BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making i...BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.展开更多
Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors(PEComas)because PEComas are mainly benign tumors and may not require surgical intervention.By analyzing the...Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors(PEComas)because PEComas are mainly benign tumors and may not require surgical intervention.By analyzing the causes,properties and clinical manifestations of PEComas,we summarize the challenges and solutions in the diagnosis of PEComas.展开更多
BACKGROUND The most common causes of scrotal enlargement in patients include primary tumor of the scrotum,inflammation,hydrocele of the tunica vaginalis,and indirect inguinal hernia;scrotal enlargement caused by exter...BACKGROUND The most common causes of scrotal enlargement in patients include primary tumor of the scrotum,inflammation,hydrocele of the tunica vaginalis,and indirect inguinal hernia;scrotal enlargement caused by external tumors of the scrotum is rare.The patient had both a greater omentum tumor and an inguinal hernia,and the tumor protruded into the scrotum through the hernia sac,which is even rarer.Moreover,omental tumors are mostly metastatic,and primary omental fibroma is rare.CASE SUMMARY Here,we report a rare case of a 25-year-old young man with scrotal enlargement and pain for 3 months.Preoperative examination and multidisciplinary discu-ssions considered intra-abdominal tumor displacement and inguinal hernia,and intraoperative exploration confirmed that the greater omentum tumor protruded into the scrotum.Therefore,tumor resection and tension-free inguinal hernia repair were performed.The final diagnosis was benign fibroma of the greater omentum accompanied by an indirect inguinal hernia.CONCLUSION This unusual presentation of a common inguinal hernia disease illustrates the necessity of performing detailed history taking,physical examination,and imaging before surgery.展开更多
In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarc...In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.展开更多
The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant...The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.展开更多
Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium homeostasis.Most commonly HPT presents with asymptoma...Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium homeostasis.Most commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and hypercalcemia.Brown tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical practice.The tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic mass.Furthermore,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone lesion.The diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and PTH.Although when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic tumors.Treatment of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical intervention.However,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.展开更多
BACKGROUND Collision tumors involving the small intestine,specifically the combination of a hamartomatous tumor and a lipoma,are extremely rare.To our knowledge,no previous case report has described a collision tumor ...BACKGROUND Collision tumors involving the small intestine,specifically the combination of a hamartomatous tumor and a lipoma,are extremely rare.To our knowledge,no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine.CASE SUMMARY Here,we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm×32 mm×30 mm in the terminal ileum.Based on computed tomography scan findings,the mass was initially suspected to be a lipoma.A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line.A biopsy of the upper portion suggested a juvenile polyp(JP).Owing to the patient’s advanced age,multiple comorbidities,and poor surgical tolerance,a modified endoscopic submucosal dissection was performed.Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top,demonstrating evidence of rupture and associated bleeding.The patient’s overall health remained satisfactory,with no recurrence of hematochezia during the six-month follow-up period.CONCLUSION This case report provides new evidence for the understanding of gastrointestinal collision tumors,emphasizing their diverse clinical presentations and histopathological characteristics.It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.展开更多
BACKGROUND This case of gestational gingival tumor is huge and extremely rare in clinical practice.As the growth location of this gingival tumor is in the upper anterior tooth area,it seriously affects the pregnant wo...BACKGROUND This case of gestational gingival tumor is huge and extremely rare in clinical practice.As the growth location of this gingival tumor is in the upper anterior tooth area,it seriously affects the pregnant woman's speech and food,causing great pain to the patient.The use of Nd:YGA water mist laser to remove the gingival tumor resulted in minimal intraoperative bleeding,minimal adverse reactions,and good postoperative healing,which is worthy of clinical promotion and application.CASE SUMMARY The patient,a pregnant woman,reported a large lump in her mouth on the first day of postpartum treatment.Based on medical history and clinical examination,the diagnosis was diagnosed as gestational gingival tumor.Postoperative pathological biopsy also confirmed this diagnosis.The use of Nd:YAG water mist laser to remove the tumor resulted in minimal intraoperative bleeding,clear surgical field of view,short surgical time,and good postoperative healing.CONCLUSION In comparison to traditional surgery,Nd:YAG water mist laser surgery is minimally invasive,minimizes cell damage,reduces bleeding,ensures a clear field of vision,and virtually eliminates postoperative edema,carbonization,and the risk of cross infection.It has unique advantages in oral soft tissue surgery for pregnant patients.Therefore,the clinical application of Nd:YAG water mist laser for the treatment of gestational gingival tumors is an ideal choice.展开更多
BACKGROUND Recently,vessels encapsulating tumor clusters(VETC)was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in a...BACKGROUND Recently,vessels encapsulating tumor clusters(VETC)was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in an invasion independent manner,and was regarded as an independent risk factor for poor prognosis in hepatocellular carcinoma(HCC).AIM To develop and validate a preoperative nomogram using contrast-enhanced computed tomography(CECT)to predict the presence of VETC+in HCC.METHODS We retrospectively evaluated 190 patients with pathologically confirmed HCC who underwent CECT scanning and immunochemical staining for cluster of differentiation 34 at two medical centers.Radiomics analysis was conducted on intratumoral and peritumoral regions in the portal vein phase.Radiomics features,essential for identifying VETC+HCC,were extracted and utilized to develop a radiomics model using machine learning algorithms in the training set.The model’s performance was validated on two separate test sets.Receiver operating characteristic(ROC)analysis was employed to compare the identified performance of three models in predicting the VETC status of HCC on both training and test sets.The most predictive model was then used to constructed a radiomics nomogram that integrated the independent clinical-radiological features.ROC and decision curve analysis were used to assess the performance characteristics of the clinical-radiological features,the radiomics features and the radiomics nomogram.RESULTS The study included 190 individuals from two independent centers,with the majority being male(81%)and a median age of 57 years(interquartile range:51-66).The area under the curve(AUC)for the combined radiomics features selected from the intratumoral and peritumoral areas were 0.825,0.788,and 0.680 in the training set and the two test sets.A total of 13 features were selected to construct the Rad-score.The nomogram,combining clinicalradiological and combined radiomics features could accurately predict VETC+in all three sets,with AUC values of 0.859,0.848 and 0.757.Decision curve analysis revealed that the radiomics nomogram was more clinically useful than both the clinical-radiological feature and the combined radiomics models.CONCLUSION This study demonstrates the potential utility of a CECT-based radiomics nomogram,incorporating clinicalradiological features and combined radiomics features,in the identification of VETC+HCC.展开更多
BACKGROUND Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection(ESD);however,the preoperative evaluation of tumor size is often different from histolog...BACKGROUND Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection(ESD);however,the preoperative evaluation of tumor size is often different from histological assessment.Analyzing influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable ESD.METHODS This was a retrospective study conducted at a single institution.A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were collected.We first assessed the difference in size with an absolute per-centage of the scaling discrepancy.Subsequently,we compared the clinicopatho-logical characteristics of the correct scaling group(>-33%and<33%)with that of the incorrect scaling group(<-33%or>33%),which was further subdivided into the underscaling group(-33%or less of the discrepancy)and overscaling group(33%or more of the discrepancy),respectively.As secondary outcome measures,parameters on size estimation were compared between the underscaling and correct scaling groups,as well as between the overscaling and correct scaling groups.Finally,multivariate analysis was performed in terms of the following relevant parameters on size estimation:Pathological size,location,and possible influential factors(P<0.1)in the univariate analysis.RESULTS The mean of absolute percentage in the scaling discordance was 21%,and 91 lesions were considered to be incorrectly estimated in size.The incorrect scaling was significantly remarkable in larger lesions(40 mm vs 28 mm;P<0.001)and less experience(P<0.001),and these two factors were influential on the underscaling(75 lesions;P<0.001).Conversely,compared with the correct scaling group,16 lesions in the overscaling group were significantly small(20 mm vs 28 mm;P<0.001),and the small lesion size was influential on the overscaling(P=0.002).CONCLUSION Lesions indicated for colorectal ESD tended to be underestimated in large tumors,but overestimated in small ones.This discrepancy appears worth understanding for optimal procedural preparation.展开更多
Background:This study aimed to investigate the potential of intratumoral microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers as predictive biomarkers for antitumor efficacy in patients w...Background:This study aimed to investigate the potential of intratumoral microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers as predictive biomarkers for antitumor efficacy in patients with non-small cell lung cancer.Methods:This study observed patients with metastatic non-driver mutation non-small cell lung cancer who were initially diagnosed at the First Affiliated Hospital of Dalian Medical University’s Department of Oncology from August 2021 to July 2022 and completed at least four cycles of chemotherapy combined with immune checkpoint inhibitor treatment.Lung biopsy tissues,fecal,and peripheral blood samples were collected from these patients.Based on the efficacy of the combined chemotherapy and immunotherapy,patients were divided into an effective group and an ineffective group.The tumor microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers were compared between the two groups.The lung and fecal microbiota were analyzed using 16S rRNA high-throughput sequencing.Flow cytometry was used to detect T-cell subsets,and enzyme-linked immunosorbent assay was employed to measure inflammatory factors.Results:A total of 21 patients were observed.There were significant differences in the tumor microbiota between the responsive and non-responsive groups,particularly the proportion of the genera Sphingomonas and Pseudomonas.The gut microbiome composition changed after treatment,but there were no differences between the two groups before treatment.There were no significant differences in T-cell subsets and inflammatory markers between the responsive and non-responsive groups.Conclusion:The composition of intratumoral microbiota in non-small cell lung cancer patients may serve as an indicator of response to chemotherapy combined with immunotherapy.The predictive value of gut microbiota,T-cell subsets,and inflammatory markers appears limited.Future research should further validate the predictive role of changes in gut microbiota on treatment outcomes.展开更多
Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residin...Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residing in tumor tissues are commonly known as tumor-associated macrophages(TAMs)and promote or inhibit tumor growth depending on the activation state2.展开更多
This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors(pan-NETs),emphasizing tailored approaches for specific subtypes.Cytoreductive surgery and soma...This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors(pan-NETs),emphasizing tailored approaches for specific subtypes.Cytoreductive surgery and somatostatin analogs(SSAs)play pivotal roles in managing tumors,while palliative options such as molecular targeted therapy,peptide receptor radionuclide therapy,and chemotherapy are reserved for SSA-refractory patients.Gastrinomas,insul-inomas,glucagonomas,carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies.Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research.This review underscores the evolving landscape of pan-NET treatment,offering renewed hope and improved outcomes for patients facing this complex disease.展开更多
Breast cancer detection heavily relies on medical imaging, particularly ultrasound, for early diagnosis and effectivetreatment. This research addresses the challenges associated with computer-aided diagnosis (CAD) of ...Breast cancer detection heavily relies on medical imaging, particularly ultrasound, for early diagnosis and effectivetreatment. This research addresses the challenges associated with computer-aided diagnosis (CAD) of breastcancer fromultrasound images. The primary challenge is accurately distinguishing between malignant and benigntumors, complicated by factors such as speckle noise, variable image quality, and the need for precise segmentationand classification. The main objective of the research paper is to develop an advanced methodology for breastultrasound image classification, focusing on speckle noise reduction, precise segmentation, feature extraction, andmachine learning-based classification. A unique approach is introduced that combines Enhanced Speckle ReducedAnisotropic Diffusion (SRAD) filters for speckle noise reduction, U-NET-based segmentation, Genetic Algorithm(GA)-based feature selection, and Random Forest and Bagging Tree classifiers, resulting in a novel and efficientmodel. To test and validate the hybrid model, rigorous experimentations were performed and results state thatthe proposed hybrid model achieved accuracy rate of 99.9%, outperforming other existing techniques, and alsosignificantly reducing computational time. This enhanced accuracy, along with improved sensitivity and specificity,makes the proposed hybrid model a valuable addition to CAD systems in breast cancer diagnosis, ultimatelyenhancing diagnostic accuracy in clinical applications.展开更多
Brain tumors are a pressing public health concern, characterized by their high mortality and morbidity rates.Nevertheless, the manual segmentation of brain tumors remains a laborious and error-prone task, necessitatin...Brain tumors are a pressing public health concern, characterized by their high mortality and morbidity rates.Nevertheless, the manual segmentation of brain tumors remains a laborious and error-prone task, necessitatingthe development of more precise and efficient methodologies. To address this formidable challenge, we proposean advanced approach for segmenting brain tumorMagnetic Resonance Imaging (MRI) images that harnesses theformidable capabilities of deep learning and convolutional neural networks (CNNs). While CNN-based methodshave displayed promise in the realm of brain tumor segmentation, the intricate nature of these tumors, markedby irregular shapes, varying sizes, uneven distribution, and limited available data, poses substantial obstacles toachieving accurate semantic segmentation. In our study, we introduce a pioneering Hybrid U-Net framework thatseamlessly integrates the U-Net and CNN architectures to surmount these challenges. Our proposed approachencompasses preprocessing steps that enhance image visualization, a customized layered U-Net model tailoredfor precise segmentation, and the inclusion of dropout layers to mitigate overfitting during the training process.Additionally, we leverage the CNN mechanism to exploit contextual information within brain tumorMRI images,resulting in a substantial enhancement in segmentation accuracy.Our experimental results attest to the exceptionalperformance of our framework, with accuracy rates surpassing 97% across diverse datasets, showcasing therobustness and effectiveness of our approach. Furthermore, we conduct a comprehensive assessment of ourmethod’s capabilities by evaluating various performance measures, including the sensitivity, Jaccard-index, andspecificity. Our proposed model achieved 99% accuracy. The implications of our findings are profound. Theproposed Hybrid U-Net model emerges as a highly promising diagnostic tool, poised to revolutionize brain tumorimage segmentation for radiologists and clinicians.展开更多
Cancer,a disease as intricate as it is devastating,continues to challenge the medical and scientific community[1].Its complex nature is epitomized by the tumor microenvironment and tumor heterogeneity.As we delve deep...Cancer,a disease as intricate as it is devastating,continues to challenge the medical and scientific community[1].Its complex nature is epitomized by the tumor microenvironment and tumor heterogeneity.As we delve deeper into the realms of cancer research,the advent of transcriptome analysis has emerged as a powerful torchbearer,illuminating our understanding of these enigmatic facets of cancer biology[2].展开更多
BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the esta...BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.展开更多
Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq dat...Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.展开更多
Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T...Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.展开更多
基金National Key R&D Program of China,No.2022YFF1203300.
文摘BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.
基金Supported by Nantong Municipal Health Commission,No.MSZ2022036.
文摘Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors(PEComas)because PEComas are mainly benign tumors and may not require surgical intervention.By analyzing the causes,properties and clinical manifestations of PEComas,we summarize the challenges and solutions in the diagnosis of PEComas.
文摘BACKGROUND The most common causes of scrotal enlargement in patients include primary tumor of the scrotum,inflammation,hydrocele of the tunica vaginalis,and indirect inguinal hernia;scrotal enlargement caused by external tumors of the scrotum is rare.The patient had both a greater omentum tumor and an inguinal hernia,and the tumor protruded into the scrotum through the hernia sac,which is even rarer.Moreover,omental tumors are mostly metastatic,and primary omental fibroma is rare.CASE SUMMARY Here,we report a rare case of a 25-year-old young man with scrotal enlargement and pain for 3 months.Preoperative examination and multidisciplinary discu-ssions considered intra-abdominal tumor displacement and inguinal hernia,and intraoperative exploration confirmed that the greater omentum tumor protruded into the scrotum.Therefore,tumor resection and tension-free inguinal hernia repair were performed.The final diagnosis was benign fibroma of the greater omentum accompanied by an indirect inguinal hernia.CONCLUSION This unusual presentation of a common inguinal hernia disease illustrates the necessity of performing detailed history taking,physical examination,and imaging before surgery.
文摘In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.
基金supported by the National Natural Science Foundation of China(Grant No.82173601)Yili&Jiangsu Joint Institute of Health(Grant No.yl2021ms02).
文摘The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.
文摘Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium homeostasis.Most commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and hypercalcemia.Brown tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical practice.The tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic mass.Furthermore,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone lesion.The diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and PTH.Although when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic tumors.Treatment of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical intervention.However,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.
基金Supported by the National Natural Science Foundation of China,No.82204994and Sanming Project of Medicine in Shenzhen,No.
文摘BACKGROUND Collision tumors involving the small intestine,specifically the combination of a hamartomatous tumor and a lipoma,are extremely rare.To our knowledge,no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine.CASE SUMMARY Here,we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm×32 mm×30 mm in the terminal ileum.Based on computed tomography scan findings,the mass was initially suspected to be a lipoma.A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line.A biopsy of the upper portion suggested a juvenile polyp(JP).Owing to the patient’s advanced age,multiple comorbidities,and poor surgical tolerance,a modified endoscopic submucosal dissection was performed.Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top,demonstrating evidence of rupture and associated bleeding.The patient’s overall health remained satisfactory,with no recurrence of hematochezia during the six-month follow-up period.CONCLUSION This case report provides new evidence for the understanding of gastrointestinal collision tumors,emphasizing their diverse clinical presentations and histopathological characteristics.It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.
文摘BACKGROUND This case of gestational gingival tumor is huge and extremely rare in clinical practice.As the growth location of this gingival tumor is in the upper anterior tooth area,it seriously affects the pregnant woman's speech and food,causing great pain to the patient.The use of Nd:YGA water mist laser to remove the gingival tumor resulted in minimal intraoperative bleeding,minimal adverse reactions,and good postoperative healing,which is worthy of clinical promotion and application.CASE SUMMARY The patient,a pregnant woman,reported a large lump in her mouth on the first day of postpartum treatment.Based on medical history and clinical examination,the diagnosis was diagnosed as gestational gingival tumor.Postoperative pathological biopsy also confirmed this diagnosis.The use of Nd:YAG water mist laser to remove the tumor resulted in minimal intraoperative bleeding,clear surgical field of view,short surgical time,and good postoperative healing.CONCLUSION In comparison to traditional surgery,Nd:YAG water mist laser surgery is minimally invasive,minimizes cell damage,reduces bleeding,ensures a clear field of vision,and virtually eliminates postoperative edema,carbonization,and the risk of cross infection.It has unique advantages in oral soft tissue surgery for pregnant patients.Therefore,the clinical application of Nd:YAG water mist laser for the treatment of gestational gingival tumors is an ideal choice.
基金The study was reviewed and approved by the Second Hospital of Shandong University Institutional Review Board,IRB No.KYLL-2023LW044.
文摘BACKGROUND Recently,vessels encapsulating tumor clusters(VETC)was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in an invasion independent manner,and was regarded as an independent risk factor for poor prognosis in hepatocellular carcinoma(HCC).AIM To develop and validate a preoperative nomogram using contrast-enhanced computed tomography(CECT)to predict the presence of VETC+in HCC.METHODS We retrospectively evaluated 190 patients with pathologically confirmed HCC who underwent CECT scanning and immunochemical staining for cluster of differentiation 34 at two medical centers.Radiomics analysis was conducted on intratumoral and peritumoral regions in the portal vein phase.Radiomics features,essential for identifying VETC+HCC,were extracted and utilized to develop a radiomics model using machine learning algorithms in the training set.The model’s performance was validated on two separate test sets.Receiver operating characteristic(ROC)analysis was employed to compare the identified performance of three models in predicting the VETC status of HCC on both training and test sets.The most predictive model was then used to constructed a radiomics nomogram that integrated the independent clinical-radiological features.ROC and decision curve analysis were used to assess the performance characteristics of the clinical-radiological features,the radiomics features and the radiomics nomogram.RESULTS The study included 190 individuals from two independent centers,with the majority being male(81%)and a median age of 57 years(interquartile range:51-66).The area under the curve(AUC)for the combined radiomics features selected from the intratumoral and peritumoral areas were 0.825,0.788,and 0.680 in the training set and the two test sets.A total of 13 features were selected to construct the Rad-score.The nomogram,combining clinicalradiological and combined radiomics features could accurately predict VETC+in all three sets,with AUC values of 0.859,0.848 and 0.757.Decision curve analysis revealed that the radiomics nomogram was more clinically useful than both the clinical-radiological feature and the combined radiomics models.CONCLUSION This study demonstrates the potential utility of a CECT-based radiomics nomogram,incorporating clinicalradiological features and combined radiomics features,in the identification of VETC+HCC.
基金The study was reviewed and approved by the Nippon Medical School,Graduate School of Medicine Institutional Review Board(Approval No.30-02-1077).
文摘BACKGROUND Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection(ESD);however,the preoperative evaluation of tumor size is often different from histological assessment.Analyzing influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable ESD.METHODS This was a retrospective study conducted at a single institution.A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were collected.We first assessed the difference in size with an absolute per-centage of the scaling discrepancy.Subsequently,we compared the clinicopatho-logical characteristics of the correct scaling group(>-33%and<33%)with that of the incorrect scaling group(<-33%or>33%),which was further subdivided into the underscaling group(-33%or less of the discrepancy)and overscaling group(33%or more of the discrepancy),respectively.As secondary outcome measures,parameters on size estimation were compared between the underscaling and correct scaling groups,as well as between the overscaling and correct scaling groups.Finally,multivariate analysis was performed in terms of the following relevant parameters on size estimation:Pathological size,location,and possible influential factors(P<0.1)in the univariate analysis.RESULTS The mean of absolute percentage in the scaling discordance was 21%,and 91 lesions were considered to be incorrectly estimated in size.The incorrect scaling was significantly remarkable in larger lesions(40 mm vs 28 mm;P<0.001)and less experience(P<0.001),and these two factors were influential on the underscaling(75 lesions;P<0.001).Conversely,compared with the correct scaling group,16 lesions in the overscaling group were significantly small(20 mm vs 28 mm;P<0.001),and the small lesion size was influential on the overscaling(P=0.002).CONCLUSION Lesions indicated for colorectal ESD tended to be underestimated in large tumors,but overestimated in small ones.This discrepancy appears worth understanding for optimal procedural preparation.
文摘Background:This study aimed to investigate the potential of intratumoral microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers as predictive biomarkers for antitumor efficacy in patients with non-small cell lung cancer.Methods:This study observed patients with metastatic non-driver mutation non-small cell lung cancer who were initially diagnosed at the First Affiliated Hospital of Dalian Medical University’s Department of Oncology from August 2021 to July 2022 and completed at least four cycles of chemotherapy combined with immune checkpoint inhibitor treatment.Lung biopsy tissues,fecal,and peripheral blood samples were collected from these patients.Based on the efficacy of the combined chemotherapy and immunotherapy,patients were divided into an effective group and an ineffective group.The tumor microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers were compared between the two groups.The lung and fecal microbiota were analyzed using 16S rRNA high-throughput sequencing.Flow cytometry was used to detect T-cell subsets,and enzyme-linked immunosorbent assay was employed to measure inflammatory factors.Results:A total of 21 patients were observed.There were significant differences in the tumor microbiota between the responsive and non-responsive groups,particularly the proportion of the genera Sphingomonas and Pseudomonas.The gut microbiome composition changed after treatment,but there were no differences between the two groups before treatment.There were no significant differences in T-cell subsets and inflammatory markers between the responsive and non-responsive groups.Conclusion:The composition of intratumoral microbiota in non-small cell lung cancer patients may serve as an indicator of response to chemotherapy combined with immunotherapy.The predictive value of gut microbiota,T-cell subsets,and inflammatory markers appears limited.Future research should further validate the predictive role of changes in gut microbiota on treatment outcomes.
基金the National Key R&D Program of China(Grant Nos.2020YFA0509400 and 2019YFA0110300 to JC)the National Natural Science Foundation of China(Grant Nos.82150117 and 82071745 to JC and 31900570 to GJ)+2 种基金the Nanshan Scholarship of Guangzhou Medical University start-up fund(to GJ)the Science and Technology Program of Guangzhou(Grant No.202002030069 to JC)the Guangdong Project(Grant No.2019QN01Y212 to JC)。
文摘Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residing in tumor tissues are commonly known as tumor-associated macrophages(TAMs)and promote or inhibit tumor growth depending on the activation state2.
文摘This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors(pan-NETs),emphasizing tailored approaches for specific subtypes.Cytoreductive surgery and somatostatin analogs(SSAs)play pivotal roles in managing tumors,while palliative options such as molecular targeted therapy,peptide receptor radionuclide therapy,and chemotherapy are reserved for SSA-refractory patients.Gastrinomas,insul-inomas,glucagonomas,carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies.Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research.This review underscores the evolving landscape of pan-NET treatment,offering renewed hope and improved outcomes for patients facing this complex disease.
基金funded through Researchers Supporting Project Number(RSPD2024R996)King Saud University,Riyadh,Saudi Arabia。
文摘Breast cancer detection heavily relies on medical imaging, particularly ultrasound, for early diagnosis and effectivetreatment. This research addresses the challenges associated with computer-aided diagnosis (CAD) of breastcancer fromultrasound images. The primary challenge is accurately distinguishing between malignant and benigntumors, complicated by factors such as speckle noise, variable image quality, and the need for precise segmentationand classification. The main objective of the research paper is to develop an advanced methodology for breastultrasound image classification, focusing on speckle noise reduction, precise segmentation, feature extraction, andmachine learning-based classification. A unique approach is introduced that combines Enhanced Speckle ReducedAnisotropic Diffusion (SRAD) filters for speckle noise reduction, U-NET-based segmentation, Genetic Algorithm(GA)-based feature selection, and Random Forest and Bagging Tree classifiers, resulting in a novel and efficientmodel. To test and validate the hybrid model, rigorous experimentations were performed and results state thatthe proposed hybrid model achieved accuracy rate of 99.9%, outperforming other existing techniques, and alsosignificantly reducing computational time. This enhanced accuracy, along with improved sensitivity and specificity,makes the proposed hybrid model a valuable addition to CAD systems in breast cancer diagnosis, ultimatelyenhancing diagnostic accuracy in clinical applications.
基金Institutional Fund Projects under Grant No.(IFPIP:801-830-1443)The author gratefully acknowledges technical and financial support provided by the Ministry of Education and King Abdulaziz University,DSR,Jeddah,Saudi Arabia.
文摘Brain tumors are a pressing public health concern, characterized by their high mortality and morbidity rates.Nevertheless, the manual segmentation of brain tumors remains a laborious and error-prone task, necessitatingthe development of more precise and efficient methodologies. To address this formidable challenge, we proposean advanced approach for segmenting brain tumorMagnetic Resonance Imaging (MRI) images that harnesses theformidable capabilities of deep learning and convolutional neural networks (CNNs). While CNN-based methodshave displayed promise in the realm of brain tumor segmentation, the intricate nature of these tumors, markedby irregular shapes, varying sizes, uneven distribution, and limited available data, poses substantial obstacles toachieving accurate semantic segmentation. In our study, we introduce a pioneering Hybrid U-Net framework thatseamlessly integrates the U-Net and CNN architectures to surmount these challenges. Our proposed approachencompasses preprocessing steps that enhance image visualization, a customized layered U-Net model tailoredfor precise segmentation, and the inclusion of dropout layers to mitigate overfitting during the training process.Additionally, we leverage the CNN mechanism to exploit contextual information within brain tumorMRI images,resulting in a substantial enhancement in segmentation accuracy.Our experimental results attest to the exceptionalperformance of our framework, with accuracy rates surpassing 97% across diverse datasets, showcasing therobustness and effectiveness of our approach. Furthermore, we conduct a comprehensive assessment of ourmethod’s capabilities by evaluating various performance measures, including the sensitivity, Jaccard-index, andspecificity. Our proposed model achieved 99% accuracy. The implications of our findings are profound. Theproposed Hybrid U-Net model emerges as a highly promising diagnostic tool, poised to revolutionize brain tumorimage segmentation for radiologists and clinicians.
基金National Nature Science Foundation for young scientist in Jiangsu Province(BK20220729).
文摘Cancer,a disease as intricate as it is devastating,continues to challenge the medical and scientific community[1].Its complex nature is epitomized by the tumor microenvironment and tumor heterogeneity.As we delve deeper into the realms of cancer research,the advent of transcriptome analysis has emerged as a powerful torchbearer,illuminating our understanding of these enigmatic facets of cancer biology[2].
文摘BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
基金Liuzhou City's Top Ten Hundred Talents Project,Liuzhou Science and Technology Project(Grant Nos.2021CBC0126 and 2021CBC0123)Guangxi Zhuang Autonomous Region Health and Family Planning Commission Projects(Z20210561,Z20210903)+1 种基金liuzhou Scienceand Technology Plan Projects(2021CBC0121,2021CBC0128).
文摘Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.
基金supported by National Major Science and Technology Projects of China 2017ZX10105015-001-002。
文摘Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.