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Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma
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作者 XINFENG ZHANG SHUANG LI +8 位作者 MEIRU SONG YUE CHEN LIANGZHENG CHANG ZHERUI LIU HONGYUAN DAI YUTAO WANG GANGQI YANG YUN JIANG YINYING LU 《Oncology Research》 SCIE 2024年第4期679-690,共12页
Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expr... Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs. 展开更多
关键词 Hepatocellular carcinoma(HCC) Focal adhesion kinase(FAK) Proteolytic targeting chimera technology(PROTAC) Epithelial-mesenchymal transformation(EMT) METASTASIS
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The effects of hyperbaric oxygen therapy on paroxysmal sympathetic hyperactivity after cardiopulmonary resuscitation: a case series
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作者 Hongyu Wang Yihao Li +2 位作者 Meng Zhao Caihong Ren Sisen Zhang 《World Journal of Emergency Medicine》 SCIE CAS CSCD 2023年第6期477-480,共4页
The onset of cardiac arrest (CA) is sudden and critical.Due to cerebral ischaemia and hypoxia, the prognosis for post-cardiopulmonary resuscitation (CPR) patients is poor. Paroxysmal sympathetic hyperexcitability (PSH... The onset of cardiac arrest (CA) is sudden and critical.Due to cerebral ischaemia and hypoxia, the prognosis for post-cardiopulmonary resuscitation (CPR) patients is poor. Paroxysmal sympathetic hyperexcitability (PSH) is a potentially life-threatening condition, which is characterized by episodes of increased heart rate and blood pressure,sweating, hypothermia, and forced posture.[1] Hypoxicischaemic encephalopathy post-CPR can lead to PSH,which often indicates a worse prognosis. 展开更多
关键词 SYMPATHETIC RESUSCITATION PROGNOSIS
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The efficacy and safety of NeuroWell antidepressant dietary supplement,Deanxit,and their combination in the treatment of mild-to-moderate depression:A randomized clinical trial
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作者 Honglei Yin Zhuxin Sui +25 位作者 Yutong Wang Dechen Liu Qinglu Wang Yanchao Wang Lei Sun Jinfeng Li Zhen Li Yue Liu Shang Guo Wenwen Wang Hongtao Yin Ping Liu Kezhong Zhang Huaibo Zhang Yajun Liu Yanqiu Liu Qiqi Zhou Dianfang Wei Hui Zhang Shanshan Wang Yaochao Ning Shuang Geng Xuejun Wen Youping Deng Hongwei Wang Yunliang Wang 《Genes & Diseases》 SCIE 2024年第6期36-39,共4页
Depression is the leading global cause of,disability,affecting about 300 milion people worldwide.1;2 Depending on the number and severity of symptoms,depressive episodes can be classified as mild,moderate,and severe.P... Depression is the leading global cause of,disability,affecting about 300 milion people worldwide.1;2 Depending on the number and severity of symptoms,depressive episodes can be classified as mild,moderate,and severe.Previous studies have typically focused on the treatment of severe refractory depression,while there have been few studies on the treatment of mild-to-moderate depression. 展开更多
关键词 treatment clinical typically
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The Effects of Glomerular Endothelial Cell Autophagy on Diabetic Nephropathy
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作者 Zhang Ao Fan Lijing +4 位作者 Zhang Zeyu Zhu Danqi Hu Biying Xie Ting Liao Zhennan 《临床医学工程》 2019年第S01期3-3,共1页
Diabetic nephropathy is one of the most common causes of end-stage renal disease worldwide and is associated with increased mortality in patients with type 1 and type 2 diabetes.Autophagy is a highly conserved"au... Diabetic nephropathy is one of the most common causes of end-stage renal disease worldwide and is associated with increased mortality in patients with type 1 and type 2 diabetes.Autophagy is a highly conserved"autophagy"pathway and is an important mechanism for maintaining glomerular and tubular homeostasis.Emerging evidence suggests that targeted autophagy pathway activation and restoration of autophagy activity may have renal protection.Glomerular endothelial cells are an important key factor in the development of diabetic nephropathy.Endothelial dysfunction is involved in the development of diabetic and non-diabetic glomerular injury and renal fibrosis.Evidence of glomerular endothelial dysfunction in the late stages of diabetic nephropathy,such as thrombotic microangiopathy,including impairment of glomerular capillary microaneurysms and glomerular membrane lysis autophagy,is related to the pathogenesis of diabetic nephropathy.Here,we mainly introduced the research progress of the effects of glomerular endothelial cell autophagy on diabetic nephropathy. 展开更多
关键词 Diabetic nephropathy AUTOPHAGY Glomerular endothelial cells
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Automatic detection of small bowel lesions with different bleeding risks based on deep learning models 被引量:1
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作者 Rui-Ya Zhang Peng-Peng Qiang +5 位作者 Ling-Jun Cai Tao Li Yan Qin Yu Zhang Yi-Qing Zhao Jun-Ping Wang 《World Journal of Gastroenterology》 SCIE CAS 2024年第2期170-183,共14页
BACKGROUND Deep learning provides an efficient automatic image recognition method for small bowel(SB)capsule endoscopy(CE)that can assist physicians in diagnosis.However,the existing deep learning models present some ... BACKGROUND Deep learning provides an efficient automatic image recognition method for small bowel(SB)capsule endoscopy(CE)that can assist physicians in diagnosis.However,the existing deep learning models present some unresolved challenges.AIM To propose a novel and effective classification and detection model to automatically identify various SB lesions and their bleeding risks,and label the lesions accurately so as to enhance the diagnostic efficiency of physicians and the ability to identify high-risk bleeding groups.METHODS The proposed model represents a two-stage method that combined image classification with object detection.First,we utilized the improved ResNet-50 classification model to classify endoscopic images into SB lesion images,normal SB mucosa images,and invalid images.Then,the improved YOLO-V5 detection model was utilized to detect the type of lesion and its risk of bleeding,and the location of the lesion was marked.We constructed training and testing sets and compared model-assisted reading with physician reading.RESULTS The accuracy of the model constructed in this study reached 98.96%,which was higher than the accuracy of other systems using only a single module.The sensitivity,specificity,and accuracy of the model-assisted reading detection of all images were 99.17%,99.92%,and 99.86%,which were significantly higher than those of the endoscopists’diagnoses.The image processing time of the model was 48 ms/image,and the image processing time of the physicians was 0.40±0.24 s/image(P<0.001).CONCLUSION The deep learning model of image classification combined with object detection exhibits a satisfactory diagnostic effect on a variety of SB lesions and their bleeding risks in CE images,which enhances the diagnostic efficiency of physicians and improves the ability of physicians to identify high-risk bleeding groups. 展开更多
关键词 Artificial intelligence Deep learning Capsule endoscopy Image classification Object detection Bleeding risk
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Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer 被引量:1
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作者 Jin-Yu Shi Xin Che +7 位作者 Rui Wen Si-Jia Hou Yu-Jia Xi Yi-Qian Feng Ling-Xiao Wang Shi-Jia Liu Wen-Hao Lv Ya-Fen Zhang 《World Journal of Clinical Oncology》 2024年第3期391-410,共20页
BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proli... BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment. 展开更多
关键词 HER2+breast cancer Ferroptosis Tumor mutation burden Single-cell RNA sequencing PROGNOSIS
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Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis 被引量:1
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作者 QIN Ke Wei LIU Jian Fei +2 位作者 WU Cheng Lin ZHANG Chen ZHOU Li Jun 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2023年第2期135-145,共11页
Objective This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol(RSV)regulate necroptosis during Vibrio vulnificus(V.vulnificus)-induced sepsis and the potential mechanism.Methods T... Objective This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol(RSV)regulate necroptosis during Vibrio vulnificus(V.vulnificus)-induced sepsis and the potential mechanism.Methods The effect of RSV on V.vulnificus cytolysin(VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays.Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction,western blot,and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V.vulnificus-induced sepsis mouse model.Results RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells.RSV also inhibited the inflammatory response,had a protective effect on histopathological changes,and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages,lung,spleen,and liver tissues of V.vulnificus-induced septic mice in vivo.Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V.vulnificusinduced septic mice.RSV also improved the survival of V.vulnificus-induced septic mice.Conclusion Our findings collectively demonstrate that RSV prevented V.vulnificus-induced sepsis by attenuating necroptosis,highlighting its potency in the clinical management of V.vulnificus-induced sepsis. 展开更多
关键词 Vibrio vulnificus RESVERATROL NECROPTOSIS SEPSIS INFLAMMATION
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Application of convolutional neural network-based endoscopic imaging in esophageal cancer or high-grade dysplasia: A systematic review and meta-analysis
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作者 Jun-Qi Zhang Jun-Jie Mi Rong Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2023年第11期1998-2016,共19页
BACKGROUND Esophageal cancer is the seventh-most common cancer type worldwide,accounting for 5%of death from malignancy.Development of novel diagnostic techniques has facilitated screening,early detection,and improved... BACKGROUND Esophageal cancer is the seventh-most common cancer type worldwide,accounting for 5%of death from malignancy.Development of novel diagnostic techniques has facilitated screening,early detection,and improved prognosis.Convolutional neural network(CNN)-based image analysis promises great potential for diagnosing and determining the prognosis of esophageal cancer,enabling even early detection of dysplasia.METHODS PubMed,EMBASE,Web of Science and Cochrane Library databases were searched for articles published up to November 30,2022.We evaluated the diagnostic accuracy of using the CNN model with still image-based analysis and with video-based analysis for esophageal cancer or HGD,as well as for the invasion depth of esophageal cancer.The pooled sensitivity,pooled specificity,positive likelihood ratio(PLR),negative likelihood ratio(NLR),diagnostic odds ratio(DOR)and area under the curve(AUC)were estimated,together with the 95%confidence intervals(CI).A bivariate method and hierarchical summary receiver operating characteristic method were used to calculate the diagnostic test accuracy of the CNN model.Meta-regression and subgroup analyses were used to identify sources of hetero-geneity.RESULTS A total of 28 studies were included in this systematic review and meta-analysis.Using still image-based analysis for the diagnosis of esophageal cancer or HGD provided a pooled sensitivity of 0.95(95%CI:0.92-0.97),pooled specificity of 0.92(0.89-0.94),PLR of 11.5(8.3-16.0),NLR of 0.06(0.04-0.09),DOR of 205(115-365),and AUC of 0.98(0.96-0.99).When video-based analysis was used,a pooled sensitivity of 0.85(0.77-0.91),pooled specificity of 0.73(0.59-0.83),PLR of 3.1(1.9-5.0),NLR of 0.20(0.12-0.34),DOR of 15(6-38)and AUC of 0.87(0.84-0.90)were found.Prediction of invasion depth resulted in a pooled sensitivity of 0.90(0.87-0.92),pooled specificity of 0.83(95%CI:0.76-0.88),PLR of 7.8(1.9-32.0),NLR of 0.10(0.41-0.25),DOR of 118(11-1305),and AUC of 0.95(0.92-0.96).CONCLUSION CNN-based image analysis in diagnosing esophageal cancer and HGD is an excellent diagnostic method with high sensitivity and specificity that merits further investigation in large,multicenter clinical trials. 展开更多
关键词 Esophageal cancer High-grade dysplasia Convolutional neural network Deep learning Systematic review META-ANALYSIS
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Six-year analysis of key monitoring for bacterial strain distribution and antibiotic sensitivity in a hospital
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作者 Zong-Ying Li Dong Yang Chong-Hua Hao 《World Journal of Clinical Cases》 SCIE 2023年第30期7294-7301,共8页
BACKGROUND With the widespread use of antimicrobial drugs,bacterial resistance has become a significant problem,posing a serious threat to public health.The prevalence of clinical infection strains in hospitals and th... BACKGROUND With the widespread use of antimicrobial drugs,bacterial resistance has become a significant problem,posing a serious threat to public health.The prevalence of clinical infection strains in hospitals and their drug sensitivities are key to the appropriate use of antibiotics in clinical practice.AIM To identify prevalent bacteria and their antibiotic resistance profiles in a hospital setting,thereby guiding effective antibiotic usage by clinicians.METHODS Specimens from across the institution were collected by the microbiology laboratory.The VITEK 2 compact fully automatic analyzer was used for bacterial identification and antibiotic sensitivity testing,and the WHONET5.6 software was utilized for statistical analysis.RESULTS A total of 12062 bacterial strains of key monitoring significance were detected.Staphylococcus aureus demonstrated widespread resistance to penicillin,but none of the strains were resistant to vancomycin or linezolid.Moreover,219 strains of methicillin-resistant coagulase-negative staphylococci and 110 strains of methicillin-resistant Staphylococcus aureus were detected.Enterococcus faecalis showed moderate resistance to the third-generation quinolones ciprofloxacin and levofloxacin,but its resistance to nitrofurantoin and tetracycline was low.Enterococcus faecium displayed significantly lower resistance to third-and fourthgeneration quinolones than Enterococcus faecalis.The resistance of two key monitoring strains,Escherichia coli and Klebsiella pneumoniae,to piperacillin/tazobactam was 5%-8%.However,none of the Escherichia coli and Klebsiella pneumoniae strains were resistant to meropenem.The resistance of Acinetobacter baumannii to piperacillin/sulbactam was nearly 90%.Nonetheless,the resistance to tigecycline was low,and Pseudomonas aeruginosa demonstrated minimal resistance in the antibiotic sensitivity test,maintaining a resistance of<10%to the cephalosporin antibiotics cefotetan and cefoperazone over the last 6 years.The resistance to amikacin remained at 0.2%over the past 3 years.CONCLUSION Our hospital’s overall antibiotic resistance rate was relatively stable from 2017 to 2022.The detection rates of key monitoring strains are reported quarterly and their resistance dynamics are monitored and communicated to the entire hospital,which can guide clinical antibiotic selection. 展开更多
关键词 Antibiotic sensitivity test Monitoring bacterial antibiotic resistance Antimicrobial drugs Antimicrobial stewardship Combination therapies Antibiotic stewardship
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Characterization of prognosis and immune infiltration by a novel glutamine metabolism-related model in cutaneous melanoma
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作者 MENGQIN ZHU TIANYI XU +4 位作者 HAN ZHANG XIN FAN YULAN WANG JIAJIA ZHANG FEI YU 《BIOCELL》 SCIE 2023年第9期1931-1945,共15页
Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM r... Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM remain unclear.Therefore,we aimed to explore the effects of GM-related genes on survival,clinicopathological characteristics,and the tumor microenvironment in SKCM.In this study,682 SKCM samples were obtained from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Consensus clustering was used to classify SKCM samples into distinct subtypes based on 41 GM-related genes.Differences in survival,immune infiltration,clinical characteristics,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways as well as differentially expressed genes(DEGs)between subgroups were evaluated.A prognostic model was constructed according to prognostic DEGs.Differential analyses in survival,immune infiltration,tumor microenvironment(TME),tumor mutation burden(TMB),stemness,and drug sensitivity between risk groups were conducted.We identified two distinct GM-related subtypes on SKCM and found that GM-related gene alterations were associated with survival probability,clinical features,biological function,and immune infiltration.Then a risk model based on six DEGs(IL18,SEMA6A,PAEP,TNFRSF17,AIM2,and CXCL10)was constructed and validated for predicting overall survival in SKCM patients.The results showed that the risk score was negatively correlated with CD8+T cells,activated CD4+memory T cells,M1 macrophages,andγδT cells.The group with a low-risk score was accompanied by a better survival rate with higher TME scores and lower stemness index.Moreover,the group with high-and low-risk score had a significant difference with the sensitivity of 75 drugs(p<0.001).Overall,distinct subtypes in SKCM patients based on GM-related genes were identified and the risk model was constructed,which might contribute to prognosis prediction,guide clinical therapy,and develop novel therapeutic strategies. 展开更多
关键词 Glutamine metabolism Cutaneous melanoma Immune infiltration Overall survival
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Role of triggering receptor expressed on myeloid cells-1 in kidney diseases:A biomarker and potential therapeutic target
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作者 Yuxi Fan Ye Xu +5 位作者 Zhi Huo Hedong Zhang Longkai Peng Xin Jiang Angus W.Thomson Helong Dai 《Chinese Medical Journal》 SCIE CAS CSCD 2024年第14期1663-1673,共11页
Triggering receptor expressed on myeloid cells-1(TREM-1)is a member of the immunoglobulin superfamily.As an amplifier of the inflammatory response,TREM-1 is mainly involved in the production of inflammatory mediators ... Triggering receptor expressed on myeloid cells-1(TREM-1)is a member of the immunoglobulin superfamily.As an amplifier of the inflammatory response,TREM-1 is mainly involved in the production of inflammatory mediators and the regulation of cell survival.TREM-1 has been studied in infectious diseases and more recently in non-infectious disorders.More and more studies have shown that TREM-1 plays an important pathogenic role in kidney diseases.There is evidence that TREM-1 can not only be used as a biomarker for diagnosis of disease but also as a potential therapeutic target to guide the development of novel therapeutic agents for kidney disease.This review summarized molecular biology of TREM-1 and its signaling pathways as well as immune response in the progress of acute kidney injury,renal fibrosis,diabetic nephropathy,immune nephropathy,and renal cell carcinoma. 展开更多
关键词 TREM-1 Kidney diseases Inflammatory response BIOMARKER Therapeutic targets
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Anti-hypertensive and endothelia protective effects of Fufang Qima capsule(复方芪麻胶囊) on primary hypertension via adiponectin/adenosine monophosphate activated protein kinase pathway 被引量:3
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作者 ZHAO Zhiyue SHI Zhenyu +8 位作者 ZHANG Zhenzhen LI Yinghong ZENG Xiaohui CHEN Yuxing YAO Nan ZHOU Min SU Hui WANG Qinghai JIN LiLi 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2021年第6期919-926,共8页
OBJECTIVE:To investigate the potential mechanism of the vascular remodeling effect and provide additional information about anti-hypertension activity of Fufang Qima capsule(复方芪麻胶囊,QM).METHODS:Spontaneous hypert... OBJECTIVE:To investigate the potential mechanism of the vascular remodeling effect and provide additional information about anti-hypertension activity of Fufang Qima capsule(复方芪麻胶囊,QM).METHODS:Spontaneous hypertensive rats(SHRs)were used to study the underlying mechanism of the anti-hypertension activity of QM.In this study,SHRs were randomly divided into 5 groups:model group,Telmisartan group(7.2 mg/kg,p.o.),and three QM groups(0.9298,1.8596,and 3.7192 g/kg,p.o.).Wistar Kyoto rats(WKY)were used as normal control group.Blood pressure(BP),aorta,perivascular adipose tissue(PVAT)histology were investigated to evaluate the effect of QM.Nitric oxide(NO)and endothelial nitric oxide synthase(eNOS)phosphorylation were measured.Adiponectin(APN)secretion,as well as APN signal pathway proteins including APN,adiponectin receptors(R1 and R2)and adenosine 5’-monophosphate-activated protein kinase(AMPK)were all analyzed.RESULTS:QM significantly reduced BP and ameliorated the vascular pathological change,i.e.intima media thicken and collagen fiber hyperplasia.Meanwhile,QM increased concentration of NO and the phosphorylation of eNOS in the aorta.The anti-hypertensive and endothelia-protective effect of QM could be attributed to activating APN/AMPK pathway by up-regulating the expression of APN in PVAT and APN Receptor 2,AMPKαand phosphorylated AMPKαin the aorta.CONCLUSION:The QM alleviation effect mechanism for primary hypertension was via modulating the APN/AMPK signal pathway. 展开更多
关键词 hypertension ADIPONECTIN AMP-activated protein kinases nitric oxide synthase typeⅢ Fufang Qima capsule
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Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model
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作者 Xia Qiu Hedong Zhang +15 位作者 Zhouqi Tang Yuxi Fan Wenjia Yuan Chen Feng Chao Chen Pengcheng Cui Yan Cui Zhongquan Qi Tengfang Li Yuexing Zhu Liming Xie Fenghua Peng Tuo Deng Xin Jiang Longkai Peng Helong Dai 《Chinese Medical Journal》 SCIE CAS CSCD 2024年第12期1453-1464,共12页
Background:Homoharringtonine(HHT)is an effective anti-inflammatory,anti-viral,and anti-tumor protein synthesis inhibitor that has been applied clinically.Here,we explored the therapeutic effects of HHT in a mouse hear... Background:Homoharringtonine(HHT)is an effective anti-inflammatory,anti-viral,and anti-tumor protein synthesis inhibitor that has been applied clinically.Here,we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods:Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver,kidney,and hematology.A mouse heart transplantation model was constructed,and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan-Meier analysis,immunostaining,and bulk RNA sequencing analysis.The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells(Tregs)differentiation.Results:HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo.Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days(P<0.001)without non-immune toxicity.The allografts had long-term survival after continuous HHT treatment for 28 days.HHT significantly reduced lymphocyte infiltration in the graft,and interferon-γ-secreting CD4^(+)and CD8^(+)T cells in the spleen(P<0.01).HHT significantly increased the number of peripheral Tregs(about 20%,P<0.001)and serum interleukin(IL)-10 levels.HHT downregulated the expression of T cell receptor(TCR)signaling pathway-related genes(CD4,H2-Eb1,TRAT1,and CD74)and upregulated the expression of IL-10 and transforming growth factor(TGF)-βpathway-related genes and Treg signature genes(CTLA4,Foxp3,CD74,and ICOS).HHT increased CD4^(+)Foxp3^(+)cells and Foxp3 expression ex vivo,and it enhanced the inhibitory function of inducible Tregs.Conclusions:HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels,thereby promoting mouse heart allograft acceptance.These findings may have therapeutic implications for organ transplant recipients,particularly those with viral infections and malignancies,which require a more suitable anti-rejection medication. 展开更多
关键词 Heart transplantation HOMOHARRINGTONINE Immunosuppressive agents T-lymphocytes Regulatory Graft acceptance
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Advances in single-cell sequencing technology in microbiome research
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作者 Yinhang Wu Jing Zhuang +3 位作者 Yifei Song Xinyi Gao Jian Chu Shuwen Han 《Genes & Diseases》 SCIE CSCD 2024年第4期201-219,共19页
With the rapid development of histological techniques and the widespread applica-tion of single-cell sequencing in eukaryotes,researchers desire to explore individual microbial.genotypes and functional expression,whic... With the rapid development of histological techniques and the widespread applica-tion of single-cell sequencing in eukaryotes,researchers desire to explore individual microbial.genotypes and functional expression,which deepens our understanding of microorganisms.In this review,the history of the development of microbial detection technologies was revealed and the difficulties in the application of single-cell sequencing in microorganisms were dissected as well.Moreover,the characteristics of the currently emerging microbial single-cell sequencing(Microbe-seq)technology were summarized,and the prospects of the application of Microbe-seq in microorganisms were distilled based on the current development status.Despite its mature development,the Microbe-seq technology was still in the optimization stage.A retrospective study was conducted,aiming to promote the widespread application of single-cell sequencing in microorganisms and facilitate further improvement in the technol-ogy. 展开更多
关键词 Bacterialantibiotic resistance Host immunity Host-phage interaction Microbial single-cell sequencing MICROORGANISMS Single cell Single-cell sequencing technology
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Ribonucleotide reductase subunit M1 blocks glucose catabolism via phosphorylation of pyruvate kinase M2 in human esophageal squamous cell cancer
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作者 Jian Yang Lingxiao Wang +5 位作者 Hui Sun Zhenxiang Zhao Yanchuan Ma Zhen Hu Liqin Zhai Yonggang Wang 《Genes & Diseases》 SCIE CSCD 2024年第3期69-71,共3页
Esophageal squamous cell cancer(EScC)is one of the malignant tumors with high morbidity and mortality all over the world.^(1) In recent years,combined chemotherapy has gradually been the effective treatment method for... Esophageal squamous cell cancer(EScC)is one of the malignant tumors with high morbidity and mortality all over the world.^(1) In recent years,combined chemotherapy has gradually been the effective treatment method for EscC patients.Therefore,it is imperative to explore potential therapeutic targets for the treatment of EsCC.We previously reported a high-frequency amplification of pyrimidine metabolic pathway-related genes in EsCC tissues. 展开更多
关键词 SQUAMOUS ESOPHAGEAL cancer
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Metabolic syndrome is associated with significant hepatic fibrosis and steatosis in patients with nonalcoholic steatohepatitis
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作者 Qian-Qian Li Yu-Ting Xiong +8 位作者 Danni Wang Ke-Xin Wang Chang Guo Yi-Ming Fu Xiao-Xia Niu Chun-Yan Wang Jian-Jun Wang Dong Ji Zhi-Fang Bai 《iLIVER》 2024年第2期28-34,共7页
Background and aims:Nonalcoholic steatohepatitis(NASH),an inflammatory form of non-alcoholic fatty liver disease,can progress to advanced liver fibrosis,cirrhosis,and liver cancer.Metabolic syndrome(MetS)parallels the... Background and aims:Nonalcoholic steatohepatitis(NASH),an inflammatory form of non-alcoholic fatty liver disease,can progress to advanced liver fibrosis,cirrhosis,and liver cancer.Metabolic syndrome(MetS)parallels the prevalence of non-alcoholic fatty liver disease/NASH and increases patients’risk of advanced liver disease.This study aimed to determine whether MetS was associated with the histological progression of NASH.Methods:Patients with liver biopsy-proven NASH were retrospectively screened and categorized into two groups for each histological feature:with(<2 points)or without(2 points)significant hepatic steatosis/inflammation/fibrosis.Multivariable logistic regression was used to explore the association between MetS and histological features.Results:In total,386 patients with a median age of 33.0 years were enrolled;among them,35.2%were female,and 41.2%had MetS.The proportion of significant hepatic fibrosis and steatosis in those with MetS was significantly higher than in those without MetS(p<0.05).Multivariable logistic regression analyses showed that MetS remained significantly associated with significant hepatic fibrosis(adjusted odds ratio:1.852,95%confidence interval:1.042-3.292,p=0.036),and severe hepatic steatosis(adjusted odds ratio:2.008,95%confidence interval:1.030-3.914,p=0.041).Conclusion:MetS was associated with significant hepatic fibrosis and steatosis in patients with NASH.Our results suggest that NASH patients with MetS should be closely monitored and given targeted intervention and treatment,which may help to prevent disease progression and mitigate the growing burden of NASH. 展开更多
关键词 Nonalcoholic steatohepatitis Metabolic syndrome Liver biopsy Hepatic fibrosis High-risk factor
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Risk factors related to significant hepatic inflammation in patients with acute drug-induced liver injury
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作者 Yu-Ting Xiong Jian-Fei Wang +11 位作者 Le Li Zhi-Fang Bai Yan Liu Ang Huang Ke-Xin Wang Yiming Fu Wucai Yang Chang Guo Mengwen He Wen-Chang Wang Chun-Yan Wang Dong Ji 《iLIVER》 2024年第2期35-42,共8页
Background and aims:Currently,research on biopsy-proven acute drug-induced liver injury(DILI)remains limited.This study aimed to identify clinical characteristics and risk factors for significant hepatic inflammation ... Background and aims:Currently,research on biopsy-proven acute drug-induced liver injury(DILI)remains limited.This study aimed to identify clinical characteristics and risk factors for significant hepatic inflammation in patients with acute DILI.Methods:An ambispective cohort study was conducted on biopsy-proven acute DILI patients admitted to our hospital from 2012 to 2018.Using the Scheuer scoring system,patients were categorized into G0-2 or G3-4 groups and followed up for 12 months after first admission.Clinical characteristics and outcomes were retrieved from medical records.Results:The median age of the 157 enrolled patients(65.6%female)was 40.4(interquartile range(IQR),31.9-49.1)years.The median latency and length of hospitalization were 30.0(IQR,5.0-60.0)and 18.0(IQR,12.0-26.0)days.The proportions of patients in the G0-2 and G3-4 groups were 54.8%and 45.2%,respectively.Logistic regression analysis revealed that females(odds ratio(OR):2.623,95%confidence interval(CI):1.169-5.887,p=0.019),higher body mass index(OR:1.168,95%CI:1.029-1.325,p=0.016),higher total bilirubin(OR:1.004,95%CI:1.000-1.007,p=0.047),and lower prothrombin activity(OR:0.976,95%CI:0,957-0.995,p=0.013)were associated with significant hepatic inflammation.The predominance of the hepatocellular injury pattern(60.5%)at admission transformed into a predominance of the cholestatic pattern(60.5%)at discharge.During follow-up,23 patients(14.6%)developed chronic DILI,with nine patients(5.7%)progressing to cirrhosis.Moreover,15 female patients(9.6%)developed autoimmunity(3cases in the G0-2 group vs 12 cases in the G3-4 group,p<0.05).Conclusion:Acute DILI patients with high-risk factors were more likely to develop significant hepatic inflammation,and females with significant inflammation were at a higher risk of developing autoimmunity during follow-up. 展开更多
关键词 Acute drug-induced liver injury Liver biopsy Hepatic inflammation FEMALE AUTOIMMUNITY CHRONICITY
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CACA guidelines for holistic integrative management of rectal cancer
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作者 Committee of Colorectal Cancer Society Chinese Anti-Cancer Association Guiyu Wang +87 位作者 Daiming Fan Jin Gu Kefeng Ding Xuedong Fang Lin Shen Zhongfa Xu Jianmin Xu Jianchun Cai Lianming Cai Sanjun Cai Gong Chen Jiansi Chen Longwei Cheng Yong Cheng Pan Chi Binbin Cui Guanghai Dai Chuangang Fu Yanhong Gu Guodong He Junhong Hu Jing Huang Rui Huang Zhongcheng Huang Zheng Jiang Zhigang Jie Haixing Ju Hai Li Jian Li Jun Li Ming Li Yaoping Li Yunfeng Li Guole Lin Haiying Liu Ming Liu Qian Liu Zhizhong Pan Yifan Peng Niansong Qian Meng Qiu Li Ren Yueming Sun Jianqiang Tang Qingchao Tang Yuan Tang Kaixiong Tao Min Tao Haijiang Wang Meng Wang Zejun Wang Zhengguang Wang Ziqiang Wang Ziwei Wang Shaozhong Wei Baocai Xing Bin Xiong Ye Xu Su Yan Bin Yang Chunkang Yang Qinghua Yao Yingjiang Ye Ying Yuan Guozhi Zhang Haizeng Zhang Hongmei Zhang Zhen Zhang Yunshi Zhong Ji Zhu Yuan Zhu Yuping Zhu Shuangmei Zou Yuliuming Wang Jingfang Lv Enrui Liu Ming Yang Qian Zhang Weiyuan Zhang Lin Zhang Jun Luo Zhaoxu Zheng Zhixun Zhao Zheng Liu Jinhua Tao Haiyang Huang Tianli Chen Xishan Wang 《Holistic Integrative Oncology》 2023年第1期1-31,共31页
Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of re... Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of rectal cancer.In recent years,the proportion of rectal cancer has trended downward,however the incidence of rectal cancer inyounger adults is increasing.The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were editedto help improve the diagnosis and comprehensive treatment in China.Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal CancerSociety,based on a careful review of the latest evidence including China’s studies,and referred to domestic and internationalrelative guidelines,also considered China’s specific national conditions and clinical practice.Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectalcancer,prevention and screening,diagnosis,treatment of nonmetastatic and metastatic rectal cancer,follow-up,and whole-course rehabilitation management.Conclusion Committee of Colorectal Cancer Society,Chinese Anti-Cancer Association,standardizes the diagnosisand treatment of rectal cancer in China through the formulation of the CACA Guidelines. 展开更多
关键词 Rectal cancer GUIDELINE SCREENING DIAGNOSIS TREATMENT Rehabilitation management Holistic integrative medicine
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