A time-averaged serum bicarbonate-based nomogram to predict the probability of residual kidney function preservation for patients undergoing peritoneal dialysis.

OBJECTIVE: Residual kidney function (RKF) is an important prognostic indicator in peritoneal dialysis (PD) patients. So far, there are no prediction tools available for RKF, and the association between serum bicarbonate and RKF has received little attention in patients with PD. We aimed to develop a nomogram for the preservation of RKF based on the time-averaged serum bicarbonate (TA-Bic) levels. PATIENTS AND METHODS: A prediction model was established by conducting a retrospective cohort study of 151 PD patients who had been treated at the First Affiliated Hospital of Anhui Medical University. The nomogram was developed using a multivariate Cox regression model. The discrimination, calibration, and clinical utility of the model were evaluated by the C-index, receiver operating curve (ROC) curve, calibration curve, and decision curve analysis. RESULTS: In the elderly PD onset, higher baseline values of residual glomerular filtration rate, total Kt/V and higher TA-Bic levels were identified as protective predictors of RKF loss. The nomogram was conducted on the basis of the minimum value of the Akaike Information Criterion and Bayesian Information Criterion with a reasonable C-index of 0.766, showing great discrimination, proper calibration, and high potential for clinical practice. Through the total score of the nomogram, the patients were classified into the high-risk group and low-risk group, and a higher cumulative incidence of complete RRF loss was found in the high-risk group compared with the patients in the low-risk group. CONCLUSIONS: The novel predictive nomogram model can predict the probability of RKF preservation in long-term PD patients with high accuracy. Future studies are needed to externally validate the current nomogram before clinical application.

Prognostic and immune roles of UROC1 in human cancers: from mechanism exploration of NAFLD and HCC to pan-cancer analysis.

OBJECTIVE: Both non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are prevalent diseases worldwide. This study aimed to explore the underlying mechanisms of NAFLD and HCC and identify new therapeutic targets for human cancers. MATERIALS AND METHODS: NAFLD and HCC gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were utilized to identify co-expressed genes associated with NAFLD and HCC. Public databases were consulted to find common targets of NAFLD and HCC. Enrichment analysis and CIBERSORT techniques were employed to analyze the pathways enriched with DEGs and the attributes of infiltrating immune cells. Furthermore, the expression data of UROC1 and clinical information of patients were acquired from The Cancer Genome Atlas (TCGA) database. Finally, the expression of the UROC1 was validated by immunohistochemistry (IHC). RESULTS: Through a comprehensive bioinformatics analysis, eight hub genes (CCL2, CCR2, IL6, CSF3R, ATL2, SESN3, UROC1, FIGNL1) were identified. Enrichment analysis indicated that inflammatory and immune response may be common features between NAFLD and HCC. CIBER-SORT analysis revealed an imbalance of plasma cells and macrophages in NAFLD and HCC. Pan-cancer analysis demonstrated that UROC1 expression was related to clinical outcomes and tumor immunity in various cancers. Moreover, a strong correlation was exhibited between UROC1 expression and crucial elements, including tumor mutation burden (TMB), microsatellite instability (MSI), multiple immune checkpoints (ICP), and tumor microenvironment (TME). Importantly, an adverse clinical prognosis of HCC was linked to decreased UROC1 expression, which was consistent with IHC results. CONCLUSIONS: We identified eight hub genes (CCL2, CCR2, IL6, CSF3R, ATL2, SESN3, UROC1, FIGNL1), which may become early diagnostic and therapeutic targets for NAFLD and HCC. The pan-cancer analysis of UROC1 provides new evidence for its broad application prospects in the field of HCC and other cancers.

Risk factors and etiological characteristics of urinary tract infection in hospitalized continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: This study aimed to explore the risk factors and etiological characteristics of urinary tract infection (UTI) in continuous ambulatory peritoneal dialysis (CAPD) patients. PATIENTS AND METHODS: A total of 90 CAPD patients with UTI comprised the infection group, while 32 CAPD patients without UTI constituted the control group. The risk factors and etiological characteristics of UTI were analyzed. RESULTS: Of the 90 bacterial strains isolated, 30 were Gram-positive (33.3%) and 60 were Gram-negative (66.7%). Urinary stones or urinary tract structural changes were more prevalent in the infection group (71.1%) than in the control group (46.9%) (χ² = 6.076, p = 0.018). The proportion of patients with residual diuresis less than 200 ml was higher in the infection group (50%) than in the control group (15.6%) (χ² = 11.533, p = 0.001). The distribution of primary disease differed between the two groups. Patients in the infection group had higher CAPD vintage, levels of triglycerides, fasting blood glucose, blood creatinine, blood phosphorus, and calcium-phosphorus product than those in the control group. Multivariate binary logistic regression analysis indicated that residual diuresis less than 200 ml (OR = 3.519, p = 0.039) and urinary stones or structural changes (OR = 4.727, p = 0.006) were independent risk factors for UTI. CONCLUSIONS: Urine cultures of CAPD patients with UTI contained a complex distribution of pathogenic bacteria. Urinary stones or structural changes and residual diuresis less than 200 ml were independent risk factors for UTI.

SIRT3 retards intervertebral disc degeneration by anti-oxidative stress by activating the SIRT3/FOXO3/SOD2 signaling pathway.

OBJECTIVE: The objective of this paper is to determine whether SIRT3 could retard intervertebral disc degeneration and study the mechanism. MATERIALS AND METHODS: We chose the 3-month mice to establish intervertebral disc degeneration model and study the effect of SIRT3 on the intervertebral disc by Western blotting, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), immunohistochemistry. Mouse nucleus pulposus cells were cultured to study the exact mechanism. RESULTS: The expression of SIRT3 was decreased in degenerated human nucleus pulposus. Intervertebral discs of mice treated with theacrine expressed more collagen II and less collagen X. In addition, nucleus pulposus cells stimulated with interleukin-1ß (IL-1ß) expressed less SIRT3 than that in the control group and nucleus pulposus cells with SIRT3 overexpress vectors expressed more collagen II FOXO3a and superoxide dismutase 2 (SOD2), indicating that SIRT3 could improve the intervertebral disc degeneration by anti-oxidative stress. CONCLUSIONS: SIRT3 is a protective factor for intervertebral discs and can reduce oxidative stress in the intervertebral disc.

FK506 reduces albuminuria through improving podocyte nephrin and podocin expression in diabetic rats.

OBJECTIVE AND DESIGN: Several works in the setting of early experimental diabetic nephropathy using anti-inflammatory drugs, such as the calcineurin inhibitor FK506, have shown prevention of the development or amelioration of renal injury including proteinuria. The exact mechanisms by which anti-inflammatory drugs lower the albuminuria have not been still clarified well. MATERIALS: The diabetic rats were induced by using streptozotocin. TREATMENT: The diabetic rats were subjected to oral FK506 treatment at a dose of 0.5 or 1.0 mg/kg daily for 4 weeks. METHODS: Renal histology for the ultrastructural evaluation was determined by electron microscope, followed by analyses of renal nephrin and podocin and detection of renal iNOS(+) macrophages and NF-κB-p-p65(+). RESULTS: Elevated 24-h urinary albumin excretion rate was markedly attenuated by FK506 treatment. In diabetic model rats, FK506 treatment at a dose of 0.5 or 1.0 mg/kg significantly increased the expression of nephrin and podocin when compared to control. As expected, rats in control diabetic group had an increase in GBM thickening and foot process effacement when compared to normal rats; increased GBM thickening and foot process effacement were ameliorated by FK506 treatment with 0.5 and 1.0 mg/kg. Histologically, there was marked accumulation of ED-1(+)cells (macrophages) in diabetic kidneys, and FK506 treatment failed to inhibit it. In contrast, FK506 treatment at 0.5 and 1.0 mg/kg doses significantly inhibited the elevated ED-1(+)/iNOS(+) cells in the kidneys of diabetic rats. ED-1(+)/NF-κB-p-p65(+) cells were significantly increased in positive diabetic kidneys compared to those of normal rats. FK506 treatment at 0.5 and 1.0 mg/kg significantly attenuated the elevated ED-1(+)/NF-κB-p-p65(+) cells in diabetic kidneys. Additionally, a positive correlation was observed between ED-1(+)/iNOS(+) cells and albuminuria (r = 0.87, p < 0.05). Likewise, ED-1(+)/iNOS(+) cells were correlated negatively with both nephrin and podocin protein (r = -0.70, p < 0.05; r = -0.68, p < 0.05, respectively). CONCLUSION: Our results show that FK506 not only upregulates expression of nephrin and podocin but also inhibits macrophage activation to protect against podocyte injury.

Renoprotective effects of combination of angiotensin converting enzyme inhibitor with mycophenolate mofetil in diabetic rats.

OBJECTIVE AND DESIGN: Previously it was shown that blocking of the renin-angiotensin system (RAS) by angiotensin converting enzyme (ACE) inhibitors, or suppression of inflammatory responses by immunosuppressive drugs such as mycophenolate mofetil (MMF) could attenuate renal injury in diabetic rats. Whether RAS blockade combined with an immunosuppressive drug provides superior renoprotection against diabetic nephropathy has not been clearly delineated. MATERIALS: Diabetes was induced by injection of streptozotocin after uninephrectomy. TREATMENT: Rats were randomly separated into five groups: control, diabetes, diabetes treated with enalapril (an ACE inhibitor, 10 mg/kg/d by gastric gavage), diabetes treated with MMF (10 mg/kg/d by gastric gavage), or diabetes treated with a combination of both agents and were followed for 8 weeks. METHODS: 24 h urinary albumin excretion rate (AER) was determined, renal injury was evaluated, immunohistochemistry for ED-1 macrophage marker, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were performed, and expression of transforming growth factor (TGF)-beta1 protein was determined by Western blotting analysis. RESULTS: Diabetes was associated with a considerable increase in AER. Both enalapril and MMF retarded the increase in albuminuria, which was nearly completely abrogated by combination therapy. Increased glomerular volume and tubulointerstitial injury index in diabetic rats was attenuated by treatment with either enalapril or MMF and further reduced by the combination of the two. Elevated malondialdehyde levels in renal tissue were reduced by enalapril or MMF and, more effectively, by combined enalapril with MMF. Renal overexpression of ICAM-1 was not retarded by enalapril and attenuated by MMF or combined enalapril with MMF. Combination therapy was associated with a superior suppression of diabetes-induced macrophage recruitment and overexpression of MCP-1 and TGFbeta1 compared to either monotherapy in renal tissue. CONCLUSION: The combination of enalapril and MMF confers superiority over monotherapy in renoprotection, a mechanism which may be at least partly correlated with synergistic suppression of increased macrophage recruitment and overexpression of MCP-1 and TGF-beta1 in renal tissue in diabetic rats.

Measurement of the total cross section for hadronic production by e(+)e(-) annihilation at energies between 2.6-5 GeV

Using the upgraded Beijing Spectrometer, we have measured the total cross section for e(+)e(-) annihilation into hadronic final states at center-of-mass energies of 2.6, 3.2, 3.4, 3.55, 4.6, and 5.0 GeV. Values of R, sigma(e(+)e(-)-->hadrons)/sigma(e(+)e(-)-->&mgr;(+)&mgr;(-)), are determined.