Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

OBJECTIVE: To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis. METHODS: TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions. RESULTS: HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13. CONCLUSION TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals ; Apoptosis/drug effects* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Alkaloids/therapeutic use* ; Gelsemium/chemistry* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Xenograft Model Antitumor Assays

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective To observe the effect of intra-arterial nimodipine perfusion after interventional embolization in the treatment of symptomatic cerebral vasospasm(SCVS)after aneurysmal subarachnoid hemorrhage(aSAH)and explore its influence on vascular endothelial function.Methods Patients with SCVS after aSAH were divided into treatment group and control group according to cohort methods.Both groups received interventional embolization based on symptomatic supportive treatment,and were given conventional 3H treatments such as blood dilution,dilatation and pressure enhancement after surgery,and the treatment group was additionally given intra-arterial perfusion of nimodipine(20％nimodipine was injected by electronic pump through the femoral artery sheath at a rate of 0.2 mg·min-1 for 2 mg once a day,vascular sheath was removed and nimodipine tablet after 7 days of medication was taken orally for 60-120 mg twice a day after meals),and both groups were treated for 14 days.The cerebrovascular blood flow velocity,laboratory indicators,postoperative complications and prognosis were compared between the two groups.Results There were 41 cases in treatment group,and 38 cases in control group.After 2 weeks of treatment,the average blood flow velocities of anterior cerebral artery(ACA)in treatment group and control group were(84.32±5.27)and(93.46±5.61)cm·s-1,the average blood flow velocities of middle cerebral artery(MCA)were(86.05±5.94)and(95.23±6.37)cm·s-1,the average blood flow velocities of posterior cerebral artery(PCA)were(59.41±4.82)and(71.56±5.39)cm·s-1 respectively(all P＜0.05).The levels of serum endothelin-1(ET-1)in treatment group and control group after 2 weeks of treatment were(76.32±10.58)and(94.16±10.98)pg·mL-1;the levels of vascular endothelial growth factor(VEGF)were(127.45±14.83)and(164.85±15.62)ng·mL-1;the levels of soluble fms-like tyrosine kinase-1(sFlt-1)were(103.67±15.34)and(114.98±16.43)ng·L-1;the levels of plasma soluble intercellular adhesion molecule-1(sCAM-1)were(234.81±62.79)and(285.36±90.24)ng·mL-1;the levels of hypoxia-inducible factor-2α(HIF-2α)were(98.74±7.56)and(102.49±8.35)pg·mL-1;the levels of serum nitric oxide(NO)were(43.16±4.91)and(39.72±5.37)mmol·L-1,all with significant difference(all P＜0.05).The incidence rates of delayed cerebral vasospasm(DCVS)and hydrocephalus were 4.88％and 9.76％in treatment group after surgery,lower than 21.05％and 28.95％in control group(all P＜0.05).The proportion of Glasgow outcome scale(GOS)score of 5 points in treatment group at 3 months after surgery was higher than that in control group(78.05％vs 55.26％,P＜0.05).Conclusion After interventional embolization,intra-arterial perfusion of nimodipine for SCVS after aSAH can help to relieve the inflammatory response,improve the vascular endothelial function and reduce the cerebral blood flow velocity,and it plays a positive role on reducing the cerebral tissue injury and improving the prognosis of patients.

Objective To investigate the protective effect of berberine on the injury of colon epithelial cells induced by dextran sulfate sodium(DSS).Methods NCM-460 cells were randomly divided into blank group(conventional culture),model group(40 mg·mL-1 DSS)and low-dose group(5 μmol·L-1 berberine),high-dose group(10 μmol·L-1 berberine),siRNA group(10 μmol·L-1 berberine+transfected siRNA plasmid),si-SelS group(10 μmol·L-1 berberine+transfected si-SelS plasmid).The expressions of selenioprotein S(SelS)were detected by Western blot;cell proliferation was detected by cell counting kit-8(CCK-8)and 5-ethynyl-2'-deoxyuridine(EdU)tests;trans epithellal electric resistance(TEER)levels were detected by Milli-cell ERS;superoxide dismutase(SOD)was detected by kit method;apoptosis was detected by flow cytometry.Results The relative expression levels of SelS protein in blank group,model group,high-dose group,siRNA group and si-SelS group were 1.02±0.13,0.42±0.05,0.90±0.08,0.89±0.10 and 0.30±0.03,respectively;the cell optical density at 48 h were 0.85±0.05,0.48±0.04,0.70±0.08,0.68±0.05 and 0.51±0.05,respectively;the EdU positive cell rates were(33.78±2.72)％,(11.90±2.00)％,(25.74±1.94)％,(24.29±1.96)％and(15.17±1.16)％,respectively;TEER values were(100.00±3.64)％,(43.47±4.19)％,(73.28±7.38)％,(76.25±7.68)％and(53.49±4.42)％,respectively;SOD activities were(13.32±0.73),(5.33±0.55),(9.63±1.13),(9.69±0.88)and(6.40±0.57)U·mL-1,respectively;the apoptosis rates were(3.21±0.02)％,(24.59±2.35)％,(10.90±1.09)％,(11.11±1.24)％and(16.73±1.56)％,respectively.The above indexes in the model group were compared with those in the blank group,and those in the high-dose group were compared with those in the model group.The above indexes of si-SelS group were statistically significant compared with those of siRNA group(all P＜0.05).Conclusion Berberine can inhibit oxidative stress and improve DSS induced colon epithelial cell barrier damage by up-regulating SelS.

Objective:To study the expression levels and clinical significance of microR-NA-183-5p(miR-183-5p)and thioesterase superfamily member 4(THEM4)in colon cancer tissues.Methods:A total of 96 patients with colon cancer who in Hebei China Petroleum Central Hospital gathered as the research objects.During the course of radical resection of colon cancer patients,the colon cancer tissues and adjacent normal tissues were collected.The relative expression levels of miR-183-5p and THEM4 mRNA in colon cancer tissues and adjacent normal tissues were detected.Analysis of the correlation between miR-183-5pand THEM4mRNA in colon cancer and their relation-ship with prognosis.COX regression was used to analyze the risk factors affecting the prognosis of pa-tients with colon cancer.Results:Compared with adjacent normal tissues,the expression level of miR-183-5p in colon cancer tissues increased(P＜0.05),and the expression level of THEM4 mRNA decreased(P＜0.05).MiR-183-5p was negatively correlated with THEM4 mRNA expression in colon cancer tissue(r=-0.529,P＜0.05).The survival rate of the high expression group of miR-183-5p lower than that of the low expression group(P＜0.05),the survival rate of the high expression group of THEM4 was obviously higher than that of the low expression group(P＜0.05).TNM stage(Ⅲ-Ⅳ),high expres-sion of miR-183-5p and low expression of THEM4 were risk factors for poor prognosis in patients with colon cancer(P＜0.05).Conclusion:The expression level of miR-183-5p in cancer tissues of patients with colon cancer is increased,and the expression level of THEM4 is decreased,both are closely relat-ed to the clinicopathological characteristics and prognosis of patients.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P＞0.05).The highest thrombotic rate was 26.09％(12/46)in JAK2 group,then 12.5％(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78％),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P＜0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)％,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)％in triple-negative group(P＜0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P＜0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P＜0.05,P＜0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P＜0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.

Objective:To investigate the clinical characteristics and influence of co-mutated gene on acute myeloid leukemia patients(AML)with FMS-like tyrosine kinase-3(FLT3)mutations.Methods:A total of 273 FLT3+AML patients were enrolled,and the co-mutation gene data of the patients were collected to further analyze the prognosis of the patients.FLT3 and other common mutations were quantified by PCR amplification products direct sequencing and second-generation sequencing(NGS).Results:When patients were divided into FLT3 ITD+,FLT3 TKD+,FLT3 ITD++TKD+and FLT3 ITD-+TKD-group according to the type of FLT3 mutations,it was found that the frequencies of TET2,GATA2,NRAS and ASXL1 mutation were significantly different among the 4 groups(all P＜0.05).When patients were divided into allelic ratio(AR)≥0.5 and＜0.5 group,it was found that the frequencies of FLT3 ITD+,FLT3 ITD-+TKD-,NPM1,NRAS and C-kit were significantly different between the two groups(all P＜0.05).When patients were divided into normal and abnormal karyotype group,it was found that the frequencies of FLT3 ITD+,FLT3 TKD+,NPM1,GATA2 and C-kit were significantly different between the two groups(all P＜0.05).The median overall survival(OS)of AML patients with FLT3 TKD+(including FLT3 ITD++TKD+)was longer than that of patients with FLT3 ITD+alone(P＜0.05).The OS and relapse-free survival(RFS)of AML patients with FLT3++TET2+were both shorter than those of patients with FLT3++TET2-(both P＜0.05).Conclusion:The mutation frequencies of co-mutated genes are correlated with subtypes of FLT3,karyotype and AR.AML patients with FLT3 TKD+have longer OS than patients with FLT3 ITD+alone,and patients with co-mutation of TET2 have shorter median OS and RFS.

Aim To investigate the mechanisms of Ke-chuanting granules(KCT)inhibiting the IL-33/ILC2s pathway and pathogenic T cells to intervene in allergic airway inflammation.Methods Network pharmacolo-gy was utilized to analyze the potential targets and mechanisms of KCT-treated asthma.Allergic asthma models were induced in mice using OVA.Lung histo-pathology was conducted to observe injury changes.ELISA and quantitative PCR were utilized to measure key inflammatory factors and their mRNA expression levels in Th2-type asthma.Western blot was used to detect the phosphorylation levels of relevant proteins in the MAPK pathway.Flow cytometry was performed to evaluate the proportions of ILC2s,Th1,Th 17,Th2 and Treg cells.Results Network pharmacology iden-tified 227 main active components and 143 key targets of KCT in treating asthma,primarily enriched in signa-ling pathways such as MAPK and IL-17.Further vali-dation experiments demonstrated that KCT significantly alleviated lung inflammatory injury in asthmatic mice,reduced the number of B cells,production of I L-4,TNF-α and TGF-β,downregulated JNK phosphoryla-tion levels in lung tissue,as well as mRNA levels of Il-33,Bcl11b,Rorα,Tcf-7,Jun,Mapk3 and Mapk14.KCT intervention reduced the numbers of ILC2s and Th 17 cells in lungs and spleens of mice,and inhibited Th2 cell infiltration in lungs.Conclusions KCT ex-hibits therapeutic effects on allergic airway inflamma-tion in asthma,closely associated with the inhibition of the IL-33/ILC2s pathway,pathogenic T cell subsets,and JNK-MAPK signaling pathway.