Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is a common complication, and its prevention remains challenging. Although aggressive infusion of lactated Ringer's solution (hereafter Lactated Ringer's) has shown preventive effects, the efficacy of standard infusion rates remains unclear. To evaluate whether lactated Ringer's administered at a standard rate reduces the incidence or severity of post-ERCP pancreatitis compared with non-lactated Ringer's solutions. This single-center retrospective study compared patients who received non-lactated Ringer's solutions before January 2019 with those who received lactated Ringer's after January 2019, at a standard rate. The outcomes were post-ERCP pancreatitis incidence, severity, C-reactive protein (CRP) level, and systemic inflammatory response syndrome (SIRS). Of 1194 patients included (median age, 71years; 60% male), pancreatitis occurred in 5.6% (30/529) of the non-lactated Ringer's group and 5.3% (35/665) of the lactated Ringer's group (P = 0.76). Severe or moderately severe pancreatitis occurred in six patients each in both groups (approximately 1%). Mean CRP level at 24h was similar between the groups (1.26 vs. 1.44mg/dL, P = 0.75), and SIRS rates at 24/48h did not differ significantly (P = 0.61 and 1.00). Multivariate analysis identified pancreatic injection, naïve papilla, and female sex as independent risk factors; fluid type was not associated with outcome (OR 1.09, P = 0.76). Lactated Ringer's at a standard infusion rate did not reduce the incidence or severity of post-ERCP pancreatitis compared with a non-lactated Ringer's solution. Further research is required to optimize fluid therapy for preventing this complication.

This study aimed to compare the predictive value of preoperative midstream urine culture (PMUC), intraoperative renal pelvic urine culture (RPUC), and stone culture (SC) for postoperative urinary tract infections (UTIs) following percutaneous nephrolithotomy (PCNL). We retrospectively analyzed 234 patients who underwent supine-PCNL between January 2020 and April 2025. UTI was diagnosed based on systemic inflammatory response syndrome criteria and elevated inflammatory markers. Demographic, peri-, intra- and post-operative data were compared between patients with and without UTI. Multivariate logistic regression identified independent predictors. UTI occurred in 14.1%(n = 33) of patients postoperatively, with 72.7% presenting with fever. Culture positivity rates were significantly higher in postoperative UTI-patients (PMUC = 27.3% vs. 7.5%, SC: 39.4% vs. 8.0% and RPUC: 30.3% vs. 6.0%; p < 0.001). In UTI-patients, only 15.2% of postoperative urine cultures obtained before antibiotic treatment showed bacterial growth, which was lower than intraoperative cultures. UTI was higher in female patients (60.6% vs. 39.4%) and in those with an ASA score of 3 (p = 0.001 and p = 0.020). Female gender (OR = 3.71, p = 0.004), ASA-3 score (OR = 5.13, p = 0.029), positive SC (OR = 5.83, p = 0.001), and RPUC (OR = 3.67, p = 0.023) were independent predictors of postoperative UTI. PMUC was not associated (p = 0.65) with postoperative UTI in the multivariate analysis. Intraoperative SC and RPUC showed a stronger association with postoperative UTI compared with PMUC and may be considered for routine use. Female gender and ASA-3 score were identified as independent risk factors. In patients who develop UTI, prior empirical or prophylactic antibiotic use may limit pathogen detection in postoperative urine cultures; therefore, intraoperative cultures play a critical role in early and targeted treatment.

Recent advances in ROS-modulating materials for sepsis treatment.

Sepsis, a life-threatening condition driven by a dysregulated host response, poses significant challenges for early diagnosis and early intervention. This study aimed to identify robust biomarkers capable of distinguishing sepsis from non-infectious systemic inflammation (SIRS). We analyzed public Gene Expression Omnibus (GEO) data sets using a multi-modal workflow. This included differential expression analysis, weighted gene co-expression network analysis (WGCNA), and an evaluation of 113 machine learning (ML) models to build a predictive signature. We further investigated hub genes using immune infiltration, single-cell RNA sequencing (scRNA-seq), and two-sample Mendelian randomization (MR) to infer causality. Key findings were validated experimentally (in vitro and in vivo). The optimal LASSO + RF model identified a 12-gene signature strongly associated with the septic state, achieving a high area under the curve (AUC) of 0.998 and robust external validation (AUCs > 0.93). This high discriminatory power highlights its potential for stratifying patients. Notably, MR analysis provided causal evidence linking elevated EIF4G3 expression to increased sepsis risk. ScRNA-seq located the expression of hub genes, including DNAJC5, to myeloid cells. Experimental validation confirmed the upregulation of EIF4G3 and DNAJC5 in sepsis models. This study identifies and validates a highly accurate 12-gene signature for distinguishing sepsis from SIRS. The causal evidence for EIF4G3 and robust validation of DNAJC5 underscore their potential as biomarkers for early diagnosis and differentiation from SIRS. This signature holds significant promise for the early identification of high-risk patients, enabling timely intervention and improving outcomes.

The utility of interleukin-6 compared to conventional sepsis biomarkers in pregnancy - A real-world cohort study.

To evaluate associations between the neutrophil-to-lymphocyte ratio (NLR), nonsurvival, illness severity, and infectious etiologies. This was a retrospective multicenter study that included 100 healthy horses and 444 horses presenting with acute diarrhea to 5 equine referral hospitals. Inclusion criteria were diarrhea duration < 48 hours, complete hemograms, and outcome data. Illness severity was assessed using systemic inflammatory response syndrome. The results of pathogen testing for Salmonella spp, equine coronavirus, Clostridium spp, and Neorickettsia risticii/findlayensis were reviewed when available. Data were analyzed using nonparametric statistics and univariate and multivariable logistic regression models. Median NLR [IQR] did not differ between healthy horses (2.06 [1.43 to 2.58]) and horses with colitis (1.93 [0.86 to 3.76]). The NLR was not significantly associated with nonsurvival; however, horses with an NLR < 1.43 demonstrated higher odds of nonsurvival. Horses meeting ≥ 2 systemic inflammatory response syndrome criteria had a lower NLR (1.56 [0.69 to 2.85]) compared with those meeting 0 to 1 criteria (2.54 [1.08 to 4.70]). Horses with an identified infectious cause had lower NLR than those without (1.38 [0.78 to 2.98] vs 2.37 [0.92 to 4.00]), with the lowest NLR observed in equine coronavirus-infected horses (0.73 [0.40 to 1.56]). The NLR alone had limited prognostic performance (area under the curve, 0.51), but multivariable models with NLR had good discriminatory ability (area under the curve, 0.84). While NLR alone is insufficient as a prognostic marker, it may reflect underlying immune dysregulation that contributes to disease severity. The NLR is an inexpensive, readily available biomarker that may help clinicians identify horses at risk of severe systemic inflammation and identify infectious colitis when interpreted with other clinical and laboratory findings.

To compare the efficacy and safety of flexible negative-pressure ureteral access sheath combined with flexible ureteroscopic lithotripsy (FURL) versus FURL alone in the treatment of upper urinary tract infectious stones. This retrospective cohort study included 91 patients with upper urinary tract infectious stones (confirmed as struvite or carbonate apatite by postoperative stone composition analysis) who underwent surgery at the First Affiliated Hospital of Xiamen University between January 2023 and January 2025. Based on the surgical approach, patients were divided into two groups: the FANS-UAS combined with FURL group (n = 60) and the FURL alone group (n = 31). Baseline characteristics, stone-free rates (immediate and long-term), and complications were collected and compared between the groups. Compared to the FURL alone group, the FANS-UAS group had a lower proportion of struvite stones (73.33% vs. 93.55%, P < 0.05) and a lower rate of intraoperative stone basket usage (66.67% vs. 100%, P < 0.05). However, patients in the FANS-UAS group were older, had a larger maximum stone diameter, and higher stone CT values (all P < 0.05). Regarding efficacy and safety: The FANS-UAS group demonstrated a significantly higher immediate stone-free rate (53.34% vs. 12.91%, P < 0.05), but also had a longer operative time, greater estimated intraoperative blood loss, and higher postoperative levels of serum creatinine and cystatin C (all P < 0.05). Concurrently, the FANS-UAS group showed significantly lower rates of systemic inflammatory response syndrome (1.67% vs. 6.45%, P < 0.05), lower hospitalization costs, and a lower rate of postoperative adjuvant therapy (3.33% vs. 45.17%, P < 0.05). However, no statistically significant differences were observed between the two groups in terms of long-term stone-free rate, postoperative pain scores, length of hospital stay, transfusion rate, fever rate, renal pelvis/ureteral injury rate, or reoperation rate (all P > 0.05). Although these differences did not reach statistical significance, the observed numerical trends in some outcomes may hold clinical relevance and warrant further validation through larger-scale studies. The combination of FANS-UAS and FURL is a safe and effectivemethod for treating upper urinary tract infectious stones. Its advantages include a higher immediate stone-free rate, lower hospitalization costs, reduced need for postoperative adjuvant therapy, a lower incidence of sepsis, and faster postoperative recovery, while achieving a long-term stone-free rate comparable to FURL alone. This approach represents a viable new treatment option.

Elastase, a serine protease, has been implicated in chronic obstructive pulmonary disease and systemic inflammatory response syndrome. In this study, we evaluated the effects of phillyrin and phillygenin, 2 major Forsythia lignans, on elastase inhibition. Both compounds exhibited competitive inhibition, as confirmed by enzymatic kinetics, spectroscopy, and molecular docking. Phillygenin exhibited stronger activity (IC50 0.5 mmol/L, K i 4.0 × 10-4 mol/L) than phillyrin (IC50 1.5 mmol/L, K i 9.7 × 10-4 mol/L), likely due to reduced steric hindrance. Spectroscopic analysis revealed ligand-induced conformational changes in elastase, characterized by increased α-helix and random coil content and decreased β-sheet structures. Docking revealed interactions involving π-cation, π-sigma, hydrogen bonds, hydrophobic forces, electrostatics, and van der Waals effects. These results provide mechanistic insights into the inhibitory effects of phillyrin and phillygenin and highlight their potential as therapeutic agents for elastase-related diseases.

Systemic inflammatory response syndrome (SIRS) is recognized to be an exaggerated defense response to various stressors, including trauma. CD4+ T-regulatory cells (CD4+ Tregs) are key mediators in balancing inflammatory processes. Recent findings demonstrated that platelets and CD4+ Tregs interact after injury and SIRS. Therapeutic strategies to modulate the activation of these and other immune cells in SIRS are currently lacking. Ancrod has immunomodulatory effects on CD4+ Tregs that could be beneficial in the treatment of SIRS. Therefore, we studied the impact of ancrod on activation levels of CD4+ Tregs and CD4+ non-Tregs, platelets, and antigen-presenting cells (APC) in vitro and in vivo. We tested the in vitro effect of ancrod (0-15 IU) and the in vivo effect of 8 IU ancrod vs. saline. After collection of spleens and platelet-rich plasma of male C57Bl/6N mice, cells were isolated and incubated with ancrod for 2 hours. Furthermore, we tested the effect of stimulation. CD4+ Tregs, CD4+ non-Tregs, APC and platelet activation were analyzed by flow cytometry. Our results demonstrate that ancrod exerts selective effects on different cell populations. Ancrod affects the adaptive and innate immune responses. Furthermore, we identified a differential effect of ancrod on CD4+ Tregs versus CD4+ non-Tregs depending on the mode of cellular stimulation. Additionally, our findings suggest a dose-dependent role of ancrod in the modulation of platelet activation. Our findings provide the first evidence supporting the potential of ancrod in selectively modulating immune cells, highlighting ancrod as a promising candidate for further investigation.

Goal of the study: To find correlation between gender and eye refractive error as myopia. Introduction: For example, myopia is one of the most prevalent disorders of the eye. The prevalence increased in the past few decades (now 80-90% in school-leavers). Considering and severe forms of others, associated with a risk of concomitant ophthalmic problems [1-3]. Material and methods: There were analyzed articles from PubMed database from the last 5 years 2020-2025, mentioned such words as “myopia”, “gender”, “refractive error”. And also, hypercarbia pCO2 AV &gt; 6 mmHg. pCO2 and microcirculatory-mitochondrial distress syndrome, shock. Results: It was found that higher prevalence of myopia were among girls than boys, both at 9-13 years range. Moreover, in multivariable regression models, younger age of myopia onset or longer duration of myopia progression was associated with high myopia. Environmental risk factors for myopia related to socioeconomic status and lifestyle have been identified. The problem is particularly pronounced in affluent, industrialised areas of East Asia [4]. Conclusion: Generation specific gender preponderance was largely explained by lifestyle factors in youth [5]. The results suggest that in the generations to come, particularly girls should be guided to adhere to protective behavior. There was a higher prevalence of myopia among girls than boys. And we consider this issue by studying for factors affecting mitochondrial genes, whose mitochondrial functions, require coordinated interactions with products encoded by the nuclear genome. Based on the study at Stanford University, males had higher expression of mitochondrial genes and mitochondrial targeted proteins (MTPs) involved in oxidative phosphorylation (OXPHOS), while females had elevated expression of non-OXPHOS MTPs, indicating strongly sex-dimorphic energy metabolism at the whole organism level [6]. In energy homeostasis, the role of glucose deserves attention as an energy substrate in regulating the menstrual cycle [7]. Thus, improvement of local ocular functions depending on gender differences will be achieved future medical [8] in the context of systemic improvement of mitochondrial functions and targeted therapy. Violations of systemic perfusion pressure cause ischemia of the affected microcirculatory bed with critical damage to mitochondria with manifested hypercarbia pCO2 AV &gt; 6 mmHg. pCO2. AV difference of hypercarbia has become an alarm signal, which is used as a marker of ischemia in terminal conditions with the development of microcirculatory-mitochondrial distress syndrome, MMDS, and the establishment of single or (poli) multiple organ dysfunction syndrome (MODS), Systemic inflammatory response syndrome (SIRS) and/or infectious, non-infectious, Acute respiratory distress syndrome (ARDS), CHAOS -[C]ardiovascular Compromise: shock; [H]omeostasis; [A]poptosis;[O]rgan Dysfunction; [S]uppression of the Immune System with the development, Acute Vascular Distress Syndrome (AVDS) [9-51]. Definition of SPP (~70 mmHg), is the difference between the mean arterial pressure, MAP (90 mmHg), and the capillary resistance pressure, CRP (20 mmHg) [52]

In 2024, new international consensus criteria for pediatric sepsis and septic shock (2024 criteria) were introduced, replacing the 2005 criteria. The 2024 criteria use the Phoenix Sepsis Score (PSS) to define sepsis (score ≥2) and septic shock (cardiovascular PSS ≥1) in children with suspected infection, moving away from the 2005 reliance on systemic inflammatory response syndrome (SIRS). This study compares the two criteria in terms of diagnostic consistency, disease severity, prognosis, and early identification. Pediatric patients with infection admitted to the PICU at the Capital Institute of Pediatrics from May 2023 to May 2025 were prospectively enrolled. Those diagnosed with sepsis within 0-6 h of admission were included. Data on demographics, infection sites, pathogens, laboratory markers (platelets, albumin, creatinine, lactate), organ dysfunction scores (PCIS), and clinical outcomes (mechanical ventilation, CRRT, MODS, DIC, mortality) were collected. Diagnostic agreement was assessed using Kappa statistics, and performance was compared using McNemar's test. The 2005 criteria served as the reference for calculating sensitivity, specificity, and predictive values of the 2024 criteria. The 2024 criteria identified fewer sepsis (80 vs. 240) and septic shock (49 vs. 86) cases. Diagnostic agreement was poor (Kappa = 0.161, P < 0.001), with significant differences in severity markers (lactate, PCIS, MODS) and outcomes. The 2024 criteria better reflected sepsis severity but were associated with potential underdiagnosis of early septic shock. For septic shock, 20 cases met vasoactive criteria only, risking missed early diagnosis. Cardiovascular thresholds in the 2024 PSS may be overly strict, delaying recognition. No significant difference in predicted mortality was observed between criteria. The 2024 sepsis criteria improve specificity but may overlook early septic shock. The 2024 septic shock criteria are stricter, potentially delaying diagnosis and treatment. Prospective studies and AI-supported early warning models are needed for better early identification and outcomes.

Systemic inflammatory response syndrome after cardiopulmonary bypass: prevalence, predictors, and outcomes.

Proteomics-guided Biomarker Discovery, Validation, and Pathway Perturbation in Infection-related Acute Decompensation of Cirrhosis.

To compare the clinical outcomes of sepsis patients when an augmented systemic inflammatory response syndrome (SIRS+) and the Epic sepsis predictive model version 1 (ESPMv1) alert were active in the emergency department at two county hospitals. This retrospective study from January 2018 to January 2024, evaluated the clinical outcomes of 881201 emergency department patients of which 29852 patients were septic. From January 2018 to June 2022 sepsis notices were presented to physicians based on a SIRS plus organ dysfunction criteria and from December 2022 to January 2024 using the ESPMv1 alert. Sepsis was defined according to the Sepsis-3 definition with the onset of sepsis defined as two or more points on the Sequential Organ Function Assessment (SOFA) score in patients where physicians ordered at least one blood culture and antibiotic. SIRS+ alerting occurred when 2 of 4 criteria was reached plus one organ dysfunction measurement. The ESPMv1 alerting occurred at the Epic recommended threshold of six. We evaluated the times to blood cultures, antibiotics and ICU admission requests, and in-hospital death rates. SIRS+ alerts had a sensitivity of 14.25%, specificity 96.1%, positive predicative value (PPV) of 7.8% and negative predative value (NPV) of 98%. The ESPMv1 had a sensitivity of 15.6%, specificity 95.4%, positive predictive value of 8.1%, and negative predictive value of 98% for diagnosing sepsis. No statistical differences in time to antibiotics (5.1 vs 5.9 h), time to blood culture draws (3.6 vs 3.5 h) or time to ICU admission (10.4 vs 9.6 h) were observed. We did observe a difference in hospital death rates between the two time periods (11% vs 8%) but no statistical difference when adjusting for unvaccinated covid-19 (OR 0.95 [0.87-1.03]). No statistically significant clinical differences or performance metrics were observed between SIRS+ based alerting and ESPMv1 alerts in an undifferentiated emergency department population. Both alerting systems had similarly poor diagnostic characteristics.

Emergency laparotomy and its perioperative care is associated with high morbidity and mortality. At our institution, 30-day mortality was approximately 12% in 2013-2017. We introduced a perioperative protocol for emergency laparotomies in 2019. Retrospective cohort of emergency laparotomies 2019-2022. Reoperations, trauma and converted laparoscopies (appendectomy and cholecystectomy) were excluded. Primary outcome was mortality at 30, 90, and 180days. Secondary outcomes were postoperative complications (Clavien-Dindo; CD) and hospital-based outcomes. Six hundred eighty-two patients undergoing emergency laparotomy were included. Age was 72 (IQR 23) years and 66.4% (n=453) were aged ≥65years 56.6% (n=386) were ASA class III or IV and 6.5% (n=44) were not living at home at admission. The most frequent surgical findings were bowel obstruction (64.2%; n=438) and gastrointestinal perforations (n=134; 19.4%). Stoma creation (29.9%; n=204), adhesiolysis (28.6%; n=195), and anastomosis (27.4%; n=187) were common. Mortality at 30days was 6.9% (n=47), 90days 11.0% (n=75), and 180days 12.8% (n=87). Mortality was higher for patients ≥80years than < 65years (23.9% vs. 4.4%; p<0.001). Mortality predictors were admission not from home (p=0.043), disseminated cancer (p<0.001), and septic shock (p=0.003) or systemic inflammatory response syndrome (p=0.017). CD IIIb-IVb occurred in 81 patients (11.9%). ICU admission was 16.6% (n=113) and LOS 8 (IQR 7) days. Mortality and complication rates after the introduction of a perioperative emergency laparotomy protocol were low despite a comorbid aged-patient cohort. Particular focus on the elderly, frail, and septic patients considered for emergency laparotomy is recommended.

Inhibition of RIPK1 prevents keratinocyte cell death and reduces skin inflammation in type 1 mediated chronic inflammatory skin diseases.

Background: Sepsis remains a leading cause of morbidity and mortality among pediatric patients, particularly in resource-limited settings. Biomarkers such as serum C-reactive protein (CRP), ferritin, and vitamin D have emerged as crucial indicators in diagnosing and monitoring sepsis severity. Aims and Objectives: This study aimed to evaluate the levels of these biomarkers at 0 and 48 h post-admission in pediatric sepsis patients. By examining the relationship between CRP, ferritin, and vitamin D, we aimed to determine their combined utility in risk stratification and prognosis. Materials and Methods: This study is an observational and descriptive study conducted in the pediatric intensive care unit and medical wards at R.G. Kar Medical College and Hospital, Kolkata. The study involves 100 pediatric patients aged 6 months–12 years, diagnosed with sepsis as defined by the systemic inflammatory response syndrome criteria. Detailed clinical investigation and laboratory investigations such as blood cultures, complete blood count, liver and renal function tests, and other relevant tests will be conducted. Statistical analysis was performed by the Statistical Package for the Social Sciences version 24. Significance levels were denoted as P≤0.05. Results: Elevated CRP and ferritin levels correlate with sepsis severity, whereas vitamin D deficiency is prevalent among critically ill children. Conclusion: The study highlights the importance of integrating these biomarkers in clinical practice to improve early detection and management of pediatric sepsis.

It has become increasingly recognized that heart failure with a preserved ejection fraction (HFpEF) results from an inflammatory process, congestion, and metabolic dysbiosis rather than an intrinsic structural heart abnormality. Recent studies have highlighted the close link between the heart, the liver, and the pancreas, which are organically connected via the same inflammatory processes and pathways. Liver congestion and fibrosis are responsible for the inflammatory process and the lack of metabolic adaptation, whereas pancreatic ischaemia and insufficiency of the exocrine glands aggravate malnutrition and cachexia, worsening the heart condition. Acute pancreatitis may cause heart failure and arrhythmia through injury and systemic inflammatory response syndrome (SIRS), an inflammatory process mediated by the cytokines released during the injury process. Recognition of this hepato-pancreato-cardiac axis offers a paradigm shift towards integrated management of HFpEF, emphasizing anti-inflammatory, metabolic, and haemodynamic interventions. Future research integrating multi-organ imaging, inflammatory biomarkers, and therapeutic trials such as GLP-1 receptor agonists, SGLT2 inhibitors, and cytokine blockers will be critical to disrupt this tri-organ inflammatory circuit and improve outcomes in HFpEF.

Background and Objectives: Acute pancreatitis (AP) is an acute inflammatory disease ranging from mild, self-limiting forms to severe presentations associated with high morbidity and mortality. Early prognostic assessment is crucial for guiding clinical management. This study aimed to evaluate the prognostic value of the red cell distribution width-to-albumin ratio (RDW/Alb, RAR) in relation to clinically relevant outcomes, including intensive care unit (ICU) admission and in-hospital mortality, in patients with AP. Materials and Methods: This retrospective study included 282 patients diagnosed with AP who were hospitalized at Mersin University Hospital between January 2019 and February 2024. Clinical, laboratory, and radiological data were retrospectively analyzed. The predictive performance of RAR was evaluated and compared with established clinical scoring systems, including bedside index for severity in acute pancreatitis (BISAP), systemic inflammatory response syndrome (SIRS), harmless acute pancreatitis score (HAPS), and pancreatitis activity scoring system (PASS). Results: The median RDW-to-albumin ratio (RAR) was 3.9 (range: 2.6-36.7). Receiver operating characteristic (ROC) curve analysis demonstrated that RAR showed good predictive performance for ICU admission (Area Under the Curve (AUC): 0.781; p < 0.001; optimal cut-off: 4.15) and high predictive performance for in-hospital mortality (AUC: 0.927; p < 0.001; optimal cut-off: 5.26). RAR exhibited limited but statistically significant discriminatory performance when compared with the BISAP score (AUC: 0.591; p = 0.017), whereas no significant predictive performance was observed in relation to PASS, HAPS, or SIRS scores. Conclusions: Within the context of this retrospective cohort, RAR is a simple, inexpensive, and readily available biomarker that may be associated with ICU admission and in-hospital mortality in patients with AP. Given the absence of standard severity endpoints such as persistent organ failure or pancreatic necrosis, these findings should not be interpreted as evidence of conventional disease severity prediction but rather as hypothesis-generating observations that warrant validation in larger prospective studies.

Sepsis, an infection‑triggered systemic inflammatory response syndrome, ranks as the third leading cause of death worldwide due to its high incidence and mortality. Sepsis‑induced myocardial dysfunction (SIMD) is a frequent and serious complication that notably increases patient morbidity and mortality. The underlying pathophysiology of SIMD involves a complex interplay of inflammation, oxidative stress, mitochondrial impairment and apoptosis, yet no effective therapies have been established. Thus, uncovering the molecular mechanisms of SIMD, identifying novel therapeutic targets and developing efficacious agents are key. For centuries, natural products have been used in traditional medical systems across China and Asia to manage cardiovascular disease. These compounds can confer cardioprotection by modulating inflammatory pathways, decreasing oxidative stress, inhibiting apoptotic cell death and improving mitochondrial function. The present review aimed to summarize the clinical manifestations and pathophysiology of SIMD and how natural products exert their protective effects. The present study aimed to explore structure‑activity relationships and highlight key molecular targets and representative natural product binding affinities for SIMD‑related proteins. In summary, the present study presents a comprehensive overview of the multi‑targeted strategies employed by natural products against SIMD and provides guidance for the discovery of SIMD‑focused dietary supplements and lead compounds, laying the groundwork for future translational research.