后路枕骨髁螺钉技术研究进展

正枕骨、寰椎和枢椎共同构成了枕颈部活动的结构功能单位,即枕颈交界区~([1-2])。炎症、创伤、肿瘤及畸形等因素会导致枕颈交界区失稳,从而引起颈脊髓或神经根的损伤、麻痹及难以忍受的疼痛,甚至危及生命~([3-4])。后路内固定融合技术是治疗枕颈部失稳的重要手段,目前常用术式为枕骨螺钉技术,该技术较钢丝固定技术有更好的生物力学稳定     

Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections

Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p?<?0.001). The psoriasis group also had a significantly high mean melting temperature (78.62?±?0.20) when compared with the inactive SLE group (78.49?±?0.29, p?<?0.05) and control group (78.44?±?0.25, p?<?0.01). There was no significant difference in melting temperature between inactive SLE and healthy controls. Disease activity in SLE was directly associated with methylation of the FOXP3 TSDR. On the other hand, patients with chronic microbial infections had significantly lower FOXP3 TSDR mean melting temperature (demethylated) when compared with healthy controls (78.28?±?0.21 vs 78.44?±?0.25, p?<?0.05). Our results suggest that the use of HRM-PCR to detect FOXP3 TSDR methylation status is a reliable and easy method to predict natural regulatory T cell levels in peripheral blood in different disease conditions. Determining FOXP3 TSDR methylation status can be a useful tool in diagnosis, and monitoring the severity of autoimmune diseases and chronic microbial infections.     

Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma development and growth in vivo

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf^V600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr^CreERT2/+; Braf^{LSL‐V600E/+}; Pten^flox/flox) to Sirt5^?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5^?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf^V600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.     

Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation

Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT). When myeloablated BALB/c MyD88 knock-out recipients were transplanted with C57BL/6 (B6) donor cells, they developed significantly more severe GVHD than wild-type (WT) BALB/c hosts. The increased morbidity and mortality in MyD88^–/– mice correlated with increased serum levels of lipopolysaccharide and elevated inflammatory cytokines in GVHD target organs. Additionally, MyD88 deficiency in BMT recipients led to increased donor T cell expansion and more donor CD11c⁺ cell intestinal infiltration with apoptotic cells but reduced proliferation of intestinal epithelial cells compared with that in WT BMT recipients. Decreased expression of tight junction mRNA in epithelial cells of MyD88^–/– mice suggested that MyD88 contributes to intestinal integrity. Cox-2 expression in the GVHD-targeted organs of WT mice is increased upon GVHD induction, but this enhanced expression was obviously inhibited by MyD88 deficiency. The present findings demonstrate an unexpected role for host MyD88 in preventing GVHD after allogeneic BMT.     

Denial of Human Rights: We Must Change the Paradigm of Dementia Care

In far too many instances treatment of persons with dementia has reflected a fundamental denial of basic human rights. At times, these individuals are treated worse than the treatment of animals when the five basic freedoms of animals, described by Pachana in her editorial, are implemented. A number of such examples of dehumanizing (and “de-animalizing”) persons with dementia are presented. A case is made for the position that this is the direct result of the “medicalization” of dementia and “Alzheimer Disease.” This has led to the disenfranchisement of persons with dementia and their caregivers regarding the treatment of dementia, while medical “expertise” has led to a paradigm of learned helplessness while waiting for “the cure.” While the medicalization of dementia has been a financial success in terms of funding failed researcher to find a cure, it has been a catastrophe for the quality of life of persons with dementia and their caregivers. It is time to take control of the treatment of dementia back, and especially to listen to the voices of persons with dementia. It is time to take action NOW – to become disruptive to the current paradigm. The emperor and his cure have no clothes. We deserve better. We must make this change in paradigm our mission, to demand it, and to accept nothing less. Power to the people.     

High-magnitude mechanical strain inhibits the differentiation of bone-forming rat calvarial progenitor cells

Purpose: Orthodontic tooth movement occurs during the bone remodeling induced by therapeutic mechanical strain. It is important to investigate the relation between the strength of mechanical stress and bone formation activity. The aim of this study was to determine the effect of high-magnitude mechanical strain on bone formation in detail.

Materials and methods: Osteoblast-like cells isolated from fetal rat calvariae were loaded with 18% cyclic tension force (TF) for 48?h. To phenotypically investigate the effect of TF, we measured the number and the size of bone nodules stained by von Kossa technique on day 21 after cell seeding and determined the calcium content of bone nodules on day 14. Furthermore, we examined the gene expression of BMP-2, Runx2 and Msx2, which are important factors for bone nodule formation, on days 1, 4 and 7 after TF loading.

Results: The maximum bone nodule size in the control group was 1620 and 719?μm in the TF group. Furthermore, the mean number of bone nodules sized over 360?μm in the TF group was significantly decreased compared to the control group. The calcium content was also significantly decreased to 42% by TF loading. The mRNA expression of BMP-2, Runx2 and Msx2 was decreased 1 and 4 days after TF loading.

Conclusion: The differentiation of bone forming progenitor cells into bone nodule forming cells was inhibited by TF due to the decreased expression of bone formation related factors such as BMP-2, Runx2 and Msx2.     

Vasoactive Intestinal Peptide Immunoregulatory Role at the Periapex: Associative and Mechanistic Evidences from Human and Experimental Periapical Lesions

IntroductionThe balance between the host proinflammatory immune response and the counteracting anti-inflammatory and reparative responses supposedly determine the outcome of periapical lesions. In this scenario, the vasoactive intestinal peptide (VIP) may exert a protective role because of its prominent immunoregulatory capacity. In this study, we investigated (in a cause-and-effect manner) the potential involvement of VIP in the development of human and experimental periapical lesions.MethodsPeriapical granulomas (n = 124) and control samples (n = 48) were comparatively assessed for VIP and multiple immunologic/activity marker expression through real-time polymerase chain reaction. Experimental periapical lesions (C57Bl/6 wild-type mice) were evaluated regarding endogenous VIP expression correlation with lesion development and the effect of recombinant VIP therapy in lesion outcome. CCR4KO and IL4KO strains and anti-glucocorticoid-induced TNFR-related protein inhibition were used to test the involvement of Treg and Th2 cells in VIP-mediated effects.ResultsVIP expression was more prevalent in periapical granulomas than in controls, presenting a positive association with immunoregulatory factors and an inverse association/correlation with proinflammatory mediators and the receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio. Endogenous VIP expression up-regulation was temporally associated with lesion immunoregulation and a decline of bone loss. VIP therapy in mice prompted the arrest of lesion development, being associated with an anti-inflammatory and proreparative response that limits the proinflammatory, Th1, Th17, and osteoclastogenic response in the periapex. The VIP protective effect was dependent of Treg migration and activity and independent of interleukin 4.ConclusionsOur results show that VIP overexpression in human and experimental periapical lesions is associated with lesion inactivity and that VIP therapy results in the attenuation of experimental lesion progression associated with the immunosuppressive response involving Treg cells.     

绝经后女性2型糖尿病伴骨质疏松患者骨密度与骨代谢指标的相关性分析

目的分析研究绝经后女性2型糖尿病伴骨质疏松症患者骨密度与骨代谢指标的相关性。方法选取2013年10月至2017年05月于重庆医科大学附属第一医院内分泌内科住院的绝经后女性2型糖尿病患者385名。搜集其基本资料、骨代谢指标及骨密度等。根据T值将这些患者分为骨质疏松组(233例)、骨量减少组(101例)和骨量正常组(51例),比较三组间骨代谢指标的变化,并对骨密度(bone mineral density,BMD)与各项骨代谢指标进行相关性分析。结果 1型前胶原氨基末端前肽(Type I procollagen N-terminal propeptide,P1NP)、骨钙素(bone Gla protein,BGP)在骨质疏松组显著高于骨量减少组、骨量正常组(P0.05);随着骨密度的降低,1型胶原羧基端肽β特殊序列(β-Carboxyl terminal peptide,β-CTX)逐渐升高,骨质疏松组、骨量减少组与骨量正常组相比较差异有统计学意义(P0.05);Spearman等级相关分析示P1NP、BGP、β-CTX与骨密度呈负相关,25(OH)D_3与骨密度呈现正相关。结论绝经后女性2型糖尿病伴骨质疏松症患者骨密度与骨代谢指标有一定的相关性,有助于预测骨折风险并及时抗骨质疏松治疗。     

续筋接骨方治疗骨折临床观察

目的研究续筋接骨方治疗骨折的临床疗效。方法选取2018年1月—2018年6月在辽宁中医药大学附属第三医院就诊的骨折患者60例,所有患者按照随机数字表法分为对照组与观察组,每组30例。观察组口服续筋接骨方联合正骨后小夹板固定治疗,对照组患者采用正骨后小夹板固定治疗。分析2组患者干预3个月后的血清骨代谢指标、骨密度、生活质量改善情况以及疗效判定。结果干预前,2组的血清Ⅰ型前胶原羧基端肽β特殊序列(β-CTX)、血清Ⅰ型前胶原氨端肽原(PINP)、骨特异性碱性磷酸酶(ALP)水平、钙、磷及骨密度比较,差异无统计学意义(P>0.05);干预后,2组的β-CTX、PINP、骨特异性ALP水平、钙、磷及骨密度较干预前改善,观察组的改善效果优于对照组,差异均有统计学意义(P<0.05)。干预前,2组的物质生活、社会功能、躯体健康以及心理健康评分比较,差异无统计学意义(P>0.05);干预后,2组的物质生活、社会功能、躯体健康以及心理健康评分较干预前升高,观察组的各项生活质量评分高于对照组,差异均有统计学意义(P<0.05)。观察组的治疗恢复率高于对照组,差异有统计学意义(P<0.05)。结论续筋接骨方可以改善骨折患者骨代谢功能及生活质量。