Robotic surgery shows distinct advantages in protecting the pelvic autonomic nerves and relieving post-operative sexual dysfunction.

Full robotic gastrectomy with intracorporeal robot-sewn anastomosis for gastric cancer is safe and does not increase the complication risk during or after surgery. J. Surg. Oncol. 2016;113:397-404. © 2016 Wiley Periodicals, Inc.

Osteoporosis is a global bone disease characterized by reduced bone mineral density (BMD) and increased risk of fractures. The risk of developing osteoporosis increases with aging, especially after menopause in women. Discovering the signaling pathways that play a significant role in aging‐ and menopause‐induced osteoporosis should accelerate osteoporosis drug discovery. In this study, we found that bile acid membrane receptor Tgr5 knockout C57BL/6J mice had similar bone mass as wild‐type mice during early and middle‐age (before 4 months old) bone remodeling; however, Tgr5‐/‐ markedly decreased bone mass in aged (more than 7 months old) and ovariectomized (OVX) mice compared with wild‐type mice. Moreover, Tgr5 knockout strongly induced osteoclast differentiation but had no effect on osteoblast activity. Treatment with different TGR5 agonists consistently inhibited osteoclast differentiation. Importantly, our results showed that Tgr5 regulates osteoclastogenesis by the AMP‐activated protein kinase (AMPK) signaling pathway, which is a central metabolic pathway involved in the pathophysiology of aging and age‐related diseases. The bile acid nuclear receptor FXR is an established regulator of bone metabolism. We screened the derivatives of betulinic acid (BA), a known TGR5 agonist, to identify novel dual agonists of FXR and TGR5. The derivative SH‐479, a pentacyclic triterpene acid, could activate both TGR5 and FXR, with a better inhibitory effect on osteoclastogenesis compared with agonists solely activating FXR or TGR5 and additionally enhanced osteoblastogenesis. Furthermore, SH‐479 therapeutically abrogated bone loss in C57BL/6J mice through the bone remodeling pathways. Together, our results demonstrate that dual targeting the bile acid membrane receptor TGR5 and nuclear receptor FXR is a promising strategy for osteoporosis. © 2018 American Society for Bone and Mineral Research.

We aimed to investigate plasma growth differentiation factor-15 (GDF-15) levels in pediatric pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD), and assess the association with hemodynamic parameters. Plasma GDF-15 levels were measured in children with PAH-CHD (n = 46) and compared to children with CHD without PAH (n = 39). Normal individuals (n = 30) served as health control group. Plasma GDF-15 levels were significantly elevated in patients with PAH-CHD compared with those with CHD without PAH (median 1415 ng/L, interquartile range [IQR] 926.7-2111.7 ng/L vs. 890.6 ng/L, IQR 394.7-1094.3 ng/L, p < 0.01). Elevated plasma GDF-15 levels were positively related to Functional Class, uric acid, N-terminal pro-B-type natriuretic peptide (NT-proBNP), pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary blood flow/systemic blood flow and pulmonary vascular resistance, and a lower mixed venous oxygen saturation (Sv). The area under the curve (AUC) for adding GDF-15 to NT-proBNP was not superior to the AUC of NT-pro BNP alone (AUC difference 0.0295, p = 0.324) (NT-proBNP, AUC 0.823, 95% CI 0.725-0.897; GDF-15 plus NT-proBNP, AUC 0.852, 95% CI 0.759-0.92), whereas it revealed a slightly greater specificity and positive predictive value. The diagnostic power of NT-pro BNP was not inferior to GDF-15 (AUC difference 0.0443, p = 0.43). Plasma GDF-15 levels might be a surrogate marker for pediatric PAH-CHD.

No abstract

Femoral neck compression strength index (fCSI), a novel phenotypic parameter that integrates bone density, bone size, and body size, has significant potential to improve hip fracture risk assessment. The genetic factors underlying variations in fCSI, however, remain largely unknown. Given the important roles of the receptor activator of the nuclear factor-κB ligand/receptor activator of the nuclear factor-κB/osteoprotegerin (RANKL/RANK/OPG) pathway in the regulation of bone remodeling, we tested the associations between RANKL/RANK/OPG polymorphisms and variations in fCSI as well as its components (femoral neck bone mineral density [fBMD], femoral neck width [FNW], and weight). This was accomplished with a sample comprising 1873 subjects from 405 Caucasian nuclear families. Of the 37 total SNPs studied in these three genes, 3 SNPs, namely, rs12585014, rs7988338, and rs2148073, of RANKL were significantly associated with fCSI (P = 0.0007, 0.0007, and 0.0005, respectively) after conservative Bonferroni correction. Moreover, the three SNPs were approximately in complete linkage disequilibrium. Haplotype-based association tests corroborated the single-SNP results since haplotype 1 of block 1 of the RANKL gene achieved an even more significant association with fCSI (P = 0.0003) than any of the individual SNPs. However, we did not detect any significant associations of these genes with fBMD, FNW, or weight. In summary, our findings suggest that the RANKL gene may play an important role in variation in fCSI, independent of fBMD and non-fBMD components. KeywordsFemoral neck compression strength index; Femoral neck bone mineral density; Femoral neck width; RANKL/RANK/OPG gene; Quantitative transmission disequilibrium test Osteoporosis is a systemic skeletal disorder characterized by impaired bone strength and an elevated risk of osteoporotic fractures. Osteoporosis represents a major health problem throughout the world and the most serious consequence of osteoporosis is hip fracture, which has a high associated morbidity and mortality [1]. Currently, measurements of bone mineral density (BMD) are widely used to assess hip fracture risk [2,3]. However, BMD alone can only account for about 50-70% of total bone strength variation [4]. Among other risk factors of hip fracture, femoral neck width (FNW) and body weight have been repeatedly reported to be correlated with hip fracture risk [5][6][7][8][9][10]. Femoral neck compression strength index (fCSI) [11], a function of femoral neck BMD (fBMD), FNW, and weight based on structural engineering principles, may have the potential to improve hip fracture risk assessment. Karlamangla et al. [11] observed that a 1-standard-deviation (SD) decrease in fCSI was associated with an approximately 2.56-fold increase in hip fracture risk (P < 0.0001), while a 1-SD decrease in fBMD was associated with only a 1.96-fold increase in hip fracture (P = 0.0013). [18][19][20]. In the current study, for the first time, we comparatively examined the influence of RANKL/RANK/OPG gene variant...

BACKGROUND: The insulin-like growth factor 1 (IGF1) gene, which plays a crucial role in hypothalamicpituitary-ovarian hormone-controlled metabolic processes, may influence the onset of menarche. Our study aimed to test association between IGF1 polymorphisms with the variation of age at menarche (AAM) in Caucasian females. METHODS: We recruited a sample of 1048 females from 354 Caucasian nuclear families and genotyped 19 single-nucleotide polymorphisms (SNPs) spanning the entire IGF1 gene. Pairwise linkage disequilibrium among SNPs was measured, and the haplotype blocks were inferred. Both single SNP markers and haplotypes were tested for association with AAM using the quantitative transmission disequilibrium test. RESULTS: Significant association (P 5 0.0153) between AAM and SNP3 (rs6214) in block1 was detected. CONCLUSIONS: Our results suggested a potential effect of SNP3 in the IGF1 gene on AAM variation in Caucasian women for the first time. However, further independent studies are needed to confirm our findings.

Objectives: This study aimed to investigate the roles of connective tissue growth factor (CTGF) and transforming growth factor-β₁ (TGF-β₁) in atrial fibrosis in patients with chronic atrial fibrillation. Methods: Up to 40 cases involving simple mitral valve replacement surgery were divided into 2 groups: the chronic atrial fibrillation (cAF) group (n = 28) and the sinus rhythm group (n = 12). Echocardiography was used to measure the cardiac cavity size and analyze the cardiac function. Right atrial specimens were obtained during the operation. The collagen volume fraction in the atrial specimens was examined. The mRNA and protein levels of TGF-β₁, Smad3 and CTGF were also investigated. Results: Compared with the sinus rhythm group, the cAF group had higher collagen content in the right atrial tissues. The mRNA and protein levels of TGF-β₁, Smad3 and CTGF were also significantly elevated in the cAF group (p < 0.05). The mRNA and protein levels of TGF-β₁ and CTGF in the cAF group correlated positively with the collagen volume fraction. The positive correlation between the expression of TGF-β₁ and CTGF was also demonstrated. Conclusions: CTGF is upregulated via the TGF-β₁/Smad pathway in the atrial myocardium of cAF patients. Furthermore, the TGF-β₁/Smad pathway may play an important role in the structural remodeling during atrial fibrosis.