BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy f...BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery,guide perioperative treatment strategies for gastric cancer patients,and prevent serious complications.METHODS In total,998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model,and 398 patients were included in the validation group.The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected.Three machine learning methods,lasso regression,random forest,and artificial neural networks,were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy,and their prediction efficacy and accuracy were evaluated.RESULTS The constructed complication model,particularly the random forest model,could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy.It exhibited stable performance in external validation and is worthy of further promotion in more centers.CONCLUSION Using the risk factors identified in multicenter datasets,highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established.We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.展开更多
AIM: To clarify the role of high in normal-1 (HIN-1) gene promoter methylation during gastric cancer development. METHODS: Gastric cancer cell lines and tissue specimens were analyzed for expression of HIN-1 mRNA and ...AIM: To clarify the role of high in normal-1 (HIN-1) gene promoter methylation during gastric cancer development. METHODS: Gastric cancer cell lines and tissue specimens were analyzed for expression of HIN-1 mRNA and protein using the semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The methylation of the HIN-1 gene promoter was detected in gastric carcinoma cells and tissues using methylation-specific polymerase chain reaction. The 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay and flow cytometry were used to assess the changes in behaviors of gastric cancer cells with or without 5-aza-2’-deoxycytidine treatment. RESULTS: HIN-1 was not expressed in 4 of 5 gastric cancer cell lines. The demethylation reagent 5-aza-2’-deoxycytidine was able to induce or upregulate HIN-1 expression in gastric cancer cell lines, which is associated with reduction of tumor cell viability. Furthermore, methylation of the HIN-1 gene promoter was shown in 57.8% (26/45) of the primary gastric cancer and 42.1% (17/38) of adjacent tissue samples, but was not shown in normal gastric mucosa (0/10). From the clinicopathological data of the patients, methylation of the HIN-1 gene promoter was found to be associated with tumor differentiation (P = 0.000). CONCLUSION: High methylation of HIN-1 gene promoter results in silence of HIN-1 expression in gastric cancer. 5-aza-2’-deoxycytidine reverses HIN-1 methylation and reduces viability of gastric cancer cells.展开更多
SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains elusive.In this study,com...SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains elusive.In this study,comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed.Compared to normal controls,SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs,with drastic transcriptomic changes in cerebral cortex and right ventricle.Intriguingly,cerebral cortex exhibited a hyperinflammatory state evidenced by sig-nificant upregulation of inflammation response-related genes.Meanwhile,expressions of coagulation,angio-genesis and fibrosis factors were also up-regulated in cerebral cortex.Based on our findings,neuropilin 1(NRP1),a receptor of SARS-CoV-2,was significantly elevated in cerebral cortex post infection,accompanied by active immune response releasing inflammatory factors and signal transmission among tissues,which enhanced infection of the central nervous system(CNS)in a positive feedback way,leading to viral encephalitis.Overall,our study depicts a multi-tissue/organ tran-scriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2,and provides important insights into the mechanistic basis for COVID-19-asso-ciated clinical complications.展开更多
After implantation,complex and highly specialized molecular events render functionally distinct organ formation,whereas how the epigenome shapes organ-specific development remains to be fully elucidated.Here,nano-hmC-...After implantation,complex and highly specialized molecular events render functionally distinct organ formation,whereas how the epigenome shapes organ-specific development remains to be fully elucidated.Here,nano-hmC-Seal,RNA bisulfite sequencing(RNA-BisSeq),and RNA sequencing(RNA-Seq)were performed,and the first multilayer landscapes of DNA 5-hydroxymethylcytosine(5hmC)and RNA 5-methylcytosine(m^(5)C)epigenomes were obtained in the heart,kidney,liver,and lung of the human foetuses at 13-28 weeks with 123 samples in total.We identified 70,091 and 503 organ-and stage-specific differentially hydroxymethylated regions(DhMRs)and m^(5)C-modified mRNAs,respectively.The key transcription factors(TFs),T-box transcription factor 20(TBX20),paired box 8(PAX8),krueppel-like factor 1(KLF1),transcription factor 21(TCF21),and CCAAT enhancer binding protein beta(CEBPB),specifically contribute to the formation of distinct organs at different stages.Additionally,5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes.Our integrated studies reveal a putative essential link between DNA modification and RNA methylation,and illustrate the epigenetic maps during human foetal organogenesis,which provide a foundation for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.展开更多
Background Total gastrectomy for carcinoma in the remnant stomach(CRS)remains a technically demanding procedure.Whether robotic surgery is superior,equal,or inferior to laparoscopic surgery in patients with CRS is unc...Background Total gastrectomy for carcinoma in the remnant stomach(CRS)remains a technically demanding procedure.Whether robotic surgery is superior,equal,or inferior to laparoscopic surgery in patients with CRS is unclear.This study was designed to compare the efficacy and safety of robotic total gastrectomy(RTG)and laparoscopic total gastrectomy(LTG)for the treatment of CRS.Methods In this cohort study,we retrospectively analysed the data from patients who underwent RTG or LTG for CRS at Southwest Hospital(Chongqing,China)between May 2006 and October 2019.The surgical outcomes,post-operative complications,and survival outcomes between the two groups were compared.Results Compared with LTG,RTG was associated with similar effective operation time(272.0 vs 297.9 min,P=0.170),higher total costs(105,967.2 vs 81,629.5 RMB,P<0.001),and less estimated blood loss(229.2 vs 288.8 mL,P=0.031).No significant differences were found between the robotic and laparoscopic groups in terms of conversion rate,time to first flatus,time to first soft diet,post-operative hospital stay,post-operative complications,R0 resection rate,and number of retrieved lymph nodes(all P>0.05).The 3-year disease-free survival and 3-year overall survival rates were comparable between the two groups(65.5%vs 57.5%,P=0.918;69.0%vs 60.0%,P=0.850,respectively).Conclusions RTG is a safe and feasible procedure for the treatment of CRS and could serve as an optimal treatment for CRS.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is an RNA virus of the Coronaviridae family causing the outbreak and worldwide pandemic of coronavims disease 2019(COVID-19)(Zhou et al.,2020b;Zhu...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is an RNA virus of the Coronaviridae family causing the outbreak and worldwide pandemic of coronavims disease 2019(COVID-19)(Zhou et al.,2020b;Zhu et al.,2020b).As an emergent and unprecedented global threat to public health,it has affected about 162 million individuals with over 3.3 million deaths until the middle of May.In attributed to the extensive studies on SARS-CoV-2,several kinds of vaccines are currently available which brings hope to human society for alleviating and eventually preventing COVID-19 epidemic(Zhu et al.,2020a;Xia et al.,2021).However,a better understanding of viral pathogenesis,particularly the viral-host interaction,are needed to develop effective interventions.展开更多
基金Natural Science Foundation of Fujian Province,No.2021J011360,and No.2020J011230Natural Science Foundation of Xiamen,China,No.3502Z20214ZD1018,and No.3502Z20227096+2 种基金Medical Innovation Project of Fujian Provincial Health Commission,No.2021CXB019Youth Scientific Research Project of Fujian Provincial Health Commission,No.2022QNB013Bethune Charitable Foundation,No.HZB-20190528-10.
文摘BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery,guide perioperative treatment strategies for gastric cancer patients,and prevent serious complications.METHODS In total,998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model,and 398 patients were included in the validation group.The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected.Three machine learning methods,lasso regression,random forest,and artificial neural networks,were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy,and their prediction efficacy and accuracy were evaluated.RESULTS The constructed complication model,particularly the random forest model,could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy.It exhibited stable performance in external validation and is worthy of further promotion in more centers.CONCLUSION Using the risk factors identified in multicenter datasets,highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established.We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.
基金Supported by National Basic Research Program (973 Program No. 2010CB912802)the Postdoctoral Fund of China, No. 20080441314
文摘AIM: To clarify the role of high in normal-1 (HIN-1) gene promoter methylation during gastric cancer development. METHODS: Gastric cancer cell lines and tissue specimens were analyzed for expression of HIN-1 mRNA and protein using the semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The methylation of the HIN-1 gene promoter was detected in gastric carcinoma cells and tissues using methylation-specific polymerase chain reaction. The 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay and flow cytometry were used to assess the changes in behaviors of gastric cancer cells with or without 5-aza-2’-deoxycytidine treatment. RESULTS: HIN-1 was not expressed in 4 of 5 gastric cancer cell lines. The demethylation reagent 5-aza-2’-deoxycytidine was able to induce or upregulate HIN-1 expression in gastric cancer cell lines, which is associated with reduction of tumor cell viability. Furthermore, methylation of the HIN-1 gene promoter was shown in 57.8% (26/45) of the primary gastric cancer and 42.1% (17/38) of adjacent tissue samples, but was not shown in normal gastric mucosa (0/10). From the clinicopathological data of the patients, methylation of the HIN-1 gene promoter was found to be associated with tumor differentiation (P = 0.000). CONCLUSION: High methylation of HIN-1 gene promoter results in silence of HIN-1 expression in gastric cancer. 5-aza-2’-deoxycytidine reverses HIN-1 methylation and reduces viability of gastric cancer cells.
基金supported by grants from National Key R&D Program of China(2020YFC0848900)CAS Key Research Projects of the Frontier Science(QYZDY-SSW-SMC027)+5 种基金National Natural Science Foundation of China(31625016 and 81788101)K.C.Wong Education Foundation(GJTD-2019-08)Chinese Academy of Medical Sciences(CAMS)Initiative for Innovative Medicine(2016-I2M-2-001,2017-I2M-2-006,2020-I2M-CoV19-003,2020-I2M-CoV19-007)the Youth Innovation Promotion Association,CAS(2018133)China National Postdoctoral Program for Innovative Talents(BX2021291)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).
文摘SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains elusive.In this study,comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed.Compared to normal controls,SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs,with drastic transcriptomic changes in cerebral cortex and right ventricle.Intriguingly,cerebral cortex exhibited a hyperinflammatory state evidenced by sig-nificant upregulation of inflammation response-related genes.Meanwhile,expressions of coagulation,angio-genesis and fibrosis factors were also up-regulated in cerebral cortex.Based on our findings,neuropilin 1(NRP1),a receptor of SARS-CoV-2,was significantly elevated in cerebral cortex post infection,accompanied by active immune response releasing inflammatory factors and signal transmission among tissues,which enhanced infection of the central nervous system(CNS)in a positive feedback way,leading to viral encephalitis.Overall,our study depicts a multi-tissue/organ tran-scriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2,and provides important insights into the mechanistic basis for COVID-19-asso-ciated clinical complications.
基金supported by the National Key R&D Program of China(Grant Nos.2019YFA0110900,2019YFA0802202,2019YFA0802200 and 2020YFA0803401)the National Natural Science Foundation of China(Grant Nos.31870817 and 32170819)+2 种基金the Scientific and Technological Innovation Talent Project of Universities of Henan Province,China(Grant No.20HASTIT045)the Shanghai Municipal Science and Technology Major Project,China(Grant No.2017SHZDZX01)the China Postdoctoral Science Foundation(Grant No.2021M692927).
文摘After implantation,complex and highly specialized molecular events render functionally distinct organ formation,whereas how the epigenome shapes organ-specific development remains to be fully elucidated.Here,nano-hmC-Seal,RNA bisulfite sequencing(RNA-BisSeq),and RNA sequencing(RNA-Seq)were performed,and the first multilayer landscapes of DNA 5-hydroxymethylcytosine(5hmC)and RNA 5-methylcytosine(m^(5)C)epigenomes were obtained in the heart,kidney,liver,and lung of the human foetuses at 13-28 weeks with 123 samples in total.We identified 70,091 and 503 organ-and stage-specific differentially hydroxymethylated regions(DhMRs)and m^(5)C-modified mRNAs,respectively.The key transcription factors(TFs),T-box transcription factor 20(TBX20),paired box 8(PAX8),krueppel-like factor 1(KLF1),transcription factor 21(TCF21),and CCAAT enhancer binding protein beta(CEBPB),specifically contribute to the formation of distinct organs at different stages.Additionally,5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes.Our integrated studies reveal a putative essential link between DNA modification and RNA methylation,and illustrate the epigenetic maps during human foetal organogenesis,which provide a foundation for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.
文摘Background Total gastrectomy for carcinoma in the remnant stomach(CRS)remains a technically demanding procedure.Whether robotic surgery is superior,equal,or inferior to laparoscopic surgery in patients with CRS is unclear.This study was designed to compare the efficacy and safety of robotic total gastrectomy(RTG)and laparoscopic total gastrectomy(LTG)for the treatment of CRS.Methods In this cohort study,we retrospectively analysed the data from patients who underwent RTG or LTG for CRS at Southwest Hospital(Chongqing,China)between May 2006 and October 2019.The surgical outcomes,post-operative complications,and survival outcomes between the two groups were compared.Results Compared with LTG,RTG was associated with similar effective operation time(272.0 vs 297.9 min,P=0.170),higher total costs(105,967.2 vs 81,629.5 RMB,P<0.001),and less estimated blood loss(229.2 vs 288.8 mL,P=0.031).No significant differences were found between the robotic and laparoscopic groups in terms of conversion rate,time to first flatus,time to first soft diet,post-operative hospital stay,post-operative complications,R0 resection rate,and number of retrieved lymph nodes(all P>0.05).The 3-year disease-free survival and 3-year overall survival rates were comparable between the two groups(65.5%vs 57.5%,P=0.918;69.0%vs 60.0%,P=0.850,respectively).Conclusions RTG is a safe and feasible procedure for the treatment of CRS and could serve as an optimal treatment for CRS.
基金This work was supported by grants from National Key R&D Program of China(2020YFC0848900,2021YFC0863300,2020YFA0707602,2020YFC0846400,2020YFC0841100)CAS Key Research Projects of the Frontier Science(QYZDY-SSW-SMC027)+4 种基金National Natural Science Foundation of China(31625016 and 81788101)CAMS Innovation Fund for Medical Sciences(2016-I2M-2-001,2016-I2M-2-006,and 2020-I2M-C〇V19-012)Yunnan Key R&D Project(202003AC100003)K.C.Wong Education Foundation(GJTD-2019-08)the Youth Innovation Promotion Association,CAS(2018133).
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is an RNA virus of the Coronaviridae family causing the outbreak and worldwide pandemic of coronavims disease 2019(COVID-19)(Zhou et al.,2020b;Zhu et al.,2020b).As an emergent and unprecedented global threat to public health,it has affected about 162 million individuals with over 3.3 million deaths until the middle of May.In attributed to the extensive studies on SARS-CoV-2,several kinds of vaccines are currently available which brings hope to human society for alleviating and eventually preventing COVID-19 epidemic(Zhu et al.,2020a;Xia et al.,2021).However,a better understanding of viral pathogenesis,particularly the viral-host interaction,are needed to develop effective interventions.