急性冠脉综合征患者早期风险识别与管理策略应用研究

目的 探讨急性冠脉综合征(acute coronary syndrome,ACS)患者早期风险识别与管理策略应用效果。方法 选取2018年8月-2019年5月入住笔者所在医院心血管内科ACS患者60例。将2018年8-12月收治的30例患者设为对照组,采取常规的护理方案;2019年1-5月收治的30例患者设为观察组,采取基于国家早期预警评分(national early warning score,NEWS)联合使用欧洲五维健康量表(Euro qol five-dimensional questionnaire,EQ-5D)进行早期风险识别,并实施管理策略。结果 干预后,观察组总住院日缩短(t=-2.288,P=0.026);医生对护士病房巡视、报告病情、医护沟通满意率明显增高(P<0.05),观察组患者对护士主动观察病情、关注患者不适的满意率均高于对照组(P＜0.05)。结论 基于NEWS评分联合使用EQ-5D量表对ACS患者进行评估,利于护士在判断病情严重度基础上更好地实施护理策略,能改善疾病相关指标,提高医生和患者对护理服务的满意度。     

Serum bile acids, programmed cell death and cell proliferation in the mucosa of patients with colorectal adenomas

BACKGROUND: Deoxycholic acid induced programmed cell death and an imbalance with cell proliferation may favour colorectal tumourigenesis according to 'in vitro' studies, but information is lacking on the relationships occurring 'in vivo' in humans. AIMS: To evaluate whether serum deoxycholic acid is associated with programmed cell death and cell proliferation in colonic mucosa. METHODS: In 10 patients with colorectal adenomas, we measured fasting serum levels of bile acids; and, in normal colonic mucosa, programmed cell death by the TUNEL technique and cell proliferation by immunohistochemical staining with anti-Ki67. Total and compartmental indices for both activities were calculated. RESULTS: Among serum bile acids, only total deoxycholic acid (median: 0.89 micromol/L +/- 0.54 95% CI), showed a significant positive correlation with the total and basal compartments PCD Index (r = 0.68, p < 0.05). Total proliferation index showed no correlation with either total PCD Index, or bile acids. Within the median compartment of the crypt, cell proliferation was negatively associated with all unconjugated bile acids. CONCLUSIONS: The positive association between deoxycholic acid and programmed cell death in the basal compartment of the crypt, and the negative association of cell proliferation and unconjugated bile acids in the median compartment, do not seem to support the co-carcinogenic effect of deoxycholic acid.     

A case of tooth autotransplantation after long-term cryopreservation using a programmed freezer with a magnetic field

This case report describes the treatment of a skeletal Class III malocclusion with autotransplantation of a cryopreserved tooth. To gain an esthetic facial profile and good occlusion, extraction of bimaxillary premolars and surgical therapy were chosen. The patient had chronic apical periodontitis on the lower left first molar. Although she did not feel any pain in that region, the tooth was considered to have a poor prognosis. Therefore, we cryopreserved the extracted premolars to prepare for autotransplantation in the lower first molar area because the tooth would probably need to be removed in the future. The teeth were frozen by a programmed freezer with a magnetic field (CAS freezer) that was developed for tissue cryopreservation and were cryopreserved in −150°C deep freezer. After 1.5 years of presurgical orthodontic treatment, bilateral sagittal split ramus osteotomy was performed for mandible setback. Improvement of the facial profile and the occlusion were achieved in the retention phase. Six years after the initial visit, the patient had pain on the lower left first molar, and discharge of pus was observed, so we extracted the lower left first molar and autotransplanted the cryopreserved premolar. Three years later, healthy periodontium was observed at the autotransplanted tooth. This case report suggests that long-term cryopreservation of teeth by a CAS freezer is useful for later autotransplantation, and this can be a viable technique to replace missing teeth.     

类风湿关节炎患者外周血CD4+T细胞表面PD-1的表达及意义

目的观测类风湿关节炎（RA）患者外周血CD4+T细胞表面程序性死亡因子1（PD-1,CD279）表达的变化、探讨PD-1在RA发生、发展中的作用。方法应用流式细胞术检测40例RA患者和20例健康体检者外周血CD4+T细胞表面PD-1的阳性率,对比分析RA患者病情活动组与稳定组间PD-1表达的差异,分析PD-1阳性率与C反应蛋白（CRP）,红细胞沉降率（ESR）,类风湿因子（RF）等临床指标的相关关系。结果病情活动期RA患者外周血CD4+T细胞PD-1阳性率为（32.90±12.15）%,明显高于健康体检者（22.32±6.04）%,差异有统计学意义（P＜0.01）;稳定期RA患者的PD-1阳性率为（27.49±6.79）%,与健康体检者的差异无统计学意义（P＞0.05）。RA患者中,CD4+T细胞表面PD-1阳性率与RF呈正相关（r=0.525,P＜0.01）,与ESR呈正相关（r=0.328,P＜0.05）,与CRP无明显相关性（r=0.232,P＞0.05）。结论病情活动期RA患者外周血CD4+T细胞表面PD-1表达增加,可能对疾病的发生、发展具有重要意义。     

不同联律间期室性期前收缩刺激对窦性心率震荡的影响

目的观察不同联律间期室性期前收缩刺激对窦性心率震荡的影响。方法对20例阵发性室上性心动过速（PSVT）患者,分别通过动态心电图行自发性心率震荡检测和通过心室程序刺激行诱发性心率震荡检测,比较不同联律间期室性期前收缩刺激所诱发的窦性心率震荡参数[震荡初始（TO）和震荡斜率（TS）]的差异。结果自发性窦性心率震荡[（-2.29±1.47）%、（10.14±5.71）ms/R-R]与诱发性窦性心率震荡[（-1.71±1.36）%、（7.12±4.68）ms/R-R]比较,差异均无统计学意义（均P＞0.05）,右心室心尖部、右心室流出道室性期前收缩的联律间期与诱发性窦性心率震荡参数TO和TS均有较好的相关性（r＝-0.825、-0.793、-0.712、-0.689,P＜0.01）。结论诱发性窦性心率震荡与自发性窦性心率震荡具有一致性,心室不同刺激部位对诱发性窦性心率震荡结果无明显影响,室性期前收缩的联律间期与诱发性窦性心率震荡参数有相关性,动态心电图记录中心室不同部位和不同联律间期的室性期前收缩所计算的心率震荡参数值均有较高的可信度。     

Study of Mechanical Properties and Durability of Alkali-Activated Coal Gangue-Slag Concrete

Herein, a new geopolymer is recognized as a potential alternative cementing material of ordinary Portland cement (OPC), which is used for reducing carbon emissions and efficiently recycling the waste. Therefore this paper mainly studied the alkali-activated coal gangue-slag concrete (ACSC) was prepared by using the coal gangue-slag and Na₂SiO₃ and NaOH complex activator. The ratio of coal gangue (calcined and uncalcined) coarse aggregate replacing the gravel was 0%, 30%, 50%, 70%, and 100%. The water and salt freeze-thaw resistance, compressive strength, chloride permeation, microstructure, performance mechanism, inner freeze-thaw damage distribution, and mechanics models of ACSC were investigated. Results show that ACSC displayed excellent early age compressive strength, and the compact degree and uniformity of structure were better compared with the ordinary Portland cement (OPC) when the coal gangue replacement rate was less than 50%. The ACSC demonstrated the best chloride penetration resistance under 30% uncalcined coal gangue content, which was less than 27.75% lower than that of using OPC. At the same number cycles, especially in the salt freezing, the calcined coal gangue had lowered advantages of improving resistance freeze-thaw damage resistance. Water and salt accumulative freeze-thaw damage mechanics models of ACSC were established by using the relative dynamic elasticity modulus. The exponential function model was superior to the power function model with better precision and relativity, and the models accurately reflected the freeze-thaw damage effect.     

Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes

Programmed cell death 1 (PD-1) is an inhibitory molecule expressed by activated T cells. Its ligands (PD-L1 and -L2; PD-Ls) are expressed not only by a variety of leukocytes but also by stromal cells. To assess the role of PD-1 in CD8 T cell-mediated diseases, we used PD-1-knockout (KO) OVA-specific T cell-receptor transgenic (Tg) CD8 T cells (OT-I cells) in a murine model of mucocutaneous graft-versus-host disease (GVHD). We found that mice expressing OVA on epidermal keratinocytes (K14-mOVA mice) developed markedly enhanced GVHD-like disease after transfer of PD-1-KO OT-I cells as compared to those mice transferred with wild-type OT-I cells. In addition, K14-mOVA × OT-I double Tg (DTg) mice do not develop GVHD-like disease after adoptive transfer of OT-I cells, while transfer of PD-1-KO OT-I cells caused GVHD-like disease in a Fas/Fas-L independent manner. These results suggest that PD-1/PD-Ls-interactions have stronger inhibitory effects on pathogenic CD8 T cells than does Fas/Fas-L-interactions. Keratinocytes from K14-mOVA mice with GVHD-like skin lesions express PD-L1, while those from mice without the disease do not. These findings reflect the fact that primary keratinocytes express PD-L1 when stimulated by interferon-γ in vitro. When co-cultured with K14-mOVA keratinocytes for 2 days, PD-1-KO OT-I cells exhibited enhanced proliferation and activation compared to wild-type OT-I cells. In addition, knockdown of 50% PD-L1 expression on the keratinocytes with transfection of PD-L1-siRNA enhanced OT-I cell proliferation. In aggregate, our data strongly suggest that PD-L1, expressed on activated target keratinocytes presenting autoantigens, regulates autoaggressive CD8 T cells, and inhibits the development of mucocutaneous autoimmune diseases.     

人类凋亡相关新基因HDDC2功能的初步研究

利用NCBI数据库分析得到人类基因HDDC2的DNA序列,通过聚合酶链式反应克隆得到该功能基因,运用生物信息学分析该蛋白的特性,同时利用细胞生长曲线检测HDDC2促进HEK293细胞凋亡作用;使用流式细胞术检测HDDC2对HEK293细胞的作用以及HDDC2引起HEK293细胞线粒体膜的影响;运用Western blot检测HDDC2引起细胞凋亡相关基因PARP的作用。生物信息学预测HDDC2基因位于6q22.31,全长1615bp,从205到819有一个编码204个氨基酸的开放阅读框,编码一个分子量约23.4kd的蛋白。HDDC2基因含有6个外显子和5个内含子,定位于线粒体,且在人类正常组织中普遍表达,同时HDDC2基因能够明显引起HEK293细胞的程序性死亡,能够引起其磷脂酰丝氨酸的外翻和线粒体膜电位的下降,同时该基因能够引起细胞凋亡相关基因PARP的活化。人类基因HDDC2是一个可能参与到程序性细胞死亡相关的新基因,它的发现有助于发现新的药物作用靶点或者新的基因治疗药物。     

Immunomodulatory aspects in the progression and treatment of oral malignancy

Inflammation substantially affects the risk of oral malignancy. Pro-inflammatory cytokine, interferon (IFN)-γ, confers anti-tumor activity using several different mechanisms. Conversely, higher expression of interleukin (IL)-17 is associated with worse prognosis. Monocyte chemotactic protein (MCP)-1 correlates positively with poor long-term survival of head and neck squamous cell carcinoma (HNSCC) patients. IL-1α affects cancer associated fibroblasts and macrophages, and promote several malignant phenotypes including immune suppression. Some anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β, relate to pro-tumoral activities.Among immune checkpoint modulators, programmed death (PD-)1 and PD-ligand (L)1 facilitate oral squamous cell carcinoma (OSCC) cell evasion from immune surveillance, and the expression status of these has a prognostic value.OSCCs contain tumor associated macrophages (TAMs) as major stromal cells of their tumor microenvironment. Among the two distinctive states, M2 macrophages support tumor invasion, metastasis and immune suppression. Crosstalk between TAMs and OSCC or cancer-associated fibroblasts (CAF) plays an important role in the progression of OSCC.Clinical trials with blocking antibodies against IL-1α or melanoma-associated antigens have been reported as therapeutic approaches against OSCCs. The most promising approach activating antitumor immunity is the blockade of PD-1/PD-L1 axis. Manipulating the polarization of pro-tumorigenic macrophages has been reported as a novel therapeutic approach.     

Novel Immunotherapeutic Strategies in Development for Renal Cell Carcinoma

Context

The purpose of this report is to review immunotherapies under investigation for patients with renal cell carcinoma (RCC), the most common form of kidney cancer, for which the incidence and mortality rate continue to increase.

Objective

To summarize and evaluate current data on immunotherapies for RCC and discuss issues to be resolved before integration into the RCC treatment paradigm.

Evidence acquisition

A search of Medline, clinicaltrials.gov, and congress abstracts/treatment guidelines was performed in May 2012 using the following terms (and variations): metastatic renal cell carcinoma, practice guidelines, response/resistance to current treatments, immunotherapy, novel immunotherapeutic strategies, T-cell modulation, immune priming, innate immunity, and combination therapy.

Evidence synthesis

Prior to the advent of novel agents targeting the vascular endothelial growth factor and mechanistic target of rapamycin pathways, interleukin-2 (IL-2) and interferon-α were the mainstays of RCC treatment. IL-2 remains one of the only treatments capable of curing advanced RCC, albeit in few patients. Despite recent advances, unmet need still exists for patients in the adjuvant setting, those with poor prognostic factors, and those who have progressed on prior targeted therapies. Improved understanding of host–tumor immune interactions has led to development of novel immunotherapeutic agents, including antibodies against immune checkpoint proteins (eg, programmed death-1 and cytotoxic T-lymphocyte antigen-4), and various vaccines. Because many of these compounds are in development, clinical experience with them is limited, although some have demonstrated activity in preliminary studies.

Conclusions

It is not yet clear where these new immunotherapies will fit into RCC treatment paradigms, but they may provide new options for patients whose current choices are limited. Furthermore, predictive biomarkers are needed to identify patients who will derive the greatest benefit from immunotherapy.