Objective:To establish a patient-derived tumor xenograft (PDX) model of primary liver cancer (PLC), and to analyze the pathological features, proliferation and drug-related gene mutation characteristics of the primary tumor and the PDX model of primary liver cancer.Methods:A retrospective analysis was conducted on the tumor samples of 64 PLC patients who underwent hepatectomy in the Department of Hepatobiliary Surgery of Tianjin First Central Hospital from January 2019 to December 2020. Among them, there were 46 males and 18 females, with an average age of (60.7±9.4) years. The degree of tumor differentiation and whether there was vascular invasion were recorded. The pathology of the primary tumor and each generation of PDX models was observed. Immunohistochemical staining was used to detect the characteristic proteins and proliferation-related protein of PLC. The genes related to drug use in PLC PDX models were analyzed in the primary tumor.Results:Among the tumor tissues of 64 PLC patients, 31 cases (48.4%) were successfully transplanted into nude mice and passaged to subsequent generations. In the primary tumor tissues and PDX models of hepatocellular carcinoma (HCC), the cancer nodules were clearly distinguishable, the cancer cells were arranged disorderly, and distributed in nests or cords. The tumor cell nuclei were large and deeply stained. In the primary tumor tissues and each generation of PDX models of intrahepatic cholangiocarcinoma (ICC), there were ICC adenocarcinoma-like structures, with well-differentiated tumor glands and glandular structures composed of cuboidal or columnar tumor cells, presenting as small individual glands or interwoven glands. The degree of differentiation of the PDX models of HCC and ICC patients was basically consistent with that of the primary tumors. Immunohistochemistry showed that proliferating cell nuclear antigen staining of the primary tumors and PDX model transplanted tumors of HCC and ICC patients was strongly positive. The Ki-67 staining positive rate of the primary tumors and PDX model transplanted tumors of HCC was > 80%, and that of ICC was > 70%. Alpha-fetoprotein was strongly positive in the primary tumors and PDX model transplanted tumors of HCC and ICC. The common mutations of transplanted tumors and the primary tumors of P24 HCC patients were 90%, and those of P43 ICC patients were 89%, 94%, and 94%, respectively.Conclusion:The constructed PDX model is highly consistent with the biological characteristics of the primary tumor.

Aconitum (Ranunculaceae) has a long-standing history in traditional Chinese medicine (TCM), where it has been widely used to treat conditions such as rheumatoid arthritis (RA), myocardial infarction, and heart failure. However, the potency of Aconitum alkaloids, the primary active components of Aconitum, also confers substantial toxicity. Therefore, assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety. Metabolomics, a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways, provides a comprehensive view of the metabolic state across multiple systems in vivo. This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity, identifying potential sensitive biomarkers, and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM. This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing, aiming to identify more viable methods for characterizing toxic medicinal plants.
Aconitum/metabolism* ; Metabolomics/methods* ; Alkaloids/metabolism* ; Humans ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional

Objective:To explore the molecular mechanism by which interferon regulatory factor 1 (IRF1) affects hepatic ischemia-reperfusion injury (HIRI) by regulating the polarization of Kupffer cells.Methods:Twelve male healthy C57BL/6 wild-type mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation group ( n=6) and a HIRI group ( n=6); Twelve male healthy C57BL/6 IRF1 gene knockout (IRF1 -/-) mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation IRF1 -/- group ( n=6) and a HIRI IRF1 -/- group ( n=6). The levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) in mice were measured, and hematoxylin-eosin (HE) staining of liver tissues was performed for Suzuki scoring to evaluate liver injury. Fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to evaluate the mRNA levels of IRF1 and tumor necrosis factor α (TNFα) in liver tissues. Flow cytometry and qRT-PCR were used to detect the proportion and functional changes of M1/M2-type Kupffer cells in liver tissues. IRF1 was overexpressed or knocked down in the mononuclear macrophage cell line ANA1, and a co-culture and hypoxia-reoxygenation system with the hepatocyte cell line AML12 was established. Flow cytometry was used to detect the apoptosis of AML12 cells. Results:At 12 hours after hepatic ischemia-reperfusion in wild-type mice, the liver tissue injury was the most severe. Compared with the sham operation group, the levels of serum ALT [(8 073±83) U/L vs. (81±19) U/L, q=13.59] and AST [(11 170±2 890) U/L vs. (412±210) U/L, q=13.77] in the HIRI group were significantly higher, and the differences were statistically significant (both P<0.001). The Suzuki score reached 5-6 points. At 12 hours after hepatic ischemia-reperfusion in IRF1 gene knockout mice, the liver tissue injury was not obvious. There were no significant differences in the levels of serum ALT [668 (514, 2 344) U/L vs. 254 (147, 285) U/L, q=2.52, P=0.348] and AST [1 936 (1 262, 2 003) U/L vs. 628 (423, 759) U/L, q=1.22, P=0.824] between the HIRI IRF1 -/- group and the sham operation IRF1 -/- group. Compared with the HIRI group, the ratio of M1/M2-type Kupffer cells in the liver of the HIRI IRF1 -/- group decreased [(0.958±0.090) vs. (2.788±0.258), q=2.06, P<0.0001], and the mRNA expression of TNFα decreased [(4.363±0.393) vs. (12.900±5.504), q=5.59, P=0.018], and the differences between the two groups were statistically significant. In the co-culture and hypoxia-reoxygenation experiment using ANA1 cells overexpressing IRF1 and AML12 cells, the proportion of AML12 hepatocytes in late apoptosis was higher than that in the control group [(14.05±4.25) vs. (3.15±1.16), t=2.85, P=0.047], and the difference was statistically significant. In contrast, when the expression of IRF1 was knocked down, the proportion of apoptotic AML12 cells decreased [(9.26±3.04) vs. (13.36±4.64), t=2.15, P=0.098], but the difference was not statistically significant. Conclusion:The IRF1 protein can regulate the polarization of Kupffer cells into M1-type macrophages, promote the inflammatory injury of the liver tissue after ischemia-reperfusion, and increase the apoptosis of hepatocytes.

Objective:To establish a patient-derived tumor xenograft (PDX) model of primary liver cancer (PLC), and to analyze the pathological features, proliferation and drug-related gene mutation characteristics of the primary tumor and the PDX model of primary liver cancer.Methods:A retrospective analysis was conducted on the tumor samples of 64 PLC patients who underwent hepatectomy in the Department of Hepatobiliary Surgery of Tianjin First Central Hospital from January 2019 to December 2020. Among them, there were 46 males and 18 females, with an average age of (60.7±9.4) years. The degree of tumor differentiation and whether there was vascular invasion were recorded. The pathology of the primary tumor and each generation of PDX models was observed. Immunohistochemical staining was used to detect the characteristic proteins and proliferation-related protein of PLC. The genes related to drug use in PLC PDX models were analyzed in the primary tumor.Results:Among the tumor tissues of 64 PLC patients, 31 cases (48.4%) were successfully transplanted into nude mice and passaged to subsequent generations. In the primary tumor tissues and PDX models of hepatocellular carcinoma (HCC), the cancer nodules were clearly distinguishable, the cancer cells were arranged disorderly, and distributed in nests or cords. The tumor cell nuclei were large and deeply stained. In the primary tumor tissues and each generation of PDX models of intrahepatic cholangiocarcinoma (ICC), there were ICC adenocarcinoma-like structures, with well-differentiated tumor glands and glandular structures composed of cuboidal or columnar tumor cells, presenting as small individual glands or interwoven glands. The degree of differentiation of the PDX models of HCC and ICC patients was basically consistent with that of the primary tumors. Immunohistochemistry showed that proliferating cell nuclear antigen staining of the primary tumors and PDX model transplanted tumors of HCC and ICC patients was strongly positive. The Ki-67 staining positive rate of the primary tumors and PDX model transplanted tumors of HCC was > 80%, and that of ICC was > 70%. Alpha-fetoprotein was strongly positive in the primary tumors and PDX model transplanted tumors of HCC and ICC. The common mutations of transplanted tumors and the primary tumors of P24 HCC patients were 90%, and those of P43 ICC patients were 89%, 94%, and 94%, respectively.Conclusion:The constructed PDX model is highly consistent with the biological characteristics of the primary tumor.

The Healthy China 2030 Plan set the goal of reducing premature deaths from diabetes by 30% by 2030. However, there has been a lack of assessment of premature mortality for diabetes since the action plan was issued. This study used data from the Global Burden of Disease Study 2021, calculated the premature deaths for diabetes by sex, provinces, and subtypes from 1990 to 2021. We explored the temporal trend of premature mortality using the average annual percent change (AAPC) for different sexes, provinces, and subtypes from 1990 to 2021. Furthermore, we predicted premature mortality for diabetes through 2030 for China and its provinces according to the average annual change rate from 2010 to 2021. There was a first slow upward trend in premature mortality for diabetes from 0.5% in 1990 to 0.6% in 2004, and then a decline until 2021 with premature mortality of 0.4%. By 2030, only Fujian (30.3%) will achieve the desired level of reduction, with only seven provinces meeting the target for females and none for males. There is a large range in the degree of decline between inland and coastal regions, showing obvious geographic differences, and there should be a focus on balancing medical resources.
Humans ; China/epidemiology* ; Female ; Male ; Mortality, Premature/trends* ; Diabetes Mellitus/mortality* ; Goals ; Middle Aged ; Adult

Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.

Objective To explore the application and effectiveness of the apprenticeship education model in Chinese herbal medicine teaching at Western medical college.Methods By comparing classic lecture-based teaching with a combined approach integrating apprenticeship education,the study assesses the impact on student learning outcomes.Participants included students from the 2018 cohort of the eight-year clinical medicine program and the 2022 cohort of the"4+4"pilot program at Peking Union Medical College,who received classic teaching methods and apprenticeship case-based teaching methods,respectively.Upon course completion,students completed a 14-item multiple-choice questionnaire covering essential theory of Chinese medicine,as well as specific categories such as qi-regulating,blood-activating herbs,among others.Results The overall accuracy rate in the apprenticeship case-based teaching group was significantly higher than that in the classic teaching group(P＜0.01).Conclusions The apprenticeship education model of Traditional Chinese Medicine has a positive effect on teaching of Chinese herbal medicine at West-ern medical college and warrants further promotion and application.

Objective:To explore the molecular mechanism by which interferon regulatory factor 1 (IRF1) affects hepatic ischemia-reperfusion injury (HIRI) by regulating the polarization of Kupffer cells.Methods:Twelve male healthy C57BL/6 wild-type mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation group ( n=6) and a HIRI group ( n=6); Twelve male healthy C57BL/6 IRF1 gene knockout (IRF1 -/-) mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation IRF1 -/- group ( n=6) and a HIRI IRF1 -/- group ( n=6). The levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) in mice were measured, and hematoxylin-eosin (HE) staining of liver tissues was performed for Suzuki scoring to evaluate liver injury. Fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to evaluate the mRNA levels of IRF1 and tumor necrosis factor α (TNFα) in liver tissues. Flow cytometry and qRT-PCR were used to detect the proportion and functional changes of M1/M2-type Kupffer cells in liver tissues. IRF1 was overexpressed or knocked down in the mononuclear macrophage cell line ANA1, and a co-culture and hypoxia-reoxygenation system with the hepatocyte cell line AML12 was established. Flow cytometry was used to detect the apoptosis of AML12 cells. Results:At 12 hours after hepatic ischemia-reperfusion in wild-type mice, the liver tissue injury was the most severe. Compared with the sham operation group, the levels of serum ALT [(8 073±83) U/L vs. (81±19) U/L, q=13.59] and AST [(11 170±2 890) U/L vs. (412±210) U/L, q=13.77] in the HIRI group were significantly higher, and the differences were statistically significant (both P<0.001). The Suzuki score reached 5-6 points. At 12 hours after hepatic ischemia-reperfusion in IRF1 gene knockout mice, the liver tissue injury was not obvious. There were no significant differences in the levels of serum ALT [668 (514, 2 344) U/L vs. 254 (147, 285) U/L, q=2.52, P=0.348] and AST [1 936 (1 262, 2 003) U/L vs. 628 (423, 759) U/L, q=1.22, P=0.824] between the HIRI IRF1 -/- group and the sham operation IRF1 -/- group. Compared with the HIRI group, the ratio of M1/M2-type Kupffer cells in the liver of the HIRI IRF1 -/- group decreased [(0.958±0.090) vs. (2.788±0.258), q=2.06, P<0.0001], and the mRNA expression of TNFα decreased [(4.363±0.393) vs. (12.900±5.504), q=5.59, P=0.018], and the differences between the two groups were statistically significant. In the co-culture and hypoxia-reoxygenation experiment using ANA1 cells overexpressing IRF1 and AML12 cells, the proportion of AML12 hepatocytes in late apoptosis was higher than that in the control group [(14.05±4.25) vs. (3.15±1.16), t=2.85, P=0.047], and the difference was statistically significant. In contrast, when the expression of IRF1 was knocked down, the proportion of apoptotic AML12 cells decreased [(9.26±3.04) vs. (13.36±4.64), t=2.15, P=0.098], but the difference was not statistically significant. Conclusion:The IRF1 protein can regulate the polarization of Kupffer cells into M1-type macrophages, promote the inflammatory injury of the liver tissue after ischemia-reperfusion, and increase the apoptosis of hepatocytes.

Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.

Objective To analyze the epidemiological characteristics of new elderly malignant tumor cases in Tongren City from 2018 to 2022, so as to provide a theoretical basis for the prevention and control of elderly malignant tumor in this area. Methods A retrospective analysis of the epidemiological characteristics of cases aged 60 and above who were first diagnosed with malignant tumors by pathology in our hospital from 2018 to 2022 was conducted based on the International Classification of Diseases (ICD-10). Results The incidence rate of elderly malignant tumors in Tongren City increased from 123.83/100 000 in 2018 to 126.14/100 000 in 2022, and the incidence rate showed a trend of first rising and then declining. The top five tumors in incidence rate are lung cancer, rectal cancer, liver cancer, stomach cancer and cervical cancer. The tumor order has changed over the years except lung cancer, which was the first. Lung cancer was the main high incidence tumor among the elderly of all ages. With the increase of age, the number of bladder cancer patients increases significantly, and the number of colon cancer patients also shows an upward trend. The prevalence rate of lung cancer（χ²=16.032，P=0.014) , liver cancer（χ²=8.099，P=0.030) , bladder cancer（χ²=11.274 , P=0.018) , and gastric cancer（χ²=19.387 , P=0.011) in elderly people of different sexes was generally higher in men than in women, and the difference was statistically significant (P<0.05). Conclusion Lung cancer , rectal cancer and liver cancer, as the malignant tumors with high case composition and rapid increase in the elderly, can be the focus of early screening and prevention of malignant tumors in the elderly in Tongren City, and men should pay more attention.