ObjectiveTo investigate the molecular mechanisms by which salvianolic acid B （SalB） inhibits epithelial-mesenchymal transition （EMT） in non-small cell lung cancer （NSCLC） by downregulating phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase （PAICS） expression. MethodsNSCLC A549 cells and normal bronchial epithelial cells （bronchial epithelium transformed with Ad12-SV40 2B， BEAS-2B） were used as models. Cell viability was assessed using the cell counting kit-8 （CCK-8） assay after treatment with SalB （0， 50， 100， 200， 300， 400， 500 μmol·L^-1 for 24 or 48 h to determine effective and safe intervention concentrations. Cell proliferation， cell cycle distribution， and apoptosis were evaluated by 5-ethynyl-2′-deoxyuridine （EdU） staining and flow cytometry， respectively. Wound healing and Transwell invasion assays were performed to assess cell migration and invasion. RNA sequencing combined with bioinformatic analysis was conducted to identify differentially expressed genes and functional enrichment. Molecular docking was used to predict the binding ability between SalB and PAICS， and the cellular thermal shift assay （CETSA） was performed to evaluate the effect of SalB on the thermal stability of the PAICS protein. Western blot （WB） was used to detect the effects of SalB on PAICS and EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail， and Slug）. A functional rescue assay was conducted by PAICS overexpression via plasmid transfection. ResultsCompared with the control group， SalB inhibited A549 cell viability in a dose-dependent manner （P<0.05）， and the effective concentrations （≤300 μmol·L^-1） showed no significant cytotoxicity in BEAS-2B cells. Within this concentration range， SalB significantly inhibited A549 cell proliferation， migration， and invasion， and induced G₀/G₁ phase arrest and apoptosis （P<0.05）. Transcriptomic analysis showed that SalB significantly downregulated PAICS expression， and its functions were enriched in cell proliferation and EMT. Bioinformatic analysis indicated that PAICS is highly expressed in lung adenocarcinoma and is associated with poor prognosis （P<0.01）. Molecular docking showed that SalB has strong binding ability to PAICS （binding energy -9.1 kcal·mol^-1. CETSA results showed that SalB significantly increased the thermal stability of the PAICS protein （P<0.05）. WB results showed that， compared with the control group， SalB dose-dependently downregulated PAICS expression， upregulated E-cadherin， and downregulated N-cadherin， Vimentin， Snail， and Slug （P<0.05）. Functional rescue experiments showed that， compared with the empty vector group， PAICS overexpression significantly enhanced A549 cell proliferation， migration， and invasion， promoted cell cycle progression， and inhibited apoptosis （P<0.05）. Meanwhile， compared with the empty vector + SalB-H group， PAICS overexpression partially reversed the inhibitory effects of SalB on malignant phenotypes and EMT-related proteins （N-cadherin， Vimentin， Snail， and Slug）， and downregulated E-cadherin expression （P<0.05，P<0.01）， indicating that PAICS is a key functional target mediating the antitumor effects of SalB. ConclusionSalB effectively inhibits EMT progression and cell cycle progression in A549 cells by downregulating PAICS expression， thereby exerting anti-NSCLC effects. This study not only reveals that PAICS is a key functional target through which SalB regulates EMT， but also provides experimental evidence supporting SalB as a potential candidate drug for inhibiting NSCLC metastasis.

ObjectiveTo investigate the mechanisms by which eupatilin （Eup） inhibits proliferation， invasion， and metastasis of non-small cell lung cancer （NSCLC） through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation （EZH2/H3K27me3） signaling pathway. MethodsIn vivo， a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry （IHC-P） was used to detect the expression of proliferation- and invasion/metastasis-related proteins， including proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）. In vitro， cell counting kit-8 （CCK-8） assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup （0-200 μmol·L^-1） and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine （EdU） assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell （HUVEC） angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. ResultsIn the subcutaneous xenograft model， compared with the model group， Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors， and the tumor inhibition rate was significantly increased （P<0.05）. IHC-P results showed that， compared with the model group， high-dose Eup significantly reduced the expression levels of PCNA， MMP-2， MMP-9， and VEGFA in vivo （P<0.05）. In vitro， compared with the control group， Eup inhibited the proliferation， invasion， and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that， compared with the control group， Eup significantly downregulated EZH2 expression， and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that， compared with the model group， Eup significantly inhibited， in a dose-dependent manner， the expression levels of EZH2， H3K27me3， and proliferation- and invasion/metastasis-related proteins （PCNA， MMP-2， MMP-9， and VEGFA） in both in vivo and in vitro experiments （P<0.05）. In vitro， compared with the control group， overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation， migration， and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.

ObjectiveTo investigate the molecular mechanisms by which salvianolic acid B （SalB） inhibits epithelial-mesenchymal transition （EMT） in non-small cell lung cancer （NSCLC） by downregulating phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase （PAICS） expression. MethodsNSCLC A549 cells and normal bronchial epithelial cells （bronchial epithelium transformed with Ad12-SV40 2B， BEAS-2B） were used as models. Cell viability was assessed using the cell counting kit-8 （CCK-8） assay after treatment with SalB （0， 50， 100， 200， 300， 400， 500 μmol·L^-1 for 24 or 48 h to determine effective and safe intervention concentrations. Cell proliferation， cell cycle distribution， and apoptosis were evaluated by 5-ethynyl-2′-deoxyuridine （EdU） staining and flow cytometry， respectively. Wound healing and Transwell invasion assays were performed to assess cell migration and invasion. RNA sequencing combined with bioinformatic analysis was conducted to identify differentially expressed genes and functional enrichment. Molecular docking was used to predict the binding ability between SalB and PAICS， and the cellular thermal shift assay （CETSA） was performed to evaluate the effect of SalB on the thermal stability of the PAICS protein. Western blot （WB） was used to detect the effects of SalB on PAICS and EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail， and Slug）. A functional rescue assay was conducted by PAICS overexpression via plasmid transfection. ResultsCompared with the control group， SalB inhibited A549 cell viability in a dose-dependent manner （P<0.05）， and the effective concentrations （≤300 μmol·L^-1） showed no significant cytotoxicity in BEAS-2B cells. Within this concentration range， SalB significantly inhibited A549 cell proliferation， migration， and invasion， and induced G₀/G₁ phase arrest and apoptosis （P<0.05）. Transcriptomic analysis showed that SalB significantly downregulated PAICS expression， and its functions were enriched in cell proliferation and EMT. Bioinformatic analysis indicated that PAICS is highly expressed in lung adenocarcinoma and is associated with poor prognosis （P<0.01）. Molecular docking showed that SalB has strong binding ability to PAICS （binding energy -9.1 kcal·mol^-1. CETSA results showed that SalB significantly increased the thermal stability of the PAICS protein （P<0.05）. WB results showed that， compared with the control group， SalB dose-dependently downregulated PAICS expression， upregulated E-cadherin， and downregulated N-cadherin， Vimentin， Snail， and Slug （P<0.05）. Functional rescue experiments showed that， compared with the empty vector group， PAICS overexpression significantly enhanced A549 cell proliferation， migration， and invasion， promoted cell cycle progression， and inhibited apoptosis （P<0.05）. Meanwhile， compared with the empty vector + SalB-H group， PAICS overexpression partially reversed the inhibitory effects of SalB on malignant phenotypes and EMT-related proteins （N-cadherin， Vimentin， Snail， and Slug）， and downregulated E-cadherin expression （P<0.05，P<0.01）， indicating that PAICS is a key functional target mediating the antitumor effects of SalB. ConclusionSalB effectively inhibits EMT progression and cell cycle progression in A549 cells by downregulating PAICS expression， thereby exerting anti-NSCLC effects. This study not only reveals that PAICS is a key functional target through which SalB regulates EMT， but also provides experimental evidence supporting SalB as a potential candidate drug for inhibiting NSCLC metastasis.

ObjectiveTo investigate the mechanisms by which eupatilin （Eup） inhibits proliferation， invasion， and metastasis of non-small cell lung cancer （NSCLC） through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation （EZH2/H3K27me3） signaling pathway. MethodsIn vivo， a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry （IHC-P） was used to detect the expression of proliferation- and invasion/metastasis-related proteins， including proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）. In vitro， cell counting kit-8 （CCK-8） assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup （0-200 μmol·L^-1） and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine （EdU） assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell （HUVEC） angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. ResultsIn the subcutaneous xenograft model， compared with the model group， Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors， and the tumor inhibition rate was significantly increased （P<0.05）. IHC-P results showed that， compared with the model group， high-dose Eup significantly reduced the expression levels of PCNA， MMP-2， MMP-9， and VEGFA in vivo （P<0.05）. In vitro， compared with the control group， Eup inhibited the proliferation， invasion， and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that， compared with the control group， Eup significantly downregulated EZH2 expression， and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that， compared with the model group， Eup significantly inhibited， in a dose-dependent manner， the expression levels of EZH2， H3K27me3， and proliferation- and invasion/metastasis-related proteins （PCNA， MMP-2， MMP-9， and VEGFA） in both in vivo and in vitro experiments （P<0.05）. In vitro， compared with the control group， overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation， migration， and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.

Objective:To investigate the incidence and high-risk pathogenic factors of cardiovascular disease（CVD）in patients with rheumatic and autoimmune diseases，and to construct and validate a predictive model for the risk of CVD occurrence in these patients.Methods:A retrospective analysis was conducted on 239 patients with rheumatic and autoimmune diseases who underwent treatment and echocardiography at the Affiliated Hospital of Inner Mongolia Medical University between June 2020 and June 2023. General patient data，laboratory test results，and echocardiographic findings were collected. Follow-up was performed via electronic medical records or telephone surveys until December 2024 to determine the incidence of CVD，starting from the date of the first echocardiographic examination. Predictive factors were screened using univariate analysis and Lasso regression，and a Logistic regression model was constructed. Internal validation was performed using the Bootstrap method. The model's accuracy and clinical utility were assessed using the Hosmer-Lemeshow test，calibration curve，and decision curve analysis.Results:Among the 239 patients，111 developed CVD. Logistic regression analysis identified age，diastolic blood pressure，use of immunosuppressants，lymphocyte count（LYM），α-hydroxybutyrate dehydrogenase（α-HBDH）level，serum cystatin C（CysC），and right ventricular fractional area change（RVFAC）as independent predictive factors for CVD in these patients（all P<0.05）. The area under the ROC curve（AUC）for the prediction model was 0.895（95% CI = 0.856 - 0.935），and after Bootstrap validation，it was 0.894（95% CI = 0.861-0.925）. The Hosmer-Lemeshow test，calibration curve，and decision curve analysis all indicated that the model had good accuracy and clinical utility. Conclusions:Age，diastolic blood pressure，use of immunosuppressants，LYM，α-HBDH，CysC，and RVFAC may serve as independent risk factors for CVD in patients with rheumatic and autoimmune diseases. The prediction model based on echocardiography combined with laboratory indicators can，to some extent，predict the risk of CVD occurrence in these patients.

Objectives:To investigate the incidence of tyrosine kinase inhibitor (TKI) withdrawal syndrome and psychological issues, and their associated factors, in patients with chronic-phase chronic myeloid leukemia (CML-CP) after TKI discontinuation.Methods:We retrospectively analyzed the clinical data of CML-CP patients who discontinued TKI therapy at Peking University People's Hospital after September 2012. Logistic regression models were used to identify independent factors associated with the occurrence of TKI withdrawal syndrome and psychological issues.Results:A total of 158 patients were included, of whom 92 (58%) were female. The median age at discontinuation was 50 ( IQR, 35-60) years. With a median follow-up of 25 ( IQR, 11-49) months, the 4-year rate of sustained major molecular response (MMR) was 60% (95% CI: 51%-70%) . Fifty-one (32%) patients experienced TKI withdrawal syndrome at a median of 1.3 ( IQR, 0.5-2.0) months after TKI discontinuation. Fifty-one (32%) patients reported psychological issues such as anxiety. These concerns stemmed from fears of fluctuating BCR::ABL1 levels or disease relapse, and, for those who discontinued TKI for pregnancy, worries about adverse fetal effects and/or the fetus inheriting CML. Multivariable analyses revealed that older age at discontinuation [ P=0.003 when adjusting for TKI therapy duration; P=0.002 when adjusting for deep molecular response (DMR) duration], longer TKI therapy duration ( P=0.010) , and longer DMR duration before discontinuation ( P=0.005) were significantly associated with a higher risk of TKI withdrawal syndrome; a university degree or higher ( P=0.010) and TKI discontinuation due to pregnancy or adverse events ( P=0.001) were significantly associated with psychological issues after discontinuation. The occurrence of TKI withdrawal syndrome or psychological issues had no impact on the probability of major molecular response loss after discontinuation. Conclusion:TKI withdrawal syndrome and psychological issues are common in CML patients who discontinue TKI therapy. Older age at discontinuation and longer TKI therapy duration or DMR duration are significantly associated with TKI withdrawal syndrome. Higher education level and TKI discontinuation due to pregnancy or adverse events are significantly associated with psychological issues.

Objective To observe the clinical efficacy of Si-hour"Supplementing Yang and Unblocking Collaterals"Electroacupuncture Therapy based on the midnight-midday ebb-flow theory in treating hemiplegia caused by ischemic stroke.Methods A total of 160 patients diagnosed with ischemic stroke hemiplegia who were treated in the wards and outpatient departments of Huaian Hospital of Traditional Chinese Medicine between January 2023 and June 2024 were selected as study subjects.Patients were randomly divided into an observation group and a control group using a random number table,with 80 cases in each group.Both groups received conventional internal medicine rehabilitation treatment.The control group received conventional acupuncture therapy,while the observation group received Si-hour"Supplementing Yang and Unblocking Collaterals"Electroacupuncture Therapy based on the midnight-midday ebb-flow theory.Treatment was administered for 2 weeks per course,with a total of 3 courses.After completion of treatment,clinical efficacy was evaluated by observing changes in traditional Chinese medicine(TCM)syndrome scores,simplified Fugl-Meyer Assessment(FMA)scores,modified Barthel Index(MBI)scores,fractional anisotropy(FA)values in the cerebral peduncle and posterior limb of internal capsule regions,modified Edinburgh-Scandinavian Stroke Scale(MESSS)scores,as well as plasma viscosity,hematocrit(HCT),and fibrinogen(FIB)levels before and after treatment in both groups.Results(1)The total effective rate was 86.25％(69/80)in the observation group and 70.00％(56/80)in the control group.The efficacy of the observation group was significantly superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,TCM syndrome scores were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(3)After treatment,FMA and MBI scores were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(4)After treatment,FA values in the cerebral peduncle and posterior limb of internal capsule regions,as well as MESSS scores,were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(5)After treatment,plasma viscosity,HCT,and FIB levels were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).Conclusion Si-hour"Supplementing Yang and Unblocking Collaterals"Electroacupuncture Therapy based on the midnight-midday ebb-flow theory significantly improves limb motor function,enhances neural conduction,and optimizes hemorheological parameters in patients with hemiplegia caused by ischemic stroke,demonstrating notable clinical efficacy.

Shengma Gegentang is one of the classic formulas in the Catalogue of Ancient Classic Prescriptions （Second Batch）. This study reviewed ancient and modern literature and used literature tracing and bibliometric methods to analyze the historical evolution， efficacy， indications， dosage decoctions， and modern clinical disease spectrum of Shengma Gegentang. The results indicated that the earliest record of Shengma Gegentang can be found in the Taiping Huimin Heji Jufang of the Song dynasty， but its origin can be traced back to the Shaoyao Siwu Jiejitang in the Beiji Qianjin Yaofang of the Tang dynasty. The composition dosage of Shengma Gegentang is 413 g of Cimicifugae Rhizoma， 619.5 g of Puerariae Lobatae Radix， 413 g of Paeoniae Radix Alba， and 413 g of Glycyrrhizae Radix et Rhizoma， which are ground into coarse powder. Each dose is 12.39 g， and the amount of water added is 300 mL. 100 mL of solution is decocted and taken at the right time. The four drugs in the formula play the role of relieving exterior syndrome， penetrating pathogenic factors， and detoxicating together. Its indications are widely involved in internal medicine， pediatrics， surgery， ophthalmology and otorhinolaryngology， obstetrics and gynecology， sexually transmitted diseases， and other diseases， such as measles， sores， acne， spots， surgical gangrene， red eyes， toothache， chancre， and fetal poison. The epidemic diseases treated by Shengma Gegentang are complicated， including rash， pox， macula， numbness， summer diarrhea， dysentery， sha disease， febrile symptoms， spring warmth， winter warmth， and cold pestilence. At the same time， it is a plague prevention formula. Although Shengma Gegentang has a wide range of indications， it cannot be separated from the pathogenic mechanism of evil Qi blocking the muscle surface and heat in the lungs and stomach. The modern clinical disease spectrum of Shengma Gegentang involves the ophthalmology and otorhinolaryngology system， nervous system， pediatric-related diseases and syndromes， skin system， hepatobiliary system， and digestive system. It plays a key role in the treatment of epidemic diseases such as measles， chronic hepatitis B， dysentery， and tetanus.

Objective:To explore the implementation effects of an proactive health management model for elderly patients with multimorbidity in comprehensive hospitals based on the concept of people-centered integrated care (PCIC).Methods:This study was a randomized controlled trial. Elderly patients who were hospitalized in the Department of General Practice at Shanghai East Hospital Tongji University and also suffered from hypertension, type 2 diabetes and dyslipidemia from November 2022 to January 2024 were included, and were divided into the control group (traditional health management, n=25) and the intervention group (proactive health management, n=25) using the random number table method. A research team comprising experts in general medicine, pharmacy, nutrition, rehabilitation medicine, psychology, and other relevant specialties was formed. Based on literature analysis, clinical experience, and hospital resources, the team collaborated to develop a comprehensive, hospital-based proactive health management model for elderly patients with comorbidities based on the PCIC concept. Patients in the control group were managed using the traditional health management model. Patients in the intervention group were managed using the proactive health management model. Baseline clinical data was collected and the patients were followed up for 6 months. At the 6-month follow-up, data on blood pressure, fasting blood glucose, and blood lipids were collected, as well as information on polypharmacy, activities of daily living (ADL) ability, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, and unplanned rehospitalization were recorded. Results:A total of 50 patients were enrolled, with 25 patients in each group. The control group had an average age of (70.40±6.54) years, with 15 males(60.0%). The intervention group had an average age of (71.20±5.14) years, with 16 males(64.0%). At the 6-month follow-up, the standardization rates of blood pressure, fasting blood glucose, glycated hemoglobin, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG) in both groups were higher than those in the baseline (all P<0.05).In addition, patients in the intervention group had the compliance rates for higher blood pressure, fasting blood glucose, 2-hour postprandial blood glucose, HbA1c, LDL-C, non-HDL-C, and TG than the control group (all P<0.05).At the 6-month follow-up, the 10-year ASCVD high-risk patient percentage decreased in the intervention group compared with baseline ( P=0.023) and was lower than that of the control group ( P=0.045), and the unanticipated readmission rate of patients in the intervention group was also lower than that of the control group ( P=0.042). Conclusions:A proactive health management model for elderly patients with geriatric multimorbidity in a comprehensive hospital, based on the concept of PCIC, was applied to an elderly population with concurrent hypertension, type 2 diabetes and dyslipidemia. The results of the management were favorable.

Objective:To investigate the effects of transhepatic arterial chemoembolization(TACE)combined with Endostar on CD4+/CD8+T cells,5-aminoketovalonate synthase 1(ALAS1)and HIPPO-YAP signaling pathway in patients with hepatocellular carcinoma(HCC).Methods:A total of 60 HCC patients admitted to Chengdu Third People's Hospital from January 2018 to December 2021 were enrolled and randomly divided into TACE treatment group(A)and TACE combined with Endostar treatment group(B),with 30 patients in each group.T lymphocyte,ALAS1 and indicators of HIPPO-YAP signaling pathway were observed in the two groups.Results:In group A,1 subject had complete remission,2 subjects had partial remission,2 subjects had stable remission,and 4 subjects had progress;in group B,2 subjects had complete remission,4 subjects had partial remission,4 subjects had stable remis-sion,and 1 subject had progress.The total effective rate in group B(33.33%)was significantly higher than that in group A(10.00%),with significant difference among groups(P=0.028).There were no significant differences in CD4+T cells,CD8+T cells and CD4+/CD8+T cells between the two groups before treatment(P=0.972,0.995,0.917).After treatment,level of CD4+T cells in the two groups was significantly increased(P<0.001),while level of CD8+T cells was significantly decreased(P<0.001).CD4+/CD8+T cells was significantly increased(P<0.001),and the changes in group B were significant compared with group A(P<0.001).There was no significant difference in content of ALAS1 between the two groups before treatment(P=0.975);after treatment,content of ALAS1 in liver cancer tissues of the two groups was significantly increased(P<0.001),which in group B was significantly higher than that in group A(P<0.05).Before treatment,there were no significant differences in mammalian STE20-like protein kinase 2(MST2),large tumor suppressor 1(LATS1)and Yes-associated protein(YAP)between the two groups(P=0.134,0.134,0.134).After treatment,mRNA relative expressions of MST2 and LATS1 were significantly increased(all P<0.001),while mRNA relative expression of YAP were significantly decreased(P<0.001),and changes of group B were significant compared with group A(all P<0.001).After treat-ment,there were 5 more cases of no adverse reactions in group B than in group A,and the total incidence of adverse reactions(16.67%)was significantly lower than that in group A(43.33%),with a significant difference between groups(P=0.024).Conclu-sion:TACE combined with Endostar has significant therapeutic effect on HCC patients,which can effectively regulate CD4+/CD8+T cells,promote ALAS1 secretion,and activate HIPPO-YAP signaling pathway.