Silver nanoparticles(AgNPs)are employed as disinfectants due to their extensive antimi-crobial properties,but their biosafety in the livestock industry has not been comprehensively as-sessed.In this study,16 Black-skin Red-crowned chickens aged 32 weeks were randomly divided in-to four groups and sprayed with AgNP solution at the concentration of 0,0.064,0.128 or 0.256 g/L,respectively,every 72 h in their coops for 30 d.The effects of AgNPs as the disinfectant on lung tissue in chicken were investigated through calculation of organ coefficients,observation of lung tissue sections,analysis of bronchoalveolar lavage fluid,measurement of inflammatory factors,de-tection of silver residue in lung tissue,and exploration of signaling pathways in pulmonary fibrosis.The results indicated that chickens in the 0.128 and 0.256 g/L AgNPs treatment groups showed the blurred pulmonary lobule boundaries,the destroyed alveolar structure,and the significant in-crease in pulmonary fibrosis.These pathological changes were accompanied by the decrease in lung organ coefficient,the reduced SP-C content,the increased total protein concentration in lavage flu-id,and the elevated LDH and silver content in lung tissue.The levels of IL-6 and TNF-α in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than the control group,which suggested that AgNPs exposure could induce the pulmonary inflammatory responses.High concentrations of AgNPs can trigger pulmonary tissue fibrosis,damaging the structure and func-tions of lungs.The relative mRNA expression levels of NF-κB in all AgNPs treatment groups,TGF-β in the 0.128 g/L AgNPs treatment group,and Smad3 in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than these in the control group,respectively.Spraying chickens with 0.128 or 0.256 g/L AgNPs for disinfection led to pulmonary deposition of AgNPs,causing direct structural and functional damages to the lungs.It could also induce the chronic pul-monary inflammation through the NF-κB pathway and promote the TGF-β/Smad3 pathway to in-crease collagen synthesis,leading to pulmonary fibrosis.Therefore,the application of high concen-trations of AgNPs in livestock farming requires careful consideration of their potential biological safety issues.

Objective To investigate the expression characteristics of poly(rC)-binding protein 1(PCBP1)in gastric cancer tissues and their clinical significances by bioinformatics analysis combined with experimental verification,and to identify its relationship with STIP1 homology and U-Box containing protein 1(STUB1).Specifically,this study aims to verify the expression patterns of PCBP1 and STUB1 in gastric cancer and determine their relationships with clinicopathological features by immunohistochemistry to provide a theoretical framework as well as potential intervention strategies for gastric cancer.Methods Data of PCBP1 expression in gastric cancer and adjacent tissues were obtained from TIMER 2.0 online analysis website.KEGG pathway enrichment analysis was performed using gastric cancer data(STAD)in the TCGA(the Cancer Genome Atlas)database,and its potential mechanism was determined.The main regulatory factor STUB1 was found in the fer-roptosis regulatory pathway.Subsequently,PCBP1 and STUB1 expressions in 33 cases of gastric cancer tissues and corresponding adjacent tissues were detected by immunohistochemistry.The collected cases were grouped according to different degrees of differentiation,age,gender,tumor size,depth of tumor invasion,TNM stage and pathological morphology.The positive expression rates of PCBP1 and STUB1 were observed.The correlation between the two proteins and the correlation between clinical and pathological features were analyzed by c2 test.Finally,the relationship between PCBP1 and STUB1 and malignancy of gastric cancer was further explored.Results Immunohistochemical results showed that the positive expression rate of PCBP1 in cancer tissues was 69.7%,which was significantly higher than that in adjacent tissues(48.5%).The positive expression rate of STUB1 in cancer tissues was 39.4%,which was lower than that in adjacent tissues(54.5%),statistically significant difference(P<0.05).The positive expression rate of PCBP1 was correlated with tumor differentiation,lymph node metastasis and Lauren classification(P<0.05),but not with patient's age,gender,depth of inva-sion,clinical stage,nerve infiltration,and intravascular tumor thrombus(P>0.05).The positive expression rate of STUB1 was correlated with tumor differentiation,depth of invasion,lymph node metastasis and Lauren classification(P<0.05).The Spearman correlation coefficient between PCBP1(cancer)and STUB1(cancer)was-0.413,with P=0.017(P<0.05),indicating that there was a significant negative correlation between them.Conclusion PCBP1 participates in the malignant progression of gastric cancer by regulating the main regulator STUB1 in the ferroptosis pathway.Theoretically,it provides a new insight into molecular mechanism as well as a potential therapeutic strategy for treating gastric cancer.

Silver nanoparticles(AgNPs)are employed as disinfectants due to their extensive antimi-crobial properties,but their biosafety in the livestock industry has not been comprehensively as-sessed.In this study,16 Black-skin Red-crowned chickens aged 32 weeks were randomly divided in-to four groups and sprayed with AgNP solution at the concentration of 0,0.064,0.128 or 0.256 g/L,respectively,every 72 h in their coops for 30 d.The effects of AgNPs as the disinfectant on lung tissue in chicken were investigated through calculation of organ coefficients,observation of lung tissue sections,analysis of bronchoalveolar lavage fluid,measurement of inflammatory factors,de-tection of silver residue in lung tissue,and exploration of signaling pathways in pulmonary fibrosis.The results indicated that chickens in the 0.128 and 0.256 g/L AgNPs treatment groups showed the blurred pulmonary lobule boundaries,the destroyed alveolar structure,and the significant in-crease in pulmonary fibrosis.These pathological changes were accompanied by the decrease in lung organ coefficient,the reduced SP-C content,the increased total protein concentration in lavage flu-id,and the elevated LDH and silver content in lung tissue.The levels of IL-6 and TNF-α in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than the control group,which suggested that AgNPs exposure could induce the pulmonary inflammatory responses.High concentrations of AgNPs can trigger pulmonary tissue fibrosis,damaging the structure and func-tions of lungs.The relative mRNA expression levels of NF-κB in all AgNPs treatment groups,TGF-β in the 0.128 g/L AgNPs treatment group,and Smad3 in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than these in the control group,respectively.Spraying chickens with 0.128 or 0.256 g/L AgNPs for disinfection led to pulmonary deposition of AgNPs,causing direct structural and functional damages to the lungs.It could also induce the chronic pul-monary inflammation through the NF-κB pathway and promote the TGF-β/Smad3 pathway to in-crease collagen synthesis,leading to pulmonary fibrosis.Therefore,the application of high concen-trations of AgNPs in livestock farming requires careful consideration of their potential biological safety issues.

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Purpose To investigate the relationship between SERPINA4 expression and clinicopathological fea-tures and prognosis in metastatic colorectal cancer(CRC).Methods EnVision two-step immunohistochemical method was used to detect the expression of SERPINA4 protein in 104 cases of primary and metastatic tumor paraffin tissues of metastatic colorectal cancer and adjacent intestinal normal mucosa,and its relationship with clinicopathological features of patients was analyzed.qRT-PCR was used to detect the expression of SERPINA4 mRNA in 11 pairs of metastatic CRC metastases and paired primary tumor paraffin-embedded tissue samples.The survival of patients was followed up,and the relationship between SERPINA4 expression and patient prognosis was analyzed by Kaplan-Meier method.Re-sults Immunohistochemical results showed that the strong positive expression rate of SERPINA4 was 97.10％in nor-mal mucosa,71.20％in primary lesions,and 39.40％in metastatic lesions.The difference between the three groups was statistically significant(P＜0.001).qRT-PCR results showed that SERPINA4 mRNA was lowly expressed in me-tastatic lesions of metastatic CRC(P＜0.05).The expression of SERPINA4 in metastatic lesions was significantly cor-related with histological grade,N stage and M stage of the tumor(P＜0.05),but not significantly correlated with age,gender,tumor location and T stage of patients(P＞0.05).The survival time of patients with metastatic colorectal cancer with high expression of SERPINA4 was longer than that of patients with low expression.Conclusion The ex-pression of SERPINA4 is of great significance in the survival and prognosis of patients with metastatic CRC.

Purpose To investigate the relationship between SERPINA4 expression and clinicopathological fea-tures and prognosis in metastatic colorectal cancer(CRC).Methods EnVision two-step immunohistochemical method was used to detect the expression of SERPINA4 protein in 104 cases of primary and metastatic tumor paraffin tissues of metastatic colorectal cancer and adjacent intestinal normal mucosa,and its relationship with clinicopathological features of patients was analyzed.qRT-PCR was used to detect the expression of SERPINA4 mRNA in 11 pairs of metastatic CRC metastases and paired primary tumor paraffin-embedded tissue samples.The survival of patients was followed up,and the relationship between SERPINA4 expression and patient prognosis was analyzed by Kaplan-Meier method.Re-sults Immunohistochemical results showed that the strong positive expression rate of SERPINA4 was 97.10％in nor-mal mucosa,71.20％in primary lesions,and 39.40％in metastatic lesions.The difference between the three groups was statistically significant(P＜0.001).qRT-PCR results showed that SERPINA4 mRNA was lowly expressed in me-tastatic lesions of metastatic CRC(P＜0.05).The expression of SERPINA4 in metastatic lesions was significantly cor-related with histological grade,N stage and M stage of the tumor(P＜0.05),but not significantly correlated with age,gender,tumor location and T stage of patients(P＞0.05).The survival time of patients with metastatic colorectal cancer with high expression of SERPINA4 was longer than that of patients with low expression.Conclusion The ex-pression of SERPINA4 is of great significance in the survival and prognosis of patients with metastatic CRC.

Objective:To investigate the dynamic changes of inflammatory biomarkers in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support after cardiac surgery, and evaluate their predictive value for in-hospital mortality.Methods:The retrospective study included 212 patients who underwent VA-ECMO support following cardiac surgery at Beijing Anzhen Hospital, Capital Medical University, from January 2021 to May 2024. Baseline characteristics and inflammatory markers during ECMO support including procalcitonin (PCT), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and fibrinogen (FBG) were collected. Univariate analysis, ROC curves, and multivariate logistic regression were performed to assess the association of these indicators with outcomes. Results:On day 3 post-ECMO, mean PCT and CRP levels were significantly higher in the deceased group (87 cases) than in the survival group (125 cases). PCT demonstrated an area under the curve ( AUC) of 0.750 (95% CI: 0.680-0.819) for predicting mortality, while CRP had an AUC of 0.701(95% CI: 0.625-0.778). No significant differences were observed in FBG, NLR, or PLR between the two groups. Lactate levels at 24 h post-ECMO ( AUC=0.723) and SOFA scores ( OR=2.511, AUC=0.713) were also significantly associated with mortality risk in the deceased group ( P<0.05). Conclusion:Dynamic increases in PCT and CRP are independent predictors of in-hospital mortality in cardiac surgery patients supported by ECMO. Elevated lactate levels and SOFA scores, aligning with previous studies, reflect severe tissue hypoperfusion and multi-organ dysfunction in non-survivors, underscoring the necessity of dynamic monitoring of inflammatory and organ function markers for prognosis assessment.

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Objective:To evaluate potentially inappropriate medication (PIM) in hospitalized elderly patients with bacterial pneumonia, and explore its influencing factors.Methods:It was a single-center cross-sectional study. The study focused on elderly patients with bacterial pneumonia who were admitted to Xuanwu Hospital, Capital Medical University from January 2018 to November 2022. Patients′ gender, age, weight, length of hospital stay, diagnosis at admission, physical examination, diagnosis at discharge, comorbidities, medications, and laboratory test results were extracted from hospital information system and electronic medical records. Medication use of patients included in the analysis during their hospitalization were evaluated according to the classification of PIMs in the 5 lists of the Beer′s criteria of American Geriatrics Society. Based on whether PIM occurred, the patients were divided into with PIM group and without PIM group. The clinical features between the 2 groups were compared and the influencing factors of PIM were analyzed using multivariable logistic regression.Results:A total of 2 720 patients were included, in which 1 734 (63.75%) were male. The median age was 78 (70, 85) years and their ages ranged from 65 to 103 years. The number of drugs used per patient was 14 (10, 18) kinds, ranging from 1 to 57 kinds. The length of hospital stay was 12 (9, 17) days, ranging from 1 to 162 days. Charlson comorbidity index (CCI) was 6 (5, 8) points. Among the 2 720 patients, 1 894 (69.63%) experienced PIM, with a total of 6 166 cases of PIM. The top 3 drugs ranked by the number of PIM occurrence were antiplatelet agents (1 357 cases), benzodiazapine receptor agonists (956 cases), and antipsychotics (884 cases). The comparison of clinical characteristics between the 2 groups showed that differences in age, CCI, length of hospital stay, and number of medications between with PIM and without PIM patients were statistically significant (all P<0.001). Multivariable logistic regression results showed that CCI, length of hospital stay, and number of medications were independent influencing factors for PIM. The risk increased by 8% and 1% with one point increase in CCI and one day extension in length of hospital stay [odds ratio ( OR)=1.08, 95% confidence interval ( CI): 1.04-1.13, P<0.001; OR=1.01, 95% CI: 1.00-1.03, P=0.03]. PIM risk of patients with more than 15 concurrent medications had a 22.16 times higher PIM risk than those with less than 5 concurrent medications ( OR=22.16, 95% CI: 14.15-34.72, P<0.001). Conclusions:Hospitalized eldery patients with bacterial pneumonia who have more severe comorbidities, longer hospital stay, and multiple concomitant medications are at a higher risk of PIM occurrence. Rational medication use among these patients should be paid attention to in clinical practice.