Characterization of Ribosomal Binding and Antibacterial Activities Using Two Orthogonal High-Throughput Screens

We report here the affinity and antibacterial activity of a structurally similar class of neomycin dimers. The affinity of the dimer library for rRNA was established by using a screen that measures the displacement of fluorescein-neomycin (F-neo) probe from RNA. A rapid growth inhibition assay using a single drug concentration was used to examine the antibacterial activity. The structure-activity relationship data were then rapidly analyzed using a two-dimensional ribosomal binding-bacterial inhibition plot analysis.     

2例Cornelia de Lange综合征病例报告并NIPBL基因突变研究

目的：对2例生长发育迟缓伴有特殊面容及肢体发育异常的患儿进行基因检测,实现罕见病的精准诊断,为遗传咨询提供指导。方法：应用单基因检测及全外显子组高通量测序技术对临床疑似CdLS患儿进行致病基因突变筛查,并行一代测序验证以及患儿父母的验证。结果：本研究中的2例患儿均检测到国内外尚未报道的NIPBL基因突变,c.2252 dupA、p.Asn751Lysfs以及NM-015384.4：c.6179dupA,父母均无携带,为新生变异。结论：对于发育迟缓伴特殊面容及肢体异常的患儿要考虑到Cornelia de Lang综合征可能,采用基因检测手段实现精准诊断,为患者及家属遗传咨询提供依据。     

补充计量学研究可视化分析

本文对来自于中国知识基础设施工程（China National Knowledge Infrastructure,CNKI）数据库中研究补充计量学的相关文献进行收集整理,并使用CiteSpace软件进行可视化分析,分析方法有关键词聚类、作者聚类、作者合作网络等。分析结果显示中文补充计量学相关研究主要聚焦在补充计量学、学术影响力研究、科学评价研究、相关性分析研究、社交网络研究这几个方面。同时,分析结果也揭示出理论创新不足、合作研究较少等情况,建议这两方面进一步加强。     

丝氨酸羟甲基转移酶2在小鼠肝再生过程中的变化规律及作用

目的 探索丝氨酸羟甲基转移酶2(serine hydroxymethyl transferase 2,SHMT2)在小鼠肝再生过程中的表达规律,以及其对小鼠肝再生是否有促进作用.方法 SPF级C57BL/6小鼠120只分为肝切除组(2/3 PH)、假手术组(SHAM)、腺病毒干扰组(siSHMT2)及注射生理盐水对照组(Control),每组30只;肝切除组下设1、3、5、7、9d5个时相点,每个时相点6只.小鼠肝切除之后分别取1、3、5、7、9d的肝脏组织及血清,采用qPCR、Western blot和免疫组化检测SHMT2及其下游分子甘氨酸脱氢酶(glycine dehydrogenase,GLDC)的变化规律、血清中丙氨酸转氨酶(alanine transaminase,ALT)和谷草转氨酶(aspartate transaminase,AST)的浓度.取注射腺病毒干扰SHMT2第5天的肝脏组织,通过Westernblot和观察荧光强度,确定转染效果,并检测血浆中ALT和AST水平,免疫组化检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA).结果 SHMT2及其下游分子GLDC在小鼠肝再生的后第5、7天表达最高,qPCR检测结果显示,SHMT2第5天的表达量是第1天的1.63倍(P＜0.05).在干扰SHMT2之后,小鼠第5天再生肝脏的质量由(0.79±0.13)g降低至(0.63 ±0.ll)g(P ＜0.05),再生度由(36.37±2.21)％降低至(31.33±1.92)％,肝指数由(3.76±0.44)％降低至(3.13±0.29)％,并且肝功能指标ALT由(70.00±9.52) U/L升高至(154.15±16.49) U/L,AST由(140.09±32.85) U/L升高至(403.41±68.63) U/L(P＜0.05),PCNA阳性率从(53.6±2.3)％降低至(39.0±3.2)％(P＜0.05).结论 SHMT2在肝脏再生的后期高表达,促进残肝的再生,其机制可能与增强肝脏对缺血、缺氧的耐受,提高三磷酸腺苷水平有关.     

血、尿IL-18和KIM-1联合检测对冠心病患者行介入术后急性肾损伤的早期诊断意义

目的:探讨分析血、尿白细胞介素-18（interleukin 18 ,IL-18）和肾损伤分子-1（kidney injury molecule 1,KIM-1）联合检测在冠心病介入术后急性肾损伤( acute kidney injury,AKI) 早期诊断中的价值。方法：选取河南省平顶山市第二人民医院心内科收治的诊断为冠心病并行介入术治疗的患者243例,分为AKI组48例,非AKI组195例;收集所有患者术后0、2、4、6、8、10、12、24、48、72 h血液及尿液样本,检测各时间点血液样本的血清肌酐（serum creatinine,SCr）、IL-18和KIM-1,尿液样本的IL-18和KIM-1水平。结果：AKI组患者术后12、24、48、72 h SCr值均明显高于0 h基线值（P均<0.05）;AKI组术后各时间点血、尿IL-18和KIM-1水平均高于0 h基线值,IL-18在2 h（血）或4 h（尿）时达到峰值,KIM-1在6 h（血）或8 h（尿）时达到峰值（P均<0.05）;Pearson相关分析显示,AKI组术后血（2 h）、尿（4 h）IL-18和血（6 h）、尿（8 h）KIM-1水平均与术后24 h SCr呈正相关（P均<0.05）;ROC曲线分析显示,血（2 h）、尿（4 h）IL-18和血（6 h）、尿（8 h）KIM-1 ROC曲线下面积（AUC）对AKI的诊断均具有较好的诊断效能;血（2 h）、尿（4 h）IL-8和血（6 h）、尿（8 h）KIM-1联合检测诊断AKI的AUC均大于两者的单独检测。结论：对冠心病患者进行介入术后的2 h血IL-18、4 h尿IL-18、6 h血KIM-1、8 h尿KIM-1的联合检测,对早期诊断AKI具有良好的诊断效能,有一定的诊断价值,其或可成为早期诊断AKI的重要参考依据。     

系统性硬化症合并肺间质病变患者外周血中IL-8、CXCR1、CXCR2的表达及意义

目的分析系统性硬化症(SSc)合并肺间质病变(ILD)患者外周血中白介素8 (IL-8)、趋化因子受体1(CXCR1)、CXCR2表达的临床意义。方法选取2018年1月-2019年5月武汉市第五医院风湿免疫科治疗的系统性硬化症患者42例作为研究对象,其中合并ILD患者25例为SSc-ILD组,非ILD患者17例为SSc-非ILD组。另选取同期来院体检的健康者30例为健康对照组。检测3组受试者肺功能,外周血单个核细胞(PBMC)中CXCR1、CXCR2mRNA,血清IL-8、ESR、CRP、IgA、IgG、IgM、补体C3水平。采用Spearman进行检测指标的相关性分析。结果 SScILD组FEV1%、FEV1/FVC显著低于SSc-非ILD组和健康对照组(F/P=76.626/0.000,29.097/0.000),且SSc-非ILD组显著低于健康对照组(P<0.05);SSc-ILD组CXCR1、CXCR2 mRNA表达水平及血清IL-8、ESR、CRP、IgA、IgG、IgM水平显著高于SSc-非ILD组和健康对照组(F/P=581.600/0.000、401.103/0.000、149.551/0.000、34.990/0.000、37.207/0.000、189.508/0.000、117.657/0.000、12.708/0.000),且SSc-非ILD组各指标显著高于健康对照组(P<0.05);SSc患者外周血中CXCR1、CXCR2及血清IL-8水平与FEV1%呈显著负相关(r/P=-0.608/0.005、-0.538/0.048、-0.613/0.003),CXCR1、IL-8与FEV1/FVC呈显著负相关(r/P=-0.616/0.002、-0.581/0.0.15),CXCR2与FEV1/FVC无显著相关性(P>0.05);SSc合并ILD患者CXCR1、CXCR2、IL-8与CRP、ESR、IgA、IgG、IgM均呈正相关(P<0.05),与C3无显著相关性(P>0.05)。结论 IL-8与其受体CXCR1、CXCR2在系统性硬化症合并肺间质病变患者血清中均高表达,IL-8可能在SSc-ILD的发病机制中具有重要作用。     

Sex differences in estrogen receptor gene polymorphism and its association with lupus nephritis in Chinese

BACKGROUND/AIMS: Lupus nephritis (LN) is a clinical heterogeneous autoimmune disease and genetic factors contribute to the development of LN. One of the most striking characteristics in LN is the high prevalence among childbearing women, as well as that its clinical manifestation differs in women and men, suggesting the role of sex hormones in its pathogenesis. METHODS: The PvuII and XbaI restriction fragment length polymorphism (RFLP) of estrogen receptor (ER) gene were analyzed in 245 biopsy-proven LN patients (58 males and 187 females) and 172 normal controls (101 males and 71 females) by PCR-RFLP. The clinical and pathological features of 49 male and 152 female LN patients with different genotypes were analyzed. RESULTS: It was found that genotype PpXx, ppxx and Ppxx were three major genotypes of ER gene in both of lupus patients and control groups. The distribution of ER gene polymorphism was quite different in lupus patients of different genders. The frequency of the PpXx genotype in male LN patients was significantly higher than both the gender matched normal controls (p < 0.05) and the female LN patients (p < 0.05), while no difference was shown in the frequency of PpXx genotype between female LN patients and gender matched controls. Interestingly, skin rashes and arthritis were found more common in the patients with PpXx genotype. The frequency of hematological abnormalities and hypertension were higher in patients with ppxx genotype (p < 0.05), while capillary thrombi and glomerular sclerosis were more frequently complicated in the patients with ppxx genotype. In addition, the renal vasculitis and interstitial injury were more frequent in those with Ppxx genotype (p < 0.01). CONCLUSION: The distribution of ER gene polymorphism in LN patients is distinct with different gender. The PpXx genotype of ER gene may be associated with the susceptibility of SLE in male. ER gene polymorphism is probably one of the genetic factors contributing to the development of clinical heterogeneity and sexually dimorphic manifestations of LN.     

Increased HLA-A*11 in Chinese children with steroid-responsive nephrotic syndrome

Human leukocyte antigen (HLA) associations have been frequently reported in childhood steroid-responsive nephrotic syndrome (SRNS) in other populations. The aim of this study was to characterize the immunogenetic background of Singaporean Chinese patients with childhood SRNS. We determined the HLA class I (HLA-A* and HLA-B*) as well as class II (HLA-DRB1*, HLA-DQB1*) gene polymorphisms using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique, in patients with SRNS (n=64) and normal controls (n=236 for HLA-A*, n=80 for HLA-B*, HLA-DRB1* and HLA-DQB1*). The frequency of HLA-A*11 allele was significantly higher in the SRNS patients compared to controls (78.1% vs 54.2%, respectively; relative risk, RR=3.01, Pc=0.011). However, there was no significant difference in the allele frequencies of HLA-B*, HLA-DRB1* and HLA-DQB1* between the SRNS patients and controls, unlike that in previous studies. Our data suggest that the immunogenetic background of Singaporean Chinese with childhood SRNS was different from that in other populations. As HLA-A*11 has been strongly associated with other autoimmune diseases, it is conceivable that the HLA-A*11-specific motif may play a role in the development of the abnormal T-cell-mediated immune response that may be responsible for triggering the proteinuria seen in SRNS. Received: 24 April 2001 / Revised: 14 November 2001 / Accepted: 18 November 2001     

140例胃间质瘤的外科治疗分析

Objective To analyze the outcome of the patients with gastric gastrointestinal stromal tumor (GIST) after surgical treatment and identify the associated risk factors. Methods Clinical data and the tissue slices including immunohistochemistry staining of 140 patients with gastric GIST from January 1990 to December 2008 were retrospectively reviewed. SPSS 16.0 for Windows software package was used for statistical analysis. Results The overall survival rates of 1-, 3-, 5-year were 96.8%,86.7% and 79.3%, respectively. The survival rates of 1-, 3-, 5-year were 98.1%, 90.0% and 85.4% in patients who underwent complete tumor resection. But the survival rates of 1-, 3-, 5-year were 38.1%, 0 and 0 in patients with incomplete tumor resection. The differences were statistically significant (P＜0.05). Gender, preoperative metastasis, tumor size, pathology type, karyokinesis, recurrence and metastasis were associated with survival rates in patients with complete tumor resection by univariate analysis. However, only tumor size, karyokinesis, recurrence and metastasis were associated with survival rates by Cox regression multivariable analysis (P＜0.05). Conclusion Surgery remains the main treatment for gastric GIST. Local complete resection is the principal treatment.