1.Clinical manifestation and imaging diagnostic analysis of fat embolism syndrome
Qian DAN ; Hai-Yan WU ; Yun-Jie HUANG ; Fei LUO ; Xu-Xue LI
China Journal of Orthopaedics and Traumatology 2024;37(3):306-310
Objective To explore characteristics of clinical and imaging findings in patients with fat embolism syndrome.Methods From January 2021 to October 2022,clinical manifestations of 13 patients with fat embolism due to fracture or or-thopaedic surgery were retrospectively analyzed,including 11 males and 2 females,aged from 17 to 60 years old.Mental and respiratory abnormalities and changes in vital signs occurred after admission or after surgery,and patient's chest and brain imaging results were abnormal.The patient's mental and respiratory abnormalities,vital signs,chest and brain imaging results were continuously monitored.Results The main clinical manifestations of fat embolism syndrome were abnormal pulmonary respiration in 13 patients,abnormal central nervous function in 7 patients,and spotted rash in 2 patients.Chest CT showed dif-fuse distribution of ground glass shadows in 13 patients,and severe symptoms were"snowstorm".Nine patients with ground glass fusion consolidation,5 patients with multiple nodules and 4 patients accompanied by bilateral pleural effusion.Head CT findings of 5 patients were negative,and head MRI findings of 1 patient showed multiple T1WI low signal,T2WI high signal shadow,DWI high signal shadow,and"starry sky sign"in basal ganglia,radiative crown,hemioval center,thalamus,frontal parietal cortex and subcortex.Conclusion Fat embolism syndrome has a high mortality rate.Clinical manifestations of respira-tory system and nervous system are not specific,and the skin spot rash has a characteristic manifestation.The"blizzard"sign is the specific manifestation of chest X-ray and CT examination of fat embolism,and the"starry sky"sign is the typical manifesta-tion of diffusion-weighted sequence of brain MRI examination of fat embolism.
2.Structure-based discovery of orally efficient inhibitors via unique interactions with H-pocket of PDE8 for the treatment of vascular dementia.
Xu-Nian WU ; Qian ZHOU ; Ya-Dan HUANG ; Xi XIE ; Zhe LI ; Yinuo WU ; Hai-Bin LUO
Acta Pharmaceutica Sinica B 2022;12(7):3103-3112
Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC50 = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.
3.The metabolic networks of ferroptosis and links to lung diseases.
Hai-Peng CHENG ; Dan-Dan FENG ; Shao-Jie YUE ; Zi-Qiang LUO
Acta Physiologica Sinica 2020;72(5):566-574
Ferroptosis is a newly discovered non-apoptotic form of regulated cell death driven by iron-dependent lipid peroxidation. The present studies have shown that many metabolic processes and homeostasis are affected by ferroptosis. It is related to many lung diseases, including acute lung injury, chronic obstructive pulmonary disease and pulmonary fibrosis, etc. Currently, the research on ferroptosis is still in its infancy. Previous studies have confirmed that ferroptosis is regulated by a variety of genes, and the mechanism is complex, mainly involving iron homeostasis and lipid peroxidation metabolism. This review summarizes some regulation networks of metabolic processes associated with ferroptosis and discusses the roles of ferroptosis in the pathophysiological progression of many lung diseases. We expected to provide new ideas and references for the treatment of these diseases.
Ferroptosis
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Humans
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Iron
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Lipid Peroxidation
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Metabolic Networks and Pathways
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Pulmonary Disease, Chronic Obstructive
4.Investigation of Relationship Between Spleen and Alzheimer' s Disease Based on Glucose, Lipid and Energy Metabolisms
Qin ZHENG ; Jun LUO ; De-lin ZHANG ; Yu TANG ; Mei-fang ZHU ; Dan-feng TANG ; Hai-xia WU ; Yuan-yuan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(5):178-185
Alzheimer' s disease (AD) is a chronic neurodegenerative disease, which is seriously affecting people' s lives. Until now, the pathogenesis of AD is still unknown which result in its worldwide difficulties in prevention and treatment. Some studies have shown that AD might be a metabolic disease associated with glucose, lipid and energy metabolisms. Traditional Chinese medicine (TCM) believes that the spleen is acquired foundation and the origination of Qi and blood. The function of spleen is not only closely related to the metabolism of substance and energy, but also related to the aging of human body. In this article, we summarized and analyzed the interrelationship of metabolism, AD and spleen, as well as the effect of spleen-invigorating prescription on AD. The purpose of the paper is to analyze the possible mechanism of TCM treating AD from the perspective of regulating metabolism, explore the potential value of spleen-strengthening TCM in the treatment or prevention of AD, and provide new ideas for exploring the drug development and TCM therapy of AD.
5.Diagnostic Performance of ⁶⁸Gallium Labelled Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging for Staging the Prostate Cancer with Intermediate or High Risk Prior to Radical Prostatectomy: A Systematic Review and Meta-analysis
Hui WU ; Ting XU ; Xiao WANG ; Yong Bo YU ; Zhong Yuan FAN ; Dan Xia LI ; Lei LUO ; Xue Cheng YANG ; Wei JIAO ; Hai Tao NIU
The World Journal of Men's Health 2020;38(2):208-219
PURPOSE: To compare the diagnostic efficiency of ⁶⁸Gallium labelled prostate-specific membrane antigen positron emission tomography (⁶⁸Ga-PSMA PET) and magnetic resonance imaging (MRI) for staging the lymph node metastases (LNMs) in the prostate cancer.MATERIALS AND METHODS: A broad search of scientific databases including PubMed, EMBASE, Web of Science, Cochrane Database, and Chinese Biomedicine Literature Database (updated prior to November 1st, 2018) was conducted systematically by two reviewers. In this paper, we evaluated the methodological quality of each included article independently and performed a systematic review and meta-analysis to reveal the summary of the diagnostic performance of ⁶⁸Ga-PSMA PET and MRI in properly identifying LNMs of intermediate- and/or high-risk prostate cancer.RESULTS: Thirteen eligible articles comprising 1,597 patients were included. For LNMs detection, the pooled sensitivity and specificity of ⁶⁸Ga-PSMA PET were 0.65 (95% confidence interval [CI]: 0.49–0.79) and 0.94 (95% CI: 0.88–0.97), respectively, while the corresponding values of MRI were 0.41 (95% CI: 0.26–0.57) and 0.92 (95% CI: 0.86–0.95). The area under the symmetric receiver-operating characteristic (SROC) curve for ⁶⁸Ga-PSMA PET and MRI were 0.92 and 0.83, respectively.CONCLUSIONS: In intermediate- or high-risk pre-treatment prostate cancer, ⁶⁸Ga-PSMA PET had a higher sensitivity and a slightly different specificity in probing the LNMs when comparing with MRI. Moreover, the area under the SROC curve indicated that ⁶⁸Ga-PSMA PET was a more effective weapon for predicting the LNMs prior to radical surgery.
6. Environmental enrichment ameliorates lipopolysaccharide-induced cognitive impairment by inhibiting NOD-like recepter protein 3 in fla mmasome activation in mice
Lei NIU ; Shi-Shi LUO ; Wei LI ; Wen-Yu CAO ; Zheng-Hai LIU ; Dan LUO ; Zhi-Wen LIU ; Yang XU
Acta Anatomica Sinica 2020;51(2):172-177
Objective To investigate the effect of environmental enrichment (EE) on lipopolysaccharide (LPS) induced cognitive dysfunction in mice. Methods A total of thirty six 3 weeks old Kunming mice experienced 8 weeks of EE or standard environment (SE) feeding. After 8 weeks, they were divided into three groups: standard environment+ normal saline (SE+NS) group, standard environment+lipopolysaccharide (SE+LPS) group, environmental enrichment+ lipopolysaccharide (EE+LPS) group. The open field test was used to measure the locomotive of mice, and the cognitive function was determined by novelty object recognition test. The expression of microglial marker ionized calcium binding adaptor molecule-1 (IBA-1) in hippocampus was determined by immunohistochemical staining. The expression of microglial activation marker CD68 and NOD-like receptor protein 3 (NLRP3) inflammasome related protein in the hippocampus was detected by Western blotting. Results In the open field test, there was no difference in the activity among the three groups. Compared with the SE + NS group, SE + LPS group showed decreased discrimination ratio in novelty object recognition task, with remarkably up-regulated expression of CD68 in the hippocampus (P< 0. 01) . In addition, SE+LPS group exhibited significantly enhanced expression of NLRP3, apoptosis associated speck-like protein (ASC), Caspase-1 and interleukin-1β(IL-1β) in the hippocampus compared with SE + NS group (P < 0. 05) . Compared with the SE + LPS group, EE+LPS group showed enhanced discrimination ratio in the object recognition task, with down-regulated expression of CD68, NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the hippocampus (P < 0. 01) . Conclusion Environmental enrichment can alleviate LPS induced cognitive dysfunction, which might be attributed to the inhibiting of microglia and NLRP3 activation in the hippocampus.
7.Current situation of heavy metal pollution,detection and removal techniques in medicinal marine organisms in China.
Dan-Dan KONG ; Xin-Yue LI ; Ying MENG ; Jiao-Yang LUO ; Shi-Hai YANG ; Mei-Hua YANG
China Journal of Chinese Materia Medica 2019;44(23):5022-5030
As an important branch of traditional medicines,medicinal marine organisms have many advantages,including biological diversity,remarkable biological activity,especial for the treatment of anti-cancer,anti-virus,anti-coagulation,analgesia,anti-bacterial,cardiovascular and cerebrovascular diseases. In recent years,with the continuous exploration of marine organisms by human beings,many marine organisms with specific biological activities and medicinal prospects have been found,which have attracted great attention around the world and thus called " new hope" to solve human health problems. However,due to the rapid development of modern industry,heavy metal pollution not only poses a great threat to medicinal marine living resources,but also hinders the development of marine biomedical industry and threatens human health. In view of this,this paper introduced the development trend of medicinal marine organisms and the current situation of heavy metal pollution and focusing on the analysis technology and chemical removal technology of heavy metals in medicinal marine organisms,which is to provide reference for the heavy metals control in marine medicines and the development and utilization of marine medicines.
Aquatic Organisms
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China
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Environmental Monitoring
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Medicine, Chinese Traditional
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Metals, Heavy/analysis*
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Water Pollutants, Chemical/analysis*
8.Safety evaluation of heavy metals contaminated Xiaochaihu Tang using health risk assessment model.
Xin-Yue LI ; Dan-Dan KONG ; Rong WANG ; Jiao-Yang LUO ; Shi-Hai YANG ; Mei-Hua YANG
China Journal of Chinese Materia Medica 2019;44(23):5058-5064
In order to further improve the quality and safety evaluation standards of traditional Chinese medicine compound preparation,Xiaochaihu Tang compound preparations were selected to analyze the pollution level of heavy metals deeply,and the potential health risks were evaluated under taking such kind of compound preparations. In this study,the contents of copper( Cu),arsenic( As),cadmium( Cd),mercury( Hg),and lead( Pb) in different Xiaochaihu Tang compound preparations were determinated by the method of inductively coupled plasma mass spectrometry( ICP-MS). Moreover,combined with target hazard coefficient method and in vitro artificial system,the bioaccessibility and health risk level was investigated in three main consumption ways including powder,decoction and granule. The result was showed that,under the maximum residual limit set by International Standard Organization,only one batch of raw herb was eight times exceeded the Hg MRL,however,in water decoctions and granules,the heavy metal residue rate was reduced to 2. 02%( Hg in granules)-42. 85%( Cd in granules). So,the heavy metal pollutions and health risks can be reduced to safe region in spite of the serious pollution in raw herbs. Besides,the THQ and CR values of the three consumption methods were lower than the standard values of non-carcinogenic and carcinogenic risks of each heavy metal. It can be seen that even if the heavy metals in the raw herbs exceed the standard,the use of Xiaochaihu Tang decoction and granules can reduce the harm of heavy metals to the human body. Above all,the establishment of this health risk assessment model can be provided experimental basis and reference value for improving the safety evaluation standard of other heavy metals contained traditional Chinese medicine( TCM) compound preparations,and further improving the quality control methods of other different toxic compounds in clinical use.
China
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Drug Contamination
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Drugs, Chinese Herbal/analysis*
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Environmental Pollution
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Humans
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Metals, Heavy/analysis*
;
Risk Assessment
9.Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via MyD88’s effects on the gut microbiota
Hui wen XIAO ; Yuan LI ; Dan LUO ; Jia li DONG ; Li xin ZHOU ; Shu yi ZHAO ; Qi sheng ZHENG ; Hai chao WANG ; Ming CUI ; Sai jun FAN
Experimental & Molecular Medicine 2018;50(1):e433-
Although radiation therapy is a cornerstone of modern management of malignancies, various side effects are inevitably linked to abdominal and pelvic cancer after radiotherapy. Radiation-mediated gastrointestinal (GI) toxicity impairs the life quality of cancer survivors and even shortens their lifespan. Hydrogen has been shown to protect against tissue injuries caused by oxidative stress and excessive inflammation, but its effect on radiation-induced intestinal injury was previously unknown. In the present study, we found that oral gavage with hydrogen-water increased the survival rate and body weight of mice exposed to total abdominal irradiation (TAI); oral gavage with hydrogen-water was also associated with an improvement in GI tract function and the epithelial integrity of the small intestine. Mechanistically, microarray analysis revealed that hydrogen-water administration upregulated miR-1968-5p levels, thus resulting in parallel downregulation of MyD88 expression in the small intestine after TAI exposure. Additionally, high-throughput sequencing showed that hydrogen-water oral gavage resulted in retention of the TAI-shifted intestinal bacterial composition in mice. Collectively, our findings suggested that hydrogen-water might be used as a potential therapeutic to alleviate intestinal injury induced by radiotherapy for abdominal and pelvic cancer in preclinical settings.
Animals
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Body Weight
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Down-Regulation
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Gastrointestinal Microbiome
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Gastrointestinal Tract
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Humans
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Hydrogen
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Inflammation
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Intestine, Small
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Mice
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Microarray Analysis
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Oxidative Stress
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Pelvic Neoplasms
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Quality of Life
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Radiotherapy
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Survival Rate
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Survivors
10.Muscarinic receptor 3 agonist promotes epithelial-meschymal transition in human lung cancer A549 cells by activating PI3K/AKT signaling pathway
Jing XING ; Geng-Peng LIN ; Hai-Dan LUO ; Zhi-Min ZENG ; Hui-Ling YANG ; Yu-Biao GUO
Chinese Journal of Pathophysiology 2018;34(3):423-427
AIM: To investigate the possible signaling pathway that promotes epithelial-mesenchymal transi-tion(EMT)of the lung cancer A549 cells stimulated with muscarinic receptor 3(M3R)agonist carbachol.METHODS:The lung cancer cells A549 were treated with 400 μmol/L carbachol.The morphological changes of the cells were observed under inverted phase contrast microscope.The migration and invasion abilites were measured by Wound healing and Tran-swell assays.qPCR was used to detect the mRNA level of vimentin and E-cadherin.The protein levels of p-AKT,vimentin and E-cadherin were determined by Western blot.RESULTS:After treatment with carbachol,the A549 cells showed loss of the close connection and the cell morphology was transformed from irregular polygon to spindle -like cells.The results of Wound healing and Transwell assays showed that the migration and invasion abilites of the A 549 cells were enhanced.Car-bachol increased the vimentin expression and decreased the E-cadherin expression at mRNA and protein level(P<0.05). The phosphorylation of AKT in the A549 cells was up-regulated(P<0.05).These changes was inhibited by M3R antago-nist 4-DAMP.CONCLUSION:Carbachol promotes EMT in the human lung cancer A 549 cells by activating PI3K/AKT signaling pathway.

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