1.Study of lncRNA-miRNA-mRNA ceRNA regulatory network mediated by serum exosomes in coronary heart disease and prediction and experimental validation of potential target herbal medicines
Lu MA ; Lei YANG ; Huang DING ; Wan-Yu LI ; Wei TAN ; Yan-Ling LI ; Yan-Yan ZHANG ; Xiao-Dan LIU ; Zhao-Wen ZENG ; Chang-Qing DENG ; Wei ZHANG
Chinese Pharmacological Bulletin 2024;40(6):1153-1164
Aim To analyze serum exosome sequencing data from patients with coronary heart disease(CHD)and normal subjects by using bioinformatics-related methods to construct a competitive endogenous ln-cRNA-miRNA-mRNA(ceRNA)regulatory network,to mine the predicted potential Chinese medicines,and to perform preliminary validation of the biological processes and core Chinese medicines involved in the ceRNA network.Methods We used exoRbase data-base to obtain the expression matrix of differential genes,combined with the raw letter method to con-struct the ceRNA network,and performed GO analysis and KEGG analysis on the differential mRNAs in the network,and used COREMINE database to predict the biological processes and core target genes involved in the ceRNA network,and to screen the herbal medi-cines with potential therapeutic effects;AVECs oxida-tive damage cell model was constructed in vitro,and the cytoskeleton,tube-forming function,cell prolifera-tion,LDH leakage rate,ROS level and p-AKT,AKT,p-PI3K and AKT protein expression were examined to verify the action pathways and targets of the core Chi-nese medicine Salvia miltiorrhiza for the treatment of coronary heart disease.Results Compared with nor-mal subjects,395 mRNAs,80 miRNAs,60 lncRNA differential genes,and 80 miRNAs were predicted in serum exosomes of coronary heart disease,and the constructed ceRNA sub-network,mainly consisted of 21 lncRNAs,80 miRNAs,and 82 mRNAs;AKT1,VEGFA,IL1B and other genes in the network.The abnormally expressed mRNAs were involved in biologi-cal processes such as oxidative stress and signaling pathways such as PI3 K/Akt,and Dan Shen,Chuanx-iong and Panax notoginseng were most closely related to exosome-mediated biological processes and core genes in coronary heart disease.The active ingredients of tanshinone ⅡA,the core Chinese medicine,could pro-mote vascular endothelial cell proliferation,tube for-mation,skeleton formation and repair,reduce LDH leakage rate and ROS level,and promote the expres-sion of p-AKT and p-PI3K protein.Conclusion There is a complex ceRNA regulatory network trans-duction in coronary artery disease serum exosomes,and traditional Chinese medicine can be used to treat CHD through multi-target intervention,and Dan Shen,Chuanxiong and Panax notoginseng are expected to be candidate sources of traditional Chinese medicine,a-mong which the active ingredient of Dan Shen,tanshi-none ⅡA,activates PI3 K/Akt signaling pathway to play a protective role against oxidative stress-injured cells,and treats CHD.
2.Study on relationship between hemoglobin glycation index and metabolic syndrome and its components
Yali ZHAO ; Meixia XIAO ; Yan LIU ; Zhiping ZENG ; Shengming SHI
China Modern Doctor 2024;62(16):61-65
Objective To investigate the relationship between hemoglobin glycation index(HGI)and metabolic syndrome(MS)and its components.Methods A cross-sectional study was conducted to randomly select 823 patients from the First People's Hospital of Huzhou from September 2022 to September 2023.HGI is calculated based on fasting blood glucose(FPG)and glycosylated hemoglobin(HbA1c)values.The patients were divided into low HGI group(HGI<-0.250%,274 cases),medium HGI group(-0.250%≤HGI≤0.214%,275 cases)and high HGI group(HGI>0.214%,274 cases)by HGI quantile method.The general data and metabolic indexes of each group were compared,and the correlation between HGI and MS and its components was analyzed by multiple Logistic regression.Results With the increase of HGI level,the prevalence rate of MS showed an upward trend(P<0.05).The prevalence rate of MS in low,medium and high HGI groups was 24.8%,42.5%and 55.5%,respectively.Multiple Logistic regression analysis showed that elevated HGI level was risk factor for MS,central obesity,hypertension,hyperglycemia,hypertriglyceridemia and low high-density lipoprotein hyperlipidemia(P<0.05).The risk of MS,central obesity,hypertension,hyperglycemia,hypertriglyceridemia and low high-density lipoprotein hyperlipidemia in high HGI group was 4.005 times(95%CI:2.763-5.808),3.765 times(95%CI:2.604-5.443),1.596 times(95%CI:1.089-2.337),2.655 times(95%CI:1.809-3.895),2.024 times(95%CI:1.404-2.918)and 2.247 times(95%CI:1.537-3.284)of that in low HGI group,respectively.Conclusion HGI is related to MS and its components,and HGI may be a new indicator to prevent and monitor MS.
3.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
4.The Association of Intestinal Flora Metabolite TMAO with Non-alcoholic Fatty Liver Disease
Yuanyuan LI ; Yaxian SONG ; Yushan XU ; Xiaofu ZENG ; Hui YUAN ; Zhao XU ; Yan JIANG
Journal of Kunming Medical University 2024;45(2):77-84
Objective To explore the role of TMAO from gut microbiota in non-alcoholic fatty liver disease(NAFLD),we detected the serum level of TMAO and its precursor metabolites in NAFLD,as well as the expression level of Eubacterium rectum,Bacteroidetes multiforme,Lactobacillus and bifidobacterium in the intestinal flora.Methods We collected 118 subjects and divided into NAFLD group(86 cases)and healthy control group(32 cases)randomly.We also detected the serum level of TMAO and its precursor metabolites in subjects by high performance liquid chromatography tandem mass spectrometry detection(LC-MS),and the expression of target bacterial DNA was detected by qRT-PCR.Results Serum TMAO,TMA and choline levels were significantly increased in NAFLD(P<0.05),and liver fat content was positively correlated with TMAO(P<0.05).The expression level of Lactobacillus and Eubacterium rectum in NAFLD group were increased(P<0.05);the expression level of Bifidobacterium and Bacteroides multiform were decreased(P<0.05).The serum TMAO level was positively correlated with Eubacterium rectum(r=0.280,P<0.05),and negatively correlated with Bifidobacterium(r=-0.332,P<0.05).Conclusion The level of TMAO in serum shows a positive correlation with NAFLD.The structure of intestinal flora in individuals with NAFLD is altered and linked to TMAO.This suggests that the intestinal flora may have a significant impact on the development of NAFLD through TMAO.
5.One case of melioidosis sepsis complicated with hemophagocytic syndrome with an onset of"renal mass"
Song HUANG ; Qiang CHEN ; Yu ZENG ; Zhao-Yan CHEN
Chinese Journal of Infection Control 2024;23(2):238-241
Melioidosis is an infectious disease caused by Burkholderia pseudomallei.Its clinical manifestations are diverse,often recurring and accompanied by sepsis,and it is prone to misdiagnosis and mistreatment,resulting in a high mortality.This paper analyzes a case of melioidosis sepsis combined with hemophagocytic syndrome,and fur-ther summarizes the clinical characteristics,diagnosis and treatment of the disease based on domestic and foreign li-teratures,so as to reduce misdiagnosis and mistreatment of the disease and improve survival rate of patient.
6.Analyses of the risk factors for the progression of primary antiphospholipid syndrome to systemic lupus erythematosus
Siyun CHEN ; Minmin ZHENG ; Chuhan WANG ; Hui JIANG ; Jun LI ; Jiuliang ZHAO ; Yan ZHAO ; Ruihong HOU ; Xiaofeng ZENG
Chinese Journal of Internal Medicine 2024;63(2):170-175
Objectives:Analyze the clinical characteristics of patients with primary antiphospholipid syndrome (PAPS) progressing to systemic lupus erythematosus (SLE).Explore the risk factors for the progression from PAPS to SLE.Methods:The clinical data of 262 patients with PAPS enrolled in Peking Union Medical College Hospital from February 2005 to September 2021 were evaluated. Assessments included demographic data, clinical manifestations, laboratory tests (serum levels of complement, anti-nuclear antibodies, anti-double-stranded DNA antibodies), treatment, and outcomes. Kaplan-Meier analysis was used to calculate the prevalence of SLE in patients with PAPS. Univariate Cox regression analysis was employed to identify the risk factors for PAPS progressing to SLE.Results:Among 262 patients with PAPS, 249 had PAPS (PAPS group) and 13 progressed to SLE (5.0%) (PAPS-SLE group). Univariate Cox regression analysis indicated that cardiac valve disease ( HR=6.360), positive anti-double-stranded DNA antibodies ( HR=7.203), low level of complement C3 ( HR=25.715), and low level of complement C4 ( HR=10.466) were risk factors for the progression of PAPS to SLE, whereas arterial thrombotic events ( HR=0.109) were protective factors ( P<0.05 for all). Kaplan-Meier analysis showed that the prevalence of SLE in patients suffering from PAPS with a disease course>10 years was 9%-15%. Hydroxychloroquine treatment had no effect on the occurrence of SLE in patients with PAPS ( HR=0.753, 95% CI 0.231-2.450, P=0.638). Patients with≥2 risk factors had a significantly higher prevalence of SLE compared with those with no or one risk factor (13-year cumulative prevalence of SLE 48.7% vs. 0 vs. 6.2%, P<0.001 for both). Conclusions:PAPS may progress to SLE in some patients. Early onset, cardiac-valve disease, positive anti-dsDNA antibody, and low levels of complement are risk factors for the progression of PAPS to SLE (especially in patients with≥2 risk factors). Whether application of hydroxychloroquine can delay this transition has yet to be demonstrated.
7.Research status of anti-inflammatory effect of traditional Chinese medicine based on NLRP3 inflammatory body
Fu-Mei XU ; Jun-Yuan ZENG ; Lei ZHAO ; Qi-Li ZHANG ; Peng-Fei XIA ; Yin-Qiang JIA ; Jie WANG ; Peng-Xia FANG ; Yan-Li XU
The Chinese Journal of Clinical Pharmacology 2024;40(6):923-927
Inflammasome is a kind of intracellular polyprotein complex,which is an important component of the complex system of local inflammatory microenvironment after human tissue damage.When the inflammasome is activated,it induces the activation of cysteine aspartate proteinase 1(caspase-1),mediates the maturation and secretion of proinflammatory cytokines,such as interleukin(IL)-1 β and IL-18,and induces cell death,which plays an important role in regulating the host immune response to pathogen infection and tissue repair of cell damage.Nod-like receptor protein 3(NLRP3)inflammatory body,which is composed of NLRP3,pro-cysteine aspartic acid specific protease-1(pro-caspase-1)and apoptosis-related spot-like protein(ASC),is the most deeply and widely studied type of inflammatory body,which plays an important role in the regulation of inflammation.When NLRP3 inflammatory bodies are activated,inflammatory mediators are produced and released,which participate in the occurrence and development of a variety of inflammatory diseases.Some studies have shown that traditional Chinese medicine can improve the pathological state of a variety of diseases by inhibiting NLRP3 inflammatory bodies,and play a role in the prevention and treatment of a variety of inflammatory diseases,including cardiovascular diseases,joint inflammation,diabetes and so on.This paper systematically combs the mechanism of NLRP3 inflammatory bodies,and summarizes the latest research reports on the effects of traditional Chinese medicine compound prescription,traditional Chinese medicine monomers and traditional Chinese medicine extracts on NLRP3 inflammatory bodies in the treatment of inflammatory diseases,in order to provide new ideas for the further study of the pathogenesis and drug treatment of many inflammatory diseases.
8.Study on the effect of synaptic nuclear protein γ on migration and invasion of oral squamous cell carcinoma cells
Zuo-Dong REN ; Zhao-Wei ZHUANG ; Juan ZHAO ; Wu-Mei YUAN ; Yan ZENG
The Chinese Journal of Clinical Pharmacology 2024;40(9):1267-1271
Objective Lentivirus-mediated interference with synaptic nuclear protein γ(SNCG)in human oral squamous cell carcinoma was established to study the role of SNCG in the migration and invasion of oral squamous cell carcinoma.Methods Oral cancer CAL27 cells were infected with LV-shNC and LV-shSNCG constructed by lentivirus vector,respective,and then selected with puromycin to obtain cell lines stably interfering with SNCG,which were named NC group and experimental group,respectively.Detect the expression of SNCG through real-time quantitative polymerase chain reaction(qRT-PCR)and Western blot experiments;Transwell and scratch experiments were used to detect changes in migration and invasion ability.Results Compared with the NC group,the experimental group showed an 80%reduction in SNCG mRNA expression(P<0.01).The relative expression level of SNCG protein was also decreased in the experimental group compared to the NC group(P<0.01).In the NC group and the experimental group,the migration area percentages at 36 hours were 0.54±0.06 and 0.40±0.02,respectively;and at 48 hours were 0.83±0.01 and 0.47±0.05,respectively.The experimental group showed decrease in migration area compared to the NC group,and these differences were statistically significant(P<0.05,P<0.001).Compared to the NC group,the migration and invasion cell numbers in the experimental group(98.00±13.49 and 88.00±5.72)were significantly reduced to(48.00±2.16 and 49.00±2.94),and these differences were statistically significant(P<0.01,P<0.001).Conclusion Interference of SNCG expression can significantly reduce the migration and invasion ability of oral squamous cell carcinoma cells.
9.Interpretation on the Consensus on Targeted Drug Therapy for Spondyloarthritis
Xiaoxi YANG ; Xinping TIAN ; Mengtao LI ; Xiaomei LENG ; Yan ZHAO ; Xiaofeng ZENG
Medical Journal of Peking Union Medical College Hospital 2024;15(1):58-67
Spondyloarthritis (SpA) is a group of chronic inflammatory diseases which predominantly involve spine and/or peripheral joints. SpA can be disabling and seriously affect the quality of life and function of patients. With the increasing clinical use of targeted drug therapy, precise and standardized use becomes the focus. China's first Consensus on Targeted Drug Therapy for Spondyloarthritis was developed by National Clinical Research Center for Dermatologic and Immunologic Diseases using international norms for consensus development. The consensus addresses 13 important clinical questions, ranging from principles, patient eligibility, pre-treatment screening, treatment initiation, drug selection and switch, co-medication, to adverse event monitoring of targeted drug therapy in SpA, and recommends treatment for specific patients, playing a key role in guiding clinical practices.
10.Comparison of clinical features and outcomes of proliferative, fibrotic, and mixed subtypes of IgG4-related disease: A retrospective cohort study
Linyi PENG ; Xinlu ZHANG ; Jiaxin ZHOU ; Jieqiong LI ; Zheng LIU ; Hui LU ; Yu PENG ; Yunyun FEI ; Yan ZHAO ; Xiaofeng ZENG ; Wen ZHANG
Chinese Medical Journal 2024;137(3):303-311
Background::Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients’ clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.Methods::We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.Results::We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils ( P = 0.010), total IgE ( P = 0.006), high-sensitivity C-reactive protein ( P <0.001), erythrocyte sedimentation rate ( P <0.001), complement C4 ( P <0.001), IgG ( P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA ( P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014). Conclusions::Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.Trial Registration::ClinicalTrials. gov, NCT01670695.

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