Huanglian Jiedutang （HLJDT）， as a classical formula for clearing heat and removing toxins， has been widely applied in the treatment of various clinical diseases in recent years， particularly during the fire-heat stage of stroke， where it has attracted considerable attention. Based on previous studies， this paper systematically elaborates on the research progress on the active components of HLJDT， its clinical application in ischemic stroke， and advances in studies on its mechanisms of action. Modern pharmacological studies have demonstrated that HLJDT contains multiple active components， including baicalin， geniposide， and berberine. In the treatment of ischemic stroke， these components exert therapeutic effects through multi-target， multi-pathway， and multi-level mechanisms. Clinical studies have shown that HLJDT can increase cerebral blood flow， reduce cerebral infarct volume， and improve post-stroke physical dysfunction in patients with ischemic stroke. Experimental studies have indicated that HLJDT can improve neurological function scores and increase cerebral perfusion in experimental stroke models. In addition， the mechanisms underlying the anti-ischemic stroke effects of HLJDT may be related to anti-inflammatory and antioxidant activities， promotion of angiogenesis， and regulation of amino acid and energy metabolism. Although existing studies have confirmed that HLJDT exhibits multi-target and multi-pathway synergistic therapeutic characteristics， further large-sample randomized controlled trials are still needed to verify its long-term efficacy and to further elucidate the dynamic interaction network among components， targets， and pathways. Combined with network pharmacology and molecular docking analyses， this study further clarifies the synergistic targets of the core components （berberine， baicalin， and geniposide）， providing a theoretical basis for in-depth research and clinical translation of HLJDT in the treatment of ischemic stroke.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective:To evaluate the diagnostic performance of resting echocardiography in detecting severe coronary artery stenosis.Methods:A total of 136 patients with suspected coronary artery disease（CAD）who presented to Sichuan Provincial People's Hospital between January 2021 and December 2024 were prospectively enrolled. All patients underwent both coronary computed tomography angiography（CCTA）and transthoracic echocardiography within one week. Based on CCTA results，the patients were divided into non-severe stenosis group（ n=78）and severe stenosis group（ n=58）. Echocardiographic parameters including left atrial maximum volume（LAVmax），left ventricular global longitudinal strain（GLS），left ventricular longitudinal strain of endo-myocardium，mid-myocardium，epi-myocardium（LSendo，LSmid，LSepi），early diastolic mitral inflow velocity（E），early diastolic mitral annular velocity of the lateral and septal walls（e'），and E/e' were measured. Predictive factors for severe coronary stenosis were identified using LASSO regression，and a nomogram model was developed via multivariate Logistic regression. Model performance was evaluated using ROC curves，calibration curves，and decision curve analysis. Results:Multivariate Logistic regression analysis revealed LSendo，LAVmax，and E/e' as independent predictors of severe coronary artery stenosis. The nomogram constructed based on these predictors achieved an area under the curve of 0.798（95% CI=0.723-0.873），with sensitivity and specificity of 0.756 and 0.759，respectively. Conclusions:The resting echocardiography-based nomogram model demonstrates good diagnostic efficacy for severe coronary artery stenosis. It may serve as a noninvasive tool to assist in risk stratification and clinical decision-making in patients with suspected CAD.

Objective:To evaluate the diagnostic performance of resting echocardiography in detecting severe coronary artery stenosis.Methods:A total of 136 patients with suspected coronary artery disease（CAD）who presented to Sichuan Provincial People's Hospital between January 2021 and December 2024 were prospectively enrolled. All patients underwent both coronary computed tomography angiography（CCTA）and transthoracic echocardiography within one week. Based on CCTA results，the patients were divided into non-severe stenosis group（ n=78）and severe stenosis group（ n=58）. Echocardiographic parameters including left atrial maximum volume（LAVmax），left ventricular global longitudinal strain（GLS），left ventricular longitudinal strain of endo-myocardium，mid-myocardium，epi-myocardium（LSendo，LSmid，LSepi），early diastolic mitral inflow velocity（E），early diastolic mitral annular velocity of the lateral and septal walls（e'），and E/e' were measured. Predictive factors for severe coronary stenosis were identified using LASSO regression，and a nomogram model was developed via multivariate Logistic regression. Model performance was evaluated using ROC curves，calibration curves，and decision curve analysis. Results:Multivariate Logistic regression analysis revealed LSendo，LAVmax，and E/e' as independent predictors of severe coronary artery stenosis. The nomogram constructed based on these predictors achieved an area under the curve of 0.798（95% CI=0.723-0.873），with sensitivity and specificity of 0.756 and 0.759，respectively. Conclusions:The resting echocardiography-based nomogram model demonstrates good diagnostic efficacy for severe coronary artery stenosis. It may serve as a noninvasive tool to assist in risk stratification and clinical decision-making in patients with suspected CAD.

Objective:To analyze the prognostic outcomes of 1 147 patients who underwent liver transplantation at Qingdao University Affiliated Hospital and to summarize measures to enhance the efficacy of liver transplantation.Methods:A retrospective analysis was conducted on the clinical and follow-up data of 1 147 liver transplant patients at Qingdao University Affiliated Hospital.Results:The overall postoperative 1-, 3-, and 5-year survival rates for the 1 147 liver transplant patients were 87.20%, 73.40%, and 65.60%, respectively. The survival rates for benign disease liver transplant recipients were 88.01%, 84.98%, and 81.39% at 1, 3, and 5 years post-transplant, respectively, compared to recipients transplanted for malignancies of 78.11%, 64.41%, and 60.06% (all P<0.001). Among the mid vs more recent period, patients' 1-year and 3-year postoperative survival rates were 84.20%, 70.80% vs 90.50%, 71.70%, respectively,significantly in favor of recently enrolled patients ( P=0.022). In the complex surgery group, patients' 1-, 3-, and 5-year survival rates were 82.70%, 65.50%, 56.70%, while in less complicated group, it was 89.00%, 76.50%, 69.20% ( P<0.001). The primary causes of death for benign disease recipients were multi-organ failure (4.1%), while in recipients with malignant disease primary cause of death was tumor recurrence (23.7%). Postoperative complications included primary graft dysfunction, delayed graft function recovery, portal vein thrombosis, hepatic artery thrombosis, biliary stricture, post-transplant lymphoproliferative disorder, and graft-versus-host disease, with occurrence rates of 1.05%, 6.89%, 1.92%, 0.44%, 2.00%, 0.61%, and 0.44%, respectively. Conclusions:With the continuous improvement in surgical techniques and perioperative care levels, the 3-year survival rate of recipients at our center has increased. Malignant diseases and complex liver transplantation remain crucial factors affecting recipient prognosis, highlighting the need to further enhance comprehensive treatment capabilities for patients with malignant diseases and complex surgeries.

Objective To investigate the application of organoid technology in colorectal cancer research and analyze the factors influencing the success rate of organoid cultivation. Methods A total of 24 samples of colorectal cancer patients treated at Tianjin Fifth Central Hospital and cultured organoids using specific culture media and Matrigel. The samples were collected within 30 minutes post-excision and stored at 4℃ to minimize contamination and protein degradation. During the cultivation process,the authors recorded instances of bacterial or fungal contamination and the organoid growth,and test for their histological structure and expression of tumor markers. Additionally,by analyzing clinical information from the patients who provided the samples,explore potential factors that may affect the success rate of culturing colorectal cancer organoids. Results A success rate of 70.8％ (17/24) was achieved in the cultivation of organoid. The success rate of organoid culture was significantly different from that of tumor stage (all P<0.05),with significantly higher successful organoid cultivation rate for stage Ⅱ and stage Ⅲ tumor tissues than those for stageⅠand Ⅳ[83.3％ (5/6),90.9％ (10/11) vs. 33.4％ (1/3),25.0％ (1/4)]. Additionally,samples with a Ki-67 positive area proportion of 55％-70％ exhibited the highest success rate (100％). Phenotypic experiments on the organoids indicated that their pathological histological structure and the expression of tumor markers were consistent with those of the primary tissues,suggesting that the organoids retained the histological characteristics of the primary lesions. Conclusions This study successfully established a colorectal cancer organoid model revealing the impact of tumor staging and the proportion of Ki-67 positive areas on the success rate of culture. The organoid model effectively retains the histological characteristics of the primary lesion,providing a powerful in vitro tool for the research and treatment of colorectal cancer.

Objective To compare the different therapeutic efficacies between radiofrequency and cryoballoon ablation in atrial fibrillation(AF)patients with enlarged left atrium.Methods A total of 106 AF patients with enlarged left atrium(LAVI)>34ml/m2 who visited our center between December 2016 and May 2022 for catheter ablation were enrolled.They were divided into radiofrequency group(R-group)and cryoballoon group(C-group)according to the procedure.The recurrence of AF was compared between the two groups.Results The median follow-up time was 12 months and no death occurred.The rate of loss of follow-up was 3.8%.The overall recurrence rate of AF after ablation was 36.8%.There was no significant difference in clinical baseline between the two groups(P>0.05).The radiofrequency group had longer operation time(P<0.001),shorter X-ray time and less exposure(P<0.05);There was no significant difference in clinical baseline and postoperative complications between the two groups(P>0.05).The results of survival analysis showed that there was no significant difference in the survival rate of patients without atrial fibrillation/atrial flutter/atrial tachycardia between the two groups(P>0.05).Conclusion For AF patients with enlarged left atrium,the clinical effects of the two methods were similar.Cryoballoon takes a shorter time,while radiofrequency has a lower X-ray time and exposure dose for physicians and patients.Therefore,appropriate ablation methods should be selected according to the actual situation.

Objective To investigate the application of organoid technology in colorectal cancer research and analyze the factors influencing the success rate of organoid cultivation. Methods A total of 24 samples of colorectal cancer patients treated at Tianjin Fifth Central Hospital and cultured organoids using specific culture media and Matrigel. The samples were collected within 30 minutes post-excision and stored at 4℃ to minimize contamination and protein degradation. During the cultivation process,the authors recorded instances of bacterial or fungal contamination and the organoid growth,and test for their histological structure and expression of tumor markers. Additionally,by analyzing clinical information from the patients who provided the samples,explore potential factors that may affect the success rate of culturing colorectal cancer organoids. Results A success rate of 70.8％ (17/24) was achieved in the cultivation of organoid. The success rate of organoid culture was significantly different from that of tumor stage (all P<0.05),with significantly higher successful organoid cultivation rate for stage Ⅱ and stage Ⅲ tumor tissues than those for stageⅠand Ⅳ[83.3％ (5/6),90.9％ (10/11) vs. 33.4％ (1/3),25.0％ (1/4)]. Additionally,samples with a Ki-67 positive area proportion of 55％-70％ exhibited the highest success rate (100％). Phenotypic experiments on the organoids indicated that their pathological histological structure and the expression of tumor markers were consistent with those of the primary tissues,suggesting that the organoids retained the histological characteristics of the primary lesions. Conclusions This study successfully established a colorectal cancer organoid model revealing the impact of tumor staging and the proportion of Ki-67 positive areas on the success rate of culture. The organoid model effectively retains the histological characteristics of the primary lesion,providing a powerful in vitro tool for the research and treatment of colorectal cancer.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

ObjectiveTo investigate the relationship between lower limb muscle strength and walking speed in older adults, and to analyze the mediating role of flexibility and dynamic balance. MethodsFrom November to December, 2021, a total of 155 older adults at the Shanghai Senior Sports and Health Home were included. Their basic health information was collected, and the lower limb muscle strength, flexibility, dynamic balance and walking speed were tested. A mediated effects analysis was conducted. ResultsThere was a pairwise correlation among lower limb muscle strength, flexibility, dynamic balance and walking speed in older adults (r > 0.210, P < 0.01). In the mediated effects model, after controlling for age and gender, lower limb muscle strength did not directly predict walking speed in older adults (β = 0.029, P = 0.699), however, lower limb muscle strength could influence walking speed through the partial mediation of dynamic balance (effect = 0.0130, 95% CI 0.0073~0.0197) and the chain mediation of lower flexibility and dynamic balance (effect = 0.0019, 95% CI 0.0003~0.0043). ConclusionLower limb muscle strength can indirectly affect walking speed in older adults through the mediators of flexibility and dynamic balance, or the dynamic balance alone.