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Table of Content

    05 November 2021, Volume 41 Issue 11
    Original Articles
    Epidemiological investigation of thalassemia in childbearing age population of Dai nationality in Yingjiang County, Dehong Prefecture, Yunnan Province, China
    XIE Mei-juan, TENG Cong-cong, LONG Lan, LIU Yong-xing, CHEN Xin-chao, ZHANG Jie
    2021, 41(11):  1559-1563. 
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    Objective To investigate the gene carrying rate, mutation spectrum and frequency of thalassemia in the childbearing age population of Dai nationality in Yingjiang County, Dehong Prefecture, Yunnan Province, China and to provide a theoretical basis for strategy maiming for the prevention and control of thassemia birth defects. Methods Totally 400 cases of childbearing age population of Dai nationality in Yingjiang County were subjected to routine blood testing, capillary electrophoresis, and next generation sequencing. Results Among the 400 cases 219(54.75%) thalassemia gene carriers were found. There were 133(33.25%) carriers having α-thalassaemia gene. The most common genotype was -α3.7, followed by--SEA and -α4.2. There were 47(11.75%) carriers of β-thalassemia gene, and the mutation type CD26 (G>A) was the most common type. There were 39(9.75%, 39/400) carriers of composite α and β thalassemia. According to comparative analysis of the hematological characteristics of various α-thalassemias, mean corpsular hemoglobin(MCH) of --SEA and Hb A2 of αCSα were relatively low. According to comparative analysis of the hematological characteristics of β-thalassemia, mean corpusular volume(MCV) of CD17 (A>T) was relatively low. Conclusions The carrying rate of thalassaemia in Yingjiang County is 54.75%, indicating it is a high incidence area of thalassaemia. The most common types are -α3.7 and CD26 (G>A). The results reported here may provide evidence for genetic counseling in areas with high incidence of thalassaemia.
    Effect of exosomes miR-106a derived from human gastric cancer cell line AGS on the phenotype of peritoneal mesothelial cell line HMrSV5
    ZHU Meng, ZHANG Ning, TAO Wei
    2021, 41(11):  1564-1569. 
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    Objective To investigate the effect of exosomes derived from human gastric cancer cell line AGS and miR-106a on the phenotype of peritoneal mesothelial cells line HMrSV5. Methods Exosomes from AGS cells were isolated and incubated with HMrSV5 cells. Then exosome secretion inhibitor GW4869 was added. miR-106a expression was detected by qPCR, HMrSV5 cells proliferation and apoptosis were detected by EdU and flow cytometry technology. After the AGS cells were transfected with miR-106a mimic or inhibitor, the migration of HMrSV5 cells was detected by Transwell assay, and the expression of Smad7, TIMP2, MMP2, MMP9 and α-SMA was detected by Western blot. After treatment with TGF-β, the expression of Smad7, Smad2/3 and p-Smad2/3 was detected by Western blot. Results The exosomes of AGS cells highly expressed miR-106a (P<0.01), and incubation with HMrSV5 cells significantly inhibited its proliferation and promoted the early apoptosis rate(P<0.05). After transfection of miR-106a mimic, the exosomes from AGS cells promoted the migration of HMrSV5 cells (P<0.001). Meanwhile, the expression of Smad7 and TIMP2 was decreased, but the expression of MMP2, MMP9 and α-SMA was increased. After treatment with TGF-β, the expression of Smad7 decreased but the expression of Smad2/3 and p-Smad2/3 increased. Conclusions Exosomes derived from human gastric cancer AGS cells can promote apoptosis, inhibit proliferation and enhance migration of human peritoneal mesothelial HMrSV5 cells, which may be related to the transport of miR-106a targeting Smad7 and TIMP2.
    Differential protein profiling in brain and spinal arteriovenous malformations
    WANG Nai-li, MENG Shu, QIU Wen-ying, WANG Xia
    2021, 41(11):  1570-1576. 
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    Objective To explore the differences of protein profiling between brain arteriovenous malformation (bAVM) and spinal AVM (sAVM). Methods Proteins were extracted from bAVM,sAVM,control cerebrovascular and control spinal vessel specimens. The protein level in each group was measured by TMT-labeled quantitative proteomics. Results Totally 3 102 protein samples from bAVM, sAVM,control cerebrovascular and control spinal vessel were examined by high-throughput quantitative proteomics. Among them the expression level of 852 proteins was dramatically changed in bAVM and 205 proteins in sAVM. Bioinformatic analysis showed that 304 proteins were highly expressed only in bAVM, most of them were mitochondria proteins, mainly enriched in electron transport chain and calcium regulation pathways, 97 proteins were specifically highly expressed in sAVM associated with extracellular matrix organization. Conclusions The mitochondrial dysfunction and calcium regulation imbalance may play important roles in the process of bAVM. Disturbed extracellular matrix organization and glycoproteins are potentially involved in sAVM progression.
    Acetylation of carboxyl-terminal domain selectively regulates p53-mediated gene transcriptionn
    YAN Xiao-jun, XU Wen-bin, WANG Dong-lai
    2021, 41(11):  1577-1582. 
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    Objective To explore whether carboxyl-terminal domain (CTD) acetylation contributes to selectively regulating p53-mediated transcription of a subset of genes. Methods Based on p53-null lung cancer cell line H1299, a pair of inducible cell strains expressing the wildtype p53 (p53-WT) and the CTD acetylation-mimicking p53 (p53-6KQ) were constructal, respectively, and a response to doxycycline (Doxy) treatment was generated. RNA-sequencing was applied to analyze the changes of the transcriptional profiles regulated by p53-WT or p53-6KQ. Bio-informatic analysis was performed to annotate p53-6KQ-specific candidates, and their potential biological functions. Results The p53-inducible cell strains were successfully established. 306 differentially expressed genes that were specifically regulated by p53-6KQ were identified. These genes were functionally enriched in the biological processes involving in cell fate determination, transcription, neuron development and tumor necrosis factor signaling pathway. Conclusions The CTD acetylation may selectively and functionally regulate a subset of p53 target genes.
    Assiociation between Fas polymorphisms and serum sFas level with rheumatoid arthritis patients in southwest China
    CHENG Xiao-gang, JIN Hong, CHEN Wei, LUO Dan, SHAN Juan, XU Yan
    2021, 41(11):  1583-1587. 
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    Objective To clarify the association between Fas gene polymorphisms and the level of soluble Fas(sFas) in the serum of rheumatoid arthritis (RA) patients in southwest China. Methods Fas rs2234767 and rs1800682 single mucleotide polymorphisms(SNP) were genotyped in a case-control study with 183 RA patients and 195 controls, using polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP). sFas level in peripheral blood of RA patients and healthy people with different genotypes were detected by ELISA. Results There was no statistically significant difference between the patients with RA and the healthy subjects with respect to Fas rs2234767 and rs1800682 genotype distribution. However, patients carrying the rs1800682G/G genotype had a significantly decreased sFas level in serum compared with those carrying the AA genotype (P<0.05). Conclusions Fas polymorphisms do not represent a major genetic risk factor for RA susceptibility. However, Fas rs1800682 polymorphism may influence sFas level in serum and response in patients with rheumatoid arthritis of Chinese population in southwest.
    miR-295 inhibits high glucose-induced apoptosis of mouse osteoblast cell line MC3T3-E1
    QU Ye, LIU Li-zhu, XU Rui-min, WU Kai-di, DAI Wei-hong
    2021, 41(11):  1588-1593. 
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    Objective To investigate the effect of microRNA (miR)-295 on high glucose-induced apoptosis of mouse osteoblast cell line(MC3T3-E1) and underlying the mechanism. Methods MC3T3-E1 cells cultured in vitro were divided into three groups: control (Ctrl) group, high glucose (HG) group (induced by 22 mmol/L glucose), (HG + miR-control) group (induced by high glucose after miR-control transfection) and (HG+miR-295) group (induced by high glucose after transfection of miR-295 mimic). The expression of miR-295 in MC3T3-E1 cells was detected by real-time fluorescent quantitative PCR, the survival rate of MC3T3-E1 cells was detected by methyl thiazolyl tetrazolium (MTT) assay, the apoptosis rate of MC3T3-E1 cells was detected by flow cytometry, the protein expression of Wnt/β-catenin pathway related proteins β-catenin, Dickkopf homolog 1 (DKK1), c-Myc and B-cell lymphoma-2 (Bcl-2) were detected by Western blot, double luciferase reporter gene assay was used to detect the targeting relationship between miR-295 and DKK1. Results Compared with those in the Ctrl group, the expression levels of miR-295, cell survival rate and the protein expression levels of β-catenin, c-Myc and Bcl-2 in MC3T3-E1 cells in HG group were significantly lower, the apoptosis rate and protein expression level of DKK1 were significantly higher (P<0.05); Compared with those in (HG + miR-control) group, the expression level of miR-295 (P<0.05), cell survival rate and the protein expression levels of β-catenin, c-Myc and Bcl-2 in MC3T3-E1 cells in (HG + miR-295) group were significantly higher (P<0.05), the apoptosis rate and protein expression level of DKK1 were significantly lower(P<0.05). Dkk1 might be the target gene of miR-295. Conclusions miR-295 may inhibit high glucose-induced MC3T3-E1 cell apoptosis by down-regulating DKK1 expression and activating Wnt/β-catenin pathway.
    Up-regulation of miR-125a-5p inhibits proliferation and invasion of acute myeloid leukemia cell lines
    GAO Qiu-ying, XUN Li-ru, LI Lan, HOU Li-min, ZHOU Wei, WANG Hui
    2021, 41(11):  1594-1605. 
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    Objective To find the regulatory effect of miR-125a-5p on the growth and invasion of acute myeloid leukemia (AML) cell lines. Methods The expression of miR-125a-5p and TRIM71 in bone marrow specimens of AML patients, AML cell lines (U937 and HL60) and PBMC were examined by RT-qPCR. The U937 and HL60 cells were divided into control group (control), miR-125a-5p mimic group (miR-125a-5p mimic), miRNA negative control group (miR-NC), TRIM71 over-expression plasmid group (pcDNA3.1-TRIM71) and control plasmid group(pcDNA3.1-NC). U937 and HL60 cells were transfected with miR-125a-5p mimic, pcDNA3.1-TRIM71 and negative control using Lipofectamine 2000. Cell proliferation was measured by MTT assay; Cell invasion was measured by Matrigel invasion assay; And cell apoptosis was detected by flow cytometry. The expression of TRIM71, Bax, Bcl-2, NF-κB p65 was detected by RT-qPCR or Western blot. The targeted regulation relationship between miR-125a-5p and TRIM71 was verified by luciferase reporter gene assay. Results Compared with healthy controls or PBMC, miR-125a-5p expression levels in bone marrow samples of AML patients and AML cell lines were significantly reduced (P<0.05). The proliferation and invasion of U937 and HL60 cells in miR-125a-5p mimic group were significantly reduced, while the apoptosis rate was significantly increased (P<0.05). Compared with control group, the proliferation and invasion of U937 and HL60 cells in pcDNA3.1-TRIM71 group significantly were increased(P<0.05). Luciferase reporter gene assay detection showed that miR-125a-5p mimic effectively inhibited the luciferase activity of pGL3-TRIM71-WT. Compared with miR-125a-5p mimic group, the cell viability and cell invasion rate of (miR-125a-5p mimic+pcDNA3.1-TRIM71) group were increased significantly, while the apoptosis rate was decreased significantly(P<0.05). The expression level of nucleus NF-κB p65 protein in (miR-125a-5p mimic+pcDNA3.1-TRIM71) group was significantly increased(P<0.05). Conclusions Up-regulation of miR-125a-5p may inhibit proliferation and invasion of AML cell lines and induce apoptosis by targeting at TRIM71. In addition, miR-125a-5p can inhibit the proliferation of AML cells by inhibiting the activation of the NF-κB signaling pathway.
    AMPK activator alleviates pancreatic injury in rat models with severe acute pancreatitis
    HUANG Wei, KONG Li-jun, YE Ya-qun, WANG Hong-wei
    2021, 41(11):  1606-1611. 
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    Objective To investigate the protective effect of AMPK activator AICAR on pancreatic injury in rats with severe acute pancreatitis (SAP) by inhibiting inflammatory and oxidative stress. Methods The rats were randomly divided into three groups with 6 in each as follows: sham operation group(NC group),model group(SAP group)and experimental group[(SAP+AICAR) group, given AICAR 400 mg/kg intervention 2 h before modeling]. 5% sodium bezoar cholic acid was pumped into the bile duct with a dosage of 0.1 mL/kg for modeling. The rats were anesthetized with isoflurane 24 hours after modeling, and 5-7 mL of blood from the abdominal aorta was collected, and the heart was cut off for euthanasia.The ratio of p-AMPK/AMPK was determined by Western blot to determine AMPK activation; Pathological injury and edema of pancreas were observed by HE staining; The expressions of monocyte chemotaxis protein 1(MCP-1) and the myeloper-oxidase(MPO) positive cells were counted with immunohistochemical staining; The contents of amylase,lipase,IL-6 and TNF-α in serum were determined by ELISA. The content of malondialdehyde (MDA) and the activity of super-oxide dismutase (SOD) in pancreatic tissues were determined. Results The level of pancreatic phosphorylated AMPK in SAP group was significantly lower than that in NC group (P<0.05), and the level of pancreatic phosphorylated AMPK in experimental group was significantly higher than that in SAP group (P<0.01).The pathological score and pancreatic moisture content of the SAP group were significantly higher than those of the NC group (P<0.05), and the pathological score and pancreatic moisture content of the experimental group were significantly lower than those of the SAP group (P<0.01).The expression of MCP-1, the number of MPO positive cells, the contents of amylase,lipase,IL-6 and TNF-α in serum, the content of MDA and the activity of SOD in pancreatic tissue in SAP group were significantly higher than those in NC group(P<0.05).The expression of MCP-1, the counting of MPO positive cells, the contents of amylase,lipase,IL-6 and TNF-α in serum, the content of MDA and the activity of SOD in pancreatic tissue in experimental group were significantly lower than those in SAP group (P<0.01). Conclusions AMPK activator inhibites inflammatory and oxidative stress responses in SAP rats and alleviates pancreatic injury as well as pancreatic edema.
    miR-26a inhibits the proliferation, migration and invasion of uterine leiomyoma cells through targeting IGF-1
    XIANG Xue-qin, CUI Quan-zhe, TONG Yu-na, ZHAN Wen-bin, LU Jing
    2021, 41(11):  1612-1617. 
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    Objective To investigate the effect and mechanism of miR-26a which targets at insulin like growth factor 1(IGF-1) on the proliferation, migration and invasion of uterine leiomyoma cells. Methods The primary cultured uterine leiomyoma cells were divided into miR-NC group(mimics negative control sequence and was transfected into cells), miR-26a group(miR-26a mimics was transfected into cells), (miR-26a+pcDNA3.1) group(miR-26a mimics and blank vector were transfected into cells) and (miR-26a + IGF-1) group(miR-26a mimics and IGF-1 over-expression vector were transfected into cells). The expression of miR-26a was detected by RT-qPCR; MTT method and Transwell chamber were used to detect cell proliferation, invasion and migration. Western blot was used to detect the expression of PCNA, E-cadherin and MMP-2. Dual luciferase reporter gene assay verified the targeting relationship between miR-26a and IGF-1. Results The miR-26a expression of uterine leiomyoma cells in miR-26a group was significantly increased (P<0.05). Compared with miR-NC group, the cell proliferation, migration and invasion in miR-26a group decreased significantly, the expression of PCNA and MMP-2 decreased significantly, while the expression of E-cadherin increased significantly (P<0.05). There was a targeting relationship between miR-26a and IGF-1. Over-expression of IGF-1 attenuated the inhibition of miR-26a on the proliferation, migration and invasion of uterine leiomyoma cells and the expression of PCNA and MMP-2, and promoting effect of E-cadherin expression. Conclusions Over-expression of miR-26a may inhibit proliferation, migration and invasion of uterine leiomyoma cells by targeting at IGF-1.
    Effects of HIF-1α agonist or inhibitor on intestinal mucosal permeability in rats with sepsis
    WANG Yu-long, TENG Wen-bin, SHAN Yue, YAO Liu-xu, HE Rui, LI Yu-hong, ZHU Sheng-mei
    2021, 41(11):  1618-1623. 
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    Objective To investigate the effects of sepsis and HIF-1α agonist or inhibitor on intestinal mucosal barrier(IBM) function. Methods SD rats were randomly divided into four groups with 6 in each as follows:sham operation group (sham), sepsis group treated with cecal ligation and perforation (CLP), (sepsis+HIF-1α agonist)/(sepsis+DMOG) group receiving intra-peritoneal injection of HIF-1α agonist DMOG (40 mg/kg) for 7 consecutive days before CLP, (sepsis+HIF-1α inhibitor)/(sepsis+BAY87-2243) group orally administered with HIF-1α inhibitor BAY87-2243(9 mg/kg) for 3 consecutive days before CLP. Plasma intestinal permeability markers of diamine oxidase (DAO), intestinal type fatty acid binding protein 2 (FABP2), D-lactic acid and fluorescein isothiocyanate-dextran (FD4) were detected by ELISA. Morphological changes of intestinal mucosa were detected by HE staining. HIF-1α and TJs protein expression were detected by Western blot. Results Sepsis caused pathological damage, increased permeability (P<0.05), up-regulation of HIF-1α and down-regulation of tight junctions (TJs) expression in intestinal mucosa of rats with sepsis(P<0.05); Addition of DMOG alleviated intestinal mucosal pathological damage and decreased intestinal mucosal per- meability (P<0.05); While rats treated with BAY87-2243 showed the opposite result. Conclusions HIF-1α agonist can significantly reduce intestinal mucosal permeability in sepsis, and this effect is significantly counteracted by its inhibitor. It is suggested that HIF-1α upregulation may protect intestinal mucosa aganist sepsis.
    Promoting effect of Shenmai injection on myocardial angiogenesis in rat models with myocardial infarction
    ZENG Yu-ling, LI Shi-ge, ZHAN De-jin
    2021, 41(11):  1624-1628. 
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    Objective To study the promoting effect of Shenmai injection on myocardial angiogenesis in myocardial infarction(MI) rats. Methods Forty-one MI model rats were divided into model group, low and high-dose groups, with 10 rats each, and 11 rats in the positive group. Low and high-dose groups were treated with 1, 2 mol/kg of Shenmai injection injected intraperitoneally, positive group was treated with 2 mg/kg enalapril. HE staining was used to observe the pathological changes of myocardial tissue in each group. Immunohistochemical staining was used to observe the capillary density in the infarct area. Western blot was used to detect the relative expression of PI3K, AKT, p-AKT and VEGF protein. Results The pathological changes of the low and high-dose groups and the positive group were reduced. Compared with the sham operation group, the capillary density and arteriole density, the expression of PI3K and VEGF protein, and p-AKT/AKT in the model group were increased (P<0.05). Compared with the model group, the capillary density and arteriole density, the expression of PI3K and VEGF protein, and p-AKT/AKT in the low and high-dose groups and the positive group were increased (P<0.05). Conclusions Shenmai injection may promote myocardial angiogenesis in MI rats in a dose-dependent manner. It is speculated that the mechanism of this drug is related to the activation of PI3K/AKT signaling pathway.
    Astragaloside Ⅳ reduces renal vascular endothelial injury in uremic rat model
    ZHU Wen-sheng, ZHENG Zhong-yu, LI Xiao-xia, DENG Jian-nan, ZHANG Ji-chun
    2021, 41(11):  1629-1636. 
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    Objective To investigate the protective effect of astragaloside Ⅳ on vascular endothelium of uremic rat model by regulating nuclear factor-E2-related factor2 (Nrf2)/hemeoxygenase1 (HO-1) signaling pathway. Methods SD rats were randomly divided into sham operation group, model group, low- (100 mg/kg), high- (200 mg/kg) dose astragaloside Ⅳ groups, Nrf2 inhibitor group (2 mg/kg) and high-dose astragaloside Ⅳ+Nrf2 inhibitor(200 mg/kg+2 mg/kg) group, with 12 rats in each after the performance of intraperitoneal,the renal function index like serum creatinine (Scr), urea nitrogen (BUN), β2-microglobulin (β2-MG)and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were detected by ELISA method, the pathological changes of renal vascular structure were observed by electron microscopy; Reactive oxygen species (ROS) were detected by immuno-fluorescence technology; the expression of CD31 and Nrf2 in renal tissue was detected by immuno-fluorescence co-localization; the expression of HO-1 and endothelial nitric oxide (eNOS) in renal tissue were detected by immuno-histochemistry; the expression of angiopoietin-like protein 6(ANGPTL6) and monocyte chemoattractant protein-1 (MCP-1) were detected by Western blot. Results Compared with those in the sham operation group, the erythrocyte aggregation, endothelial cell swelling and enlargement, lumen stenosis and compression in peri-tubular capillaries were serious in model group, the secretion of toxins such as Scr, BUN and β2-MG in serum, the levels of TNF-α and IL-6, renal tissue ROS(P<0.05), positive expression of renal vascular tissue HO-1 and eNOS, the positive co-expression of CD31 and Nrf2, protein expression levels of ANGPTL6 and MCP-1 in renal tissue were increased (P<0.05). Compared with those in the model group, the erythrocyte aggregation in peri-tubular capillary lumen, the swelling and enlargement of endothelial cells were alleviated in the low- and high-dose astragaloside Ⅳ groups, the levels of serum toxin and inflammation, renal tissue ROS, the expression of ANGPTL6, MCP-1, and eNOS was decreased (P<0.05), and the expression of HO-1, co-expression of CD31 and Nrf2 in renal vascular tissues were increased (P<0.05); the erythrocyte aggregation in peri-tubular capillary lumen, the swelling and enlargement of endothelial cells were further aggravated in Nrf2 inhibitor group, and the change trends of the above indexes were opposite to those in the astragaloside Ⅳ groups(P<0.05). Conclusions Astragaloside Ⅳ may alleviate renal vascular endothelial injury in uremic rat model by promoting the activation of anti-inflammatory and anti-oxidant pathways mediated by the Nrf2/HO-1 pathway.
    Clinical Sciences
    Efficacy and safety evaluation of ivabradine in patients with non-ischemic heart failure
    LIU Ying-xian, SONG Yan-jun, CHEN Wei, LIN Xue, LAI Jin-zhi, LI Jing-yi, WU Wei
    2021, 41(11):  1637-1642. 
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    Objective To investigate the efficacy and safety of ivabradine on cardiomyopathy and heart failure(HF) with non-ischemic etiology. Methods A single-center retrospective study was carried out. Patients who admitted to Peking Union Medical College Hospital from January 2018 to February 2020, with non-ischemic heart failure, left ventricular ejection fraction (LVEF) less than 50%, and treatment of ivabradine for at least 3 months were enrolled. Results Thirty-eight patients (24 males), with a median age of 31.5 (26.0-44.0) years old, were divided into primary (n=17) and secondary (n=21) cardiomyopathies groups. Ivabradine of 5 mg/d was taken in 65.8% of the patients as the initial dose, and 10-15 mg/d was tolerated in 57.9% of patients after 3 months. Six patients withdrew the ivabradine treatment. The mean value of heart rates decreased from (93.7±13.5) beats/min to (75.9±12.4) beats/min after 3 months in all patients and from (99.0±11.4) beats/min to (78.6±13.8) beats/min in the group with secondary cardiomyopathies (P<0.001, respectively), while no significant changes in blood pressure were observed. NYHA classification, left ventricular end-diastolic diameter and LVEF were signifi- cantly improved in both groups after treatment (P<0.05). After a median follow-up of 9.5 months, 4 patients died, all of them were patients with secondary cardiomyopathies; Thirteen patients with heart failure re-admitted to hospital, including 10 with secondary and 3 with primary cardiomyopathies (47.6% vs 17.6%,P<0.001). Only one case of ivabradine-related bradycardia was observed. Conclusions Ivabradine is safe and effective in patients with non-ischemic cardiomyopathy to control heart rates and to improve cardiac functions, especially for heart failure secondary to systemic diseases accompanied by sinus tachycardia.
    Human papilloma virus (HPV) infection and cervical lesions screened in 3 144 women at Xiamen, Fujian province, China
    XU Hui-juan, LIU Kun, ZHENG Jing-mei, JIANG Qiu-li, LU Hua-dong, XU Jian-fang
    2021, 41(11):  1643-1647. 
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    Objective To analyze the status of human papilloma virus (HPV) infection and its correlation with cervical lesions in women screened for cervical cancer. Methods 3 144 women in Xiamen of China metropolitan area received cervical screening in Zhongshan Hospital, Fudan University (Xiamen Branch) from May 2019 to June 2020 were selected as the research subjects. Their cervical exfoliated cells were collected for HPV genotyping by Bohui biochip method, and cervical cytological pathological examination was performed by ThinPrep cytological test operating system. Results The infection rate of HPV in 3 144 women was 22.3%, among which the rate of high risk was 18.6% and the rate of low risk was 3.8%. The top 10 subtypes of HPV infection were type 52,58,16,56,44,42,81,51,53 and 39.According to the analysis of the infection of 5 groups in different age groups, the highest positive detection rate was 39.4% in the age group over 60 years old, and positive rate of HPV infection varied with different age groups (P<0.01). In HPV-positive patients, single high-risk HPV infection was more common (59.0%), and double high-risk HPV infection was the main type of multiple infection (12.2%). Conclusions There are significant differences in HPV infection among different age groups in this area, and this epidemiology evidence may support the policy development of screening cervical tissue lesions.
    Evaluation of analgesic effect of cocktail therapy combined with adductor block on patients undergoing unicompartmental knee arthroplasty
    ZHANG Hao-sha-qiang, JI Sha-sha, WANG Zhi-gang, TIAN Ye
    2021, 41(11):  1648-1652. 
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    Objective To analyze the results of unicompartmental knee arthroplasty (UKA) in patients with single compartment of knee osteoarthritis, and to evaluate the clinical outcomes and safety with different analgesias. Methods Totally 45 cases were recruited from January 2017 to December 2019 including 18 males and 27 females. The mean age was (63.41±1.19) year-old. They were divided into three groups with 15 in each.Patients in group A received cocktail treatment after surgery. Patients in group B received adductor canal blockade treatment by ultrasound guide after surgery. and those in group C received both cocktail treatment and adductor canal blockade treatment by ultrasound guide after surgery. VAS score and KSS score were compared and analyzed according to postoperative follow-up results. Results VAS scores and KSS scores of the three groups before surgery were not different but VAS scores and KSS scores of the two groups were significantly reduced after treatment (P<0.05). Post-operative VAS score and KSS score were significantly different between the two groups (P<0.05). Conclusions As an effective final treatment for single compartment of knee osteoarthritis, UKA is the most effective treatment in the early and middle stages of knee preserving surgery. Combining cocktail treatment and adductor canal blockade treatment by ultrasound guide after surgery can provide a safe post-operative analgesia for unicompartmental knee arthroplasty.
    Technology and Methodology
    Nucleic acid extraction-free isothermal amplification based on magnetic beads capture and ligation
    QIU Li-zhen, YANG Ming-zhu, PIAN Hong-ru, ZHENG Zhi
    2021, 41(11):  1653-1657. 
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    Objective Capture and ligation probe-loop-mediated isothermal amplification CLIP-LAMP method with-out nucleic acid extraction based on magnetic beads was established to provide a new technique for the detection of human immunodeficiency virus (HIV) in large volume samples. Methods Our team earched a conservative sequence of the virus and used specific soft-ware to design a corresponding capture probe and detection probe. Streptavidin-coated magnetic beads was bound to biotin-labeled DAN molecules, connecting capture probe. The nucleic acid extraction was deleted because the capture probe was able to bind target DNA or RNA directly and specifically. After the ligation step, the detection probe was used as the final template to participate in the fluorescence quantitative loop-mediated isothermal amplification reaction.This method was used for the detection of HIV in vitro transcription (IVT) to assess the sensitivity and specificity of the method. Results This method was successfully applied to the detection of HIV IVT with the detection rate of 32 CPs/μL. The method was capable of processing 1 ml of samples, and the detection was completed in two hours. Conclusions The nucleic acid extraction-free loop-mediated isothermal amplification based on magnetic beads capture provides a new method and for rapid and simple detection of HIV and potentially other pathogenic microbes in large volume samples.
    Case Report
    A rare case of blood stream infection caused by yeast-Rhodotorula glutinis
    FENG Xiao-kai, HE Huai-wu, ZHANG Jia-hui, CHENG Wei, LONG Yun, GUO Fu-ping
    2021, 41(11):  1658-1661. 
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    Objective To report a rare severe case of blood stream infection by Rhodotorula glutinis(R.glutinis)and to share our experience in the diagnosis and treatment with colleagues. Methods The report described a case of catheter-associated R.glutinis bloodstream infection was analyzed after cardiac surgery and reviewed relevant literature. Results R.glutinis bloodstream infection is uncommon in the world. It is difficult to make early diagnosis or tend to leading mis-diagnosis. This kind infection is inclined to occur in immuno-compromised individuals, and its clinical features are repeated high fever, failure of treatment with broad-spectrum antibiotics, normal G test (fungal D-glucose Sugar) results. The diagnosis depends on pathogen culture. R. glutinis is resistant to caspofungin and fluconazole but is sensitive to other antifungal drugs, such as amphotericin B, itraconazole and voriconazole. Patient responded well to intravenous amphotericin B and continued oral posaconazole antifungal therapy. Conclusions For critically ill patients who are not respond to broad-spectrum antibiotics and empirical antifungal (caspofungin and fluconazole) treatment, doctors should be aware of the possibility of bloodstream infection caused by yeast-R.glutinis, and treat patient with sensitive antifungal drugs and timely and avoid potential misdiagnosis.
    Mini Reviews
    Advances in the role of interferon-induced proteins with tetratricopeptide repeats(TPR) in digestive system tumors
    ZHANG Yue-yi, LI Mei-zi, YANG Ying-yun, YANG Ai-ming
    2021, 41(11):  1662-1665. 
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    This paper reviews the basic characteristics of interferon-induced proteins with tetratricopeptide repeats(IFITs), its biological function and molecular mechanism in the development of digestive system tumors and its value in the diagnosis and treatment.
    Research progress of dCTP pyrophosphatase 1 regulating nucleotide metabolism and phenotype of tumor cells
    LI Jing, ZHANG Mei-gui, BAI Zhong-tian
    2021, 41(11):  1666-1670. 
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    Deoxycytidine triphosphate pyrophosphatase 1(dCTP pyrophosphatase 1, DCTPP1) is a newly discovered pyrophosphatase targeting deoxycytidine triphosphate (dCTP). It regulates cytosine metabolism by not only hydrolyzing conventional and modified dCTP, but also participating in the steady-state regulation of other pyrimidine nucleotides. In the process of tumor cells, the high expression of DCTPP1 is facilitate to stabilize the balance of deoxynucleoside triphosphate pool (dNTP pool),methylation of the genome, and maintainance of stability of the tumor cell genome. Besides, DCTPP1 promotes malignant phenotypes such as tumor cell proliferation and metastasis through different signal pathways, and it is related to tumor drug resistance and poor clinical prognosis. DCTPP1 may become a “star” target for the development of anti-tumor drugs. In-depth research on its regulatory mechanism is expected to provide a new strategy for the development of targeted inhibitors of tumor nucleotide metabolism.
    Research progress on mRNA methylation and diseases
    LI Ran, HAO Yan-lei
    2021, 41(11):  1671-1679. 
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    mRNA methylation modification, including N6-methyladenosine (m6A), N5-methylcytidine (m5C) and N1-methyladenosine (m1A), etc., represents more than 60% of all mRNA modifications and varies distribution on mRNA. “Writers” “erasers” “readers” participate in the dynamic and reversible biological process of mRNA methylation modification, which can lead to tumor, virus infection, metabolism diseases, heart or nervous system diseases, etc. when abnormalities occur in a certain link. At present, there are many methylation modification detection technologies, among which the most popular one is high-throughput sequencing.
    Research progress of cellular coagulation factor ⅩⅢ
    XUE Yu-jia, LI Zi-jian
    2021, 41(11):  1680-1683. 
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    Coagulation factor ⅩⅢ (FⅩⅢ) is a member of the plasma transglutaminase family.Plasma FⅩⅢ (pFⅩⅢ)consists of two catalytic A subunits and two non-catalytic B subunits(FⅩⅢ-A2B2)combined with non-covalent bonds to form a heterotetramer.The cellular FⅩⅢ(cFⅩⅢ) exists in a form of A subunit homodimer(FⅩⅢ-A2).Although it is currently believed that cellular FⅩⅢ can be internalized and externalized from the cell through an unknown mechanism and cross-linked extracellular substrates to function in a variety of pathophysiological events,its specific functions and mechanisms need to be clarified by further systematic research.
    Research progress on the mechanism of diarrhea in patients with COVID-19
    ZHANG Shao-gang, WANG Dong, SONG Jie, ZHANG Xiao-lan
    2021, 41(11):  1684-1687. 
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    Patients with corona virus disease 2019(COVID-19) mainly have fever, cough and other respiratory symptoms, but it is necessary to be aware that some patients are complicated by digestive symptoms, such as diarrhea, nausea and vomiting, and even a few patients show atypical symptoms such as diarrhea as the first presentation. This article reviews the mechanism of SARS-CoV-2 infection with digestive tract symptoms,change of intestinal microbiota, therapeutic drugs, psychosocial factors, cytokine storm and aggravation of primary underlying diseases, etc., so as to sharpen clinicians vigilance against COVID-19 patients with digestive system symptoms, and provide theoretical basis for corresponding treatment.
    Medical Education
    Construction and evaluation of a typical case-based cloud platform for clinical skill training
    XU Xin, NI Yi-hong, FEI Wen-hai, JIA Hong-ying
    2021, 41(11):  1688-1691. 
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    The informatics development for medical education is an important content and connotation of medical education teaching reform in China. It has a role in promoting the development of medical higher education. The current informatics development for clinical skill training has the strengthens like easy to construct, to update and to manage. This technology is reusable and meets the individual needs of learners, but the weakness is fail to highlight the process of autonomous learning and difficult to mobilize learners' enthusiasm. This study discusses the construction process and evaluation system of a typical cased based cloud platform for the training of clinical skills, in order to make full use of informatics technology to promote the quality of clinical practice training.
    Effect of a mentor-based visiting scholar training program on academic productivity and career advancement
    ZHENG Xi-xi, ZHENG Ke, YE Wei, CHEN Li-meng, LI Xue-mei
    2021, 41(11):  1692-1695. 
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    Objective To evaluate the effect of a mentor-based visiting scholar training program. Methods Cross-sectional questionnaires were used to investigate the impact of mentor-based training program on the research productivity and career advancement of visiting scholars. Results Compared with no mentoring (n=28), visiting scholars with mentors (n=32) acquired more research funds (P<0.05) and published more scholarly articles (27 articles vs 11 articles) despite a non-significant difference between the number of people who published articles. The difference in career advancement was not significant in the year post visiting scholarship. Ninety three percent of the participants were willing to recommend the mentor-based training program to others. Conclusions Mentor-based visiting scholar training program is an effective way to enhanced medical education and has a positive impact on academic productivity.
    Application of 4Rs principle in animal experiments for the research of human functions
    CAI Wei-wei, DU Bin, CHEN Jun-liang, TANG Shai-di, QIU Li-ying
    2021, 41(11):  1696-1700. 
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    Objective To evaluate 4Rs principle applied in animal experiments for research and to optimize training outcomes with animal model. Methods The 4Rs principle was applied in four parts of training process with animal models including “replacing animal experiments with human physiological experiments” “integrating experimental projects, reducing the use of animals” “optimizing experimental process for minimizing animal suffering” and “strengthening ethical concepts, responsibility in research with experimental animals”. After class, feedbacks from students were collected through questionnaire survey and the data was analyzed. Results There were 92.0% medical students showed sympathize for the laboratory animals in the process of animal experiments; took care of the welfare of experimental animals while achieving training objectives. Conclusions The 4Rs principle provides a new idea and method for animal experiment and cultivates learners' animal ethics.
    Application of a Moodle-based blended teaching in medical education
    ZHANG Yan-li, WANG Zhi-gang, SHI Fu-ren, YANG Xiao-lin
    2021, 41(11):  1701-1706. 
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    The construction of a professional learning management system(LMS)platform is one of the important tasks in modern medical education reform. Peking Union Medical College (PUMC) had built the LMS based on open-source software modular object-oriented dynamic learning environment(Moodle)that supports the implementation of blended teaching methods. First, a teaching model for performing blended teaching effectively based on Moodle was built. Under the guidance of such model, the autonomous learning environment was established, which provided orderly, abundant and various learning resources for 46 medicine related courses in PUMC. In such a virtual environment, the students' self-directed learning could guided, supervised and provided feedback. The teachers could combine the virtual learning environment with classroom teaching closely, and develop more innovative and exploratory teaching activities. Furthermore, the data from whole learning process could be accumulated by Moodle easily to evaluate the teaching quality. Through Moodle, modern teaching methods could be applied in the medical education in PUMC effectively and efficiently.
    Application of PDCA circulation method in the management of teaching rounds of residents in department of ultrasound
    ZHENG Fan, CHEN Wen, ZHAO Bo, CUI Li-gang
    2021, 41(11):  1707-1710. 
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    Objective To evaluate PDCA circulation method in the management of teaching rounds of residents in department of diagnostic ultrasound. Methods PDCA circulation method was applied to the teaching rounds in department of ultrasound in Peking University Third Hospital from 2013—2019, and each circulation lasted for one year. PDCA circulation consists of four stages: plan, performance(do), check, and action. During the practice, the problems of the teaching round forms and contents were reviewed and modified to pick up content which were more suitable to department of diagnostic ultrasound. The improvement in teachers'assessment and training was also made according to the limitations in teacher training. Results PDCA circulation method improved the training quality of residents. All the residents in the third training year were competent to clinical performance and the residents all passed the phase Ⅰ skill examination of the standardized training in the past three years. Conclusions PDCA circulation method improves quanlity of teaching rounds and the training outcomes of residents in the department of diagnostic ultrasound.
    Application of network-based teaching for clinical practice in neonatology during COVID-19 pandemic
    ZHANG Le-jia, LI Zheng-hong, WANG Lin, WAN Wei-lin, DING Guo-fang, SONG Hong-mei
    2021, 41(11):  1711-1714. 
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    Objective To evaluate the strengthens and feasibility of network-based teaching for clinical training in neonatology during COVID-19 pandemic. Methods Because of COVID-19 pandemic, the interns of Peking Union Medical College Hospital accepted the network-based teaching in the training of neonatology from February to May 2020. Compared with those who received traditional training from November 2019 to January 2020, the Systematic Evatuation of Teaching Quality(SETQ) questionnaire and Pediatric Voluntary Self-assessment Forms were conducted to evaluate the quality of teaching and of knowledge mastery. Results There were no significant differences in teaching quality between two groups. While network-based teaching has favored knowledge mastery for rare diseases, complicated clinical operation and the interpretation of auxiliary examinations (P<0.05). Conclusions Network-based teaching and the traditional pathway have their strengthens respectively and can be complementary in the intern training of neonatology.