Shenyang Ninth People's Hospital

BackgroundThe aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, commonly referred to as the DeRitis ratio, serves as an indicator of liver disease severity and has been linked to several cardiovascular risk factors. This study aimed to explore the relationship between the DeRitis ratio (AST/ALT) and long-term adverse outcomes in patients diagnosed with acute coronary syndrome (ACS).MethodsWe selected 8,429 patients with ACS from the OPT-CAD database who were admitted between 2012 and 2014 and had complete AST and ALT measurements. Following propensity score matching (PSM), 5,680 patients were included in the final analysis. A retrospective survival analysis was conducted to evaluate the relationship between the DeRitis ratio and the occurrence of net adverse clinical events (NACE) within 5 years post-discharge. The primary outcome was NACE, defined as a composite of all-cause mortality, stroke, non-fatal myocardial infarction (MI), and major bleeding [Bleeding Academic Research Consortium (BARC) types 2–5].ResultsFollowing PSM, the cumulative incidence of NACE within 5 years was significantly higher in the group with a DeRitis ratio ≥1 compared to the group with a DeRitis ratio <1 (HR: 1.21; 95% CI: 1.05–1.38; P = 0.0071). After adjusting for confounding factors using Cox multivariable analysis, the association persisted as significant (HR: 1.21; 95% CI: 1.06–1.39; P = 0.006). Subgroup analysis indicated that the high-ratio group had a significantly increased risk of major bleeding (HR: 1.27; 95% CI: 1.01–1.59; P = 0.037). However, the cumulative risk of all-cause death showed a strong trend towards increase but did not reach statistical significance (HR: 1.23; 95% CI: 0.99–1.51; P = 0.052). There were no significant differences between the groups in the cumulative risks of non-fatal myocardial infarction (MI) (HR: 1.22; 95% CI: 0.89–1.67; P = 0.21), or stroke (HR: 1.01; 95% CI: 0.78–1.32; P = 0.92).ConclusionThe DeRitis ratio ≥1 is significantly associated with elevated risk of NACE during the 5-year post-discharge period in ACS patients. Additionally, an elevated DeRitis ratio is correlated with a higher incidence of major bleeding events.

Microplastic pollution increasingly affects human health. Polystyrene nanoparticles (PS-NPs) and microplastics (PS-MPs) may impair Sertoli cells (SCs), vital for male fertility. To compare PS-NPs (80nm)/PS-MPs (8µm) toxicity on rat SCs, focusing on oxidative stress, apoptosis, epithelial barrier integrity, endocytosis pathways, and miRNA-mediated ceRNA networks. SCs viability was assessed via CCK-8. Trans-epithelial electrical resistance (TER) was measured to assess the epithelial barrier function. Particle internalization was evaluated by confocal microscopy and flow cytometry.Endocytosis was detected by using specific inhibitors. Whole-transcriptome sequencing profiling identified differential expression of miRNAs, lncRNAs, circRNAs, and mRNAs, with subsequent ceRNA network construction. Pro-inflammatory factors and apoptosis were detected by RT-qPCR and flow cytometry, respectively. At 100µg/mL, PS-NPs reduced cell viability to 77% versus 94% for PS-MPs (p<0.05) and decreased TER by 81% versus 63% for PS-MPs (p<0.01). PS-NPs were internalized via clathrin- and caveolin-dependent pathways, while PS-MPs remained extracellular. RNA-seq revealed PS-MPs activated inflammation pathways (Ank3/Daxx), while PS-NPs triggered oxidative stress and apoptosis pathways (Map2k4/Grin2a). PS-NPs induced higher apoptosis (17%vs. 9.3%, p<0.01), Reactive oxygen species (3.7-fold vs. 1.87-fold), and more severe catalase activity reduction (67%vs. 17%, p<0.01) compared to PS-MPs. PS-NPs pose greater toxicity to SCs than PS-MPs due to cellular internalization, disrupting barrier integrity via oxidative stress/apoptosis. PS-MPs primarily trigger extracellular inflammation. Distinct ceRNA networks underpin their differential mechanisms. These results highlight risks of environmental microplastic fragmentation into nanoplastics, emphasizing the need for further research on microplastic impacts on male fertility.

Lung cancer associated with cystic airspaces (LCCA) refers to primary lung cancers presenting with cystic airspaces accompanied by solid components, representing a relatively uncommon imaging and pathological phenotype. Although high-resolution imaging techniques, such as computerized tomography, are the primary diagnostic tools, early diagnosis remains challenging due to the similarity of its symptoms to other pulmonary diseases. Treatment options include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, due to the unique nature of LCCA, treatment requires a highly individualized approach. The main challenges currently faced include improving diagnostic accuracy, determining the optimal treatment strategies, and advancing the understanding of its underlying biological characteristics. Future research will focus on optimizing diagnostic techniques, developing targeted therapies for specific molecular markers, exploring the application of immunotherapies, and promoting multidisciplinary collaboration. With continuous advancements in technology and personalized treatment strategies, significant improvements in the diagnosis and treatment of LCCA are anticipated. This review summarizes the epidemiology, imaging features, pathological characteristics, pathogenesis, treatment strategies, and challenges of LCCA, and offers perspectives on future research directions.

BACKGROUNDSeptic shock represents one of the most severe critical illness types, characterized by significant hemodynamic disorders and neuropsychiatric symptoms. This study aimed to investigate the association mechanism between hemodynamic indicators and neuropsychiatric symptoms in patients with septic shock, revealing potential pathophysiological connections.AIMTo investigate the link between hemodynamic parameters and neuropsychiatric symptoms in septic shock.METHODSA retrospective case-control study involving 132 patients with septic shock. Multiple assessment tools were employed, including the Confusion Assessment Method, Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Scale, and Mini-Mental State Examination, systematically evaluating patients’ neuropsychiatric symptoms and hemodynamic indicators.RESULTSPatient mean age was 52.4 ± 12.3 years, with 68.5% males. Multivariate analysis revealed significant correlations between neuropsychiatric symptom severity and mean arterial pressure < 65 mmHg [odds ratio (OR) = 2.7], lactate levels > 4 mmol/L (OR = 3.1), and elevated interleukin-6 inflammatory factors (OR = 2.4). Neuropsychiatric symptom incidence rates were: Delirium 37.1%; anxiety 28.8%; depression 24.2%; and posttraumatic stress disorder 19.7%.CONCLUSIONHemodynamic disorders in patients with septic shock are closely associated with neuropsychiatric symptoms, influencing central nervous system function through complex inflammatory and neurotransmitter pathways.

Abstract Background Ciprofol(HSK3486) is a novel 2,6-disubstituted phenol derivate, a short-acting intravenous sedative, which has similar efficacy characteristics as propofol with less incidence of side effect. Both ciprofol and propofol are often used in outpatient hysteroscopic surgery for sedation. However, the relative potency of these two drugs has not been fully determined in this context. Methods The effective dose in 50% of subjects(ED50) value for ciprofol and propofol were calculated by Up-and-Down Sequential Allocation Method. A total of 60 parturients undergoing daytime hysteroscopy were randomly divided into two groups, which were intravenously injected with ciprofol at an initial dose of 0.4mg/kg (group C) or propofol at an initial dose of 2mg/kg (group P) at 2 min after intravenous injection of sufentanil 0.15ug/kg. A successful response is defined as the absence of patient movement in the case of cervical dilation. Conversely, the presence of patient movement is defined as failure. After successful or failed responses, each follow-up patient in the corresponding group was reduced or increased with propofol 0.5mg/kg or ciprofol 0.1mg/kg, respectively. Results The estimated ED50 value for ciprofol and propofol in restraining reaction of hysteroscopy dilatation was 0.444 mg/kg (95% CI, 0.385-0.503mg/kg) and 1.985 mg/kg (95% CI, 1.801–2.170 mg/kg), respectively. The incidence of respiratory depression, hypoxemia and injection pain in ciprofol was significantly lower than those in propofol(P &lt; 0.05). Conclusion The ED50 of ciprofol and propofol in preventing hysteroscopy dilatation reaction was 0.444 mg/kg (95% CI, 0.385-0.503mg/kg) and1.985 mg/kg (95% CI, 1.801–2.170 mg/kg) for outpatient hysteroscopy. The potency-ratio of ciprofol and propofol observed in our study was 1.0:4.5(95%CI,1:3.9-1:5.1). Trial registration The study was approved by the Ethical Committee of Women’s Hospital, Zhejiang University School of Medicine (Hangzhou, China) (No. IRB-20220157-R) and was registered at the Chinese Clinical Trials.gov (NO. ChiCTR2200065954) before patient enrollment. All participants signed an informed consent form. Trial registration The study was registered at Chinese Clinical Trial Registry http://www.chictr.org.cn/ (Registration date:19/11/22; Trial ID: ChiCTR2200065954).

Abstract Purpose: Hypoxia-inducible factor proline hydroxylase inhibitors (HIF-PHIs) may affect the STING-TBK1-IRF3 pathway by targeting the polarization of macrophages to prevent the progression of Renal interstitial fibrosis (RIF). However, the mechanism of action remains unclear. Methods: A total of 60 patients were enrolled in the clinical study with 30 each for control and RIF group. Kidney tissue and blood samples were collected and the expression of M1-type macrophage markers (MHC-II, CD86) and components of the STING pathway (STING, P-IRF3, IRF3), together with MCP-1/CCL2 and TNF-α were examined. THP-1 and HK-2 cells were treated with a STING pathway activator (SR-717) and inhibitor (H151). A mouse model of kidney fibrosis was also established to examine the effects of HIF-PHI. Results: The expression levels of MCP-1/CCL2, TNF-α, iNOS, CD86 and STING protein were significantly higher in RIF patients than controls. Treatment of THP-1 cells with SR-717 led to a significant increase in CD86, MHC-II, TNF-α , IL-6 and IFN-γ expression levels (P&lt;0.05), while H151 had no effect (P&gt;0.05). The expression of ECM deposition markers including α-SMA, fibronectin, and collagen IV was higher in TGF-β-induced HK-2 cells, but reduced following H151 treatment (P&lt;0.05). HIF-PHI treatment of RIF mice led to a significant reduction in serum creatinine and blood urine nitrogen, CD86 and MHC-II, STING, α-SMA, collagen IV, and fibronectin expression levels (P&lt;0.05). Conclusions: HIF-PHIs reduced the infiltration of M1-type macrophages and release of inflammatory factors in the kidneys of mice through inhibition of the STING-TBK1-IRF3 pathway, thereby reducing kidney damage and ECM deposition.