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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei Institute of clinical Pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China department of clinical Pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex ***-derived macrophages(MDMs)infiltration are associated with RA *** have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor ***,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been ***,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)*** inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)*** experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting *** further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγ***,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 ***,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and ***,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular *** GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

Impacts of pancreatic exocrine insufficiency on gut microbiota

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 271-279页

作者： Yulin GUO Feng CAO Fei LI department of General Surgery Xuanwu Hospital of Capital Medical UniversityBeijing 100053China Acute Pancreatitis clinical Center of Capital Medical University Beijing 100053China

Pancreatic exocrine insufficiency(PEI)can be induced by various kinds of diseases,including chronic pancreatitis,acute pancreatitis,and *** main pathogenetic mechanism of PEI involves the decline of trypsin synthesis,disorder of pancreatic fluid flow,and imbalance of secretion *** studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis,with the abundance of Lactobacillus and Bifidobacterium increasing the most,which could be partially reversed by pancreatic enzyme replacement *** studies have also confirmed the association between PEI and the dysbiosis of gut *** exocrine secretions and changes in duodenal p H as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut *** turn,the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional *** forward,more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.

关键词： Pancreatic exocrine insufficiency Gut microbiota Gut microbiome Pancreatic enzyme replacement therapy

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

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World Journal of Stem Cells 2024年第2期16卷 70-88页

作者： Min Meng Wei-Wei Zhang Shuang-Feng Chen Da-Rui Wang Chang-Hui Zhou department of Central Laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina department of clinical Laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues *** diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung *** umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage ***,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung *** searched the Public clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary *** this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical ***,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in *** brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

关键词： Pulmonary diseases Mesenchymal stem cells Human umbilical cord Cell therapy clinical trials

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

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Cancer Biology & Medicine 2024年第5期21卷 416-432页

作者： Yuexiang Liang Guannan Sheng Yu Guo Yiping Zou Hanhan Guo Zhifei Li Shaofei Chang Quan Man Song Gao Jihui Hao department of Pancreatic Cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China department of Gastrointestinal Oncology The First Affiliated Hospital of Hainan Medical UniversityHaikou 570102China department of Gastrointestinal Pancreatic Surgery Shanxi Provincial People’s HospitalTaiyuan 030012China

Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell ***-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine ***,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains ***:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were *** of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was ***:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and *** GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic *** tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and ***:Ki-67 is a valuable prognostic indicator for *** of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

关键词： Pancreatic ductal adenocarcinoma prognosis Ki-67 differentiation TNM stage

Chinese national clinical practice guidelines on prevention, diagnosis and treatment of early colorectal cancer

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中华医学杂志(英文版) 2024年第17期137卷 2017-2039页

作者： Li Jingnan Yao Hongwei Lu Yun Zhang Shutian Zhang Zhongtao Society of Digestive Endoscopy of the Chinese Medical Association Colorectal Surgery Group of the Chinese Medical Association Chinese Association of Gastroenterologist & Hepatologist National clinical Research Center for Digestive Diseases Chinese Medical Journal clinical Practie Guideline Collaborative department of Gastroenterology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing China department of General Surgery Beijing Friendship Hospital Capital Medical University National Clinical Research Center for Digestive Diseases Beijing China department of General Surgery The Affiliated Hospital of Qingdao University Qingdao Shandong China department of Gastroenterology Beijing Friendship Hospital Capital Medical University National Clinical Research Center for Digestive Disease Beijing China

Background: The incidence and mortality of colorectal cancer (CRC) in China are increasing in recent years. The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent, screen, and diagnose CRC at an early stage. With the development of endoscopic and surgical techniques, the choice of treatment for early CRC is also worth further discussion, and accordingly, a standard follow-up program after treatment needs to be ***: This clinical practice guideline (CPG) was developed following the recommended process of the World Health Organization, adopting Grading of Recommendations Assessment, Development and Evaluation (GRADE) in assessing evidence quality, and using the Evidence to Decision framework to formulate clinical recommendations, thereby minimizing bias and increasing transparency of the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline’s completeness and ***: This CPG comprises 46 recommendations concerning prevention, screening, diagnosis, treatment, and surveillance of CRC. In these recommendations, we have indicated protective and risk factors for CRC and made recommendations for chemoprevention. We proposed a suitable screening program for CRC based on the Chinese context. We also provided normative statements for the diagnosis, treatment, and surveillance of CRC based on existing clinical evidence and ***: The 46 recommendations in this CPG are formed with consideration for stakeholders’ values and preferences, feasibility, and acceptability. Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China.

关键词： Colorectal cancer Early detection of cancer Prevention Screening Diagnosis Treatment Follow-up Guideline

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients:An Open-Label,Multicenter,and Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2024年第8期30卷 675-683页

作者： HE Qiu LIN Fu-xin SU Jin-ye ZHUO Ling-yunn ZHU Qing SUN Xiao-chuan JIANG Rong-cai YAO Zhi-gang WANG Lei DANG Yan-wei LIU De-zhong LIU Yang FANG Wen-hua WANG Fang-yu LIN Yuan-xiang WANG An-xin WANG Deng-liang KANG De-zhi department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated Hospital of Fujian Medical UniversityFuzhou350004China department of Neurosurgery Binhai Branch of National Regional Medical CenterThe First Affiliated HospitalFujian Medical UniversityFuzhou350209China clinical Research and Translation Center The First Affiliated Hospital of Fujian Medical UniversityFuzhou350004China Fujian clinical Research Center for Neurological Diseases The First Affiliated Hospital of Fujian Medical UniversityFuzhou350004China Fujian Provincial Institutes of Brain Disorders and Brain Sciences The First Affiliated Hospital of Fujian Medical UniversityFuzhou350004China department of Neurosurgery The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu Province215000China department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing400000China department of Neurosurgery Tianjin Medical University General HospitalTianjin300000China department of Neurosurgery The Third Hospital of ShijiazhuangShijiazhuang050000China department of Neurosurgery The First College of Clinical Medical ScienceChina Three Gorges UniversityYichangHubei Province443000China department of Neurosurgery Yichang Central People’s HospitalYichangHubei Province443000China department of Neurosurgery Xiangyang No.1 People’s Hospital Affiliated to Hubei University of MedicineXiangfanHubei Province441100China department of Neurosurgery Zhoukou Central HospitalZhoukouHenan Province466000China department of Neurosurgery The Third Hospital of MianyangMianyangSichuan Province621000China department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing100000China China National clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijing100000China department of clinical Epidemiology and clinical Trial Capital Medical UniversityBeijing100000China Beijing Municipal Key Laboratory of clinical

Objective To investigate whether Naoxueshu Oral Liquid(NXS)could promote hematoma absorption in post-craniotomy hematoma(PCH)*** This is an open-label,multicenter,and randomized controlled trial conducted at 9 hospitals in *** aged 18–80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL,or intraventricular hemorrhage following cranial surgery were *** were randomly assigned at a 1:1 ratio to the NXS(10 mL thrice daily for 15 days)or control groups using a randomization code *** medical care was administered in both *** primary outcome was the percentage reduction in hematoma volume from day 1 to day *** secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7,the absolute reduction in hematoma volume from day 1 to day 7 and 15,and the change in neurological function from day 1 to day 7 and *** safety was closely monitored throughout the ***,subgroup analysis was performed based on age,gender,history of diabetes,and etiology of intracerebral hemorrhage(ICH).Results A total of 120 patients were enrolled and randomly assigned between March 30,2018 and April 15,*** patient was lost to follow-up in the control ***,there were 119 patients(60 in the NXS group and 59 in the control group)included in the *** the full analysis set(FAS)analysis,the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group[median(Q1,Q3):85%(71%,97%)vs.76%(53%,93%),P0.05).Furthermore,no adverse events were reported during the *** the FAS analysis,the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups:male patients,patients younger than 65 yea

关键词： post-craniotomy hematoma Naoxueshu Oral Liquid hematoma absorption randomized controlled trial Chinese medicine

Gp78 regulates PMP22 and causes ER stress and autophagy in EV71-VP1-overexpressing mouse Schwann cells

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BIOCELL 2024年第4期48卷 653-664页

作者： DANPING ZHU GUANGMING LIU KUAN FENG SUYUN LI DANDAN HU SIDA YANG PEIQING LI Pediatric Emergency department Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouChina department of Child Health Care Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouChina Pediatric Neurology department Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouChina

Background:During Enterovirus type 71(EV71)infection,the structural viral protein 1(VP1)activates endoplasmic reticulum(ER)stress associated with peripheral myelin protein 22(PMP22)accumulation and induces ***,the speciﬁc mechanism behind this process remains ***:In this research,we used the VP1-overexpressing mouse Schwann cells(SCs)models co-transfected with a PMP22 silencing or Autocrine motility factor receptor(AMFR/gp78)overexpressing vector to explore the regulation of gp78 on PMP22 and its relationship with autophagy and ***:The activity of gp78 could be inﬂuenced by EV71-VP1,leading to a decrease in the ubiquitination and degradation of PMP22,resulting in PMP22 accumulation in *** VP1-overexpressing mouse SCs,all three ER stress sensors,including pancreatic endoplasmic reticulum kinase(PERK),activating transcription factor 6(ATF6)and inositol-requiring enzyme 1(IRE1)and the related downstream signals(C/EBP-homologous protein(CHOP)and Caspase 12)were activated,as well as the ER-resident chaperone Glucose-regulated protein 78(GRP78).In addition,VP1 upregulated the autophagy marker Microtubule-associated protein 1 light chain 3 beta(LC3B),while PMP22 silencing or gp78 overexpression reversed the ***,PMP22 silencing or gp78 overexpression increased proliferation of EV71-VP1-transfected mouse ***:Gp78 could regulate PMP22 accumulation through ubiquitination degradation and cause ER stress and autophagy in EV71-VP1-overexpressing mouse ***,the gp78/PMP22/ER stress axis might emerge as a promising therapeutic target for myelin and neuronal damage induced by EV71 infection.

关键词： Enterovirus type 71 AMFR/gp78 PMP22 Autophagy Schwann cells

Establishment and characterization of a canine chondrosarcoma cell line:Mango

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动物疾病（英文） 2024年第3期4卷 186-197页

作者： Meilin Wang Xiao Wang Lixin He Hongbo Gao Wenxuan Li Huili Feng Qingyuan Zhao Wenwen Zhang Chengzong Li Bohan Zhang Changwei Qiu department of clinical Veterinary Medicine College ofVeterinary MedicineHuazhong Agricultural UniversityWuhan 430070China

In the global progress of bone tumor research,established stable and long-lasting transgenic chondrosarcoma(CSA)cell lines are rare,mainly of murine and human origin,while the establishment of canine CSA cell lines has yet to be *** study established a canine CSA cell line to facilitate the basic clinical study of canine *** five cases of canine osteolytic disease were collected,and more than 10 bone tumor samples from dogs with typical clinical signs were used for primary cell culture.A cell line with stable passaging for more than 100 generations and mouse tumorigenic ability was successfully *** to the clinical characteristics of the dog and the histopatho-logical results of the primary tumor,CSA was diagnosed,and the CSA cell line was designated ***-tochemical(IHC)results showed that the immunoreactivity of bone gamma-carboxyglutamate protein(BGLAP),secreted protein acidic and rich in cysteine(SPARC),alkaline phosphatase(ALPL),vimentin(VIM)and S100 were ***,the immunoreactivity of pan-cytokeratin(PCK),chromogranin A(CGA),and platelet endothelial cell adhesion molecule-1(CD31)was ***(IF)results showed that the protein expressions in the Mango cell line were consistent with the IHC identification of the primary *** Mango cell line's doubling time was 43.92 h,and the cell formation rate exceeded 20％.There were abnormal chromosome numbers,hetero staining with toluidine blue,and certain calcification *** could be passaged stably and continuously with-out changing the cell morphology and *** vivo,the cells were successfully injected into the nude mice model with a tumorigenic rate of 100％.The immunophenotype of the xenograft tumor was consistent with that of the primary ***,we effectively established a canine CSA cell *** a promising cell material,this cell line can be used to construct a tumor-bearing model conducive to the subsequent basic re

关键词： Canine chondrosarcoma Cell line Establishment Characterization Tumorigenicity

Diagnostic and prognostic performances of GALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study

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World Journal of Gastroenterology 2024年第17期30卷 2343-2353页

作者： Oraphan Jitpraphawan Witchakorn Ruamtawee Mala Treewatchareekorn Supatsri Sethasine Division of Gastroenterology and Hepatology Department of MedicineNavamindradhiraj UniversityDusit 10300BangkokThailand clinical Research Center Research Facilitation DivisionNavamindradhiraj UniversityDusit 10300BangkokThailand Division of clinical Chemistry and Immunology Navamindradhiraj UniversityDusit 10300BangkokThailand

BACKGROUND The GALAD score has improved early hepatocellular carcinoma(HCC)detection *** role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular *** To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis,tumor features,and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum *** This prospective,diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira *** patients had HCC staging allocation using the Barcelona Clinic Liver Cancer(BCLC)***,HCC etiology,and HCC features were *** and the GALAD score were obtained at *** performance of the GALAD score and biomarkers were prospectively *** Exactly 115 individuals were diagnosed with *** GALAD score increased with disease *** BCLC-0/A and BCLC-B/C/D,the GALAD score predicted HCC staging with an area under the curve(AUC)of 0.868(95%CI:0.80–0.93).For identifying the curative HCC,the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein(AFP)(0.753)and Lens culinaris agglutinin-reactive fraction of AFP-L3(0.706),and as good as that of Protein induced by vitamin K absence-II(PIVKA-II)(0.897).For detecting aggressive features,the GALAD score gave an AUC of 0.839(95%CI:0.75–0.92)and significantly outperformed compared to that of AFP(0.761)and AFP-L3(0.697),with a trend of superiority to that of PIVKA-II(0.772).The performance to predict 1-year mortality of GALAD score(AUC:0.711,95%CI:0.60–0.82)was better than that of AFP(0.541)and as good as that of PIVKA-II(0.736).The optimal cutoff value of GALAD score was≥6.83,with a specificity of 72.63%for exhibiting substantial reduction in the 1-year *** The GALAD model can diagnose HCC at the curative stage,includin

关键词： Alpha-fetoprotein Barcelona clinic liver cancer GALAD score Hepatocellular carcinoma Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein Protein induced by vitamin K absence-II