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Background: To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children. Methods: A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed. Results: A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury. Conclusions: Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients. [ABSTRACT FROM AUTHOR]

N-Methyl-N-Nitrosourea (MNU) is a compound that induces oxidative stress resulting in high levels of oxidants and damage to body cells. Red okra contains polyphenol and flavonoid active ingredients as antioxidants. This study aims to analyze the effect of ethanol extract of red okra pods (ROPE) on oxidant levels, antioxidant enzymes, and damage to rat kidney proximal tubule cells due to NMU. This study used 30 rats divided into six treatment groups, namely CN (normal), N (negative control; MNU 50 mg/kg BW), P (positive control; MNU and MTX 50 mg/kg BW), T1 (MNU and ROPE 50 mg/kg BW), T2 (MNU and ROPE 100 mg/kg BW), and T3 (MNU and ROPE 200 mg/kg BW). The treatment was carried out on all groups after eight weeks. The results indicate that malondialdehyde (MDA) and nitrogen oxide (NO) decrease with the ROPE treatment. The glutathione reductase (GSH) activity as an antioxidant enzyme increased T1 and T2, while glutathione peroxidase (GPx) showed an increase in T2 and T3. Furthermore, the biochemical marker of the rat kidney showed lower blood urea nitrogen (BUN) and creatinine (Cre) levels in all treatment groups. Then, the repair of damaged proximal tubule cells showed an increase in normal cells and lower swollen cells; however, there was a degradation in necrotic cells in T2 and T3. It can be indicated that the ROPE can act as an antioxidant that can reduce MDA and NO levels, increase GSH and GPx levels, and reduce damage to proximal renal tubule cells due to MNU. [ABSTRACT FROM AUTHOR]

• Hs3st3a1, Hs3st3b1 and Hs3st6 , which generate 3- O -sulfated HS domains, are enriched in kidney podocytes. • Hs3st3a1 -/-; Hs3st3b1 -/- kidneys have loss of the highly 3 -O- sulfated UA-GlcNS6S-IdoA2SGlcNS3S6S tetrasaccharides, which may modify HS and growth factor signaling. • Hs3st3a1 -/-; Hs3st3b1 -/- mice have smaller kidneys with smaller glomeruli and disrupted glomerular ultrastructure. Heparan sulfate (HS) is an important component of the kidney anionic filtration barrier, the glomerular basement membrane (GBM). HS chains attached to proteoglycan protein cores are modified by sulfotransferases in a highly ordered series of biosynthetic steps resulting in immense structural diversity due to negatively charged sulfate modifications. 3- O -sulfation is the least abundant modification generated by a family of seven isoforms but creates the most highly sulfated HS domains. We analyzed the kidney phenotypes in the Hs3st3a1, Hs3st3b1 and Hs3st6 -knockout (KO) mice, the isoforms enriched in kidney podocytes. Individual KO mice show no overt kidney phenotype, although Hs3st3b1 kidneys were smaller than wildtype (WT). Furthermore, Hs3st3a1-/-; Hs3st3b1-/- double knockout (DKO) kidneys were smaller but also had a reduction in glomerular size relative to wildtype (WT). Mass spectrometry analysis of kidney HS showed reduced 3- O -sulfation in Hs3st3a1-/- and Hs3st3b1-/- , but not in Hs3st6-/- kidneys. Glomerular HS showed reduced HS staining and reduced ligand-and-carbohydrate engagement (LACE) assay, a tool that detects changes in binding of growth factor receptor-ligand complexes to HS. Interestingly, DKO mice have increased levels of blood urea nitrogen, although no differences were detected in urinary levels of albumin, creatinine and nephrin. Finally, transmission electron microscopy showed irregular and thickened GBM and podocyte foot process effacement in the DKO compared to WT. Together, our data suggest that loss of 3- O -HS domains disrupts the kidney glomerular architecture without affecting the glomerular filtration barrier and overall kidney function. [ABSTRACT FROM AUTHOR]

A urea quantification method integrated with a pipette-tip-based biosensor and a smartphone was developed for the on-site diagnosis of blood urea nitrogen. When a sample solution containing phenol red is drawn into a pipette tip with urease immobilized on its inner wall, the color of the solution changes owing to an enzymatic reaction. The urea concentration can be quantified by photographing the pipette tip with a smartphone and quantifying the color intensity of the solution. In actual urea measurements, the detection limit (3σ) was estimated to be 1.3 mg/dL, indicating that the method has sufficient performance to quantify urea in serum. Furthermore, the method was found to reduce sample consumption and analysis time to 1/10 and 1/3, respectively, compared with conventional methods using microwell plates. This method requires only a micropipette and a smartphone to carry out measurements and does not require bench-top precision equipment or special training. Therefore, the method is expected to develop into a practical analytical platform for biomarker diagnostics that can be used in the field. [ABSTRACT FROM AUTHOR]

Objective To assess the outcome of patients with cancer-related sepsis requiring continuous renal replacement therapy (CRRT) in a single-center pediatric intensive care unit (PICU). Method Children with sepsis who necessitate CRRT from January 2017 to December 2021 were enrolled. The patients with leukemia/lymphoma or solid tumors were defined as underlying cancer. Multivariate logistic regression analysis was performed to identify the death risk factors in patients with cancer-related sepsis. Results A total of 146 patients were qualified for inclusion. Forty-six (31.5%) patients with cancer-related sepsis and 100 (68.5%) non-cancer-related sepsis. The overall PICU mortality was 28.1% (41/146), and mortality was significantly higher in cancer-related sepsis patients compared with non-cancer patients (41.3% vs. 22.0%, p = 0.016). Need mechanical ventilation, p-SOFA, acute liver failure, higher fluid overload at CRRT initiation, hypoalbuminemia, and high inotropic support were associated with PICU mortality in cancer-related sepsis patients. Moreover, levels of IL-6, total bilirubin, creatinine, blood urea nitrogen, and international normalized ratio were significantly higher in non-survivors than survivors. In multivariate logistic regression analysis, pediatric sequential organ failure assessment (p-SOFA) score (OR:1.805 [95%CI: 1.047–3.113]) and serum albumin level (OR: 0.758 [95%CI: 0.581 -0.988]) were death risk factors in cancer-related sepsis receiving CRRT, and the AUC of combined index of p-SOFA and albumin was 0.852 (95% CI: 0.730–0.974). Conclusion The overall PICU mortality is high in cancer-related sepsis necessitating CRRT. Higher p-SOFA and lower albumin were independent risk factors for PICU mortality. [ABSTRACT FROM AUTHOR]

Background: At present, the clinical methods for preventing and treating contrast-induced nephropathy (CIN) are limited, and statins can play a better role during this process. So, we aimed to assess the atorvastatin on renal function in nephropathy patients after percutaneous coronary intervention (PCI). Methods: In this work, 100 elderly patients with coronary heart disease (CHD) were selected into an experimental group (Exp group, 50 cases, 40 mg/d po atorvastatin) and a control group (Ctrl group, 50 cases, 10 mg/d po atorvastatin). The renal function indicators, blood routine indicators, and the incidence of adverse reactions (ARs) were compared between patients in Exp and Ctrl groups. Results: After surgery, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (CysC), high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL6) in patients in the Exp group were much lower, and the levels of estimated glomerular filtration rate (eGFR) and superoxide dismutase (SOD) were higher (all P < 0.05). Meanwhile, the incidences of ARs during hospitalization between patients in the Exp and Ctrl groups were all 8%, showing no observable difference (P > 0.05). Compared with conventional doses of atorvastatin, high-dose atorvastatin can effectively prevent renal function damage in patients with CIN, decrease the inflammation and oxidative stress in patients, and will not increase the risk of ARs during hospitalization. Conclusion: Taken together, high-dose atorvastatin can be applied in treating patients with CHD after PCI due to its excellent efficacy and high safety. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Sarcopenia is a prominent issue among aging populations and associated with poor health outcomes. This study aimed to examine the predictive value of questionnaire and biomarker data for sarcopenia, and to further develop a user‐friendly calculator for community‐dwelling middle‐aged and older adults.We used two waves (2011 and 2013) of the China Health and Retirement Longitudinal Study (CHARLS) to predict sarcopenia, defined by the Asian Working Group for Sarcopenia 2019 criteria. We restricted the analytical sample to adults aged 45 or above (N = 2934). Five machine learning models were used to construct Q‐based (only questionnaire variables), Bio‐based (only biomarker variables), and combined (questionnaire plus biomarker variables) models. Area under the receiver operating characteristic curve (AUROC) was used for performance assessment. Temporal external validation was performed based on two datasets from CHARLS. Important predictors were identified by Shapley values and coefficients.Extreme gradient boosting (XGBoost), considering both questionnaire and biomarker characteristics, emerged as the optimal model, and its AUROC was 0.759 (95% CI: 0.747–0.771) at a decision threshold of 0.20 on the test set. Models also performed well on the external datasets. We found that cognitive function was the most important predictor in both Q‐based and combined models, and blood urea nitrogen was the most important predictor in the Bio‐based model. Other key predictors included education, haematocrit, total cholesterol, drinking, number of chronic diseases, and instrumental activities of daily living score.Our findings offer a potential for early screening and targeted prevention of sarcopenia among middle‐aged and older adults in the community setting. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) was one of the most prevalent comorbidities among patients with coronavirus disease 2019 (COVID-19). Interactions between different metabolic parameters contribute to the susceptibility to the virus; thereby, this study aimed to rank the importance of clinical and laboratory variables as risk factors for COVID-19 or as protective factors against it by applying machine learning methods. Method: This study is a retrospective cohort conducted at a single center, focusing on a population with T2DM. The patients attended the Yazd Diabetes Research Center in Yazd, Iran, from February 20, 2020, to October 21, 2020. Clinical and laboratory data were collected within three months before the onset of the COVID-19 pandemic in Iran. 59 patients were infected with COVID-19, while 59 were not. The dataset was split into 70% training and 30% test sets. Principal Component Analysis (PCA) was applied to the data. The most important components were selected using a 'sequential feature selector' and scored by a Linear Discriminant Analysis model. PCA loadings were then multiplied by the PCs' scores to determine the importance of the original variables in contracting COVID-19. Results: HDL-C, followed by eGFR, showed a strong negative correlation with the risk of contracting the virus. Higher levels of HDL-C and eGFR offer protection against COVID-19 in the T2DM population. But, the ratio of BUN to creatinine did not show any correlation. Conversely, the AIP, TyG index and TG showed the most positive correlation with susceptibility to COVID-19 in such a way that higher levels of these factors increase the risk of contracting the virus. The positive correlation of diastolic BP, TyG-BMI index, MAP, BMI, weight, TC, FPG, HbA1C, Cr, systolic BP, BUN, and LDL-C with the risk of COVID-19 decreased, respectively. Conclusion: The atherogenic index of plasma, triglyceride glucose index, and triglyceride levels are the most significant risk factors for COVID-19 contracting in individuals with T2DM. Meanwhile, high-density lipoprotein cholesterol is the most protective factor. [ABSTRACT FROM AUTHOR]

Purpose: Excessive fluoride induces kidney injury by reducing the antioxidant capacity and causing oxidative stress. Our previous studies have shown that moderately forced treadmill running alleviates oxidative injury. However, the impact of voluntary wheel-running exercise on fluoride-intoxicated mice remains unclear. In this study, we investigated the effects of voluntary wheel-running exercise on oxidative stress-induced renal injury in fluoride-intoxicated mice. Methods: 80 Institute of Cancer Research (ICR) mice (half male and half female), were randomly divided into one of eight experimental groups: four receiving distilled water and the other four ingesting 100 mg/L sodium fluoride. Each group was subdivided to incorporate different exercise regimens--no wheelrunning, daytime, nighttime, and all-day wheel-running exercises. After 6 months, mice were euthanized for subsequent analyses. Results: HE staining revealed that 6 months of fluoride exposure caused structural damage in the kidneys of mice, elevated blood urea nitrogen (BUN), and uric acid (UA) levels in the serum. Levels of malondialdehyde (MDA), reactive oxygen species (ROS), hydrogen peroxide (H2O2), and catalase (CAT) enzyme activity significantly increased. In contrast, glutathione (GSH) content and total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) enzyme activities obviously decreased. Interestingly, these above changes were reversed by free-wheel movement. Correlation analysis demonstrated that negative relationships exist between ROS, MDA, H2O2 levels, CAT enzyme activity, and movement distance. Additionally, T-SOD and GSH-PX enzyme activities were positively associated with exercise distance. Conclusions: Voluntary wheel-running exercise mitigated renal injury induced by sodium fluoride in mice, and the extent of renal recovery was positively correlated with the distance covered during voluntary wheel-running exercise. [ABSTRACT FROM AUTHOR]

Background: Predicting long-term survival in intensive care unit patients with intracerebral hemorrhage (ICH) is crucial. This study aimed to develop a platelet-to-white blood cell ratio (PWR) incorporated nomogram for long-term survival prediction. Methods: A retrospective analysis was conducted on 1,728 ICH patients in the MIMIC-IV 2.2 database. The independent prognostic value of PWR for 1- year mortality was assessed. A nomogram was developed using LASSO and Cox regression to predict 1-year survival, incorporating PWR and other factors. The performance of the nomogram was evaluated through calibration curves, area under the curve, Delong test, net reclassification index, integrated discrimination improvement, and decision curve analysis. Results: The nomogram, which included age, weight, Glasgow Coma Scale (GCS) score, mechanical ventilation, glucose, red blood cell (RBC) count, blood urea nitrogen (BUN), and PWR, showed good predictive performance for 1-year survival. The C-index was 0.736 (95% CI = 0.716--0.756) for the training set and 0.766 (95% CI = 0.735--0.797) for the testing set. Higher age and ventilation increased mortality risk, while higher weight, GCS score, RBC count, and PWR decreased risk. The nomogram outperformed conventional scores. Conclusions: A nomogramincorporating PWR as a prognostic factor accurately predicts long-term survival in ICH patients. However, validation in large-scale multicenter studies and further exploration of biomarkers are needed. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is one of the most important comorbidities of diabetic patients, which places large physiological and economic burdens on patients. Safflower yellow, a natural pigment extracted from the petals of safflower, has been put into adjuvant therapy. Databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, MEDLINE and etc. will be searched for relevant articles. A meta-analysis was carried out to assess the efficacy and safety of safflower yellow adjuvant to conventional treatment regimen using mean differences (MD) and rate ratios (RR). A cost-effectiveness analysis was also conducted based on the result of meta-analysis. Finally, 28 articles involving 2251 patients were included in meta-analysis. The results showed that compared with conventional treatment, the fasting blood-glucose (FBG) [MD = 0.40], urinary albumin ejection rate (UAER) within 24 h [MD = 48.16], serum creatinine (Scr) [MD = 9.63], blood urea nitrogen (BUN) [MD = 1.73] were significantly lower and the clinical efficacy [RR = 1.28] was more remarkable in safflower yellow adjuvant to conventional treatment group. Our analysis suggested that safflower yellow adjuvant to conventional treatment regimen not only had better clinical efficacy but more cost-effective than conventional treatment regimen. [ABSTRACT FROM AUTHOR]

Objectives: Aimed to assess the treatment outcome of post-streptococcal acute glomerulonephritis and its associated factor among children of less than 15 years at a referral hospital in Amhara Northeast Ethiopia, 2022. Results: In this study, 322 Post- post-streptococcal acute glomerulonephritis children with a response rate of 97% were included. Of these, 33.54% of them had a poor treatment outcome. Age less than or equal to 5 years (AOR = 3.2, 95% CI (1.5–7.3), Creatinine level > 1.3 mg/dl (AOR = 5.5,95% CI (2.5–11.7), blood urea nitrogen leve ≥ 119 mg/dl (AOR = 4.9,95% CI (1.1–19) and length of stay > 10 days(AOR = 2.6,95% CI (1.18–5.9) were statistically significant with poor outcome of children with post-streptococcal acute glomerulonephritis and management during admission to reduce poor treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic importance of sex in lupus nephritis (LN). Methods: A retrospective cohort of 1048 biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018, was analyzed. Demographics, clinical characteristics, laboratory findings, and renal pathology were assessed. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Sex-associated risks were evaluated using Cox regression models. Results: Among the1048 patients, 178 (17%) were male and 870 (83%) were female. Male patients exhibited more aggressive features: higher blood pressure, earlier disease onset, and elevated levels of serum creatinine (Scr), uric acid, blood urea nitrogen. Intriguingly, male patients also displayed more severe histopathological alterations, such as more total crescents, cellular crescents formations, higher level of glomerular leukocyte infiltration and Activity Index (AI), even when overall renal pathology was comparable between sexes. During a median follow-up of 112 months, mortality was registered in 141 patients (15.3%). Mortality rates were conspicuously higher in males (24.2% males vs. 13.4% females, p = 0.0029). Secondary outcomes did not show significant sex differences. Cox regression analysis highlighted male, age of renal biopsy, eGFR, and Chronicity Index (CI) as independent risk factors for survival in LN patients. Notably, infections emerged as the leading cause of mortality among LN patients, with a significant higher rate in male patients. Conclusion: In our cohort with LN, there was a higher rate of all-cause mortality and proportion of infection-related death in male. Recognizing and further exploring these sex disparities is crucial for optimized LN patients care. [ABSTRACT FROM AUTHOR]

Simplified rapid hydration has been proven to be non-inferior to standard hydration in preventing contrast-associated acute kidney injury among chronic kidney disease patients undergoing coronary angiography. The current investigation aimed to further confirm the feasibility and safety of the newly proposed hydration method-simplified rapid hydration (SH) in each risk stratification by Mehran risk score (MRS). Eligible patients (n = 954) randomized to the SH group and standard hydration group were allocated into 2 groups based on MRS: low to moderate-risk and high to very high-risk groups. Primary endpoints were the incidence of contrast-associated acute kidney injury (CA-AKI) and acute heart failure (AHF) (SH vs standard hydration). Secondary endpoints included serum creatinine (Scr), blood urea nitrogen (BUN), cystatin-C (Cys-C), and C-reactive protein (CRP) at 24 h, 48 h, and 72 h after PCI procedure, and the incidence of major adverse cardiac events (MACE). MRS was associated with a higher incidence of CA-AKI (OR = 1.101, 95%CI 1.049–1.156, P < 0.001). In the low to moderate-risk and high to very-high-risk groups, the incidence of CA-AKI in the SH and standard hydration group was 3.3% versus 4.9% (P = 0.5342), 10% versus 12% (P = 0.6392), respectively. Meanwhile, there might be subtle differences in renal function indexes and inflammatory indicators between SH and the control group at different time points. The preventive effect of SH in CA-AKI was similar to standard hydration regardless of MRS-guided risk stratification. [ABSTRACT FROM AUTHOR]

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Backgrounds: Crush syndrome (CS) is the leading cause of death after earthquakes, second only to direct trauma. Acute kidney injury (AKI) is the most severe complication of CS. Research based on the CS-AKI mouse model and kidney function assessment by glomerular filtration rate (GFR) helps to elucidate the pathogenesis of CS-AKI, which contributes to effective treatment measures. Methods: Mice were modeled by the multi-channel small animal crushing platform. We set up different CS-AKI modeling parameters by applying different crushing weights (0.5 kg, 1.0 kg, 1.5 kg), crushing durations (6 h, 12 h, 16 h), and decompression durations (6 h, 12 h, 24 h). The GFR, serum creatinine (SCr), blood urea nitrogen (BUN), kidney tissue Kim-1 mRNA and Ngal mRNA expression levels, and HE staining were examined to evaluate the results of different protocols. Results: The results showed that with the crushing weight increased, the kidney function assessment’s gold standard GFR significantly decreased, and the levels of SCr and BUN increased. Meanwhile, the longer crushing durations found a higher extension of inflammatory cell infiltration in the kidney. The degree of kidney injury continued to worsen with the duration of decompression, indicating severe damage after reperfusion, which was associated with tubular injury and a sustained elevation of the inflammatory state. Conclusion: We successfully constructed CS-AKI mouse models with different severities under the above parameters. Applying 1.5 kg for 16 h and then decompressing for 24 h induced severe AKI. These findings provide clues for further exploration of the mechanism and treatment of traumatic AKI. [ABSTRACT FROM AUTHOR]

Background: Existing studies investigating the impact of serum calcium (Ca), phosphate (P), 25 hydroxyvitamin D (25[OH]D), and parathyroid hormone (PTH) levels on kidney function have produced inconsistent results. Further research is needed to establish the direct causal relationship between these factors and kidney function. Methods: The study used genome-wide association study datasets for exposure and outcome, mainly derived from the UK Biobank and CKDGen Consortium, with sample sizes ranging from 3,310 to 480,699 individuals of European ancestry. Heritability and genetic correlations among these phenotypes were assessed using linkage disequilibrium score regression (LDSC) and phenotypes with a heritability z-score <4 were excluded from further analyses. Pleiotropic analyses were performed to identify potential horizontal pleiotropic variants at gene and LD-independent locus levels. Mendelian randomization (MR) analysis, using instrumental variables (IVs) based on two distinct selection criteria, was conducted to investigate the potential causal relationships between serum Ca, P, 25(OH)D, PTH, and kidney function. Results: PTH was excluded from further analysis due to a heritability z-score < 4. Genetic correlations were observed between serum Ca and urine albumin-tocreatinine ratio (UACR) (rg = 0.202, P-value = 5.0E-04), between serum 25(OH)D and estimated glomerular filtration rate using serum creatinine (eGFRcrea) (rg = -0.094; P-value = 1.4E-05), and between serum25(OH)D and blood urea nitrogen (BUN) (rg = 0.127; P-value = 1.7E-06). In univariableMR analysis using IVs based on two different selection criteria, it consistently demonstrated that genetically predicted serum Ca consistently showed an increase in UACR (beta 0.11, P-value 2.0E-03; beta 0.13, P-value 2.0E-04). Similarly, serum P was associated with a decrease in eGFRcrea (beta -0.01, P-value 2.0E-04; beta -0.005, P-value 2.0E -03) and an increase in BUN (beta 0.02, P-value 3.0E-03; beta 0.02, P-value 7.5E -07). The influence of serum P on kidney function was further supported in multivariable MR analysis. However, genetically predicted 25(OH)D did not have a significant impact on kidney function. Conclusions: Elevated serum Ca or P levels could both impair kidney function, whereas 25(OH)D has no impact on renal function. [ABSTRACT FROM AUTHOR]

AbstractCurrently, 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]

Summary Although chronic kidney disease (CKD) is associated with obesity, few studies have used visceral adipose tissue (VAT) as an indicator to investigate its causal effect on CKD. Therefore, Mendelian randomization (MR) was employed to study the causal effects of VAT on CKD and its potential mediation by hypertension. Genome‐wide association study (GWAS) statistics on VAT exposure were obtained from the UK Biobank, while GWAS datasets of CKD outcomes were obtained from CKDGen and FinnGen (validation study). Furthermore, VAT was considered the exposure, with the estimated glomerular filtration rate based on creatinine (eGFR (crea)), estimated glomerular filtration rate based on cystatin C (eGFR(cys)), and blood urea nitrogen (BUN) employed to assess the causal effect of VAT on kidney test indicators. Lastly, a two‐step MR method was used to study the mediating role of hypertension in the pathogenesis of VAT among patients with CKD. VAT exhibited a positive causal association with CKD, irrespective of whether the GWAS datasets from CKDGen (odds ratio [OR] = 1.18, 95% CI: 1.08 to 1.29, P = 1.433140e−04) or FinnGen (1.47, 1.30 to 1.67, p = 2.500000e−09). VAT was not causally associated with eGFR (crea) (1.00, 0.99 to 1.00, p = 0.53), was negatively associated with eGFR (cys) (0.95, 0.93 to 0.97, P = 5.070000e−10), and was positively associated with BUN (1.02,1.01 to 1.02, P = 7.824860e−04). The mediating effect of VAT on CKD via hypertension was 45.8% (95% CI: 26.4 65.1). VAT has a positive causal effect on CKD, with hypertension playing a significant role. However, the effects of VAT on renal function indicators require further investigation. [ABSTRACT FROM AUTHOR]

Background: Major surgeries are being carried for certain ailments. Surgeries can be major or minor depending on the extent of intervention. Major surgeries are prone to cause lots of complications such as shock, haemorrhage, wound infection, deep vein thrombosis, pulmonary complications, organ rejection, reactions to anaesthetics etc. Early identification of complications could reduce morbidity and mortality. Laboratory variables used in the assessment of hypovolemia include blood urea nitrogen, sodium, osmolality, hematocrit, and arterial blood gas. This study was undertaken to assess the utility of blood urea nitrogen: creatinine ratio (BCR) in the utility of assessment of hypovolemia in the first post-operative day in individuals who had major surgeries. Methods and materials: The retrospective cross-sectional study included participants from the Departments of Orthopedic Surgery, Obstetrics and Gynecology, General Surgery and Cardiothoracic Surgery. Patients who underwent major surgeries between January 2019 and January 2020 were included. Study participants of 30 to 60 years of both genders were recruited into the study. Data were collected from the Medical Records of a tertiary care hospital in Chennai, India. Ethics approval was obtained, the institutional ethics committee (Ref: CSP/21/SEP/99/479 dated 30–12-2021). Waiver of consent was obtained since the patients were treated and discharged from the hospital. The data were analyzed by SPSS version 16. P value ≤ 0.05 was taken to be significant. Results: BCR showed statistically significant difference across the groups with P = 0.02. BCR showed statistically significant difference between cardiac patients with total knee replacement and total abdominal hysterectomy surgeries. BCR showed positive correlation with age, fluids intake and negative correlation with pulse rate and respiratory rate. Conclusion: BCR is a simple diagnostic tool for identifying hypovolemia in individuals who undergo major surgeries especially in the first postoperative day. It is significantly altered across the groups with highest value in individuals who have undergone knee replacement surgeries. BCR has high specificity and positive predictive value. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) is one of the complications of diabetes. This study was conducted to investigate the effect of curcumin-piperine on laboratory factors and macular vascular in DR. Materials and Methods: The present study was a randomized, placebo-controlled, double-blind, parallel-arm clinical trial that was conducted on 60 patients with DR aged 30-65 years. Patients were randomized into two groups to receive (i) 1010 mg/day of curcumin-piperine (two tablets per day, each tablet containing 500 mg curcuminoids and 5 mg piperine) (n = 30) or (ii) the matched placebo (n = 30) for 12 weeks. The investigated factors included optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), oxidative stress factors, C-reactive protein (CRP), fasting blood glucose (FBG), triglycerides (TGs), blood urea nitrogen (BUN), and creatinine. Results: The trial was completed by 27 patients in the intervention group and 29 patients in the placebo group. Curcumin-piperine significantly increased total antioxidant capacity (0.86 ± 0.66 vs. 0.45 ± 0.89; P = 0.022) and superoxide dismutases (0.77 ± 2.11 vs. -0.45 ± 3.08; P = 0.031), while it decreased and malondialdehyde (MDA) (-1.06 ± 5.80 vs. 1.89 ± 6.12; P = 0.043) and creatinine (-0.04 ± 0.16 vs. 0.03 ± 0.05; P = 0.042) compared with placebo. However, this supplement had no significant effect on CRP, FBG, TG, BUN, OCT, and OCTA. There were no adverse reactions. Conclusion: Curcumin-piperine is effective in improving oxidative stress and reducing creatinine in DR. Further trials are necessary to confirm these promising findings. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus affects the whole vascular system, leading to both microvascular and macrovascular complications [1]. Diabetic nephropathy is the dreadful microvascular complication of diabetes mellitus, which lead to end stage kidney disease (ESKD), which increase the risk of cardiovascular mortality [2]. Duplex sonography of the renal artery provides an easily applicable, non-invasive, and well-established way to assess changes in renal vasculature caused by diabetes [5]. In this study, detecting subtle changes in renal vasculature with renal artery Doppler, particularly RI (RESISITIVE INDEX) values, and correlating with biochemical parameters such as creatinine, and urine albumin, helps the physician for accurate management of diabetes patients preventing complications. Objective: Evaluation of renal sono-morphological characteristics using gray scale ultrasound and renal vascular resistance by doppler in patients with diabetic renal disease. Correlation among renal ultrasound, colour doppler, and biochemical parameters in diabetic renal disease. Methods: A time-bound, cross-sectional study, was conducted in the Department of Radio-diagnosis, M.G.M. Medical College and M.Y. Associate Hospital, Indore, Madhya Pradesh, India after receiving approval from Institutional Scientific and Ethical Committee. The duration of the study was from September 2022 to September 2023. A total of 108 patients of type II diabetes mellitus were included in the study. Results: out of total 108 of patients who were diagnosed with type II diabetes mellitus, maximum no of patients (28.7%) in age group of 50-60 years. In our study, male preponderance was observed in our study with 65.74% patients being male. On basis of biochemical parameters divided in 4 subgroups majority of patients 38% were fall under subgroup IV (renal failure) followed by subgroup I(preclinical) 27.8 %, subgroup II (incipient nephropathy) 18.5% and subgroup III (overt nephropathy) 18.5%. Majority of patients in subgroup IV (renal failure) 76.2 to 81.5% revealed gradeII/III renal parenchymal echogenicity changes. In our study most of the patients belonging to subgroup I (80%) had normal RI value while most of the patients belonging to subgroup II (70%), subgroup III (80%) and subgroups IV (94.74%) had increased RI values indicating raised renal vascular resistance as the disease progresses. R.I shows strong positive correlations with Blood Urea Nitrogen (BUN), Urine protein (Alb) and Creatinine levels higher R.I may coincide with elevated levels of these renal function markers. Conclusion: our study demonstrates Renal Doppler is a non-invasive modality that can be used in association with biochemical parameters of patients with diabetic nephropathy. An increasing intra-renal resistive index value could prompt the physician to a more rigid control of blood sugars and hypertension in this subgroup of diabetic patients delaying the progression to end-stage renal failure. [ABSTRACT FROM AUTHOR]

Nephrotoxicity occurs when the body is exposed to certain drugs or toxins. When kidney damage occurs, the kidney fails to eliminate excess urine and waste. Solanesol (C45H74O) is a tri‐sesquiterpenoid alcohol first isolated from tobacco, and it is widely distributed in plants of the Solanaceae family. Solanesol (SNL) is an intermediate in the synthesis of coenzyme Q10 (CoQ10), an antioxidant which protects nerve cells. This study investigated the protective effect of SNL at doses of 30 and 60 mg/kg in gentamicin‐induced nephrotoxicity in Wistar albino rats. Animals were distributed into six groups and administered 100 mg/kg gentamicin‐intraperitoneal injection for 14 days. Biochemical assessments were performed on kidney homogenate, blood, and serum. Treatment with SNL was shown as lower serum levels of creatinine, blood urea nitrogen (BUN), thiobarbituric acid reactive substances (TBARS), and Tumor necrosis factor alpha)TNF‐α ((p <.001). It also restored reduced glutathione (GSH) and mitochondrial complex enzymatic activity as protective measures against gentamicin‐induced nephrotoxicity. SNL were shown to reduce inflammation and oxidative stress markers (p <.001). Histological findings furtherly augmented the protective effects of SNL. Long‐term SNL therapy also restored mitochondrial electron transport chain complex enzymes, such as complex‐I (p <.001). In conclusion, these findings suggest that SNL can represent a protective therapeutic option for drug‐induced nephrotoxicity, a long‐term adverse effect of aminoglycoside antibiotics such as gentamicin. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has affected the global health system and economies largely. Therefore, knowledge about the clinical and laboratory profiles of patients with COVID-19 would help in the management and prognosis of the disease. The immunological and hematological indices have emerged as critical determinants for the severity of the disease and the prognosis; however, association with COVID-19 is clouded. The present study is aimed to characterize the immunological and hematological profiles of patients with COVID-19 in correlation with the disease severity. The study included 1,019 polymerase chain reaction (PCR)–confirmed patients with COVID-19 who were classified into serious and nonserious groups, considering severity criteria. Clinical laboratory investigations included hematological, biochemical, and immunological parameters regarding leukocyte counts, hemoglobin levels, and inflammatory markers. Our analysis of immunological and hematological differences between serious and nonserious patients with COVID-19 indicates that serious cases reflected elevated levels of pro-inflammatory markers such as lactate dehydrogenase, C-reactive protein (CRP), D-dimer, and ferritin, representing immune system dysregulation and systemic inflammation. Furthermore, in serious cases, discrepancies had also been noticed for many hematological parameters than nonserious ones, which also contained leukocyte count and hemoglobin level. Additionally, the CRP, D-dimer, blood urea nitrogen, alanine transaminase, and albumin levels could be independent predictors of COVID-19 severity by multivariate logistic regression analysis. Cutoff values for these biomarkers were defined by receiver operating characteristic curve analysis defining optimal parameters for the risk stratification and prognostication. The current investigation provides a comprehensive understanding of immunological and hematological correlation with COVID-19 severity, refining clinical decision-making and therapeutic interventions to improve patient outcomes. [ABSTRACT FROM AUTHOR]

To explore mortality risk factors and to construct an online nomogram for predicting in-hospital mortality in traumatic brain injury (TBI) patients receiving invasive mechanical ventilation (IMV) in intensive care unit (ICU). We retrospectively analyzed TBI patients on IMV in ICU from Medical Information Mart for Intensive Care IV database and 2 hospitals. Least absolute shrinkage and selection operation regression and multiple logistic regression were used to detect predictors of in-hospital mortality and to construct an online nomogram. The predictive performance of nomogram was evaluated using area under the receiver operating characteristic curves (AUC), calibration curves, decision curve analysis, and clinical impact curves. Five hundred ten from Medical Information Mart for Intensive Care IV database were enrolled for nomogram construction (80%, n = 408) and internal validation (20%, n = 102). One hundred eighty-five from 2 hospitals were enrolled for external validation. Least absolute shrinkage and selection operation-logistic regression revealed predictors of in-hospital mortality among TBI patients on IMV in ICU included Glasgow Coma Scale (GCS) after ICU admission, Acute Physiology Score III (APS III) after ICU admission, neutrophil and lymphocyte ratio after IMV, blood urea nitrogen after IMV, arterial serum lactate after IMV, and in-hospital tracheotomy. The AUC, calibration curves, decision curve analysis, and clinical impact curves indicated the nomogram had good discrimination, calibration, clinical benefit, and applicability. The multimodel comparisons revealed the nomogram had higher AUC than GCS, APS III, and Simplified Acute Physiology Score II. We constructed and validated an online nomogram based on routinely recorded factors at admission to ICU and at the beginning of IMV to target prediction of in-hospital mortality among TBI patients on IMV in ICU. [ABSTRACT FROM AUTHOR]

Background • Septic shock poses a significant threat to life safety, with continuous blood purification as a primary treatment modality. Enhancing the therapeutic efficacy of continuous blood purification holds crucial implications for septic shock management. Objective • This study aims to observe the therapeutic efficacy of glucocorticoid-assisted continuous blood purification (CBP) in septic shock patients, providing valuable insights for future clinical treatments. Methods • A total of 200 septic shock patients admitted between October 2020 and January 2023 were selected and categorized into an observation group and a control group. The observation group (n=118) received glucocorticoid- assisted CBP, while the control group (n=82) received standard CBP. Changes in various parameters, including pH, blood urea nitrogen, serum creatinine, bicarbonate, inflammatory cytokines, T lymphocyte subsets, mean arterial pressure, pulmonary vascular permeability index, intrathoracic blood volume index, and cardiac index, were recorded before and after treatment. Complications during treatment were also documented. Results • Post-treatment bicarbonate and cardiac index showed no significant difference between the two groups (P > .05). However, the observation group exhibited higher pH, mean arterial pressure, CD3+, CD4+, and CD8+ levels than the control group, as well as lower blood urea nitrogen, serum creatinine, inflammatory cytokines, and CD4+/CD8+ ratio (P < .05). Moreover, no notable difference in complication rates was identified between the groups (P > .05). Conclusions • Glucocorticoids-assisted continuous blood purification therapy effectively improves vital signs and immune function in septic shock patients, offering a more reliable guarantee for patient life safety. [ABSTRACT FROM AUTHOR]

Several studies with kaempferol (KP) and linearolactone (LL) have demonstrated their antiparasitic activity. However, the toxicity of these treatments is unknown. Therefore, this study aimed to evaluate the possible toxicological effects of intraperitoneal (i.p.) administration of KP or LL on the amoebic liver abscess model (ALA) in Mesocricetus auratus. An ALA was induced in male hamsters with 1.5 × 105Entamoeba histolytica (E. histolytica) trophozoites inoculated in the left hepatic lobe. The lesion evolved for 4 days, and then KP (5 mg/kg body weight/day) or LL (10 mg/kg body weight/day) was administered for 4 consecutive days. Then, magnetic resonance imaging (MRI), paraclinical analyses, and necropsy for histopathological evaluation were performed. There was similar ALA inhibition by KP (19.42%), LL (28.16%), and metronidazole, the antiamoebic control (20.87%) (p ≤ 0.05, analysis of variance [ANOVA]). There were hepatic and renal biochemical alterations in all treatment groups, mainly for KP (aspartate aminotransferase: 347.5 ± 37.5 U/L; blood urea nitrogen: 19.4 ± 1.9 g/dL; p ≤ 0.05, ANOVA). Lesions found in the organs were directly linked to the pathology. In conclusion, KP and LL decreased ALA development and exerted fewer toxicological effects compared with metronidazole. Therefore, both compounds exhibit therapeutic potential as an alternative treatment of amoebiasis caused by E. histolytica. However, additional clinical studies in different contexts are required to reaffirm this assertion. [ABSTRACT FROM AUTHOR]

Purpose: Some studies showed the possible role of copper intake on bone mineral density (BMD) in adults or the elderly, but the association remained uncertain in children and adolescents. Our research explored the association between copper intake and BMD in individuals aged 8–19 years from the National Health and Nutrition Examination Survey (NHANES) 2011–2016. Methods: In the present study, 6,965 individuals aged 8–19 (mean age 13.18 ± 3.38 years) were enrolled from the NHANES 2011–2016. Copper intake was evaluated by averaging two 24-hour copper dietary intake recalls. Multivariate linear regression analyses were used to explore the association between copper intake and total BMD, subtotal BMD, and total spine BMD in children and adolescents. Stratified analyses and interaction tests were performed by age, gender, and race. Results: Participants of the higher quartile of copper intake were more likely to be older, men, Non-Hispanic White, and Other Hispanic. They have higher values of poverty income ratio (PIR), serum phosphorus, blood urea nitrogen, serum vitamin D, and BMD and lower values of body mass index (BMI), cholesterol, total protein, and serum cotinine. In the fully adjusted model, we found positive associations between copper intake and total BMD (β = 0.013, 95CI: 0.006, 0.019)), subtotal BMD (β = 0.020, 95CI: 0.015, 0.024), and total spine BMD (β = 0.014, 95CI: 0.009, 0.019). Stratified analyses showed that the association was stronger in men, individuals aged 14–19, Non-Hispanic White, and Other Hispanic. Conclusions: Our study suggests that copper intake is positively associated with BMD in U.S. children and adolescents. The study emphasizes the role of copper intake on bone health in the early stages of life. However, more investigations are needed to verify our findings and their underlying mechanisms. [ABSTRACT FROM AUTHOR]

Hypoactive delirium, characterized by decreased movement and arousal, is a common subtype of delirium in the intensive care unit (ICU) that is difficult to recognize. It is associated with higher mortality, longer hospital stays, and long-term brain injury. Hypoactive delirium is more common in the elderly, patients with previous cognitive impairment, and at end-of-life. Diagnosis of hypoactive delirium can be challenging as symptoms overlap with dementia and depression. The primary approach to managing hypoactive delirium focuses on prevention and the use of the ABCDEF bundle, which promotes early mobility and reduced sedation. There is currently no evidence-based pharmacological treatment for delirium, but reducing exposure to sedative drugs is recommended. [Extracted from the article]

Introduction: The fasting blood glucose test is widely used for diabetes screening. However, it may fail to detect early‐stage diabetes characterized by elevated postprandial glucose levels. Hence, we developed and internally validated a nomogram to predict the diabetes risk in older adults with normal fasting glucose levels. Materials and Methods: This study enrolled 2,235 older adults, dividing them into a Training Set (n = 1,564) and a Validation Set (n = 671) based on a 7:3 ratio. We employed the least absolute shrinkage and selection operator regression to identify predictors for constructing the nomogram. Calibration and discrimination were employed to assess the nomogram's performance, while its clinical utility was evaluated through decision curve analysis. Results: Nine key variables were identified as significant factors: age, gender, body mass index, fasting blood glucose, triglycerides, alanine aminotransferase, the ratio of alanine aminotransferase to aspartate aminotransferase, blood urea nitrogen, and hemoglobin. The nomogram demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.824 in the Training Set and 0.809 in the Validation Set. Calibration curves for both sets confirmed the model's accuracy in estimating the actual diabetes risk. Decision curve analysis highlighted the model's clinical utility. Conclusions: We provided a dynamic nomogram for identifying older adults at risk of diabetes, potentially enhancing the efficiency of diabetes screening in primary healthcare units. [ABSTRACT FROM AUTHOR]

We aimed to investigate clinical and laboratory characteristics of acute alcohol intoxication (AAI) in adolescents who presented to the pediatric emergency department (ED) at a tertiary referral center from 2006 to 2019. All consecutive adolescents with AAI (n = 335) and their sex- and age-matched control subjects (n = 335) with undetectable ethanol levels were included in this case-matched study. Mean serum ethanol level was 156.4 ± 58.4 (range: 50.8-341.2) mg/dL in the acute alcohol intoxication (AAI) group. Glasgow coma scores were lower in AAI group (14 [14-15] vs 15 [15-15], P <.001). Acidosis (16.3%), hyperlactatemia (60.9%), hypoglycemia (1.7%), hypernatremia (2.2%), hypokalemia (12.3%), hyperchloremia (20.4%), hypocalcemia (13.9%), hypermagnesemia (9.7%), and hyperalbuminemia (10.4%) were significantly more common in the AAI group than the control group. Blood pH, lactate, Na+, K+, Ca++, Mg++, albumin, blood urea nitrogen (BUN), and uric acid levels were correlated with serum ethanol levels. This study shows that AAI frequently leads to mild to moderate metabolic/biochemical derangements in adolescents. [ABSTRACT FROM AUTHOR]

The article focuses on a 3-year-old boy with autism and speech delay who presented with general malaise and refusal to eat, leading to dehydration concerns. Topics include his clinical presentation with constipation and poor intake, his initial emergency room evaluation for dehydration, and his physical examination findings, which showed mild signs of dehydration but no other acute symptoms.s.

Aim: Renal ischemia‐reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulphide (H2S) exerts a protective effect in renal IRI. The present study was carried out to investigate the effects of exogenous H2S on renal IRI by regulating autophagy in mice. Methods: Mice were randomly assigned to control, IRI and NaHS (an H2S donor, 28, 56 and 100 μmol/kg) groups. Renal IRI was induced by clamping the bilateral renal pedicles with non‐traumatic arterial clamp for 45 min and then reperfused for 24 h. Mice were administered intraperitoneally with NaHS 20 min prior to renal ischemia. Sham group mice underwent the same procedures without clamping. Serum and kidney tissues were harvested 24 h after reperfusion for functional, histological, oxidative stress, and autophagic determination. Results: Compared with the control group, the concentrations of serum creatinine (Scr), blood urea nitrogen (BUN), and malondialdehyde (MDA), the protein levels of LC3II/I, Beclin‐1 and P62, as well as the number of autophagosomes were significantly increased, but the activity of superoxide dismutase (SOD) was decreased after renal IRI. NaHS pre‐treatment dramatically attenuated renal IRI‐induced renal dysfunction, histological changes, MDA concentration and p62 expression in a dose‐dependent manner. However, NaHS increased the SOD activity and the protein levels of LC3II/I and Beclin‐1. Conclusion: These results indicate that exogenous H2S protects the kidney from IRI through enhancement of autophagy and reduction of oxidative stress. Novel H2S donors could be developed in the treatment of renal IRI. [ABSTRACT FROM AUTHOR]

Aims: As one of the most serious complications of sepsis, acute kidney injury (AKI) is pathologically associated with excessive inflammation. 2,5‐Dihydroxyacetophenone (DHAP) is isolated from Radix rehmanniae praeparata and exhibit potent anti‐inflammatory property. This research aimed at determining the role of DHAP in sepsis‐associated AKI (SA‐AKI) and the underlying mechanism. Methods: Plasma creatinine (Cre), blood urea nitrogen (BUN), tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) levels of SA‐AKI patients were detected to evaluate their clinical characteristics. SA‐AKI rat models were established by using caecum ligation puncture (CLP) surgery. CLP‐induced rats were administered via oral gavage with 20 or 40 mg DHAP after 2 h of CLP surgery. Subsequently, survival rates, serum indexes, histopathological changes, inflammatory factors, renal function indexes and extracellular regulated protein kinases (ERK) and nuclear factor‐κB (NF‐κB) signalling pathways were detected. Results: SA‐AKI patients exhibited markedly higher levels of plasma Cre, BUN, TNF‐α and IL‐1β than healthy people. Compared with sham rats, CLP‐induced septic rats showed significantly decreased survival rate, increased serum lactate dehydrogenase activity and serum lactate level, obvious renal histopathological injury, upregulated TNF‐α, IL‐1β and TGF‐β1 levels, elevated serum creatinine, BUN and serum cystatin C concentrations, serum neutrophil gelatinase‐associated lipocalin and kidney injury molecule‐1 levels and reduced renal artery blood flow. All the above CLP‐induced changes in septic rats were mitigated after DHAP administration. Additionally, CLP‐induced elevation in phosphorylated‐ERK1/2 and nuclear NF‐κB p65 protein levels was inhibited by DHAP treatment. Conclusion: DHAP hinders SA‐AKI progression in rat models by inhibiting ERK and NF‐κB signalling pathways. [ABSTRACT FROM AUTHOR]

Aristolochic acid nephropathy (AAN) is a rapidly progressive kidney disease caused by medical or environmental exposure to aristolochic acids (AAs). This study aimed to identify serum metabolites associated with the severity of acute AAN and investigate the underlying mechanisms. Male C57BL/6 mice were treated with vehicle and 3 doses of aristolochic acid I (AAI) (1.25, 2.5, and 5 mg/kg/d) for 5 days by intraperitoneal injection. The results showed that AAI dose-dependently increased blood urea nitrogen (BUN) and serum creatinine (Scr) levels and renal pathological damage. Non-targeted metabolomics revealed that differences in serum metabolite profiles from controls increased with increasing AAI doses. Compared with the control group, 56 differentially expressed metabolites (DEMs) that could be affected by all 3 doses of AAI were obtained. We further identified 13 DEMs whose abundance significantly correlated with Scr and BUN levels and had good predictive values for diagnosing AAI exposure. Among the 13 DEMs, lipids and lipid-like molecules constituted the majority. Western blotting found that AAI suppressed renal fatty acid oxidation (FAO)-related enzymes expression. In conclusion, these findings provided evidence for developing biomarkers for monitoring AAs exposure and AAN diagnosis and indicated activation of FAO as a potential direction for the treatment of AAN. [Display omitted] • AAI induced nephrotoxicity in a dose-dependent manner. • AAI exposure exacerbated serum metabolic profile disturbances in a dose-dependent manner. • 13 DEMs were identified to be correlated with Scr and BUN levels and had good predictive values for diagnosing AAI exposure. • AAI suppressed renal fatty acid oxidation. [ABSTRACT FROM AUTHOR]

Objective: This experiment aimed to evaluate the effects of replacing concentrates with cassava root-top silage (CARTOS) on feed intake, digestibility, rumen fermentation, blood parameters, and growth performance of beef cattle. Methods: Twenty crossbred bulls with a body weight (BW) of 226±56 kg were randomly assigned to one of five treatments for 90 d in a randomized complete block design having four blocks based on BW. The concentrates were replaced by CARTOS at levels of 0%, 25%, 50%, 75%, and 100% dry matter (DM). Animals were fed dietary treatments at 1.8% BW, with rice straw offered ad libitum. Results: The DM and crude protein (CP) intake were decreased (p<0.01, p = 0.04) when the diet’s CARTOS level was increased. The digestibility of DM, OM, and CP were not different among treatments, while fiber digestibility was increased with the inclusion of CARTOS (p = 0.03). The addition of CARTOS to replace concentrates did not change ruminal pH or volatile fatty acid proportions except for acetic acid, which increased with the addition of CARTOS (p = 0.03). The ruminal ammonia-nitrogen (NH3-N) was decreased (p<0.01) with increasing levels of CARTOS. The blood glucose and blood urea nitrogen decreased (p = 0.01) with the addition of CARTOS at 100%, whereas total protein and hematological parameters did not change with increasing levels of CARTOS. The use of CARTOS to substitute concentrates at 75% and 100% decreased average daily gain (ADG) and gain to feed ratio (G:F) (p<0.01); therefore, the addition of CARTOS up to 50% maintained ADG and G:F in beef cattle. Conclusion: CARTOS can replace concentrates up to 50% in beef cattle diets without adversely affecting feed intake, nutrient digestibility, rumen fermentation characteristics, blood parameters, or growth performance of beef cattle. [ABSTRACT FROM AUTHOR]

Objective(s): Prior research has indicated that hydroxycitric acid (HCA) can impede the formation of calcium oxalate (CaOx) crystals, yet the specific mechanisms underlying its therapeutic effects remain unclear. In this study, we delved into the protective effects of HCA against glyoxylate-induced renal stones in rats and sought to elucidate the underlying metabolic pathways. Materials and Methods: Forty rats were randomly assigned to five groups: control group, model group, L-HCA-treated group, M-HCA-treated group, and H-HCA-treated group. Von Kossa staining was conducted on renal sections, and blood urea nitrogen and serum creatinine were determined by biochemical analysis. Meanwhile, body weight and urine volume were also measured. We subjected urine samples from the rats to analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Next, we employed a metabolomic approach to scrutinize the metabolic profiles of each group. Results: HCA significantly reduced blood urea nitrogen and serum creatinine, and increased body weight and urine volume. It also reduced CaOx crystal deposition. A total of 24 metabolites, exhibiting a significant reversal pattern following HCA administration, were identified as urine biomarkers indicative of HCA’s preventive effects against CaOx crystal-induced renal injury. These metabolites are primarily associated with glycine, serine, and threonine metabolism; phenylalanine metabolism; tricarboxylic acid cycle; taurine and hypotaurine metabolism; and tryptophan metabolism. Conclusion: It was demonstrated that HCA has a protective effect against CaOx crystal-induced kidney injury in rats by modulating various metabolic pathways. Additionally, results suggest that HCA holds promise as a potential clinical therapeutic drug for both the prevention and treatment of renal stones. [ABSTRACT FROM AUTHOR]

Rhabdomyolysis is a pathological condition caused by muscle tissue degradation. In this condition, intracellular contents enter the bloodstream, and acute kidney injury (AKI) develops. Verbascoside (VB) is one of the most common phenylethanoid glycosides and has antioxidant and anti-inflammatory effects. This study investigated the effects of VB on AKI induced by rhabdomyolysis in rats. Male Wistar rats were divided into six groups (n = 6): (1) control group (normal saline), (2) 50% glycerol (10 ml/kg, IM, single injection, only on the first day), (3)–(5) 50% glycerol (same as group 2) + VB (30, 60, and 100 mg/kg, IP, 4 days), and (6) VB (100 mg/kg). Serum and kidney tissue samples were collected on day 5. Subsequently, serum creatinine (Cr), blood urea nitrogen (BUN), renal glutathione (GSH), malondialdehyde (MDA), lipocalin associated with neutrophil gelatinase (NGAL), tumor necrosis factor-alpha (TNF-α), and pathological changes were investigated. The injection of glycerol elevated levels of kidney damage markers, including Cr and BUN in serum, MDA, TNF-α, and NGAL, along with a reduction in GSH levels in the kidney tissue. The administration of VB (100 mg/kg) significantly lowered the levels of these markers, indicating the therapeutic effect of VB against AKI caused by rhabdomyolysis. Histopathological examinations revealed enhanced myoglobin cast formation and tubular necrosis in the glycerol group, which was reduced in rats that received VB, although this reduction did not reach statistical significance. VB can reduce rhabdomyolysis-induced AKI through its anti-inflammatory and antioxidant effects and decrease kidney damage severity. [ABSTRACT FROM AUTHOR]

The disorder of the "gut-kidney axis" exacerbates renal function decline in chronic kidney disease (CKD), and current CKD therapy is insufficient to address this issue. Hirudin has a palliative effect on the decline of renal function. However, whether hirudin can delay CKD by regulating the "intestinal renal axis" disorder remains unclear. Unilateral ureteral ligation (UUO) induced CKD rat model, and the rats were treated with bifidobacterium and hirudin for 36 days. After 14 and 36 days of modeling, kidney and colon tissues were collected for pathology, western blot (WB) assay, and quantitative real-time PCR (qPCR) detection. Serum samples were collected for renal function testing. Fecal samples were used for 16S rRNA sequencing and research on fecal bacterial transplantation. Lipopolysaccharide combine with adenosine 5'-triphosphate (LPS + ATP)-induced intestinal epithelial cell injury was treated with a nod-like receptor pyrin domain-associated protein 3 (NLRP3) inhibitor and hirudin. Protein expression was detected using WB and qPCR. The kidneys and colons of the CKD rats exhibited varying degrees of lesions. Creatinine (CRE), blood urea nitrogen (BUN), N-acetyl-β-D-glucosidase (NAG) enzyme, and serum uremic toxins were elevated. The expression of claudin-1 and occludin was decreased, NLRP3 inflammatory-related proteins were increased, and the gut microbiota was disrupted. These pathological changes were more pronounced after 36 days of modeling. Meanwhile, high-dose hirudin treatment significantly improved these lesions and restored the intestinal flora to homeostasis in CKD rats. In vitro, hirudin demonstrated comparable effects to NLRP3 inhibitors by upregulating claudin-1 and occludin expression, and downregulating NLRP3 inflammatory-related proteins expression. The dysbiosis of the gut microbiota and impaired intestinal epithelial barrier function in CKD are associated with renal dysfunction in CKD. Hirudin delays the progression of CKD by regulating the disorder of the "gut-kidney axis" and inhibiting the activation of the NLRP3-ASC-caspase-1 pathway. [ABSTRACT FROM AUTHOR]

Background: The brain and kidneys share similar low-resistance microvascular structures, receiving blood at consistently high flow rates and thus, are vulnerable to blood pressure fluctuations. This study investigates the causative factors of cerebral microbleeds (CMBs), aiming to quantify the contribution of each risk factor by constructing a multivariate model via stepwise regression. Methods: A total of 164 hospitalized patients were enrolled from January 2022 to March 2023 in this study, employing magnetic susceptibility-weighted imaging (SWI) to assess the presence of CMBs. The presence of CMBs in patients was determined by SWI, and history, renal function related to CMBs were analyzed. Results: Out of 164 participants in the safety analysis, 36 (21.96%) exhibited CMBs and 128 (78.04%) did not exhibit CMBs, and the median age of the patients was 66 years (range: 49-86 years). Multivariate logistic regression identified hypertension (OR = 13.95%, 95% CI: 4.52, 50.07%), blood urea nitrogen (BUN) (OR = 1.57, 95% CI: 1.06-2.40), cystatin C (CyC) (OR = 4.90, 95% CI: 1.20-22.16), and urinary β-2 microglobulin, (OR = 2.11, 95% CI: 1.45-3.49) as significant risk factors for CMBs. The marginal R-square (RM²) was 0.25. Among all determinants, hypertension (47.81%) had the highest weight, followed by UN (11.42%). Quasicurves plotted using the bootstrap method (999 times) showed good agreement between the predictive model and actual observations. Conclusion: Hypertension, BUN, urinary β-2 microglobulin, CyC were risk factors for CMBs morbidity, and controlling the above indicators within a reasonable range will help to reduce the incidence of CMBs. [ABSTRACT FROM AUTHOR]

The occurrence of acute kidney injury (AKI) is elevated, one of the main causes is ischemia-reperfusion (I/R). However, no specific therapy is currently available to treat I/R-induced AKI (I/R-AKI). Treg cells have been demonstrated to perform an anti-inflammatory role in a range of autoimmune and inflammatory illnesses. However, there is limited available information about the possible functions of CD8 + CD103 + iTregs in I/R-AKI. We utilized renal tubular epithelial cells (RTECs) subjected to hypoxia-reoxygenation (H/R) and I/R-AKI mouse model to investigate whether CD8 + CD103 + iTregs could attenuate AKI and the underlying mechanism. In vitro, co-cultured with CD8 + CD103 + iTregs alleviated H/R-induced cell injury. After treatment of CD8 + CD103 + iTregs rather than control cells, a significant improvement of I/R-AKI was observed in vivo, including decreased serum creatinine (sCr) and blood urea nitrogen (BUN) levels, reduced renal pathological injury, lowered tubular apoptosis and inhibition of the transition from AKI to chronic kidney disease (CKD). Mechanically, CD8 + CD103 + iTregs alleviated H/R-induced cell injury and I/R-AKI partly by suppressing RTECs pyroptosis via inhibiting the NLRP3/Caspase-1 axis. Our study provides a novel perspective on the possibility of CD8 + CD103 + iTregs for the treatment of I/R-AKI. [ABSTRACT FROM AUTHOR]

Background: Vancomycin trough concentration is closely associated with clinical efficacy and toxicity. Predicting vancomycin trough concentrations in pediatric patients is challenging due to significant inter-individual variability and rapid physiological changes during maturation. Aim: This study aimed to develop a machine learning model to predict vancomycin trough concentrations and determine optimal dosing regimens for pediatric patients < 4 years of age using ML algorithms. Method: A single-center retrospective observational study was conducted from January 2017 to March 2020. Pediatric patients who received intravenous vancomycin and underwent therapeutic drug monitoring were enrolled. Seven ML models [linear regression, gradient boosted decision trees, support vector machine, decision tree, random forest, Bagging, and extreme gradient boosting (XGBoost)] were developed using 31 variables. Performance metrics including R-squared (R2), mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) were compared, and important features were ranked. Results: The study included 120 eligible trough concentration measurements from 112 patients. Of these, 84 measurements were used for training and 36 for testing. Among the seven algorithms tested, XGBoost showed the best performance, with a low prediction error and high goodness of fit (MAE = 2.55, RMSE = 4.13, MSE = 17.12, and R2 = 0.59). Blood urea nitrogen, serum creatinine, and creatinine clearance rate were identified as the most important predictors of vancomycin trough concentration. Conclusion: An XGBoost ML model was developed to predict vancomycin trough concentrations and aid in drug treatment predictions as a decision-support technology. [ABSTRACT FROM AUTHOR]

Aims: The COVID‐19 infection has been described as affecting myocardial injury. However, the relation between left ventricular global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS), disease severity and all‐cause mortality in COVID‐19 is unclear. Methods and Results: The study consisted of 220 patients with COVID‐19, including 127 (57.5%) with mild, 43 (19.5%) with moderate and 50 (22.7%) with severe/critical conditions. Myocardial dysfunction was analysed by GLS, GCS and GRS using two‐dimensional speckle‐tracking echocardiography. Hazard ratios and Kaplan–Meier curves were produced to assess the association between strains and cardiac biomarker indices with a composite outcome of all‐cause mortality. With an average follow‐up period of 11 days, 19 patients reached the endpoint (death). Significant associations were found for the three strain parameters and the levels of blood urea nitrogen (BUN) (r = 0.206, 0.221 and 0.355, respectively). Cardiac troponin I (cTnI) was closely related to the GLS and GCS (r = 0.240 and 0.324, respectively). In multivariable Cox regression, GCS > −21.6% was associated with all‐cause death {hazard ratio, 4.007 [95% confidence interval (CI), 11.347–11.919]}. Conclusions: GLS, GCS and GRS are significantly related to myocardial dysfunction in patients with COVID‐19. Worsening GCS poses an increased risk of death in COVID‐19. [ABSTRACT FROM AUTHOR]

Introduction: The accurate prediction of COVID-19 mortality risk, considering influencing factors, is crucial in guiding effective public policies to alleviate the strain on the healthcare system. As such, this study aimed to assess the efficacy of decision tree algorithms (CART, C5.0, and CHAID) in predicting COVID-19 mortality risk and compare their performance with that of the logistic model. Methods: This retrospective cohort study examined 5080 cases of COVID-19 in Babol, a city in northern Iran, who tested positive for the virus via PCR from March 2020 to March 2022. In order to check the validity of the findings, the data was randomly divided into an 80% training set and a 20% testing set. The prediction models, such as Logistic regression models and decision tree algorithms, were trained on the 80% training data and tested on the 20% testing data. The accuracy of these methods for the test samples was assessed using measures like ROC curve, sensitivity, specificity, and AUC. Results: The findings revealed that the mortality rate for COVID-19 patients who were admitted to hospitals was 7.7%. Through cross validation, it was determined that the CHAID algorithm outperformed other decision tree and logistic regression algorithms in specificity, and precision but not sensitivity in predicting the risk of COVID-19 mortality. The CHAID algorithm demonstrated a specificity, precision, accuracy, and F-score of 0.98, 0.70, 0.95, and 0.52 respectively. All models indicated that factors such as ICU hospitalization, intubation, age, kidney disease, BUN, CRP, WBC, NLR, O2 sat, and hemoglobin were among the factors that influenced the mortality rate of COVID-19 patients. Conclusions: The CART and C5.0 models had outperformed in sensitivity but CHAID demonstrates a better performance compared to other decision tree algorithms in specificity, precision, accuracy and shows a slight improvement over the logistic regression method in predicting the risk of COVID-19 mortality in the population under study. [ABSTRACT FROM AUTHOR]

Background: Early identification of frail patients and early interventional treatment can minimize the frailty-related medical burden. This study investigated the use of machine learning (ML) to detect frailty in hospitalized older adults with acute illnesses. Methods: We enrolled inpatients of the geriatric medicine ward at Taichung veterans general hospital between 2012 and 2022. We compared four ML models including logistic regression, random forest (RF), extreme gradient boosting, and support vector machine (SVM) for the prediction of frailty. The feature window as well as the prediction window was set as half a year before admission. Furthermore, Shapley additive explanation plots and partial dependence plots were used to identify Fried's frailty phenotype for interpreting the model across various levels including domain, feature, and individual aspects. Results: We enrolled 3367 patients. Of these, 2843 were frail. We used 21 features to train the prediction model. Of the 4 tested algorithms, SVM yielded the highest AUROC, precision and F1-score (78.05%, 94.53% and 82.10%). Of the 21 features, age, gender, multimorbidity frailty index, triage, hemoglobin, neutrophil ratio, estimated glomerular filtration rate, blood urea nitrogen, and potassium were identified as more impactful due to their absolute values. Conclusions: Our results demonstrated that some easily accessed parameters from the hospital clinical data system can be used to predict frailty in older hospitalized patients using supervised ML methods. [ABSTRACT FROM AUTHOR]

This article discusses a gatekeeping intervention implemented in a Belgian hospital to improve the appropriateness of blood urea nitrogen (BUN) testing. The intervention involved a new regulation that restricted reimbursement for BUN analysis in patients with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73m2. The study found that the intervention led to a significant decrease in the number of BUN tests performed, as well as a change in prescribing behavior among clinicians. The intervention did not have a significant impact on the quality of care or patient safety indicators. Additionally, there was a substantial decrease in total costs associated with BUN testing. The article suggests that gatekeeping interventions could be effective in reducing inappropriate ordering of other tests in the future, but further research is needed to confirm the outcomes. [Extracted from the article]

This study aimed to evaluate the potential of ethanolic extract of propolis on the secondary lesions of the liver, renal, and pancreatic that were derived by primary colorectal cancer, and comparison of the ethanolic extract of propolis with the vitamin E. The groups included the control, ethanolic extract of propolis, vitamin E, dimethylhydrazine, dimethylhydrazine + ethanolic extract of propolis, and dimethylhydrazine + vitamin E. After 13 weeks of treatment, the blood and tissue samples were taken from all the rats, and alanine transaminase, aspartate transaminase, alkaline phosphatase, uric acid, creatinine, blood urea nitrogen, insulin, amylase, and lipase indices along with the tissue pathological examination of the kidney, liver, and pancreas were evaluated. Ethanolic extract of propolis effectively alleviated the colorectal cancer‐induced secondary lesions in the liver by significantly lowering the alanine transaminase significantly. Ethanolic extract of propolis significantly decreased uric acid in rats; and also significantly elevated the pancreatic insulin. In addition, inflammation and cell necrosis indices in all these tissues were significantly reduced when ethanolic extract of propolis was consumed compared to the dimethylhydrazine group. It seemed ethanolic extract of propolis showed high antioxidant, anticancer, and anti‐inflammatory potentials, and can be used practically to reduce the side lesions of colorectal cancer. [ABSTRACT FROM AUTHOR]

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Objective: We aimed to investigate human epididymis protein 4 (HE4) as a potential biomarker in patients with pediatric-onset systemic lupus erythematosus (pSLE), particularly on the association of serum HE4 levels with disease activity and other laboratory tests. Methods: We included 137 patients with pSLE and 75 age- and sex-matched healthy controls (HCs). Serum HE4 level was measured by a chemiluminescent microparticle on an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Comparisons between groups were performed using the independent Student t-test, Mann-Whitney U test, Chi-square test, or Fisher's exact test, as appropriate. We also determined the relationships between HE4 and clinical parameters and evaluated disease activity using SLE Disease Activity Index (SLEDAI) and renal SLEDAI (rSLEDAI). Results: Serum HE4 levels in patients with pSLE (44.6 pmol/L; IQR, 32.5-73.5) were significantly higher than those in HCs (38.9 pmol/L; IQR, 34-46.1). HE4 levels were significantly higher in moderate to severe disease activities (57.4 pmol/L, IQR 37.7-164.5) than in mild disease activities (38.8 pmol/L, IQR 30.1-48.5) or HCs (38.9 pmol/L, IQR 34.0-46.1), as well as in active renal disease activities (77.2 pmol/L, IQR 47.4-224.1) than in inactive renal disease activities (36.1 pmol/L, IQR 27.8-46.7). The ROC curve analysis showed that HE4 could discriminate pSLE with renal (AUC, 0.717; 95% CI, 0.632-0.801), hematological (AUC, 0.740; 95% CI, 0.648-0.831), and cardiovascular involvement (AUC:0.775, 95% CI 0.669-0.880). Serum HE4 levels significantly correlated with several indicators related to renal morbidity, such as creatinine, blood urea nitrogen, uric acid, cystatin C, urine protein/24 h, etc. Conclusion: Serum HE4 levels in pSLE were elevated and highly associated with disease activity and systemic involvement, indicating HE4 as a potential biomarker for pSLE. [ABSTRACT FROM AUTHOR]