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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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 99mTc-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 m2. Compared with CKD-EPI2009Scr, CKD-EPI2012Scr-cys formula had better diagnostic value with larger area under the receiver operating characteristic curve (ROCAUC, 0.879, p = 0.006), especially in young participants (ROCAUC, 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. [ABSTRACT FROM AUTHOR]