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Acta Pharmaceutica Sinica B 2024年第7期14卷 2959-2976页

作者： Chaofan Peng Peng Yang Dongsheng Zhang Chi Jin Wen Peng Tuo Wang Qingyang Sun Zhihao Chen Yifei Feng Yueming Sun Department of General Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China colorectal institute of nanjing medical university Nanjing 210029China The First School of Clinical Medicine Nanjing Medical UniversityNanjing 210029China Jiangsu Province Engineering Research Center of colorectal Cancer Precision Medicine and Translational Medicine Nanjing 210029China

Excessive fructose diet is closely associated with colorectal cancer(CRC)***,fructose’s specific function and precise mechanism in colorectal cancer liver metastasis(CRLM)is rarely ***,this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM,and the expression of KHK-A,not KHK-C,in liver metastasis was higher than in paired primary ***,KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at ***2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of *** and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells’migration ability and anoikis resistance during CRLM ***-46 treatment,targeting the phosphorylation of PKM2,inhibited the pro-metastatic effect of ***,c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A,forming a positive feedback loop.

关键词： CRC CRLM Fructose KHK-A PKM2

Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1849-1860页

作者： Yong-Xia Ye Liu Yang Zheng Kang Mei-Qin Wang Xiao-Dong Xie Ke-Xin Lou Jun Bao Mei Du Zhe-Xuan Li Department of Radiology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina Department of colorectal Surgery Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina1 Department of Pathology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina colorectal Center The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina

BACKGROUND Lymph node(LN)staging in rectal cancer(RC)affects treatment decisions and patient *** radiologists,the traditional preoperative assessment of LN metastasis(LNM)using magnetic resonance imaging(MRI)poses a *** To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable *** In this retrospective study,270 LNs(158 nonmetastatic,112 metastatic)were randomly split into training(n=189)and validation sets(n=81).LNs were classified based on pathology-MRI *** MRI features[size,shape,margin,T2-weighted imaging(T2WI)appearance,and CE-T1-weighted imaging(T1WI)enhancement]were *** radiomics models used 3D features from T1WI and T2WI ***,a nomogram model combining conventional MRI and radiomics features was *** model used univariate analysis and multivariable logistic *** employed the receiver operating characteristic curve,with DeLong test for comparing diagnostic *** performance was assessed using calibration and decision curve *** The nomogram model outperformed conventional MRI and single radiomics models in evaluating *** the training set,the nomogram model achieved an area under the curve(AUC)of 0.92,which was significantly higher than the AUCs of 0.82(P<0.001)and 0.89(P<0.001)of the conventional MRI and radiomics models,*** the validation set,the nomogram model achieved an AUC of 0.91,significantly surpassing 0.80(P<0.001)and 0.86(P<0.001),*** The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

关键词： Radiomics Lymph node metastasis Rectal cancer Magnetic resonance imaging

The value of toxicological analysis in acute poisoning patients with uncertain exposure histories:a retrospective and descriptive study from an institute of poisoning

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World Journal of Emergency Medicine 2024年第2期15卷 98-104页

作者： Qifang Shi Gen Ba Zhenyu Xia Zhengsheng Mao Hao Sun Jinsong Zhang institute of Poisoning Nanjing Medical UniversityNanjing 211100China Department of Emergency Medicine the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Forensic Medicine Nanjing Medical UniversityNanjing 211166China The Key Laboratory of Modern Toxicology of Ministry of Education Nanjing Medical UniversityNanjing 211166China

BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison *** aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis ***:This was a retrospective and descriptive study from an institute of *** registration information and test reports spanning the period from April 1,2020 to March 31,2022,were *** with uncertain exposure histories and who underwent toxicological analysis were *** manifestations and categories of toxics were ***:Among the 195 patients with positive toxicological analysis results,the main causes of uncertain exposure history was disturbance of consciousness(62.6%),unawareness(23.6%)and unwillingness or lack of cooperation(13.8%).The predominant clinical manifestations were disturbed consciousness(62.6%),followed by vomiting and nausea(14.4%)and liver function abnormalities(8.7%).A comparison of clinical manifestations between patients with positive and negative(n=99)toxicological analyses results revealed significantly different proportions of disturbances in consciousness(63%vs.21%),dizziness(1.5%vs.5.1%),multi-organ failure(1.5%vs.7.1%),and local pain(0 vs 4%).The main categories of substances involved were psychiatric medications(23.1%),sedatives(20.5%),insecticides(13.8%),and herbicides(12.8%).CONCLUSION:The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific,and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.

关键词： Acute poisoning Toxic exposure Toxicological analysis Clinical manifestation

Knockdown of neuronal DAF-15/Raptor promotes healthy aging in ***

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Journal of Genetics and Genomics 2024年第5期51卷 507-516页

作者： Xiao Zang Qi Wang Hanxin Zhang Yiyan Zhang Zi Wang Zixing Wu Di Chen Model Animal Research Center of medical School Nanjing UniversityNanjingJiangsu 210061China Zhejiang university-university of Edinburgh institute School of MedicineZhejiang UniversityHainingZhejiang 314400China Department of colorectal Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China

The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across *** studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis ***,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal ***,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the *** ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in *** or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and *** neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic *** profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in *** findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.

关键词： Aging targetof rapamycin DAF-15 DAF-16 C.elegans

Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 77-82页

作者： Wen-Jian Mao Jing Zhou Guo-Fu Zhang Fa-Xi Chen Jing-Zhu Zhang Bai-Qiang Li Lu Ke Wei-Qin Li Department of Critical Care Medicine Jinling HospitalNanjing Medical UniversityNanjing 210002China Department of Critical Care Medicine Jinling HospitalMedical School of Nanjing UniversityNanjing 210002China National institute of Healthcare Data Science Nanjing UniversityNanjing 210010China

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been ***,whether it affects long-term outcomes is *** study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP ***:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were *** primary outcome was 90-day readmission after *** proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day ***:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did *** who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did *** the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two *** Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission ***:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.

关键词： Anticoagulation Splanchnic venous thrombosis Acute necrotizing pancreatitis Readmission Long-term outcomes

Phosphatidic acid-enabled MKL1 contributes to liver regeneration:Translational implication in liver failure

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Acta Pharmaceutica Sinica B 2024年第1期14卷 256-272页

作者： Jiawen Zhou Xinyue Sun Xuelian Chen Huimin Liu Xiulian Miao Yan Guo Zhiwen Fan Jie Li Yong Xu Zilong Li State Key Laboratory of Natural Medicines Department of PharmacologyChina Pharmaceutical UniversityNanjing 211198China institute of Biomedical Research Liaocheng UniversityLiaocheng 252200China Department of Pathology Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Infectious Diseases Nanjing Drum Tower Hospital Affiliated with Nanjing University Medical SchoolNanjing 210008China institute of Viruses and Infectious Diseases Nanjing UniversityNanjing 210008China

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver *** the present study we investigated the contribution of megakaryocytic leukemia 1(MKL1),a transcriptional modulator,to liver *** report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure *** with MKL1 deletion exhibited defective regenerative response in the *** analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative ***2 mediated phosphorylation primed MKL1 for its interaction with *** interest,phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid(PA).PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver ***,PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure *** conclusion,our data reveal a novel mechanism whereby MKL1 contributes to liver *** for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

关键词： Liver failure Liver regeneration Transcription regulation Transcription factor Hepatocytes Phosphatidic acid Phospholipase d2 Translational medicine

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

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Neuroscience Bulletin 2024年第5期40卷 621-634页

作者： Xiuxiu Liu Ying Zhang Yanming Zhao Qian Zhang Feng Han medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases Ministry of EducationNanjing211166China International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical UniversityNanjing211166China institute of Brain Science The Affiliated Brain Hospital of Nanjing Medical UniversityNanjing211166China Gusu School Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou210019China

Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous *** pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous *** current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting *** this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic *** early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic *** this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.

关键词： Epileptogenesis Neurovascular unit Molecular mechanisms Drug targets

MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder

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General Psychiatry 2024年第1期37卷 151-162页

作者： Panpan Hu Qiuchen Cao Hu Feng Yun Liu Yan Chen Jingfan Xu Weixi Feng Huaiqing Sun Huachen Ding Chun Wang Junying Gao Ming Xiao Jiangsu Key Laboratory of Neurodegeneration Nanjing Medical UniversityNanjingJiangsuChina Department of Neurology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChina nanjing Brain Hospital Affliated to nanjing medical university NanjingJiangsuChina Functional Brain Imaging institute of nanjing medical university NanjingJiangsuChina

Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains *** To explore the mechanism of microRNA-451a(miR-451a)in the pathology and behaviours of *** Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress(CRS).Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex(mPFC)via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological ***,molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against *** The serum levels of miRNA-451awere significantly lower in patients with MDD,with a negative correlation with the Hamilton Depression Scale ***,a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS ***,miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible *** miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS ***,miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2,subsequently protecting dendritic spine *** Together,these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.

关键词： therapeutic medial behaviour

Garg incontinence scores: New scoring system on the horizon to evaluate fecal incontinence. Will it make a difference?

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World Journal of Gastroenterology 2024年第3期30卷 204-210页

作者： Petr Tsarkov Inna Tulina Parvez Sheikh Darya D Shlyk Pankaj Garg Department of colorectal Surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia Department of Oncologic colorectal Surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia Department of colorectal Surgery Saifee HospitalMumbai 400004MaharashtraIndia Department of colorectal Surgery Garg Fistula Research InstitutePanchkula 134113HaryanaIndia

The main aim of this opinion review is to comment on the recent article published by Garg et al in the World Journal of Gastroenterology 2023;29:4593–*** authors in the published article developed a new scoring system,Garg incon-tinence scores(GIS),for fecal incontinence(FI).FI is a chronic debilitating disease that has a severe negative impact on the quality of life of the *** IV criteria define FI as multiple episodes of solid or liquid stool passed into the clothes at least twice a *** associated social stigmatization often leads to significant under-reporting of the condition,which further impairs *** important point is that the complexity and vagueness of the disease make it difficult for the patients to properly define and report the magnitude of the problem to their *** to this,the management becomes even more *** issue is resolved up to a considerable extent by a scoring *** were several scoring systems in use for the last three *** prominent of them were the Cleveland Clinic scoring system or the Wexner scoring system,*** Hospital or Vaizey’s scores,and the FI severity ***,there were several shortcomings in these scoring *** the opinion review,we tried to analyze the strength of GIS and compare it to the existing scoring *** main pitfalls in the existing scoring systems were that most of them gave equal weightage to different types of FI(solid,liquid,flatus,etc.),were not comprehensive,and took only the surgeon’s perception of FI into *** GIS,almost all shortcomings of previous scoring systems had been addressed:different weights were assigned to different types of FI by a robust statistical methodology;the scoring system was made comprehensive by including all types of FI that were previously omitted(urge,stress and mucus FI)and gave priority to patients’rather than the physicians’perceptions while developing the scoring *** to this,GIS in

关键词： Fecal incontinence Scoring system Urge Stress Flatus

Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

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Science China(Life Sciences) 2024年第1期67卷 113-121页

作者： Hui Zhu Taishun Li Peizhen Xu Lijun Ding Xianghong Zhu Bin Wang Xiaoqiu Tang Juan Li Pengfeng Zhu Huiyan Wang Chenyan Dai Haixiang Sun Jianwu Dai Yali Hu Department of Obstetrics and Gynecology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Biostatistics Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Gynecology Changzhou Maternal and Child Health Care HospitalChangzhou Medical CenterNanjing Medical UniversityChangzhou 213004China Clinical Center for Stem Cell Research Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Hematology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100190China

Intrauterine adhesion is a major cause of female reproductive *** we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so *** verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical *** 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January *** per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control *** ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)*** group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic *** incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were *** conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and

关键词： intrauterine adhesion Asherman’s syndrome uterine infertility autologous bone marrow stem cells transplantation endometrial regeneration ongoing pregnancy rate