Contrasting effects of nitrogen enrichment on ecosystem temporal stability before and after nitrogen saturation in a subalpine grassland.

Increased atmospheric nitrogen deposition generally increases plant biomass production until reaching soil N saturation, which could increase the uncertainty of changes in ecosystem temporal stability and their mechanisms. Yet, the response of ecosystem stability to N enrichment and their underlying mechanisms are uncertain, especially when N saturation reached. Here, we conducted a multi-level N addition (0, 2, 5, 10, 15, 25, and 50 g N m-2 year-1; high added rates reached N saturation) experiment from 2018 to 2022 to estimate the effect of simulated N deposition on ecosystem biomass stability in a subalpine grassland located on the Qilian mountain of north-eastern Tibetan Plateau. Our results show that community biomass production increased with an increase in N addition in the first N addition experiment year, but decreased with increase in N addition rates after N saturation in subsequent years. We first find a negative quadratic relationship between biomass temporal stability and added N rate, whereby above N saturation threshold (5 g N m-2 year-1 at this site), increases in N addition reduces biomass temporal stability. The changes in biomass temporal stability are largely determined by dominant species stability, species asynchronous, and species richness. These results provide a better understanding of N-induced effect on ecosystem stability and their underlying mechanisms, which is important to evaluate functioning and services of ecological systems under global change scenarios.

Specnuezhenide suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis.

Diabetes osteoporosis is a chronic complication of diabetes mellitus (DM) and is associated with osteoclast formation and enhanced bone resorption. Specnuezhenide (SPN) is an active compound with anti-inflammatory and immunomodulatory properties. However, the roles of SPN in diabetic osteoporosis remain unknown. In this study, primary bone marrow macrophages (BMMs) were pretreated with SPN and were stimulated with receptor activator of nuclear factor kappa B ligand (RANKL; 50 ng/mL) to induce osteoclastogenesis. The number of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. The protein levels of cellular oncogene fos/nuclear factor of activated T cells c1 (c-Fos/NFATc1), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinases (MAPKs) were evaluated by western blot analysis. NF-κB luciferase assays were used to examine the role of SPN in NF-κB activation. The DM model group received a high-glucose, high-fat diet and was then intraperitoneally injected with streptozotocin (STZ). Micro-CT scanning, serum biochemical analysis, histological analysis were used to assess bone loss. We found that SPN suppressed RANKL-induced osteoclast formation and that SPN inhibited the expression of osteoclast-related genes and c-Fos/ NFATc1. SPN inhibited RANKL-induced activation of NF-κB and MAPKs. In vivo experiments revealed that SPN suppressed diabetes-induced bone loss and the number of osteoclasts. Furthermore, SPN decreased the levels of bone turnover markers and increased the levels of runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), calcium (Ca) and phosphorus (P). SPN also regulated diabetes-related markers. This study suggests that SPN suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis, and provides an experimental basis for the treatment of diabetic osteoporosis.

Survival Benefit of Pyloric Lymph Node Dissection for Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction Based on Tumor Diameter: A Large Cohort Study.

BACKGROUND: It is unclear whether the dissection of pyloric lymph nodes (PLNs, No. 5 and No. 6 lymph nodes) is necessary for adenocarcinoma of the esophagogastric junction (AEG) with a tumor diameter >4 cm based on current guidelines. This study aimed at evaluating whether pyloric node lymphadenectomy is essential for patients with Siewert type II/III AEG according to different tumor diameters. METHODS: This study included 300 patients on whom transabdominal total gastrectomy was performed for Siewert type II/III AEG at a high-volume center in China from January 2006 to December 2015. The index of estimated benefit from lymph node dissection (IEBLD) was used to analyze the priority of pyloric lymphadenectomy. RESULTS: In Siewert type II AEG, the 5-year overall survival (OS) and the 5-year disease-free survival (DFS) were similar between patients with PLN-positive cancer and patients of stage III AEG without PLN metastasis (23.1% vs. 30.6%, p = 0.505; 23.1% vs. 27.1%, p = 0.678). However, in Siewert type III AEG, the OS and the DFS of patients with PLN-positive cancer were significantly lower than that of patients with stage III without PLN metastasis (7.9% vs. 27.8%, p = 0.021; 0 vs. 26.8%, p = 0.005). According to the IEBLD, the dissection of PLNs did not appear to be beneficial in either Siewert type II AEG or type III AEG, whereas a stratified analysis revealed that PLN dissection yielded a high therapeutic benefit for Siewert type II AEG with tumor diameters >4 cm. CONCLUSION: We recommended that the PLNs be dissected in Siewert type II AEG when a tumor diameter is >4 cm. Total gastrectomy should be optional for Siewert type II AEG with a tumor diameter >4 cm and Siewert type III AEG.

Modification of the 2012 CKD-EPI equations for the elderly Chinese.

BACKGROUND: Our previous studies demonstrated that 2012 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were inaccurate enough for estimating glomerular filtration rate in elderly Chinese. Thus, this study was constructed to modify these equations. METHODS: A total of 839 subjects (aged ≥60 years) from four hospitals in China between October 2009 and December 2014 were included. A random sample of 674 (80.3 %) subjects was used as a training sample set, and the remaining 165 (19.7 %) subjects as the verification set. The equations were modified using the hill-climbing algorithm. RESULTS: Compared with the original CKD-EPI equations, the accuracy assessment indexes (bias, precision, accuracy and misclassification) were obviously improved after modification. Bland-Altman analysis also demonstrated that this modification attempt gained success to some extent. CONCLUSIONS: The modified 2012 CKD-EPI equations could be more accurate than the original equations for elderly Chinese individuals.

Estimating glomerular filtration rate by serum creatinine or/and cystatin C equations: An analysis of multi-centre Chinese subjects.

AIM: Various equations based on serum creatinine or/and cystatin C, required further validation in a Chinese population. We compared the performance of six Chinese equations (Mascr, Peiscr, Macys, Fengcys, Mascr-cys and Fengscr-cys) with the CKD-EPI equations in multi-centre Chinese subjects and evaluated their applicability in clinical practice. METHODS: A total of 1522 adult patients from four different hospitals of China were enrolled in the study. (99m) Tc-DTPA renal dynamic imaging was used as the reference GFR (rGFR), and serum creatinine and cystatin C were measured by standardized assays. An optimal score system was implemented in the study. RESULTS: The average rGFR of recruited subjects was 67.30±28.89 mL/min per 1.73m(2) . All estimated GFR (eGFR) correlated well with rGFR. In accordance with Bland-Altman analysis, the Fengscr-cys equations achieved optimal overall performance (score 14 vs 0-6), with least bias (median difference, -0.57 mL/min per 1.73m(2) ; median absolute difference, 8.83 mL/min per 1.73m(2) ), best precision (17.99 mL/min per 1.73m(2) ), highest accuracy (percentage of eGFR within 15%, 30% and 50% of the rGFR (P15 , P30 and P50 ; 49.7%, 78.7% and 91.8%, respectively); root-mean-square-error (RMSE, 16.28)). The Fengcys equation, a typical cystatin C based equation, was another well-behaved formula with an impressive performance. The Ma equations performed much poorer than the CKD-EPI equations. Consistent results can be observed in the GFR- /age- and sex-specific subgroups, while none equation yielded ideal accuracy in GFR<60 mL/min per 1.73 m(2) subgroup. CONCLUSION: The Fengscr-cys equation appeared to achieve the best performance for GFR estimation in overall Chinese adult patients. However, further research is warranted to improve the accuracy of available equations in GFR less than 60 mL/min per 1.73 m(2) individuals.

Diagnostic accuracy of serum cystatin C in chronic kidney disease: a meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is a major health problem worldwide with dramatically increasing incidence and prevalence. Serum cystatin C (sCysC) has been clarified by many studies as a relatively accurate marker to evaluate renal function. STUDY DESIGN: Meta-analysis of diagnostic test studies. SETTING AND POPULATION: Various clinical settings of CKD, including adult patients with diabetes, renal transplant patients, and so on. SELECTION CRITERIA: A computerized search of PubMed, Cochrane clinical trial database, and Current Contents (from inception until June 16, 2014) was performed to identify potentially relevant articles. INDEX TESTS: Increased sCysC concentration. REFERENCE TESTS: The measured glomerular filtration rate measured by nuclear medicine techniques such as 99Tc-diethylene triamine pentacaetic acid (99Tc-DTPA) or 51Cr-ethylenediamine tetra-acetic acid (51Cr-EDTA), or calculated by Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula or 24 hours creatinine clearance rate. RESULTS: In total 19 studies were included in this study. Across all settings, the diagnostic odds ratio (DOR) of sCysC in predicting CKD was 40 (95% CI, 26 - 61) when sensitivity and specificity was 0.85 (95% CI, 0.81 - 0.89) and 0.87 (95% CI, 0.84 - 0.90), respectively. The area under the curve for the receiver-operating characteristic (AUROC) of sCysC to predict CKD was 0.92 (95% CI, 0.90 - 0.94). For the diagnostic value of sCysC in diabetics with CKD, the DOR was 51 (95% CI, 22 - 122), with sensitivity and specificity of 0.89 and 0.87, respectively. Subgroup analysis showed that sCysC was of better diagnostic value in the West than in Asia, and the diagnostic value of sCysC assayed by particle-enhanced nephelometric immunoassay (PENIA) was higher than sCysC assayed by particle-enhanced turbidimetric immunoassay (PETIA). CONCLUSION: SCysC appears to be a good biomarker in the definition of CKD. However, its performance is different in subgroups restricted by clinical settings, race, and sCysC assay.

Application of creatinine- and/or cystatin C-based glomerular filtration rate estimation equations in elderly Chinese.

BACKGROUND: No conventional creatinine- or cystatin C-based glomerular filtration rate (GFR) estimation equation performed consistently outstandingly in elderly Chinese in our previous studies. This research aimed to further evaluate the performance of some recently proposed estimation equations based on creatinine and cystatin C, alone or combined, in this specific population. MATERIALS AND METHODS: The equations were validated in a population totaling 419 participants (median age 68 [range 60-94] years). The estimated GFR (eGFR) calculated separately by ten equations was compared with the reference GFR (rGFR) measured by the (99m)Tc-DTPA renal dynamic imaging method. RESULTS: Median serum creatinine, cystatin C, and rGFR levels were 0.93 mg/L, 1.13 mg/L, and 74.20 mL/min/1.73 m(2), respectively. The Chinese population-developed creatinine- and cystatin C-based (Cscr-cys) equation yielded the least median absolute difference (8.81 vs range 9.53-16.32, P<0.05, vs the Chronic Kidney Disease Epidemiology Collaboration serum creatinine equation), the highest proportion of eGFR within 15% and 30% of rGFR (P15 and P30, 55.13 and 85.44, P<0.05 and P<0.01, vs the Chronic Kidney Disease Epidemiology Collaboration serum creatinine equation), and the lowest root mean square error (14.87 vs range 15.30-22.45) in the whole cohort. A substantial agreement of diagnostic consistency between eGFR and rGFR (with a kappa 0.61-0.80) was also observed with the Cscr-cys equation. Moreover, measures of performance in the Cscr-cys equation were consistent across normal to mildly injured GFR strata and individuals aged ≤ 80 years. Among all the Cscr-cys equations, the elderly Chinese-developed creatinine-based (CEscr) equation performed best in this specific population. Nevertheless, none of the equations achieved ideal manifestation in the moderately to severely GFR-injured group or in individuals aged ≥ 80 years. CONCLUSION: The Cscr-cys equation appeared to be optimal in elderly Chinese among the investigated equations. If cystatin C is not available, the CEscr equation is an acceptable alternative. A multicenter study with abundant subjects to develop an apposite formula for elderly Chinese is assumed to be essential.

Comparisons between the 2012 new CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations and other four approved equations.

OBJECTIVE: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) reported two equations in 2012: one based on cystatin C concentration (CKD-EPI2012cys) and the other using both serum creatinine and cystatin C concentrations (CKD-EPI2012Scr-cys). We compared the adaptability of new formulae with other four equations. METHODS: Participants (n = 788; median age, 54 [range, 19-94] years) were recruited from the First Affiliated Hospital of Nanjing Medical University. The reference glomerular filtration rate (rGFR) was measured by a (99)mTc-DTPA renal dynamic imaging method, and the estimated glomerular filtration rate (eGFR) was calculated separately by the Chinese adapted Modification of Diet in Renal Disease equation (C-MDRD), MacIsaac, Ma, serum creatinine-based CKD-EPI equation (CKD-EPI2009Scr), CKD-EPI2012cys and CKD-EPI2012Scr-cys equations. We compared the performance of six equations with rGFR. RESULTS: Median rGFR was 76.35 (interquartile range, 59.03-92.50) mL/min/1.73 m(2). Compared with CKD-EPI2009Scr, CKD-EPI2012Scr-cys formula had better diagnostic value with larger area under the receiver operating characteristic curve (ROC(AUC), 0.879, p = 0.006), especially in young participants (ROC(AUC), 0.883, p = 0.005). CKD-EPI2012cys equation did not perform better than other available equations. Accuracy (the proportion of eGFR within 30% of rGFR [P30]) of the CKD-EPI2012Scr-cys equation (77.03%) was inferior only to MacIsaac equation (80.2%) in the entire participants, but performed best in young participants with normal or mildly-injured GFR. Neither of the two new CKD-EPI equations achieved any ideal P30 in the elderly participants with moderately-severely injured GFR. Linear regression analysis demonstrated a consistent result. In this study, CKD-EPI2012Scr-cys had a relatively better diagnosis consistency of GFR stage between the eGFR and rGFR in the whole cohort. CONCLUSION: CKD-EPI2012Scr-cys appeared less biased and more accurate in overall participants. Neither of the new CKD-EPI equations achieved ideal accuracy in senior participants with moderately-severely injured GFR. A large-scale study with more subjects and cooperating centers to develop new formulae for the elderly is assumed to be necessary.

Reference intervals for serum cystatin C and factors influencing cystatin C levels other than renal function in the elderly.

OBJECTIVE: The present study aimed to establish reference intervals for serum cystatin C (Scys-C) stratified by stages of chronic kidney disease, explore factors influencing Scys-C and compare the performance of Scys-C with serum creatinine (Scr) in the young and elderly. METHODS: A total of 800 participants, 516 young (<60 years) and 284 old (≥60 years) subjects were included in this study. Scys-C and Scr were assayed by the partical-enhanced immunoturbidimetry method and enzymatic method respectively. 95% reference interval was adopted to evaluate reference intervals. Influencing factors were characterized by multivariate linear regression analysis. Relationship between reference glomerular filtration rate (rGFR) and Scys-C or Scr was determined by correlation coefficient. RESULTS: Reference intervals for Scys-C were calculated to be 0.71-1.38 mg/L, 0.83-1.67 mg/L, 1.02-2.61 mg/L, 1.32-4.48 mg/L, 1.95-6.11 mg/L in the aged in CKD G1, G2, G3a, G3b and G4-5 stages, respectively. Body mass index(BMI), nephritis, kidney neoplasm and hypertension were demonstrated as factors affecting Scys-C in the elderly while gender, nephritis and kidney neoplasm were clarified as influencing factors in the young group. Scr levels were affected by more factors, such as body surface area and hematological disease. Correlation coefficient between rGFR and Scys-C or Scr showed that serum Scys-C was superior to Scr, especially in the subjects with mildly decreased renal function (-0.593 vs. -0.520). CONCLUSIONS: Factors other than renal function influenced Scys-C when applying to evaluate glomerular filtration rate (GFR), such as BMI, nephritis, kidney neoplasm and hypertension, and Scys-C had higher correlation with GFR than Scr in the elderly.