AIM:To address the diagnostic value of the regular arrangement of collecting venules(RAC)among old age patients. METHODS:A total of 390 consecutive patients whose Helicobacter pylori(H.pylori)status was known and who ...AIM:To address the diagnostic value of the regular arrangement of collecting venules(RAC)among old age patients. METHODS:A total of 390 consecutive patients whose Helicobacter pylori(H.pylori)status was known and who received upper gastrointestinal endoscopy,were retrospectively studied for the presence or absence of RAC as well as gastric mucosal atrophy.The sensitivity, specificity,positive predictive value,negative predic-tive value and accuracy of RAC to detect normal gastric mucosa were assessed and were compared among two different age groups of patients. RESULTS:The mean age±standard deviation(SD)of included patients(n=390),was 62.9±13 years.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of RAC to detect normal gastric mucosa were 91.7%,66.1%,18.8%,99%and 68.1%respectively.Although the sensitivity,specificity,positive predictive value,negative predictive value and accuracy of RAC among patients<60 years(n= 139)was 94.7%,71.2%,46.2%,98.1%and 76.1%,respectively,it was 80%,64.3%,5.1%,93%and 64.6%, respectively,among patients≥60 years(n=251). Younger Patients(<60 years),have highly significant rates of RAC sensitivity,positive predictive value,and accuracy(P≤0.001,≤0.001 and≤0.02,respectively).Older patients had highly significant rates of H. pylori infection and gastric mucosal atrophy(P≤0.01). CONCLUSION:Although RAC is a valuable sign for real-time identification of normal gastric mucosa,its accuracy seems to be affected by the patient's age.展开更多
Background:Tertiary lymphoid structure(TLS),ectopic lymphoid aggregates formed in response to chronic inflammation,have emerged as potential prognostic biomarkers and mediators of anti-tumor immunity in various cancer...Background:Tertiary lymphoid structure(TLS),ectopic lymphoid aggregates formed in response to chronic inflammation,have emerged as potential prognostic biomarkers and mediators of anti-tumor immunity in various cancers.However,the heterogeneity of TLS spatial distribution,maturity,and their prognostic and immunological significance in prostate cancer(PCa)remain poorly characterized.Methods:We utilized immunohistochemistry,multispectral fluorescence immunohistochemistry(mIHC)and spatial multi-omics analyses to evaluate the heterogeneity of TLS and its relationship with immune components in the tumor microenvironment(TME).Prognostic implications were assessed in 701 PCa patients from the TCGA and Fudan University Shanghai Cancer Center cohorts.The association between TLS heterogeneity and immunoreactivity was assessed through the quantification of immune cell infiltration.CellTreck and robust cell type decomposition deconvolution algorithms were used to decipher the colocalization features of each cell,cell-cell communication and ligand-receptor features within TLS regions.Results:In PCa,TLSs were detected in approximately 20%of patients across both cohorts,with intratumoral TLS(intra-TLS)being twice as prevalent as peritumoral TLS(peri-TLS).Patients harboring intra-TLS exhibited significantly longer disease-free and progression-free survival.Compared to peri-TLS,intra-TLS were more mature,characterized by increased T-effector cell infiltration,activation of interferon pathways,and the presence of follicular dendritic cell centers and B cell aggregates.Notably,compared with immature TLS,mature TLS were markedly associated with reduced PD-L1 expression,lower regulatory T cells(Tregs)infiltration,and increased high endothelial venules(HEVs)density,indicative of an immunologically active microenvironment.Spatial multi-omics analysis revealed that mature TLS exhibited enriched immune cell diversity and HEVs density,suggesting enhanced anti-tumor immunity.Furthermore,cell-cell communication analysis identified significant interactions between CCL5+dendritic cells and ACKR1+activated B cells within mature TLS,reflecting the enhanced capacity of mature TLS to orchestrate robust antigen presentation and B-cell-driven immune responses.Conclusions:In conclusion,this study highlights the prognostic and immunological implications of TLS heterogeneity in PCa,demonstrating that the spatial distribution and maturity of TLSs are closely linked to TME activation and improved clinical outcomes.These findings provide novel insights into the immune landscape of PCa and establish a foundation for immune-based precision stratification and therapeutic development.展开更多
Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infecti...Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infection and evaluate gastric cancer risk.In 2013,the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification,a new grading system for endoscopic gastritis.The Kyoto classification organized endoscopic findings related to H.pylori infection.The Kyoto classification score is the sum of scores for five endoscopic findings(atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness with or without regular arrangement of collecting venules)and ranges from 0 to 8.Atrophy,intestinal metaplasia,enlarged folds,and nodularity contribute to gastric cancer risk.Diffuse redness and regular arrangement of collecting venules are related to H.pylori infection status.In subjects without a history of H.pylori eradication,the infection rates in those with Kyoto scores of 0,1,and≥2 were 1.5%,45%,and 82%,respectively.A Kyoto classification score of 0 indicates no H.pylori infection.A Kyoto classification score of 2 or more indicates H.pylori infection.Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8,respectively.A Kyoto classification score of 4 or more might indicate gastric cancer risk.展开更多
To accelerate our endeavors to overcome cancer,Chinese Journal of Cancer has launched a program of publishing 150most important questions in cancer research and clinical oncology.In this article,nine more questions ar...To accelerate our endeavors to overcome cancer,Chinese Journal of Cancer has launched a program of publishing 150most important questions in cancer research and clinical oncology.In this article,nine more questions are presented as followed.Question 6.Why do nasopharyngeal carcinomas rarely metastasize to the brain?Question 7.Can distant spread of cancer cells be blocked by inhibiting the remodeling of high endothelial venules in the sentinel lymph node?Question 8.What sort of live-imaging techniques can be developed to directly observe the dynamic processes of metastasis?Question 9.How does chronic hepatitis prevent liver metastasis from colorectal cancer?Question 10.How many types of host cells contribute to forming the pre-metastatic niche in the lung favorable for metastasis?Question 11.Why do cancers rarely metastasize to the small bowel?Question 12.Why do glioblastomas rarely metastasize outside the central nervous system?Question 13.Despite increased understanding of the molecular genetic events leading to the development and progression of high-grade gliomas,these tumors are the most therapeutically refractory among all human cancers.What then would be the most effective therapeutic approaches to treat what in essence can be regarded as a whole brain malignancy,since even a surgical resection of greater than 99%of tumor tissues is invariably associated with recurrence?Question 14.The blood–brain barrier(BBB)effectively limits a wide variety of potential therapeutic agents from reaching glioma cells widely dispersed in the brain.What therapeutic approaches can be used to breach the BBB and allow therapeutic agents to seek out and kill these tumor cells?展开更多
Endoscopic visualisation of gastric atrophy is usually not feasible with conven.tional endoscopy. Magnifying endoscopy is helpful to analyze the subepithelial microvascular architecture as well as the mucosal surface ...Endoscopic visualisation of gastric atrophy is usually not feasible with conven.tional endoscopy. Magnifying endoscopy is helpful to analyze the subepithelial microvascular architecture as well as the mucosal surface microstructure without tissue biopsy. Using this technique we were able to describe the normal gastric microvasculature pattern and we also identified characteristic patterns in two cases of autoimmune atrophic gastritis.展开更多
Heat shock proteins (HSPs) serve to correct proteins’ conformation, send the damaged proteins for degradation (quality control function). Heat shock factors (HSFs) are their transcription factors. The protein complex...Heat shock proteins (HSPs) serve to correct proteins’ conformation, send the damaged proteins for degradation (quality control function). Heat shock factors (HSFs) are their transcription factors. The protein complexes mTOR1 and 2 (with the same core mTOR), the phosphoinositide-dependent protein kinase-1 (PDK1), the seine/threonine-specific protein kinase (Akt), HSF1, plus their associated proteins form a network participating in protein synthesis, bio-energy generation, signaling for apoptosis with the help of HSPs. A cancer cell synthesizes proteins at fast rate and needs more HSPs to work on quality control. Shutting down this network would lead to cell death. Thus inhibitors of mTOR (mTORI) and inhibitors of HSPs (HSPI) could drive cancer cell to apoptosis—a “passive approach”. On the other hand, HSPs form complexes with polypeptides characteristic of the cancer cells;on excretion from the cell, they becomes antigens for the immunity cells, eventually leading to maturation of the cytotoxic T cells, forming the basic principle of preparing cancer-specific, person-specific vaccine. Recent finding shows that HSP70 can penetrate cancer cell and expel its analog to extracellular region, giving the hope to prepare a non-person-specific vaccine covering a variety of cancers. Activation of anti-cancer immunity is the “active approach”. On the other hand, mild hyperthermia, with increase of intracellular HSPs, has been found to activate the immunity response, and demonstrate anti-cancer effects. There are certain “mysteries” behind the mechanisms of the active and passive approaches. We analyze the mechanisms involved and provide explanations to some mysteries. We also suggest future research to improve our understanding of these two approaches, in which HSPs play many roles.展开更多
文摘AIM:To address the diagnostic value of the regular arrangement of collecting venules(RAC)among old age patients. METHODS:A total of 390 consecutive patients whose Helicobacter pylori(H.pylori)status was known and who received upper gastrointestinal endoscopy,were retrospectively studied for the presence or absence of RAC as well as gastric mucosal atrophy.The sensitivity, specificity,positive predictive value,negative predic-tive value and accuracy of RAC to detect normal gastric mucosa were assessed and were compared among two different age groups of patients. RESULTS:The mean age±standard deviation(SD)of included patients(n=390),was 62.9±13 years.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of RAC to detect normal gastric mucosa were 91.7%,66.1%,18.8%,99%and 68.1%respectively.Although the sensitivity,specificity,positive predictive value,negative predictive value and accuracy of RAC among patients<60 years(n= 139)was 94.7%,71.2%,46.2%,98.1%and 76.1%,respectively,it was 80%,64.3%,5.1%,93%and 64.6%, respectively,among patients≥60 years(n=251). Younger Patients(<60 years),have highly significant rates of RAC sensitivity,positive predictive value,and accuracy(P≤0.001,≤0.001 and≤0.02,respectively).Older patients had highly significant rates of H. pylori infection and gastric mucosal atrophy(P≤0.01). CONCLUSION:Although RAC is a valuable sign for real-time identification of normal gastric mucosa,its accuracy seems to be affected by the patient's age.
基金supported by grants from Non-communicable Chronic Diseases-National Science and Technology Major Project(grant number:2023ZD0510300)National Natural Science Foundation of China(grant numbers:82403377,82473192,82474506,81760463)+4 种基金China Postdoctoral Science Foundation(grant number:2024M750538)Shanghai Anticancer Association EYAS PROJECT(grant numbers:SACA-CY23A02,SACA-CY23C04)Beijing Xisike Clinical Oncology Research Foundation(grant numbers:Y-Young2024-0138,Y-HR2020MS-0948)Central Government Funds for Guiding Local Scientific and Technological Development(grant number:2021ZY0037)Natural Science Found of In-ner Mongolia(grant number:2023MS08015).
文摘Background:Tertiary lymphoid structure(TLS),ectopic lymphoid aggregates formed in response to chronic inflammation,have emerged as potential prognostic biomarkers and mediators of anti-tumor immunity in various cancers.However,the heterogeneity of TLS spatial distribution,maturity,and their prognostic and immunological significance in prostate cancer(PCa)remain poorly characterized.Methods:We utilized immunohistochemistry,multispectral fluorescence immunohistochemistry(mIHC)and spatial multi-omics analyses to evaluate the heterogeneity of TLS and its relationship with immune components in the tumor microenvironment(TME).Prognostic implications were assessed in 701 PCa patients from the TCGA and Fudan University Shanghai Cancer Center cohorts.The association between TLS heterogeneity and immunoreactivity was assessed through the quantification of immune cell infiltration.CellTreck and robust cell type decomposition deconvolution algorithms were used to decipher the colocalization features of each cell,cell-cell communication and ligand-receptor features within TLS regions.Results:In PCa,TLSs were detected in approximately 20%of patients across both cohorts,with intratumoral TLS(intra-TLS)being twice as prevalent as peritumoral TLS(peri-TLS).Patients harboring intra-TLS exhibited significantly longer disease-free and progression-free survival.Compared to peri-TLS,intra-TLS were more mature,characterized by increased T-effector cell infiltration,activation of interferon pathways,and the presence of follicular dendritic cell centers and B cell aggregates.Notably,compared with immature TLS,mature TLS were markedly associated with reduced PD-L1 expression,lower regulatory T cells(Tregs)infiltration,and increased high endothelial venules(HEVs)density,indicative of an immunologically active microenvironment.Spatial multi-omics analysis revealed that mature TLS exhibited enriched immune cell diversity and HEVs density,suggesting enhanced anti-tumor immunity.Furthermore,cell-cell communication analysis identified significant interactions between CCL5+dendritic cells and ACKR1+activated B cells within mature TLS,reflecting the enhanced capacity of mature TLS to orchestrate robust antigen presentation and B-cell-driven immune responses.Conclusions:In conclusion,this study highlights the prognostic and immunological implications of TLS heterogeneity in PCa,demonstrating that the spatial distribution and maturity of TLSs are closely linked to TME activation and improved clinical outcomes.These findings provide novel insights into the immune landscape of PCa and establish a foundation for immune-based precision stratification and therapeutic development.
文摘Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infection and evaluate gastric cancer risk.In 2013,the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification,a new grading system for endoscopic gastritis.The Kyoto classification organized endoscopic findings related to H.pylori infection.The Kyoto classification score is the sum of scores for five endoscopic findings(atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness with or without regular arrangement of collecting venules)and ranges from 0 to 8.Atrophy,intestinal metaplasia,enlarged folds,and nodularity contribute to gastric cancer risk.Diffuse redness and regular arrangement of collecting venules are related to H.pylori infection status.In subjects without a history of H.pylori eradication,the infection rates in those with Kyoto scores of 0,1,and≥2 were 1.5%,45%,and 82%,respectively.A Kyoto classification score of 0 indicates no H.pylori infection.A Kyoto classification score of 2 or more indicates H.pylori infection.Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8,respectively.A Kyoto classification score of 4 or more might indicate gastric cancer risk.
文摘To accelerate our endeavors to overcome cancer,Chinese Journal of Cancer has launched a program of publishing 150most important questions in cancer research and clinical oncology.In this article,nine more questions are presented as followed.Question 6.Why do nasopharyngeal carcinomas rarely metastasize to the brain?Question 7.Can distant spread of cancer cells be blocked by inhibiting the remodeling of high endothelial venules in the sentinel lymph node?Question 8.What sort of live-imaging techniques can be developed to directly observe the dynamic processes of metastasis?Question 9.How does chronic hepatitis prevent liver metastasis from colorectal cancer?Question 10.How many types of host cells contribute to forming the pre-metastatic niche in the lung favorable for metastasis?Question 11.Why do cancers rarely metastasize to the small bowel?Question 12.Why do glioblastomas rarely metastasize outside the central nervous system?Question 13.Despite increased understanding of the molecular genetic events leading to the development and progression of high-grade gliomas,these tumors are the most therapeutically refractory among all human cancers.What then would be the most effective therapeutic approaches to treat what in essence can be regarded as a whole brain malignancy,since even a surgical resection of greater than 99%of tumor tissues is invariably associated with recurrence?Question 14.The blood–brain barrier(BBB)effectively limits a wide variety of potential therapeutic agents from reaching glioma cells widely dispersed in the brain.What therapeutic approaches can be used to breach the BBB and allow therapeutic agents to seek out and kill these tumor cells?
基金Supported by an unrestricted grant to Dr. Ragunath by Olympus Keymed United Kingdom
文摘Endoscopic visualisation of gastric atrophy is usually not feasible with conven.tional endoscopy. Magnifying endoscopy is helpful to analyze the subepithelial microvascular architecture as well as the mucosal surface microstructure without tissue biopsy. Using this technique we were able to describe the normal gastric microvasculature pattern and we also identified characteristic patterns in two cases of autoimmune atrophic gastritis.
文摘Heat shock proteins (HSPs) serve to correct proteins’ conformation, send the damaged proteins for degradation (quality control function). Heat shock factors (HSFs) are their transcription factors. The protein complexes mTOR1 and 2 (with the same core mTOR), the phosphoinositide-dependent protein kinase-1 (PDK1), the seine/threonine-specific protein kinase (Akt), HSF1, plus their associated proteins form a network participating in protein synthesis, bio-energy generation, signaling for apoptosis with the help of HSPs. A cancer cell synthesizes proteins at fast rate and needs more HSPs to work on quality control. Shutting down this network would lead to cell death. Thus inhibitors of mTOR (mTORI) and inhibitors of HSPs (HSPI) could drive cancer cell to apoptosis—a “passive approach”. On the other hand, HSPs form complexes with polypeptides characteristic of the cancer cells;on excretion from the cell, they becomes antigens for the immunity cells, eventually leading to maturation of the cytotoxic T cells, forming the basic principle of preparing cancer-specific, person-specific vaccine. Recent finding shows that HSP70 can penetrate cancer cell and expel its analog to extracellular region, giving the hope to prepare a non-person-specific vaccine covering a variety of cancers. Activation of anti-cancer immunity is the “active approach”. On the other hand, mild hyperthermia, with increase of intracellular HSPs, has been found to activate the immunity response, and demonstrate anti-cancer effects. There are certain “mysteries” behind the mechanisms of the active and passive approaches. We analyze the mechanisms involved and provide explanations to some mysteries. We also suggest future research to improve our understanding of these two approaches, in which HSPs play many roles.
