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    Cell and Molecular Biology
    Expression and biological function of NNMT in stroma of lung adenocarcinoma #br#
    2021, 49 (2):  113-118.  doi: 10.11958/20200999
    Abstract ( 792 )   PDF (995KB) ( 4932 )  
    Objective To investigate the expression level of nicotinamide N-methyltransferase (NNMT) in the stroma
    of lung cancer, and the influence of overexpressed NNMT on the biological function of lung adenocarcinoma cells.
    Methods(1) Tissue specimens were collected from 150 patients with lung adenocarcinoma. Immunohistochemical staining
    was used to detect the NNMT expression level in cancer tissues and stromal cells, and the relationship between NNMT
    expression and the clinicopathological characteristics and prognosis of the patients were analyzed. (2) A lung fibroblast cell
    line HFL-1 with stable NNMT expression was constructed by the transfection of overexpressed NNMT plasmid (NNMT
    group) and control plasmid (control group) respectively. The expression levels of NNMT were detected by real-time
    fluorescence quantitative PCR (qPCR), immunofluorescence and Western blot assay. (3) The culture supernatant of the overexpressed NNMT and the control group of HFL-1 cells were collected and co-cultured with lung adenocarcinoma A549 and
    PC9 cells, respectively. Then, the effects of the two kind of culture supernatant on the proliferation, clonal formation and
    migration of A549 and PC9 cells were compared through cell proliferation experiment, plate clonal formation experiment,
    scratch healing experiment and Transwell migration experiment.
    Results(1) Immunohistochemical staining showed that
    NNMT was highly expressed in 65 cancer cell samples and 83 mesenchymal cell samples of 150 patients. The NNMT
    expression was higher in patients with lymph node metastasis and pathological stage Ⅲ-Ⅳ. The overall survival rate was
    significantly lower in patients with high expression of NNMT in tumor stroma than those with low expression of NNMT. (2)
    HFL-1 cells with stable overexpression of NNMT were successfully constructed. Western blot assay, qPCR and cell
    immunofluorescence staining indicated that the NNMT expression was higher in the NNMT group than that in the control
    group. (3) Cell co-culture results showed that compared with the control group, the culture medium of lung fibroblast cell
    line expressing NNMT could significantly promote the proliferation, clone formation and migration of A549 and PC9 cells.
    ConclusionNNMT is closely related to the malignant progression of lung adenocarcinoma, which may be a potential target
    for tumor-targeted biological therapy.


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    Effects of exosomes from high glucose-treated macrophage on the injury of glomerular podocytes via inhibiting autophagy #br# #br#
    RAO Chao-feng, XUE Xiao-nan, ZHU Ming-ying, LUO Fu-li
    2021, 49 (2):  119-125.  doi: 10.11958/20201991
    Abstract ( 810 )   PDF (1502KB) ( 4641 )  
    ObjectiveTo investigate the effect of high glucose (HG)-treated Raw264.7 macrophage derived exosomes
    (Exos) on the podocyte injury, and to explore whether its mechanism is related to the inhibition of autophagy.
    Methods
    The exosomes from high glucose-treated Raw264.7 cells (HG-Exos) and primary podocyte cells were incubated for 24 h, and
    the internalization of Exos in primary podocyte cells was detected. Primary podocytes were treated with different doses of
    Exos (0, 7, 14, 28, 56 and 112 mg/L) extracted by HG to investigate the effects of HG-Exos on podocyte survival and
    autophagy. The primary podocytes were divided into control group, HG-Exos group, chloroquine group, HG-Exos +
    chloroquine group, rapamycin group and HG-Exos + rapamycin group. The formation of autophagy was observed by
    transmission electron microscopy. The effects of HG-Exos on the proliferation of primary podocyte cells were evaluated by
    CCK-8 assay. The expressions of LC3B, Beclin 1 and Nephrin protein were detected by Western blot assay.
    Results
    Raw264.7 cells treated by the HG produced an increased number of Exos compared to Raw264.7 cells treated with normal
    glucose (
    P0.05). Confocal laser microscopy showed that PKH67-labeled Exos were localized to the perinuclear region of
    podocytes. CCK-8 assay showed that the podocyte viability reduced dose- and time-dependently after exposure to HGExos. Western blot assay showed that HG-Exos decreased the accumulation of Nephrin, Beclin 1 and the conversion of
    LC3- Ⅰ to LC3- Ⅱ in podocytes. Compared to 0 mg/L HG-Exos group, the autophagic double-membrane compartments
    containing lamellar structures in podocytes were significantly increased in the 7, 14 and 28 mg/L HG-Exos groups (
    P 0.05). The expressions of Nephrin, Beclin 1 and LC3B, and the number of autophagosomes were significantly higher in
    rapamycin group and HG-Exos group + rapamycin group than those of HG-Exos group, chloroquine group and HG-Exos +
    chloroquine group (
    P0.05). ConclusionHG-treated macrophage derived exosomes can decrease podocyte activity and
    increase podocyte damage, and its mechanism is related to the reduction of podocyte autophagy.

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    The effect of over-expression of miRNA-495 combined with temozolomide on proliferation and apoptosis of glioma cells #br#
    ZHANG Yuan-yuan, ZHU Shu-xia, ZHANG Yue-hua, ZHANG Yan-yan
    2021, 49 (2):  125-130.  doi: 10.11958/20201721
    Abstract ( 698 )   PDF (1044KB) ( 4975 )  
    Objective To explore the effect of over-expression of miRNA-495 combined with temozolomide (TMZ) on
    the proliferation and apoptosis in the glioma cells and the related mechanisms.
    Methods MiRNA-495 mimics and negative
    control sequences (miRNA-495 NC) were transfected into U251 cells and A172 cells by Lipofectamine
    TM 2000 in glioma.
    The relative expression levels of
    miRNA-495 and HMGN5 mRNA were detected by quantitative real-time PCR (qPCR). The
    protein expression levels of HMGN5 and MMP-9 were detected by Western blot assay. The effects of transfection on the
    proliferation of U251 and A172 cells were detected by CCK-8. After the action of miRNA-495 mimics and TMZ alone or in
    combination on U251 cells, the apoptosis rate and proliferation inhibition rate of U251 cells were detected by flow cytometry
    and CCK-8 assay.
    Results In the glioma U251 and A172 cells, the relative expression of miRNA-495 was increased in the
    miRNA-495 mimics group compared with that of the blank control group and the miRNA-495 NC group. The relative
    expressions of
    HMGN5 mRNA, HMGN5 and MMP-9 protein were decreased in the miRNA-495 mimics group compared with those of the blank control group and the miRNA-495 NC group. The ability of cell proliferation was significantly
    decreased (
    P0.05). Compared with the TMZ group and the miRNA-495-mimics group, the cell proliferation in U251 cells
    was significantly inhibited, and the apoptosis was significantly decreased in TMZ+miRNA-495 mimics group.
    Conclusion
    The over expression of miRNA-495 and in combination with TMZ can co-inhibit the proliferation and promote apoptosis of
    glioma cells, which may be related with the inhibition of HMGN5/MMP-9 signaling pathway.


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    Study on the mechanism of improving the activity of human retinal pigment epithelial cells by lutein through the SIRT1/NLRP3 signaling pathway #br#
    WAN Fang, MA Li-fang
    2021, 49 (2):  131-135.  doi: 10.11958/20202452
    Abstract ( 767 )   PDF (368KB) ( 5069 )  
    Objective  To investigate the improvement effect and mechanism of lutein on roxidative stress,
    inflammation and cell activity in human retinal pigment epithelial cells (ARPE-19 cells) induced by high concentration of
    glucose.
    Methods After treatment of ARPE-19 cells with different concentrations of lutein solution and high concentration
    of glucose, CCK-8 was used to detect changes in cell viability. Enzyme-linked immunosorbent assay was used to detect
    changes in inflammatory cytokine levels. The CM-H
    2DCFDA probe method was used to detect the changes in reactive
    oxygen species (ROS) levels. The changes in the expression levels of
    SIRT1 and NLRP3 were detected by real-time
    quantitative PCR.
    Results In the environment of high glucose, the expression levels of interleukin (IL)-1β, IL-6 and tumor
    necrosis factor (TNF)-α in ARPE-19 cells were significantly increased, ROS levels were significantly increased, and cell
    viability was significantly decreased than those of control group (
    P0.05). After treating ARPE-19 cells with lutein, the
    expression level of
    SIRT1 was significantly up-regulated (P0.05), and the expression level of NLRP3 mRNA was
    significantly down-regulated (
    P0.05). Conclusion Lutein can improve oxidative stress and inflammatory response in
    human retinal pigment epithelial cells through the SIRT1/NLRP3 signaling pathway, thereby increasing the cell viability.

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    Experimental Study
    Effects of selenium yeast combined with vitamin D on thyroid related hormones and antibodies in experimental autoimmune thyroiditis rats #br#
    HOU Li-ping, GENG Jian-lin, GU Wei, LIU Qing-qing
    2021, 49 (2):  136-141.  doi: 10.11958/20201366
    Abstract ( 1630 )   PDF (568KB) ( 3889 )  
    Objective To observe the effects of selenium yeast and vitamin D on related hormones and antibodies in
    experimental autoimmune thyroiditis (EAT) rats.
    Methods Of the 55 female SD rats, 45 were sensitized with porcine
    thyroglobulin (pTG) + drinking high iodine water to establish the EAT rat model. The successfully modeled rats (
    n=40) were
    randomly divided into the model group, the selenium yeast group, the vitamin D group and the combined group. There were
    10 rats for each group. The remaining 10 rats were used as the control group. Four weeks after boosting the immunity, the
    selenium yeast group was administered intragastrically selenium yeast solution + intraperitoneal injection of normal saline,
    vitamin D group was intragastrically administered normal saline + intraperitoneal injection of vitamin D
    3, the combined group
    was intragastrically administered selenium yeast solution + intraperitoneal injection of vitamin D
    3, and the control group and
    model group were intragastrically administered normal saline + intraperitoneal injection of normal saline. After 6 weeks, the
    serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroglobulin antibody (TGAb),
    thyroid peroxidase autoantibody (TPOAb), interferon-γ (IFN-γ), interleukin (IL)-4 and IFN-γ/IL-4 were compared between
    five groups. HE staining was used to compare the pathological changes of thyroid tissues in each group. The relative

    expression levels of p38MAPK, cyclooxygenase-2 (COX-2) mRNA and relative expression levels of p38MAPK, pp38MAPK, and COX-2 proteins in thyroid tissues were compared between five groups. Results The results of HE staining
    showed that the thyroid follicles had normal morphology in the control group. The thyroid follicle structure was damaged,
    lymphocyte infiltration and interstitial fibrosis in the model group. There was some improvement in selenium yeast group,
    vitamin D group and combined group than those of model group, and the improvement was the most obvious in the combined
    group. Compared with the model group, the serum levels of FT3, FT4, TSH, TGAb, TPOAb, IFN-γ, IFN-γ/IL-4, the relative
    expression levels of p38MAPK, COX-2 mRNA and the relative expression levels of p-p38MAPK, COX-2 proteins in thyroid
    tissues were significantly decreased in selenium yeast group, vitamin D group and combined group (
    P0.05), and the serum
    IL-4 level was increased in selenium yeast group, vitamin D group and combined group (
    P0.05). Compared with selenium
    yeast group and vitamin D group, the serum levels of FT3, FT4, TSH, TGAb, TPOAb, IFN-γ, IFN-γ/IL-4, and the relative
    expression levels of p38MAPK, COX-2 mRNA and the relative expression levels of p-p38MAPK, COX-2 proteins in thyroid
    tissues were significantly decreased, and the serum level of IL-4 increased in the combined group (
    P0.05). Conclusion
    Selenium yeast combined with vitamin D can effectively inhibit thyroid tissue damage and protect thyroid tissue in EAT rats,
    which may be related with the regulatory role by inhibiting the MAPK signaling pathway.

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    Study on the fertility improvement of obese mice by inhibiting granulosa cell inflammation using celastrol #br#
    SONG Dong-hong, MA Li-fang, YU Yang
    2021, 49 (2):  141-146.  doi: 10.11958/20202104
    Abstract ( 613 )   PDF (398KB) ( 4543 )  
    ObjectiveTo explore the effects of celastrol on increasing embryonic development potential and fertility in
    obese mice by improving the inflammatory state of granulosa cells. MethodsThe obese mouse model was established by
    high-fat diet. qPCR method was used to detect the levels of inflammatory genes, apoptosis genes and hormone synthesis
    genes in granulosa cells. The fertility was detected by mating experiment, and the improvement results were shown in the
    comparison between the high-fat diet and the normal diet groups. Obese mice in the high-fat diet group were fed celastrol.
    qPCR method was used to detect the expression of correlated genes in granulosa cells. The oocytes were fertilized by intracytoplasmic sperm injection method, and the embryonic development rate was calculated using the number of zygotes, 2-cell
    embryos and blastocysts. The birth rate and other indicators were indicated by embryo transfer methods.
    ResultsCompared
    with normal diet mice, the inflammatory genes
    Il-1β, Il-6 and apoptosis genes Bax, Bak1, Fadd, Traf2, Casp8 and Casp9
    mRNA were significantly increased in granulosa cells in addition to the increased body weight, whereas hormone synthesis
    genes
    Cyp11a1 and Cyp19a1 expression were significantly decreased in high-fat diet mice (P0.01). The embryonic
    developmental rate, pregnancy rate and birth rate of obese mice also decreased significantly (
    P0.01). Compared with mice
    in the high-fat diet group, the expressions of inflammation genes, apoptosis genes and hormone synthesis genes were
    significantly improved in granulosa cells of celastrol group (
    P0.01), and there were no significant differences when
    compared with the mice in the normal diet group (
    P0.01). The ovulation rate, embryonic development rate and birth rate
    were significantly better in celastrol group than those in high-fat diet group (
    P0.01). Conclusion Celastrol can reduce
    inflammatory gene expression in granulosa cells, relieve granulosa cell excessive apoptosis, restore granulosa cell hormone
    secretion function, and therefore improve the fertility of obese mice.

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    Study on the mechanism of Taohong Siwu Decoction in the treatment of postherpetic neuralgia in rats based on EphrinBs/EphBs pathway #br#
    XU Jun-tao, WANG Li, WANG Ying, MA Fei, FANG Yu-fu
    2021, 49 (2):  147-152.  doi: 10.11958/20201426
    Abstract ( 596 )   PDF (474KB) ( 4929 )  
     ObjectiveTo observe the effect of Taohong Siwu Decoction on postherpetic neuralgia (PHN) rats and to
    explore the role of EphrinBs/EphBs pathway in it.
    Methods A total of 60 SD rats were divided into blank group, model
    group (PHN model was established by chronic infection of varicella-zoster virus), positive group (27 mg·kg
    -1·d-1 of
    pregabalin was given by intragastric administration after modeling), treatment group (5 g·kg
    -1·d-1 of Taohong Siwu Decoction
    was given by intragastric administration after modeling), treatment + EphB2-Fc group (after intrathecal injection of 5 μg
    EphB2-Fc on the 3rd day of modeling, 5 g·kg
    -1·d-1 of Taohong Siwu Decoction was given by intragastric administration) and
    treatment + EphrinB2-Fc group (after intrathecal injection of 5 μg EphrinB2-Fc on the 3rd day of modeling, 5 g·kg
    -1·d-1 of
    Taohong Siwu Decoction was given by intragastric administration) using random number table. The mechanical pain
    threshold of rats was measured by behavioral method at the 1st, 7th and 14th days after administration. The levels of
    interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the spinal cord of rats were measured by enzyme-linked
    immunosorbent assay (ELISA). Terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used
    to detect apoptosis of spinal cord neurons. Fluorescence was used to detect the cysteinyl aspartate specific proteinase 3
    (Caspase-3) activity in spinal cord. Western blot assay was used to detect the expressions of EphrinB2 and EphB2 in
    EphrinBs/EphBs pathway.
    Results Compared with the blank group, the mechanical pain threshold was significantly lower
    in model group, while the levels of IL-1β, TNF- α, apoptosis index of spinal nerve cells, Caspase-3 activity and the
    expression levels of EphrinB2 and EphB2 proteins were significantly higher (
    P0.05). Compared with the model group, the
    mechanical pain threshold of the rats treated with Taohong Siwu Decoction was significantly higher on the 7th day and 14th
    day after administration (
    P0.05). However, the levels of IL-1β, TNF-α in the spinal cord, apoptosis index of spinal nerve
    cells, Caspase-3 activity and the expression levels of EphrinB2 and EphB2 proteins were significantly decreased (
    P0.05).
    The expression of EphB2 protein in the spinal cord of rats treated with EphBs blocker EphB2-Fc was significantly lower than
    that of the treatment group (
    P0.05). After treatment with EphBs agonist EphrinB2-Fc, the expression level of EphrinB2
    protein in the spinal cord of rats was significantly lower than that of the treatment group, while the expression level of EphB2
    protein was significantly higher than that of the treatment group (
    P0.05). ConclusionTaohong Siwu Decoction may
    reduce the release of inflammatory factors and the apoptosis of spinal nerve cells by inhibiting EphrinBs/EphBs pathway, and
    play an analgesic role in PHN rats.


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    The protective effect of ginkgo diterpene lactone meglumine on cerebral ischemia-reperfusion #br#
    PENG Jin-liang, XIONG Li-jiao, LIU Xiang-hong
    2021, 49 (2):  153-158.  doi: 10.11958/20200810
    Abstract ( 989 )   PDF (987KB) ( 4921 )  
    ObjectiveTo investigate the protective effect and possible mechanism of ginkgo diterpene lactone
    meglumine (GDLM) on cerebral ischemia-reperfusion (I-R) injury and oxyglucose deprived (OGD) hippocampal neurons.
    Methods In vivo experiments: 30 SD rats were divided into sham operation group (Sham), I-R group and GDLM group by
    random number table method. GDLM group was injected with GDLM 10 mg/kg by tail vein after I-R modeling, and Sham
    and I-R groups were given equal dose of normal saline. The brain tissue was stained with TTC. Hippocampus tissues were
    stained by Nissl and TUNEL, and Bradford method was used to quantitatively detect the changes in MDA content, gSH-PX
    and SOD activity of hippocampus oxidative stress indexes in 3 groups.
    In vitro experiments: primary fetal hippocampal
    neurons were cultured and divided into control group (Con), OGD/reoxygenation (R) model group and GDLM group. OGD/R
    and GDLM groups were treated with oxyglucose deprivation and reoxygenation, while the control group was not treated. The
    survival rate of neurons was calculated by MTT assay, apoptosis rate of neurons was measured by TUNEL and Annexin VFITC/PI flow cytometry, and PI3K, pAKt, mTOR protein expression levels were measured by Western blot assay.
    Results
    In vivo experiment: compared with Sham group and I-R group, cerebral infarction volume and apoptosis rate of hippocampal
    neurons were significantly reduced in GDLM group, and morphological improvement was significant. MDA expression level
    was significantly decreased in GDLM group, while SOD and GSH-PX activities were significantly increased (
    P0.01). In
    vitro experiment: compared with OGD/R group, the cell survival rate was increased and apoptosis rate was decreased in
    GDLM group, and the expressions of PI3K, pAKt and mTOR were significantly increased (
    P0.01). ConclusionGDLM can inhibit the neuron apoptosis of cerebral ischemia-reperfusion and oxygen-deprived reoxygenated hippocampal
    neurons, and has a neuroprotective effect, which may be related to its regulation of PI3K/AKt/mTOR signaling pathway and
    oxidative stress.


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    Clinical Study
    The predictive value of preoperative systemic immune-inflammation index for tumor recurrence in patients with non-muscular invasive bladder cancer #br#
    CAO Zhi-wen, SONG Dong-kui△, WEI Xiao-song, JIN Bing-zhai, MA Qi-yue
    2021, 49 (2):  159-164.  doi: 10.11958/20201927
    Abstract ( 734 )   PDF (561KB) ( 4936 )  
    ObjectiveTo investigate the predictive value of preoperative systemic immune-inflammatory index (SII)
    for tumor recurrence in non-invasive bladder cancer (NMIBC) patients who underwent transurethral resection of bladder
    tumor (TURBT).
    MethodsThe clinical data of 201 patients newly diagnosed with NMIBC were retrospectively analyzed.
    Clinical data such as laboratory examination and pathological results were collected. Neutrophil-to-lymphocyte ratio (NLR),
    platelet-to-lymphocyte ratio (PLR) and SII were calculated based on the blood routine results one week before surgery. The
    receiver operating characteristic (ROC) curves were used to compare the accuracy of the three indicators in predicting tumor
    recurrence in NMIBC patients. According to the optimal cut-off value of SII, the patients were divided into high SII and low
    SII groups, and the differences in the clinical characteristics of the patients were compared between the two groups. Patients
    were followed up after surgery. The recurrence curves of patients in high SII and low SII groups were plotted using the
    Kaplan-Meier method. Multivariate Cox regression model was used to analyze the independent risk factors affecting tumor
    recurrence in NMIBC patients, and then these factors were included and a nomogram was constructed to predict the 1-year,
    2-year and 3-year recurrence-free survival rate of NMIBC patients. The prediction accuracy and consistency of nomogram
    were determined by the concordance index (C-index) and the calibration curve.
    ResultsThe areas under the curve (AUC)
    of NLR, PLR and SII for predicting tumor recurrence in patients with NMIBC were 0.664, 0.656, and 0.729, respectively.
    There was higher accuracy of SII in predicting tumor recurrence in NMIBC patients than that of NLR and PLR (
    Z=2.398,
    2.454, respectively, both
    P<0.05). The optimal cut-off value of SII was 385, and 201 patients were divided into low SII group
    (SII<385,
    n=130 ) and high SII group (SII≥385, n=71). Compared with the low SII group, the proportion of tumor volume 3
    cm, the proportion of pathological T1 stage and tumor recurrence rate were higher in high SII group (all
    P0.05). The
    median follow-up time of all patients was 62 (33-84) months after surgery, and 45 patients (22.4%) recurred during the
    follow-up period. Multivariate Cox regression analysis showed that high SII (
    HR=2.829, 95%CI: 1.416-5.654), tumor T1
    stage (
    HR=3.091, 95%CI: 1.660-5.757), tumor size >3 cm (HR=2.339, 95%CI: 1.152-4.751) and multiple tumors (HR=
    2.083, 95%
    CI: 1.033-4.202) were independent risk factors for postoperative tumor recurrence (all P0.05). The C-index for
    internal verification of nomogram was 0.768 (95%
    CI: 0.699-0.837). The calibration curves indicated good agreement
    between the nomogram predictions and the actual observations.
    ConclusionPreoperative SII can be used as an indicator to
    predict tumor recurrence in patients with NMIBC. The prediction accuracy of SII is higher than that of NLR and PLR. The
    nomogram according to independent risk factors has high predictive value.


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    Analysis of risk factors of sepsis-induced acute kidney injury progressing to chronic kidney disease #br#
    CHEN De-zhu, ZENG Fan-kun, ZHONG Jian, ZHANG Li
    2021, 49 (2):  165-168.  doi: 10.11958/20202395
    Abstract ( 791 )   PDF (343KB) ( 5139 )  
    Objective To investigate the risk factors of sepsis-induced acute kidney injury (AKI) progressing to
    chronic kidney disease (CKD) in critically ill patients.
    MethodsA total of 134 sepsis patients from intensive care unit of
    Shunde Hospital of Guangzhou University of Chinese Medicine were enrolled. According to the 3-month follow-up of renal
    function after discharge, the patients were divided into progression to CKD group (CKD,
    n=40) and non-progression to CKD
    group (non-CKD,
    n =94). The clinical characteristics of patients with sepsis-induced AKI and the risk factors of progressing
    to CKD were analyzed. The working characteristic curve (ROC) of subjects was used to evaluate the predictive values of risk
    factor for sepsis-induced AKI progressing to CKD.
    ResultsThere were 40 patients (29.9% of 134 patients) with sepsisinduced AKI progressed into CKD. Compared with non-CKD group, there were a higher SOFA score, blood creatinine,
    lactate and higher proportion of mechanical ventilation, renal replacement therapy, AKI ≥ 2 grade, and lower level of eGFR
    and serum albumin in CKD group. The high serum levels of creatinine and lactic acid, AKI ≥ 2 and hypoalbuminemia were
    independent risk factors for progression of sepsis-induced AKI to CKD. ROC curve showed that the increased serum
    creatinine (≥158.7 μmol/L) was important index with higher specificity and sensitivity for predicting the progression of
    sepsis-induced AKI to CKD (AUC was 0.875,
    P0.001). ConclusionClose monitoring the related risk factorssuch as
    serum creatinine, lactate, albumin levels and AKI grading
    is conducive to improve the renal prognosis of patients with
    septic AKI in ICU.

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    The analysis of the expression and significance of Elafin in lung cancer based on data mining #br#
    PENG Xu-hong, JIANG Jing, QU Jia-yao, LI Xiang-ning, WANG Li, LI Jia, DUAN Li-li
    2021, 49 (2):  169-174.  doi: 10.11958/20201729
    Abstract ( 700 )   PDF (1126KB) ( 4447 )  
    ObjectiveTo investigate the expression and significance of Elafin in lung cancer by database through
    database data.
    MethodsElafin gene expression in lung cancer was analyzed by Oncomine database and verified by realtime fluorescence quantitative PCR (qPCR) in lung cancer tissues. Kaplan-Meier database was used to analyze the
    relationship between Elafin expression and the prognosis of lung cancer patients. The correlated genes of Ealfin were
    obtained from Linkedomics database. GO and KEGG analysis and protein-protein interaction network were analyzed by
    GSEA tools and string databases, respectively.
    Results Compared with normal tissue, the mRNA level of Elafin was
    significantly higher in lung cancer. Survival analysis showed that disease-free survival and overall survival were significantly
    decreased in patients with high expression of Elafin. Linkedomics database showed that there were 7 697 correlated genes in
    Elafin. GO and KEGG analysis showed that Elafin and correlated genes may related to humoral immune response,
    granulocyte activation, IL-17 pathway and NF-κB pathway. The Elafin protein PPI network showed that Elafin may interact
    with LOR, CSTA and FLG.
    Conclusion The high expressed Elafin in lung cancer tissues is associated with the prognosis of
    lung cancer patients, which may be used as a potential target for diagnosis and treatment of lung cancer.

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    Clinical significance of oxygen therapy in primary spontaneous pneumothorax #br#
    GU Song-tao, LI Yue-chuan, JIA Wei, ZHANG Dong-rui, MA Hui, ZHANG Yong-xiang, JIAO Li-na, ZHANG Ya-ting
    2021, 49 (2):  175-178.  doi: 10.11958/20203566
    Abstract ( 681 )   PDF (338KB) ( 3620 )  
    Objective To study the changes of oxygen partial pressurep(O2)and carbon dioxide partial pressure
    p(CO2)of the pleural cavity gas before and after oxygen therapy in patients with primary spontaneous pneumothorax (PSP).
    Methods One hundred and twenty hospitalized PSP patients were divided into two groups: closed pneumothorax group (n=
    57) and open pneumothorax group (
    n=51) according to the p(O2) and p(CO2) of the arterial blood gas, expiratory gas and
    pleural cavity gas. The two groups were given high concentration oxygen mask for 6 hours, and then the blood gas, expiratory
    gas and pleural cavity gas were measured again. The levels of
    p(O2) and p(CO2) of the arterial blood, expiratory gas and
    thoracic oxygen partial pressure before and after oxygen therapy were compared and analyzed.
    Results There were no
    significant differences in values of
    p(O2) and p(CO2) in arterial blood gas before and after oxygen therapy between the two
    groups (
    P0.05). There were no significant differences in values of Δp(O2) in arterial blood gas after oxygen therapy between
    the two groups (
    P0.05). There were no significant differences in values of p(O2) and p(CO2) in expiratory gas before and
    after oxygen therapy between the two groups (
    P0.05). The level of p(O2) of pleural cavity gas was lower after oxygen therapy
    than that before oxygen therapy in patients with closed pneumothorax (
    P0.05). The level of p(O2) of pleural cavity gas was
    higher after oxygen therapy than that before oxygen therapy in patients with open pneumothorax (
    P0.05). There were no
    significant differences in values of
    p(CO2) of pleural cavity gas before and after oxygen therapy between the two groups (P
    0.05). Conclusion The high concentration oxygen therapy is beneficial to the absorption of pleural cavity gas and
    recruitment of lung in patients with close pneumothorax, but the effect on open pneumothorax is not obvious.

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    The predictive effect of inferior vena cava collapsibility index on postspinal anesthesia hypotension in elderly patients #br#
    ZHANG Yu, FAN Shi-wen, YIN Jiang-wen, ZHAI Jing-wen, GE Ming-yue, QIN Xin-lei, DAI Zhi-gang
    2021, 49 (2):  179-184.  doi: 10.11958/20202638
    Abstract ( 750 )   PDF (511KB) ( 4439 )  
    Objective To investigate the predictive effect of ultrasound measurement of inferior vena cava
    collapsibility index (IVC-CI) on postspinal anesthesia hypotension (PSAH) in elderly patients and whether preoperative
    hypertension affects IVC-CI predictive value of PSAH.
    MethodsA total of 163 elderly patients undergoing elective
    surgery under spinal anesthesia (SA) were enrolled in this study. According to the preoperative diagnosis of hypertension,
    patients were divided into patients with hypertension group (H group) and patients without hypertension group (N group).
    Then according to the occurrence of PSAH during 30 min after SA, the two group were subdivided into hypotension group (D
    group) and non-hypotension group (F group). The maximum inferior vena cava diameters (dIVC
    max) and IVC-CI were
    measured before and after SA. The systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were
    recorded before SA and 30 min after SA.
    Results There were 49 patients (30.1%) had hypotension after SA. The baseline
    values of age, body mass index (BMI), waist circumference, incidence of PSAH, SBP, MAP and HR were significantly higher
    in group H than those in group N (
    P0.05). Before SA and after SA, dIVCmax was significantly smaller in group D than that of
    group F (
    P0.05). Before SA and after SA, IVC-CI was significantly greater in group D than that of group F (P0.01).
    Before SA and 30 min after SA, IVC-CI was negatively correlated with the lowest SBP and MAP in N group (
    P0.01). In H
    group, before SA and 30 min after SA, IVC-CI was negatively correlated with the lowest SBP and MAP (
    P0.01). Before
    and after SA, the area under ROC curve (AUC) of PSAH predicted by IVC-CI was significantly larger than that of dIVC
    max
    (P0.01). ConclusionBefore and after spinal anaethesia, IVC-CI can predict the occurrence of PSAH of the elderly
    patients with hypertension, and which can be used as a noninvasive method for predicting PSAH in the elderly patients.

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    Clinical Study
    Cystic lung disease in primary Sjögrens syndrome: imaging characteristics and associated risk factors #br#
    LI De-fu, ZHU Ting-ting, PANG Ying
    2021, 49 (2):  185-190.  doi: 10.11958/20202360
    Abstract ( 566 )   PDF (536KB) ( 4090 )  
    Objective To explore the imaging characteristics and associated risk factors of cystic lung disease (CLD) in
    primary Sjögren's syndrome (pSS) and to provide reference for its treatment and prognosis.
    MethodsThe clinical and
    imagine data of 181 patients with pSS in our hospital were retrospectively analyzed. According to the presence or absence of
    pulmonary cystic lesions on chest CT, the patients were divided into two groups: the group with cystic lesions (51 cases) and
    the group without cystic lesions (130 cases). The characteristics of chest CT of CLD related to pSS were analyzed. The
    differences of clinical symptoms, physical signs and laboratory examinations were compared between the two groups by casecontrol univariate analysis. The important clinical variables and univariate
    P value ≤ 0.1 variables were included in the
    multivariate Logistic regression analysis of possible risk factors.
    Results Compared with the non-cystic lesion group, there
    were longer course of disease and a higher proportion of dyspnea and dry mouth symptoms in cystic lesion group (
    P0.05).
    IgG, IgA, IgM, RF values, anti-SSB antibody, anti-Ro52 antibody positive ratio were higher in cystic lesion group than those
    of the non-cystic lesion group (
    P0.05). The pulmonary cystic lesions were mainly round, randomly distributed and of
    different sizes, with septum, blood vessels passing through or wrapping around, which could be combined with ground glass
    opacity, nodular and bronchial wall thickening, rarely increased in follow-up. Multiple Logistic regression analysis revealed
    that the positive anti SSB antibody was an independent risk factor of pSS related CLD (
    P0.05). Conclusion The main
    characteristics of pSS related CLD are random distribution, intrathecal separation, vascular penetration or vascular wrapping.
    Patients with pSS positive for anti-SSB antibodies have a higher risk of developing CLD.

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    Comparison of clinical effects of pedicled flap combined with connective tissue transplantation and flap flap operation in the treatment of lip face gingival tumor #br#
    ZHANG Jian-quan, GAO Li-rong, WANG Yi-jun, DING Chun-yan, NIE Ting-hong, CHEN Chuan-hong
    2021, 49 (2):  190-194.  doi: 10.11958/20201816
    Abstract ( 581 )   PDF (443KB) ( 3836 )  
    Objective To analyze retrospectively the clinical effects of pedicled flap combined with connective tissue
    transplantation and flap surgery in the treatment of soft tissue defects in the surgical area after resection of gingival tumor on
    the lib and buccal side.
    MethodsThe clinical data of 80 patients with lib and buccal gingival tumor who were hospitalized
    in stomatology department of Tianjin Baodi Hospital from January 2017 to February 2019 were analyzed retrospectively.
    According to the different operation methods, 38 patients who underwent flap operation to correct the soft tissue defects in
    the operation area were included in the control group, 42 patients who underwent pedicled flap combined with connective
    tissue transplantation to correct the soft tissue defects in the operation area were included in the observation group. The
    sulcus bleeding index (SBI), gingival index (GI) and periodontal probing depth (PD) were recorded before operation, 3 months
    and 6 months after the operation in the 2 groups. The keratinized gingival width (KGW) and root coverage (RC) were
    compared immediately, 3 months and 6 months after the operation between the 2 groups.
    Results The levels of SBI, GI and
    PD were significantly decreased 3-month and 6-month after operation in the 2 groups, and those were significantly lower in
    observation group than those in the control group (P0.05). KGW was significantly higher immediately after operation in the
    control group than that in the observation group (
    P0.05), but it was significantly lower at 3 months and 6 months after
    operation in the control group than that in the observation group (
    P0.05). The RC values were significantly higher
    immediately after operation and 3 months and 6 months after operation in the observation group than those in the control
    group (
    P0.05). The excellent and good rates of aesthetic effect and patient satisfaction 6 months after operation were
    97.6% and 97.6% in the observation group, which were significantly higher than 84.2% and 78.9% in the control group (
    P
    0.05). ConclusionFor patients with gingival tumors that only affect the lip and buccal side, the effect of pedicled flap
    combined with connective tissue transplantation to correct soft tissue defects in the operation area is satisfactory. Compared
    with the use of flap surgery to correct soft tissue defects in the operation area, the aesthetic effect is better, and the patient's
    surgical satisfaction is higher.


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    Applied Essay
    Ultrasonographic radiomics in differential diagnosis of breast carcinoma with medullary features and breast fibroadenoma #br#
    ZHANG Yu, LIU Liang-sheng, MA Wen-juan, LU Hong, LIU Pei-fang, ZHU Ying
    2021, 49 (2):  195-198.  doi: 10.11958/20202405
    Abstract ( 792 )   PDF (528KB) ( 4763 )  
    Objective To compare the ultrasonographic radiomics features of breast carcinoma with medullary features
    (CMF) and breast fibroadenoma (FA), and to comfirm the quantitative parameters of differential diagnosis so as to provide the
    imaging basis for clinical diagnosis and treatment.
    Methods Data of ultrasonographic images containing 43 CMF lesions
    and 129 FA lesions (control group) confirmed by pathology from January 2015 to December 2019 were retrospectively
    analyzed. Radiomics features were evaluated and compared between the two groups. The area under the curve, cut-off value,
    accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated.
    Results The
    aspect ratio (0.623
    vs. 0.495) and concavity rate (0.107 vs. 0.047) were higher in CMF group than those of FA group. The gray
    mean value (35.651
    vs. 49.990), correlation (0.903 vs. 0.935) and homogeneity (0.780 vs. 0.811) were lower in CMF group
    than those of FA group (
    P0.01). The AUC and accuracy of aspect ratio, concavity rate and correlation were relatively
    higher, which can reach to 0.70. The sensitivity of aspect ratio, concavity rate, gray mean value, correlation and homogeneity
    were higher, and which can be up to 0.80, but the specificity was lower.
    ConclusionThe aspect ratio, concavity rate, gray
    mean value, correlation and homogeneity of ultrasonographic radiomics features provide evidence for the differential
    diagnosis of breast carcinoma with medullary features and breast fibroadenoma, and which has certain clinical significance.

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    The predictive value of CT island sign, black hole sign and their combined signs for the hematoma enlargement in patients with early stage of primary intracerebral hemorrhage #br#
    WANG Dan-dan, WANG Xue-jian, PAN Nan-nan
    2021, 49 (2):  199-202.  doi: 10.11958/20200831
    Abstract ( 684 )   PDF (412KB) ( 4204 )  
    Objective To explore the value of CT island sign, black hole sign and their combined signs in predicting
    early hematoma enlargement (HE) in patients with primary intracerebral hemorrhage.
    Methods A total of 328 patients with
    primary intracerebral hemorrhage were retrospectively collected. They were divided into HE group (100 cases) and non-HE
    group (228 cases) according to the presence of the early HE. The related clinical data and imaging characteristics (island
    sign, black hole sign, and island sign/black hole sign) were collected, and the above factors were compared between the two
    groups. The Logistic regression analysis was used for the significant factors in the two groups. The consistency of
    interpretation of imaging signs was analyzed by
    Kappa consistency. The clinical values of the three signs in predicting the
    early HE compared.
    Results The proportion values of admission systolic blood pressure, initial hematoma volume, history
    of hypertension, island sign, black hole sign, and island sign/black hole sign were higher in the HE group than those in the
    non-HE group (
    P0.05). The admission GCS score was lower in the HE group than that in the non-HE group (P0.05).
    Logistic regression analysis showed that the lower admission GCS, island sign, black hole sign, and island sign/black hole
    sign were all independent risk factors for the early HE (
    P0.05). The two doctors had high consistency in the interpretation
    of the island sign, black hole sign and island sign/black hole sign. The Kappa values were 0.858, 0.881 and 0.896,
    respectively. The sensitivity values of the island sign, black hole sign and island sign/black hole sign for the predicting early
    HE were 32.0%, 93.0%, 29.0%, and specificity were 93.9%, 49.0%, 88.2%. The Youden index values were 0.250, 0.229 and
    0.372 respectively; the Youden index of the island sign/black hole sign was larger than that of the island sign and black hole
    sign.
    Conclusion Compared with the single sign, the island sign combined with the black hole sign shows a better
    predictive ability for the early HE in primary intracerebral hemorrhage patients.

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    Drug Clinical Evaluations
    The influence of shenling baizhu powder and metformin on miR-146a, GLP-1 and blood lipid in type 2 diabetes mellitus obesity #br#
    PENG Jun-hua, GE Suo-hua, ZHANG Huan-yan, YU Xue-bing, SUN Lu-yang
    2021, 49 (2):  203-207.  doi: 10.11958/20200931
    Abstract ( 1849 )   PDF (406KB) ( 3903 )  
    ObjectiveTo study the influence of shenling baizhu powder and metformin on the miR-146a, glucagon like
    peptide-1(GLP-1), interleukin-12 (IL-12) and serum total cholesterol (TC), triglyceride(TG) and low density lipoprotein
    cholesterol (LDL-C) in type 2 diabetic mellitus (T2DM) obesity.
    MethodsA total of 86 patients with T2DM obesity were divided
    into experimental group (patients treated with shenling baizhu powder and metformin) and control group (patients treated with
    metformin) by randomly method. The treatment lasted for 6 months. The venous blood samples of patients were collected on the
    day before treatment, 1 week, 3 months and 6 months after treatment. miR-146a was detected by qPCR, and the level of blood
    lipid was detected by biochemical colorimetry, the serum levels of GLP-1 and IL-12 were detected by enzyme linked
    immunosorbent assay (ELISA).
    ResultsCompared with the control group, the levels of miR-146a and GLP-1 were increased,
    serum IL-12 was decreased three months after treatment in experimental group, while the serum levels of TC and TG were also
    decreased six months after treatment (
    P0.05). With the prolongation of treatment time, the serum levels of miR-146a and GLP-
    1 showed an increasing trend in experimental group and control group (
    P0.05), while the level of IL-12 showed a decreasing
    trend in experimental group and control group (
    P0.05). The serum levels of TC, TG, LDL-C and body mass index (BMI) were
    started decreasing 3 months after treatment in experimental group (
    P0.05). The expression level of miR-146a was positively
    correlated with serum GLP-1 levels in T2DM (
    r=0.874, P0.01), and negatively correlated with IL-12, TC, TG and LDL-C levels
    (
    r= -0.744, -0.456, -0.397 and -0.629, P0.01). The serum level of GLP-1 was negatively correlated with IL-12, TC, TG and
    LDL-C levels (
    r = -0.807, -0.482, -0.452 and -0.693, P0.01). Conclusion The shenling baizhu powder combined with metformin can effectively improve serum levels of TG and TC in T2DM obesity. The mechanism may be related with increasing
    the levels of miR-146a and GLP-1, decreasing the inflammatory factors and IL-12 level.


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    Effects of dexmedetomidine with oral transmucosal on emergence agitation in children with general anesthesia #br#
    YUAN Zhi-hao, HAN Jian-ge, WANG Xin-yue
    2021, 49 (2):  207-211.  doi: 10.11958/20200346
    Abstract ( 741 )   PDF (395KB) ( 4315 )  
    ObjectiveTo investigate the efficacy of premedication with oral transmucosal buccal dexmedetomidine
    (DEX) on the incidence of emergence agitation in children undergoing tonsillectomy under sevoflurane anesthesia.
    MethodsA total of 90 children who were scheduled for tonsillectomy under general anesthesia were randomly divided into
    three groups: DEX-Ⅰ group, DEX-Ⅱ group and control group, with 30 patients in each group. The DEX-Ⅰ group and the
    DEX- Ⅱ group were given dexmedetomidine 1 μg/kg and 2 μg/kg via buccal mucosa at 30 minutes before surgery,
    respectively. The control group was given normal saline in the same manner at the same time point. Preoperative sedation
    score, intraoperative mean arterial pressure (MAP), heart rate (HR) and oxygen saturation, extubating time, Watcha
    s
    agitation scale at 5 min, 10 min, 15 min, 30 min, 45 min and 60 min after admission to post anesthesia care unit (PACU),
    modified OPS pain score at the same time point and occurrence of perioperative adverse events were recorded. Postoperative
    agitation was considered when Watcha
    s agitation score was ≥3. ResultsThere were no significant differences in
    demographics, preoperative sedation score, duration of operation and extubating time between the 3 groups. The Watcha
    s
    agitation scores at the four time points of 5, 10, 15 and 60 min after entering PACU were lower in DEX-Ⅰ and DEX-Ⅱ
    groups than those of the control group. There were no significant differences in the four time point scores between DEX-Ⅰ
    group and DEX-Ⅱ group. The modified OPS pain scores at the four time points of 5, 10, 15 and 30 min after entering PACU
    were lower in DEX-Ⅰ and DEX-Ⅱ groups than those of control group. There were no significant differences in the four time
    point scores between the two DEX groups. Compared with the control group, the HR and MAP were significantly lower in
    DEX groups, but within the normal clinical range. No adverse events were observed during perioperative period in all three
    groups.
    ConclusionPreoperative administration of dexmedetomidine 1-2 μg/kg via the buccal mucosa can effectively
    reduce the incidence of postoperative agitation in children with general anesthesia.

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    Evidience-Based Medicine
    Association between MTHFR gene polymorphism and susceptibility to autism spectrum disorders: a meta-analysis
    ZHANG Yu-xin, GAI Cong, YANG Lu-ping, MA Hao-jie, ZHANG Jin-kun, SUN Hong-mei, HU Die
    2021, 49 (2):  212-218.  doi: 10.11958/20202256
    Abstract ( 592 )   PDF (708KB) ( 3933 )  
    ObjectiveTo investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene
    polymorphism and susceptibility to autism spectrum disorders (ASD).
    MethodsThe relevant studies on MTHFR gene
    C677T polymorphism and susceptibility to ASD databases until June 30, 2020 were searched in databases of CNKI, Wanfang
    data, PubMed, Embase, Proquest and Web. Meta-analysis was conducted by using STATA 14.0.
    ResultsA total of 16
    articles were included, including 2 149 cases in the case group and 2 251 cases in the control group. Meta-analysis showed
    that
    MTHFR C677T polymorphism was significantly associated with an increased risk of autism in the allelic model (T vs. C,
    OR=1.51, 95%CI: 1.15-1.99P=0.003) and dominant genetic model (TT+CT vs. CC, OR=1.67, 95%CI: 1.21-2.29, P=
    0.002). Analysis of ethnic subgroups showed that the
    MTHFR C677T polymorphism of Caucasians was closely related to the
    occurrence of autism only in the dominant genetic genotype (
    OR=1.30, 95%CI: 1.04-1.63P=0.024), while the Asians were
    related in both the allelic model (
    OR=1.85, 95%CI: 1.13-3.01, P=0.014) and the dominant genetic model (OR=1.9995%CI:
    1.18-3.36P=0.010). Conclusion
    susceptibility to ASD.
    The MTHFR C677T gene polymorphism is significantly associated with the
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    Review
    Vascular normalization and immunotherapy in hepatocellular carcinoma #br#
    YU Xian-zhe, ZHU Ling-ling, LI Jian-guo
    2021, 49 (2):  219-224.  doi: 10.11958/20202079
    Abstract ( 649 )   PDF (453KB) ( 4919 )  
    Hepatocellular carcinoma (HCC) is one of the most common malignancies. Most patients are diagnosed late
    and lose the opportunity for surgery at the late stage. At this time, medication becomes an important treatment, including
    chemotherapy, targeting, immunity, traditional Chinese medicine and endocrine therapy. Immunotherapy is a new way of
    cancer treatment, but the abnormal tumor angiogenesis forms an immunosuppressive tumor microenvironment, which limits
    the development of immunotherapy. Antiangiogenic therapy has become a new strategy to improve immunotherapy by
    inhibiting tumor vascular growth and repairing abnormal tumor vascular system. This article reviews the relationship between
    blood vessel normalization and immunotherapy in HCC and the combination of them.

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