Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes.The etiology and pathologi...Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes.The etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and multistage.However,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic studies.Herein,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle conditions.Advanced symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in mice.In-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene detections.Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the model.Based on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to HCC.Collectively,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.展开更多
The significance of the construction of ecological civilization lies not only in the protection and management of the ecological environment in China, but also in the improvement of people's awareness of the prote...The significance of the construction of ecological civilization lies not only in the protection and management of the ecological environment in China, but also in the improvement of people's awareness of the protection of the natural environment and the unique understanding of the relationship between man and man, society and man and nature, the deep analysis of the relationship between between economic development and environmental protection. Taking the ecological civilization as the angle of view, taking 20 foreign-funded enterprises in Hohhot, Baotou, Erdos and Chifeng of Inner Mongolia Autonomous Region as the research object, using the questionnaire method, the basic data of the enterprises are analyzed by mathematical statistics. The conclusion is that the driving factors of the basic social responsibility of the foreign-funded enterprises mainly come from the requirements of relevant laws and regulations. The main driving force of the medium-level corporate responsibility comes from the promotion of corporate brand image, and the main driving force of corporate responsibility comes from obtaining legal business.展开更多
基金supported by the National Institutes for Food and Drug Control,State Key Laboratory of Drug Regulatory Science。
文摘Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes.The etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and multistage.However,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic studies.Herein,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle conditions.Advanced symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in mice.In-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene detections.Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the model.Based on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to HCC.Collectively,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.
文摘The significance of the construction of ecological civilization lies not only in the protection and management of the ecological environment in China, but also in the improvement of people's awareness of the protection of the natural environment and the unique understanding of the relationship between man and man, society and man and nature, the deep analysis of the relationship between between economic development and environmental protection. Taking the ecological civilization as the angle of view, taking 20 foreign-funded enterprises in Hohhot, Baotou, Erdos and Chifeng of Inner Mongolia Autonomous Region as the research object, using the questionnaire method, the basic data of the enterprises are analyzed by mathematical statistics. The conclusion is that the driving factors of the basic social responsibility of the foreign-funded enterprises mainly come from the requirements of relevant laws and regulations. The main driving force of the medium-level corporate responsibility comes from the promotion of corporate brand image, and the main driving force of corporate responsibility comes from obtaining legal business.