Intestinal barrier damage is a prominent feature of non-alcoholic fatty liver disease （NAFLD） and serves as a critical factor driving the progression from simple fatty liver to non-alcoholic steatohepatitis （NASH）， fibrosis， and cirrhosis. The "turbid pathogenic factors entering the blood" theory integrates classical traditional Chinese medicine （TCM） principles with contemporary disease evolution trends and research findings. It posits that endogenous turbid pathogenic factors within the body infiltrate the blood vessels， leading to impure and viscous blood quality， thereby triggering various diseases. Based on this theory， this article elucidated the pathogenic mechanism of NAFLD-associated intestinal barrier damage. It argued that in NAFLD， the liver loses its dredging function， and the spleen becomes obstructed and dysfunctional. Moreover， essential nutrients fail to be properly transformed， resulting in the internal generation of turbid pathogenic factors. This subsequently initiates a series of pathological changes， namely， "infiltration of phlegm-turbidity into the blood， eroding the intestinal mucosa"， "infiltration of glucose-turbidity into the blood， macerating and eroding the intestinal mucosa"， "infiltration of heat-turbidity into the blood， scorching and eroding the intestinal mucosa"， and "infiltration of stasis-turbidity into the blood， stagnating and eroding the intestinal mucosa"， ultimately causing intestinal barrier damage. Furthermore， guided by the "turbid pathogenic factors entering the blood" theory， this article explored TCM intervention strategies： employing medicinals targeting the liver meridian to address the root cause and reduce the generation and deposition of turbid pathogenic factors in the liver， administering blood-system medicinals to clear the blood and purge turbidity， thereby intercepting the progression of the disease mechanism， and applying tonifying medicinals to bolster healthy Qi and defend against turbid invasion， allowing the damaged intestinal mucosa to gradually heal. This article presented novel theoretical and medicinal perspectives for analyzing NAFLD-associated intestinal barrier damage based on the "turbid pathogenic factors entering the blood" theory， aiming to provide new entry points and broader horizons for related research and clinical practice.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Objective:To analyze the condition of subclinical atherosclerosis (SCA) in patients with psoriatic arthritis (PsA) and to provide a reference for better management of the associated cardiovascular risk in patients with PsA.Methods:Based on the cohort of PsA patients (PKUPsA) in the Department of Rheumatism and Immunology, Peking University First Hospital, 240 PsA patients without previous clinical atherosclerotic disease between July 2018 and June 2024 were included. The demographic data traditional cardiovascular disease risk factors, PsA related indicators and medications were collected when all patients were entered into the cohort. Increased intima-media thickness and/or arterial plaque formation in bilateral carotid arteries examined by ultrasonography are defined as the presence of SCA. Based on this, patients were divided into SCA and no SCA groups, and the two groups were compared and analyzed. Statistics were performed using the Mann-Whitney U test, independent sample t test, χ2 test and Logistic regression analysis. Results:Eighty-five of 240 patients (35.4%) had SCA, including 55 (22.9%) with cIMT thickening and 51 (21.2%) with carotid plaque. Compared with the PsA patients without SCA, patients with SCA were older [55.0 (42.0, 62.5) vs. 42.0(35.0, 53.0) year of age, Z=-4.90, P<0.001], had longer disease course of arthritis [4.6 (1.0, 10.1) vs. 3.0(1.0, 6.1) years, Z=-1.98, P=0.048], more patients with combined hypertension [34.1%(29/85) vs. 15.5%(24/155), χ2=11.08, P<0.001], hyperlipidemia [47.1%(40/85) vs. 27.1%(42/155), χ2=1.22, P=0.002] and the taking of statins [14.1%(12/85) vs. 5.8%(9/155), χ2=4.75 , P=0.029], hypoglycemic agents [10.6%(9/85) vs. 3.9%(6/155), χ2=4.23, P=0.040] and antihypertensive drugs [17.6%(15/85) vs 6.5%(10/155), χ2=7.37, P=0.007]. They also had a higher blood glucose level[5.37 (5.17, 6.09)mmol/L vs. 5.26(4.97, 5.67)mmol/L, Z=-2.82 , P=0.005], low-density lipoprotein [(3.05± 0.76)mmol/L vs. (2.78±0.75)mmol/L, t=2.60, P=0.010] and blood uric acid level[351 (312, 412)μmol/L vs. 333(279, 408)μmol/L, Z=-2.10, P=0.036]. Multivariate analysis showed that older [ OR (95% CI) =1.059 (1.033, 1.086), P<0.001], increased low density lipoprotein [ OR (95% CI) =1.519 (1.018, 2.267), P=0.041] and increased blood uric acid levels [ OR (95% CI)=1.004 (1.001, 1.007), P=0.017] were an independent risk of SCA in PsA patients. Conclusion:More than 1/3 of PsA patients with SCA without past history of clinical atherosclerosis with SCA, advanced age, increased blood low density lipoprotein level, and elevated uric acid level are independent risk factors for PsA with SCA, so attention should be paid to the assessment and management of cardiovascular-related risk. Early intervention can help to improve patient prognosis.

Objective:Treat-to-target strategies for psoriatic arthritis (PsA) have been proposed for several years, however, the status of target and goal achievement in China is unknown. Therefore, we aimed to investigate the target achievement of PsA patients, and differences of treatment goals were further analyzed.Methods:A total of 360 PsA patients from Peking University First Hospital PsA patient cohort (PKUPsA) between January 2016 and March 2024 were included. We retrospectively analyzed the disease activity of patients at their enrollment. Minimal disease activity (MDA), disease activity index for PsA (DAPSA), clinical DAPSA (cDAPSA) and disease activity score based on 28 joint counts (DAS28) were evaluated. Interclass correlation coefficient (ICC) was used to test the consistency of all these assessments.Results:Three hundred and sixty patients were included in this study, with 149 females (41.4%), median age 47 (36, 57) years and duration of PsA for 2.0(1.0, 6.8) years. 129 (35.8%) patients reported family history of PsO. The most common comorbidities were hyperlipidemia (101, 28.1%) and hypertension (78, 21.7%). There were 217 (60.3%), 75 (20.8%) and 18 (5.0%) patients treated with conventional synthetic DMARDs, biologics and JAK inhibitors respectively. Forty-nine (13.6%) patients ever received intra-articular injection of glucocorticoid. Based on the different definitions, the rates of target achievement were 33.9% (MDA), 56.1% (DAPSA), 60.8% (DAS28-ESR), 63.9% (DAS28-CRP) and 64.2% (cDAPSA). The main limiting factors for MDA attainment among those who had achieved DAPSA or DAS-defined targets were pain VAS, Psoriasis Area and Severity Index (PASI), tender/swollen joint count, patient global assessment, HAQ, and number of enthesitis, based on leeds Enthesitis Index(LEI). The ICCs of these evaluation methods were 0.489~0.819 ( P<0.001). The consistency was the best between DAPSA and cDAPSA, medium between DAS28-CRP and DAS28-ESR, and worst between MDA and DAS28-CRP. Moreover, DAPSA was more consistent with DAS28 than cDASPA. MDA showed moderate consistency with all other assessments. Conclusion:33.9%~64.2% of PsA patients achieved targets based on different definitions. MDA was the most stringent target, while cDAPSA was the most loose one. In general, MDA was not well consistent with other assessments.

Objective:To explore the differences in the CVD risk and lipid profiles in psoriatic arthritis (PsA) patients with different disease activity and investigate lipid management status in Chinese patients with PsA.Methods:Patients were enrolled from PKUPsA-PC cohort in Peking University First Hospital from January 2016 to January 2024. Data were collected at their first visit, including disease activity score, lipid profiles and treatment. Two modified CVD risk prediction models (modified China-PAR and modified FRS-CVD) were applied to predict the CVD risk over 10 years. All enrolled patients were subsequently stratified into low, intermediate and high-risk groups. The status of lipid target achievement was assessed based on lipid management recommendations proposed by prediction models. In addition, DAPSA was used to stratify PsA patients into remission, low, moderate and high-disease activity groups, and the differences in CVD risk and lipid profiles among PsA patients with different disease activity status were explored. The t test was used for comparison between 2 groups for measures that conformed to normal distribution; the Mann-Whitney U test was used for comparison between 2 groups for measures that were skewed; and the chi-square test was used for comparison between 2 groups for categorical data.Results:Three hundred and seven PsA patients were included in this study. They were aged 47 (36, 57) years with 121 (39.4%) female, disease duration of skin lesions of 14 (7, 23) years and disease duration of PsA for 3 (1, 8) years. There were 148 (48.2%) patients with dyslipidemia, and 38 (25.7%) of them were receiving lipid lowering drugs. By the modified China-PAR model, there were 174 (56.7%), 76 (24.8%) and 57 (18.5%) in the low-, moderate- and high-risk groups. By the modified FRS-CVD model, there were 173 (56.4%), 58 (18.9%) and 76 (24.7%) patients in the corresponding groups. According to the recommendations for lipid management based on FRS-CVD model, 80 (26.1%) patients did not achieve the target of lipid profile, including 9/174 (5.2%) in the modified model low-risk group, 20/76 (26.3%) in the intermediate-risk group, and 51/57 (89.5%) in the high-risk group, but there were only 12 (15.0%) patients receiving statin therapy. Compared with the remission and low disease activity groups, patients in the moderate-to-high disease activity group were older [50 (37, 60) years vs. 43 (35, 55) years, Z=-2.42, P=0.016]; had a higher proportion of hypertension (30.3% vs. 15.0%, χ2=9.60, P=0.002); and had lower HDL-C levels [1.1 (0.9, 1.3) mmol/L vs. 1.2 (1.0, 1.4) mmol/L, Z=-3.18, P=0.001]. Under the modified China-PAR and modified FRS-CVD risk prediction models, a higher proportion of patients with high disease activity in PsA were stratified at high 10-year CVD risk compared with the remission and low disease activity groups (29.5% vs. 19.6%, χ2=3.81, P=0.005) and (23.5% vs. 12.4%, χ2=6.00, P=0.014). Conclusion:Nearly half of the PsA patients are at medium-high risk to CVD. CVD risk is significantly higher in patients with moderate to high disease activity than in patients with remission and low disease activity. HDL-c levels are lower in patients with high disease activity. Nevertheless a quarter of patients did not achieve the target of lipid profile, and few patients are receiving statin. More attention should be paid to CVD risk evaluation and lipid management as a part of treat-to-target strategy to improve the prognosis.

Objective To investigate the mechanism of Fuzheng Yangxin Prescription in improving cardiac function in rats with heart failure with reduced ejection fraction(HFrEF)through regulation of AMPK/mTOR signaling pathway.Methods An HFrEF rat model was established via left anterior descending coronary artery ligation.Rats were randomized divided into sham-operation group,model group,Fuzheng Yangxin Prescription group and Entresto group,followed by 28 days of intervention.Echocardiography was used to measure left ventricular internal dimension at end-systole(LVIDs),left ventricular internal dimension at end-diastole(LVIDd),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),HE staining and Masson staining were used to observe myocardial morphology and fibrosis,serum contents of NT-proBNP and inflammatory factors(TNF-α,IL-1β,IL-6)were detected by ELISA,Western blot was performed to analyze p-AMPK,p-mTOR and protein expressions of autophagy markers(Beclin1,LC3,p62).Results Compared with sham-operation group,the LVIDs and LVIDd in model group significantly increased(P<0.05),while LVEF and LVFS significantly decreased(P<0.05),the structure of myocardial cells was disordered and arranged loosely,the deposition of collagen fibers in the infarct area was increased,and the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly increased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly decreased(P<0.05),while the protein expressions of p-mTOR and p62 significantly increased(P<0.05);compared with the model group,the LVIDs and LVIDd of rats in Fuzheng Yangxin Prescription group significantly decreased(P<0.05),the LVEF and LVFS were significantly increased(P<0.05),the disorder of myocardial cell arrangement and fibrosis were alleviated,the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly decreased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly increased(P<0.05),while the protein expressions of p-mTOR and p62 significantly decreased(P<0.05).Conclusion Fuzheng Yangxin Prescription may regulate autophagy by activating AMPK/mTOR pathway and improve cardiac function in HFrEF rats.

Objective:To investigate the impacts of total salvianolic acid(TSA)on macrophage polarization and mesenchymal macrophage infiltration in liver cancer bearing mice by regulating the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods:Mice were randomly separated into liver cancer group,TSA low concentra-tion group,TSA medium concentration group,TSA high concentration group,TSA high concentration+TLR4 inhibitor(TAK242)group and control group,with 12 mice in each group.Except for control group,mice in all other groups were injected subcutaneously into the right axilla to construct liver cancer models by intraperitoneal transmission of third-generation H22 cell suspension.After suc-cessful modeling,administration was carried out once a day for 2 weeks.Changes in tumor weight,tumor volume,spleen index and thymus index were detected.Immunofluorescence was applied to detect proportions of CD86 and CD206 positive cells in tumor tissue.ELISA was applied to detect levels of inducible nitric oxide synthase(iNOS),IL-6 and IL-10 in tumor tissues.Flow cytometry was ap-plied to detect proportion of CD11b+F4/80+in tumor tissue.Western blot was applied to detect TLR4,p-NF-κB P65 and MyD88 pro-teins in tumor tissue.The life quality and survival rate of mice were observed.Results:Compared with control group,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were reduced in liver cancer group,while proportion of CD206 positive cells and level of IL-10 in tumor tissue were increased(P<0.05).Compared with liver cancer group,tumor weight and volume of mice in TSA low,medium,high concentration groups were decreased,while survival rate,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were increased,proportion of CD206 positive cells,level of IL-10,and proportion of CD11b+F4/80+in tumor tissue decreased(P<0.05).TAK242 reversed the effects of high concentration TSA on macrophage polarization and myeloid macrophage infiltration in liver cancer bearing mice.Conclusion:TSA may promote M1 polari-zation of macrophages in liver cancer bearing mice and inhibit myeloid macrophage infiltration by activating the TLR4/MyD88/NF-κB pathway.

Objective To investigate the effects of scoparone(Sco)on proliferation and invasion of colon cancer cell line HCT116,and its effect on the expression of epidermal growth factor receptor(EGFR).Methods 1)HCT116 cells were divided into control group,50Sco group,100Sco group and 200Sco group.The cells in con-trol group were incubated with culture medium for 48 hrs.The 50Sco group,100Sco group and 200Sco group were incubated with 50,100 and 200 μmol/L scoparone for 48 hrs respectively.2)HCT116 cells were divided into con-trol group,NC-200Sco group,NC-LV+200Sco group and EGFR-LV+200Sco group.The control group was incuba-ted with normal culture medium for 48 hrs.NC-200Sco group was incubated with 200 μmol/L scoparone for 48 hrs.NC-LV and EGFR-LV were infected into HCT116 cells in NC-LV+200Sco group and EGFR-LV+200Sco group,then incubated with 200 μmol/L scoparone for 48 hrs.Cell proliferation was detected by MTT assay and EdU stai-ning,cell apoptosis was detected by flow cytometry and cell invasion was detected by Transwell assay.EGFR mRNA was detected by RT-qPCR,the level of EGFR,Bcl-2,Bax,matrix metalloproteinase(MMP)-2 and MMP-9 protein was detected by Western blot.Results Compared to the control group,the cell viability,proportion of EdU positive cells and counting number of invasive cells in 50Sco group,100Sco group and 200Sco group all decreased(P＜0.05).Cell apoptosis rate and Bax protein expression increased(P＜0.05),the protein expression of Bcl-2,MMP-2 and MMP-9 decreased(P＜0.05).mRNA and protein expression of EGFR were de-creased(P＜0.05).Compared with NC-200 Sco group and NC-LV+200Sco group,the expression level of mRNA and protein of EGFR in EGFR-LV+200Sco group was increased(P＜0.05).Cell viability,proportion of EdU posi-tive cells and counting number of invasive cells all increased(P＜0.05).The cell apoptosis rate and Bax protein expression level were decreased(P＜0.05).The protein expression of Bcl-2,MMP-2 and MMP-9 was increased(P＜0.05).Conclusions Scoparone has anti-colon cancer cell activity and inhibits proliferation as well as invasion of colon cancer cells through inhibition of EGFR.

Rhinovirus (RV) has been reported as one of the main viral causes of human respiratory infections and has received increasing attention in recent years due to its strong association with various respiratory diseases. Studies have shown that RV not only causes the common cold but also plays a critical role in lower respiratory tract conditions such as bronchiolitis, pneumonia, and asthma. Notably, RV is implicated in both the onset and exacerbation of asthma. This review systematically summarizes a wide range of RV-associated respiratory diseases in the available literature. Although there are currently no specific antiviral therapies or vaccines targeting RV, advances in the development of polyvalent vaccines and antiviral drugs provide promising directions for future prevention and treatment. Clarifying the relationship between RV and diseases will provide strong support for optimizing treatment strategies and preventing and controlling respiratory diseases.

Objective To investigate the mechanism of Fuzheng Yangxin Prescription in improving cardiac function in rats with heart failure with reduced ejection fraction(HFrEF)through regulation of AMPK/mTOR signaling pathway.Methods An HFrEF rat model was established via left anterior descending coronary artery ligation.Rats were randomized divided into sham-operation group,model group,Fuzheng Yangxin Prescription group and Entresto group,followed by 28 days of intervention.Echocardiography was used to measure left ventricular internal dimension at end-systole(LVIDs),left ventricular internal dimension at end-diastole(LVIDd),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),HE staining and Masson staining were used to observe myocardial morphology and fibrosis,serum contents of NT-proBNP and inflammatory factors(TNF-α,IL-1β,IL-6)were detected by ELISA,Western blot was performed to analyze p-AMPK,p-mTOR and protein expressions of autophagy markers(Beclin1,LC3,p62).Results Compared with sham-operation group,the LVIDs and LVIDd in model group significantly increased(P<0.05),while LVEF and LVFS significantly decreased(P<0.05),the structure of myocardial cells was disordered and arranged loosely,the deposition of collagen fibers in the infarct area was increased,and the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly increased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly decreased(P<0.05),while the protein expressions of p-mTOR and p62 significantly increased(P<0.05);compared with the model group,the LVIDs and LVIDd of rats in Fuzheng Yangxin Prescription group significantly decreased(P<0.05),the LVEF and LVFS were significantly increased(P<0.05),the disorder of myocardial cell arrangement and fibrosis were alleviated,the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly decreased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly increased(P<0.05),while the protein expressions of p-mTOR and p62 significantly decreased(P<0.05).Conclusion Fuzheng Yangxin Prescription may regulate autophagy by activating AMPK/mTOR pathway and improve cardiac function in HFrEF rats.