Associations of polymorphisms in the SOST gene and bone mineral density in postmenopausal Chinese Women

Summary

The bone mineral density (BMD) of a total of 1,379 healthy postmenopausal Chinese women was measured. Ten tagging SNPs of the sclerostin (SOST) gene were genotyped. Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in postmenopausal Chinese women.

Introduction

The purpose of the study was to determine the associations between polymorphisms of SOST gene and BMD in postmenopausal Chinese women.

Methods

A total of 1,379 independent healthy postmenopausal Chinese women including 703 in our previous study were recruited. The BMD of the lumbar spine 1–4 (L1–4) and left proximal femur including total hip and femoral neck were measured by dual-energy X-ray absorptiometry. Ten tagging SNPs (rs1234612, rs1513670, rs1634330, rs1708635, rs2023794, rs7220711, rs74252774, rs851057, rs851058, and rs865429) of the SOST gene were genotyped.

Results

The rs2023794 and rs74252774 and the haplotype ACCATTCT of SOST gene were associated with age and body mass index (BMI) adjusted L1–4 BMD (P values were 0.010, 0.007, and 0.007, respectively) even after performing the Bonferroni multiple-significance-test correction. There was a clear trend in these regions that the CC genotype of the rs2023794 and the TT genotype of the rs74252774 have higher BMD values than other genotypes. The contributions of the rs2023794 and rs74252774 to the phenotypic variation of L1–4 BMD were 0.6 and 0.7 %, respectively. We failed to find any association between the 10 SNPs and 6 haplotypes of the SOST gene and BMD at the hip site in this study.

Conclusions

Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in a large sample of postmenopausal Chinese women.     

Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells

Our previous findings have demonstrated that bee venom (BV) has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB) activity assay. BV (1–5 μg/mL) inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax) was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF)-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway.     

颌骨区伴有软骨样分化的胚胎性横纹肌肉瘤一例

颌骨区的横纹肌肉瘤(rhabdomyosarcoma,RMS)非常罕见。该例发生于下颌骨的胚胎性RMS,患者女,13岁,下颌骨体右侧部见不规则团块状密度影,局部见膨胀性骨质破坏区,镜下肿瘤主要由幼稚的原始间叶样细胞组成,散在分布横纹肌母细胞,局部见软骨样组织,免疫组织化学染色结蛋白、MyoD1和myogenin阳性。骨的RMS常见于软组织RMS累及或转移到骨,骨原发的RMS很少见,应注意与其他小圆细胞肿瘤、骨肉瘤及去分化软骨肉瘤鉴别。     

慢性牙周炎口腔变黑普雷沃氏菌分离鉴定及促进食管鳞癌演进

目的分离、鉴定口腔变黑普雷沃氏菌(Prevotella nigrescens,P.nigrescens),探讨其对食管鳞癌是否有促进作用。方法胰豆胨肝粉琼脂(GAM)培养基厌氧原代培养慢性牙周炎患者龈沟液,挑选黑色菌落分离纯化;革兰染色、16S rRNA基因测序鉴定分离的单克隆细菌;该细菌感染食管鳞癌细胞NE6-T后细胞生物学性状变化。结果慢性牙周炎患者龈沟液厌氧原代培养120 h后可见多个菌落,其中灰黑色菌落经连续划线法分离纯化为黑色、圆形光滑单克隆菌落。该细菌革兰染色阴性、串珠状排列,16S rDNA序列与P.nigrescens F0103同源性为99.78%(P.nigrescens LY01)。LY01感染促进NE6-T细胞体外增殖、迁移、侵袭和裸鼠皮下荷瘤生长,并诱导Ki67表达上调和p-STAT3激活。结论慢性牙周炎口腔P.nigrescens可能促进了食管鳞癌发展。     

Aza‐Michael Addition Chemistry for Tuning the Phase Separation of PDMS/PEG Blend Coatings and Their Anti‐Fouling Potentials

Free adjustment of micro/nanophase‐separation degrees in coatings is not easily accessible, which is a big handicap in the development of phase‐separation‐related applications. Here, by utilizing the reactivity difference between two phases, a two‐step aza‐Michael addition pre‐crosslinking strategy, demonstrated by acryloxy‐terminated polydimethylsiloxane/polyethylene glycol (PEG) blend coatings, is proposed for the first time to tune microphase separation degrees, and promote compatibility of the biphasic amphiphilic polymer blends. Followed by a systematic study of the two‐step pre‐crosslinking time, surface morphologies of samples with desired phase‐separation degrees are unveiled using optical microscopy, AFM, and XPS. The wettability, and anti‐fouling properties — for example, anti‐protein and anti‐marine bacterial (Shewanella) adhesion — of these coatings are assessed. Less protein adsorption is observed on those surfaces with lower receding water contact angles. Shewanella adhesion is efficiently discouraged by the introduction of PEG segments, but the trend evolved with surface wettability and micro/nanophase structure in a complex way.     

5-ALA-photodynamic therapy in refractory vulvar lichen sclerosus et atrophicus

Objective: As a chronic inflammatory skin disease of unknown etiology, vulvar leukoplakia mainly affects postmenopausal and peri-menopausal females. The main clinical manifestations of vulvar lichen sclerosus et atrophicus (VLSA) include itching, burning pain, and sexual dysfunction, which can lead to a decline in the quality of life. The existing treatment options include topical corticosteroid ointment, estrogen, and traditional Chinese medicine. However, their therapeutic effects on VLSA remain unsatisfactory. In the present study, we aimed to investigate the clinical efficacy and safety of photodynamic therapy (PDT) in combination with 5-aminoketovaleric acid (ALA) for the treatment of vulvar leukoplakia. Methods: A total of 30 patients with VLSA who failed routine treatment were treated with ALA-PDT. The patients were irradiated at a power density of 60-90 mW/cm² with a red light at a wavelength of 635±15 nm for 20 min. Twenty percent of ALA water-in-oil emulsion was applied to the lesion and sealed with plastic film for 3 h. The treatment was repeated three times every 2 weeks. The objective and subjective symptoms and signs of vulvar lesions based on the horizontal visual analogue scale were recorded at 6 months after each treatment and the last treatment. Results: All patients completed three cycles of ALA-PDT and follow-up. The clinical symptoms of pruritus completely disappeared in 27 cases. Itching changed from severe to mild in three cases. The pathological changes of all subjects were improved. The main side effects of ALA-PDT were pain, erythema, and swelling. The side effects were temporary and tolerable. All patients reported their results as “satisfied” or “very satisfied”. Conclusions: ALA-PDT was an effective and safe approach for the treatment of VLSA.     

CiteSpace知识图谱可视化分析中医药防治绝经后骨质疏松症

文题释义： CiteSpace知识图谱：CiteSpace基于Java语言,将应用数学、统计学、文献计量学、信息科学等各学科的理论和方法相结合,对领域内研究文献的引文、作者、关键词进行时间空间多元共现分析,把数据分析映射在二维、三维图形中,从宏观、微观等多层面展现学术网络结构和动态变化,形成领域的知识图谱。 绝经后骨质疏松症：主要发生于绝经后女性的骨质疏松症,是由于雌激素缺乏导致骨量减少及骨组织结构变化。该病隐匿发生,临床主要有骨痛、驼背或身高变矮、局部压痛叩击痛等表现,发生骨折或合并症后严重影响老年人的身体健康和生活质量,甚至缩短寿命。背景：中医药防治绝经后骨质疏松症有着悠久的历史,相关领域内研究逐步发展壮大,但目前针对该领域内研究文献的发表情况、核心作者、研究力量等要素分析及系统综述较少。 目的：针对中医药防治绝经后骨质疏松症的相关文献研究进行CiteSpace知识图谱绘制及可视化分析,了解该领域研究过程、研究热点、发展趋势,为其后续发展提供依据与可行性建议。方法：计算机检索中国知识基础设施工程(CNKI)数据库1993至2019年关于中医药防治绝经后骨质疏松症的相关文献,统计分析纳入文献年度发文量、科研基金资助情况、高频被引文献等,并将纳入文献以RefWorks格式导出使用CiteSpace V软件生成发文机构、作者、关键词等信息的知识图谱,进行可视化分析。结果与结论：①共纳入453篇文献,该领域研究自1993年开展并逐渐获得重视,研究文献以期刊论文为主要形式;②各类科研基金中以国家自然科学基金的资助项目最多;③核心作者有12人,主要研究者有郑洪新、梁文娜、葛建荣等,并形成相应的主要研究团队;④主要研究机构有广州中医药大学附属骨伤科医院、辽宁中医药大学等中医药院校及其附属医院;⑤研究形成了9个具有代表性的关键词聚类,并随时间推移呈现研究方向的转变趋势;⑥由以上分析可见,中医药防治绝经后骨质疏松症的相关研究历经20余年,形成多个研究力量、研究主题,其发展仍处于上升期;如能从国家发展战略高度整合优势资源,促进不同地区、机构合作,进一步发掘中医药特色,有望促进中医药走向世界,兴旺发展。 ORCID: 0000-0003-0247-9863(李绍烁) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

富血小板血浆联合负压引流治疗慢性难愈性创面的Meta分析

文题释义：富血小板血浆：是一种调节炎症反应、刺激和加速组织愈合的新型生物技术,其富含各种生长因子,包括血小板源生长因子、转化生长因子β、成纤维细胞生长因子、血管内皮生长因子等,通过多种机制(包括调节炎症、血管生成及新组织的合成和重塑)在内部帮助创建最有利于组织稳态恢复的生物环境。慢性难愈性创面：目前对于慢性难愈性创面的定义尚未达成明确的共识,一般是指由于各种因素引起的经过常规治疗干预,不能在可预期的时间内按生物学规律完全愈合的创面,其潜在病因可能与全身性疾病或局部疾病有关。   背景：富血小板血浆与负压引流疗法已被广泛应用于各种慢性创面的治疗,并取得了良好的临床效果,但两者联合应用于慢性难愈性创面的效果尚缺乏来自随机对照研究的证据。 目的：评价富血小板血浆联合负压引流疗法治疗慢性难愈性创面的效果。方法：使用计算机对国内外数据库(CNKI、维普网、万方数据库、SinoMed、Web of Science、PubMed、EMbase等)进行检索,检索范围从建库至2019年6月,所有关于富血小板血浆联合负压引流疗法治疗慢性难愈性创面效果的随机对照试验,对纳入研究的文献采用Cochrane系统评价方法进行评价,采用Review manager 5.3软件进行Meta分析,分析的结局指标包括创面愈合率、创面愈合时间、住院时间、疼痛评分、细菌阳性率。结果与结论：①共纳入11篇随机对照试验,包括743例慢性创面患者,观察组均采用富血小板血浆联合负压引流疗法进行干预,对照组采用常规换药或者单纯负压引流疗法进行干预;②Meta分析显示与对照组比较,观察组创面愈合率升高[RR=2.19,95%CI(1.82,2.62),P < 0.000 01]、创面愈合时间缩短[SMD=-0.81,95%CI(-1.00,-0.62),P < 0.000 01]、住院时间缩短[MD=-7.11,95%CI(-8.12,-6.11),P < 0.000 01]、细菌阳性率降低[RR=0.35,95%CI(0.22,0.54),P < 0.000 01];两组疼痛评分比较差异无显著意义[SMD=-5.97,95%CI(-14.33,2.40),P=0.16];③结果表明,富血小板血浆联合负压引流疗法能促进慢性难愈性创面的愈合,降低感染发生率。 ORCID: 0000-0003-2057-9542(顾蓥璇) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Polarized immune responses modulated by layered double hydroxides nanoparticle conjugated with CpG

Modulation of the immune response is an important step in the induction of protective humoral and cellular immunity against pathogens. In this study, we investigated the possibility of using a nanomaterial conjugated with the toll-like receptor (TLR) ligand CpG to modulate the immune response towards the preferred polarity. MgAl-layered double hydroxide (LDH) nanomaterial has a very similar chemical composition to Alum, an FDA approved adjuvant for human vaccination. We used a model antigen, ovalbumin (OVA) to demonstrate that MgAl-LDH had comparable adjuvant activity to Alum, but much weaker inflammation. Conjugation of TLR9 ligand CpG to LDH nanoparticles significantly enhanced the antibody response and promoted a switch from Th2 toward Th1 response, demonstrated by a change in the IgG2a:IgG1 ratio. Moreover, immunization of mice with CpG-OVA-conjugated LDH before challenge with OVA-expressing B16/F10 tumor cells retarded tumor growth. Together, these data indicate that LDH nanomaterial can be used as an immune adjuvant to promote Th1 or Th2 dominant immune responses suitable for vaccination purposes.