Knockdown of NRAGE induces odontogenic differentiation by activating NF-κB signaling in mouse odontoblast-like cells

Purpose: Neurotrophin receptor-interacting MAGE homologue (Nrage) plays an important role in bone development and the metabolism of normal skeletal structures. Our previous study showed that Nrage inhibited the odontogenic differentiation of mouse dental pulp cells. However, the potential roles and mechanism of Nrage in regulating odontogenic differentiation are unknown. The aim of this study was to investigate the molecular mechanism of Nrage in odontogenic differentiation of mouse odontoblast-like cells.

Materials and methods: Endogenous expression of Nrage was stably downregulated by lentivirus-mediated shRNA. Mineralized nodules formation was detected by alizarin red S staining. Dmp-1, Dspp, and ALP mRNA and protein levels were detected by qRT-PCR and western blotting, respectively. In addition, ALPase activity was detected. Confocal microscopy and co-immunoprecipitation (co-IP) were used to analyze the interactions between NRAGE and NF-κB signaling molecules. An IKK inhibitor was also used in the study.

Results: NRAGE expression in odontoblasts was downregulated during mouse first maxillary molar development. Moreover, NRAGE expression was downregulated during odontogenic differentiation of odontoblast-like cells. NRAGE knockdown significantly upregulated DMP1 and DSP expression, increased ALPase activity, and promoted mineralized nodule formation. In addition, NRAGE knockdown increased the translocation of NF-κB1 to the nucleus and phosphorylation levels of p65. Co-IP results showed that NRAGE bound to IKKβ. Most importantly, the promoting effect of Nrage knockdown on odontoblastic differentiation was reduced after treatment with an IKK inhibitor.

Conclusions: Our data confirmed that NRAGE is an important regulator of odontogenic differentiation of odontoblasts by inhibiting the NF-κB signaling pathway through binding to IKKβ.

Abbreviations: Nrage: neurotrophin receptor-interacting MAGE homologue; DSP: dentin sialophospho protein; DMP-1: dentin matrix protein-1; BMP: bone morphogenetic protein; Wnt: wingless; NF-κB: nuclear factor of activated B cells; DAPI: 4′,6-diamidino-2-phenylindole; KO: knockout; DPCs: dental pulp cells; AA: ascorbic acid; β-Gly: β-glycerophosphate; Dex: dexamethasone; co-IP: co-immunoprecipitation; IκB: inhibitor of NF-κB; IKK: IκB kinase     

分析比较急性髌骨外侧脱位与膝关节多发韧带损伤后内侧髌股韧带损伤的特点

 目的 分析比较急性髌骨外侧脱位(lateral patellar dislocation,LPD)与膝关节多发韧带损伤(multiligament knee injuries,MLKIs)后内侧髌股韧带(medial patellofemoral ligament,MPFL)损伤的特点。方法 回顾性分析急性LPD 92例和MLKIs 83例患者的MRI资料,根据患者年龄分为青少年组(年龄≤18岁)84例和成人组(年龄＞18岁)91例,对LPD和MLKIs伴发MPFL损伤程度、部位进行统计学分析。结果 青少年LPD组50例中,MPFL部分撕裂20例,完全撕裂25例,未损伤5例;青少年MLKIs组34例患者中,MPFL部分撕裂9例,完全撕裂6例,未损伤19例;两组比较,差异有统计学意义(χ²=21.725,P<0.05)。青少年LPD组MPFL髌骨侧损伤19例,股骨侧14例,体部2例,多部位损伤10例;青少年MLKIs组MPFL髌骨侧损伤3例,股骨侧7例,多部位损伤5例;青少年LPD组和MLKIs组间MPFL髌骨侧、股骨侧、多部位损伤发生率差异均具有统计学意义(χ²=19.753,9.644,8.193,P值均小于0.01)。成人LPD组42例中,MPFL部分撕裂17例,完全撕裂19例,未损伤6例;成人MLKIs组49例中,MPFL部分撕裂13例,完全撕裂7例,未损伤29例;两组比较,差异有统计学意义(χ²=20.771,P<0.05)。成人LPD组MPFL髌骨侧损伤11例,股骨侧15例,体部2例,多部位损伤8例;成人MLKIs组MPFL髌骨侧损伤4例,股骨侧9例,多部位损伤7例;LPD组和MLKIs组间MPFL髌骨侧、股骨侧、多部位损伤发生率差异均具有统计学意义(χ²=14.773,12.777,6.822,P均<0.01)。结论 急性LPD比MLKIs更易导致MPFL损伤,MPFL髌骨侧损伤、股骨侧损伤和多部位损伤LPD也较MLKIs更常见。     

T-Cell Immunoglobulin- and Mucin-Domain-Containing Molecule 3 Genetic Variants and HIV+ Non-Hodgkin Lymphomas

T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in inflammatory diseases such as rheumatoid arthritis, hepatitis B and C, and human immunodeficiency virus (HIV)-related inflammation. Recent studies have shown that chronic inflammation may greatly affect the pathogenesis of non-Hodgkin lymphomas (NHL). The aim of this study was to investigate whether polymorphisms in the TIM-3 gene were associated with susceptibility to non-NHL and HIV-related NHL. Three polymorphisms in TIM-3 gene (?1516G/T, ?574G/T, and +4259T/G) were identified by polymerase chain reaction-restriction fragment length polymorphism in 434 NHL patients, 62 HIV-related NHL cases, and 512 healthy controls. Results showed that the prevalence of ?574GT genotype and +4259TG genotype were significantly increased in the NHL cases than in controls (odds ratio (OR)?=?2.72, 95 % confidence interval (CI)?=?1.50–4.92, p?=?0.0006 and OR?=?2.59, 95 % CI?=?1.49–4.49, p?=?0.0005, respectively). The ?1516G/T polymorphism did not reveal significant difference between patients and healthy controls. When analyzing the TIM-3 polymorphisms in HIV-related NHL patients, data showed that HIV+ NHL patients had higher prevalence of ?574GT or +4259TG genotypes than those cases without HIV infection (OR?=?3.48, 95 % CI?=?1.67–7.28, p?=?0.0005 and OR?=?2.92, 95 % CI?=?1.42–6.01, p?=?0.0026, respectively). These results suggested polymorphisms in TIM-3 gene could be new risk factors for NHL as well as HIV-related NHL and suggested a possible role of the inflammatory factor in these diseases.     

A case of delayed cyst formation post brain AVM stereotactic radiosurgery for arteriovenous malformation: Case report

Arteriovenous malformations (AVMs) are a rare cause of cerebrovascular abnormality with incidence of about 1 in 100,000 people per year and point prevalence of about 0.2%. AVMs are associated with serious complications such as intracranial haemorrhage (2–4% a year, 16% and 29% at 10 and 20 years after diagnosis), seizures (10–30%), focal neurologic deficits, and headaches. The management options are surveillance, endovascular embolization, microsurgical excision and stereotactic radiosurgery (SRS).In SRS Stereotactically focused high energy beams of photons induce progressive thrombosis by fibro-intimal hyperplasia and subsequent luminal obliteration. These changes usually take one to three years known as “latency period”. Complications are reported in 8% of patients undergoing SRS, including radiographic parenchymal lesions, cranial nerve deficits, seizures, headaches, and cyst formation.Cyst formation is reported in about 1.2 % of patients undergoing SRS. While the exact mechanism of post SRS cyst formation is unclear, it is hypothesized that it might be due to damage to the blood brain barrier and increased vessel wall permeability. Delayed cyst formation is reported with latency period between 3 and 10 years after radiotherapy for treatment of cerebrovascular AVMs. However, cystic formation with longer latency periods (in one case upto 17 years) after radiotherapy for other causes such as nasopharyngeal cancers have been reported.Here we report a case of delayed cyst formation after SRS for cerebrovascular AVM with latency period of 20 years.     

Effect of Perceived Organizational Support on Fatigue of Chinese Nurses during the COVID-19 Pandemic: Resilience as a Mediator

As working for the nurse is believed to be one of the most stressful professions, nurses are particularly at risk of experiencing fatigue. Especially during the COVID-19 pandemic, fatigue among nurses may affect physical and mental health seriously, which is attracting increasing attention of researchers and clinical practitioners to find effective prevention measures to alleviate nurses’ fatigue. This study aims to investigate the mediational effect of resilience on the relationship between nurses’ perceived organizational support and fatigue. A total of 476 nurses from secondary and above hospitals in Hebei province, China during March and April in 2020, were investigated with Perceived Organizational Support Scale, Resilience Scale and Work Fatigue Inventory. Structural equation modeling was conducted to explore the mechanisms of nurses’ perceived organizational support on fatigue. Results revealed that perceived organizational support can decrease the nurses’ mental/physical/emotional fatigue through the mediating role of resilience. These findings guide for hospital managers to identify effective prevention strategies to alleviate the fatigue of clinical nurses.     

左卡尼汀通过抑制钙/钙调素依赖蛋白激酶Ⅱ信号通路抑制过氧化氢诱导的大鼠心肌细胞凋亡

 目的： 观察左卡尼汀对过氧化氢（H2O2）诱导的大鼠心肌细胞凋亡的保护作用及其机制。方法：利用200 μmol/L H2O2刺激12 h,建立体外原代培养新生乳鼠心肌细胞凋亡模型。Ca2+螯合剂1,2-双(2-氨基苯氧基)乙烷-N, N, N′, N′-四乙酸(BAPTA)、钙调素依赖蛋白激酶II (CaMKII)特异性抑制剂KN93及左卡尼汀分别于加入H2O2前30 min或1 h加入,以检测这3种药物对H2O2刺激下心肌细胞活力、细胞凋亡、细胞内静息钙浓度（［Ca2+］i）及磷酸化CaMKII (p-CaMKII)表达的影响。利用MTT比色法检测心肌细胞活力;流式细胞仪检测细胞凋亡率;利用激光共聚焦扫描检测［Ca2+］i;蛋白质免疫印迹法检测cleaved caspase-3及p-CaMKII的表达。结果：模型组经200 μmol/L H2O2作用12 h后,细胞活力显著下降,细胞凋亡率显著增加。BAPTA、KN93及左卡尼汀预处理显著抑制上述细胞损伤。进一步研究发现,H2O2 诱导的 ［Ca2+］i水平升高、cleaved caspase-3及p-CaMKII的表达增加均可被上述3种药物不同程度地抑制。结论：左卡尼汀可抑制H2O2所致的心肌细胞凋亡,该心肌保护作用可能与其抑制Ca2+/CaMKⅡ信号通路有关。     

着鞋类型和步速对膝关节载荷的影响

目的探讨着鞋类型(裸足、普通鞋、极简鞋)与步行速度(快步走、常速行走)对膝关节生物力学指标的影响,为科学健身提供理论参考。方法采用Vicon三维运动捕捉系统、Kisler三维测力台同步采集10名男性在裸足、穿着不同鞋常速行走与快步走时下肢运动生物力学指标。采用双因素(2种行走方式×3种着鞋类型)重复测量方差分析对各指标进行统计分析。结果相对于快步走,常速行走时足底压力中心(center of pressure,COP)向外偏移较大,额状面膝关节力臂、膝关节内收外力矩和第1峰值负载率均较小,但额状面膝关节冲量矩较大;相对于穿着普通跑鞋,裸足或穿着极简鞋时,步幅变小,COP向外偏移较大,额状面膝关节力臂、膝关节内收外力矩、第1峰值负载率和额状面膝关节冲量矩较小。结论为降低额状面膝关节冲量矩以及峰值负载率,建议着极简鞋采用小步幅进行快步走锻炼。     

The role of innate immunity in myasthenia gravis

Myasthenia gravis (MG) is a T cell-driven, B cell-mediated and autoantibody-dependent autoimmune disorder against neuromuscular junctions (NMJ). Accumulated evidence has emerged regarding the role of innate immunity in the pathogenesis of MG. In this review, we proposed two hypothesis underlying the pathological mechanism. In the context of gene predisposition, on the one hand, Toll-like receptors (TLRs) pathways were initiated by viral infection in the thymus with MG to generate chemokines and pro-inflammatory cytokines such as Type I interferon (IFN), which facilitate the thymus to function as a tertiary lymphoid organ (TLO). On the another hand, the antibodies against acetylcholine receptors (AChR) generated by thymus then activated the classical pathways on thymus and neuromuscular junction (NMJ). Futher, we also highlight the role of innate immune cells in the pathogenic response. Finally, we provide some future perspectives in developing new therapeutic approaches particularly targeting the innate immunity for MG.     

改良体位护理在腹腔镜直肠癌Dixon手术患者中的应用

目的 观察改良体位护理方法在腹腔镜直肠低位前切除手术患者中的应用效果。 方法 选取行腹腔镜直肠低位前切除术的手术患者210例,采用随机数字表法将其分为传统组和改良组,各105例。传统组采用截石位支腿架及肩档进行常规体位摆放,改良组采用自制下肢体位垫及头颈肩约束带进行改良体位摆放。比较2组体位摆放时间、患者下肢麻木情况、肩部疼痛评分及医生对手术体位摆放的满意度。 结果 改良组体位摆放时间短于传统组(t=-5.020,P=0.007),患者下肢麻木、肩部疼痛评分均低于传统组(t=-6.732,P=0.002;t=-4.232,P=0.003),医生对手术体位的满意度评分高于传统组(t=3.623,P=0.001)。 结论 在腹腔镜直肠低位前切除术体位护理时,采用改良体位摆放法能明显缩短体位摆放时间,增加患者舒适度,减少体位相关并发症,提高医生满意度。     

Splenic Kaposi’s sarcoma in a human immunodeficiency virus-negative patient: A case report

BACKGROUNDKaposi’s sarcoma (KS) is a malignancy that usually affects the skin of the lower extremities, and may involve internal organs. It originates from the vascular endothelium. It is well known that the development of KS is associated with human herpes virus 8 (i.e. HHV8) infections. Sporadic KS cases have mainly been found in Africa. Isolated splenic KS in Asia has rarely been reported. We present here a case of KS primarily involving the spleen in a human immunodeficiency virus (HIV)-negative Chinese patient.CASE SUMMARYA 50-year-old male patient was admitted to hospital due to abdominal distension and discomfort, reduced food intake and weight loss. Medical examination revealed that the patient had moderate anemia, a low platelet count, slight fatty liver and a huge mass in the spleen. Spleen lymphoma was considered. An anti-HIV test was negative. The whole spleen was surgically excised. The final pathological diagnosis was nodular stage spleen KS, and the patient underwent total splenectomy. He recovered well and was discharged from hospital 12 d after surgery. Two weeks later, the patient developed liver metastasis and died within 1 mo after surgery.CONCLUSIONKS is difficult to diagnose and pathological examination is necessary. KS has a poor prognosis and should be diagnosed and treated early to improve survival.