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Chronic kidney disease (CKD) is a major health concern, with renal interstitial fibrosis (RIF) as a key feature. Effective management of RIF is crucial for treating CKD. Yiqi Juanshen decoction (YQJSD), as traditional Chinese medicine, has shown promising results in CKD treatment. This study evaluates YQJSD's effectiveness in ameliorating RIF and explores the underlying molecular mechanisms using the unilateral ureteral obstruction (UUO) model. YQJSD has been shown to effectively reduce serum creatinine and blood urea nitrogen levels, decrease extracellular matrix deposition, and down-regulate the expression of α-SMA, COL4α1, Fibronectin (FN). Mechanistically, YQJSD exerts its effects by modulating multiple pathways: it inhibits the NF-κB signaling pathway, inhibiting the expression of pro-inflammatory cytokines like NF-κB1, IL-1β, TNF-α, and CCR1. Simultaneously, YQJSD suppresses the epithelial-mesenchymal transition (EMT) by downregulating the expression of Snail1, Vimentin, Twist1, and FSP1, while increasing E-cadherin expression. Moreover, YQJSD can regulate the PI3K/AKT signaling pathway by decreasing the expression of LOXL2 and PIK3R1, along with p-AKT1/2/3. This modulation of the LOXL2/PI3K/AKT pathway contributes to the inhibition of both EMT and inflammation, highlighting a critical role in the therapeutic intervention against RIF. These findings suggest that YQJSD may serve as a promising therapeutic management of RIF in CKD patients. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) have been shown to provide significant protection against renal ischemia–reperfusion injury (IRI). Hypoxia has emerged as a promising strategy to enhance the tissue repair capabilities of MSCs. However, the specific effects of hypoxia on MSCs and MSC-EVs, as well as their therapeutic potential in renal IRI, remain unclear. In this study, we investigated the alterations occurring in MSCs and the production of MSC-EVs following hypoxia pre-treatment, and further explored the key intrinsic mechanisms underlying the therapeutic effects of hypoxic MSC-EVs in the treatment of renal IRI. Methods: Human umbilical cord MSCs were cultured under normoxic and hypoxic conditions. Proliferation and related pathways were measured, and RNA sequencing was used to detect changes in the transcriptional profile. MSC-EVs from both normoxic and hypoxic conditions were isolated and characterized. In vivo, the localization and therapeutic effects of MSC-EVs were assessed in a rat renal IRI model. Histological examinations were conducted to evaluate the structure, proliferation, and apoptosis of IRI kidney tissue respectively. Renal function was assessed by measuring serum creatinine and blood urea nitrogen levels. In vitro, the therapeutic potential of MSC-EVs were measured in renal tubular epithelial cells injured by antimycin A. Protein sequencing analysis of hypoxic MSC-EVs was performed, and the depletion of Glutathione S-Transferase Omega 1 (GSTO1) in hypoxic MSC-EVs was carried out to verify its key role in alleviating renal injury. Results: Hypoxia alters MSCs transcriptional profile, promotes their proliferation, and increases the production of EVs. Hypoxia-pretreated MSC-EVs demonstrated a superior ability to mitigate renal IRI, enhancing proliferation and reducing apoptosis of renal tubular epithelial cells both in vivo and in vitro. Protein profiling of the EVs revealed an accumulation of numerous anti-oxidative stress proteins, with GSTO1 being particularly prominent. Knockdown of GSTO1 significantly reduced the antioxidant and therapeutic effects on renal IRI of hypoxic MSC-EVs. Conclusions: Hypoxia significantly promotes the generation of MSC-EVs and enhances their therapeutic effects on renal IRI. The antioxidant stress effect induced by GSTO1 is identified as one of the most critical underlying mechanisms. Our findings highlight that hypoxia-pretreated MSC-EVs represent a novel and promising therapeutic strategy for renal IRI. [ABSTRACT FROM AUTHOR]

Introduction: Renal transplantation is a critical treatment for end-stage renal disease, but graft failure remains a significant concern. Accurate prediction of graft survival is crucial to identify high-risk patients. This study aimed to develop prognostic models for predicting renal graft survival and compare the performance of statistical and machine learning models. Methodology: The study utilized data from 278 renal transplant recipients at the Ethiopian National Kidney Transplantation Center between September 2015 and February 2022. To address the class imbalance of the data, SMOTE resampling was applied. Various models were evaluated, including Standard and penalized Cox models, Random Survival Forest, and Stochastic Gradient Boosting. Prognostic predictors were selected based on statistical significance and variable importance. Results: The median graft survival time was 33 months, and the mean hazard of graft failure was 0.0755. The 3-month, 1-year, and 3-year graft survival rates were found to be 0.979, 0.953, and 0.911, respectively. The Stochastic Gradient Boosting (SGB) model demonstrated the best discrimination and calibration performance, with a C-index of 0.943 and a Brier score of 0.000351. The Ridge-based Cox model closely followed the SGB model's prediction performance with better interpretability. The key prognostic predictors of graft survival included an episode of acute and chronic rejections, post-transplant urological complications, post-transplant nonadherence, blood urea nitrogen level, post-transplant regular exercise, and marital status. Conclusions: The Stochastic Gradient Boosting model demonstrated the highest predictive performance, while the Ridge-Cox model offered better interpretability with a comparable performance. Clinicians should consider the trade-off between prediction accuracy and interpretability when selecting a model. Incorporating these findings into the clinical practice can improve risk stratification and personalized management strategies for kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is the leading risk factor for end-stage renal disease (ESRD). Hydroxyurea (HU), a sickle cell disease (SCD) drug approved by FDA, shows protective effect in nephropathy. This study aims to understand whether the application of HU could be effective to treat DKD. Methods: The streptozotocin (STZ)-induced diabetic mice, and high glucose (HG)-treated human renal mesangial cells (HRMCs) were used to investigate the effect of HU on DKD. Serum creatinine and blood urea nitrogen levels reflecting renal function were evaluated. Histology was used to evaluate pathological changes. Indicators of inflammation and apoptosis were detected. Lastly, the mTOR-S6K pathway was explored by detecting the protein expression of S6K and phosphorylated S6K. Results: In STZ-induced diabetic mice, administration of HU (20 mg/kg) in drinking water for 16 weeks resulted in significant reductions in creatinine and urea nitrogen levels, alongside mitigating histopathological damage. Additionally, HU effectively suppressed the inflammatory response and apoptosis within the kidneys. HRMC cells were cultivated in HG conditions, and HU effectively attenuated the HG-induced inflammation and apoptosis. Moreover, HU treatment significantly inhibited the mTOR signaling pathway in both in both in vivo and in vitro experiments. Conclusion: This study unveils a new role of HU in alleviating diabetic kidney disease by modulating inflammation and apoptosis through the mTOR-S6K pathway. However, since HU did not significantly affect blood glucose levels, its therapeutic potential may be best realized when used in combination with standard antidiabetic therapies. Such a combination approach could simultaneously address hyperglycemia and renal dysfunction, offering a more comprehensive management strategy for DKD. [ABSTRACT FROM AUTHOR]

Blood urea nitrogen (BUN) is a key metric when evaluating the renal function of a given patient. Individuals with chronic kidney disease also often present with abnormal thyroid functionality. The specific association between BUN and thyroid function, however, is not well understood. This study was thus developed to explore how BUN levels within the normal range are related to thyroid activity among adults in the USA. The National Health and Nutrition Examination Survey (NHANES) dataset was leveraged for these analyses. Linear regression and smoothed curve fitting approaches were employed to examine the association between BUN levels and measures of thyroid function, with appropriate weighted and subgroup analyses. The 2007–2012 NHANEs cycles included 6231 eligible adults with BUN levels from 2.5–8.0 mmol/l. Under adjusted models, a higher BUN level was associated with reductions in FT3 (β=–0.01; p=0.047), TT3 (β=–1.08; p=0.003), and TT4 (β=–0.10; p=0.003) levels. In subgroup analyses, BUN levels were respectively found to be negatively correlated with FT3 and TT4 levels in subjects who were inactive and active. These findings are consistent with reduced FT3, TT4, and TT4 levels being correlated with higher BUN levels within the normal range among American adults. In non-physically active subjects, FT3 levels were more closely related to increasing BUN levels, whereas TT4 levels were more closely related to BUN levels among physically active subjects. However, additional research will be vital to clarify the mechanisms that underlie these results. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the relationship between 17 urinary metabolites of volatile organic compounds (mVOCs) in adolescents and renal function parameters (estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), urinary albumin, serum uric acid (SUA), and blood urea nitrogen (BUN)). In adjusted generalised linear models (GLM), mVOCs were positively correlated with eGFR, urinary albumin, and BUN, and mVOCs were negatively correlated with ACR and SUA. Weighted Quartile Sum (WQS) index correlated with eGFR [β(95%CI): 0.040 (0.028, 0.052)], urine albumin [β(95%CI): 0.275 (0.203, 0.622)], SUA [β(95%CI): 0.040 (0.025, 0.055)] and BUN [β(95%CI): 0.102 (0.082, 0.122)]. In Bayesian Kernel Machine Regression (BKMR) model, total compound effect was positively correlated with eGFR, positive associations were observed in high concentration of the mixture with urine albumin and ACR. Findings suggest that single and mixed exposures to mVOCs may affect renal parameters in adolescents. [ABSTRACT FROM AUTHOR]

The study published in Clinical Chemistry & Laboratory Medicine discusses the impact of a gatekeeping intervention on the appropriateness of blood urea nitrogen (BUN) testing in a Belgian academic hospital. The intervention led to a significant reduction in both tests performed and ordered, resulting in substantial cost savings without compromising the quality of care. The study highlights the effectiveness of gatekeeping interventions in reducing inappropriate laboratory tests and changing clinicians' prescribing behavior, suggesting its potential application in other testing contexts. [Extracted from the article]

OBJECTIVE: The adoption of continuous glucose monitors (CGMs) in inpatient settings in the pediatric population has been slow because of a scarcity of data on their reliability in hospitalized children. RESEARCH DESIGN AND METHODS: We retrospectively reviewed the accuracy of the Dexcom G6 CGM system in pediatric patients with diabetes admitted to our academic children's hospital from March 2018 to September 2023. We cross-referenced the Dexcom Clarity database against an internal database of inpatient admissions to identify all children with CGM data admitted to the hospital. We recorded sensor glucose readings from Clarity and values for point-of-care (POC) glucose, blood urea nitrogen (BUN), and pH from the electronic medical record. CGM accuracy and clinical reliability were measured by mean absolute relative difference (MARD) and Clarke error grid (CEG) analyses. RESULTS: There were 3,200 admissions of children with diabetes in this period, of which 277 (from 202 patients age 2-18 years) had associated CGM data. Paired CGM and POC measurements (n = 2,904) were compared, resulting in an MARD of 15.9%, with 96.6% of the values in zones A and B of the CEG analysis. Approximately 62% of paired values fell within a 15% or 15 mg/dL difference, whichever was larger (15%/15 mg/dL range), 74% within 20%/20, and 88% within 30%/30. Serum pH, sodium, and BUN had no impact on CGM values or absolute relative difference in linear regression analysis. CONCLUSIONS: CGMs demonstrated acceptable accuracy in hospitalized children with diabetes. CGM data should be integrated into hospital electronic records to optimize management. [ABSTRACT FROM AUTHOR]

Currently, the combination of atezolizumab and bevacizumab (Atez/Bev) is recommended as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC). However, there is a lack of research on the levels of nutrient elements in advanced HCC patients receiving Atez/Bev treatment. In this study, data from 35 patients with advanced HCC and 37 healthy individuals of similar age and sex were included. The levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were significantly increased in patients with HCC. These levels returned to the reference range after three rounds of Atez/Bev treatment. Additionally, the levels of blood urea nitrogen and creatinine (Cr) increased after Atez/Bev treatment. In HCC patients, the levels of calcium (Ca), iron (Fe), and copper (Cu) were significantly higher, while the levels of sodium (Na), magnesium (Mg), and zinc (Zn) were significantly lower compared to healthy individuals. These changes were reversed after Atez/Bev treatment. In conclusion, our findings indicate that treatment with Atez/Bev influences the levels of Ca, Fe, Cu, Na, Mg, and Zn in patients with HCC. The alterations in these elements caused by Atez/Bev treatment require mechanistic research in the future. [ABSTRACT FROM AUTHOR]

Purpose: Patients with heart failure and concomitant renal impairment are often prescribed loop diuretics, such as furosemide, as the primary treatment. The present meta-analysis is focused on analyzing the safety and efficacy of the implementation of tolvaptan as a novel approach in patients with renal impairment and heart failure. Methods: Two reviewers conducted a screening of articles using online databases, including PubMed, Google Scholar, and Embase. Following a comprehensive literature search, seven articles that met all inclusion criteria (patients with heart failure and renal impairment) were selected for analysis. Subsequently, various primary and secondary outcomes were evaluated. Results: The primary outcomes of our study included urine volume, worsening renal function, blood urea nitrogen (BUN) levels, and creatinine levels. Tolvaptan demonstrated superior efficacy in increasing urine output with a standardized mean difference of 2.18 (95% CI 0.62–3.75, p = 0.006) and resulted in a lower incidence of worsening renal function with odds ratio 0.41 (95% CI 0.22–0.77, p = 0.006). Additionally, there was no significant difference in the tolvaptan and conventional treatment groups in changing serum creatinine levels with a standardized mean difference of − 0.37 (95% CI − 0.86 to 0.12, p = 0.135), but tolvaptan tends to decrease blood urea nitrogen levels with a standardized mean difference − 0.18 (95% CI − 0.30 to − 0.06, p = 0.004) in comparison to conventional treatment group. Conclusion: While tolvaptan administration was related to better renal outcomes, unresolved heterogeneities and various factors could have influenced our findings. Further research is needed to evaluate the role of tolvaptan in the treatment of this patient population. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to build a model‐based predictive approach to evaluate the gastrointestinal side effects following an initial metformin medication. Materials and Methods: The model was developed from data from four randomised clinical cohorts. A prediction model was established using integrated or simplified indicators. Ten machine learning models were used for the construction of predictive models. The Shapley values were used to report the features' contribution. Results: Four randomised clinical trial cohorts, including 1736 patients with type 2 diabetes, were first included in the analysis. Seventy percent of participants (1216) were allocated to the training set, 15% (260) were assigned to the internal validation set and 15% (260) were assigned to the test set. The Extra Tree model had the highest area under curve (AUC) (0.87) in the validation and test set. The top five crucial indicators were blood urea nitrogen (BUN), sex, triglyceride (TG), high‐density lipoprotein‐cholesterol (HDL‐C) and total cholesterol (TC), and these five indicators were selected for constructing a simplified predictive model (AUC = 0.76). An online web‐based tool was established based on the predictive model with integrated 17 features and top five indicators. Conclusions: To predict gastrointestinal side effects in diabetic patients for initial use of metformin, a few easily obtained features are needed to establish the model. The model can be applied to the Chinese population in clinical practice. [ABSTRACT FROM AUTHOR]

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AbstractObjectiveMaterials and MethodsConclusionChronic inflammation contributes to myocardial complications in diabetes, marked by tissue fibrosis, necrosis, and apoptosis. Zingiber officinale, Allium sativum, and Moringa oleifera have individually demonstrated efficacy in diabetes management. In this study, it is hypothesised that a combination of these herbs in a polyherbal formulation would protect against diabetic cardiomyopathy.Diabetes was induced in male Sprague Dawley rats using strepetozotocin at a single dose of (55 mg/kg of body weight, i.p) in citrate buffer. Polyherbal formulation was administred as a treatment for 8 weeks.Rats receiving treatment with polyherbal formulation showed decreased blood glucose, plasma creatinine, Blood Urea Nitrogen, Creatine kinase- myocardial band, lactate dehydrogenase, aspartate aminotransferase, Troponin-I, NADPH oxidase 4, and Ras-related C3 botulinum toxin substrate-1. In contrast, Superoxide dismutase, catalase, and glutathione enzyme activities were increased.Thus, a polyherbal formulation containing herbs was able to attenuate the progression of diabetes mellitus and diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Aims: This study aims to evaluate the efficacy and safety of tripterygium glycosides combined with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) in treating Diabetic nephropathy and provide high-level evidence to support its standardized application. Methods: Literatures were retrieved from PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, Wanfang and VIP databases, the search time frame was defined as from the time of establishment to April 2023. This study only included randomized controlled trials of tripterygium glycosides combined with ACEI/ARB in the treatment of diabetic nephropathy, and the final included studies were identified according to the inclusion and exclusion criteria, and meta-analysis of data was performed using RevMan 5.3 software. Results: A total of 44 RCTs with 3537 DN patients were included in the study. Compared with the control group, tripterygium glycosides combined with ACEI/ARB significantly reducing 24 h-UTP (24 h urine total protein) [SMD = −1.46, 95% CI (−1.70, −1.23), P < 0.00001], increasing effective rate [RR = 1.23, 95% CI (1.17,1.29), P < 0.00001], elevating serum albumin [SMD = 0.85, 95% CI (0.69, 1.02), P < 0.00001], improving serum creatinine [SMD = −0.35, 95% CI (−0.59, −0.11), P = 0.004], with no difference in BUN (blood urea nitrogen) [SMD = −0.17, 95% CI (−0.48,0.13), P = 0.27], the adverse reactions rate was higher than those of the control group [RR = 1.96, 95%CI (1.43, 2.68), P < 0.0001]. Conclusion: This study showed that the combination of tripterygium glycosides and ACEI/ARB was more effective than ACEI/ARB alone. However, the side effects of the combined treatment group were higher than those of the control group, especially liver function damage, which also suggested that its safety in the treatment of diabetic nephropathy was worth considering. Therefore, although tripterygium glycosides provided a choice for the clinical treatment of diabetic nephropathy, its side effects limited its clinical application. In future studies, we need to further optimize tripterygium glycosides and reduce its side effects to ensure the safety of clinical application. [ABSTRACT FROM AUTHOR]

Background: Although extracorporeal membrane oxygenation (ECMO) is an effective technique for life support, the incidence of acute kidney injury (AKI) during ECMO support remains high. Dexmedetomidine (DEX), which has been widely used for sedation during ECMO, possesses several properties that help reduce the occurrence of AKI. This study aimed to investigate the protective effect of DEX on kidney function during ECMO. Methods: A total of 18 male Sprague–Dawley (SD) rats were randomly divided into three groups: Sham, ECMO, and ECMO + DEX groups. ECMO was established through the right jugular vein for venous drainage and right femoral artery for arterial infusion and lasts for four hours. Hematoxylin and eosin staining was used to evaluate the kidney Paller score for the rats in each group. Enzyme-linked immunosorbent assay was used to measure the levels of kidney injury biomarkers and cytokines in the serum. Reagent kits were used to measure the blood urea nitrogen (BUN) and creatinine (Cr) levels, which helped determine kidney function. Immunohistochemical staining was used to evaluate neutrophil infiltration in the kidney. Results: The pathological Paller score was substantially lower in the ECMO + DEX group. The levels of Kidney Injury Molecule-1 (KIM-1) and N-acetyl-β-D-glucosaminidase (NAG) were also significantly reduced. The kidney functionality, as indicated by BUN and Cr, was significantly improved compared with the ECMO group. The levels of cytokines IL-6, IL-1β, and TNF-α, were also significantly decreased in the ECMO + DEX group. Conclusion: This study demonstrated that dexmedetomidine could reduce inflammatory response and alleviate AKI during ECMO support. [ABSTRACT FROM AUTHOR]

Objective: To analyze the characteristics of pulmonary nodules (PNs) and related influencing factors in patients with type 2 diabetes mellitus (T2DM). Methods: Retrospectively analyzed the clinical and biochemical characteristics of 224 patients with PNs and 488 patients with non-PNs in patients with T2DM, and compared the clinical data of 72 patients with large nodules (≥ 5 mm) and 152 patients with small nodules (< 5 mm) in the pulmonary nodules (PNs) group. Results: Compared to the non-PNs group, the PNs Patients in the group had a longer duration of diabetes, higher age, serum creatinine (SCR), blood urea nitrogen (BUN) and the lower albumin (ALB) and body mass index (BMI); women, diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), and estimated glomerular filtration rate (eGFR) < 60 ml/min1.73m2 were more represented in the PNs group; there were fewer patients with overweight in the PNs group. Age and eGFR < 60 ml/min/1.73m2 were independent risk factors for PNs in patients with T2DM, and overweight was associated with a reduced risk of PNs. Compared with the small nodule group, patients in the large nodule group had higher fasting blood glucose (FBG) and lower fasting insulin (FINS); meanwhile, patients with decreased homeostasis model assessment-β (HOMA-β) and high smoking index (SI) were higher in the large nodule group; decreased HOMA-β and high SI were independent risk factors for large nodules. Conclusions: Age and eGFR < 60 ml/min/1.73m2 were independent risk factors for pulmonary nodules in patients with T2DM, and overweight may be a protective factor. Moreover, decreased islet B-cell function and smoking may contribute to the presence of PNs with a diameter of over 5 mm. [ABSTRACT FROM AUTHOR]

AbstractThe purpose of this trial was to assess the effects of methylphenidate on the kidney tissues and to investigate the protective effect of adenosine triphosphate (ATP) against possible methylphenidate nephrotoxicity in rats. The rats were separated into; healthy control (HG), methylphenidate (MPHG), ATP (ATPG), and ATP+ methylphenidate (AMPG). The ATPG and AMPG groups were administered ATP 4 mg/kg bw/d, and the HG and MPHG groups received distilled water intraperitoneally. One hour from, ATP and distilled water administration, methylphenidate 10 mg/kg bw/d was applied via oral gavage to the AMPG and MPHG groups once daily for 30 d (1 × 1). Animals were euthanized after 30 d and tissues were collected. The levels of certain oxidant/antioxidant parameters, pro-inflammatory cytokines, and Blood urea nitrogen (BUN) and creatinine levels were measured. Kidneys were also examined histopathologically. ATP inhibited the increase in oxidant and decrease antioxidant levels induced by methylphenidate. The amounts of pro-inflammatory cytokines were increased in methylphenidate-treated kidney tissue compared with the HG and AMPG groups. However, ATP increased oxidative damage markers and cytokines levels close to the healthy group. Serum BUN and creatinine levels increased with methylphenidate but ATP prevented BUN and creatinine from rising in the ATPG and MPHG groups. ATP also reduced the histopathological damage increased by methylphenidate. The potential efficacy of ATP in treating kidney damage induced by methylphenidate use. [ABSTRACT FROM AUTHOR]

Objective: Chronic kidney disease (CKD) is a major global health problem. In clinical practice, the Chinese patent herbal medicine Jianpi-Yishen (JPYS) formula is commonly used to treat CKD. However, the molecular mechanisms by which JPYS targets and modulates the host immune response remain unclear. Methods: This study utilized network pharmacology, RNA sequencing (RNA-seq), and metabolic analyses using in vivo and in vitro models to investigate the impact of the JPYS formula on inflammation and the immune system. Specifically, the study focused on macrophage polarization and metabolic changes that may slow down the progression of CKD. Results: A total of 14,946 CKD-related targets were identified from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases through network pharmacology analyses. 227 potential targets of the JPYS formula were predicted using the TCMSP database. Additionally, network diagram demonstrated that 11 targets were associated with macrophage activity. In vivo studies indicated that the JPYS formula could reduce blood urea nitrogen and serum creatinine in adenine-induced CKD rats. Furthermore, the formula inhibited inflammatory damage and abnormal macrophage infiltration in this CKD model. RNA-seq, proteomic and metabolic analyses identified the regulation of amino acid metabolism by betaine, specifically referring to glycine, serine, and threonine metabolism, as a key target of the JPYS formula in slowing the progression of CKD. In addition, in vitro studies suggested that JPYS may enhance tryptophan metabolism in M1 macrophage polarization and betaine metabolism in M2 macrophage polarization. Conclusions: The JPYS formula has been shown to have beneficial impact on CKD; a key mechanism is the mitigation of inflammatory damage through the interaction between amino acid metabolism and macrophage polarization. Of specific importance in this context are the roles of tryptophan in M1 polarization and betaine in M2 polarization. [ABSTRACT FROM AUTHOR]

Objective: The impact of lipid-lowering medications on chronic kidney disease (CKD) remains a subject of debate. This Mendelian randomization (MR) study aims to elucidate the potential effects of lipid-lowering drug targets on CKD development. Methods: We extracted 11 genetic variants encoding targets of lipid-lowering drugs from published genome-wide association study (GWAS) summary statistics, encompassing LDLR, HMGCR, PCSK9, NPC1L1, APOB, ABCG5/ABCG8, LPL, APOC3, ANGPTL3, and PPARA. A Mendelian randomization analysis was conducted targeting these drug-related genes. CKD risk was designated as the primary outcome, while estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) were assessed as secondary outcomes. Additionally, mediation analysis was performed utilizing 731 immune cell phenotypes to identify potential mediators. Results: The meta-analysis revealed a significant association between ANGPTL3 inhibitors and a reduced risk of CKD (OR [95% CI] = 0.85 [0.75-0.96]). Conversely, LDLR agonists were significantly linked to an increased risk of CKD (OR [95% CI] = 1.11 [1.02-1.22]). Regarding secondary outcomes, lipid-lowering drugs did not significantly affect eGFR and BUN levels. Mediation analysis indicated that the reduction in CKD risk by ANGPTL3 inhibitors was mediated through modulation of the immune cell phenotype, specifically HLA-DR on CD14+ CD16+ monocytes (Mediated proportion: 4.69%; Mediated effect: -0.00899). Conclusion: Through drug-targeted MR analysis, we identified a causal relationship between lipid-lowering drug targets and CKD. ANGPTL3 and LDLR may represent promising candidate drug targets for CKD treatment. [ABSTRACT FROM AUTHOR]

Objective: it was to evaluate the efficacy and safety of rapamycin-eluting stents at different doses in the treatment of coronary artery narrowing in miniature pigs. Methods: a total of 20 miniature pigs were randomly assigned into four groups: S1 group (low-dose rapamycin-coated stent, 55 µg/mm2), S2 group (medium-dose rapamycin-coated stent, 120 µg/mm2), S3 group (high-dose rapamycin-coated stent, 415 µg/mm2), and D0 group (bare metal stent). The stent size was 3.0 mm × 18 mm, with an over-expansion ratio of 1.1. Each group consisted of five pigs. Stent implantation was followed by euthanasia and tissue collection after 1 month. Vascular measurements, inflammatory response scores, cardiovascular injury scores, endothelialization scores, liver and kidney function indices, and myocardial injury markers were compared among the groups. Results: the neointimal thickness in the S2 and S3 groups was significantly lower than that in the S1 and D0 groups (S1 group: 24.08 ± 3.95, S2 group: 1.86 ± 0.28, S3 group: 2.72 ± 0.74, D0 group: 22.85 ± 3.15, P < 0.05). The residual lumen area in the S2 and S3 groups was significantly larger than that in the S1 and D0 groups (S1 group: 2.73 ± 0.51, S2 group: 4.25 ± 0.78, S3 group: 3.91 ± 0.73, D0 group: 2.91 ± 0.44, P < 0.05). The neointimal area in the S2 and S3 groups was significantly smaller than that in the S1 and D0 groups (S1 group: 3.44 ± 0.84, S2 group: 1.78 ± 0.25, S3 group: 2.07 ± 0.41, D0 group: 3.43 ± 0.72, P < 0.05). The degree of lumen narrowing in the S2 and S3 groups was significantly lower than that in the S1 and D0 groups (S1 group: 44.25 ± 3.66%, S2 group: 14.19 ± 2.01%, S3 group: 15.29 ± 2.45%, D0 group: 21.79 ± 3.51%, P < 0.05). The inflammation scores of coronary artery walls in the S2 and S3 groups of miniature pigs were markedly lower than those in the S1 and D0 groups (P < 0.05). The cardiovascular injury scores (P = 0.072) and endothelialization scores (P = 0.085) differed slightly among the four groups (P > 0.05). Post-operative liver function indicators (alanine transaminase, aspartate transaminase), kidney function indicators (blood urea nitrogen, serum creatinine), and myocardial injury markers (creatine kinase, creatine kinase-MB) also showed neglectable differences among the four groups (P > 0.05). Conclusion: medium and high doses of rapamycin-eluting stents effectively inhibit neointimal hyperplasia and local vascular inflammatory response in miniature pigs without causing damage to liver and kidney functions or myocardial cells. These stents demonstrate high efficacy and safety. Rapamycin-coated coronary stents, as an effective treatment for coronary artery stenosis, may achieve further improvement in therapeutic efficacy through optimization of drug dosage and stent design. [ABSTRACT FROM AUTHOR]

Background: There is evidence from clinical trials that coenzyme Q10 significantly improves mitochondrial function and decreases oxidative stress and cardiovascular disease in adult hemodialysis patients. However, we have never fully investigated its role in pediatric patients before. This study aimed to assess the effects of coenzyme Q10 supplementation on oxidative stress and inflammatory markers in pediatric hemodialysis patients. This was a prospective, randomized, double-blinded, placebo-controlled trial. Thirty-six pediatric hemodialysis patients were recruited and simply randomized to receive either oral coenzyme Q10 (3–5 mg/kg) daily or placebo daily for 12 weeks. Results: Using the Mann–Whitney test, children in the intervention group showed a significant reduction in the median percent change of blood urea nitrogen from baseline of − 58.18 versus − 9.6 in the placebo group (p = 0.002). The median percent change of serum malondialdehyde significantly decreased by − 55.68 in the intervention group, while it increased by 39.75 in the placebo group (p < 0.001). Additionally, the median percent change from baseline in serum tumor necrosis factor-α levels significantly decreased by − 46.69 in the intervention group and increased by 8.5 in the placebo group (p = 0.03). Conclusion: Supplementation of oral coenzyme Q10 may have beneficial effects on oxidative stress and inflammatory markers in pediatric hemodialysis patients. This study emphasized the potential efficacy of an average coenzyme Q10 dose of 4 mg/kg/day in pediatric hemodialysis patients; this gives the green light for other researchers to confidently evaluate larger doses as an attempt to control the systemic inflammation in this patient population. Further research is needed to determine whether coenzyme Q10 treatment improves clinical outcomes such as infection, hospitalization, cardiovascular events, and mortality in pediatric hemodialysis patients. Trial Registration Clinical trials.gov, NCT05170893, Registered 28 December 2021, https://clinicaltrials.gov/study/NCT05170893?cond=NCT05170893&rank=1. [ABSTRACT FROM AUTHOR]

Rationale: Acute kidney injury (AKI) is a clinical syndrome associated with a multitude of conditions. Although renal replacement therapy (RRT) remains the cornerstone of treatment for advanced AKI, its implementation can potentially pose risks and may not be readily accessible across all healthcare settings and regions. Elevated lactate levels are implicated in sepsis-induced AKI; however, it remains unclear whether increased lactate directly induces AKI or elucidates the underlying mechanisms. Methods: For human, the measurement of lactate in arterial blood gas is performed using the direct determination of L-lactate through an electrode oxidation method by a blood gas analyzer. For mice, enzyme-linked immunosorbent assay (ELISA) kits were employed to quantify the concentrations of lactate and AKI biomarkers in blood and cell supernatant. The mouse model of AKI was performed with a single intraperitoneal (i.p.) administration of lactate (30 mg/kg) and low-dose LPS (2 mg/kg) for 24 h. Proteomic analysis was conducted to identify lactylated proteins in kidney tissues. Techniques such as, immunoprecipitation, western blotting and immunofluorescence were used to evaluate the levels of HMGB1 lactylation, neutrophil extracellular traps (NETs)and to assess related molecular signaling pathways. Main results: Our findings indicate that lactate serves as an independent predictor of AKI in patients with acute decompensated heart failure (ADHF). We observed that co-administration of lactate with low-dose lipopolysaccharide (LPS) resulted in lactate overproduction, which subsequently elevated serum levels of creatinine (Cre) and blood urea nitrogen (BUN). Furthermore, the combined application of lactate and low-dose LPS was shown to provoke HMGB1 lactylation within renal tissues. Notably, pretreatment with HMGB1 small interfering RNA (siRNA) effectively diminished lactate-mediated HMGB1 lactylation and alleviated the severity of AKI. Additionally, lactate accumulation was found to enhance the expression levels of NETs in the bloodstream, with circulating NETs levels positively correlating with HMGB1 lactylation. Importantly, pre-administration of HMGB1 inhibitors (glycyrrhizin) or lactate dehydrogenase A (LDH-A) inhibitors (oxamate) reversed the upregulation of NETs induced by lactate and low-dose LPS in both the blood and polymorphonuclear neutrophils (PMNs) cell supernatant, thereby ameliorating AKI associated with lactate accumulation. Conclusions: These findings illuminate the role of lactate-mediated HMGB1 lactylation in inducing AKI in mice through the activation of the HMGB1-NETs signaling pathway. [ABSTRACT FROM AUTHOR]

In recirculating aquaculture systems (RAS), the impact of dissolved oxygen (DO) fluctuations on turbot is still not fully understood. This study investigated these impacts by selecting 135 turbot (average dry weight: 6.0 ± 0.5 g) and exposing them to three DO levels: hypoxia (4.0 ± 0.5 mg/L), normoxia (7.5 ± 0.5 mg/L), and hyperoxia (23.5 ± 0.5 mg/L). These groups were labeled as LF (low oxygen), NF (normal oxygen), and HF (high oxygen). The study aimed to explore the adaptive mechanisms of turbot under hypoxic and hyperoxic conditions, using microbiome, transcriptome, and hematological analyses over a 40-day period. The results suggest that hyperoxia significantly enhances turbot growth without compromising the composition of intestinal microbiome, whereas hypoxia markedly impairs growth and induces alterations in intestinal microbiome. Transcriptomic analysis revealed various pathways implicated in adaptation to both hypoxic and hyperoxic conditions, encompassing amino acid metabolism, protein metabolism, lipid metabolism, carbohydrate metabolism, the PPAR signaling pathway, etc. However, pathway changes are not completely consistent. For instance, pancreatic secretion is crucial for hyperoxia adaptation, while the HIF1α pathway plays a key role in hypoxia adaptation and tissue repair. Furthermore, genes ATP6 , HIF1 , HSP90 , and CYP450 exhibited high expression levels during hypoxia, whereas Hbae5 and Man-SL showed elevated expression during hyperoxia. In hematological indicators, there are ways to help adapt to hypoxia and hyperoxia, including increased red blood cell (RBC) and hemoglobin (HGB) counts; gas and ion balance; elevated blood urea nitrogen (BUN) and malondialdehyde (MDA); increased polyphenol oxidase (PPO) and lysozyme (LZM) activity. Although turbot have adaptive mechanisms to both hypoxia and hyperoxia, extended exposure to hypoxia detrimentally affects growth, whereas hyperoxia facilitates it. These findings provide significant insights into the adaptive mechanisms of turbot in response to fluctuating DO levels. [ABSTRACT FROM AUTHOR]

Introduction: Standing milkvetch (Astragalus adsurgens) is widely distributed in the wild in Eurasia and North America and has been bred for cultivated forage in China. Yellow stunt and root rot disease caused by Alternaria gansuense is the primary disease of standing milkvetch. A. gansuense promotes the production of swainsonine in the plant. This study aimed to determine the safety of standing milkvetch that is infected with A. gansuense as forage for animals. Methods: Two-week-old specific pathogen-free (SPF) male white mice were fed a commercial mouse feed (CMF), healthy plant feed (HPF) and diseased plant feed (DPF) for 3 or 6 weeks. We observed histological changes in the liver and kidney tissues of the mice and measured their daily feed intake, daily water intake, body weight, feed utilization, organ coefficients, and activities of serum enzymes. Results: The results showed that the daily feed intake of the mice that were fed DPF and HPF was significantly higher (p < 0.05) than those fed CMF at 3 and 6 weeks. The highest increase was observed in the daily water intake of the mice fed HPF (p < 0.05) followed by DPF and CMF. However, the mice fed DPF gained the least weight (p < 0.05). There was a significantly higher percentage of liver weight to body weight of the mice fed DPF (p < 0.05) than those fed HPF for 3 weeks and those fed CMF for 3 and 6 weeks. There were significantly higher levels of concentrations of alanine aminotransferase in the mice fed DPF and HPF than those fed CMF for 3 weeks (p < 0.05) and 6 weeks (p < 0.01). However, there was no significant difference in the mice fed HPF than those fed DPF. There were significantly higher of lactate dehydrogenase concentration (p < 0.001), while the blood urea nitrogen was lower in the mice fed DPF than those fed HPF and CMF at 3 weeks. There was a significantly higher percentage of numbers of lymphocytes in the blood of the mice fed DPF (p < 0.05) than those fed HPF, but the percentages of monocytes and eosinophils were significantly lower. Comparatively, there were more apparent pathological changes in the liver and kidney tissues of the mice fed with DPF than in those fed with HPF. Discussion: These findings indicate that standing milkvetch was toxic to white mice, and infection with A. gansuense increased its toxicity. Therefore, we conclude that standing milkvetch plants infected by A. gansuense must never be used as animal feed under any circumstances. Additionally, the amount of healthy standing milkvetch fed to animals should be appropriate, avoiding long-term or excessive feeding. [ABSTRACT FROM AUTHOR]

It is desirable to mitigate nitrogen (N) losses in the forms of nitrate to groundwater and nitrous oxide to the atmosphere from urine patches deposited by grazing cattle. Concentrations of milk and blood urea pools within the body are positively correlated with daily urinary nitrogen excretion. In this study, blood urea nitrogen concentrations (BUN) in mobs of Hereford beef cattle were influenced by feed type. BUN heritability was 0.28 suggesting that BUN can be manipulated by selective breeding, while its repeatability was 0.47. No deleterious relationships of BUN with growth rate or carcass composition traits were revealed but work is required to investigate the influence of genetic manipulation of BUN on urinary nitrogen concentration and volume. [ABSTRACT FROM AUTHOR]

Introduction: The risk of kidney fibrosis is significantly elevated in individuals with diabetes, chronic nephritis, trauma, and other underlying conditions. Concurrently, human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and their extracellular vesicles (MSC-Exos) have gained prominence in regenerative medicine. In light of these observations, we are undertaking a meta-analysis to elucidate the influence of hUCB-MSCs and MSC-Exos on kidney fibrosis. Methods: To identify eligible trials, we conducted a comprehensive search of the CNKI, PubMed, Web of Science and Wanfang databases from inception to 24 October 2022. Furthermore, the methodological quality of the included studies was evaluated using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool. Besides, the weighted standard mean difference (SMD) with a 95% confidence interval (CI) was calculated using the Review Manager 5.4 software. The Stata (12.0) software was employed to assess the impact of factors on outcome heterogeneity and publication bias in the study. A total of 645 related research studies were retrieved, of which 14 that involved 219 experimental animals were included in the study. Results: In comparison to the control treatment, treatment with Human UCB MSC and MSC-Exos was observed to significantly enhance renal function in animal models of kidney fibrosis. This was evidenced by a reduction in serum creatinine (Scr) levels (p < 0.00001) and blood urea nitrogen (BUN) levels (p < 0.00001), as well as reduction of CD68+ macrophages (p < 0.00001), TdT-mediated dUTP Nick-End labeling (TUNEL)+ tubular cells(p < 0.00001), α-SMA levels (p = 0.0009) and TGF-β1 (p < 0.00001). P < 0.05 is deemed to indicate a statistically significant difference. Alpha-smooth muscle actin (α-SMA) is a specific protein that is normally expressed in myofibroblasts. The term "CD68+ macrophages" refers to macrophages that express the CD68 protein on their cell surface. Both macrophages and myofibroblasts have been linked to the development of kidney fibrosis. In this study, the quantity of CD68+ macrophages and α-SMA was employed as a means of gauging the extent of renal fibrosis. Additionally, transforming growth factor beta 1 (TGF-β1) is a significant cytokine implicated in the pathogenesis of kidney fibrosis. TUNEL-positive tubular cells represent tubular cells undergoing apoptosis. It is hypothesized that this may result in a reduction of tubular apoptosis and a delay in kidney fibrosis, due to the inhibition of the transformation of macrophages into myofibroblasts (MMT) and the disruption of the kidney fibrogenic niche. Conclusion: The principal findings of this preclinical systematic review indicate that hUCB MSC and MSC-Exos have a substantial protective impact against kidney fibrosis. Kidney transfer remains the final option for traditional renal fibrosis treatment. The lack of donors and high cost make it challenging for many patients to access appropriate treatment. Although this study still suffers from three shortcomings: sample size, methodological consistency and translational challenges, the hUCB MSC and MSC-Exos have been demonstrated to reduce tubular apoptosis and inhibit fibrotic progression. The hUCB MSC and MSC-Exos offer a promising alternative due to their lower price and accessibility. Nevertheless, further high-quality studies are required in the future to address the methodological limitations identified in this review. Systematic Review Registration: Identifier INPLASY2022100104. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, forage resources in many countries have been facing the problems of limited planting area and high cost. Rice and Zizania latifolia are widely cultivated, and they produce large amounts of rice straw or sheath and leaves when harvested. However, most of these are discarded or burned, resulting in a waste of resources and environmental pollution. Effective utilization of these by-products is the key to solving the problem of feed shortage in livestock production. The aim of this study was to investigate the effects of fermented total mixed ration containing rice straw and sheath and leaves of Zizania latifolia on heifer growth from the perspective of metabolism and host genetics. Feeding fermented total mixed ration containing 35% rice straw and 31% sheath and leaves of Zizania latifolia could improve the nutrient intake and antioxidant capacity of heifers. And the key metabolites involved in energy metabolism and oxidative balance can be used as candidate markers for heifers' average daily gain. This integrated omics approach highlights the potential to increase livestock productivity and promote sustainable agricultural practices. With the increasing demand for enhancing livestock production performance and optimizing feed efficiency, this study aimed to investigate the effects of fermented total mixed ration (FTMR) containing different proportions of rice straw and sheath and leaves of Zizania latifolia on systemic nutrient metabolism and oxidative metabolism under host genetic regulation and on growth performance of heifers. A total of 157 heifers aged 7–8 months were selected, and their hair was collected for whole-genome sequencing. They were randomly assigned into four groups of 18 to 21 cattle each and fed FTMR containing varying levels of rice straw (21% in LSF, 28% in MSF, 35% in HSF) or 31% sheath and leaves of Zizania latifolia (ZF) for a two-month period. At the end of trial, blood and urine samples were collected to measure biochemical indexes and metabolomics. The results showed that high rice straw content and ZF diets could increase blood glucose and non-protein nitrogen in heifers, that is, blood glucose and urea nitrogen levels in HSF and ZF groups were higher than those in LSF and MSF groups (p < 0.05). Meanwhile, the two diets could improve the antioxidant level of heifers. Urine metabolomics analysis between the groups identified three differential metabolic pathways, including 11 metabolites. Among them, l-homoserine and o-acetylserine had significant SNPs associated with them, which promoted glutathione metabolism. Although there was no significant effect of diet on heifers' average daily gain (ADG) in body weight (p > 0.05), there was substantial inter-individual variation in metabolites among all animals, as further correlation analyses illustrated. Twenty-eight metabolites were significantly associated with ADG (R > 0.3, p < 0.05). Four of them were identified as biomarkers, primarily regulating energy metabolism and oxidative balance. In conclusion, feeding HSF and ZF FTMR enhances glutathione metabolism and antioxidant capacity in heifers, positioning key metabolites as candidates for ADG markers. This integrative omics approach underscores the potential for enhancing livestock productivity and promoting sustainable agricultural practices. [ABSTRACT FROM AUTHOR]

Simple Summary: Quantification of enzymic activity, metabolites, and hematological responses is useful for determining the physiological, nutritional, metabolic, and clinical status of high-risk beef calves. In the initial days after calves arrive at the feedlot, they regain lost water and body weight, stabilize or improve their immunity, and establish a social structure. The ruminal microorganisms are adapted to grain-based diets; therefore, it is expected that blood and serum parameters change during the initial days after arrival. However, to date, information on changes in health indicators, such as blood and serum parameters, during adaptation in the first 56 d of arrival is scarce. According to the results of this study, the more days at reception, the more blood and serum parameter values related to health and immunity were improved, whereas the concentration of blood parameters related to tissue injury was minimized; this behavior indicates an improvement in the physiological, nutritional, metabolic, and clinical status of high-risk beef calves during their stay. Apparently, at least 42 d is the minimum period after arrival to permit calves to reach more adequate physiological and metabolic conditions before starting the fattening phase. The objective of this study was to evaluate the changes in enzymic activity, metabolites, and hematological responses during the first 56-d of arrival of newly received calves, which were qualified at reception as high-risk but diagnosed as clinically healthy. A total of 320 blood samples were taken from 64 crossbred bull calves (average initial body weight = 148.3 ± 1.3 kg) at different times from arrival (d 0, 14, 28, 42, and 56 of received). Calves included in the study were received in June (n = 20), November (n = 24), and April (n = 20); thus, experimental treatments were arranged in a generalized complete block design (three blocks = month of arrival). The following parameters were determined: total white blood cells (WBC): lymphocytes (LYM), lymphocytes % (LYM%), monocytes (MON), monocytes % (MON%), granulocytes (GRA), granulocytes % (GRA%), platelets (PLT), and mean platelet volume (MPV); red blood cells (RBC): red blood cell distribution width test % (RDW%), hematocrit (HCT), and mean corpuscular volume (MCV); hemoglobin (HGB): mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). The enzymatic activity and metabolites analyzed were alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), globulin (GLO), ALB/GLO ratio, blood urea nitrogen (BUN), creatinine (CRE), total bilirubin (TBIL), total cholesterol (TCHO), triglycerides (TG); (4) calcium (Ca), glucose (GLU), sodium (Na+), potassium (K+), and chlorine (Cl−). It was observed that ALP, ALT, TP, ALB, GLO, ALB/GLO ratio, TCHO, TG, Ca, and GLU increased as days from reception increased (linear effect, p ≤ 0.04), whereas CRE and TBIL were reduced (linear effect, p ≤ 0.02). A quadratic response (p ≤ 0.001) was observed to GGT and AST values being maximal on days 1 and 56 after arrival (p ≤ 0.001). Na+, K+, and Cl− concentrations were not affected by prolonged days after arrival. Finally, blood cells of LYM, LYM%, PLT, RBC, HGB, HCT%, MCV, and MCH increased (linear effect, p ≤ 0.001) as the number of days after arrival increased. Whereas MON% was linearly decreased (p ≤ 0.05). It was concluded that even when all parameters were within the range of reference intervals (RIs) determined for healthy cattle, during the period of monitoring, as the days after arrival lengthened, blood serum parameters related to health and immunity increased, and metabolites related to tissue injury decreased. In contrast, plasmatic electrolytes (Na+, K+, and Cl−) were slightly reduced as the day after arrival increased. Apparently, at least 42 d is the minimum period after arrival to permit calves to reach more adequate physiological and metabolic conditions before starting the fattening phase. [ABSTRACT FROM AUTHOR]

Objective: Blood urea nitrogen (BUN) is a commonly used biomarker for assessing kidney function and neuroendocrine activity. Previous studies have indicated that elevated BUN levels are associated with increased mortality in various critically ill patient populations. The focus of this study was to investigate the relationship between BUN and 28-day mortality in intensive care patients. Methods: This was a multi-centre retrospective cohort study that made use of data from the eICU Collaborative Research Database. The primary exposure variable was BUN, and the outcome was 28-day mortality. The following variables were included as covariates: age, gender, BMI, white blood cell count, creatinine, GCS score, APACHE IV score, and diabetes. The statistical analyses included univariate and multivariate logistic regression, as well as generalized additive modelling, which was employed to assess the non-linear relationship between BUN and mortality. Results: A total of 63,757 elderly patients were included in the study, with a 28-day mortality of 6.5%. The univariate analysis indicated that elevated BUN quartiles were associated with an increased risk of mortality. The results of the multivariate analysis further confirmed the non-linear relationship between BUN and mortality. When BUN was less than 32 mg/dL, there was a significant positive association, with an adjusted odds ratio of 1.230 (95% CI: 1.154–1.311, p<0.0001) for every 10 mg/dL increase in BUN. However, when BUN was greater than or equal to 32 mg/dL, BUN level had no significant effect on mortality. Conclusion: BUN showed a nonlinear, threshold correlation with 28-day mortality in critically ill patients. The higher the BUN, the greater the risk of death if the BUN is below the threshold. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) emerges as a singular subclass of heart failure, bereft of specific therapeutic options. Magnesium, an indispensable trace element, is essential to the preservation of cardiac integrity. However, the association between magnesium supplementation and mortality in HFpEF patients remains unclear. This study extracted HFpEF patient data from the MIMIC-IV database between 2008 and 2019. Propensity score matching was conducted to ensure that patients receiving magnesium supplementation (including magnesium sulfate and magnesium oxide) were balanced with those not receiving it in terms of baseline characteristics. The primary analysis focused on the 28-day all-cause mortality rate, with secondary endpoints encompassing ICU and one-year mortality rates, along with the duration of hospitalization. After matching, the study's final cohort balanced at 1970 patients, with 985 patients per group. The results showed that magnesium intake significantly contributed to a decrease in the 28-day all-cause mortality rate (hazard ratio [HR], 0.682; 95% confidence interval [CI], 0.539–0.863), particularly in subgroups such as older patients (HR, 0.65; 95% CI 0.52–0.81), females (HR, 0.55; 95% CI 0.41–0.73), and those with hypertension (HR, 0.62; 95% CI 0.48–0.79) or without diabetes (HR, 0.54; 95% CI 0.41–0.71). Although magnesium treatment improved both ICU and one-year mortality rates, it concurrently resulted in extended ICU and hospital stays. Mediation analysis indicated that blood urea nitrogen partially mediated the association between magnesium intake and mortality, accounting for approximately 22.73% of the observed effect. Magnesium supplementation has illustrated a significant potential for mitigating the mortality rate in the HFpEF patient, particularly among the elderly, female, and individuals with hypertension. Therefore, magnesium supplementation stands as a potentially valuable supplementary treatment modality for patients with HFpEF. Further comprehensive research is warranted to explore its effects more deeply. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is defined by the release of pro-inflammatory factors, leading to structural damage in renal tubules and subsequent tubular cell injury and death. Delivering drugs specifically to renal tubules to mitigate tubular cell damage holds potential for AKI treatment. In this work, we developed functional liposomes (LZM-PLNPs-TP) designed to bypass the glomerular filtration barrier and target tubules by leveraging the unique structural and pathological characteristics of glomeruli and tubules. LZM-PLNPs-TP, incorporating lysozyme (LZM) and cationic liposome, and carrying the anti-inflammatory and antioxidant drug Triptolide (TP), demonstrated favorable stability, efficient drug release, and good cytocompatibility in wide TP concentrations (0–100 ng/mL). These liposomes exhibited the enhanced renal accumulation, tubular retention, and cellular targeting through endocytosis by peritubular capillary endothelial cells. The administration of LZM-PLNPs-TP at a minimal TP dosage (0.01 mg/kg) demonstrated significant protection through the mitigation of oxidative stress and inflammation in ischemia/reperfusion injury (IRI) mice, while the naked TP (0.01 mg/kg) exhibited lower efficacy. Following treatment with LZM-PLNPs-TP, levels of serum creatine, blood urea nitrogen, superoxide dismutase, malondialdehyde, as well as the inflammatory cytokines IL-1β and IL-6 in renal IRI mice were found to be significantly reduced by factors of 2.9, 1.7, 0.7, 1.3, 2.1, and 1.9, respectively, compared to mice treated with TP alone. In summary, this study presents an LZM-targeted drug delivery system that synergistically enhances tubular reabsorption and cellular uptake, offering a promising strategy for AKI treatment. We have designed specialized liposomes (LZM-PLNPs-TP) with targeting capabilities towards renal tubules to enhance cellular internalization, offering a promising therapeutic strategy for AKI treatment. Our research confirms that the increased accumulation of LZM-PLNPs-TP in renal tubules is facilitated by peritubular capillary endothelial cells rather than glomerular filtration. LZM-PLNPs-TP demonstrated effective mitigation of oxidative stress, inflammation suppression, and significant improvement in kidney injury, ultimately leading to the restoration of renal function in murine models of AKI induced by ischemia/reperfusion. This study introduces LZM-targeted liposomes that enhance tubular reabsorption and cellular uptake synergistically, providing a promising therapeutic approach for AKI management. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent. Objective: The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis sativa in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity. Methods: Podocytes cell viability was assessed using MTS assay with cisplatin (30µM) in presence or absence of Cannabis oil extract (COE) at 0.5, 1 and 2µg/ml for 24h. Acute renal injury was established in adult female C57BL/6 mice with 20mg/kg, i.p. single dose cisplatin. Mice were divided into control group (vehicle), COE group, cisplatin group and cisplatin plus COE (2.5, 5 and 20mg/kg, i.p.). Animal body weight, serum creatinine, blood urea nitrogen (BUN), and proteinuria were measured. Results: Cell viability assay and western blot analysis revealed that COE prevented apoptosis induced by cisplatin in cultured immortalized rat podocytes. In addition, in vitro scratch assay demonstrated the ability of COE to promote and restore the migratory capacity of podocytes in cisplatin-treated cells. Interestingly, COE treatment improved urinary and serum parameters characterized by a significant decrease in serum creatinine, urea, and proteinuria at various COE doses. Western blot analysis showed that COE inhibited COX-2 protein induction as well as apoptosis marker production (Bax/Bcl2 ratio) in cisplatin-treated mice when compared to mice treated with cisplatin alone. Conclusion: Collectively, the aforementioned findings indicate that COE could be a promising approach to protect against cisplatin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Background and aim: Zinc oxide and copper oxide nanoparticles are known for their promising biological activities. This study aims to synthesize zinc oxide nanoparticles and copper-doped zinc oxide nanoparticles to harness the combined cytotoxic and anticancer effects of them in vitro and in vivo studies. Methods: Zinc oxide nanoparticles, both doped and undoped, were synthesized using a chemical co-precipitation method. All synthetized nanoparticles were examined for shape, crystal structure and morphology/ microstructure using X-ray diffractometers, scanning electron microscopy and transmission electron microscopy. The hydrodynamic diameter and zeta-potential was measured by dynamic light scattering. Energy Dispersive Spectroscopy evaluated copper doping in zinc oxide nanoparticles. The anticancer effects were tested on bone cancer fibroblast cells and normal lung fibroblast cells using cell viability test, colony formation assay, and lactate dehydrogenase assay at concentrations of 0, 1, 10, 17.5, 25, 50, 100, and 200 μg/ml. In vivo experiments assessed serum markers (Aspartate aminotransferase, Alanine transaminase, blood urea nitrogen and creatinine) and liver malondialdehyde levels in response to 5 mg/kg and 50 mg/kg doses. Results: zinc oxide nanoparticles exhibited a spherical morphology and good dispersion, with an average grain size ranging from 15–39 nm. Copper-doped zinc oxide nanoparticles displayed a mixture of rod-like and grain-like structures, and a larger average grain size of 18–68 nm. X-ray diffraction analysis confirmed the wurtzite crystal structure for both types of nanoparticles. While individual grain sizes varied, the mean particle size for all samples, including those with increasing copper doping, was approximately 100 ± 0.1 nm. Both nanoparticles exhibited a negative zeta potential. In vitro studies revealed that copper-doped zinc oxide nanoparticles, zinc oxide nanoparticles, and bulk zinc oxide exhibited cytotoxic activity (cell viability < 80%) and induced apoptosis in bone cancer fibroblast cells at 17.5 μg/ml after 72 h (P < 0.05). The copper-doped zinc oxide nanoparticles demonstrated higher cytotoxicity compared to zinc oxide nanoparticles and bulk zinc oxide at higher concentrations (P < 0.05). The copper-doped zinc oxide nanoparticles also showed significant inhibition of cell proliferation over 10 days at 17.5 μg/ml (P < 0.05). In vivo studies indicated no significant changes in serum Aspartate aminotransferase, Alanine transaminase, blood urea nitrogen, and creatinine levels at 5 mg/kg. However, a 50 mg/kg dose of zinc oxide nanoparticles and copper-doped zinc oxide nanoparticles significantly increased these serum markers and liver malondialdehyde levels (P < 0.05). Histological analysis revealed liver injury in rats treated with 50 mg/kg but not at 0.5 mg/kg. Conclusions: The copper-doped zinc oxide nanoparticles exhibit enhanced cytotoxicity and anticancer activity compared to zinc oxide nanoparticles and bulk zinc oxide, particularly at higher concentrations. High doses of these nanoparticles could induce significant biochemical changes and liver injury in vivo, highlighting the need for careful dose management. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is the single largest cause of end-stage renal disease (ESRD). Inflammation reaction mediated by NLRP3 inflammasome and Nrf2-related oxidative stress have been considered to play a very important role in the progress of diabetic nephropathy (DN). Effective drugs for the treatment of diabetic nephropathy still need to be explored. Chlorogenic acid (CGA) is a kind of polyphenol with a Nrf2 activation property widely existed in nature. The aims of this study were to evaluate the renoprotective effect of CGA and to elucidate the anti-inflammation mechanisms involved. In the present study, we established a diabetic rat model to investigate the renoprotective effect of CGA in vivo. The results show that the level of serum creatinine (Scr), blood urea nitrogen (BUN), and urinary protein excretion in diabetic rats were significantly decreased after CGA intervention. CGA administration can active the Nrf2 pathway and inhibit NLRP3 inflammasome activation. Notably, Nrf2 siRNA transfection nullified the inhibitory effects of CGA on NLRP3 inflammasome activation in vitro. To summarize, our present study provided evidence that chlorogenic acid can slow the progression of diabetic nephropathy progression, and the effect is associated with suppression of NLRP3 inflammasome activation via through modulation of the Nrf2 pathway, suggesting its therapeutic implications for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to explore the risk factors associated with intensive care unit- acquired weakness (ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nutrition (EEN) and the role of biomarkers in managing ICU-AW. METHODS: This retrospective, observational cohort study included 180 patients at risk of malnutrition admitted to the emergency intensive care unit of the First Affiliated Hospital of Xiamen University Hospital from January 2022 to December 2023. Patients were divided into ICU-AW group and non-ICU-Aw group according to whether they developed ICU-AW, or categorized into EEN and parenteral nutrition (PN) groups according to nutritional support. ICU-AW was diagnosed using the Medical Research Council score. The primary outcome was the occurrence of ICU-AW. RESULTS: The significant factors associated with ICU-AW included age, sex, type of nutritional therapy, mechanical ventilation (MV), body mass index (BMI), blood urea nitrogen (BUN), and creatinine (Cr) levels (P<0.05). The PN group developed ICU-AW earlier than did the EEN group, with a significant difference observed (log-rank P<0.001). Among biomarkers for ICU-AW, the mean prealbumin (PAB)/ C-reactive protein (CRP) ratio had the highest diagnostic accuracy (area under the curve [AUC] 0.928, 95% confidence interval [95% CI] 0.892-0.946), surpassing the mean Cr/BUN ratio (AUC 0.740, 95% CI 0.663-0.819) and mean transferrin levels (AUC 0.653, 95% CI 0.574-0.733). CONCLUSION: Independent risk factors for ICU-AW include female sex, advanced age, PN, MV, lower BMI, and elevated BUN and Cr levels. EEN may potentially delay ICU-AW onset, and the PAB/CRP ratio may be an effective diagnostic marker for this condition. [ABSTRACT FROM AUTHOR]

Clove oil obtained from Syzygium aromaticum (L.) is traditionally employed to treat inflammation associated with rheumatism, gastric disorders, and as an analgesic. Chemo-herbal combinations are known to have potent anti-inflammatory and analgesic effects, while mitigating the drug related side effects. The purpose of this study was to evaluate anti-inflammatory, analgesic and antipyretic effects of a combination of flurbiprofen and clove oil in a micro-emulsion (FCM) form using various in vivo models. Micro-emulsion of flurbiprofen and clove oil (FCM) was prepared following reported protocols and three different dose combinations (25, 12.5 and 6.25 mg/kg) were evaluated in carrageenan and histamine-induced acute inflammation, CFA-induced arthritis, yeast-induced pyrexia, and acetic acid-induced writhing models. qPCR studies were conducted to explore the possible mechanism of action. GC–MS of clove oil was performed to explore its chemical composition. FCM 25 mg/kg treated group exhibited significantly better (p < 0.05) effects compared to clove oil (CM) and flurbiprofen (FBR) (25 mg/kg) treated groups in both acute and chronic models. Histopathological study of joints showed a reduction in infiltration of inflammatory cells, bone erosion, and tissue oedema in FCM (25 mg/kg) treated group as compared to other treatment groups. Significant up-regulation in mRNA expression of anti-inflammatory (IL-4, IL-10) and down-regulation of pro-inflammatory genes (NF-κB, IL-6, TNF-α, IL-1β and COX-2) was observed in all the FCM-treated groups but, 25 mg/kg-treated group showed comparatively better results. Gross macroscopic examination of stomach sections also showed relatively less deleterious effects of test treatments (CM and FCM) as compared with FBR treated group. Serum levels of liver enzymes (alanine aminotransferase (ALT), and alkaline phosphatase (ALP)), blood urea nitrogen (BUN) and creatinine were also found to be normal as compared to FBR and tween-water (TW) treated groups. GC–MS of clove oil revealed that it was rich in eugenol contents. This study reveals that a combination of flurbiprofen and clove oil in a micro-emulsion form could be a promising approach to enhance therapeutic actions and to mitigate synthetic drugs related side effects in clinical settings. It might implicate a synergistic action on the modulation of inflammatory genes expression. Further research is warranted to explore the full potential of this combination in treating various inflammatory conditions. [ABSTRACT FROM AUTHOR]

Septic acute kidney injury (AKI) is an important risk factor for developing chronic kidney disease (CKD). Hu antigen R (HuR) is recognized as a crucial modulator in inflammation. We hypothesized that elevated HuR contributes to the transition from septic AKI to CKD by promoting persistent inflammation and fibrosis, and inhibition of HuR may reverse septic kidney injury. Mice subjected to lipopolysaccharide (LPS) injections every other day were concurrently treated without or with either KH39 or niclosamide (NCS) for 7 days. Control mice received saline injections. Repeated LPS injections led to a significant increase in HuR expression in the kidneys, which was effectively suppressed by KH39 or NCS treatment. LPS-induced kidney injury was characterized by elevated plasma blood urea nitrogen levels and urinary albuminuria, along with histological signs of inflammatory cell infiltration and fibrosis, as determined by periodic acid-Schiff and Masson's trichrome staining, and immunofluorescent staining for markers such as a-smooth muscle actin, fibronectin, collagen III, and F4/80. Treatment with either KH39 or NCS mitigated these changes observed in LPS-injured kidneys. Additionally, increased expression of CD147, a molecule implicated in inflammatory cell recruitment and tubular injury, was inhibited by KH39 or NCS treatment. These effects on HuR and CD147 expression were further validated in vitro in cultured macrophages and tubular cells. This study suggests that HuR elevation in LPS-stimulated macrophages and kidney cells contributes to the progression of septic kidney injury, possibly through HuR-CD147 interactions, underscoring the therapeutic potential of HuR inhibitors for this condition. [ABSTRACT FROM AUTHOR]

BACKGROUND: Due to the high-risk nature of sepsis, emergency departments urgently need a simple evaluation method to assess the degree of inflammation and prognosis in sepsis patients, providing a reference for diagnosis and treatment. OBJECTIVE: To investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) combined with the blood urea nitrogen-to-serum albumin ratio (BAR) in sepsis. METHODS: A total of 377 sepsis patients admitted to Lishui People's Hospital from June 2022 to June 2023 were selected as the study subjects. Based on their prognosis, they were divided into a survival group (255 cases) and a death group (82 cases). The clinical data of the two groups were compared. Multivariate logistic analysis was used to identify factors influencing sepsis prognosis, and ROC curve analysis was used to assess the predictive efficacy of NLR, BAR, and their combination. RESULTS: Compared with survivors, non-survivors had higher NLR and BAR, with statistically significant differences (p < 0.05). After adjusting for confounding factors, NLR (OR = 1.052) and BAR (OR = 1.095) were found to be independent prognostic factors for sepsis patients (both p < 0.05). The AUC of NLR combined with BAR was 0.798 (95% CI 0.745–0.850, p < 0.05), higher than the AUC of NLR alone (0.776) and BAR alone (0.701). CONCLUSIONS: The combination of NLR and BAR has a high predictive value for the prognosis of sepsis patients. Its simple calculation makes it particularly suitable for use in emergency departments. [ABSTRACT FROM AUTHOR]

BACKGROUND: Discussed based on the network interactive platform of structured care for patients with chronic renal failure (CRF) in the process of hemodialysis. OBJECTIVE: This study seeks to elucidate the application value of structured nursing, deployed through network interaction platforms, in sustaining patients undergoing maintenance hemodialysis. METHODS: A total of 62 patients diagnosed with Chronic Renal Failure (CRF) between April 2022 and August 2023 were randomly allocated into two distinct care groups: conventional and structured nursing care based on a web-interactive platform. Both cohorts were comparatively analyzed with respect to psychological states, quality of life within therapeutic interventions, and relationships with complications. Renal function indicators, including Creatinine Clearance (Ccr), Serum Creatinine (SCr), and Blood Urea Nitrogen (BUN), were subjected to Pearson analysis to appraise their predictive value in prognostication, while Receiver Operating Characteristic (ROC) curve analysis was constructed to further discern their diagnostic precision. RESULTS: Post-intervention, notable improvements were observed in the emotional states of patients in both cohorts, with the structured care group exhibiting significantly lower Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores (p < 0.05). Furthermore, patients under the web-interactive structured nursing regimen demonstrated superior overall adherence, a reduced incidence rate of complications, and markedly higher scores in quality of life assessments compared to those under conventional care (p < 0.05). The derived cut-off values for Ccr, SCr, and BUN were 32.5 ml/min, 251.5 umol/L, and 14.5 mmol/L, respectively, with sensitivities and specificities pegged at 0.645% and 0.645% for Ccr, 0.774% and 0.548% for SCr, and 0.774% and 0.774% for BUN. The corresponding areas under the ROC curve (AUC) for each parameter were 0.816, 0.653, and 0.856, respectively. CONCLUSION: Comprehensive hemodialysis care for patients with chronic renal failure can improve self-care ability to improve quality of life and reduce the incidence of complications, which has great potential for clinical progress and is worthy of further research. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influences of asiaticoside (AS) on inflammatory response and oxidative stress in rats with mesangial proliferative glomerulonephritis (MsPGN) by regulating the rat sarcoma (Ras) /extracellular signal regulated kinase (ERK) /mitogen activated protein kinase (MAPK) signaling pathway. Methods: Sixty SPF SD rats were randomly divided into sham operation group (Sham group), MsPGN model group (Model group), low-dose AS group (AS-L group, 40 mg/kg), high-dose AS group (AS-H group, 80 mg/kg), high-dose AS+Ras/ERK/MAPK signaling pathway activator group (AS-H+anisomycin group, 80 mg/kg AS+10 mg/kg anisomycin), with 12 rats in each group. Rat model of MsPGN was established by modified serum immunization. The 24 h urine protein content of rats in each group was detected by Coomassie brilliant blue method. HE staining and PSA staining were used to observe the pathological changes of renal tissue of rats in each group. TUNEL staining was used to detect apoptosis of rat glomerular cells in each group. Levels of serum creatinine (Scr), superoxide dismutase (SOD), blood urea nitrogen (BUN), malondialdehyde (MDA), and levels of IL-18, IL-1β, TNF-α, SOD and MDA in renal tissues were measured by ELISA. Protein levels of Ras, pERK1/2, ERK1/2, MAPK and p-MAPK in renal tissues of rats in each group were detected by Western blot. Results: ①AS alleviated inflammatory reaction and oxidative stress injury in MsPGN rats. Compared with Sham group, 24 h urine protein content, glomerular cell apoptosis rate, serum Scr, BUN, MDA levels, renal tissue IL-18, IL-1β, TNF-α, MDA levels in model group were significantly increased (P<0.05), while SOD level in serum and renal tissue was significantly decreased (P<0.05) . HE staining showed that the glomerulus of rats had severe mesangial hyperplasia, a large amount of matrix deposition, and the basement membrane was significantly thickened. Compared with model group, 24 h urine protein content, glomerular cell apoptosis rate, serum Scr, BUN, MDA levels, renal tissue IL-18, IL-1β, TNF-α, MDA levels in AS-H group rats were significantly decreased (P<0.05), while SOD level in serum and renal tissue was significantly increased (P<0.05), HE staining showed alleviated mesangial hyperplasia injury. ②AS downregulated the Ras/ERK/MAPK signaling pathway. Compared with Sham group, expression of Ras protein and phosphorylation level of ERK1/2 and MAPK in Model group were significantly increased (P<0.05); compared with Model group, expression of Ras protein, phosphorylation level of ERK1/2 and MAPK in AS-H group were significantly decreased (P<0.05), and anisomycin reduced the inhibitory effect of AS on inflammatory response and oxidative stress injury in MsPGN rats (P<0.05) . Conclusion: AS may reduce the inflammatory reaction and oxidative stress injury in MsPGN rats by down-regulating Ras/ERK/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension and dyslipidemia are major cardiovascular risk factors that often coexist. Hyperlipidemia is a crucial modifiable risk factor in preventing cardiovascular disease. Aim: We aimed to explore the relationship between lipid levels and the grading of hypertension in a community-based adult population. Methods: A total of 63,091 non-employed individuals were included in this study. Measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), fasting plasma glucose (FPG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (STB), serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c). Chi-square and t-tests were used to obtain basic population characteristics. Multivariate logistic regression was used to evaluate the association between the prevalence of hypertension and lipid profiles, as well as to identify influencing factors. A P-value < 0.05 was considered statistically significant. Statistical charts were utilized to analyze the relationship between lipid parameters and hypertension grades. Results: A total of 30,588 men and 32,503 women with an average age of 64.57 ± 12.5 years participated in this study. After adjusting STB and TC, every 1 mmol/L increase in TG and LDL-c was associated with a 6.0% and 6.5% increase in the prevalence of hypertension, respectively. Conversely, for every 1 mmol/L increase in HDL-c, the prevalence of hypertension decreased by 4.1%. Increases in TG and LDL-c levels were observed across all grades of hypertension, while very high HDL-c was significantly associated in grade III hypertension (1.54→1.66 mmol/L). Additionally, age, BMI, FPG, ALT, AST, SCr, and BUN significantly influenced the association between hypertension and lipid levels. Conclusion: Hyperlipidemia and hypertension often coexist in health examination populations. Elevated levels of TG and LDL-C are associated with all grades of hypertension, while extremely high HDL-C level is linked to more severe hypertension. [ABSTRACT FROM AUTHOR]

Background/aims: Homocysteine (Hcy) has been associated with an increased risk of diabetic nephropathy (DN) in patients, but there is still controversy. This study aims to investigate the causal relationship between plasma Hcy and DN. Methods: A Mendelian randomization (MR) study using data from 2 samples was employed to infer causal relationships. The aggregated genetic data associated with Hcy was derived from the largest genome-wide association study (GWAS) to date, involving 44,147 individuals of European ancestry.Data on SNP-diabetic nephropathy, creatinine, and urea nitrogen were obtained from the IEU GWAS database. The analysis method employed a fixed-effect or random-effect inverse variance-weighted approach to estimate effects.Additional analysis methods were used to assess stability and sensitivity. The potential for pleiotropy was evaluated using the MR-Egger intercept test. Results: Using 12 SNPs as instrumental variables, two-sample MR analysis revealed no evidence of a causal relationship between genetically predicted plasma Hcy levels and diabetic nephropathy, as well as creatinine and blood urea nitrogen levels. This finding is consistent with the results obtained from other testing methods. Conclusions: Two-sample Mendelian Randomization analysis found no evidence of a causal relationship between plasma homocysteine levels and diabetic nephropathy, creatinine, or urea. [ABSTRACT FROM AUTHOR]

Background: The dysregulation of microRNAs (miRNAs) has been detected in patients with gastric cancer (GC), which inspired the use of miRNAs as a novel biomarker for GC. In this study, we investigated the previously reported miRNA dysfunction in cancer tissues as a potential plasma biomarker for GC using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Methods: The published miRNA abnormalities were searched in the microRNA Cancer Association Database. Plasma samples were collected from patients with GC (n = 26) and controls (n = 17). The sensitivity and specificity of polyadenylation RT-PCR (PA-RT) and stem-loop RT-PCR (SL-RT) were compared. Statistical comparisons between patients with GC and controls were performed to identify miRNA biomarkers, and correlation analyses between the threshold cycle (Ct) values of miRNAs and various blood biochemical parameters were performed to elucidate the confounding factors. Results: mir-17, mir-21, mir-31, mir-99b, mir-222, and U6 were selected. PA-RT showed greater sensitivity and lower specificity than SL-RT (PA-RT vs. SL-RT, mean Ct: 19.6 vs. 29.2; coefficient of variation: 0.42 vs. 0.10). Adopting SL-RT owing to its higher specificity, only mir-222 was significantly upregulated in patients with GC (GC vs. control, miRNA expression: 15.4 vs. 5.27, p = 0.0098). Regarding the correlation between blood biochemical parameters and cells with miRNA expression, mir-31 and mir-99b were correlated with blood urea nitrogen, mir-17, mir-21, and mir-99b were negatively correlated with platelets, and mir-21 was correlated with neutrophils. No obvious correlations were noted between mir-222 expression and blood parameters. Receiver operating characteristic (ROC) curve analysis indicated that mir-222 identified GC patients with a maximum area under the curve (0.73, 95% confidence interval 0.57–0.89). Conclusions: Plasma mir-222 was confirmed to be dysregulated in patients with GC, irrespective of blood biochemical parameters. [ABSTRACT FROM AUTHOR]

Patients with end-stage renal disease (ESRD) are at increased risk for bleeding complications following surgery. However, the approach to the preoperative risk assessment and risk reduction, if feasible, in ESRD patients undergoing nonelective abdominal surgery has not been comprehensively studied. We aim to determine the prevalence and risk factors for perioperative bleeding in patients on dialysis undergoing nonelective abdominal surgery. Using the American College of Surgeons National Surgical Quality Improvement Program 2005-2017 database, we identified patients on dialysis who underwent a variety of nonelective abdominal surgeries by Current Procedural Terminology code. Rates of major perioperative bleeding, defined as bleeding requiring red blood cell transfusion within 72 h after surgery, were calculated and stratified by procedure type. Multivariate logistic regression was used to identify risk factors for major perioperative bleeding. Thirty-day mortality rates were compared between those who had a major perioperative bleed and those who did not. Of 9102 patients on dialysis undergoing nonelective abdominal surgery, 2793 (30.7%) experienced major perioperative bleeding requiring transfusion and 2002 (22.0%) died within 30 d of surgery. By multivariable logistic regression, patients who were female, independent or partially dependent in activities of daily living, ventilator dependent, had disseminated cancer, or had chronic steroid use at baseline were found to be at elevated risk for major perioperative bleeding. Elevated partial thromboplastin time, blood urea nitrogen, anemia, and hypoalbuminemia were also associated with higher odds of major bleeding. Compared to patients undergoing herniorrhaphy (lowest risk), the odds of major perioperative bleeding were highest for patients undergoing hepatic surgery (odds ratio [OR] = 18.09), splenic surgery (OR = 10.86), and pancreatic surgery (OR = 9.59). Major perioperative bleeding was associated with increased 30-d mortality (34.0% versus 16.7%, P < 0.001). Patients with ESRD experience high rates of bleeding requiring transfusion following emergent abdominal surgery. Derangements in preoperative laboratories and baseline patient characteristics may be useful in assessing bleeding risk in this patient population. [ABSTRACT FROM AUTHOR]

Background/Objectives: Acute pulmonary embolism (PE) is a leading cause of cardiovascular mortality, characterized by nonspecific symptoms and variable clinical presentations. Accurate risk stratification is essential for effective management. While conventional tools like the simplified pulmonary embolism severity index (sPESI) and imaging modalities are widely used, they are often costly and have limitations in predictive accuracy. Inflammatory and coagulative markers, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean-platelet-volume-to-lymphocyte ratio (MPVLR), have shown promise in thrombotic conditions. This study explores their prognostic value in PE, focusing on their associations with risk stratification and clinical outcomes. Methods: This retrospective study included 231 adult patients diagnosed with PE at a tertiary care center. Exclusion criteria included recent infection, autoimmune diseases, or immunosuppressive therapy. Laboratory data, clinical parameters, and outcomes (e.g., hospitalization duration, complications, and mortality) were analyzed. Ratios were calculated from routine blood counts, and statistical comparisons were conducted between low- and high-risk groups based on sPESI. Results: High-risk patients (n = 203) exhibited significantly higher troponin, blood urea nitrogen, aspartate aminotransferase, lactate, the NLR (median 4.9 vs. 2.7, p = 0.005), and the MPVLR (median 7.1 vs. 3.9, p = 0.001) compared to low-risk patients. The PLR showed no significant difference between risk groups (p = 0.233). An elevated NLR, PLR, and MPVLR correlated with ICU admission, intubation, and mortality (p < 0.001, p < 0.007, and p < 0.001, respectively). The NLR was the most consistently associated with hospitalization duration and mortality, while the MPVLR and PLR were less predictive of overall hospitalization. Conclusions: The NLR, MPVLR, and PLR are cost-effective, easily calculable markers with the potential for improving risk stratification in PE patients. Among these, the NLR showed the strongest prognostic value, correlating with multiple clinical outcomes. Multicenter studies are needed to validate these findings further and establish clinical utility. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) and chronic kidney disease (CKD) represent two frequently observed clinical conditions. AKI is characterized by an abrupt decrease in glomerular filtration rate (GFR), generally associated with elevated serum creatinine (sCr), blood urea nitrogen (BUN), and electrolyte imbalances. This condition usually persists for approximately a week, causing a transient reduction in kidney function. If these abnormalities continue beyond 90 days, the condition is redefined as chronic kidney disease (CKD) or may advance to end-stage renal disease (ESRD). Recent research increasingly indicates that maladaptive repair mechanisms after AKI significantly contribute to the development of CKD. Thus, implementing early interventions to halt the progression from AKI to CKD has the potential to markedly improve patient outcomes. Although considerable research has been conducted, the exact mechanisms linking AKI to CKD are complex, and effective treatments remain limited. Kidney function is influenced by circadian rhythms, with the circadian gene Bmal1 being vital in managing these cycles. Recent research indicates that Bmal1 is significantly involved in the progression of both AKI and CKD. In this study, we conducted a retrospective analysis of Bmal1's role in AKI and CKD, reviewed recent research advancements, and investigated how Bmal1 influences the pathological mechanisms underlying the progression from AKI to CKD. Additionally, we highlighted gaps in the existing research and examined the potential of Bmal1 as a therapeutic target in kidney disease management. This work aims to provide meaningful insights for future studies on the role of the circadian gene Bmal1 in the transition from AKI to CKD, with the goal of identifying therapeutic approaches to mitigate kidney disease progression. [ABSTRACT FROM AUTHOR]

Objective The present study investigated the impact of continuous infusion therapy with low-dose terlipressin (TP) combined with norepinephrine on hemodynamics, inflammatory markers, and prognosis in patients with severe septic shock. Materials and Methods Seventy-four patients with severe septic shock were randomly assigned to either a control group (n = 37) or an observation group (n = 37). Patients in the control group received norepinephrine alone, while those in the observation group received a continuous infusion of low-dose TP in addition to norepinephrine. To assess the effect of treatment, a set of clinical parameters was evaluated in both groups before and after treatment. These parameters included hemodynamic indicators (heart rate [HR], mean arterial pressure [MAP], central venous pressure [CVP], cardiac index [CI], and systemic vascular resistance index [SVRI]), levels of serum inflammatory markers (interleukin-8 [IL-8], tumor necrosis factor-α [TNF-α], and hypersensitivity C-reactive protein [hs-CRP]), renal function indicators (blood urea nitrogen [BUN], serum creatinine [SCr], and cystatin C [Cys-C]), serum procalcitonin (PCT), and lactate, as well as lactate clearance rate (LCR). Additionally, the acute physiology and chronic health evaluation II (APACHE II) score, 28-day mortality rate, multiple organ dysfunction syndrome (MODS) incidence rate, and adverse reaction incidence were also determined. Results Compared to baseline values, MAP, CVP, CI, SVRI, and LCR increased in both groups after treatment, while HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate all decreased. Additionally, APACHE II scores also decreased. Furthermore, the observation group exhibited higher MAP, CVP, CI, SVRI, and LCR, along with lower HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate than the control group after treatment. The observation group also had lower APACHE II score, 28-day mortality rate, MODS incidence rate, and adverse reaction incidence than the control group after treatment (P  < .05). Conclusion Continuous infusion therapy with low-dose TP combined with norepinephrine was effective in treating patients with severe septic shock, improving hemodynamic parameters, reducing the levels of inflammatory markers, promoting renal function recovery, and reducing the mortality rate. [ABSTRACT FROM AUTHOR]