The 8th National Gastric Cancer Academic Conference, organized by Gastric Cancer Association of Chinese Anti- cancer Association and co-hosted by Beijing Cancer Hospital, Chinese Journal of Cancer Research （CJCR）, T...The 8th National Gastric Cancer Academic Conference, organized by Gastric Cancer Association of Chinese Anti- cancer Association and co-hosted by Beijing Cancer Hospital, Chinese Journal of Cancer Research （CJCR）, Translational Gastrointestinal Cancer （TGC）, Chinese Journal of Gastrointestinal Surgery, and Chinese Journal of Practical Surgery, was held at Beijing International Convention Center from June 15 to 16, 2013. Prof. Dr. Jiafu Ji, MD, FACS, the president of Gastric Cancer Committee, Chinese Anti-Cancer Association （CACA） and Editor-in-Chief of TGC, was the chairman of the conference （Figure 1）. Prof. Dr. Yan Sun, MD, academician of Chinese Academy of Engineering （CAE）, was the honorary chairman of the展开更多
Congestive heart failure(CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell ba...Congestive heart failure(CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.展开更多
Introduction Gastric cancer is a heterogeneous disease with large variations across geographical regions （1）. Although the global incidence of gastric cancer is declining, it remains highly prevalent in Asia as comp...Introduction Gastric cancer is a heterogeneous disease with large variations across geographical regions （1）. Although the global incidence of gastric cancer is declining, it remains highly prevalent in Asia as compared to the West （2,3）. China is one of the countries with the highest incidence of gastric cancer, and accounts for over 40% of all new gastric cancer cases in the world （4,5）. Gastric cancer is the third leading cause of cancer mortality in China （6,7）. The 7th National Gastric Cancer Academic Conference （NGCAC） was held in Beijing from June 22 to June 24 with approximately 1,200 attendees, which was organized by Gastric Cancer Committee, Chinese Anti-Cancer Association （CACA） （Figure I）. The theme of this conference was specification, integration, and transformation. Dr. Jiafu Ji, MD, FACS, the chairman of the conference, the president of Gastric Cancer Committee, CACA, pointed out that the conference was aimed at standardizing the diagnosis and treatment of gastric cancer, integrating the information platform, and transferring current research achievements （Figure 1）. It has been about thirteen years since last National gastric cancer academic conference, which was held in Nanjing in 1999. In this conference, nine pioneer experts （Drs Yan-Zhen Lin, Ji-Fu Wang, Guang-Wei Xu, Jun-Qing Chen, Wen-Fan Zhang, Yin-Chang Zhang, Mao-Lin Jin, Xiang-Fu Zhang, and Xi-Shan Hao） were awarded Lifetime Achievement Award by Gastric Cancer Committee, CACA. There were ten sessions and more than two hundred papers or abstracts submitted, the proceeding was published in Translational Gastrointestinal Cancer Vol 1, supplement 1, June 2 012.展开更多
Colorectal cancer(CRC)is one of the most popular malignancies globally,with 930000 deaths in 2020.The evaluation of CRC-related pathogenesis and the discovery of po-tential therapeutic targets will be meaningful and h...Colorectal cancer(CRC)is one of the most popular malignancies globally,with 930000 deaths in 2020.The evaluation of CRC-related pathogenesis and the discovery of po-tential therapeutic targets will be meaningful and helpful for improving CRC treat-ment.With huge efforts made in past decades,the systematic treatment regimens have been applied to improve the prognosis of CRC patients.However,the sensitivity of CRC to chemotherapy and targeted therapy is different from person to person,which is an important cause of treatment failure.The emergence of patient-derived xenograft(PDX)models shows great potential to alleviate the straits.PDX models possess similar genetic and pathological characteristics as the features of primary tu-mors.Moreover,PDX has the ability to mimic the tumor microenvironment of the original tumor.Thus,the PDX model is an important tool to screen precise drugs for individualized treatment,seek predictive biomarkers for prognosis supervision,and evaluate the unknown mechanism in basic research.This paper reviews the recent advances in constructed methods and applications of the CRC PDX model,aiming to provide new knowledge for CRC basic research and therapeutics.展开更多
Both large-scale prospective randomized controlled trials(RCTs)and smaller investigator-initiated trials are essential for evaluating the efficacy and safety of medical interventions.Robust protocols and statistical d...Both large-scale prospective randomized controlled trials(RCTs)and smaller investigator-initiated trials are essential for evaluating the efficacy and safety of medical interventions.Robust protocols and statistical designs ensure the reliability of trial outcomes and improve the credibility of research findings.By reviewing the statistical approaches used in the TORCHLIGHT,NCC2167,and NeoTENNIS trials,this article illustrates the principles underlying large-sample confirmatory RCTs,small-sample exploratory adaptive designs,and single-arm two-stage designs.This discussion is aimed at helping researchers apply these design methods more effectively,to increase the likelihood of success in clinical studies.展开更多
1.Introduction Injury prevention is an essential element of science and medicine in sports,and it garners attention from stakeholders focused on minimizing athletes’injury risk.Catchy titles including“injury risk”o...1.Introduction Injury prevention is an essential element of science and medicine in sports,and it garners attention from stakeholders focused on minimizing athletes’injury risk.Catchy titles including“injury risk”or“injury prevention”are likely to grab the readers’attention.Meanwhile,studies on injury prevention might assess the impact of interventions on mitigating injury risk factors(e.g.,strength,range of motion(ROM))but fail to report injury data(e.g.,incidence).1,2 Likewise,observational studies may include“injury risk”in their titles,but fail to provide injury data.3 Without injury data.展开更多
There are several kinds of epigenetic networks in the human body including the cell differentiation epigenetic network(DiEN) and the host adaptation epigenetic network(AdEN).DiEN networks are static and cell/tissue-sp...There are several kinds of epigenetic networks in the human body including the cell differentiation epigenetic network(DiEN) and the host adaptation epigenetic network(AdEN).DiEN networks are static and cell/tissue-specific.AdEN networks are variable and dependent upon environmental factors.DiEN and AdEN alterations can respectively serve as biomarkers for different kinds of diseases.Cancer is a consequence of accumulated pathophysiological adaptations of tissue stem cells to exposure of environmental carcinogens.Cancer cells are de-differentiated cells that obtain the capacity of unrestricted proliferation,local invasion,and distant migration/metastasis.Both DiEN and AdEN changes can be observed in cancer tissues.Alterations of DNA methylation are the most stable epigenetic modifications and can be sensitively detected in a small cell population.These advantages make DNA methylation the optimal biomarkers for detection of initiated cells in precancerous lesions and metastasis stem cells in cancer tissues.It has been proven that p16 methylation can be used as a diagnostic biomarker to determine malignant potential of epithelium dysplasia in many organs including the stomach.In a large-scale validation study on the DNA methylome of gastric carcinomas(GC),the methylation status of more than 90 CpG islands has been analyzed by DHPLC.Furthermore,GFRA1 demethylation and methylation of SRF and ZNF382 are frequent events during gastric carcinogenesis and consistently correlate to GC metastasis and overall survival of GC patients from China,Japan,and Korea,respectively.In a population study,it has been demonstrated that gradual increasing of plasma miR-211 and other miRNA levels may be an early risk predictor for GC development.展开更多
Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are i...Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are ideal cellular targets to be acquired in multiple mutations transforming SSCs to cancer stem cells （CSCs） which cause malignancies and even recurrence after cancer treatment if CSCs fail to be eradicated （1）.展开更多
Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease(PD)has failed several times in the past.Nevertheless,in this pilot study,a translational approach was conducted,...Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease(PD)has failed several times in the past.Nevertheless,in this pilot study,a translational approach was conducted,allowing the evaluation of the plasma levels of two mitochondrial-related proteins,whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls.Methods The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions,followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states.This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients.Results From the secretome analysis,several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes.Similarly,two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls.Moreover,a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins.Both proteins are associated with apoptotic mitochondrial changes,which may correspond to potential indicators of cell death.Moreover,one of these proteins,the VPS35 protein,was reported in plasma for the first time,and its quantification was only possible due to its previous identification in the secretome analysis.Conclusions In this work,an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases,in the present case Parkinson’s Disease.The novelty and success of this pilot study may arise from the combination of:i)a translational research pipeline,where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’secretome under oxidative stress;ii)the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms,and iii)the use of SWATH-MS,an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified.展开更多
The rapidly growing field of functional,molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a"digital biopsy"for i...The rapidly growing field of functional,molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a"digital biopsy"for in vivo study of liver pathophysiology.To foster the application of bio-imaging in clinical and translational research,there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver.It can be hoped that the combination of digital,liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies,diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer.A group of experts of different disciplines(Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver,Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure)discussed criteria,methods and guidelines for facilitating the requisite application of data collection.This manuscript provides a multi-Author review of the issue with special focus on fatty liver.展开更多
Recent years have witnessed significant advances in the development of novel techniques and methodologies for identifying active ingredients in traditional Chinese medicine(TCM),substantially advancing research and de...Recent years have witnessed significant advances in the development of novel techniques and methodologies for identifying active ingredients in traditional Chinese medicine(TCM),substantially advancing research and development efforts.Spectrum-effect correlation analysis,affinity ultrafiltration,high-content screening(HCS)imaging,and cell membrane chromatography(CMC)have emerged as essential tools,effectively linking TCM chemical constituents to their biological effects,thereby enabling efficient active ingredient screening.Additionally,molecular interaction analysis provides deeper insights into TCM-biomolecule interaction mechanisms,enhancing understanding of its therapeutic potential.Computer-aided techniques facilitate TCM active ingredient identification,optimizing the screening process for efficiency and cost-effectiveness.Molecular probe technology,as an emerging methodology,enables precise and rapid screening for novel therapeutic drug discovery.Ongoing technological advancement in this field indicates promising future developments,potentially leading to more effective and targeted TCM-based therapies.展开更多
Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen...Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone...Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.展开更多
The ability to noninvasively manipulate and isolate specific cell populations in vivo is critical for advancing real-time diagnostics,precision medicine,and immunological research.Here,we present a novel and broadly a...The ability to noninvasively manipulate and isolate specific cell populations in vivo is critical for advancing real-time diagnostics,precision medicine,and immunological research.Here,we present a novel and broadly applicable optical trapping system based on a custom-designed 2×3 optical tweezer array,which enables the real-time interception and manipulation of circulating leukocytes in live animals.By utilizing intrinsic velocity differences between leukocytes and red blood cells,the system achieves stable trapping of individual leukocytes in vessels 15-20μm in diameter and decelerates multiple cells in vessels greater than 20μm.Notably,it also enables the optical blockage of lymphatic vessels exceeding 50μm,a previously unreported capability.This label-free,noninvasive approach operates without repeated blood draws and is compatible with diverse vessel geometries and flow dynamics.The system offers a generalizable solution for in vivo cell extraction and analysis,paving the way for high-precision single-cell technologies in biomedical research and clinical translation.展开更多
GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,i...GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).展开更多
Advanced oxidation processes(AOPs)that utilize the highly potent hydroxyl radical(·OH)are a cornerstone of modern environmental remediation.Among these,the Fenton reaction is renowned for its effectiveness[1].How...Advanced oxidation processes(AOPs)that utilize the highly potent hydroxyl radical(·OH)are a cornerstone of modern environmental remediation.Among these,the Fenton reaction is renowned for its effectiveness[1].However,its practical application has been persistently hampered by two fundamental constraints:a strict reliance on acidic conditions(typically pH 2-4)and the need to be continuously supplied,costly externally generated hydrogen peroxide(H_(2)O_(2))[2-4].展开更多
Myelination in the central nervous system(CNS)is a highly intricate process,exclusive to vertebrates,that relies on the coordinated interaction between oligodendrocytes(OLs)and neurons.In addition to their role in for...Myelination in the central nervous system(CNS)is a highly intricate process,exclusive to vertebrates,that relies on the coordinated interaction between oligodendrocytes(OLs)and neurons.In addition to their role in forming myelin,accumulating evidence indicates that OLs provide crucial trophic support to axons,contributing to normal CNS function.Notably,OL injury and loss are observed in a variety of human conditions,including stroke,traumatic injuries of the brain and spinal cord,as well as neurodegenerative disorders such as multiple sclerosis(MS).展开更多
Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons.Early-stage axonal dysfunction,rather than central nervous system injury,plays a key role in the disease process.However,the mole...Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons.Early-stage axonal dysfunction,rather than central nervous system injury,plays a key role in the disease process.However,the molecular mechanisms underlying this dysfunction remain unclear.To investigate the relationship between peripheral immune dysregulation and axonal dysfunction in amyotrophic lateral sclerosis,we recruited 372 patients within the first 12 months of sporadic amyotrophic lateral sclerosis onset between January 2018 and May 2024.We collected peripheral immune markers at baseline,including total leukocytes,lymphocytes,monocytes,neutrophils,basophils,eosinophils,and platelets.We also calculated four derived ratios:neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,lymphocyte-to-monocyte ratio,and systemic immune inflammation index.Multivariate analysis,adjusted for confounding factors,revealed that higher counts of total leukocytes and neutrophils,as well as higher neutrophil-related ratios,including the neutrophil to lymphocyte ratio and the systemic immune inflammation index,were significantly correlated with higher compound muscle action potential scores.Stratified analyses revealed that these associations varied by age and sex.Furthermore,mediation analysis demonstrated that axonal dysfunction plays a significant role in the relationship between immune markers and disease progression.These findings emphasize the critical role that peripheral immune dysregulation plays in amyotrophic lateral sclerosis progression by mediating peripheral nerve injury,particularly in the early stages of the disease.This study highlights the importance of the peripheral nervous system in the early stages of amyotrophic lateral sclerosis and provides new insights into disease mechanisms and potential therapeutic targets.展开更多
Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis ...Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis and development of HCs is crucial.Our current study highlights rhpn2,a member of rho-binding proteins,as essential for vestibular HC development.The rhpn2 gene is highly expressed in the crista and macula HCs.Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number,accompanied by vestibular dysfunction.Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants.Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab.Furthermore,co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA,validating the interaction of the two proteins.rhpn2 knockout leads to a decreased expression of rock2b,a canonical RhoA signaling pathway gene.Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants.This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway,providing a target for the treatment of balance disorders.展开更多
文摘The 8th National Gastric Cancer Academic Conference, organized by Gastric Cancer Association of Chinese Anti- cancer Association and co-hosted by Beijing Cancer Hospital, Chinese Journal of Cancer Research （CJCR）, Translational Gastrointestinal Cancer （TGC）, Chinese Journal of Gastrointestinal Surgery, and Chinese Journal of Practical Surgery, was held at Beijing International Convention Center from June 15 to 16, 2013. Prof. Dr. Jiafu Ji, MD, FACS, the president of Gastric Cancer Committee, Chinese Anti-Cancer Association （CACA） and Editor-in-Chief of TGC, was the chairman of the conference （Figure 1）. Prof. Dr. Yan Sun, MD, academician of Chinese Academy of Engineering （CAE）, was the honorary chairman of the
基金Supported by New York State NYSTEM foundation,No.N08G-433
文摘Congestive heart failure(CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.
文摘Introduction Gastric cancer is a heterogeneous disease with large variations across geographical regions （1）. Although the global incidence of gastric cancer is declining, it remains highly prevalent in Asia as compared to the West （2,3）. China is one of the countries with the highest incidence of gastric cancer, and accounts for over 40% of all new gastric cancer cases in the world （4,5）. Gastric cancer is the third leading cause of cancer mortality in China （6,7）. The 7th National Gastric Cancer Academic Conference （NGCAC） was held in Beijing from June 22 to June 24 with approximately 1,200 attendees, which was organized by Gastric Cancer Committee, Chinese Anti-Cancer Association （CACA） （Figure I）. The theme of this conference was specification, integration, and transformation. Dr. Jiafu Ji, MD, FACS, the chairman of the conference, the president of Gastric Cancer Committee, CACA, pointed out that the conference was aimed at standardizing the diagnosis and treatment of gastric cancer, integrating the information platform, and transferring current research achievements （Figure 1）. It has been about thirteen years since last National gastric cancer academic conference, which was held in Nanjing in 1999. In this conference, nine pioneer experts （Drs Yan-Zhen Lin, Ji-Fu Wang, Guang-Wei Xu, Jun-Qing Chen, Wen-Fan Zhang, Yin-Chang Zhang, Mao-Lin Jin, Xiang-Fu Zhang, and Xi-Shan Hao） were awarded Lifetime Achievement Award by Gastric Cancer Committee, CACA. There were ten sessions and more than two hundred papers or abstracts submitted, the proceeding was published in Translational Gastrointestinal Cancer Vol 1, supplement 1, June 2 012.
基金National Natural Science Foundation of China Grant(81802305 and 31971192).
文摘Colorectal cancer(CRC)is one of the most popular malignancies globally,with 930000 deaths in 2020.The evaluation of CRC-related pathogenesis and the discovery of po-tential therapeutic targets will be meaningful and helpful for improving CRC treat-ment.With huge efforts made in past decades,the systematic treatment regimens have been applied to improve the prognosis of CRC patients.However,the sensitivity of CRC to chemotherapy and targeted therapy is different from person to person,which is an important cause of treatment failure.The emergence of patient-derived xenograft(PDX)models shows great potential to alleviate the straits.PDX models possess similar genetic and pathological characteristics as the features of primary tu-mors.Moreover,PDX has the ability to mimic the tumor microenvironment of the original tumor.Thus,the PDX model is an important tool to screen precise drugs for individualized treatment,seek predictive biomarkers for prognosis supervision,and evaluate the unknown mechanism in basic research.This paper reviews the recent advances in constructed methods and applications of the CRC PDX model,aiming to provide new knowledge for CRC basic research and therapeutics.
基金supported by a grant from the National Science and Technology Major Project(Grant No.2024ZD0519800).
文摘Both large-scale prospective randomized controlled trials(RCTs)and smaller investigator-initiated trials are essential for evaluating the efficacy and safety of medical interventions.Robust protocols and statistical designs ensure the reliability of trial outcomes and improve the credibility of research findings.By reviewing the statistical approaches used in the TORCHLIGHT,NCC2167,and NeoTENNIS trials,this article illustrates the principles underlying large-sample confirmatory RCTs,small-sample exploratory adaptive designs,and single-arm two-stage designs.This discussion is aimed at helping researchers apply these design methods more effectively,to increase the likelihood of success in clinical studies.
基金Centre of Research,Education,Innovation,and Intervention in Sport(CIFI2D)is financed by the Portuguese Foundation for Science and Technology,under the DOI https://doi.org/10.54499/UIDB/05913/2020。
文摘1.Introduction Injury prevention is an essential element of science and medicine in sports,and it garners attention from stakeholders focused on minimizing athletes’injury risk.Catchy titles including“injury risk”or“injury prevention”are likely to grab the readers’attention.Meanwhile,studies on injury prevention might assess the impact of interventions on mitigating injury risk factors(e.g.,strength,range of motion(ROM))but fail to report injury data(e.g.,incidence).1,2 Likewise,observational studies may include“injury risk”in their titles,but fail to provide injury data.3 Without injury data.
基金supported by National Natural Science Foundation of China (30921140311 and 90919015)National Key Basic Research Program of China (2010CB529300 and 2011CB-504201)
文摘There are several kinds of epigenetic networks in the human body including the cell differentiation epigenetic network(DiEN) and the host adaptation epigenetic network(AdEN).DiEN networks are static and cell/tissue-specific.AdEN networks are variable and dependent upon environmental factors.DiEN and AdEN alterations can respectively serve as biomarkers for different kinds of diseases.Cancer is a consequence of accumulated pathophysiological adaptations of tissue stem cells to exposure of environmental carcinogens.Cancer cells are de-differentiated cells that obtain the capacity of unrestricted proliferation,local invasion,and distant migration/metastasis.Both DiEN and AdEN changes can be observed in cancer tissues.Alterations of DNA methylation are the most stable epigenetic modifications and can be sensitively detected in a small cell population.These advantages make DNA methylation the optimal biomarkers for detection of initiated cells in precancerous lesions and metastasis stem cells in cancer tissues.It has been proven that p16 methylation can be used as a diagnostic biomarker to determine malignant potential of epithelium dysplasia in many organs including the stomach.In a large-scale validation study on the DNA methylome of gastric carcinomas(GC),the methylation status of more than 90 CpG islands has been analyzed by DHPLC.Furthermore,GFRA1 demethylation and methylation of SRF and ZNF382 are frequent events during gastric carcinogenesis and consistently correlate to GC metastasis and overall survival of GC patients from China,Japan,and Korea,respectively.In a population study,it has been demonstrated that gradual increasing of plasma miR-211 and other miRNA levels may be an early risk predictor for GC development.
文摘Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are ideal cellular targets to be acquired in multiple mutations transforming SSCs to cancer stem cells （CSCs） which cause malignancies and even recurrence after cancer treatment if CSCs fail to be eradicated （1）.
基金This work was financed by the European Regional Development Fund(ERDF)through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT–Fundação para a Ciência e a Tecnologia,I.P.,under projects:POCI-01-0145-FEDER-029311(ref.:PTDC/BTM-TEC/29311/2017),PTDC/NEU-NMC/0205/2012,UIDB/04539/2020,POCI-01-0145-FEDER-016428(ref.:SAICTPAC/0010/2015),POCI-01-0145-FEDER-016795(ref.:PTDC/NEU-SCC/7051/2014),and POCI-01-0145-FEDER-029516(PTDC/MED-NEU/29516/2017).
文摘Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease(PD)has failed several times in the past.Nevertheless,in this pilot study,a translational approach was conducted,allowing the evaluation of the plasma levels of two mitochondrial-related proteins,whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls.Methods The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions,followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states.This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients.Results From the secretome analysis,several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes.Similarly,two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls.Moreover,a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins.Both proteins are associated with apoptotic mitochondrial changes,which may correspond to potential indicators of cell death.Moreover,one of these proteins,the VPS35 protein,was reported in plasma for the first time,and its quantification was only possible due to its previous identification in the secretome analysis.Conclusions In this work,an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases,in the present case Parkinson’s Disease.The novelty and success of this pilot study may arise from the combination of:i)a translational research pipeline,where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’secretome under oxidative stress;ii)the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms,and iii)the use of SWATH-MS,an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified.
基金Supported by the Italian Ministry of Health Project,No.RF-2010-2314264
文摘The rapidly growing field of functional,molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a"digital biopsy"for in vivo study of liver pathophysiology.To foster the application of bio-imaging in clinical and translational research,there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver.It can be hoped that the combination of digital,liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies,diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer.A group of experts of different disciplines(Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver,Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure)discussed criteria,methods and guidelines for facilitating the requisite application of data collection.This manuscript provides a multi-Author review of the issue with special focus on fatty liver.
基金supported by the National Natural Science Foundation of China (Nos. 22175078, 52373287, 82404846, and 22467002)the Natural Science Foundation of Jiangsu Province of China (No. BK20241597)the Fundamental Research Funds for the Central Universities (No. 2632024TD05)
文摘Recent years have witnessed significant advances in the development of novel techniques and methodologies for identifying active ingredients in traditional Chinese medicine(TCM),substantially advancing research and development efforts.Spectrum-effect correlation analysis,affinity ultrafiltration,high-content screening(HCS)imaging,and cell membrane chromatography(CMC)have emerged as essential tools,effectively linking TCM chemical constituents to their biological effects,thereby enabling efficient active ingredient screening.Additionally,molecular interaction analysis provides deeper insights into TCM-biomolecule interaction mechanisms,enhancing understanding of its therapeutic potential.Computer-aided techniques facilitate TCM active ingredient identification,optimizing the screening process for efficiency and cost-effectiveness.Molecular probe technology,as an emerging methodology,enables precise and rapid screening for novel therapeutic drug discovery.Ongoing technological advancement in this field indicates promising future developments,potentially leading to more effective and targeted TCM-based therapies.
基金supported by the National Natural Science Foundation of China,Nos.82171387 and 31830111(both to SL).
文摘Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
基金supported by the Ministry of Health National Medical Research Council (to JL)the National University of Singapore (to JJEC)
文摘Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.
基金funding from the National Key Research and Development Program of China(2021YFF0502900)special fund for Research on the National Major Research Instruments of China(62027824)+2 种基金the National Natural Science Foundation of China(U24A20314)the Key Research and Development Program of Anhui Province in China(2022a05020028)the Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province.
文摘The ability to noninvasively manipulate and isolate specific cell populations in vivo is critical for advancing real-time diagnostics,precision medicine,and immunological research.Here,we present a novel and broadly applicable optical trapping system based on a custom-designed 2×3 optical tweezer array,which enables the real-time interception and manipulation of circulating leukocytes in live animals.By utilizing intrinsic velocity differences between leukocytes and red blood cells,the system achieves stable trapping of individual leukocytes in vessels 15-20μm in diameter and decelerates multiple cells in vessels greater than 20μm.Notably,it also enables the optical blockage of lymphatic vessels exceeding 50μm,a previously unreported capability.This label-free,noninvasive approach operates without repeated blood draws and is compatible with diverse vessel geometries and flow dynamics.The system offers a generalizable solution for in vivo cell extraction and analysis,paving the way for high-precision single-cell technologies in biomedical research and clinical translation.
文摘GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).
基金Cardiff University and the Max Planck Centre for Fundamental Heterogeneous Catalysis(FUNCAT)for financial supportthe Marie Skłodowska-Curie Actions Fellowship(101107009-AtomCat4Fuel)UKRI(EP/Y029305/1)。
文摘Advanced oxidation processes(AOPs)that utilize the highly potent hydroxyl radical(·OH)are a cornerstone of modern environmental remediation.Among these,the Fenton reaction is renowned for its effectiveness[1].However,its practical application has been persistently hampered by two fundamental constraints:a strict reliance on acidic conditions(typically pH 2-4)and the need to be continuously supplied,costly externally generated hydrogen peroxide(H_(2)O_(2))[2-4].
文摘Myelination in the central nervous system(CNS)is a highly intricate process,exclusive to vertebrates,that relies on the coordinated interaction between oligodendrocytes(OLs)and neurons.In addition to their role in forming myelin,accumulating evidence indicates that OLs provide crucial trophic support to axons,contributing to normal CNS function.Notably,OL injury and loss are observed in a variety of human conditions,including stroke,traumatic injuries of the brain and spinal cord,as well as neurodegenerative disorders such as multiple sclerosis(MS).
基金Natural Science Foundation of Beijing,No.7244428(to WZ)Peking University Medicine Sailing Program for Young Scholars’Scientific and Technological Innovation,No.BMU2023YFJHPY034(to WZ)+1 种基金the National Natural Science Foundation of China,Nos.81873784(to DF),82071426(to DF)Clinical Cohort Construction Program of Peking University Third Hospital,Nos.BYSYDL2019002(to DF)and BYSYZD2021004(to DF).
文摘Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons.Early-stage axonal dysfunction,rather than central nervous system injury,plays a key role in the disease process.However,the molecular mechanisms underlying this dysfunction remain unclear.To investigate the relationship between peripheral immune dysregulation and axonal dysfunction in amyotrophic lateral sclerosis,we recruited 372 patients within the first 12 months of sporadic amyotrophic lateral sclerosis onset between January 2018 and May 2024.We collected peripheral immune markers at baseline,including total leukocytes,lymphocytes,monocytes,neutrophils,basophils,eosinophils,and platelets.We also calculated four derived ratios:neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,lymphocyte-to-monocyte ratio,and systemic immune inflammation index.Multivariate analysis,adjusted for confounding factors,revealed that higher counts of total leukocytes and neutrophils,as well as higher neutrophil-related ratios,including the neutrophil to lymphocyte ratio and the systemic immune inflammation index,were significantly correlated with higher compound muscle action potential scores.Stratified analyses revealed that these associations varied by age and sex.Furthermore,mediation analysis demonstrated that axonal dysfunction plays a significant role in the relationship between immune markers and disease progression.These findings emphasize the critical role that peripheral immune dysregulation plays in amyotrophic lateral sclerosis progression by mediating peripheral nerve injury,particularly in the early stages of the disease.This study highlights the importance of the peripheral nervous system in the early stages of amyotrophic lateral sclerosis and provides new insights into disease mechanisms and potential therapeutic targets.
基金supported by grants from the Natural Science Foundation of Jiangsu Province(BK20221377 and BK20220607)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(22KJB180023)the National Natural Science Foundation of China Grants(32200783,32350017,and 92368104),and the Qing Lan Project of Jiangsu Province.
文摘Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis and development of HCs is crucial.Our current study highlights rhpn2,a member of rho-binding proteins,as essential for vestibular HC development.The rhpn2 gene is highly expressed in the crista and macula HCs.Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number,accompanied by vestibular dysfunction.Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants.Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab.Furthermore,co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA,validating the interaction of the two proteins.rhpn2 knockout leads to a decreased expression of rock2b,a canonical RhoA signaling pathway gene.Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants.This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway,providing a target for the treatment of balance disorders.
