Chronic heart failure （CHF） is a clinical syndrome characterized by impaired ventricular ejection function due to cardiac abnormalities， representing the terminal stage of most cardiovascular diseases. With its rising prevalence and significant impact on patients' quality of life， CHF has emerged as a major global public health concern. Current Western medicine treatments mainly involve the oral administration of the "new quadruple therapy" drugs and diuretics. Despite substantial progress in pathological research and clinical treatment， challenges persist， including considerable side effects， drug resistance， and marked interindividual variability in therapeutic response. Therefore， exploring and leveraging the advantages of traditional Chinese medicine （TCM） in treating CHF has become an urgent research priority. TCM has a millennia-long history in the prevention and treatment of heart failure， accumulating extensive clinical experience. Characterized by its multi-component and multi-target properties， TCM enables holistic regulation of multiple systemic functions and intervention in the progression of heart failure， demonstrating significant clinical relevance in its management. By employing therapeutic strategies such as warming Yang， promoting diuresis， replenishing Qi， nourishing Yin， and activating blood circulation， TCM effectively improves myocardial fibrosis， inhibits oxidative stress responses， enhances myocardial contractility， and ameliorates ventricular remodeling. Modern proprietary Chinese medicines derived from classic formulas， based on the theoretical foundation of traditional prescriptions， not only exhibit favorable clinical efficacy but also offer notable advantages in convenience， stability， and safety. This review systematically examined the significant therapeutic effects and underlying mechanisms of classical TCM formulas in the treatment of CHF， and provided an overview of the clinical application of modern proprietary Chinese medicines. It aims to provide new strategies for the clinical diagnosis and treatment of CHF.

Objective To explore the mechanism by which breast cancer-derived LncRNA OIP5-AS1 regulates the migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the M2 polarization of tumor-associated macrophages (TAM). Methods MDA-MB-231 cells were divided into the control group (blank control), the NC group (transfected with NC siRNA), and the si-OIP5 group (transfected with LncRNA OIP5-AS1 siRNA). The mRNA expression levels of LncRNAs OIP5-AS1, IL-4, and IL-13 were detected by RT-qPCR. The protein expression levels of IL-4 and IL-13 in the culture supernatant were detected by ELISA. The culture supernatant from the control group was added to RPMI 1640 medium at different volume ratios to induce the polarization of M0 macrophages into TAMs. The mRNA expression of CD206 in TAMs was detected by RT-qPCR. M0-type macrophages were induced with the medium supernatant of the NC group/si-OIP5 group, and the expression of CD206 was detected by Western blot. Subsequently, a co-culture model of macrophage and MDA-MB-231 was constructed to evaluate the migration and invasion abilities of MDA-MB-231 cells and detect the expression changes in Vimentin, N-cadherin and E-cadherin. Results Compared with the control and NC groups, the si-OIP5 group showed significantly downregulated expression of LncRNA OIP5-AS1 (P<0.001) and significantly decreased IL-13 mRNA and protein levels (P<0.05). Meanwhile, no significant difference was observed in the expression of IL-4 among the groups. Conditioned medium induced CD206 expression in M0 macrophages in a volume-dependent manner, with the strongest effect at a 40% volume ratio (P<0.001). The CD206 protein level in the si-OIP5 group significantly decreased (P<0.01). In the co-culture system, the migration and invasion abilities of MDA-MB-231 cells in the si-OIP5 group significantly weakened (P<0.001), the expression of E-cadherin was upregulated, and the expression levels of N-cadherin and Vimentin were downregulated (both P<0.01). Conclusion Breast cancer-derived LncRNA OIP5-AS1 can induce TAM M2 polarization mediated by IL-13, thereby promoting the migration, invasion, and EMT of breast cancer cells.

ObjectiveTo investigate the mechanism of Guizhi Fulingwan （GFW） against hepatic fibrosis， focusing on elucidating the regulatory effect of GFW on the mitochondrial DNA （mtDNA）/NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific proteinase-1 （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsForty-two male Sprague-Dawley （SD） rats were randomly allocated into six groups （n=7）： control， model， low/medium/high-dose （0.14， 0.28， 0.56 g·kg^-1·d^-1） GFW （GFW-L， GFW-M， GFW-H）， and Dahuang Zhechong pills （DZW， 1.8 g·kg^-1·d^-1）. The rat model of hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. General conditions of the rats were observed. Serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured. Liver histopathology and collagen deposition were observed through hematoxylin and eosin （HE） staining and Masson's trichrome staining. Transmission electron microscopy （TEM） was employed to observe structural alterations and damage of cellular ultrastructures including mitochondria. Mitochondrial membrane potential （MMP， ΔΨ_m） was detected by flow cytometry. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of mtDNA and NLRP3 in the liver tissue were quantified by Real-time polymerase chain reaction （Real-time PCR）. The protein levels of key molecules in the NLRP3/Caspase-1/GSDMD signaling pathway in the liver tissue were determined by Western blot. ResultsCompared with the control group， the model group exhibited a decrease in body weight （P<0.01）， an increase in liver index （P<0.01）， elevations in serum ALT and AST levels （P<0.01）， and typical fibrotic features such as disorganized hepatocytes， inflammatory infiltration， and increased collagen deposition in the liver tissue. TEM revealed significant karyotheca degeneration， mitochondrial swelling， endoplasmic reticulum expansion， and organelle efflux in the model group. In addition， the model group showed decreased ΔΨ_m （P<0.01）， up-regulated mRNA levels of mtDNA and NLRP3 （P<0.01） and protein levels of NLRP3， Caspase-1， and GSDMD （P<0.01） in the liver tissue， and increased serum levels of IL-1β and IL-18 （P<0.01）. Compared with that in the model group， the body weight increased in GFW-L， GFW-M， and DZW groups （P<0.05） and markedly increased in the GFW-H group （P<0.01）. The liver index decreased in the GFW groups and DZW group （P<0.01）. The serum ALT level declined in the GFW-L group （P<0.05）， and the serum ALT and AST levels decreased in the GFW-M， GFW-H， and DZW groups （P<0.01）. Histopathological damage and fibrosis were alleviated to varying degrees， and TEM revealed mitigated ultrastructural injuries including mitophagy， mitochondrial swelling， and endoplasmic reticulum expansion in the drug intervention groups. The ΔΨ_m increased in GFW groups without statistical significance. The mRNA level of mtDNA in the liver tissue was down-regulated in the GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. The mRNA level of NLRP3 was down-regulated in GFW-M， GFW-H， and DZW groups （P<0.01）. Western blot analysis showed significantly down-regulated protein level of NLRP3 in all the GFW groups and the DZW group （P<0.01）. The protein level of GSDMD-N was down-regulated in GFW-H and DZW groups （P<0.01）. The protein level of cleaved Caspase-1 was down-regulated in GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. In addition， the serum levels of IL-1β and IL-18 declined in GFW-H and DZW groups （P<0.01）. ConclusionGFW can suppress pyroptosis to ameliorate CCl₄-induced hepatic fibrosis， potentially through mitigating mitochondrial damage， inhibiting inflammasome assembly and activation， and blocking pro-inflammatory cytokine release.

Moyamoya disease (MMD) is characterized by progressive stenosis or occlusion of the distal internal carotid artery and its major branches, with secondary formation of abnormal collateral vessels at the skull base. Previous studies evaluated peripheral blood molecules to reflect vascular pathology and inflammation of MMD, but their limited specificity and susceptibility to confounding factors restricted clinical utility. With advances in high-throughput omics, blood-based biomarkers with improved specificity have been identified, and bioinformatics and machine learning have facilitated biomarker screening and diagnostic model development. Meanwhile, biomarkers for different clinical scenarios have emerged, promoting a shift from “diagnostic” to “decision-making” and “predictive” biomarkers. This review summarizes recent studies in blood-based biomarkers for MMD, aiming to provide references for future in-depth studies and clinical translation.

Objective:To investigate the effect of robot-assisted total knee arthroplasty (TKA) on the incidence of postoperative deep vein thrombosis (DVT) in the lower limbs.Methods:A total of 405 patients who underwent primary unilateral TKA in the Department of Orthopaedics, Peking University Third Hospital from June 2022 to June 2024 were retrospectively analyzed, consisting of 89 males and 316 females, with a mean age of 67.84±5.60 years. Patients were divided into the conventional group ( n=215) and the robot-assisted group ( n=190) according to the surgical approach. Postoperative DVT incidence, operative time, postoperative hemoglobin and hematocrit levels, perioperative blood loss, and transfusion rate were compared between the two groups to evaluate the impact of robot-assisted TKA on thrombotic events and related clinical indicators. Results:There were no significant differences in age, sex, height, weight, body mass index, or preoperative laboratory results including hemoglobin and hematocrit levels between the two groups ( P>0.05). The postoperative DVT incidence was 26.8% (51/190) in the robot-assisted group and 34.9% (75/215) in the conventional group, with no significant difference ( P>0.05). Univariate logistic regression analysis showed that sex ( P=0.013) and age ( P=0.024) were significantly associated with DVT occurrence. Multivariate logistic regression further revealed that female patients had a significantly higher incidence of DVT than males ( OR=0.438, P=0.005), and older patients had a significantly increased risk of DVT ( OR=1.046, P=0.025); body mass index remained not significantly associated with DVT ( P=0.092). The operative time in the robot-assisted group was 88.62±18.58 min, which was significantly longer than that in the conventional group 79.23±17.68 min ( t=-5.207, P<0.001). Perioperative total blood loss was 1 079.85±344.18 ml in the robot-assisted group and 1 141.47±363.70 ml in the conventional group, with no significant difference ( t=1.745, P=0.082). The transfusion rate was 5.3% in the robot-assisted group and 5.1% in the conventional group, respectively, with no significant differences (χ 2=0.004, P=0.947). Conclusion:Compared with conventional TKA, robot-assisted TKA results in longer operative time but does not increase perioperative blood loss or the risk of postoperative DVT.

Objective To prepare CD318-specific monoclonal antibodies and evaluate their specificity, affinity, and application in immunological detection, laying the foundation for the development of CD318-targeted antibody drugs. MethodsCD318 protein was expressed and purified, and was used as an antigen to immunize mice, then mice with higher antiserum titers were screened. We prepared CD318-specific monoclonal antibodies through cell fusion and monoclonal screening, and the specificity, affinity, and application of the obtained monoclonal antibodies in immunological assays were evaluated. Then we constructed a CD318/CD3-targeting bispecific antibody and assessed its impact on T-cell cytotoxicity. Results Thirteen monoclonal antibodies were successfully generated, with the hybridoma clone 13-8-G2 exhibiting the highest titer, strongest specificity, and broadest applicability. The antibody was identified as an IgG1 isotype with a kappa light chain. The variable region of the light chain measured 318 bp, while the heavy chain variable region was 357 bp, yielding an affinity constant of approximately 7.68×10⁹. The specificity of CD318 was confirmed using flow cytometry and immunofluorescence assays. Additionally, a CD318/CD3-targeting bispecific antibody was constructed using the variable regions of this CD318 monoclonal antibody, which demonstrated enhanced T-cell cytotoxicity. Conclusion High-affinity and highly specific CD318 monoclonal antibodies were successfully prepared, laying a foundation for the development of therapeutic antibodies targeting CD318.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice ; Antibodies, Bispecific/immunology* ; Humans ; Mice, Inbred BALB C ; Antibody Specificity/immunology* ; CD3 Complex/immunology* ; Antigens, CD/genetics* ; T-Lymphocytes/immunology* ; Hybridomas/immunology* ; Female

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective::To investigate the correlation between maternal serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and gestational duration in pregnant women with pulmonary hypertension (PH).Methods::The study included pregnant individuals with PH stemming from mitral valve stenosis and mitral valve regurgitation (post-capillary PH) or pulmonary arterial hypertension (pre-capillary PH) who were admitted to Guangdong Provincial People’s Hospital between January 1, 2014 and December 31, 2020. In this retrospective cohort study, maternal serum NT-proBNP levels during pregnancy, along with other clinical data, were obtained from structured electronic medical records. These data included gestational age at delivery, echocardiographic parameters, laboratory findings, gestational duration, delivery mode, and other relevant clinical variables. Univariate and multivariate regression analyses were conducted to assess the association between NT-proBNP levels and gestational duration. Adjustments were made for potential confounding factors, and curve fitting and threshold effect analysis were employed to identify tangent points. Furthermore, stratified analyses were performed based on tricuspid regurgitation velocity, maternal age, and parity.Results::A total of 64 patients with post-capillary PH and 74 patients with pre-capillary PH were included in this study. Among patients with post-capillary PH, the results of multivariate regression analysis indicated a significant association between maternal NT-proBNP levels and gestational duration (β = -0.03, 95% confidence interval (CI) -0.05 to 0.00, P = 0.02). The fitted curve demonstrated a negative correlation between maternal NT-proBNP levels and gestational duration, with a significant break point at 379.9 ng/L ( P < 0.05). In the post-capillary PH group, the stratified analysis revealed a regression coefficient of -0.05 (95% CI:-0.06 to -0.04, P = 0.001) in patients with a tricuspid regurgitation velocity >340 mm/s. For patients >35 years old, the regression coefficient was -0.03 (95% CI -0.06 to -0.01, P = 0.02). In multiparous women, the regression coefficient was -0.03 (95% CI-0.06 to 0.00, P = 0.03). Conclusion::In pregnant women with pulmonary hypertension, maternal NT-proBNP levels are associated with gestational duration, particularly with an increased risk of preterm labor.

Objective:To investigate the effect of robot-assisted total knee arthroplasty (TKA) on the incidence of postoperative deep vein thrombosis (DVT) in the lower limbs.Methods:A total of 405 patients who underwent primary unilateral TKA in the Department of Orthopaedics, Peking University Third Hospital from June 2022 to June 2024 were retrospectively analyzed, consisting of 89 males and 316 females, with a mean age of 67.84±5.60 years. Patients were divided into the conventional group ( n=215) and the robot-assisted group ( n=190) according to the surgical approach. Postoperative DVT incidence, operative time, postoperative hemoglobin and hematocrit levels, perioperative blood loss, and transfusion rate were compared between the two groups to evaluate the impact of robot-assisted TKA on thrombotic events and related clinical indicators. Results:There were no significant differences in age, sex, height, weight, body mass index, or preoperative laboratory results including hemoglobin and hematocrit levels between the two groups ( P>0.05). The postoperative DVT incidence was 26.8% (51/190) in the robot-assisted group and 34.9% (75/215) in the conventional group, with no significant difference ( P>0.05). Univariate logistic regression analysis showed that sex ( P=0.013) and age ( P=0.024) were significantly associated with DVT occurrence. Multivariate logistic regression further revealed that female patients had a significantly higher incidence of DVT than males ( OR=0.438, P=0.005), and older patients had a significantly increased risk of DVT ( OR=1.046, P=0.025); body mass index remained not significantly associated with DVT ( P=0.092). The operative time in the robot-assisted group was 88.62±18.58 min, which was significantly longer than that in the conventional group 79.23±17.68 min ( t=-5.207, P<0.001). Perioperative total blood loss was 1 079.85±344.18 ml in the robot-assisted group and 1 141.47±363.70 ml in the conventional group, with no significant difference ( t=1.745, P=0.082). The transfusion rate was 5.3% in the robot-assisted group and 5.1% in the conventional group, respectively, with no significant differences (χ 2=0.004, P=0.947). Conclusion:Compared with conventional TKA, robot-assisted TKA results in longer operative time but does not increase perioperative blood loss or the risk of postoperative DVT.