1.A new phenolic acid isolated from Salvia miltiorrhiza ameliorates OVA-induced allergic asthma by regulation of Th17/Treg cells and inflammation through the TLR4 pathway.
Zeng MENGNAN ; Wu YUANYUAN ; Ren YINGJIE ; Jiao XIANMIAN ; Chang FANGZHUO ; Wang YUANYUAN ; Feng WEISHENG ; Zheng XIAOKE
Chinese Journal of Natural Medicines (English Ed.) 2025;23(12):100007-100007
Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L-1), a specific TLR4 blocker, against S1 (10 µmol·L-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.
2.Obesity-driven oleoylcarnitine accumulation in tumor microenvironment promotes breast cancer metastasis-like phenotype.
Chao CHEN ; Hongxia ZHANG ; Lingling QI ; Haoqi LEI ; Xuefei FENG ; Yingjie CHEN ; Yuanyuan CHENG ; Defeng PANG ; Jufeng WAN ; Haiying XU ; Shifeng CAO ; Baofeng YANG ; Yan ZHANG ; Xin ZHAO
Acta Pharmaceutica Sinica B 2025;15(4):1974-1990
Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.
3.Analysis of tissue distribution of metabolites in Crocus sativus L. corms based on DESI mass spectrometry imaging technique
Xi CHEN ; Xingguang XIE ; Kunmiao FENG ; Yingjie LU ; Ting HAN
Journal of Pharmaceutical Practice and Service 2024;42(4):169-172
Objective To explore the distribution characteristics of endogenous metabolites in Crocus sativus L. corms from different origins. Methods A method based on desorption electrospray ionization mass spectrometry imaging and optimized sample pretreatment was developed for directly visualize metabolites in C. sativus corms. Results In situ characterization of metabolites such as flavonoids, organic acids, amino acids, carotenoids, and cyclic enol ether terpene glycosides was achieved. L-Citruline, phenylacetylglycine, sativol, and geniposide were specifically distributed in the corms. Apigenin 7-(6''-O-acetyl)-glucoside, isorhamnetin-3-O-β-D-Glucoside, dhurrin 6'-glucoside, and Apigenin 7-O-diglucuronide were mainly distributed in the terminal bud. For compounds distributed in the corms, the highest abundance was found in corms from Shanghai, followed by Zhejiang and the lowest from Anhui. Conclusion The distribution of metabolites in different parts of C. sativus corms from different origins and the same origin varies significantly. Flavonoids and flavonoid derivatives such as isorhamnetin-3-O-β-D-Glucoside and apigenin derivatives are mainly distributed in the terminal buds, in addition, the natural plant protection agent dhurrin 6'-glucoside is also mainly distributed in the terminal corms, whereas amino acids, which are used as energy and material supplies, are mainly accumulated in the corms.
4.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
5.Bidirectional causal relationship between glucose-lipid metabolism, obesity indicators, and myocardial infarction: a bidirectional Mendelian randomization analysis study
Linghuan WANG ; Tingting LU ; Yingjie ZHANG ; Tianhu WANG ; Naiyuan SUN ; Sijia CHEN ; Feng CAO
Chinese Journal of Cardiology 2024;52(10):1162-1169
Objective:To explore the causal association of glucose-lipid metabolism and obesity indicators with myocardial infarction by a two-sample Mendelian randomization analysis.Methods:Single nucleotide polymorphisms (SNPs) related to phenotypes were obtained from genome-wide association study databases. The body mass index (BMI) and glycated hemoglobin dataset includes 99 998 samples and 8 126 035 SNPs; the waist-to-hip ratio dataset includes 224 459 samples and 2 562 516 SNPs; the waist circumference and hip circumference dataset includes 462 166 samples and 9 851 867 SNPs; the fasting glucose dataset includes approximately 12 million SNPs; the low-density lipoprotein cholesterol (LDL-C) dataset includes 201 678 samples and 12 321 875 SNPs; the high-density lipoprotein cholesterol (HDL-C), and triglycerides dataset includes 156 109 samples and 15 784 414 SNPs; and the body fat percentage, whole-body fat mass, trunk fat percentage, and trunk fat mass dataset includes 454 588 samples and 9 851 867 SNPs. This study primarily used inverse-variance weighted method to analyze the associations between various exposure factors and outcomes. Heterogeneity among SNPs was assessed using Cochran′s Q test, and horizontal pleiotropy of SNPs was examined using the MR-Egger method. Additionally, a multivariable MR approach was used to adjust for BMI, further validating associations between exposure factors and the risk of myocardial infarction. Results:Higher BMI ( OR=1.070, 95% CI: 1.041-1.100), waist-to-hip ratio ( OR=1.366, 95% CI: 1.113-1.677), LDL-C ( OR=1.638, 95% CI: 1.488-1.803), triglycerides ( OR=1.445, 95% CI: 1.300-1.606), waist circumference ( OR=1.841, 95% CI: 1.650-2.055), hip circumference ( OR=1.247, 95% CI: 1.132-1.372), body fat percentage ( OR=1.795, 95% CI: 1.568-2.055), whole-body fat mass ( OR=1.519, 95% CI: 1.381-1.670), trunk fat percentage ( OR=1.538, 95% CI: 1.374-1.723), and trunk fat mass ( OR=1.421, 95% CI: 1.294-1.561), as well as lower HDL-C ( OR=0.799, 95% CI: 0.729-0.875), have causal effects on myocardial infarction (all P<0.05). After adjusting for BMI, hip circumference, trunk fat percentage, and trunk fat mass were no longer associated with myocardial infarction. However, waist-to-hip ratio ( OR=1.457, 95% CI: 1.132-1.877), fasting glucose ( OR=1.191, 95% CI: 1.024-1.383), glycated hemoglobin ( OR=1.129, 95% CI: 1.034-1.233), LDL-C ( OR=1.592, 95% CI: 1.314-1.929), triglycerides ( OR=1.410, 95% CI: 1.279-1.553), waist circumference ( OR=1.922, 95% CI: 1.448-2.551), body fat percentage ( OR=1.421, 95% CI: 1.072-1.884), and whole-body fat mass ( OR=1.295, 95% CI: 1.031-1.626) remained positively associated with myocardial infarction, while HDL-C ( OR=0.809, 95% CI: 0.729-0.897) remained negatively associated. Conclusions:Abdominal obesity and dysregulation of glucose-lipid metabolism are risk factors for myocardial infarction. Screening for glucose-lipid metabolism (fasting glucose, HDL-C, LDL-C, triglycerides) and obesity-related indicators (waist circumference, waist-to-hip ratio, body fat percentage, and whole-body fat mass) is of great importance for the primary prevention of myocardial infarction.
6.Study based on the acetaldehyde dehydrogenase 2 gene polymorphism and acetaminophen-induced liver injury
Feng CHEN ; Qianhui LI ; Yingjie WU ; Liyuan LYU ; Xiaomin XU ; Fei WANG
Chinese Journal of Hepatology 2024;32(2):133-139
Objective:To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs.Methods:An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD-? t test was used for pairwise comparison. Results:ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2 +/+), heterozygous mutant (ALDH2 +/-), and homozygous mutant (ALDH2 -/-), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group ( P ?0.05), while the ALT, AST,ALP, and TBil were all elevated in the APAP experimental group. The levels of ALT ( P ??=?0.004), AST ( P ?=?0.002), and TBil ( P ?=?0.012) were significantly elevated among the mutant group compared to those in the wild-type group, and the expression levels of these indicators were also significantly elevated among the homozygous mutant group compared to those in the heterozygous mutant group ( P ?=?0.003, 0?and 0.006). In addition, the ALP levels were higher in the heterozygous mutation group than those in the homozygous mutant group ( P ?=?0.085) and wild-type group mice, but the difference was only statistically significant compared to wild-type mice ( P ?=?0.002). HE staining results showed that mice in the APAP experimental group had hepatocyte degeneration, necrosis, and increased inflammatory cell infiltration, which was mostly evident in mutant mice. Simultaneously, the F4/80 immunohistochemical staining results showed that brown granules were visible in the liver tissue of APAP experimental group mice, and its expression levels were significantly enhanced compared to the blank control group. Conclusion:APAP-induced liver function abnormalities were associated with the ALDH2 gene polymorphism. The liver injury symptoms were increased in ALDH2 mutant mice following APAP modeling, and the ALDH2 gene defect may alleviate, to some extent, APAP-induced liver function abnormalities.
7.Practice of international talent introduction in a third class general hospital in Tianjin
Miao GUO ; Dong LI ; Yingjie GUO ; Ying MAO ; Ying LI ; Boshen HAN ; Sisi QIN ; Feng ZHAO
Modern Hospital 2024;24(6):821-823,826
Taking the introduction measures of overseas outstanding young talents from a tertiary comprehensive hospital in Tianjin as a case study,this paper introduces the overall overview,application requirements,overall goals,work tasks,as-sessment management,and support measures of the hospital's Excellent Youth Science Fund project(overseas).It is believed that sufficient attention should be paid to the introduction of outstanding young talents from overseas,scientific planning should be carried out,and a comprehensive and international talent introduction management system should be constructed;Optimize serv-ices and provide various resettlement measures for the integration of international talents;Dual protection,introducing dual incen-tives of consulting allowances and research funding;Strengthen assessment and establish a task decomposition mechanism for the evaluation of international special talents;Closed loop management,striving to build a comprehensive ecosystem for the develop-ment of technology talents throughout the entire chain.
8.Bibliometric study on medical Chinese core journals literature in inner mongolia autonomous region from 2018 to 2022
Yingjie TIAN ; Rui FENG ; Shangyin MA ; Haitao DING ; Zhanguo WANG
Modern Hospital 2024;24(7):1134-1136,1141
Objective To analyze the quantity,quality,and research layout of medical scientific papers(in Chinese)published by various regions,hospitals,and institutions in Inner Mongolia Autonomous Region from 2018 to 2022,in order to understand the overall scientific and technological level of our region,providing an overview of support for medical scientific research in the entire region and provi-ding references for the rational layout of medical scientific and technological development.Methods From July to August 2023,Chinese National Knowledge Infrastructure(CNKI)was used as the data source to systematically retrieve Chinese medical literature related to Inner Mongolia Autonomous Region from 2018 to 2022.Bibliometric methods were applied to analyze the quantity and quality of literature,as well as regional and institutional distribution.Results From 2018 to 2022,there were 5 273 articles published in core journals in Inner Mongo-lia,accounting for 30.96%of the total.Among them,1095 articles(20.77%)were indexed in CSCD,1 567 articles(29.72%)in Peking University Core Journals,and5164 articles(97.93%)in Science and Technology Core Journals.The journal with the highest publication volume among the top10 core journals was"Journal of Inner Mongolia Medical University,"accounting for20.77%.The top three regions in terms of total output of core journal articles were Hohhot,Baotou,and Chifeng,while Xing'an League and Alxa League had very few pub-lications.Among different levels of hospitals,tertiary hospitals had much higher publication volumes than primary and secondary hospitals.Among different types of institutions,medical institutions had higher publication volumes than higher education institutions.The top three in-stitutions in terms of publication volumes in core journals were Affiliated Hospital of Inner Mongolia Medical University,Inner Mongolia Med-ical University,and Inner Mongolia People's Hospital.Conclusion The number of core journals in Inner Mongolia needs to be increased,and the quantity of research output varies among regions.It is necessary to strengthen scientific research management systems,improve the level of research achievements,and promote scientific and technological innovation in Inner Mongolia.
9.Para-esophageal and para-gastric vessels affect the secondary prophylactic efficacy of endoscopic treatment for varices
Ling WU ; Sanqiang WANG ; Yingjie AI ; Xiaoquan HUANG ; Feng LI ; Shiyao CHEN
Chinese Journal of Clinical Medicine 2024;31(3):347-352
Objective To evaluate the effect of para-esophageal and para-gastric vessels(PEPGV)on endoscopic secondary prophylaxis for varices.Methods The clinical data of patients with cirrhosis-related esophagogastric varices(EGV)who underwent endoscopic variceal ligation and/or obliteration,and had hepatic venous pressure gradient(HVPG)result between January 2020 and December 2020 in Zhongshan Hospital,Fudan University were retrospectively analyzed.Patients were divided into a group without PEPGV and a group with PEPGV based on CT imaging of the portal vein.The main outcome was 2-year re-bleeding.Results A total of 69 patients were included,and 27 of them had PEPGV.There was no statistical difference in baseline characteristics,blood indexes(included hemoglobin level,prothrombin time and albumin level),HVPG,and the secondary prophylactic endoscopic treatment ways between the two groups.A total of 25 patients experienced re-bleeding within 2 years after endoscopic treatment,including 15 in the group with PEPGV and 10 in the group without PEPGV.Kaplan-Meier analysis showed that the cumulative 2-year re-bleeding rate was significantly higher in the group with PEPGV than in the group without PEPGV(60.07%vs 32.79%,P=0.022).Further multivariate Cox analysis showed that PEPGV was an independent predictor of re-bleeding after endoscopic treatment in EGV patients(HR=2.33,95%CI 1.01-5.39,P=0.047).Conclusions The PEPGV is an independent predictor of re-bleeding after endoscopic treatment in EGV patients.It is suggested that when patients with EGV receive endoscopic treatment to prevent re-bleeding,portal vascular CT is suggested to evaluate PEPGV.For patients with giant extraluminal vascular masses,fully evaluating other treatment options such as transjugular intrahepatic portosystemic shunt,or adjusting endoscopic treatment ways is recommended.
10.Activation of pregnane X receptor sensitizes alcoholic steatohepatitis by transactivating fatty acid binding protein 4.
Yiwen ZHANG ; Bingfang HU ; Shaoxing GUAN ; Pan LI ; Yingjie GUO ; Pengfei XU ; Yongdong NIU ; Yujin LI ; Ye FENG ; Jiewen DU ; Jun XU ; Xiuchen GUAN ; Jingkai GU ; Haiyan SUN ; Min HUANG
Acta Pharmaceutica Sinica B 2024;14(11):4776-4788
Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

Result Analysis
Print
Save
E-mail