The Influence of Triclosan on Biomarkers of Cardiovascular Risk in Patients in the Cardiovascular and Periodontal Study (CAPS): A Randomized Controlled Trial

Background: Triclosan toothpaste is effective in controlling plaque and gingivitis and slowing progression of periodontitis; however, its influence on inflammatory biomarkers of cardiovascular disease (CVD), as well as on kidney and liver function, is unknown. Methods: Patients recruited from the Cardiovascular Unit at Prince Charles Hospital, Brisbane, Australia, were randomized to triclosan (n = 193) or placebo (n = 190) groups and assessed for total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, triglycerides, C‐reactive protein, erythrocyte sedimentation rate (ESR), hemoglobin, total white cell count (WCC), estimated glomerular filtration rate (eGFR), and liver function enzymes, annually for 5 years. A standard mixed model for each marker included group, sex, age, hypertension, diabetes, periodontal status, statin and anti‐inflammatory drug use, and smoking as covariates. Changes in eGFR, WCC, and ESR were further analyzed using transition modeling. Results: Triclosan toothpaste led to a greater decrease in TC (P = 0.03), LDL cholesterol (P = 0.04), and HDL cholesterol (P = 0.05) than placebo toothpaste. ESR increased at a slower rate in the triclosan group (P ≈ 0.06) and was less likely to increase and more likely to improve in males on statins but not anti‐inflammatory drugs in the triclosan group versus the placebo group. Markov modeling of the binary response for eGFR (greater than or less than/equal to the baseline median value) showed that patients with diabetes in the placebo group were significantly (P ≈ 0.05) more likely to deteriorate than either patients with diabetes in the triclosan group or patients without diabetes in each group. Conclusions: These data suggest that triclosan toothpaste may influence some inflammatory biomarkers of CVD, but not kidney or liver function. However, it is unclear if this influence is clinically significant.     

结直肠癌患者血清肿瘤标志物联合检测的临床意义

目的探讨血清肿瘤标志物联合检测在结直肠癌(CRC)患者病情监测中的临床意义。方法 116例CRC患者根据不同肿瘤分期分为Ⅰ~Ⅱ期组50例和Ⅲ~Ⅳ期组66例,比较2组血清肿瘤标志物水平。同时比较化疗后12个月和24个月时复发转移与未复发转移者血清肿瘤标志物水平差异。结果Ⅰ~Ⅱ期组患者血清癌胚抗原(CEA)、糖链抗原19-9(CA19-9)和CA242水平均显著低于Ⅲ~Ⅳ期组,差异有统计学意义(P0.05);2组血清甲胎蛋白(AFP)、CA724水平比较,差异无统计学意义(P0.05);化疗后12个月,复发转移与无复发转移患者血清CEA、CA199、CA242、CA724水平比较,差异有统计学意义(P0.05);2组血清AFP水平比较,差异无统计学意义(P0.05);化疗后24个月,复发转移与无复发转移患者血清CEA、CA199、CA242、AFP、CA724水平比较,差异有统计学意义(P0.05)。结论血清肿瘤标志物联合检测在评估CRC患者病情、监测化疗后是否复发转移上具有一定临床价值。     

非类风湿关节炎患者中类风湿关节炎相关血清标志物阳性的临床意义

目的探讨非类风湿关节炎(RA)患者中RA相关血清标志物阳性的临床意义。方法选取2012年1月至2014年6月该院收治的患者292例。其中,RA患者177例,非RA患者115例。采用酶联免疫吸附试验与免疫荧光法检测患者RA相关血清标志物的水平,包括类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体、抗RA33抗体及抗角蛋白抗体(AKA)。结果 RA组RF阳性率(78.53%)、抗CCP抗体阳性率(64.97%)、抗RA33抗体阳性率(15.82%)、AKA阳性率(19.77%)均明显高于非RA组(11.30%、1.74%、4.35%、0.87%),差异有统计学意义(P0.05)。结论非RA患者中RA相关血清标志物阳性率低于RA,但临床上仍需仔细鉴别,才能准确诊断。     

免疫比浊法检测肌红蛋白的性能验证及临床应用评估

目的对免疫比浊法检测肌红蛋白(Mb)的检测性能进行评价,并对Mb的临床应用进行评估。方法检测150例健康人(健康对照组)血清Mb水平,建立参考值范围,评估免疫比浊法检测Mb的准确度、精密度、线性。对80例急性冠脉综合征(ACS)患者按心电图结果分组后,比较ACS组血清Mb浓度与健康对照组是否存在差异。对于存在差异的ACS患者,进一步收集疾病对照组,通过绘制ROC曲线,评价Mb与其他心肌标志物的诊断性能。结果健康人血清Mb参考范围为70.22mg/L(男)、52.22mg/L(女),差异有统计学意义(t=4.39,P0.05)。2个水平质控检测结果为100.31、295.50mg/L,均在厂商允许偏差范围内,批内、批间变异系数(CV)均在5%以内,0~800 mg/L范围内线性良好。ACS组、非ACS组、健康对照组的Mb水平分别为(285.28±314.63)、(76.24±40.77)、(44.96±12.62)mg/L,差异有统计学意义(P0.05)。Mb在ACS组中的ROC曲线下面积(AUC)为0.878。在ACS组中,Mb的诊断敏感度为80.0%,优于肌钙蛋白I(cTnI)的43.7%和肌酸激酶同工酶(CK-MB)的57.5%。结论免疫比浊法检测Mb的检测性能符合要求。     

抗水通道蛋白-4抗体应用于中枢神经系统脱髓鞘疾病的鉴别诊断价值

目的探讨血清抗水通道蛋白-4(AQP-4)抗体应用于多发性硬化和视神经脊髓炎患者疾病诊断的临床意义。方法选择2013年3月至2014年10月该院收治的74例多发性硬化以及视神经脊髓炎患者,回顾性分析其临床资料,对血清中AQP-4抗体水平进行检查。结果视神经脊髓炎疾病患者各类型的阳性率分别为视神经炎(ON)51.89%、长节段横贯性脊髓炎(LETM)68.42%、视神经脊髓型多发性硬化(OSMS)57.14%、视神经脊髓炎(NMO)81.25%;而传统型多发性硬化(CMS)患者的AQP-4抗体检测为阴性。视神经脊髓炎疾病谱的患者脊髓受累均大于3个椎体节段;多发性硬化脊髓受累均小于3个节段。视神经脊髓炎多为急性或亚急性起病,多见于中年女性,发病年龄平均(42.1±13.9)岁,与CMS比较,差异无统计学意义(P0.05)。AQP-4抗体对于视神经脊髓炎敏感性为81.25%,特异性为100.00%。结论 AQP-4抗体可以作为视神经脊髓炎疾病以及多发性硬化鉴别诊断的重要指标。     

乙型肝炎病毒前S1抗原与HBV DNA和HBV-M及肝功能的相关性探讨

目的探讨兰州地区乙型肝炎病毒(HBV)感染者血清中前S1抗原(Pre-S1Ag)与HBV DNA、HBV-M及肝功能之间的相关性。方法对905例HBV感染者(HBV感染组)及100例健康体检者(健康对照组)进行Pre-S1Ag、HBV-M、HBV DNA和肝功能检测。结果 905例标本中,Pre-S1Ag和HBV DNA阳性率分别为68.51%(620/905)和67.96%(615/905),差异均无统计学意义(χ2=30.064,P0.05);570例HBeAg阳性组中,HBV Pre-S1阳性率为85.08%(485/570),显著高于HBeAg阴性组的Pre-SAg1阳性率40.30%(135/335),差异有统计学意义(χ2=108.881,P0.01)。Pre-S1Ag阳性组与阴性组ALT、AST异常率分别为53.22%、25.96%和51.29%、32.98%,差异有统计学意义(χ2ALT=53.148,P0.001,χ2AST=66.635,P0.001)。结论 Pre-S1Ag是乙肝病毒感染与复制的可靠指标,与HBV-DNA阳性相关度高,是对HBeAg的重要补充和加强,可为指导临床治疗提供更及时可靠的实验依据。     

高频超声诊断甲状腺结节的多因素分析及病例对照研究

目的采用高频超声对甲状腺结节的多因素进行诊断分析,并对其病例进行对照研究,为甲状腺结节的准确诊断提供可靠的方法。方法通过整体随机抽样的方法,对某地区的居民进行问卷调查、甲状腺的高频超声和尿碘值的检测;将高频超声检测结果甲状腺结节为阳性的和甲状腺没有病变的群体按照年龄、性别、职业和城乡的区别配比,分为两组,每组400例,对两个组别进行病例对照研究;对研究结果进行单因素和多因素的Logistic回归分析相关的危险因素。结果结合单因素和多因素分析,结果显示甲状腺结节的保护因素和患者的年收入相关,年收入越高的患甲状腺结节的概率越低,有吸烟史的患甲状腺结节的概率越高,检测分析甲状腺结节患病率低的尿碘值一般在100~190μg/L(P0.05)。结论通过高频超声对甲状腺结节的患者进行单一因素和多因素对比分析,结果发现饮食习惯和使用的碘量和甲状腺结节的发生率有一定的相关性,尿碘值的高低也影响着甲状腺结节的发生率。高频超声在诊断甲状腺结节方面起着一定的作用,可以作为临床诊断甲状腺结节推广使用。     

MDX‐1097 induces antibody‐dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide

MDX‐1097 is an antibody specific for a unique B cell antigen called kappa myeloma antigen (KMA) that consists of cell membrane‐associated free kappa light chain (κFLC). KMA was detected on kappa human multiple myeloma cell lines (κHMCLs), on plasma cells (PCs) from kappa multiple myeloma (κMM) patients and on κPC dyscrasia tissue cryosections. In primary κMM samples, KMA was present on CD38+ cells that were CD138 and CD45 positive and/or negative. MDX‐1097 exhibited a higher affinity for KMA compared to κFLC and the latter did not abrogate binding to KMA. MDX‐1097‐mediated antibody‐dependent cellular cytotoxicity (ADCC) and in vitro exposure of target cells to the immunomodulatory drug lenalidomide resulted in increased KMA expression and ADCC. Also, in vitro exposure of peripheral blood mononuclear cells (PBMCs) to lenalidomide enhanced MDX‐1097‐mediated ADCC. PBMCs obtained from myeloma patients after lenalidomide therapy elicited significantly higher levels of MDX‐1097‐mediated ADCC than cells obtained prior to lenalidomide treatment. These data establish KMA as a relevant cell surface antigen on MM cells that can be targeted by MDX‐1097. The ADCC‐inducing capacity of MDX‐1097 and its potentiation by lenalidomide provide a powerful rationale for clinical evaluation of MDX‐1097 alone and in combination with lenalidomide.     

Ricolinostat (ACY‐1215) induced inhibition of aggresome formation accelerates carfilzomib‐induced multiple myeloma cell death

Proteasome inhibition induces the accumulation of aggregated misfolded/ubiquitinated proteins in the aggresome; conversely, histone deacetylase 6 (HDAC6) inhibition blocks aggresome formation. Although this rationale has been the basis of proteasome inhibitor (PI) and HDAC6 inhibitor combination studies, the role of disruption of aggresome formation by HDAC6 inhibition has not yet been studied in multiple myeloma (MM). The present study aimed to evaluate the impact of carfilzomib (CFZ) in combination with a selective HDAC6 inhibitor (ricolinostat) in MM cells with respect to the aggresome‐proteolysis pathway. We observed that combination treatment of CFZ with ricolinostat triggered synergistic anti‐MM effects, even in bortezomib‐resistant cells. Immunofluorescent staining showed that CFZ increased the accumulation of ubiquitinated proteins and protein aggregates in the cytoplasm, as well as the engulfment of aggregated ubiquitinated proteins by autophagosomes, which was blocked by ricolinostat. Electron microscopy imaging showed increased autophagy triggered by CFZ, which was inhibited by the addition of ACY‐1215. Finally, an in vivo mouse xenograft study confirmed a decrease in tumour volume, associated with apoptosis, following treatment with CFZ in combination with ricolinostat. Our results suggest that ricolinostat inhibits aggresome formation, caused by CFZ‐induced inhibition of the proteasome pathway, resulting in enhanced apoptosis in MM cells.     

Effect of transient scrotal hyperthermia on sperm parameters,seminal plasma biochemical markers,and oxidative stress in men

In this experimental prospective study, we aimed to analyze the effect of transient scrotal hyperthermia on the male reproductive organs, from the perspective of sperm parameters, semen plasma biochemical markers, and oxidative stress, to evaluate whether different frequencies of heat exposure cause different degrees of damage to spermatogenesis. Two groups of volunteers (10 per group) received testicular warming in a 43°C water bath 10 times, for 30 min each time: group 1: 10 consecutive days; group 2: once every 3 days. Sperm parameters, epididymis and accessory sex gland function, semen plasma oxidative stress and serum sex hormones were tested before treatment and in the 16-week recovery period after treatment. At last, we found an obvious reversible decrease in sperm concentration (P = 0.005 for Group 1 and P= 0.008 for Group 2 when the minimums were compared with baseline levels, the same below), motility (P = 0.009 and 0.021, respectively), the hypoosmotic swelling test score (P = 0.007 and 0.008, respectively), total acrosin activity (P = 0.018 and 0.009, respectively), and an increase in the seminal plasma malondialdehyde concentration (P = 0.005 and 0.017, respectively). The decrease of sperm concentration was greater for Group 2 than for Group 1 (P = 0.031). We concluded that transient scrotal hyperthermia seriously, but reversibly, negatively affected the spermatogenesis, oxidative stress may be involved in this process. In addition, intermittent heat exposure more seriously suppresses the spermatogenesis compared to consecutive heat exposure. This may be indicative for clinical infertility etiology analysis and the design of contraceptive methods based on heat stress.