11):  1127-1130.  doi: 10.11958/20240581 Abstract ( 205 )   HTML ( 164 )   PDF (910KB) ( 23 )   Objective To explore effects of a derivative of imperatorin (IMP-1) on the activity and resistance proteins of alveolar type Ⅱ (ATⅡ) cells in chronic obstructive pulmonary disease (COPD). Methods AT Ⅱ cells were divided into the blank group (well growing AT Ⅱ cells cultured in conventional medium), the cigarette smoke extract (CSE) group (induced culture with 2% CSE added) and the IMP-1 group (intervention with 10 μ mol/L of IMP-1 on CSE induced AT Ⅱ cells). Proliferation rates of AT Ⅱ cells at 24, 48 and 72 hours were measured using MTT method. Apoptosis of ATⅡ cells was detected by Hoechst 33342 staining. The proportion of cells in each cycle was analyzed by flow cytometry. The number of ATⅡ cell clones was detected by soft AGAR clone formation assay. Multidrug resistance gene 1(MDR1) and multidrug resistance associated protein 1 (MRP1) were detected by Western blot assay. Results Compared with the blank group, the apoptosis rate and the proportion of G0/G1 phase of ATⅡ cell cycle were increased in the CSE group, and the proliferation rate and the proportion of S, G2/M phase were decreased at 24 h, 48 h and 72 h (P<0.05). Compared with the CSE group, the cell proliferation rate, the proportion of S and G2/M phases and the number of cell clones were increased in the IMP-1 group, and the proportion of G0/G1 phase in ATⅡ cell cycle and the protein levels of MDR1 and MRP1 were decreased in the IMP-1 group (P<0.05). Conclusion IMP-1 may downregulate the expression of MDR1 and MRP1 proteins induced by CSE in AT Ⅱ cells, inhibiting the progression of AT Ⅱ cells from S phase to G2 phase and from G2 phase to M phase, thereby inhibiting abnormal cell activation and increasing apoptosis. Figures and Tables | References | Related Articles | Metrics

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Mechanism of oxLDL/β2GPⅠ/aβ2GPⅠ complex promoting the angiogenesis in vascular endothelial cells through TLR4//MyD88/NF-κB signaling pathway ZHANG Guiting, HE Chao 2024, 52 (11):  1131-1136.  doi: 10.11958/20240680 Abstract ( 235 )   HTML ( 165 )   PDF (4461KB) ( 23 )   Objective To investigate effects of oxidized low density lipoprotein/β2 glycoprotein-Ⅰ/anti-β2 glycoprotein-Ⅰ antibody (oxLDL/β2GPⅠ/aβ2GPⅠ) complex on the proliferation, migration and angiogenesis of vascular endothelial cells and its mechanism. Methods Human umbilical vein endothelial cells (HUVEC) were cultured to logarithmic growth phase and grouped into the control group (normal culture), the oxLDL group (50 mg/L oxLDL), the oxLDL/β2GPⅠ/aβ2GPⅠ group (50 mg/L oxLDL/100 mg/L β2GPⅠ/100 mg/L aβ2GPⅠ) and the VEGF group (100 μg/L VEGF). The gene expressions of VEGF, vascular endothelial cadherin (VE-cadherin), matrix metalloproteinase (MMP)-2 and MMP-9 were detected by real-time quantitative fluorescent PCR (qPCR). Cell counting kit-8 (CCK-8) method was employed to detect cell proliferation. Cell migration and invasion were determined by scratch healing test and Transwell assay. Matrigel tube formation assay was used to observe the angiogenesis of HUVEC. The relative protein expression of TLR4, MyD88 and NF-κB were examined by Western blot assay. Results Compared with the control group, the proliferation activity of cells at 48 h of treatment was increased in the oxLDL/β2GPⅠ/aβ2GPⅠ group (P<0.05). Moreover, compared with the control group, cell migration and angiogenesis were increased in the oxLDL/β2GPⅠ/aβ2GPⅠ group, and the mRNA levels of VEGF, VE-cadherin, MMP-2 and MMP-9 were elevated (P<0.05). Compared with the control group, levels of TLR4 and MyD88 were elevated in the oxLDL/β2GPⅠ/aβ2GPⅠ complex group (P<0.05), as well as levels of p-NF-κB p65/NF-κB p65 (P<0.05). Conclusion oxLDL/β2GPⅠ/aβ2GPⅠ complex may promote the proliferation, migration and tube formation of vascular endothelial cells by regulating TLR4/MyD88/NF-κB signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Study on the role of ginsenoside Rg1 in IL-6-induced neuronal ferroptosis in rats HUANG Xiaolei, GE Tingting, ZHAO Junsong, NI Zhihua 2024, 52 (11):  1137-1140.  doi: 10.11958/20231989 Abstract ( 204 )   HTML ( 164 )   PDF (939KB) ( 29 )   Objective To investigate the protective effect and mechanism of ginsenoside Rg1 (G-Rg1) on interleukin-6 (IL-6)-induced neuronal injury in rats by regulating Janus activated kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods After culture, rat hippocampal neurons were divided into the control group (normal culture), the IL-6 model group (50 μg/L IL-6 was used to treat rat hippocampal neurons for 18 h to simulate the inflammatory environment in brain), the G-Rg1 low dose (10 μmol/L) group and the G-Rg1 high dose (40 μmol/L) group. After 48 h of normal culture, the survival rate of hippocampal neurons was determined by MTT method. The total iron load of neurons was detected by spectrophotometry, and levels of ferroptosis markers glutathione (GSH) and glutathione peroxidase 4 (GPX4) were detected. The mRNA expression level of ferroportin 1 (FPN1) in hippocampal neurons was detected by qRT-PCR. The expression of proteins related to the neuronal JAK/STAT3 signaling pathway was detected by Western blot assay. Results Compared with the CON group, the neuronal survival rate, GSH content, GPX4 content and FPN1 mRNA expression level were decreased in the IL-6 model group, and the total iron load, p-JAK and p-STAT3 protein expression levels were increased (P<0.05). Compared with the IL-6 model group, the neuronal survival rate, GSH content, GPX4 content and FPN1 mRNA expression level were increased in the low-dose and high-dose G-Rg1 groups, and the total iron load, p-JAK and p-STAT3 protein expression levels were decreased (P<0.05). Changes of the above indicators were more significant in the high-dose G-Rg1 group than those in the low-dose G-Rg1 group (P<0.05). Conclusion The mechanism of G-Rg1 alleviating ferroptosis of hippocampal neurons in rats may be related to the inhibition of IL-6/JAK/STAT3 signaling pathway, up-regulation of FPN1 expression, and prevention of iron overload. Figures and Tables | References | Related Articles | Metrics

Experimental Research

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The effect of electroacupuncture on paclitaxel-induced neuropathic pain in rats OUYANG Jie, ZHAO Haiqian, KONG Yun, NIU Qin, CHEN Ying, SI Yongyu 2024, 52 (11):  1141-1145.  doi: 10.11958/20240609 Abstract ( 205 )   HTML ( 4 )   PDF (1049KB) ( 13 )   Objective To observe the effect of electroacupuncture (EA) on the expression of NKCC1, KCC2 and activation of microglia in spinal dorsal horn of paclitaxel (PTX)-induced neuropathic pain rats and its possible mechanism. Methods Male SD rats were randomly divided into the vehicle group (vehicle), the PTX group, the PTX + EA group and the PTX + sham EA group, with 12 rats in each group. The rat model of PTX-induced neuropathic pain was established by intraperitoneal injection of PTX. After modeling, EA was applied to "Zusanli" and "Yanglingquan" for 7 days in the PTX + EA group. Paw withdrawal threshold and paw withdrawal latency were tested at 2 days before and 1, 3, 5, 7, 14 and 21 days after PTX injection. Immunofluorescence and Western blot assay were used to detect expression levels of sodium-potassium-chloride cotransporter 1 (NKCC1), potassium-chloride cotransporters 2 (KCC2) and microglia markers - ionized calcium binding adapter molecule 1 (Iba1) in spinal dorsal horn. Results Compared with the vehicle group, mechanical and thermal hyperalgesia of both hind feet were found in the PTX group, and the expression of NKCC1 and the number of activated microglia in dorsal horn tissue of spinal cord were increased. Compared with the PTX group, mechanical and thermal hyperalgesia were significantly improved in the PTX+EA group at day 14 and 21, and the expression levels of NKCC1 and Iba1 in dorsal horn tissue of spinal cord were decreased. There was no significant difference in KCC2 expression between the four groups. Conclusion Electroacupuncture can effectively relieve paclitaxol-induced neuropathic pain, which may be related to the inhibition of NKCC1 expression and microglia activation in spinal dorsal horn of rats. Figures and Tables | References | Related Articles | Metrics

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Roxadustat improves myocardial ischemia-reperfusion injury in mice by inhibiting apoptosis and inflammatory response CAI Dengta, CHANG Jingyi, JIA Shanshan, TU Yinqiong 2024, 52 (11):  1146-1151.  doi: 10.11958/20240445 Abstract ( 217 )   HTML ( 2 )   PDF (3736KB) ( 557 )   Objective To investigate the improvement effect and related mechanism of roxadustat on myocardial ischemia-reperfusion (I/R) injury in mice. Methods Twenty four male C57BL/6N mice were randomly divided into the sham operation group, the control group and the roxadustat group, with eight mice in each group. A mouse myocardial I/R model was established. The control group was given 100 μL saline injection containing 5% dimethyl sulfoxide by gavage. The roxadustat group was given 25 mg/kg roxadustat by gavage. The left anterior descending coronary artery of mice in both groups was ligated for 40 minutes, and then reperfusion for 24 hours to establish the myocardial I/R model. In the sham operation group, only the left anterior coronary artery was pierced without ligation. The area of myocardial infarction in mice was detected by triphenyltetrazolium chloride (TTC) staining. The apoptosis of mouse cardiomyocytes was detected by TdT-mediated dUTP nick and labeling (TUNEL) staining. The expression of apoptosis-related proteins bcl-2 associated X protein (Bax), Caspase3 and inflammatory cell markers F4/80 and myeloperoxidase (MPO) were detected by immunohistochemistry staining. The damage of myocardial cells was observed by hematoxylin-eosin (HE) staining. Results The area of myocardial infarction after myocardial I/R was reduced in the roxadustat group compared to the control group and the sham operation group (P<0.05). The number of apoptotic cells was higher in the control group and the roxadustat group than that in the sham operation group, and the number of apoptotic cells was lower in the roxadustat group than that in the control group (P<0.05). The expression levels of Bax and Caspase3 proteins in myocardial tissue were higher in the control group and the roxadustat group than those in the sham operation group, while those of the roxadustat group was lower than those of the control group (P<0.05). The expression levels of F4/80 and MPO proteins in myocardial tissue were lower in the roxadustat group than those in the control group (P<0.05). In the control group, the myocardial tissue arrangement was disordered, and there was an increase in interstitial vacuoles. Compared with the control group, the myocardial cells were arranged more neatly in the roxadustat group, and the interstitial vacuoles were reduced. Conclusion Roxadustat can reduce the myocardial infarction area after I/R injury, inhibit myocardial cell apoptosis, alleviate myocardial injury, reduce infiltration of myocardial macrophages and neutrophils, and reduce inflammatory injury. Figures and Tables | References | Related Articles | Metrics

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Effect of remimazolam on apoptosis of intestinal epithelial cells in burned rats by regulating TLR4/MyD88/NF-κB signaling pathway LONG Hua, CHEN Yifei, WANG Qingshu 2024, 52 (11):  1152-1157.  doi: 10.11958/20240667 Abstract ( 223 )   HTML ( 2 )   PDF (1016KB) ( 9 )   Objective To investigate the effect of remimazolam (Rem) on apoptosis of intestinal epithelial cells in burned rats by regulating Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods The successfully constructed burned rat model was randomly divided into the model group, the Rem low dose treatment (Rem-L) group, the Rem medium dose treatment (Rem-M) group and the Rem high dose treatment (Rem-H) group, and Rem-H+TLR4 activator (LPS) group. Healthy rats were taken as the control group. After blood samples were collected from tail vein of rats and intestinal tissue samples were taken after euthanasia. Serum levels of inflammatory cytokines interleukin-1β and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). HE staining was applied to observe the morphology of intestinal tissue. TUNEL detection kit was used to detect apoptosis. Immunohistochemistry was used to detect the expression of tight junction proteins ZO-1 and Occludin. Immunoblotting experiments were used to detect the expression levels of apoptotic proteins Bax and TLR4/MyD88/NF-κB signaling pathway proteins. Results Compared with the control group, cell arrangement was disordered with inflammation, and IL-1β and IL-6 levels and apoptosis rate were increased, expression levels of Bax, TLR4, MyD88 and p-NF-κB/NF-κB were up-regulated, and expression levels of ZO-1 and Occludin were down-regulated in the model group (P<0.05). Compared with the model group, inflammatory infiltration of intestinal mucosa was gradually reduced in the Rem-L, Rem-M and Rem-H groups, the apoptosis rate, IL-1β and IL-6 levels were decreased, the expression levels of Bax, TLR4, MyD88 and p-NF-κB/NF-κB were down-regulated, and the expression of ZO-1 and Occludin was up-regulated in a dose-dependent manner (P<0.05). Compared with the Rem-H group, the tissue inflammation was aggravated, the apoptosis rate, levels of IL-1β and IL-6 were increased, expression levels of Bax, TLR4, MyD88 and p-NF-κB/NF-κB were up-regulated, and expression levels of ZO-1 and Occludin were down-regulatedin in the Rem-H+LPS group (P<0.05). Conclusion Remimazolam may alleviate the damage of intestinal epithelial cells in burned model rats by inhibiting TLR4/MyD88/NF-κB signaling pathway, thus protecting intestinal mucosa. Figures and Tables | References | Related Articles | Metrics

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Impact of sufentanil on liver injury in burn-induced sepsis rats by regulating JAK2/STAT3 signaling pathway XU Fang, LIANG Yi, HE Yong, XU Julong 2024, 52 (11):  1158-1163.  doi: 10.11958/20240681 Abstract ( 198 )   HTML ( 3 )   PDF (1968KB) ( 14 )   Objective To investigate the effect of sufentanil (suf) on hepatic injury in burn sepsis rats by regulating Janus kinase 2 (JAK2)/signal transduction and transcriptional activator 3 (STAT3) signaling pathway. Methods SD rats were randomly divided into the control group, the model group, the suf low-dose group (0.75 μg/kg), the suf high-dose group (3 μg/kg), the imipenem group (90 mg/kg) and the suf high-dose + kumamycin group (3 μg/kg suf+4 mg/kg kumamycin). Serum liver function indexes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. The pathological changes of liver tissue were observed by HE staining. The contents of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6 were detected by enzyme-linked immunosorbent assay (ELISA). Terminal deoxynucleotide transferase mediated dUTP nick end labeling (TUNEL) staining was used to detect hepatocyte apoptosis. Western blot assay was used to detect the expression of p-JAK2 and p-STAT3 proteins in liver tissue. Results Compared with the control group, the model group showed elevated serum levels of ALT and AST, swelling of liver cells and infiltration of numerous inflammatory cells in liver tissue. The levels of TNF-α, MCP-1 and IL-6 in liver tissue, apoptosis rate of liver cells, and expression levels of p-JAK2 and p-STAT3 proteins were increased (P<0.05). Compared with the model group, serum levels of ALT and AST were reduced in the suf low-dose group and the suf high-dose group, and pathological damages of liver tissue were improved. The contents of TNF-α, MCP-1 and IL-6 in liver tissue, the apoptosis rate of liver cells, and the expression levels of p-JAK2 and p-STAT3 proteins were reduced (P<0.05). Moreover, changes in above indicators were significantly higher in the suf high dose group of suf than those in the suf low dose group（P<0.05）, and there was no significant difference compared with the imipenem group. Kumamycin inhibited the improvement effect of high-dose suf on liver injury in rats with burn sepsis （P>0.05）. Conclusion Sufentanil may improve liver injury in burn-induced sepsis rats by inhibiting the JAK2/STAT3 signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Effects of ligustilide regulating RhoA/ROCK signaling pathway on biological behavior of esophageal cancer cells HAO Kaikai, WANG Xiaomin, LIU Zheng, LIU Dongyang, LI Jing 2024, 52 (11):  1164-1170.  doi: 10.11958/20240758 Abstract ( 217 )   HTML ( 4 )   PDF (1382KB) ( 27 )   Objective To investigate effects of ligustilide (LIG) on proliferation, apoptosis, angiogenic mimicry and Ras homolog gene family member A (RhoA)/Rho associated coiled coil containing protein kinase 1 (ROCK) signaling pathway in esophageal cancer cells. Methods Esophageal cancer cell line EC-109 was treated with LIG at concentrations of 0, 12.5, 25, 50, 100, and 200 μmol/L to detect cell activity, and the suitable concentration was selected for subsequent experiments. EC-109 cells were grouped into the control group, the LIG low, medium and high concentration groups (LIG-L, LIG-M and LIG-H groups), and the LIG-H+RhoA activator Naciclassine group (LIG-H+Naciclassine group). Edu was applied to detect cell proliferation, and flow cytometry was applied to detect cell apoptosis. Angiogenetic mimicry was observed. Western blot assay was applied to detect expression levels of proteins related to cell proliferation and apoptosis, and RhoA, ROCK proteins. Nude mouse tumor transplantation experiment was applied to verify the effect of LIG on the growth of esophageal cancer tumors. Immunohistochemistry was applied to detect expression levels of angiogenesis related factors (VEGF), RhoA and ROCK proteins in transplanted tumors. Results Compared with the control group, the vascular mimicry tubular structure of EC-109 cells decreased sequentially in the LIG-L group, the LIG-M group and the LIG-H group. The positive rate of Edu, the expression levels of Cyclin D1, Ki67, Bcl-2, RhoA and ROCK reduced in turn. P21, cell apoptosis rate, the expression of Bax and Caspase-3 increased in sequence (P<0.05). Naciclasine, RhoA activator, partially reversed the effect of LIG on cell proliferation, apoptosis and vasculogenic mimicry of esophageal cancer cells. Nude mouse transplantation tumor experiment showed that compared with the control group, the growth rate of transplanted tumor showed down, tumor volume decreased and the expression levels of RhoA, ROCK and VEGF decreased in the LIG group (P<0.05). Conclusion Ligustilide inhibits the proliferation and angiogenic mimicry of esophageal cancer cells by inhibiting RhoA/ROCK signaling pathway, and promotes the apoptosis of esophageal cancer cells. Figures and Tables | References | Related Articles | Metrics

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Ameliorating effect of calycosin regulating SIRT3/SOD2 signaling pathway on airway epithelial cell damage in mice NIE Jia, GUO Yongying, YU Xiangyan, PEI Yuzhen, LIU Yun, KANG Zenglu, SU Yinghao 2024, 52 (11):  1171-1176.  doi: 10.11958/20240829 Abstract ( 168 )   HTML ( 2 )   PDF (1444KB) ( 20 )   Objective To investigate effects of calycosin (CA) on cigarette smoke (CS) induced airway epithelial cell damage in mice and the sirtuin 3/superoxide dismutase 2 (SIRT3/SOD2) signaling pathway in mice. Methods A total of 90 mice were randomly separated into the control group, the cigarette smoke (CS) group, the CA low-dose treatment group (CA-L group), the CA high-dose treatment group (CA-H group) and the CA high-dose treatment plus SIRT3 inhibitor 3-TYP group (CA-H+3-TYP group), with 18 mice in each group. Tidal volume (TV) and peak expiratory flow rate (PEF) of lung function were detected by whole body plethysmography system. Serum levels of inflammatory factors [interleukin (IL) -6, tumor necrosis factor (TNF) -α] and oxidative stress indicators [reactive oxygen species (ROS), SOD] were detected by enzyme-linked immunosorbent assay (ELISA). The injury of airway epithelial cells in lung tissue was observed by HE staining. The expression levels of barrier related proteins (OCLN and ZO-1) in airway epithelial cells were detected by immunohistochemistry. Immunoblotting was applied to detect the expression of SIRT3/SOD2 signaling pathway related proteins. Results Compared with the control group, levels of TV, PEF, MAN and SOD and the expression levels of OCLN, ZO-1, SIRT3 and SOD2 were decreased in the CS group, while the levels of MLI, IL-6, TNF-α and ROS were increased (P<0.05). Compared with the control group, the lung tissue structure was significantly damaged, the alveolar enlargement was obvious, the surrounding alveolar was accompanied by inflammatory cell infiltration, and the airway epithelial cells were obviously shed in the CS group. Different doses of CA alleviated lung tissue destruction, improved alveolar structure, reduced inflammatory cell infiltration, reduced airway epithelial cell shedding, increased levels of TV, PEF, MAN, SOD and OCLN, ZO-1, SIRT3 and SOD2, and decreased levels of MLI, IL-6, TNF-α and ROS. The effect of high dose CA was more significant than that of low dose CA (P<0.05). SIRT3/SOD2 signaling pathway inhibitor 3-TYP partially reversed the ameliorative effect of CA on CS induced airway epithelial cell injury in mice. Conclusion CA can ameliorate CS induced airway epithelial cell damage in mice, and its mechanism is related to the activation of the SIRT3/SOD2 signaling pathway. Figures and Tables | References | Related Articles | Metrics

Clinical Research

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Construction and validation of chemotherapy resistance prediction model for ovarian cancer YU Ping, ZHOU Min, SU Dan 2024, 52 (11):  1177-1182.  doi: 10.11958/20240546 Abstract ( 197 )   HTML ( 4 )   PDF (998KB) ( 36 )   Objective To investigate the influencing factors on the occurrence of chemo-resistance after postoperative chemotherapy in ovarian cancer patients, and construct a prediction model and evaluate the model efficacy. Methods The clinical data of 407 ovarian cancer patients who underwent tumor cytoreduction and chemotherapy were collected. At the endpoint of follow-up, patients were divided into the recurrence group (n=363) and the non-recurrence group (n=44). Patients in the recurrence group were re-divided into the resistant group (n=59) and the sensitive group (n=304) according to the chemotherapy resistance. Variables were screened using univariate analysis and Lasso regression. Logistic model was established. R software was used to build a nomogram and evaluate it. Results Compared with the non-recurrence group, the age of the recurrence group was lower, and the proportion of low differentiation and the proportion of FIGO stage Ⅲ-Ⅳwere higher (P<0.05). Compared with the sensitive group, in the resistant group, lymph node enlargement, non-serous pathological type, the proportion of FIGO stage Ⅲ-Ⅳ, positive rate of immunohistochemical recombinant proteins Ki-67, protein 53 (P53), vascular endothelial growth factor (VEGF) and nephroblastoma gene 1 (WT-1) were higher. The change rate of glycan antigen 125 (CA125) before and after surgery, the change rates of Rome index (ROMA) (premenopausal) before and after chemotherapy and the positive rate of immunohistochemical protein 16 (P16) were lower (P<0.05). The eight variables screened by Lasso regression were used as independent variables for Logistic regression. Results showed that there were enlarged lymph nodes in preoperativeCT imaging, the pathological type was non-serous, the FIGO stages were Ⅲ-Ⅳ, and immunohistochemistry results of WT1 and VEGF were positive. P16 negative was an independent risk factor for chemo-resistance in ovarian cancer patients. Accordingly, the area under the receiver operating characteristic curve of the nomogram model established was 0.837 (0.783-0.880), and the result of Hosmer-Lemeshow test indicated a good model fit. The calibration curve and the clinical decision curve (DCA) suggested a high calibration and clinical use of the model. Conclusion We have successfully constructed a Logistic model of chemotherapy resistance in ovarian cancer based on clinical data, and the nomogram prediction model can effectively assess the risk of chemo-resistance in ovarian cancer. Figures and Tables | References | Related Articles | Metrics

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Risk factors and prediction model of acute respiratory failure in patients with hypertriglyceridemic acute pancreatitis LIANG Yaobing, FU Zhenhua, ZHAO Ziyue, LUO Jianming, CHENG Dongyu, JIANG Haixing, QIN Shanyu 2024, 52 (11):  1183-1187.  doi: 10.11958/20240541 Abstract ( 220 )   HTML ( 4 )   PDF (913KB) ( 24 )   Objective To analyze risk factors of acute respiratory failure (ARF) in patients with hypertriglyceridemia acute pancreatitis (HTG-AP) and construct a risk prediction model. Methods A total of 222 HTG-AP patients were included in this study and divided into the non-ARF group (176 cases) and the ARF group (46 cases) according to diagnostic guidelines for ARF. Clinical data of the two groups were compared and the predictive factors were screened. These selected factors were then utilized in a multivariate Logistic regression analysis to construct a Logistic regression model. Subsequent evaluation of the model's predictive ability, accuracy and clinical utility was conducted through ROC, curve analysis, calibration plot examination and decision curve analysis (DCA), respectively. Results Compared with the non-ARF group, the levels of high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL)-C and albumin (ALB) were decreased in the ARF group (P<0.05), while the levels of creatinine (Cr), urea nitrogen (BUN), aspartate aminotransferase (AST) and C-reactive protein (CRP) were increased, and the incidence of pleural fluid and ascites was also increased (P<0.05). Multivariate Logistic regression analysis showed that higher levels of Cr and AST, lower levels of ALB, HDL-C and ascites were independent risk factors for HTG-AP complicated ARF (P<0.05). Based on these results, a column-line prediction model for HTG-AP complicated ARF was established. After internal verification, the area under curve (AUC) of receiver operating characteristic (ROC) curve of the nomogram model was 0.952 (95%CI: 0.923-0.981), the Youden index was 0.808 and the sensitivity and specificity were 93.33% and 87.43%, respectively. The calibration curve showed that the probability of HTG-AP concurrent ARF predicted by the model was in good agreement with the actual probability. The DCA curve showed that the model had certain clinical value. Conclusion The nomogram prediction model combined could provide a scheme for the clinical prevention of HTG-AP complicated with ARF. Figures and Tables | References | Related Articles | Metrics

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Correlation analysis and risk factors of subclinical peripheral neuropathy and TIR in type 2 diabetes mellitus TU Jing, XIA Chenxi, LI Ting 2024, 52 (11):  1188-1192.  doi: 10.11958/20240569 Abstract ( 224 )   HTML ( 3 )   PDF (893KB) ( 33 )   Objective To investigate the correlation between subclinical peripheral neuropathy (sDPN) and time in range (TIR) in type 2 diabetes mellitus (T2DM), and to explore the risk factors of sDPN. Methods A total of 485 T2DM patients without DPN symptoms and underwent EMG examination during hospitalization were divided into the sDPN group (n=209) and the non-sDPN group (n=276) according to nerve function conduction examination. The differences of age, course of the disease, blood pressure, complications, biochemical index and continuous glucose monitoring index were compared between the two groups of patients. The correlation between sDPN and TIR was analyzed. Logistic regression analysis was used to analyze influence factors of sDPN. Results Compared with the non-sDPN group, patients in the sDPN group were older and had longer diabetes course, higher systolic blood pressure (SBP), urinary albumin/urinary creatinine (UACR), blood glucose 1 h postprandial (1 h-PG), 2 h-PG, TBR, mean blood glucose fluctuation range (MAGE), standard deviation of blood glucose level (SD) and glycemic coefficient of variation (CV) levels, higher proportion of hypertension (HT), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic peripheral vascular disease (PAD), and lower levels of total cholesterol (TC), right limb ankle brachial index (R-ABI), L-ABI, hemoglobin A1c (HbA1c) and TIR. The differences in the above indexes were statistically significant (P<0.05). The occurrence of sDPN was positively correlated with TBR (rs=0.104, P<0.05), and negatively correlated with TIR (rs=-0.093, P<0.05). Logistic regression analysis showed that increased TBR (OR=1.093,95%CI: 1.009-1.183), combined with DN (OR=3.004, 95%CI: 1.020-8.849) and DR (OR=9.736, 95%CI: 3.499-27.087) were independent risk factors for sDPN, and increased R-ABI (OR=0.005,95%CI: 0.000-0.424) was protective factor for sDPN. Conclusion sDPN was negatively correlated with TIR. For patients with T2DM complicated with DN, DR and decreased ABI, it is necessary to timely improve neuroelectrophysiological examination to identify sDPN as soon as possible and give early intervention. Figures and Tables | References | Related Articles | Metrics

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Research of predictive factors of axillary lymph node metastasis in breast cancer under the context of DIP payment of medical insurance XIE Haoran, LI Yihao, LIU Cheng, XIA Yuting, QIU Shenglei, XIONG Bin, FENG Qizhen 2024, 52 (11):  1193-1196.  doi: 10.11958/20240235 Abstract ( 242 )   HTML ( 2 )   PDF (805KB) ( 31 )   Objective To explore the predictive factors of axillary lymph node metastasis in breast cancer, and to provide a basis for clinical decision-making under the DIP payment mode of medical insurance. Methods A total of 715 patients with breast cancer were divided into the metastasis group (n=309) and the non-metastasis group (n=406) according to the postoperative paraffin pathological results. Data of age >60 years old, menopausal status, body mass index (BMI) >24 kg/m2, hyperglycemia (GLU >6.1 mmol/L), high triglycerides (TG >1.7 mmol/L), maximum diameter of the tumor, the distance between the tumor and nipple and the quadrant where the tumor located were compared between the two groups. The expression levels of estrogen receptor (ER), progesterone receptor (PR), nuclear proliferation antigen (Ki-67) and human epidermal growth factor receptor-2 (Her-2) in breast cancer tissue samples were detected by histological grading and immunohistochemistry. The consistency, sensitivity and specificity of chest CT and breast ultrasound were examined, taken the pathological diagnosis as the gold standard. Results Compared with the non-metastatic group, the proportion of maximum diameter of tumor>2 cm, histological grade Ⅲ, high Ki-67 and high ER expression, tumor located in the outer upper quadrant, the distance >3 cm between tumor and nipple were increased in the metastatic group, and the proportion of high level of TG was decreased in the metastatic group (P<0.05). The consistency between chest CT and pathological diagnosis was better than that of breast ultrasound (Kappa was 0.493 and 0.353 respectively, P<0.05). Logistic regression analysis showed that histological grade Ⅲ, high expression of ER, maximum diameter of tumor >2 cm, and chest CT diagnosis were risk factors for axillary lymph node metastasis (P<0.05). Conclusion The combined application of the predictive factors of axillary lymph node metastasis of breast cancer could provide certain reference for clinical decision-making under the background of DIP payment mode of medical insurance. Figures and Tables | References | Related Articles | Metrics

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Clinical efficacy comparison of ankle arthroscopy combined with closed reduction guide and open reduction in the treatment of trimalleolar fracture LI Jixin, WANG Lei, ZHANG Yuhang, WEI Zengbo, YANG Jianlei, LIU Youjun, YU Tongjun 2024, 52 (11):  1197-1201.  doi: 10.11958/20240936 Abstract ( 250 )   HTML ( 4 )   PDF (1054KB) ( 41 )   Objective To compare the clinical efficacy of ankle arthroscopy combined with closed reduction guide and conventional surgical incision in the treatment of trimalleolar fracture. Methods A total of 60 patients with ankle fracture were divided into two groups according to different surgical plans: the ankle arthroscopy combined with closed reduction guide surgery group (arthroscopy group) and the conventional incision surgery group (incision group), with 30 cases in each group. The operative time, intraoperative blood loss and complications of the two groups were observed and compared. Pain and functional recovery of patients were evaluated by the American Orthopaedic Foot & Ankle Society (AOFAS) ankle and hind foot scores and Foot and Ankle Disability Index (FADI) scores. Results All 60 patients were followed up. Compared with the arthroscopy group, patients in the incision group had a longer surgical time, a shorter incision length in the medial malleolus, a reduced number of cases of skin numbness and reduced bleeding (P<0.05). The AOFAS score and the FADI score at 12 months after surgery were higher in the arthroscopic group than those of the incision group (P<0.05). After 12 months of surgery, the AOFAS score in patients without cartilage injury of the arthroscopic group were higher than those of patients with cartilage injury (P<0.05), while there were no significant differences in pain and force line scores between patients with cartilage injury and patients without cartilage injury (P>0.05). Conclusion The application of ankle arthroscopy combined with closed reduction guide in the treatment of trimalleolar fracture can achieve better postoperative results, but it has no obvious advantages in operation time and incision infection compared with the incision surgery. Figures and Tables | References | Related Articles | Metrics

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Predictive value of uric acid/albumin ratio for coronary heart disease in patients with chronic kidney disease GU Yunyun, ZHONG Chongming, YANG Haiyan 2024, 52 (11):  1202-1206.  doi: 10.11958/20240522 Abstract ( 253 )   HTML ( 5 )   PDF (880KB) ( 76 )   Objective To investigate the clinical significance and level changes of uric acid (UA)/albumin(ALB) ratio (UAR) in patients with chronic kidney disease (CKD) complicated with coronary heart disease (CHD). Methods A total of 175 patients with CKD were divided into the simple CKD group (control group, n=94) and the CKD complicated with CHD group (experimental group, n=81). The differences of blood routine, blood lipid, renal function and UAR were compared between the two groups. The influencing factors of CKD complicated with CHD were analyzed by binary Logistic regression. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of each index for CKD complicated with CHD. Results There were no significant differences in white blood cell count (WBC), monocytes (Mon), total cholesterol (TC), total triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) between the two groups. The levels of neutrophils (Neu), red cell distribution width variation coefficient (RDW-CV), blood urea nitrogen (BUN), creatinine (Cr), UA and UAR levels were higher in the experimental group than those in the control group (Ρ<0.05). The levels of lymphocyte (Lym), red blood cell count (RBC), mean corpuscular hemoglobin concentration (MCHC), platelet (PLT), estimated glomerular filtration rate (eGFR) and albumin (Alb) were lower in the experimental group than those in the control group (Ρ<0.05). Logistic regression analysis showed that lower levels of RBC and MCHC, and higher levels of UAR were independent risk factors for CKD complicated with CHD. ROC curve showed that the area under the UAR curve was the largest in RBC, MCHC and UAR detection, which was 0.912 (95%CI: 0.870-0.953), the sensitivity was 90.10%, the specificity was 77.70%, the Yoden index was 0.678 and the cutoff value was 10.935. The AUC of combined detection of RBC, MCHC and UAR was 0.987 (95%CI: 0.974-0.999), the sensitivity was 93.80% and the specificity was 97.90%. Conclusion The increased serum UAR level in patients with CKD is a predictor of CHD. The combined detection of UAR, RBC and MCHC has higher prediction efficiency. Figures and Tables | References | Related Articles | Metrics

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Clinical value of routine electroencephalogram combined with serum miR-146a and miR-129-5p levels in diagnosis of drug-resistant epilepsy patients WU Meina, DAI Weizheng, PAN Yudun, FU Maolin, CHEN Xiaoyu 2024, 52 (11):  1207-1210.  doi: 10.11958/20240666 Abstract ( 238 )   HTML ( 2 )   PDF (882KB) ( 37 )   Objective To investigate the clinical diagnostic value of routine electroencephalogram (EEG) combined with serum miR-146a and miR-129-5p levels in drug-resistant epilepsy. Methods Sixty patients with refractory epilepsy admitted to our hospital from June 2021 to June 2023 were included in the refractory epilepsy group, and 40 healthy volunteers were included in the control group. Human microvascular endothelial drug-resistant cells (HBMECs) continuously exposed to PHT2 were cultured in vitro and transfected with miR-NC (the miR-NC group), miR-146a mimics (the miR-146a mimics group) and miR-129-5p mimics (the miR-129-5p mimics group), respectively. Western blod assay was used to detect the expression of high-mobility group protein B1 (HMGB1) in each group. Serum miR-146a and miR-129-5p levels were detected by fluorescent quantitative PCR (polymerase chain reaction), and serum HMGB1 protein expression was detected by Western blod assay. The sensitivity, specificity and accuracy of routine EEG, serum miR-146a and miR-129-5p levels and combined diagnosis of drug-resistant epilepsy were evaluated using the comprehensive consultation results of several expert physicians as the gold standard, and ROC curves were drawn. Results Compared with the control group, the expression of HMGB1 was significantly decreased in the drug-resistant group. Compared with the miR-NC group, HMGB1 expression was significantly decreased in the miR-129-5p mimics group and the miR-146a mimics group (P<0.05). Compared with the healthy group, the serum HMGB1 protein expression was down-regulated and miR-146a and miR-129-5p expression levels were significantly up-regulated in the refractory epilepsy group. ROC curve analysis indicated that the area under the curve, sensitivity, specificity and accuracy of conventional EEG combined with serum miR-146a and miR-129-5p levels were higher in the diagnosis of refractory epilepsy than that of single diagnostic method. Conclusion The combination of routine EEG and serum miR-129-5p and miR-146a levels can provide help for the diagnosis of drug-resistant patients. Figures and Tables | References | Related Articles | Metrics

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The relationship between ALT/ALP ratio, PLR and hepatic injury in elderly patients with septic shock YU Hong, YANG Chaodong, LIU dan 2024, 52 (11):  1211-1215.  doi: 10.11958/20240637 Abstract ( 209 )   HTML ( 1 )   PDF (818KB) ( 63 )   Objective To investigate the prognostic value of alanine aminotransferase (ALT)/alkaline phosphatase (ALP) ratio, platelet (PLT) count/lymphocyte (LYM) ratio (PLR) in elderly patients with septic shock complicated with liver injury. Methods The clinical data of 116 patients with septic shock complicated with liver injury were retrospectively analyzed. According to the degree of liver injury, patients were divided into the mild group (39 cases), the moderate group (47 cases) and the severe group (30 cases). According to the survival of patients 28 days after admission, patients were divided into the death group (69 cases) and the survival group (47 cases). Acute physiological score, chronic healthⅡ(APACHE Ⅱ) score and sequential organ failure (SOFA) score were collected. PLT and LYM in peripheral blood were detected, and PLR was calculated. ALT and ALP were measured and ALT/ALP ratio was calculated. White blood cell count, blood lactic acid, C-reactive protein and other laboratory indicators were detected. Multivariate Logistic regression was used to analyze prognostic factors of patients with septic shock complicated with liver injury. The predictive values of ALT/ALP ratio and PLR on the prognosis of patients with septic shock complicated with liver injury were analyzed by receiver operating characteristic (ROC) curve. Results Serum ALT and ALP levels, ALT/ALP ratio, PLT and PLR were increased successively in the mild group, the moderate group and the severe group, while LYM was decreased successively in the three groups (P<0.05). The age, APACHE Ⅱ score, SOFA score, PLR, ALT/ALP ratio and blood lactic acid level were higher in the death group than those in the survival group (P<0.05). There was no significant difference in liver injury degree between the two groups (P<0.05). Multivariate Logistic regression analysis showed that high SOFA score, high PLR, high ALT/ALP ratio and moderate to severe liver injury were risk factors for death in patients with septic shock complicated with liver injury. ROC curve analysis showed that the combined ALT/ALP ratio and PLR prediction efficiency [area under the curve 0.915 (95%CI: 0.849-0.959), sensitivity and specificity 94.20% and 89.36%, respectively] was superior to single prediction (P<0.05). Conclusion Increased ALT/ALP ratio and PLR are associated with aggravation of liver injury and poor prognosis in patients with septic shock. ALT/ALP ratio and PLR can be used as prognostic markers. Figures and Tables | References | Related Articles | Metrics

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Evaluation values of PIV, IL-6, HBP and PAB levels in patients with severe community-acquired pneumonia GONG Xiujuan, ZHAO Huixia, ZHANG Xiaoqing, ZHANG Lianxia 2024, 52 (11):  1216-1220.  doi: 10.11958/20240710 Abstract ( 233 )   HTML ( 3 )   PDF (874KB) ( 29 )   Objective To analyze levels of pan-immune-inflammation value (PIV), interleukin-6 (IL-6), heparin-binding protein (HBP) and prealbumin (PAB) in patients with severe community-acquired pneumonia (CAP), and their values in evaluating the therapeutic effect at 72 h after admission. Methods According to the initial (72 h) treatment outcome, 120 patients with severe CAP (the severe group) were divided into the effective group (n=87) and the failed group (n=33). Meanwhile, 120 patients with non-severe CAP admitted in the same period were selected as the non-severe group. PIV, IL-6, HBP and PAB levels on the day after admission were compared between the severe group, the non-severe group, the failed group and the effective group. The value of above indicators in evaluating the condition of CAP and the therapeutic effect at 72 h after admission separately and in combination were analyzed using receiver operating characteristic (ROC) curves. Results Compared with the non-severe group, there were higher PIV, IL-6 and HBP levels, and lower PAB levels in the servere grouop (P<0.05). ROC curves indicated that for evaluating severe CAP using a single indicator, the area under the curve (AUC) of PIV was the highest [0.830 (95%CI: 0.780-0.881)]. The AUC of PIV combined with IL-6, HBP and PAB for evaluating severe CAP was 0.929 (95%CI: 0.892-0.967), which was higher than that of evaluation using a single indicator (P<0.05). Compared with the effective group, there were higher PIV, IL-6 and HBP levels, and lower PAB level in the failed group (P<0.05). ROC curves indicated that for evaluating the therapeutic effect on severe CAP at 72 h after admission using a single indicator the AUC of PIV was the highest [0.777 (95%CI: 0.692-0.862)]. The AUC of PIV combined with IL-6, HBP and PAB for evaluating the therapeutic effect on severe CAP at 72 h after admission was 0.916 (95%CI: 0.846-0.986), which was higher than that of evaluation using a single indicator (P<0.05). Conclusion Detection of PIV combined with IL-6, HBP and PAB has a good value in evaluating the condition of patients with CAP and the therapeutic effect on severe CAP at 72 h after admission. Figures and Tables | References | Related Articles | Metrics

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Progress of the aryl hydrocarbon receptor in inflammatory skin diseases LIU Haoying, SHI Tianwei 2024, 52 (11):  1221-1225.  doi: 10.11958/20240117 Abstract ( 193 )   HTML ( 4 )   PDF (929KB) ( 405 )   The aryl hydrocarbon receptor (AhR), also known as dioxin receptor, is a ligand-dependent transcription factor. Because of its important role in occurrence and development of cancer, it has been widely studied. AhR is now considered to be an important regulator of host-environment interactions in immune and inflammatory responses and is involved in pathogenesis of many skin diseases. Because AhR is highly expressed in all types of skin cells and regulates many genes that are critical to skin function, it has the potential to be a new target for the treatment of inflammatory skin diseases. This paper presents and analyzes research findings on the relationship between AhR and inflammatory skin diseases to help accelerate the development of new drugs. Figures and Tables | References | Related Articles | Metrics

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Research progress on the mechanism of dura mater in the growth and development of skull/meninges/brain tissue system LIU Song, LI Wenbin, SHAO Guo, ZHANG Chunyang, FENG Shijun 2024, 52 (11):  1226-1232.  doi: 10.11958/20240842 Abstract ( 276 )   HTML ( 3 )   PDF (868KB) ( 1797 )   Dura mater is a tough collagen connective tissue attached to inner surface of skull and wrapped around brain. As a buffer bridge between brain tissue and skull, its physiological function and role in skull development and repair have always been a focus of research. Recent studies have found that dura mater not only directly participates in skull development during skull growth, but also secretes a variety of cytokines that control the development of central nervous system. There are abundant material exchange and cell communication between the two. This article reviews the role of dura in development and repair of skull, and provides clues for further discovery of the relevant mechanisms of dura in development and repair of skull. Figures and Tables | References | Related Articles | Metrics