1.Study on intercellular communication and key genes of smooth muscle cells in human coronary atherosclerosis based on single cell sequencing technology
Chunying SI ; Jianru WANG ; Xiaohui LI ; Yongxia WANG ; Huaimin GUAN
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(2):169-182
Objective·To use single-cell RNA sequencing(scRNA-Seq)technology to interpret the cellular communication landscape of coronary atherosclerosis(CA),and to explore the dominant cell subsets and their key genes.Methods·The GSE131778 data set was downloaded and preprocessed,and quality controlling,dimension reduction clustering and annotation were carried out.Then cell communication analysis was conducted by using CellChat package to identify dominant cell subsets.The FindAllMarker function was used to screen differentially expressed genes(DEGs)between the dominant cell subpopulation and other cell subpopulations,and its protein-protein interaction(PPI)network was constructed.The DEGs ranked in the top five of the Degree algorithm were taken as key genes.Then,the key genes were matched and mined with the cell communication network analyzed by CellChat to obtain the ligand-receptor pairs(L-R)and the signal pathways mediated by the key genes,and the results were visualized.At the same time,the atherosclerosis mouse model was constructed and RT-PCR was used to detect the expression of key genes in carotid atherosclerosis lesions.Results·A total of 11 cell subsets were identified in CA lesions,including smooth muscle cells,endothelial cells,macrophages,monocytes,etc.Cell communication results showed that CellChat detected 70 significant L-R and 26 related signal pathways in 11 cell subsets.Smooth muscle cell was the dominant cell subgroup with the most significant interaction frequency and intensity with other cell subgroups in the active state of communication.The results of DEGs screening showed that there were 206 DEGs between smooth muscle cell subsets and other cell subsets,among which ITGB2,PTPRC,CCL2,DCN and IGF1 were identified as key genes.The results of cell communication mediated by key genes showed that CCL2 and ACKR1 formed L-R and participated in the communication network between smooth muscle cells and endothelial cells through mediating CCL signaling pathway.ITGB2 formed receptor complexes with ITGAM and ITGAX respectively,and then formed L-R with C3 to mediate the complement signal pathway,participating in the communication network among smooth muscle cells,macrophages and monocytes.The validation results of hub genes in animal experiments were consistent with the results of bioinformatics analysis.Conclusion·Smooth muscle cells are the dominant cells in the pathological process of CA,and have extensive communication networks with other cells.They can construct cellular communication networks with endothelial cells,macrophages and monocytes through CCL and complement signaling pathways mediated by CCL2-ACKR1,C3-(ITGAM+ITGB2)and C3-(ITGAX+ITGB2).
2.Metabolic reconfiguration in vitiligo: progress and future
Chunying LI ; Jianru CHEN ; Shuli LI
Chinese Journal of Dermatology 2024;57(1):8-11
Based on the results of the latest basic research on vitiligo, this article elucidates the significance of reconfiguration of glucose metabolism, lipid metabolism, amino acid metabolism, and metabolism of gut microbiota in the pathogenesis of vitiligo, attempts to delineate a panoramic picture of metabolic reconfiguration in vitiligo, and discusses the importance of dialectically and uniformly grasping the crosstalk between multiple metabolic pathways, and of thinking about the mechanisms of action of multiple metabolic pathway reconfiguration in the occurrence of vitiligo in individuals from a holistic perspective in future basic studies, in order to promote the understanding of the vitiligo pathogenesis and explore potential treatment methods for vitiligo.
3.Analysis of depression-like behavioral performances of mouse models of vitiligo
Weiwei SUN ; Jianru CHEN ; Shuli LI ; Tianwen GAO ; Chunying LI
Chinese Journal of Dermatology 2024;57(2):147-154
Objective:To observe and analyze depression-like behavioral performances of mouse models of vitiligo.Methods:Fifteen female C57BL/6 mice aged about 9 weeks were modeled for vitiligo. Whether the mouse models of vitiligo were successfully constructed or not was determined by macroscopy and full-thickness epidermal immunofluorescence staining of mouse tail tissues on day 23 after the start of the experiment; on day 8 (pre-modeling stage) and day 21 (early modeling stage), the elevated plus maze test and the open field test were used to evaluate the behavioral performances of the mice, including the number of entry into the open arms, percentages of time spent in the open arms, percentages of time spent in the central area and total distance traveled, aiming to assess whether depression-like behaviors were exhibited in the mouse models of vitiligo. To further clarify the degree of the impact of vitiligo modeling on the depression-like state in mice, 20 female C57BL/6 mice were equally divided into 2 groups: vitiligo modeling group and vitiligo modeling + chronic restraint stress group; the mice in the vitiligo modeling + chronic restraint stress group were subjected to chronic restraint stress on day 9, that is, these mice were placed in centrifuge tubes and restrained for about 6 hours every day for 28 consecutive days; on days 7, 22, 29 and 38 after the start of vitiligo modeling, the above-mentioned behavioral indicators were determined by the elevated plus maze test and open field test in the 2 groups. Repeated measurement data in a single group were compared before and after treatment by using paired t-test, and repeated measurement data at multiple time points were compared by using two-way repeated measures analysis of variance. Results:By macroscopy, the mice gradually developed well-defined white patches on the tail skin during vitiligo modeling, which were similar to the clinical manifestations of vitiligo patients; on day 23, full-thickness epidermal immunofluorescence staining of the mouse tail tissues was conducted and showed obvious infiltration of CD8 + T cells and a decrease in the number of Melan-A-positive epidermal melanocytes under a laser confocal microscope, which were consistent with typical pathological characteristics of vitiligo; based on the macroscopic results and immunofluorescence findings, a total of 12 mouse models of vitiligo were successfully constructed on day 23. The elevated plus maze test showed that the number of entry into the open arms and the percentages of time spent in the open arms were significantly lower in the 12 mouse models of vitiligo on day 21 (2.33 ± 1.78 times, 5.01% ± 5.27%, respectively) than in those on day 8 (10.75 ± 2.30 times, 29.20% ± 12.48%, t = 9.63, 6.36, respectively, both P < 0.001) ; the open field test showed that the percentages of time spent in the central area and total distance traveled were also significantly lower in the mouse models on day 21 (2.31% ± 1.53%, 2 518.31 ± 528.38 cm, respectively) than in those on day 8 (4.47% ± 2.65%, 3 533.45 ± 465.47 cm, t = 2.40, 5.47, P = 0.036, < 0.001, respectively). In the chronic restraint stress test, a total of 14 mouse models of vitiligo were successfully constructed on day 23, including 5 in the vitiligo modeling group and 9 in the vitiligo modeling + chronic restraint stress group. There were no significant differences in the number of entry into the open arms, percentages of time spent in the open arms, percentages of time spent in the central area, and total distance traveled between the vitiligo modeling group and the vitiligo modeling + chronic restraint stress group on days 7, 22, 29, and 38 ( F = 0.21, 0.20, 0.46, 2.35, P = 0.889, 0.893, 0.719, 0.134, respectively) ; moreover, all the above indicators significantly changed over time (all P < 0.001), except for the total distance traveled ( P = 0.422) . Conclusion:The mouse models of vitiligo developed depression-like behavior at the early modeling stage, and the degree of depression could not be further deepened by chronic restraint stress on the basis of vitiligo modeling.
4.Effectiveness of TCM Health Management for Myocardial Infarction based on Tertiary Management System: A Single-arm Cohort Study of 255 Patients
Hongxin GUO ; Mingjun ZHU ; Rui YU ; Xingyuan LI ; Guangcao PENG ; Xinlu WANG ; Jianru WANG ; Bin LI ; Qifei ZHAO ; Yongxia WANG
Journal of Traditional Chinese Medicine 2024;65(8):821-829
ObjectiveTo evaluate the efficacy of TCM health management based on tertiary management system for patients with myocardial infarction (MI). MethodsA total of 277 patients with non-acute MI were enrolled and given comprehensive TCM health management strategies including health education, lifestyle adjustment, risk factors control, medication and TCM appropriate techniques management through a tertiary management system with "the patient as the core, village/community physicians as the main executive body, and tertiary TCM hospital specialists as the leading body", for a period of 12 months by using a prospective single-arm cohort study. Through patient reporting and medical records surveys, various indicators before and after 12-month management were collected and compared. The primary efficacy indicators were readmission rate and recurrent exacerbation rate, and the secondary efficacy indicators included disease awareness-related indicators, lifestyle behavior-related indicators, cardiovascular risk factor-related indicators and Canadian cardiovascular society (CCS) cardiac function classification. ResultsA total of 255 patients completed the study and were included in the final analysis. The recurrent exacerbation and readmission rates of patients after management were 23.14% (59 cases) and 20.25% (49 cases), respectively, significantly lower than 36.08% (92 cases) and 53.72% (130 cases) before management (P<0.05). Except for knowledge on diabetes diagnostic criteria with no significant difference before and after management (P>0.05), awareness of other knowledge with regard to the prevention and treatment of cardiovascular and cerebrovascular diseases were improved after management (P<0.01), as well as the total score (P<0.01). In terms of daily life behaviors, the rates of salty diet, sweet diet and greasy diet were significantly lower than baseline, while the rate of moderate exercise was significantly higher (P<0.05 or P<0.01); the rates of ongoing smoking and vigorous exercise were not significantly changed (P>0.05). For cardiovascular risk factors, patients' total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, total depression assessment scale score, and total anxiety assessment scale score were significantly reduced after management (P<0.01). Systolic blood pressure and body mass index (BMI) were both higher after management (P<0.05 or P<0.01), and there was no statistically significant difference in diastolic blood pressure (P>0.05). In terms of the cardiovascular disease risk factors reaching the standard levels, the rate of LDL cholesterol <1.8 mmol/L significantly increased (P<0.01), while the rate of BMI <24 kg/m2 and the rate of systolic blood pressure <140 mmHg both decreased significantly (P<0.05 or P<0.01) from baseline; the diastolic blood pressure and rate of fasting glucose <7.0 mmol/L were not significantly changed (P>0.05). The patients' CCS cardiac function classification was significantly reduced (P<0.05). ConclusionTCM health management based on the tertiary management system can enhance MI patients' awareness of the disease, change poor lifestyle habits, reduce risk factors such as blood lipids and blood glucose, improve anxiety and depression, increase activity tolerance, and reduce their recurrence exacerbation and readmission rates, which is worthy of clinical promotion.
5.Screening and experimental validation of hub genes for myocardial isch-emia-reperfusion injury based on bioinformatics
Jianru WANG ; Xingyuan LI ; Shiyang XIE ; Yanling CHENG ; Hongxin GUO ; Mingjun ZHU ; Rui YU
Chinese Journal of Pathophysiology 2024;40(3):473-483
AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.
6.A Cross-Sectional Study of Secondary Prevention Status and Influencing Factors of Stable Angina in 1061 Patients with Coronary Heart Disease
Rui YU ; Yingqiang ZHAO ; Peng LI ; Jianru WANG ; Xinlu WANG ; Qifei ZHAO ; Yuan GAO ; Hongxin GUO ; Mingjun ZHU
Journal of Traditional Chinese Medicine 2024;65(20):2126-2134
ObjectiveTo investigate the current status of secondary prevention of stable angina in patients with coronary heart disease in three regions of China, namely Henan Province, Xinjiang Uygur Autonomous Region, and Tianjin City, and analyze the the influencing factors. MethodsA cross-sectional study was conducted to include patients with stable angina with coronary heart disease in Henan, Tianjin and Xinjiang from August 10, 2020 to March 14, 2021. General information, traditional Chinese medicine (TCM) syndrome elements, prescriptions and other data of patients were collected, and clinical characteristics, blood pressure, blood lipid and blood glucose of patients were analyzed; the patients were divided into groups according to whether their blood pressure, blood lipid and blood glucose were up to standard. With the most common syndrome element as the main variable, region, age and gender as covariables, Logistic regression equation was incorporated to analyze the influencing factors for the patients' blood pressure, blood lipid and blood glucose being up to standard. ResultsA total of 1061 coronary heart disease patients with stable angina were included, including 658 in Henan, 210 in Xinjiang, and 193 in Tianjin. The clinical characteristics of patients in the three regions showed statistical different in age, sex, disease course, complication, blood pressure, blood lipid, blood glucose, smoking, drinking, living habits, and medication treatment (P<0.05 or P<0.01). For the included patients, qi deficiency (79.55%, 844/1061) and blood stasis (39.96%, 424/1061) were the main syndrome elements. The overall compliance rate of blood pressure was 48.89% (506/1035), blood lipids 12.68% (133/1049) and blood glucose 48.18% (504/1046). Qi deficiency was the independent factor affecting the blood pressure of coronary heart disease patients with stable angina combined with hypertension (P = 0.029,95%CI [1.048, 2.369]), and the independent factors influencing the blood lipid standard of coronary heart disease patients with stable angina (P = 0.011, 95%CI [1.133, 2.646]), but not the independent factors affecting blood glucose standard in coronary heart disease patients with diabetes (P>0.05). ConclusionCoronary artery disease patients with stable angina have geographical variability in clinical characteristics and distribution of TCM syndrome elements, and the overall control of blood pressure, blood lipids, and blood glucose is poor, and qi deficiency syndrome is an independent risk factor affecting the control of blood pressure and blood lipids.
7.Bibliometric analysis of the application of machine learning in pharmacovigilance
Limin LI ; Wenyu WU ; Fenfang WEI ; Biyu TANG ; Jianru WU
Chinese Journal of Pharmacoepidemiology 2024;33(7):801-811
Objective To explore the application status and development trend of machine learning in the field of pharmacovigilance worldwide,and to provide reference for the research on the application of machine learning in the field of pharmacovigilance.Methods Relevant literature was searched in the Web of Science with the key words of"machine learning"and"pharmacovigilance"from the inception to March 1,2023.R language and other software were used to quantitatively analyze the literature data in this field.The clustering,co-occurrence and emergence visual analysis were carried out on the characteristics of annual published papers,institutions,countries,keywords and other aspects.Results A total of 904 literature were included.The number of literature published showed a fluctuating upward trend since 1994.There was cross-regional,cross-regional and cross-agency cooperation among the cooperative network institutions.The top 5 countries in the number of publications were the United States,China,Japan,South Korea and India,China and the United States had relatively close cooperation in this field.Signal detection,social media and electronic health records were high-frequency keywords in this field.Clustering and association rule analysis showed that this field focused on three aspects signal recognition,unstructured text mining and analysis,and processing and analysis of electronic medical information.At present,machine learning has made significant progress in signal recognition,social media information mining,and unstructured text processing of electronic medical information,which broaden the data sources of pharmacovigilance,improve the real-time monitoring ability of adverse drug reactions,bringing innovation impetus to the field of pharmacovigilance.Conclusion The rapid development of big data and artificial intelligence technologies has led to an increasing integration of machine learning into the field of pharmacovigilance,which promotes technical exchanges and cooperation and cross-disciplinary integration.It is necessary to optimize each machine learning algorithm to improve its accuracy and stability in pharmacovigilance,strengthen the protection measures of data privacy and security to ensure the safety of patient information.Integrating expertise in the fields of science,medicine,and data statistics with a view to promoting technological progress in the field of pharmacovigilance.
8.Intramycardial hematoma following congenital cardiac surgery in children: a single -center experience
Ye LU ; Xumei LIU ; Li WANG ; Yan GUO ; Jianru LI ; Xiaobi LIANG ; Yan LIAO ; Li MA ; Weidan CHEN
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(11):657-659
Objective:To summarize the clinical features of 8 cases with intramycardial hematoma(IMH) following congenital cardiac surgery in children.Methods:We retrospectly searched 8 patients with intramycardial hematoma after congenital cardiac surgery in Guangzhou Women and Children’s Medical Center from 2008 to 2024.Results:Mean age and mean weight at surgery were(13±15) months and(7.8±3.5)kg respectively. 6 of 8 cases were interventricular septal hematoma. In the other 2 patients, intramycardial hematoma was located in left ventrical free wall. All IMH were postoperatively detected by transthoracic echocardiaography. Two patients were managed with ECMO intraoperatively. Finally, all patients were discharged successfully with good clinical results. Mean time to IMH resolution in six patients was(33.5±4.6) days and mean left ventricular ejection fraction(LVEF) was 0.60±0.09. Another patient was followed up for 3 months and the IMH was not absorbed. One patient was lost to follow-up.Conclusion:IMH is a rare complication after congenital heart disease. The absorption of hematoma is a dynamic process and mean time to IMH resolution is about 1month. In IMH patients with hemodynamic instability, ECMO can be a good treatment to create opportunities for hematoma absorbtion.
9.Correlation between differentially immune-related genes and immune cells in progression of atherosclerosis and exploration of potential intervention of traditional Chinese medicine
Xingyuan LI ; Xiaohui LI ; Guangcao PENG ; Jianru WANG
Chinese Journal of Immunology 2023;39(12):2553-2559,2565
Objective:To explore the correlation between differential immune-related genes(DIRGs)and immune cells in the progression of atherosclerosis(AS)and general rule of Chinese medicine for intervening DIRGs.Methods:Firstly,GSE28829 data set was obtained from GEO database,and immune-related genes were downloaded from ImmPort database and MSigDB database.Secondly,differentially expressed genes between early AS plaques(EAP)and advanced AS plaques(AAP)of GSE28829 were screened by limma package,and their intersections with immune-related genes were known as DIRGs.clusterProfiler package was used to enrich the DIRGs.Protein interaction network of DIRGs was constructed and Hub genes were screened.Then,the infiltration patterns of 22 kinds of immune cells were analyzed by CIBERSORT to screen differential immune cells,and the correlation between them and Hub genes were analyzed by Pearson method.Finally,Coremine Medical database was used to predict Chinese herbs for in-tervening DIRGs,the property and flavor of Chinese herbs were collected.Results:Total 63 DIRGs were obtained,and 10 Hub genes(CD86,TLR2,TYROBP,CCR1,ITGB2,CCL2,CCL4,CSF1R,CXCR4,CTSS)were screened out.Enrichment analysis results showed that the molecular functions,biological processes and signaling pathways of DIRGs were closely related to immune regulation.Analysis of immune cell infiltration showed that proportions of regulatory T cells,activated dendritic cells and resting mast cells in EAP were increased.Proportions of memory B cells,γδ T cells,M0 macrophages and M2 macrophages were increased in AAP.Correla-tion analysis showed that CD86 was positively correlated with M2 macrophages in EAP.In AAP,CD86,CTSS,CXCR4,CSF1R,ITGB2 and TYROBP were positively correlated with M0 macrophages,while CCL4 and CCL2 were negatively correlated with resting mast cells.Results of frequency showed that Chinese herbs for intervening DIRGs mainly distributed to liver and lung meridians,and their property and taste were cold and bitter.Conclusion:This study found that in the progression of AS,10 DIRGs were the most important,and 7 kinds of immune cells were dysregulated,among which CD86,CTSS,CXCR4,CSF1R,ITGB2,TYROBP,CCL4 and CCL2 were correlated with resting mast cells,M0 and M1 macrophages.At the same time,immune mechanism of AS progression was closely related to liver meridian,lung meridian,bitter,sweet,cold and warm.The results can provide reference and ideas for Chinese herbs clinical prescription to treat AS and further exploratory the immunological mechanism of AS progression.
10.Research progress of measurement tools for health-related quality of life in patients with spinal metastases
Mengchen YIN ; Wenlong YU ; Lin LI ; Xin GAO ; Luosheng ZHANG ; Dingbang CHEN ; Quan HUANG ; Xinghai YANG ; Junming MA ; Jianru XIAO ; Wen MO
Chinese Journal of Orthopaedics 2023;43(16):1115-1122
The Health-Related Quality of Life (HRQoL) pertains to patients' subjective contentment concerning their physical, psychological, and social well-being throughout disease treatments. Predominantly employed HRQoL metrics in spinal metastases comprise the 36-item Short-Form Health Survey (SF-36), EuroQoL Five Dimensions Questionnaire (EQ-5D), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Functional Assessment of Cancer Therapy-General (FACT-G). In clinical applications, due to their broad application and diverse disease types, combined with the lack of specificity in the scale content and the prolixity of their questionnaires, these tools often fail to capture the nuanced experiences of patients, thereby compromising the reliability and validity of the results. The Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ), developed by the Spine Oncology Study Group, offers a tailored metric for spinal metastases, encapsulating both specificity and inclusivity. Its proven robust reliability and validity make it invaluable for decision-making and therapeutic efficacy appraisals. The Patient-Reported Outcome Measurement Information System (PROMIS), a novel metric suitable across many medical disciplines, facilitates cross-sector data acquisition, substantially augmenting the precision, sensitivity, and credibilityof assessments, and is pivotal in clinical investigations and interventions. As it continually evolves, PROMIS consistently outperforms traditional metrics in evaluative capacities, exhibiting impressive and consistent proficiency in prognostications, preoperative assessments, and therapeutic outcome evaluations within the spinal metastasis domain. Presently, Chinese research on the HRQoL of spinal metastasis patients remains scant, and choosing an apt, precise, and dependable metric holds significant clinical relevance. Drawing upon extant scholarly publications, this review concluded the current global HRQoL tools for spinal metastases, aiming to furnish insights for the clinical management and research pertaining to spinal metastases.

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