Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains

Smokers are at a higher risk of delayed union or nonunion after fracture repair. Few specific interventions are available for prevention because the molecular mechanisms that result in these negative sequelae are poorly understood. Murine models that mimic fracture healing in smokers are crucial in further understanding the local cellular and molecular alterations during fracture healing caused by smoking. We exposed three murine strains, C57BL/6J, 129X1/SvJ, and BALB/cJ, to cigarette smoke for 3 months before the induction of a midshaft transverse femoral osteotomy. We evaluated fracture healing 4 weeks after the osteotomy using radiography, micro-computed tomography (μCT), and biomechanical testing. Radiographic analysis demonstrated a significant decrease in the fracture healing capacity of smoking 129X1/SvJ mice. μCT results showed delayed remodeling of fracture calluses in all three strains after cigarette smoke exposure. Biomechanical testing indicated the most significant impairment in the functional properties of 129X1/SvJ in comparison with C57BL/6J and BALB/cJ mice after cigarette smoke exposure. Thus, the 129X1/SvJ strain is most suitable in simulating smoking-induced impaired fracture healing. Furthermore, in smoking 129X1/SvJ murine models, we investigated the molecular and cellular alterations in fracture healing caused by cigarette smoking using histology, flow cytometry, and multiplex cytokine/chemokine analysis. Histological analysis showed impaired chondrogenesis in cigarette smoking. In addition, the important reparative cell populations, including skeletal stem cells and their downstream progenitors, demonstrated decreased expansion after injury as a result of cigarette smoking. Moreover, significantly increased pro-inflammatory mediators and the recruitment of immune cells in fracture hematomas were demonstrated in smoking mice. Collectively, our findings demonstrate the significant cellular and molecular alterations during fracture healing impaired by smoking, including disrupted chondrogenesis, aberrant skeletal stem and progenitor cell activity, and a pronounced initial inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR).     

METTL3-Mediated m6A mRNA Methylation Modulates Tooth Root Formation by Affecting NFIC Translation

N6-methyladenosine (m⁶A), as a eukaryotic mRNA modification catalyzed by methyltransferase METTL3, is involved in various processes of development or diseases via regulating RNA metabolism. However, the effect of METTL3-mediated m⁶A modification in tooth development has remained elusive. Here we show that METTL3 is prevalently expressed in odontoblasts, dental pulp cells, dental follicle cells, and epithelial cells in Hertwig's epithelial root sheath during tooth root formation. Depletion of METTL3 in human dental pulp cells (hDPCs) impairs proliferation, migration, and odontogenic differentiation. Furthermore, conditional knockout of Mettl3 in Osterix-expressing cells leads to short molar roots and thinner root dentin featured by decreased secretion of pre-dentin matrix and formation of the odontoblast process. Mechanistically, loss of METTL3 cripples the translational efficiency of the key root-forming regulator nuclear factor I-C (NFIC). The odontogenic capacity of METTL3-silenced hDPCs is partially rescued via overexpressing NFIC. Our findings suggest that m⁶A methyltransferase METTL3 is crucial for tooth root development, uncovering a novel epigenetic mechanism in tooth root formation. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Early bioprosthesis failure in mitral valve replacement

The causes of early bioprosthesis failure include infective endocarditis, pannus formation, and structural valve deterioration. We reported a patient who suffered from early mitral bioprosthesis failure due to leaflets restricted by the subvalvular apparatus and early pannus formation. In patients with symptoms relapse and mitral regurgitation recurrence early after mitral valve replacement, early pannus formation needs to be anticipated, and surgical intervention should be performed if symptoms persist after medical treatment.     

Self-reported snoring is associated with chronic kidney disease in obese but not in normal-weight Chinese adults

BackgroundThe relationship between sleeping disorders and chronic kidney disease (CKD) has already been reported. Snoring, a common clinical manifestation of obstructive sleep apnea–hypopnea syndrome, is of clinical value in assessing sleeping disorder severity. However, investigations of the connection between snoring and CKD are limited, especially in normal-weight populations. This study assessed the relationship between snoring frequency and CKD in obese and normal-weight people in China.MethodsA community-based retrospective cross-sectional study of 3250 participants was performed. Study participants were divided into three groups – the regularly snoring group, occasionally snoring group, and never snoring group – based on their self-reported snoring frequency. CKD was defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m². Multiple logistic regression analysis was used to explore the relevance between snoring frequency and CKD prevalence.ResultsThe CKD prevalence in obese participants was higher than that in normal-weight participants. Frequent snorers had a higher prevalence of CKD than those who were not frequent snorers in the obese group. Snoring frequency was correlated with CKD prevalence in obese participants independent of age, sex, smoking and drinking status, systolic blood pressure, triglyceride level, high-density lipoprotein, and homeostasis model assessment of insulin resistance (odds ratio: 2.66; 95% CI: 1.36–5.19; p=.004), while the same relationships did not exist in normal-weight participants (odds ratio: 0.79; 95% CI: 0.32–1.98; p=.614).ConclusionsSnoring appears to be independently associated with CKD in obese but not in normal-weight Chinese adults.     

差错反感文化在护士内部人身份认知与道德勇气间的中介作用

目的 探讨差错反感文化对护士内部人身份认知与道德勇气的影响及机制,为提高其道德勇气提供依据.方法 抽取湖南省湘西自治州7所二级医院的693名护士,采用一般资料调查表、差错反感文化量表、内部人身份认知量表及道德勇气量表进行调查.结果 护士的差错反感文化、内部人身份认知、道德勇气总分分别为(26.05±4.92)分、(27.99±3.15)分、(84.28±9.48)分.差错反感文化与道德勇气呈负相关,内部人身份认知与道德勇气呈正相关(均P＜0.01),差错反感文化在内部人身份认知与道德勇气间发挥部分中介作用,间接效应占总效应的15.74％.结论 护士的道德勇气总体水平较高,可以通过合理管理差错反感文化、增强内部人身份认知来提高护士道德勇气.     

透析中运动干预对维持性血液透析患者的影响

目的 探讨维持性血液透析患者透析中运动干预的实施效果.方法 将患者随机分为观察组29例和对照组30例,对照组按常规进行透析护理,包括生命体征监测、记录治疗参数和健康教育,透析中不进行运动干预;观察组在常规护理基础上根据自制的透析中运动方案进行运动干预,其中有氧运动40 min、阻力运动20 min.比较两组干预前和干预6个月后的透析充分性、运动能力、炎症指标和生活质量.结果 干预6个月后观察组透析充分性、运动能力、炎症指标测评结果和生理健康评分显著优于对照组(P＜0.05,P＜0.01).结论 对维持性血液透析患者进行透析中运动干预,能够提高患者透析充分性,增强运动能力,改善炎症指标,提升生理健康水平.     

腹腔镜结直肠癌手术中转开腹列线图预测模型的构建

目的分析腹腔镜结直肠癌手术发生中转开腹的危险因素,建立列线图预测模型指导临床决策,并分析其短期预后影响。方法收集2017年5月至2020年5月西安交通大学第一附属医院行腹腔镜手术的764例结直肠癌患者的病例资料,分为中转开腹组(60例)及腹腔镜组(704例)。采用Logistic回归分析中转开腹的独立危险因素,并用R语言构建中转开腹列线图预测模型。通过受试者工作特征曲线(ROC)下面积评估列线图预测模型效能。通过绘制校准图进行一致性检验。并比较两组患者术中及术后恢复情况。结果本研究共纳入患者764例,其中60例发生中转开腹,中转开腹率为7.9%(60/764)。肿瘤位置位于直肠[比值比(OR)=1.846,P<0.05)]、美国麻醉医生协会(ASA)评分Ⅲ、Ⅳ级(OR=2.381,P<0.05)、腹部手术史(OR=3.652,P<0.01)、肿瘤长径≥5 cm(OR=2.704,P<0.05)和体重指数(OR=1.109,P<0.05)是发生中转开腹的独立危险因素,上述数据差异均有统计学意义。成功构建列线图预测模型,模型ROC曲线下面积为0.794。校正曲线显示预测结果与实际结果有较好的重合度。中转开腹组手术时间高于腹腔镜组(210 min比190 min,Z=-2.670,P<0.05);中转开腹组出血量高于腹腔镜组(170 ml比120 ml,Z=-6.018,P<0.01);中转开腹组术后住院天数高于腹腔镜组(10 d比9 d,Z=-2.134,P<0.05)。中转开腹组肠梗阻发生率高于腹腔镜组[10.0%(6/60)比4.3%(15/704),χ²=4.055,P<0.05];伤口感染率高于腹腔镜组[15.0%(9/60)比4.7%(33/704),χ²=11.318,P<0.05],上述数据差异均有统计学意义。结论肿瘤位置位于直肠、ASA评分Ⅲ、Ⅳ级、腹部手术史、肿瘤长径≥5 cm和体重指数是腹腔镜结直肠癌手术发生中转开腹的独立危险因素,据此建立的预测模型具有可靠的预测能力。