Table of Content

    05 July 2022, Volume 42 Issue 7
    Original Articles
    Expression profile of lncRNA in miR-150 over-expressed cell line HK-2
    HAO Xiang-nan, LUAN Jun-jun, MA Cong, ZHANG Yi-xiao, ZHOU Hua
    2022, 42(7):  1013-1019.  doi:10.16352/j.issn.1001-6325.2022.07.1013
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    Objective To analyze differential expression of long non-coding RNA (lncRNA) after miR-150 over-expression by human renal tubular epithelial cell line HK-2 and explore the role of miR-150 in renal tubular injury through regulating the expression of lncRNA. Methods HK-2 cells with miR-150 mimic and scramble were sequenced by Illumina NovaSeq 6000 sequencer. The differentially expressed lncRNA expression profile, GO analysis and KEGG analysis were performed to verify miR-150-lncRNA-JAK2-STAT1/3-COL1 pathway. Results Compared with the scramble group, 362 differential expression lncRNAs were detected in miR-150 mimic group, of which, 252 lncRNAs were down-regulated and 110 lncRNAs were up-regulated both more than 1.5-fold. The results showed that the miR-150 regulated lncRNA and function in biological process, cell components and molecular mechanisms through enrichment analysis of KEGG pathway, miR-150-lncRNA-JAK2-STAT1/3-COL1 pathway was found and then verified by Western blot. Conclusions LncRNAs regulated by miR-150 may play some roles in pathogenesis and molecular mechanisms in human renal tubular injury.
    Deubiquitinase OTUB1 is involved in the cellular response to copper deficiency
    ZHANG Yu-fei, ZHU Ji-yan, QU Si-yao, ZHANG Zhu-qin, LIU De-pei
    2022, 42(7):  1020-1025.  doi:10.16352/j.issn.1001-6325.2022.07.1020
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    Objective By establishing a copper deficiency cell model to explore whether there are copper-dependent enzymes involved in cardiac hypertrophy caused by copper deficiency. Methods The Ctr1 knockout H9c2 cell strain was established by CRISPR/Cas9 technology; The proteins in wildtype (WT), Ctr1-/-, and copper chelator TTM-treated H9c2 cells were collected, and the protein was screened by copper affinity resin pull down experiment combined with mass spectrometry analysis to find out an enzyme which could interact with copper; The downstream signaling pathway of this enzyme in copper-deficient cells was detected by Western blot. Results The H9c2 cell strain with knockout of Ctr1 was successfully established, and the copper level in this cell strain was significantly reduced (P<0.05). Mass spectrometry analysis screened out the deubiquitinase OTUB1 that could interact with copper; The level of ubiquitination in copper-deficient H9c2 cells was increased; Under the condition of copper deficiency, the level of OTUB1 target protein DEPTOR decreased, and the mTOR signaling pathway was activated in H9c2 cells. Conclusions The deubiquitinase OTUB1 is involved in the cellular response to copper deficiency, suggesting that it may be involved in the development of copper deficiency-induced cardiac hypertrophy.
    Protein tyrosine phosphatase 4A3(PTP4A3) promotes enucleation in mouse fetal liver-derived erythroid cells
    HU Xin-jun, YU Dong-lin, FAN Hong, HAN Gai-jing, XUE Zheng, LYU Xiang
    2022, 42(7):  1026-1030.  doi:10.16352/j.issn.1001-6325.2022.07.1026
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    Objective To investigate the expression and function of protein tyrosine phosphatase 4A3(PTP4A3) in terminal erythroid differentiation and underlying molecular mechanism. Methods RT-qPCR was used to detect the expression of Ptp4a3 during terminal differentiation. Knockdown of Ptp4a3 expression in mouse fetal liver induced erythroid differentiation system by short hairpin RNA(shRNA) interference, the knockdown efficiency was verified by RT-qPCR after GFP positive cells were sorted by flow cytometry, and the effect of Ptp4a3 knockdown on erythroid differentiation and enucleation was detected by flow cytometry. Transcriptional profiling was performed to explore the potential downstream pathways of Ptp4a3. Results Ptp4a3 was among the top 100 ranked expressing genes during mouse terminal erythroid differentiation, and its expression gradually increased following the differentiation process. In mouse fetal liver-derived erythroid cells, Ptp4a3 was successfully knocked down by shRNA interference. Flow cytometry analysis showed that Ptp4a3 knockdown significantly decreased the proportion of enucleated erythrocytes(P<0.05). Transcriptome analysis revealed that Ptp4a3 knockdown resulted in upregulation of cell cycle-related genes. Conclusions PTP4A3 is highly expressed in late stage of terminal erythroid differentiation. Knockdown Ptp4a3 significantly reduces enucleation erythroid of cells.
    Application of a new micro-cannula for the establishment of a Parkinsonian mouse model
    ZUO Fu-xing, YUAN Qing, CAI Hong-qing, HAN Rui-qin, WAN Jing-hai
    2022, 42(7):  1031-1034.  doi:10.16352/j.issn.1001-6325.2022.07.1031
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    Objective To explore the feasibility of a modified micro-cannula for intra-cerebral administration of 6-hydroxydopamine(6-OHDA) in order to establish a Parkinsonian mouse model. Methods Twenty female mice(C57BL/6J) were randomly divided into 2 groups with 10 in each: experimental group (new micro-cannula) and control group (regular Hamilton syringe). Following unilateral injection of 6-OHDA, the behavioral test and histological microscopy were performed. Results All mice in experimental group showed the morphology of apomorphine-induced rotational asymmetry, but the same results were found in only 5 mice from control group. Total number of rotations away from the lesion side in 30 minutes showed 6-OHDA-induced motor deficits at day 7 in both groups, which was significantly attenuated at day 28 in control group (P<0.05). After 28 days of 6-OHDA injection, significant reduction in the number of rotations was observed in control mice as compared with that of experimental group (P<0.05). As immunohistochemistry showed that the total number of remaining dopaminergic neurons significantly decreased in the substantial nigra of the experimental mice as compared with the control mice(P<0.05). Moreover, more local astrocytes underwent activation, part of which acquired the properties of neural precursor cells in control mice. Conclusions Intrastriatal injection of 6-OHDA using the new micro-cannula is a feasible technology in the development of a more reliable Parkinsonian model of mice.
    Preparation of caffeic acid-grafted gelatin hydrogel and its antioxidant function
    HAO Bo-ya, ZENG Fei, WEN Tao, MENG Jie, XU Hai-yan, LIU Jian
    2022, 42(7):  1035-1041.  doi:10.16352/j.issn.1001-6325.2022.07.1035
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    Objective To fabricate caffeic acid-grafted gelatin (CA-gel) hydrogels and investigate effects of the grafting ratios on the physicochemical properties of the hydrogels, and evaluate the antioxidant function of hydrogels. Methods CA-gel gelatin was synthesized by controlling the ratio of caffeic acid and gelatin, and the hydrogels were formed with laccase as the cross-linking agent. The molecular structure of caffeic acid-grafted gelatin was characterized by HPLC and 1H-NMR. The grafting degree of caffeic acid was determined by UV-Vis spectrophotometer and the gelation time of hydrogel was determined by vial-tilting method. The elastic modulus was measured by microsphere indentation method. The swelling ratio and degradation rate of the hydrogel were calculated according to mass change before and after swelling and degradation, and the scavenging effect on DPPH radical(DPPH·) was determined by the change of absorbance of DPPH radical solution. Cell counting kit-8 was used to evaluate the cytotoxicity of the hydrogels and the protective effect on fibroblasts in high oxidative stress microenvironment. Results Caffeic acid was grafted onto gelatin molecules with following respective parameters: grafting degrees were 33.0 μmol/g, 61.8 μmol/g and 74.4 μmol/g, the gelation time was 33 min, 42 min and 47 min, the swelling ratios of the hydrogels were 896.5%, 835.3% and 803.9%, the elastic modulus of the hydrogels were 7.2 kPa, 29.4 kPa and 34.5 kPa, and the scavenging effects on DPPH radical of the hydrogels were 38.5%, 41.9% and 49.8%, respectively. In addition, the degradation rate decreased with the increase of grafting degree. The hydrogels were non-cytotoxic and displayed protective effect on the fibroblasts in the peroxide-existing environment. Conclusions CA-gel hydrogels have adjustable gelation time, biodegradation rate, elastic modulus and free radical scavenging activity and show a significant protective effect against fibroblasts in high oxidative stress microenvironment as well.
    Timed Up and Go test is associated with cognitive impairment in elders from East China
    LIU Yan-li, MA Ya-jun, PAN Yan, ZHAO Rui-xue, ZHAO Tun, JIANG Xiao-yan, LI Shu-juan
    2022, 42(7):  1042-1046.  doi:10.16352/j.issn.1001-6325.2022.07.1042
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    Objective To explore a potential relationship of Timed Up and Go (TUG) test to cognitive functions among elders. Methods The participants were from Rugao Longevity and Ageing Study conducted in Jiangsu province, China. TUG test was completed, recording gaits stability, test time and the overall scale. Cognitive function was evaluated using Chinese version of revised Hasegawa's Dementia Scale (HDS-R). Results A total of 1 655 participants (aged 75-84 years old) completed the TUG test and cognitive evaluation were included in this study. Among them, 872(52.7%) in cognitive impairment group and 783(47.3%) in non-cognitive impairment group, the gait stability, time and scale of TUG test were inverse associated with HDS-R and its subcomponents, respectively(P<0.001). Logistic regression analysis showed that unsteady gait(OR=1.11, 95% CI:1.08-1.14, P<0.001), longer time (OR=2.50, 95% CI:1.76-3.55, P<0.001) and deteriorated scale (OR=1.62, 95% CI:1.39-1.89, P<0.001) in TUG test were independently associated with increased risk of cognitive impairment. Conclusions Worse motor function performance on TUG test is significantly associated with cognitive impairment. The application of TUG test is potential method in early risk screening of cognitive impairment in community and has certain feasibility.
    Lnc000727 promotes differentiation of human bone marrow mesenchymal stem cells into osteoblasts
    PU Chao, ZHANG Shan-shan, WU Qing-xia, LUO Xu-wei, WANG Liang, ZHANG Bo
    2022, 42(7):  1047-1052.  doi:10.16352/j.issn.1001-6325.2022.07.1047
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    Objective To explore the effect of lnc000727 on the differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) into osteoblasts. Methods Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression of lnc000727. The alkaline phosphatase (ALP) method was used to determine the differentiation of osteoblasts. The expression of lnc000727 in hBM-MSCs was over-expressed or inhibited by liposome transfection. The osteogenic differentiation markers Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and pontin were detected by RT-qPCR and Western blot. Pontin (OPN) mRNA and protein expression. The expression of key proteins in the Wnt/β-catenin pathway was analyzed. Results During the differentiation of hBM-MSCs osteoblasts, the expression of lnc000727 and ALP activity increased significantly(P<0.05). Inhibition of lnc000727 could down-regulate ALP activity and inhibit the expression of osteogenic differentiation markers RUNX2, OCN, OPN and the expression of Wnt and β-catenin (P<0.05); over-expression of lnc000727 could up-regulate ALP activity and promote the expressions of osteogenic differentiation markers RUNX2, OCN and OPN, and the expressions of Wnt and β-catenin (P<0.05). Conclusions Lnc000727 promotes the differentiation of hBM-MSCs into osteoblasts, thereby inhibits the occurrence and development of osteoporosis.
    Ophiopogonin B inhibits proliferation and migration of human esophageal squamous cell carcinoma cell line EC9706
    ZHONG Ming, YU Xiu-yi, GUO Wei-xi, FANG Zheng
    2022, 42(7):  1053-1059.  doi:10.16352/j.issn.1001-6325.2022.07.1053
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    Objective To explore the effect of ophiopogonin B(OP-B) on the biological behavior of esophageal squamous cell carcinoma cell line(EC9706) and its mechanism related to the regulation of Down syndrome cell adhesion molecule antisense 1 (DSCAM-AS1) and miR-199a-3p expression. Methods EC9706 cells were divided into control group, experiment groups with low, medium and high dosage of OP-B, si-NC group, si-DSCAM-AS1 group and (pcDNA-DSCAM-AS1+OP-B) group. Colony formation and CCK-8 method were used to detect EC9706 proliferation. Flow cytometry and scratch healing test were used to analyze the apoptosis rate and migration of EC9706 cells. RT-qPCR was performed to detect the expression of DSCAM-AS1 and miR-199a-3p. The targeting relationship between DSCAM-AS1 and miR-199a-3p was verified using dual luciferase reporter gene experiment. Results OP-B reduced EC9706 viability, colony formation counting, migration distance and DSCAM-AS1 expression (P<0.05), increased cell apoptosis rate and miR-199a-3p expression (P<0.05). DSCAM-AS1 interacted directly with miR-199a-3p. After interference to DSCAM-AS1 expression, the cell viability, colony formation and migration distance of EC9706 cells were significantly reduced(P<0.05), while apoptosis rates were significantly increased(P<0.05). Over-expression of DSCAM-AS1 antagonized the effects of OP-B on the proliferation, apoptosis and migration of EC9706 cells(P<0.05). Conclusions OP-B inhibits proliferation and migration of esophageal squamous cell carcinoma cells and induces cell apoptosis. The mechanism is potentially explained by down-regulating DSCAM-AS1/miR-199a-3p pathway.
    Deleted in breast cancer 1(DBC1) affects the sensitivity of breast cancer cell lines to etoposide
    HAN Xue-ying, CUI Feng, LI Jun
    2022, 42(7):  1060-1066.  doi:10.16352/j.issn.1001-6325.2022.07.1060
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    Objective To compare the sensitivity of deleted in breast cancer 1 (DBC1) in triple-negative breast cancer cell lines HCC-70 and MDA-MB-231 to DNA damage agents. Methods The HCC-70 cell strain with DBC1 knockdown was generated by lentivirus infection. Etoposide was used to induce DNA damage. The DNA damage repair proteins and cell cycle regulation proteins were detected by Western blot; the cell survival rates were detected by CCK8 test; the apoptosis was measured by flow cytometry. Results Etoposide changed cell survival rate and apoptosis of HCC-70 cells but not statistically significant, while the decrease of the survival rate and apoptosis level of MDA-MB-231 cells was significant (P< 0.001). There was a negative correlation between the expression of DBC1 protein in HCC-70 and MDA-MB-231 cells; after knocking down DBC1 in HCC-70 cells to close to the level of MDA-MB-231 cells, the level of Bloom's syndrom helicase(BLM), p21, cell survival rate (P<0.001) and apoptosis rate (P<0.01) were similar to those of MDA-MB-231 cells; the combination of ML216, an inhibitor of BLM, and etoposide significantly decreased the survival rate of MDA-MB-231 cells increased apoptosis (P<0.01). Conclusions DBC1 is able to affect the sensitivity of breast cancer cells to DNA damage reagent etoposide and ML216 can increase the sensitivity of etoposide to breast cancer cells with low expression of DBC1.
    Serum IFN-γ is increased in patients with active vitiligo
    ZHAO Xiao-ling, HE Run-zhi, SUN Yu-jiao, ZHANG Xiao-chong, YANG Lin-fang, WANG Rui, CHENG Fang
    2022, 42(7):  1067-1070.  doi:10.16352/j.issn.1001-6325.2022.07.1067
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    Objective To examine serum C-reactive protein (CRP), tumor necrosis factor-α(TNF-α), tumor necrosis factor-β(TNF-β), E-cadherin (E-cad), human interferon-γ (IFN-γ) and cluster of differentiation 8 (CD8) in patients with vitiligo. Methods From May 2017 to December 2018, 60 patients with vitiligo (30 cases in active phase group and 30 cases in stable stage group) and 30 cases as control group collected from physical examination center joined the research program. The content of serum CRP, TNF-α, TNF-β, E-cad, IFN-γ and CD8 were compared among the three groups by enzyme-linked immunosorbent assay (ELISA). Results The content of serum CRP, TNF-α, TNF-β and IFN-γ in patients with active and stable vitiligo were significantly higher(P<0.05). The content of serum IFN-γ in patients with active vitiligo was significantly higher than that in patients with stable vitiligo(P<0.05)and significantly decreased after 6 months of treatment(P<0.05). Conclusions The content of serum IFN-γ might be used as a biomarker in laboratory to evaluate the activity of vitiligo.
    Lnc-SLC2A12-10:1 silencing inhibits the proliferation, migration and invasion of gastric cancer cell line AGS
    LIU Lei, LI Shi-bao, ZHANG Hao-liang
    2022, 42(7):  1071-1076.  doi:10.16352/j.issn.1001-6325.2022.07.1071
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    Objective To investigate the effect of long non-coding RNA(lncRNA) lnc-SLC2A12-10:1 silencing on the proliferation, migration and invasion of gastric cancer cell line AGS. Methods Gene interference technology was used to construct the lnc-SLC2A12-10:1 silenced gastric cancer cell strain AGS, and RT-qPCR was used to verify the interference efficiency by lnc-SLC2A12-10:1 silencing. The proliferation of AGS cell was examined by CCK-8 method. The cell migration and invasion were evaluated by wound healing and Transwell assay. Bioinformatics prediction software was applied to predict lnc-SLC2A12-10:1 targeting miRNA and to verify them with RT-qPCR. Results Lnc-SLC2A12-10:1 shRNA effectively silenced expression of lnc-SLC2A12-10:1, and lnc-SLC2A12-10:1 silencing inhibited the proliferation of gastric cancer cells (P<0.05). Lnc-SLC2A12-10:1 silencing also inhibited the migration and invasion of AGS cells (P<0.05). It had been demonstrated that lnc-SLC2A12-10:1 targeting miRNAs might be hsa-miR-105-5p and hsa-miR-150-3p. Conclusions Lnc-SLC2A12-10:1 silencing can significantly inhibit the proliferation, migration and invasion of AGS cells.
    Clinical analysis of the resistance of Helicobacter pylori to commonly prescribed antibiotics in Chinese mainland
    ZHAO Xia, XU Wei-wei, LIU Yi-meng, SUO Zhi-min
    2022, 42(7):  1077-1082.  doi:10.16352/j.issn.1001-6325.2022.07.1077
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    Objective To find the trends and regional differences of the resistance of Helicobacter pylori(Hp) to metronidazole, clarithromycin, levofloxacin, amoxicillin, furazolidone and tetracycline in recent years in the mainland of China. Methods By searching several databases, the literatures on the resistance of Hp to six commonly prescribed antibiotics in mainland of China were collected and analyzed with Stata15 software. The antibiotic resistance in Huaihe Hospital of Henan University was reviewed and compared. Results The investigation results from 2013 to 2020 showed that rate of Hp metronidazole resistance was the highest and the clarithromycin was the second, while the rate of resistance to amoxicillin was the lowest one. The amoxicillin resistance in the south of China was significantly higher than that in the north of China. The resistance to metronidazole, clarithromycin, levofloxacin and amoxicillin reached (or closed to) the highest level from 2019 to 2020. At present, the resistance to amoxicillin and furazolidone was low and the resistance to clarithromycin was the highest in Huaihe Hospital of Henan University. Conclusions The resistance of Hp to antibiotics in the mainland of China was at a relatively high level. The resistance rate to metronidazole and clarithromycin was high, while that to amoxicillin was low. The antibiotic resistance of HP was more popular in the south of China.
    Establishment and validation of lung-specific metastatic cell subline of mouse breast cancer
    WANG Zi-yuan, DUAN Zhao-jun, LUO Yun-ping
    2022, 42(7):  1083-1091.  doi:10.16352/j.issn.1001-6325.2022.07.1083
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    Objective To screen and establish a spontaneously high organotrophic cell subline of metastatic breast cancer and to validate characteristic and the organotropism of the lung metastasis cell subline obtained from the screening. Methods By using the experimental lung metastasis, mouse breast cancer cells line 4T07 were injected into tail vein of mouse. Retrieving metastatic tumor cells in the lung and enriching them in vitro; By using the spontaneous metastasis model, the mammary fat pad was inoculated with tumor cells. Combined with the in vitro expansion culture of lung metastasis and repeated three times, a lung organotrophic cell sub-line and model of spontaneous lung metastasis were obtained; A highly metastatic cell subline stably expressing luciferase was obtained by transfection and screening. Cell morphology was microscopied with HE staining and an in vivo imaging system was performed to detect the migration and lung-specific metastasis. Flow cytometry was used to analyze the changes of immune cells in primary site, metastasis and spleen. Wound healing and Transwell assays were performed to detect migration of cell lines in vitro. Results A mouse breast cancer lung-specific metastatic cell subline (4T07LuM) was successfully established. in vivo imaging results validated that the fluorescent signal was mainly concentrated in the lung after injection of 4T07LuM cells labeled with luciferase in situ. HE staining microscopy results verified tumor metastasis in the lung. In addition, according to the results of Transwell and wound healing assays, 4T07LuM, compared to the parental cells 4T07, had shown a significantly more invasive migration(P<0.001). Finally, according to the results of flow cytometry detection, 4T07LuM cell had showed significantly altered the immune cell ratios as compared to that of 4T07 cell. The immune microenvironment in vivo was more inclined to an immuno-suppressed state. Conclusions Cell sublines with high organ-specific metastasis ability are obtained through combination of serial screening of experimental and spontaneous metastasis and in vitro culture expansion.
    VAV1 is a potential target and a new biomarker for the prognosis of atherosclerosis
    XIE Si-an, XU Jun-xuan, NING Ting-ting, ZHANG Nan, ZHU Sheng-tao, LIU Si
    2022, 42(7):  1092-1098.  doi:10.16352/j.issn.1001-6325.2022.07.1092
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    Objective To verify the expression of vav guanine nucleotide exchange factor 1 (VAV1) in the progression of atherosclerosis (AS) based on bioinformatics analysis and biological experiments and, to verify its potential regulatory role in vascular smooth muscle cells (VSMCs). Methods Three datasets of AS were obtained from Gene Expression Omnibus (GEO)and differentially expressed genes (DEGs) were identified. Hub genes were screened by GEO2R, Jvenn, STRING and Cytoscape. The expression and localization of VAV1 and SMMHC in vessels were detected by immuno-fluorescence staining(IFC).Western blot and real-time PCR were used to detect the expression of VAV1, SMMHC and SM22α. The contraction and proliferation of VSMCs were detected by collagen gel contraction assay and 5-ethynyl-2 deoxyuridine (EdU) staining. Results Totally 66 up-regulated genes and 88 down-regulated genes were identified in three datasets. Screening 10 Hub genes including VAV1 may be related to the progression of AS. IFC showed that the expression of VAV1 in AS plaque was significantly higher than that in normal vascular tissue (P<0.05) and mainly located in VSMCs; Knocking down VAV1 promoted the contraction of VSMCs and inhibited its proliferation(P<0.05). Conclusions The expression of VAV1 in AS plaques is increased, which is associated with the decreased contractility of VSMCs. VAV1 is a potential prognostic biomarker and therapeutic target of AS.
    SIRT5 promotes the proliferation of human breast cancer cells by regulating the succinylation of ALDH5A1
    KANG You-li, ZHAO Dan, DU Wen-jing, LI Li
    2022, 42(7):  1099-1107.  doi:10.16352/j.issn.1001-6325.2022.07.1099
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    Objective To analyze the expression of SIRT5 in pan-cancer and its relationship with prognosis and to explore the mechanism of SIRT5 regulating breast cancer proliferation through aldehyde dehydrogenase 5 family member A1(ALDH5A1). Methods cBioPortal,TNMplot,GEPIA and The Kaplan-Meier Plotter were used to analyze the differential expression of SIRT5 in a variety of tumors and its correlation with prognosis. The interacting proteins co-precipitated with the SIRT5 were analyzed by mass spectrometry. Pathway enrichment was performed for the interaction proteome, and for the combined analysis of the interaction proteome and the acylation proteome. Finally, the ALDH5A1 was focused. Then, the interaction between SIRT5 and ALDH5A1 was determined by an in vivo and in vitro immunoprecipitation(IP).SIRT5 was over-expressed or knocked down to detect acylation level and enzyme activity of ALDH5A1. Finally, the effects of SIRT5 and ALDH5A1 on breast cancer proliferation were determined by cell proliferation and cloning experiments. Results SIRT5 was highly expressed in a variety of tumors such as breast cancer and was positively correlated with poor prognosis (P<0.05). There were multiple overlaps between SIRT5 interacting proteins and acylomics and the overlapped proteins were mainly enriched in metabolic pathways such as amino acid metabolism. SIRT5 directly interacted with ALDH5A1. SIRT5 could enhance the enzyme activity of ALDH5A1 by inducing the desuccinylation of ALDH5A1, thus promoting the proliferation of breast cancer cells (P<0.05). Conclusions The function of SIRT5 in tumors may be specific to a heterogeneous environment and it can play a tumor-promoting role through ALDH5A1 in breast cancer. The results reported here may provide a theoretical basis for subsequent clinical targeted therapy.
    Sedation effect of different regimens of dexmedetomidine in day-case ophthalmic surgery
    YUE Jian-ying, LI Ming, XI Chun-hua
    2022, 42(7):  1108-1112.  doi:10.16352/j.issn.1001-6325.2022.07.1108
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    Objective To compare the sedative effect of different regimens of dexmedetomidine in day-case ophthalmic surgery. Methods Fifty patients, ASA Ⅰ-Ⅱ, who underwent elective ophthalmic surgery, were randomly divided into two groups with 25 in each: The dexmedetomidine(group A) and dexmedetomidine midazolam plus sufentanil (group B). In group A, the loading dose of dexmedetomidine was 0.7 μg/kg, followed by 0.5 μg/(kg·h) dexmedetomidine. In group B, the loading dose was midazolam 1.5 mg and sufentanil 5 μg, followed by 0.5 μg/(kg·h) dexmedetomidine. Intra-operative heart rate (HR), mean arterial pressure (MAP), bispectral index (BIS), oxygen saturation (SPO2) and Ramsay scores, Aldrete score, satisfaction score of patient and surgeon were recorded. Results At T2, T4-T6 time points, the Ramsay scores of group B were lower than that of group A (P<0.05). The MAP was lower in group B than group A at T3-T7 time points; The HR was higher(P<0.05) in group B than group A at T2 and T3 time points. Patient satisfaction was significant different between the two groups, the IOWA scores of group B was higher than that of group A(P<0.05).There were no significant differences between the two groups in BIS, SPO2 and surgeon satisfaction. Conclusions The combination of dexmedetomidine midazolam plus sufentanyl appears to have more advantages in day-case ophthalmic surgery regarding hemodynamic stability, sedation effect and patient satisfaction.
    Clinical Sciences
    Value of serum sodium fluctuation in early warning of in-hospital death
    CHANG Qing, LIANG Si-yu, CHEN Shi, ZHANG Guo-jie, CHEN Qian, WANG Shi-rui, BAI Xi, PAN Hui
    2022, 42(7):  1113-1118.  doi:10.16352/j.issn.1001-6325.2022.07.1113
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    Objective To verify the accuracy and cost of the value of serum sodium fluctuation in predicting adverse clinical outcomes, and to propose a warning value of serum sodium fluctuations for early warning of in-hospital death and summarize the methodology for setting warning values. Methods This investigation covered all patients admitted to Peking Union Medical College Hospital from January 1, 2014 to December 31, 2014. Patients with normal serum sodium at the time of admission and older than 18 years old were included. Patients without serum sodium retested during the hospitalization were excluded. Clinical characteristics including gender, age, primary diagnosis, and causes of death were documented and laboratory examinations were collected including all serum sodium values during hospitalization. The highest and lowest values among all measurements of serum sodium during hospitalization were identified. The difference between the highest and lowest serum sodium value was defined as the fluctuation value of serum sodium level.The area under the curve (AUC) of sodium fluctuations predicting in-hospital death was calculated. The specificities and sensitivities were calculated with the cut-off points of 10, 12, 14, 16, 18, 20, 22, and 24 mmol/L. A warning related to death in the hospital was defined as a true warning, and a warning unrelated to death in the hospital was defined as a false warning. The number of false warnings was defined as the cost of warning.The ratio of the true warnings to the total warnings was defined as the efficiency of warning. An appropriate cut-off point was selected for combined accuracy, cost, and efficiency of warning. Results In total, 33 323 hospitalization records met the inclusion criteria, of which 191 patients (0.57%) died. 148 records of death were analyzed. Among these patients, 53 died from tumor (35.6%), 52 died from infection (34.9%), 46 died from respiratory failure (30.9%), and 26 died from heart failure (17.4%), 6 died from sudden death (4.0%), 5 died from cerebral hemorrhage (3.4%), 6 died from bleeding from other parts (4.0%), and 1 died from cerebral herniation (0.7%).There were 75 patients (50.7%) experienced serum sodium fluctuations within 10 days before death. The average serum sodium fluctuation was (13.36±8.62)mmol/L, and the highest was 35 mmol/L. Serum sodium fluctuation predicted in-hospital death with an AUC of 85.2% (95% CI:81.8%-88.5%). Predicting in-hospital death with a serum sodium fluctuation greater than 20 mmol/L had a specificity of 99.0% and a sensitivity of 28.8%. If serum sodium fluctuation greater than 20 mmol/L was set as a warning value, 28.8% of hospital deaths would be identified, the number of warnings would be 397, the number of true warnings would be 55, the cost of warning would be 342, and the efficiency of warning would be 13.9%. Conclusions Serum sodium fluctuation greater than 20 mmol/L could be used as a biomarker value for early warning of in-hospital death with high accuracy and low management cost. Serum sodium fluctuations greater than 20 mmol/L is a warning value point and can be potentially used as a predicting warning to suppot the identification of critically ill patients and thus to improve the management of inpatients at high risk of death.
    Mini Reviews
    Research advances in the role of interferon regulatory factor 4(IRF4) in chronic inflammatory diseases
    LUAN Ge, WANG Ming, WANG Cheng-shuo, ZHANG Luo
    2022, 42(7):  1119-1123.  doi:10.16352/j.issn.1001-6325.2022.07.1119
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    Interferon regulatory factor 4 (IRF4) is expressed in a variety of immune cells and participates in the regulation of a variety of immune responses. IRF4 is related to a variety of chronic inflammatory diseases and respiratory allergic diseases. Inhibiting the expression or the function of IRF4 can reduce or delay the occurrence and development of the disease. Studying the role and mechanism of IRF4 in chronic rhinopathy and airway allergic diseases will help provide new strategies for disease treatment.
    Research progress on vascular calcification mechanism for chronic kidney disease
    XIONG Hao, YUAN Fang
    2022, 42(7):  1124-1128.  doi:10.16352/j.issn.1001-6325.2022.07.1124
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    Cardiovascular events are the main cause of death in chronic kidney disease(CKD) and end stage renal disease(ESRD).Studies have shown that vascular calcification is an independent risk factor for cardiovascular events.In addition to the prevention of cardiovascular events,paying attention to the mechanism of vascular calcification, keeping balance of pro-calcification factors and anti-calcification factors should be the primary concerns in prevention and treatment of chronic kidney disease with CKD-mineral and bone disorder(CKD-MBD) in CKD patients.
    Research progress on the role of ferroptosis in Alzheimer's disease
    XU Juan, LI Ye
    2022, 42(7):  1129-1133.  doi:10.16352/j.issn.1001-6325.2022.07.1129
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    Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly. The symptoms of progressive neuronal loss and death in AD, as well as the hyper-oxidative stress associated with abnormal brain iron levels, may be related to ferroptosis, a new way of cell death. Two characteristics of ferroptosis, iron homeostasis and lipid peroxidation, may potentially link ferroptosis to AD. The research on potential role of ferroptosis may provide new ideas for the treatment of AD.
    Progress on cholesterol metabolism and non-alcoholic steatohepatitis
    LI Xiao-xiao, SHU Xiang-bing, ZHANG Li
    2022, 42(7):  1134-1138.  doi:10.16352/j.issn.1001-6325.2022.07.1134
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    Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD). Cholesterol is an essential substance for biological process. Intestinal absorption of dietary cholesterol, as well as circulating lipoprotein exchange, intracellular cholesterol synthesis and metabolism influence hepatic lipid metabolism. It is indicated that the dysfunction of organelles and the secretion of inflammatory cytokines contributed to the activation of cholesterol-loaded macrophage. Besides, cholesterol and bile acid metabolism can also trigger to the development and progression of NASH.
    Application of single-cell RNA sequencing technologies in aortic dilatation diseases
    ZHENG Kai, REN Hua-liang, ZHANG Wang-de, LI Chun-min
    2022, 42(7):  1139-1143.  doi:10.16352/j.issn.1001-6325.2022.07.1139
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    Aortic dilation disease, represented by aortic dissection and aortic aneurysm, is the most dangerous disease in vascular surgery. The pathogenesis of this disease is not very clear. Single-cell RNA sequencing (scRNA-seq) technology can study cell heterogeneity and identify new cell states and populations at the single cell level, which provides a new tool for studying the occurrence and development mechanism of aortic disease.
    Research progress of sepsis complicated with capillary leakage syndrome
    LIN Bai-bai, QIAN Feng-hua, QIAN Yi-ming, ZHAO Lei, SUN Qi, CHU Meng-yao, SHEN Meng-wen
    2022, 42(7):  1144-1147.  doi:10.16352/j.issn.1001-6325.2022.07.1144
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    Sepsis is a common and fatal disease with high mortality. Sepsis is a life-threatening organ dysfunction caused by abnormal host response to infection. Some patients also complicate with hypo-albuminemia, hypotension, oliguria, edema and other phenomena, namely capillary leakage syndrome (CLS). Sepsis with CLS is a complex disease urgently needs active treatment, but a successful treatment must be based on in-depth understanding of the pathogenesis and combined with clinical treatment experience.
    Progress on the role of melatonin in dilated cardiomyopathy
    LIU Jia, XU Kai, SHI Rui-zheng, ZHANG Guo-gang
    2022, 42(7):  1148-1151.  doi:10.16352/j.issn.1001-6325.2022.07.1148
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    Dilated cardiomyopathy (DCM) is characterized by decreased systolic function and left or biventricular enlargement. There is no single specific medicine to delay the progression of DCM. Melatonin (Mel) plays a key role in many cardiovascular diseases by regulating cell damage, oxidative stress and other pathological processes,delaying myocardial remodeling and protecting cardiac function. There is a close relationship between DCM and Mel. It is confirmed that Mel plays an important role in delaying the progression of DCM.
    Medical Education
    Inspiration from vitreoretinal fellow training program in Columbia University
    HAN Liang, ZHUO Yan-ling
    2022, 42(7):  1152-1155.  doi:10.16352/j.issn.1001-6325.2022.07.1152
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    The resident standardized training program of ophthalmology in China has been carried out widely. However, the vitreoretinal fellow training program has not been established. This article describes the vitreoretinal fellow training program both in Department of Ophthalmology of Columbia University and Ophthalmology Center of Peking University Third Hospital, and the differences of the two programs are also analyzed. It aims to build a Chinese vitreoretinal fellow training program, so more qualified vitreoretinal doctors will be trained through this program.
    Satisfaction of nursing intern students with palliative care
    LIANG Si-yu, ZHENG Ying, GE Nan, QU Xuan, LI Hong-yan, WANG Wei, NING Xiao-hong
    2022, 42(7):  1156-1159.  doi:10.16352/j.issn.1001-6325.2022.07.1156
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    Objective Nursing intern students are important observers in the clinical environment. Comprehensive data about palliative care in medical environment can come from a survey that asked nursing intern students about the behaviors of faculty. Methods This survey included a total of 126 third-year nursing intern students from Peking Union Medical College. A self-designed questionnaire was used to investigate the extent to which the students were satisfied about faculty's behaviors related to palliative care, including communication, symptom control and difficult conversations. The students aged 20 to 21. Results There were 63.5%(80/126) students satisfied with the pain management, 34.1%(43/126) and 35.7%(45/126) students were satisfied with the daily communication and conversations to overcome barriers between faculty and patients. Only 33.3%(42/126) were satisfied with the care to the family members after patient'deaths. Nursing intern students who recently experienced the death of patients had significantly lower satisfaction with clinical environment dealing with decedent's family members than those without this experience(25.21 vs 28.41, P<0.01). Students who received training of palliative care had shown significantly lower satisfaction with clinical environment than those without the training (26.18 vs 31.90, P<0.001). Conclusions Nursing intern students are unsatisfied with the clinical environment for the training of palliative care indicating some weakness in the performance of palliative care in hospital and the need to improve clinical teaching of palliative care.
    Stepped teaching model in the training of transperineal prostate biopsy
    ZHOU Zhi-en, LIANG Zhen, YAN Wei-gang, ZHOU Yi, ZUO Yu-zhi, SHI Bing-bing
    2022, 42(7):  1160-1163.  doi:10.16352/j.issn.1001-6325.2022.07.1160
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    Objective To evaluate the teaching effect of stepped training model in transrectal ultrasound-guided transperineal prostate biopsy(PB). Methods Forty doctor trainees in the department of urology of Peking Union Medical College Hospital were randomly divided into two groups: experimental group and control group, with 20 trainees in each group. The experimental group received the stepped teaching model; The control group received the traditional training model. Both groups participated in the training of transperineal PB guided by transrectal ultrasound. One week later, all the members were tested for manipulation and surveyed by the teaching satisfaction questionnaires. Results Eighteen trainees in the experimental group could successfully perform transperineal PB independently, while only twelve trainees in the control group could operate independently, and the completion time of the experimental group was less than that of the control group(P<0.01). The questionnaire survey showed that the teaching satisfaction score of trainees in the experimental group was higher than that in the control group(P<0.01). Conclusions The stepped teaching model of transperineal PB guided by transrectal ultrasound is effective in clinical training.
    Construction of evaluation index system for online medical teaching resources
    WANG Jun, ZHANG Kun, ZHANG Shu-hua, DENG Ming-jun, ZHANG Hua
    2022, 42(7):  1164-1168.  doi:10.16352/j.issn.1001-6325.2022.07.1164
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    Online teaching is an effective supplement to traditional teaching. Especially under the influence of from pandemic COVID-19,online education has played an indispensable and important role. However, with the fast development of teaching resources, there is a need for building of standards and norms, quality of resource construction and the outcome evaluation of technology application in online education.This article tries to analyze the deficiencies of performance evaluation in the construction of medical online teaching resources, establish a reasonable evaluation framework, formulate different resource evaluation systems combined with qualitative and quantitative analysis and to introduce theories such as Deming Cycle, and to establish a long-term dynamic evaluation mechanism in order to implement effective evaluation of medical online teaching resources, therefore to guide the optimization of online teaching resources unitilizaion, promote the application of smart technology and thus improve the learning outcomes of education.