Background: Renal involvement resulting from hyperuricemia, known as hyperuricemia nephropathy (HN), is characterized by chronic tubulointerstitial inflammation caused by extensive urate crystal deposition. Managing this condition requires straightforward preventive or therapeutic interventions, primarily through dietary measures. Methods: In this study, the mouse model of HN was established using yeast extract combined with potassium oxonate. The effect and potential mechanism of β‐sitosterol in treating HN were investigated through biochemical indexes, pathological changes, untargeted metabolomics, and network pharmacology. Results: β‐Sitosterol reduced the levels of four biomarkers of HN: uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), and xanthine oxidase (XOD). It also mitigated inflammatory injury in renal tissues and reversed the abnormal expression of four key urate transporter proteins: glucose transporter protein 9 (GLUT9), organic anion transporter 1 (OAT1), ATP‐binding cassette transporter G2 (ABCG2), and urate transporter 1 (URAT1). To explore the mechanism of β‐sitosterol in treating HN, this study employed network pharmacology and metabolomics to analyze 27 intersecting gene targets and 14 differential metabolites. The findings indicated that glutathione (GSH) metabolism might be a crucial pathway. Treatment with β‐sitosterol increased the levels of reduced GSH as well as the activity and expression of 6‐phosphogluconate dehydrogenase (G6PDH) in mice, thereby effectively modulating GSH metabolism. This study proposes a novel strategy using β‐sitosterol for treating HN, providing a promising approach for addressing this condition.
To investigate the clinical characteristic differences of cementless total hip arthroplasty (THA) between with and without subtrochanteric femoral shortening osteostomy in Crowe type IV developmental dysplasia of the hip (DDH).Between January 2006 and March 2012, 21 patients (21 hips) with Crowe type IV DDH who underwent primary THA were enrolled according to inclusion criteria. According to whether subtrochanteric femoral shortening osteostomy was performed during THA or not, the patients were divided into 2 groups: THA with osteostomy group (n = 9) and THA without osteotomy group (n = 12). There was no significant difference in gender, age, body mass index, and hip Harris score between 2 groups (P > 0.05) except leg length discrepancy (t = -3.170, P = 0.005). The operation time, blood loss, postoperative drainage, complications, and radiography data were compared to evaluate the clinical characteristics.The operation time, blood loss, and postoperative drainage of osteotomy group were all significantly greater than those of no osteotomy group (P < 0.05). All patients achieved primary healing of incision; 1 patient (1 hip) had transient sciatic nerve symptom in osteotomy group. The average follow-up time was 53 months (range, 28-88 months). The X-ray films showed good fracture healing at 3-6 months after operation in osteostomy group. No prosthetic loosening or dislocation was found. The hip Harris score was 90.67 ± 4.06 in osteostomy group and 92.17 ± 3.27 in no osteostomy group, showing no significant difference between 2 groups (t = -0.938, P = 0.360). The leg length discrepancy was (0.22 ± 0.26) cm in osteostomy group and (0.18 ± 0.27) cm in no osteostomy group, showing no significant.difference (t = 107.000, P = 0.546). The leg length discrepancy was found in 6 patients of osteotomy group and 5 patients of no osteotomy group. One patient complained of thigh pain in osteotomy group; 2 patients had slight limp (Trendelenburg +) in no osteotomy group.THA can improve joint function and increase limb length in the treatment of Crowe type IV DDH. Subtrochanteric shortening osteotomy is an effective treatment which can be performed according to preoperative template measurement, leg length shortening, and the soft tissue tension.
Objectives Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy. Methods and results Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage ( P < 0.001). Further, employing multivariate logistic regression analysis adjusted for age, sex and height, the investigation revealed that patients harboring at least one variant allele in CYP2C9 exhibited a heightened risk of bleeding events compared to those with the wild-type genotype (odds ratio = 2.16, P = 0.04). Moreover, a meta-analysis conducted to consolidate findings confirmed the associations of both CYP2C9 (rs1057910) and VKORC1 (rs9923231) with stable warfarin dosage. Notably, CYP2C9 variant genotypes were significantly linked to an increased risk of hemorrhagic complications ( P < 0.00001), VKORC1 did not demonstrate a similar association. Conclusion The associations found between specific genetic variants and both stable warfarin dosage and bleeding risk might be the potential significance of gene detection in optimizing warfarin therapy for improving patient efficacy and safety.
Soil extracellular enzyme activity (EEAs) and enzymatic stoichiometry (ES) can provide a crucial indication of changes in soil ecosystem's nutrient availability and the microbial resource limitations. However, the changing characteristics of soil EEAs and ES at different stages of the native succession process and their key drivers are unclear. In order to investigate the soil EEAs, ES and driving factors of soil under vegetation at different succession stages, we adopted the "spatio-temporal substitution" method to collect the surface soil of bryophyte community, herbaceous community, shrub community and tree community in the new volcanic lava platform of Wudalianchi Volcanic Nature Reserve. We measured seven soil EEA, including carbon(C)-acquiring enzyme (β-1,4-glucosidase (BG)), N-acquiring enzymes (β-N-acetyl-glucosaminidase (NAG) and leucine aminopeptidase (LAP)) and phosphorus (P)-acquiring enzyme (acid phosphatase (AP)) activities. The length and angle of vectors defined by ratios of enzyme activities (BG/(NAG + LAP) vs. BG/AP) were used to indicate relative microbial investments in C- (length), and N- and P- (angle) acquiring enzymes. Our results showed that the contents of TC, TN, TP, MBC, DOC and NO3-N in shrub community soil were significantly higher than those in bryophyte, herb and tree communities, and increased by 441%, 246%, 137%, 5570%, 12% and 484%, respectively. The highest soil EEA of C-, N- and P-acquiring were found in shrub community, and the soil EEAs/MBC of C-, N- and P-acquiring were the highest in bryophyte community. Enzyme C:N, C:P and N:P ratios increased progressively in the order of bryophyte, herb and shrub community, but the enzyme C:N, C:P and N:P ratios of tree community were both far less than shrub community. Vector lengths increased progressively in the order of bryophyte (1.16), herb (1.27), tree (1.29) and shrub (1.40), and Vector angles decreased progressively in the order of bryophyte (49.15°), herb (45.65°), Tree (45.31°) and shurb (44.54°), suggested that as succession progresses, soil microbial nutrients transforms from P limitation (angle＞45°) to N limitation (angle＜45°). Redundancy analysis showed that TC, TN, EC and C:N were important drivers of variation in soil EEAs and ES in vegetation at different succession stages. Our findings highlight that the primary succession process cause nutrient limitation transformation. Soil ES might be a sensitive indicator mediated by soil microorganisms to the relative resource limitation at different stages of the primary succession process.
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