ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.

By tracing back to the classical literature of traditional Chinese medicine （TCM）， this paper proposes a TCM philosophy integrating "dao （道）-shen（神）-formula" as a unified whole. It systematically elaborates the formula-constructing thought that "the monarch drug follows dao， and the formula carries dao"， analyzes shen （spirit/ life vitality） from the perspectives of its substance， manifestation and function， and explains the pivotal role of shen in connecting dao and formula. Taking Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》） as an example， the paper explores how the "dao-shen-formula" union is implemented in classics. Based on the Inner Canon of Yellow Emperor （《黄帝内经》）， the paper articulates a practical pathway for the "dao-shen-formula" union， namely "observing shen to differentiate the mechanism → restoring dao to regulate shen → achieving harmony of shen and restoration of dao"， thereby transforming abstract concepts into operable and verifiable practical approaches. It is hoped that this study will provide theoretical foundation and practical guidance for the shift from treating diseases to treating the person， and from correcting deviations to restoring dao in TCM.

By tracing back to the classical literature of traditional Chinese medicine （TCM）， this paper proposes a TCM philosophy integrating "dao （道）-shen（神）-formula" as a unified whole. It systematically elaborates the formula-constructing thought that "the monarch drug follows dao， and the formula carries dao"， analyzes shen （spirit/ life vitality） from the perspectives of its substance， manifestation and function， and explains the pivotal role of shen in connecting dao and formula. Taking Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》） as an example， the paper explores how the "dao-shen-formula" union is implemented in classics. Based on the Inner Canon of Yellow Emperor （《黄帝内经》）， the paper articulates a practical pathway for the "dao-shen-formula" union， namely "observing shen to differentiate the mechanism → restoring dao to regulate shen → achieving harmony of shen and restoration of dao"， thereby transforming abstract concepts into operable and verifiable practical approaches. It is hoped that this study will provide theoretical foundation and practical guidance for the shift from treating diseases to treating the person， and from correcting deviations to restoring dao in TCM.

Rheumatoid arthritis belongs to arthralgia in the theory of traditional Chinese medicine, with cold dampness obstruction pattern (CDO) and damp heat obstruction pattern (DHO) as the main pattern types. Fine therapeutic effects have been obtained in clinical practice following the differentiation of CDO and DHO. However, suitable animal models are not available currently. For adapting to the clinical diagnosis, as well as carrying out basic research of integrated Chinese and Western medicine and preclinical study on new Chinese medicine in a better way, the “Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold Dampness Obstruction Pattern and Damp Heat Obstruction Pattern” (referred to as “Guidelines”) were compiled by our research group in cooperation with renowned experts in clinical, pharmaceutical, zoological, and methodological research fields. According to the theory of disease and syndrome integration, experts standardized the establishment methods for animal models of rheumatoid arthritis with CDO and DHO. The Guidelines were compiled via the nominal group method according to the principle of evidence coming in main place, consensus as the auxiliary, and experience as the references. Contents such as animal species, arthritis induction methods, external stimulation conditions, and assessment indicators were specified in the Guidelines based on the comprehensive evaluation of pathogenesis homology, behavioral phenotypic consistency, and drug therapy predictability between animal models and human diseases. The Guidelines will be applicable to the research on syndromes in rheumatoid arthritis, elucidation of acting mechanism, and development of new medicine, and provide reference for standardizing other types of animal models with the integration of disease and syndrome, to promote the modernization of Chinese medicine research.

Objective:To investigate effect and mechanism of hydroxysafflor yellow A(HSYA)activating neuronal autophagy on cerebral ischemia-reperfusion injury through a combination of in vitro and in vivo experiments.Methods:SD rat MCAO/R model was established by improved suture method.Rats were randomly divided into sham surgery(Sham)group,MCAO/R group and MCAO/R+HSYA group,following indicators were detected to determine extent of cerebral ischemia-reperfusion nerve damage:Z-Longa neu-rological function score was detected,TTC staining to measure cerebral infarction area,and TUNEL staining to measure cell apopto-sis;Western blot was used to detect protein expressions of autophagy related markers LC3,Beclin1,P62 and SIRT1 in rat brain tis-sue;immunofluorescence staining was used to observe expression of LC3 co-localization with neurons.OGD/R injury model of SH-SY5Y cells was established and randomly divided into Normal group,OGD/R group,OGD/R+HSYA group,OGD/R+SIRT1 inhibitor(EX-527)group and OGD/R+EX-527+HSYA group.Western blot was used to detect protein expressions of LC3,Beclin1,P62 and SIRT1.Results:Compared with Sham group,model group rats showed impaired neurological function,significantly increased neu-robehavioral scores,widespread cerebral infarction,significantly increased neuronal cell apoptosis,significantly increased autophagy related protein Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,significantly decreased P62 expression,significantly increased LC3/NeuN co-stained cells,and decreased SIRT1 expression;compared with model group,HSYA intervention group showed a significant decrease in neurological functional scores,a significant reduction in cerebral infarction area,a significant decrease in neuronal cell apoptosis,a further increase in Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,a further decrease in P62 expression,number of LC3/NeuN and P62/NeuN co-stained cells also increased,and SIRT1 expression significantly increased.Expression trends of Beclin1,LC3-Ⅱ/LC3-Ⅰ,P62 and SIRT1 of cells between normal group,model group and HSYA intervention group were same as animal experiment;compared with model group,expressions of SIRT1,Beclin1 and LC3-Ⅱ/LC3-Ⅰ in OGD/R+EX-527 group were significantly reduced,while expression of P62 was significantly increased;compared with OGD/R+EX-527 group,there was no significant change in SIRT1 expression in OGD/R+EX-527+HSYA group,LC3-Ⅱ/LC3-Ⅰ and Beclin1 expression were significantly increased,and P62 expres-sion was significantly decreased.Conclusion:HSYA can significantly improve neurological deficits in rats after cerebral ischemia-reperfusion,reduce cerebral infarction area,and decrease neuronal cell apoptosis rate,whose neuroprotective effect may be related to its activation of SIRT1,which significantly enhances neuronal autophagy.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To investigate the relationship between serum soluble thrombomodulin(sTM),soluble interleukin-2 receptor(sIL-2R)and short-term prognosis in patients with acute exacerbation chronic obstructive pulmonary disease(AECOPD)combine with type Ⅱ respiratory failure(RF).Methods:251 patients with AECOPD combine with type Ⅱ RF who were admitted to our hospital from April 2021 to April 2024 were selected,the serum sTM and sIL-2R levels of all patients were detected,and the prognosis of 10 d after admission of patients was counted,patients were divided into death group(n=40)and survival group(n=211)according to different prognosis.Influencing factors were analyzed by multivariate logistic regression analysis,predictive value was analyzed by receiver operating characteristic(ROC)curve.Results:Serum sTM and sIL-2R levels in death group were higher than those in survival group(P＜0.05).long course of chronic obstructive pulmonary disease(COPD)and severe RF,high sTM and high sIL-2R were risk factors for death of 10 d after admission of patients with AECOPD combine with type Ⅱ RF(P＜0.05).The area under the curve(AUC)of serum sTM and sIL-2R detection in predicting death of 10 d after admission of patients with AECOPD combine with type Ⅱ RF was 0.801 and 0.810,respectively,the AUC of joint detection of serum sTM and sIL-2R was 0.859,which was higher than that of each index alone.Conclusion:Serum sTM and sIL-2R levels in patients with AECOPD combine with type Ⅱ RF are significantly increase,which are relate to the occurrence of poor prognosis of 10 d after admission,serum sTM and sIL-2R are expect to be used as auxiliary predictive markers for short-term prognosis of patients with AECOPD combine with type Ⅱ RF,and long course of COPD and severe RF,APACHE Ⅱ score are the influencing factors of poor prognosis in patients with AECOPD combine with type Ⅱ RF.