ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent mucosal inflammation. Although biologics and small-molecule therapies can effectively suppress inflammation, only 13%-34% of patients achieve deep histological remission, and most experience relapse within 2-3 years. Existing biomarkers, including C-reactive protein (CRP), fecal calprotectin, and endoscopic measures, have limited ability to detect subclinical molecular abnormalities, suggesting that disease-driving factors may persist even during clinical remission. Recently, Pang et al. reported a study in Science that investigated the role of epithelial cell-death signaling using a prospective adult IBD cohort comprising 80 participants and more than 900 biopsy specimens. By integrating bulk and spatial transcriptomics, patient-derived organoids, and 24-36 months of longitudinal follow-up, the authors characterized epithelial cell-death programs associated with IBD persistence. They found that the necroptosis-associated marker pRIPK3 could be detected in the absence of overt histological inflammation and persisted during advanced therapy. IFN‑γ and TNF reshaped the transcriptional landscape of specific colonic epithelial cells, inducing an inflammatory macrophage-like program termed cluster B and triggering RIPK1-independent RIPK3 signaling. This was followed by NOS2/iNOS-mediated mitochondrial apoptosis driving colonocyte death, whereas PUMA-dependent apoptosis contributed to intestinal stem-cell loss. Higher baseline pRIPK3 levels were associated with subsequent disease activity, although their independent predictive value remains to be established. These findings suggest that persistent IBD may reflect not only residual immune inflammation but also inflammation-induced pathological epithelial states. Future therapeutic strategies may therefore need to extend beyond inflammation control toward “molecular repair”, including targeting noncanonical RIPK3 signaling, modulating iNOS/PUMA-dependent mitochondrial apoptosis, and developing relapse-risk stratification strategies based on tissue biomarkers such as pRIPK3. Such approaches may help shift the therapeutic goal from “clinical remission” toward “molecular healing”.

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.
Hypertension/physiopathology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Antihypertensive Agents/therapeutic use* ; Nonprescription Drugs/therapeutic use* ; Blood Pressure/drug effects*

Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

Objective To investigate the differential expression genes(DEGs)related to angiogenesis in rosacea(RA)by utilizing bioinformatics analysis in order to screen the key genes and verify their mRNA expression levels.Methods The gene microarray dataset GSE65914 was retrieved from the Gene Expression Omnibus(GEO)repository.Analyzed by R programming,the dataset was refined to identify DEGs related to RA,and then cross-referenced with angiogenesis-related genes from the GeneCards database to get a subset specific to RA angiogenesis.The process of identifying key genes was augmented by employing protein-protein interaction(PPI)network analysis and Cytoscape-based computational algorithms.The mRNA expression levels of the aforementioned pivotal genes were detected by real-time fluorescent quantitative reverse transcription PCR(RT-qPCR).Results A total of 947 RA-associated DEGs were identified from GEO dataset,and then 202 genes related to RA angiogenesis were further delineated.PPI network analysis and Cytoscape algorithm finally identified 3 key genes,that is,CXCL8,IL-1B,and STAT1.The results of RT-qPCR showed that the mRNA expression levels of MIP-2,GCP-2,IL-1B and STAT1 in RA lesions were significantly higher than those in normal controls(P<0.05).Conclusion With aid of bioinformatics analysis,our study has screened and validated key genes associated with angiogenesis in RA,namely CXCL8,IL-1B,and STAT1,which providing a theoretical basis for elucidating the potential mechanisms underlying RA-induced angiogenesis and developing targeted therapeutic strategies.

Objective To investigate the effect of nutritional deficiency on autophagic flux in human hepatoblastoma HepG2 cells and the autophagy-dependent molecular pathway mediated by ATG5 against nutritional stress.Methods Lentiviral siRNA knockdown of ATG5 was performed to knock down the expression in HepG2 cells,and the transfection was verified by Western blotting and qRT-PCR.HBSS was used to treat HepG2 cells for 0,1,2,3,4,5,6 and 7 h for starvation-induced autophagy.Monodansylcadaverine(MDC)fluorescence staining was employed to detect the formation of intracellular autophagic vesicles.Western blotting was performed to measure the expression changes in microtubule-associated protein 1A/1B-light chain 3(LC3),autophagy receptor protein(sequestosome 1,P62),autophagy-related gene 5(ATG5)and nutrient stress pathway(AMPK/mTOR pathway)related proteins.CCK-8 assay was utilized to test cell proliferation.Results Compared with the HepG2 cells under conventional culture medium,starvation induction resulted in more autophagic vacuoles(accumulation of autofluorescent marker,MDC),which peaked at 6 h of starvation(P<0.000 1),up-regulated protein levels of LC3B-Ⅱ and ATG5(P<0.05),decreased protein expression of P62(P<0.05),gradual activation of the AMPK/mTOR pathway with elapse of starvation time,and increase in the intensity of autophagic flux.However,in the HepG2 cells with ATG5 knockdown,starvation treatment led to decreased ATG5 expression,no significant difference in LC3B-II and P62 changes,inhibited autophagic flux,and suppressed cell proliferation(P<0.000 1).Conclusion Human hepatoblastoma HepG2 cells can regulate autophagic flux to against nutritional stress by inducing ATG5 expression.

Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China