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Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction

Chinese Journal of Natural Medicines 2024年第5期22卷 402-415页

作者： XIU Ye WANG Sihao ZHANG Ping LI Chengwei WU Zhixin WEN Jincai XU Yingjie LV Guiji ZHAO Xiaomei DONG Xu CHEN Yichong LI Junjie WANG Yan ZOU Liang XIAO Xiaohe BAI Zhaofang School of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing 100039China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100039China

In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and *** this,the clinical approval of drugs targeting the cGAS-STING pathway has been *** Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our *** found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku hospital Pediatrics-1(THP-1)*** inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling *** vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.

关键词： Total glucosides of gaeony cGAS-STING pathway Inflammation LPS/D-GalN STING inhibitor

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Compatibility with Fructus Ligustri Lucidi Effectively Mitigates Idiosyncratic Liver Injury of Epimedii Folium by Modulating NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 159-170页

作者： Xiao-Mei Zhao Zhi-Xin Wu Yan Wang Ying-Jie Xu Ye Xiu Xu Dong Jun-Jie Li Gui-Ji Lv Si-Hao Wang Yu-Rong Li Zhao-Fang Bai Xiao-He Xiao Department of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina Department of military Patient Management The Fifth Medical Center of PLA General HospitalBeijingChina Department of Hepatology China military Institute of Chinese Materia The Fifth Medical Center of PLA General HospitalBeijingChina Departmentof Hepatology National Key Laboratory of Kidney DiseasesBeijingChina

Background: Idiosyncratic drug-induced liver injury(IDILI) is a serious side effect of drugs, Epimedii Folium(EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome. Fructus Ligustri Lucidi(FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Aims and Objectives: Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Results: Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. Conclusions: FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.

关键词： Epimedii Folium Fructus Ligustri Lucidi idiosyncratic drug-induced liver injury NOD-like receptor family pyrin domain containing 3 inflammasome traditional Chinese medicine

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Efficacy of a Nutritional Cream Intervention to Treat Depression in Rescuers:A Randomized Controlled Trial

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Biomedical and Environmental Sciences 2024年第7期37卷 754-761页

作者： Qiao Wang Hengyu Luan Chunyan Li Rufang Gong Qiongxuan Li Jiayi Deng Xiaoyong Sai Department of Statistics and Epidemiology The Graduate School of the Chinese PLA General HospitalBeijing 100853China Comprehensive Internal Medicine Western Medical Branch of PLA General HospitalBeijing 100144China Department of Respiratory The First Medical Center of PLA General HospitalBeijing 100853China Department of Pharmacy Intravenous Admixture Services(PIVAS) The First Medical Center of PLA General HospitalBeijing 100853China

Objective To explore the effectiveness of a nutritional intervention in rescuers who screened positive for *** A randomized controlled trial design was *** June to August,2022,4,460 rescuers were screened using the Self-Rating Depression Scale(SDS),and 1,615 positive cases were ***-one volunteers were recruited and randomly divided into a nutritional intervention group and a control *** intervention group received health education and nutritional intervention(a compound paste therapy primarily composed of red roses and Seville orange flowers),while the control group received psychological *** scores were assessed before and after the *** There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention(P<0.05).Furthermore,the SDS scores of the intervention group were significantly lower than those of the control group,both before and after the intervention(P<0.05).No severe adverse reactions were observed during safety *** The nutritional intervention effectively reduced the depression scores in *** nutritional intervention is recommended for rescuers who initially screen positive for depression.

关键词： Nutritional intervention Rescuers Depression Randomized controlled trial

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Phospholipase A2 enzymes pla2G2A and pla2G12B as potential diagnostic and prognostic biomarkers in cholangiocarcinoma

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 289-306页

作者： Chen Qiu Yu-Kai Xiang Xuan-Bo Da Hong-Lei Zhang Xiang-Yu Kong Nian-Zong Hou Cheng Zhang Fu-Zhou Tian Yu-Long Yang Center of Gallbladder Disease Shanghai East HospitalInstitute of Gallstone DiseaseSchool of MedicineTongji UniversityShanghai 200092China general Surgery Center Chengdu Military General HospitalChengdu 610083Sichuan ProvinceChina

BACKGROUND Phospholipase A2(pla2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface ***,these enzymes play a significant role in the development of diverse *** To systematically and comprehensively explore the expression of the pla2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression *** study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on pla2G2A and *** Set Enrichment Analysis was utilized to pinpoint associated ***,relevant hub genes and microRNAs for pla2G2A and pla2G12B were predicted,and their correlation with the prognosis of CCA was *** pla2G2A and pla2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy *** expression of pla2G2A was correlated with poorer overall survival in CCA ***,the study delineated pathways and miRNAs associated with these *** Our findings suggest that pla2G2A and pla2G12B may serve as novel potential diagnostic and prognostic markers for *** increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.

关键词： pla2G2A pla2G12B Diagnostic Prognostic biomarkers cholangiocarcinoma

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Biophysical-driven piezoelectric and aligned nanofibrous scaffold promotes bone regeneration by re-establishing physiological electrical microenvironment

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Nano Research 2024年第8期17卷 7376-7393页

作者： Aoao Wang Xinbo Ma Yafeng Yang Guoliang Shi Liwei Han Xiantong Hu Rui Shi Jun Yan Quanyi Guo Yantao Zhao Senior Department of Orthopedics the Fourth Medical Center of PLA General HospitalBeijing 100048China Department of Chemistry Capital Normal UniversityBeijing 100048China National Center for Orthopaedics Beijing Research Institute of Traumatology and OrthopaedicsBeijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Xijing 986 hospital Department The Fourth Military Medical UniversityXi'an 710032China Institute of Orthopedics Chinese PLA General HospitalBeijing Key Laboratory of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLABeijing 100853China

The initial healing stages of bone fracture is a complex physiological process involving a series of spatially and temporally overlapping events,including pathogen clearance,immunological modulation,and *** this study,we have developed a piezoelectric and aligned nanofibrous scaffold composed of ZnO@PCL/PVDF with multiple antibacterial,immunomodulatory,and osteogenic effects using electrospinning *** scaffold’s piezoelectric signal output under ultrasound(US)control can be similar to the physiological electrical signals of healthy bone tissue,creating a truly biomimetic electrical microenvironment in the bone *** vitro studies have shown that ZnO@PCL/PVDF scaffold significantly enhances the proliferation,migration,and osteogenic differentiation of MC3T3-E1 cells under piezoelectric drive provided by ***,the scaffold exhibits inhibitory effects on the growth of *** and ***,as well as the ability to induce M2 macrophage polarization,indicating potent antibacterial and immunomodulatory *** vivo experiments demonstrated that the ZnO@PCL/PVDF scaffold can accelerate the repair of mandibular defects in rats,effectively inhibit bacterial colonization,and reduce inflammatory ***,this study confirms that the newly developed ZnO@PCL/PVDF scaffold effectively promotes bone repair by truly mimicking the endogenous electrical microenvironment and precisely regulating the temporospatial disorders of initial bone healing,thus providing a simple and effective solution for bone defects.

关键词： piezoelectricity bone defect bacterial infection ZnO nanoparticles immunomodulation osteogenesis

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Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model

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Neuroscience Bulletin 2024年第8期40卷 1037-1052页

作者： Chenrui Yin Kefei Luo Xinyue Zhu Ronghang Zheng Yu Wang Guangdan Yu Xiaorui Wang Fei She Xiaoying Chen Tao Li Jingfei Chen Baduojie Bian Yixun Su Jianqin Niu Yuxin Wang Department of Histology and Embryology Third Military Medical UniversityChongqing 400038China Department of Respiratory Diseases Central Medical Branch of PLA General HospitalBeijing 100853China China Astronaut Research and Training Center Beijing 100094China Department of Emergency the Fourth Medical Center of the Chinese PLA General HospitalBeijing 100142China Army 953 hospital Shigatse Branch of Xinqiao HospitalThird Military Medical University(Army Medical University)Shigatse 857000China Research Centre Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen 518107China

Posttraumatic stress disorder(PTSD)is a complex mental disorder notable for traumatic experience *** current first-line treatments are linked with clinically important symptom reduction,a large proportion of patients retained to experience considerable residual symptoms,indicating pathogenic mechanism should be illustrated *** studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory ***,its role in PTSD remains to be *** this study,we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and ***,but not risperidone or sertraline,has a more profound rescue effect on neuropsychological behaviors and myelin *** mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt *** data demonstrated the correlation between PTSD and abnormal myelination,suggesting that the oligodendroglial lineage could be a target for PTSD treatment.

关键词： PTSD Fear memory Myelination Oligodendroglial differentiation Fluoxetine Wnt signaling

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No Incidence of Liver Cancer Was Observed in A Retrospective Studyof Patients with Aristolochic Acid Nephropathy

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Chinese Journal of Integrative Medicine 2024年第2期30卷 99-106页

作者： SU Tao FANG Zhi-e GUO Yu-ming WANG Chun-yu WANG Jia-bo JI Dong BAI Zhao-fang YANG Li XiAO Xiao-he Renal Division Department of MedicinePeking University First HospitalBeijing(100034)China Department of Pharmacy Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Department of Hepatology Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China China military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Phase I Clinical Trials Unit Department of Medicine for Infectious DiseasesFifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Department of Pharmacy Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250000)China National Key Laboratory of Kidney Diseases Beijing(100039)China

Objective:To assess the risk of aristolochic acid(AA)-associated cancer in patients with AA nephropathy(AAN).Methods:A retrospective study was conducted on patients diagnosed with AAN at Peking University First hospital from January 1997 to December ***-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of *** primary endpoint was the incidence of liver cancer,and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to ***:A total of 337 patients diagnosed with AAN were included in this *** the initiation of taking AA to the termination of follow-up,39 patients were diagnosed with *** cases of liver cancer were observed throughout the entire follow-up period,with urinary cancer being the predominant type(34/39,87.17%).Logistic regression analysis showed that age,follow-up period,and diabetes were potential risk factors,however,the dosage of the drug was not significantly associated with urinary ***:No cases of liver cancer were observed at the end of ***,a high prevalence of urinary cancer was observed in AAN *** a direct causality between AA and HCC is challenging.

关键词： aristolochic acid hepatocellular carcinoma urinary cancer drug safety retrospective study

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Effi cacy of partial and complete resuscitative endovascular balloon occlusion of the aorta in the hemorrhagic shock model of liver injury

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World Journal of Emergency Medicine 2024年第1期15卷 10-15页

作者： Yi Shan Yang Zhao Chengcheng Li Jianxin Gao Guogeng Song Tanshi Li Department of Emergency Medicine Chinese PLA Medical SchoolBeijing 100853China Department of Emergency Medicine the Sixth Medical Center of PLA General HospitalBeijing 100048China Department of Emergency Medicine School of MedicineSouth China University of TechnologyGuangzhou 510006China Department of Emergency Medicine the First Medical Center of PLA General HospitalBeijing 100853China

BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic ***,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBOA)can alleviate ischemic burden;however,its security and eff ectiveness prior to operative hemorrhage control remains ***,we aimed to estimate the effi cacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic ***:Twenty Landrace pigs were randomized into control(no aortic occlusion)(n=5),intervention with complete REBOA(cREBOA)(n=5),continuous pREBOA(C-pREBOA)(n=5),and sequential pREBOA(S-pREBOA)(n=5)*** the cREBOA and C-pREBOA groups,the balloon was inflated for 60 *** hemodynamic and laboratory values were compared at various observation time *** samples immediately after animal euthanasia from the myocardium,liver,kidneys,and duodenum were collected for histological assessment using hematoxylin and eosin ***:Compared with the control group,the survival rate of the REBOA groups was prominently improved(all P<0.05).The total volume of blood loss was markedly lower in the cREBOA group(493.14±127.31 mL)compared with other groups(P<0.01).The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups(P<0.05).At 120 min,the S-pREBOA group showed higher alanine aminotransferase(P<0.05)but lower blood urea nitrogen compared with the cREBOA group(P<0.05).CONCLUSION:In this trauma model with liver injury,a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure,despite persistent *** tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures,and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.

关键词： Non-compressible torso hemorrhage Liver injury Ischemia-reperfusion injury Resuscitative endovascular balloon occlusion of the aorta

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Robot-assisted treatment of secondary epilepsy caused by parasitic infection:a case report

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Acta Epileptologica 2024年第2期7卷 143-150页

作者： Juan Luo Xin Chen Sixun Yu Haifeng Shu Department of Neurosurgery Affiliated Hospital of Southwest Medical UniversityLuzhou Sichuan 646000China Department of Neurosurgery General Hospital of the Western Theater Command of the PLAChengdu Sichuan 610083China

Background Cerebral sparganosis represents the most severe manifestation of sparganosis,with a relatively low global *** cases of secondary epileptic seizures caused by sparganosis infection in the functional areas of the brain,what advanced neurosurgical techniques should be employed to precisely identify and excise the epi-leptic lesions in the deep functional areas of the brain,aiming to achieve maximal removal while minimising the risk of neurological deficits?This remains a current challenge for epilepsy *** presentation A 24-year-old Chinese male was admitted to our hospital,presenting with a history of left limb twitching persisting for over a *** main clinical symptoms presented twitching and numbness of his left limb without loss of *** the premise of inappropriate anti-seizure treatment,recurrent epilepsy attacked *** patient’s diagnosis was considered as“space-occupying lesions in the several lobes of brain,secondary epilepsy”after comprehensive assessment and *** experts considered that the patient’s space-occupying lesions in the right frontal and parietal lobes were highly suspected to be infected by *** report delved into the application of neurosurgery robot-assisted frameless stereotaxic technology and intraopera-tive stereotactic electroencephalography(SEEG)monitoring technology to accurately locate and optimize removal of parasite-related epileptic lesions situated in functional areas of the *** a result,the patient had achieved seizure freedom,leaving no symptoms of neurological *** With the highly integrated development of imaging technology,mechanical technology,computer control technology,and artificial intelligence,surgical robots are poised to play a larger role across various neurosur-gical specialties in the *** benefits for patients and the promising application of this technology,its utilization holds significant value.

关键词： Cerebral sparganosis Secondary epilepsy Robot Frameless stereotaxic technology

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Predicting Acute Mountain Sickness Using Regional Sea-Level Cerebral Blood Flow

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Biomedical and Environmental Sciences 2024年第8期37卷 887-896页

作者： Hao Zhang Jie Feng Shiyu Zhang Wenjia Liu Lin Ma Chinese pla Medical School Beijing 100853China Department of Radiology First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Radiology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China

Objective To investigate the role of sea-level cerebral blood flow(CBF)in predicting acute mountain sickness(AMS)using three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL).Methods Forty-eight healthy volunteers reached an altitude of 3,650 m by air after undergoing a head magnetic resonance imaging(MRI)including 3D-pCASL at sea *** CBF values of the bilateral anterior cerebral artery(ACA),middle cerebral artery(MCA),posterior cerebral artery(PCA),and posterior inferior cerebellar artery(PICA)territories and the laterality index(LI)of CBF were compared between the AMS and non-AMS *** analyses were performed to determine the relationship between CBF and AMS,and the predictive performance was assessed using receiver operating characteristic(ROC)*** The mean cortical CBF in women(81.65±2.69 mL/100 g/min)was higher than that in men(74.35±2.12 mL/100 g/min)(P<0.05).In men,the cortical CBF values in the bilateral ACA,PCA,PICA,and right MCA were higher in patients with AMS than in those *** CBF in the right PCA best predicted AMS(AUC=0.818).In women,the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of *** Although the mechanism and prediction of AMS are quite complicated,higher cortical CBF at sea level,especially the CBF of the posterior circulatory system,may be used for prediction in male volunteers using non-invasive 3D-pCASL.

关键词： Acute mountain sickness High-altitude headache Cerebral blood flow Arterial spin labeling Magnetic resonance imaging

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