Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving resear...Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.展开更多
Magnetostrictive Fe-Ga alloys have captivated substantial focus in biomedical applications because of their exceptional transition efficiency and favorable cytocompatibility.Nevertheless,Fe-Ga alloys always exhibit fr...Magnetostrictive Fe-Ga alloys have captivated substantial focus in biomedical applications because of their exceptional transition efficiency and favorable cytocompatibility.Nevertheless,Fe-Ga alloys always exhibit frustrating magnetostriction coefficients when presented in bulk dimensions.It is well-established that the magnetostrictive performance of Fe-Ga alloys is intimately linked to their phase and crystal structures.In this study,various concentrations of boron(B)were doped into Fe_(81)Ga_(19) alloys via the laser-beam powder bed fusion(LPBF)technique to tailor the crystal and phase structures,thereby improving the magnetostrictive performance.The results revealed the capacity for quick solidification of the LPBF process in expediting the solid solution of B element,which increased both lattice distortion and dislocations within the Fe-Ga matrix.These factors contributed to an elevation in the density of the modified-D0_(3) phase structure.Moreover,the prepared Fe-Ga-B alloys also exhibited a(001)preferred grain orientation caused by the high thermal gradients during the LPBF process.As a result,a maximum magnetostriction coefficient of 105 ppm was achieved in the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy.In alternating magnetic fields,all the LPBF-prepared alloys showed good dynamic magnetostriction response without visible hysteresis,while the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy presented a notable enhancement of~30%in magnetostriction coefficient when compared with the Fe_(81)Ga_(19) alloy.Moreover.the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy exhibited favorable biocompatibility and osteogenesis,as confirmed by increased alkaline phosphatase(ALP)activity and the formation of mineralized nodules.These findings suggest that the B-doped Fe-Ga alloys combined with the LPBF technique hold promise for the development of bulk magnetostrictive alloys that are applicable for bone repair applications.展开更多
Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether k...Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.展开更多
Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely int...Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.展开更多
Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the ...Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the scarcity of these NENs has hindered extensive clinical investigations,thereby leading to a dearth of robust evidence for guiding clinical practice and impeding the establishment of standardized approaches for diagnosis and treatment.However,with the increasing awareness of population screening,as well as the increasing popularity of colonoscopy screening programs,the incidence of colorectal NENs has gradually increased.Moreover,some high-grade NENs are highly malignant and invasive,thereby leading to poor treatment outcomes and prognoses.These challenges have elicited increased attention from clinical physicians,thus prompting researchers to explore relevant studies using limited specimens and clinical data.This scenario has resulted in preliminary findings that provide evidence for addressing diagnostic and therapeutic challenges associated with NENs of the colon and rectum.In this article,we review recent literature reports and summarize the advances regarding the diagnosis and treatment of colorectal NENs.展开更多
BACKGROUND The combination of immune checkpoint inhibitors and antiangiogenic drugs has shown promising efficacy in advanced hepatocellular carcinoma(HCC).However,tumor regression and progression-free survival(PFS)var...BACKGROUND The combination of immune checkpoint inhibitors and antiangiogenic drugs has shown promising efficacy in advanced hepatocellular carcinoma(HCC).However,tumor regression and progression-free survival(PFS)vary considerably among patients receiving this therapy.AIM To identify predictive biomarkers in HCC patients treated with sintilimab(programmed cell death protein-1 inhibitor)plus lenvatinib(tyrosine kinase inhibitor).METHODS In this single-center study in China,patients with unresectable HCC received sintilimab every 21 days and daily oral lenvatinib.Treatment response was assessed by modified response evaluation criteria in solid tumors.Tumor biopsies underwent RNA sequencing,immune microenvironment profiling,and whole-exome sequencing.Differentially expressed genes(DEGs)and immune cell subsets between response groups were identified,followed by survival analyses.All potential predictors of PFS,together with clinical variables,were included in Cox regression to identify independent prognostic factors.RESULTS Between August 2019 and November 2021,33 patients with hepatitis-B-virus-related HCC were enrolled;by January 2024,13 had undergone potentially curative surgery or ablation.RNA sequencing identified 94 DEGs between responders(n=22)and non-responders(n=11)using Fisher’s exact test or Wilcoxon rank-sum test(all P<0.05).High long intergenic non-protein coding RNA 01554(LINC01554)and whirlin expression were associated with longer PFS in Kaplan-Meier analysis(P<0.05).DEG-immune cell analysis showed positive correlations with pro-B and plasma cells in responders,and negative correlations with CD4+central memory T(Tcm),T helper 1,and natural killer T cells in non-responders;none significantly predicted PFS,although CD4+Tcm cells approached significance(P<0.10).Whole-exome sequencing revealed Fanconi anemia complementation group D2 mutations enriched in non-responders(P<0.05),while cut-like homeobox 1 mutations predicted poorer PFS(P=0.011).Cox regression identified solitary tumor[P=0.02,hazard ratio(HR)=0.31],high LINC01554(P=0.01,HR=0.16),and elevated CD4+Tcm cells(P=0.05,HR=0.29)as independent predictors of prolonged PFS.CONCLUSION Sintilimab plus lenvatinib showed heterogeneous efficacy in HCC.High LINC01554 expression,elevated CD4+Tcm cells,and solitary tumors may serve as predictive biomarkers for prolonged disease control.展开更多
Objective:The trial was designed to evaluate the efficacy of prophylactic hyperthermic intraperitoneal chemotherapy(HIPEC)with cisplatin for patients with locally advanced gastric cancer(LAGC).Methods:Between March 20...Objective:The trial was designed to evaluate the efficacy of prophylactic hyperthermic intraperitoneal chemotherapy(HIPEC)with cisplatin for patients with locally advanced gastric cancer(LAGC).Methods:Between March 2015 and November 2016,a phase Ⅱ clinical trial was performed.Fifty consecutive patients with LAGC were randomly assigned to two groups:the experimental group(radical gastrectomy+HIPEC with cisplatin+adjuvant chemotherapy)and the control group(radical gastrectomy+adjuvant chemotherapy).Survival rates were closely monitored.Results:The 5-year overall survival(OS)rate of all patients was 80.0%.The 5-year OS rate in the experimental group was lower than that in the control group,at 75.8%and 88.2%,respectively,with no statistical significance.In addition,5-year recurrence-free survival(RFS)rates of patients who underwent HIPEC or not were also 75.8%and 88.2%,respectively.In the multivariate analysis,only pT stage[risk ratio(RR)=7.079,P=0.018]was significantly associated with prognosis.The most common recurrence pattern was peritoneal recurrence in both groups.The experimental group had a lower incidence of peritoneal recurrence than the control group with no statistical significance.Conclusions:This trial clearly revealed that prophylactic HIPEC with cisplatin neither decrease the risk of peritoneal recurrence nor improve the prognosis of patients with LAGC.Thus,HIPEC with cisplatin is not recommended as a prophylactic treatment for peritoneal recurrence of LAGC after radical gastrectomy.展开更多
BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcino...BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcinoma(AC)components,with each component ranging from 1%to 99%of the tumour,be classified as a distinct entity.We hereby term this adenoneuroendocrine mixed gastric cancer(G-ANEC).Research on lymph node(LN)involvement in GMANEC has focused mainly on metastasis status,with limited studies on metastatic composition.AIM To investigate the LN metastasis patterns of G-ANEC,the clinicopathological features associated with these metastasis patterns,and to explore adjuvant chemotherapy regimens for G-ANEC.METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022.Utilizingχ2 tests in IBM statistical product and service solutions statistics and R software.RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion,tumour invasion depth,Lauren classification,and tumour location(P values:0.008,0.015,0.01,and 0.004,respectively).When the SOX/XELOX regimen was applied for adjuvant chemotherapy,patients with LN metastasis comprising only AC exhibited better overall survival(OS)(94.25±11.07 months vs 54.36±11.36 months)than did those with NEC.When LN metastasis components contained NEC,there was a trend towards improved OS(64±10.77 months vs 54.35±11.36 months)and disease-free survival(71.28±9.92 months vs 66.28±11.93 months)in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen.CONCLUSION We found a significant correlation between the NEC percentage,tumour invasion depth,Lauren classification,and tumour location and LN metastasis patterns in G-ANEC.For G-ANEC,a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs.Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.展开更多
BACKGROUND Retroperitoneal fibrosis is a rare fibro-inflammatory condition which can be classified into idiopathic(accounting for over 75%)and secondary types(due to malignancies,infections,medications,radiotherapy or...BACKGROUND Retroperitoneal fibrosis is a rare fibro-inflammatory condition which can be classified into idiopathic(accounting for over 75%)and secondary types(due to malignancies,infections,medications,radiotherapy or other conditions).Idiopathic retroperitoneal fibrosis(IRPF)typically affects the abdominal aorta and iliac arteries along with the surrounding retroperitoneal area.This case review aims to summarize the imaging characteristics of IRPF arising from the peritoneal space.CASE SUMMARY An abdominal mass was discovered in a 52-year-old man during a routine physical examination,he had not complained of abdominal pain,distension,nausea,vomiting,diarrhea,fever,and had no significant past medical or family history.Abdominal magnetic resonance imaging revealed a soft tissue mass with poorly defined margins surrounding the duodenum,exhibiting slight to moderate high signal intensity on both T1-weighted and T2-weighted images.Diffusionweighted imaging with aβvalue of 800 mm²/second demonstrated slightly to moderate high signal intensity.Dynamic contrast enhanced images showed uneven enhancement on the arterial phase,with significant enhancement observed on the delayed phase.The mass infiltrated adjacent structures,including the head of the pancreas,the hepatic flexure of the colon,and part of the intestine,raising suspicion for malignant tumors such as sarcoma or lymphoma.However,surgery confirmed the diagnosis of IRPF.The patient underwent routine followup for one year,with no recurrence.CONCLUSION IRPF is a rare condition that presents considerable diagnostic challenges when lesions arise from the peritoneal space.In cases where imaging findings are atypical,a further puncture biopsy may be necessary to confirm the diagnosis.展开更多
BACKGROUND KRAS mutation status and primary tumor location serve as critical prognostic factors for colorectal liver metastases(CLMs).Emerging evidence suggests a potential interaction between these two variables that...BACKGROUND KRAS mutation status and primary tumor location serve as critical prognostic factors for colorectal liver metastases(CLMs).Emerging evidence suggests a potential interaction between these two variables that may influence clinical outcomes.AIM To investigate the association of KRAS mutations with recurrence in patients with CLM who underwent radiofrequency ablation(RFA)according to the primary tumor location.METHODS This retrospective study analyzed 164 patients with KRAS-determined CLM treated with percutaneous RFA between January 2012 and December 2018.The clinicopathological characteristics,recurrence patterns,and survival outcomes were systematically evaluated.RESULTS A total of 164 patients(mean age:58.0±9.8 years,range:34-83 years)who underwent percutaneous RFA of 325 CLMs(mean size:2.2±1.0 cm,range:0.7-5.0 cm)were included in the study.Eighty-nine(54.3%)patients had wild-type KRAS,and 75(45.7%)patients had mutated KRAS.Compared with wild-type patients,patients with KRAS mutations presented significantly higher local tumor progression rates(30.7%vs 14.6%,P=0.013).Among 126 patients(76.8%)who experienced post-RFA recurrence,61.6%developed intrahepatic metastases,and 53.7%developed extrahepatic metastases.Primary tumor location significantly modified KRASrelated outcomes:Compared with wild-type patients,left-sided colorectal cancer(CRC)patients with KRAS mutations presented higher intrahepatic recurrence rates(77.2%vs 52.5%,P=0.003)and shorter median intrahepatic recurrence-free survival(15 vs 25 months,P=0.007).No significant differences in KRAS expression were detected in right-sided tumors.CONCLUSION KRAS mutation status predicts differential recurrence patterns after CLM ablation,with significant prognostic implications,specifically in left-sided CRCs.These findings underscore the importance of integrating molecular profiling and primary tumor characteristics in therapeutic decision-making for patients with metastatic CRC.展开更多
Acral melanoma,the most common melanoma subtype in East Asia,is associated with a poor prognosis.This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians.We conduct whole...Acral melanoma,the most common melanoma subtype in East Asia,is associated with a poor prognosis.This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians.We conduct whole-genome sequencing of 55 acral melanoma tumors and perform data mining with relevant clinical data.Our findings reveal a unique mutational profile in East Asian acral melanoma,characterized by fewer point mutations and structural variations,a higher prevalence of NRAS mutations,and a lower frequency of BRAF mutations compared to patients of European descent.Notably,we identify previously underestimated ultraviolet radiation signatures and their significant association with BRAF and NRAS mutations.Structural rearrangement signatures indicate distinct mutational processes in BRAF-driven versus NRAS-driven tumors.We also find that homologous recombination deficiency with MAPK pathway mutations correlated with poor prognosis.The structural variations and amplifications in EP300,TERT,RAC1,and LZTR1 point to potential therapeutic targets tailored to East Asian populations.The high prevalence of whole-genome duplication events in BRAF/NRAS-mutated tumors suggests a synergistic carcinogenic effect that warrants further investigation.In summary,our study provides important insights into the genetic underpinnings of acral melanoma in East Asians,creating opportunities for targeted therapies.展开更多
Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and pro...Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and prognosis in patients with estrogen receptor-positive(ER+)breast cancer.Methods:This prospective study enrolled nine female patients with breast cancer(mean age 45.5±11.5 years).Eight patients were confirmed to have ER+disease.All participant underwent both[^(68)Ga]Ga-RM2 PET/CT and[^(18)F]FDG PET/CT scans within a one-week interval.The maximum standardized uptake values(SUV_(max))was measured for primary tumors,lymph nodes,and metastatic lesions.The physiological distribution of[^(68)Ga]GaRM2 was also evaluated.Results:No adverse events were observed.Metastatic were identified in lymph nodes(n=29 lesions),bone(n=19),liver(n=7),brain(n=3),and multiple other sites.[^(68)Ga]Ga-RM2 demonstrated a significantly higher median SUV_(max)than[^(18)F]FDG across all lesions[7.5(interquartile range,IQR,3.4-14.0)vs.4.0(IQR,2.3-6.1);P<0.001].Similarly,the tumor-to-background ratio(TBR)was significantly superior with[^(68)Ga]Ga-RM2 for all type of lesions:primary tumors[12.3(IQR,10.4-18.3)vs.7.0(IQR,6.0-10.0);P<0.001],lymph node metastases[17.8(IQR,4.4-39.0)vs.4.7(IQR,2.7-10.2);P<0.001],hepatic metastases[5.4(IQR,3.7-8.3)vs.1.0(IQR,0.9-1.5);P<0.001],and osseous metastases[13.9(IQR,7.3-18.0)vs.4.3(IQR,1.6-5.9);P<0.001].Physiological uptake of[^(68)Ga]Ga-RM2 was the highest in the pancreas(SUV_(max),77.82±22.64),with moderate uptake in the kidneys(2.82±0.62),heart(1.83±0.29),and liver(1.33±0.41).Conclusions:[^(68)Ga]Ga-RM2 PET/CT demonstrates superior uptake metrics for the detection of metastatic lesions,particularly in the brain and breast,suggesting its potential as a valuable complementary imaging modality to[^(18)F]FDG PET/CT.These promising foundings warrant further validation in larger cohorts to confirm their clinical impact and to standardize imaging protocols.展开更多
Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO...Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.展开更多
Objective:A risk-based sequential screening strategy,from questionnaire-based assessment to biomarker measurement and then to endoscopic examination,has the potential to enhance gastric cancer(GC)screening efficiency....Objective:A risk-based sequential screening strategy,from questionnaire-based assessment to biomarker measurement and then to endoscopic examination,has the potential to enhance gastric cancer(GC)screening efficiency.We aimed to evaluate the ability of five common stomach-specific serum biomarkers to further enrich high-risk individuals for GC in the questionnaire-identified high-risk population.Methods:This study was conducted based on a risk-based screening program in Ningxia Hui Autonomous Region,China.We first performed questionnaire assessment involving 23,381 individuals(7,042 outpatients and 16,339 individuals from the community),and those assessed as“high-risk”were then invited to participate in serological assays and endoscopic examinations.The serological biomarker model was derived based on logistic regression,with predictors selected via the Akaike information criterion.Model performance was evaluated by the area under the receiver operating characteristic curve(AUC).Results:A total of 2,011 participants were ultimately included for analysis.The final serological biomarker model had three predictors,comprising pepsinogenⅠ(PGI),pepsinogenⅠ/Ⅱratio(PGR),and anti-Helicobacter pylori immunoglobulin G(anti-H.pylori IgG)antibodies.This model generated an AUC of 0.733(95%confidence interval:0.655-0.812)and demonstrated the best discriminative ability compared with previously developed serological biomarker models.As the risk cut-off value of our model rose,the detection rate increased and the number of endoscopies needed to detect one case decreased.Conclusions:PGI,PGR,and anti-H.pylori Ig G could be jointly used to further enrich high-risk individuals for GC among those selected by questionnaire assessment,providing insight for the development of a multi-stage riskbased sequential strategy for GC screening.展开更多
Objective:Although the role of circular RNAs(circRNAs)in tumor progression and immune regulation is well-known,the specific circ RNA molecules that mediate immune responses after radiotherapy(RT)and the underlying mec...Objective:Although the role of circular RNAs(circRNAs)in tumor progression and immune regulation is well-known,the specific circ RNA molecules that mediate immune responses after radiotherapy(RT)and the underlying mechanisms have not been identified.Methods:Cytometry with time-of-flight(CyTOF)was used to analyze blood samples from patients with liver cancer exhibiting abscopal effects(AEs)after stereotactic body radiotherapy(SBRT)to quantify the number of dendritic cells(DCs)and CD8+T cells and interferon-beta(IFN-β)level.circTMEM56 and IFN-βlevels were measured in 76 patients with liver cancer using q PCR and ELISA.Immunohistochemistry validated circTMEM56 and CD141 staining in tissues.The interaction between circTMEM56,miR-136-5p,and STING,as well as the impact on anti-tumor immunity,was verified using circTMEM56-specific probes,dual-luciferase activity assays,proteomics analysis,and western blot analysis.Results:The role of circTMEM56 in enhancing anti-tumor immunity and response to RT in hepatocellular carcinoma(HCC)was determined.Higher circTMEM56 levels were linked to an improved RT response and better clinical outcomes in patients with HCC.circTMEM56 enhanced cGAS-STING signaling,increased the number of tumor-infiltrating CD8+T cells,and elevated the serum IFN-βlevels.Moreover,circTMEM56 administration significantly boosted the response to RT in tumors with low circTMEM56 expression.Conclusions:High circTMEM56 expression in HCC modulates the distant effects of HCC RT by activating the cGAS-STING pathway to reshape the tumor microenvironment.This study provides a new approach to improve RT efficacy for HCC.展开更多
Breast cancer(BC)is now the most common cancer and the fifth leading cause of cancer-associated mortality among women in China1.Germline pathogenic variants(PVs)of BC susceptibility genes,such as the well-known BRCA1/...Breast cancer(BC)is now the most common cancer and the fifth leading cause of cancer-associated mortality among women in China1.Germline pathogenic variants(PVs)of BC susceptibility genes,such as the well-known BRCA1/2 genes,increase the risk of BC and other cancers(ovarian and pancreatic cancer)^(2,3).Recent studies have demonstrated substantial benefits of poly(adenosine diphosphate ribose)polymerase inhibitors in the treatment of BC patients who carry BRCA1/2 PVs^(4).展开更多
Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesio...Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.展开更多
Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to deg...Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.展开更多
Human cytomegalovirus(HCMV)poses a significant risk of neural damage during pregnancy.As the most prevalent intrauterine infectious agent in low-and middle-income countries,HCMV disrupts the development of neural stem...Human cytomegalovirus(HCMV)poses a significant risk of neural damage during pregnancy.As the most prevalent intrauterine infectious agent in low-and middle-income countries,HCMV disrupts the development of neural stem cells,leading to fetal malformations and abnormal structural and physiological functions in the fetal brain.This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
基金supported by Key Research and Development Plan of Hunan Province(2024DK2006)the Fundamental Research Funds for the Central Universities of Central South University(1053320221769)+2 种基金Hunan Provincial Respiratory Disease Rehabilitation and Nursing Engineering Research Center Innovation Capacity Building Project(No.202012)the Zhangjiajie Science and Technology Development Key Special Project(No.202304)the National Key Clinical Specialty Major Scientific Research Project(No.20230382).
文摘Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.
基金supported by the National Natural Science Foundation of China(Nos.52275395,51935014,and 82072084)the Science and Technology Innovation Program of Hunan Province(No.2023RC3046)+4 种基金the Young Elite Scientists Sponsorship Program byCAST(No.2020QNRC002)the NationalKeyResearchand Development Program of China(No.2023YFB4605800)the Central South University Innovation-Driven Research Programme(No.2023CXQD023)the Jiangxi Provincial Natural Science Foundation of China(No.20224ACB204013)the Project of State Key Laboratory of Precision Manufacturing for Extreme Service Performance,Central South University.
文摘Magnetostrictive Fe-Ga alloys have captivated substantial focus in biomedical applications because of their exceptional transition efficiency and favorable cytocompatibility.Nevertheless,Fe-Ga alloys always exhibit frustrating magnetostriction coefficients when presented in bulk dimensions.It is well-established that the magnetostrictive performance of Fe-Ga alloys is intimately linked to their phase and crystal structures.In this study,various concentrations of boron(B)were doped into Fe_(81)Ga_(19) alloys via the laser-beam powder bed fusion(LPBF)technique to tailor the crystal and phase structures,thereby improving the magnetostrictive performance.The results revealed the capacity for quick solidification of the LPBF process in expediting the solid solution of B element,which increased both lattice distortion and dislocations within the Fe-Ga matrix.These factors contributed to an elevation in the density of the modified-D0_(3) phase structure.Moreover,the prepared Fe-Ga-B alloys also exhibited a(001)preferred grain orientation caused by the high thermal gradients during the LPBF process.As a result,a maximum magnetostriction coefficient of 105 ppm was achieved in the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy.In alternating magnetic fields,all the LPBF-prepared alloys showed good dynamic magnetostriction response without visible hysteresis,while the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy presented a notable enhancement of~30%in magnetostriction coefficient when compared with the Fe_(81)Ga_(19) alloy.Moreover.the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy exhibited favorable biocompatibility and osteogenesis,as confirmed by increased alkaline phosphatase(ALP)activity and the formation of mineralized nodules.These findings suggest that the B-doped Fe-Ga alloys combined with the LPBF technique hold promise for the development of bulk magnetostrictive alloys that are applicable for bone repair applications.
基金funded by the National Natural Science Foundation of China(No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501400-2023ZD0501402)+4 种基金Beijing Hospitals Authority’s Ascent Plan(DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZLRK202325)China Postdoctoral Science Foundation(2024M760152)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(No.BMU2022XKQ004)Science Foundation of Peking University Cancer Hospital(Nos.BJCH2024BJ02,XKFZ2410,BJCH2025CZ04,and 2022-27)。
文摘Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.
基金support by grants from Capital’s Funds for Health Improvement and Research(Grant No.2024-2-1024)Beijing Natural Science Foundation(Grant No.7232018).
文摘Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.
文摘Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the scarcity of these NENs has hindered extensive clinical investigations,thereby leading to a dearth of robust evidence for guiding clinical practice and impeding the establishment of standardized approaches for diagnosis and treatment.However,with the increasing awareness of population screening,as well as the increasing popularity of colonoscopy screening programs,the incidence of colorectal NENs has gradually increased.Moreover,some high-grade NENs are highly malignant and invasive,thereby leading to poor treatment outcomes and prognoses.These challenges have elicited increased attention from clinical physicians,thus prompting researchers to explore relevant studies using limited specimens and clinical data.This scenario has resulted in preliminary findings that provide evidence for addressing diagnostic and therapeutic challenges associated with NENs of the colon and rectum.In this article,we review recent literature reports and summarize the advances regarding the diagnosis and treatment of colorectal NENs.
基金Supported by Clinical Research Fund for Distinguished Young Scholars of Beijing Cancer Hospital,No.LGH2019101 and No.LGH2022005Special Fund for Clinical Research of Wu Jieping Medical Foundation,No.320.6750.19088-38.
文摘BACKGROUND The combination of immune checkpoint inhibitors and antiangiogenic drugs has shown promising efficacy in advanced hepatocellular carcinoma(HCC).However,tumor regression and progression-free survival(PFS)vary considerably among patients receiving this therapy.AIM To identify predictive biomarkers in HCC patients treated with sintilimab(programmed cell death protein-1 inhibitor)plus lenvatinib(tyrosine kinase inhibitor).METHODS In this single-center study in China,patients with unresectable HCC received sintilimab every 21 days and daily oral lenvatinib.Treatment response was assessed by modified response evaluation criteria in solid tumors.Tumor biopsies underwent RNA sequencing,immune microenvironment profiling,and whole-exome sequencing.Differentially expressed genes(DEGs)and immune cell subsets between response groups were identified,followed by survival analyses.All potential predictors of PFS,together with clinical variables,were included in Cox regression to identify independent prognostic factors.RESULTS Between August 2019 and November 2021,33 patients with hepatitis-B-virus-related HCC were enrolled;by January 2024,13 had undergone potentially curative surgery or ablation.RNA sequencing identified 94 DEGs between responders(n=22)and non-responders(n=11)using Fisher’s exact test or Wilcoxon rank-sum test(all P<0.05).High long intergenic non-protein coding RNA 01554(LINC01554)and whirlin expression were associated with longer PFS in Kaplan-Meier analysis(P<0.05).DEG-immune cell analysis showed positive correlations with pro-B and plasma cells in responders,and negative correlations with CD4+central memory T(Tcm),T helper 1,and natural killer T cells in non-responders;none significantly predicted PFS,although CD4+Tcm cells approached significance(P<0.10).Whole-exome sequencing revealed Fanconi anemia complementation group D2 mutations enriched in non-responders(P<0.05),while cut-like homeobox 1 mutations predicted poorer PFS(P=0.011).Cox regression identified solitary tumor[P=0.02,hazard ratio(HR)=0.31],high LINC01554(P=0.01,HR=0.16),and elevated CD4+Tcm cells(P=0.05,HR=0.29)as independent predictors of prolonged PFS.CONCLUSION Sintilimab plus lenvatinib showed heterogeneous efficacy in HCC.High LINC01554 expression,elevated CD4+Tcm cells,and solitary tumors may serve as predictive biomarkers for prolonged disease control.
基金supported by the National Nature Science Foundation of China(No.81402308)Science Foundation of Peking University Cancer Hospital(No.2021-24)+2 种基金Natural Science Foundation of Beijing Municipal(No.7242020)Science Foundation of Peking University Cancer Hospital(No.BJCH2025GG04)the National Nature Science Foundation of China(No.82173151).
文摘Objective:The trial was designed to evaluate the efficacy of prophylactic hyperthermic intraperitoneal chemotherapy(HIPEC)with cisplatin for patients with locally advanced gastric cancer(LAGC).Methods:Between March 2015 and November 2016,a phase Ⅱ clinical trial was performed.Fifty consecutive patients with LAGC were randomly assigned to two groups:the experimental group(radical gastrectomy+HIPEC with cisplatin+adjuvant chemotherapy)and the control group(radical gastrectomy+adjuvant chemotherapy).Survival rates were closely monitored.Results:The 5-year overall survival(OS)rate of all patients was 80.0%.The 5-year OS rate in the experimental group was lower than that in the control group,at 75.8%and 88.2%,respectively,with no statistical significance.In addition,5-year recurrence-free survival(RFS)rates of patients who underwent HIPEC or not were also 75.8%and 88.2%,respectively.In the multivariate analysis,only pT stage[risk ratio(RR)=7.079,P=0.018]was significantly associated with prognosis.The most common recurrence pattern was peritoneal recurrence in both groups.The experimental group had a lower incidence of peritoneal recurrence than the control group with no statistical significance.Conclusions:This trial clearly revealed that prophylactic HIPEC with cisplatin neither decrease the risk of peritoneal recurrence nor improve the prognosis of patients with LAGC.Thus,HIPEC with cisplatin is not recommended as a prophylactic treatment for peritoneal recurrence of LAGC after radical gastrectomy.
基金Supported by the National Key Research and Development Program of China,No.2023YFF1204702the National Natural Science Foundation of China,No.82173151+2 种基金Capital’s Funds for Health Improvement and Research,No.CFH 2022-4-1025Beijing Hospitals Authority Clinical Medicine Development of Special Funding,No.XMLX202119Science Foundation of Peking University Cancer Hospital,No.PY202329.
文摘BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcinoma(AC)components,with each component ranging from 1%to 99%of the tumour,be classified as a distinct entity.We hereby term this adenoneuroendocrine mixed gastric cancer(G-ANEC).Research on lymph node(LN)involvement in GMANEC has focused mainly on metastasis status,with limited studies on metastatic composition.AIM To investigate the LN metastasis patterns of G-ANEC,the clinicopathological features associated with these metastasis patterns,and to explore adjuvant chemotherapy regimens for G-ANEC.METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022.Utilizingχ2 tests in IBM statistical product and service solutions statistics and R software.RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion,tumour invasion depth,Lauren classification,and tumour location(P values:0.008,0.015,0.01,and 0.004,respectively).When the SOX/XELOX regimen was applied for adjuvant chemotherapy,patients with LN metastasis comprising only AC exhibited better overall survival(OS)(94.25±11.07 months vs 54.36±11.36 months)than did those with NEC.When LN metastasis components contained NEC,there was a trend towards improved OS(64±10.77 months vs 54.35±11.36 months)and disease-free survival(71.28±9.92 months vs 66.28±11.93 months)in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen.CONCLUSION We found a significant correlation between the NEC percentage,tumour invasion depth,Lauren classification,and tumour location and LN metastasis patterns in G-ANEC.For G-ANEC,a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs.Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.
文摘BACKGROUND Retroperitoneal fibrosis is a rare fibro-inflammatory condition which can be classified into idiopathic(accounting for over 75%)and secondary types(due to malignancies,infections,medications,radiotherapy or other conditions).Idiopathic retroperitoneal fibrosis(IRPF)typically affects the abdominal aorta and iliac arteries along with the surrounding retroperitoneal area.This case review aims to summarize the imaging characteristics of IRPF arising from the peritoneal space.CASE SUMMARY An abdominal mass was discovered in a 52-year-old man during a routine physical examination,he had not complained of abdominal pain,distension,nausea,vomiting,diarrhea,fever,and had no significant past medical or family history.Abdominal magnetic resonance imaging revealed a soft tissue mass with poorly defined margins surrounding the duodenum,exhibiting slight to moderate high signal intensity on both T1-weighted and T2-weighted images.Diffusionweighted imaging with aβvalue of 800 mm²/second demonstrated slightly to moderate high signal intensity.Dynamic contrast enhanced images showed uneven enhancement on the arterial phase,with significant enhancement observed on the delayed phase.The mass infiltrated adjacent structures,including the head of the pancreas,the hepatic flexure of the colon,and part of the intestine,raising suspicion for malignant tumors such as sarcoma or lymphoma.However,surgery confirmed the diagnosis of IRPF.The patient underwent routine followup for one year,with no recurrence.CONCLUSION IRPF is a rare condition that presents considerable diagnostic challenges when lesions arise from the peritoneal space.In cases where imaging findings are atypical,a further puncture biopsy may be necessary to confirm the diagnosis.
基金Supported by Capital Health Development Research Project,No.2020-2-2152National Natural Science Foundation of China,No.82472002.
文摘BACKGROUND KRAS mutation status and primary tumor location serve as critical prognostic factors for colorectal liver metastases(CLMs).Emerging evidence suggests a potential interaction between these two variables that may influence clinical outcomes.AIM To investigate the association of KRAS mutations with recurrence in patients with CLM who underwent radiofrequency ablation(RFA)according to the primary tumor location.METHODS This retrospective study analyzed 164 patients with KRAS-determined CLM treated with percutaneous RFA between January 2012 and December 2018.The clinicopathological characteristics,recurrence patterns,and survival outcomes were systematically evaluated.RESULTS A total of 164 patients(mean age:58.0±9.8 years,range:34-83 years)who underwent percutaneous RFA of 325 CLMs(mean size:2.2±1.0 cm,range:0.7-5.0 cm)were included in the study.Eighty-nine(54.3%)patients had wild-type KRAS,and 75(45.7%)patients had mutated KRAS.Compared with wild-type patients,patients with KRAS mutations presented significantly higher local tumor progression rates(30.7%vs 14.6%,P=0.013).Among 126 patients(76.8%)who experienced post-RFA recurrence,61.6%developed intrahepatic metastases,and 53.7%developed extrahepatic metastases.Primary tumor location significantly modified KRASrelated outcomes:Compared with wild-type patients,left-sided colorectal cancer(CRC)patients with KRAS mutations presented higher intrahepatic recurrence rates(77.2%vs 52.5%,P=0.003)and shorter median intrahepatic recurrence-free survival(15 vs 25 months,P=0.007).No significant differences in KRAS expression were detected in right-sided tumors.CONCLUSION KRAS mutation status predicts differential recurrence patterns after CLM ablation,with significant prognostic implications,specifically in left-sided CRCs.These findings underscore the importance of integrating molecular profiling and primary tumor characteristics in therapeutic decision-making for patients with metastatic CRC.
基金supported by the National Key Research and Development Program(2023YFC2506404)the Natural Science Foundation of China(82272848,82425047,82272676)+2 种基金Beijing Municipal Administration of Hospitals'Ascent Plan(DFL20220901)Beijing Natural Science Foundation(7242021,L248021)Sichuan Provincial Science and Technology Department Key Research and Development Program(2024YFHZ0004)。
文摘Acral melanoma,the most common melanoma subtype in East Asia,is associated with a poor prognosis.This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians.We conduct whole-genome sequencing of 55 acral melanoma tumors and perform data mining with relevant clinical data.Our findings reveal a unique mutational profile in East Asian acral melanoma,characterized by fewer point mutations and structural variations,a higher prevalence of NRAS mutations,and a lower frequency of BRAF mutations compared to patients of European descent.Notably,we identify previously underestimated ultraviolet radiation signatures and their significant association with BRAF and NRAS mutations.Structural rearrangement signatures indicate distinct mutational processes in BRAF-driven versus NRAS-driven tumors.We also find that homologous recombination deficiency with MAPK pathway mutations correlated with poor prognosis.The structural variations and amplifications in EP300,TERT,RAC1,and LZTR1 point to potential therapeutic targets tailored to East Asian populations.The high prevalence of whole-genome duplication events in BRAF/NRAS-mutated tumors suggests a synergistic carcinogenic effect that warrants further investigation.In summary,our study provides important insights into the genetic underpinnings of acral melanoma in East Asians,creating opportunities for targeted therapies.
基金supported by the National Natural Science Foundation of China(No.82372001,82171973,82171980)the Youth Talent Support Program(No.A002863)Scientific Research Foundation of Peking University Cancer Hospital(No.BJCH2024CZ02)。
文摘Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and prognosis in patients with estrogen receptor-positive(ER+)breast cancer.Methods:This prospective study enrolled nine female patients with breast cancer(mean age 45.5±11.5 years).Eight patients were confirmed to have ER+disease.All participant underwent both[^(68)Ga]Ga-RM2 PET/CT and[^(18)F]FDG PET/CT scans within a one-week interval.The maximum standardized uptake values(SUV_(max))was measured for primary tumors,lymph nodes,and metastatic lesions.The physiological distribution of[^(68)Ga]GaRM2 was also evaluated.Results:No adverse events were observed.Metastatic were identified in lymph nodes(n=29 lesions),bone(n=19),liver(n=7),brain(n=3),and multiple other sites.[^(68)Ga]Ga-RM2 demonstrated a significantly higher median SUV_(max)than[^(18)F]FDG across all lesions[7.5(interquartile range,IQR,3.4-14.0)vs.4.0(IQR,2.3-6.1);P<0.001].Similarly,the tumor-to-background ratio(TBR)was significantly superior with[^(68)Ga]Ga-RM2 for all type of lesions:primary tumors[12.3(IQR,10.4-18.3)vs.7.0(IQR,6.0-10.0);P<0.001],lymph node metastases[17.8(IQR,4.4-39.0)vs.4.7(IQR,2.7-10.2);P<0.001],hepatic metastases[5.4(IQR,3.7-8.3)vs.1.0(IQR,0.9-1.5);P<0.001],and osseous metastases[13.9(IQR,7.3-18.0)vs.4.3(IQR,1.6-5.9);P<0.001].Physiological uptake of[^(68)Ga]Ga-RM2 was the highest in the pancreas(SUV_(max),77.82±22.64),with moderate uptake in the kidneys(2.82±0.62),heart(1.83±0.29),and liver(1.33±0.41).Conclusions:[^(68)Ga]Ga-RM2 PET/CT demonstrates superior uptake metrics for the detection of metastatic lesions,particularly in the brain and breast,suggesting its potential as a valuable complementary imaging modality to[^(18)F]FDG PET/CT.These promising foundings warrant further validation in larger cohorts to confirm their clinical impact and to standardize imaging protocols.
基金supported by the following funds:The National Natural Science Foundation of China(Nos.52275393,51935014,and 82072084)Jiangxi Provincial Natural Science Foundation of China(No.20224ACB204013)+2 种基金The Project of State Key Laboratory of Precision Manufacturing for Extreme Service Performancethe National Key Research and Development Program of China(No.2023YFB4605800)the Independent Exploration and Innovation Project of Central South University(No.1053320221707).
文摘Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.
基金supported by the Tencent Charity Foundationthe Ningxia Hui Autonomous Region Key Research and Development Program(No.2021BEG 02025)+1 种基金the Flexible Introduction of Technological Innovation Teams of Ningxia Hui Autonomous Region(No.2021RXTDLX15)the Natural Science Foundation of China(No.82160644)。
文摘Objective:A risk-based sequential screening strategy,from questionnaire-based assessment to biomarker measurement and then to endoscopic examination,has the potential to enhance gastric cancer(GC)screening efficiency.We aimed to evaluate the ability of five common stomach-specific serum biomarkers to further enrich high-risk individuals for GC in the questionnaire-identified high-risk population.Methods:This study was conducted based on a risk-based screening program in Ningxia Hui Autonomous Region,China.We first performed questionnaire assessment involving 23,381 individuals(7,042 outpatients and 16,339 individuals from the community),and those assessed as“high-risk”were then invited to participate in serological assays and endoscopic examinations.The serological biomarker model was derived based on logistic regression,with predictors selected via the Akaike information criterion.Model performance was evaluated by the area under the receiver operating characteristic curve(AUC).Results:A total of 2,011 participants were ultimately included for analysis.The final serological biomarker model had three predictors,comprising pepsinogenⅠ(PGI),pepsinogenⅠ/Ⅱratio(PGR),and anti-Helicobacter pylori immunoglobulin G(anti-H.pylori IgG)antibodies.This model generated an AUC of 0.733(95%confidence interval:0.655-0.812)and demonstrated the best discriminative ability compared with previously developed serological biomarker models.As the risk cut-off value of our model rose,the detection rate increased and the number of endoscopies needed to detect one case decreased.Conclusions:PGI,PGR,and anti-H.pylori Ig G could be jointly used to further enrich high-risk individuals for GC among those selected by questionnaire assessment,providing insight for the development of a multi-stage riskbased sequential strategy for GC screening.
基金funded by the National Key Research and Development Program of China(Grant No.2023YFC3402700)Shanghai Municipal Natural Science Foundation(Grant No.22ZR1411200)+2 种基金China Postdoctoral Science FundGeneral Fund(Grant No.2022M720779)Research Fund of Zhongshan Hospital Affiliated to Shanghai Fudan University for Young Scientists(Grant No.2023ZSQN26)National Natural Science Foundation of China(Grant Nos.82403999 and 82073479)。
文摘Objective:Although the role of circular RNAs(circRNAs)in tumor progression and immune regulation is well-known,the specific circ RNA molecules that mediate immune responses after radiotherapy(RT)and the underlying mechanisms have not been identified.Methods:Cytometry with time-of-flight(CyTOF)was used to analyze blood samples from patients with liver cancer exhibiting abscopal effects(AEs)after stereotactic body radiotherapy(SBRT)to quantify the number of dendritic cells(DCs)and CD8+T cells and interferon-beta(IFN-β)level.circTMEM56 and IFN-βlevels were measured in 76 patients with liver cancer using q PCR and ELISA.Immunohistochemistry validated circTMEM56 and CD141 staining in tissues.The interaction between circTMEM56,miR-136-5p,and STING,as well as the impact on anti-tumor immunity,was verified using circTMEM56-specific probes,dual-luciferase activity assays,proteomics analysis,and western blot analysis.Results:The role of circTMEM56 in enhancing anti-tumor immunity and response to RT in hepatocellular carcinoma(HCC)was determined.Higher circTMEM56 levels were linked to an improved RT response and better clinical outcomes in patients with HCC.circTMEM56 enhanced cGAS-STING signaling,increased the number of tumor-infiltrating CD8+T cells,and elevated the serum IFN-βlevels.Moreover,circTMEM56 administration significantly boosted the response to RT in tumors with low circTMEM56 expression.Conclusions:High circTMEM56 expression in HCC modulates the distant effects of HCC RT by activating the cGAS-STING pathway to reshape the tumor microenvironment.This study provides a new approach to improve RT efficacy for HCC.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82272932,81974422,and 92359201).
文摘Breast cancer(BC)is now the most common cancer and the fifth leading cause of cancer-associated mortality among women in China1.Germline pathogenic variants(PVs)of BC susceptibility genes,such as the well-known BRCA1/2 genes,increase the risk of BC and other cancers(ovarian and pancreatic cancer)^(2,3).Recent studies have demonstrated substantial benefits of poly(adenosine diphosphate ribose)polymerase inhibitors in the treatment of BC patients who carry BRCA1/2 PVs^(4).
基金funded by the National Natural Science Foundation of China(Grant No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant Nos.2023ZD0501400-2023ZD0501402)+3 种基金Beijing Hospitals Authority’s Ascent Plan(Grant No.DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(Grant No.ZLRK202325)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(Grant No.BMU2022XKQ004)the Science Foundation of Peking University Cancer Hospital(Grant Nos.BJCH2024BJ02,XKFZ2410,and 2022-27).
文摘Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.
基金supported by the National Natural Science Foundation of China(82103298)Basic Research Project of Science and Technology Cooperation in Qiandongnan Prefecture(No.2023-16).
文摘Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.
基金supported by the Natural Science Foundation of Shandong Province(ZR2019MC059)the Traditional Chinese Medicine Science Project of Shandong Province(M-2023093)the Weifang Municipal Science and Technology Development Program(2025YX037).
文摘Human cytomegalovirus(HCMV)poses a significant risk of neural damage during pregnancy.As the most prevalent intrauterine infectious agent in low-and middle-income countries,HCMV disrupts the development of neural stem cells,leading to fetal malformations and abnormal structural and physiological functions in the fetal brain.This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.
