Radiochemotherapy-induced oral mucositis(OM)is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy.Erosion and ulcers are the main features of OM that seriously affe...Radiochemotherapy-induced oral mucositis(OM)is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy.Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment.To date,differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties,which has increased the uncertainty of treatment effects.On the basis of current research evidence,this expert consensus outlines risk factors,clinical manifestations,clinical grading,ancillary examinations,diagnostic basis,prevention and treatment strategies and efficacy indicators for OM.In addition to strategies such as basic oral care,antiinflammatory and analgesic agents,anti-infective agents,pro-healing agents,and photobiotherapy recommended in previous guidelines,we also emphasize the role of traditional Chinese medicine in OM prevention and treatment.This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention,diagnosis,and treatment,standardizing clinical practice,reducing OM occurrence,promoting healing,and improving the quality of life of patients.展开更多
Objective:The previously integrated tumor-inflammation-nutrition(HI-GC)score has demonstrated dynamic monitoring value for recurrence and clinical decision-making in patients with postsurgical gastric cancer(GC).Howev...Objective:The previously integrated tumor-inflammation-nutrition(HI-GC)score has demonstrated dynamic monitoring value for recurrence and clinical decision-making in patients with postsurgical gastric cancer(GC).However,its failure to incorporate clinical-pathological factors limits its capacity for baseline risk assessment.This study aimed to develop a model that accurately identifies patients for adjuvant chemotherapy and dynamically evaluates recurrence risk.Methods:This retrospective,multicenter,longitudinal cohort study,spanning nine hospitals,included 7,085patients with GC post-radical gastrectomy.A baseline prognostic model was constructed using 117 machinelearning algorithms.The dynamic survival decision tree model(dy SDT)was employed to combine the baseline model with the HI-GC score.Results:A Cox regression model incorporating six factors was used to create a nomogram[Harrell's C-index:training cohort:0.765;95%confidence interval(95%CI):0.747,0.783;validation set:0.810;95%CI:0.747,0.783],including p T stage,positive lymph node ratio,p N stage,tumor size,age,and adjuvant chemotherapy.The best-performing machine learning model exhibited similar predictive accuracy to the nomogram(C-index:0.770).For the short-term dy SDT at 1 month,the mortality hazard ratios(HRs)for groups IIa,IIb,andⅢwere 2.61(95%CI:2.24,3.04),5.02(95%CI:4.15,6.06),and 8.88(95%CI:7.57,10.42),respectively,compared to group I.Stratified analysis revealed a significant interaction between adjuvant chemotherapy and overall survival in each subgroup(P<0.001).The long-term dy SDT at 1 year showed HRs of 3.25(95%CI:2.12,4.97)for group II,6.73(95%CI:4.29,10.56)for groupⅢa,and 17.88(95%CI:10.71,29.84)for groupⅢb.Conclusions:The dy SDT effectively stratifies mortality risk and provides valuable assistance in clinical decision-making after gastrectomy.展开更多
Objective:The systemic inflammation index and body mass index(BMI)are easily accessible markers that can predict mortality.However,the prognostic value of the combined use of these two markers remains unclear.The goal...Objective:The systemic inflammation index and body mass index(BMI)are easily accessible markers that can predict mortality.However,the prognostic value of the combined use of these two markers remains unclear.The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.Methods:A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included.Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio(NLR).High systemic inflammation was defined as NLR≥3,and underweight was defined as BMI<18.5 kg/m2.Results:Among 2,542 patients,NLR≥3 and underweight were common[627(25%)and 349(14%),respectively].In the entire cohort,NLR≥3 or underweight independently predicted overall survival(OS)[hazard ratio(HR):1.236,95%confidence interval(95%CI):1.069–1.430;and HR:1.600,95%CI:1.350–1.897,respectively]and recurrence-free survival(RFS)(HR:1.230,95%CI:1.054–1.434;and HR:1.658,95%CI:1.389–1.979,respectively).Patients with both NLR≥3 and underweight(vs.neither)had much worse OS(HR:2.445,95%CI:1.853–3.225)and RFS(HR:2.405,95%CI:1.802–3.209).Furthermore,we observed similar results in subgroup analyses according to pathological stage,age,and postoperative chemotherapy.Conclusions:Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival.Underweight combined with severe inflammation could enhance prognostication.Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.展开更多
Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
Cancer is one of the leading causes of death worldwide.The early diagnosis of cancer remains one of the greatest cancer research challenges.Epigenetic alterations,such as altered DNA methylation,that occur during the ...Cancer is one of the leading causes of death worldwide.The early diagnosis of cancer remains one of the greatest cancer research challenges.Epigenetic alterations,such as altered DNA methylation,that occur during the early stages of carcinogenesis have been proposed as candidate cancer biomarkers.In recent years detection of small amounts of methylated DNA in samples,including blood and stool,has demonstrated the feasibility of DNA methylation as a molecular cancer biomarker.The translational promise of aberrant DNA methylation includes screening and detecting cancer,evaluating prognosis,assessing treatment efficacy,and detecting minimal residual disease(Figure 1).展开更多
Large language models(LLMs)such as ChatGPT,Claude,Llama,and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases.With their exceptional long-context reasoning capabiliti...Large language models(LLMs)such as ChatGPT,Claude,Llama,and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases.With their exceptional long-context reasoning capabilities,LLMs are proficient in clinically relevant tasks,particularly in medical text analysis and interactive dialogue.They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results.Building on their image-recognition abilities,multimodal LLMs(MLLMs)show promising potential for diagnosis based on radiography,chest computed tomography(CT),electrocardiography(ECG),and common pathological images.These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records.Despite these promising developments,significant challenges persist regarding the use of LLMs in medicine,including concerns regarding algorithmic bias,the potential for hallucinations,and the need for rigorous clinical validation.Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice.This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking,ethical supervision,and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs.Future directions include the integration of proprietary clinical knowledge,the investigation of open-source and customized models,and the evaluation of real-time effects in clinical diagnosis and treatment practices.展开更多
Chimeric Antigen Receptor(CAR)T cell therapy has demonstrated significant clinical potential in solid tumors,including glioblastoma,gliomas and gastrointestinal cancers,extending its success from hematological maligna...Chimeric Antigen Receptor(CAR)T cell therapy has demonstrated significant clinical potential in solid tumors,including glioblastoma,gliomas and gastrointestinal cancers,extending its success from hematological malignancies to solid tumors,and revolutionizing cancer immunotherapy.Although response rates in the majority of solid tumors have been limited,promising results are emerging.Identifying potential factors that might hinder the clinical efficacy of CAR-T cell therapy in solid tumors and learning from successful trials are crucial for improving efficacy and facilitating its clinical application.展开更多
The success of chimeric antigen receptor T(CAR-T)cells therapy for hematologic malignancies has sparked interest in potential applications for solid tumors.However,unlike the homogeneous,dynamic,and nutrient-rich hema...The success of chimeric antigen receptor T(CAR-T)cells therapy for hematologic malignancies has sparked interest in potential applications for solid tumors.However,unlike the homogeneous,dynamic,and nutrient-rich hematologic environment,CAR-T cells must overcome the complex tumor microenvironment.Ensuring efficient contact with tumor cells remains a primary challenge to enhance the efficacy of CAR-T cell therapy.Abnormal tumor angiogenesis,disordered chemokine production,dense extracellular matrix,and stromal cells all act as biological barriers that hinder contact of CAR-T cells with tumor cells.This review summarizes specific strategies to promote vascular normalization,modulate chemokine production,target physical barriers,combine different therapeutic approaches,and innovative cell delivery methods to enhance infiltration of CAR-T cells into solid tumors.These strategies will help to overcome current limitations and enhance the effectiveness of CAR-T cell therapy for solid tumors.展开更多
Background Antitumor drugs(such as chemotherapy,targeted therapy,immunotherapy,etc.)and local treatments like surgery and radiotherapy are widely used in cancer treatment,but they often carry the risk of liver injury,...Background Antitumor drugs(such as chemotherapy,targeted therapy,immunotherapy,etc.)and local treatments like surgery and radiotherapy are widely used in cancer treatment,but they often carry the risk of liver injury,which seriously affects the prognosis and quality of life of patients.Therefore,liver protection is of crucial importance in cancer treatment.Methods Relevant experts organized by the Oncology Hepatology Committee of China Anti-Cancer Association Association formulated this guideline based on the latest research achievements and clinical practice experience at home and abroad,aiming to provide comprehensive and systematic guidance for clinicians on liver protection.Results This guideline elaborates on the importance of liver protection during cancer treatment,comprehensively introduces the pathophysiological mechanisms,diagnosis,treatment,and preventive measures of antitumor treatment-related liver injury.Conclusion This guideline is helpful for clinicians to formulate individualized treatment plans,improve the treatment outcome and quality of life of cancer patients,and provides an important reference for the clinical practice of liver protection in cancer treatment.展开更多
As some studies have reported that strategies targeting the gut microbiota such as fecal microbiota transplantation(FMT) with or without other microecological therapy might have efficacy in treating slow transit const...As some studies have reported that strategies targeting the gut microbiota such as fecal microbiota transplantation(FMT) with or without other microecological therapy might have efficacy in treating slow transit constipation(STC), we conducted a singlecenter, open-label trial to study the long-term effect of FMT combined with soluble dietary fiber(pectin) on STC. Thirty-one adult patients with STC were enrolled into the trial. Patients received 6-day FMT procedures repeatedly for the first 3 months and soluble dietary fiber(pectin) daily during the follow-up. The rate of clinical remission and improvement, stool consistency, the Wexner constipation scale, and assessment of constipation-related symptoms were evaluated at week 4 and 1 year later. The clinical remission and improvement rates at week 4 were 69.0%(20/29) and 75.9%(22/29), respectively. At the end of the study,48.3%(14/29) of patients continued to have at least three complete spontaneous bowel movements per week and 58.6%(17/29)of patients showed clinical improvements. Stool consistency, the Wexner constipation scale, and constipation symptoms improved both at short-term and long-term follow-up. The results indicated that FMT in combination with soluble dietary fiber(pectin) had both short-term and long-term efficacy in treating STC.展开更多
Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in China.DNA damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellul...Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in China.DNA damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses;however,its critical role in GC remains poorly understood.The present study aimed to investigate the poten-tial relationship and the underlying mechanism between DDIT4 and GC development.Methods:We used western blotting,real-time polymerase chain reaction,and immunohistochemical or immunoflu-orescence to determine DDIT4 expression in GC cells and tissues.High-content screening,cell counting kit-8 assays,colony formation,and in vivo tumorigenesis assays were performed to evaluate cell proliferation.Flow cytometry was used to investigate cell apoptosis and cell cycle distribution.Results:DDIT4 was upregulated in GC cells and tissue.Furthermore,downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle arrest.In contrast,ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated chemosensitivity.Further analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation,and increased chemosensitivity upon DDIT4 downregulation.Conclusion:DDIT4 promotes GC proliferation and tumorigenesis,providing new insights into the role of DDIT4 in the tumorigenesis of human GC.展开更多
Background and aim:Gutmicrobiotamay contribute to regulate colonicmotility,which is involved in the etiology of constipation.Fecalmicrobiota transplantation(FMT)has been demonstrated to restore intestinal homeostasis....Background and aim:Gutmicrobiotamay contribute to regulate colonicmotility,which is involved in the etiology of constipation.Fecalmicrobiota transplantation(FMT)has been demonstrated to restore intestinal homeostasis.The aimof this study was to evaluate the clinical outcomes and prognostic factors of FMT for the treatment of slow transit constipation(STC).Methods:Fifty-two patients with STC received standardized FMT and were followed up for 6 months.Bowel habit,colonic transit time,constipation-related symptoms(PAC-SYM score),quality of life(PAC-QOL score),treatment satisfaction scores and adverse events were monitored.The primary efficacy endpoint was the proportion of patients having on average three or more complete spontaneous bowel movements(CSBMs)per week.Results:The primary efficacy endpoint was achieved in 50.0%,38.5%and 32.7%of patients over week intervals 3–4,9–12 and 21–24,respectively(P<0.01 for all comparisons).Significant improvements were also observed in other bowel movement assessments,colonic transit time,constipation-related symptoms and quality of life;but all improvements diminished at weeks 12 and 24.Incompleteness of evacuation served as the only factor associated with efficacy.No serious treatmentrelated adverse events were observed.Conclusion:This study suggested FMT was effective and safe for STC,while a late loss of efficacy was also observed.A lower degree of sensation of incompleteness predicted a better outcome.展开更多
The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury(RI).RI is a common disease involving multiple human body parts and organs,yet effective treatments are curre...The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury(RI).RI is a common disease involving multiple human body parts and organs,yet effective treatments are currently limited.Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI.This article summarizes 10 common types of RI and their possible mechanisms.It also highlights the changes and potential microbiota-based treatments for RI,including probiotics,metabolites,and microbiota transplantation.Additionally,a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.展开更多
Dear Editor,Early diagnosis is critical for successful treatment of gastric adenocarcinoma(GA).However,the sensitivities of tumor markers carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9)and CA72-4 for GA dete...Dear Editor,Early diagnosis is critical for successful treatment of gastric adenocarcinoma(GA).However,the sensitivities of tumor markers carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9)and CA72-4 for GA detection are approximately 20%[1],and the sensitivities of all markers combined for early gastric cancer detection is still very low[2].DNA methylation plays a major role in tumorigenesis and therefore has obvious potential as a non-invasive biomarker for cancer detection[3].Through genome-wide methylation analysis and histological verification,we previously identified ring finger protein 180(RNF180)as a novel preferentially methylated gene in GA[4,5].展开更多
Ubiquitin specific protease 33 （USP33） is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down...Ubiquitin specific protease 33 （USP33） is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down-regulated in multi- ple cohorts of lung cancer patients and that low expression of USP33 is associated with poor prognosis. USP33 medi- ates Slit-Robo signaling in lung cancer cell migration. Downregulation of USP33 reduces the protein stability of Robol in lung cancer cells, providing a previously unknown mechanism for USP33 function in mediating Slit activity in lung cancer ceils. Taken together, USP33 is a new player in lung cancer that regulates Slit-Robo signaling. Our data suggest that USP33 may be a candidate tumor suppressor for lung cancer with potential as a prognostic marker.展开更多
While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a f...While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a fraction of them receive the clinical benefit.There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy.Here,we carried out retrospective analyses of 1,020 formalin-fixed,paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC.We identified two proteomic subtypes:the chemo-sensitive group(CSG)and the chemo-insensitive group(CIG)in the discovery set.The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only(64.2%vs.49.6%;Cox P-value=0.002),whereas no such improvement was observed in CIG(50.0%vs.58.6%;Cox P-value=0.495).We validated these results in an independent validation set.Further,differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC.A prospective study is warranted to test these findings for future GC patient care.展开更多
The incidence of early-onset gastric cancer(EOGC)is consistently increasing,and its etiology is notably complex.This increase may be attributed to distinctive factors that differ from those associated with late-onset ...The incidence of early-onset gastric cancer(EOGC)is consistently increasing,and its etiology is notably complex.This increase may be attributed to distinctive factors that differ from those associated with late-onset gastric cancer(LOGC),including genetic predispositions,dietary factors,gastric microbiota dysbiosis,and screening of high-risk cases.These factors collectively contribute to the onset of cancer.EOGC significantly differs from LOGC in terms of clinicopathological and molecular characteristics.Moreover,multiple differences in prognosis and clinical management also exist.This study aimed to systematically review the latest research advancements in the epidemiological characteristics,etiological factors,clinicopathological and molecular features,prognosis,and treatment modalities of EOGC.展开更多
Concern about health risks associated with rising obesity has become nearly universal, with the mean body mass index （BMI） and the prevalence of obese and overweight individuals increasing substantially worldwide du...Concern about health risks associated with rising obesity has become nearly universal, with the mean body mass index （BMI） and the prevalence of obese and overweight individuals increasing substantially worldwide during the previous three decades. Unfortunately, prevention and treatment of obesity and related complications have proven complex, and successful strategies to tackle this pathology remain limited. Epidemiological studies have highlighted potential environmental exposures, including diet, energy expenditure, early life influences, sleep deprivation, endocrine disruptors, chronic inflammation, and microbiome sta- tus, contributing to higher risk of obesity （Franks and McCarthy, 2016）. Among these, the microbiome has received extensive attention during the previous decade.展开更多
基金supported by the National Natural Science Foundation of China(U23A20445)the Science and Technology Program of Guangzhou(202206080009)。
文摘Radiochemotherapy-induced oral mucositis(OM)is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy.Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment.To date,differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties,which has increased the uncertainty of treatment effects.On the basis of current research evidence,this expert consensus outlines risk factors,clinical manifestations,clinical grading,ancillary examinations,diagnostic basis,prevention and treatment strategies and efficacy indicators for OM.In addition to strategies such as basic oral care,antiinflammatory and analgesic agents,anti-infective agents,pro-healing agents,and photobiotherapy recommended in previous guidelines,we also emphasize the role of traditional Chinese medicine in OM prevention and treatment.This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention,diagnosis,and treatment,standardizing clinical practice,reducing OM occurrence,promoting healing,and improving the quality of life of patients.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501400)the National Key R&D Program of China(No.2022YFC2505100)the National Natural Science Foundation of China(No.82202837,82421002 and 82350122)。
文摘Objective:The previously integrated tumor-inflammation-nutrition(HI-GC)score has demonstrated dynamic monitoring value for recurrence and clinical decision-making in patients with postsurgical gastric cancer(GC).However,its failure to incorporate clinical-pathological factors limits its capacity for baseline risk assessment.This study aimed to develop a model that accurately identifies patients for adjuvant chemotherapy and dynamically evaluates recurrence risk.Methods:This retrospective,multicenter,longitudinal cohort study,spanning nine hospitals,included 7,085patients with GC post-radical gastrectomy.A baseline prognostic model was constructed using 117 machinelearning algorithms.The dynamic survival decision tree model(dy SDT)was employed to combine the baseline model with the HI-GC score.Results:A Cox regression model incorporating six factors was used to create a nomogram[Harrell's C-index:training cohort:0.765;95%confidence interval(95%CI):0.747,0.783;validation set:0.810;95%CI:0.747,0.783],including p T stage,positive lymph node ratio,p N stage,tumor size,age,and adjuvant chemotherapy.The best-performing machine learning model exhibited similar predictive accuracy to the nomogram(C-index:0.770).For the short-term dy SDT at 1 month,the mortality hazard ratios(HRs)for groups IIa,IIb,andⅢwere 2.61(95%CI:2.24,3.04),5.02(95%CI:4.15,6.06),and 8.88(95%CI:7.57,10.42),respectively,compared to group I.Stratified analysis revealed a significant interaction between adjuvant chemotherapy and overall survival in each subgroup(P<0.001).The long-term dy SDT at 1 year showed HRs of 3.25(95%CI:2.12,4.97)for group II,6.73(95%CI:4.29,10.56)for groupⅢa,and 17.88(95%CI:10.71,29.84)for groupⅢb.Conclusions:The dy SDT effectively stratifies mortality risk and provides valuable assistance in clinical decision-making after gastrectomy.
基金supported by the National Major Research and the Innovation Program of China(Grant No.2016YFC1303200)the National Key R&D Program of China(Grant No.2017YFC0908300)the National Natural Science Foundation of China(Grant No.81972761)。
文摘Objective:The systemic inflammation index and body mass index(BMI)are easily accessible markers that can predict mortality.However,the prognostic value of the combined use of these two markers remains unclear.The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.Methods:A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included.Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio(NLR).High systemic inflammation was defined as NLR≥3,and underweight was defined as BMI<18.5 kg/m2.Results:Among 2,542 patients,NLR≥3 and underweight were common[627(25%)and 349(14%),respectively].In the entire cohort,NLR≥3 or underweight independently predicted overall survival(OS)[hazard ratio(HR):1.236,95%confidence interval(95%CI):1.069–1.430;and HR:1.600,95%CI:1.350–1.897,respectively]and recurrence-free survival(RFS)(HR:1.230,95%CI:1.054–1.434;and HR:1.658,95%CI:1.389–1.979,respectively).Patients with both NLR≥3 and underweight(vs.neither)had much worse OS(HR:2.445,95%CI:1.853–3.225)and RFS(HR:2.405,95%CI:1.802–3.209).Furthermore,we observed similar results in subgroup analyses according to pathological stage,age,and postoperative chemotherapy.Conclusions:Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival.Underweight combined with severe inflammation could enhance prognostication.Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
基金supported by the National Natural Science Foundation of China(Grant Nos.82202837,81730016,and 81972761)the National Key R&D Program of China(Grant Nos.2016YFC1303200,2022YFC2505100,and 2017YFC0908300)。
文摘Cancer is one of the leading causes of death worldwide.The early diagnosis of cancer remains one of the greatest cancer research challenges.Epigenetic alterations,such as altered DNA methylation,that occur during the early stages of carcinogenesis have been proposed as candidate cancer biomarkers.In recent years detection of small amounts of methylated DNA in samples,including blood and stool,has demonstrated the feasibility of DNA methylation as a molecular cancer biomarker.The translational promise of aberrant DNA methylation includes screening and detecting cancer,evaluating prognosis,assessing treatment efficacy,and detecting minimal residual disease(Figure 1).
基金supported by grants from the National Key Research&Development Program of China(No.2022YFC2505100)the National Natural Science Foundation of China(No.81970557).
文摘Large language models(LLMs)such as ChatGPT,Claude,Llama,and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases.With their exceptional long-context reasoning capabilities,LLMs are proficient in clinically relevant tasks,particularly in medical text analysis and interactive dialogue.They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results.Building on their image-recognition abilities,multimodal LLMs(MLLMs)show promising potential for diagnosis based on radiography,chest computed tomography(CT),electrocardiography(ECG),and common pathological images.These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records.Despite these promising developments,significant challenges persist regarding the use of LLMs in medicine,including concerns regarding algorithmic bias,the potential for hallucinations,and the need for rigorous clinical validation.Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice.This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking,ethical supervision,and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs.Future directions include the integration of proprietary clinical knowledge,the investigation of open-source and customized models,and the evaluation of real-time effects in clinical diagnosis and treatment practices.
基金supported by grants from the National Nature Science Foundation of China(82421002,82350122).
文摘Chimeric Antigen Receptor(CAR)T cell therapy has demonstrated significant clinical potential in solid tumors,including glioblastoma,gliomas and gastrointestinal cancers,extending its success from hematological malignancies to solid tumors,and revolutionizing cancer immunotherapy.Although response rates in the majority of solid tumors have been limited,promising results are emerging.Identifying potential factors that might hinder the clinical efficacy of CAR-T cell therapy in solid tumors and learning from successful trials are crucial for improving efficacy and facilitating its clinical application.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.82203042 and 82350122)
文摘The success of chimeric antigen receptor T(CAR-T)cells therapy for hematologic malignancies has sparked interest in potential applications for solid tumors.However,unlike the homogeneous,dynamic,and nutrient-rich hematologic environment,CAR-T cells must overcome the complex tumor microenvironment.Ensuring efficient contact with tumor cells remains a primary challenge to enhance the efficacy of CAR-T cell therapy.Abnormal tumor angiogenesis,disordered chemokine production,dense extracellular matrix,and stromal cells all act as biological barriers that hinder contact of CAR-T cells with tumor cells.This review summarizes specific strategies to promote vascular normalization,modulate chemokine production,target physical barriers,combine different therapeutic approaches,and innovative cell delivery methods to enhance infiltration of CAR-T cells into solid tumors.These strategies will help to overcome current limitations and enhance the effectiveness of CAR-T cell therapy for solid tumors.
文摘Background Antitumor drugs(such as chemotherapy,targeted therapy,immunotherapy,etc.)and local treatments like surgery and radiotherapy are widely used in cancer treatment,but they often carry the risk of liver injury,which seriously affects the prognosis and quality of life of patients.Therefore,liver protection is of crucial importance in cancer treatment.Methods Relevant experts organized by the Oncology Hepatology Committee of China Anti-Cancer Association Association formulated this guideline based on the latest research achievements and clinical practice experience at home and abroad,aiming to provide comprehensive and systematic guidance for clinicians on liver protection.Results This guideline elaborates on the importance of liver protection during cancer treatment,comprehensively introduces the pathophysiological mechanisms,diagnosis,treatment,and preventive measures of antitumor treatment-related liver injury.Conclusion This guideline is helpful for clinicians to formulate individualized treatment plans,improve the treatment outcome and quality of life of cancer patients,and provides an important reference for the clinical practice of liver protection in cancer treatment.
基金supported by the National Natural Science Foundation of China (81670493)by the National Gastroenterology Research Project (2015BAI13B07)
文摘As some studies have reported that strategies targeting the gut microbiota such as fecal microbiota transplantation(FMT) with or without other microecological therapy might have efficacy in treating slow transit constipation(STC), we conducted a singlecenter, open-label trial to study the long-term effect of FMT combined with soluble dietary fiber(pectin) on STC. Thirty-one adult patients with STC were enrolled into the trial. Patients received 6-day FMT procedures repeatedly for the first 3 months and soluble dietary fiber(pectin) daily during the follow-up. The rate of clinical remission and improvement, stool consistency, the Wexner constipation scale, and assessment of constipation-related symptoms were evaluated at week 4 and 1 year later. The clinical remission and improvement rates at week 4 were 69.0%(20/29) and 75.9%(22/29), respectively. At the end of the study,48.3%(14/29) of patients continued to have at least three complete spontaneous bowel movements per week and 58.6%(17/29)of patients showed clinical improvements. Stool consistency, the Wexner constipation scale, and constipation symptoms improved both at short-term and long-term follow-up. The results indicated that FMT in combination with soluble dietary fiber(pectin) had both short-term and long-term efficacy in treating STC.
基金supported by the National Natural Science Foundation of China(Nos.81430072,81421003,81602641,81572929).
文摘Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in China.DNA damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses;however,its critical role in GC remains poorly understood.The present study aimed to investigate the poten-tial relationship and the underlying mechanism between DDIT4 and GC development.Methods:We used western blotting,real-time polymerase chain reaction,and immunohistochemical or immunoflu-orescence to determine DDIT4 expression in GC cells and tissues.High-content screening,cell counting kit-8 assays,colony formation,and in vivo tumorigenesis assays were performed to evaluate cell proliferation.Flow cytometry was used to investigate cell apoptosis and cell cycle distribution.Results:DDIT4 was upregulated in GC cells and tissue.Furthermore,downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle arrest.In contrast,ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated chemosensitivity.Further analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation,and increased chemosensitivity upon DDIT4 downregulation.Conclusion:DDIT4 promotes GC proliferation and tumorigenesis,providing new insights into the role of DDIT4 in the tumorigenesis of human GC.
基金supported by the National Natural Science Foundation of China(81670493)the National Gastroenterology Research Project(2015BAI13B07).
文摘Background and aim:Gutmicrobiotamay contribute to regulate colonicmotility,which is involved in the etiology of constipation.Fecalmicrobiota transplantation(FMT)has been demonstrated to restore intestinal homeostasis.The aimof this study was to evaluate the clinical outcomes and prognostic factors of FMT for the treatment of slow transit constipation(STC).Methods:Fifty-two patients with STC received standardized FMT and were followed up for 6 months.Bowel habit,colonic transit time,constipation-related symptoms(PAC-SYM score),quality of life(PAC-QOL score),treatment satisfaction scores and adverse events were monitored.The primary efficacy endpoint was the proportion of patients having on average three or more complete spontaneous bowel movements(CSBMs)per week.Results:The primary efficacy endpoint was achieved in 50.0%,38.5%and 32.7%of patients over week intervals 3–4,9–12 and 21–24,respectively(P<0.01 for all comparisons).Significant improvements were also observed in other bowel movement assessments,colonic transit time,constipation-related symptoms and quality of life;but all improvements diminished at weeks 12 and 24.Incompleteness of evacuation served as the only factor associated with efficacy.No serious treatmentrelated adverse events were observed.Conclusion:This study suggested FMT was effective and safe for STC,while a late loss of efficacy was also observed.A lower degree of sensation of incompleteness predicted a better outcome.
基金supported by the National Key Research and Development Program of China (2021YFA0717004)Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine.
文摘The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury(RI).RI is a common disease involving multiple human body parts and organs,yet effective treatments are currently limited.Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI.This article summarizes 10 common types of RI and their possible mechanisms.It also highlights the changes and potential microbiota-based treatments for RI,including probiotics,metabolites,and microbiota transplantation.Additionally,a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.
基金supported by the National Key R&D Program of China(Grant no.2016YFC1303200,2022YFC2505100,2017YFC0908300,and 2018YFC1313101)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant no.TJYXZDXK-009A)Beijing Munic-ipal Science&Technology Commission,Administrative Commission of Zhongguancun Science Park(Grant no.Z201100005420007).
文摘Dear Editor,Early diagnosis is critical for successful treatment of gastric adenocarcinoma(GA).However,the sensitivities of tumor markers carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9)and CA72-4 for GA detection are approximately 20%[1],and the sensitivities of all markers combined for early gastric cancer detection is still very low[2].DNA methylation plays a major role in tumorigenesis and therefore has obvious potential as a non-invasive biomarker for cancer detection[3].Through genome-wide methylation analysis and histological verification,we previously identified ring finger protein 180(RNF180)as a novel preferentially methylated gene in GA[4,5].
基金ACKNOWLEDGEMENTS We gratefully thank Dr. Zhipei Zhang for the assistance in lung cancers sample collection. We thank Mang Zheng for technical assistance. We thank other members of Wu lab for stimulating dis- cussion and helpful suggestions. This work was supported by the National Basic Research Program （973 Program） （2010CB529603 and 2013CB917803） and the National Natural Science Foundation of China （Grant No. 91132710）. RK was supported by China Post- doctoral Science Foundation （20110490615）. JYW is supported by NIH （Nos. RO1AG033004 and RO1CA175360）. JYW designed the study PW, XC and RK performed the experiments and analyzed the data+2 种基金 XL, YN and KW provided tissue samples and important suggestions LZ, JL and JYW supervised the experiments and analyzed the data PW and JYW wrote the paper.
文摘Ubiquitin specific protease 33 （USP33） is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down-regulated in multi- ple cohorts of lung cancer patients and that low expression of USP33 is associated with poor prognosis. USP33 medi- ates Slit-Robo signaling in lung cancer cell migration. Downregulation of USP33 reduces the protein stability of Robol in lung cancer cells, providing a previously unknown mechanism for USP33 function in mediating Slit activity in lung cancer ceils. Taken together, USP33 is a new player in lung cancer that regulates Slit-Robo signaling. Our data suggest that USP33 may be a candidate tumor suppressor for lung cancer with potential as a prognostic marker.
基金supported by the National Key Research and Development Program of China(2017YFC1308900,2017YFC0908404,2018YFA0507503,2017YFA0505103)Beijing Municipal Government Key Research and Development Program(Z181100001918020,Z161100002616036)+4 种基金the National Natural Science Foundation of China(31870828,81972790,81672319)the Guangdong Provincial Key R&D Programmes(2019B020229002)the Science and Technology Program of Guangzhou(201902020009)the National Key Basic Research Program of China(2014CBA02002)the National Key Technology Support Program(2015BAI13B07).
文摘While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a fraction of them receive the clinical benefit.There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy.Here,we carried out retrospective analyses of 1,020 formalin-fixed,paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC.We identified two proteomic subtypes:the chemo-sensitive group(CSG)and the chemo-insensitive group(CIG)in the discovery set.The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only(64.2%vs.49.6%;Cox P-value=0.002),whereas no such improvement was observed in CIG(50.0%vs.58.6%;Cox P-value=0.495).We validated these results in an independent validation set.Further,differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC.A prospective study is warranted to test these findings for future GC patient care.
基金supported by the National Natural Science Foundation of China(Nos.82202837,81730016,and 81972761)
文摘The incidence of early-onset gastric cancer(EOGC)is consistently increasing,and its etiology is notably complex.This increase may be attributed to distinctive factors that differ from those associated with late-onset gastric cancer(LOGC),including genetic predispositions,dietary factors,gastric microbiota dysbiosis,and screening of high-risk cases.These factors collectively contribute to the onset of cancer.EOGC significantly differs from LOGC in terms of clinicopathological and molecular characteristics.Moreover,multiple differences in prognosis and clinical management also exist.This study aimed to systematically review the latest research advancements in the epidemiological characteristics,etiological factors,clinicopathological and molecular features,prognosis,and treatment modalities of EOGC.
文摘Concern about health risks associated with rising obesity has become nearly universal, with the mean body mass index （BMI） and the prevalence of obese and overweight individuals increasing substantially worldwide during the previous three decades. Unfortunately, prevention and treatment of obesity and related complications have proven complex, and successful strategies to tackle this pathology remain limited. Epidemiological studies have highlighted potential environmental exposures, including diet, energy expenditure, early life influences, sleep deprivation, endocrine disruptors, chronic inflammation, and microbiome sta- tus, contributing to higher risk of obesity （Franks and McCarthy, 2016）. Among these, the microbiome has received extensive attention during the previous decade.
