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Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping

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Journal of Pharmaceutical Analysis 2024年第3期14卷 335-347页

作者： Ding-Jun Hao Yue Qin Shi-Jie Zhou Bu-Huai Dong Jun-Song Yang Peng Zou Li-Ping Wang Yuan-Ting Zhao Department of Spine Surgery Honghui HospitalXi'an Jiaotong UniversityXi'an710054China Department of Anesthesiology Honghui HospitalXi'an Jiaotong UniversityXi'an710054China Department of Cardiovascular Medicine Honghui HospitalXi'an Jiaotong UniversityXi'an710054China State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy West China HospitalSichuan UniversityChengdu610041China

Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is *** study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived cardiomyocytes(CMs)and an adult mouse model of myocardial ***-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,*** single-cell RNA sequencing data were retrieved for bioinformatic *** results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent *** a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by ***11 expression was unaffected by rhHapln1 ***,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and *** mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial *** addition,rmHapln1 induced hiPSC-CM *** conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling ***1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.

关键词： Hapln1 Versican GDF11 iPSC-CMs Cardiomyocyte proliferation

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Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

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World Journal of Gastroenterology 2024年第16期30卷 2195-2208页

作者： xiao-Jun Zhang Yan Yu He-Ping Zhao Lei Guo Kun Dai Jing Lv Department of Clinical Laboratory Honghui HospitalXi’an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina Department of Spinal Surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina Department of Clinical Laboratory Yanliang Railway Hospital of Xi’anXi’an 710089Shaanxi ProvinceChina

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in *** to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still *** addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor *** aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of ***,personalized treatments could be developed to maximize the advantages of immunotherapy.

关键词： Esophageal cancer Esophageal squamous cell carcinoma Esophageal adenocarcinoma Tumor immune microenvironment Immunosuppression Immunotherapy

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Clinical characteristics of acute non-varicose upper gastrointestinal bleeding and the effect of endoscopic hemostasis

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World Journal of Clinical Cases 2024年第9期12卷 1597-1605页

作者： xiao-Juan Wang Yu-Peng Shi Li Wang Ya-Ni Li Li-Juan Xu Yue Zhang Shuang Han Department of Gastroenterology Honghui Hospital Affiliated to Medicine College of Xi’an Jiaotong UniversityXi'an 710054Shaanxi ProvinceChina

BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage *** condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality *** To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic *** We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record *** pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and *** Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among ***,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial *** admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal *** routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding ***-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite ***,diet-related bleeding was more common

关键词： Acute non-varicose upper gastrointestinal bleeding Clinical characteristics Cause of disease Endoscopic homeostatic therapy

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Skeletal interoception in osteoarthritis

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Bone Research 2024年第2期12卷 241-254页

作者： Dinglong Yang Jiawen Xu Ke Xu Peng Xu Department of Joint Surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054China Department of Orthopedic Surgery and Orthopedic Research Institute West China HospitalSichuan UniversityChengdu 610041China

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the *** its various forms,skeletal interoception specifically regulates the metabolic homeostasis of ***(OA)is a complex joint disorder involving cartilage,subchondral bone,and *** subchondral bone undergoes continuous remodeling to adapt to dynamic joint *** findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in *** skeletal interoception is also a potential mechanism for chronic synovial inflammation in *** this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral *** also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

关键词： homeostasis inflammation releasing

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Latest insights into the global epidemiological features,screening,early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2024年第20期30卷 2638-2656页

作者： Yi-xin Zhao He-Ping Zhao Meng-Yao Zhao Yan Yu xi Qi Ji-Han Wang Jing Lv Department of Clinical Laboratory Honghui HospitalXi’an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina Institute of Medical Research Northwestern Polytechnical UniversityXi’an 710072Shaanxi ProvinceChina

As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in *** squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing *** to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in ***,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of *** the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical *** the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ***,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.

关键词： Esophageal squamous cell carcinoma Epidemiology Diagnosis Genomics Proteomics Metabolomics

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Clinical features and prognostic factors of duodenal neuroendocrine tumours:A comparative study of ampullary and nonampullary regions

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 907-918页

作者： Sa Fang Yu-Peng Shi Lu Wang Shuang Han Yong-Quan Shi Department of Gastroenterology Honghui HospitalXi’an Jiaotong UniversityXi'an 710054Shanxi ProvinceChina Department of Gastroenterology The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710032Shaanxi ProvinceChina Department of Gastroenterology Xijing Hospital Affiliated to Air Force Medical UniversityXi'an 710032Shaanxi ProvinceChina

BACKGROUND Duodenal neuroendocrine tumours(DNETs)are rare ***,the incidence of DNETs has been increasing in recent years,especially as an incidental finding during endoscopic ***,there is no consensus regarding the ideal treatment of *** there are few studies on the clinical features and survival analysis of *** To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine *** The clinical data of DNETs diagnosed in the First Affiliated hospital of Air Force Military Medical University from June 2011 to July 2022 were ***-docrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group;neuroendocrine tumours in any part of the duo-denum outside the ampullary area were divided into the nonampullary region *** a retrospective study,the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were *** Twenty-nine DNET patients were *** male to female ratio was 1:1.9,and females comprised the *** ampullary region group accounted for 24.1%(7/29),while the nonampullary region group accounted for 75.9%(22/29).When diagnosed,the clinical symptoms of the ampullary region group were mainly abdominal pain(85.7%),while those of the nonampullary region groups were mainly abdominal distension(59.1%).There were differences in the composition of staging of tumours between the two groups(Fisher's exact probability method,P=0.001),with nonampullary stage II tumours(68.2%)being the main stage(P<0.05).After the diagnosis of DNETs,the survival rate of the ampullary region group was 14.3%(1/7),which was lower than that of 72.7%(16/22)in the nonampullary region group(Fisher's exact probability method,P=0.011).The survival time of the ampullary region group was shorter than that of the nonampullary region group(P<0.000).The median survival time of the ampullary

关键词： Duodenum Neuroendocrine Tumour Ampullary Nonampullary Clinical features Prognostic

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Sponge as Scaffolds in Bone and Cartilage Tissue Engineering

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Chemical Research in Chinese Universities 2024年第5期40卷 786-797页

作者： LUO Lei GONG Yining YAN Liang BU Yazhong Yan’an University Yan’an716000P.R.China Department of Spine Surgery Honghui HospitalXi’an Jiaotong UniversityXi’an710054P.R.China Institute of Medical Engineering Department of BiophysicsSchool of Basic Medical SciencesHealth Science CenterXi’an Jiaotong UniversityXi’an710061P.R.China

In recent years,tissue scaffolds have emerged as a new therapeutic method for bone and cartilage regeneration,with sponge scaffolds gaining increasing *** scaffolds possess several favorable characteristics,including appropriate biodegradability,excellent biocompatibility,good processability,powerful osteogenic ability,a unique porous structure,and adjustable pore size and *** attributes make sponge scaffolds a promising option for bone and cartilage ***,to date,there is a lack of comprehensive reviews summarizing the use of sponge scaffolds in this *** this review,our objective is to provide a comprehensive overview of the research progress and development trends of sponge ***,we introduce the various materials used for sponge ***,we summarize the different preparation methods employed for creating sponge ***,we discuss the functional additives that can be incorporated into the ***,we present some special structures that can be achieved in sponge *** aim is for this review to offer valuable insights and serve as a comprehensive resource for the design of sponge scaffolds in cartilage and bone regeneration.

关键词： Bone Sponge Scaffold Tissue regeneration

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SPOCK2， a novel potential target for cereal intake in knee osteoarthritis

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Food Science and Human Wellness 2024年

作者： Erliang Li Jin Sun Haishi Zheng Jiachen Wang Peng Xu Department of Orthopedics， The First Affiliated hospital of xi'an Jiaotong University Department of Joint Surgery， honghui hospital， xi'an Jiaotong University Department of Orthopaedics， The Tangdu hospital of Air Force Military Medical University

Lifestyle is related to many chronic diseases， such as knee osteoarthritis （KOA）. Food intake is important because it can be controlled. However， the causal relationship of food intake and KOA still remain unclear. To identify the relationship between food intake and KOA and to screen relevant targets. First， we performed two-sample Mendelian randomization （MR） analysis. A total of 16 kinds of food intake datasets were included， the inverse variance-weighted analysis showed that the KOA was negatively correlated with cereal intake (odds ratio[OR]0.48; 95% CI 0.35-0.68; P = 1.98 × 10-5). Second， potential drug targets of KOA in plasma were explored， SPOCK2 as the causal protein for plasma with KOA， and increased SPOCK2 (OR 0.84; 95% CI 0.77 – 0.92; P = 5.52 × 10- 5)， decreased the risk of KOA. Integrated transcriptomic analysis （P = 0.0285） and in vivo （P = 0.0395） showed consistent results. Finally， by metabolomics analysis and molecular docking， seven co-expressed small molecules were detected in cereal and were bound to SPOCK2. Our findings indicate the cereal intake was negatively correlated with KOA， and support the SPOCK2 as a novel potential target for cereal intake in KOA. Our study will provide clinical dietary guidance for KOA patients and provide a theoretical basis for the development of novel， side-effect-free drugs for KOA.

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Etomidate protects retinal ganglion cells from hydrogen peroxide-induced injury via Nrf2/HO-1 pathway

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1606-1613页

作者： Xuan Zhao De-Gang Fan xin-Chao Zhang Si-Wei You Fang Kuang Ming-Mei Wu Department of Histology and Embryology School of Basic Medical SciencesXi’an Medical UniversityXi’an 710021Shaanxi ProvinceChina Department of Neurobiology the Basic Medical Science Academythe Fourth Military Medical UniversityXi’an 710032Shaanxi ProvinceChina Department of Spinal Surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina College of Life Sciences Northwestern UniversityXi’an 710069Shaanxi ProvinceChina

AIM:To determine whether etomidate(ET)has a protective effect on retinal ganglion cells(RGCs)injured with hydrogen peroxide(H_(2)O_(2))and to explore the potential mechanism underlying the antioxidative stress effect of ***:Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and *** injury model of H_(2)O_(2)-induced RGCs oxidative stress was established in *** were pretreated with different concentrations of ET(1,5,and 10μmol/L)for 4h,followed by further exposure to H_(2)O_(2)at 1000μmol/*** counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12,24,and 48h after H_(2)O_(2)*** levels of nitric oxide,malondialdehyde,and glutathione in culture media were measured at these time *** reverse transcription polymerase chain reaction(qRT-PCR)and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase(iNOS),nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12,24,and 48h after H_(2)O_(2)stimulation and in the retina at 12h after optic nerve transection(ONT).RESULTS:The applications of 5 and 10μmol/L of ET significantly increased the viability of *** from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and HO-1 in ETpretreated RGCs at 12,24 and 48h after H_(2)O_(2)stimulation,as well as in ET-treated retinas at 12h after *** blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein,along with an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in ***:ET is a neuroprotective agent in primary cultured RGCs injured by H_(2)O_(2).The effect of ET is dosedependent with the

关键词： etomidate retinal ganglion cell neuroprotection hydrogen peroxide-induced injury nuclear factor erythroid 2-related factor 2 heme oxygenase 1

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Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1073-1078页

作者： Chu-Yuan Lou Yong Wang Jia-Yuan xing Teng Ma Lei Tao xiao-Tang Wang Run-Sheng Wang Neuroophthalmic Center Xi’an People’s Hospital(Xi’an Fourth Hospital)Xi’an 710004Shaanxi ProvinceChina

AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(Group RTX,n=18)in addition to high-dose glucocorticoids were *** groups underwent hormone shock therapy during the acute ***,Group INB received inebilizumab injections during the remission phase,while Group RTX received rituximab injections.A comparison of aquaporins 4(AQP4)titer values,peripheral blood B lymphocyte counts,and visual function recovery was conducted before and 8wk after ***,adverse reactions and patient tolerability were analyzed after using inebilizumab treatment ***:Following inebilizumab treatment,there was a significantly improvement in the visual acuity of NMOSD patients(Pximab,which has previously demonstrated substantial therapeutic efficacy(P>0.05).Furthermore,inebilizumab exhibited higher safety levels than that of rituximab ***:The combination of inebilizumab and high-dose glucocorticoids proves to be *** comparison to rituximab injections,inebilizumab displays better tolerance and ***,it demonstrates a partial effect in preventing optic nerve ***,it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

关键词： neuromyelitis optica spectrum disorders inebilizumab rituximab glucocorticoids

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