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Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 716-731页

作者： Hsiang-Chun Lai Ju-Chien Cheng Hei-Tung Yip Long-Bin Jeng Sheng-Teng Huang Graduate Institute of Chinese medicine School of Chinese MedicineCollege of Chinese MedicineChina Medical UniversityTaichung 404328TaiwanChina department of Medical Laboratory Science and Biotechnology China Medical UniversityTaichung 404TaiwanChina Management Office for Health Data China Medical University HospitalTaichung 404327TaiwanChina Organ transplantation Center China Medical University HospitalTaichung 40447TaiwanChina department of Chinese medicine China Medical University HospitalSchool of Chinese MedicineChina Medical UniversityTaichung 40447TaiwanChina

BACKGROUND Type 2 diabetes mellitus(DM)is an independent risk factor for hepatocellular carcinoma(HCC),while insulin is a potent *** a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for *** To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin *** We used data acquired from the Taiwan,Chinaese National Health Insurance research database between 2000 and *** identified patients with DM who were prescribed insulin for>3 *** herb user group was further defined as patients prescribed herbal medication for DM for>3 months per annum during RESULTS We initially enrolled 657144 DM patients with regular insulin use from 2000 to *** these,46849 patients had used a herbal treatment for DM,and 140547 patients were included as the matched control *** baseline variables were similar between the herb users and *** patients with regular herb use had a 12%decreased risk of HCC compared with the control group[adjusted hazard ratio(aHR)=0.88,95%CI=0.80–0.97].The cumulative incidence of HCC in the herb users was significantly lower than that of the *** with a herb use of>5 years cumulatively exhibited a protective effect against development of HCC(aHR=0.82,P<0.05).Of patients who developed HCC,herb users exhibited a longer survival time than nonusers(aHR=0.78,P=0.0001).Additionally,we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the *** analysis indicated that Astragalus propinquus(Huang Qi)plus Salvia miltiorrhiza Bunge(Dan Shen),and Astragalus propinquus(Huang Qi)plus Trichosanthes kirilowii Maxim.(Tian Hua Fen)were the most frequent combination of single ***,Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and *** This large-scale retrospective cohort study reveals th

关键词： Hepatocellular carcinoma Diabetes mellitus Insulin Herb Taiwan,Chinaese National health insurance research database

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Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction:An exploratory proposal based on basic and clinical data

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World Journal of Gastroenterology 2024年第1期30卷 34-49页

作者： Yu-Wei Zhou Yue Ren Miao-Miao Lu Ling-Ling Xu Wei-Xin Cheng Meng-Meng Zhang Lin-Ping Ding Dong Chen Jian-Guo Gao Juan Du Ci-Liang Jin Chun-Xiao Chen Yun-Fei Li Tao Cheng Peng-Lei Jiang Yi-Da Yang Peng-Xu Qian Peng-Fei Xu Xi Jin department of Gastroenterology The First Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina department of Gastroenterology The Second Hospital of JiaxingJiaxing 314000Zhejiang ProvinceChina Endoscopy Center Children’s Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina department of Gastroenterology The Second People’s Hospital of Yuhang DistrictHangzhou 310000Zhejiang ProvinceChina department of Gastroenterology Hangzhou Shangcheng District People’s HospitalHangzhou 310003Zhejiang ProvinceChina department of Colorectal Surgery The First Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina department of Gastroenterology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Women’s Hospital and Institute of Genetics Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina Center of Stem Cell and Regenerative medicine and Bone Marrow Transplantation CenterThe First Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina department of Infectious Disease The First Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Crohn’s disease(CD)is caused by immune,environmental,and genetic *** can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains *** biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known *** achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost *** this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary *** supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid *** benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic *** importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

关键词： Inflammatory bowel disease Crohn’s disease Lymphatic system Inside-out model Immune cells Zebrafish

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Recent advances and remaining challenges in lung cancer therapy

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Chinese Medical Journal 2024年第5期137卷 533-546页

作者： Tasha Barr Shoubao Ma Zhixin Li Jianhua Yu department of Hematology and Hematopoietic Cell transplantation City of Hope National Medical CenterLos AngelesCalifornia 91010USA Comprehensive Cancer Center City of HopeLos AngelesCalifornia 91010USA department of Immuno-Oncology Beckman Research InstituteLos AngelesCalifornia 91010USA

Lung cancer remains the most common cause of cancer *** the continued research into new drugs and combination therapies,outcomes in lung cancer have been improved,and clinical benefits have been expanded to a broader patient ***,the overall cure and survival rates for lung cancer patients remain low,especially in metastatic *** the available lung cancer treatment options,such as surgery,radiation therapy,chemotherapy,targeted therapies,and alternative therapies,immunotherapy has shown to be the most *** exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer *** progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many US Food And Drug Administration(FDA)-approved drugs targeting the programmed cell death ligand-1 protein(e.g.,durvalumab,atezolizumab),the programmed cell death-1 receptor(e.g.,nivolumab,pembrolizumab),and cytotoxic T-lymphocyte-associated antigen 4(e.g.,tremelimumab,ipilimumab).Cytokines,cancer vaccines,adoptive T cell therapies,and Natural killer cell mono-and combinational therapies are rapidly being studied,yet to date,there are currently none that are FDA-approved for the treatment of lung *** this review,we discuss the current lung cancer therapies with an emphasis on immunotherapy,including the challenges for future research and clinical applications.

关键词： Lung cancer Therapy Immunotherapy Combination therapy Adoptive T cell therapies

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Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1878-1889页

作者： Fouzia Fazal Muhammad Arsalan Khan Sumayya Shawana Rahma Rashid Muhammed Mubarak department of Pathology Jinnah Medical and Dental CollegeKarachi 74800SindhPakistan department of General Surgery Sindh Institute of Urology&Transplantation(SIUT)Karachi 74200SindhPakistan department of Pathology Bahria University of Health SciencesKarachi 74400SindhPakistan department of Pathology SIUTKarachi 74200SindhPakistan

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic ***-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 *** We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological *** A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC *** CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 ***,histopathological,and clinical parameters were *** TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both *** tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological *** Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue *** demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and *** suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

关键词： Colorectal cancer Macrophages Tumor stroma M2 subset Tumor front Tumor stage Lymphovascular invasion Prognosis Tumor-associated macrophages Immunohistochemistry

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Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation,fluid sheer stress,and inflammatory pathways in obesity-related glomerulopathy

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Genes & Diseases 2024年第4期11卷 314-326页

作者： Yinyin Chen Yushun Gong Jia Zou Guoli Li Fan Zhang Yiya Yang Yumei Liang Wenni Dai Liyu He Hengcheng Lu department of nephrology Hunan Provincial People's HospitalThe First Affliated Hospital of Hunan Normal UniversityHunan Clinical Research Center for Chronic Kidney DiseaseChangshaHunan 410000China department of nephrology The Second Xiangya Hospital of Central South UniversityHunan Key Laboratory of Kidney Disease and Blood PurificationChangshaHunan 410011China Cardiovascular Research Institute of Jiangxi Province Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi 330006China

Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal *** have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene *** define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA *** report for the first time that immune cells,including T cells and B cells,are decreased in ORG *** analysis indicated that SPP1 was significantly up-regulated in T cells and B *** gene is related to inflammation and cell *** of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress ***,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and ***,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

关键词： Fluid shear stress Inflammation Obesity-related glomerulopathy Oxidative phosphorylation Single-cell RNA seq

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Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus:State of art and future perspectives

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 221-227页

作者： Paschalis Gavriilidis Timothy M Pawlik Daniel Azoulay department of Surgery Colchester General HospitalTurner RoadColchester CO45JLUK department of Surgery The Ohio State Wexner Medical CenterJames Comprehensive Cancer CenterColumbusOHUSA department of Hepato-Biliary and Liver transplantation surgery Paul Brousse University HospitalParis-Saclay UniversityVillejuif 94800France

Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage *** vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if *** sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic ***:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic *** elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical *** review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of ***:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

关键词： Hepatectomy Liver surgery Liver neoplasms Portal vein tumor thrombus

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Hydrogel-Assisted Electrokinetics for High-Resolution and Non-invasive Flow Monitoring in Microfluidic Chips

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Chinese Journal of Chemistry 2024年第6期42卷 571-577页

作者： Na Zhao Yanni Ma Zehua Yu Jun Huang Xiangqian Fu Tao Qiu Kang Liu MOE Key Laboratory of Hydraulic Machinery Transients School of Power and Mechanical EngineeringWuhan UniversityWuhanHubei430072 China department of Urology Renmin Hospital of Wuhan UniversityWuhanHubei430072 China department of Organ transplantation Renmin Hospital of Wuhan UniversityWuhanHubei430072 China

Convenient non-invasive flow monitoring would facilitate the operation and control in microfluidic chips,but is challenging due to the small space of microchannels and complex operation required in traditional optical *** this work,we propose a novel non-invasive strategy to probe microfluidic flows via streaming potential *** sealing one side of the microchannel with a piece of hydrogel film,streaming potential inside the channel can be clearly detected by electrodes at outer surface of the hydrogel due to ion diffusion in the *** is detected without sensors contacting with the internal ***,the electrodes shape like a tiny probe,which can move around mapping the flow distribution in a chip with the spatial resolution of 1 mm and flow rate detection limit of 3μL·min–*** inside the channels can also be detected,due to the fluctuation of streaming voltage when gas-liquid interface flows through the electrode,showing an easy and potential way for multi-functional flow monitoring in microfluidic chips.

关键词： Microfluidics Hydrogels Electrokinetics Flow monitoring Non-invasive Sensor Charge transport

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The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis

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Acta Pharmaceutica Sinica B 2024年第2期14卷 712-728页

作者： Xiaoxuan Zhong Xiang Wei Yan Xu Xuehai Zhu Bo Huo Xian Guo Gaoke Feng Zihao Zhang Xin Feng Zemin Fang Yuxuan Luo Xin Yi Ding-Sheng Jiang Division of Cardiovascular Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Key Laboratory of Organ transplantation Ministry of EducationNHC Key Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhan 430030China School of Life Science and Technology Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China department of Cardiology Renmin Hospital of Wuhan UniversityWuhan 430060China

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart ***,we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum-and PDGF-BB-induced vascular smooth muscle cells(VSMCs),and in tissues of carotid artery injury-induced neointimal ***2 overexpression in VSMCs(Smyd2-vTg)facilitates,but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in *** sequencing revealed that SMYD2 knockdown represses the expression of serum response factor(SRF)target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC ***3 directly interacts with and deacetylates SRF,which enhances SRF transcriptional activity in ***,SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its ***966,a specific inhibitor of HDAC3,not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs,but also inhibits carotid artery injury-induced neointima formation in ***3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent *** results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

关键词： Neointimaformation Histonemethylation Histoneacetylation SRFacetylation SMYD2 HDAC3 LLY-507 RGFP966

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Effect of phosphatase and tensin homolog-induced putative kinase 1/ E3 ubiquitin ligase Parkin mediated mitochondrial autophagy on chronic kidney disease myocardial injury and the intervention mechanism of Shen Shuai recipe(肾衰方)

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Journal of Traditional Chinese medicine 2024年

作者： ZHANG Gedi LIU Gengxin GUO Min LUO Fuli YAN Ziyou GE Wei department of Anorectal Affiliated Hospital of Jiangxi University of Chinese medicine department of nephrology Affiliated Hospital of Jiangxi University of Chinese medicine School of Graduate Jiangxi University of Chinese medicine

Objective: To study whether Shenshuai recipe (肾衰方， SSR) can play a protective role on chronic kidney disease myocardial injury model through phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/E3 ubiquitin ligase Parkin (Parkin) mitochondrial autophagy pathway. Methods: Forty-eight nephrectomized rats were randomly divided into six groups: sham-operated group， model group， Benazepril group， low， medium and high-dose groups of SSR. The rats were given the corresponding intervention for six weeks， then were sacrificed. Serum was examined by enzyme linked immunosorbent assay (ELISA). Cardiac ultrasound was used to detect cardiac function in 5/6 nephrectomized rats. Myocardial tissue was examined by light and electron microscopy; PINK1， Parkin， microtubule-associated protein1 light chain 3 II (LC3B)， sequestosome 1 (P62)， BECN1 (Beclin-1) and dynamin-related protein 1 (Drp-1) were measured by real time polymerase chain reaction (RT-PCR)， Western blot (WB) and immunohistochemistry (IHC). Results: The expression levels of Blood Urea Nitrogen (BUN) and Creatinine (SCr) in the model group were significantly higher than those in the sham-operated group， indicating that modeling was successful. SSR can protect myocardium by reducing the relative expression of creatine kinase myocardial isoenzyme and hypersensitivity cardiac troponin I (P < 0.05). SSR can improve cardiac function in rats after ultrasound testing. SSR can improve the pathological manifestations of myocardial tissue after Masson staining. SSR can increase the number of autophagosomes and autophagiclysosomes in 5/6 nephrectomized rats (P < 0.05). Determined by RT-PCR， WB and IHC， SSR can increase the relative expression of PINK1， Parkin， and LC3B (P < 0.05)， and decrease the relative expression of P62， Beclin-1 and Drp-1 (P < 0.05). Conclusions: The PINK1/Parkin mitochondrial autophagy pathway in myocardial tissues in 5/6 nephrectomy CKD myocardial injury rats was inhibited. SSR can activate PINK

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TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization

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Neuroscience Bulletin 2024年第1期40卷 17-34页

作者： Siying Qu Shengfeng Hu Huiting Xu Yongjian Wu Siqi Ming Xiaoxia Zhan Cheng Wang Xi Huang Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China The State Key Laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Allergy and Clinical ImmunologyThe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China department of Laboratory medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Division of nephrology Department of Medicinethe Fifth Affliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)***,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in ***,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse *** knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE ***,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE *** conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.

关键词： Multiple sclerosis Experimental autoimmune encephalomyelitis T helper 17 Triggering receptor expressed on myeloid cells 2

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