Targeted-gene silencing of BRAF to interrupt BRAF/MEK/ERK pathway synergized photothermal therapeutics for melanoma using a novel FA-GNR-siBRAF nanosystem

Melanoma is significantly associated with mutant BRAF gene, a suitable target for siRNA-based anti-melanoma therapy. However, a tumor-specific delivery system is a major hurdle for clinical applications. Here, we developed a novel nano-carrier, FA-GNR-siBRAF for safe topical application, which consists of folic acid (FA) as the tumor-targeting moiety, golden nanorods (GNR) providing photothermal capability to kill tumor cells under laser irradiation, and siRNA specifically silencing BRAF (siBRAF). The in vitro and in vivo results revealed that FA-GNR-siBRAF displayed high transfection rates, and subsequently induced remarkable gene knockdown of BRAF, resulting in suppression of melanoma growth due to the interruption of the MEK/ERK pathway. Combinatorial photothermal effects and BRAF knockdown by FA-GNR-siBRAF effectively killed tumor cells through apoptosis, with enhanced efficiency than individual treatments. Therefore, the FA-GNR-siBRAF simultaneously induced BRAF gene silencing and photothermal effects which achieved synergistic efficacy in the treatment of melanoma, paving a new path for developing clinical treatment methods for melanoma.     

低渗丙酮酸钠口服补液盐对50%总体表面积烫伤大鼠血管通透性、胃肠及脏器功能的影响

目的探讨低渗丙酮酸钠口服补液盐对严重烧伤大鼠血管通透性、胃肠及脏器功能的影响。 方法选择雄性SD大鼠80只,建立50%总体表面积(TBSA)Ⅲ度烫伤模型,按随机数字表法将大鼠分为4组：烫伤不补液组(NR组)、低渗丙酮酸钠口服补液盐组(PR组)、低渗枸橼酸钠口服补液盐组(CR组)、假烫伤对照组(SR组),每组20只。NR组、PR组及CR组采用96 ℃水浴浸泡大鼠背部15 s、双下肢15 s、腹部8 s,造成50%TBSAⅢ度烫伤模型(经病理切片证实,为严重烧伤);SR组采用37 ℃水浴浸泡相同时间。PR组、CR组于伤后即刻开始采用灌胃输入的方法口服补液,补液量和速度均依据Parkland公式,即每1%TBSA补液4 mL/kg,伤后第1个8 h补补液量的一半,之后16 h补另一半,每0.5 h均严格按照计算所得补液量灌注。SR组自由饮水,NR组不予口服补液。观察烫伤后8、24 h各组大鼠各脏器组织含水率、脏器功能指标变化及胃肠功能变化。数据比较采用单因素方差分析、t检验及χ²检验。 结果(1)伤后8、24 h,4组大鼠的脏器组织(心脏、肝脏、肺、肾脏和肠)含水率比较,差异均有统计学意义(P值均小于0.05);与NR比较,其余3组大鼠脏器组织含水率均降低,差异均有统计学意义(P值均小于0.05)。伤后8 h,PR组心脏、肝脏、肺、肾脏和肠的组织含水率分别为(75.66±1.21)%、(72.83±1.12)%、(75.91±1.24)%、(77.67±1.17)%、(79.16±1.01)%,均低于CR组(79.48±1.25) %、(74.16±1.12) %、(78.87±0.88) %、(79.39±1.19)%、(81.23±0.86)%,差异均有统计学意义(t＝3.698、4.368、5.112、5.287、4.257,P值均小于0.05);伤后24 h,PR组心脏、肝脏、肺、肾脏和肠的组织含水率分别为(71.78±1.08)%、(66.89±1.11)%、(71.42±1.18)%、(71.64±1.17)%、(73.91±1.03)%,均低于CR组(77.12±1.22)%、(71.13±1.09)%、(75.81±1.14)%、(76.78±1.15)%、(78.42±0.94)%,差异均有统计学意义(t＝4.165、4.572、4.981、4.653、5.017,P值均小于0.05)。(2)伤后8、24 h 4组大鼠各脏器功能指标[磷酸肌酸激酶同工酶(CK-MB)、血清谷丙转氨酶(ALT)、肌酐]比较,差异均有统计学意义(P值均小于0.05);与NR组比较,PR组和CR组大鼠伤后8、24 h CK－MB、ALT、肌酐均明显下降,差异均有统计学意义(P值均小于0.05); 伤后8 h,PR组CK-MB、ALT和肌酐分别为(2575.6±165.1)U/L、(270.3±61.2)U/L、(46.1±6.4)μmol/L,均低于CR组(3949.4±165.5)U/L、(542.6±60.1)U/L、(66.7±6.8)μmol/L,差异均有统计学意义(t＝2.396、5.465、5.146,P值均小于0.05);伤后24 h,PR组CK-MB、ALT和肌酐分别为(1652.8±167.8)U/L、(226.9±12.1)U/L、(38.2±4.8)μmol/L,均低于CR组(3247.2±121.2)U/L、(418.1±10.9)U/L、(51.1±5.4)μmol/L,差异均有统计学意义(t＝2.382、4.957、4.060,P值均小于0.05)。(3)伤后8、24 h,PR组胃排空率(85.1±1.4)%、(91.2±1.8)%,均高于CR组(45.7±1.8)%、(66.1±1.4)%,差异均有统计学意义(χ²＝37.327,38.421,P值均小于0.05)。(4)伤后8、24 h,PR组肠吸收总量(20.07±0.78) 、(44.07±2.54) mL,均高于CR组(14.81±0.69)、(31.53±1.62) mL,差异均有统计学意义(χ²＝4.716、5.217,P值均小于0.05)。 结论低渗丙酮酸钠口服补液盐能显著改善严重烫伤大鼠血管通透性、胃肠及脏器功能,可能对严重烫伤大鼠的复苏提供一定的治疗作用。     

Effect of salinity variations on the performance of activated sludge system

Objective To investigate the influence of salinity variations on the performance of activated sludge systems, treating domestic wastewater. Methods The completely mixed reactor was used and operated in a batch-wise mode. The activated sludge taken from the Gaobeidian Wastewater Treatment Plant was used as a seeding sludge. Total organic carbon (TOC),oxygen uptake rate (OUR) and suspended solids (SS) were used as parameters to characterize the performance of the treatment systems. TOC was measured using a TOC-analyzer (TOC-5000, Japan). The OUR value was measured with a dissolved oxygen meter (YSI model-58). SS was measured gravimetrically. Results The TOC removal efficiency and the OUR value of activated sludge were not deteriorated when the NaCl shock concentration was less than 0.5 g/L. However, when the NaCl shock concentrations were up to 10g/t, and 20 g/L, the OUR of activated sludge was reduced by 35% and TOC removal efficiency was dropped by 30%, compared with the control experiment without NaCl shock loading. Conclusion The effect of NaCl shock loading on the activated sludge wastewater treatment system is dependant upon the NaCl concentrations and the degree of influence can be inferred through the change of substrate utilization rate at different shock NaCl loadings.     

异基因造血干细胞移植治疗白血病

目的探讨异基因造血干细胞移植(Allo-HSCT)治疗白血病的疗效、造血重建及生存情况.方法白血病患者10例,其中同胞间HLA相合的异基因外周血干细胞移植(Allo-PBSCT)7例,无亲缘关系HLA不全相合脐血移植(UCBT)3例.结果9/10例受者获造血重建,UCBT患者造血重建速度较HLA相合的同胞PBSCT慢,1例UCBT移植后35天造血未重建,回输自体外周血干细胞后,仍未能重建造血,于72天死亡.其余至今均无病生存.结论Allo-HSCT是目前治愈白血病的有效方法,对于无同胞HLA相合的供者,选择细胞数量较高、HLA 1～2个位点不合的UCBT仍然有效可行.     

Meta‐analysis approaches to combine multiple gene set enrichment studies

In the field of gene set enrichment analysis (GSEA), meta‐analysis has been used to integrate information from multiple studies to present a reliable summarization of the expanding volume of individual biomedical research, as well as improve the power of detecting essential gene sets involved in complex human diseases. However, existing methods, Meta‐Analysis for Pathway Enrichment (MAPE), may be subject to power loss because of (1) using gross summary statistics for combining end results from component studies and (2) using enrichment scores whose distributions depend on the set sizes. In this paper, we adapt meta‐analysis approaches recently developed for genome‐wide association studies, which are based on fixed effect and random effects (RE) models, to integrate multiple GSEA studies. We further develop a mixed strategy via adaptive testing for choosing RE versus FE models to achieve greater statistical efficiency as well as flexibility. In addition, a size‐adjusted enrichment score based on a one‐sided Kolmogorov‐Smirnov statistic is proposed to formally account for varying set sizes when testing multiple gene sets. Our methods tend to have much better performance than the MAPE methods and can be applied to both discrete and continuous phenotypes. Specifically, the performance of the adaptive testing method seems to be the most stable in general situations.     

巨大型牙骨质-骨化纤维瘤1例

牙骨质-骨化纤维瘤是一种少见的良性肿瘤,是来自牙周膜的良性肿瘤,由胶原纤维、成纤维细胞、成牙骨质细胞构成。本文报告1例巨大型牙骨质-骨化纤维瘤,并对其临床表现及治疗进行讨论。     

Type II collagen and aggrecan mRNA expressions in rabbit condyle following disc displacement

The aim of this investigation was to study the remodelling of cartilage in the mandibular condyle following disc displacement (DD) of the temporomandibular joint (TMJ). Forty adult Japanese white rabbits were used in this study. The right joints of 28 of the 40 rabbits had their discs surgically displaced. Four of the 28 were killed at 4 days or 1, 2, 4, 6, 8 and 12 weeks after surgery. The messenger RNA (mRNA) expression levels of aggrecan and type II collagen in cartilages were measured using in situ hybridization techniques. Results showed that aggrecan mRNA expression reduced in the first week after DD. The expression began to recover after 4 weeks and reached a normal level after 6 weeks. Type II collagen mRNA expression reduced from 4 weeks and the expression recovered after 8 weeks. This suggests that the chondrocyte reacting to the displacement of the TMJ disc, alters its matrix gene expression patterns and it is may be the cause of the shape changes of TMJ after DD.     

Cytokine networks in destructive periodontal disease

BACKGROUND Cytokines are important regulatory proteins, produced by activated cells, which act by binding high affinity cell surface receptors. They are involved in almost all aspects of cell biology and form interacting networks, with cascades of sequential cell activation. They often show overlapping activities ( redundancy ) or the same cytokine may have a variety of different effects (pleiotropy). In excess, certain cytokines are damaging and proinflammatory. Tumour necrosis factor a (TNFα) and interleukin-I (IL-I) are markedly proinflammatory, inducing bone resorption, collagenase and prostaglandin E₂ production.
OBJECTIVE: This paper focuses on the role of TNFa and IL-l in the cytokine networks of destructive chronic per-iodontitis; specifically their regulation by T cell cytokines, receptor antagonists and inhibitory soluble forms of the IL-l and TNF receptors.
CONCLUSION: A hypothesis is proposed that destructive periodontal disease may be due to disregulation of these inhibitors, rather than an overproduction of IL-l and TNFα per se.