The association between peripheral eosinophil count and chronic kidney disease: evidence from NHANES 1999-2018.

BACKGROUND: Renal impairment has been previously linked to peripheral eosinophil count (PEC), prompting an investigation into its potential relationship with chronic kidney disease (CKD). This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) to comprehensively explore the association between PEC and CKD. METHODS: Survey-weighted generalized multivariate linear regression was employed to evaluate the associations between PEC, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), with meticulous adjustment for potential covariates. To assess non-linear correlations, a restricted cubic spline analysis was conducted. Sensitivity analysis was performed to test the stability of results. RESULTS: The study included a total of 9224 participants with non-dialysis CKD. In the multivariate linear regression model, after comprehensive adjustment for potential covariates, PEC showed a negative association with eGFR (ß per 100 cells/uL increase in PEC, -0.71; 95% CI, -1.04, -0.37), while demonstrating a positive trend with UACR (ß per 100 cells/uL increase in PEC, 10.21; 95% CI, 1.37, 19.06). The restrictive cubic spline curve analysis suggested that these associations occurred within the range of 0 to 400 cells/uL for PEC. Sensitivity analysis supported the stability of the observed results. CONCLUSIONS: Circulating eosinophil levels are negatively correlated with eGFR and demonstrate a positive trend with UACR, when PEC falls within the range of less than 400 cells/uL among adults with CKD. Further research is warranted to validate these findings.

predictive model of nosocomial infection in patients with upper urinary tract stones after flexible ureterorenoscopy with laser lithotripsy: A retrospective study.

Objectives: To construct a predictive model of nosocomial infection in patients with upper urinary tract (UUT) stones after flexible ureterorenoscopy with laser lithotripsy (FURSLL). Methods: Medical records of 196 patients with UUT stones who underwent FURSLL in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from December 2019 to December 2022 were retrospectively analyzed. Patients were divided into infected group or uninfected group based on the presence of infection during postoperative hospitalization. Univariate and multivariate logistic regressions were used to identify risk factors of postoperative nosocomial infections. A nomogram prediction model was constructed using R software. The predictive ability of the model was assessed using the receiver operating characteristic (ROC) curve. Results: A total of 54 patients (27.6%) developed nosocomial infections after FURSLL. Logistic regression analysis showed that older age, diabetes, preoperative urinary system infection, ureteral stricture, hydronephrosis, double J-stent retention time, and stone diameter were risk factors of nosocomial infection. The nomogram model was constructed based on these risk factors. The ROC showed that the area under the curve (AUC) of the model was 0.930 (95% CI: 0.890-0.970), and the sensitivity and specificity were 92.6% and 81.7%, respectively, indicating that the prediction model was effective. Conclusions: Risk of nosocomial infection in patients with UUT stones after FURSLL is affected by older age, diabetes, preoperative urinary system infection, ureteral stenosis, hydronephrosis, double J-stent retention time, and stone diameter. The nomogram prediction model, constructed based on the above factors, has good predictive value.

Association between pulmonary function and rapid kidney function decline: a longitudinal cohort study from CHARLS.

BACKGROUND: Pulmonary function has been reported to be associated with chronic kidney disease. However, the relationship between lung function and rapid kidney function decline remains unclear. METHODS: Participants aged ≥45 years with complete data from the 2011 and 2015 interviews of the China Health and Retirement Longitudinal Study (CHARLS) were included. Lung function, assessed by peak expiratory flow (PEF), and kidney function, assessed by estimated glomerular filtration rate (eGFR), were tested at the baseline and endpoint surveys. Rapid kidney function decline was defined as a decrease in eGFR ≥3 mL/min/1.73 m²/year, and ΔeGFR represented the difference between baseline and endpoint eGFR. Multivariate logistic regression models and linear regression models were employed to evaluate the association between PEF and the risk of rapid eGFR decline, as well as the correlation between PEF and ΔeGFR. RESULTS: A total of 6159 participants were included, with 1157 (18.78%) individuals experiencing a rapid decline in eGFR. After adjusting for potential covariates, higher baseline PEF (Quartile 4 vs Quartile 1, OR=0.95, 95% CI 0.92 to 0.98) and elevated PEF % predicted (OR=0.96, 95% CI 0.94 to 0.99) were found to be associated with a lower risk of rapid eGFR decline. ΔeGFR decreased by 0.217 and 0.124 mL/min/1.73 m² for every 1 L/s increase in baseline PEF (ß (95% CI): -0.217 (-0.393 to -0.042)) and 10% increase in PEF % predicted (ß (95% CI): -0.124 (-0.237 to -0.011)), respectively. During the follow-up period, ΔeGFR decreased as PEF increased over time among participants in Quartile 1 (ß per 1 L/s increase in ΔPEF=-0.581, 95% CI -1.003 to -0.158; ß per 10% increase in ΔPEF % predicted=-0.279, 95% CI -0.515 to -0.043). CONCLUSIONS: Higher PEF was associated with a slower longitudinal eGFR decline in middle-aged and older adults.

Huaju Xiaoji Formula Regulates ERS-lncMGC/miRNA to Enhance the Renal Function of Hypertensive Diabetic Mice with Nephropathy.

Background: Better therapeutic drugs are required for treating hypertensive diabetic nephropathy. In our previous study, the Huaju Xiaoji (HJXJ) formula promoted the renal function of patients with diabetes and hypertensive nephropathy. In this study, we investigated the therapeutic effect and regulation mechanism of HJXJ in hypertensive diabetic mice with nephropathy. Methods: We constructed a mouse hypertensive diabetic nephropathy (HDN) model by treating mice with streptozotocin (STZ) and nomega-nitro-L-arginine methyl ester (LNAME). We also constructed a human glomerular mesangial cell (HGMC) model that was induced by high doses of sugar (30 mmol/mL) and TGFß1 (5 ng/mL). Pathological changes were evaluated by hematoxylin and eosin (H&E) staining, periodic acid Schiff (PAS) staining, and Masson staining. The fibrosis-related molecules (TGFß1, fibronectin, laminin, COL I, COL IV, α-SMA, and p-smad2/3) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression of endoplasmic reticulum stress, fibrosis molecules, and their downstream molecules were assessed using qPCR and Western blotting assays. Results: Administering HJXJ promoted the renal function of HDN mice. HJXJ reduced the expression of ER stress makers (CHOP and GRP78) and lncMGC, miR379, miR494, miR495, miR377, CUGBP2, CPEB4, EDEM3, and ATF3 in HDN mice and model HGMCs. The positive control drugs (dapagliflozin and valsartan) also showed similar effects after treatment with HJXJ. Additionally, in model HGMCs, the overexpression of CHOP or lncMGC decreased the effects of HJXJ-M on the level of fibrosis molecules and downstream target molecules. Conclusion: In this study, we showed that the HJXJ formula may regulate ERS-lncMGC/miRNA to enhance renal function in hypertensive diabetic mice with nephropathy. This study may act as a reference for further investigating whether combining HJXJ with other drugs can enhance its therapeutic effect. The findings of this study might provide new insights into the clinical treatment of hypertensive diabetic nephropathy with HJXJ.

Platelet extracellular vesicles: Darkness and light of autoimmune diseases.

Autoimmune diseases are characterized by a breakdown of immune tolerance, leading to inflammation and irreversible end-organ tissue damage. Platelet extracellular vesicles are cellular elements that are important in blood circulation and actively participate in inflammatory and immune responses through intercellular communication and interactions between inflammatory cells, immune cells, and their secreted factors. Therefore, platelet extracellular vesicles are the "accelerator" in the pathological process of autoimmune diseases; however, this robust set of functions of platelet extracellular vesicles has also prompted new advances in therapeutic strategies for autoimmune diseases. In this review, we update fundamental mechanisms based on platelet extracellular vesicles communication function in autoimmune diseases. We also focus on the potential role of platelet extracellular vesicles for the treatment of autoimmune diseases. Some recent studies have found that antiplatelet aggregation drugs, specific biological agents can reduce the release of platelet extracellular vesicles. Platelet extracellular vesicles can also serve as vehicles to deliver drugs to targeted cells. It seems that we can try to silence or inhibit microRNA carried by platelet extracellular vesicles transcription and regulate the target cells to treat autoimmune diseases as platelet extracellular vesicles can transfer microRNA to other cells to regulate immune-inflammatory responses. Hopefully, the information presented here will provide hope for patients with autoimmune diseases.

Autoimmune diseases patients are characterized by autoimmune disorders, whose immune system cannot distinguish between auto- and foreign-antigens. Autoimmune diseases is the third significant disease threatening human health after cardiovascular disease and cancer. However, the exact etiology of autoimmune diseases has yet to be fully elucidated. Several studies have shown that platelet extracellular vesicle content is elevated in multiple autoimmune disorders and positively correlates with disease activity. However, our knowledge about the details of the mechanisms still remains limited and fragmentary. This article updates the communication function of platelet extracellular vesicles in accelerating autoimmune and inflammatory responses. The interesting thing is every coin has two sides. We put forward a new treatment idea for AD based on the particular volume and powerful intercellular communication function of platelet extracellular vesicles. Inhibition of the communication function of platelet extracellular vesicles seems to be considered in the future, or silence or block miRNA of platelet extracellular vesicles involved in the pathogenesis of AD. We can even use it as a drug carrier to deliver the drug to the relevant target cells, thereby enhancing the role of the medicine in regulating immune response and inhibiting inflammation. This paper not only provides a deeper understanding of the pathogenesis of autoimmune diseases but also provides theoretical support for the use of platelet extracellular vesicles to achieve targeted therapy.

Glucocorticoid reduction induced chorea in pediatric-onset systemic lupus erythematosus: A case report.

BACKGROUND: Pediatric-onset systemic lupus erythematosus (SLE) is typically more severe than adult-onset SLE, with a higher incidence of nervous system involvement. Chorea is a relatively rare neurological complication reported in 2.4%-7% of SLE patients. In particular, chorea induced by glucocorticoid dose reduction is even rarer. Herein, we report the case of a girl with SLE, who developed chorea during the process of glucocorticoid therapy reduction. CASE SUMMARY: We describe a 14-year-old girl who was diagnosed with SLE. She was treated with methylprednisolone and rituximab, and her symptoms improved. On the second day after the methylprednisolone dose was reduced according to the treatment guidelines, the patient developed chorea. Her condition improved after adjusting her glucocorticoid regimen. CONCLUSION: This case is a reminder that extra attention to chorea is required in SLE patients during glucocorticoid dose reduction.

Association Between Serum Klotho and All-Cause Mortality in Chronic Kidney Disease: Evidence From a Prospective Cohort Study.

INTRODUCTION: This study aimed to investigate the relationship between circulating soluble Klotho concentration and all-cause mortality in individuals with chronic kidney disease (CKD). METHODS: We conducted a prospective cohort study involving 2,456 participants with CKD from the National Health and Nutrition Examination Survey (NHANES) cycles spanning from 2007 to 2016. Complex sampling-weighted multivariate Cox proportional hazards models were used to estimate the association between serum Klotho level and all-cause mortality, presenting hazard ratios (HR) and 95% confidence intervals (CI). Additionally, a restricted cubic spline analysis was performed to explore potential non-linear associations. RESULTS: During a median of 82 months of follow-up, 550 (22.40%) all-cause deaths were recorded. The median serum Klotho concentration was 760 pg/ml (interquartile ranges, 624, 958). After adjusting for potential covariates, the risk of all-cause mortality decreased by 4% for every 100 pg/ml increase in Klotho (HR = 0.96, 95% CI, 0.92, 0.99). The HR for the fourth quartile of Klotho compared to the first quartile was 0.73 (95% CI, 0.56, 0.96). The restricted cubic spline model revealed a distinctive "L"-shaped association between serum Klotho and all-cause mortality among patients with CKD, with a Klotho concentration of 760 pg/ml at the inflection point. When Klotho concentration was less than 760 pg/ml, a significant negative correlation between Klotho and all-cause mortality was observed (HR per 100 pg/ml increase in Klotho = 0.86, 95% CI, 0.78, 0.95). CONCLUSION: This study documented a distinctive "L"-shaped association between serum Klotho levels and all-cause mortality among individuals with CKD. Further research is needed to validate these findings.

Myelodysplastic syndrome-like response after voriconazole treatment of systemic lupus erythematosus complicated with fungal infection: a case report.

Background: Voriconazole is mainly used to treat progressive and potentially life-threatening infections in immunocompromised patients. The adverse drug reactions related to voriconazole are varied. In some rare cases, the use of voriconazole can result in myelodysplastic syndrome (MDS)-like adverse reactions. Case presentation: Here, we present a rare case of systemic lupus erythematosus patient with a fungal infection that developed MDS-like adverse reactions after treatment with voriconazole. The patient was admitted to the hospital because of 3 days of chest tightness and dyspnea. After the admission, the patient's sputum culture showed Candida albicans infection, and voriconazole was prescribed to be taken orally. After using voriconazole, drug-related adverse reactions such as visual impairment, nausea, vomiting, hiccup, middle and lower abdominal pain, disorders of consciousness, delirium, hallucination, slow response, and subcutaneous ecchymosis appeared, as well as the gradually increased serum creatinine, oliguria, and aggravated lower limb edema. In addition, there was a decrease in peripheral blood cells, and MDS-like changes in bone marrow were indicated by bone marrow biopsy. After discontinuing voriconazole, drug-related adverse symptoms disappeared, and hematocytopenia and the changes in MDS were significantly improved, which was confirmed by a subsequent bone marrow puncture at a 6 months interval. Conclusion: This case reminded us that when using voriconazole for treatment, individual differences in patients should be considered, and the blood concentration of voriconazole should be closely monitored. Otherwise, potential drugs that affect voriconazole metabolism should be noted, and related adverse symptoms of patients should be closely observed during medication to reduce the occurrence of adverse drug events.

Controlling the electronic structure of Fe-MOF electrocatalyst for enhanced water splitting and urea oxidation: A plasma-assisted approach.

The design of high-performance electrocatalysts for water splitting and urea oxidation reactions requires effective regulation of their electronic structure and electrochemical surface area (ECSA). In this study, we developed an in-situ grown Fe-MOF electrocatalyst on Fe foam (FF) by using a combination of easy hydrothermal synthesis and advanced plasma technology (Fe-MOF/FF). By varying the plasma treatment time, we could tailor the surface morphology and electronic structure of the Fe-MOF/FF microrods. Meanwhile, density functional theory (DFT) calculations investigated the catalytic mechanism, revealing that plasma-treated Fe-MOF/FF has a lower energy barrier for water splitting and H* adsorption during the HER process, and higher catalytic activity for UOR. Additionally, the electronic density of optimized Fe-MOF/FF is significantly expanded near the Fermi level. Remarkably, our catalysts achieved exceptional activity in both water splitting and urea electrolysis, requiring only 1.54 V and 1.472 V, respectively, at 10 mA cm-2, with excellent stability. Our findings highlight the potential of plasma technology as a powerful tool for developing multifunctional electrocatalysts for clean energy and industrial wastewater treatment applications.

The potential of Chinese medicines in the treatment of hyperuricemia.

The annual incidence of gout is increasing along with lifestyle and dietary changes. Accumulation of urate crystals in joints and tissues when the amount of uric acid exceeds its saturation concentration causes acute inflammation that leads to gout. Reducing the serum uric acid concentration is the key to treating gout. Allopurinol, febuxostat, benzbromarone, and other drugs are effective, but side effects of treatment such as toxicity and recurrence after drug withdrawal cannot be ignored. Recent studies have found that many Chinese medicines are effective and safe, provide durable efficacy, and are associated with low recurrence rates. This article reviews recent investigations of Chinese medicines for lowering uric acid, including components such as berberine, luteolin, and others; single medicines such as Smilax glabra Roxb., Reynoutria japonica Houtt., and Plantago asiatica L.; and compounds such as Wuling Powder and Compound Tufuling Granules. Mechanisms of lowering uric acid, including inhibiting uric acid production and promoting uric acid excretion are discussed. Clinical studies and basic research are reviewed.

BMAL1 regulates MUC1 overexpression in ovalbumin-induced asthma.

Asthma often presents with a daily rhythm; however, the underlying mechanisms remain unclear. Circadian rhythm genes have been proposed to regulate inflammation and mucin expression. Here, ovalbumin (OVA)-induced mice and serum shock human bronchial epidermal cells (16HBE) were used in in vivo and in vitro models, respectively. We constructed a brain and muscle ARNT-like 1 (BMAL1) knockdown 16HBE cell line to analyze the effects of rhythmic fluctuations on mucin expression. Serum immunoglobulin E (IgE) and circadian rhythm genes in asthmatic mice showed rhythmic fluctuation amplitude. Mucin (MUC) 1 and MUC5AC expression was increased in the lung tissue of the asthmatic mice. MUC1 expression was negatively correlated with that of the circadian rhythm genes, particularly BMAL1 (r = -0.546, P = 0.006). There was also a negative correlation between BMAL1 and MUC1 expression (r = -0.507, P = 0.002) in the serum shock 16HBE cells. BMAL1 knockdown negated the rhythmic fluctuation amplitude of MUC1 expression and upregulated MUC1 expression in the 16HBE cells. These results indicate that the key circadian rhythm gene, BMAL1, causes periodic changes in airway MUC1 expression in OVA-induced asthmatic mice. Targeting BMAL1 to regulate periodic changes in MUC1 expression may, therefore, improve asthma treatments.

ABA-triggered ROS burst in rice developing anthers is critical for tapetal programmed cell death induction and heat stress-induced pollen abortion.

High temperatures (HT) cause pollen abortion and poor floret fertility in rice, which is closely associated with excessive accumulation of reactive oxygen species (ROS) in the developing anthers. However, the relationships between accumulation of abscisic acid (ABA) and ROS, and their effects on tapetum-specific programmed cell death (PCD) in HT-stressed anthers are poorly characterised. Here, we determined the spatiotemporal changes in ABA and ROS levels, and their relationships with tapetal PCD under HT exposure. Mutants lacking ABA-activated protein kinase 2 (SAPK2) functions and exogenous ABA treatments were used to explore the effects of ABA signalling on the induction of PCD and ROS accumulation during pollen development. HT-induced pollen abortion was tightly associated with ABA accumulation and oxidative stress. The higher ABA level in HT-stressed anthers resulted in the earlier initiation of PCD induction and subsequently abnormal tapetum degeneration by activating ROS accumulation in developing anthers. Interactions between SAPK2 and DEAD-box ATP-dependent RNA helicase elF4A-1 (RH4) were required for ABA-induced ROS generation in developing anthers. The OsSAPK2 knockout mutants showed the impaired PCD responses in the absence of HT. However, the deficiency of SAPK2 functions did not suppress the ABA-mediated ROS generation in HT-stressed anthers.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

INTRODUCTION: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P < 0.05), and a lower rate of shortening surveillance schedule ( P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.

Expression and regulatory characteristics of peripheral blood immune cells in primary Sjögren's syndrome patients using single-cell transcriptomic.

Immune cell subgroups in peripheral blood mononuclear cells (PBMCs) in primary Sjogren's syndrome (pSS) are thought to regulate immune responses, but the nature and functions of these subgroups remain unclear. Here we performed single-cell RNA sequencing (scRNA-seq) of about 68,500 PBMCs from three patients with pSS and three healthy controls (HCs). We found that CD14+ monocytes from pSS patients expressed high levels of the transcription factor CEBPD, and the direct regulation of target genes expression by CEBPD tends to participate in the TNF-α signaling via NF-κB in monocytes. FOLR3 and IL1B were upregulated separately in CD14+ monocyte subsets from different pSS patients. We proposed a system for classifying CD56-CD16+ NK cells based on FCER1G expression. Compared with HCs, pSS patients showed a significantly higher ratio of CD56-CD16+FCER1G+ NK cells to CD56-CD16+FCER1G- NK cells. Our analysis provides a reference dataset and reveals its immune heterogeneity among PBMCs in pSS.

A systematic review and meta-analysis of gut microbiota in diabetic kidney disease: Comparisons with diabetes mellitus, non-diabetic kidney disease, and healthy individuals.

Background: Gut microbiota has been reported to play an important role in diabetic kidney disease (DKD), however, the alterations of gut bacteria have not been determined. Methods: Studies comparing the differences of gut microbiome between patients with DKD and non-DKD individuals using high-throughput sequencing technology, were systematically searched and reviewed. Outcomes were set as gut bacterial diversity, microbial composition, and correlation with clinical parameters of DKD. Qualitative data were summarized and compared through a funnel R script, and quantitative data were estimated by meta-analysis. Results: A total of 15 studies and 1640 participants were included, the comparisons were conducted between DKD, diabetes mellitus (DM), non-diabetic kidney disease (NDKD), and healthy controls. There were no significant differences of α-diversity between DKD and DM, and between DKD and NDKD, however, significant lower microbial richness was found in DKD compared to healthy controls. Different bacterial compositions were found between DKD and non-DKD subjects. The phylum Actinobacteria were found to be enriched in DKD compared to healthy controls. At the genus level, we found the enrichment of Hungatella, Bilophila, and Escherichia in DKD compared to DM, patients with DKD showed lower abundances of Faecalibacterium compared to those with NDKD. The genera Butyricicoccus, Faecalibacterium, and Lachnospira were depleted in DKD compared to healthy controls, whereas Hungatella, Escherichia, and lactobacillus were significantly enriched. The genus Ruminococcus torques group was demonstrated to be inversely correlated with estimated glomerular filtration rate of DKD. Conclusions: Gut bacterial alterations was demonstrated in DKD, characterized by the enrichment of the genera Hungatella and Escherichia, and the depletion of butyrate-producing bacteria, which might be associated with the occurrence and development of DKD. Further studies are still needed to validate these findings, due to substantial heterogeneity. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022340870.

Associations between whole blood trace elements concentrations and HbA1c levels in patients with type 2 diabetes.

Previous researches have been conducted to study the associations of trace elements on Type 2 diabetes (T2D) risk. The present study focuses on the evaluation of potential associations between trace elements and Hemoglobin A1c (HbA1c) in patients with T2D, via the determination of their levels in human whole blood. 100 diabetes without complications, 75 prediabetes and 40 apparently healthy subjects were studied. The levels of eleven trace elements including lithium (Li), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr) and molybdenum (Mo) were measured using inductively coupled plasma mass spectrometry (ICP-MS). The levels of fasting glucose, HbA1c, Hemoglobin, lipid, liver function, kidney function, thyroid function and demographic data were obtained from the Laboratory Information System. Nonparametric correlation (Spearman) was used to analyze the relationship between trace elements and HbA1c. The contents of V, Cr, Mn, Fe, Co, Cu, Zn and Mo in diabetes increased comparing with the healthy subject while Li decreased. But the levels of Li, V, Cr, Mn, Co, Se and Mo negatively correlated with HbA1c in the diabetes subjects (r value: - 0.2189, - 0.2421, - 0.3260, - 0.2744, - 0.2812, - 0.2456, - 0.2240; 95% confidence interval - 0.4032 to - 0.0176, - 0.4235 to - 0.0420, - 0.4955 to - 0.1326, - 0.4515 to - 0.0765, - 0.4573 to - 0.0838, - 0.4266 to - 0.0458, - 0.4076 to - 0.0229; p < 0.05, p < 0.05, p < 0.001, p < 0.01, p < 0.01, p < 0.05, p < 0.05). Accordingly, the contents of V, Cr, Mn and Se showed lower in HbA1c ≥ 7.0% group in contrast to HbA1c < 7.0% group. No correlation of HbA1c (or FBG) and trace elements was found in the healthy subjects. Trace element levels and metabolic abnormalities of blood glucose may be mutually affected. The extra supplement of trace elements needs to be cautious.

Potential Molecular Mechanisms of Ephedra Herb in the Treatment of Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking.

Objective: To explore the possible mechanisms of Ephedra herb (EH) in the treatment of nephrotic syndrome (NS) by using network pharmacology and molecular docking in this study. Methods: Active ingredients and related targets of EH were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the gene names corresponding to the proteins were found through the UniProt database. Then, target genes related to NS were screened out from GeneCards, PharmGKB, and OMIM databases. Next, the intersection targets were obtained successfully through Venn diagram, which were also seen as key target genes of EH and NS. Cytoscape 3.9.0 software was used to construct the effective "active ingredient-target" network diagram, and "drug-ingredient-target-disease (D-I-T-D)" network diagram. After that, the STRING database was used to construct a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment involved in the targets were performed by the DAVID database and ClueGO plugin in Cytoscape. Finally, AutoDockTools software was used for molecular docking to verify the binding strength between main active ingredients and key target proteins. Results: A total of 22 main active ingredients such as quercetin, kaempferol, luteolin, and naringenin were obtained, which could act on 105 targets related to NS. Through PPI network, 53 core targets such as AKT1, TNF, IL6, VEGFA, and IL1B were found, which might play a crucial role in the treatment of NS. Meanwhile, these targets were significantly involved in PI3K-Akt signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway, hepatitis B, and pathways in cancer through GO and KEGG enrichment analysis. The docking results indicated that active ingredients such as kaempferol, luteolin, quercetin, and naringenin all had good binding to the target protein AKT1 or TNF. Among them, luteolin and naringenin binding with AKT1 showed the best binding energy (-6.2 kcal/mol). Conclusion: This study indicated that the potential mechanism of EH in treating NS may be related to PI3K-Akt signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway, which provided better approaches for exploring the mechanism in treating NS and new ideas for further in vivo and in vitro experimental verifications.

Metabolomics combined with network pharmacology to explore the mechanisms of modified Guishen pill to ameliorate polycystic ovary syndrome.

BACKGROUND: The modified Guishen pill (MGP) has a prominent therapeutic effect on polycystic ovary syndrome (PCOS). However, its mechanism is still unclear. This study aimed to uncover the mechanism of MGP for PCOS treatment through a comprehensive strategy integrating metabolomics and network pharmacology. METHODS: A letrozole-induced PCOS model was used to evaluate ovarian function in rats. Plasma metabolomics was used to authenticate differential metabolites and enriched related pathways using the MetaboAnalyst platform. Network pharmacology was utilized to explore the endogenous targets of MGP treatment for PCOS. Finally, the potential targets and related biological functions were verified experimentally. RESULTS: MGP improved PCOS symptoms by regulating abnormal levels of sex hormones and alleviating ovarian pathological changes in rats; fifty-four potential differential metabolites involved in MGP treatment for PCOS, and the hub genes derived from network pharmacology were consistent with the metabolomic analysis results to varying degrees. The comprehensive analysis identified that a key novel target for endothelial nitric oxide synthase (eNOS/NOS3), five key metabolites (ornithine, citrulline, l-glutamic acid, acetylornithine, and hydroxyproline), and one pathway (arginine and proline metabolism) were related to the therapy of PCOS with MGP. Subsequently, we verified the localization and expression of eNOS in the ovaries, and it significantly improved insulin resistance, apoptosis, and oxidative stress in letrozole-induced PCOS rats. CONCLUSION: Our work reveals the complex mechanism of MGP therapy for PCOS. This study is a successful paradigm for elucidating the pharmacological mechanism of the traditional Chinese medicine compound.

Regulating the electronic structure of Fe-based metal organic frameworks by electrodeposition of Au nanoparticles for electrochemical overall water splitting.

Reasonable regulating the electronic structure is one of the effective strategies for improving the conductivity of metal-organic frameworks (MOFs) based electrocatalysts. Herein, a series of Fe-MOF/Au composites grown in situ on Fe Foam (FF) were prepared through a hydrothermal and the controlled electrodeposition time strategy, in which the Fe Foam acts both as the conductive substrate and a self-sacrificing template. The electronic structure of the Fe-MOF/Au/FF composites can be finely adjusted by tailoring the electrodeposition time. Therefore, the Fe-MOF/Au/FF composites possess enhanced conductivity, accompanied by increased electrochemical activity of specific areas and oxygen evolution (OER), hydrogen evolution (HER) and overall water splitting properties. In particular, the optimized Fe-MOF/Au-8/FF composites used as bifunctional electrocatalysts for overall water splitting require only small voltage of 1.61 V to achieve a current density of 10 mA cm-2. This strategy will provide new inspiration and creativity to enhance the electrocatalytic performance of MOF-based electrocatalysts for hydrogen conversion and application.