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Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

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Neural Regeneration Research 2024年第11期19卷 2522-2531页

作者： Shaojun Wang Siti Tong Xin Jin Na Li Pingxiu Dang Yang Sui Ying Liu Dajiang Wang division of Ophthalmology The Third Medical Center of PLA General HospitalBeijingChina Department of Ophthalmology Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain *** models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular *** results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and *** single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular *** extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct *** found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of *** study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular *** data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

关键词： apoptosis axon degeneration high intraocular pressure microglia ocular hypertension photoreceptor cells retina retinal degeneration retinal ganglion cells single-cell RNA sequencing

No-touch isolation technique in emergency pancreaticoduodenectomy for neoplastic hemorrhage: Two case reports and review of literature

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1910-1917页

作者： Akihiro Cho Satoshi Katagiri Masao Ota Shunsuke Onizawa Ryota Higuchi Toshiya Sugishita Yukiko Niwa Takeshi Ishita Toshihiko Mouri Akita Kato Moe Iwata division of Gastroenterological Surgery Tokyo Women’s Medical UniversityYachiyo Medical CenterChiba 276-8524Japan

BACKGROUND Emergency pancreaticoduodenectomy(EPD)is a rare event for complex periam-pullary *** intraoperative blood loss is correlated with poor post-operative *** SUMMARY Two patients underwent EPD using a no-touch isolation technique,in which all arteries supplying the pancreatic head region were ligated and divided before manipulation of the pancreatic head and *** operative times were 220 and 239 min,and the blood loss was 70 and 270 g,*** patients were discharged on the 14^(th) and 10^(th) postoperative day,***-two patients underwent EPD for the treatment of neoplastic *** mean operative time was 361.6 min,and the mean blood loss was 747.3 *** comp-lication rate was 37.5%.The in-hospital mortality rate was 9.38%.CONCLUSION The no-touch isolation technique is feasible,safe,and effective for reducing intraoperative blood loss in EPD.

关键词： No-touch isolation technique Pancreaticoduodenectomy Emergency pancre-aticoduodenectomy Neoplastic bleeding Superior mesenteric artery first approach Case report

GRK2-YAP signaling is implicated in pulmonary arterial hypertension development

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Chinese medical Journal 2024年第7期137卷 846-858页

作者： Peng Ye Yunfei Deng Yue Gu Pengfei Liu Jie Luo Jiangqin Pu Jingyu Chen Yu Huang Nanping Wang Yong Ji Shaoliang Chen division of Cardiovascular Molecular Laboratory Third Clinical CollegeNanjing Medical UniversityNanjingJiangsu 210006China division of Cardiovascular Laboratory Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China division of Cardiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200080China division of Pulmonary Surgery Wuxi People’s HospitalNanjing Medical UniversityWuxiJiangsu 300247China Institute of Vascular Medicine The Chinese University of Hong KongHongkong 999077China Health Science Center East China Normal UniversityShanghai 200241China School of Pharmacy Nanjing Medical UniversityNanjingJiangsu 210004China division of Cardiology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China

Background:Pulmonary arterial hypertension(PAH)is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells(PASMCs),endothelial dysfunction,and extracellular matrix remodeling.G protein-coupled receptor kinase 2(GRK2)plays an important role in the maintenance of vascular tone and blood ***,the role of GRK2 in the pathogenesis of PAH is ***:GRK2 levels were detected in lung tissues from healthy people and PAH patients.C57BL/6 mice,vascular smooth muscle cell-specific Grk2-knockout mice(Grk2^(∆SM22)),and littermate controls(Grk2^(flox/flox))were grouped into control and hypoxia mice(n=8).Pulmonary hypertension(PH)was induced by exposure to chronic hypoxia(10%)combined with injection of the SU5416(cHx/SU).The expression levels of GRK2 and Yes-associated protein(YAP)in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence *** mRNA expression levels of Grk2 and Yes-associated protein(YAP)in PASMCs were quantified with real-time polymerase chain reaction(RT-PCR).Wound-healing assay,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)assay,and 5-Ethynyl-2′-deoxyuridine(EdU)staining were performed to evaluate the proliferation and migration of ***,the interaction among proteins was detected by immunoprecipitation ***:The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH ***,cHx/SU-induced PH was attenuated in Grk2^(∆SM22) mice compared with littermate *** amelioration of PH in Grk2^(∆SM22) mice was accompanied by reduced pulmonary vascular *** vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration,whereas this effect was severely intensified by overexpression of *** also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs,resulting in excessive PA

关键词： Pulmonary arterial hypertension GRK2 YAP Pulmonary artery smooth muscle cell Hypoxia

Genomic medicine and cancer clinical trial in Thailand

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Cancer Biology & Medicine 2024年第1期21卷 10-15页

作者： Lucksamon Thamlikitkul Napa Parinyanitikul Virote Sriuranpong division of medical Oncology Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand division of medical Oncology Department of MedicineFaculty of MedicineChulalongkorn University&The King Chulalongkorn Memorial HospitalBangkok 10330Thailand

Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and *** the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option for systemic *** chemotherapy empirically affects all dividing cells,the targets are virtually *** this regard,toxic effects on normal tissue are essentially inevitable.

关键词： chemotherapy cancer Cancer

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua LU Yao SHEN Ge LIU Ru Yu GAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANG Lu XIE Yao LI Ming Hui Department of Hepatology division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for Infectious Diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of Hepatology division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and *** This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow *** In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<*** Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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Oncology Research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER division of Oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for Hematology and Oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers *** main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma *** therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second *** availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented ***,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk *** recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within *** review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy Gene expression Omics

Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings division of Genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of medical Science University of TorontoTorontoONCanada division of Neurosurgery and Spine Program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

Bowel function and inflammation: Is motility the other side of the coin?

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World Journal of Gastroenterology 2024年第14期30卷 1963-1967页

作者： Alba Panarese division of Gastroenterology and Digestive Endoscopy Department of Medical SciencesCentral Hospital-Azienda OspedalieraTaranto 74123Italy

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the *** the flip side,functions also arise from its role as an interface with the ***,the gut houses microorganisms,collectively known as the gut microbiota,which interact with the host,and is the site of complex immune *** role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut,especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and *** editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.

关键词： Motility Inflammation Pathogenesis Vitamin D Microbiota Gut Chronic intestinal pseudo-obstruction

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 154-159页

作者： Badi Rawashdeh Richard Bell Abdul Hakeem Raj Prasad division of Transplant Surgery Department of General SurgeryMedical College of WisconsinMilwaukeeWI53226USA Leeds Teaching Hospital LeedsUK

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver *** three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of *** transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and *** is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five *** better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA *** review carefully charts the development and history of LT as a treatment option for colorectal cancer liver *** revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.

关键词： Liver transplantation Colorectal cancer liver metastases Non-resectable liver metastases