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Recent advances in cancer-associated fibroblast:Biomarkers,signaling pathways,and therapeutic opportunities

Chinese Medical Journal 2024年第6期137卷 638-650页

作者： Donger Zhou Lei Zheng Department of Hepatobiliary-Pancreatic surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Sidney Kimmel Comprehensive Cancer Center The Skip Viragh Pancreatic Cancer Center for Clinical Research and Careand The Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins University School of MedicineBaltimoreMD 21287USA

Anti-cancer therapies usually focus on tumor cells,but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression,which may be the prognostic factors and potential therapeutic targets.Cancer-associated fibroblasts(CAFs)are the essential component in the tumor environment,exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis,immune systems,and metabolism.Single-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity,and many subtypes have been defined.However,the precise functions of these subtypes need to be studied and validated.Studies of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic targets.Some clinical trials,including phase III trials targeting CAFs,have been performed recently.However,few of these trials have generated promising results,which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown,and in-depth investigations of CAFs should be performed.This review summarizes the research on CAFs,focusing on the heterogeneity of their phenotypes and functions,specific signaling pathways,and the therapeutic strategies involving CAFs.Additionally,we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

关键词： Cancer-associated fibroblasts Tumor microenvironment Anti-cancer therapy Targeted therapy

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Predicting short-term major postoperative complications in intestinal resection for Crohn’s disease:A machine learning-based study

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World Journal of Gastrointestinal surgery 2024年第3期16卷 717-730页

作者： Fang-Tao Wang Yin Lin Xiao-Qi Yuan Ren-Yuan Gao Xiao-Cai Wu Wei-Wei Xu Tian-Qi Wu Kai Xia Yi-Ran Jiao Lu Yin Chun-Qiu Chen Diagnostic and Treatment Center for Refractory Diseases of Abdomen surgery Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China

BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease(CD),the incidence of postoperative complications is high,significantly impacting the recovery and prognosis of patients.Consequently,additional stu-dies are required to precisely predict short-term major complications following intestinal resection(IR),aiding surgical decision-making and optimizing patient care.AIM To construct novel models based on machine learning(ML)to predict short-term major postoperative complications in patients with CD following IR.METHODS A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022.The study participants were randomly allocated to either a training cohort or a validation cohort.The logistic regression and random forest(RF)were applied to construct models in the training cohort,with model discrimination evaluated using the area under the curves(AUC).The validation cohort assessed the performance of the constructed models.RESULTS Out of the 259 patients encompassed in the study,5.0%encountered major postoperative complications(Clavien-Dindo≥III)within 30 d following IR for CD.The AUC for the logistic model was 0.916,significantly lower than the AUC of 0.965 for the RF model.The logistic model incorporated a preoperative CD activity index(CDAI)of≥220,a diminished preoperative serum albumin level,conversion to laparotomy surgery,and an extended operation time.A nomogram for the logistic model was plotted.Except for the surgical approach,the other three variables ranked among the top four important variables in the novel ML model.CONCLUSION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complic-ations in patients with CD,with the RF model showing more superiority.A preoperative CDAI of≥220,a di-minished preoperative serum albumin level,and an extended operation time might be the most crucial variables.The findings of this study can assist clinicians in

关键词： Crohn’s disease Postoperative complications Nomogram Random forest Intestinal resection

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Effect of drug therapies on self-reported chemosensory outcomes after COVID-19

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World Journal of Otorhinolaryngology-Head and Neck surgery 2024年第2期10卷 88-96页

作者： Marco A.Fornazieri Bruno M.Cunha Samuel P.Nicácio Lucas K.Anzolin JoséL.B.da Silva Aristides Fernandes Neto Deusdedit Brandão Neto Richard L.Voegels Fábio D.R.Pinna Department of surgery Londrina State UniversityLondrinaBrazil Department of medicine Pontifical Catholic University of ParanáLondrinaBrazil Department of Otorhinolaryngology University of São PauloSao PauloBrazil Department of Otorhinolaryngology:Head and Neck surgery Perelman School of MedicineSmell and Taste CenterUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA

Objective:The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection on self-reported alterations in taste and/or smell function.Methods:Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019(post-COVID-19)chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the disease.The dependent measure—self-reported total recovery of chemosensory symptoms—was subjected to stepwise logistic regression.Independent predictors included demographic and clinical variables,in addition to specific medications used to mitigate disease symptoms(i.e.,systemic corticosteroids,oseltamivir,vitamin C,ibuprofen,hydroxychloroquine,azithromycin,ivermectin,nitazoxanide,anticoagulants,and zinc).Results:The median time between COVID-19 symptom onset and the interviews was 81 days(interquartile range:60-104).Of the 714 subjects,249(34.9%)reported total recovery of their chemosensory function;437(61.2%)had at least one treatment since the beginning of the disease.Women and those with more comorbidities had undergone more treatments.The recovery rates of the treated and nontreated groups did not differ significantly.Nonetheless,respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell recovery.Those who took oral zinc were less likely to improve.Conclusions:No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal,although nitrazoxide trended in a positive direction.Oral zinc had a negative effect on the reported recovery of these senses.

关键词： chemosensory disorder coronavirus infections COVID-19 drug therapy SARS-CoV-2 smell loss taste loss

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Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng State Key Laboratory of Southwestern Chinese medicine Resources Chengdu University of Traditional Chinese Medicine school of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina school Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the patient.However,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this disease.Such a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous system.Further,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention strategies.As treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention strategy.As the most vital component of the limbs,skeletal muscles have become potential points of concern.Despite this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal muscle.The current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke survivors.In addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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Anti-N-methyl-D-aspartate receptor type autoimmune encephalitis with severe pneumonia:a case report

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World Journal of Emergency medicine 2024年第2期15卷 142-146页

作者： Yi Gu Xiandong Liu Tiancao Dong Qian Yang Xiaowei Bao Dongyang Zhao Lunxian Tang Department of Internal Emergency medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China school of medicine Tongji UniversityShanghai 200120China

Autoimmune encephalitis(AE)is a type of encephalitis caused by autoimmune disease.AE was included on a list of the first batch of 121 rare diseases published by the Chinese National Health Commission on 11^(th)May 2018.Currently,patients with AE account for 10%-20% of encephalitis cases,with 54%-80% of those cases classified as the anti-N-methyl-D-aspartate receptor(NMDAR)type,which is the most common type.[1]In 2010,China reported the first case of a patient withanti-NMDARtype AE.

关键词： encephalitis autoimmune aspartate

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Spilled gallstone mimicking intra-abdominal seeding of gallbladder adenocarcinoma: A case report

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World Journal of Gastrointestinal surgery 2024年第2期16卷 622-627页

作者： Cheng-Ken Huang Ruey-Hwa Lu Chien-Cheng Chen Po-Chun Chen Wen-Chang Hsu Meng-Jui Tsai Chin-Tsung Ting Division of Gastrointestinal surgery Department of SurgeryRen-Ai BranchTaipei City HospitalTaipei 106TaiwanChina Division of General surgery Department of SurgeryZhongxing BranchTaipei City HospitalTaipei 103TaiwanChina school of medicine Institute of Traditional MedicineNational Yang-Ming UniversityTaipei 112TaiwanChina Department of Health and Welfare University of TaipeTaipe 104TaiwanChina

BACKGROUND Gallbladder rupture is common in laparoscopic cholecystectomy because the gallbladder is usually in acute or chronic inflammation status.The gallstones may sometime be spilled into the peritoneal cavity,resulting in intra-abdominal ab-scess if the gallstones were not retrieved.The diagnosis of intra-abdominal ab-scess caused by unretrieved gallstone can usually be correctly identified in the routine imaging studies,such as abdominal ultrasonography or computed tomo-graphy(CT).Here we present a case of abscess formation from unretrieved gall-stone following laparoscopic cholecystectomy,which mimics the imaging findings of metastatic gallbladder ade-nocarcinoma.CASE SUMMARY This case described a 78-year-old man who received laparoscopic cholecystectomy and gallbladder adenocarcinoma was diagnosed after surgery.After adjuvant chemotherapy,the following up abdominal CT showed several small nodules at right upper abdomen and peritoneal carcinomatosis is considered.Repeated laparoscopic surgery for the excision of seeding tumor was conducted and the pathological diagnosis of the nodules and mass was inflammatory tissues and gallbladder stone.CONCLUSION Spilled gallstones are a common complication during laparoscopic cholecystectomy and some gallstones fail to be retrieved due to the size or the restricted view of laparoscopic surgery.For spilled gall bladder stones,surgeons may consider regular computerized tomography follow-up,and if necessary,laparoscopic examination can be used as a means of confirming the diagnostic and treatment.

关键词： Laparoscopic cholecystectomy Gallstone spillage Gallbladder cancer Mimicked cancerous Case report

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Genetic landscape and clinical significance of cuproptosis-related genes in liver hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 516-519页

作者： Dingtao Hu Yichuan Wang Xu Shen Tiantian Mao Xijun Liang Tengjiao Wang Weifeng Shen Yugang Zhuang Jin Ding Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghai 200433China Department of Emergency Shanghai Tenth People's HospitalTongji UniversitySchool of MedicineShanghai 200072China Bioinformatics Analysis Laboratory Center for Translational MedicineNaval Medical UniversityShanghai 200433China The Department of Hepatic surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China

Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in LIHC.We then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical cohorts.The detailed methods were described in the supplementary material.

关键词： clinical metabolism hepatocellular

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Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1

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Chinese Journal of Integrative medicine 2024年第6期30卷 534-542页

作者： LI Jie CHEN Ya-feng GAO Lei LI Yi-jie FENG Dian-xu Department of General surgery Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai200062China

Objective To investigate the effect of honokiol(HON)and the role of high-mobility group protein B1(HMGB1)on the pathogenesis of severe acute pancreatitis(SAP).Methods Thirty mice were numbered according to weight,and randomly divided into 5 groups using a random number table,including control,SAP,SAP and normal saline(SAP+NS),SAP and ethyl pyruvate(SAP+EP),or SAP+HON groups,6 mice in each group.Samples of pancreas,intestine,and blood were collected 12 h after SAP model induction for examination of pathologic changes,immune function alterations by enzyme linked immunosorbent assay(ELISA),and Western blot.In vitro experiments,macrophages were divided into 5 groups,the control,lipopolysaccharide(LPS),LPS+DMSO(DMSO),LPS+anti-HMGB1 monoclonal antibody(mAb),and LPS+HON groups.The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled.The location and acetylation of HMGB1 were measured by Western blot.Finally,pyridone 6 and silencing signal transducer and activator of the transcription 1(siSTAT1)combined with honokiol were added to determine whether the Janus kinase(JAK)/STAT1 participated in the regulation of honokiol on HMGB1.The protein expression levels of HMGB1,JAK,and STAT1 were detected using Western blot.Results Mice with SAP had inflammatory injury in the pancreas,bleeding of intestinal tissues,and cells with disrupted histology.Mice in the SAP+HON group had significantly fewer pathological changes.Mice with SAP also had significant increases in the serum levels of amylase,lipase,HMGB1,tumor necrosis factor-α,interleukin-6,diamine oxidase,endotoxin-1,and procalcitonin.Mice in the SAP+HON group did not show these abnormalities(P<0.01).Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability,decreased the levels of junctional adhesion molecule C,and elevated intercellular permeability(P<0.01).HON treatment blocked these effects.Studies of macrophages indicated that LPS led to low nucle

关键词： severe acute pancreatitis intestinal barrier dysfunction honokiol high-mobility group protein B1 Januskinase signal transducerand activatorof transcription1

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Intranasal administration of stem cell-derived exosomes for central nervous system diseases

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Neural Regeneration Research 2024年第6期19卷 1249-1255页

作者： Shuho Gotoh Masahito Kawabori Miki Fujimura Department of Neurosurgery Hokkaido University Graduate School of Medicine

Exosomes, lipid bilayer-enclosed small cellular vesicles, are actively secreted by various cells and play crucial roles in intercellular communication. These nanosized vesicles transport internalized proteins, mRNA, miRNA, and other bioactive molecules. Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders. These exosomes exhibit multifaceted properties including antiapoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Furthermore, exosomes offer several advantages over stem cell therapy, such as high preservation capacity, low immunogenicity, the ability to traverse the blood-brain barrier, and the potential for drug encapsulation. Consequently, researchers have turned their attention to exosomes as a novel therapeutic avenue. Nonetheless, akin to the limitations of stem cell treatment, the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application. To overcome this hurdle, intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system. By exploiting the olfactory and trigeminal nerve axons, this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier. Notably, exosomes, owing to their small size, can readily access the nerve pathways using this method. As a result, intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments. In this comprehensive review, we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases. Furthermore, we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

关键词： central nervous system disease exosome extracellular vesicle intranasal administration stem cell

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Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2024年第13期30卷 1899-1910页

作者： Ante Tonkic Marko Kumric Ivna Akrapovic Olic Doris Rusic Piero Marin Zivkovic Daniela Supe Domic Zeljko Sundov Ivan Males Josko Bozic Biology of Neoplasms University of Split School of MedicineSplit 21000Croatia Department of Pathophysiology University of Split School of MedicineSplit 21000Croatia Department of Gastroenterology University Hospital of SplitSplit 21000Croatia Department of Pharmacy University of Split School of MedicineSplit 21000Croatia Department of Medical Laboratory Diagnostics University Hospital of SplitSplit 21000Croatia Department of Health Studies University of SplitSplit 21000Croatia Department of Internal medicine University of Split School of MedicineSplit 21000Croatia Department of surgery University Hospital of SplitSplit 21000Croatia

BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many others.AIM To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases.An additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with IBD.METHODS This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched controls.All patients underwent an extensive workup,including colonoscopy with subsequent histopathological analysis.Disease activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring systems.GDF-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence immunoassay.RESULTS In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was established.Specifically,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to IBD patients with normal hemoglobin levels,GDF-15

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Growth-differentiation factor-15 Anemia Extraintestinal manifestations

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