CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

Objective To analyze the research status and hotspots in the field of astragalus polysaccharides;To provide references for further research.Methods Research literature about astragalus polysaccharides was retrieved from CNKI,Wanfang Data,VIP,PubMed,and Web of Science databases from 1st,Jan.2013 to 1st,July 2023.NoteExpress 3.7 software was used to manage the literature and ultimately establish a database.Excel 2019,CiteSpace 6.2.2R and VOSviewer 1.6.18 were used to visually analyze the publication volume,authors,institutions,and keywords of the included literature.Results A total of 2 462 articles were included,with 1 284 Chinese articles and 1 178 English articles.The main research institutions were Gansu University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,and Beijing University of Chinese Medicine.The core authors of Chinese literature were Liu Yongqi,Wang Hongxin,Lu Meili,etc.The core authors of English literature included Zhang Wei,Li Ke,Yang Xiaojun,etc.High-frequency keywords of Chinese literature included Astragali Radix,rats,polysaccharides,cell apoptosis,and oxidative stress,etc.High frequency keywords in English literature included expression,in vitro,oxidative stress,apoptosis,etc.Conclusion The research on astragalus polysaccharides focuses on their pharmacological effects and mechanisms.Intestinal flora,immune regulation,autophagy and apoptosis are the hot action mechanisms in this field.The focus of disease research involves tumor and diabetes,and antiviral,anti infection and other pharmacological effects are the research trend.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a common liver disease and may become the leading cause of severe liver disease in the future. The Global Burden of Disease (GBD) study assesses MAFLD's impact in countries and regions worldwide, providing insights into its prevalence. METHODS: Prevalence data for MAFLD from 1990 to 2021 by country and region in all sex and age groups were collected from the Global Health Data Exchange. The categorization of countries and geographic areas by development was performed using the Sociodemographic Index (SDI). RESULTS: Between 1990 and 2021, the global crude prevalence rate of MAFLD increased from 10.6% to 16.1% (beta-coefficient: 0.2%, 95% confidence interval [CI]: 0.2-0.2%, P  <0.001), and the age-standardized prevalence rate was increased from 12.1% to 15.0% (beta-coefficient: 0.1%, 95% CI: 0.1-0.1%, P  <0.001). In 2021, MAFLD was estimated to have affected 1.3 billion people worldwide. Significant uptrends were observed in all regions, super regions, and SDI categories. The fastest increase from 1990 to 2021 and the highest prevalence rate in 2021 were experienced by countries and territories with high-middle and middle SDI. An increase in the prevalence of MAFLD from 1990 to 2021 was demonstrated in all but six countries. CONCLUSIONS In 2021, the number of patients affected by MAFLD was doubled compared to 1990, and the prevalence rate increased by over 50%. The burden of MAFLD, as measured by prevalence, was more prominent in countries and territories with middle SDI and in those located in North African and Middle Eastern, possibly due to changes in lifestyle in these areas over the past 30 years.
Humans ; Global Burden of Disease ; Prevalence ; Male ; Female ; Middle Aged ; Adult ; Global Health ; Fatty Liver/epidemiology* ; Aged

Objective:To explore the clinical characteristics of patients with porto-sinusoidal vascular disease (PSVD) complicated with esophageal and gastric varices, and to evaluate the effect of portal vein pressure (PVP) on esophageal and gastric varices bleeding and rebleeding after endoscopic treatment.Methods:Patients who were hospitalized in the Department of Gastroenterology of the Zhongshan Hospital, Fudan University due to portal hypertension from July 2022 to October 2024, underwent liver biopsy for diagnosis of PSVD, and received direct PVP measurement were included. Their clinical manifestations, liver histopathological characteristics were analyzed, and the prognosis was followed up.Results:A total of 29 patients were included, and 19 patients had experienced rupture and bleeding of esophageal and gastric varices. Compared with the non-bleeding group, the hemoglobin level of patients in the bleeding group was lower and the international normalized ratio was higher (all P<0.05). There was no statistically significant difference between the two groups in other laboratory examination indicators, complications of portal hypertension, combined diseases, etc. (all P>0.05). The pathology of liver biopsy suggests that dilation of the hepatic sinuses and abnormalities of the central vein are common pathological changes. The direct PVP of patients in the bleeding group was significantly higher than that in the non-bleeding group [28.0(24.5-31.0)mmHg vs 18.5(10.5-23.8)mmHg, P=0.011]. However, there was no statistically significant difference in the measured values of liver wedge pressure, free pressure and hepatic venous pressure gradient (HVPG) between the two groups of patients (all P>0.05). Correlation analysis revealed that there was no significant correlation between HVPG and PVP ( R2=0.129 9, P=0.076 7). Grouped according to the median PVP value of 25 mmHg, the risk of esophageal and gastric variceal rupture and bleeding in the high PVP group (≥25 mmHg) was significantly higher than that in the low PVP group (<25 mmHg) (14/16 vs 5/13, P=0.016). The risk of rebleeding after endoscopic treatment in patients with high PVP (4/13) was higher than that in patients with low PVP (0/4). Conclusions:Patients with porto-sinusoidal vascular disease complicated with portal hypertension are often accompanied by rupture and bleeding of esophageal and gastric varices. HVPG cannot accurately reflect the portal vein pressure. The risk of rupture and bleeding of esophageal and gastric varices and rebleeding in patients with elevated portal vein pressure is significantly increased.

Objective:To explore the effect of inflammatory cell levels on the anticoagulant efficacy in patients with liver cirrhosis complicated with portal vein thrombosis (PVT).Methods:A total of 106 patients with liver cirrhosis complicated with PVT who visited the Zhongshan Hospital, Fudan University from 2017 to 2022 were prospectively included. The PVT grade and recanalization were evaluated by imaging. Cox regression was used to analyze the predictive factors of anticoagulation efficacy. The time-dependent receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of inflammatory cells for predicting anticoagulation efficacy. The Kaplan-Meier method was used to compare the 1-year PVT recanalization rate of patients with different levels of inflammatory cells.Results:Univariate analysis showed that Child-Pugh score ( HR=1.41), D-dimer ( HR=0.98), platelet ( HR=0.98), C-reactive protein to lymphocyte ratio ( HR=1.01), monocyte ( HR=0.21), lymphocyte ( HR=0.34), and prothrombin time( HR=1.32) was related to the improvement of PVT (all P<0.05). Multivariate analysis confirmed that lymphocytes ( HR: 0.41, 95% CI: 0.20-0.85, P=0.016) and prothrombin time ( HR: 1.23, 95% CI: 1.01-1.50, P=0.036) were independent predictors of anticoagulant efficacy. Grouped according to the ROC cutoff value, the 1-year recanalization rate of PVT in the high-level lymphocyte group (4.55% vs 32.84%, P=0.012) and the high-level monocyte group (5.56% vs 31.4%, P=0.028) was significantly lower than that in the low-level group. After excluding patients undergoing splenectomy, the recurrence rate in the high-level lymphocyte group was still lower than that in the low-level group (6.25% vs 33.77%, P=0.038). Conclusions:Among patients with liver cirrhosis accompanied by PVT, high levels of lymphocytes and monocytes are the key factors for the poor efficacy of anticoagulation therapy. For PVT patients with poor anticoagulation efficacy, the therapeutic strategy of anti-inflammatory combined with anticoagulation can be considered for exploration in the future.

Objective:To analyze the application of Sengstaken-Blakemore tubes combined with endoscopic intervention on the prognosis of patients with acute esophageal and gastric variceal rupture and bleeding due to portal hypertension in liver cirrhosis, and to explore the impact of Sengstaken-Blakemore tubes combined with endoscopic intervention on the prognosis of patients.Methods:A retrospective study included patients with liver cirrhosis who visited the Zhongshan Hospital, Fudan University from January 2023 to July 2024 due to acute upper gastrointestinal bleeding, had no response to drug treatment and unstable hemodynamics, and received the Sengstaken-Blakemore tubes compression hemostasis. According to whether endoscopic intervention was received or not, the patients were divided into the endoscopic intervention group and the non-endoscopic intervention group. The medication and subsequent treatment of the patients were analyzed, and the survival of the patients 28 days after bleeding was followed up. Kaplan-Meier survival analysis and Cox regression analysis were used to evaluate the effect of endoscopic intervention on the 28-day mortality rate of patients.Results:A total of 31 cases successfully had three-lumen two-cystic tubes indwelled. Among them, 8 cases further received endoscopic examination and intervention, and 23 cases did not receive endoscopic examination. During the 28-day follow-up after bleeding, a total of 20 cases died. The Kaplan-Meier survival analysis showed that the 28-day mortality rate in the endoscopic intervention group was significantly lower than that in the non-endoscopic intervention group (25.0% vs 78.3%, P=0.007). Multivariate Cox regression analysis showed that endoscopic intervention was an independent protective factor for 28-day mortality ( HR: 0.14, 95% CI: 0.03-0.63, P=0.01). In addition, the severity of bleeding and prothrombin time were also important factors affecting the prognosis of patients. Conclusions:The Sengstaken-Blakemore tubes, as an important hemostasis method for acute esophageal and gastric variceal rupture and bleeding, can buy time for subsequent endoscopic treatment, but the risk of complications is relatively high. Creating conditions for early endoscopic intervention as early as possible can significantly reduce the mortality rate of patients and improve the prognosis of patients with liver cirrhosis.

Portal hypertension, as a clinical manifestation of the progression of various liver diseases, its concurrent rupture and bleeding of esophageal and gastric varices, ascites and hepatic encephalopathy, etc., seriously affect the prognosis of patients and have always been a key concern in clinical diagnosis and treatment. Although traditional imaging techniques play a key role in the diagnosis and evaluation of portal hypertension, their diagnostic efficacy is limited by subjective film reading, making it difficult to accurately quantify and deeply analyze the pathophysiological characteristics. In recent years, radiomics has gradually demonstrated its potential in the diagnosis and management of portal hypertension by extracting a large number of quantitative features from medical images and constructing predictive models in combination with artificial intelligence algorithms such as machine learning. This article systematically reviews the research progress of radiomics in portal hypertension, with a focus on discussing the current application status of radiomics characteristics in risk assessment, hemodynamic analysis, and prognosis prediction of portal hypertension, in order to promote the progress of radiomics from technical verification to clinical transformation.

Objective:To explore the clinical characteristics of patients with porto-sinusoidal vascular disease (PSVD) complicated with esophageal and gastric varices, and to evaluate the effect of portal vein pressure (PVP) on esophageal and gastric varices bleeding and rebleeding after endoscopic treatment.Methods:Patients who were hospitalized in the Department of Gastroenterology of the Zhongshan Hospital, Fudan University due to portal hypertension from July 2022 to October 2024, underwent liver biopsy for diagnosis of PSVD, and received direct PVP measurement were included. Their clinical manifestations, liver histopathological characteristics were analyzed, and the prognosis was followed up.Results:A total of 29 patients were included, and 19 patients had experienced rupture and bleeding of esophageal and gastric varices. Compared with the non-bleeding group, the hemoglobin level of patients in the bleeding group was lower and the international normalized ratio was higher (all P<0.05). There was no statistically significant difference between the two groups in other laboratory examination indicators, complications of portal hypertension, combined diseases, etc. (all P>0.05). The pathology of liver biopsy suggests that dilation of the hepatic sinuses and abnormalities of the central vein are common pathological changes. The direct PVP of patients in the bleeding group was significantly higher than that in the non-bleeding group [28.0(24.5-31.0)mmHg vs 18.5(10.5-23.8)mmHg, P=0.011]. However, there was no statistically significant difference in the measured values of liver wedge pressure, free pressure and hepatic venous pressure gradient (HVPG) between the two groups of patients (all P>0.05). Correlation analysis revealed that there was no significant correlation between HVPG and PVP ( R2=0.129 9, P=0.076 7). Grouped according to the median PVP value of 25 mmHg, the risk of esophageal and gastric variceal rupture and bleeding in the high PVP group (≥25 mmHg) was significantly higher than that in the low PVP group (<25 mmHg) (14/16 vs 5/13, P=0.016). The risk of rebleeding after endoscopic treatment in patients with high PVP (4/13) was higher than that in patients with low PVP (0/4). Conclusions:Patients with porto-sinusoidal vascular disease complicated with portal hypertension are often accompanied by rupture and bleeding of esophageal and gastric varices. HVPG cannot accurately reflect the portal vein pressure. The risk of rupture and bleeding of esophageal and gastric varices and rebleeding in patients with elevated portal vein pressure is significantly increased.

Objective:To explore the effect of inflammatory cell levels on the anticoagulant efficacy in patients with liver cirrhosis complicated with portal vein thrombosis (PVT).Methods:A total of 106 patients with liver cirrhosis complicated with PVT who visited the Zhongshan Hospital, Fudan University from 2017 to 2022 were prospectively included. The PVT grade and recanalization were evaluated by imaging. Cox regression was used to analyze the predictive factors of anticoagulation efficacy. The time-dependent receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of inflammatory cells for predicting anticoagulation efficacy. The Kaplan-Meier method was used to compare the 1-year PVT recanalization rate of patients with different levels of inflammatory cells.Results:Univariate analysis showed that Child-Pugh score ( HR=1.41), D-dimer ( HR=0.98), platelet ( HR=0.98), C-reactive protein to lymphocyte ratio ( HR=1.01), monocyte ( HR=0.21), lymphocyte ( HR=0.34), and prothrombin time( HR=1.32) was related to the improvement of PVT (all P<0.05). Multivariate analysis confirmed that lymphocytes ( HR: 0.41, 95% CI: 0.20-0.85, P=0.016) and prothrombin time ( HR: 1.23, 95% CI: 1.01-1.50, P=0.036) were independent predictors of anticoagulant efficacy. Grouped according to the ROC cutoff value, the 1-year recanalization rate of PVT in the high-level lymphocyte group (4.55% vs 32.84%, P=0.012) and the high-level monocyte group (5.56% vs 31.4%, P=0.028) was significantly lower than that in the low-level group. After excluding patients undergoing splenectomy, the recurrence rate in the high-level lymphocyte group was still lower than that in the low-level group (6.25% vs 33.77%, P=0.038). Conclusions:Among patients with liver cirrhosis accompanied by PVT, high levels of lymphocytes and monocytes are the key factors for the poor efficacy of anticoagulation therapy. For PVT patients with poor anticoagulation efficacy, the therapeutic strategy of anti-inflammatory combined with anticoagulation can be considered for exploration in the future.

Objective:To analyze the application of Sengstaken-Blakemore tubes combined with endoscopic intervention on the prognosis of patients with acute esophageal and gastric variceal rupture and bleeding due to portal hypertension in liver cirrhosis, and to explore the impact of Sengstaken-Blakemore tubes combined with endoscopic intervention on the prognosis of patients.Methods:A retrospective study included patients with liver cirrhosis who visited the Zhongshan Hospital, Fudan University from January 2023 to July 2024 due to acute upper gastrointestinal bleeding, had no response to drug treatment and unstable hemodynamics, and received the Sengstaken-Blakemore tubes compression hemostasis. According to whether endoscopic intervention was received or not, the patients were divided into the endoscopic intervention group and the non-endoscopic intervention group. The medication and subsequent treatment of the patients were analyzed, and the survival of the patients 28 days after bleeding was followed up. Kaplan-Meier survival analysis and Cox regression analysis were used to evaluate the effect of endoscopic intervention on the 28-day mortality rate of patients.Results:A total of 31 cases successfully had three-lumen two-cystic tubes indwelled. Among them, 8 cases further received endoscopic examination and intervention, and 23 cases did not receive endoscopic examination. During the 28-day follow-up after bleeding, a total of 20 cases died. The Kaplan-Meier survival analysis showed that the 28-day mortality rate in the endoscopic intervention group was significantly lower than that in the non-endoscopic intervention group (25.0% vs 78.3%, P=0.007). Multivariate Cox regression analysis showed that endoscopic intervention was an independent protective factor for 28-day mortality ( HR: 0.14, 95% CI: 0.03-0.63, P=0.01). In addition, the severity of bleeding and prothrombin time were also important factors affecting the prognosis of patients. Conclusions:The Sengstaken-Blakemore tubes, as an important hemostasis method for acute esophageal and gastric variceal rupture and bleeding, can buy time for subsequent endoscopic treatment, but the risk of complications is relatively high. Creating conditions for early endoscopic intervention as early as possible can significantly reduce the mortality rate of patients and improve the prognosis of patients with liver cirrhosis.