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Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 343-353页

作者： Li-Xiang Liu Hao Wang Bo Gao Ting-Ting Xu Qing-Gang Yuan Shi-Zhen Zhou Chao Ding Ji Miao Wen-Xian Guan Department of General Surgery Nanjing Drum Tower HospitalNanjing Drum Tower Hospital Clinical CollegeNanjing Medical UniversityNanjing 210008Jiangsu ProvinceChina Department of General Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008Jiangsu ProvinceChina Department of clinical Nutrition Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008Jiangsu ProvinceChina School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210008Jiangsu ProvinceChina Department of General Surgery Nanjing Drum Tower Clinical College of Xuzhou Medical UniversityNanjing 210008Jiangsu ProvinceChina

BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer prognosis.This study invest-igated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer,and compared the predictive ability of the CONUT score with other indexes.AIM To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection.METHODS This retrospective analysis included 217 patients with newly diagnosed colorectal.The CONUT score was calculated based on the serum albumin level,total lymphocyte count,and total cholesterol level.The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve.The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis.RESULTS Using the cutoff value of the CONUT score,patients were stratified into CONUT low(n=189)and CONUT high groups(n=28).The CONUT high group had worse overall survival(OS)(P=0.013)and relapse-free survival(RFS)(P=0.015).The predictive performance of CONUT was superior to the modified Glasgow prognostic score,the prognostic nutritional index,and the neutrophil-to-lymphocyte ratio.Meanwhile,the predictive performances of CONUT+tumor node metastasis(TNM)stage for 3-year OS[area under the receiver operating characteristics curve(AUC)=0.803]and 3-year RFS(AUC=0.752)were no less than skeletal muscle mass index(SMI)+TNM stage.The CONUT score was negatively correlated with SMI(P<0.01).CONCLUSION As a nutritional indicator,the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer,and its predictive ability was superior to other indexes.The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

关键词： Controlling nutritional status Colorectal cancer Prognostic marker Sarcopenia Skeletal muscle

GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease

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Neuroscience Bulletin 2024年第4期40卷 451-465页

作者： Huiqin Li Xiang Cao Xinya Gu Mengqi Dong Lili Huang Chenglu Mao Shengnan Xia Haiyan Yang Xinyu Bao Yongbo Yang Yun Xu Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalState Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical DiseasesNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of Neurology Nanjing210008China nanjing Neurology medical Center Nanjing210008China

Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels.Immune inflammation is associated with the occurrence and development of MMD.However,the mechanisms underlying the formation of the abnormal vascular network remain unclear.Twenty-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in MMD.We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and chemotaxis.In summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

关键词： Moyamoya disease Vascular endothelial cells GM-CSF VEGF

MFG-E8 Alleviates Cognitive Impairments Induced by Chronic Cerebral Hypoperfusion by Phagocytosing Myelin Debris and Promoting Remyelination

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Neuroscience Bulletin 2024年第4期40卷 483-499页

作者： Xiaohong Dong Zhi Zhang Xin Shu Zi Zhuang Pinyi Liu Renyuan Liu Shengnan Xia Xinyu Bao Yun Xu Yan Chen Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of Neurology Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing210008China Department of Neurology Drum Tower Hospital of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of Neurology Nanjing210008China

Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter injury.Microglia phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white matter.However,milk fat globule-epidermal growth factor-factor 8(MFG-E8),a microglial phagocytosis-related protein,has not been well studied in hypoperfusion-related cognitive dysfunction.We found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis(BCAS).MFG-E8 knockout mice demonstrated more severe BCAS-induced cognitive impairments in the behavioral tests.In addition,we discovered that the deletion of MFG-E8 aggravated white matter damage and the destruction of myelin microstructure through fluorescent staining and electron microscopy.Meanwhile,MFG-E8 overexpression by AAV improved white matter injury and increased the number of mature oligodendrocytes after BCAS.Moreover,in vitro and in vivo experiments showed that MFG-E8 could enhance the phagocytic function of microglia via theαVβ3/αVβ5/Rac1 pathway and IGF-1 production to promote the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes.Interestingly,we found that MFG-E8 was mainly derived from astrocytes,not microglia.Our findings suggest that MFG-E8 is a potential therapeutic target for cognitive impairments following cerebral hypoperfusion.

关键词： White matter injury Cognitive dysfunction MFG-E8 Remyelination Microglial phagocytosis

The diagnostic value of tenascin-C in acute aortic syndrome

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Journal of Geriatric Cardiology 2024年第3期21卷 359-368页

作者： Ming MA Wei CHEN Hai-Long CAO Jun PAN Qing ZHOU Xin-Long TANG Dong-Jin WANG Department of Thoracic and Cardiovascular Surgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingChina Department of Thoracic and Cardiovascular Surgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingChina Department of Thoracic surgery Kunshan Hospital of Traditional Chinese MedicineJiangsuChina

OBJECTIVES Misdiagnosis of acute aortic syndrome(AAS)significantly increases mortality.Tenascin-C(TN-C)is an extracellular matrix glycoprotein related to cardiovascular injury.The elevation of TN-C in AAS and whether it can discriminate suddenonset of acute chest pain in Chinese remains unclear.METHODS We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back pain.Measures to discriminate AAS from acute coronary syndrome(ACS)were compared and calculated.RESULTS From October 2016 to September 2021,376 undiagnosed patients with chest or back pain were enrolled.166 of them were finally diagnosed as AAS,100 were ACS and 110 without cardiovascular diseases(NCV).TN-C was significantly elevated in AAS at 18.18 ng/mL(IQR:13.10–27.68)compared with 7.51 ng/mL(IQR:5.67–11.38)in ACS(P<0.001)and 3.68 ng/mL(IQR:2.50–5.29)in NCV(P<0.001).There was no significant difference in TN-C level among the subtypes of AAS.Of the 166 AAS patients,the peaked level of TN-C was at acute stage(P=0.012),then a slight of decrease was observed at subacute stage.The area under receiver operating characteristic curve for AAS patients versus NCV was 0.979(95%CI:0.964-0.994)for TN-C.At a cutoff level of 11.474 ng/mL,TN-C has a sensitivity of 76.0%,specificity of 85.5%,accuracy of 82.0%,positive predictive value(PPV)of 76.0%,negative predictive value(NPV)of 85.5%.Diagnostic performance of TN-C was superior to D-dimer and hs-cTnT.CONCLUSIONS The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and NCV.TN-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

关键词： acute cardiovascular elevated

Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

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Nano Research 2024年第4期17卷 2949-2959页

作者： Lin Yang Xueying An Wang Gong Wenshu Wu Bin Liu Xiaoyan Shao Yansi Xian Rui Peng Baosheng Guo Qing Jiang Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic SurgeryNanjing Drum Tower Hospital Clinical College of Nanjing Medical University321 Zhongshan RoadNanjing 210008China Branch of National clinical Research Center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China State Key Laboratory of Pharmaceutical Biotechnology Medical SchoolNanjing University&Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy.Here,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption interface.Firstly,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation.Furthermore,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

关键词： osteoporosis α-cyperone osteoclast phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) liposome

Traditional Chinese Medicine Integrated Responsive Microneedles for Systemic Sclerosis Treatment

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Research 2024年第1期2023卷 139-147页

作者： Xi Luan Xiaoxuan Zhang Min Nie Yuanjin Zhao Department of Rheumatology and Immunology Nanjing Drum Tower HospitalSchool of PharmacyClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China

Traditional Chinese medicine,such as Tripterygium wilfordii and Paeonia lactiflora,has potential values in treating systemic sclerosis(SSc)and other autoimmune diseases,while their toxic side effect elimination and precise tropical drug delivery are still challenges.Here,we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus(BP)microneedles(MNs)with the desired features for the SSc treatment.By employing a template-assisted layer-by-layer curing method,such MNs with triptolide(TP)/paeoniflorin(Pae)needle tips and BP-hydrogel needle bottoms could be well generated.The combined administration of TP and Pae can not only provide anti-inflammatory,detoxification,and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug delivery.Besides,the additive BPs possess good biocompatibility and near-infrared(NIR)responsiveness,imparting the MN photothermal-controlled drug release capability.Based on these features,we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia,reduce collagen deposition,and reduce epidermal thickness in the SSc mouse models.These results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.

关键词： needle precise template

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 injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although 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 unclear.To 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 injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,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 branching.Collectively,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

Ovarian function in patients with systemic lupus erythematosus:Pathogenesis,drug application and prospective therapies

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World Journal of Experimental Medicine 2024年第2期14卷 29-34页

作者： Min Xu Li-Li Tian Xiao-Liu Li Cheng Bao Hai-Wei Zhang Hong-Wei Chen Department of Rheumatology and Immunology Nanjing Drum Tower HospitalClinical College of Nanjing University of Chinese MedicineNanjing 210008Jiangsu ProvinceChina School of Life Science Nanjing Normal UniversityNanjing 210023Jiangsu ProvinceChina Department of Rheumatology and Immunology Nanjing Drum Tower HospitalNanjing 210008Jiangsu ProvinceChina Department of Rheumatology and Immunology Nanjing Pukou People’s HospitalNanjing 211800Jiangsu ProvinceChina Department of Rheumatology and Immunology Nanjing Drum Tower HospitalThe Affiliated Hospital of School of MedicineNanjing UniversityNanjing 210008Jiangsu ProvinceChina

Systemic lupus erythematosus(SLE)is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women.Currently,glucocorticoids and immunosuppressants are widely used to treat SLE patients.However,ovarian dysfunction occurs following the use of these drugs in women with SLE.Here,we summarize recent progress in terms of understanding ovarian injury,the effects of drug application and strategies to improve ovarian function in women with SLE.This review could be helpful to precisely cure SLE in women desiring to have offspring.

关键词： Systemic lupus erythematosus Ovarian reserve Ovarian insufficiency Mesenchymal stem cells Fertility Autoimmune disease

Making Elimination of Perinatal Hepatitis B Infection a Reality:The Chinese Contribution

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Maternal-Fetal Medicine 2024年第2期6卷 67-69页

作者： Jie Tang Kuanhui Xiang Yi-Hua Zhou Department of Obstetrics and Gynecology Wujin Hospital Affiliated with Jiangsu UniversityChangzhou 213017China Department of Obstetrics and Gynecology Wujin Clinical College of Xuzhou Medical UniversityChangzhou 213000China Department of Microbiology and Infectious Disease Center School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Peking university-YHLO Joint Laboratory for Molecular Diagnostic of Infectious Disease Peking UniversityBeijing 100191China Departments of Laboratory Medicine and Infectious Diseases and Obstetrics&Gynecology Nanjing Drum Tower HospitalNanjing University Medical SchoolNanjing 210008China.

Chronic hepatitis B virus(HBV)infection,referred to the presence of hepatitis B surface antigen(HBsAg)over 6 months,is a serious health issue because of its severe sequelae such as cirrhosis and hepatocellular carcinoma.Prevention of mother-to-child transmission(MTCT)of HBV is most important to control hepatitis B because a vast majority of HBV acquisition in infancy will become chronic carriers.

关键词： mother hepatitis cirrhosis