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Prognostic significance and relationship of SMAD3 phosphoisoforms and VEGFR-1 in gastric cancer:A clinicopathological study

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 118-132页

作者： Shi-Lin Lv Pei Guo Jun-Rong Zou Ren-Sheng Chen Ling-Yu Luo De-Qiang Huang hospital of Gastroenterology Institute of Digestive DiseasesThe First Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of Pathology Shenzhen Hospital of Southern Medical UniversityShenzhen 518000Guangdong ProvinceChina institute of Urology The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina Department of Pathology The First Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer ***3 phosphorylation is a crucial prognostic marker in gastric *** To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric *** This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April *** were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)*** expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC *** and survival information of the patients was recorded by Outdo Biotech from May 2007 to July *** relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation *** relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival *** TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous *** positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multiva

关键词： Gastric cancer pSMAD3L(S204) pSMAD3C(S423/425) Survival Transforming growth factor-β1 VEGFR-1

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The switch triggering the invasion process:Lipid metabolism in the metastasis of hepatocellular carcinoma

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Chinese Medical Journal 2024年第11期137卷 1271-1284页

作者： Jiaqian Zhang Zhicheng Zhang Zhangfan Wu Yufei Wang Zerui Zhang Limin Xia Department of Gastroenterology Institute of Liver and Gastrointestinal DiseasesHubei Key Laboratory of Hepato-Pancreato-Biliary DiseasesTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for digestive diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’anShaanxi 710032China

In humans,the liver is a central metabolic organ with a complex and unique histological *** carcinoma(HCC),which is a highly aggressive disease with a poor prognosis,accounts for most cases of primary liver *** an emerging hallmark of cancers,metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs,including the ***,rewiring of the liver metabolic microenvironment,including lipid metabolism,is driven by HCC cells,propelling the phenotypes of HCC cells,including dissemination,invasion,and even metastasis in *** resulting formation of this vicious loop facilitates various malignant behaviors of HCC ***,few articles have comprehensively summarized lipid reprogramming in HCC ***,we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver,and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying *** addition,we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy,aiming to offer new perspectives for targeted therapy.

关键词： Hepatocellular carcinoma Invasion Metastasis Lipid metabolism Tumor microenvironment

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Impact of short-term ambient air pollution exposure on the risk of severe COVID-19

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Journal of Environmental Sciences 2024年第1期135卷 610-618页

作者： Baihuan Feng Jiangshan Lian Fei Yu Dan Zhang Weizhen Chen QiWang Yifei Shen Guoliang Xie Ruonan Wang Yun Teng Bin Lou Shufa Zheng Yida Yang Yu Chen Department of Laboratory Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province Hangzhou 310000China institute of Laboratory Medicine Zhejiang UniversityHangzhou 310000China Department of Infectious diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are *** the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using *** with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure *** exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,*** for NO_(2)remained significant in two-pollutant models after adjusting for other *** analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic *** findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

关键词： Air pollution COVID-19 Severity Transcriptomics Immune response

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Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration Research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

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Acute suppurative terminal cholangitis:Clinical characteristics of a new subtype of acute cholangitis

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Hepatobiliary & Pancreatic diseases International 2024年第3期23卷 293-299页

作者： Rong-Tao Zhu Ye Li Chi-Xian Zhang Wei-Jie Wang Ruo-Peng Liang Jian Li Kai Bai Yu-Ling Sun Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Zhengzhou Key Laboratory of Hepatobiliary and Pancreatic diseases Zhengzhou 450052China institute of Hepatobiliary and Pancreatic diseases Zhengzhou UniversityZhengzhou 450052China Department of Pathology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well *** explore this subtype of acute cholangitis,we described our clinical experience with ***:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August *** analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and ***:A total of 32 ASTC patients were included in the *** majority of the patients had a history of biliary operations,and clinical manifestations were occult and *** positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance *** with effective antibiotics was provided as soon as diagnosis was *** treatment,most patients had a good *** levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor ***:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.

关键词： Acute suppurative terminal cholangitis Acute cholangitis Gram-negative bacterial infections Diagnosis Treatment

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PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key Laboratory of Molecular Biology for Infectious diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： Cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

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Epigenetic regulation of SARS-Cov-2 spike protein modulates cellular viability and nascent RNA transcription in neuronal cells

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Genes & diseases 2024年第2期11卷 535-538页

作者： Xi Kong Peng Lu Jinyue Zhang Zheng Bao Chenghao Kuang Bingqing Xie Jianhua Peng Ning Ma Yong Jiang Shigang Yin Laboratory of Neurological diseases and Brain Function The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan 646000China institute of Epigenetics and Brain Science Southwest Medical UniversityLuzhouSichuan 646000China Department of Neurosurgery The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan 646000China Inflammation and Allergic diseases Research Unit The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan 646000China

SARS-CoV-2 has been demonstrated to be highly susceptible to neuron-and glial-like cells,1 but there is no consensus regarding how the virus affects neurons following *** is therefore unknown if and how SARS-CoV-2 maintains the homeostasis of neuronal ***,we revealed that the receptor-binding domain(RBD)of the SARS-CoV-2 spike protein acted as an extracellular remodeling component to undermine epigenetic regulation,perturbnascentRNA(nsRNA)transcription,promote mitochondrial biogenesis,and increase cellular viability in SH-SY5Y cells.

关键词： invasion homeostasis maintain

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Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling

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Genes & diseases 2024年第5期11卷 470-483页

作者： Zhirong Zhang Jiayao Yang Rui Liu Jing Ma Kai Wang Xiaojun Wang Ni Tang Key Laboratory of Molecular Biology for Infectious diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Cancer stem cells(CSCs)play a crucial role in tumor initiation,recurrence,metastasis,and drug ***,the current understanding of CSCs in hepatocellular carcinoma(HCC)remains *** a comprehensive analysis of the database,it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR),a critical enzyme involved in cholesterol synthesis,is up-regulated in HCC tissues and liver ***,high expression of HMGCR is associated with a poor prognosis in patients with ***,HMGCR promotes the stemness and metastasis of HCC both in vitro and in *** screening various signaling pathway inhibitors,we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in ***,HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger *** of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in ***,simvastatin,an FDA-approved cholesterol-lowering drug,has been shown to inhibit stemness and metastasis of HCC by targeting *** together,our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling,and simvastatin holds the potential for clinical suppression of HCC metastasis.

关键词： Cancer stem cells Hedgehog Hepatocellular carcinoma Metastasis Statin

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Hepatocellular carcinoma:An analysis of the expression status of stress granules and their prognostic value

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2571-2591页

作者： Qing-Shuai Ren Qiu Sun Shu-Qin Cheng Li-Ming Du Ping-Xuan Guo Department of Cardiovascular Surgery North China University of Science and Technology Affiliated HospitalTangshan 063000Hebei ProvinceChina Department of Hepatobiliary Kailuan General HospitalTangshan 063000Hebei ProvinceChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjin 300000China Department of Traditional Chinese Medicine Kailuan General HospitalTangshan 063000Hebei ProvinceChina Department of Anesthesiology Kailuan General HospitalNorth China University of Science and TechnologyTangshan 063000Hebei ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is *** To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in *** The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical *** hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,*** prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software *** models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction *** We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score *** findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC *** Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological *** Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

关键词： Stress granule genes Hepatocellular carcinoma Gastrointestinal neoplasms Bioinformatics prognosis Prognostic value

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Is appendoscope a new option for the treatment of acute appendicitis?

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World Journal of Gastroenterology 2024年第28期30卷 3386-3392页

作者： Shu-Jiong Feng Yi-Feng Zhou Jian-Feng Yang Hong-Zhang Shen Guang-Xing Cui Xiao-Feng Zhang Department of Gastroenterology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhou 310000Zhejiang ProvinceChina Department of Gastroenterology Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang ProvinceHangzhou 310000Zhejiang ProvinceChina Department of Gastroenterology Hangzhou Institute of Digestive DiseasesHangzhou 310000Zhejiang ProvinceChina

Acute appendicitis is a common surgical *** is commonly caused by obstruction of the appendiceal lumen due to fecaliths,tumors,or lymphoid *** over a century,appendectomy has been the primary treatment for acute *** Groves performed the first open appendectomy in *** 1983,Kurt Semm completed the first laparoscopic appendectomy,heralding a new era in ***,appendectomy is associated with certain complications and a rate of negative *** have suggested controversy over the impact of appendectomy on the development of inflammatory bowel disease and Parkinson’s disease,but an increasing number of studies indicate a possible positive correlation between appendectomy and colorectal cancer,gallstones,and cardiovascular *** the recognition that the appendix is not a vestigial organ and the advancement of endoscopic technology,Liu proposed the endoscopic retrograde appendicitis *** is an effective minimally invasive alternative for treating uncomplicated acute *** team has developed an appendoscope with a disposable digital imaging system operated through the biopsy channel of a colonoscope and successfully applied it in the treatment of *** article provides an overview of the progress in endoscopic treatment for acute appendicitis and offers a new perspective on the future direction of appendiceal disease treatment.

关键词： Acute appendicitis Endoscopic technology Endoscopic retrograde appendicitis therapy Appendoscope Appendiceal disease treatment

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