Dermatofibrosarcoma protuberans with the nut sack
Aging is a universal process that renders individuals vulnerable to many diseases. Although this process is irreversible, dietary modulation and caloric restriction are often considered to have antiaging effects. Dietary modulation can increase and maintain circulating ketone bodies, especially β-hydroxybutyrate (β-HB), which is one of the most abundant ketone bodies in human circulation. Increased β-HB has been reported to prevent or improve the symptoms of various age-associated diseases. Indeed, numerous studies have reported that a ketogenic diet or ketone ester administration alleviates symptoms of neurodegenerative diseases, cardiovascular diseases, and cancers. Considering the potential of β-HB and the intriguing data emerging from in vivo and in vitro experiments as well as clinical trials, this therapeutic area is worthy of attention. In this review, we highlight studies that focus on the identified targets of β-HB and the cellular signals regulated by β-HB with respect to alleviation of age-associated ailments.HCN channels regulate excitability and rhythmicity in the hippocampal CA1 pyramidal cells. Perturbation in the HCN channel current (Ih) is associated with neuropsychiatric disorders, such as autism spectrum disorders. Recently, protein arginine methyltransferase 7 (PRMT7) was shown to be highly expressed in the hippocampus, including the CA1 region. However, the physiological function of PRMT7 in the CA1 neurons and the relationship to psychiatric disorders are unclear. Here we showed that PRMT7 knockout (KO) mice exhibit hyperactivity and deficits in social interaction. The firing frequency of the CA1 neurons in the PRMT7 KO mice was significantly higher than that in the wild-type (WT) mice. Compared with the WT CA1 neurons, the PRMT7 KO CA1 neurons showed a more hyperpolarized resting potential and a higher input resistance, which were occluded by the Ih-current inhibitor ZD7288; these findings were consistent with the decreased Ih and suggested the contribution of Ih-channel dysfunction to the PRMT7 KO phenotypes. The HCN1 protein level was decreased in the CA1 region of the PRMT7 KO mice in conjunction with a decrease in the expression of Shank3, which encodes a core scaffolding protein for HCN channel proteins. A brief application of the PRMT7 inhibitor DS437 did not reproduce the phenotype of the PRMT7 KO neurons, further indicating that PRMT7 regulates Ih by controlling the channel number rather than the open probability. Moreover, shRNA-mediated PRMT7 suppression reduced both the mRNA and protein levels of SHANK3, implying that PRMT7 deficiency might be responsible for the decrease in the HCN protein levels by altering Shank3 expression. These findings reveal a key role for PRMT7 in the regulation of HCN channel density in the CA1 pyramidal cells that may be amenable to pharmacological intervention for neuropsychiatric disorders.The innate immune response is active in invertebrate larvae from early development. Induction of immune response pathways may occur as part of the natural progression of larval development, but an up-regulation of pathways can also occur in response to a pathogen. Here, we took advantage of a protozoan ciliate infestation of a larval geoduck clam culture in a commercial hatchery to investigate the molecular underpinnings of the innate immune response of the larvae to the pathogen. Navitoclax Larval proteomes were analyzed on days 4-10 post-fertilization; ciliates were present on days 8 and 10 post-fertilization. Through comparisons with larval cultures that did not encounter ciliates, proteins implicated in the response to ciliate presence were identified using mass spectrometry-based proteomics. Ciliate response proteins included many associated with ribosomal synthesis and protein translation, suggesting the importance of protein synthesis during the larval immune response. There was also an increased abundance of proteins typically associated with the stress and immune responses during ciliate exposure, such as heat shock proteins, glutathione metabolism, and the reactive oxygen species response. These findings provide a basic understanding of the bivalve molecular response to a mortality-inducing ciliate and improved characterization of the ontogenetic development of the innate immune response.To investigate the clinical efficacy of pre-operative simulation using a three-dimensional (3D) printing model for surgical treatment of old and complex tibial plateau fractures. Forty-two patients with old and complex tibial plateau fractures were retrospectively reviewed from January 2014 to January 2018, which were divided into a conventional planning group (n = 22) and a planning with 3D printing group (n = 20). In the planning with 3D printing group, preoperative equal-ratio fracture models prepared using the 3D printing technique were used to perform pre-operative simulation and guide the real surgical operation. In the conventional planning group, the operation was performed based on pre-operative computed tomography (CT) images. Surgery duration, blood loss and the number of fluoroscopy during operations were recorded. During follow-up, the quality of fracture reduction and complications were also recorded. Knee functions were evaluated using the hospital for special surgery (HSS) scoring system. The tive planning and to making the surgical procedure accurate and personalized. However, its clinical effectiveness need to be further assessed by a prospective randomized-controlled study.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Idiopathic sudden sensorineural hearing loss (ISSNHL) is an emergency disease requiring immediate diagnosis and treatment. The incidence of ISSNHL in the Western countries' population was estimated to 5-20 per 100,000 inhabitants. The etiology of ISSNHL remains unknown. Its pathogenesis is most often suggested to be due to a disturbed microcirculation and infection. Previous studies have reported that comorbidities, including hypertension, diabetes mellitus (DM), and hyperfibrinogenemia are risk factors of ISSNHL. This study aimed at investigating the clinical characteristics, laboratory parameters and comorbidities of patients with ISSNHL. Our study suggests that the annual incidence of ISSNHL in China mainland is 19 per 100 000. The clinical characteristics and prevalence of comorbidities of ISSNHL patients are different according to age distribution and hearing results. Moreover, the patients with vertigo, hypertension, DM and high TG suffered more often from severe hearing loss compared with the counterparts.