In April 2017,the first edition Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines were released.These guidelines were based on medical evidence,as well as the accessibility and cost effectiveness o...In April 2017,the first edition Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines were released.These guidelines were based on medical evidence,as well as the accessibility and cost effectiveness of various anticancer drugs in China.The CSCO BC guidelines include regimens with a high level of evidence,good product accessibility and high consistent consensus among Chinese experts as level I recommendations.Regimens with a high level of evidence but poor product accessibility or expert consensus are included as level II recommendations.展开更多
The Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines have been widely implemented in China since the first release in 2017.The Guideline Working Committee has also published multiple versions in E...The Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines have been widely implemented in China since the first release in 2017.The Guideline Working Committee has also published multiple versions in English,Arabic,and other languages to facilitate communications with international experts.展开更多
This article comprehensively reviews research progress in prostate cancer radiation therapy.It provides an overview of fundamental principles,encompassing the disease’s epidemiology,pathological mechanisms,and radiat...This article comprehensively reviews research progress in prostate cancer radiation therapy.It provides an overview of fundamental principles,encompassing the disease’s epidemiology,pathological mechanisms,and radiation sensitivity,alongside technological advancements.The clinical application,technological progress,and efficacy evaluation of moderate hypofractionated radiation therapy and ultra hypofractionated radiation therapy are discussed.Diagnostic and monitoring techniques specific to radiation therapy are analyzed,alongside prevailing controversies and challenges.Finally,the review outlines future prospects,including novel radiotherapy techniques,multidisciplinary collaboration trends,and the evolving role of radiation within comprehensive treatment.The findings demonstrate continuous technological and clinical evolution in prostate cancer radiotherapy,yet emphasize the need for further exploration to optimize treatments and improve patient survival and quality of life.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
BACKGROUND Immune cells,including neutrophils,natural killer(NK)cells,T cells,NKT cells and macrophages,participate in the progression of acute liver injury and hepatic recovery.To date,there has been no systematic st...BACKGROUND Immune cells,including neutrophils,natural killer(NK)cells,T cells,NKT cells and macrophages,participate in the progression of acute liver injury and hepatic recovery.To date,there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery.AIM To investigate the infiltration changes of various immune cells in acute liver injury models over time,and to study the relationship between the changes in leukocyte cellderived chemotaxin 2(LECT2)and the infiltration of several immune cells.METHODS Carbon tetrachloride-and concanavalin A-induced acute liver injury models were employed to mimic toxin-induced and autoimmune-mediated liver injury respectively.The quantitative changes in various immune cells were monitored at different time points.Serum samples were collected,and liver tissues were harvested.Ly6G,CD161,CD4,CD8 and F4/80 staining were used to indicate neutrophils,NK/NKT cells,CD4^(+)T cells,CD8^(+)T cells and macrophages,respectively.Lect2-KO mice were used to detect the function of LECT2.RESULTS During the injury and repair process,different types of immune cells began to increase,reached their peaks and fell into decline at different time points.Furthermore,when the serum alanine transaminase(ALT)and aspartate transaminase(AST)indices reverted to normal levels 7 d after the injury,the infiltration of immune cells still existed even 14 d after the injury,showing an obvious lag effect.We found that the expression of LECT2 was upregulated in acute liver injury mouse models,and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice.Compared with wild-type mice,Lect2-KO mice had different immune cell infiltration.CONCLUSION The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair.LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.展开更多
Owing to its heterogeneous and highly aggressive nature,hepatocellular carcinoma(HCC)has a high recurrence rate,which is a non-negligible problem despite the increasing number of available treatment options.Recent cli...Owing to its heterogeneous and highly aggressive nature,hepatocellular carcinoma(HCC)has a high recurrence rate,which is a non-negligible problem despite the increasing number of available treatment options.Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC.In the event of liver remnant recurrence,the currently available treatment options include repeat hepatectomy,salvage liver transplantation,tumor ablation,transcatheter arterial chemoembolization,stereotactic body radiotherapy,systemic therapies,and combination therapy.In this review,we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC.Additionally,we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.展开更多
BACKGROUND Hepatic ischemia-reperfusion injury(IRI)poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory responses.The changes in glutamine synthetase(GS)expression ...BACKGROUND Hepatic ischemia-reperfusion injury(IRI)poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory responses.The changes in glutamine synthetase(GS)expression during hepatic IRI remain unclear.AIM To investigate the dynamic expression of GS during hepatic IRI.METHODS Following hepatic ischemia for 1 h and reperfusion,liver tissue samples were collected at 0.5,6,and 24 hours postreperfusion for fixation,embedding,section-ing.Hematoxylin and eosin staining and GS staining were performed.RESULTS GS expression rapidly decreases in hepatocytes around the central vein after IRI,reaching its lowest point at 6 hours postreperfusion,and then gradually recovers.CONCLUSION GS is highly sensitive to IRI,highlighting its potential role as an indicator of liver injury states and a target for therapeutic intervention.展开更多
Dear Editor,Most battlefield casualties occur prior to the arrival of medical facilities.Uncontrollable hemorrhage accounts for more than 90%of those potentially survivable battlefield casualties[1].In both military a...Dear Editor,Most battlefield casualties occur prior to the arrival of medical facilities.Uncontrollable hemorrhage accounts for more than 90%of those potentially survivable battlefield casualties[1].In both military and civilian conditions,non-compressible torso hemorrhage always caused rapid exsanguination and high mortality rates before definitive treatment[2].More than half of the deaths due to non-compressible torso hemorrhage occur before hospital care can be provided[2].Therefore,early and rapid pre-hospital hemorrhage control is essential to reduce mortality.展开更多
BACKGROUND Radiotherapy(RT)is a cornerstone of cancer treatment.Compared with conven-tional high-dose radiation,low-dose radiation(LDR)causes less damage to normal tissues while potentially modulating immune responses...BACKGROUND Radiotherapy(RT)is a cornerstone of cancer treatment.Compared with conven-tional high-dose radiation,low-dose radiation(LDR)causes less damage to normal tissues while potentially modulating immune responses and inhibiting tumor growth.LDR stimulates both innate and adaptive immunity,enhancing the activity of natural killer cells,dendritic cells,and T cells.However,the me-chanisms underlying the effects of LDR on the immune system remain unclear.AIM To explore the history,research hotspots,and emerging trends in immune response to LDR literature over the past two decades.METHODS Publications on immune responses to LDR were retrieved from the Web of Science Core Collection.Bibliometric tools,including CiteSpace and HistCite,were used to identify historical features,active topics,and emerging trends in this field.RESULTS Analysis of 1244 publications over the past two decades revealed a significant surge in research on immune responses to LDR,particularly in the last decade.Key journals such as INR J Radiat Biol,Cancers,and Radiat Res published pivotal studies.Citation networks identified key studies by authors like Twyman-Saint Victor C(2015)and Vanpouille-Box C(2017).Keyword analysis revealed hotspots such as ipilimumab,stereotactic body RT,and targeted therapy,possibly identifying future research directions.Temporal variations in keyword clusters and alluvial flow maps illustrate the evolution of research themes over time.CONCLUSION This bibliometric analysis provides valuable insights into the evolution of studies on responses to LDR,highlights research trends,and identifies emerging areas for further investigation.展开更多
The Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise and rename the 2019“Chinese Guidelines on the Management of Liver Cirrhosis”to“Chinese Guideline...The Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise and rename the 2019“Chinese Guidelines on the Management of Liver Cirrhosis”to“Chinese Guidelines for Clinical Diagnosis,Treatment,and Management of Cirrhosis(2025)”.These updated guidelines are aimed at providing recommendations for the clinical diagnosis and management of liver cirrhosis across the compensated,decompensated,and recompensated stages,as well as guidance on cirrhosis reversal and associated complications.展开更多
Breast cancer stands as the most prevalent malignancy among women worldwide and a leading cause of cancer-related mortality,posing a persistent challenge to global public health1.In recent decades,the landscape of bre...Breast cancer stands as the most prevalent malignancy among women worldwide and a leading cause of cancer-related mortality,posing a persistent challenge to global public health1.In recent decades,the landscape of breast cancer care has been profoundly reshaped by the rapid development of precision medicine,targeted therapy,immunotherapy,and clinical translational research.展开更多
BACKGROUND Per-oral endoscopic myotomy(POEM)is emerging as a prefer treatment option for pediatric achalasia.However,data are limited on the long-term efficacy of POEM in children and adolescents with achalasia.AIM To...BACKGROUND Per-oral endoscopic myotomy(POEM)is emerging as a prefer treatment option for pediatric achalasia.However,data are limited on the long-term efficacy of POEM in children and adolescents with achalasia.AIM To evaluate the safety and long-term efficacy of POEM for pediatric patients with achalasia and compare those outcomes with adult patients.METHODS This retrospective cohort study was conducted in patients with achalasia who underwent POEM.Patients aged under 18 years were included in the pediatric group;patients aged between 18 to 65 years who underwent POEM in the same period were assigned to the control group.For investigation of long-term followup,the pediatric group were matched with patients from the control group in a 1:1 ratio.The procedure-related parameters,adverse events,clinical success,gastroesophageal reflux disease(GERD)after POEM,and quality of life(QoL)were evaluated.RESULTS From January 2012 to March 2020,POEM was performed in 1025 patients aged under 65 years old(48 in the pediatric group,1025 in the control group).No significant differences were observed in the occurrence of POEM complications between the two groups(14.6%vs 14.6%;P=0.99).Among the 34 pediatric patients(70.8%)who underwent follow-up for 5.7 years(range 2.6-10.6 years),clinical success was achieved in 35 patients(35/36;97.2%).No differences were observed in post-POEM GERD occurrence(17.6%vs 35.3%;P=0.10).QoL was significantly improved in both groups after POEM.CONCLUSION POEM is safe and effective for pediatric patients with achalasia.It can achieve significant symptoms relief and improve QoL.展开更多
Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squ...Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.展开更多
BACKGROUND Metastasis of pancreatic cancer to the colon is rare and the features need to be further elucidated.Herein,we report a rare case of pancreatic cancer with simultaneous liver and colon metastases.CASE SUMMAR...BACKGROUND Metastasis of pancreatic cancer to the colon is rare and the features need to be further elucidated.Herein,we report a rare case of pancreatic cancer with simultaneous liver and colon metastases.CASE SUMMARY A 48-year-old man with intrahepatic space-occupying lesions based on a computed tomography scan was admitted to our hospital for further treatment.Abdominal magnetic resonance imaging revealed a 6.4 cm×4.2 cm mass in the tail of the pancreas and multiple low-density masses in the liver parenchyma.In addition,a mass of 2.2 cm×1.6 cm with surface congestive erosions in the sigmoid colon was detected by colonoscopy.Histopathological examination of biopsies from both the liver and colon lesions revealed a moderately to poorly differentiated adenocarcinoma.Immunohistochemical staining of the colon tumor was positive for cytokeratin(CK)7 and CK,but negative for colorectal adenocarcinoma-related markers CK 20,CDX2,and SATB2,thus indicating that the metastasis originated from the pancreas.Next-generation sequencing for genomic profiling of the liver and colon metastases both found mutations in KRAS(p.G12D)and TP53(c.376-1delG),with microsatellite stable and low tumor mutational burden without actionable or cancer-predisposing gene mutations detected.The patient was subsequently treated with 12 cycles of FOLFIRINOX which led to a sustainable response,followed by ongoing maintenance treatment with irinotecan plus fluorouracil.CONCLUSION For this rare case,careful evaluation of histopathological and immunohistochemical staining results are required.The genomic profiling of colon lesions was revealed for the first time,and FOLFIRINOX showed good treatment efficacy in this patient.展开更多
Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a cruc...Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor control.However,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade.Using single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in TIL-Bs.HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering.This classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to immunotherapy.We found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients.Overall,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.展开更多
BACKGROUND Intestinal ischemia-reperfusion(I/R)injury(II/RI)is a critical condition that results in oxidative stress,inflammation,and damage to multiple organs.Zinc,an essential trace element,offers protective benefit...BACKGROUND Intestinal ischemia-reperfusion(I/R)injury(II/RI)is a critical condition that results in oxidative stress,inflammation,and damage to multiple organs.Zinc,an essential trace element,offers protective benefits in several tissues during I/R injury,but its effects on intestinal II/RI remain unclear.METHODS C57BL/6 mice were pretreated with zinc sulfate(ZnSO4,10 mg/kg)daily for three days before I/R injury was induced via superior mesenteric artery occlusion(SMAO)and abdominal aortic occlusion(AAO)models.Tissue and serum samples were collected to evaluate intestinal,liver,and kidney damage using Chiu’s score,Suzuki score,and histopathological analysis.Caco-2 cells and intestinal organoids were used for in vitro hypoxia-reoxygenation injury models to measure reactive oxygen species(ROS)and superoxide dismutase(SOD)levels.RESULTS Zinc pretreatment significantly reduced intestinal damage in the SMAO and AAO models(P<0.001).The serum levels of liver enzymes(alanine aminotransferase,aspartate aminotransferase)and kidney markers(creatinine and urea)were lower in the zinc-treated mice than in the control mice,indicating reduced hepatic and renal injury.In vitro,zinc decreased ROS levels and increased SOD activity in Caco-2 cells subject to hypoxia-reoxygenation injury.Intestinal organoids pretreated with zinc exhibited enhanced resilience to hypoxic injury compared to controls.CONCLUSION Zinc pretreatment mitigates II/RI and reduces associated multiorgan damage.These findings suggest that zinc has potential clinical applications in protecting against I/R injuries.展开更多
Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is associated with coronary artery disease(CAD),but existing risk assessment tools lack precision and scalability.We developed an AI-drive...Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is associated with coronary artery disease(CAD),but existing risk assessment tools lack precision and scalability.We developed an AI-driven multimodal framework integrating traditional Chinese medicine(TCM)tongue-based diagnosis with clinical biomarkers to stratify CAD risk in MAFLD.Methods:In this cross-sectional study with prospective data collection,which comprised 1073 MAFLD patients stratified by CAD status(MAFLD without CAD,n=942;MAFLD with CAD,n=131),baseline characteristics were compared using chi-square tests for categorical variables and Mann-Whitney U tests for continuous vari-ables,with p<0.05 considered significant.We developed two distinct deep learning models:Model-1(non-invasive)using ResNet18 combined tongue image features with demographic and comorbidity data,and Model-2(comprehensive)incorporated blood biomarkers alongside the features used in Model-1.Multimodal feature fusion was achieved through a dedicated cross-attention network.Model performance was rigorously evaluated using 10-fold cross-validation,with area under the curve(AUC),sensitivity,and specificity as primary metrics.Focal loss was employed to address class imbalance.Results:The coexistence of CAD was associated with significantly higher rates of hypertension,diabetes,and familial cardiovascular history in patients with MAFLD(p<0.001),along with distinct metabolic profiles:elevated systemic inflammation(neutrophil-lymphocyte ratio),advanced fibrosis(FIB-4),elevated fasting glucose levels,and attenuated hepatic inflammation(ALT and AST).Model-1 achieved an AUC of 0.858(sensitivity 0.778,specificity 0.908),while Model-2 demonstrated superior discrimination(AUC 0.933),particularly in tertiary care.Conclusion:Our AI-driven dual-model framework addresses the critical unmet need for CAD identification in MAFLD patients,providing a community-scalable screening tool(Model-1)and a precision clinical assessment model(Model-2),while offering empirical support for TCM tongue diagnosis.Pending external validation to confirm its generalizability,this approach may serve as a cost-efficient non-invasive screening strategy for this high-risk population.展开更多
Radiation-induced lung injury(RILI)is a common complication of radiotherapy.Although berberine(BBR)has been suggested to be associated with reduced RILI incidence,the underlying mechanisms remain unknown.Here,we inves...Radiation-induced lung injury(RILI)is a common complication of radiotherapy.Although berberine(BBR)has been suggested to be associated with reduced RILI incidence,the underlying mechanisms remain unknown.Here,we investigated whether the gut microbiota mediates the radioprotective effects of BBR using a C57BL/6 RILI mouse model with 20 Gy thoracic irradiation(n=6 per group).BBR(100 mg/kg)and inosine(INO,300 mg/kg)were administered orally in vivo.Antibiotic depletion and fecal microbiota transplantation were performed to assess microbiota dependence.Lung injury was assessed by histology,pulmonary function,and cytokine levels.Gut microbiota was analyzed by 16S rRNA sequencing,and metabolites were profiled using LC-MS/MS.Transcriptomic and epigenomic alterations were assessed by RNA sequencing,ATAC sequencing,and CUT&Tag analysis.Molecular docking and surface plasmon resonance were used to assess metabolite-protein interactions.We demonstrated that BBR alleviated RILI in a microbiota-dependent manner.BBR increased Akkermansia muciniphila abundance and metabolite INO levels.Mechanistically,INO was associated with reduced neuron navigator 3(NAV3)expression,accompanied by decreased chromatin accessibility and increased histone H3 lysine 27 trimethylation(H3K27me3)at the NAV3 locus.Together,these findings reveal a gut microbiota-mediated mechanism underlying BBR-mediated protection against RILI,and suggest microbiota-informed biomarkers for risk stratification.展开更多
Background and Aims:Stem cell transplantation is a potential treatment option for liver cirrhosis(LC).Accurately and noninvasively monitoring the distribution,migration,and prognosis of transplanted stem cells using i...Background and Aims:Stem cell transplantation is a potential treatment option for liver cirrhosis(LC).Accurately and noninvasively monitoring the distribution,migration,and prognosis of transplanted stem cells using imaging methods is important for in-depth study of the treatment mechanisms.Our study aimed to develop Au-Fe3O4 silica nanoparticles(NPs)as tracking nanoplatforms for dualmodal stem cell imaging.Methods:Au-Fe3O4 silica NPs were synthesized by seed-mediated growth method and co-precipitation.The efficiency and cytotoxicity of the NPslabeled bone marrow-derived mesenchymal stem cells(BMMSCs)were evaluated by Cell Counting Kit-8 assays,ICPMS,phenotypic characterization,and histological staining.The biodistribution of labeled BM-MSCs injected through different routes(the hepatic artery or tail vein)into rats with LC was detected by magnetic resonance imaging(MRI),photoacoustic imaging(PAI),and Prussian blue staining.Results:Synthesized Au-Fe3O4 silica NPs consisted of a core(star-shaped Au NPs)and an outside silica layer doped with Fe3O4 NPs.After 24 h coincubation with 2.0 OD concentration of NPs,the viability of BM-MSCs was 77.91%±5.86%and the uptake of Au and Fe were(22.65±1.82)µg/mL and(234.03±11.47)µg/mL,respectively.The surface markers of labeled BM-MSCs unchanged significantly.Labeled BMMSCs have osteogenic and adipogenic differentiation potential.Post injection in vivo,rat livers were hypointense on MRI and hyperintense on PAI.Prussian blue staining showed that more labeled BM-MSCs accumulated in the liver of the hepatic artery group.The severity of LC of the rats in the hepatic artery group was significantly alleviated.Conclusions:Au-Fe3O4 silica NPs were suitable MRI/PAI dual-modal imaging nanoplatforms for stem cell tracking in regenerative medicine. Transhepatic arterial infusion of BMMSCs was the optimal route for the treatment of LC.展开更多
As members of the immune checkpoint family, PD-1 and its ligand PD-L1 play critical roles in maintaining the balance between autoimmunity and tolerance. The interaction of PD-1/PD-L1 is also involved in tumor evasion ...As members of the immune checkpoint family, PD-1 and its ligand PD-L1 play critical roles in maintaining the balance between autoimmunity and tolerance. The interaction of PD-1/PD-L1 is also involved in tumor evasion inside the tumor microenvironment, caused by reduced T cell activation, proliferation, cytotoxic secretion, and survival. Previous research has shown that the expression level of PD-1/PD-L1 may be regulated by ubiquitin-mediated proteasome degradation, which is an important mode of post-translational modification (PTM). PD-1/PD-L1 ubiquitin modification research in tumor immunotherapy is the subject of the present review, which aims to assess the most recent developments in this area. We offer a short explanation of PD-1/PD-L1 as well as some basic background information on the UPS system and discuss many routes that target E3s and DUBs, respectively, in the regulation of PD-1/PD-L1 in tumor immunotherapy. In addition, we offer numerous innovative prospective research areas for the future, as well as novel immunotherapy concepts and ideas. Taken together, the information compiled herein should serve as a comprehensive repository of information about tumor immunotherapy that is currently available, and it should be useful in the design of future studies, as well as the development of potential targets and strategies for future tumor immunotherapy.展开更多
基金This work was supported by the Capital Clinical Characteristic Application Research(Grant No.Z181100001718215)the innovative projects of PLA General Hospital(Grant No.CX19011).
文摘In April 2017,the first edition Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines were released.These guidelines were based on medical evidence,as well as the accessibility and cost effectiveness of various anticancer drugs in China.The CSCO BC guidelines include regimens with a high level of evidence,good product accessibility and high consistent consensus among Chinese experts as level I recommendations.Regimens with a high level of evidence but poor product accessibility or expert consensus are included as level II recommendations.
基金supported by the China Postdoctoral Science Foundation(Grant No.2023T160788)the Beijing Science and Technology Plan(Grant No.Z181100001718215).
文摘The Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines have been widely implemented in China since the first release in 2017.The Guideline Working Committee has also published multiple versions in English,Arabic,and other languages to facilitate communications with international experts.
文摘This article comprehensively reviews research progress in prostate cancer radiation therapy.It provides an overview of fundamental principles,encompassing the disease’s epidemiology,pathological mechanisms,and radiation sensitivity,alongside technological advancements.The clinical application,technological progress,and efficacy evaluation of moderate hypofractionated radiation therapy and ultra hypofractionated radiation therapy are discussed.Diagnostic and monitoring techniques specific to radiation therapy are analyzed,alongside prevailing controversies and challenges.Finally,the review outlines future prospects,including novel radiotherapy techniques,multidisciplinary collaboration trends,and the evolving role of radiation within comprehensive treatment.The findings demonstrate continuous technological and clinical evolution in prostate cancer radiotherapy,yet emphasize the need for further exploration to optimize treatments and improve patient survival and quality of life.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金Supported by the National Key R&D Program of ChinaNo. 2018YFA0108200 and No. 2018YFC1106400+5 种基金the National Natural Science Foundation of ChinaNo. 31972926, No. 32000607, No. 82270645 and No. 92068206Guangdong Basic and Applied Basic Research FoundationNo. 2020A1515111111 and No. 2019A1515110145China Postdoctoral Science FoundationNo. 2019M660205
文摘BACKGROUND Immune cells,including neutrophils,natural killer(NK)cells,T cells,NKT cells and macrophages,participate in the progression of acute liver injury and hepatic recovery.To date,there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery.AIM To investigate the infiltration changes of various immune cells in acute liver injury models over time,and to study the relationship between the changes in leukocyte cellderived chemotaxin 2(LECT2)and the infiltration of several immune cells.METHODS Carbon tetrachloride-and concanavalin A-induced acute liver injury models were employed to mimic toxin-induced and autoimmune-mediated liver injury respectively.The quantitative changes in various immune cells were monitored at different time points.Serum samples were collected,and liver tissues were harvested.Ly6G,CD161,CD4,CD8 and F4/80 staining were used to indicate neutrophils,NK/NKT cells,CD4^(+)T cells,CD8^(+)T cells and macrophages,respectively.Lect2-KO mice were used to detect the function of LECT2.RESULTS During the injury and repair process,different types of immune cells began to increase,reached their peaks and fell into decline at different time points.Furthermore,when the serum alanine transaminase(ALT)and aspartate transaminase(AST)indices reverted to normal levels 7 d after the injury,the infiltration of immune cells still existed even 14 d after the injury,showing an obvious lag effect.We found that the expression of LECT2 was upregulated in acute liver injury mouse models,and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice.Compared with wild-type mice,Lect2-KO mice had different immune cell infiltration.CONCLUSION The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair.LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.
文摘Owing to its heterogeneous and highly aggressive nature,hepatocellular carcinoma(HCC)has a high recurrence rate,which is a non-negligible problem despite the increasing number of available treatment options.Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC.In the event of liver remnant recurrence,the currently available treatment options include repeat hepatectomy,salvage liver transplantation,tumor ablation,transcatheter arterial chemoembolization,stereotactic body radiotherapy,systemic therapies,and combination therapy.In this review,we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC.Additionally,we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.
文摘BACKGROUND Hepatic ischemia-reperfusion injury(IRI)poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory responses.The changes in glutamine synthetase(GS)expression during hepatic IRI remain unclear.AIM To investigate the dynamic expression of GS during hepatic IRI.METHODS Following hepatic ischemia for 1 h and reperfusion,liver tissue samples were collected at 0.5,6,and 24 hours postreperfusion for fixation,embedding,section-ing.Hematoxylin and eosin staining and GS staining were performed.RESULTS GS expression rapidly decreases in hepatocytes around the central vein after IRI,reaching its lowest point at 6 hours postreperfusion,and then gradually recovers.CONCLUSION GS is highly sensitive to IRI,highlighting its potential role as an indicator of liver injury states and a target for therapeutic intervention.
文摘Dear Editor,Most battlefield casualties occur prior to the arrival of medical facilities.Uncontrollable hemorrhage accounts for more than 90%of those potentially survivable battlefield casualties[1].In both military and civilian conditions,non-compressible torso hemorrhage always caused rapid exsanguination and high mortality rates before definitive treatment[2].More than half of the deaths due to non-compressible torso hemorrhage occur before hospital care can be provided[2].Therefore,early and rapid pre-hospital hemorrhage control is essential to reduce mortality.
文摘BACKGROUND Radiotherapy(RT)is a cornerstone of cancer treatment.Compared with conven-tional high-dose radiation,low-dose radiation(LDR)causes less damage to normal tissues while potentially modulating immune responses and inhibiting tumor growth.LDR stimulates both innate and adaptive immunity,enhancing the activity of natural killer cells,dendritic cells,and T cells.However,the me-chanisms underlying the effects of LDR on the immune system remain unclear.AIM To explore the history,research hotspots,and emerging trends in immune response to LDR literature over the past two decades.METHODS Publications on immune responses to LDR were retrieved from the Web of Science Core Collection.Bibliometric tools,including CiteSpace and HistCite,were used to identify historical features,active topics,and emerging trends in this field.RESULTS Analysis of 1244 publications over the past two decades revealed a significant surge in research on immune responses to LDR,particularly in the last decade.Key journals such as INR J Radiat Biol,Cancers,and Radiat Res published pivotal studies.Citation networks identified key studies by authors like Twyman-Saint Victor C(2015)and Vanpouille-Box C(2017).Keyword analysis revealed hotspots such as ipilimumab,stereotactic body RT,and targeted therapy,possibly identifying future research directions.Temporal variations in keyword clusters and alluvial flow maps illustrate the evolution of research themes over time.CONCLUSION This bibliometric analysis provides valuable insights into the evolution of studies on responses to LDR,highlights research trends,and identifies emerging areas for further investigation.
基金Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project(2025ZD01906300&2025ZD01906303).
文摘The Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise and rename the 2019“Chinese Guidelines on the Management of Liver Cirrhosis”to“Chinese Guidelines for Clinical Diagnosis,Treatment,and Management of Cirrhosis(2025)”.These updated guidelines are aimed at providing recommendations for the clinical diagnosis and management of liver cirrhosis across the compensated,decompensated,and recompensated stages,as well as guidance on cirrhosis reversal and associated complications.
文摘Breast cancer stands as the most prevalent malignancy among women worldwide and a leading cause of cancer-related mortality,posing a persistent challenge to global public health1.In recent decades,the landscape of breast cancer care has been profoundly reshaped by the rapid development of precision medicine,targeted therapy,immunotherapy,and clinical translational research.
基金Supported by National Natural Science Foundation of China,No.82070682。
文摘BACKGROUND Per-oral endoscopic myotomy(POEM)is emerging as a prefer treatment option for pediatric achalasia.However,data are limited on the long-term efficacy of POEM in children and adolescents with achalasia.AIM To evaluate the safety and long-term efficacy of POEM for pediatric patients with achalasia and compare those outcomes with adult patients.METHODS This retrospective cohort study was conducted in patients with achalasia who underwent POEM.Patients aged under 18 years were included in the pediatric group;patients aged between 18 to 65 years who underwent POEM in the same period were assigned to the control group.For investigation of long-term followup,the pediatric group were matched with patients from the control group in a 1:1 ratio.The procedure-related parameters,adverse events,clinical success,gastroesophageal reflux disease(GERD)after POEM,and quality of life(QoL)were evaluated.RESULTS From January 2012 to March 2020,POEM was performed in 1025 patients aged under 65 years old(48 in the pediatric group,1025 in the control group).No significant differences were observed in the occurrence of POEM complications between the two groups(14.6%vs 14.6%;P=0.99).Among the 34 pediatric patients(70.8%)who underwent follow-up for 5.7 years(range 2.6-10.6 years),clinical success was achieved in 35 patients(35/36;97.2%).No differences were observed in post-POEM GERD occurrence(17.6%vs 35.3%;P=0.10).QoL was significantly improved in both groups after POEM.CONCLUSION POEM is safe and effective for pediatric patients with achalasia.It can achieve significant symptoms relief and improve QoL.
基金supported by the National Natural Science Foundation of China (82103508, 81871866, 82173252, 81672996)the Natural Science Foundation of Shaanxi Province (2022JQ?862)。
文摘Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.
文摘BACKGROUND Metastasis of pancreatic cancer to the colon is rare and the features need to be further elucidated.Herein,we report a rare case of pancreatic cancer with simultaneous liver and colon metastases.CASE SUMMARY A 48-year-old man with intrahepatic space-occupying lesions based on a computed tomography scan was admitted to our hospital for further treatment.Abdominal magnetic resonance imaging revealed a 6.4 cm×4.2 cm mass in the tail of the pancreas and multiple low-density masses in the liver parenchyma.In addition,a mass of 2.2 cm×1.6 cm with surface congestive erosions in the sigmoid colon was detected by colonoscopy.Histopathological examination of biopsies from both the liver and colon lesions revealed a moderately to poorly differentiated adenocarcinoma.Immunohistochemical staining of the colon tumor was positive for cytokeratin(CK)7 and CK,but negative for colorectal adenocarcinoma-related markers CK 20,CDX2,and SATB2,thus indicating that the metastasis originated from the pancreas.Next-generation sequencing for genomic profiling of the liver and colon metastases both found mutations in KRAS(p.G12D)and TP53(c.376-1delG),with microsatellite stable and low tumor mutational burden without actionable or cancer-predisposing gene mutations detected.The patient was subsequently treated with 12 cycles of FOLFIRINOX which led to a sustainable response,followed by ongoing maintenance treatment with irinotecan plus fluorouracil.CONCLUSION For this rare case,careful evaluation of histopathological and immunohistochemical staining results are required.The genomic profiling of colon lesions was revealed for the first time,and FOLFIRINOX showed good treatment efficacy in this patient.
基金supported by grants from the National Natural Science Foundation of China(82173362)China Postdoctoral Science Foundation(2022M720175,2023M734003)National Science Foundation of China(82304069).
文摘Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor control.However,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade.Using single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in TIL-Bs.HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering.This classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to immunotherapy.We found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients.Overall,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.
文摘BACKGROUND Intestinal ischemia-reperfusion(I/R)injury(II/RI)is a critical condition that results in oxidative stress,inflammation,and damage to multiple organs.Zinc,an essential trace element,offers protective benefits in several tissues during I/R injury,but its effects on intestinal II/RI remain unclear.METHODS C57BL/6 mice were pretreated with zinc sulfate(ZnSO4,10 mg/kg)daily for three days before I/R injury was induced via superior mesenteric artery occlusion(SMAO)and abdominal aortic occlusion(AAO)models.Tissue and serum samples were collected to evaluate intestinal,liver,and kidney damage using Chiu’s score,Suzuki score,and histopathological analysis.Caco-2 cells and intestinal organoids were used for in vitro hypoxia-reoxygenation injury models to measure reactive oxygen species(ROS)and superoxide dismutase(SOD)levels.RESULTS Zinc pretreatment significantly reduced intestinal damage in the SMAO and AAO models(P<0.001).The serum levels of liver enzymes(alanine aminotransferase,aspartate aminotransferase)and kidney markers(creatinine and urea)were lower in the zinc-treated mice than in the control mice,indicating reduced hepatic and renal injury.In vitro,zinc decreased ROS levels and increased SOD activity in Caco-2 cells subject to hypoxia-reoxygenation injury.Intestinal organoids pretreated with zinc exhibited enhanced resilience to hypoxic injury compared to controls.CONCLUSION Zinc pretreatment mitigates II/RI and reduces associated multiorgan damage.These findings suggest that zinc has potential clinical applications in protecting against I/R injuries.
基金supported by Beijing Natural Science Foundation Haidian Original Innovation Joint Fund(L222134).
文摘Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is associated with coronary artery disease(CAD),but existing risk assessment tools lack precision and scalability.We developed an AI-driven multimodal framework integrating traditional Chinese medicine(TCM)tongue-based diagnosis with clinical biomarkers to stratify CAD risk in MAFLD.Methods:In this cross-sectional study with prospective data collection,which comprised 1073 MAFLD patients stratified by CAD status(MAFLD without CAD,n=942;MAFLD with CAD,n=131),baseline characteristics were compared using chi-square tests for categorical variables and Mann-Whitney U tests for continuous vari-ables,with p<0.05 considered significant.We developed two distinct deep learning models:Model-1(non-invasive)using ResNet18 combined tongue image features with demographic and comorbidity data,and Model-2(comprehensive)incorporated blood biomarkers alongside the features used in Model-1.Multimodal feature fusion was achieved through a dedicated cross-attention network.Model performance was rigorously evaluated using 10-fold cross-validation,with area under the curve(AUC),sensitivity,and specificity as primary metrics.Focal loss was employed to address class imbalance.Results:The coexistence of CAD was associated with significantly higher rates of hypertension,diabetes,and familial cardiovascular history in patients with MAFLD(p<0.001),along with distinct metabolic profiles:elevated systemic inflammation(neutrophil-lymphocyte ratio),advanced fibrosis(FIB-4),elevated fasting glucose levels,and attenuated hepatic inflammation(ALT and AST).Model-1 achieved an AUC of 0.858(sensitivity 0.778,specificity 0.908),while Model-2 demonstrated superior discrimination(AUC 0.933),particularly in tertiary care.Conclusion:Our AI-driven dual-model framework addresses the critical unmet need for CAD identification in MAFLD patients,providing a community-scalable screening tool(Model-1)and a precision clinical assessment model(Model-2),while offering empirical support for TCM tongue diagnosis.Pending external validation to confirm its generalizability,this approach may serve as a cost-efficient non-invasive screening strategy for this high-risk population.
基金supported by the National Natural Science Foundation of China(grant number 82373515 to J.L.).
文摘Radiation-induced lung injury(RILI)is a common complication of radiotherapy.Although berberine(BBR)has been suggested to be associated with reduced RILI incidence,the underlying mechanisms remain unknown.Here,we investigated whether the gut microbiota mediates the radioprotective effects of BBR using a C57BL/6 RILI mouse model with 20 Gy thoracic irradiation(n=6 per group).BBR(100 mg/kg)and inosine(INO,300 mg/kg)were administered orally in vivo.Antibiotic depletion and fecal microbiota transplantation were performed to assess microbiota dependence.Lung injury was assessed by histology,pulmonary function,and cytokine levels.Gut microbiota was analyzed by 16S rRNA sequencing,and metabolites were profiled using LC-MS/MS.Transcriptomic and epigenomic alterations were assessed by RNA sequencing,ATAC sequencing,and CUT&Tag analysis.Molecular docking and surface plasmon resonance were used to assess metabolite-protein interactions.We demonstrated that BBR alleviated RILI in a microbiota-dependent manner.BBR increased Akkermansia muciniphila abundance and metabolite INO levels.Mechanistically,INO was associated with reduced neuron navigator 3(NAV3)expression,accompanied by decreased chromatin accessibility and increased histone H3 lysine 27 trimethylation(H3K27me3)at the NAV3 locus.Together,these findings reveal a gut microbiota-mediated mechanism underlying BBR-mediated protection against RILI,and suggest microbiota-informed biomarkers for risk stratification.
基金funded by grants from The National Natural Science Foundation of China (No.81671800)。
文摘Background and Aims:Stem cell transplantation is a potential treatment option for liver cirrhosis(LC).Accurately and noninvasively monitoring the distribution,migration,and prognosis of transplanted stem cells using imaging methods is important for in-depth study of the treatment mechanisms.Our study aimed to develop Au-Fe3O4 silica nanoparticles(NPs)as tracking nanoplatforms for dualmodal stem cell imaging.Methods:Au-Fe3O4 silica NPs were synthesized by seed-mediated growth method and co-precipitation.The efficiency and cytotoxicity of the NPslabeled bone marrow-derived mesenchymal stem cells(BMMSCs)were evaluated by Cell Counting Kit-8 assays,ICPMS,phenotypic characterization,and histological staining.The biodistribution of labeled BM-MSCs injected through different routes(the hepatic artery or tail vein)into rats with LC was detected by magnetic resonance imaging(MRI),photoacoustic imaging(PAI),and Prussian blue staining.Results:Synthesized Au-Fe3O4 silica NPs consisted of a core(star-shaped Au NPs)and an outside silica layer doped with Fe3O4 NPs.After 24 h coincubation with 2.0 OD concentration of NPs,the viability of BM-MSCs was 77.91%±5.86%and the uptake of Au and Fe were(22.65±1.82)µg/mL and(234.03±11.47)µg/mL,respectively.The surface markers of labeled BM-MSCs unchanged significantly.Labeled BMMSCs have osteogenic and adipogenic differentiation potential.Post injection in vivo,rat livers were hypointense on MRI and hyperintense on PAI.Prussian blue staining showed that more labeled BM-MSCs accumulated in the liver of the hepatic artery group.The severity of LC of the rats in the hepatic artery group was significantly alleviated.Conclusions:Au-Fe3O4 silica NPs were suitable MRI/PAI dual-modal imaging nanoplatforms for stem cell tracking in regenerative medicine. Transhepatic arterial infusion of BMMSCs was the optimal route for the treatment of LC.
基金supported by the National Natural Science Foundation of China(82103508,81871866,82173252)Shaanxi Special Support Plan-Program for Leading Talents of Science and Technology Innovation(China)(No.2019 Special Support Plan)+1 种基金the Natural Science Foundation of Shaanxi Province(China)(2016SF-308,2019SF-033,2022SF-145)Project of Tangdu Hospital,the Fourth Military Medical University(China)(No.2018 Key Talents).
文摘As members of the immune checkpoint family, PD-1 and its ligand PD-L1 play critical roles in maintaining the balance between autoimmunity and tolerance. The interaction of PD-1/PD-L1 is also involved in tumor evasion inside the tumor microenvironment, caused by reduced T cell activation, proliferation, cytotoxic secretion, and survival. Previous research has shown that the expression level of PD-1/PD-L1 may be regulated by ubiquitin-mediated proteasome degradation, which is an important mode of post-translational modification (PTM). PD-1/PD-L1 ubiquitin modification research in tumor immunotherapy is the subject of the present review, which aims to assess the most recent developments in this area. We offer a short explanation of PD-1/PD-L1 as well as some basic background information on the UPS system and discuss many routes that target E3s and DUBs, respectively, in the regulation of PD-1/PD-L1 in tumor immunotherapy. In addition, we offer numerous innovative prospective research areas for the future, as well as novel immunotherapy concepts and ideas. Taken together, the information compiled herein should serve as a comprehensive repository of information about tumor immunotherapy that is currently available, and it should be useful in the design of future studies, as well as the development of potential targets and strategies for future tumor immunotherapy.
