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Table of Content

    05 April 2022, Volume 42 Issue 4
    Original Articles
    Multiple omics verified that LAMC2 is a key factor regulating the pan-cancer microenvironment
    SU Lu-Ying, HUANG Rong, ZOU Ding-feng, XU Fu, LI Kai, LU Yan, MIAO Shi-ying, WANG Lin-fang, SONG Wei
    2022, 42(4):  545-552.  doi:10.16352/j.issn.1001-6325.2022.04.001
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    Objective The multiadhesion extracellular matrix protein LAMC2 was systematically analyzed with multiple databases. Multiple omics data demonstrates that LAMC2 is a key molecule affecting tumor development and clinical prognosis of patients. Methods The protein and RNA expressions of LAMC2 in various tumors and normal tissues were analyzed by database. The relationship between LAMC2 expression and survival rate of patients with different tumor types was investigated and immune infiltration analysis was performed. Finally, relationship between LAMC2 expression and immune invasion in tumor microenvironment of different tumor types was investigated. Results The expression of LAMC2 mRNA and protein was found to be higher in many tumors than in adjacent tissues and concentrated in malignant tumor cells in some tumors. In addition, LAMC2 expression has been found to be detrimental to the clinical prognosis of generalized carcinoma and was associated with immune invasion of various tumors. Conclusions LAMC2 is an important oncogene and may be an important target for effective treatment of tumors. These results provide a theoretical basis for subsequent molecular targeted therapy.
    mTOR activation up-regulates MGST1 and enhances cellular antioxidant capacity
    LI Jie, PU Yang, ZHANG Meng-di, ZHANG Peng-ju, XU Yin-zhe
    2022, 42(4):  553-559.  doi:10.16352/j.issn.1001-6325.2022.04.027
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    Objective To investigate the molecular mechanism of enhanced antioxidant capacity in mammalian target of rapamycin (mTOR) over-activated cell. Methods Differential gene analysis, functional and pathway enrichment analysis in mTOR activated cell were conducted by using gene expression omnibus (GEO) database.The mTOR-hyperactive tsc2-/-MEFs were treated with high dose spermidine to examine their antioxidant capacity.The core gene was screened by protein-protein interaction analysis. The expression of this core gene in mTOR activated cell was examined by q-PCR and Western blot. Core gene-knockdown cell line of mTOR activated cell was estab-lishedto study cell proliferation and antioxidant capacity. Core gene expression and prognosis of patient were analyzed in the TCGA liver cancer and melanoma data. Results The genes of the redox signaling in mTOR activated cells were significantly up-regulated.The mTOR activated cells were more resistant to high dose of spermidine(P<0.05).The core gene MGST1 was screened out due to its highest score of protein-protein interaction analysis(P<0.05). q-PCR and Western blot showed that MGST1 expression was significantly increased in mTOR activated cells(P<0.05). The expression of MGST1 decreased in rapamycin-treated mTOR activated cells. mTOR activated cell line was more sensitive to oxidative stress after MGST1 knockdown(P<0.05).Higher MGST1 expression was significantly associated with poor prognosis of patients based on TCGA liver cancer and melanoma data(P<0.05). Conclusions mTOR hyperactivation promotes the expression of MGST1 and enhances the antioxidant capacity of cells.
    Up-regulation of GSDMD-N and p-MLKL in rheumatoid arthritis synovial tissues
    LU Shan, ZHANG Bing-qing, YE Cai-ying, ZHU Lei
    2022, 42(4):  560-564.  doi:10.16352/j.issn.1001-6325.2022.04.002
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    Objective To explore the expression of pyroptosis marker protein GSDMD-N and necroptosis marker protein p-MLKL in rheumatoid arthritis (RA) synovial tissues and potential significance. Methods The clinical data of the enrolled patients were recorded,including gender, age, erythrocyte sedimentation rate (ESR) and hypersensitive C-reactive protein (hsCRP). HE staining and microscopy were performed on RA and osteoarthritis (OA) synovium, Krenn score was used to evaluate the pathological synovitis. The synovial proteins of RA and OA were extracted.The expression of the related proteins of pyroptosis and necroptosis was detected by Western blot, and the correlation of GSDMD-N and p-MLKL with ESR, CRP and pathological synovitis were analyzed. Results Compared with OA,the expression level of GSDMD-N and p-MLKL in RA synovial tissues was significantly increased(P<0.05), and was positively correlated with ESR and Krenn score(P<0.05). GSDMD-N was also positively correlated with CRP level(P<0.05). Conclusions Both pyroptosis and necroptosis in RA synovium show at positive correlation with disease activity and synovial inflammation, which might be involved in the process of RA synovitis and be potential targets for the treatment of RA.
    Escherichia coli in vitro recombinant system transports FhaB mutants
    HUANG Pi-ying, CAI Kun, WEI Liang-wan, WANG Xing-yuan, WANG Zhe, CHU Yin-di, FAN En-guo
    2022, 42(4):  565-569.  doi:10.16352/j.issn.1001-6325.2022.04.003
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    Objective To explore the mechanism of two-partner secretion with an in vitro reconstitution system. Methods Spheroplasts were used to construct FhaB mutants with different molecular weights, and then combined with FhaC containing proteoliposomes to perform the translocation experiments followed by digestion with proteinase K to test the transportation of substrates with different sizes in vitro by this recombinant system. Results After successful construction of the mutant, 37 ku, 60 ku and 80 ku bands secreted by spheroplasts were detected, and FhaC-containing protein liposomes could transport these three substrates with molecular weight as high as 80 ku. Conclusions The recombinant transport system constructed in vitro may transport substrates with large molecular weight and the mechanism of the two-partner secretion can be studied by this system.
    Carboxyamidotriazole-orotate inhibits proliferation and mitochondrial metabolism in human pancreatic cancer gemcitabine-resistant cell strain
    CHEN Qiu-xia, YANG Li-xing, MA Rui, ZHAO Yong-jing, WANG Yu-cheng, JU Rui, GUO Lei
    2022, 42(4):  570-576.  doi:10.16352/j.issn.1001-6325.2022.04.024
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    Objective To investigate the effects of carboxyamidotriazole-orotate (CTO) on proliferation, apoptosis and metabolism of human pancreatic cancer gemcitabine-resistant cell line (ASPC-1-GEM, AG cells). Methods Cell viability was detected by sulforhodamine B(SRB); apoptosis was detected by annexin V/PI staining and flow cytometry; cell division rate was examined by CFSE microscopy and flow cytometry; The oxygen consumption rate (OCR) was detected by Seahorse bio-energy assay; intracellular NAD+ and NADH contents were detected with MTT and NAD+/NADH ratio was calculated. Autophagy-related protein expression was detected by Western blot. Results Comparing with the control group, the living AG cells were significantly reduced and the proportion of apoptotic cells was increased in CTO-treated group. The drug effect was time-dose dependent. The fluorescence intensity of CFSE staining of AG cells was significantly increased in the 20 μmol/L CTO group (P<0.05); Compared with the control group, intracellular nicotinamide adenine dinucleotidehydrogen(NADH) content was increased after incubation with different concentrations of CTO treatment(P<0.05 or P<0.01) and no significant change in the content of nicotinamide adenine dinucleotide (NAD+) NDA+/NADH ratio was decreased(P<0.01). The OCR in AG cells was significantly reduced and the expression of autophagy-related proteins was significantly inhibited in the CTO-treated group (P<0.05). Conclusions CTO inhibits the proliferation of gemcitabine-resistant pancreatic cancer cells by inducing apoptosis, impairing mitochondrial respiration, and down-regulating the expression of autophagy-related proteins in AG cells.
    Factors related to hypertension in Kazakhs with different occupations in Altay city, Xinjiang Uygur Autonomous Region
    DU Jin, SHEN Yu-bing, YANG Cui-hong, CHEN Ya-li, JIANG Jing-mei
    2022, 42(4):  577-582.  doi:10.16352/j.issn.1001-6325.2022.04.026
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    Objective To investigate factors related to hypertension and their importance degrees in Kazakhs,from Altay city, Xinjiang Uygur Autonomous Region, with different occupations (citizen, farmer, and nomad) for target hypertension prevention. Methods According to the proportions of three occupation populations, 1 668 Kazakhs aged 30 years or older were selected by random cluster sampling from 2012 to 2013, in Hongdun Town, Altay City, Xinjiang. Hypertension related factors were investigated. We used random forest model to explore the factors related to hypertension and their importance degrees in different occupational groups. Results 1 646 participants were included in this study. We ranked the importance of hypertension related factors by feature importance scores. The top five hypertension related factors were waist circumference,triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), body mass index (BMI), and age for citizen; age, LDL-C, total cholesterol (TC), TG, and waist circumference for farmer. Age, BMI, waist circumference, TC, and LDL-C for nomad (feature importance scores>0.06). The prediction accuracy of random forest models of hypertension for citizen, farmer, and nomad were 0.82, 0.69, and 0.76, respectively. Conclusions In different occupational groups, obesity and blood lipids were related to hypertension in different degrees, so the target of hypertension prevention should be carried out for different occupational groups. With the process of urbanization, urban residents should be well informed to controlling central obesity.
    Propofol reduces anoxia-reoxygenation-induced injury of cardiomyocytes
    CHEN Si, YANG Fu-guo, PENG Hong-jun, CAO Wei-le, WANG Zhen-yu
    2022, 42(4):  583-589.  doi:10.16352/j.issn.1001-6325.2022.04.004
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    Objective To investigate the effect of propofol (Pro) on cardiomyocyte damage induced by anoxia-reoxygenation through regulating JNK/p38 MAPK pathway. Methods Divided the cells into control group, anoxia-reoxygenation (A/R) group, anoxia-reoxygenation+propofol of low, medium and high dose (A/R+Pro-L, A/R+Pro-M, A/R+Pro-H) group, anoxia-reoxygenation+propofol+p38 MAPK pathway inhibitor (A/R+Pro+SB203580) group. Flow cytometry was used to detect cell apoptosis; Western blot was used to detect the expression of Bcl-2, Bax, cleaved caspase-3 and JNK/p38 MAPK signaling pathway related proteins; ELISA was applied to detect LDH content, MDA content, SOD activity and CAT activity. Results In A/R group Bcl-2 protein expression SOD and CAT activity were significantly inhibited cell apoptosis rate, Bax protein, cleaved caspase-3 protein expression, LDH, MDA, p-JNK protein, p-p38 MAPK protein expression were promoted(P<0.05). Compared with A/R group, A/R+Pro-L group, A/R+Pro-M group, A/R+Pro-H group all showed significantly promoted cell Bcl-2 protein expression, SOD, CAT activity; inhibition of cell apoptosis, Bax protein, cleaved caspase-3 protein, LDH, MDA, p-JNK protein and p-p38 MAPK protein(P<0.05). Compared with the A/R+Pro group, the A/R+Pro+SB203580 group showed significantly promoted cell Bcl-2 protein expression, SOD, CAT activity and inhibited cell apoptosis, p-JNK protein, p-p38 MAPK protein, Bax protein, cleaved caspase-3 protein, LDH and MDA (P<0.05). Conclusions Propofol may slow down anoxia-reoxygenation induced cardiomyocyte apoptosis and oxidative stress through regulating the JNK/p38 MAPK pathway.
    miRNAs may involve in ventricular septal defect through regulating the MAPK pathway
    JIANG Hui, ZHANG Lin
    2022, 42(4):  590-598.  doi:10.16352/j.issn.1001-6325.2022.04.006
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    Objective To investigate the role of miRNAs in pathogenesis of ventricular septal defect. Methods The miRNAs differential expression in whole blood samples from ventricular septal defect (VSD) group and normal group was analyzed by miRNAs expression microarray experiment and the target genes were predicted by biological information databases miRbase, Targetscan and Miranda. Target gene signaling pathways were screened through KEGG and REACTOME pathway databases, the transcription and protein expression of key genes in key signaling pathways were detected by RT-qPCR and Western blot. Results A total of 22 cases of differentially expressed miRNA were obtained in the experiment, and 12 744 target genes were predicted. A total of 126 pathways were found and the MAPK pathway, which was closely related to heart development, and was deeply analyzed. Among them, the transcription and protein expression of RASA1 and NF1 in ERK pathway were significantly increased (P<0.05), the transcription and protein expression of RAS were significantly decreased(P<0.05), and the expression levels of ERK and MEK1 phosphorylated proteins were also significantly decreased(P<0.05); the transcription and protein expression of TNF, TNFRSF1A and TRAF2 in the p38/MAPK sub-pathway were significantly increased(P<0.05), the expression of p38 phosphorylated proteins was significantly increased(P<0.05), The transcrip-tion, total protein and phosphorylated protein expression of MEF2C were significantly increased(P<0.05). The above pathways were found to be regulated by 12 miRNA. Conclusions The abnormal expression of 22 differentially expressed miRNAs leads to a variety of known cardiac development-related gene expression disorders. Among them, 12 abnormally expressed miRNAs inhibit the ERK pathway and thus inhibit the differentiation of cardiomyocytes and over-activate the expression of p38/MAPK pathway to promote the abnormal apoptosis of cardiomyocytes, and ultimately lead to the occurrence of VSD.
    miR-655-3p targeting KIF20A inhibits migration and invasion of lung adenocarcinoma cell line A549
    DU Xue-mei, ZHANG Yun-mei, ZHOU Wen-ting, LYU Hong
    2022, 42(4):  599-606.  doi:10.16352/j.issn.1001-6325.2022.04.007
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    Objective To investigate the effects of miR-655-3p targeting kinesin family member 20A (KIF20A) on cell proliferation, migration and invasion of lung adenocarcinoma cells. Methods RT-qPCR was used to detect the expression of miR-655-3p in human lung adenocarcinoma cell lines H460, A549, HCC-2935, and H1299. A549 cells at logarithmic proliferation stage were divided into: blank group, miR-NC group, miR-655-3p mimics group, si-NC group, si-KIF20A group, miR-655-3p mimics+OE-NC group, miR-655-3p mimics+OE-KIF20A group. RT-qPCR was used to detect the miR-655-3p expression. Western blot was used to detect the KIF20A, matrix metalloproteinase 2 (MMP-2), MMP-9,RAS/mitogen-activated protein kinas (MAPK) pathway related protein expression; CCK-8 was used to detect cell proliferation; transwell experiment was used to detect cell migration and inva-sion; dual luciferase reporter gene detection experiment was used to verify the targeting relationship between miR-655-3p and KIF20A. Results miR-655-3p was less expressed in human lung adenocarcinoma cell lines, and has the lowest expression in A549 cells. Over-expression of miR-655-3p or silencing KIF20A inhibited A549 cell proliferation, migration, invasion and MMP-2, MMP-9, phosphorylation extracellular regulatory protein kinase 1/2(p-ERK1/2), phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein expression (P<0.05). The miR-655-3p targeted at and negatively regulated the expression of KIF20A. Up-regulation of KIF20A inhibited the effects of over-expression of miR-655-3p on the proliferation, migration, invasion and RAS/MAPK pathway related proteins of A549 cells. Conclusions Over-expression of miR-655-3p may down-regulate KIF20A and inhibit the proliferation, migration and invasion of lung adenocarcinoma cells. This mechanism may be related to the inhibition of the RAS/MAPK pathway.
    Cordycepin inhibits bronchial epithelial-mesenchymal transition in asthmatic rats
    TANG Li-ping, YAN Jin, FAN Fang, WANG Hao, HUANG Na
    2022, 42(4):  607-615.  doi:10.16352/j.issn.1001-6325.2022.04.022
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    Objective To investigate the mechanism of cordycepin (Cor) in the inhibition of epithelial-mesenchymal transition in asthmatic rats. Methods Rats were randomly divided into 4 groups (n=10): control group, ovalbumin (OVA) group, OVA+10 mg/kg Cor group, OVA+50 mg/kg Cor group. After 7 days of treatment, the cell counting in bronchoalveolar lavage fluid (BALF) was measured; hematoxylin-eosin (HE) staining was used to evaluate airway inflammation and airway remodeling. Masson's trichrome staining was used to detect epithelial collagen deposition. Human bronchial epithelioid cells 16HBE were divided into 3 groups: control group, TGF-β1 group and TGF-β1+Cor group. Immuno-fluorescence staining was used to detect the expression of c-Jun in the cells. Cell proliferation and migration were examined by cell counting kit-8 (CCK-8) and Transwell. The protein expression of E-cadherin, N-cadherin, α-SMA, vimentin, Smad3, p-Smad3, ERK1/2 and p-ERK1/2 was detected by immuno-histochemical staining or Western blot. Results With comparison with specific control groups, the following results were recorded. The collagen fiber area and cell count of OVA group increased significantly(P<0.05). The collagen fiber area and cell count of OVA+10 mg/kg Cor group and OVA+50 mg/kg Cor group both decreased (P<0.05). E-cadherin staining degree and protein expression of OVA group decreased, while the staining degree of α-SMA increased and the protein expression of N-cadherin, α-SMA and vimentin increased (P<0.05); E-cadherin staining degree and protein expression of OVA+10 mg/kg Cor group and OVA+50 mg/kg Cor group increased, while the staining degree of α-SMA decreased and the protein expression of N-cadherin, α-SMA and vimentin decreased (P<0.05). Compared with control group, the cell viability and the number of migrating cells in the TGF-β1 group increased (P<0.05); compared with the TGF-β1 group, the cell viability and the number of migrating cells in the TGF-β1+Cor group were both decreased (P<0.05). The expression level of E-cadherin protein in TGF-β1 group decreased, while the protein expression of N-cadherin, α-SMA, vimentin, p-Smad3 and p-ERK1/2 increased (P<0.05). The E-cadherin protein expression level of TGF-β1+Cor group increased, while the N-cadherin, α-SMA, vimentin, p-Smad3 and p-ERK1/2 protein expression levels decreased (P<0.05). The relative fluorescence intensity of c-Jun in TGF-β1 group increased (P<0.05); The relative fluorescence intensity of c-Jun in TGF-β1+Cor group decreased (P<0.05). Conclusions Cordycepin inhibits EMT in asthma by inhibiting Smad3 and ERK1/2 signaling pathway and c-Jun.
    Aldose reductase inhibitors inhibit the oxidative stress response of human bronchial epithelial cell line BEAS-2 induced by house dust mite
    BAO Min, LIN Mei, ZHEN Hai-ning, HE Fang, DING Min, YUAN Zhu-qing, CHEN Ya-jun, XUE Xin-xin
    2022, 42(4):  616-621.  doi:10.16352/j.issn.1001-6325.2022.04.021
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    Objective To investigate the inhibition of house dust mite induced oxidative stress with human bronchial epithelial cell line BEAS-2B by aldose reductase inhibitor (ARIs). Methods BEAS-2B was divided into control group, model group, NF-κB inhibitor group (PDTC group) and ARIs intervention group (ARIs group). Oxidative stress reaction (MDA and ROS content, SOD activity) was detected by ELISA. The contents of IL-5, IL-13 and IFN-γ were measured by ELISA. MTT was used to detect cell viability. Cell apoptosis was detected by flow cytometry. The expressions of NF-κB, NF-κB P65 and P38 MAPK proteins were detected by Western blot. Results SOD activity, IFN-γ content and cell survival rate in model group were lower than those in control group (P<0.05), MDA, IL-5, IL-13 content and cell apoptosis rate were higher than those in control group (P<0.05). Compared with model group, SOD activity, IFN-γ content and cell survival rate in PDTC and ARIs groups were increased(P<0.05), MDA, IL-5, IL-13 content and cell apoptosis rate were decreased (P<0.05). Compared with control group, the expression of NF-κB, NF-κB P65 and P38 MAPK protein in model group was significantly increased(P<0.05). The expression of NF-κB, NF-κB P65 and P38 MAPK protein in PDTC group and ARIs group were significantly decreased (P<0.05). Conclusions Aldose reductase inhibitors improve the oxidative stress response of human bronchial epithelial cells induced by house dust mites, promote the proliferation of BEAS-2B cells and inhibit apoptosis.
    Ketamine alleviates spinal cord ischemia-reperfusion injury of rats
    CHEN Yong, PANG Hong-li, XU Yuan-zheng, MAO Shan-shan, HONG Dao-xian
    2022, 42(4):  622-627.  doi:10.16352/j.issn.1001-6325.2022.04.025
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    Objective To investigate the effects of ketamine on spinal cord ischemia-reperfusion injury (SCII) and ERK1/2 signaling pathway in rats. Methods The rats were randomly divided into sham operation group (S group), SCII group (model was established by Zivin method), low and high-dose ketamine groups (given 50 and 100 mg/kg ketamine respectively every day for 14 days),with 8 rats in each group. The hind limb movement of rats was evaluated, inflammatory factors and oxidative stress indexes of spinal cord tissue were detected. The spinal cord neurons were microscopied by Nissl staining, apoptosis rate was detected by TUNEL assay, and protein expression was detected by Western blot. Results Compared with the S group, the Tarlov score in SCII group decreased after surgery and increased gradually with time,the number of normal nerve cells in the spinal cord decreased and the apoptosis rate increased,the levels of IL-1β, TNF-α, IL-6, VCAM-1 and malonaldehyde (MDA), myeloperoxidase (MPO) was found to be increased (P<0.05), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were significantly decreased (P<0.05), the expression of p-ERK1/2 and the ratio of p-ERK/ERK1/2 increased(P<0.05);Compared with SCII group, The changes of above indexes in ketamine group was reduced (P<0.05), and was more obvious in the low dose group. Conclusions Low dose ketamine can reduce the degree of SCII, and ERK1/2 signaling pathway may be involved in this process.
    Changes of BMP-2 and BMP-4 in early phase of sepsis
    WEN Yan, LIN Jin-can, HUANG Ying-hong, XIAO Wen-biao, ZHANG Min-wei, LIN Jian-dong
    2022, 42(4):  628-632.  doi:10.16352/j.issn.1001-6325.2022.04.020
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    Objective To study the change of serum bone morphogenetic protein (BMP)-2 and BMP-4 during the development of sepsis and its mechanisms. Methods Blood was collected for quantifying serum BMP-2 and BMP-4 from patients with sepsis (sepsis group), patients without sepsis (non-sepsis group) in 24 hours of ICU admission and from healthy volunteers (control group). Concentration of serum BMP-2 and BMP-4 was determined by ELISA. The expression of BMP-2, pSmad1/5, and BMPRⅡ of lip polysaccharide (LPS)-treated rat pulmonary microvascular endothelial cells (RPMECs) was detected by Western blot. Results Serum BMP-2 and BMP-4 were significantly increased in sepsis group (P<0.05) and the level of BMP-2 was significantly higher in sepsis group than that in non-sepsis group (P<0.05). BMP-2 was found to be a marker for differential diagnosis of separating sepsis LPS may significantly increase the expression of BMP-2 of RPMECs but decrease the expression of phosphorylated Smad1/5 (pSmad1/5) and BMP receptor Ⅱ (BMPRⅡ) (P<0.05). Conclusions BMP-2 is a potential diagnostic marker and act as apro-inflammatory factor in early phase of sepsis.
    Down-regulation of lncRNA-H19 expression promotes apoptosis and autophagy of human keloid fibroblasts
    HUANG Yun, XU Xi-sheng, CHEN Kai, HE Xiu
    2022, 42(4):  633-639.  doi:10.16352/j.issn.1001-6325.2022.04.023
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    Objective To investigate the effects of down-regulation of long non-coding RNA-H19 (lncRNA-H19) expression on apoptosis and autophagy of human keloid fibroblast cell line and to explore potential mechanism. Methods Human scar fibroblasts cell line (KFs) and normal human dermal fibroblasts cell line (HDFs) were collected and KFs cells were infected with lncRNA-H19F low-expressing adenovirus (si-lncRNA-H19) and empty virus vector without si-lncRNA-H19 (si-eGFP). They were divided into HDFs group, KFs group, si-lncRNA-H19+KFs group and si-eGFP+KFs group. KFs cells were co-transfected with si-lncRNA, mTOR over-expressing adenovirus (Ad-mTOR) and empty vector (Ad-eGFP-m), then divided into KFs group, si-lncRNA-H19+Ad-mTOR group,si-eGFP+Ad-mTOR group, si-lncRNA-H19+Ad-eGFP group and si-eGFP+Ad-eGFP group. RT-qPCR was used to detect the expression of lncRNA-H19; flow cytometry was used to detect the cell apoptosis ; autophagy was examined by EM microscopy with fluorescence (acridine orange,AO) staining; immuno-histochemical method was used to detect the positive expression of autophagy pathway-mammalian target of rapamycin (mTOR); Western blot was used to detect the expression of apoptosis and autophagy-related proteins. Results Compared with the HDFs group, the expression of lncRNA-H19 and mTOR activity in the KFs group increased and the number of autophagic vesicles and the expression of apoptosis and autophagy-related proteins decreased (P<0.05); after down-regulating lncRNA-H19 in KFs cells, the activity of mTOR in KFs cells decreased and apoptosis/autophagy increased (P<0.05). Up-regulating mTOR while down-regulating lncRNA-H19 lead to more autophagy and apoptotic in KFs cells as compared to that resulted from down-regulation of lncRNA-H19 alone (P<0.05). Conclusions Down-regulation of lncRNA-H19 expression may promote the autophagy and apoptosis of KFs cells through inhibiting activation of mTOR pathway.
    Clinical Sciences
    Impact of hospital-community-family integrated rehabilitation model on elderly patients with debilitating syndrome
    ABDUKLIMU Nurman, HAN Zheng-feng, MA Yan
    2022, 42(4):  640-645.  doi:10.16352/j.issn.1001-6325.2022.04.005
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    Objective To explore the impact of the integrated rehabilitation model of hospital-community-family on the debilitating state, quality of life and the expression level of inflammatory factors in the elderly. Methods A total of 116 patients with debilitating syndrome who were hospitalized from January 2019 to July 2020 in the First Affiliated Hospital of Xinjiang Medical University were selected and randomly divided into a control group and an intervention group, 58 cases in each group. The intervention group carried out “hospital-community-family” integrated system rehabilitation intervention on the basis of basic rehabilitation, and the control group adopted basic rehabilitation nursing. The debilitating state, quality of life and expression levels of inflammatory factors in two groups were recorded. Results After 3 months of intervention, the scores of Fried frailty phenotype, the three dimensions of physiological functions of life quality, physical pain and general health the level of inflammatory factors CRP and IL-6 in the intervention group were significantly different from those before the intervention (P<0.05). After 6 months of intervention, in addition to the above items, the four dimensions of energy, social function, emotional intelligence and mental health were also significantly different from those before the intervention (P<0.05). Conclusions The integrated hospital-community-family integrated mental rehabilitation model can effectively improve life quality of frail elderly patients and facilitate their rehabilitation.
    Mini Reviews
    Research progress on assessment of serum biomarkers related to senile frailty
    DAI Jing-rong, LI Jie, HE Xu, LI Yan
    2022, 42(4):  646-650.  doi:10.16352/j.issn.1001-6325.2022.04.018
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    The assessment of senile frailty still implemented with scales and questionnaires. This subjective assessment method is prone to vary greatly with the assessors and scales. Therefore, it is particularly important to explore the Objective diagnosis basis of frailty.With the continuous development of population cohort and observational studies, great progress has been made in the serology of senile frailty.This article mainly reviews the influence mechanism of serum inflammatory factors, hormones, vitamins, homocysteine and related protein molecules on frailty and provides new ideas to further exploring the Objective diagnosis basis of frailty in the elderly.
    Research progress of oncolytic virus combined with PD-1/PD-L1 inhibitors
    GAN Zi-ying, TANG Hui
    2022, 42(4):  651-655.  doi:10.16352/j.issn.1001-6325.2022.04.019
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    Oncolytic viruses are often used in combination with immune checkpoint inhibitors represented in two ways by programmed cell death 1/programmed cell death-Ligand 1 (PD-1/PD-L1). One is oncolytic virus combined with PD-1/PD-L1 inhibitors, which is modified by gene recombination and natural weak toxicity, and another one is oncolytic virus with gene recombination carrying PD-1/PD-L1 antibody gene.
    Progress of gut-kidney axis in the pathogenesis of crescentic glomerulonephritis
    YIN Huan-huan, SHI Xiao-xiao, CHEN Li-meng
    2022, 42(4):  656-660.  doi:10.16352/j.issn.1001-6325.2022.04.016
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    Crescent glomerulonephritis (CreGN) is the most dangerous glomerulonephritis and always leads to end stage renal disease (ESRD). The immunological mechanism plays an important role in its pathogenesis and prognosis. Recently, the role of the gut and intestinal microbiota in a variety of kidney diseases including CreGN has been disclosed. The “gut-kidney axis” will directly affect the immune response in the kidney and subsequent pathophysiology through the intestinal microbiota and gut-derived immune cells.
    Advances in diagnosis and evaluation of lymphoma through the detection of circulating cell free DNA
    BAI Xiao-teng, SUN Xiao-hong, ZHAO Xiang-yu, LI Zi-jian
    2022, 42(4):  661-666.  doi:10.16352/j.issn.1001-6325.2022.04.017
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    Circulating cell-free DNA(cf DNA) detection in peripheral blood is becoming increasingly convenient and inexpensive with the development of genetic testing technology. It provides a new option for diagnosis, prognosis prediction, post-treatment evaluation and disease surveillance of lymphoma patients. Especially in targeted therapy, lymphoma typing and diagnosis tend to be based on genetic characteristics, and the advantages of cf DNA detection from peripheral blood sample increasingly prominent.
    Research progress of correlation between thyroid cancer and diabetes mellitus
    FU Jing-lan, DENG Yuan-yuan, ZHANG Ying, ZHANG Xin-xu, CHEN Shi-jing, LIU Hui-xia
    2022, 42(4):  667-670.  doi:10.16352/j.issn.1001-6325.2022.04.014
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    Thyroid cancer (TC) is the most common malignant tumor of the endocrine system. Diabetes mellitus (DM) is a chronic metabolic disease caused by pancreatic β-cell dysfunction or insulin resistance. In recent years, with the increased morbidity of TC and DM , many studies have shown potential relationship between the occurrence and development of these two diseases.
    Extracellular vesicles in the pathogenesis of atrial fibrillation
    HE Dan, RUAN Zhong-bao
    2022, 42(4):  671-674.  doi:10.16352/j.issn.1001-6325.2022.04.008
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    Extra cellular vesicles (EVs) are small vesicles secreted or shed from cell membranes in circulating and body fluids and play a key role in intercellular communication. EVs can provide biomarkers for atrial fibrillation (AF) diagnosis, risk stratification and assessment and can be used as drug delivery vehicles for potential targeted therapies of AF.
    Research progress of DNA damage repair and its effect on perioperative cognitive dysfunction
    RONG Yu-lan, SHI Cheng-mei, GUO Xiang-yang
    2022, 42(4):  675-678.  doi:10.16352/j.issn.1001-6325.2022.04.009
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    The dynamic balance between DNA double-strand break (DSB) accumulation and repair is one of the important factors to maintain genomic stability. The homologous recombination (HR) and the non-homologous ending joining (NHEJ) are the two major pathways to repair DSB.In mature neurons of the central nervous system, the NHEJ is the main repair pathway of DSB.Recent studies in the molecular mechanism of NHEJ and peri-operative cognitive dysfunction (POCD) revealed several molecular mechanisms underlying the DNA damage repair and its links to POCD, which may provide a new therapeutic target.
    Medical Education
    Construction of pharmacy teaching case resource library in tertiary A-level public hospital
    KANG Yi, WU Wei-dong, ZHANG Dong-su, SU Ye, LIU He, AN Zhuo-ling
    2022, 42(4):  679-683.  doi:10.16352/j.issn.1001-6325.2022.04.015
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    Objective To construct a teaching case resource library for pharmacy teaching, which meets the needs from the new health care-oriented reformation in tertiary A-level public hospital. Methods A case compiling group was organized to collect, sort and retrieve cases. The case compilation was completed according to the specification for the preparation of professional cases for Master candidates of Pharmacy degree. After case modification, review and screening, the cases were chosen to be included in the group and finally to create a case resource database. Results Totally 34 typical cases in literature and 109 high-frequency drug and administration examples from pharmacy department, a certain hospital, Capital medical university from January 1st to August 31, 2021 were selected to build the database. Conclusions The case resource library for pharmacy training in tertiary A-level public hospital was constructed which may effectively support the training of qualified clinical pharmacists.
    Practice of OSCE in assessment for standardized training of residents in Beijing
    ZHANG Yu, ZHU Dan-tong, LUO Lin-zhi, ZHAO Jun, DONG Hai-tao
    2022, 42(4):  684-687.  doi:10.16352/j.issn.1001-6325.2022.04.012
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    Objective structured clinical examination (OSCE) is a tool to evaluate medical students' clinical competence in a simulated clinical setting, so it has been regarded as a clinical competency assessment method based on KAS model ( knowledge, skills and attitudes). Development of OSCE is a complicated system engineering process. A reasonable design is the foundation of the successful completion of OSCE, and a professional team of excellent examination service is the guarantee of the efficient operation of OSCE. This article takes Peking Union Medical College Hospital as an example to introduce the practice of OSCE in the evaluation of clinical competence of trainees after resident standardized training in Beijing.
    A survey on the current role of radiologists in the multidisciplinary team of inflammatory bowel disease in China
    LIU Jing-juan, LIU Wei, YANG Hong, XUE Hua-dan, QIAN Jia-ming, JIN Zheng-yu
    2022, 42(4):  688-691.  doi:10.16352/j.issn.1001-6325.2022.04.011
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    Objective To review the current status and development of radiologists in the multidisciplinary team (MDT) working in a inflammatory bowel disease (IBD). Methods A nationwide questionnaire survey was conducted to investigate the general situation of the MDT in IBD in China, particularly about the composition of radiologists, the presentation form of MDT consulting images and the participating pattern of radiologists. Results A total of 28 domestic MDT centers of IBD participated in the survey, all of then were tertiary hospitals and 23(82.1%) were located in the eastern part of the country. Among them, 27 MDT expert groups had radiologists. In the MDT center with radiologist participation, there were 21(77.8%) were senior doctors with more than 10 years of working experience, and 26 radiologists specialized in gastrointestinal and abdominal imaging (13 for each, 48.1%). 22(81.5%) radiologists reviewed all the cases in advance, and 26(96.3%) radiologists participated deeply in MDT discussions to provide professional radiological diagnosis and recommendations. Conclusions In the healthcare mode of the new era, radiologists are playing an increasingly important role in the diagnosis, treatment and management of IBD patients.
    Implementation and evaluation of department rotation examination in resident standardized training
    SHI Xiao-chun, HUANG Can, LI Hang
    2022, 42(4):  692-695.  doi:10.16352/j.issn.1001-6325.2022.04.010
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    Objective To introduce and evaluate the department rotation examination system of the department of internal medicine in Peking Union Medical College Hospital (PUMCH). Methods Residents enrolled in Peking Union Medical College Hospital Internal Medicine Training Program between September 2017 and August 2019 were evaluated. The test results of medical theory and clinical practice were analyzed. Results The results of examination were different with statistically significant among different departments(F=34.164,P<0.001). The poorest test result was got in the department of medical intensive care unit(MICU), test result of the department of infectious disease came next. Furthermore, test results of residents from PUMCH were better than undergraduate residents and residents from Beijing Training Base;and test results of undergraduate residents were better than residents from Beijing Training Base. Conclusions Department rotation examination plays an important role in evaluating clinical competence of internal medicine residents. Targeted training and stratifying management can be performed according to the test results, which may promote the effectiveness of the resident standardized training.
    Short-term semi-immersion training based on a learning pyramid model theory can improve the capacity building to find early gastric cancer
    CHEN Xi, PANG Hai-yu, QIN Chun-di, GUO Yuan-hong, YANG Ai-ming, LAI Ya-min
    2022, 42(4):  696-700.  doi:10.16352/j.issn.1001-6325.2022.04.013
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    Objective To explore the effect of short-term semi-immersion teaching and training based on the learning pyramid model to improve the capacity building of to find early gastric cancer by digestive endoscope physicians. Methods Thirty digestive refresher doctors were randomly selected from our center for 4-week semi-immersion training. The capacity of the trainees to recognize early gastric cancer was tested before and after 4 weeks of training, and the accuracy of the test was compared. Results The accuracy of the test before training, after theoretical lesson and after 4 weeks of training were 44.58%±16.39%, 48.54%±16.95% and 68.75%±12.06% respectively. The test accuracy after theory lesson plus 4 weeks of training was higher than that before training and after only theoretical lesson (P<0.001).The test accuracy after theoretical lesson was higher than that before the training(P<0.05). When grouping by the number of cases in previous gastroscopy, no matter before training or after theoretical lesson, the test accuracy with experience in testing was higher than group with less experience. However, the test accuracy of the two groups almost reached a same level after 4 weeks of training(P<0.01). With the extension of training time, the test accuracy gradually increased (P<0.001). There was an interaction between grouping and training time (P<0.001).In the correlation analysis, the number of cases of the previous gastroscopy performance was positively correlated with the test accuracy before training and after theoretical lesson (r=0.668,<0.001,r=0.581, P<0.01). Conclusions Semi-immersion training guided by the learning pyramid model can effectively improve the capacity of digestive endoscope physicians to recognize early gastric cancer.