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Biological Evaluation of Lysionotin:a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma

chinese Journal of Integrative Medicine 2024年第9期30卷 826-834页

作者： SHAO Xin-xin CHEN Cong LIU Jie LI Qing-jun HE Shan QI Xiang-hua FU Xian-jun WANG Zhen-guo The First Clinical College of Medicine Shandong University of Traditional Chinese MedicineJinan250355China Institute for Literature and Culture of chinese Medicine Shandong University of Traditional Chinese MedicineJinan250355China Key Laboratory of Classical Theory of traditional chinese Medicine Ministry of EducationShandong University of Traditional Chinese MedicineJinan250355China College of Pharmacy Shandong University of Traditional Chinese MedicineJinan250355China Experimental Center Shandong University of Traditional Chinese MedicineJinan250355China Neurology Department Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan250014China Marine traditional chinese Medicine Research Center Qingdao Academy of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineQingdao266114Shandong ProvinceChina

Objective:To explore the potential mechanism of lysionotin in treating ***:First,target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of *** binding between 5-lipoxygenase(5-LO)and lysionotin was detected by surface plasmon resonance(SPR)and molecular docking,and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis,***,the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry(LC-MS/MS).The protein expression,intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot,flow cytometry and fluorescence labeling,***:Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO,a key enzyme involved in the arachidonic acid metabolism pathway,to inhibit the proliferation of *** docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds,forming bonds with His600,Gln557,Asn554,and *** analysis further confirmed the interaction between 5-LO and ***,enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50%inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58µmol/L,respectively,and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid(P<0.05),and moreover,the LC-MS/MS results indicated that lysionotin can enter glioma cells well(P<0.01)and inhibit their *** blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO(P<0.05)and downstream leukotriene B4 receptor(P<0.01).In addition,the results showed that lysionotin affected intracellular calcium ion concentration by inh

关键词： 5-lipoxygenase inhibitor lysionotin 5-lipoxygenase leukotriene B4 calcium ion cytoskeleton

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Ankylosing spondylitis coexisting with Clonorchis sinensis infection: A case report

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World Journal of Clinical Cases 2024年第5期12卷 1018-1024页

作者： Tian-Xin Yi Wei Liu Wen-Fei Leng Xiao-Chuan Wang Liang Luo Department of Rheumatology Traditional Chinese Medicine Hospital Dianjiang ChongqingChongqing 408300China Department of Orthopaedic Traditional Chinese Medicine Hospital Dianjiang ChongqingChongqing 408300China Department of chinese Medicine The People's Hospital of Yubei District of Chongqing CityChongqing 401120China

BACKGROUND Ankylosing spondylitis(AS)is a chronic immune-mediated inflammatory *** prevailing theory links AS onset to infections in susceptible ***,infections may impair the immune *** studies have investigated links between AS and various infections-bacterial,viral,fungal,and other microorganism ***,limited attention has been given to the association between AS and Clonorchis sinensis(***)*** SUMMARY A 27-year-old male with a 10-yr history of AS presented to our hospital with inflammatory lower back pain as the primary *** years ago,the patient had achieved a stable condition after treatment with biological ***,he experienced a recurrence of lumbosacral pain with an unexplained cause 10 d before hospital admission.A lumbosacral magnetic resonance imaging(MRI)scan revealed bone marrow edema in the left sacroiliac joint,and laboratory indicators were ***,the presence of *** eggs was detected in the *** patient was prescribed praziquantel,resulting in the disap-pearance of *** eggs in subsequent routine stool tests and relief from lumbosacral pain.A follow-up MRI scan performed after 4 months revealed a reduction in bone marrow edema around the left sacroiliac *** *** infections could potentially trigger the exacerbation of *** should pay attention to investigating the presence of *** Ankylosing spondylitis(AS)is a chronic inflammatory and rheumatic disease resulting from an imbalance between innate and acquired immune responses[1].While it can affect any part of the spine,its primary symptoms are persistent back pain and stiffness in the lower back and *** prevalence of AS per 10000 individuals is 23.8 in Europe,31.9 in North America,16.7 in Asia,10.2 in Latin America,and 7.4 in Africa[2].Infections commonly occur in the first 3 months and may act as potential triggers for the

关键词： Ankylosing spondylitis Clonorchis sinensis Parasites Infection Case report

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Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions

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chinese Journal of Integrative Medicine 2024年第6期30卷 565-576页

作者： KE Jun-yu SONG Jin-bin LI Long HE Zhen-fan HUANG Zhuo-jian LIU Zheng-lin CHEN Gui-rong WANG Hai-yan WEN Su-ru ZHOU Heng-li MA Hui-lin DU Qun WU Yong-qiang LI Yan-wu CHEN Xin-lin School of Basic medical Sciences Guangzhou University of Chinese MedicineGuangzhou510006China Department of Surgery II Gaozhou Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese MedicineGaozhou525200China Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou510405China The First Clinical medical College of Guangzhou University of traditional chinese Medicine Guangzhou510405China

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

关键词： macrophage ulcerative colitis colon cancer chinese medicine

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Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 700-709页

作者： Kai Liu Chun-Xiao Wu Hui Liang Tao Wang Ji-Yuan Zhang Xiao-Tao Wang Department of Radiation and Oncology Traditional Chinese Hospital of Lu’an affiliated to Anhui University of Traditional Chinese MedicineLu’an 237000Anhui ProvinceChina Department of Gastroenterology Ehu branch of Xishan People’s Hospital of Wuxi CityWuxi 214116Jiangsu ProvinceChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Guangzhou University of Traditional Chinese MedicineGuangzhou 510400Guangdong ProvinceChina Department of Gastrointestinal Surgery Hunan Provincial People’s HospitalChangsha 410002Hunan ProvinceChina Department of traditional chinese medicine Ehu branch of Xishan People’s Hospital of Wuxi CityWuxi 214116Jiangsu ProvinceChina

BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all *** is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with *** To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced *** This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January *** baseline attributes were compared using either the Chi-square test or the Fisher exact probability *** chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver *** The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver *** objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),***,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),*** median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than *** median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than *** Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.

关键词： Gastric cancer Spread of cancer to the liver Treatment with immunotherapy Effectiveness of treatment

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Investigating the causal associations between five anthropometric indicators and nonalcoholic fatty liver disease:Mendelian randomization study

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World Journal of Clinical Cases 2024年第7期12卷 1215-1226页

作者： Xian-Pei Xiao Yong-Jun Dai Yu Zhang Meng Yang Jian Xie Guo Chen Zheng-Jun Yang Department of Oncology Luojiang District People's Hospital of Deyang CityDeyang 618000Sichuan ProvinceChina Department of Orthopaedics Luojiang District People's Hospital of Deyang CityDeyang 618000Sichuan ProvinceChina Department of Infectious Diseases Hospital of Chengdu University of Traditional Chinese MedicalChengdu 610500Sichuan ProvinceChina

BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating *** To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization(MR)*** The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators,including hip circumference(HC),waist circumference(WC),waist-to-hip ratio(WHR),body mass index(BMI),and body fat percentage(BF).Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen ***-wide significant single nucleotide polymorphisms were chosen as instrumental *** MR(UVMR)and multivariable MR(MVMR)designs with analytical approaches,including inverse variance weighted(IVW),MR-Egger,weighted median(WM),and weighted mode methods,were used to assess the causal relationships between anthropometric indicators and *** Causal relationships were revealed by UVMR,indicating that a higher risk of NAFLD was associated with a perunit increase in WC[IVW:odds ratio(OR)=2.67,95%CI:1.42-5.02,P=2.25×10^(−3)],and BF was causally associated with an increased risk of NAFLD(WM:OR=2.23,95%CI:1.07-4.66,P=0.033).The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and ***,no causal association between BF and NAFLD was *** addition,other causal relationships of HC,WHR(BMI adjusted),and BMI with the risk of NAFLD were not retained after FDR *** This study establishes a causal relationship,indicating that an increase in WC is associated with a higher risk of *** demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.

关键词： Anthropometric indicator Waist circumference Nonalcoholic fatty liver disease Mendelian randomization Genetic variant

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Clinical significance of platelet mononuclear cell aggregates in patients with sepsis and acute respiratory distress syndrome

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World Journal of Clinical Cases 2024年第5期12卷 966-972页

作者： Chong-Min Huang Juan-Juan Li Wei-Ke Wei Department of Intensive Medicine The Second People's Hospital of Haining CityHaining 314419Zhejiang ProvinceChina Department of Integrated traditional chinese and Western Medicine Qingyang HospitalHangzhou 310023Zhejiang ProvinceChina

BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific *** of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion *** adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this *** We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March *** them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control *** diagnosis,venous blood samples were imme-diately collected from all *** cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the ***,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic *** The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic va

关键词： Sepsis Acute respiratory distress syndrome Platelet leukocyte aggregates Platelet mononuclear cell aggregates,Biomarker

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The Effect of Predictive Nursing Intervention on Cardiac Function and Clinical Outcomes in CCU Patients with Acute Myocardial Infarction After Interventional Therapy

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Journal of Clinical and Nursing Research 2024年第8期8卷 237-242页

作者： Tingting Wang Cui Xia Xuzhou city hospital of traditional chinese Medicine Xuzhou 221000Jiangsu ProvinceChina

Objective:To evaluate the impact of predictive nursing on the care of acute myocardial infarction(AMI)patients in the Coronary Care Unit(CCU)after interventional ***:From September 2021 to September 2023,84 AMI patients admitted to the CCU were randomly divided into two groups:the experimental group(42 patients)received predictive nursing,and the reference group(42 patients)received conventional *** function and clinical outcomes were compared between the ***:Before nursing,there was no difference in cardiac function between the two groups(P>0.05).After nursing,the cardiac function of the experimental group was better than that of the reference group(P0.05).After nursing,the psychological scores of the experimental group were lower than those of the reference group(P<0.05).Conclusion:Predictive nursing can improve the cardiac function and clinical outcomes of AMI patients after interventional therapy and can also regulate patients’negative psychological states.

关键词： Predictive nursing CCU Acute myocardial infarction Interventional therapy Cardiac function

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Reduced expression of semaphorin 3A in osteoclasts causes lymphatic expansion in a Gorham-Stout disease(GSD)mouse model

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 38-50页

作者： Dongfang ZHANG Hao XU Chi QIN Kangming CAI Jing ZHANG Xinqiu XIA Jingwen BI Li ZHANG Lianping XING Qianqian LIANG Wensheng WANG Laboratory of Molecular Medicine College of Life Science and State Key Laboratory of Cell Differentiation and RegulationHenan Normal UniversityXinxiang453007China Longhua hospital&Spine Institute Shanghai University of Traditional Chinese MedicineShanghai200032China Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education(Shanghai University of Traditional Chinese Medicine)Shanghai201203China Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochester14642USA

Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow *** the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely *** this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of *** to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in *** the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in *** an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in *** found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like *** staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the *** on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

关键词： Semaphorin 3A Gorham-Stout disease Osteoclast Osteolysis Lymphatic endothelial cell

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Paradoxical herniation associated with hyperbaric oxygen therapy after decompressive craniectomy: A case report

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World Journal of Clinical Cases 2024年第10期12卷 1793-1798页

作者： Zhong-Xing Ye Xin-Xin Fu Yang-Zong Wu Ling Lin Liang-Qi Xie Yu-Ling Hu Yi Zhou Zhu-Gui You Hai Lin Department of Neurosurgery The Second People's Hospital of Fujian Province(The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine)Fuzhou 350001Fujian ProvinceChina Department of Neurosurgery The Second Hospital of LongyanLongyan 364000Fujian ProvinceChina Department of Neurosurgery Zhangping City HospitalLongyan 364400Fujian ProvinceChina

BACKGROUND Whether hyperbaric oxygen therapy(HBOT)can cause paradoxical herniation is still *** SUMMARY A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after *** was administered 22 d after surgery due to speech *** herniation appeared on the second day after treatment,and the patient’s condition worsened after receiving mannitol treatment at the rehabilitation *** timely skull repair,the paradoxical herniation was resolved,and the patient regained consciousness and had a good recovery as observed at the follow-up *** Paradoxical herniation is rare and may be caused by ***,the underlying mechanism is unknown,and the understanding of this phenomenon is *** use of mannitol may worsen this *** skull repair can treat paradoxical herniation and prevent serious complications.

关键词： Decompressive craniectomy Hyperbaric oxygen therapy Mannitol Paradoxical herniation Case report

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Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway

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Journal of Pharmaceutical Analysis 2024年第6期14卷 914-925页

作者： Guiqin Ye Xin Sun Jiuzhou Li Yuanyuan Mai Ruilan Gao Jianbin Zhang Cancer Center Department of Medical OncologyKey Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang ProvinceZhejiang Provincial People's HospitalAffiliated People's HospitalHangzhou Medical CollegeHangzhou310014China Clinical Laboratory Yuhuan City HospitalTaizhouZhejiang317600China Hangzhou medical College Hangzhou311300China Department of Neurosurgery Binzhou People's HospitalBinzhouShandong256600China Institute of Hematology Research The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310060China

Lung cancer ranks the top of malignancies that cause cancer-related deaths *** leaves of Morus alba L are traditional chinese medicine widely applied in respiratory *** previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully *** synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic *** and its probe exerted similar growth-inhibitory effect on human lung cancer *** proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory ***-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 *** docking analysis demonstrated that MAN bound to E158 residue of PD-L1 *** downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T *** suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 *** vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic *** together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung *** modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

关键词： Moracin N Click chemistry PD-L1 T cell Lung cancer

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