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    Management of chronic cardiovascular and cerebrovascular diseases colum
    Plasma metabolic signature of cardiovascular and cerebrovascular diseases from a large cohort study
    ZHANG Mengji, HUANG Lin, LI Zheng, MA Zhuoran, WEI Lin, YUAN Ancai, HU Liuhua, ZHANG Wei, QIAN Kun, PU Jun
    2022, 42 (3):  259-266. 
    doi: 10.3969/j.issn.1674-8115.2022.03.001

    Abstract ( 100 )   HTML ( 1 )   PDF (2401KB) ( 115 )  
    Objective

    ·To explore the metabolic differences for the occurrence and development of cardiovascular and cerebrovascular diseases, the study performed the plasma metabolic analysis by nano-enhanced laser desorption ionization-mass spectrometry (NELDI-MS) on a large cohort.

    Methods

    ·People were enrolled from general population establishment and follow-up cohort in Pudong New Area, Shanghai. Plasma samples were prospectively collected from 14 419 cohort people who met the criteria from February to August 2019. All the cohort people were divided into coronary heart disease (CHD) group (n=1 608), stroke group (n=461), cardiovascular and cerebrovascular diseases (CHD+stroke) group (n=145) and the control group (n=12 205). The plasma metabolic fingerprints (PMFs) of the enrolled samples were collected by NELDI-MS and then analyzed by statistical analysis for identifying the typical metabolic biomakers in patients with stroke, patients with CHD, and patients with both CHD and stroke.

    Results

    ·Three hundred and forty-five metabolic signal peaks were extracted as PMFs. Six metabolic biomarkers with differential regulations were identified as the potential risk factor for cardiovascular and cerebrovascular diseases respectively by mass spectrometry data analysis. Further, the six metabolic biomarkers were mapped into the altered ketone body and fatty acid metabolism clusters. In the cluster of ketone body metabolism, the intensities of amidosulfonic acid, acetoacetic acid and methylmalonic acid were significantly increased in patients with CHD, but significantly decreased in patients with stroke and cardiovascular cerebrovascular diseases. In the cluster of fatty acid metabolism, the intensities of glucose, galacturonic acid and α-linolenic acid were significantly decreased in patients with cardiovascular and cerebrovascular diseases, but significantly increased in patients with stroke. According to the above six metabolic biomakers, three related metabolic pathways were identified in the cluster of ketone body metabolism, and two related metabolic pathways were identified in the cluster of fatty acid metabolism.

    Conclusion

    ·The novel solid-phase MS approach used in this study has realized the high-efficiency collection of PMFs in a large cohort of people. Six plasma metabolic biomarkers with differential regulation are identified in cohort people with cardiovascular and cerebrovascular diseases, shedding light on the molecular pathological mechanisms of cardiovascular and cerebrovascular diseases from metabolic perspectives. It is expected to provide metabolic clues for the pathogenesis of cardiovascular and cerebrovascular diseases.

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    Association of triglyceride-glucose index with cardiovascular disease in people without traditional risk factors
    ZHANG Tong, TIAN Xue, ZUO Yingting, ZHENG Manqi, ZHANG Yijun, WU Shouling, CHEN Shuohua, MA Gaoting, TONG Xu, WANG Anxin, MO Dapeng
    2022, 42 (3):  267-274. 
    doi: 10.3969/j.issn.1674-8115.2022.03.002

    Abstract ( 130 )   PDF (1658KB) ( 63 )  
    Objective

    ·To examine the association of triglyceride-glucose index with cardiovascular disease (CVD) in participants without atherosclerotic CVD (ASCVD) risk factors.

    Methods

    ·This study included 32 532 participants [64.01% male, mean age (48.26±12.89) years] who had no history of CVD and no ASCVD risk factors (including dyslipidemia, hypertension, smoking and diabetes) at baseline from Kailuan Study during 2006?2007. Participants were divided into 4 groups according to the quintiles of TyG index at baseline (Q1, Q2, Q3 and Q4). TyG index was calculated as ln[triglyceride (mg/dL)×fasting blood glucose (mg/dL)/2]. The outcome was the first occurrence of CVD from baseline to the end of follow-up (December 31, 2019). Baseline characteristics were compared with one-way ANOVA or Kruskal-Wallis test for continuous variables, and chi-square for categorized variables. Multivariable-adjusted Cox proportional hazards models were performed to evaluate the associations. Restricted cubic spline with 5 knots at the 5th, 25th, 50th, 75th and 95th percentile was used to explore the dose-response association between TyG index and incident CVD. A two-sided P<0.05 was considered statistically significant.

    Results

    ·During a median follow-up of 12.97 (12.67, 13.17) years, we observed 1 324 incident CVD events (including 1 084 cases of stroke and 255 cases of myocardial infarction). Compared with participants in the Q1 group, the multivariable adjusted hazard ratios in the Q2, Q3 and Q4 group were 1.16 (95%CI 0.97?1.38), 1.29 (95%CI 1.08?1.53) and 1.60 (95%CI 1.35?1.90) for CVD, 1.12 (95%CI 0.93?1.36), 1.21 (95%CI 1.00?1.46) and 1.44 (95%CI 1.20?1.73) for stroke, and 1.32 (95%CI 0.84?2.06), 1.64 (95%CI 1.07?2.51) and 2.41 (95%CI 1.60?3.65) for myocardial infarction, respectively. Sensitivity analyses yielded similar results. Subgroup analysis showed that the association between TyG index and CVD was consistent across different gender populations, and there was no significant interaction between gender and TyG index in relation to the risk of CVD. Multivariable-adjusted spline regression model showed a J-shaped association between TyG index and the risk of CVD, stroke and myocardial infarction. Similar results were observed when stroke and myocardial infarction were the interest of outcomes.

    Conclusion

    ·Among the individuals without traditional ASCVD risk factors, there is an increased risk of incident CVD with increasing TyG index level.

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    Evaluation of the management effect of "Internet+"-based wearable ECG devices in coronary heart disease patients undergoing PCI
    LIANG Cunyu, ZHAO Qian, SONG Ning, MEN Li, CHEN Qingjie, CHU Junkun, PU Jun, LI Xiaomei, YANG Yining
    2022, 42 (3):  275-281. 
    doi: 10.3969/j.issn.1674-8115.2022.03.003

    Abstract ( 75 )   PDF (958KB) ( 55 )  
    Objective

    ·To explore the application effect of the wearable electrocardiogram (ECG) device based on “Internet+” on chronic disease management of patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).

    Methods

    ·Patients with CHD hospitalized in the Heart Center of the First Affiliated Hospital of Xinjiang Medical University from April 2021 to September 2021 and treated with PCI were randomly divided into control group and intervention group, with 60 cases in each group. All patients in the control group were treated with the management mode of health education and routine follow-up before discharge, while those in the intervention group were treated with additional ECG monitoring daily and during exercise by using the remotely wearable ECG device in the “Internet+” chronic disease management mode managed and promoted on social media platform. The changes of the resting heart rate (RHR) and its compliance rate, the scores of Perceived Knowledge Scale for CHD (PKS-CHD) and the scores of Coronary Artery Disease Self-Management Scale (CSMS) in the two groups after intervention as well as the detection rates of arrhythmia and ST segment changes in electrocardiogram were observed.

    Results

    ·Before intervention, there was no significant difference in RHR and PKS-CHD scores between the two groups. After intervention, there were significant differences in RHR compliance rate, RHR, the total score of PKS-CHD, the scores of five dimensions (risk factors, inducing factors, clinical manifestations, drug knowledge and secondary prevention) of PKS-CHD, the total score of CSMS and the scores of five dimensions (bad habits management, general life management, symptom management, disease knowledge management, and compliance management) of CSMS between the two groups (all P<0.05). The detection rate of arrhythmia (44.8%) and ST segment changes (22.4%) in the intervention group were higher than those in the control group (26.8% and 8.9%, respectively), and the differences were statistically significant (both P<0.05).

    Conclusion

    ·The application of the wearable ECG device based on “Internet+” in chronic disease management of CHD patients after PCI can improve the compliance rate by decreasing RHR, the self-management behavior and knowledge level, as well as the detection rate of arrhythmia and ST segment changes.

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    Baseline characteristics and lifestyle factors of single and co-morbidity of cardio-cerebrovascular diseases in Shanghai Community Elderly Cohort
    JIANG Huiru, LI Zheng, MA Zhuoran, WEI Lin, YUAN Ancai, HU Liuhua, CHEN Xiaoyu, GUO Yunyue, ZHANG Wei, PU Jun
    2022, 42 (3):  282-289. 
    doi: 10.3969/j.issn.1674-8115.2022.03.004

    Abstract ( 65 )   PDF (1021KB) ( 69 )  
    Objective

    ·To explore the epidemiology and risk factors of single and co-morbidity of cardio-cerebrovascular diseases based on a large-scale prospective cohort of elderly people in the community.

    Methods

    ·The subjects of the study came from Shanghai Community Elderly Cohort. The baseline survey of this cohort began in February 2019 and ended in August 2019, collecting information including demographic information, diseases and family history, lifestyle and psychological status of cohort members. According to self-reported coronary heart disease and/or stroke, all cohort members were divided into four groups, which were single coronary heart disease group, single stroke group, cardio-cerebrovascular disease group (with both coronary heart disease and stroke), and control group (without coronary heart disease and stroke). Baseline information, disease history, lifestyle factors, psychological and sleep status among the four groups were analysed.

    Results

    ·A total of 17 948 eligible subjects participated in the cohort study, including 2 050 cohort members with single coronary heart disease, 724 cohort members with single stroke, 269 cohort members with cardio-cerebrovascular disease, and 14 905 cohort members without coronary heart disease and stroke. The average age of these four groups were (70.4±6.2) years, (71.8±7.1) years, (73.2±7.0) years and (68.3±5.9) years, respectively. The proportions of hypertension (76.6%), hyperlipidemia (38.3%) and diabetes (26.0%) were the highest in the cardio-cerebrovascular disease group, followed by the single stroke group (74.2%, 26.8% and 25.8%, respectively), and the single coronary heart disease group (72.9%, 21.1% and 21.7%, respectively), and the control group had the lowest proportion (54.6%, 8.7% and 15.4%, respectively). The proportions of depression symptoms (16.0%), anxiety symptoms (13.1%), sedentary habit (2.2%), and poor or fairly poor sleep (38.6%) in the cardio-cerebrovascular disease group were the highest, followed by the single stroke group (10.1%, 6.6%, 2.2% and 27.2%, respectively) and the single coronary heart disease group (7.9%, 4.8%, 0.5% and 27.0%, respectively). The proportion of regular exercise was the lowest in the cardio-cerebrovascular disease group (29.5%), while the proportion was the highest in the control group (39.2%).

    Conclusion

    ·Patients with coronary heart disease or stroke, especially those with both coronary heart disease and stroke, have a high proportion of co-morbidity with primary diseases, unhealthy lifestyles and psychological disorders.

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    Innovative research team achievement column
    Electron microscopic study of Shelterin quinary complex structure in fission yeast
    LU Yanjia, SUN Hong, WU Zhenfang, LEI Ming
    2022, 42 (3):  290-297. 
    doi: 10.3969/j.issn.1674-8115.2022.03.005

    Abstract ( 91 )   PDF (3677KB) ( 66 )  
    Objective

    ·To study the structure of the Shelterin quinary complex (Rap1-Poz1-Tpz1-Ccq1-Pot1) in fission yeast Schizosaccharomyces pombe (S. pombe)by negative-staining and electron microscopy.

    Methods

    ·The Shelterin quinary complex was reconstituted via expression and purification of recombinant proteins in Escherichia coli with histidine-small ubiquitin-related modifier (His-SUMO) and glutathione S-transferase (GST) tags. The target protein complex was isolated via sequential Ni-NTA and glutathione sepharose affinity purification followed by gel filtration chromatography (SuperoseTM6 10/300 GL). The protein samples were stained by 0.75% uranium formate, and then observed by 120 kV transmission electron microscope (TEM) with a magnification of 92 000. The micrographs with good particle dispersity were obtained and the 3D structure of Shelterin complex was reconstructed by single particle image analysis by using EMAN2 and Relion3.0. Finally, UCSF Chimera was used to analyze the reconstruction model of Shelterin complex.

    Results

    ·The recombinant S. pombe Shelterin quinary complex with high purity, component integrity and good homogeneity was obtained by using a tandem affinity purification scheme with Ni-NTA and GST-based chromatography. Eighty-three micrographs were collected through 120 kV TEM, in which 18 659 particles were picked for 3D model reconstruction. After that, the rough 3D structure of the complex was obtained. Molecular docking of the available crystal structures of Shelterin subcomplex into the reconstructed model revealed that the complex existed in a dimeric form and determined the positioning of each component in the complex.

    Conclusion

    ·The low-resolution 3D model of S. pombe Shelterin quinary complex (Rap1-Poz1-Tpz1-Ccq1-Pot1) is obtained.

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    Basic research
    Effect of ferroptosis on regeneration after muscle injury
    DU Yuting, ZHANG Jing, HUANG Ying, ZHANG Jing
    2022, 42 (3):  298-306. 
    doi: 10.3969/j.issn.1674-8115.2022.03.006

    Abstract ( 129 )   PDF (2816KB) ( 48 )  
    Objective

    ·To investigate the role of ferroptosis in muscle regeneration after injury induced by cardiotoxin (CTX).

    Methods

    ·CTX was injected into the tibialis anterior (TA) of fifteen 8-week-old male C57BL/6J mice at the upper, middle and lower points. After injection, TA tissue of the mice was collected at 0 d, 3 d and 7 d respectively (n=5) to detect injury by hematoxylin-eosin (H-E) staining. Meanwhile, quantitative real-time PCR (qPCR) and Western blotting were used respectively to detect the expression levels of muscle regeneration-related indexes and ferroptosis-related genes from RNA and protein levels, respectively. At the same time, forty-five 8-week-old C57BL/6J male mice were divided into 3 groups before CTX injection: saline control group, iron chelator deferoxamine (DFO) treatment group and ferroptosis inhibitor UAMC-3203 treatment group (n=15). CTX was injected into TA, and muscle tissue was collected at 0 d, 3 d and 7 d respectively. RNA sequencing (RNA-seq) technology and bioinformatics were used to analyze the effect of ferroptosis inhibitor pretreatment on muscle injury and regeneration after CTX injection. H-E staining and qPCR were utilized to analyze the effect of ferroptosis inhibitor on the expression levels of muscle regeneration-related genes.

    Results

    ·The muscle injury and regeneration model was successfully established by CTX injection, as revealed by H-E staining. The increase of ferroptosis-related genes including acyl-CoA synthetase long chain family member 4 (Acsl4) and heme oxygenase-1 (Hmox-1) at both RNA and protein levels was observed, suggesting the occurrence of ferroptosis during muscle injury. There was severe muscle injury at day 3, which was detected by the up-regulation of myogenic differentiation antigen (Myod), myogenin (Myog), and tenascin-c (Tnc), followed by declines at day 7. According to the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of RNA-seq differential genes, it was found that UAMC-3203 treatment group had significant changes in neutrophil degranulation, production of reactive oxygen species (ROS) and phospholipids in phagocytosis compared with CTX injection alone. And the expression of cathepsin S (Ctss) was much higher in the UAMC-3203 treatment group. More importantly, the expression of muscle regeneration-related genes were dramatically inhibited by both UAMC-3203 and DFO injection.

    Conclusion

    ·Inhibition of ferroptosis slows down the process of muscle regeneration to a certain degree, suggesting that ferroptosis may play a key role in facilitating muscle regeneration.

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    Effect of decreased 5⁃hydroxytryptamine synthesis during puberty development on the onset of puberty in female rats
    DONG Ting, YIN Xiaoqin, LI Yan, LI Pin
    2022, 42 (3):  307-311. 
    doi: 10.3969/j.issn.1674-8115.2022.03.007

    Abstract ( 72 )   PDF (1213KB) ( 17 )  
    Objective

    ·To preliminarily explore the effects of decreased 5-hydroxytryptamine (5-HT) synthesis in the hypothalamus during puberty development on the onset of puberty in female rats.

    Methods

    ·Seventy two 21-day-old female SD rats were randomly divided into para-chlorophenylalanine (PCPA) group and normal saline group (control group), with 36 rats in each group. The rats in the PCPA group were injected with PCPA intraperitoneally every day (to establish the model of decreased 5-HT synthesis), while the rats in the control group were injected with the same amount of normal saline. The administration treatment lasted until 1 d before death. The rats were sacrificed at the age of 28 days, 35 days and 42 days, respectively. The expression of gonadotropin-releasing hormone (GnRH) gene in the hypothalamus of the two groups was detected by quantitative real-time PCR (qPCR). The content of 5-HT and GnRH in the hypothalamus and the level of luteinizing hormone (LH) in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). At the same time, since the age of 28 days, the vaginal opening time in the two groups was observed and recorded from 9:00 to 10:00.

    Results

    ·The ELISA results of 5-HT content showed that the rats in the control group had the lowest level at 28 days and the highest level at 42 days, and showed an overall increasing trend, which was consistent with the trend of the PCPA group. Compared with the control group, the content of 5-HT in the PCPA group was lower at the above three time points (all P<0.05). qPCR and ELISA results of GnRH content showed that compared with the control group, the expressions of GnRH mRNA and GnRH protein in the PCPA group were lower at the above three time points (all P<0.05). The results of ELISA showed that compared with the control group, LH levels of the PCPA group were lower at the age of 28 days and 35 days, and the difference was statistically significant (both P<0.05). The observation results showed that compared with the control group, vaginal opening time of the PCPA group was delayed (P=0.035).

    Conclusion

    ·The decrease of 5-HT synthesis during puberty development can lead to decrease of GnRH synthesis in the hypothalamus, decrease of LH level in peripheral blood and delay of vaginal opening, thus delaying the onset of puberty in female SD rats.

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    MMP14 expression in pancreatic cancer and its correlation with characteristics of tumor immune microenvironment
    XU Jingxuan, DU Shaoqian, CAO Yuan, WANG Hongxia, HUANG Weiyi
    2022, 42 (3):  312-322. 
    doi: 10.3969/j.issn.1674-8115.2022.03.008

    Abstract ( 91 )   PDF (6030KB) ( 40 )  
    Objective

    ·To explore the expression of matrix metalloproteinase 14 (MMP14) in pancreatic cancer tissues and its correlation with clinical characteristics, and analyze its correlation with the characteristics of tumor immune microenvironment in pancreatic cancer.

    Methods

    ·GEPIA (Gene Expression Profiling Interactive Analysis) platform was used to analyze the MMPs expression in 30 common tumor tissues. R software was used to integrate transcriptomic data of 167 normal pancreatic tissues from GTEx (Genotype-Tissue Expression) database with 178 pancreatic cancer tissues and 4 para-tumor tissues from TCGA (The Cancer Genome Atlas) database to compare the differences of MMP14 expression. GEPIA platform was used to perform survival analysis in the patients with different MMP14 expression levels. Perl and R project software were used to analyze the correlation of MMP14 expression and clinical characteristics. R project software and GSEA v3.0 software were used for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) functional enrichment analysis. CIBERSORT analysis was used to calculate the proportions of immune cell subsets in the tumor immune microenvironment, and analyze correlation of MMP14 expression and the proportion of immune cell subsets. Six fresh surgical samples of pancreatic cancer tissues and paired para-tumor tissues were collected to detect various immune cell subsets by flow cytometry. t-SNE dimensionality reduction and statistical analysis were used to explore the characteristics of tumor immune microenvironment in pancreatic cancer. A tissue microarray was used to conduct multiplex immunohistochemistry (mIHC) to detect MMP14 expression and the proportions of immune cell subsets to verify bioinformatics analysis results.

    Results

    ·In the bioinformatics database, compared with the other members of MMPs, MMP14 was highly expressed in a variety of tumors, and MMP14 expression in pancreatic cancer was higher than that in the other cancers. The expression of MMP14 in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues and para-tumor tissues (P=0.000). The expression of MMP14 in the TNM stage II tumor was higher than that in the stage I tumor (P=0.012). The expressions of MMP14 in the histological grade 2 (G2) and grade 3 (G3) tumors were higher than those in the grade 1 (G1) tumor (P=0.000). The survival prognosis of the patients in MMP14-low expression group was significantly better than that in high expression group (P=0.033). KEGG and GO analysis results showed that MMP14 was enriched in the pancreatic cancer pathway and immune-related pathways. The expression level of MMP14 was negatively correlated with the percentages of CD8+ T cells and monocytes (P<0.05) , and positively correlated with the percentage of macrophages (P=0.000). Flow cytometry analysis suggested that tumor microenvironment of pancreatic cancer was immunosuppressive. The results of mIHC showed that MMP14 expression in the tumor tissues was higher than that in the para-tumor tissues (P=0.000). Tumor tissues with higher TNM stage and histological grade expressed relatively higher MMP14 levels (P<0.05). In the tumor tissues with high MMP14 expression level, the percentage of CD8+ T cells decreased (P=0.001) and the percentage of macrophages increased (P=0.000), which were consistent with bioinformatics analysis results.

    Conclusion

    ·Compared with normal pancreatic tissues and para-tumor tissues, the expression of MMP14 significantly increases in pancreatic tumor tissues and the high expression is associated with poor prognosis of the patients; in the pancreatic tumor tissues with high MMP14 expression, the percentage of CD8+ T cells decreases and the percentage of macrophages increases; with high MMP14 expression, the tumor microenvironment of pancreatic cancer is highly immunosuppressive.

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    Effect of miR-124-1 mediated by exosomes of bone marrow-derived mesenchymal stem cells on the regulation of transformation of M2 microglia
    HAO Lei, JIN Ge, YANG Yongtao, WANG Junwei, SUN Yang, QIN Cuiling, ZHAN Qunling
    2022, 42 (3):  323-330. 
    doi: 10.3969/j.issn.1674-8115.2022.03.009

    Abstract ( 62 )   PDF (2743KB) ( 39 )  
    Objective

    ·To investigate the effect of exosomes (Exo) of bone marrow-derived mesenchymal stem cells (BMMSCs) overexpressing miR-124-1 gene on the regulation of transformation of M2 microglia (MG).

    Methods

    ·BMMSCs of rats were isolated and cultured. BMMSCs-Exo were extracted. BMMSCs and BMMSCs-Exo were identified by flow cytometry, transmission electron microscope (TEM) and Western blotting, respectively. MiR-124-1 gene was synthesized and its lentiviral vector was constructed. The expression changes of miR-124-1 gene in BMMSCs and BMMSCs-Exo were observed. BMMSCs-Exo overexpressing miR-124-1 gene (Exo/124-1) was co-cultured with HAPI microglia cell line activated by lipopolysaccharide (LPS). Cells from Exo group and EXO/124-1 group were collected, respectively. HAPI cells cultured with LPS only (LPS group) were compared with untreated HAPI cells (normal group). Quantitative real-time PCR (qPCR) and Western blotting were used to detect the mRNA and protein expression of M1 molecules [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] and M2 molecules(CD206, IL-10) in HAPI cells.

    Results

    ·BMMSCs and BMMSCs-Exo were successfully isolated, cultured and identified. Exo/124-1 significantly expressed miR-124-1 gene. BMMSCs-Exo could carry miR-124-1 gene, significantly down-regulating the expression of IL-6 (compared with the normal group and the LPS group, the down-regulation percentage were 55.71% and 73.04%, respectively at the gene level, and the percentages were 52.32% and 76.95%, respectively at the protein level) and TNF-α (compared with the normal group and the LPS group, the down-regulation percentage were 51.95% and 68.91%, respectively at the gene level, and 52.14% and 77.47%, respectively at the protein level) of HAPI cells tested by qPCR and Western blotting. Exo/124-1 up-regulated the expression of CD206 (compared with the normal group and the LPS group, the down-regulation percentage were 46.90% and 76.99%, respectively at the gene level, and 65.13% and 85.11%, respectively at the protein level) and IL-10 (compared with the normal group and the LPS group, the down-regulation percentage were 43.09% and 72.36%, respectively at the gene level, and 55.19% and 78.18%, respectively at the protein level) in HAPI cells.

    Conclusion

    ·BMMSCs-Exo can mediate miR-124-1 to regulate the polarization of HAPI cells to M2 type.

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    Clinical research
    Values of fecal calprotectin, C-reactive protein and interleukin-6 in diagnosing gastrointestinal mucosal injury in patients with Crohn's disease
    MA Jirong, SHEN Wei, GU Yi, SHEN Wenyan, ZHOU Jingyi
    2022, 42 (3):  331-336. 
    doi: 10.3969/j.issn.1674-8115.2022.03.010

    Abstract ( 103 )   PDF (1218KB) ( 36 )  
    Objective

    ·To investigate the values of fecal calprotectin (FC), C-reactive protein (CRP) and interleukin 6 (IL-6) in diagnosing the gastrointestinal mucosal injury in the patients with Crohn′s disease (CD).

    Methods

    ·A total of 52 CD patients admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2019 to June 2020 were enrolled in the study. The patients were divided into uninjured mucosa group and injured mucosa group based on the gastrointestinal endoscopic results, and the clinical features of the two groups were compared. The level of IL-6 was detected by cytometric bead array. The content of FC was detected by immunofluorescence chromatography. CRP in the whole blood was detected by nephelometry. IL-6 and CRP were detected within 24 h of admission, while FC was detected within 72 h. The results were compared between the two groups. The independent influence factors of mucosal injury were analyzed by multivariate Logistic regression. The receiver operating characteristic (ROC) curve was used to determine the values of IL-6, CRP, FC and their combination in judging mucosal injury.

    Results

    ·Among the 52 patients, there were 21 patients in the uninjured mucosa group and 31 in the injured mucosa group. There were no significant differences in the age and gender between the two groups. The significant difference was only identified in the distribution of disease behavior in the Montreal Classification (P<0.05). The levels of IL-6, CRP and FC in the injured mucosa group were 11.1 (3.67, 17.54) pg/mL, 8.02 (2.13, 30.96) mg/L and 448.4 (212.90, 639.50) μg/g, respectively, which were significantly higher than those in the uninjured mucosa group (P<0.05). Logistic regression analysis suggested that only FC was an independent factor for judging the injured status of gastrointestinal mucosa in the CD patients (OR=1.006, P<0.05). The areas under the ROC curves (AUCs) of IL-6, CRP and FC for judging the state of gastrointestinal mucosal injury were 0.71, 0.88 and 0.85, respectively (all P<0.05). The AUCs of FC+CRP and FC+IL-6 were 0.91 and 0.84, respectively (both P<0.05). The AUC of FC+IL-6+CRP was 0.92 (P<0.05). By comparing the ROC curves of the two-item combined detection and the three-item combined detection, no significant difference could be identified in the AUC between FC+CRP and FC+IL-6+CRP. However, a significant difference was identified between FC+IL-6 and FC+IL-6+CRP (P=0.045). Meanwhile, the sensitivities and specificities of both FC+CRP and FC+IL-6+CRP were 77% and 100%, respectively.

    Conclusion

    ·The combined detection of FC and CRP, as well as the combined detection of FC, IL-6 and CRP, can effectively judge the gastrointestinal mucosal injury in patients with CD, the diagnostic values of which are similar; based on the simplicity and the cost, the combined detection of FC and CRP is more recommended clinically.

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    Effect of lower limb exoskeleton robot on recovery of function in patients after arthroscopic meniscus repair
    WANG Yanhong, HAN Jiyu, WAN Daqian
    2022, 42 (3):  337-343. 
    doi: 10.3969/j.issn.1674-8115.2022.03.011

    Abstract ( 84 )   PDF (1538KB) ( 42 )  
    Objective

    ·To investigate the effect of lower limb exoskeleton robot on function recovery of lower limbs in the patients during the rehabilitation period after arthroscopic meniscus repair, and compare its effect with the effect of continuous passive motion (CPM) training.

    Methods

    ·Ninety patients undergoing meniscus repair under arthroscopy after injury in the Orthopaedic Department of Tongji Hospital, Tongji University, from June 2020 to June 2021 were selected as the objects. The trial did not carry out double-blind grouping and allocation concealment. The patients were randomly divided into conventional rehabilitation therapy combined with CPM training group (conventional group, 45 cases) and conventional rehabilitation therapy combined with lower limb exoskeleton robot training group (exoskeleton group, 45 cases). The baseline data of the patients were collected before the rehabilitation training. The knee Lysholm score, the knee subjective function score of the International Knee Documentation Committee (IKDC), the Hospital for Special Surgery (HSS) score and the range of motion of knee joint were compared and analyzed between the two groups before (4 d after surgery) and after (after 2 months of rehabilitation training) the rehabilitation training. Adverse events during the test were recorded.

    Results

    ·There was no significant difference in gender, age, course of disease, location and classification of knee injury between the conventional group and the exoskeleton group (P>0.05). All the patients completed 2 months of rehabilitation training. After the meniscus repair, there was no significant difference in the excellent and good rates of Lysholm score and IKDC score, HSS score and knee range of motion between the conventional group and the exoskeleton group before rehabilitation (P>0.05). After 2 months of rehabilitation training, the excellent and good rates of Lysholm score and IKDC score, and HSS score in the two groups were significantly higher than those before rehabilitation (P<0.05), and the excellent and good rates of Lysholm score and IKDC score, and HSS score in the conventional group were significantly lower than those in the exoskeleton group (P<0.05). There was no significant difference in the improvement of knee range of motion before and after rehabilitation in the conventional group (P>0.05), while there was significant difference in the exoskeleton group (P=0.000), and the knee range of motion in the exoskeleton group after rehabilitation was significantly wider than that in the conventional group (P=0.001). During the rehabilitation training, no significant adverse effects were reported in both groups.

    Conclusion

    ·For the patients in the rehabilitation period after meniscus repair under arthroscopy, combined with the conventional rehabilitation therapy, lower limb exoskeleton rehabilitation robot is more effective than CPM in promoting the recovery of knee function and improving the range of motion of knee joint.

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    Clinical analysis of left atrial spontaneous echo contrast before and after left atrial appendage closure in patients with atrial fibrillation
    ZHAO Zhihong, WANG Saihua, HAO Shuwen, SONG Xiang, LUO Jun, WU Yingbiao, ZHU Qian, FANG Ming, TIAN Bei, GU Wei, NING Zhongping
    2022, 42 (3):  344-349. 
    doi: 10.3969/j.issn.1674-8115.2022.03.012

    Abstract ( 77 )   PDF (883KB) ( 26 )  
    Objective

    ·To investigate the occurrence of left atrial spontaneous echo contrast (LA SEC) both before and after left atrial appendage closure (LAAC) in the atrial fibrillation (AF) patients, and its relationship with device-related thrombus (DRT) and clinical prognosis.

    Methods

    ·This study was a retrospective, cross-sectional study. A total of 126 nonvalvular AF patients receiving LAAC with LAmbre and completing transesophageal echocardiography (TEE) review were enrolled from August 2018 to December 2020 in Shanghai Pudong New Area Zhoupu Hospital, Shanghai University of Medicine & Health Sciences. The proportion of AF patients with LA SEC was 19.8% (25/126) before LAAC. The AF patients were divided into LA SEC group (n=25) and non-LA SEC group (n=101), and the clinical data, LAAC-related data, and perioperative complications were analyzed. TEE review time median was 72 d after LAAC. The patients were redivided into LA SEC group (n=58) and non-LA SEC group (n=68) for analysis. The average follow-up was (12±6) months. The incidence of DRT was compared, and the incidences of ischemic stroke and cerebral hemorrhage events were followed up.

    Results

    ·Before LAAC, the proportion of oral anticoagulation was low, the left atrium diameter and the left ventricle diameter increased, and the left ventricle ejection fraction decreased in the LA SEC group. The incidence of LA SEC after LAAC reviewed by TEE increased to 46.0%, including 38.1% (48/126) new occurred LA SEC patients, and 40.0% (10/25) LA SEC patients with LA SEC. The redivided LA SEC group had longer left atrial appendage orifice diameter and lower application rate of anticoagulant treatment regimen. There was no significant difference in the incidence of death, ischemic stroke/transient ischemic attack, and cerebral hemorrhage between the two groups (all P>0.05).

    Conclusion

    ·The AF patients undergoing LAAC with LA SEC before operation are characterized by low anticoagulation ratio, left atrium and left ventricle enlargement, and decreased left ventricle ejection fraction. After LAAC with LAmbre, the LA SEC patients diagnosed by TEE review have longer left atrial appendage ostium diameter and lower anticoagulant treatment regimen ratio. LA SEC does not affect the clinical prognosis.

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    Correlation between FRA-2 mRNA expression, DNA methylation level and metabolic syndrome
    DU Qingqing, HOU Zexin, LI Jun, HU Ying, CAO Guolei, LI Siyuan
    2022, 42 (3):  350-356. 
    doi: 10.3969/j.issn.1674-8115.2022.03.013

    Abstract ( 74 )   PDF (1434KB) ( 25 )  
    Objective

    ·To investigate the relationship between Fos-related antigen-2 (FRA-2) mRNA, DNA methylation levels and metabolic syndrome (MS).

    Methods

    ·A case-control study was used to include 160 patients with MS risk factors (obesity, hyperlipidemia, hypertension and hyperglycemia) who were admitted to the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Shihezi University School of Medicine from June 2020 to June 2021. They were divided into MS group (number of MS risk factors ≥3, n=80) and non-MS group (number of MS risk factors 1?2, n=80). In addition, healthy subjects at the same period were included in the control group (0 risk factor, n=80). The age, body mass index (BMI), waist circumference (WC), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were collected and recorded; Fasting plasma glucose (FPG), triacylglycerol (TAG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting serum insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR) were determined. FRA-2 mRNA expression level was detected by reverse transcription-polymerase chain reaction (RT-PCR), and FRA-2 DNA methylation level was determined by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). Kruskal-wallis H test was used for gender comparison, ANOVA was used for age comparison, and covariance analysis was used for comparison of clinical biochemical indicators, FRA-2 mRNA expression level and FRA-2 DNA methylation level. Spearman method was used to analyze the correlation between the methylation level of FRA-2 DNA CpG unit and MS-related clinical biochemical indexes, and between the expression level of FRA-2 mRNA and the methylation level of FRA-2 DNA. The relationship between FRA-2 DNA methylation level and the number of MS risk factors was analyzed by linear regression analysis.

    Results

    ·Compared with the control group and the non-MS group, the age, BMI, WC, DBP, SBP, FPG, TAG, TC, LDL-C and HOMA-IR in the MS group were increased (all P<0.05), while HDL-C was decreased (P=0.000); the expression of FRA-2 mRNA in the MS group was decreased (F=49.155, P=0.000). Compared with the control group, the methylation levels of four FRA-2 DNA CpG units in the non-MS group and the MS group were increased (all P<0.05). Compared with the non-MS group, the methylation levels of five FRA-2 DNA CpG units in the MS group were increased (all P<0.05). The results of linear regression analysis showed that the number of MS risk factors was positively correlated with the level of FRA-2 DNA methylation (β=0.012, P=0.000). Spearman method analysis results showed that among the 10 detected FRA-2 DNA CpG units, CpG 3, CpG 8, CpG 9.10, CpG 12.13.14 and CpG 19 were correlated with WC, SBP, DBP, FPG, TAG and HDL-C (all P<0.05). The mRNA expression level of FRA-2 was negatively correlated with the DNA methylation level of FRA-2 (r=-0.607, P=0.000).

    Conclusion

    ·There is a certain correlation between the methylation level of FRA-2 gene and the occurrence of MS. Increasing the methylation level of FRA-2 DNA and thus down-regulating the mRNA expression may play a role in the occurrence of MS.

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    Evidence-based medicine
    Summary of the best evidence summary on prevention strategies for diaper dermatitis in infants
    LI Yan, JIANG Yan, KANG Qiongfang, LU Qunfeng
    2022, 42 (3):  357-363. 
    doi: 10.3969/j.issn.1674-8115.2022.03.014

    Abstract ( 76 )   PDF (1118KB) ( 151 )  
    Objective

    ·To search, appraise and retrieve the best evidence on prevention strategies for diaper dermatitis in infants, and provide evidence-based guidance for reducing the diaper dermatitis.

    Methods

    ·BMJ Best Practice, UpToDate, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, Registered Nurses' Association of Ontario, Joanna Briggs Institute (JBI) Center of Evidence-Based Healthcare Database, Database of Abstracts of Reviews of Effectiveness, Cochrane Library, Campbell, Medline, PubMed, SinoMed, Chinese Nursing Association, and Chinese Pediatric Society, Chinese Medical Association were systematacially searched to collect relevant evidence on preventing diaper dermatitis in infants. The evidence including clinical decisions, guidelines, evidence summaries, systematic reviews and expert consensuses published from database construction to June 2021. Two researchers evaluated the quality of the literature, and extracted recommendations and research conclusions from the included literature.

    Results

    ·Totally 8 articles were involved, including 2 clinical decisions, 1 evidence summary, 4 systematic reviews and 1 expert consensus. Finally, 26 pieces of best evidence about air, barrier, cleaning, diaper and education were summarized.

    Conclusion

    ·Pediatric professionals should optimize the clinical process to prevent diaper dermatitis, which is on the basis of evidence, cultural characteristics, resource allocation and patient characteristics. Family education is also important, aiming at reducing the incidence rate of diaper dermatitis in infants.

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    Review
    Advances in gut microbiota in the pathogenesis and treatment of inflammatory bowel disease
    LI Bowen, LIU Ningning, WANG Hui
    2022, 42 (3):  364-368. 
    doi: 10.3969/j.issn.1674-8115.2022.03.015

    Abstract ( 103 )   PDF (819KB) ( 57 )  

    The gut microbiota plays a critical role in human health. Inflammatory bowel disease (IBD) is an immunological disease caused by various environmental factors, including the gut microbiota, in genetically susceptible individuals. Although most studies have indicated the role of gut microbiota and their metabolites in contribution to the occurrence and development of intestinal diseases by inducing inflammation and immune disorders. However, the causal relationship between microbiota and IBD pathogenesis cannot be determined. In this review, the alteration of bacterial, fungal and viral microbiota and the potential functional pathways during IBD pathogenesis are summarized. Besides, the current therapeutic approaches targeting microbiota and the promising perspectives are introduced.

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    Research progress of non-coding RNA in myopia
    TEN Weijung, YUAN Ying, KE Bilian
    2022, 42 (3):  369-374. 
    doi: 10.3969/j.issn.1674-8115.2022.03.016

    Abstract ( 78 )   PDF (819KB) ( 37 )  

    Non-coding RNA is a type of RNA that cannot be translated into protein, which was once considered “transcriptional noise”, including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). Research has found that non-coding RNA is involved in the physiological and pathological processes of several human diseases, such as cell proliferation, differentiation, apoptosis, and embryonic development. Recently, it has been considered that the expression profile changes of non-coding RNA in scleral tissue, retinal pigment epithelium cells (RPE), and aqueous humor of myopia patients and myopia animal models. The differential expression of non-coding RNA may contribute to the development of myopia by regulating the scleral extracellular matrix remodeling process, and choroidal blood flow and thickness. Therefore, this article aims to review the research progress in non-coding RNA of myopia to provide new directions and ideas for the diagnosis and treatment of myopia in the future.

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    Review of the role of circulating exosomal microRNA in bronchial asthma
    CHEN Yiting, ZHAO Anda, LI Rong, KANG Wenhui, LI Shenghui
    2022, 42 (3):  375-380. 
    doi: 10.3969/j.issn.1674-8115.2022.03.017

    Abstract ( 57 )   PDF (841KB) ( 24 )  

    Bronchial asthma is a heterogeneous disease with complex pathological characteristics. At present, there is no sensitive and effective diagnostic method, and the severity is often underestimated, resulting in delayed treatment. Recently, circulating exosomal microRNAs (miRNAs) have been regarded as important communication mediators between cells. miRNAs are considered as potential disease biomarkers due to their high stability and convenience in specimen collection, as well as their high sensitivity and specificity in diagnosing and predicting various diseases. However, due to the late start of the research on circulating exosomal miRNAs, results on diagnosis, identification, efficacy prediction and prognosis evaluation of asthma are not consistent, and obstacles are still existing in its practical clinical application. Current evidence suggested that multiple circulating exosomal miRNAs could play a synergistic role in the occurrence and development of asthma, and individual physiological characteristics would be important factors affecting the association between circulating exosomal miRNAs and asthma. The differences and changes of the exact miRNA types and quantities before and after treatment in asthmatic patients with different disease progression and phenotypes need to be further refined and clarified. This review summarizes the recent advances in the association of circulating exosomal miRNAs with asthma, in terms of diagnoses, severity and phenotypic identifications, and curative effect and prognosis evaluations, in order to provide new ideas and directions for the early diagnosis and precise treatment of asthma.

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    Review of MRI-based three-dimensional digital model reconstruction of female pelvic floor organs
    CHEN Liqi, XUE Zhuowei, WU Qingkai
    2022, 42 (3):  381-386. 
    doi: 10.3969/j.issn.1674-8115.2022.03.018

    Abstract ( 99 )   PDF (834KB) ( 35 )  

    Changes in the structure and function of female pelvic floor organs, muscles and surrounding connective tissue are the main causes of pelvic floor disorders (PFD), and a detailed understanding of the spatial anatomy of the pelvic floor under physiological and pathological conditions can help clinicians make accurate diagnoses and optimize treatment strategies. The widespread use of magnetic resonance imaging (MRI) technology has improved clinicians' understanding of the pelvic floor structure, but presentation of the pelvic floor structure is still limited to two-dimensional planar images and the three-dimensional (3D) spatial structure cannot be visualized. The 3D reconstruction technology based on MRI can transform the structure of the female pelvic floor organs into digital models for observation, measurement and even 3D printing for inverse analysis, which greatly promotes the clinical understanding of the pathogenesis and treatment of PFD and provides basis for individualized treatment. However, the existing MRI-based 3D reconstruction technology is not yet mature, for example different advantages and disadvantages of different commercial softwares, different algorithms of different image recognition techniques, lack of uniform evaluation criteria for 3D reconstruction models, and difficulty of balancing modeling efficiency and quality, which limit it as an effective medical research tool for PFD. This paper reviews the research of 3D digital model reconstruction of female pelvic floor tissue and organs based on MRI, aiming to provide reference for clinical diagnosis, treatment and scientific research of PFD.

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    Research progress in the role and mechanism of abnormal mitophagy in Alzheimer's disease
    LIN Yijia, CHENG Lizhen, MIAO Ya
    2022, 42 (3):  387-392. 
    doi: 10.3969/j.issn.1674-8115.2022.03.019

    Abstract ( 75 )   PDF (790KB) ( 31 )  

    Alzheimer's disease (AD) is a neurodegenerative disease and one of the main types of senile dementia. In recent years, abnormal mitophagy often occurs in AD patients. Relevant studies have shown that mitophagy is an important way to control the quality and quantity of mitochondria, that is, cells can remove damaged or dysfunctional mitochondria through selective autophagy to maintain the normal physiological function and energy supply. This article reviews the abnormal changes of mitophagy in AD and its role and mechanism in the occurrence and development of AD, in order to offer new ideas for controlling and delaying the process of AD by targeted induction of mitophagy.

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    Research progress in the mechanism of interactive regulation between circular RNA and oxidative stress
    ZHAO Jiuhong, TONG Jiating, SHEN Zhijun, LÜ Yehui
    2022, 42 (3):  393-399. 
    doi: 10.3969/j.issn.1674-8115.2022.03.020

    Abstract ( 60 )   PDF (876KB) ( 19 )  

    Circular RNA (circRNA) is a class of covalent closed-loop non-coding RNA, existing widely in various tissue and having important biological functions. circRNA can play a regulatory role at the transcriptional or post-transcriptional level by interacting with RNA-binding proteins, regulating mRNA stability and acting as competitive endogenous RNAs. Oxidative stress, a state in which there is an imbalance between the accumulation and removal of reactive oxygen species (ROS) in the body, plays an important role in the onset and development of many diseases. Under oxidative stress conditions, numerous recent studies have shown that differentially expressed circRNA regulate the expression of inflammatory factors and apoptotic genes by acting as miRNA sponges, thereby interfering with cell survival and apoptosis. According to the regulatory effects, circRNA can participate in the damage caused by oxidative stress and play a pro-oxidative stress role. circRNA can also play an anti-oxidative stress role by upregulating antioxidant genes and reducing the effects of oxidative stress. circRNA and oxidative stress interact and induce each other, and mutually they participate in the occurrence and development of a variety of diseases. This paper reviews the relevant literature from the overview of oxidative stress, the role of circRNA under oxidative stress in different systemic diseases, and the potential mechanism of circRNA-oxidative stress interactions, aiming to provide reference for further research.

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