1.Celecoxib improves right heart function in mice after acute high-altitude hypoxia exposure by increasing 12,13-diHOME level
Wei ZHANG ; Xinyu BAO ; Xiaoyue LAI ; Xiaoqin WAN ; Yan TAN ; Hongjun YIN ; Xiaoshi CAI ; Dingyuan TIAN ; Ziyang WANG ; Pan ZHENG ; Fang DENG ; Zhihui ZHANG
Journal of Army Medical University 2025;47(19):2289-2301
Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.
2.Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy.
Chaoqun WANG ; Hongjun YU ; Shounan LU ; Shanjia KE ; Yanan XU ; Zhigang FENG ; Baolin QIAN ; Miaoyu BAI ; Bing YIN ; Xinglong LI ; Yongliang HUA ; Zhongyu LI ; Dong CHEN ; Bangliang CHEN ; Yongzhi ZHOU ; Shangha PAN ; Yao FU ; Hongchi JIANG ; Dawei WANG ; Yong MA
Chinese Medical Journal 2025;138(22):2993-3003
BACKGROUND:
Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI.
METHODS:
In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy.
RESULTS:
A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent.
CONCLUSION
Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals
;
Arsenic Trioxide
;
Autophagy/physiology*
;
Reperfusion Injury/prevention & control*
;
Mice
;
Male
;
Proto-Oncogene Proteins c-akt/physiology*
;
Arsenicals/therapeutic use*
;
Oxides/therapeutic use*
;
Liver/metabolism*
;
Extracellular Signal-Regulated MAP Kinases/metabolism*
;
Mice, Inbred C57BL
3.Co-word cluster analysis of hotspots on self-management of patients with chronic heart failure at home and abroad in the past decade
Hongjun LIU ; Chunzhi ZHANG ; Yuqiu CHENG ; Yu GUO ; Zeya SHI ; Shuhui YIN
Chinese Journal of Modern Nursing 2025;31(15):2039-2045
Objective:To analyze and discuss the current status, hotspots and development dynamics of self-management in chronic heart failure (CHF) patients at home and abroad based on China National Knowledge Infrastructure and Web of Science databases.Methods:Literature on self-management of CHF patients was searched in China National Knowledge Infrastructure and Web of Science. The search period was from January 1, 2014 to May 31, 2024. Keyword cluster analysis was performed using Cite Space 6.3.R1 software.Results:A total of 411 articles in Chinese and 878 articles in English were included. In the past ten years, the annual publication volume of English literature was generally even, and the distribution trend of annual publication volume of Chinese literature showed an upward and then a downward trend. The hotspots of self-management of CHF patients in the Chinese literature mainly focused on health education, self-efficacy, and disease prognosis, and the hotspots of self-management of CHF patients in the English literature mainly focused on quality of life, disease management, and self-care.Conclusions:Analyzing the current status, hotspots and developmental dynamics of self-management in CHF patients can provide a reference for how to effectively promote self-management in CHF patients and conduct related research in the future.
4.Co-word cluster analysis of hotspots on self-management of patients with chronic heart failure at home and abroad in the past decade
Hongjun LIU ; Chunzhi ZHANG ; Yuqiu CHENG ; Yu GUO ; Zeya SHI ; Shuhui YIN
Chinese Journal of Modern Nursing 2025;31(15):2039-2045
Objective:To analyze and discuss the current status, hotspots and development dynamics of self-management in chronic heart failure (CHF) patients at home and abroad based on China National Knowledge Infrastructure and Web of Science databases.Methods:Literature on self-management of CHF patients was searched in China National Knowledge Infrastructure and Web of Science. The search period was from January 1, 2014 to May 31, 2024. Keyword cluster analysis was performed using Cite Space 6.3.R1 software.Results:A total of 411 articles in Chinese and 878 articles in English were included. In the past ten years, the annual publication volume of English literature was generally even, and the distribution trend of annual publication volume of Chinese literature showed an upward and then a downward trend. The hotspots of self-management of CHF patients in the Chinese literature mainly focused on health education, self-efficacy, and disease prognosis, and the hotspots of self-management of CHF patients in the English literature mainly focused on quality of life, disease management, and self-care.Conclusions:Analyzing the current status, hotspots and developmental dynamics of self-management in CHF patients can provide a reference for how to effectively promote self-management in CHF patients and conduct related research in the future.
5.Analysis of Molecular Mechanism of Angong Niuhuangwan in Alleviating Traumatic Brain Injury Based on Single Cell Sequencing
Zhiru YIN ; Liangliang TIAN ; Guangzhao CAO ; Jingjing ZHANG ; Hongjun YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):35-45
ObjectiveTo reveal the molecular mechanism of Angong Niuhuangwan(AGNH) in improving traumatic brain injury(TBI) based on single cell sequencing. MethodSeventy-five male SD rats were randomly divided into the sham group, model group, piracetam group(3.6 g·kg-1), AGNH low- and high-dose groups(0.09, 0.27 g·kg-1), with 15 rats in each group. In addition to the sham group, the other 4 groups used the modified Feeney free-fall impact method to prepare TBI model, and the drugs were administered by gavage immediately after modeling, 24 hours later, the modified neurological deficit score(mNSS) was performed, and brain tissue was isolated to determine the degree of cerebral edema. Hematoxylin-eosin(HE) staining was used to observe the injury degree in the cortex, CA1 region and CA3 region of brain tissue. The expression levels of cyclooxygenase-2(COX-2), interferon regulatory factor 1(IRF1), Janus kinase 2(JAK2) and suppressor of cytokine signaling 3(SOCS3) were observed by immunofluorescence(IF) staining. The levels of interleukin(IL)-6, IL-18, IL-1β, IL-17A, tumor necrosis factor-α(TNF-α), Caspase-1 and nucleotide binding oligomerization domain(NOD)-like receptor heat protein domain associated protein 3(NLRP3) inflammasome were determined by enzyme-linked immunosorbent assay(ELISA). The regulation of AGNH on each cell population was analyzed by single cell sequencing, and differentially expressed genes were analyzed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG), which led to construct microglia differentially expressed gene network to search for the key targets, and validated by ELISA and IF. ResultCompared with the sham group, the mNSS and brain water content were significantly increased in the model group(P<0.01). Compared with the model group, mNSS and brain water content in the low and high dose AGNH groups were decreased(P<0.05,P<0.01). HE staining results showed that compared with the sham group, the cells in the cerebral cortex and hippocampus of rats in the model group were seriously lost, and the cells were arranged loosely(P<0.01). Compared with the model group, AGNH could significantly increase the density of neurons in the CA1 and CA3 regions of the cerebral cortex and hippocampus, making the arrangement more compact, as well as improved cell morphology(P<0.05,P<0.01). ELISA and IF staining showed that AGNH could reduce the levels of Caspase-1, IL-17A, TNF-α, NLRP3 and COX-2 in brain tissue of TBI rats(P<0.05, P<0.01). A total of 13 cell subsets were identified by single cell sequencing, among which microglia played an important role in neuroimmunity. The results of GO enrichment analysis of differentially expressed genes in microglia showed that AGNH improved TBI in response to inflammation and TNF-α. KEGG enriched IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, etc. The results of network analysis showed that the key targets of AGNH in regulating TBI might be IL-6, IL-1β, JAK2, SOCS3, IRF1. IF and ELISA verification results showed that compared with the sham group, SOCS3 expression in microglia was decreased in the model group, and the expressions of IL-6, IL-1β, JAK2 and IRF1 were increased(P<0.01). Compared with the model group, AGNH could increase the expression of SOCS3, decrease the expression of IL-6, IL-1β, JAK2, IRF1 (P<0.05, P<0.01). ConclusionAGNH can reduce the degree of brain edema and brain injury, decrease the expression of inflammatory factors, and inhibit the expression of NLRP3 and its downstream Caspase-1 in TBI rats, which may act on the targets of IL-6, IL-1β, JAK2, IRF1 and SOCS3 in microglia.
6.Association between the Wnt signaling pathway and hepatic fibrosis
Qin FAN ; Hongjun LI ; Xiaoxia LI ; Yin YANG ; Haiyan CHEN ; Jiamao CHENG
Journal of Clinical Hepatology 2022;38(2):443-447
Hepatic fibrosis (HF) is a self-healing pathological process after all kinds of chronic liver injuries and can cause diseases such as liver cirrhosis and liver cancer. The Wnt signaling pathway is highly conserved in species evolution and widely exists in invertebrates and vertebrates, and many studies have confirmed that the Wnt signaling pathway is closely associated with the development and progression of HF. This article reviews the mechanisms of the classical and non-classical Wnt signaling pathways in regulating hepatic stellate cells, hepatic macrophages, and hepatic progenitor cells, so as to provide new ideas for subsequent studies on the mechanism of the Wnt signaling pathway in regulating HF and further exploration of therapeutic targets that can reverse HF.
7.Progress on drug treatment of acute respiratory distress syndrome
Chinese Pediatric Emergency Medicine 2022;29(10):764-767
Acute respiratory distress syndrome(ARDS) refers to non-cardiac respiratory failure caused by various internal and external factors in the lung, and is a common clinical critical illness.As in adults, lung-protective ventilation strategies combined with pharmacological support remain the mainstay of treatment for children with ARDS.A large number of clinical studies have been carried out on drug therapy, and some progress has been made.This article reviewed alveolar surfactants, hormones, nitric oxide, angiotensin converting enzyme 2, immune nutrition, etc., in order to provide references for subsequent treatment.
8.Characteristics of psychiatric contact consultation in inpatients with the COVID-19 in Wuhan: a retrospective analysis
Jie ZHANG ; Jiong TAO ; Xuan LI ; Hongjun PENG ; Ping YIN ; Fengchun WU ; Xianglan WANG ; Yaoguang GUO ; Enyi LIU ; Zhiyong ZHONG ; Aifeng LI ; Tianyi ZHAI ; Xuewu LI ; Fei FENG ; Xiangxin LIU ; Hongbo HE
Chinese Journal of Psychiatry 2020;53(4):282-286
Objective:This article summarized the characteristics of inpatients with the COVID-19 by psychiatric contact consultation in Wuhan.Method:This was a retrospective study. A total of 105 patients consulted by the Guangdong psychological medical team from March 1, 2020 to March 7, 2020 were selected. Data were collected by 20 psychiatrists responsible for the contact consultation, including age, gender, the main reasons for the contact consultation and the psychiatric treatment plan. The consultant doctor decided whether to enter the isolation ward according to the patient′s condition introduced by the attending physician, and whom were followed up within a week. Descriptive statistical analysis was used to analyze the data.Results:There were 105 patients from 5 designated hospitals, aged (58.3±18.9) years, 62.9% (66/105) were females, and 102 (97.1%) were consulted face-to-face in the isolated ward. Main reasons for consultation were anxiety (65, 61.9%), depression (27, 25.7%), insomnia (6, 5.7%), agitation (6, 5.7%), and illusion (1, 1%). Seventy-seven of those patients (73.3%) received individualized psychotherapy, 1(1.0%) was prescribed with psychiatric medication, and 27 (25.7%) were treated with both measures. Follow-up showed that psychological symptoms relieved in 102 cases (97.1%).Conclusion:Psychosocial symptoms such as anxiety and depression are common in infected patients, and thereby psychiatric contact and consultation is in great demand in the treatment of COVID-19. Early intervention of mental health professionals in the diagnosis and treatment of patients plays a positive role in the recovery of them.
9.Characteristics of psychiatric contact consultation in inpatients with the COVID-19 in Wuhan: a retrospective analysis
Jie ZHANG ; Jiong TAO ; Xuan LI ; Hongjun PENG ; Ping YIN ; Fengchun WU ; Xianglan WANG ; Yaoguang GUO ; Enyi LIU ; Zhiyong ZHONG ; Aifeng LI ; Tianyi ZHAI ; Xuewu LI ; Fei FENG ; Xiangxin LIU ; Hongbo HE
Chinese Journal of Psychiatry 2020;53(4):282-286
Objective:This article summarized the characteristics of inpatients with the COVID-19 by psychiatric contact consultation in Wuhan.Method:This was a retrospective study. A total of 105 patients consulted by the Guangdong psychological medical team from March 1, 2020 to March 7, 2020 were selected. Data were collected by 20 psychiatrists responsible for the contact consultation, including age, gender, the main reasons for the contact consultation and the psychiatric treatment plan. The consultant doctor decided whether to enter the isolation ward according to the patient′s condition introduced by the attending physician, and whom were followed up within a week. Descriptive statistical analysis was used to analyze the data.Results:There were 105 patients from 5 designated hospitals, aged (58.3±18.9) years, 62.9% (66/105) were females, and 102 (97.1%) were consulted face-to-face in the isolated ward. Main reasons for consultation were anxiety (65, 61.9%), depression (27, 25.7%), insomnia (6, 5.7%), agitation (6, 5.7%), and illusion (1, 1%). Seventy-seven of those patients (73.3%) received individualized psychotherapy, 1(1.0%) was prescribed with psychiatric medication, and 27 (25.7%) were treated with both measures. Follow-up showed that psychological symptoms relieved in 102 cases (97.1%).Conclusion:Psychosocial symptoms such as anxiety and depression are common in infected patients, and thereby psychiatric contact and consultation is in great demand in the treatment of COVID-19. Early intervention of mental health professionals in the diagnosis and treatment of patients plays a positive role in the recovery of them.
10.Recommendations in Guideline for Emergency Management of Anaphylaxis
Xiaotong LI ; Suodi ZHAI ; Qiang WANG ; Yuqin WANG ; Jia YIN ; Yuguo CHEN ; Rongchang CHEN ; Hongjun ZHANG ; Kehu YANG ; Tianzuo LI ; Ya'an ZHENG ; Qingbian MA ; Fang LIU ; Chang CUI ; Hangci ZHENG
Adverse Drug Reactions Journal 2019;21(2):85-91
The recommendations of Guideline for Emergency Management of Anaphylaxis answered 15 clinical questions about diagnosis,preparation for treatment,treatment measures,and post-treatment management of anaphylaxis and a total of 26 recommendations were formed.In the recommendations,the quality of evidence was divided into 4 levels:high,moderate,low,and very low.And the strength of recommendation was divided into 2 levels:strong and weak.The strength of recommendations was mainly determined by weighing the advantages and disadvantages,instead of relying on the quality of evidence.Emergency management of anaphylaxis in clinical practice could be carried out with reference to the recommendations of this guideline.

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