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Ruxolitinib improves the inflammatory microenvironment,restores glutamate homeostasis,and promotes functional recovery after spinal cord injury

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Neural Regeneration Research 2024年第11期19卷 2499-2512页

作者： Jiang Cao Xiao Yu Jingcheng Liu Jiaju Fu Binyu Wang Chaoqin Wu sheng Zhang Hongtao Chen Zi Wang Yinyang Xu Tao sui Jie Chang Xiaojian Cao Department of Orthopedics The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Trauma surgery Subei People’s Hospital of JiangsuClinical Medical College of Yangzhou UniversityYangzhouJiangsu ProvinceChina Department of Orthopedics Zhongda HospitalSoutheast UniversityNanjingJiangsu ProvinceChina Department of Orthopedic surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina

The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord ***,a JAK-sTAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine *** studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains *** address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord *** sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory ***,ruxolitinib inhibited the phosphorylation of JAK2 and sTAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of sTAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic ***,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.

关键词： astrocytes EAAT2 excitotoxicity glutamate homeostasis JAK-sTAT pathway locomotor function neurotoxicity ruxolitinib spinal cord injury transcriptome analysis

Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1613-1625页

作者： Xiao-Min Zhang Ting Yang Ying-Ying Xu Bao-Zhong Li Wei shen Wen-Qing Hu Cai-Wen Yan Liang Zong Department of Central Laboratory Changzhi People’s HospitalThe Affiliated Hospital of Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina Department of Gastrointestinal surgery Yizheng People’s HospitalThe Affiliated Hospital of Yangzhou UniversityYangzhou 225000Jiangsu ProvinceChina Department of General surgery Anyang Tumor HospitalAnyang 455000Henan ProvinceChina Department of General surgery Wuxi People’s Hospital Affiliated to Nanjing Medical UniversityWuxi 214023Jiangsu ProvinceChina Department of Gastrointestinal surgery Changzhi People’s HospitalThe Affiliated Hospital of Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina Department of Gastroenterology Changzhi People’s HospitalThe Affiliated Hospital of Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric ***,it is unclear whether this combination is superior to chemotherapy *** To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal *** We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric *** employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(Os),progression-free survival(PFs),objective response rate,and adverse events(AEs).REsULTs Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion *** meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer Os than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFs result was consistent with that of Os(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were *** performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPs)and noted extended Os and PFs durations within the CPs≥1,CPs≥5,and CPs≥10 subgroups of the PD-1 inhibitor+chemotherapy ***

关键词： Programmed cell death protein-1 inhibitor Chemotherapy Oesophageal squamous cell carcinoma Gastric/gastroesophageal junction adenocarcinoma Overall survival Progression-free survival Objective response rate Adverse event

sinomenine increases osteogenesis in mice with ovariectomyinduced bone loss by modulating autophagy

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World Journal of stem Cells 2024年第5期16卷 486-498页

作者： Hai-Xiang Xiao Lei Yu Yu Xia Kai Chen Wen-Ming Li Gao-Ran Ge Wei Zhang Qing Zhang Hong-Tao Zhang De-Chun Geng Department of Orthopedics The Fourth Affiliated Hospital of Soochow UniversitySuzhou Dushu Lake HospitalMedical Centre of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Orthopedics Jingjiang People’s Hospital Affiliated to Yangzhou UniversityJingjiang 214500Jiangsu ProvinceChina Department of Orthopedics The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Orthopedics Hai’an People’s HospitalHai’an 226600Jiangsu ProvinceChina Department of Orthopedics The Affiliated Huai’an Hospital of Xuzhou Medical UniversityHuai’an Second People’s HospitalXuzhou 223002Jiangsu ProvinceChina Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina

BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMsCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMsCs is a potential therapeutic option to increase osteoblast viability and ameliorate *** To explore the effects of sinomenine(sIN)on the osteogenic differentiation of BMsCs and the underlying *** For in vitro experiments,BMsCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of sIN and the autophagy inhibitor *** vivo,the therapeutic effect of sIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse *** sIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMsCs,thereby promoting the osteogenic differentiation of BMsCs and effectively alleviating bone loss in ovariectomized mice in *** The Chinese medicine sIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.

关键词： sinomenine Osteogenesis Autophagy Ovariectomy Osteoporosis

Circ_0004592:An auxiliary diagnostic biomarker for gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2757-2768页

作者： shan Kong Yan-Hua Xu Ming Zheng shao-Qing Ju Heng-Chuan shi Department of Laboratory Medicine Jiangsu Province Official HospitalNanjing 210000Jiangsu ProvinceChina Department of Laboratory Medicine Northern Jiangsu People’s HospitalYangzhou 225000Jiangsu ProvinceChina Department of Laboratory Medicine The Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina

BACKGROUND Gastric cancer(GC)has a high mortality rate,and robust diagnostic biomarkers are currently ***,the clinical relevance of circular RNAs(circRNAs)as GC biomarkers remains largely *** To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of *** High-throughput sequencing of circRNAs was performed to screen for potential target ***_0004592 expression was examined in GC tissues,cells,and *** samples were collected from healthy subjects’patients,as well as from patients with benign lesions,precancerous lesions,and GC,whereafter the diagnostic accuracy of circ_0004592 was *** correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further *** Circ_0004592 was upregulated in both the tissue and plasma of patients with ***,circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with *** the same patient,the postoperative plasma level of circ_0004592 was lower than that in the preoperative ***,circ_0004592 level was significantly correlated with tumor differentiation,tumor depth,and lymph node *** area under the curve(AUC)of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy *** based on circ_0004592,carcinoembryonic antigen,and cancer antigen 199 achieved a superior AUC and was highly *** Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

关键词： Biomarker Circular RNA Diagnosis Gastric cancer Plasma

Chinese Guidelines for the Diagnosis and Management of Atrial Fibrillation

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Journal of Geriatric Cardiology 2024年第3期21卷 251-314页

作者： Chang-sheng MA shu-Lin WU shao-Wen LIU Ya-Ling HAN Chinese society of Cardiology Chinese Medical Association Heart Rhythm Committee of Chinese society of Biomedical Engineering Beijing Anzhen hospital Capital Medical University Guandong Provincial people’s hospital shanghai First people’s hospital General hospital of northern Theater Command 不详

Atrial fibrillation(AF)is the most common sustained cardiac arrhythmia,significantly impacting patients’quality of life and increasing the risk of death,stroke,heart failure,and *** the past two decades,there have been significant breakthroughs in AF risk prediction and screening,stroke prevention,rhythm control,catheter ablation,and integrated *** this period,the scale,quality,and experience of AF management in China have greatly improved,providing a solid foundation for the development of guidelines for the diagnosis and management of *** further promote standardized AF management,and apply new technologies and concepts to clinical practice in a timely and comprehensive manner,the Chinese society of Cardiology of the Chinese Medical Association and the Heart Rhythm Committee of the Chinese society of Biomedical Engineering have jointly developed the Chinese Guidelines for the Diagnosis and Management of Atrial *** guidelines have comprehensively elaborated on various aspects of AF management and proposed the CHA2Ds2-VAsc-60 stroke risk score based on the characteristics of AF in the Asian *** guidelines have also reevaluated the clinical application of AF screening,emphasized the significance of early rhythm control,and highlighted the central role of catheter ablation in rhythm control.

关键词： prevention sustained diagnosis

Meta-analysis of the clinical efficacy of the Gamma3 nail vs Gamma3U-blade system in the treatment of intertrochanteric fractures

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World Journal of Orthopedics 2024年第3期15卷 285-292页

作者： Xuan Wu Bo Gao Department of Orthopedic Zhong Da HospitalSchool of MedicineSoutheast UniversityNanjing 210000Jiangsu ProvinceChina Department of Orthopedic The Affiliated Taizhou Second People's Hospital of Yangzhou UniversityTaizhou 225500Jiangsu ProvinceChina

BACKGROUND The traditional Gamma3 nail is a mainstream treatment for femoral intertrochanteric *** reports that the Gamma3U-blade system can increase the stability of the Gamma3 nail and reduce complication ***,comparative studies between the Gamma3U-blade and Gamma3 systems are limited;hence,this meta-analysis was performed to explore the clinical efficacy of these two surgical *** To investigate the clinical efficacy of Gamma3 and Gamma3 U-blade for intertrochanteric *** A computerized search for Chinese and English literature published from 2010 to 2022 was conducted in PubMed,Cochrane,CNKI,Wanfang,and VIP *** search keywords were gamma 3,gamma 3 U blade,and intertrochanteric ***,literature tracking was performed on the references of published *** data were analyzed using Revman 5.3 *** individuals checked the inputs for *** variables were described using mean difference and standard deviation,and outcome effect sizes were expressed using ratio OR and 95%confidence interval(CI).High heterogeneity was considered at(P50%),moderate heterogeneity at I2 from 25%to 50%,and low heterogeneity at(P≥0.05,I2sULTs Following a comprehensive literature search,review,and analysis,six articles were selected for inclusion in this *** selection comprised five articles in English and one in Chinese,with publication years spanning from 2016 to *** study with the largest sample size,conducted by seungbae in 2021,included a total of 304 *** analysis:A total of 1063 patients were included in this *** main outcome indicators were:surgical time:The Gamma3U blade system had a longer surgical time compared to Gamma3 nails(P=0.006,I2=76%).Tip-apex distance:No statistical significance or heterogeneity was observed(P=0.65,I2=0%).Harris Hip score:No statistical significance was found,and low heterogeneity was detected(P=0.

关键词： Gamma3 nail Gamma3U-Blade system Femoral intertrochanteric fractures Meta-analysis

Analysis of the Effect of Intensive Nursing Care on Improving sleep Quality During the Perioperative Period of severed Finger Reimplantation

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Journal of Clinical and Nursing Research 2024年第6期8卷 322-327页

作者： Yan Zhu Chao Huang Jingjiang people's hospital affiliated to yangzhou university Jingjiang 214500Jiangsu ProvinceChina

Objective:To investigate the clinical effect of perioperative intensive nursing on patients who underwent severed finger reimplantation and its influence on sleep ***:62 patients who underwent severed finger reimplantation between January 2023 and December 2023 were *** were divided into two groups:the observation group(n=31)and the control group(n=31).The control group received basic nursing interventions,while the observation group received intensive nursing *** comparison parameters included visual analog pain score(VAs),incidence of vascular crises,length of hospitalization,Pittsburgh sleep Quality Index(PsQI),Hamilton Depression score(HAM-D),Hamilton Anxiety score(HAM-A),and patient ***:Postoperative VAs score,incidence of vascular crisis,hospitalization time,PsQI score,and HAM-A and HAM-D scores of the observation group were lower than those of the control group(Psatisfaction of the observation group was higher than that of the control group(Psion:Perioperative intensive nursing care for patients undergoing severed finger reimplantation demonstrates significant *** reduces postoperative pain,lowers the incidence of vascular crises,shortens hospitalization durations,enhances sleep quality,alleviates negative emotions,and improves nursing *** findings underscore the importance and applicability of such care practices.

关键词： Intensive nursing care Replantation of severed fingers Perioperative period sleep quality

Analysis of the Mechanism of Intervention of Fangxiangxiaozhi Prescription on Dyslipidemia Based on Network Pharmacology and Molecular Docking

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Journal of Clinical and Nursing Research 2024年第4期8卷 30-43页

作者： Lijun Zhang Tingting He Jingyun sun Yalin Qian Traditional Chinese Medicine Department Northern Jiangsu People’s HospitalYangzhou 225000China

Objective: To explore the mechanism of intervention of Fangxiangxiaozhi prescription on dyslipidemia by using network pharmacology and molecular docking. Methods: The traditional Chinese Medicine systems Pharmacology Database and Analysis Platform (TCMsP), Pubchem, Uniprot, and other databases were adopted to screen the active ingredients and the corresponding targets of Fangxiangxiaozhi prescription. Dyslipidemia-related targets were identified using the databases of Disgenet and GeneCards. Then, the intersection target of drugs and diseases was demonstrated via a Venn diagram. Cytoscape3.7.2 was used to construct a “drugs-active ingredients-intersection targets” network map and the key active ingredients with the top 7-degree values were determined. The protein interaction network and topology analysis of the intersection target genes were carried out by combining sTRING11.0 and Cytoscape3.7.2. Moreover, the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the intersection target genes were carried out using the Metascape database. Lastly, the key active ingredients and targets were molecular docked by AutoDockTools, Pymol, and other software. Results: There were 51 active components and 509 target genes of which 74 intersect with dyslipidemia. The key targets included tumor necrosis factor (TNF), interleukin-6 (IL-6), AKT1, PPAR gamma (PPARG), VEGFA, and PPARα. GO enrichment analysis obtained 1040 biological processes, 33 cell components, and 84 molecular functions;KEGG enrichment analysis obtained 148 pathways. The molecular docking results showed that the key targets and compounds exhibited good binding force. Conclusion: The active ingredients of Fangxiangxiaozhi prescription regulated several pathways through multiple targets to intervene in dyslipidemia. This study can serve as a foundation for further research.

关键词： Fangxiangxiaozhi prescription Dyslipidemia Network pharmacology Molecular docking

Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

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Journal of Animal science and Biotechnology 2024年第1期15卷 201-217页

作者： Hao Zhang Xia Zha Yi Zheng Xiaoyun Liu Mabrouk Elsabagh Hongrong Wang Honghua Jiang Mengzhi Wang Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition College of Animal Science and TechnologyYangzhou UniversityYangzhou 225009P.R.China Joint International Research Laboratory of Agriculture and Agri‑Product safety Ministry of Education of ChinaYangzhou UniversityYangzhou 225009P.R.China Department of Animal Production and Technology Faculty of Agricultural Sciences and TechnologiesNiğde Omer Halisdemir UniversityNigde 51240Turkey Department of Nutrition and Clinical Nutrition Faculty of Veterinary MedicineKafrelsheikh UniversityKafrelSheikhEgypt Department of Pediatrics Northern Jiangsu People’s HospitalClinical Medical CollegeYangzhou UniversityYangzhou 225001China state Key Laboratory of sheep Genetic Improvement and Healthy Production Xinjiang Academy of Agricultural Reclamation ScienceShihezi 832000China

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of *** hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERs).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERs in these complications,remain to be *** In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates *** OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERs activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERs antagonist)and DMEM/F12 complete medium(control),for 24 *** In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,Os,inflammatory responses,autophagy and ERs in type A *** vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERs,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier ***,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),Os,inflamm

关键词： Autophagy Bisphenol A Endoplasmic reticulum stress Fetal growth restriction Inflammatory responses sheep