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    05 November 2022, Volume 42 Issue 11
    Invited Reviews: Applications of Artificial Intelligence in Medicine
    Application of artificial intelligence in cancer research and clinical practice
    CHEN Ming-yang, CAI Zi-ting, XUE Peng, JIANG Yu, QIAO You-lin
    2022, 42(11):  1637-1643.  doi:10.16352/j.issn.1001-6325.2022.11.1637
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    The rapid development of artificial intelligence (AI) has brought new opportunities for cancer prevention and control. This review give a brief overview of the origin and basic elements of AI. Then it comprehensively carded the application of AI systems in the field of cancer, reviewed the important research progress of AI in several major types of cancer around image-based cancer screening and diagnosis. Finally, this review summarized the challenges in algorithm, implementation and ethics and future development as well as more ideas for the application of AI technology in the oncological research.
    Application of artificial intelligence in cardiovascular disease research and clinical practice
    WU Yue-heng, YU Xi-yong
    2022, 42(11):  1644-1649.  doi:10.16352/j.issn.1001-6325.2022.11.1644
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    This paper briefly described the application of artificial intelligence (AI) in disease management and clinical research for diagnosis, prediction, treatment, and basic research of cardiovascular diseases (CVDs) and analyzed challenges in this field.The review highlighted extensive progress of AI technology application in the diagnosis and prediction of CVDs. For example, AI combined with ECG and cardiovascular imaging achieved an accurate diagnosis. Moreover, AI may integrate imaging data with other clinical data and so supported early screening and predicting of coronary artery disease, congenital heart disease, heart failure, and other CVDs risk. This paper also pointed out that AI-assisted cardiovascular interventional therapy and clinical decision-making are still on the way of development and AI-assisted multi-omics research is far from clinical application, which is the main direction of future research. In this paper, the problems faced by AI in the diagnosis, prediction, treatment, and basic research of CVDs were summarized and the application prospects of AI in the cardiovascular field have been prospected.
    Application of artificial intelligence in diabetes research and clinic performance
    WANG Yan-lei, DONG Wen-li, ZHANG Qiu
    2022, 42(11):  1650-1655.  doi:10.16352/j.issn.1001-6325.2022.11.1650
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    Artificial intelligence technology is the outcome of economic globalization. With the advent of the digital age, artificial intelligence plays an increasingly important role in various fields including the constantly updated and iterative healthcare and clinical service. Diabetes is a chronic non-communicable disease characterized by hyperglycemia. Many scholars are committed to researching diabetes prediction, intelligent diagnosis, early screening of complication and health management from an innovative perspective, so as to promote the health state of people. This paper mainly summarizes the application of artificial intelligence in diabetes research and clinical practice in recent years and puts forward future prospects for the intelligence and automation of diabetes diagnosis and treatment.
    Original Articles
    Effect of calcium channel blocker on steroid hormone profile of primary cultured aldosterone producing adenoma cells
    GAO Yin-jie, YU Song-lin, YIN Yi-cong, CUI Yun-ying, ZHANG Yu-shi, QIU Ling, TONG An-li
    2022, 42(11):  1656-1660.  doi:10.16352/j.issn.1001-6325.2022.11.1656
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    Objective To explore the influence of calcium channel blocker(CCB), verapamil, on steroid hormone profile of primary cultured aldosterone producing adenoma(APA)cells. Methods The adrenal tumor tissues of 6 APA patients with hypokalemia operated in Peking Union Medical College Hospital were cultured and treated with different concentrations of verapamil. The steroid hormone profile was detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS). Results The level of aldosterone in 50 μmol/L verapamil group was lower than that in 10 μmol/L verapamil group and control group(P<0.01). The levels of aldosterone precursor, 11-deoxycorticosterone in verapamil 10 μmol/L group was lower than that in control group (P<0.05). The levels of 18-oxocortisol(18-OXOF) and 18-hydroxycortisol(18-OHF) in verapamil 50 μmol/L group and verapamil 10 μmol/L group were lower than that in the control group (P<0.05). In addition, verapamil also had some inhibitory effects on glucocorticoids such as cortisol and cortisone, and adrenal derived sex hormones such as dehydroepiandrosterone sulfate(DHEA-S) and 11 beta-hydroxytestosterone(11β-OHT). Conclusions In addition to inhibit-ing aldosterone secretion in primary cultured APA cells, CCB has significant inhibitory effects on a variety of other steroid hormones, such as precursor 11-deoxycorticosterone, cortisol, metabolites, 18-OXOF and 18-OHF.
    Preparation and identification of the epitope peptide polyclonal antisera against capsid proteins of EV71
    LI Chen, ZHANG Ting, WANG Zhi-rong, XU Xue-mei
    2022, 42(11):  1661-1666.  doi:10.16352/j.issn.1001-6325.2022.11.1661
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    Objective To prepare polyclonal antisera against enterovirus 71(EV71) capsid proteins. Methods Five B cell epitope prediction softwares were used to analyze capsid proteins of EV71 and four peptides against viral protein were synthesized, VP1(aa.204-223), VP2(aa.133-163), VP3(aa.139-148+aa.173-191) and VP4(aa.1-23). They were conjugated with keyhole limpet hemocyanin(KLH). BALB/c mice were subcutaneously immunized with six doses of KLH-peptides adjuvanted with MF59/CpGC274 at two-week interval. Serum sample was collected and examined with ELISA and Western blot. Results The four antisera were bound to both EV71 virus and denatured virus effectively. VP2 antiserum showed activity with denatured virus and the other three had similar binding activity to EV71 virus and denatured virus. The four antiserum samples were bound to both EV71 virus-like particle (VLP) and denatured VLP effectively. VP1 and VP2 antiserum could bind to VP1, VP0 of EV71 VLP separately. VP2 antiserum showed the highese binding activity and VP1 antiserum showed a inperior binding activity as compared to the formers. VP1 and VP2 antiserum were bound specifically and efficiently to EV71 virus. VP0 of empty particles and VP2 of intact EV71 virus particles could be simultaneously identified by VP2 antiserum. VP3 and VP4 antiserum failed to binding to no obvious binding to VLP and virus. Conclusions Four epitope peptide polyclonal antisera against EV71 are successfully prepared, which can provide ootential detection tools used in ELISA and Western blot and may be used for QC evaluation of EV71 vaccine.
    Silencing circ_0006104 inhibits the proliferation, activation and collagen synthesis by mouse cardiac fibroblasts through up-regulation of miR-370-3p
    LI Ya-fei, DU Ying-qiang, WANG Ze-mu, ZHANG Jun
    2022, 42(11):  1667-1674.  doi:10.16352/j.issn.1001-6325.2022.11.1667
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    Objective To explore the function and mechanism of circular RNA 0006104 (circ_0006104) in regulating proliferation, activation and extracellular matrix (ECM) synthesis of cardiac fibroblasts (CFs) induced by angiotensin Ⅱ (Ang Ⅱ). Methods The primary CFs of neonatal mice were isolated and divided into control group, circ_0006104 knockdown group, Ang Ⅱ group,Ang Ⅱ + circ_0006104 knockdown group and Ang Ⅱ + circ_0006104 knockdown+ miR-370-3p inhibitor.EDU immunofluorescence staining was used to detect the proliferation level of CFs; Western blot was used to detect activation related gene (α-SMA); RT-qPCR was used to detect the expression of collagen Ⅰ and Ⅲ (Col and Col Ⅲ). Results Circ_0006104 was screened by RNA-seq high-throughput sequencing results. In the primary CFs of neonatal mice, silencing circ_0006104 had no effect on the proliferation, activation and ECM synthesis of CFs under physiological conditions, while silencing circ_0006104 could significantly inhibit the proliferation, activation and ECM synthesis of CFs induced by Ang Ⅱ (P<0.05). The molecules of circ_0006104 could bind to and negatively regulate miR-370-3p. The combined experimental results showed that inhibition of miR-370-3p significantly reversed the inhibitory effects of circ_0006104 silencing on the proliferation, activation and ECM synthesis of CFs induced by Ang Ⅱ (P<0.05). Conclusions Knockdown of circ_0006104 inhibits Ang Ⅱ-induced CFs fibrosis by binding and negatively regulating miR-370-3p.
    Screening of differential lncRNAs and expression analysis of lncRNA ZEB2-AS1 in ovarian cancer tissues
    DONG Hui, WANG Ting-ting, MA Xiao-hong, MA Sheng-zong, DING Yong-hui
    2022, 42(11):  1675-1680.  doi:10.16352/j.issn.1001-6325.2022.11.1675
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    Objective To screen the valuable core(long non-coding RNAs,lncRNAs) from the tissue of ovarian cancer (OC) through expression profiling chip, and carry out expression verification and analysis. Methods Thirty-six tissue samples of ovarian cancer and of 22 normal ovaries were collected from January 2018 to June 2019 in the General Hospital of Ningxia Medical University and then expression profile chips were used to detect differentially expressed lncRNAs and mRNAs molecules, while real-time PCR was to verify the expression of lncRNAs. The expression of key core lncRNAs were measured by in situ hybridization, and the potential functions of lncRNAs were evaluated by bioinformatics. Results Compared with normal tissues, 4 982 different lncRNAs fragments were found in cancer tissues. The high expression of zinc finger E-box binding homeobox protein 2-AS1 (ZEB2-AS1) was the most significant one (P<0.05); ZEB2-AS1 was over-expressed in multiple cancer tissues including liver cancer, colon cancer and kidney cancer;The expression level was correlated with tumor size, pathological grade, pathological type and clinical stage (P<0.05).The high expression led to a decrease in overall survival and disease-free survival rate(P<0.05). ZEB2-AS1 had microRNA binding sites, which was in agreement with the expression of the corresponding neighboring gene ZEB2. Conclusions The abnormal expression of ZEB2-AS1 in OC suggests potential research value in future.
    Salidroside inhibits the proliferation and epithelial mesenchymal transformation of NSCLC cell by negatively regulation of TACC2 expression
    HE Shao-bo, LUO Fu-hua, JIANG Chuan-ming, LIU Xuan-mei
    2022, 42(11):  1681-1689.  doi:10.16352/j.issn.1001-6325.2022.11.1681
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    Objective To investigate the effect of salidroside (SAL) on the proliferation, apoptosis and epithelial mesenchymal transformation (EMT) of non-small cell lung cancer (NSCLC) cell line and to clarify the molecular mechanism. Methods The cancer tissues from 22 lung cancer patients and adjecent tissues were collected, and the different lung cancer cell lines (A549, H358, H1299, H1650) were cultured in vitro. RT-qPCR was used to detect the expression of transforming acidic coiled-coid protein 2(TACC2) in cancer tissues and the lung cancer cell lines. After cells (A549 and H1299) were treated with SAL at different concentrations, the apoptosis and proliferation rates were analyzed by flow cytometry and CCK-8, respectively. The expression of E-cadherin, N-cadherin, TACC2 and the phosphorylation level of P38/MAPK in NSCLC cell were detected by Western blot. Plasmid (pcDNA3.0-TACC2) was transfected into A549 and H1299 cell to detect the effects of TACC2 over-expression on the levels of apoptosis, proliferation and EMT. Results The relative expression of TACC2 in lung cancer tissue significantly increased as compared with adjecent tissues.Meanwhile, the expression of TACC2 in NSCLC cell was also markedly higher than human lung fibroblasts cell line(HFL-1)(P<0.05). Different concentrations of SAL can significantly inhibit the proliferation and increase the apoptosis of cells(P<0.05). Western blot results showed that the expression of TACC2 and N-cadherin was significantly down-regulated, while E-cadherin expression was up-regulated in A549 and H1299 cells after treatment with SAL. Transfection with pcDNA3.0-TACC2 plasmid could significantly reduced the inhibited effect of SAL on the proliferation and EMT of A549 and H1299 cells (P<0.05). In addition, the phosphorylation of intracellular p38/MAPK was significantly reduced after treatment with various SAL concentrations (P<0.05). Conclusions SAL can inhibit the levels of proliferation and EMT in NSCLC cell by negatively regulates the expression of TACC2, which may be related to the inhibition of p38/MAPK signaling pathway.
    miR-34c-5p knockdown inhibits hypoxia induced cell apoptosis of bone marrow derived mesenchymal stem cells in rats
    DONG Yang, ZHANG Fen, LI Xing-xing, WU Jie, XU Zhong-cheng
    2022, 42(11):  1690-1696.  doi:10.16352/j.issn.1001-6325.2022.11.1690
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    Objective To explore the effect of miR-34c-5p knockdown on improving the survival rate of bone marrow derived mesenchymal stem cells (BM-MSCs). Methods The BM-MSCs were divided into normoxia group, hypoxia group, normoxia inhibitor NC group, hypoxia inhibitor NC group, normoxia microRNA(miR) inhibitor group and hypoxia miR inhibitor group. The expression level of miR-34c-5p, IGF, HGF, bFGF and VEGF was detected by real-time quantitative PCR (RT-qPCR) and ELISA. Cell apoptosis was detected by flow cytometry and TUNEL. The protein expression levels of cleaved caspase-3, -9, Bcl-2 and Bax were detected by Western blot. ATP/ADP was detected by biochemical kits, and glucose uptake was detected by flow cytometry. Results Compared with hypoxic inhibitor NC group, miR-34c-5p knockdown significantly inhibited BM-MSCs apoptosis(P<0.01), reduced protein expression of cleaved caspase-3, -9 and Bax and increased protein expression by Bcl-2 (P<0.01). The expression of IGF, HGF, bFGF and VEGF (P<0.05, P<0.01) were significantly increased; ATP/ADP rate and cell capacity of glucose transporting also increased (P<0.05, P<0.01). Conclusions miR-34c-5p knockdown may antagonize hypoxia induced cell apoptosis of BM-MSCs in rat.
    miR-760 inhibits proliferation, invasion and migration of human esophageal squamous cell carcinoma cell lines
    YUAN Sheng-wu, CHEN Juan, LIU Kai
    2022, 42(11):  1697-1703.  doi:10.16352/j.issn.1001-6325.2022.11.1697
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    Objective To investigate the effects of miR-760 on the proliferation, invasion and migration of esophageal squamous cell carcinoma (ESCC) cells through targeted regulation of basic leucine zipper ATF-like transcription factor 3 (BATF3). Methods The cancer tissues and adjacent tissues of ESCC patients were collected, and normal human esophageal squamous epithelial cells Het-1A and human ESCC cell lines EC9706, KYSE150, ECA109, TE-10 were cultured in vitro. RT-qPCR was used to detect the expression of miR-760 and BATF3 mRNA. miR-760-mimics were transfected into TE-10 cells for up-regulating the expression of miR-760. CCK-8 method was used to detect cell proliferation and Transwell chamber was used to detect cell invasion as well as migration. Western blot was used to detect the expression of proliferation-related proteins cyclin D1, p21 and epithelial-mesenchymal transition related proteins MMP2, vimentin, and E-cadherin. Dual luciferase reporter gene experiment was used to confirm the targeting relationship between miR-760 and BATF3. Results Compared with the adjacent tissues and Het-1A cell, the expression of miR-760 was significantly reduced in ESCC tissues and in cell lines, while the expression of BATF3 increased (P<0.05). The TE-10 cells with the highest expression of miR-760 were selected for subsequent experiments. Over-expression of miR-760 reduced the activity of TE-10 cells and the counting numbers of invasion and migration cells(P<0.05). The expression of cyclin D1 and vimentin proteins increased the expression of p21 and E-cadherin proteins (P<0.05). The results showed that miR-760 negatively regulated the expression of BATF3 (P<0.05). Up-regulation of BATF3 expression reversed the inhibitory effects by over-expression of miR-760 on the proliferation, invasion and migration of TE-10 cells(P<0.05). Conclusions Over-expression of miR-760 may inhibit the proliferation, invasion and migration of ESCC cells, which may be related to the targeted inhibition of BATF3 expression.
    Down-regulation of miR-27a alleviates lung injury in septic rat models
    LI Jia-jin, LIU Jun, HE Song-yu, CHEN Hao-yun
    2022, 42(11):  1704-1708.  doi:10.16352/j.issn.1001-6325.2022.11.1704
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    Objective To investigate the effects of miR-27a on lung pathology, inflammatory factors, oxidative stress indices and peroxisome proliferator activated receptor γ(PPAR-γ) protein expression in septic lung injury rats. Methods Rats were randomly divided into sham group, sepsis rat model group (sepsis group), miR-27a NC plasmid intervention group (NC group) and miR-27a inhibitor plasmid intervention group (miR-27a group), with 10 rats in each. Inflammatory factors and oxidative stress indexes were assessed by ELISA; Wet/dry mass ratio of lung tissue was compared; Pathological changes of lung tissue were microscoped with HE staining; miR-27a and PPAR-γ expression in lung tissue were detected by Western blot. Results Serum level of TNF-α, IL-6 and MDA in the sepsis group was higher than that in the sham group, while the superoxide dismutase(SOD) activity significantly decreased (P<0.05). The contents of TNF-α, IL-6, and MDA in miR-27a group were significantly less than those in the sepsis group, while the SOD activity was significantly higher(P<0.05). Compared with the sham group, the wet/dry weight ratios of lung tissues in the sepsis group were increased (P<0.05). Compared with the sepsis group, the wet/dry weight ratio of lung tissues in the miR-27a group was significantly decreased (P<0.05). A large number of vascular endothelial cells, alveolar epithelial cells, and macrophages with positive expression of PPAR-γ were found in the lung tissues from sham group. The expression of PPAR-γ in the sepsis group was decreased compared with that in the sham group, and the expression of PPAR-γ in the lung tissues of the miR-27a group was significantly increased(P<0.05). The expression of miR-27a in lung tissues of rats from sepsis group was significantly higher than those in the sham group, and the concentration of PPAR-γ protein was lower than that in the sham group (P<0.05). Conclusions Down-regulation of miR-27a may reduce lung injury in septic rats.
    Resveratrol relieves hypoxia-reoxygenation-induced mitophagy in TCMK1 cells
    JIANG Luo-jia, XU Hai-bo
    2022, 42(11):  1709-1715.  doi:10.16352/j.issn.1001-6325.2022.11.1709
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    Objective To study the effect of resveratrol (Res) on mitochondrial function and mitophagy in mouse renal tubular epithelial cell line TCMK1 induced by hypoxia-reoxygenation (H/R). Methods The H/R model cell was established in vitro, and TMCK1 cells were pre-treated with Res or (and) mitophagy inhibitor 1 (Mdivi-1) for 2 h. CCK-8 method was used to measure cell viability. Flow cytometry was applied to determine cell mitochondrial membrane potential(MMP) and reactive oxygen species(ROS). Western blot was adapted for determining the protein expression levels of optic atrophy (OPA), dynamin-related protein(DRP) and cleaved caspase-3. Cellular immunofluorescence was used to observe the co-localization of mitochondrial outer membrane translocase (TOMM20) and autophagolysosome-associated membrane protein 2 (LAMP2). Results There was significantly reduction in the survival rate of TCMK1 cells in H/R group versus control (P<0.05). The intracellular calcium ion, ROS and MMP contents were significantly reduced (P<0.05), and the expression of OPA was significantly reduced(P<0.05). The expression of DRP was significantly improved (P<0.05), and the number of mitochondria and LAMP2 co-localized significantly decreased. As compared to the H/R group, 10 μmol/L Res could significantly increase the survival rate of TMCK1 cells (P<0.05), and inhibit the release of ROS, calcium overload and the decrease of MMP in TCMK1 cells after H/R injury (P<0.05). While Res could promote the expression of OPA and inhibite the expression of DRP (P<0.05), increase the number of cells with co-localized mitochondria and LAMP2. Compared with (HR+Res) group, the expression of cleaved caspase-3 and Bax increased, while the expression of Bcl2 decreased after Mdivi-1 was administered on the basis (P<0.05). Conclusions Res attenuation of H/R-induced TCMK1 cell damage is medicated at leaet in part by activation of mitophagy and maintaining mitochondrial dynamic homeostasis as one of potential mechanisms.
    Effect of IL-35 on soluble CD40 ligand-induced injury of vascular endothelial cells
    LI Ming, SUN Hai-ling, LIU Juan-li, GUO Wei-wei
    2022, 42(11):  1716-1720.  doi:10.16352/j.issn.1001-6325.2022.11.1716
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    Objective To investigate the concentration of soluble CD40 ligand (sCD40L) and interleukin (IL)-35 in peripheral blood of patients with deep vein thrombosis (DVT), and to study the protective effect of IL-35 on sCD40L-induced vascular endothelial cell injury. Methods Peripheral venous blood 3 mL was collected respectively from 30 patients with acute deep vein thrombosis patients (DVT group) and 30 healthy controls (HC group). Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of serum IL-35, sCD40L, IL-1β, and IL-18. Human umbilical vein endothelial cells (HUVECs) were cultured and divided into three groups: control group (phosphate buffer), sCD40L group (25 μg/mL sCD40L), and IL-35 group (20 ng/mL IL-35 and 25 μg/mL sCD40L). CCK8 kit was used to detect the viability of HUVECs and ELISA was used to detect the level of IL-1β and IL-18 in the cell culture supernatant. The protein expression of GSDMD-N and cleaved caspase-1 in HUVECs was detected by Western blot. Results The level of IL-35 in peripheral blood of DVT patients was signifi- cantly lower than that in HC group, while the level of sCD40L, IL-1β, and IL-18 was significantly higher(P<0.05). Furthermore, there was a negative correlation between IL-35 and sCD40L in DVT patients. In vitro, IL-35 inhibited the damage of cells viability induced by sCD40L, and reduced the concentration of IL-1β and IL-18 in culture supernatant from sCD40L group. The protein expression of GSDMD-N and cleaved caspase-1 in cells was decreased too. Conclusions The level of IL-35 in peripheral blood of DVT patients is decreased, while the level of sCD40L is increased. IL-35 has a protective effect on sCD40L-induced vascular endothelial cell injury, which may have some impacts on the pathogenesis of thrombosis.
    Transcription factor AP-1 inhibitor T5524 alleviates cholestatic liver injury in mouse models
    LI Sheng-tao, LU Zhuo-heng, LUO Jia, YAN Zheng, TANG Zhi-yuan
    2022, 42(11):  1721-1726.  doi:10.16352/j.issn.1001-6325.2022.11.1721
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    Objective To explore the effect and underlying mechanism of transcription factor activator protein-1 (AP-1) in cholestatic liver injury. Methods ICR mice were randomly divided into control group, cholestatic liver injury model group and AP-1 inhibitor(T-5244) intervention model group(5 in each group). α-naphthyl isothiocyanate(ANIT) and T-5224 were dissolved in corn oil respectively. The mice were fasted for 12 h overnight before the experiment. The control group was treated with corn oil by oral gavage. The cholestatic liver injury model group and the T-5244 intervention model group were treated with ANIT 120 mg/kg(a single dose). The T-5244 intervention group was intraperitoneally injected with T-5224 inhibitor AP-1 100 mg/kg 0.5~1 h before ANIT treatment. The T-5224 treatment was repeated 24 h later. After 48 hrs, all mice were sacrificed to collect serum, liver and gallbladder. The biochemical markers, histopathological changes and liver injury among different groups were analyzed and compared. Results Compared with the control group, the biomarker of liver injury, aspartate alanine aminotransferase (ALT), and aminotransferase (AST), increased from (7.2±1.6)μmol/L and (2.5±0.5) μmol/L to (132.0±48.4)μmol/L and (94.2±22.2)μmol/L in cholestatic liver injury group. It confirmed a successful development of cholestatic model. In contrast with the cholestatic liver injury group, the two biomarkers in the T-5224 intervention group were reduced to (48.4±12.8)μmol/L and (23.1±2.6)μmol/L respectively. At the protein level, activation of AP-1 was inhibited. Expression of CXCL10, CCL2 were inhibited by 90% and 79% respectively in the T-5224 intervention group, and liver injury was significantly reversed. Conclusions AP-1 mediated chemotaxis plays an important role in ANIT-induced cholestatic liver injury.
    Puerarin attenuates LPS-induced renal inflammatory response of mice
    FENG Na, TANG Jie, HE Xi-ju, TIAN Zong-ying, SHI Dan-dan, YU Jing-jing
    2022, 42(11):  1727-1730.  doi:10.16352/j.issn.1001-6325.2022.11.1727
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    Objective To investigate whether puerarin (PUE) can alleviate lipopolysarccharide(LPS)-induced renal inflammatory response in mice. Methods Thirty health control, 45 severe infection with no renal injury(N-SI group), 30 severe infection with renal injury(SI group) were enrolled in this study, Serum samples were collected. 50 mice were randomly divided into 5 groups, including control(Ctrl) group, LPS group, and LPS+PUE(10, 25, 50 mg/kg·d, IP) groups. PUE was applied 1 h after LPS administration. And mice were sacrificed after 24 h and blood sample was collected. MDA, SOD, IL-33 and IL-6 expression were detected by ELISA. Results BUN, Scr, IL-6 and IL-33 in SI group were significantly increased compared with control group and N-SI group (P<0.05). BUN and Scr of LPS group were significantly increased compared with control group. PUE decreased BUN, Scr, MDA, IL-33 and IL-6 expression and increased activity of SOD as compared with LPS group(P<0.05). Conclusions PUE can alleviate LPS-induced renal inflammatory response in mice.
    Pseudolaric acid B inhibits the proliferation of human diffuse large B-cell lymphoma cell line SU-DHL-4 via miR-4282
    YUAN Jun, HAN Hu, DONG Wei, WANG Rui-cang, HAO Hong-ling, ZHANG Xue-jun
    2022, 42(11):  1731-1736.  doi:10.16352/j.issn.1001-6325.2022.11.1731
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    Objective To observe the effect of pseudolaric acid B(PAB) on the proliferation and apoptosis of human diffuse large B-cell lymphoma cell line SU-DHL-4 possibly and to explore the potential mechanism through regulating miR-4282. Methods SU-DHL-4 cells were divided into control group, PAB-L group, PAB-M group, PAB-H group; According to liposome method, miR-NC and miR-4282 were transfected into the cells and were marked as miR-NC group, miR-4282 group; The anti-miR-NC, anti-miR-4282 were transfected into the cells,cultured with 20 μmol/L PAB, denoted as (PAB+anti-miR-NC)group and(PAB+anti-miR-4282)group. Cell pro- liferation was detected by CCK8 assay, and cell apoptosis was detected by flow cytometry. The expression of Ki-67,cleaved caspase-3, cleaved caspase-9 protein was detected by Western blot and miR-4282 expression was detected by RT-qPCR. Results Compared with the control group, Ki-67 protein expression in PAB-L group, PAB-M group, and PAB-H group was decreased while miR-4282 expression, and the apoptosis rate, cell inhibition rate, protein expression of cleaved caspase-3, cleaved caspase-9 were increased (P<0.05). Compared with the miR-NC group, Ki-67 protein expression in miR-4282 group decreased, while miR-4282 expression, the apoptosis rate, cell inhibition rate, protein expression of cleaved caspase-3, cleaved caspase-9 were all increased (P<0.05). Inhibition of miR-4282 expression reduced the effect of PAB on the proliferation and apoptosis of SU-DHL-4 cells. Conclusions PAB may inhibit the proliferation of human diffuse large B-cell lymphoma cell SU-DHL-4 and promote apoptosis through increased expression of miR-4282.
    miR-99a inhibits the proliferation, migration and invasion of cervical cancer HeLa cell line through down-regulating RRM2
    HE Chun-hua, LIU Leng, ZHANG Xiao-liu
    2022, 42(11):  1737-1743.  doi:10.16352/j.issn.1001-6325.2022.11.1737
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    Objective To investigate the targeting relationship between miR-99a and ribonucleotide reductase subunit M2 (RRM2)and to analyze their effects on proliferation, invasion and migration of cervical cancer (CC)-oringinated HeLa cell line. Methods HeLa cells were divided into control group, negative control group (inhibitor-NC), inhibition of miR-99a expression group (miR-99a-inhibitor) and co-transfection group (RRM2-siRNA+miR-99a-inhibitor). MTT assay and plate colony experiment were used to detect the proliferation ability of HeLa cells. Scratch test and Transwell test were used to detect cell migration and invasion ability respectively. Western blot was used to detect protein expression of RRM2, proliferating cell nuclear antigen (PCNA), E-cadherin, N-cadherin and vimentin.Immunofluorescence method was used to detect the localization and expression of E-cadherin, N-cadherin and vimentin. Bioinformatics and dual-luciferase reporter gene experiments verified the targeting relationship between miR-99a and RRM2. RT-qPCR were used to detect the expression levels of miR-99a and RRM2 mRNA in HeLa cells in each group. Results Down-regulating the expression of miR-99a increased proliferation of HeLa cells (100.00 vs. 128.86±4.25, P<0.05). Up-regulated colony formation improved scratch healing rate, and increased the number of invasive cells and the expression of RRM2, PCNA, N-cadherin and vimentin protein, decreased E-cadherin protein expression (P<0.05). Inhibition of RRM2 expression reversed the effect of down-regulation of miR-99a on the biological behavior of HeLa cells(P<0.05). Dual-luciferase reporter gene experiment and RT-qPCR confirmed that miR-99a had a targeting relationship with RRM2 (P<0.05). Conclusions Inhibition of miR-99a may target at up-regulating the expression of RRM2 to promote the development of HeLa cells, which is expected to become a new potential therapeutic target for CC.
    Pinocembrin inhibits the proliferation, migration and invasion of gastric cancer cell line AGS
    LI Xun, FU Xiao-xia, FAN Li-wei, WANG Jing-kun, ZHANG Dong-jiao, ZHAO Yan-huan, ZHANG Lei, ZHAO Yu-hong
    2022, 42(11):  1744-1750.  doi:10.16352/j.issn.1001-6325.2022.11.1744
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    Objective To explore the effect and mechanism of pinocembrin on the proliferation, migration and invasion of gastric cancer cell line AGS. Methods AGS cells were divided into different test groups according to concentrations of pinocembrin(50, 100, 200, 400 μmol/L), NC group, 200 μmol/L pinocembrin + anti-miR-NC group, 200 μmol/L pinocembrin + anti-miR-34a-5p group. The proliferation, apoptosis, migration, invasion ability and protein expression of AGS cells were detected by CCK-8 assay, flow cytometry, Transwell chamber assay and Western blot. The expression of miR-34a-5p was detected by real-time fluorescent quantitative PCR (RT-qPCR). Results Different concentrations of pinocembrin reduced the proliferation activity of AGS cells (P<0.05) and the proportion of in G0/G1 phase cells was increased while the proportion of S phase cells decreased. The expressions of MMP2, MMP9, p-PI3K and p-AKT protein decreased. The cell migration and invasion were inhibited. The expression of miR-34a-5p was increased (P<0.05), which reduced the inhibitory effect of pinocembrin on the prolifera- tion, migration and invasion of AGS cells. Conclusions Pinocembrin can inhibit the proliferation, migration and invasion of AGS cells by improving the expression of miR-34a-5p.
    Correlation analysis of common/severe COVID-19 delta with serum albumin in Zhangjiajie
    CHEN Yu-zhou, DAI Jing-rong, LI Qian, LIANG Ya-ting, WU Song-lin
    2022, 42(11):  1751-1754.  doi:10.16352/j.issn.1001-6325.2022.11.1751
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    Objective To analyze the correlation between the classification of infection by delta variant of coronavirus disease 2019(COVID-19 delta) in Zhangjiajie City and the differences in general health conditions and clinical characteristics of confirmed cases. Methods Seventy-three confirmed patients admitted to Zhangjiajie People's Hospital from July 20, 2021 to September 30, 2021 were enrolled into this research project. According to the diagnostic and typing criteria of Novel Coronavirus Protocol for the Diagnosis and Treatment of Pneumonia (Trial Edition 8), the patients were classified as mild, ordinary and severe groups and compared for general condition, clinical manifestations and laboratory data. Results Of the 73 patients, 22 (30.1%) were in the mild group and 51 (69.9%) were in the normal and severe groups. There were statistically significant differences in age, gender, globulin, albumin, fibrinogen, amyloid A, C-reactive protein, ESR and D-dimer between the two groups (P<0.05).Binary Logistic regression analysis showed that serum albumin was an independent influencing factor for common/severe group (OR=0.762,95% CI:0.585~0.993, P<0.05). Conclusions Serum albumin is a protective factor for infection by common/severe COVID-19 delta variant. Albumin supplementation may play an important role in the prevention of ordinary/severe of COVID-19 delta.
    Clinical Sciences
    Risk factors for postoperative complications in posterior scoliosis correction surgeries of pediatric patiens
    MA Man-jiao, MA Lu-lu, ZHANG Xiu-hua, ZHANG Jian-guo, SHEN Jian-xiong, HUANG Yu-guang
    2022, 42(11):  1755-1759.  doi:10.16352/j.issn.1001-6325.2022.11.1755
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    Objective To investigate the postoperative complication rate in pediatric patients who underwent posterior scoliosis correction surgeries, and to identify its risk factors. Methods This study was a retrospective cohort study. Anesthetic data of pediatric patients who underwent posterior scoliosis correction surgeries from January 2015 to December 2017 in Peking Union Medical College Hospital were collected and analyzed. The clinical variables were subsequently compared between patients in whom postoperative complication occured (complication group) and those in whom did not (non-complication group). Binary Logistic regression analysis was performed to identify risk factors of postoperative complication in these patients. Results The study enrolled 580 patients. The postoperative complication rate was 5.7% and the independent risk factors leading to it included preoperative Cobb angle larger than 69.5° (OR=3.043, 95% CI:1.436-6.448, P<0.01) and perioperative allogeneic transfusion(OR=2.364, 95% CI:1.095-5.102, P<0.05). The postoperative transfer rate to Intensive Care Unit(ICU)(P<0.01) in complication group was higher, with longer hospital stay length (P<0.001) than that in the non-complication group. Conclusions The risk factors for postoperative complication in pediatric patients receiving posterior scoliosis correction surgeries include preoperative Cobb angle larger than 69.5° and perioperative allogeneic transfusion.
    Reduction of lung infection rates after cardiac surgery with target monitoring
    ZHANG Ying-qi, HUANG Yu-zhu, PAN Ming-hu, GUO Xiu-ling, LIU Li
    2022, 42(11):  1760-1763.  doi:10.16352/j.issn.1001-6325.2022.11.1760
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    Objective To monitor the incidence of pulmonary infection after cardiac surgery by target monitoring for reducing the incidence of postoperative pulmonary infection. Methods Surgical targets monitoring was used to follow 425 patients undergoing cardiac surgery in a tertiary general hospital from January 2017 to December 2018. There were 25 cases of postoperative pulmonary infection, and the infection rate was 5.88%. From 2019 and 2020, the PDCA cycle mode was applied to compare the rate of pulmonary infection after cardiac surgery. Results In 2019, 11 cases in 265 patients with cardiac surgery had postoperative pulmonary infection, and the infection rate was 4.15%; In 2020, 6 cases in 200 patients with cardiac surgery had postoperative pulmonary infection, and the infection rate was 3%. Conclusions Through surgical target monitoring, it is found that the application of the PDCA cycle mode can jointly participate in the prevention and control of nosocomial infection with multiple disciplines, and continuously improve the quality. At the same time, it can effectively reduce the incidence of pulmonary infection after cardiac surgery, and greatly improve the life and quality of life of patients.
    Case Report
    Cytokine release syndrome caused by immune checkpoint inhibitor: a case report
    SI Xiao-yan, WANG Han-ping, ZHANG Li, WANG Meng-zhao, ZHANG Xiao-tong
    2022, 42(11):  1764-1766.  doi:10.16352/j.issn.1001-6325.2022.11.1764
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    Objective To investigate the diagnosis and treatment of cytokine release syndrome (CRS) caused by immune checkpoint inhibitor(ICI). Methods A case of ICI pembrolizumab leading to CRS was analyzed in Department of Pulmonary and Critical Care Medicine of Peking Union Medical College Hospital. ResultsA 52-year-old woman with advanced adenosquamous lung cancer developed fever and hypotension after receiving pembrolizumab. Results of laboratory test showed an obviously increased serum ferritin, C response protein, interleukin-6 and abnormal liver function. Without positive infectious results, she was ultimately diagnosed as CRS. The patient was treated with steroids and tocilizumab with good clinical response. Conclusions CRS caused by ICIs develops rapidly and lead to severe results. It is important to consider CRS in patient who developed systemic inflammatory response syndrome after ICIs. Steroids combined tocilizumab is a potential choice of treatment.
    Mini Reviews
    Research progress on the role of secretory protein Metrnl in different diseases
    ZHANG Lan-yue, ZHANG Xue-dong
    2022, 42(11):  1767-1770.  doi:10.16352/j.issn.1001-6325.2022.11.1767
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    Metrnl is a new cytokine with homologous orignination from neurotrophic factor Meteorin. Meanwhile, as a secreting protein, its gene and products show low tissue specificity and is widely expressed in different tissues of host. Similar to neurotrophic factor, adipocytokines, inflammatory factor and muscle factor, the protein plays a role in neural development, immune inflammatory response and metabolism and so on.
    Research progress of umbilical cord mesenchymal stem cells in repairing skin wounds
    WU Wen-zhe, SUN Jian-wei, FU Chang-xiu, HUANG Li-chen-lu, ZHENG Yong-qin, HE Jun-dong
    2022, 42(11):  1771-1775.  doi:10.16352/j.issn.1001-6325.2022.11.1771
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    Umbilical cord mesenchymal stem cells (UC-MSCs) are a kind of adult stem cells with low immunogenicity, which are easy to collect and to expand in vitro. UC-MSCs can regulate wound inflammation, promote angiogenesis and cell proliferation, inhibit scar formation and induce the formation of skin appendages. UC-MSCs combined with other drugs can promote the adhesion, survival, migration and proliferation of UC-MSCs.
    Use of artificial intelligence in bone age assessment
    WANG Feng-dan, Cidanwangjiu, JIAO Yang, PAN Hui, YIN Wu, JIN Zheng-yu
    2022, 42(11):  1776-1780.  doi:10.16352/j.issn.1001-6325.2022.11.1776
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    Artificial intelligence (AI) system which can achieve stable, efficient and automatic bone age (BA) evaluation has been gradually embedded into clinical workflow. Herein, the routine BA methods were briefly reviewed and then followed by explanation of some terms commonly used in the area of AI. Then authors reviewed the research progresses of AI bone age software both in China and abroad in recent years, including the sources of training and validation dataset, the construction of algorithms and modules, and its performance in testing dataset. Finally, the challenges of applying AI in BA assessment were presented and some suggestions were given.
    Research progress on the role of ferroptosis in the treatment of tumors
    WANG Feng-yu, LI Gen, LIN Xiao-yi, YAO Xin-yue, CHEN Yu
    2022, 42(11):  1781-1784.  doi:10.16352/j.issn.1001-6325.2022.11.1781
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    Ferroptosis, as a regulated and non-apoptotic form of cell death, provides a new research direction for tumor therapy. Ferroptosis is involved in the development of drug resistance in some tumors and also in the treatment process of many tumor therapies, which is a neglected mechanism in tumor therapy. This article will introduce the relationship between ferroptosis and different tumor treatment therapies from the aspects of tumor chemotherapy, tumor radiation therapy and tumor immunotherapy, and summarize the strategies of improving tumor treatment effect by ferroptosis, in order to provide reference for tumor treatment.
    Progress in the diagnosis and treatment of Rosai-Dorfman disease
    LIU Ting, CAO Xin-xin
    2022, 42(11):  1785-1790.  doi:10.16352/j.issn.1001-6325.2022.11.1785
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    Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis. Its etiology and pathogenesis are yet incompletely elucidated. The clinical manifestations of RDD are highly heterogeneous. It is easy to be misdiagnosed or missed diagnosis. There is no standard treatment at present. Therefore, the progression in pathogenesis, diagnosis and treatment are reviewed. The treatment of RDD is best tailored to the individual clinical circumstances. Observation is suitable for patients with uncomplicated lymphadenopathy or asymptomatic cutaneous RDD. For RDD patients with extra nodal unifocal disease or organ compression, surgery is recommended. Systemic therapy can be considered for patients with systemic, recurrent or refractory RDD.
    Research progress of application of pharmaceutical preparation chitosan
    ZOU Xing-long, CHEN Zhu-xian, SUN Juan-juan, CAI Jiang-ying, SU Lu, MA Wei, FU Si-wu
    2022, 42(11):  1791-1794.  doi:10.16352/j.issn.1001-6325.2022.11.1791
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    As the only alkaline polysaccharide in nature, chitosan(CTS) is haracterized by its unique physiological activity, good film-forming capacity, well adsorption and antibacterial properties. Various pharmaceutical preparations and clinical applications of CTS and its derivatives have proved the practicability of CTS products in the field of pharmaceutical preparations. CTS and its derivatives have a good development prospect in the field of medicine and clinical application.
    Role of Tamm-Horsfall protein in acute kidney injury
    XU Yi-wen, LI Qing-chu
    2022, 42(11):  1795-1798.  doi:10.16352/j.issn.1001-6325.2022.11.1795
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    The Tamm-Horsfall protein (THP), also known as uromodulin (UMOD), is a kidney-derived protein released bidirectionally in the blood and urine. Blood and urinary THP may be markers of early predictive diagnosis of acute kidney injury(AKI) and possibly as one of the indicators of AKI severity. At the same time, THP plays a role in protecting kidney function in AKI through inhibiting reactive oxygen species accumulation, anti-inflammatory response and regulating macrophages. So it is a potential target in the clinical treatment of AKI.
    Research progress on the role of mitochondrial SIRT3 in organ fibrosis
    QI Jun-qing, CAO Meng-fei, ZHAO Qian-ru, YIN Jun
    2022, 42(11):  1799-1803.  doi:10.16352/j.issn.1001-6325.2022.10.1799
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    Organ fibrosis is the main cause of organ dysfunction, and there is no effective anti-fibrosis clinical therapy yet. SIRT3 is an important mitochondrial deacetylase that plays a role in organ fibrosis by regulating mitochondrial protein acetylation level to protect mitochondria from various types of damage. SIRT3 can retard or inhibit the process of organ fibrosis by regulating mitochondrial metabolism, oxidative stress, mitochondrial dynamics, mitochondrial DNA damage, autophagy and apoptosis.
    Research progress on the effect of acoustic stimulation on the neuropsychiatric system
    LIU Li-na, CHENG Yin-long, DING Meng, LI Zhe, LIU Xiao-yu
    2022, 42(11):  1804-1808.  doi:10.16352/j.issn.1001-6325.2022.11.1804
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    Sound wave has been proved to affect physical and mental health. Results of several research projects showed that sonic stimulation like music, white noise, waves with specific frequencies and natural sound can improve cognition, regulate psychological status. However, long-term noise exposure will cause psychological diseases and impair cognitive function. Herein, this article summarized global research progress about the effects of sound waves on the neuropsychiatric system in order to provide guidance for the development of sonic therapy and for control noise pollution control.
    Medical Education
    Application of self-monitoring of blood glucose-based experience teaching method in clinical training of endocrinology
    LIU Wei, Fu Yao, LUO Ying-ying, ZHANG Rui, CAI Xiao-ling, HAN Xue-yao, JI Li-nong
    2022, 42(11):  1809-1812.  doi:10.16352/j.issn.1001-6325.2022.11.1809
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    Objective To evaluate the effectiveness and satisfaction of the experiential teaching method based on self-monitoring of blood glucose (SMBG) in endocrinological training module. Methods Forty-two eight-year medical students who were undergoing clinical clerkship rotation in the Department of Endocrinology, Peking University People's Hospital from April 2018 to December 2018 were enrolled in the study. They were randomly divided into the experimental group and the control group with twenty-one in each. The experimental group adopted SMBG-based experiential teaching and the control group was given traditional theoretical teaching. In-class tests were conducted to evaluate the teaching effect after class, and a satisfaction survey was taken out after internship. Results The score of in-class test from experimental group was 8.7±1.4, which was significantly higher than that from control group (7.2±2.3 )(P<0.01). The questionnaire survey showed that teaching satisfaction score from the students of experimental group was 141.2±0.6, which was higher than that of students from control group(129.8±0.7),(P<0.01). Conclusions In the endocrinological training module, the application of SMBG-based experiential teaching used in clinical training of endocrinology has achieved good teaching results and is well acknowledged by trainees of clerkship rotation.
    Medical Supervision
    Strengthening the management and supervision of leaders in medical research institutes based on the Organization Department
    WANG Dan-yang, XU Bao-yi
    2022, 42(11):  1813-1816.  doi:10.16352/j.issn.1001-6325.2022.11.1813
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    Objective To recommend strategies to strengthen management and supervision by leaders in research institute through investigating and understanding the current situation analyzing the challenges and barriers from the view angle of Organization Department. Methods A self-designed questionnaire was conducted to investigate the current situation, the challenges, the objects and methods, problems and strengthening strategy of management and supervision for team of leadership in the institute. The staff of research institutes engaged in the management and supervision of leading cadres were interviewed. Results There were 69.61% of the respondents considered that “scientific performance and fair assessment and evaluation of leader personel ” was the difficulty of management and supervision and 75.69% of the respondents considered that “strengthening the routine management and supervision of leading team members and implementing the supervision rules and regulations strictly” was the focus of management and supervision. The results also showed that 70.72% of the respondents considered that “superior supervision” was the most direct and effective supervision and 90.61% of the respondents considered that the “top leaders of the party and government” was the key objects of management and supervision. Conclusions Strengthening the management and supervision of leading team members of scientific research institutes will be implemented by establishing and perfecting the management and supervision system, strengthening the education and training of, clarifying the key management and supervision objects and innovative management / supervision methods.