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    Cell and Molecular Biology
    Transcriptome sequencing and analysis of the inhibited STYK1/NOK gene in BHK21 cells #br#
    GAO Jing-ya, ZHANG Li, XIE Yan, GUO Qing-jun, TIAN Da-zhi, LI Jun-jie, JIANG Wen-tao, LIU Li
    2020, 48 (4):  241-247.  doi: 10.11958/20193827
    Abstract ( 499 )   PDF (1212KB) ( 3635 )  
    Objective To analyze the gene expression of hamster kidney normal BHK21 cells after inhibiting serine
    threonine tyrosine kinase 1 (STYK1/NOK) by transcriptome analysis, and analyze its possible signaling pathways.
    Methods
    BHK21 cells were divided into empty vector group (transfected with 6 µg empty vector pBs/U6), low concentration
    transfection group (2 µg si-STYK1/NOK plasmid + 4 µg empty vector pBs/U6) and high concentration transfection group ( 6 µg si-STYK1/NOK plasmid). Western blot assay was used to detect STYK1 / NOK protein expression in 48 hours after
    transfection. Based on the detection results, the empty RNA group and high transfection concentration group were selected to extract total RNA for the transcriptome sequencing. The sequences obtained by sequencing were filtered and compared to obtain differentially expressed genes. After obtaining the differentially expressed genes, R software was used to analyze the
    biological functions of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The interactions in the STRING protein interaction database were used to analyze the differential gene-protein interaction networks. QRT-PCR was used to verify the key differentially expressed genes methylenetetrahydrofolate dehydrogenase 2 (Mthfd2), activating
    transcription factor 5 (
    Atf5), phospholipase A2 group Ⅱ A (Pla2g2a) and 6-phosphofructo-2-kinase/fructose-2, 6-
    biphosphatase 3 (
    Pfkfb3). CCK-8 method was used to detect cell proliferation in empty vector group and high transfection
    concentration group.
    Results Western blot results showed that the expression of STYK1/NOK protein was significantly
    inhibited in the high-concentration transfection group. Analysis of the transcriptome sequencing results revealed a total of 44
    differentially expressed genes, including 19 up-regulated genes and 25 down-regulated genes in the empty vector group and the high-concentration transfection group. GO enrichment analysis found that the differentially expressed genes mainly
    affected biological regulation, cellular processes, metabolic regulation, cellular biological processes, cells, cellular parts,
    extracellular regions, ligands and catalytic activity. KEGG pathway analysis found that the differentially expressed genes
    were mainly concentrated in the immune system, cancer, cell cycle, signal transduction and amino acid metabolism. The
    qRT-PCR results showed that the relative expression levels of
    Mthfd2 and Atf5 were significantly increased in the high
    concentration transfection group (
    P0.05), and the relative expression levels of Pfkfb3 and Pla2g2a were significantly
    decreased (
    P0.05), which was consistent with the sequencing results. Cell proliferation experiments showed that the cell
    proliferation was significantly higher in the high-concentration transfection group than that in the empty vector group (
    P
    0.01). Conclusion The inhibition of STYK1 / NOK expression can result in the enhanced expression of proto-oncogenes,
    the promoted expression of tumor suppressor genes and the decreased cell proliferation in BHK21 cells.


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    The role of high mobility group protein 1 in aldosterone-induced autophagy of renal tubular epithelial cells #br#
    MAO Nan, LIN Ding-biao, MA Xin, CHEN Hong-xi, ZHOU Wan-qiu, WANG Shao-qing
    2020, 48 (4):  248-252.  doi: 10.11958/20191827
    Abstract ( 602 )   PDF (557KB) ( 4145 )  
    Objective To investigate the role of high mobility group protein 1 (HMGB1) in aldosterone (ALDO) -
    induced autophagy of rat renal tubular epithelial cells.
    Methods Rat renal tubular epithelial cells (NRK-52E) in
    logarithmic growth phase were divided into control group, ALDO group (10 nmol/L), HMGB1 antibody group (1 mg/L), IgG
    group (1 mg/L), ALDO + HMGB1 antibody group (1 mg/L HMGB1 antibody pretreatment for 1 h, then 10 nmol/L ALDO
    stimulation for 24 h) and positive control group (Rosup, 100 µmol/L). After 24 h treatment, the changes of reactive oxygen
    species (ROS) levels in NRK-52E cells were detected by flow cytometry after labeling with fluorescent probe DCFH-DA. In
    addition, the cultured NRK-52E cells were divided into control group, ALDO group (10 nmol/L), N-acetylcysteine group
    (NAC, 50 µmol/L) and NAC+ALDO group (50 µmol/L NAC pretreatment for 1 hour, followed by 10 nmol/L ALDO). The
    expression of IL-1β protein was detected by Western blot assay 24 hours after treatment. The expression of HMGB1 protein was observed 24 hours after 10 nmol/L ALDO stimulation.Finally, the expressions of LC3-Ⅱ, Beclin-1 and p62 proteins were detected by Western blot assay after pretreatment with 1 mg/L HMGB1 antibody for 1 hour and stimulation with 10
    nmol/L ALDO for 24 hours. Results Flow cytometry showed that ROS production in NRK-52E cells increased significantly
    in ALDO group compared with those of control group (
    P0.05). Compared with ALDO group, the intracellular ROS level
    decreased significantly in ALDO+HMGB1 antibody group (
    P0.05). Western blot results showed that compared with control
    group, the expressions of IL-1β, HMGB1, LC3- Ⅱ and Beclin-1 proteins were up-regulated in ALDO group, and the
    expression of p62 protein was down-regulated (
    P0.05). Compared with ALDO group, the expression of IL-1β protein was
    down-regulated in NAC+ALDO group (
    P0.05), the expression of LC3-Ⅱ protein was down-regulated and the expression
    of p62 protein was increased in ALDO+HMGB1 antibody group (
    P0.05). There was no significant difference in the
    expression of Beclin-1 protein (
    P0.05). Conclusion ALDO can induce autophagy by promoting ROS production,
    increasing the secretion of HMGB1 and stimulating the release of IL-1β in NRK-52E cells. Inhibiting the release of HMGB1
    can reverse this phenomenon and provide new targets and ideas for the prevention and treatment of chronic kidney diseases.


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    Phthalocyanine zinc photodynamic therapy-induced ROS of Lovo cells #br#
    LI Tao, WANG Yu, CHEN Wei, XIA Chun-hui, LUN Zhi-qiang
    2020, 48 (4):  253-257.  doi: 10.11958/20192627
    Abstract ( 652 )   PDF (1196KB) ( 4408 )  
    Objective To investigate the P38MAPK-mediated mitochondrial damage induced by TαPcZn-PDT in
    Lovo cells.
    Methods Lovo cells were divided into control group, siRNA-negative group, siRNA-P38MAPK group,
    TαPcZn-PDT group and TαPcZn-PDT/siRNA-
    P38MAPK group. The cells in each group were treated and irradiated by red
    light for 10 minutes and then incubated for 3 hours. After incubation, RT-PCR and Western blot assay were used to detect
    the effect of p38MAPK silencing. The cell ROS levels were detected by DCFH-DA probe. JC-I/7-AAD double-labeled
    staining was used to detect changes of cell mitochondrial membrane potential (Δ
    Ψm). Annexin V-FlOUS/7-AAD doublelabeled staining was used to detect the cell apoptotic rate. Results After siRNA interference, the protein expressions of
    P38MAPK mRNA significantly decreased. TαPcZn-PDT induced the increase of ROS, the depolarization of mitochondrial
    Δ
    Ψm and the apoptotic rate. After siRNA silencing P38MAPK, the ROS was decreased, the number of depolarized cells was
    decreased and the apoptosis was weakened, which was induced by TαPcZn-PDT in Lovo cells.
    Conclusion That silencing
    of
    P38MAPK can significantly inhibit the production and release of ROS and decrease the depolarization of mitochondrial
    Δ
    Ψm, thus attenuate the apoptosis induced by TαPcZn-PDT.
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    Experimental Study
    The effect of neutralizing interleukin-17 on the expressions of collagen and#br# apoptosis-related factors in model mice with idiopathic pulmonary fibrosis #br#
    ZHAO Tie-jun, SONG Gui-qin, ZHANG Hao-ting, CUI Wei-liang, HUANG Yong, WANG Wen-dong, ZHANG Xiao-yun
    2020, 48 (4):  258-262.  doi: 10.11958/20192555
    Abstract ( 594 )   PDF (639KB) ( 4513 )  
    Objective To investigate the effect of neutralizing interleukin-17 (IL-17) on the expressions of collagen
    and apoptosis-related factors in model mice with idiopathic pulmonary fibrosis induced by bleomycin.
    Methods Thirtytwo male C57BL/6 mice were randomly divided into normal control group, model group, neutralizing antibody group and
    antibody control group. The mouse model of idiopathic pulmonary fibrosis was induced by intratracheal infusion of bleomycin (BLM, 5 U/kg). Mice in the neutralizing antibody group and the antibody control group were injected with IL-17 monoclonal antibody or isotype control antibody through the caudal vein every 4 days from the day 3 after BLM instillation, and the
    model group and the normal control group were given the same amount of normal saline. At the day 28, all mice were
    euthanized, the lung fibrosis degree was assessed by Masson staining. The mRNA contents of collagen typeⅠand type Ⅲ in lung tissues were determined by real-time fluorescent quantitative PCR, and the expression levels of Cleaved-cysteinasparate protease (Cleaved-caspase)-3 and Cleaved-caspase-9 were detected by Western blot assay.
    Results Compared with the model group, the degree of pulmonary fibrosis was significantly declined in the neutralizing antibody group (P0.01), the mRNA expressions of collagen typeⅠand type Ⅲ were obviously decreased (P0.01), and the protein expressions of Cleaved-caspase-3 and Cleaved-caspase-9 were markedly reduced (P0.01), but there were no significant differences in these data between model group and the antibody control group. Conclusion Neutralizing endogenous IL-17 may improve pulmonary fibrosis by regulating the expressions of Cleaved-caspase-3 and Cleaved-caspase-9 proteins.
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    Effects of myricetin on spermatogenesis and hormone levels in male#br# mice exposed to lead poisoning #br#
    CHEN Zong-yao, LI Le-le, WANG Zhen-tao, XU Shi-lin, LI Yao, WANG Yan-chun, FAN Hong-yan
    2020, 48 (4):  262-266.  doi: 10.11958/20191939
    Abstract ( 541 )   PDF (834KB) ( 3399 )  
    Objective To study the effect of myricetin on spermatogenesis impairment in male mice exposed to lead
    and discuss its mechanism.
    Methods Sixty Kunming mice were randomly divided into control group, lead group,
    methyltestosterone group, myricetin (low, medium and high doses) groups, 10 mice in each group. The spermatogenic
    disorder model was established by intraperitoneal injection of lead acetate (20 mg/kg, 7 d). From the second day of modeling, different doses of myricetin (100, 200 and 400 mg/kg, for 42 d) were given to low, medium and high dose myricetin groups. The sperm density, the testis index and changes of sperm aberration rate were observed in mouse groups. The serum levels of
      testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sorbitol dehydrogenase (SDH) and
    malondialdehyde (MDA) in the testis tissue were detected. The pathological changes of testicular tissues were observed by
    HE staining.
    Results Compared with lead exposed group, the sperm density increased, the testis index increased and the
    distortion rate of sperm reduced in myricetin groups. The serum levels of LH and FSH decreased and T increased, the
    content of MDA in testis decreased and the activity of SDH increased in myricetin groups (
    P0.05). Pathological results
    showed that there were decline of spermatogenic cells, and few spermiogenesis in most of seminiferous tubule in lead
    exposed group. No above changes were found in high dose myricetin group.
    Conclusion Myricetin can improve
    spermatogenesis, reduce the oxidative stress damage of testicular tissue caused by lead acetate and promote testosterone
    secretion, increase testicular and sperm activity, thereby improving the spermatogenic function of testes
    .
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    Effects of 1, 25-dihydroxyvitamin D3 on ROS regulating airway#br# remodeling through TGF-β1/(Smad2/3) #br#
    ZHANG He, ZHANG Yun, WANG Song-ping
    2020, 48 (4):  267-270.  doi: 10.11958/20192502
    Abstract ( 651 )   PDF (627KB) ( 4349 )  
    Objective To explore the effect of 1, 25-dihydroxyvitamin D31, 25-(OH)2D3on reactive oxygen species
    (ROS) through transforming growth factor- β1(TGF- β1)/(Smad2/3) and molecular mechanism of regulating airway
    remodeling.
    Methods Twenty-four healthy female Balb/c mice were randomized into control group (group A), asthma group
    (group B), and asthma treated with 1, 25-(OH)
    2D3 group (group C). The group B and group C were sensitized with ovalbumin via intraperitoneal injection at the day 0, 7, and 14, and ovalbumin was also given by aerosol inhalation, once a day from the day 21 to 27, and once every other day from day 28 to 77 to build the airway remodeling model of bronchial asthma of mice.
    Group C was given 100 ng of 1, 25-(OH)
    2D3 via intraperitoneal injection half an hour before each aerosol challenge, and the experimental process lasted at least 77 days. The lung tissues of mice were collected for HE staining, AB-PAS staining, and Masson staining to analyze the airway pathological changes, high secretion of airway mucus, and airway remodeling status. The computer image analysis system was used to evaluate the airway remodeling. Airway ROS expression was tested by immunofluorescence. The expression levels of TGF- β1 and Smad2/3 were tested with Western blot assay. Results Compared with group A, the airways was significantly damaged in group B with large amount of inflammatory cell infiltration, increased mucus secretion and increased subepithelial collagen deposition. Compared with group B, the pathological and morphological damages were significantly relieved in group C, but still more severe than those of group A. The expression levels of ROS, TGF-β1 and Smad2/3 proteins were significantly higher in group B than those in group A. Compared with group B, the expressions of ROS, TGF- β1 and Smad2/3 proteins were reduced in group C, but still higher than those in group A (P0.01). Conclusion 1, 25- (OH)2D3 may reduce the ROS level by inhibiting the expressions of TGF- β1/(Smad2/3), and thereby regulating the airway remodeling in mice.
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    Experimental study on the effect of Xiaojie-An on ultrast ructure of uterine fibroids in rats
    YE Juan, HAO Di, WANG Zi, LI Xu, SUN Guo-zhen, JIA Shu-jie
    2020, 48 (4):  271-274.  doi: 10.11958/20193097
    Abstract ( 553 )   PDF (943KB) ( 3463 )  
    Objective To investigate the effect of Xiaojie-An on ultrastructural changes of uterine flesh tumour cells
    and reveal the possible mechanism for the treatment of uterine fibroids.
    Methods The rat model of hysteromyoma was
    established by intramuscular injection of estradiol benzoate three times a week for five weeks. The model rats were randomly
    divided into 5 groups according to their body weights including model group, Xiaojie-An groups (high, medium and low
    doses), positive drug group and control group. After treatment for 4 weeks, the changes of uterine morphology, serum estrogen
    and progesterone were observed, and the diameter of uterus above cervix, cervical transverse diameter of uterus from the root
    of left angular uterus were measured. The ultrastructure changes of uterine cells were observed under electron microscope.
    Results The uterine coefficient, ovarian coefficient, angular diameter and root diameter of angular fraction were all bigger
    in the model group than those in the control group (
    P0.05). The uterine coefficient, horn diameter and root diameter were
    all smaller in the positive drug group than those of Xiaojie-An groups (high, medium and low doses,
    P0.05). There were no
    significant difference in above indexes between (high, medium and low dose Xiaojie-An groups. Results of transmission
    electron microscopy showed that the treatment with Xiaojie-An could effectively improve the ultrastructural changes of
    uterine fibroids and inhibit the abnormal proliferation of smooth muscle cells. Pathological examination showed that the
    secretory changes in endometrium of the control group, with varying degrees of eosinophilic leukocyte infiltration in the
    interstitium and no abnormalities in the muscular layer. In the model group, the endometrium showed secretory changes, the
    smooth muscle layer of the uterus was thickened, the number of muscle cells increased, hypertrophy, irregular arrangement
     and small amount of neutrophils infiltration. High dose group and positive drug control group showed the better improvement.
    Conclusion Xiaojie-An can reduce the volume of uterus, improve the ultrastructure of myoma cells, and then achieve the
    therapeutic effect.


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    Clinical Study
    Relationship between serum phosphorus levels and health-related quality of life in#br# patients with maintenance hemodialysis #br#
    WANG Shuang, CHEN Hai-yan, LI Bo, WANG Bo, JIA Lan, WEI Fang, JIANG Ai-li
    2020, 48 (4):  275-278.  doi: 10.11958/20192925
    Abstract ( 779 )   PDF (369KB) ( 4389 )  
    Objective To investigate the relationship between serum phosphorus levels and health-related quality of
    life (HDQOL) in hemodialysis patients.
    Methods A total of 190 patients with maintenance hemodialysis were selected. The
    patients with blood phosphorus level >1.78 mmol/L were selected as the hyperphosphatemia group (
    n=108), and the patients with blood phosphorus level ≤1.78 mmol/L were selected as the non-hyperphosphatemia group (n =82). Data of age, gender, smoking history, hemodialysis access, frequency/week of hemodialysis treatment, complications and other clinical data were recorded. All the laboratory indicators before hemodialysis were recorded: serum calcium (Ca2+ ), serum phosphorus (P),
    serum albumin (ALB), total parathyroid hormone (iPTH), total cholesterol (Tc), high density lipoprotein cholesterol (HDL-C),
    low density lipoprotein cholesterol (LDL-C), triglyceride (TG), serum creatinine (Cr), blood uric acid (UA) and alkaline
    phosphatase. The differences in iPTH, ALB and other indicators were compared between the two groups. Multivariate
    Logistic analysis was performed to analyze the risk factors related to serum phosphorus level. The questionnaire of Kidney
    Disease Quality of Life 36 (KDQOL-36) was used to evaluate the quality of life, and the scores of five subscales in the
    KDQOL-36 were calculated. The differences of each subscale were compared between the two groups, and the relationship
    between blood phosphorus level and quality of life was analyzed.
    Results Compared with the non-hyperphosphatemia
    group, the patient age was smaller, the number of arteriovenous internal fistula were more, and the levels of Cr, ALB, iPTH
    and Ca
    2+ were higher in hyperphosphatemia group (P0.05). Multivariate Logistic analysis indicated that high ALB (OR=
    1.243,95%
    CI:1.082-1.427) and high iPTH (OR=1.001,95%CI:1.000-1.002) were risk factors for hyperphosphatemia (P
    0.05). The subscale scores were significantly lower in the hyperphosphatemia group than those of the non-hyperphosphatemia group (P0.05). Conclusion The serum phosphorus level affects the quality of life of patients with
    maintenance hemodialysis, while the quality of life is worse in hyperphosphatemia.


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    Predictive values of early changes of platelet in 28-day mortality of patients with#br# severe heat stroke #br#
    LI Ya-jie, YU Jian-feng, ZHOU Yi, YANG Qiao-yun, ZHU Qi-lian, LI Yong-chang
    2020, 48 (4):  279-283.  doi: 10.11958/20193076
    Abstract ( 647 )   PDF (466KB) ( 3895 )  
    Objective To explore the predictive value of early changes of platelet in the evaluation of 28-day prognosis
    in the patients with severe heat stroke.
    Methods A retrospective study was conducted. The patients with severe heat stroke
    admitted to the Second People
    s Hospital of Changzhou from September 2010 to September 2018 were enrolled. These
    patients were divided into survival group and death group according to 28-day outcome. The general condition and platelet
    counting at 0 (PLT
    0), 72 hours (PLT72) after admission were collected. Receiver operating characteristic curve (ROC) was
    plotted according to the platelet counting, the changes of platelet (ΔPLT), the change rates of platelet (ΔPLT%) and acute
    physiology and chronic health status score (APACHEⅡ) for evaluating the predictive value of 28-day prognosis. KaplanMeier survival curve was used to analyze the 28-day cumulative survival rate between two groups of patients, who were subdivided according to the PLT
    0, PLT72, ΔPLT% and APACHEⅡ scores. Results (1) A total of 116 patients with severe heat stroke were enrolled in this study, including 90 cases in the survival group and 26 cases in the death group. The mortality was 22.4%. The rate of using vasoactive drugs, the length of invasive mechanical ventilation and APACHE Ⅱ scores were significantly higher in the death group than those in the survival group (P0.05). (2) The platelet levels showed the downward trend in both groups. Values of PLT0 and PLT72 were significantly lower in the death group than those in the survival group (P0.05). Meanwhile, the decrease ranges of ΔPLT and ΔPLT% were significantly larger in the death group  than those in the survival group (P0.05). (3) ROC curve analysis showed that values of APACHEⅡ scores, the PLT0, PLT72
    and ΔPLT% could predict 28-day mortality in the patients with severe heat stroke, with the largest area under ROC curve
    0.841 of PLT
    72 (P0.05). (4) Kaplan-Meier survival analysis showed that the 28-day survival rate was significantly higher
    than the cut-off value when the PLT
    0 and PLT72 were higher (both P0.05). Conclusion The PLT at 72 hours after
    admission may play an important role in predicting prognosis of the patients with severe heat stroke, The continuous decline
    of PLT indicates poor prognosis in patients with severe heat stroke.


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    Predictive value of red blood cell distribution width for outcome of intravenous#br# thrombolysis in patients with acute ischemic stroke #br#
    XUE Juan-juan, LU Wei, XIA Xiao-shuang, LI Xin△
    2020, 48 (4):  284-288.  doi: 10.11958/20191578
    Abstract ( 783 )   PDF (426KB) ( 4308 )  
    Objective To explore the predictive value of red blood cell distribution width (RDW) for the outcome of
    intravenous thrombolysis in patients with acute ischemic stroke (AIS).
    Methods A total of 122 patients with AIS admitted
    to the Department of Neurology, the Second Hospital of Tianjin Medical University for the treatment of intravenous
    thrombolysis between January 2017 and January 2019 were enrolled retrospectively. Three months after treatment, the
    clinical outcome was assessed by the modified Rankin scale (mRS). The score of 0-2 was defined as good outcome, and>2
    was defined as poor outcome. Clinical basic data, blood count and biochemical data were compared between the two groups.
    Multivariate Logistic regression analysis was used to determine the independent risk factors for poor outcome. Receiver
    operator characteristic (ROC) curve was used to analyze the predictive value of RDW for poor outcome after intravenous
    thrombolysis in patients with AIS.
    Results In 122 patients, 69(56.6%) showed good outcome and 53(43.4%) showed poor
    outcome. The proportions of hypertension, stroke, heart disease, atrial fibrillation and the values of age, baseline National
    Institutes of Health Stroke Scale (NIHSS) score, fasting blood glucose (FBG), high sensitivity C-reactive protein (hs-CRP),
    uric acid (UA) and RDW were significantly higher in poor outcome group than those in good outcome group (
    P0.05).
    Multivariate Logistic regression analysis showed that high FBG level, high NIHSS score and elevated RDW were the
    independent risk predictors of poor outcome after intravenous thrombolysis in patients with AIS. The cutoff RDW value for
    predicting poor outcome after intravenous thrombolysis in patients with AIS was more than 13.15% with a sensitivity of

    62.3% and a specificity of 84.1% (area under the curve, 0.754; 95% confidence interval 0.665-0.843). Conclusion The
    elevated RDW is an independent risk factor for poor outcome after intravenous thrombolysis in patients with AIS. RDW has a certain predictive value for outcome after intravenous thrombolysis in patients with AIS.

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    Effects of different doses of ketamine intravenous anesthesia on the early#br# cognitive function after segmental mastectomy #br#
    LI Xiang-qian, BING Yan-chun, YANG Wan-rong, WANG Hong-min, MA Jing
    2020, 48 (4):  289-293.  doi: 10.11958/20193314
    Abstract ( 641 )   PDF (392KB) ( 4348 )  
    Objective To investigate the effects of different doses of ketamine-assisted total intravenous anesthesia on
    the early cognitive function and pain in patients undergoing segmental mastectomy.
    Methods A total of 120 patients
    undergoing elective segmental mastectomy under total intravenous anesthesia were selected and randomly divided into four groups (
    n=30), including the control group (groupA) without ketamine and the observation group given ketamine at 0.5 mg/kg (group B), 1.0 mg/kg (group C) and 1.5 mg/kg (group D), respectively. The changes in mean arterial pressure (MAP) and heart rate (HR) of the four groups of patients were observed and recorded before anesthesia induction (t0), after laryngeal mask
    placement (t
    1), 1 minute after skin incision (t2), and 25 minutes after skin incision (t3). The Visual Analogue Scale (VAS) was closely followed at 2 hours (T1), 6 hours (T2), 12 hours (T3) and 24 hours (T4) after surgery. The scoring methods of Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate the early postoperative cognitive dysfunction (POCD) 1 day (T0) before surgery, and 2 hours (T1), 6 hours (T2), 12 hours (T3) and 24 hours (T4) after surgery. Results The changes of MAP and HR in each time point during the operation were the smallest and stable in the group B (P0.05), and the different value of adjacent time point was the largest in group A (P0.05). The VAS scores of T1-T3 were lower in group B, C and D than those in group A (P0.05), and there was no significant difference between groups B, C and D (P0.05). There were no significant differences in MMSE and MoCA scores at T0 and T4 time points between the four groups (P0.05). T1 time point was significantly lower in group Dgroup Cgroup B group A (P0.05). T2 time point was group A group B group C and D (P0.05). The scores of T3 time points were significantly higher than those of T2 (P0.05). Conclusion Ketamine can reduce the early cognitive function in patients after segmental mastectomy with dose dependent manner, but no effect on the cognitive function 24 hours after operation. The low dose of ketamine has good analgesia effect and more stable vital signs during the operation.

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    The pathological mechanism of lumbar spinal stenosis with L3 degenerative spondylolisthesis #br#
    WANG Kun, SUN Xiao-liang△, WU Guo-feng, ZHOU Jian, SUN Han, YUAN Feng
    2020, 48 (4):  294-297.  doi: 10.11958/20192859
    Abstract ( 612 )   PDF (449KB) ( 3748 )  
    Objective To compare the imaging differences between patients with lumbar spinal stenosis combined with
    L
    3 degenerative spondylolisthesis (DS) and patients without L3 DS, and to explore the possible pathological mechanism of LDS. Methods A total of 300 patients with lumbar spinal stenosis treated with lumbar posterior lumbar surgery were
    selected in the Third Affiliated Hospital of Suzhou University from May 2012 to June 2017. Thirty-five patients from them
    with L
    3 DS alone were selected as L3 DS group. Forty patients with matched age and gender and DS without lumbar spinal
    stenosis were selected as non-DS groups. All patients received a standing lumbar vertebrae, a full length spine and lumbar
    MRI, and measured pelvic projection angle (PI), pelvic tilt angle (PT), sacral tilt angle (SS), lumbar lordosis angle (LL) on Xray films. The facet joint angles of L
    3/4 and L4/5, and disc heights of L3/4, L4/5 and L5/S1 were measured on MRI. Statistical analysis was performed on all results. Results There were no significant differences in spine-pelvis sagittal plane
    parameters PI, PT, SS and LL between the two groups (
    P0.05). Among the height parameters of intervertebral disc, the
    slopes of L
    3, L4 and L5 were significantly greater in the L3 DS group than those in the non-DS group (P0.01). The sagittal angle of l3/4 facet joints was significantly higher in the L3 DS group than that in the non-DS group (P0.01). There were no significant differences in disc heights of L3/4, L4/5 and L5/S1 between the two groups (P0.05). The lumbar disc height of L4/5 was more lower in the L3 DS group than that in the non-L3 DS group (45.83% vs. 11.11%, χ2=5.357, P0.01). Conclusion The increase of slope of L3 segment, the sagittal angle of l3/4 facet joint and the excessive stress may be the important reasons leading to the occurrence of L3 DS.
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    The relationship between high-sensitivity C-reactive protein/albumin ratio and#br# recurrent cerebral infarction #br#
    JIN Xia-xia, XU Jiu-fei, WANG Jing, SHEN Bo
    2020, 48 (4):  298-301.  doi: 10.11958/20192412
    Abstract ( 716 )   PDF (384KB) ( 4551 )  
    Objective To investigate the relationship between high-sensitivity C-reactive protein to albumin (hs-CRP/
    Alb) ratio and recurrence cerebral infarction (RCI).
    Methods A total of 69 RCI patients hospitalized in Taizhou hospital
    affiliated to Wenzhou medical university from January 2018 to December 2018 were selected as case group, and 107 first
    cerebral infarction (FCI) patients were selected as control group. The clinical data were recorded. The levels of blood routine examination, erythrocyte sedimentation rate (ESR), glycosylated hemoglobin A1c (HbA1c), hs-CRP, alanine transaminase (ALT), aspartate transaminase (AST), low density lipoprotein cholesterol (LDL-C), glucose (Glu), homocysteine (Hcy), Alb,
    total bilirubin (TBil), direct bilirubin (DBil) and prealbumin (PA) were detected, and hs-CRP/Alb were calculated.
    Independent risk factors of cerebral infarction recurrence were analyzed by logistic regression, and the value of hs-CRP to
    albumin ratio in predicting cerebral infarction recurrence was evaluated by ROC curve.
    Results In the univariate analysis,
    the prevalence of diabetes, average hospital stay, average hospitalization cost, HbA1c, hs-CRP, TBil, DBil and hs-CRP/Alb
    ratio were significantly higher in the RCI group than those in the FCI group, while Alb and PA were lower than FCI group
    (
    P0.05). There were no significant differences in gender, hypertension, WBC, Glu, ALT, AST and LDL-C between the two
    groups (
    P0.05). Multivariate Logistic regression analysis showed that DM (OR=3.834, 95%CI: 1.176-12.503, P=0.026
    and hs-CRP/Alb ratio (OR=8.513, 95%CI: 1.139-63.638P=0.037) were independent risk factors for RCI. The ROC curve
    showed that the area under the curve of hs-CRP/Alb ratio predicting RCI was 0.635 (95%
    CI: 0.551-0.719, P=0.033). When
    the cut off value was 0.07, the sensitivity and specificity were 59.4% and 61.7% respectively.
    Conclusion The hs-CRP/
    Alb ratio is an independent risk factor for cerebral infarction recurrence, and the hs-CRP/Alb ratio at the time of admission
    is helpful for predicting the recurrence of cerebral infarction.

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    A case report of influenza A combined with methicillin-resistant staphylococcus aureus sepsis #br#
    WANG Li-jing, WANG Xiao-min
    2020, 48 (4):  302-305.  doi: 10.11958/20192435
    Abstract ( 940 )   PDF (1142KB) ( 4094 )  
    Co-infection of influenza A virus and other bacteria is one of the main causes of high pathogenicity and
    mortality of influenza A. The common bacterial species co-infected with influenza A are staphylococcus aureus,
    streptococcus pneumoniae and other bacteria. Clinicians are not well aware of it and are prone to misdiagnosis and wrong
    treatment. This paper retrospectively analyzed the pathogenic characteristics, clinical manifestations, treatment and outcome of severe influenza with methicillin-resistant staphylococcus aureus (MRSA) sepsis in an 8-year-old girl hospitalized in our hospital, so as to improve the understanding of the disease. The recognition of severe influenza in children with bacteria infection is beneficial to early identification and improving the success rate of treatment.

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    Chylous leakage caused by multiple jejunum diverticulum combined with#br# mesentery volulus in the elderly: a case report #br#
    SONG Bing, ZHANG Wen-jing
    2020, 48 (4):  306-308.  doi: 10.11958/20192774
    Abstract ( 529 )   PDF (521KB) ( 3477 )  
    Intestinal volvulus complicated with intestinal obstruction is one of acute abdominal diseases in surgery. The
    onset and progression of intestinal volvulus are rapid, and most of them are complicated with intestinal blood supply disorder. If not treated in time, intestinal perforation, intestinal necrosis and peritonitis often occur, which seriously endangers the life of patients. There are many cases of intestinal obstruction and necrosis caused by mesentery volvulus, however the lymphatic leakage caused by it is rarely reported. This article reports the diagnosis and treatment of an elderly patient with chylous leakage caused by multiple jejunum diverticulum combined with mesentery volulus and discusses the treatment of chylous leakage caused by small mesentery torsion.

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    CD22 CAR-T salvage therapy for a refractory acute B lymphocytic leukemia patient with TP53#br# positive mutation and short-term recurrence after remission from CD19 CAR-T therapy #br#
    MU Juan, LYU Hai-rong, LI Jing-yi, JIANG Yan-yu, ZHANG Rui, MENG Juan-xia, YUAN Ting , DENG Qi
    2020, 48 (4):  308-312.  doi: 10.11958/20192232
    Abstract ( 503 )   PDF (614KB) ( 4059 )  
    The mortality rate of the acute lymphocyte disease is extremely high, and CAR-T cell immunotherapy
    provides a new choice. This paper introduced a refractory acute B-lymphoblastic leukemia (B-ALL) patient with TP53
    positive mutation and short-term recurrence after remission from CD19 CAR-T therapy. The case was successfully treated
    by CD22 CAR-T combined with allogeneic hematopoietic stem cell transplantation. The proportions of peripheral blood
    CD19 CAR-T and CD22 CAR-T cells were analyzed by flow cytometry. The expression of CAR gene in peripheral blood was
    detected by PCR method. The efficacy and the side effects of CD19 CAR-T and CD22 CAR-T therapy were observed in this
    patient. The CD19 CAR-T and CD22 CAR-T cell treatments both achieved complete remission on the day 14, and the side
    effects were minor. But bone marrow recurrence 2 weeks after remission from CD19 CAR-T cell therapy with abnormal 19
      CAR gene expression in peripheral blood and increased TP53 mutation level. The patient was successfully treated with CD22
    CAR-T cells bridged with haploid hematopoietic stem cell transplantation therapy. In a word, the purity of CD3
    + cells should
    be further improved in the process of CAR-T cell manufacture. CD22 CAR-T therapy could be used as a salvage measures
    for the patient with relapse of CD19 CAR-T therapy.


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    Epidemiological Investigation
    Analysis on the epidemic characteristics of respiratory pathogens in hospitalized children with#br# acute respiratory tract infections in Tianjin from 2013 to 2018 #br#
    ZONG Xiao-long, MA Li-feng, LI Zhen-yu, HAN Yue, TIAN Yu-xin, ZHAO Qi, WEI Dian-jun
    2020, 48 (4):  313-319.  doi: 10.11958/20192626
    Abstract ( 676 )   PDF (433KB) ( 3837 )  
    Objective To explorer the profile and epidemiological characteristics of hospitalized children with acute
    respiratory tract infection (ARI) in Tianjin, china, from 2013 to 2018.
    Methods Sputum and/or throat swab specimen and
    serum sample were obtained from children within 24 hours after admission. Respiratory bacteria were identified by
    biochemical reaction and Analytical Profile Index. IgM antibodies against nine common respiratory pathogens including
    influenza virus A (IFA), influenza virus B (IFB), parainfluenza virus serotype 1,2,3 (PIVs), respiratory syncytial virus (RSV),
    adenovirus (ADV), mycoplasma pneumonia (MP), chlamydia pneumonia(CP), coxiella burnetii (COX) and legionella
    pneumophila serogroup 1 (LP-1) were detected by indirect immunofluorescence antibody test (IFAT). Total antibodies
    against MP were further semi-quantified by passive particle agglutination test (PPAT), titer ≥ 1
    160 was confirmed as recent infection. Results A total of 7 832 children hospitalized with ARI were included in the study, of whom 5 353 children were completed bacterial identification, 7 449 children were performed with IFAT and PPAT, and 4 970 children with all above etiological tests. Of the 7 832 children enrolled in the study, 3 291 (42.0%) were positive for one or more pathogen. Twenty percent of the 5 353 patients were performed with bacterial identification with at least one bacterium. The top five common
    bacteria were
    streptococcus pneumoniae (5.3%), Klebsiella pneumoniae (4.0%), Escherichia coli (2.7%), staphylococcus aureus (1.9%) and haemophilus influenzae (1.6%) respectively. Among the five tested viruses, IFB (2.8%) and PIVs (0.6%) were the most commonly identified. MP was the most commonly detected pathogen throughout the year, with a mean positive rate of 29.3% (2 241/7 449) and the seasonal peak form September to December. The presences of more than one pathogen were found, atypical pathogenic/bacterial, atypical pathogenic/viral and bacterial/viral combinations were detected in 3.8, 3.0 and 0.6% respectively. Logistic regression analysis showed that co-infection was independently associated with the increased risk of progression to severe pneumonia (OR=1.91695%CI: 1.415-2.595P0.01). Conclusion This study suggests that MP and co-infection combined pathogen are the most commonly identified pathogen in the hospitalized children with ARI from 2013 to 2018, with a rising tendency in recent years. S. pneumoniae, K. pneumoniae, E. coli, S. aureus and H. influenzae are commonly indentified bacteria in children with severe lower respiratory tract infection. Co-infection is associated with the increased risk for progression and exacerbation of illness.

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    Evidience-Based Medicine
    Systematic review and Meta-analysis of tripterygium wilfordii hook F and acitretin on the#br# randomized controlled trial for treatment of psoriasis vulgaris #br#
    CHENG Yi, HU Cai-xia, CUI Yu, WANG Wen-qing
    2020, 48 (4):  320-326.  doi: 10.11958/20192547
    Abstract ( 710 )   PDF (1044KB) ( 3444 )  
    Objective To analyze the efficacy and safety of tripterygium wilfordii hook F (TwHF) alone or combination
    with acitretin in the treatment of psoriasis vulgaris, and provide evidence-based reference for clinical treatment.
    Methods
    Pubmed, Cochrane, CNKI and Wanfang database were searched up to December 2018. Data of the randomized controlled
    trial (RCT) of TwHF alone or in combination with acitretin for psoriasis vulgaris were collected. The primary end-point was
    the proportions of patients achieved 60% to 89%, and 90% to 100% improvement in psoriasis area and severity index (PASI) respectively, which were considered as effective rate and cure rate. Adverse drug reactions were analyzed. A systematic review and meta-analysis were conducted for extracted data and quality evaluation by Rev Man 5.3 software.
    Results A total of 1 258 patients from 13 clinical trials were included in this study. There were no statistically significant differences in effective rate (RR=1.0895%CI0.79-1.47P=0.65) and cure rate (RR=1.2295%CI0.67-2.22P=0.52) between TwHF group (n=284) and acitretin group (n=273). The effective rate (RR=1.48, 95%CI1.33-1.64, P0.01) and cure rate (RR=1.44, 95%CI1.19-1.75, P0.01) were better in TwHF and acitretin combination group (n=368) than those of acitretin group (n=365). Compared with acitretin group, the incidence of gastrointestinal reactions (RR=0.54, 95%CI0.33-0.91, P0.05) and abnormal liver function (RR=0.37, 95%CI0.18-0.78, P0.05) were decreased in the combined group. There were no significant differences in dry skin or mucosa (RR=0.66, 95%CI0.34-1.27, P=0.21) and elevated blood lipid (RR=0.59, 95%CI0.31-1.11, P=0.10). Conclusion TwHF can effectively treat psoriasis vulgaris. TwHF combined with acitretin is superior to acitretin monotherapy in the treatment of psoriasis vulgaris.
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    Consensus on surgical treatment of myasthenia gravis of the Jing-Jin-Ji experts #br#
    Myasthenia Gravis Union of Jing-Jin-Ji
    2020, 48 (4):  327-332.  doi: 10.11958/20193666
    Abstract ( 766 )   PDF (431KB) ( 3790 )  
    Myasthenia gravis (MG) is an autoimmune disease with dystransmission at the neuromuscular junction
    (NMJ), which is mediated by acetylcholine receptor antibody, dependent on cellular immunity and participated by
    complement. MG is closely related to thymic diseases, so in addition to the medical treatment, thymectomy is an important
    way to treat MG. Based on the latest literature at home and abroad, and the experience of more than ten experts in Beijing, Tianjin and Hebei, this paper has written an expert consensus on antibody typing, preoperative examination, surgical indications, surgical methods, postoperative treatment and follow-up of MG, hoping to guide the surgical treatment of MG.

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    Review
    Research progress of circular RNA in breast cancer #br#
    LIU Jing-jing, ZHOU Dong-dong, ZHANG Jin
    2020, 48 (4):  333-337.  doi: 10.11958/20192761
    Abstract ( 761 )   PDF (376KB) ( 4403 )  
    Circular RNAs (circRNAs) are non-coding RNAs with closed-loop structure. In recent years, with the rapid
    development of high-throughput RNA sequencing (RNA-seq) technologies and bioinformatics, more and more circRNAs
    have been found in tumor tissues. Studies have shown that circRNAs can regulate the transcription and translation of target genes through the mechanism of miRNA sponge or binding to proteins in cells, and thus widely participate in the
    pathophysiological processes including growth, differentiation, development and apoptosis of cells, providing a new direction for the prevention, diagnosis and treatment of related diseases. Breast cancer is the most common malignant tumor in women, with a high degree of heterogeneity. The establishment of therapeutic targets based on tumor molecular biological characteristics has become the key to individualized and accurate treatment. In this review, the formation mechanism and biological function of circRNAs and their effects on the occurrence, development and prognosis of breast cancer are summarized as follows.

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    Advances in research on microglia and sepsis associated encephalopathy #br#
    ZHUANG Xin-qi, XIE Ke-liang, YU Yong-hao, LU Yue-chun, LYU Guo-yi
    2020, 48 (4):  338-342.  doi: 10.11958/20193358
    Abstract ( 809 )   PDF (382KB) ( 4000 )  
    Sepsis associated encephalopathy (SAE), characterized by brain dysfunction, is a common complication in
    septic patients and seriously affects the prognosis and quality of life. Recent researches have discovered that microglia, as the immune cells in the central nervous system, can produce inflammatory transformation under septic condition and promote the development of cerebral inflammation and SAE. Targeting microglia may provide new ideas and directions for the treatment of SAE. In this paper, the characteristics of microglia were briefly described, and the relationship between microglia and SAE was expounded. The effects of microglia activation on the central nervous system were analyzed, the signaling pathway for microglia regulation was discussed, and its clinical application in the future was prospected.

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    Research progress of STAT3 signaling pathway in insulin resistance #br#
    LIU Hong-fei, WEI Cui-ying
    2020, 48 (4):  343-347.  doi: 10.11958/20192717
    Abstract ( 728 )   PDF (382KB) ( 5810 )  
    Insulin resistance (IR) is an important mechanism of type 2 diabetes. It affects the transmission of various
    signaling pathways, thereby disrupting glucose metabolism. Signaling and the transcriptional activation factor 3 (STAT3)
    pathway are important pathways that regulate gene transcription. There is evidence that STAT3 signaling pathway is a key
    factor of IR, which can regulate the mitogen-activated protein kinase (MAPK) pathway, insulin receptor substrate-1 (IRS-1) /phosphatidyl inositol 3 kinase (P13K) / protein kinase B (PKB) pathway and other insulin-related pathways. The STAT3
    signaling pathway is activated by the upstream cytokine interleukin-22 (IL-22) and is involved in the regulation of glucose
    metabolism. It is a current research hotspot. This article reviews the relationship between the STAT3 pathway and IR to
    further clarify the pathogenesis of glucose metabolism.

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    Research advances in diuretic resistance in patients with heart failure #br#
    WANG Dan-ni, FENG Jin-ping, FENG Chao, CHEN Shu-tao
    2020, 48 (4):  347-352.  doi: 10.11958/20193347
    Abstract ( 688 )   PDF (420KB) ( 3782 )  
    Heart failure is the final stage of the development of various heart diseases. In recent years, the prevalence of
    heart failure in China has gradually increased and is becoming the most important cardiovascular disease in the 21 st
    century. Diuretics are the key and basis for the treatment of heart failure. The drug treatment of heart failure mainly includes two aspects, one is to delay the progress of the disease, mainly including endorphin inhibitor (sakutravalsartan), angiotensin converting enzyme inhibitor (ACEI), angiotensin II receptor antagonist (ARB), beta blocker, aldosterone receptor antagonist 
    and other drugs; the other is to improve symptoms such as dyspnea and edema, including diuretics and vasodilators. Considering the key role of congestion in heart failure, diuretics are the cornerstone of heart failure treatment. However, due to various reasons, 25% -30% of the patients have diuretic resistance, which significantly reduces the therapeutic effect in patients with heart failure. This article reviews the definition, pathogenesis and therapeutic strategy of diuretic resistance.
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