Primary cilia in satellite cells are the mechanical sensors for muscle hypertrophy

Skeletal muscle atrophy is commonly associated with aging, immobilization, muscle unloading, and congenital myopathies. Generation of mature muscle cells from skeletal muscle satellite cells (SCs) is pivotal in repairing muscle tissue. Exercise therapy promotes muscle hypertrophy and strength. Primary cilium is implicated as the mechanical sensor in some mammalian cells, but its role in skeletal muscle cells remains vague. To determine mechanical sensors for exercise-induced muscle hypertrophy, we established three SC-specific cilium dysfunctional mouse models—Myogenic factor 5 (Myf5)-Arf-like Protein 3 (Arl3)^−/−, Paired box protein Pax-7 (Pax7)-Intraflagellar transport protein 88 homolog (Ift88)^−/−, and Pax7-Arl3^−/−—by specifically deleting a ciliary protein ARL3 in MYF5-expressing SCs, or IFT88 in PAX7-expressing SCs, or ARL3 in PAX7-expressing SCs, respectively. We show that the Myf5-Arl3^−/− mice develop grossly the same as WT mice. Intriguingly, mechanical stimulation-induced muscle hypertrophy or myoblast differentiation is abrogated in Myf5-Arl3^−/− and Pax7-Arl3^−/− mice or primary isolated Myf5-Arl3^−/− and Pax7-Ift88^−/− myoblasts, likely due to defective cilia-mediated Hedgehog (Hh) signaling. Collectively, we demonstrate SC cilia serve as mechanical sensors and promote exercise-induced muscle hypertrophy via Hh signaling pathway.

Exercise is considered as the primary intervention to improve muscle strength and to counteract muscle atrophy. While physical exercise training is considered a suitable intervention to improve muscle strength and endurance in healthy individuals, some people are resistant to the beneficial effects of exercise (1–3). It has been debated whether exercise is beneficial or harmful for patients with myopathic disorders (4) and type 2 diabetes (5). This so-called “exercise resistance” is considered congenital, and one recently identified causative factor involved in exercise resistance is hepatokine selenoprotein P (2, 6).Primary cilia have a mechanosensory function in bone cells (7), renal cells (8), and airway smooth muscle cells exert a role in sensing oscillatory fluid flow and transducing extracellular mechano-chemical signals into intracellular biochemical responses (9). Intriguingly, low muscle tone is a clinical feature often present in congenital ciliopathies with unclear underlying mechanisms (10). Arf-like Protein 3 (ARL3) is a highly conserved ciliary protein across ciliated organisms. ARL3, a regulator of intraflagellar transport in primary cilia, has been reported involving with various ciliary signaling functions (11, 12) and maintaining cell division polarity (13). Arl3 mutations cause Joubert syndrome (14, 15). Arl3^−/− knockout does not affect cilia structure but compromises ciliary function (16).Cells utilize primary cilia to convert environmental cues, mechanical or chemical, into various cellular signaling essential for development (17–21). During skeletal muscle development, Hedgehog (Hh) signaling helps to initiate the myogenic program (22). In myoblast cells, Fu et al. (23) showed that primary cilia are assembled during the initial stages of myogenic differentiation but disappear as cells progress through myogenesis. The ablation of primary cilia suppresses Hh signaling and myogenic differentiation while enhancing proliferation. However, there are still significant gaps in our understanding of how exercise and mechanical signals activate the Hh signaling pathway. In the present study, we hypothesize that primary cilia in satellite cells (SCs) transduce mechanical stimulation through activation of Hh signaling and promote muscle hypertrophy induced by exercise.Hypertrophy of skeletal muscle is a complex biological process that involves multiple cell types, including SCs, fibro-adipogenic precursors, endothelial cells, fibroblasts, pericytes, and immune cells. Removing cilia from fibro-adipogenic precursors can reduce intramuscular adipogenesis and increase myofibril size during muscle healing (24). SCs play an essential role in muscle hypertrophy and exercise adaptation (25, 26), especially in young mice (27). Mechanical signals can interrupt SC suppression in a skeletal muscle loss model induced by ovariectomy. Diminished SC number and elevated adipogenic gene expression in muscle caused by ovariectomy are averted by mechanical stimulation (28). Experiments in vitro indicate that mechanical stimulation enhances the fusion of SCs (29). SCs are a heterogeneous population of stem cells and committed progenitors (30). Paired box protein Pax-7 (Pax7) is a traditional marker of SCs and acts at different levels in a nonhierarchical regulatory network controlling SC-mediated muscle hypertrophy (31). A major target gene of Pax7 is Myogenic factor 5 (Myf5), and loss of Pax7 significantly decreases Myf5 expression in myoblasts (32). However, Myf5 is present in Pax3/Pax7 double mutants, indicating Myf5 activation occurs independently of Pax3/Pax7 (33). Furthermore, 10% of Pax7-expressing satellite cells have never expressed Myf5 (30). Parise et al. (34) observed an approximately sixfold increase in the number of Myf5-expressing cells by 48 h following exercise, which remained elevated until at least 96 h after exercise. We established three mouse models of Myf5-Arl3^−/−, Pax7-Intraflagellar transport protein 88 homolog (Ift88^−/−), and Pax7-Arl3^−/− to investigate the SC during mechanical stimulation and exercise. In the present study, we provide exciting evidence that SC cilia act as the key mechanical sensor for exercise-induced hypertrophy.     

Growing Teratoma Syndrome in the Setting of Sarcoidosis: A Case Report and Literature Review

Growing teratoma syndrome (GTS) is rare and can mimic disease recurrence in patients with a history of immature teratoma. Benign hypermetabolic lymphadenopathy found on staging and surveillance computed tomography (CT) and positron emission tomography (PET) may lead to the presumption of metastatic malignancy. We report a case of a 38 year old with mixed mature and immature teratomas who developed new peritoneal masses after adjuvant chemotherapy despite a normalization of tumor markers. In addition to low FDG uptake observed in these peritoneal masses, a PET scan showed hypermetabolic lymphadenopathy and pulmonary and spleen lesions suggesting widespread metastases. Subsequent surgical resection confirmed a mixed pathology with GTS and sarcoidosis. We reviewed the current literature evidence of GTS and sarcoidosis as a benign cause of lymphadenopathy in cancer patients. We emphasize the importance of a tissue diagnosis before instituting therapy for presumed cancer recurrence to avoid potentially fatal diagnostic traps and management errors. A multiple disciplinary team approach is imperative in managing patients with suspected recurrent immature teratomas.     

一种乳腺立体定位穿刺导向架的研制

针对临床上乳腺穿刺手术中精确定位穿刺枪的需求．设计出一款能匹配于国产乳腺机的立体定位穿刺导向架．以帮助医生提高手术质量。该装置包括运动模块、位移测量模块及显示模块,可实现三个方向相互垂直的直线运动,能实时显示三方向的运动位移。实验结果表明．该装置能与国产乳腺机良好匹配．使用感觉良好．各个运动方向的定位精度和重复性均较好．通过观察显示值．操作者可以准确改变穿刺枪的空间位置。     

知母宁抗乙肝病毒作用的体内外实验研究

目的:观察知母宁的抗乙肝病毒作用。方法:观察不同浓度知母宁对体外培养的2.2.15细胞分泌HBsAg、HBeAg的抑制作用及对乙肝模型鸭DHBV-DNA的影响。结果:知母宁浓度为4mg/mL时对2.2.15细胞分泌HBeAg有明显的抑制作用;以200mg/kg治疗乙肝模型鸭10d后DHBV-DNA水平明显降低。结论:知母宁有抗乙肝病毒的作用,其机制可能与抑制HBV-DNA的复制有关。     

Proteomic analysis of human hippocampal subfields provides new insights into the pathogenesis of Alzheimer’s disease and the role of glial cells

The hippocampus and entorhinal cortex (EC), the earliest affected areas, are considered relative to early memory loss in Alzheimer''s disease (AD). The hippocampus is composed of heterogeneous subfields that are affected in a different order and varying degrees during AD pathogenesis. In this study, we conducted a comprehensive proteomic analysis of the hippocampal subfields and EC region in human postmortem specimens obtained from the Chinese human brain bank. Bioinformatics analysis identified region‐consistent differentially expressed proteins (DEPs) which associated with astrocytes, and region‐specific DEPs which associated with oligodendrocytes and the myelin sheath. Further analysis illuminated that the region‐consistent DEPs functioned as connection of region‐specific DEPs. Moreover, in region‐consistent DEPs, the expression level of S100A10, a marker of protective astrocytes, was increased in both aging and AD patients. Immunohistochemical analysis confirmed an increase in the number of S100A10‐positive astrocytes in all hippocampal subfields and the EC region of AD patients. Dual immunofluorescence results further showed that S100A10‐positive astrocytes contained apoptotic neuron debris in AD patients, suggesting that S100A10‐positive astrocytes may protect brain through phagocytosis of apoptotic neurons. In region‐specific DEPs, the proteome showed a specific reduction of oligodendrocytes and myelin markers in CA1, CA3, and EC regions of AD patients. Immunohistochemical analysis confirmed the loss of myelin in EC region. Above all, these results highlight the role of the glial cells in AD and provide new insights into the pathogenesis of AD and potential therapeutic strategies.     

Comparison of the Effectiveness of Simple Plate Fixation and Plate Combined with Local Fixation of Broken Ends in the Treatment of Oblique Fracture of Midshaft Clavicle

ObjectiveTo compare the clinical efficacy of performing simple plate fixation with that using a plate combined with fracture end fixation to investigate the necessity of fracture end fixation outside the plate in cases of oblique fracture of the middle clavicle.MethodsThis was a retrospective follow‐up study of patients with middle clavicle oblique fractures (Robinson types 2A1 and 2A2) between 2015 and 2020. Patients were divided into two groups according to their treatment options: the simple plate fixation (SPF) group (n = 79; 43 men and 36 women; average age, 46.37 ± 14.54 years) and the plate combined with fracture local fixation (PLFP) group (n = 81; 36 men and 45 women; average age, 48.42 ± 12.55 years). Intraoperative blood loss, operation time, postoperative fracture healing time, postoperative shoulder function score (Constant–Murley and disabilities of the arm, shoulder, and hand [DASH] scores), clinical complications, and postoperative subjective satisfaction were compared between the two groups.ResultsOne hundred sixty patients with a sufficient follow‐up period were included in the final analysis: 79 in the SPF group (follow‐up time: 16.24 ± 3.94 months) and 81 in the PLFP group (follow‐up time: 16.15 ± 3.43 months). Age, sex, body mass index, follow‐up duration, fracture classification, and cause of injury were not significantly different between the two groups. There was no significant difference in blood loss, Constant–Murley and DASH scores, follow‐up period, and postoperative subjective satisfaction between the two groups (P > 0.05). The fracture healing time was shorter in the PLFP group than in the SPF group (4.41 ± 0.99 vs. 4.87 ± 1.60 months, P < 0.05), but the operation duration was longer in the PLFP group than in the SPF group (65.48 ± 16.48 min, P < 0.05). There were seven (complication rate, 8.86%) and five (complication rate, 6.17%) cases that had complications in the SPF and PLFP groups, respectively. There was no significant difference in the complication rates between the two groups (P > 0.05).ConclusionAlthough the healing time was shorter in the PLFP group than in the SPF group, the clinical efficiency of the two methods in the treatment of oblique fracture of the middle clavicle was similar.     

山东省居民高盐饮食对死亡和期望寿命的影响

目的分析山东省居民归因高盐饮食相关疾病死亡和寿命损失。方法利用2016年山东省与原卫生部联合减盐防控高血压项目终末期评估调查获得的24 h尿钠和血压值,结合2016年全省居民死因监测数据,按照比较风险评估理论,计算各类疾病归因分值(PAF)和因高盐饮食导致死亡,利用寿命表法计算归因期望寿命损失。结果2016年山东省因高盐饮食导致死亡32987人,占相关疾病死亡的11.74%,占全部死亡的4.95%。男性因高盐死亡比例(13.51%)高于女性(9.17%)。高盐饮食导致死亡的疾病主要是心脑血管疾病(90.82%),其次为胃癌(8.10%)和慢性肾病(1.08%)。城市居民PAF(13.87%)高于农村(10.87%)。高盐饮食导致山东省居民期望寿命减少0.58岁。高盐饮食所致不同疾病对期望寿命损失作用不同,缺血性心脏病位居首位,其次为脑出血和脑梗死。结论山东省居民归因高盐饮食死亡的比例较高,心脑血管疾病是高盐饮食导致死亡的重要原因。高盐饮食严重影响山东省居民健康,还需加强减盐干预工作。     

儿童胆道穿孔的超声诊断分析

目的 探讨超声检查在儿童胆道穿孔诊断中的价值及诊断要点.方法 回顾性分析重庆医科大学附属儿童医院1996年9月至2019年6月经手术确诊为胆道穿孔的41例患儿临床资料和超声声像图表现.采用四格表分析超声检查提示胆道扩张和胆囊壁增厚对胆道穿孔的诊断效果.结果 胆道穿孔患儿主要临床表现:呕吐31例、腹痛23例、腹胀21例、...     

Pre-attack and pre-episode symptoms in cluster headache: a multicenter cross-sectional study of 327 Chinese patients

BackgroundThere have been a few studies regarding the pre-attack symptoms (PAS) and pre-episode symptoms (PES) of cluster headache (CH), but none have been conducted in the Chinese population. The purpose of this study was to identify the prevalence and features of PAS and PES in Chinese patients, as well as to investigate their relationships with pertinent factors.MethodsThe study included patients who visited a tertiary headache center and nine other headache clinics between January 2019 and September 2021. A questionnaire was used to collect general data and information about PAS and PES.ResultsAmong the 327 patients who met the CH criteria (International Classification of Headache Disorders, 3rd edition), 269 (82.3%) patients experienced at least one PAS. The most common PAS were head and facial discomfort (74.4%). Multivariable logistic regression analysis depicted that the number of triggers (OR = 1.798, p = 0.001), and smoking history (OR = 2.067, p = 0.026) were correlated with increased odds of PAS. In total, 68 (20.8%) patients had PES. The most common symptoms were head and facial discomfort (23, 33.8%). Multivariable logistic regression analysis showed that the number of triggers were associated with increased odds of PES (OR = 1.372, p = 0.005).ConclusionsPAS are quite common in CH patients, demonstrating that CH attacks are not comprised of a pain phase alone; investigations of PAS and PES could help researchers better understand the pathophysiology of CH.