Originally proposed by John McCarthy in 1955,artificial intelligence(AI)has achieved a breakthrough and revolutionized the processing methods of clinical medicine with the increasing workloads of medical records and d...Originally proposed by John McCarthy in 1955,artificial intelligence(AI)has achieved a breakthrough and revolutionized the processing methods of clinical medicine with the increasing workloads of medical records and digital images.Doctors are paying attention to AI technologies for various diseases in the fields of gastroenterology and hepatology.This review will illustrate AI technology procedures for medical image analysis,including data processing,model establishment,and model validation.Furthermore,we will summarize AI applications in endoscopy,radiology,and pathology,such as detecting and evaluating lesions,facilitating treatment,and predicting treatment response and prognosis with excellent model performance.The current challenges for AI in clinical application include potential inherent bias in retrospective studies that requires larger samples for validation,ethics and legal concerns,and the incomprehensibility of the output results.Therefore,doctors and researchers should cooperate to address the current challenges and carry out further investigations to develop more accurate AI tools for improved clinical applications.展开更多
BACKGROUND Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC).However,the prognostic and predictive factors rem...BACKGROUND Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC).However,the prognostic and predictive factors remain unclear.AIM To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC.METHODS Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS.In order to assess the predictive factors of PA-TACE benefit,the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model.RESULTS A total of 378 patients (PA-TACE vs surgery alone,189:189) from three centerswere included after a propensity-score 1:1 matching analysis.Compared to the group receiving surgery alone,PA-TACE prolonged the OS rate in patients with resected HCC (P <0.001).The Barcelona Clinic Liver Cancer system and ferritinto-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups.Age (P=0.023) and microscopic vascular invasion (MVI)(P=0.002) were also identified in the PA-TACE group,while gender (P=0.027),hepatitis B virus(P=0.034) and albumin-bilirubin grade (P=0.027) were also selected in the surgery alone group.In addition,PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone)<1].Notably,a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P=0.038) and without MVI (P=0.048).CONCLUSION FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS.Moreover,high FHR and the absence of MVI were important predictive factors,which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.展开更多
BACKGROUND There is a controversy as to whether laparoscopic surgery leads to a poor prognosis compared to the open approach for early gallbladder carcinoma (GBC)We hypothesized that the laparoscopic approach is an al...BACKGROUND There is a controversy as to whether laparoscopic surgery leads to a poor prognosis compared to the open approach for early gallbladder carcinoma (GBC)We hypothesized that the laparoscopic approach is an alternative for early GBC.AIM To identify and evaluate the safety and feasibility of laparoscopic surgery in the treatment of early GBC.METHODS A comprehensive search of online databases,including MEDLINE (PubMed),Cochrane libraries,and Web of Science,was performed to identify noncomparative studies reporting the outcomes of laparoscopic surgery and comparative studies involving laparoscopic surgery and open surgery in early GBC from January 2009 to October 2019.A fixed-effects meta-analysis was performed for 1-and 5-year overall survival and postoperative complications,while 3-year overall survival,operation time,blood loss,the number of lymph node dissected,and postoperative hospital stay were analyzed by random-effects models.RESULTS The review identified 7 comparative studies and 8 non-comparative studies.1068 patients (laparoscopic surgery:613;open surgery:455) were included in the meta-analysis of 1-,3-,and 5-year overall survival with no significant differences observed [(HR=0.54;95%CI:0.29-1.00;12=0.0%;P=0.051),(HR=0.75;95%CI:0.34-1.65;I^2=60.7%;P=0.474),(HR=0.71;95%CI:0.47-1.08;I^2=49.6%;P=0.107),respectively].There were no significant differences in operation time[weighted mean difference (WMD)=18.69;95%CI:-19.98-57.36;I^2=81.4%;P=0.343],intraoperative blood loss (WMD=-169.14;95%CI:-377.86-39.57;I2=89.5%;P=0.112),the number of lymph nodes resected (WMD=0.12;95%CI:-2.95-3.18;I^2=73.4%;P=0.940),and the complication rate (OR=0.69;95%CI:0.30-1.58;I2=0.0%;P=0.377) between the two groups,while patients who underwent laparoscopic surgery had a reduced length of hospital stay (WMD=-5.09;95%CI:-8.74--1.45;I2=91.0%;P=0.006).CONCLUSION This systematic review and meta-analysis confirms that laparoscopic surgery is a safe and feasible alternative to open surgery with comparable survival and operation-related outcomes for early GBC.展开更多
Adavosertib(ADA)is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer(GBC).However,drug resistance due to DNA damage response compensation pathways and high toxicity limits furt...Adavosertib(ADA)is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer(GBC).However,drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications.Herein,estrone-targeted ADA-encapsulated metal–organic frameworks(ADA@MOF-EPL)for GBC synthetic lethal treatment by inducing conditional factors are developed.The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment.Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species(ROS),which leads to a further increase in DNA damage,resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality.The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity.Moreover,ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors,revealing its potential as a broad-spectrum antitumor drug.展开更多
Recently,genetically targeted cancer therapies have been a topic of great interest.Synthetic lethality provides a new approach for the treatment of mutated genes that were previously considered unable to be targeted i...Recently,genetically targeted cancer therapies have been a topic of great interest.Synthetic lethality provides a new approach for the treatment of mutated genes that were previously considered unable to be targeted in traditional genotype-targeted treatments.The increasing researches and applications in the clinical setting made synthetic lethality a promising anticancer treatment option.However,the current understandings on different conditions of synthetic lethality have not been systematically assessed and the application of synthetic lethality in clinical practice still faces many challenges.Here,we propose a novel and systematic classification of synthetic lethality divided into gene level,pathway level,organelle level,and conditional synthetic lethality,according to the degree of specificity into its biological mechanism.Multiple preclinical findings of synthetic lethality in recent years will be reviewed and classified under these different categories.Moreover,synthetic lethality targeted drugs in clinical practice will be briefly discussed.Finally,we will explore the essential implications of this classification as well as its prospects in eliminating existing challenges and the future directions of synthetic lethality.展开更多
Background:To date,no comprehensive analysis of gallbladder cancer(GBC)management has been reported.We aimed to identify the publication characteristics and research trends in managing GBC over the past three decades....Background:To date,no comprehensive analysis of gallbladder cancer(GBC)management has been reported.We aimed to identify the publication characteristics and research trends in managing GBC over the past three decades.Methods:We selected the 100 most cited articles and performed a bibliometric analysis to summarize the publication characteristics,explore research hotspots,and identify research trends in the management of GBC.Results:The total citations of the included articles ranged from 123 to 1822.Period II(2001–2010)yielded the highest number of included articles,whereas the lowest was in Period III(2011–2020).The United States and Japan published the most papers,in which the Memorial Sloan–Kettering Cancer Center and Nagoya University were the leading institutions,respectively.The most influential authors were Blumgart LH and Fong YM from the United States.Cooperation among countries,institutions,and authors was weak.The Annals of Surgery contributed the most articles with the highest number of total citations.The most researched topic was surgery,followed by systemic therapy and adjuvant therapy.Since Period I,the percentage of surgery-related publications continuously decreased(Periods II and III versus Period I,both p<0.001),with a concomitant increase in those of adjuvant therapy(Period III versus Period I,p=0.004)and systemic therapy(Period II versus Period I,p=0.004;Period III versus Period I,p=0.002).Conclusions:Surgery remains the preferred treatment,while there is a tendency toward adjuvant and systemic therapy in GBC management.An increase in local and international collaboration for managing GBC is required.展开更多
Background:Cachexia is a global burden that is caused by chronic diseases such as cancer.It is characterized by inflammation and progressive loss of muscle and adipose tissue,aggravating the patient’s health.Glycemic...Background:Cachexia is a global burden that is caused by chronic diseases such as cancer.It is characterized by inflammation and progressive loss of muscle and adipose tissue,aggravating the patient’s health.Glycemic metabolism disorders exacerbate cachexia and mutually reinforce each other.Thus far,no research has established a connection between the two.Therefore,we aim to explore the influence of glucose metabolism on cachexia using Mendelian randomization(MR)and provide a theoretical basis for the early prediction of cachexia.Methods:We used glycemic traits(type 2 diabetes(T2D),fasting glucose(FG),fasting insulin(FI),hemoglobin A1c(HbA1c),and 2-hour postprandial glucose(2hPG))as exposures;and cachexia traits(hand grip strength(HGS),appendicular lean mass(ALM),and walking pace(WP))as outcomes.22 mediators were included for mediating effects.Multivariable and mediation MR were used to assess the impact of glycemic metabolism on cachexia.Results:In univariate MR,higher FI increased HGS(β=0.113,95%confidence interval(CI):0.060-0.166)and WP(β=0.066,95%CI:0.021-0.112).Higher HbA1c was associated with higher ALM(β=0.067,95%CI:0.017-0.117).Higher 2hPG was associated with weaker HGS(β=−0.037,95%CI:−0.054 to−0.021).In multivariable MR,only FI maintained a relationship with HGS after adjustments for T2D(β=0.103,95%CI:0.026-0.181),FG(β=0.101,95%CI:0.034-0.169),HbA1c(β=0.115,95%CI:0.055-0.176),and 2hPG(β=0.101,95%CI:0.033-0.169).In mediation MR,three mediators were found to be significant between FI and HGS:waist circumference(WC)(48.1%),lumbar spine bone mineral density(LSBMD)(21.3%)and insulin-like growth factor 1(IGF-1)(6.7%).Conclusions:Using multivariable and mediation MR,our finding suggests that higher FI increases HGS with an independent effect.WC,LSBMD,and IGF-1 mediate between FI and HGS.This study offers a theoretical framework for the early prediction and assessment of the prognosis of cachexia in cancer patients with glycemic metabolism disorders.展开更多
基金Zhejiang Medical and Health Science and Technology Project,No.2019321842National Natural Science Foundation of China,No.81827804Zhejiang Clinical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases,No.2018E50003.
文摘Originally proposed by John McCarthy in 1955,artificial intelligence(AI)has achieved a breakthrough and revolutionized the processing methods of clinical medicine with the increasing workloads of medical records and digital images.Doctors are paying attention to AI technologies for various diseases in the fields of gastroenterology and hepatology.This review will illustrate AI technology procedures for medical image analysis,including data processing,model establishment,and model validation.Furthermore,we will summarize AI applications in endoscopy,radiology,and pathology,such as detecting and evaluating lesions,facilitating treatment,and predicting treatment response and prognosis with excellent model performance.The current challenges for AI in clinical application include potential inherent bias in retrospective studies that requires larger samples for validation,ethics and legal concerns,and the incomprehensibility of the output results.Therefore,doctors and researchers should cooperate to address the current challenges and carry out further investigations to develop more accurate AI tools for improved clinical applications.
基金Supported by Opening Fund of Engineering Research Center of Cognitive Healthcare of Zhejiang Province,No.2018KFJJ09National Natural Science Foundation of China,No.81827804
文摘BACKGROUND Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC).However,the prognostic and predictive factors remain unclear.AIM To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC.METHODS Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS.In order to assess the predictive factors of PA-TACE benefit,the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model.RESULTS A total of 378 patients (PA-TACE vs surgery alone,189:189) from three centerswere included after a propensity-score 1:1 matching analysis.Compared to the group receiving surgery alone,PA-TACE prolonged the OS rate in patients with resected HCC (P <0.001).The Barcelona Clinic Liver Cancer system and ferritinto-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups.Age (P=0.023) and microscopic vascular invasion (MVI)(P=0.002) were also identified in the PA-TACE group,while gender (P=0.027),hepatitis B virus(P=0.034) and albumin-bilirubin grade (P=0.027) were also selected in the surgery alone group.In addition,PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone)<1].Notably,a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P=0.038) and without MVI (P=0.048).CONCLUSION FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS.Moreover,high FHR and the absence of MVI were important predictive factors,which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.
基金the Zhejiang Medical Health Science and Technology Project,No.2016133597 and No.2019321842Natural Science Foundation of Zhejiang Province,No.LQ18H160003.
文摘BACKGROUND There is a controversy as to whether laparoscopic surgery leads to a poor prognosis compared to the open approach for early gallbladder carcinoma (GBC)We hypothesized that the laparoscopic approach is an alternative for early GBC.AIM To identify and evaluate the safety and feasibility of laparoscopic surgery in the treatment of early GBC.METHODS A comprehensive search of online databases,including MEDLINE (PubMed),Cochrane libraries,and Web of Science,was performed to identify noncomparative studies reporting the outcomes of laparoscopic surgery and comparative studies involving laparoscopic surgery and open surgery in early GBC from January 2009 to October 2019.A fixed-effects meta-analysis was performed for 1-and 5-year overall survival and postoperative complications,while 3-year overall survival,operation time,blood loss,the number of lymph node dissected,and postoperative hospital stay were analyzed by random-effects models.RESULTS The review identified 7 comparative studies and 8 non-comparative studies.1068 patients (laparoscopic surgery:613;open surgery:455) were included in the meta-analysis of 1-,3-,and 5-year overall survival with no significant differences observed [(HR=0.54;95%CI:0.29-1.00;12=0.0%;P=0.051),(HR=0.75;95%CI:0.34-1.65;I^2=60.7%;P=0.474),(HR=0.71;95%CI:0.47-1.08;I^2=49.6%;P=0.107),respectively].There were no significant differences in operation time[weighted mean difference (WMD)=18.69;95%CI:-19.98-57.36;I^2=81.4%;P=0.343],intraoperative blood loss (WMD=-169.14;95%CI:-377.86-39.57;I2=89.5%;P=0.112),the number of lymph nodes resected (WMD=0.12;95%CI:-2.95-3.18;I^2=73.4%;P=0.940),and the complication rate (OR=0.69;95%CI:0.30-1.58;I2=0.0%;P=0.377) between the two groups,while patients who underwent laparoscopic surgery had a reduced length of hospital stay (WMD=-5.09;95%CI:-8.74--1.45;I2=91.0%;P=0.006).CONCLUSION This systematic review and meta-analysis confirms that laparoscopic surgery is a safe and feasible alternative to open surgery with comparable survival and operation-related outcomes for early GBC.
基金supported by the National Natural Science Foundation of China(82202873,32200566)the Natural Science Foundation of Zhejiang Province(LQ22H160003)the Fundamental Research Funds for the Central Universities(2262022-00141)。
文摘Adavosertib(ADA)is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer(GBC).However,drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications.Herein,estrone-targeted ADA-encapsulated metal–organic frameworks(ADA@MOF-EPL)for GBC synthetic lethal treatment by inducing conditional factors are developed.The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment.Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species(ROS),which leads to a further increase in DNA damage,resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality.The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity.Moreover,ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors,revealing its potential as a broad-spectrum antitumor drug.
基金supported by the Opening Fund of Engineering Research Center of Cognitive Healthcare of Zhejiang Province(No.2018KFJJ09)Scientific Research Fund of Zhejiang Provincial Education Department(Y201941406)+2 种基金National Natural Science Foundation of China(Nos.81827804 and 81800540)Zhejiang Clinical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases(No.2018E50003)Science and Technology Innovative Activity Plan and New Seedling Talent Plan for College Students in Zhejiang Province(No.2020R401217)。
文摘Recently,genetically targeted cancer therapies have been a topic of great interest.Synthetic lethality provides a new approach for the treatment of mutated genes that were previously considered unable to be targeted in traditional genotype-targeted treatments.The increasing researches and applications in the clinical setting made synthetic lethality a promising anticancer treatment option.However,the current understandings on different conditions of synthetic lethality have not been systematically assessed and the application of synthetic lethality in clinical practice still faces many challenges.Here,we propose a novel and systematic classification of synthetic lethality divided into gene level,pathway level,organelle level,and conditional synthetic lethality,according to the degree of specificity into its biological mechanism.Multiple preclinical findings of synthetic lethality in recent years will be reviewed and classified under these different categories.Moreover,synthetic lethality targeted drugs in clinical practice will be briefly discussed.Finally,we will explore the essential implications of this classification as well as its prospects in eliminating existing challenges and the future directions of synthetic lethality.
基金supported by the Scientific Research Fund of Zhejiang Provincial Education Department(grant number:Y202148325)the National Natural Science Foundation of China(grant numbers:81800540,81827804).
文摘Background:To date,no comprehensive analysis of gallbladder cancer(GBC)management has been reported.We aimed to identify the publication characteristics and research trends in managing GBC over the past three decades.Methods:We selected the 100 most cited articles and performed a bibliometric analysis to summarize the publication characteristics,explore research hotspots,and identify research trends in the management of GBC.Results:The total citations of the included articles ranged from 123 to 1822.Period II(2001–2010)yielded the highest number of included articles,whereas the lowest was in Period III(2011–2020).The United States and Japan published the most papers,in which the Memorial Sloan–Kettering Cancer Center and Nagoya University were the leading institutions,respectively.The most influential authors were Blumgart LH and Fong YM from the United States.Cooperation among countries,institutions,and authors was weak.The Annals of Surgery contributed the most articles with the highest number of total citations.The most researched topic was surgery,followed by systemic therapy and adjuvant therapy.Since Period I,the percentage of surgery-related publications continuously decreased(Periods II and III versus Period I,both p<0.001),with a concomitant increase in those of adjuvant therapy(Period III versus Period I,p=0.004)and systemic therapy(Period II versus Period I,p=0.004;Period III versus Period I,p=0.002).Conclusions:Surgery remains the preferred treatment,while there is a tendency toward adjuvant and systemic therapy in GBC management.An increase in local and international collaboration for managing GBC is required.
基金supported by the National Natural Science Foundation of China(82202873)the State Key Laboratory of Advanced Drug Delivery and Release Systems(DSQZ-QN-202303).
文摘Background:Cachexia is a global burden that is caused by chronic diseases such as cancer.It is characterized by inflammation and progressive loss of muscle and adipose tissue,aggravating the patient’s health.Glycemic metabolism disorders exacerbate cachexia and mutually reinforce each other.Thus far,no research has established a connection between the two.Therefore,we aim to explore the influence of glucose metabolism on cachexia using Mendelian randomization(MR)and provide a theoretical basis for the early prediction of cachexia.Methods:We used glycemic traits(type 2 diabetes(T2D),fasting glucose(FG),fasting insulin(FI),hemoglobin A1c(HbA1c),and 2-hour postprandial glucose(2hPG))as exposures;and cachexia traits(hand grip strength(HGS),appendicular lean mass(ALM),and walking pace(WP))as outcomes.22 mediators were included for mediating effects.Multivariable and mediation MR were used to assess the impact of glycemic metabolism on cachexia.Results:In univariate MR,higher FI increased HGS(β=0.113,95%confidence interval(CI):0.060-0.166)and WP(β=0.066,95%CI:0.021-0.112).Higher HbA1c was associated with higher ALM(β=0.067,95%CI:0.017-0.117).Higher 2hPG was associated with weaker HGS(β=−0.037,95%CI:−0.054 to−0.021).In multivariable MR,only FI maintained a relationship with HGS after adjustments for T2D(β=0.103,95%CI:0.026-0.181),FG(β=0.101,95%CI:0.034-0.169),HbA1c(β=0.115,95%CI:0.055-0.176),and 2hPG(β=0.101,95%CI:0.033-0.169).In mediation MR,three mediators were found to be significant between FI and HGS:waist circumference(WC)(48.1%),lumbar spine bone mineral density(LSBMD)(21.3%)and insulin-like growth factor 1(IGF-1)(6.7%).Conclusions:Using multivariable and mediation MR,our finding suggests that higher FI increases HGS with an independent effect.WC,LSBMD,and IGF-1 mediate between FI and HGS.This study offers a theoretical framework for the early prediction and assessment of the prognosis of cachexia in cancer patients with glycemic metabolism disorders.
