Rspo1通过Wnt/β-catenin信号通路调节成骨细胞分化的研究进展

在成骨细胞的分化增殖中,经典Wnt /β-catenin通路起着重要的调节作用;此通路中的任何一个因子都能影响成骨细胞的分化增殖。近几年里,大量研究证明R-脊椎蛋白家族巳成为Wnt/β-catenin信号通路的重要调节因子。本文就Rspo1通过Wnt/β-catenin信号通路调控影响成骨细胞分化增殖的研究进展作一综述。     

中药配失眠三针对失眠症的疗效分析

目的观察中医药方法治疗脑梗死后痰热内扰型失眠症临床疗效。方法按随机数字表法将240例脑梗死后痰热内扰型失眠症患者分为治疗1组、治疗2组和对照组。治疗1组采用清热安神汤治疗;治疗2组采用清热安神汤加失眠三针治疗;对照组采用艾司唑仑治疗,治疗30d和停药30d,分别进行临床总有效率和复发率的观察。结果治疗1组总有效率为94.94%,治疗2组总有效率96.25%,对照组总有效率为83.12%,治疗1组、治疗2组与对照组比较总有效率,差异有统计学意义(P0.05);治疗1组与治疗2组比较总有效率差异无统计学意义(P0.05)。治疗1组复发率为21.54%,治疗2组复发率4.35%,对照组复发率56.25%,治疗1组、治疗2组与对照组比较复发率差异有统计学意义(P0.05);治疗1组与治疗2组比较复发率,差异有统计学意义(P0.01)。结论清热安神汤、清热安神汤加失眠三针治疗脑梗死后痰热内扰型失眠症疗效显著,清热安神汤加失眠三针治疗后复发率显著低于其他两种治疗方法。     

Delayed-onset of progressive pseudorheumatoid dysplasia in a Chinese adult with a novel compound <Emphasis Type="Italic">WISP3</Emphasis> mutation: a case report

Background

Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive genetic disease that is characterized by pain, stiffness and enlargement of multiple joints with an age of onset between 3 and 8 years old. Mutations in the WISP3 (Wnt1-inducible signal pathway) gene are known to be the cause of PPD.

Case presentation

We present a case of delayed-onset PPD in a Chinese man. The 35-year-old proband presented with an almost 20-year history of pain and limitations in mobility in multiple joints. Based on the clinical manifestations, the patient was diagnosed with PPD; however, there was no specific evidence to confirm this diagnosis. Through mutational analyses, two WIPS3 mutations in exon 4, including a novel frameshift mutation (c.670dupA) in the paternal allele and an already described nonsense mutation (c.756C?>?A, p.Cys252*) in the maternal allele, were identified in the proband. Thus, the patient was diagnosed with PPD. Furthermore, we found that the proband’s son only carried one of the mutations (c.670dupA) and therefore determined that he would not be affected by PPD in the future.

Conclusions

In this case, we successfully diagnosed the disease that the proband was affected precisely after the reunion of clinical diagnosis and genetic analysis. These findings demonstrate the clinical utility of genetic analysis to diagnose skeletal dysplasia and guide genetic counseling.

     

Smoking quantity determines disease activity and function in Chinese patients with ankylosing spondylitis

The objective of this study was to systemically and comprehensively evaluate the associations between smoking and disease outcomes in patients with ankylosing spondylitis (AS). Information on smoking, clinical features, and sociodemographic characteristics was collected by a questionnaire administered directly to the patient. Group differences were analyzed by t test or chi-square test. Logistic regression analysis was conducted with the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte sedimentation rate as the dependent variables and different stratification of smoking duration, smoking intensity, and cumulative smoking as independent variables. In order to compare our results with previous studies, meta-analysis was performed to calculate standardized mean difference (SMD) for relationship between outcomes and smoking status. A total of 1178 AS patients were analyzed. Compared with non-smokers, the risk of having active disease (BASDAI ≥?4) was higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15 pack-years (OR?=?1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67], respectively); and smokers had increasing risk of BASDAI ≥?4 with increasing years of smoking, or cigarettes per day, or pack-years (p_-trend?=?0.010, 0.008 and 0.006, respectively). The risk of having active disease was higher in patients who smoked at least 15 cigarettes per day or 15 pack-years (OR?=?1.74 [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of cigarettes per day and pack-years. Smokers had an increased risk of BASFI ≥?4 (p_-trend?=?0.040 and 0.007, respectively). By meta-analysis, current, former and ever smokers had significantly higher BASDAI (SMD?=?0.34 [0.18, 0.48], 0.10 [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD?=?0.35 [0.16, 0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non-smokers. Smoking is a risk factor for greater disease activity and worse functioning in AS patients.     

Increased expression of GAB1 promotes inflammation and fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2‐associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)‐induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6‐fold higher in peripheral blood mononuclear cells (PBMC), 2.5‐fold higher in CD4 + T cells, and 2‐fold higher in skin from of SSc patients (P < .01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8‐fold higher) in SSc skin. Additionally, BLM‐induced SSc mice showed mRNA levels of Gab1 2‐fold higher than saline‐treated controls, and Gab1 expression correlated positively with collagen content. A further in vitro study showed silencing of GAB1 suppressed inflammatory gene expression in TNF‐α induced fibroblasts. Additionally, GAB1 deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF‐β induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes.     

Correction to: The IgG galactosylation ratio is higher in spondyloarthritis patients and associated with the MRI score

Clinical Rheumatology - In the original version of the above article the References 19 and 20 were incorrect which cannot describe the development of the SPARCC score.     

临床医学影像技术在高原病诊断和治疗评估中的应用

高原病是指人体进入高海拔低压低氧环境后,因适应能力不全或失调而引发的一系列临床综合征。该病已成为高原旅居者面临的重大公共健康问题,严重时可危及生命。因此,亟需开发高原病的早期诊断、治疗监测的新方法。X线、CT、MRI、超声、SPECT和PET等临床医学影像技术已成为高原病临床诊疗决策的实用工具。笔者综述了多种医学影像技术在高原病诊断和治疗评估中的应用,以期为高原病的精准诊治提供新思路。     

Matrix metalloproteinase-2 polymorphisms and clinical outcome of Chinese patients with nonsmall cell lung cancer treated with first-line, platinum-based chemotherapy

BACKGROUND:

Matrix metalloproteinase‐2 (MMP‐2) is well known for its critical role in cell survival and cancer development. It also plays an important role in hematopoietic recovery after chemotherapy‐induced myelosuppression. In this study, the authors investigated the association of MMP‐2 polymorphisms with treatment efficacy and the occurrence of severe toxicity in patients with nonsmall cell lung cancer (NSCLC) who were receiving first‐line, platinum‐based chemotherapy.

METHODS:

A pharmacogenetic association study was performed in 663 Chinese patients who had inoperable stage III/IV NSCLC and were receiving first‐line, platinum‐based regimens. Information about objective response, progression‐free survival, overall survival, grade 3 or 4 gastrointestinal toxicity (nausea/vomiting), and hematologic toxicity (neutropenia, anemia, thrombocytopenia) was available. Sixteen tag single nucleotide polymorphisms (SNPs) of MMP‐2 were assessed.

RESULTS:

In 7 polymorphisms, significant associations were observed with the incidence of grade 3 or 4 neutropenia. The variant homozygotes of reference SNP rs12934241 exhibited the most significant effect on the risk of neutropenia, leading to an incidence rate that increased from 12.3% (for the C/C genotype) to 50% (for the T/T genotype; odds ratio, 8.33; P = 8.8 × 10^?5). Stratified analyses indicated that rs12934241 exhibited a much stronger influence in the cisplatin‐gemcitabine regimen subgroup than subgroups that received other regimens (P_interaction = .003). Further haplotype analyses produced results that were consistent with results from single‐SNP analyses. However, no significant association was observed between MMP‐2 polymorphisms and treatment efficacy, including response rate, clinical benefit, progression‐free survival, and overall survival.

CONCLUSIONS:

To the authors' knowledge, this study provides the first evidence for a predictive role of MMP‐2 polymorphisms in the variability of severe chemotherapy‐related neutropenia among Chinese patients with platinum‐treated, advanced NSCLC. Cancer 2012;3587–3598. © 2011 American Cancer Society.     

疏血通注射液治疗心脑血管疾病的药理及临床研究进展

摘 要 目的： 促进疏血通注射液正确的临床应用,为其进一步研究提供可参考的资料。方法: 查阅有关疏血通注射液研究文献,并对其药理及临床研究进行介绍。结果:本文总结了疏血通注射液研究发展状况,对药理和临床研究进行了综述。结论: 疏血通注射液联合用药或单独用药治疗某些心脑血管疾病、尤其是缺血性脑中风具有显著疗效。但疏血通中起关键作用的活性成分还有待进一步研究。