Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

OBJECTIVE: To explore the clinical characteristics, therapeutic responses and prognostic features of E2A-PBX1 fusion gene for childhood acute lymphoblastic leukemia (ALL). METHODS: A total of 837 pediatric patients with ALL who were initially diagnosed in our hospital from July 2010 to November 2017 were retrospectively analyzed, 48 children with positive E2A-PBX1 fusion gene were detected by the real-time quantitative PCR techniques and their data were retrospectively collected for analysis. RESULTS: Among 48 cases with positive E2A-PBX1 fusion gene, there were 26 males and 22 females, with onset ages ranging from 9 months to 13 years old. There were 2 cases (4.2%) in the low-risk group, 32 cases (66.7%) in the intermediate-risk group, and 14 cases (29.1%) in the high-risk group at initial diagnosis. The white blood cell (WBC) counts of 25 cases (53.2%) at initial diagnosis were <50×10⁹/L, 11 cases (23.4%) were (50-100)×10⁹/L, and 11 cases (23.4%) ≥100×10⁹/L. The main immunophenotype was common-B ALL (44 cases, 91.7%). Other leukemia fusion genes such as BCR-ABL1, MLL-AF4, and TEL-AML1 were not observed in this cohort of patients. All patients received the treatment of NPCLC-ALL2008 protocol, and 5 cases (10.4%) occurred poor prednisone response. All the 48 cases achieved complete remission (CR) after the induction treatments. The last follow-up date was April 30, 2023. A total of 5 children relapsed, including 1 case with intermediate risk and 4 cases with high risk. The recurrence rate in the high-risk group was significantly higher than that in the intermediate- and low-risk groups (both P < 0.05). Most relapsed children had elevated WBC counts at initial diagnosis. Among them, WBC counts ≥100×10⁹/L was observed in 4 cases. The recurrence rate among children with WBC counts ≥100×10⁹/L was significantly higher than that with WBC counts <100×10⁹/L (P < 0.01). Four deaths occurred in this cohort, of which 3 died of leukemia recurrence. The 10-year event-free survival rate and 10-year overall survival rate of the 48 children with positive E2A-PBX1 fusion gene were 87.5%±4.8% and 91.7%±4.0%, respectively. CONCLUSION In ALL children with positive E2A-PBX1 fusion gene, those with elevated WBC counts and high risk stratification at initial diagnosis are more likely to experience recurrence. Recurrence is the main cause of death in this group. It is suggested that such kind of children receive more intensive chemotherapy or undergo hematopoietic stem cell transplantation as early as possible to further improve prognosis.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Oncogene Proteins, Fusion/genetics* ; Prognosis ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; Retrospective Studies ; Infant ; Homeodomain Proteins

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective To determine the effects of ciprofol and propofol on hemodynamics and cardiac work were determined by hemodynamic monitoring,so as to provide reference for anesthesia induction in car-diac surgery.Methods A total of 90 patients scheduled for mitral valve replacement under cardiopulmonary bypass from June 2022 to June 2023 were randomly divided into two groups:the ciprofol group (group P,n=45) and the propofol group (group B,n=45).The heart rate (HR),oxygen saturation (SpO2),index of con-sciousness (ICO1),mean arterial pressure (MAP),central venous pressure (CVP),stroke volume (SV),car-diac output (CO),systemic vascular resistance (SVR),cardiac cycle efficiency (CCE),stroke volume variation (SVV),maximum pressure gradient reflecting myocardial contractility (dp/dt) were recorded before adminis-tration (T0) and five min after administration (T1).Results In group P,ICO1,MAP,SV,CO,and SVR at T1 were lower than those at T0,and CCE was higher than that at T0 (P<0.01,P<0.05).In group B,ICO1, MAP,CVP,SV,CO,SVR,CCE,SVV,dp/dt at T1 were significantly lower than those at T0 (P<0.01,P<0.05).There was no statistically significant difference in HR,SpO2,ICO1,MAP,CVP and hemodynamic indi-cators between group B and group P at T0 (P>0.05).There was no statistically significant difference in HR, SpO2,ICO1,CVP and SVV between group B and group P at T1 (P>0.05).MAP,SV,CO,SVR,CCE and dp/dt at T1 in group P were higher than those in group B (P<0.05).Conclusion Ciprofol can better maintain hemodynamic stability and reduce cardiac impairment during the induction phase of mitral valve replacement surgery under cardiopulmonary bypass.

Objectives:To establish a comprehensive system of Cardiovascular Academic Performance Evaluation(CAPE)and rank global TOP100 medical institutions in the fields of cardiovascular diseases(CVD). Methods:CVD-related terms were extracted from Medical Subject Headings(MeSH),Embase thesaurus(EMtrees)and International Classification of Diseases(ICD)by CVD-related professionals,as well as by librarians and information professionals.Terminology databases(named as Fuwai Subject Headings)were established,and nine sub-disciplines were proposed,including ischemic heart diseases,hypertension,vascular diseases,arrhythmia,pulmonary vascular diseases,heart failure,congenital heart diseases,cardiomyopathy,and valvular heart diseases.The mapping patterns of sub-discipline,cardiovascular terminology and entry terms were pre-defined.The CVD-related research literature published from January 1,2016 to December 31,2022 were retrieved from Web of Science,PubMed and Scopus.Based on this,metadata were fused and duplicates were excluded.Fuwai Subject Headings were searched and matched into four respects for each literature,including subject words,titles,keywords,and abstracts,which was used to generate an information table of"Position—CVD terminology—Frequency",and to calculate CVD correlation scores and sub-discipline scores.We standardized the names of medical institutions and scholars,and make a ranking system for CAPE based on original articles with strong cardiovascular correlation(correlation score≥4).When evaluating the science and technological performance for Chinese hospitals in cardiovascular diseases,National Natural Science Foundation Projects,authorized invention patents,prize achievements,research platforms,and registered data of drug clinical trials in Center for Drug Evaluation(CDE)were considered besides research papers. Results:During 2016 and 2022,1 545 103 CVD research literatures were found worldwide.After excluding meeting abstracts,books,biographies,news,videos,audio texts,retracted publications,and corrections,1 178 019 CVD research literatures were further evaluated.518 058 literatures were indexed as"strongly correlated to CVD"using Fuwai Subject Headings.Besides papers,other data sources were also collected,including 11 143 CVD-related Natural Science Foundation Projects,19 382 CVD-related effective authorized invention patents,103 CVD-related national prize achievements,24 CVD-related national research platforms,and 2 084 CDE registered data of CVD-related drug clinical trials.Research teams from nine sub-disciplines reviewed and validated research literature in respective fields,and classification rules of corresponding sub-disciplines were created and improved based on their opinions.Finally,eleven individual indexes were chosen to construct CAPE system for ranking global TOP100 medical institutions in overall CVD field and TOP30 in nine sub-disciplines.From 2016 to 2022,the number of cardiovascular disease research papers published by Chinese institutes has increased by 123.5%,with a total of approximately 76.8 thousands papers published(about 30 papers per day on average),ranked the second under the United States(approximately 114.1 thousands papers).However,the proportion of papers published by the Chinese Journal Citation Reports(JCR)and the Chinese Academy of Sciences only ranked eighth in the world.In the comprehensive academic performance of original cardiovascular research papers in global hospitals from 2020 to 2022,only two Chinese medical institutions ranked in the TOP20 as evaluated by CAPE system. Conclusions:Based on multi-source data from 2016 to 2022,CAPE initiated to establish a cardiovascular academic performance evaluation system.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.