BackgroundMore than 1000 scientific papers have been devoted to flatfoot issue. However, a bimodal distribution of flatfoot indices in school-aged children has never been discovered. The purposes of this study were to establish a new classification of flatfoot by characteristic in frequency distribution of footprint index and to endue the classification with discrepancy in physical fitness.Methods/Principal FindingsIn a longitudinal survey of physical fitness and body structure, weight bearing footprints and 3 physical fitness related tests were measured in 1228 school-aged children. Frequency distribution of initial data was tested by Kolmogorov-Smirnov test for normality and a unique bimodal distribution of footprint index was identified. The frequency distribution of footprint index manifests two distinct modes, flatfoot and non-flatfoot, by deconvolution and bootstrapping procedures. A constant intersection value of 1.0 in Staheli's arch index and 0.6 in Chippaux-Smirak index could distinguish the two modes of children, and the value was constant in different age, sex, and weight status. The performance of the one leg balance was inferior in flatfoot girls (median, 4.0 seconds in flatfoot girls vs. 4.3 seconds in non-flatfoot girls, p = 0.04, 95% CI 0.404–0.484).DiscussionThe natural bimodality lends itself to a flatfoot classification. Bimodality suggests development of the child's foot arch would be a leap from one state to another, rather than a continuous growth as body height and weight. The underlying dynamics of the human foot arch and motor development will trigger research prospects.

Diabetic nephropathy (DN) represents one of the most devastating complications for patients with diabetes. The anti-diabetic activities of Magnoflorine (MF) were reported, with underlying mechanism unknown. Lysine-specific demethylase 3A (KDM3A) was identified in the renal injuries. In the current study, we investigated the functional role of MF in DN progression with the involvement of KDM3A. We reported that in the animal model of DN induced by streptozotocin (STZ) injection, MF attenuated inflammatory response and fibrosis in the kidneys. In cultured mesangial cells, MF similarly ameliorated abnormal proliferation and lowered the expression of inflammation- and fibrosis-related factors stimulated by high glucose (HG) treatment. Upon MF treatment, there was a decline in KDM3A-positive cells in renal tissues of rats, accompanying an augment in KDM3A ubiquitination. KDM3A upregulation in vitro by a proteasome inhibitor MG132 comparably dampened the inhibitory role of MF in inflammatory response and fibrosis. Further analyses revealed that MF increased transforming growth factor β-induced factor 1 (TGIF1) transcriptional activity by promoting ubiquitination and degradation of KDM3A, thus inhibiting the activation of TGF-β1/Smad2/3 signaling pathway. TGIF1 silencing weakened the repressive role of MF in mesangial cells as well. In conclusion, MF contributes to TGIF1 transcription via an epigenetic mechanism.

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Although pressure therapy is the mainstay of treatment for hypertrophic scars, its actual mechanism remains unknown. An in vitro study was designed to investigate the effects of positive pressure on the growth of human scar-derived fibroblasts through its transforming growth factor beta1 (TGF-beta1) secretion. A pneumatic pressure system connecting to a cell culture chamber was designed. Six-well cultured plates with fibroblasts implanted were treated with different pressure settings. Cells were treated with constant pressure 20 mm Hg above atmosphere pressure (group A n = 18) or with 40 mm Hg above atmosphere pressure (group B n = 18) daily for nine successive days. Cells without pressure were treated as the control study (group C n = 6). Each experimental group was divided into daily pressure applied at 24 hours (n = 6), 18 hours (n = 6), and 12 hours (n = 6). Cell counting was performed on the 2nd, 4th, 7th, 9th, 11th, and 14th day after implantation. On day 4, the concentration of transforming growth factor beta1 was measured, and cell doubling time was calculated. Compared with the control group, there was a significant decrease in cell count and the concentration in the 18-hour and 24-hour 20 mm Hg or 40 mm Hg pressure treated group. The cell doubling time was significantly increased in the 24-hour 20 mm Hg or 40 mm Hg pressure treated groups, and the 18-hour 40 mm Hg pressure treated group. (P < .05) Pressure inhibits the growth and activity of human scar fibroblasts, and a higher pressure application can shorten the daily application period. There should be an optimal pressure level corresponding to a daily application period to achieve the most effective results on pressure therapy for scars.

Background: Excessive amounts of heavy metals such as cadmium, chromium, cobalt, lead, thallium, and manganese are extremely harmful to the human body. These elements can accumulate in bone and impact bone metabolism. In this study, we investigated the relationship between age and the concentrations of these elements in human bone and blood. Methods: Bone and blood samples were obtained from both older and younger patients. The concentrations of the elements under investigation were measured by inductively coupled plasma mass spectrometry (ICP-MS), and the specific concentrations in the bone and blood were then calculated. Results: The results showed that with increasing age, the concentrations of chromium, cobalt, and thallium in bone decreased significantly, while the concentration of cadmium in bone markedly increased. However, there was no clear correlation between age and the concentrations of these heavy metals in blood. Notably, there was a close correlation between the concentration of cobalt in bone and the presence of osteopenia. Conclusions: Senescence of the human body is accompanied by the shifting of cobalt, chromium, and thallium from the bone to the outer-bone. However, the concentration of cadmium in bone increases with age. These changes are very likely to be related to the equilibrium of bone metabolism in senescent individuals. In addition, only cobalt was shown to be significantly related to osteopenia.