Biochemical Markers of Bone Turnover in Camurati–Engelmann Disease: A Report on Four Cases in One Family

Moderate increases in ``classical' biochemical markers of bone turnover have been described only in some patients with Camurati–Engelmann disease. However, the determination of the following ``new' markers has not been previously performed: serum osteocalcin (BGP), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), aminoterminal propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxyterminal of type I collagen (ICTP), urinary pyridinoline (PYR), crosslinked N-telopeptides of type I collagen (NTX), and Crosslaps (CL). Such a determination may improve the evaluation of the disease activity. To evaluate the usefulness of biochemical markers of bone turnover reflecting Camurati–Engelmann disease activity we measured the levels of all these markers in four affected patients. The results were compared with bone scintigraphic indices of disease activity. Except for PICP and TRAP, bone formation and resorption markers were abnormal in all patients and were related to bone scan indices of disease activity. Among the markers of bone formation PINP, BAP, and BGP showed the highest values, whereas NTX and CL were the most sensitive markers of bone resorption. These results suggest that the determination of NTX or CL, and PINP or either BAP and BGP, associated with bone scan evaluation, provides the best assessment of Camurati–Engelmann disease activity. Received: 14 June 1996 / Accepted: 31 December 1996     

Localisation of the gene causing diaphyseal dysplasia Camurati-Engelmann to chromosome 19q13

Camurati-Engelmann disease, progressive diaphyseal dysplasia, or diaphyseal dysplasia Camurati-Engelmann is a rare, autosomal dominantly inherited bone disease, characterised by progressive cortical expansion and sclerosis mainly affecting the diaphyses of the long bones associated with cranial hyperostosis. The main clinical features are severe pain in the legs, muscular weakness, and a waddling gait. The underlying cause of this condition remains unknown.In order to localise the disease causing gene, we performed a linkage study in a large Jewish-Iraqi family with 18 affected subjects in four generations. A genome wide search with highly polymorphic markers showed linkage with several markers at chromosome 19q13. A maximum lod score of 4.9 (theta=0) was obtained with markers D19S425 (58.7 cM, 19q13.1) and D19S900 (67.1 cM, 19q13. 2). The disease causing gene is located in a candidate region of approximately 32 cM, flanked by markers D19S868 (55.9 cM, 19q13.1) and D19S571 (87.7 cM, 19q13.4).     

Comprehensive analysis of the lncRNA-miRNA-mRNA regulatory network for bladder cancer

BackgroundLong non-coding RNAs (lncRNAs) are essential regulators for various human cancers. However, these lncRNAs need to be further classified for cancer. In the present study, we identified novel competing endogenous RNA (ceRNA) network for bladder cancer (BC) and explored the gene functions of the ceRNA regulatory network.MethodsDifferential gene expression analysis were performed on The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) datasets to identify differentially expressed messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs). Based on the competing endogenous RNA (ceRNA) hypothesis, a lncRNA-miRNA-mRNA network was constructed using the StarBase database and visualization by Cytoscape software. Functional enrichment analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed via R package ClusterProfiler. The protein-protein interaction network was constructed by STRING database and visualization by Cytoscape. Finally, we used CIBERSORT and the TIMER database to analyze the immune infiltrations for BC.ResultsThe regulatory network was constructed via TCGA BLCA cohort. The differential expressions of lncRNA, miRNA, and mRNA were 186, 200, and 2,661, respectively. There were 106 lncRNA, miRNA, and mRNA included in the ceRNA network. In this network, Calcium Voltage-gated Channel Auxiliary Subunit Alpha2delta1 (CACNA2D1, P<0.001), domain containing engulfment adaptor1 (GULP1, P=0.001), latent transforming growth factor beta binding protein 1 (LTBP1, P=0.006), myosin light chain kinase (MYLK, P=0.001), serpin family E member 2 (SERPINE2, P=0.002), spectrin beta non-erythrocytic 2 (SPTBN2, P=0.047), and hsa-miR-590-3p (P<0.001) significantly affected the prognosis of BC patients. Functional enrichment analyses showed that the biological functions included negative regulation of protein phosphorylation, cell morphogenesis, and sensory organ morphogenesis. Important cancer pathways of KEGG included parathyroid hormone synthesis secretion action, the notch signaling pathway, MAPK signaling pathway, the Rap1 signaling pathway, signaling pathways regulating the pluripotency of stem cells, and the transforming growth factor-β signaling pathway. Our findings demonstrated that the ceRNA network has important biological functions and a significant influence on the prognosis of BC.ConclusionsThe lncRNA-miRNA-mRNA network constructed in the present study could provide useful insight into the underlying tumorigenesis of BC, and can determine new molecular biomarkers for the diagnosis and therapeutical treatment of BC.     

5—氨基水杨酸与乙基纤维素溶混性的计算机模拟

使用计算机辅助分子建模（ＣＡＭＭ）、分子力学和蒙特卡罗方法,模拟了５－氨基水杨酸（５－ＡＳＡ,Ｃ７Ｈ７ＮＯ３,美沙拉灵（ｓｐ－５７－６））与乙基纤维素（ＥＣ）的溶混性。模拟结果显示,在２７３Ｋ至３１６Ｋ的温度范围内,５－氨基水杨酸与乙基纤维素能以任何比例混溶。得出Ｅｍｉｘ（Ｔ）＝Ａ＋ＢＴ＋Ｃ／Ｔ模型,Ａ＝０．３６９４Ｅ＋０４,Ｂ＝－０．２６１０Ｅ－０２,ａｎｄＣ＝０．１８１８Ｅ＋０４,以及Ｅｍｉｘ（Ｔ）模型标准方差,Ｓ＝０．２６５４Ｅ－０３ｋｃａｌ／ｍｏｌ。对乙基纤维素及５－氨基水杨酸与乙基纤维素混溶过程的能量和构象分析表明,混溶过程中有乙基纤维素分子内和乙基纤维素与乙基纤维素分子间氢键形成。对两相混溶体系进行了热力学分析。     

High Bilirubin Levels Interfere with Serum Tartrate-Resistant Acid Phosphatase Determination: Relevance as a Marker of Bone Resorption in Jaundiced Patients

Serum tartrate-resistant acid phosphatase (TRAcP) activity is considered to be a biochemical marker of bone resorption. Recently, a lack of specificity of collagen-related markers for assessing bone turnover has been observed in patients with chronic liver disease. Thus, it could be of great interest to determine serum TRAcP activity in such patients. However, nonspecificity of the analytical reaction could occur when hemolyzed, lipemic, or icteric specimens are analyzed. Therefore, we have studied the interference caused by bilirubin in the measurement of serum TRAcP activity using the Hillmann method. The interference was assessed in two pools of serum containing different bilirubin concentrations but with similar total AcP levels. Mixing proportional parts of the two pools, 10 samples were also obtained. Serum activities of total AcP and TRAcP, and the concentration of bilirubin were measured in the 10 samples. Both the actual and the expected values obtained by theoretical calculations were compared. Serum bilirubin values of 2.4 mg/dl showed a negative interference of 15% in the determination of serum TRAcP activity, whereas values of bilirubin higher than 10 mg/dl interfered totally with the measurement of serum TRAcP. Bilirubin did not interfere with the total AcP determination. This study clearly shows the interference of bilirubin in the determination of serum TRAcP. This finding should be considered when bone metabolism disorders are evaluated in jaundiced patients. Received: 6 April 1998 / Accepted: 1 October 1998     

Men suffer vertebral fractures with similar spinal T-scores to women

OBJECTIVE: To evaluate the applicability of the WHO densitometric criteria for the diagnosis of spinal osteoporosis in men and to compare it with women with vertebral fractures, as well as to analyze the role of vertebral dimensions in the development of spinal fractures. METHODS: For these purposes we analyzed, using DXA, vertebral projected area and lumbar bone mineral density (BMD), as well as T and Z-scores in lumbar spine in a cohort of 66946 individuals; 2556 of these subjects had one or more atraumatic vertebral fracture (396 men and 2160 postmenopausal women). RESULTS: Men and women with fractures showed significantly lower mean BMD, T-score and Z-score values than individuals without fractures while vertebral dimensions were similar in both groups of patients. When comparing men and women with vertebral fractures, the former showed a significantly greater projected area (46.89+/-5.5 vs. 39.13+/-4.6 cm(2) p<0.001) and lumbar BMD (0.991+/- 0.21 vs. 0.938+/- t0.19 g/cm(2) p<0.001). However, the median lumbar T-score values were similar for both sexes (-2.3 in women vs. -2.2 in men; p: NS). In addition, a similar percentage of men and women with vertebral fractures showed T-score values <-2.5 in the lumbar spine (44% vs. 46%, p=NS). CONCLUSION: We conclude that although men with vertebral fractures have greater vertebral dimensions and BMD than women, the lumbar T-scores are similar. Therefore, it seems reasonable to adopt the same T-score values for the diagnosis of osteoporosis in men and women.     

重庆市主城区妊娠早期妇女优生优育相关病原体感染状况研究

目的 分析重庆市主城区妊娠早期妇女乙肝病毒、丙肝病毒、人类免疫缺陷病毒(HIV)、梅毒螺旋体(TP)及TORCH[弓形虫(TOX)、风疹病毒(RV)、巨细胞病毒(CMV)、单纯疱疹病毒(HSV)]的感染情况,促进优生优育.方法 收集2017-2019年在重庆市妇幼保健院产科门诊建档的妊娠早期妇女59157例,采用化学发光法检测血清中乙肝表面抗原(HBsAg)、乙肝表面抗体、乙肝e抗原(HBeAg)、乙肝e抗体、乙肝核心抗体(抗-HBc)、丙肝病毒抗体(抗-HCV)、HIV抗原及抗体(HIV-Ag/Ab)、抗-TP及TORCH;采用甲苯胺红不加热试验检测梅毒非特异性抗体;采用荧光定量PCR检测HBsAg阳性妊娠早期妇女血清中HBV-DNA.结果 2017-2019年重庆市主城区妊娠早期妇女HBsAg总阳性率为5.89％,且呈逐年下降趋势,差异均有统计学意义(P<0.05);抗-HCV、HIV-Ag/Ab、抗-TP总阳性率分别为0.15％、0.05％、0.72％,2017-2019年阳性率差异无统计学意义(P>0.05).妊娠早期妇女随着年龄的增长,HBsAg阳性率逐渐升高,差异有统计学意义(P<0.05).HBV感染妊娠早期妇女以"小三阳"模式所占比例最高,为74.07％(1197/1616),其次为"大三阳"模式,占20.05％(324/1616).2017-2019年妊娠早期妇女CM V-IgG及IgM阳性检出率最高,分别为95.78％(726/758)、4.34％(33/761);TOX-IgG与IgM阳性检出率最低,分别为4.99％(71/1422)、0.92％(13/1413).2017-2019年T O RC H阳性检出率比较,差异无统计学意义(P>0.05).不同年龄妊娠早期妇女TORCH阳性检出率比较,差异无统计学意义(P>0.05).结论 重庆市主城区妊娠早期妇女存在优生优育相关病原体感染的现象,应加强对育龄夫妇的宣传教育,做好孕前和孕期筛查工作,推进优生优育,提高人口素质.     

基于数据挖掘的叶天士治疗郁证用药规律探析

[目的]探析叶天士治疗郁证的组方用药规律。[方法]采用数据挖掘方法,对《临证指南医案·郁》中38则医案中的药物进行频数、药效和性味归经的描述性分析,并对其中26味高频药物进行关联规则分析和聚类分析,总结叶氏治疗郁证的临床经验。[结果]共得到处方45首,药物93味,高频药物共26味,主要有茯苓、牡丹皮、当归、郁金、白芍、生姜、栀子、甘草等,常用的药物组合包括“甘草-当归”“薄荷-茯苓”“白芍-甘草-当归”等。药效以补虚药最多;药性以寒、温、平为主;药味苦、甘、辛多见;归肺、心、肝、脾经最多。聚类分析将高频药物分为7组,涉及理气化痰、益气生血、滋阴清热、利水安神等剂。[结论]叶氏治疗郁证主张调畅情志,辨别虚实,善用寒温药物配伍;重视肝脾同调,且疏肝养肝并行;重视理气,多法泻火,气血并治。总结提炼其治疗郁证的学术思想,对临床上郁证的治疗具有参考价值。