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New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis

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World Journal of Clinical Cases 2024年第6期12卷 1050-1062页

作者： Tsvetelina Velikova Boris Krastev Milena Gulinac Miroslav Zashev Vasko Graklanov Milena Peruhova Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Medical Center Nadezhda Medical Center NadezhdaSofia 1407Bulgaria General and Clinical Pathology Medical University of PlovdivPlovdiv 4002Bulgaria Department of General Surgery University Hospital“Heart and Brain”Burgas 8000Bulgaria First Department of Internal Diseases Medical University of PlovdivPlovdiv 4000Bulgaria Department of Hematology University Hospital“St.George”Plovdiv 4000Bulgaria Division of Gastroenterology University Hospital“Heart and Brain”Burgas 1000Bulgaria

Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 *** this revolutionary immunotherapy gains prominence in cancer treatment,understanding,diagnosing,and effectively managing IMC becomes *** represents a unique challenge due to its immune-mediated nature and potential for severe ***,a precise picture of IMC pathophysiology is currently ***,we aimed to summarize the existing data while acknowledging the need for further *** comprehensive review explores the mechanisms underlying ICIs,gastrointestinal adverse effects,and,in particular,IMC’s incidence,prevalence,and *** review also emphasizes the importance of recognizing IMC’s distinct clinical and histopathological features to differentiate it from other forms of ***,this paper highlights the urgentneed for evolving diagnostic methods,therapeutic strategies,and a multidisciplinary approach to effectively manage IMC.

关键词： Immune-checkpoint inhibitors Immune-checkpoint inhibitor-mediated colitis Inhibitor-mediated colitis management Immunotherapy-associated colitis Checkpoint inhibitor-induced colitis Gastrointestinal adverse effects Checkpoint inhibitor toxicity Inhibitor-mediated colitis therapy

Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational Medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

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Neural Regeneration Research 2024年第6期19卷 1344-1350页

作者： Tianqi Xu Jianhong Yang Yao Xu Xiaofeng Wang Xiang Gao Jie Sun Chenhui Zhou Yi Huang Department of Neurology The First Affiliated Hospital of Ningbo University Department of General Surgery The First Affiliated Hospital of Ningbo University Department of Neurosurgery The First Affiliated Hospital of Ningbo University Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation, which is associated with blood-brain barrier disruption. Brain microvascular endothelial cells are a major component of the blood-brain barrier. Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction. In this study, we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells, and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells. We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells. However, post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction. We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier. We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier. In a clinical study, we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation. We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation. These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

关键词： acute ischemic stroke blood-brain barrier brain microvascular endothelial cells mitochondrial transfer stress hyperglycemia

LncRNA NKILA inhibits HBV replication by repressing NF-κB signalling activation

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Virologica Sinica 2024年第1期39卷 44-55页

作者： Xi Zhang Yuanyuan Li Chen Huan Yubao Hou Rujia Liu Hongyun Shi Peng Zhang Baisong Zheng Yingchao Wang Hong Wang Wenyan Zhang Institute of Virology and AIDS Research The First Hospital of Jilin UniversityChangchun130012China Department of Ophthalmology The First Hospital of Jilin UniversityChangchun130012China Hepatobiliary Pancreatic Surgery The First Hospital of Jilin UniversityChangchun130012China

Hepatitis B virus(HBV)infection results in liver cirrhosis and hepatocellular carcinoma(HCC).HBx/nuclear factor(NF)-κB pathway plays a role in HBV ***,whether NF-κB-interacting long noncoding RNA(NKILA),a suppressor of NF-κB activation,regulates HBV replication remains largely *** this study,gain-and-loss experiments showed that NKILA inhibited HBV replication by inhibiting NF-κB *** turn,HBV infection down-regulated NKILA *** addition,expression levels of NKILA were lower in the peripheral blood-derived monocytes(PBMCs)of HBV-positive patients than in healthy individuals,which were correlated with HBV viral *** a negative correlation between NKILA expression level and HBV viral loads was observed in blood serum from HBV-positive *** levels of endogenous NKILA were also observed in HepG2 cells expressing a 1.3-fold HBV genome,HBV-infected HepG2-NTCP cells,stable HBV-producing HepG2.2.15 and HepAD38 cells,compared to those HBV-negative ***,HBx was required for NKILA-mediated inhibition on HBV *** decreased HBx-induced NF-κB activation by interrupting the interaction between HBx and p65,whereas NKILA mutants lack of essential domains for NF-κB inhibition,lost the ability to inhibit HBV ***,our data demonstrate that NKILA may serve as a suppressor of HBV replication via NF-κB signalling.

关键词： LncRNA NF-κB-interacting longnoncoding RNA(NKILA) NF-ĸB signalling ChronichepatitisBvirus(HBV) Viral replication HBx

Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions:an intravascular ultrasound study

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Journal of Geriatric Cardiology 2024年第5期21卷 506-522页

作者： Yi XU Tian XU Jia-Cong NONG Xiao-Han KONG Meng-Yao ZHAO Zhi-Jing GAO Yi-Fei WANG Wei YOU Pei-Na MENG Yu-He ZHOU Xiang-Qi WU Zhi-Ming WU Mei-En ZHAN Yan-Qing WANG De-Feng PAN Fei YE Department of Cardiology Nanjing First HospitalNanjing Hospital Affiliated to Nanjing Medical UniversityNanjing Medical UniversityNanjingChina Department of Cardiology Clinical Medicine School of Nanjing UniversityNanjingChina Department of Cardiology Tianchang People’s HospitalTianchangChina Department of Cardiology the Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina

OBJECTIVES To investigate whether negative remodeling(NR) detected by intravascular ultrasound(IVUS) of the side branch ostium(SBO) would affect in-stent neointimal hyperplasia(NIH) at the one-year follow-up and the clinical outcome of target lesion failure(TLF) at the long-term follow-up for patients with left main bifurcation(LMb) lesions treated with a two-stent *** A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention(PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre-and post-PCI and at the 1-year follow-up were enrolled in phase Ⅰ analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index(RI) for predicting NIH ≥ 50% was analyzed next. The phase Ⅱ analysis focused on the incidence of TLF as the primary endpoint at the 1-to 5-year follow-up for all 328 patients by grouping based on the cutoff value of *** In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic(ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893(0.778, 1.000), P = 0.002. In phase Ⅱ: the TLR rate(35.8% vs. 5.3%, P stent NIH post-PCI for distal LMb lesions with a 2-stent strategy,and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

关键词： lesions remodeling intravascular

miR-30a-5p/PHTF2 axis regulates the tumorigenesis and metastasis of lung adenocarcinoma

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BIOCELL 2024年第4期48卷 581-590页

作者： LIJUAN ZHANG QINGYIN MENG LI ZHUANG QUAN GONG XIANDA HUANG XUEQIN LI SHIJUAN LI GUOQIN WANG XICAI WANG Department of Rehabilitation and Palliative Medicine The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Emergency Department(Outpatient Chemotherapy Center) The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of Cancer BioTreatment Center The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of Cancer Institute The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina

Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective *** this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung ***:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal *** experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma ***,we examined tumorigenesis and metastasis in a nude mouse ***:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma *** of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant ***,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal ***,PHTF2 was found to be a molecular target of *** PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p ***:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung ***,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.

关键词： Lung cancer Malignant phenotype Tumor formation Tumor suppressor Oncogene

Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study

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中华医学杂志(英文版) 2024年第15期137卷 1802-1810页

作者： Xing Changyang Xie Xiujing Wu Yu Xu Lei Guan Xiangping Li Fan Zhan Xiaojun Yang Hengli Li Jinsong Zhou Qi Mu Yuming Zhou Qing Ding Yunchuan Wang Yingli Wang Xiangzhu Zheng Yu Sun Xiaofeng Li Hua Zhang Chaoxue Zhao Cheng Qiu Shaodong Yan Guozhen Yang Hong Mao Yinjuan Zhan Weiwei Ma Chunyan Gu Ying Chen Wu Xie Mingxing Jiang Tianan Yuan Lijun Department of Ultrasound Medicine Tangdu Hospital Air Force Medical University Xi’an Shaanxi China Department of Ultrasound Medicine The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China Department of Ultrasound Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China Department of Ultrasound Xi’an Hospital of Traditional Chinese Medicine Xi’an Shaanxi China Ultrasound Medical Diagnosis Center Shaanxi Provincial People’s Hospital Xi’an Shaanxi China Department of Ultrasound Hospital of Northwestern Polytechnical University Xi’an Shaanxi China Department of Ultrasound Xi’an No. Hospital The First Affiliated Hospital of Northwest University Xi’an Shaanxi China Department of Ultrasound Diagnosis The Second Affiliated Hospital Xi’an Medical College Xi’an Shaanxi China Department of Ultrasound Xi’an Gem Flower ChangQing Hospital Xi’an Shaanxi China Department of Ultrasound The Second Affiliated Hospital of Xi’an Jiaotong University China Xi’an Shaanxi China Department of Echocardiography First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China Department of Ultrasound Renmin Hospital of Wuhan University Wuhan Hubei China Department of Ultrasound Yan’an Hospital The Affiliated Hospital of Kunming Medical University Kunming Yunnan China Department of Ultrasound Yan’an University Xianyang Hospital Xianyang Shaanxi China Department of Function Examination Beijing University of Chinese Medicine Third Affiliated Hospital Beijing China Department of Ultrasound Xi’an Central Hospital Xi’an Shaanxi China Cadre’s Wards Ultrasound Department Diagnostic Ultrasound Center First Hospital of Jilin University Changchun Jilin China Department of Echocardiography Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University Urumqi Xinjiang China Department of Ultrasound First Affiliated Hospital of Anhui Medical University Hefei

Background: Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical ***: A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of ***: All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (allP for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants o

关键词： Intima-media thickness Arterial stiffness Reference values Ultrasound radio frequency signal Wave reflections

Impact of High Sodium Diet on Neovascularization and Osseointegration around Titanium Implant:An in Vivo and in Vitro study

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Biomedical and Environmental Sciences 2024年第7期37卷 739-753页

作者： Keyuan Xu Xiaoting Tang Yun Xiang Yiding Shen Zhennan Deng Pingping Ma Xinkun Shen Department of Orthopaedics The Third Affiliated Hospital of Wenzhou Medical University(Ruian People’s Hospital)Wenzhou 325016ZhejiangChina School and hospital of stomatology Wenzhou Medical UniversityWenzhou 325027ZhejiangChina

Objective A high sodium(HS)diet is believed to affect bone metabolism *** its impact on osseointegration of titanium(Ti)implants holds significant implications for postoperative dietary management of implanted *** This investigation probed the impact of sodium ions(Na^(+))on neovascularization and osteogenesis around Ti implants in vivo,utilizing micro-computed tomography,hematoxylin and eosin staining,and immunohistochemical ***,in vitro experiments assessed the effects of varied Na^(+)concentrations and exposure durations on human umbilical vein endothelial cells(HUVECs)and MC3T3-E1 *** In vivo,increased dietary sodium(0.8%-6.0%)led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants,alongside an increase in inflammatory *** vitro,an increase in Na^(+)concentration(140-150 mmol/L)adversely affected the proliferation,angiogenesis,and migration of HUVECs,especially with prolonged *** MC3T3-E1 cells initially exhibited less susceptibility to high Na^(+)concentrations compared to HUVECs during short-term exposure,prolonged exposure to a HS environment progressively diminished their proliferation,differentiation,and osteogenic *** These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration.

关键词： High-sodium Implants Vascularization Osseointegration

Voluntary wheel running ameliorated the deleterious effects of high-fat diet on glucose metabolism,gut microbiota and microbial-associated metabolites

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Food Science and Human Wellness 2024年第3期13卷 1672-1684页

作者： Ling Zhang Wenyu Zou Yongyan Hu Honghua Wu Ying Gao Junqing Zhang Jia Zheng Department of Endocrinology Peking University First HospitalBeijing 100034China Laboratory Animal Facility Peking University First HospitalBeijing 100034China

Exercise training is critical for the early prevention and treatment of obesity and diabetes ***,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and *** showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia *** profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis *** conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose *** further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.

关键词： High-fat diet Voluntary wheel running Gut microbiota Metabolomics Glucose metabolism