Natural product-based drug combinations (NPDCs) present distinctive advantages in treating complex diseases. While high-throughput screening (HTS) and conventional computational methods have partially accelerated synergistic drug combination discovery, their applications remain constrained by experimental data fragmentation, high costs, and extensive combinatorial space. Recent developments in artificial intelligence (AI), encompassing traditional machine learning and deep learning algorithms, have been extensively applied in NPDC identification. Through the integration of multi-source heterogeneous data and autonomous feature extraction, prediction accuracy has markedly improved, offering a robust technical approach for novel NPDC discovery. This review comprehensively examines recent advances in AI-driven NPDC prediction, presents relevant data resources and algorithmic frameworks, and evaluates current limitations and future prospects. AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
Artificial Intelligence ; Biological Products/chemistry* ; Humans ; Drug Combinations ; Drug Discovery/methods* ; Machine Learning ; Algorithms

The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer.

Objectives:To investigate the clinical value of cardiac magnetic resonance imaging(CMR)feature-tracking strain analysis in risk stratification of diabetic heart failure with preserved ejection fraction(HFpEF).Methods:In this retrospective study,a total of 215 patients with diabetic HFpEF who underwent CMR at Chinese Academy of Medical Sciences Fuwai Hospital from January 2012 to December 2018 were included.Myocardial strain parameters were calculated using CMR feature-tracking technology.Patients were followed up by medical records or telephone calls.Composite endpoint event,all-cause death or heart failure hospitalization during follow-up were recorded.Patients were divided into event group and event-free group.Univariable and multivariable Cox proportional hazard regression analyses were performed to determine the risk factors for the outcomes in diabetic HFpEF.The effects of hypertension and obesity on the prognosis of diabetic HFpEF patients and whether they affect the prognostic value of CMR feature-tracking strain analysis were also analyzed.Results:During a follow-up of(7.1±1.8)years,93(43.3%)patients had endpoint events(event group),including 28 all-cause deaths and 65 heart failure hospitalization.Compared with the event-free group(n=122),patients in the event group had significantly lower left ventricular ejection fraction,higher prevalence and extent of late gadolinium enhancement,and significantly reduced global longitudinal strain(GLS),global circumferential strain,global radial strain,and global systolic longitudinal strain rate(all P<0.05).The absolute GLS value was significantly lower in event group than in event-free group,regardless of the presence of hypertension and obesity.Multivariate Cox regression analysis showed that estimated glomerular filtration rate(HR=0.983,95%CI:0.972-0.993,P=0.001),left atrial volume index(HR=1.015,95%CI:1.005-1.026,P=0.004),and GLS(HR=1.142,95%CI:1.060-1.231,P<0.001)were independent risk factors for adverse cardiovascular events in diabetic HFpEF patients.However,adjusted N-terminal pro-brain natriuretic peptide was not an independent prognostic factor.The cut-offvalue of GLS to predict outcome was-14.09%from ROC curve analysis.The Kaplan-Meier curve showed that in patients with and without hypertension and obesity,patients with the GLS>-14.09%had lower event-free survival compared to patients with GLS≤-14.09%(all P<0.05),and the ability of GLS to predict adverse outcomes was not affected by hypertension and obesity.Conclusions:GLS obtained by CMR feature-tracking strain analysis is an independent predictor of adverse outcomes in diabetic HFpEF,and its ability to predict adverse outcomes is independent of hypertension and obesity.

Objective:To investigate the mechanism by which hydrogen alleviates myocardial ischemia/reperfusion injury (IRI) through ultrasound-targeted destruction of hydrogen-loaded phospholipid microbubbles in the ischemic myocardium of rats.Methods:A total of 45 rats were randomly divided into three groups: sham operation group, IRI group (model group), and hydrogen treatment group (experimental group), with 15 rats in each group. A rat model of myocardial IRI was established. Rats in the sham group received 0.2 ml of normal saline via the tail vein, those in the model group received 0.2 ml of phospholipid microbubbles without hydrogen, and those in the treatment group received 0.2 ml of hydrogen-loaded phospholipid microbubbles. After 24 hours, cardiac function was assessed by left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Serum levels of cardiac troponin I (cTnI), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Expression levels of Janus knase 2(JAK2), signal transducer and activator of transcription 3(STAT3), phosphorylated JAK2(p-JAK2), and phosphorylated STAT3(p-STAT3) proteins in myocardial tissue were detected by Western blot. Myocardial infarct size was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and myocardial histopathological changes were observed by hematoxylin-eosin (HE) staining.Results:After 24 hours of reperfusion, LVEF [(54.26±2.92) % vs (45.77±27%)] and LVFS [(24.11±1.68) % vs (19.50±1.19%)] were significantly higher in the treatment group than in the model group (both P<0.001). ELISA results showed that levels of CK-MB [(13.58±2.07) μg/L vs (20.07±1.57) μg/L], LDH [(47.76±8.32) μg/L vs (74.39±10.19) μg/L], cTnI [(7.50±0.26) μg/L vs (9.05±0.34) μg/L], and IL-6 [(121.34±8.97) ng/L vs (156.99±6.46) ng/L] were significantly lower in the treatment group compared with the model group (all P<0.001). TTC staining revealed a smaller infarct size in the treatment group [(48.77±2.68)%] than in the model group [(63.53±3.10)%, P<0.001]. Western blot analysis showed that the expression levels of JAK2 and p-STAT3 proteins were significantly lower in the treatment group than in the model group ( P<0.05). HE staining showed no pathological abnormalities in major organs (heart, liver, spleen, lung, and kidney) following hydrogen microbubble treatment. Conclusions:Ultrasound-targeted destruction of hydrogen microbubbles enables local hydrogen release in the myocardium, which downregulates IL-6 and inhibits activation of the JAK/STAT signaling pathway, thereby attenuating inflammation and reducing ischemia/reperfusion injury.

Objective To explore the protective effects of pretreatment with the Mongolian medicine Jiruhen Gurigumu-7(JG-7)and Guangzao Sanwei Tang(GZ-3)on myocardial ischemia-reperfusion injury(MIRI)in mice.Methods 60 male C57BL/6J mice were randomly divided into sham operation(Sham)group,model(Model)group,compound danshen drip pill(CDDP)positive control group,JG-7 group,GZ-3 group,and 12 mice in each group to establish the MIRI model,and the H9C2 cells were randomly divided into Control(normoxic)group,H/R(hypoxia 6 h reoxygenation 14 h)group,H/R+JG-7 group,H/R+GZ-3 group.The mice in each group were tested for cardiac function indexes after 30 min of ischemia,24 h and 7 d of reperfusion,TTC staining to detect infarct area after 24 h of MIRI,HE staining to detect myocardial tissue structure and cellular morphology after 24 h of MIRI,TUNEL apoptosis kit to detect apoptosis of myocardial cells after 24 h of MIRI,Masson staining to detect myocardial fibrosis after 7 d of MIRI.Blood was taken from the abdominal aorta,serum was separated,and the indexes after oxidative stress of MIRI were detected in each group of mice,and the survival rate of H9C2 cells after H/R was detected in each group by CCK-8 method.Results The results of TTC showed that JG-7 and GZ-3 reduced the infarct area after 24 h of MIRI in mice.ELISA and kit assays proved that JG-7 and GZ-3 reduced creatine phosphokinase isoenzyme(Creatinekinase-MB,CK-MB),Lactic dehydrogenase(LDH),malondialdehyde(MDA)levels,and increased superoxide dismutase(SOD)levels.HE staining showed that JG-7 and GZ-3 improved myocardial pathology after MIRI 24 h.The results of TUNEL apoptosis assay showed that JG-7 and GZ-3 improved apoptosis in myocardial tissues 24 h after MIRI.Masson staining results showed that JG-7 and GZ-3 could reduce the area of myocardial tissue fibrosis after MIRI 7 d.CCK-8 assay results showed that JG-7 and GZ-3 could improve the cell survival rate after H/R in H9C2 cells.Conclusion Pre-treatment with Mongolian medicine Jiruhen Gurigumu-7 and Guangzao Sanwei Tang can reduce the damage caused after ischemia-reperfusion(I/R),decrease the area of myocardial infarction and fibrosis after I/R in mice,and protect the heart.

Frequent occurrence of disaster rescue and public health emergencies has increased demand for rapidly and efficiently emergent medical rescue.This study modified a closed van which equipped a rapid testing module for physiological indicators,clinical blood transfusion module,detection and sampling module of etiology,and module for health and epidemic prevention.This research designed one kind of emergent vehicle for rapidly comprehensive detection,which integrated test vehicle,blood transfusion vehicle,biosafety testing vehicle,and vehicle for health and epidemic prevention in one vehicle.This vehicle can meet various demands of emergently medical rescue and other tasks in clinical test,which can improve the response capability and emergency handling capability for disasters and public health emergencies,at the same time,it also can save manpower.

The study was conducted among 120 general practitioners (GPs) in Shanghai Fengxian District from August 2022 to March 2024, the participants were randomly divided into two age-matched groups with 60 GPs in each group. The intervention group completed a 3-month SPOC (Small Private Online Course)program, including two weeks of narrative medicine theory (concepts, questioning skills, parallel medical record writing, and professionalism) followed by monthly writing practices (three parallel records per month) and group discussions. Both groups performed routine clinical tasks, while the control group received no narrative medicine training. Baseline data were collected, Jefferson Empathy Scale scores, and Doctor-Patient Communication Skills Evaluation Scale scores were evaluated pre- and post-intervention. There were no significant differences in empathy ( P>0.05) or communication skills ( P>0.05) between two groups before the intervention. Post-intervention, both groups showed improved empathy (both P<0.05) and communication skills (both P<0.05) after intervention, while the intervention group were outperforming the control group in both measures ( P<0.05). These findings suggest that SPOC-based narrative competence training effectively enhances the empathy and doctor-patient communication abilities of general practitioners.

The incidence of cardiovascular diseases(CVD)has been increasing year by year,with atherosclerosis(As)being the leading cause in terms of both incidnce and mortality for CVD in China.Traditional theories suggest that the pathogenesis of atherosclerotic CVD is associated with endothelial dysfunction and inflammatory responses caused by the accumulation of oxidized low density lipoprotein(ox-LDL).However,recent studies have demonstrated that perivascular adipose tissue(PVAT)can positively influence the occurrence and development of CVD through the vascular adventitia pathway.This article reviews the connection between PVAT and CVD,effective pathways for promoting CVD improve-ment,and the regulatory role of AMP-activated protein kinase(AMPK)on PVAT,aiming to explore effective intervention targets for CVD.

Yttrium-90 selective internal radiation therapy (⁹⁰Y-SIRT) is a treatment technique that delivers radioactive microspheres precisely to the arterial vascular bed of neoplasms, utilizing beta radiation to administer a high local dose of radiation to the neoplasm tissues. This technology has demonstrated significant efficacy in patients with unresectable pirmary liver cancers and liver metastases. This article systematically reviews the development history and clinical application status of ⁹⁰Y-SIRT in the treatment of liver cancer, and looks forward to future development directions.

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.