Yueyang Second People's Hospital

Abstract A 54‐day feeding trial was conducted to investigate the effects of dietary protein levels on growth performance, digestive capacity, plasma biochemical indexes, and gene expression in Hefang crucian carp ( Carassius auratus ). Six experimental diets were prepared with protein levels of 21.7%, 24.0%, 29.4%, 34.0%, 38.0%, and 43.2%, respectively. Each diet treatment was randomly assigned to triplicate groups of 25 fish, with an initial body weight of (14.60 ± 0.39) g per tank. Fish were fed twice daily to apparent satiation. The results showed that weight gain rate (WGR) and specific growth rate (SGR) exhibited an upward trend with increasing dietary protein levels, and reached the highest value in the 43.2% protein group. Conversely, protein efficiency was significantly higher in the 24.0% protein group compared to the other protein groups ( p < 0.05). As dietary protein levels increased, there was a significant rise in the condition factor (CF), while both the hepatopancreas somatic index (HSI), viscerosomatic index (VSI) and crude lipid of whole body experienced significant decreases ( p < 0.05). The intestinal trypsin activity was significantly elevated in the high‐protein groups (38.0% and 43.2% protein) compared to the low‐protein group (21.7% protein), whereas the plasma triglyceride concentrations exhibited a significant inverse relationship ( p < 0.05). However, at a dietary protein level of 43.2%, the lipid droplet content in the liver of Hefang crucian carp was significantly elevated compared to other experimental groups. Additionally, the group fed the diet with a protein level of 21.7% exhibited significantly higher lipid droplet content than the groups with protein levels of 24.0% and 34.0%. A curvilinear regression analysis indicated that the lipid droplet area in the liver was minimized at a dietary protein concentration of 29.9%. Regarding intestinal gene expression, the asct2 and lat2 genes exhibited the highest expression levels in the group supplemented with 43.2% protein. Conversely, the expression levels of pept1 and cdx2 genes initially decreased and subsequently increased as the dietary protein levels rose, achieving their peak in the low‐protein groups (21.7% and 24.0% protein) ( p < 0.05). Concerning hepatopancreas genes, the expression levels of tor , igf1 , and gh genes were significantly elevated in the 24.0% protein group compared to other treatment groups. Additionally, the expression levels of ghr were significantly higher in the 21.7% and 43.2% protein groups compared to the other treatment groups ( p < 0.05). In conclusion, Hefang crucian carp exhibited optimal growth performance at a dietary protein level of 43.2%, whereas a protein concentration of 29.9% was identified as the critical threshold for maintaining optimal liver health.

Bleomycin (BLM), a widely used antitumor drug, has been demonstrated to induce pulmonary toxicity in both chemotherapy patients and experimental animals, leading to acute lung injury (ALI). However, the lack of effective treatment options limits its clinical application. While peroxiredoxin 1 (Prdx1), a novel damage-associated molecular pattern (DAMP), has been shown to exacerbate acute liver and kidney injury by promoting inflammatory responses, its role in BLM-induced ALI remains unclear. An ALI mouse model was established via intratracheal instillation of BLM (5mg/kg). Prdx1 gene-knockout mice, recombinant murine Prdx1 protein (rPrdx1), and Prdx1-neutralizing monoclonal antibody were utilized to investigate the role of Prdx1 in BLM-induced ALI. Further mechanistic insights were explored through single-cell RNA sequencing analysis. BLM-induced damage to bronchial epithelial cells triggered Prdx1 release, which subsequently activated the NOD1/NF-κB signaling pathway in macrophages, promoting the release of inflammatory cytokines and exacerbating pulmonary inflammation and pathological damage. These findings were confirmed by single-cell RNA sequencing. Genetic knockout of Prdx1 or administration of Prdx1-neutralizing monoclonal antibody protected mice from BLM-induced ALI, and this protective effect was attenuated by introducing rPrdx1. These findings identify Prdx1 as a potential therapeutic target for BLM-induced ALI, offering a strategy to mitigate its pulmonary toxicity and facilitate the broader clinical application of BLM.

BackgroundThis study aimed to compare the diagnostic performance between bacterial culture and a rapid multiplex PCR assay (Respiratory Pathogens Multiplex Nucleic Acid Diagnostic Kit) for detecting six bacterial (Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila) and six viral targets (Influenza A/B, Respiratory syncytial virus, Adenoviruses, Human rhinovirus, Mycoplasma pneumoniae) in 728 bronchoalveolar lavage (BAL) specimens.MethodsThis multicentric observational study was conducted at six comprehensive large hospitals in Hunan Province, China (May to October 2023) and assessed performance of mPCR kit by comparison with conventional culture method.ResultsThe mPCR kit detected ≥1 pathogen in 628 specimens (positivity rate: 86.3%), demonstrating positive percentage agreement (PPA) of 84.6% (95% CI: 76.6-92.6%) and negative percentage agreement (NPA) of 96.5% (95% CI: 96.0-97.1%) versus culture. Notably, semi-quantitative concordance was 79.3% (283/357) for culture-positive specimens. Multiple pathogens were detected by mPCR in 144 samples (19.8%). Lower Ct values (≤30) correlated strongly with culture positivity.ConclusionsThe mPCR kit is a simple and rapid molecular test that could complement conventional culture method for improvement of diagnosis accuracy of Lower respiratory tract infections.

Rheumatoid arthritis (RA) is an aggressive, systemic autoimmune disease in which overactivated macrophages play a critical role in its pathogenesis. This study aimed to explore the potential role of glycolytic reprogramming in the production of proinflammatory cytokines by macrophages in RA. The Seahorse assay was conducted on RA or healthy control (HC) serum-treated human monocyte-derived macrophages (HMDMs) to evaluate glycolysis levels. RNA sequencing was performed to identify activated signaling pathways and key molecules in HMDMs stimulated by RA serum. The proinflammatory cytokines and hypoxia-inducible factor 1α (HIF-1α) were verified by Western blotting and quantitative polymerase chain reaction (qPCR). We found that HMDMs stimulated with RA serum showed higher aerobic glycolysis levels than those treated with HC serum, along with higher expression of glycolysis-related genes, including hexokinase2 (HK2), pyruvate kinase L/R (PKLR), and phosphoglycerate kinase 1 (PGK1). Furthermore, RA serum-treated macrophages exhibited a higher level of interleukin-1 beta (IL-1β), and the expression of IL-1β positively correlated with HK2. Inhibition of glycolysis by 3-bromopyruvate (3BrPA) or HK2 knockdown significantly suppressed IL-1β production in macrophages. The HIF-1α-associated signaling pathways and HIF-1α protein levels were also elevated in RA serum-treated macrophages. Inhibition of glycolysis by 3BrPA or knockdown of HK2 reduced HIF-1α. Inhibiting HIF-1α can suppress IL-1β production of RA serum-treated macrophages, and vice versa. TNF-α and IL-1β enhanced HIF-1α and IL-1β expression in macrophages, an effect attenuated by glycolysis inhibition. Blocking TNF-α and IL-1β in RA serum diminished both glycolysis and IL-1β production. Our findings demonstrate that RA serum triggers aerobic glycolysis in macrophages, which promotes HIF-1α to drive IL-1β production. Notably, IL-1β within RA serum amplifies its own expression via this glycolysis-HIF-1α axis, establishing a pathogenic positive feedback loop in RA.

To explore clinical efficacy of different technical combinations in treating ischemic diabetic foot (DF). A retrospective analysis was conducted on 35 patients with DF who were treated with vascular interventional opening technique, periosteal distraction technique and bone cement coverage technique from January 2024 to November 2024. They were divided into comprehensive group and periosteal distraction group according to whether the vascular interventional opening technique was used in combination or not. There were 5 patients in comprehensive group, including 4 males and 1 female, aged from 59 to 73 years old with an average of (64.40±5.46) years old;the duration of diabetes ranged from 0.17 to 30.00 years with an average of (14.63±12.02) years;the courses of DF ranged from 30 to 150 days with an average of (84.00±61.48) days;2 patients were grade 2, 2 patients were grade 3, and 1 patient was grade 4 according to Wagner classification;combined vascular interventional opening, periosteal distraction and bone cement coverage surgery for treatment. There were 30 patients in periosteal stretch group, including 22 males and 8 females, aged from 58 to 86 years old with an average of (72.63±7.84) years old;the duration of diabetes was 10.00 (6.75, 16.75) years;the courses of DF was 30.00 (15.00, 37.50) days;14 patients were grade 2, 11 patients were grade 3, and 5 patients were grade 4 according to Wagner classification; combined periosteal distraction and bone cement coverage surgery for treatment. Changes of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT), toe skin temperature, peripheral capillary oxygen saturation (SpO2), and visual analogue scale (VAS) for pain were compared between two groups before operation and 1 week after operation. The number of operations, healing period, healing number, toe amputation number, preoperative fever situation and the number of complications were compared between two groups. Both groups were followed up for at least 6 months. There were no statistically significant differences in the number of operations, healing period, toe amputation rate, wound healing rate and complications between two groups (P>0.05). Before operation, the toe skin temperature of comprehensive group (26.98±0.88) ℃ was lower than that of periosteal distraction group (28.17±1.45) ℃, and the difference was statistically significant (P<0.05);while there were no statistically significant difference in CRP, IL-6, PCT, toe SpO2 and VAS between two groups (P>0.05). At 1 week after operation, IL-6, toe skin temperature, toe SpO2 and VAS in comprehensive group were 12.29(7.92, 22.15) pg·ml-1, (36.02±0.23) ℃, (95.80±0.84) % and(1.40±0.55) respectively, while those in periosteal distraction group were 5.49(4.36, 7.45) pg·ml-1, (31.36±1.57) ℃, (84.53±6.38) %, (2.20±0.81);and there were statistically significant differences between two groups(P<0.05). CRP, IL-6 and VAS at 1 week after operation in both groups were decreased compared with those before operation, and the differences were statistically significant(P<0.05). The toe skin temperature and SpO2 were increased compared with those before operation, and the differences were statistically significant(P<0.001). The multi-technique combination therapy, including vascular interventional opening technique, periostealdistraction technique and bone cement covering technique, could protect each other, enhance efficacy, effectively promote the wound healing of ischemic diabetic foot ulcer, and reduce the toe amputation rate. For moderate to severe ischemic DF, the combined use of periosteal distraction and bone cement coverage techniques has a satisfactory effect. For extremely severe ischemic DF with inflow tract lesions, vascular interventional opening techniques need to be added.

Objective: Sarcopenic obesity (SO) is a combination of depleted skeletal muscle mass and obesity, with a high prevalence, undetected onset, challenging diagnosis, and poor prognosis. However, studies on SO in cancer settings are limited. We aimed to explore the association between SO and mortality and to investigate potential predictors involved in the development of SO, with a further objective of constructing a model to detect its occurrence in cancer patients. Methods: The data of 1432 cancer patients from the National Health and Nutrition Examination Survey (NHANES) from the years 1999 to 2006 and 2011 to 2016 were included. For survival analysis, univariable and multivariable Cox proportional hazard models were used to examine the associations of SO with overall survival, adjusting for potential confounders. For machine learning, six algorithms, including logistic regression, stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost), were utilized to build models to predict the presence of SO. The predictive performances of each model were evaluated. Results: From six machine learning algorithms, cancer patients with SO were significantly associated with a higher risk of all-cause mortality (adjusted HR 1.368, 95%CI 1.107–1.690) compared with individuals without SO. Among the six machine learning algorithms, the optimal LASSO model achieved the highest area under the curve (AUC) of 0.891 on the training set and 0.873 on the test set, outperforming the other five machine learning algorithms. Conclusions: SO is a significant risk factor for the prognosis of cancer patients. Our constructed LASSO model to predict the presence of SO is an effective tool for clinical practice. This study is the first to utilize machine learning to explore the predictors of SO among cancer populations, providing valuable insights for future research.

Abstract Background Glioma is one of the most common malignant tumors of the central nervous system, with a complex etiology influenced by genetic factors, metabolic diseases, lifestyle, and mental health. However, the specific roles and interactions of these factors remain inadequately studied. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES), including 1,843 participants (163 glioma patients). Multivariate linear regression, neural network analysis, and correlation analysis were conducted to systematically evaluate the effects of age, gender, race, metabolic diseases, mental health, and lifestyle on glioma risk. A predictive risk model was also constructed. Results Age (OR = 1.081, P &lt; 0.001), cardiovascular disease (OR = 2.042, P &lt; 0.001), depression (OR = 2.348, P &lt; 0.001), and alcohol consumption (P &lt; 0.001) were identified as major risk factors for glioma, while diabetes (OR = 0.581, P = 0.003) appeared to have a protective effect. Predictive modeling highlighted age as the most critical predictor (importance score = 0.602), with an area under the ROC curve (AUC) of 0.76, indicating moderate predictive capability. Conclusion This study systematically analyzed multiple risk factors for glioma using NHANES data, identifying key risk factors and constructing a predictive model. The findings provide a theoretical basis for early screening, prevention strategies, and personalized interventions for glioma. Future research should integrate longitudinal data and molecular mechanism analyses to validate these findings and explore causal relationships.

BackgroundDiabetic kidney disease (DKD) is one of the most common diabetic complications and is closely related to metabolic acidosis. The serum anion gap (AG), an important index of acid-base balance, may reflect disturbed metabolism and be correlated with increased mortality risk. However, the role of AG in all-cause mortality risk in individuals suffering from severe DKD is not yet clear.MethodsIn this study, patients identified with a diagnosis of severe DKD utilizing MIMIC-IV database were determined. They were subsequently divided into four quartiles based on their serum AG levels. The findings consisted of in-hospital deaths and ICU deaths. The relationship between serum AG levels of severe DKD patients and clinical outcomes was elucidated using Cox proportional hazards regression analysis and RCS analysis.ResultsIn total, 1,716 patients (66.43% male) received treatment, with in-hospital and ICU mortality rates reaching 16.43% and 13.17%, respectively. Multivariate Cox regression analysis revealed that elevated serum AG levels were remarkably linked to all-cause mortalities. When adjusted for confounders, elevated serum AG levels correlated notably with in-hospital mortality [HR = 1.09(95%CI:1.07,1.11)P < 0.0001] and ICU mortality [HR = 1.10(95%CI:1.07,1.12)P < 0.0001]. RCS analysis showed that serum AG levels were positively correlated in a linear fashion with all-cause death risk.ConclusionSerum AG shows a significant positive correlation with all-cause mortalities in hospitals and ICU settings among patients with severe DKD. This suggests that serum AG could serve as a potential indication for recognizing DKD individuals with an increased overall risk of all-cause death.

Suboptimal glycemic control in individuals with diabetes is one of the major contributors to the development of diabetic retinopathy (DR). However, the role of ambulatory blood pressure (ABP) in this association remains unclear. The purpose of this research was to assess the associations among ABP, glycosylated hemoglobin (HbA1c), and DR in a diabetic population, with an emphasis on individuals exhibiting suboptimal glycemic and BP control. This study included 498 diabetic patients with comprehensive ABP data. The assessment of diabetes is based on the criteria of the American Diabetes Association (ADA). We adopted Least Absolute Shrinkage and Selection Operator (Lasso) regression to identify key variables and used logistic regression to investigate associations, followed by subgroup analyses. After adjustment for covariance variables, HbA1c showed a strong correlation with DR (OR: 1.228, 95% CI: 1.010-1.368). Among participants with low ABP, the prevalence of DR rises significantly with higher HbA1c levels (OR: 1.217,95% CI:1.057-1.402), whereas in those with elevated ABP (OR:1.366,95% CI:1.122-1.662), this relationship was markedly stronger, particularly in the context of Awake systolic blood pressure (SBP). Comparable findings were noted in both categorical models, as well as in subgroup analyses. However, heterogeneity was observed in subgroup analyses stratified by age. ABP may modify the relationship between HbA1c and DR; specifically, suboptimal glycemic management in patients at elevated ABP levels exacerbates the risk of DR. Therefore, it is imperative for diabetic patients to prioritize both BP regulation and glycemic management in their comprehensive disease management strategy.