Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin

We have previously demonstrated that peptide fragments (PFs) of the human serum albumin could be developed as potential renal targeting carriers, in particular, the peptide fragment, PF-A_299–585 (A_299–585 representing the amino acid sequence of the human serum albumin). In this paper, we conjugated triptolide (TP), the anti-inflammatory Chinese traditional medicine, to PF-A_299–585 via a succinic acid spacer to give TPS-PF-A_299–585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A_299–585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A_299–585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labeled TPS-PF-A_299–585. Renal targeting was confirmed in vivo in a membranous nephropathic (MN) rodent model, where optical imaging and analyses of biochemical markers were combined to show that TPS-PF-A_299–585 was capable of alleviating the characteristic symptoms of MN. The collective data affirm PF-A_299–585 to be a useful carrier for targeting TP to the kidney.     

人类平衡型核苷转运蛋白1高表达晚期非小细胞肺癌患者术后应用不同剂量吉西他滨治疗的临床效果观察

目的 观察晚期非小细胞肺癌(NSCLC)中人类平衡型核苷转运蛋白1(hENT1)高表达患者应用不同剂量吉西他滨治疗的临床效果.方法 选取2008年7月至2013年12月于浙江金华广福医院行晚期NSCLC手术后,病理确诊晚期NSCLC患者,采用免疫组织化学SP法检测肺癌组织中hENT1抗体的表达水平.62例hENT1高表达患者入组,按随机数字表分组法分为对照组(30例)和观察组(32例).对照组采用常规剂量吉西他滨(1 000 mg/m2)联合顺铂进行化疗,观察组用低剂量吉西他滨(250 mg/m2)联合顺铂进行化疗,观察2组近期疗效、化疗不良反应.采用生活质量调查核心量表QLQ-C30和肺癌专用量表QLQ-LCl3比较2组化疗后生活质量.结果 对照组和观察组近期有效率和疾病控制率差异无统计学意义[43.3％ (13/30)比46.9％ (15/32),76.9％ (23/30)比81.2％(26/32)](x2 =0.08,x2 =0.20,P＞0.05).观察组Ⅲ、Ⅳ度白细胞减少、血小板减少及恶心、呕吐发生率低于对照组,差异有统计学意义(P＜0.05);除角色功能外,观察组化疗后总体生活评分及躯体功能、情绪功能、认知功能、社会功能、经济状况各项评分均优于对照组[(54±20)分比(54±16)分,(72±25)分比(62 ±20)分、(85 ±20)比(72±19)分、(76±28)分比(62±25)分、(61 ±24)分比(49 ±30)分、(36±24)分比(56±21)分],差异均有统计学意义(均P＜0.05).观察组除乏力症状外其他症状评分均优于对照组(P＜0.05).结论 对于晚期NSCLC术后hENT1高表达患者,在保证化疗效果的同时,相对于常规剂量吉西他滨,低剂量用药可有效降低化疗过程中不良反应,提高患者的生活质量.     

卵巢上皮性肿瘤患者人乳头状瘤病毒感染及核转录因子表达与临床相关性研究

目的探讨人乳头状瘤病毒(HPV)感染和核转录因子(NF-кB)表达与卵巢上皮性肿瘤的关系,为临床治疗提供依据。方法选取2008年1月-2013年10月71例卵巢肿瘤患者的病理标本,检测卵巢上皮肿瘤组织HPV感染和NF-кB表达情况,分析与临床、病理的相关性。结果卵巢上皮癌患者HPV的阳性率要明显高于良性肿瘤患者,分别为36.73%、9.09%,差异有统计学意义(P<0.05);卵巢上皮癌患者NF-кBp65的阳性率较良性肿瘤患者明显升高,分别为69.39%、17.17%,差异有统计学意义;HPV感染在卵巢癌不同临床病理结果比较,差异无统计学意义;卵巢上皮癌患者的临床分期、病理分级及CA125值在不同等级NF-кB阳性率的比较,差异有统计学意义(P<0.05),病理分化程度越低、临床分期越晚及CA125值越高,NF-кB阳性率越高。结论 HPV感染和NF-кB的高表达与卵巢癌的发生有一定的关系,HPV感染患者应予积极治疗,以预防卵巢癌的发生。     

宫颈高危型人乳头状瘤病毒感染中药配合保妇康治疗效果的临床研究

目的探讨宫颈高危型人乳头状瘤病毒(HPV)感染中药配合保妇康治疗临床效果,以寻找最佳的治疗方法,提高临床治疗水平。方法选取2011年12月-2013年12月130例宫颈高危型HPV感染患者为研究对象,将其分成对照组及观察组,每组各65例,对照组予保妇康治疗,观察组在对照组基础上加用中药治疗,观察治疗后两组临床效果差异性,数据采用SPSS16.0软件进行统计分析。结果治疗总有效率及HPV转阴率,对照组分别为80.00%及63.08%,观察组分别为92.31%及90.77%,两组比较差异有统计学意义(P<0.05);治疗后两组患者临床症状体征积分、中医证候积分比较,差异均有统计学意义(P<0.05);两组患者治疗后均无不良反应发生。结论中药配合保妇康治疗宫颈高危型HPV感染临床效果满意,安全性高。     

HPV E6/E7 mRNA检测用于ASCUS患者诊断分流的临床研究

目的:探讨人乳头瘤病毒(HPV)E6/E7mRNA检测用于未明确诊断意义的不典型鳞状上皮细胞(ASCUS)诊断结果的判定价值。方法:对160例薄层液基细胞学检查诊断为ASCUS者进行HPV E6/E7mRNA和高危型HPV(HR-HPV)DNA检测,结合病理学诊断资料进行统计学分析。结果:160例中病理结果为宫颈上皮内瘤变Ⅱ级(CINⅡ)及以上级别者的HPV E6/E7mRNA阳性率明显高于CINⅡ以下级别者,差异有统计学意义(P0.05),但与HR-HPV DNA检测结果无统计学差异。HPV E6/E7 mRNA检测CINII及以上级别的灵敏度(69.2%)与HR-HPV DNA检测相比无统计学差异(P0.05);特异度(73.9%)高于HR-HPV DNA检测(61.9%),差异有统计学意义(P0.05)。结论:HPV E6/E7 mRNA检测可作为ASCUS者是否需要进行阴道镜检查的一项指标依据。     

Kaposi’s sarcoma in a patient with severe relapsing polychondritis

This report describes the case of a young man who developed Kaposis sarcoma (KS) after corticosteroid treatment for severe tracheal involvement of relapsing polychondritis (RP). The etiopathogenetic mechanisms that may have led to the evolution of this unusual neoplasm are discussed. To our knowledge, this is the first case reported of concomitant RP and KS.     

Cold acclimation of obese (ob/ob) mice: effects of energy balance

Obese (ob/ob) and lean mice at 4 weeks of age were housed at 23 degrees C or 14 degrees C for 4 to 8 weeks to examine effects of acclimation to mild cold on energy balance. Energy intake of young lean mice increased by about 50% when housed at 14 degrees C, but energy intake of cold-acclimated obese mice increased by only 8%. Efficiency of energy retention (ratio of energy gain to energy intake) in obese mice declined from 22% +/- 1.2% at 23 degrees C to 10% +/- 1.8% after 4 weeks at 14 degrees C. Lean mice exhibited a less pronounced response to temperature; their efficiency of energy retention declined from 7% +/- 1.3% at 23 degrees C to 4% +/- 2.2% after 4 weeks at 14 degrees C. After 8 weeks of cold exposure, body weights and efficiency of energy retention became equal in obese and lean mice. Calculated heat production of cold-acclimated obese and lean mice was 40% higher than that of respective controls. Obese mice reacclimated to 23 degrees C after being kept for 4 weeks at 14 degrees C consumed the same amount of energy and were 16% more efficient than obese maintained at 23 degrees C; reacclimated lean mice consumed 12% more energy but were 53% less efficient than lean mice maintained at 23 degrees C. The results indicate that obese mice are able to increase heat production and markedly reduce their efficiency of energy retention when acclimated to mild cold but that they, unlike lean mice, rapidly revert to a high efficiency of energy retention after 4 weeks of reacclimation to 23 degrees C.     

The application of the skin virome for human identification

The use of skin virome offers a unique approach for human identification purposes in instances where a viable and statistically relevant human DNA profile is unavailable. The skin virome may act as an alternative DNA profile and/or an additional form of probative genetic material. To date, no study has attempted to investigate the human virome over a time series across various physical locations of the body to identify its diagnostic potential as a tool for human identification. For this study, we set out to evaluate the stability, diversity, and individualization of the human skin virome. An additional goal was to identify putative viral signatures that can be used in conjunction with traditional forensic STR loci. In order to accomplish this, human viral metagenomes were collected and sequenced from 42 individuals at three anatomical locations (left hand, right hand, and scalp) across multiple collection periods over a 6-month window of time. Assembly dependent and independent bioinformatic approaches, along with a database centered assessment of viral identification, resulted in three sets of stable putative viral markers. In total, with the three sets combined, we identified 59 viral biomarker regions, consisting of viral species and uncharacterized viral genome assemblies, that were stable over the sampling period. Additionally, we found the abundance profiles of these 59 viral biomarkers, based on presence or absence, to be significantly different across subjects (P < 0.001). Here we demonstrate that not only is the human virome applicable to be used for human identification, but we have identified many viral signatures that can putatively be used for forensic applications, thus providing a foundation to the novel field of forensic virology.     

Nutrition for the micro preemie: Beyond milk

Nutritional support is a fundamental component of the care of the extremely preterm infant, including the “micro preemie” (here defined as a baby born weighing less than 500 g), but goes beyond considerations of milk as a food. This is because milk from an infant's own mother, unlike currently available substitutes, additionally provides invaluable non-nutritive benefits.Nutritional support requires suitable devices or techniques to administer nutrients enterally or intravenously, products shown to be safe in preterm populations, and efficacy demonstrated in respect of important functional outcomes. Sadly, preterm feeding remains characterised by a deficit of evidence. In this chapter, we will briefly describe the history of preterm nutrition, discuss current enteral and parenteral practice, important evidence gaps, a summary of approaches for evaluating nutritional practice, and key considerations for future endeavour. Our discussion refers to all extremely preterm infants and it not confined to the micro preemie.