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To compare the difference in perioperative outcomes between standard pelvic lymph node dissection (sPLND) and extended pelvic lymph node dissection (ePLND) in robot-assisted radical cystectomy (RARC) and evaluate the survival outcomes. The clinical data were retrospectively collected from patients who underwent RARC between January 2016 and December 2020 in Nanjing Drum Hospital. The patients were divided into sPLND and ePLND group according to the extent of pelvic lymph node dissection. Finally, 80 pairs of patients obtained for two groups by propensity score matching (PSM) and their perioperative and survival outcomes were analyzed. The median number of dissected lymph nodes (LN) after PSM was 13 in sPLND group and 16 in ePLND group (P = 0.004). Perioperative complications were similar between 2 groups. After PSM, ePLND improved 5-year RFS and OS in all patients (85.74 vs. 61.94%, P = 0.004; 82.80 vs. 67.50%, P = 0.033), patients with ≥ T3 disease (73.66 vs. 23.86%; P = 0.007; 68.20 vs. 36.20%; P = 0.032) and patients with LN metastasis (67.70 vs. 7.33%; P = 0.004; 60.60 vs. 16.67%; P = 0.045) compared to sPLND. Extended PLND significantly increased lymph node yield without increasing complication and improved RFS and OS compared to sPLND. [ABSTRACT FROM AUTHOR]

The association between vascular calcification (VC) and kidney stone is still inconclusive. Therefore, we conducted a meta-analysis to estimate the risk of kidney stone disease in subjects with VC. To identify publications from related clinical studies, we performed a search on PubMed, Web of Science, Embase, and Cochrane Library databases from their inceptions until 1 September 2022. According to obvious heterogeneity, a random-effects model was used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Subgroup analysis was conducted trying to dissect the effects of VC in different segments and population regions in predicting kidney stone risk. Seven articles were included with a total number of 69,135 patients, of which 10,052 have vascular calcifications and 4728 have kidney stones. There was a significantly higher risk of kidney stone disease in participants with VC versus control (OR = 1.54, 95% CI: 1.13–2.10). Sensitivity analysis confirmed the stability of the results. VC can be separated into abdominal, coronary, carotid, and splenic aortic calcification while pooled analysis of abdominal aorta calcification did not indicate a significant higher kidney stone risk. An obvious higher risk of kidney stone was observed in Asian VC patients (OR = 1.68, 95% CI: 1.07–2.61). Combined evidence of observational studies suggested patients with VC may be associated with an increased risk of kidney stone disease. Despite the predictive value was relatively low, it is still worth noting that patients with VC are under the threat of kidney stone disease. [ABSTRACT FROM AUTHOR]

Renal fibrosis, which is characterized as progressive extracellular matrix accumulation, is a common feature of different stages of chronic kidney disease, and the degree of fibrosis is strongly associated with renal function. In clinical practice, precise understanding of the space distribution of fibrosis is extremely important for the diagnosis and prognosis of renal disease. Rapid advances in terahertz (THz) technology have been made, and this technology has a broad application in bio-detection, as it can interact and measure the collective vibrations and rotations of molecular groups. It is well known that hydroxyproline (HYP) is the key component of collagen, which is synthesized by fibroblasts to maintain the extracellular matrix, and HYP content detection in tissue homogenate can be achieved by classical biochemistry method. In this study, a THz microprobe system was employed to conduct THz microspatial scanning with a resolution of 20 µm. Both the content and distribution of HYP were directly characterized by the THz absorption spectrum. The absorption intensity in the THz spectrum was used to determine HYP density in renal tissues; therefore, the fibrosis change in the kidneys can be determined using THz scanning at micrometer resolution, which provides more possibilities for precise diagnosis of renal fibrosis. [ABSTRACT FROM AUTHOR]

Focal segmental glomerulosclerosis (FSGS) is a common clinical condition with manifestations of nephrotic syndrome and fibrosis of the glomeruli and interstitium. Yi-Shen-Hua-Shi (YSHS) granule has been shown to have a good effect in alleviating nephrotic syndrome (NS) in clinical and in animal models of FSGS, but whether it can alleviate renal fibrosis in FSGS and its mechanism and targets are not clear. In this study, we explored the anti-fibrotic effect and the targets of the YSHS granule in an adriamycin (ADR)-induced FSGS model and found that the YSHS granule significantly improved the renal function of ADR-induced FSGS model mice and also significantly reduced the deposition of collagen fibers and the expression of mesenchymal cell markers FN, vimentin, and α-SMA in the glomeruli of ADR-induced FSGS mice, suggesting that the YSHS granule inhibited the fibrosis of sclerotic glomeruli. Subsequently, a network pharmacology-based approach was used to identify the potential targets of the YSHS granule for the alleviation of glomerulosclerosis in FSGS, and the results showed that the YSHS granule down-regulated the expressions of BMP2, GSTA1, GATS3, BST1, and S100A9 and up-regulated the expressions of TTR and GATM in ADR-induced FSGS model mice. We also proved that the YSHS granule inhibited the fibrosis in the glomeruli of ADR-induced FSGS model mice through the suppression of the BMP2/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Grona styracifolia (Osbeck) Merr. (GS), a popular folk medicine, is clinically applied to treat nephrolithiasis. In this study, a urinary metabolic analysis was performed in a mouse model of renal calcium oxalate (CaOx) crystal deposition to identify the differentially altered metabolites in mice with oxalate-induced renal injury and explore the therapeutic mechanisms of GS against nephrolithiasis. Twenty-four mice were randomly divided into the control, oxalate and GS-treated groups. A metabolomics approach based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to analyze the metabolic profiles of the urine samples. In addition, network pharmacology analysis was performed with different databases. As a result, the protective effects of GS were verified by measuring biochemical parameters and detecting crystal deposition. Fifteen metabolites were identified as the differentially altered metabolites in mice with crystal-induced renal injury. Most were involved in amino acid and fatty acid metabolism. Thirteen of these metabolites showed a reversal trend following GS treatment. A component-target-metabolite network was further constructed and nine overlapping target proteins of GS and the differentially altered metabolites were discovered. Among these proteins, the expression of estrogen receptor 2 (ESR2) in renal tissues was significantly down-regulated while androgen receptor (AR) expression was obviously increased in the oxalate group compared with the control group. These changes were reversed by the GS treatment. In conclusion, GS exerts its therapeutic effect by regulating multiple metabolic pathways and the expression of ESR and AR in mice with oxalate-induced renal injury. [ABSTRACT FROM AUTHOR]

Sirtuin 1 (SIRT1), an NAD+-dependent deacylase, has been identified to be associated with renal tubular inflammatory conditions and metabolic disorders, which are risk factors of nephrolithiasis. To further confirm the role of the SIRT1 in kidney stone formation, the expression of SIRT1 was analyzed based on a mouse model and the genetic polymorphisms of SIRT1 gene was compared between patients with kidney stones and controls. The calcium oxalate (CaOx) crystal-induced renal injury model was established to analyzed the expression of SIRT1 in the kidney tissue of both wild-type and ApoE(−/−) mice. And a total of 430 Eastern Chinese subjects (215 patients with nephrolithiasis and 215 age- and gender-matched controls) were recruited for the present study to investigate the associations between 6 common single nucleotide polymorphisms (SNPs) (i.e., rs10509291, rs3740051, rs932658, rs33957861, rs3818292 and rs1467568) in the SIRT1 gene and the incidence of kidney stones. Pairwise linkage disequilibrium and the haplotypes of the 6 SNPs were also analyzed. The genotypes of SIRT1 gene polymorphisms were analyzed by a Snapshot assay. Reduced expression of SIRT1 was observed in the kidney of the mice in the crystal group, revealing the potential role of SIRT1 in the nephrolithiasis. However, we did not find a significant association between the 6 SNPs of the SIRT1 gene and kidney stone formation in the Eastern Chinese population. [ABSTRACT FROM AUTHOR]

Type 1 cardiorenal syndrome (CRS1) is characterized by acute cardiac disease (e.g., acute heart failure [AHF]), leading to acute kidney injury. Sirtuin 1 (SIRT1), an NAD+‐dependent deacylase, has been found to be associated with CRS1. To confirm whether a correlation exists between SIRT1 variants and the risk of CRS1, the association between the prevalence of CRS1 and single‐nucleotide polymorphisms (SNPs) within the SIRT1 gene was investigated in AHF patients. A total of 316 Chinese AHF participants (158 patients with CRS1 and 158 age‐ and sex‐matched controls) were recruited for the present observational study to investigate the association between nine common SIRT1 SNPs (i.e., rs7895833 G > A, rs10509291 T > A, rs3740051 A > G, rs932658 A > C, rs33957861 C > T, rs7069102 C > G, rs2273773 T > C, rs3818292 A > G, and rs1467568 A > G) and the susceptibility to CRS1. Significant differences in genotype distribution between the control and CRS1 groups were found for rs7895833 and rs1467568. After applying a Bonferroni adjustment, the A allele of rs7895833 was still found to be protective (p = 0.001; odds ratio [OR] = 0.77) against CRS1 in this study population. The AA genotype of rs7895833 and the GA genotype of rs1467568 were associated with a significantly reduced risk of CRS1 (OR = 0.23 and 0.49, respectively). rs7895833 and rs1467568 were further analyzed as a haplotype, and the GA haplotype (rs7895833‐rs1467568) exhibited a significant association with CRS1 (p = 0.008), while the AA haplotype showed a significant protective effect (p = 0.022). Our study showed that SIRT1 rs7895833 and rs1467568 polymorphisms had a significant effect on the risk of developing CRS1 in a population in China. [ABSTRACT FROM AUTHOR]

Background. As the malignant tumor with the highest incidence in teenagers, osteosarcoma has become a major problem in oncology research. In addition to surgical management, the pharmacotherapeutic strategy for osteosarcoma treatment is an attractive way to explore. It has been demonstrated that biochanin A has an antitumor capacity on multiple kinds of solid tumor, including osteosarcoma. But the precise mechanism of biochanin A against osteosarcoma is still needed to be discovered. Objective. To identify the potential therapeutic targets of biochanin A in treating osteosarcoma. Methods. In present study, an integrated approach including network pharmacology and molecular docking technique was conducted, which mainly comprises target prediction, network construction, gene ontology, and pathway enrichment. CCK8 test was employed to evaluate the cell viability of MG63 cells. Western-blot was used to verify the target proteins of biochanin A. Results. Ninety-six and 114 proteins were obtained as the targets of biochanin A and osteosarcoma, respectively. TP53, IGF1, JUN, BGLAP, ATM, MAPK1, ATF3, H2AFX, BAX, CDKN2A, and EGF were identified as the potential targets of biochanin A against osteosarcoma. Based on the western-blot detection, the expression of BGLAP, BAX, and ATF3 in MG63 cell line changed under the treatment of biochanin A. Conclusion. Biochanin A can effectively suppress the proliferation of osteosarcoma and regulate the expression of BGLAP, BAX, and ATF3, which may act as the potential therapeutic targets of osteosarcoma. [ABSTRACT FROM AUTHOR]

Background/Aims: Overproliferation of mesangial cells was believed to play an important role in the progress of diabetic nephropathy, one of the primary complications of diabetes. Hydrogen sulfide (H2S), a well-known and pungent gas with the distinctive smell of rotten eggs, was discovered to play a protective role in diabetic nephropathy. Methods: MTT assay was used to examine the viability of mesangial cells. Small interfering RNA was used to knock down the expression of TLR4 while specific inhibitor LY294002 to suppress the function of PI3K. H2S generation rate was determined by a H2S micro-respiration sensor. Results: Glucose of 25mM induced significant mesangial cells proliferation, which was accomplished by significantly inhibited endogenous H2S synthesis. And exogenous H2S treatment by NaHS markedly mitigated the overproliferation of mouse mesangial cells. Furthermore, it was found that H2S deficiency could result in TLR4 activation. And H2S supplementation remarkably inhibited TLR4 expression and curbed the mesangial cell overproliferation. Besides, PI3K/ Akt pathway inhibition also significantly ameliorated the cell overproliferation. Conclusion: High glucose (HG) induces mouse mesangial cell overproliferation via inhibition of hydrogen sulfide synthesis in a TLR-4-dependent manner. And PI3K/Akt pathway might also play a vital part in the HG-induced mesangial cell overproliferation. [ABSTRACT FROM AUTHOR]

A serum metabolomic method based on ultra-high-performance liquid chromatography coupled with mass spectrometry was developed to characterize hyperuricemia-related metabolic profiles and delineate the mechanism of Sanmiao wan (SMW), a traditional Chinese medicine (TCM), in treating hyperuricemic rats. With partial least-squares discriminant analysis for classification and selection of biomarkers, 13 potential biomarkers in mouse serum were identified in the screen, primarily involved in purine metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism and glycerophospholipid metabolism. Taking these potential biomarkers as screening indexes, SMW could reverse the pathological process of hyperuricemia through partially regulating the perturbed metabolic pathway except for glycerophospholipid metabolism. Our results showed that a metabolomic approach offers a useful tool to identify hyperuricemia-related biomarkers and provides a new methodological cue for systematically dissecting the underlying efficacies and mechanisms of TCM in treating hyperuricemia. [ABSTRACT FROM AUTHOR]

Background: Nephrolithiasis is a common urinary disease with a high recurrence rate of secondary stone formation. Several mechanisms are involved in the onset and recurrence of nephrolithiasis, e.g., oxidative stress, inflammation, apoptosis, and epithelial-mesenchymal transition (EMT). Vitexin, a flavonoid monomer derived from medicinal plants that exert many biological effects including anti-inflammatory and anticancer effects, has not been investigated in nephrolithiasis studies. Moreover, pyroptosis, a form of programmed cell death resulting from inflammasome-associated caspase activation, has not been studied in mice with nephrolithiasis.Purpose: We aimed to investigate the protective effect and underlying mechanisms of vitexin in nephrolithiasis, and the related role of pyroptosis in vivo and in vitro.Methods: Mouse models of nephrolithiasis were established via intraperitoneal injection of glyoxylate, and cell models of tubular epithelial cells and macrophages were established using calcium oxalate monohydrate (COM). Crystal deposition and kidney tissue injury were evaluated by hematoxylin and eosin, and von Kossa staining. Renal oxidative stress indexes including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), were analyzed. The renal expression of interleukin-1 beta (IL-1β), gasdermin D (GSDMD), osteopontin (OPN), CD44, and monocyte chemotactic protein 1 (MCP-1), and EMT-related proteins in renal tubular epithelial cells was assessed. Cell viability and the apoptosis ratio were evaluated.Results: In vivo, vitexin alleviated crystal deposition and kidney tissue injury, and decreased the level of MDA, and increased the levels of SOD, GSH, and CAT. Vitexin also reduced the levels of the pyroptosis-related proteins GSDMD, NLRP3, cleaved caspase-1, and mature IL-1β, which were elevated in mice with nephrolithiasis, and repressed apoptosis and the expression of OPN and CD44. Moreover, vitexin mitigated F4/80-positive macrophage infiltration and MCP-1 expression in the kidneys. Furthermore, an in vitro study showed that vitexin increased the viability of HK-2 cells and THP-1-derived macrophages, which was impaired by treatment with COM crystals, decreased the medium lactate dehydrogenase (LDH) level, and inhibited the expression of pyroptosis-related proteins in HK-2 cells and macrophages. Vitexin repressed EMT of HK-2 cells, with increased expression of pan-cytokeratin (Pan-ck) and decreased expression of Vimentin and alpha-smooth muscle actin (α-SMA), and downregulated the Wnt/β-catenin pathway. Moreover, vitexin suppressed tumor necrosis factor-α (TNF-α) and IL-1β mRNA expression, which was upregulated by COM in macrophages.Conclusion: Vitexin exerts protective effects against nephrolithiasis by inhibiting pyroptosis activation, apoptosis, EMT, and macrophage infiltration. In addition, GSDMD-related pyroptosis mediates nephrolithiasis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hierarchical LPC showed a high specific surface area up to 3382.32 m2/g. • The maximum adsorption capacity of MB by the LPC was as high as 1119.18 mg/g. • The adsorption kinetic was in well agreement with pseudo-second-order model. • Langmuir isotherm model fitted well to the adsorption experimental data. • The LPC exhibited the outstanding selective adsorption property to cationic dyes. Lignin is the most abundant renewable aromatic polymer in the world, but its complex structure makes it difficult for efficient utilization. In this study, lignin-based porous carbon (LPC) was prepared through hydrothermal treatment and KOH activation and then used as an adsorbent for the adsorption of methylene blue (MB). The influence of contact time, initial MB concentration, solution pH and adsorption selectivity on adsorption performance was explored. Hierarchical LPC showed a high specific surface area up to 3382.32 m2/g and a large number of active sites. The maximum adsorption capacity of MB was as high as 1119.18 mg/g. The adsorption kinetic was in well agreement with pseudo-second-order model. Langmuir isotherm model fitted well to the adsorption experimental data. The maximum adsorption capacity calculated from Langmuir isotherm model (1119.65 mg/g) approached the experimental result. Moreover, the LPC exhibited the outstanding selective adsorption property to cationic dyes, where the adsorption capacities of malachite green and rhodamine B were 2467.30 mg/g and 1657.82 mg/g, respectively. In addition to electrostatic interaction due to the negatively charged surface of LPC, hydrogen bonding and π - π stacking interactions were responsibility for the adsorption mechanism. On account of low-cost, excellent adsorption properties and favorable reusability, the LPC has the promising potential as a lignin-based absorbent for removing cationic dyes in wastewater treatment. [ABSTRACT FROM AUTHOR]

Rationale: The present understanding of the cellular characteristics and communications in crystal nephropathy is limited. Here, molecular and cellular studies combined with single-cell RNA sequencing (scRNA-seq) were performed to investigate the changes in cell components and their interactions in glyoxylate-induced crystallized kidneys to provide promising treatments for crystal nephropathy. Methods: The transcriptomes of single cells from mouse kidneys treated with glyoxylate for 0, 1, 4, or 7 days were analyzed via 10× Genomics, and the single cells were clustered and characterized by the Seurat pipeline. The potential cellular interactions between specific cell types were explored by CellChat. Molecular and cellular findings related to macrophage-to-epithelium crosstalk were validated in sodium oxalate (NaOx)-induced renal tubular epithelial cell injury in vitro and in glyoxylate-induced crystal nephropathy in vivo. Results: Our established scRNA atlas of glyoxylate-induced crystalline nephropathy contained 15 cell populations with more than 40000 single cells, including relatively stable tubular cells of different segments, proliferating and injured proximal tubular cells, T cells, B cells, and myeloid and mesenchymal cells. In this study, we found that Mrc1 + macrophages, as a subtype of myeloid cells, increased in both the number and percentage within the myeloid population as crystal-induced injury progresses, and distinctly express IGF1, which induces the activation of a signal pathway to dominate a significant information flow towards injured and proliferating tubule cells. IGF1 promoted the repair of damaged tubular epithelial cells induced by NaOx in vitro, as well as the repair of damaged tubular epithelial cells and the recovery of disease outcomes in glyoxylate-induced nephrolithic mice in vivo. Conclusion: After constructing a cellular atlas of glyoxylate-induced crystal nephropathy, we found that IGF1 derived from Mrc1 + macrophages attenuated crystal nephropathy through promoting renal tubule cell proliferation via the AKT/Rb signaling pathway. These findings could lead to the identification of potential therapeutic targets for the treatment of crystal nephropathy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Mucocutaneous separation (MCS) is one of the early stomal complications of ileal conduit diversion after radical cystectomy. It can result in abdominal infection and sepsis, prolonging patient recovery. Negative pressure wound therapy (NPWT) has been widely used for abdominal wounds after orthopedic and burn surgery. This case series describes its use in complicated MCS and ostomy retraction after ileal conduit diversion., Cases: We describe a case series of 3 patients with moderate to severe MCS with and without infection after robot-assisted radical cystectomy with ileal conduit diversion. Our patients were treated with NPWT to avoid infection and create a satisfactory environment for healing MCS. After 2 to 4 weeks of NPWT, all 3 patients had normal micturition function with no additional peristomal wounds or complications., Conclusion: Negative pressure wound therapy may be used in the management of complicated MCS after ileal conduit diversion., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2023 by the Wound, Ostomy and Continence Nurses Society.)

Nephrolithiasis is one of the most common and frequent urologic diseases worldwide. The molecular mechanism of kidney stone formation is complex and remains to be illustrated. Transcript factors (TFs) that influenced the expression pattern of multiple genes, as well as microRNAs, important posttranscriptional modulators, play vital roles in this disease progression. Datasets of nephrolithiasis mice and kidney stone patients were acquired from Gene Expression Omnibus repository. TFs were predicted from differentially expressed genes by RcisTarget. The target genes of differential-expressed microRNAs were predicted by miRWalk. MicroRNA-mRNA network and PPI network were constructed. Functional enrichment analysis was performed via Metascape and Cytoscape identified hub genes. The assay of quantitative real-time PCR (q-PCR) and immunochemistry and the datasets of oxalate diet-induced nephrolithiasis mice kidneys and kidney stone patients' samples were utilized to validate the bioinformatic results. We identified three potential key TFs (Egr1, Rxra, Max), which can be modulated by miR-181a-5p, miR-7b-3p and miR-22-3p, respectively. The TFs and their regulated hub genes influenced the progression of nephrolithiasis via altering the expression of genes enriched in the functions of fibrosis, cell proliferation and molecular transportation and metabolism. The expression changes of transcription factors were consistent in q-PCR and immunochemistry results. For regulated hub genes, they showed consistent expression changes in oxalate diet-induced nephrolithiasis mice model and human kidneys with stones. The identified and verified three TFs, which may be modulated by microRNAs in nephrolithiasis disease progression, mainly influence biological processes responding to fibrosis, proliferation and molecular transportation and metabolism. The transcript influence showed consistency in multiple nephrolithiasis mice models and kidney stone patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the regulatory mechanism of long non-coding RNAs (lncRNAs) in the occurrence and development of epithelial-mesenchymal transition (EMT) in calcium oxalate crystal-induced kidney injury. Materials and Methods: Gene core technique was used to screen differentially expressed lncRNAs and mRNAs in HK-2 cells before and after calcium oxalate monohydrate (COM) stimulation; differentially expressed mRNAs were then analyzed using GO and pathway analysis. The role of target lncRNA in EMT in renal tubular epithelial cells induced by COM was further investigated by applying a series of in vitro experiments. Results: Four differentially expressed lncRNAs (ABCA9-AS1, SPANXA2-OT1, RP11-955H22.1, and RP11-748C4.1) were up-regulated after 48 h of COM stimulation compared to the control group, where up-regulated expression of lncRNA SPANXA2-OT1 was the most significant. Thus, lncRNA SPANXA2-OT1 was further examined. Interference lncRNA SPANXA2-OT1 reversed the down-regulation of E-cadherin and Pan-ck, and up-regulated Vimentin and α-SMA induced by COM stimulation. The application of miR204 inhibitor weakened the interference effect of interfering RNA on lncRNA SPANXA2-OT1 and promoted the occurrence of EMT. Moreover, the miR204 simulator alleviated the overexpression effect of lncRNA SPANXA2-OT1 on COM-stimulated renal tubular epithelial cells and inhibited the occurrence of EMT in renal tubular epithelial cells. Also, a dual-luciferase reporter assay showed that miR-204 could bind to lncRNA SPANXA2-OT1 and Smad5, while lncRNA SPANXA2-OT1 could inhibit cell proliferation and promote cell apoptosis. Conclusion: The lncRNA SPANXA2-OT1 is involved in the occurrence and development of EMT in renal tubular epithelial cells induced by crystalline kidney injury by adsorbing miR-204 and up-regulating Smad5., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hu, Zhang, Li, Ding, Chen and Guo.)

Objective: To explore the theraputic effects and potential mechanisms of hydrogen-rich water (HRW) against oxalate-induced kidney injury. Methods: The mouse model of Calcium oxalate (CaOx) crystallization was established by feeding a soluble oxalate diet. Crystal deposition, tubular injury, fibrosis and reactive oxygen species (ROS) production in kidneys were examined by histology. Serum indexes of renal injury, inflammation and oxidative stress were detected by commercial kits. RNA sequencing (RNA-seq) was performed to screen potential pathways and the expressions of key molecules in these pathways were determined by western blotting and immunohistochemistry. Results: Crystal deposition, tubular injury, fibrosis and increased ROS production in kidneys of mice induced by oxalate diet were improved with HRW administration. The indexes of renal injury, inflammation and oxidative stress in serum of mice were upregulated by oxalate diet, which were reduced by HRW. A total of 3,566 differential genes were screened by RNA-seq and these genes were analyzed by pathway enrichment and PI3K/AKT, NF-κB, and TGF-β pathways were selected for further verification. The expressions of molecules related to PI3K-AKT pathway (PI3K, AKT, and p-AKT), NF-κB pathway (NF-κB p65, p- NF-κB p65, NLRP3, and IL-1β) and TGF-β pathway (TGF-β, TGF-βRI, TGF-βRII, p-Smad2, and p-Smad3) in renal tissues were increased by oxalate diet, which were reduced by HRW administration. Conclusion: HRW may alleviate oxalate-induced kidney injury with its anti-oxidative, anti-inflammatory and anti-fibrotic effects via inhibiting PI3K/AKT, NF-κB, and TGF-β pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Si, Liu, Cheng, Zhao, Zhou, Yu, Chen, Ding, Sun, Lu and Guo.)

Hydrogen has a significant protective effect on calcium oxalate-induced renal injury, but its effect on metabolic profiles is unknown. This study showed the effects of hydrogen on serum and urine metabolites in a renal injury model. Ultra-HPLC quadrupole time-of-flight-MS-based metabolomics was used to characterise metabolic variations. Twenty-five serum metabolites and 14 urine metabolites showed differences in the the nitrogen and oxygen inhalation (NO), nitrogen and oxygen inhalation combined with calcium oxalate induction (CaOx), and hydrogen inhalation combined with calcium oxalate induction (HO+CaOx) groups. Nineteen serum metabolites and 7 urine metabolites showed significant restoration to normal levels after hydrogen gas (H 2 ) treatment. These metabolites are primarily related to amino acid metabolism, fatty acid metabolism, and phospholipid metabolism. This study showed that a comprehensive metabolomics approach is an effective strategy to elucidate the mechanisms underlying the effects of hydrogen treatment on calcium oxalate-induced renal injury.

Background: The association between peroxisome proliferators-activated receptor γ (PPARγ) Pro12Ala polymorphism and T2DN risk is inconclusive and contradictory. Therefore, we performed a meta-analysis., Methods: All relevant studies were searched by using the PubMed and EMBASE. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Effect model selection was on the basis of heterogeneity test., Results: A total of 20 case-control studies with 9357 subjects were included in this meta-analysis. We found that PPARγ Pro12Ala polymorphism significantly associated with decreased T2DN risk (OR = 0.74; 95% CI 0.59-0.94; P = 0.01). In the subgroup analysis by race, Caucasian with PPARγ Pro12Ala polymorphism showed decreased T2DN risk (OR = 0.63; 95% CI 0.46-0.88; P = 0.006). But Asian with PPARγ Pro12Ala polymorphism did not show decreased T2DN risk (OR = 0.87; 95% CI 0.62-1.22; P = 0.41)., Conclusions: In conclusion, our meta-analysis study confirmed that PPARγ Pro12Ala polymorphism might contribute to the risk for T2DN.