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.

Objective:To analyze the color Doppler flow imaging (CDFI) features of familial exudative vitreoretinopathy (FEVR) at different stages.Methods:A retrospective study. A total of 104 patients with 201 eyes from Department of Ophthalmology of Beijing Tongren Hospital who were hospitalized for fundus examination and diagnosed with FEVR from 2018 to 2022 were included. There were 69 male cases with 133 eyes and 35 female cases with 68 eyes. The age was ranged from 2 months to 11 years, with a mean age of 2.9 years. Fundus and CDFI examination were performed in both eyes. Fluorescein fundus angiography was performed in 72 cases (144 eyes). FEVR staging was conducted according to literature standards. The presence of avascular areas in the peripheral retina or abnormal retina neovascularization was stage 1; the presence of retinal neovascularization at the vitreoretinal interface in the avascular area was stage 2; partial retinal detachment without macula involvement was stage 3; partial retinal detachment involving the macula was stage 4; complete retinal detachment was stage 5. The CDFI ultrasound features of FEVR at different stages were analyzed. The CDFI image features of FEVR patients in different stages were observed.Results:Among the 104 patients, 97 (93.3%, 97/104) cases were binocular and 7 (6.7%, 7/104) cases were monocular. In 201 eyes, stages 1 to 5 of FEVR were 49 (24.4%, 49/201), 23 (11.4%, 23/201), 39 (19.4%, 39/201), 71 (35.3%, 71/201), and 19 (9.5%, 19/201) eyes, respectively. CDFI examination showed no abnormality or mild vitreous opacity in 49 eyes vitreous body at stage 1. Vitreous opacities were observed in all 23 eyes in stage 2, and the echo of the temporal ballwall was not smooth. In 39 eyes at stage 3, the anterior globular cluster echo in temporal peripheral eyes was observed in 17 eyes and partial retinal detachment was observed in 13 eyes. In 71 eyes at stage 4, 51 eyes had temporal or infratemporal retinal folds, and 20 eyes had temporal retinal detachment. All the 19 eyes in stage 5 had total retinal detachment, of which 15 eyes had closed "funnel-shaped" retinal detachment. Among the patients with retinal folds, 13 had bilateral folds, and the fellow eyes of the other 25 patients with unilateral folds all had vitreous opacity or clump echo in front of the temporal spherical wall. Blood flow signals could be detected on the retinal folds with Doppler imaging.Conclusions:The CDFI manifestations of FEVR patients at different stages have different characteristics. The possibility of FEVR should be considered when the temporal or infratemporal retinal folds of both eyes are present, as well as the retinal folds of one eye, the contralateral vitreous body opacity, or the anterior temporal peribulbar cluster echoes are present.

Objective:To observe the ultrasonographic features of idiopathic uveal effusion syndrome (IUES).Methods:A retrospective controlled study. From January 2012 to December 2023, 13 patients with IUES (26 eyes) diagnosed by ophthalmology examination in Department of Ophthalmonogy of Beijing Tongren Hospital (IUES group) and 22 healthy people with 30 eyes (control group) were included in the study. Both eyes of all participants were examined by color Doppler ultrasound (CDU) and ultrasonic biomicroscopy (UBM). The thickness of the ocular wall at 300 μm on the temporal side of the optic disc was measured by CDU. UBM was used to measure the thickness of the nasal and temporal scleral processes. Corneal thickness (CT), anterior chamber depth (AD), lens thickness (LT) and axial length (AL) were measured by A-mode ultrasound. There were no significant differences in age ( t=0.842), sex component ratio ( χ2=0.540), eye difference ( χ2=0.108) and AL ( t=0.831) between IUES group and control group ( P>0.05). The CDU and UBM imaging features and biometrics of IUES affected eyes were observed. Independent sample t test was used for comparison between groups. Results:CDU examination results showed that in 26 eyes of IUES group, choroidal detachment occurred in 20 eyes (76.9%, 20/26), which showed arc-shaped band echo connected with peripheral and equatorial eye wall echo, with uniform low echo area below, and blood flow signal could be seen on the band echo. The echo thickened and decreased in 4 eyes (15.3%, 4/26). Nine eyes (33.3%, 9/26) were accompanied by retinal detachment, which showed that the posterior pole vitreous echo was connected to the optic disc echo, and the blood flow signal was seen on the ribbon echo. UBM results showed ciliary detachment in 22 eyes (84.7%, 22/26), showing a spongy thickening of the ciliary body with interlamellar echo separation and an echoless area between the sclera. Ciliary body echo thickened and decreased in 2 eyes (7.7%, 2/26). Shallow space between ciliary body and sclera was observed in 2 eyes (7.7%, 2/26). Compared with the control group, CT ( Z=2.054), LT ( Z=1.867), scleral thickness ( Z=2.536) and ocular wall thickness ( Z=2.094) were thickened in IUES group, and AD ( Z=1.888) were decreased, with statistical significance ( P<0.05). Conclusions:The CDU of IUES is characterized by a thickened echo of the ocular wall and a uniform low echo area under the detached choroid. UBM is characterized by a spongy thickening of the ciliary body echo with interlaminar echo separation.

Objective:To observe the color Doppler flow imaging (CDFI) features of vitreoretinal lymphoma (VRL).Methods:Retrospective case series. From January 2022 to December 2024, 71 eyes of 42 patients diagnosed with VRL at the Eye Center of Beijing Tongren Hospital were enrolled. Among them, 17 were male and 25 female; 29 had bilateral and 13 unilateral involvement. Age ranged 17-78 years (median 59 years). Eleven cases had histopathologic confirmation and 31 were clinically diagnosed. All patients underwent CDFI and optical coherence tomography (OCT). CDFI findings were analyzed, noting the presence or absence of vitreous opacities (centrifugal distribution), posterior vitreous detachment (PVD), retinal detachment, and retinal elevated lesions. With Doppler overlay, blood flow within retinal lesions was assessed. The χ 2 test was used to compare the detection rates of retinal lesions by CDFI and OCT, while Cohen’s Kappa assessed agreement in identifying the depth of lymphoma cell infiltration. Results:Among 71 eyes, vitreous opacity occurred in 66 eyes (93.0%, 66/71), of which 40 eyes (60.6%, 40/66) showed centrifugal opacity. 58 eyes (81.7%, 58/71) had posterior vitreous detachment. Retinal detachment occurred in 7 eyes (9.9%, 7/71). Retinal occupying lesions occurred in 23 eyes (32.4%, 23/61), of which 15 eyes (65.2%, 15/23) showed blood flow signals on the surface of the lesions but no blood flow signals inside the lesions by CDFI, and OCT showed that tumor cells gathered under the retinal pigment epithelium. CDFI showed blood flow signals inside the lesions in 8 eyes (34.8%, 8/23), and OCT showed that tumor cells gathered between retinal neuroepithelial layers. The lesion detection rate of OCT (69.6%, 16/23) was significantly lower than that of CDFI (100.0%, 23/23) ( χ 2= 6.066, P=0.014). OCT and CDFI showed perfect agreement in determining the depth of tumor cell infiltration (Kappa=1.0). Conclusions:The ultrasonographic manifestations of VRL include vitreous opacity, PVD, and some retinal occupying lesions. Vitreous opacity often presents a characteristic centrifugal distribution. By observing whether there is blood flow signal in retinopathy using Doppler, the level of lymphoma cell infiltration can be suggested.

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

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.

Chronic heart failure （CHF） is the final stage of cardiovascular diseases. It is a complex syndrome， with dyspnea and edema as the main clinical manifestations， and it is characterized by complex disease conditions， difficult cure， and high mortality. Ferroptosis， a new type of programmed cell death， is different from other types of programmed cell death. Ferroptosis is iron-dependent， accompanied by lipid peroxide accumulation and mitochondrial shrinkage， becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi， blood， and body fluid， which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi （heart Qi） is the root cause of CHF， and stagnation （phlegm turbidity and blood stasis） is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine （TCM） plays an important role in the treatment of CHF， improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore， this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation， aiming to provide new ideas and methods for the treatment of CHF with TCM.

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.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia