Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usual...Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usually result in treatment failure.In this study,an alginate-based hybrid hydrogel(SOG)is developed that can be injected into the resection surface of the lungs during surgery.Briefly,endoplasmic reticulum-modified liposomes(MSLs)pre-loaded with the signal transducer and activator of transcription 3(STAT3)small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.Once applied,MSLs strongly downregulated STAT3 expression in the tumor microenvironment,resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype.Meanwhile,the release of lidocaine hydrochloride(LID)was beneficial for pain relief and natural killer cell activation.Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life,including reduced MPE volume and pain relief in orthotopic NSCLC mouse models,even with a single administration.MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC,and may alter the treatment paradigms for other cancers.展开更多
The roots of Angelica dahurica are a commonly used traditional Chinese herbal medicine.It has the effects of dispelling wind and relieving pain,expelling pus and dispersing swelling,clearing the nasal orifices,and eli...The roots of Angelica dahurica are a commonly used traditional Chinese herbal medicine.It has the effects of dispelling wind and relieving pain,expelling pus and dispersing swelling,clearing the nasal orifices,and eliminating dampness.In recent years,the cultivation of A.dahurica in Hunan Province has developed rapidly,but the research on new varieties selection and standardized cultivation techniques is lagging behind.This paper reviewed the germplasm resources,variety distribution and standardized cultivation technology of A.dahurica in China,hoping to provide technical support for the development of A.dahurica industry.展开更多
Inertinite,as an important and abundant maceral group in coal,is critical for the study of palaeowildfires and their roles in the Earth’s ecosystems.Recently,there has been a significant amount of research on the rel...Inertinite,as an important and abundant maceral group in coal,is critical for the study of palaeowildfires and their roles in the Earth’s ecosystems.Recently,there has been a significant amount of research on the relationship between palaeowildfire,palaeoclimate change and palaeovegetation evolution based on inertinite data.The reflectance of fusinite and semifusinite has been used to estimate the combustion temperature and type of palaeowildfires,and then to evaluate the combustion characteristics of different types of palaeowildfires.The relative abundance of inertinite can be used to estimate the atmospheric oxygen contents.The rapid development of artificial intelligence(AI)and online tools to search scientific databases has presented an opportunity for us to find,collect,arrange,and analyse data from the earliest to latest publications on inertinite.The data extraction tool Deep Shovel is used to collect and analyse global inertinite data from the Silurian to the Neogene.The software programs such as Gplates,ArcGIS pro and Tableau are then applied to model the relative abundance of inertinite over geological time,which can be correlated with other parameters such as atmospheric oxygen contents,plant evolution and palaeoclimate changes.The distribution of inertinite in coals varied over different geological periods,being typified by the“high inertinite content-high atmospheric oxygen level”period in the Permian and the“low inertinite content-low atmospheric oxygen level”period in the Cenozoic.This study has proposed a possible model of the positive and negative feedbacks between inertinite characteristics and palaeoenvironmental factors,and has revealed the exceptional role of inertinite in palaeoenvironmental studies.Future research on inertinite will be focused on the integrated study of organic petrology and organic geochemistry of inertinite,the big data-driven research on the temporal and spatial distribution of the global inertinite,the exploration of the functions of palaeowildfires in the Earth systems in different climatic backgrounds,and the study of modern wildfires to better predict the future frequency and intensity of wildfires due to climate changes.展开更多
Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors ...Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM.Methods:This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1,2012,to December 31,2020.Propensity score matching with 1:1 ratio matching was performed.The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status.Moreover,whole-exome sequencing(WES)of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles.Results:The median follow-up was 68 months.Matching yielded 481 pairs of patients.Compared to right-sided CRLM,left-sided patients experienced with better 5-year overall survival(OS)in surgery responsiveness,with a 14.6 lower risk of death[hazard ratio(HR),1.36,95%confidence interval(CI),1.10-1.69,P=0.004].Interaction between tumor sidedness and KRAS status was statistically significant:left-sidedness was associated with better prognosis among KRAS wild-type patients(HR 1.71;95%CI:1.20-2.45;P=0.003),but not among KRAS mutated-type patients.Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53,APC,KRAS,and BRAF alterations,and identified a critical role of KRAS mutation in correlation with their survival differences.Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors(29.3%vs.15.5%,P=0.03).Conclusions:We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors.Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.展开更多
In this study, dynamic centrifuge model tests were performed for sand slopes under different earthquake ground motions and slope angle to characterize the seismic performance of slopes. Four groups of tests under vary...In this study, dynamic centrifuge model tests were performed for sand slopes under different earthquake ground motions and slope angle to characterize the seismic performance of slopes. Four groups of tests under varying seismic input amplitude were conducted. Under the action of increasing earthquake intensity, the rigidity of the soil decreases and the damping ratio increases, both of the dynamic response and the predominant period of slopes are increased. Three types of seismic waves with the same seismic intensity were applied in the model tests. It shows that the variability in the ground motion leads to the acceleration response spectra of the slopes being completely different and the Northridge seismic wave with low-frequency component is closest to the predominant period of the slope model. In addition, the effect of slope angle on the seismic performance of slopes were also clarified. The results reveal how the slope angle affects the acceleration recorded on the ground surface of the slope, both in terms of the peak ground-motion acceleration(PGA) amplification factor and the predominant period. Finally, the permanent displacement of the model slopes under different earthquake intensities were further analyzed. Based on the nonlinear growth of the permanent displacement of the slope, the test results demonstrated the failure process of the slope, which can further provide a basis for theperformance-based seismic design of slopes.展开更多
In addition to hepatocellular carcinoma,metastatic liver cancer(MLC)is another focus of hepatic surgeon.Good outcome of patients with liver metastasis(LM)from colorectal cancer or neuroendocrine tumor have been achiev...In addition to hepatocellular carcinoma,metastatic liver cancer(MLC)is another focus of hepatic surgeon.Good outcome of patients with liver metastasis(LM)from colorectal cancer or neuroendocrine tumor have been achieved.Ovarian cancer liver metastasis(OCLM)has its unique oncological characteristics and a variety of metastasis patterns,which brings a challenge to hepatic surgeon.Hepatic surgeons hold different views and techniques from gynecologists,which makes differences in the evaluation and treatment of the disease.We reviewed recent studies and,in combination with our own clinical experience,attempted to introduce the progress of surgical treatment of liver metastases from OC.In our experience,both preoperative imaging and surgical procedures are based on the assurance of R0 resection.R0 cytoreductive surgery(CRS)is the most favorable determinant for the prognosis of OC patients,and R0 liver resection(LR)is a component of R0 CRS.Gynecologists and hepatic surgeons should do their own preoperative and intraoperative evaluation for the extrahepatic and intrahepatic metastasis respectively.During the operation,regardless of the miliary nodules dissemination between the right hemidiaphragm and liver capsule,liver parenchymal infiltration(LPI)or liver parenchymal metastasis(LPM),1–2 cm resection margin should be emphasized.For patients with liver portal lymph node metastasis(LPLNM),hepatic portal skeletonization should be performed,rather than portal lymph node dissection.The operation should be as radical as possible to ensure the patients to achieve good prognosis.展开更多
基金supported by the National Natural Science Foundation of China[grant numbers 21873057,22373059]the Natural Science Foundation of Shandong Province[grant numbers ZR2023MB082]。
文摘Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usually result in treatment failure.In this study,an alginate-based hybrid hydrogel(SOG)is developed that can be injected into the resection surface of the lungs during surgery.Briefly,endoplasmic reticulum-modified liposomes(MSLs)pre-loaded with the signal transducer and activator of transcription 3(STAT3)small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.Once applied,MSLs strongly downregulated STAT3 expression in the tumor microenvironment,resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype.Meanwhile,the release of lidocaine hydrochloride(LID)was beneficial for pain relief and natural killer cell activation.Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life,including reduced MPE volume and pain relief in orthotopic NSCLC mouse models,even with a single administration.MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC,and may alter the treatment paradigms for other cancers.
基金Modern Agriculture Traditional Chinese Medicine Industrial Technology System Construction Project of Hunan ProvinceNational Traditional Chinese Medicine Industrial Technology System Construction Special Project(CARS-21)Food Crop Safety Evaluation Project。
文摘The roots of Angelica dahurica are a commonly used traditional Chinese herbal medicine.It has the effects of dispelling wind and relieving pain,expelling pus and dispersing swelling,clearing the nasal orifices,and eliminating dampness.In recent years,the cultivation of A.dahurica in Hunan Province has developed rapidly,but the research on new varieties selection and standardized cultivation techniques is lagging behind.This paper reviewed the germplasm resources,variety distribution and standardized cultivation technology of A.dahurica in China,hoping to provide technical support for the development of A.dahurica industry.
基金supported by the National Natural Science Foundation of China(Grant Nos.42321002,41572090)the Deep-time Digital Earth(DDE)Big Science Program。
文摘Inertinite,as an important and abundant maceral group in coal,is critical for the study of palaeowildfires and their roles in the Earth’s ecosystems.Recently,there has been a significant amount of research on the relationship between palaeowildfire,palaeoclimate change and palaeovegetation evolution based on inertinite data.The reflectance of fusinite and semifusinite has been used to estimate the combustion temperature and type of palaeowildfires,and then to evaluate the combustion characteristics of different types of palaeowildfires.The relative abundance of inertinite can be used to estimate the atmospheric oxygen contents.The rapid development of artificial intelligence(AI)and online tools to search scientific databases has presented an opportunity for us to find,collect,arrange,and analyse data from the earliest to latest publications on inertinite.The data extraction tool Deep Shovel is used to collect and analyse global inertinite data from the Silurian to the Neogene.The software programs such as Gplates,ArcGIS pro and Tableau are then applied to model the relative abundance of inertinite over geological time,which can be correlated with other parameters such as atmospheric oxygen contents,plant evolution and palaeoclimate changes.The distribution of inertinite in coals varied over different geological periods,being typified by the“high inertinite content-high atmospheric oxygen level”period in the Permian and the“low inertinite content-low atmospheric oxygen level”period in the Cenozoic.This study has proposed a possible model of the positive and negative feedbacks between inertinite characteristics and palaeoenvironmental factors,and has revealed the exceptional role of inertinite in palaeoenvironmental studies.Future research on inertinite will be focused on the integrated study of organic petrology and organic geochemistry of inertinite,the big data-driven research on the temporal and spatial distribution of the global inertinite,the exploration of the functions of palaeowildfires in the Earth systems in different climatic backgrounds,and the study of modern wildfires to better predict the future frequency and intensity of wildfires due to climate changes.
基金supported by National Natural Science Foundation of China(81874182,M-0334)Natural Science Foundation of Shanghai(22ZR1413300)+2 种基金National Science and Technology Major Project(2017ZX10203204-007-004)Shanghai Municipal Health Bureau(201940043)Shanghai Hospital Development Center(SHDC12019X19).
文摘Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM.Methods:This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1,2012,to December 31,2020.Propensity score matching with 1:1 ratio matching was performed.The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status.Moreover,whole-exome sequencing(WES)of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles.Results:The median follow-up was 68 months.Matching yielded 481 pairs of patients.Compared to right-sided CRLM,left-sided patients experienced with better 5-year overall survival(OS)in surgery responsiveness,with a 14.6 lower risk of death[hazard ratio(HR),1.36,95%confidence interval(CI),1.10-1.69,P=0.004].Interaction between tumor sidedness and KRAS status was statistically significant:left-sidedness was associated with better prognosis among KRAS wild-type patients(HR 1.71;95%CI:1.20-2.45;P=0.003),but not among KRAS mutated-type patients.Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53,APC,KRAS,and BRAF alterations,and identified a critical role of KRAS mutation in correlation with their survival differences.Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors(29.3%vs.15.5%,P=0.03).Conclusions:We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors.Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.
基金This work was supported by the National Natural Science Foundation of China(Nos.41625011,41807284,41831291)。
文摘In this study, dynamic centrifuge model tests were performed for sand slopes under different earthquake ground motions and slope angle to characterize the seismic performance of slopes. Four groups of tests under varying seismic input amplitude were conducted. Under the action of increasing earthquake intensity, the rigidity of the soil decreases and the damping ratio increases, both of the dynamic response and the predominant period of slopes are increased. Three types of seismic waves with the same seismic intensity were applied in the model tests. It shows that the variability in the ground motion leads to the acceleration response spectra of the slopes being completely different and the Northridge seismic wave with low-frequency component is closest to the predominant period of the slope model. In addition, the effect of slope angle on the seismic performance of slopes were also clarified. The results reveal how the slope angle affects the acceleration recorded on the ground surface of the slope, both in terms of the peak ground-motion acceleration(PGA) amplification factor and the predominant period. Finally, the permanent displacement of the model slopes under different earthquake intensities were further analyzed. Based on the nonlinear growth of the permanent displacement of the slope, the test results demonstrated the failure process of the slope, which can further provide a basis for theperformance-based seismic design of slopes.
基金This work was jointly supported by National Natural Science Foundation of China(81874182,81874056,81372314,81272393 and 81773266)the National Key Project of China(2017ZX10203204-007-004)+2 种基金the Public Health Bureau Foundation of Shanghai(201840019)the Research Talent Foundation of Fudan University Shanghai Cancer Center(YJRC1604)Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai(PWZxq2017-13).
文摘In addition to hepatocellular carcinoma,metastatic liver cancer(MLC)is another focus of hepatic surgeon.Good outcome of patients with liver metastasis(LM)from colorectal cancer or neuroendocrine tumor have been achieved.Ovarian cancer liver metastasis(OCLM)has its unique oncological characteristics and a variety of metastasis patterns,which brings a challenge to hepatic surgeon.Hepatic surgeons hold different views and techniques from gynecologists,which makes differences in the evaluation and treatment of the disease.We reviewed recent studies and,in combination with our own clinical experience,attempted to introduce the progress of surgical treatment of liver metastases from OC.In our experience,both preoperative imaging and surgical procedures are based on the assurance of R0 resection.R0 cytoreductive surgery(CRS)is the most favorable determinant for the prognosis of OC patients,and R0 liver resection(LR)is a component of R0 CRS.Gynecologists and hepatic surgeons should do their own preoperative and intraoperative evaluation for the extrahepatic and intrahepatic metastasis respectively.During the operation,regardless of the miliary nodules dissemination between the right hemidiaphragm and liver capsule,liver parenchymal infiltration(LPI)or liver parenchymal metastasis(LPM),1–2 cm resection margin should be emphasized.For patients with liver portal lymph node metastasis(LPLNM),hepatic portal skeletonization should be performed,rather than portal lymph node dissection.The operation should be as radical as possible to ensure the patients to achieve good prognosis.
