急诊科护士遭受躯体暴力的预测线索探讨

目的探讨急诊科护士发生躯体暴力的预测线索。方法对四川省和重庆市5所医院的急诊科进行观察性研究,由专人观察和记录患方的行为线索,并根据行为变化是否转化为躯体暴力分为躯体暴力组和非躯体暴力组,统计分析两组行为变化的例数和躯体暴力的行为方式,采用Logistic回归分析确定护士发生躯体暴力的特定预测线索。结果共观察287例患者,非躯体暴力组219例,转化为躯体暴力组68例,躯体暴力发生率23.7%。Logistic回归分析显示当患方出现紧握双拳(OR=6.334)、挑衅(OR=5.672)、抵制护理措施(OR=5.164)、大声争吵(OR=4.651)、紧跟护理人员(OR=3.334)或鲁莽(OR=3.172)是发生躯体暴力的最强预测线索(P0.05,P0.01)。结论急诊科发生躯体暴力比较普遍,应快速、方便、有效地评估患方潜在的躯体暴力风险,采取相应的防范措施,以减少躯体暴力风险的发生,避免急诊科护士受到身体和心理伤害。     

Stepwise in vitro affinity maturation of Vitaxin, an αvβ3-specific humanized mAb

A protein engineering strategy based on efficient and focused mutagenesis implemented by codon-based mutagenesis was developed. Vitaxin, a humanized version of the antiangiogenic antibody LM609 directed against a conformational epitope of the α_vβ₃ integrin complex, was used as a model system. Specifically, focused mutagenesis was used in a stepwise fashion to rapidly improve the affinity of the antigen binding fragment by greater than 90-fold. In the complete absence of structural information about the Vitaxin-α_vβ₃ interaction, phage-expressed antibody libraries for all six Ig heavy and light chain complementarity-determining regions were expressed and screened by a quantitative assay to identify variants with improved binding to α_vβ₃. The Vitaxin variants in these libraries each contained a single mutation, and all 20 amino acids were introduced at each complementarity-determining region residue, resulting in the expression of 2,336 unique clones. Multiple clones displaying 2- to 13-fold improved affinity were identified. Subsequent expression and screening of a library of 256 combinatorial variants of the optimal mutations identified from the primary libraries resulted in the identification of multiple clones displaying greater than 50-fold enhanced affinity. These variants inhibited ligand binding to receptor more potently as demonstrated by inhibition of cell adhesion and ligand competition assays. Because of the limited mutagenesis and combinatorial approach, Vitaxin variants with enhanced affinity were identified rapidly and required the synthesis of only 2,592 unique variants. The use of such small focused libraries obviates the need for phage affinity selection approaches typically used, permitting the use of functional assays and the engineering of proteins expressed in mammalian cell culture.     

Pretreatment with intestinal trefoil factor alleviates stress-induced gastric mucosal damage via Akt signaling

BACKGROUNDStress-related gastric mucosal damage or ulcer remains an unsolved issue for critically ill patients. Stress ulcer prophylaxis has been part of routine intensive care, but uncertainty and controversy still exist. Co-secreted with mucins, intestinal trefoil factor (ITF) is reported to promote restitution and regeneration of intestinal mucosal epithelium, although the mechanism remains unknown.AIMTo elucidate the protective effects of ITF on gastric mucosa and explore the possible mechanisms.METHODSWe used a rat model of gastric mucosal damage induced by water immersion restraint stress and lipopolysaccharide-treated human gastric epithelial cell line to investigate the potential effects of ITF on damaged gastric mucosa both in vivo and in vitro.RESULTSITF promoted the proliferation and migration and inhibited necrosis of gastric mucosal epithelia in vitro. It also preserved the integrity of gastric mucosa by upregulating expressions of occludin and zonula occludens-1. In the rat model, pretreatment with ITF ameliorated the gastric mucosal epithelial damage and facilitated mucosal repair. The protective effects of ITF were confirmed to be exerted via activation of Akt signaling, and the specific inhibitor of Akt signaling {"type":"entrez-nucleotide","attrs":{"text":"LY249002","term_id":"1257710161","term_text":"LY249002"}}LY249002 reversed the protective effects.CONCLUSIONITF might be a promising candidate for prevention and treatment of stress-induced gastric mucosal damage, and further studies should be undertaken to verify its clinical feasibility.     

反思性学习对重症监护病房护士业务培训效果的影响

目的：探讨反思性学习对重症监护病房护士业务培训的影响,为其临床应用提供参考。方法选择重症监护室护士30名,根据工作年限、学历等平均分为观察组与对照组,对照组进行常规业务培训,观察组在常规培训基础上实施反思性学习,随访3个月对两组护士的业务培训结果进行比较。结果观察组培训后基础理论知识、基本技术操作技能、交流沟通能力、病情观察能力、责任管理能力、分析问题能力与解决问题能力得分分别为（90．45±7．12）,（91．44±6．12）,（18．55±1．23）,（17．64±1．65）,（18．43±1．25）,（18．16±1．24）与（17．19±1．76）分,明显高于对照组的（82．89±7．75）,（83．54±7．54）,（17．25±1．65）,（16．45±1．65）,（17．89±1．26）,（17．36±1．22）与（16．73±1．75）分,差异有统计学意义（t值分别为8．330,5．951,3．684,4．205,4．226,4．635,5．656;P＜0．05）。观察组护士纪律性、协作性、积极性、责任心、自信心评分均高于对照组,差异有统计学意义（P＜0．05）。观察组护士的满意度高于对照组,差异有统计学意义（Z＝－2．141,P＜0．05）。结论反思性学习可有效提高重症监护病房护士的业务培训效果,促进护士整体素质的改善及护理质量满意度的提高。     

Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese patients

Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21–34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1.0 ± 0.7 IU l^-1 vs 0.4 ± 0.4 IU l⁻¹, P < 0.05) and stimulated LH (28.3 ± 22.6 IU l⁻¹ vs 1.9 ± 1.1 IU l⁻¹, P < 0.01) levels, as well as larger testicle size (5.1 ± 2.6 ml vs 1.5 ± 0.3 ml, P < 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis.     

Multiple Genes of the Renin-Angiotensin System Are Novel Targets of Wnt/β-Catenin Signaling

Activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of CKD and cardiovascular disease. However, current anti-RAS therapy only has limited efficacy, partly because of compensatory upregulation of renin expression. Therefore, a treatment strategy to simultaneously target multiple RAS genes is necessary to achieve greater efficacy. By bioinformatics analyses, we discovered that the promoter regions of all RAS genes contained putative T-cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites, and β-catenin induced the binding of LEF-1 to these sites in kidney tubular cells. Overexpression of either β-catenin or different Wnt ligands induced the expression of all RAS genes. Conversely, a small-molecule β-catenin inhibitor ICG-001 abolished RAS induction. In a mouse model of nephropathy induced by adriamycin, either transient therapy or late administration of ICG-001 abolished established proteinuria and kidney lesions. ICG-001 inhibited renal expression of multiple RAS genes in vivo and abolished the expression of other Wnt/β-catenin target genes. Moreover, ICG-001 therapy restored expression of nephrin, podocin, and Wilms’ tumor 1, attenuated interstitial myofibroblast activation, repressed matrix expression, and inhibited renal inflammation and fibrosis. Collectively, these studies identify all RAS genes as novel downstream targets of Wnt/β-catenin. Our results indicate that blockade of Wnt/β-catenin signaling can simultaneously repress multiple RAS genes, thereby leading to the reversal of established proteinuria and kidney injury.     

Relative Bioavailability of Rifampicin in Four Chinese Fixed-dose Combinations Compared with Rifampicin in Free Combinations

Background:

Decreases in the bioavailability of rifampicin (RFP) can lead to the development of drug resistance and treatment failure. Therefore, we investigated the relative bioavailability of RFP from one four-drug fixed-dose combination (FDC; formulation A) and three two-drug FDCs (formulations B, C, and D) used in China, compared with RFP in free combinations of these drugs (reference), in healthy volunteers.

Methods:

Eighteen and twenty healthy Chinese male volunteers participated in two open-label, randomized two-period crossover (formulations A and C) or one three-period crossover (formulations B and D) study, respectively. The washout period between treatments was 7 days. Bioequivalence was assessed based on 90% confidence intervals, according to two one-sided t-tests. All analyses were done with DAS 3.1.5 (Mathematical Pharmacology Professional Committee of China, Shanghai, China).

Results:

Mean pharmacokinetic parameter values of RFP obtained for formulations A, B, C, and D products were 11.42 ± 3.41 μg/ml, 7.86 ± 5.78 μg/ml, 13.05 ± 6.80 μg/ml, and 16.18 ± 3.87 μg/ml, respectively, for peak plasma concentration (C_max), 91.43 ± 30.82 μg·h⁻¹ ·ml⁻¹, 55.49 ± 37.58 μg·h⁻¹ ·ml⁻¹, 96.50 ± 47.24 μg·h⁻¹ ·ml⁻¹, 101.47 ± 33.07 μg·h⁻¹ ·ml⁻¹, respectively, for area under the concentration-time curve (AUC_{0−24 h}).

Conclusions:

Although the concentrations of RFP for formulations A, C, and D were within the reported acceptable therapeutic range, only formulation A was bioequivalent to the reference product. The three two-drug FDCs (formulations B, C and D) displayed inferior RFP bioavailability compared with the reference (Chinese Clinical Trials registration number: ChiCTR-TTRCC-12002451).