To observe the effect of acupuncture on neuronal cuproptosis after thrombolytic treatment in rats with cerebral infarction (CI), so as to explore its underlying mechanisms in prolonging the time window of thrombolysis therapy for CI.

In the first part of the present study, 40 male SD rats were randomly divided into 5 groups:sham operation, model, 4.5 h thrombolysis, 6 h thrombolysis and acupuncture+6 h thrombolysis groups, with 8 rats in each group. The CI model was prepared by modified autologous thromboembolism method. Rats of the 4.5 h thrombolysis, 6 h thrombolysis and acupuncture+6 h thrombolysis groups received thrombolysis with intravenous injection of recombinant human tissue plasminogen activator (rt-PA, 10 mg/kg) through tail vein at 4.5 h or 6 h after modeling. Manual acupuncture stimulation was applied to bilateral "Neiguan"(PC6) and "Shuigou"(CV26) at the same time with thrombolysis administration for rats of the acupuncture+6 h thrombolysis group, with the needles retained for 30 min. The cerebral blood flow was monitored using laser diffusion blood flow imaging, and neurological deficit score was evaluated 2 h and 24 h after successful modeling using Bederson's method. The CI volume was observed after triphenyltetrazole chloride staining. The immunoactivity of neuronal nuclei(NeuN) in the ischemic penumbra (IP) region of the cerebral cortex was detected by immunofluorescence staining. In the second part of the study, 24 male SD rats were randomly divided into sham operation group, model group, 6 h thrombolysis group and acupuncture+6 h thrombolysis group, with 6 rats in each group. The protein and mRNA relative expression levels of Ferredoxin-1 (FDX1) and dihydrolipoamide acetyltransferase (DLAT) in the IP region of the right cerebral cortex were detected by Western blot and real-time PCR, separately. The copper ion, pyruvate and adenosine triphosphate (ATP) contents in the IP area of the cerebral cortex tissue were detected using colorimetry.

The neurological deficit scores at both 2 h and 24 h after modeling, percentage of CI volume, the contents of copper ion and pyruvate, and the protein and mRNA expression levels of FDX1 and DLAT were significantly higher in the model group than those in the sham operation group (P<0.01), while the NeuN positive expression and ATP content were evidently lower in the model group than those in the sham operation group (P<0.01). In comparison with the model group, the neurological deficit score and percentage of CI volume in the 4.5 h thrombolysis and acupuncture+6 h thrombolysis groups, the contents of copper ion and pyruvate, and the protein and mRNA expression levels of FDX1 and DLAT in the acupuncture+6 h thrombolysis group, and the NeuN immunoactivity and ATP content in the 6 h thrombolysis group were significantly decreased (P<0.05, P<0.01), while the immunoactivity of NeuN in both 4.5 h thrombolysis and acupuncture+6 h thrombolysis groups, ATP content in the acupuncture+6 h thrombolysis group, the percentage of CI volume, contents of copper ion and pyruvate, and the expression levels of FDX1 and DLAT proteins and mRNAs in the 6 h thrombolysis group were significantly increased (P<0.05, P<0.01). Comparison among the 3 intervention groups showed that the neurological deficit score and percentage of CI volume were considerably lower in both of the 4.5 h thrombolysis and acupuncture+6 h thrombolysis groups than those in the 6 h thrombolysis group (P<0.01), while the NeuN immunoactivity was considerably higher in both of the 4.5 h thrombolysis and acupuncture+6 h thrombolysis groups than in the 6 h thrombolysis group (P<0.01). The contents of copper ion and pyruvate, and the protein and mRNA expression levels of FDX1 and DLAT were considerably lower in the acupuncture+6 h thrombolysis group than in the 6 h thrombolysis group (P<0.01), while the ATP content was considerably higher in the acupuncture+6 h thrombolysis group than in the 6 h thrombolysis group (P<0.01).

Acupuncture can prolong the time window of thrombolysis therapy for CI rats, which may be related to its function in down-regulating the protein and mRNA expressions of FDX1 and DLAT in ischemic cerebral cortex.

To explore the relation between acupoint sensitization and alterations of electrical signals of dorsal root ganglion (DRG) neurons from the perspective of ion channel dynamics in myocardial ischemia (MI) model mice.

Sixty-four male C57BL/6J mice were randomly assigned to control and model groups (n=32/group). The MI model was established by ligation of the left anterior descending (LAD) of the coronary artery. The MI was monitored by observing changes of ST segment of the standard limb-lead II of electrocardiogram (ECG-ST_II). 2, 3, 5-triphenyltetrazolium chloride (TTC) and H.E. staining were used to evaluate the infarct area and histopathological changes in the myocardial tissue. Evans blue (EB) staining was administered via tail vein injection to observe the location, distribution, and quantity of exudate points on the body surface in both groups. Nociceptive changes were evaluated by measuring mechanical pain and thermal pain thresholds. Subsequently, electrophysiological assessments were conducted in vitro to evaluate whole-cell membrane currents, intrinsic excitability, and Na⁺ channel current variations in different types of DRG neurons.

Compared with the control group, the ECG-ST_II segment in the model group was significantly elevated (P<0.000 1), suggesting an induction of MI. TTC and H.E. staining showed a significant increase in the MI area (P<0.001), accompanied by evident histopathological features such as myocardial fiber damage and inflammatory cell infiltration. The number of EB exudate points was significantly increased (P<0.01), mainly distributing in the skin innervated by the T1-T5 spinal cord segments, as well as in the acupoints of "Feishu"(BL13), "Jueyinshu"(BL14) and"Xinshu"(BL15). Mechanical retraction reflex thresholds of the left upper and lower limbs of the model group significantly reduced (P<0.000 1), and the thermal retraction latency of the left upper and lower limbs were notably shortened in the model group (P<0.01, P<0.000 1), and the mechanical pressure pain threshold on the left dorsal skin significantly reduced (P<0.001). The DRG medium-sized neurons displayed an obvious decrease in rheobase (P<0.05), along with a notable increase in whole-cell membrane current, spike number, and average instantaneous frequency (P<0.05), reflecting enhanced intrinsic excitability. The activation curves of TTX-R/TTX-S sodium channels shifted towards hyperpolarization (P<0.001), while the inactivation curves moved towards depolarization (P<0.01).

DRG medium-sized neurons in the T1-T5 spinal cord segments may influence the acupoint sensitization of the body surface by modifying their Na⁺ channel kinetic properties.

To provide a systematic review and meta-analysis of population-based cohort studies on the association of selenium status with all-cause and cause-specific mortality.

Relevant studies were identified through systematic searches of MEDLINE and ISI Web of Knowledge. Risk ratios (RRs) reported across categories of selenium biomarkers were recalculated as continuous RR estimations per standard deviation (SD) using generalized least squares for linear trend estimation and pooled in random effects meta-analyses.

The literature search identified 20 studies, including 17 studies on all-cause mortality, 9 studies on cardiovascular mortality and 7 on cancer mortality. An increase of selenium biomarker concentration by one SD was associated with 13 % lower all-cause mortality (RR [95 %-confidence interval], 0.87 [0.83-0.90]), 11 % lower cardiovascular mortality (0.89 [0.84-0.94]) and 15 % lower cancer mortality (0.85 [0.78-0.94]). Although moderate heterogeneity was observed, the inverse association with all-cause mortality was robust across countries with low or adequate selenium supply, selenium measurement methods, recruitment years, study quality scores, follow-up lengths and sample sizes. The trim and fill method showed no indications of relevant publication bias.

Selenium biomarkers are inversely associated with all-cause, cardiovascular and cancer mortality in the general population and clinical trials among selenium deficient populations are still needed.

Heart failure (HF) and neurocognitive frailty (NCF) represent an increasingly recognized clinical intersection with profound implications for patient outcomes. Recent epidemiological data reveal that 40-60% of HF patients experience cognitive impairment, with prevalence increasing proportionally with disease severity. This cognitive-functional decline manifests as structural brain abnormalities, deficits in multiple cognitive domains, and reduced physical capabilities, collectively compromising self-care, increasing healthcare utilization, and elevating mortality risk by up to twofold. This comprehensive review examines the complex bidirectional relationship between HF and NCF, synthesizing current evidence on pathophysiological mechanisms, clinical assessment approaches, and management strategies. The pathophysiology involves interrelated processes, including cerebral hypoperfusion, blood-brain barrier disruption, neuroinflammation, oxidative stress, and neurohumoral dysregulation-all contributing to accelerated brain aging and functional decline. Clinical assessment requires a multidimensional approach utilizing validated cognitive and frailty tools, biomarkers, neuroimaging, and functional measures. Management necessitates integrated strategies spanning optimized pharmacotherapy, device-based interventions, cognitive rehabilitation, structured exercise, nutritional support, and coordinated multidisciplinary care. Emerging evidence suggests that early intervention may attenuate cognitive decline and improve outcomes. As the prevalence of both conditions continues to rise, future research directions should focus on standardized assessment protocols, novel therapeutic targets, and innovative care delivery models to address this challenging clinical syndrome and improve quality of life for this vulnerable population.

Atherosclerosis (AS) is a chronic cardiovascular disease characterized by the accumulation of excess lipids within arterial walls. Since oxidative stress is one of the key drivers in its pathogenesis, antioxidative therapy serves as a promising strategy for AS treatment. Despite the potent antioxidant properties of polyphenolic salvianic acid A (SAA) and salvianolic acid B (SAB), clinical application is limited by their short half-life, insufficient target selectivity, and poor chemical stability. To overcome these limitations, we developed a biomimetic platelet membrane-coated polyphenol-cerium dioxide nanozyme complex (SS-CeO₂@PLTM) as a broad-spectrum antioxidative system for comprehensive AS treatment. The SS-CeO₂@PLTM was constructed by conjugating SAA and SAB on the surface of cerium dioxide via a one-pot method, followed by surface coating with a biomimetic platelet membrane. Systematic characterization using UV-vis spectroscopy, Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy-energy dispersive X-ray spectroscopy (TEM-EDS) elemental mapping analysis, Forster resonance energy transfer (FRET), molecular simulations, and pH-responsive release assays validated the successful synthesis and pH-responsive drug release behavior of SS-CeO₂@PLTM. It was also found that SS-CeO₂@PLTM exhibited broad-spectrum antioxidant activities, effectively scavenging superoxide anions, DPPH, H₂O₂, and intracellular reactive oxygen species (ROS) while enhancing hepatic SOD and GSH activities. Further cellular uptake and in vivo targeting assays confirmed their specific targeting for atherosclerotic plaques. SS-CeO₂@PLTM demonstrated great efficiency in attenuating oxidative stress, inhibiting lipid uptake and lipid accumulation, mediating cholesterol efflux, and inhibiting inflammatory factor (IL-1β, IL-6, and TNF-α) secretion in RAW264.7 cells. We also found that SS-CeO₂@PLTM exhibited improved lipid metabolism and diminished plaque area in apoE^-/- mice via attenuating oxidative stress and NF-κB-mediated inflammation. Furthermore, biosafety was verified via hemolysis and in vivo safety tests. This study is the first to reveal the superior efficacy of the PLTM-based nanozyme complex in targeted AS therapy, offering a paradigm shift for multifactorial cardiovascular disease management.

This study explored the efficacy and mechanisms of Shenqi Buqi Granules in treating chronic heart failure(CHF) of Qi deficiency using proteomics and bioinformatics methods. A total of 18 healthy participants(health group) and 19 patients with Qi deficiency-type CHF(experimental group) were enrolled and treated with Shenqi Buqi Granules for 12 weeks. Clinical indicators, including Qi deficiency scores, complete blood count, biochemical parameters, lipid profiles, and cardiac function, were collected from pre-and post-experimental groups. Serum proteomics analysis was performed. Differential proteins were screened through differential analysis and K-means clustering. Further analyses, including subcellular localization, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and protein-protein interaction(PPI) network construction, were conducted to identify pathways and proteins associated with Shenqi Buqi Granules treatment. Spearman correlation analysis focused on proteins most correlated with the core phenotype of CHF of Qi deficiency. The results show that Shenqi Buqi Granules treatment reduced Qi deficiency scores and brain natriuretic peptide levels of pre-experimental group. A total of 1 594 proteins were quantified in the proteomics analysis, with 98 proteins showing differential expression between healthy group and experimental group before and after treatment. Subcellular localization analysis revealed 6 protein sources, while KEGG pathway enrichment highlighted biological processes including angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. Core genes identified included CD34, CSF1, CALM1, CALML3, PPP1CA, PFN1, and 3 ribosomal large subunit proteins. Correlation analysis between core proteins and Qi deficiency scores revealed that CD34(r=-0.67, P&lt;0.05) and PPP1CA(r=0.62, P&lt;0.01) were most strongly associated with Qi deficiency scores. This study suggests that Shenqi Buqi Granules improves Qi deficiency scores and CHF symptoms by regulating angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. CD34 and PPP1CA are identified as core proteins involved in the therapeutic effects of Shenqi Buqi Granules on Qi deficiency.

The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.

Hypertension is a major risk factor for cardiovascular diseases. Controlling blood pressure can reduce the incidence of cardiovascular events and mortality. The patients with hypertension are mainly treated with antihypertensive drugs. For the patients who can't achieve the target blood pressure with a single drug, comprehensive treatment strategies become particularly important. Chinese patent medicines are prepared by modern extraction and processing technology based on the basic theory of traditional Chinese medicine(TCM). Due to the stable antihypertensive effect, target organ protection, and synergistic effect with western medicine, Chinese patent medicines are becoming one of the effective options for the treatment of hypertension. At present, there are many systematic reviews on the treatment of hypertension with Chinese patent medicines, which makes it difficult for health policy makers and health service providers to choose the best evidence for the treatment. Umbrella review can integrate multiple systematic reviews to comprehensively assess the quality of evidence and potential bias, thereby providing high-quality evidence-based medicine basis for formulating clinical guidelines and optimizing treatment strategies. In this study, the systematic reviews/Meta-analysis of Chinese patent medicines in the treatment of essential hypertension were systematically searched. Sixty-nine articles were included for the umbrella review. Literature information was extracted, and the corrected covered area(CCA) was calculated to quantitatively evaluate the overlap degree of original studies in systematic reviews/Meta-analysis. The risk of bias in systematic reviews(ROBIS) tool and Cochrane RoB tool 2.0 were used to assess the risk of bias of the included studies. A Measure Tool to Assess Systematic Reviews 2(AMSTAR 2) was used to evaluate the methodological quality of systematic reviews/Meta-analysis. The quality of evidence was evaluated based on the Grade of Recommendations Assessment, Development and Evaluation(GRADE). The results showed that the Chinese patent medicines in the categories of treating wind, resolving stasis, and reinforcing healthy Qi were effective in lowering blood pressure. The Chinese patent medicines for resolving stasis combined with conventional treatment can lower blood pressure and the levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and total cholesterol in the treatment of hypertension complicated with coronary heart disease and hypertension complicated with left ventricular hypertrophy. Moreover, the combined therapy can recover the interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass index, left ventricular end diastolic diameter, and left ventricular ejection fraction in the case of left ventricular hypertrophy. The Chinese patent medicines for resolving stasis and for replenishing Qi and restoring pulse can be used in combination with conventional treatment for hypertension complicated with arrhythmia, which can lower blood pressure while improving the outcome indicators such as the P-wave dispersion of arrhythmia, left atrial diameter, ejection fraction, heart rate, and recurrence time. Due to the heterogeneity, the efficacy evidence obtained by the umbrella review needs to be further verified through precise clinical studies and long-term follow-up.

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the &quot;heart-gut axis&quot; theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a &quot;component-target-disease&quot; network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P&lt;0.05). Moreover, markers of myocardial injury were significantly decreased(P&lt;0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P&lt;0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the &quot;heart-gut axis&quot; immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the &quot;heart-gut axis&quot; theory.

Resveratrol(Res) is a kind of polyphenolic compound, possessing multiple biological activities such as antioxidant, anti-inflammatory, cardioprotective, and anticancer effects. In recent years, the cardiovascular protective mechanism of Res has become a research hotspot. Studies have shown that Res has a protective effect on the cardiovascular system through various pathways, such as inhibiting oxidative stress, regulating ferroptosis of cells, improving ischemia-reperfusion(I/R) injury, regulating lipid metabolism, suppressing inflammatory responses, and enhancing endothelial function. It can also alleviate cardiotoxicity caused by drugs and chemicals. In terms of oxidative stress, Res reduces the level of intracellular reactive oxygen species(ROS) by enhancing the expression of proteins such as silent information regulator 1(SIRT1) and regulating mitochondrial function, thereby alleviating myocardial cell damage. Regarding ferroptosis, Res inhibits the occurrence of ferroptosis by regulating the expression of proteins related to iron metabolism. Res can also improve I/R injury through mechanisms such as activating autophagy and the mitochondrial quality control network. In regard to improving endothelial function, Res protects the function of endothelial cells by regulating multiple signaling pathways, such as downregulating the PREP1-mediated pathway. Res can also regulate lipid metabolism and inhibit the progression of atherosclerosis. In terms of inflammatory responses, Res exerts anti-inflammatory effects through mechanisms such as inhibiting the nuclear factor-kappa B(NF-κB) signaling pathway. In addition, Res has an improving effect on cardiotoxicity caused by different drugs or environmental factors. However, the clinical application of Res still faces limitations such as poor pharmacokinetic properties. In the future, in-depth exploration is needed at multiple levels from basic research to clinical application to clarify the dose-response relationship and standardize the standards of medication regimens with the expectation of providing more effective strategies for the prevention and treatment of cardiovascular diseases.