P16在宫颈癌组织中的表达及意义

目的研究P16在宫颈癌组织中的表达情况.方法用免疫组化S-P法检测15例正常宫颈组织,20例慢性宫颈炎和42例宫颈癌组织中P16的表达.结果P16宫颈癌中的阳性率为45.2%,其表达与宫颈癌的临床分期显著相关(P＜0.05).结论P16的异常表达与宫颈癌的发生和发展有关,可作为判断预后的辅助指标.     

基于化学成分与肠道菌群探讨消癌解毒方中黄连-乌梅药对的配伍机制

目的 探讨黄连-乌梅药对与消癌解毒方水煎液中部分生物碱类成分的含量差异,并比较药对与全方对小鼠肠道菌群的影响。方法 采用Extend-C₁₈(100 mm×2.1 mm,1.8 μm)色谱柱,以0.1%甲酸水（A）-乙腈（B）进行梯度洗脱,流速0.3 mL/min,柱温35 ℃,进样量2 μL;离子化模式为电喷雾离子化（ESI）,以正离子模式检测,开展方法学验证和含量测定研究。按照给药不同将小鼠分为正常组、全方高浓度组、全方低浓度组、药对高浓度组和药对低浓度组,连续灌胃给药7 d,每组分别收集粪便样本,进行16S rRNA基因测序。结果 建立的含量测定方法在一定浓度范围内线性关系良好,方法学验证结果均符合相关要求,木兰花碱与非洲防己碱在黄连、药对以及全方中的含量分别为:(4.433±0.133)(8.905±0.154) mg/g,（3.545±0.033）（9.170±0.051） mg/g,（5.287±0.038）（13.861±0.690） mg/g。全方组和药对组中拟杆菌门Bacteroides的丰度均高于正常组,而全方组和药对组中厚壁菌门Firmicutes的丰度均低于正常组。药对高浓度组中的疣微菌门Verrucomicrobia和变形菌门Proteobacteria的丰度高于其他组。结论 液质联用方法和相关参数简便、可靠,可用于有关成分的含量检测。与单味药中含量相比,经过药对配伍后,非洲防己碱含量增加,而木兰花碱含量则略有降低;经过全方配伍后,2种成分的含量均增加。此外,肠道菌群实验表明无论是药对还是全方在给药后,会不同程度地影响肠道菌群内部占比改变,其可能对调节肠道系统平衡,具有一定帮助作用,从而为进一步阐释黄连-乌梅在消癌解毒方中配伍机制提供了参考和依据。      

16p11.2微缺失相关儿童癫痫的临床表型与遗传学特征分析

目的探究16p11.2微缺失相关儿童癫痫的临床表型与遗传学特征。方法回顾性收集200例应用全外显子测序技术进行癫痫遗传学分析的癫痫患儿，其中9例癫痫患儿为16p11.2微缺失，分析9例16p11.2微缺失患儿的临床表型及遗传学特征。结果16p11.2微缺失检出率为4.5%（9/200）。9例患儿为3~10月龄的婴儿；癫痫发作形式为局灶运动性发作伴意识障碍，部分进展为全身强直-阵挛发作；发作间期脑电图为局灶或多灶性痫样放电，对抗癫痫药物反应良好。9例患儿16p11.2缺失片段大小在398~906 kb之间，缺失基因数为23~33个，且均为致病性变异，其中2例为母源性来源，1例为父源性来源，余均为新发变异。结论16p11.2微缺失在癫痫患儿中有一定的检出率，16p11.2微缺失多为新发变异，且为基因大片段缺失；16p11.2微缺失相关儿童癫痫多在出生1年内起病且为药物反应性癫痫。     

Dietary Vitamin B1 Intake Influences Gut Microbial Community and the Consequent Production of Short-Chain Fatty Acids

The gut microbiota is closely related to good health; thus, there have been extensive efforts dedicated to improving health by controlling the gut microbial environment. Probiotics and prebiotics are being developed to support a healthier intestinal environment. However, much work remains to be performed to provide effective solutions to overcome individual differences in the gut microbial community. This study examined the importance of nutrients, other than dietary fiber, on the survival of gut bacteria in high-health-conscious populations. We found that vitamin B1, which is an essential nutrient for humans, had a significant effect on the survival and competition of bacteria in the symbiotic gut microbiota. In particular, sufficient dietary vitamin B1 intake affects the relative abundance of Ruminococcaceae, and these bacteria have proven to require dietary vitamin B1 because they lack the de novo vitamin B1 synthetic pathway. Moreover, we demonstrated that vitamin B1 is involved in the production of butyrate, along with the amount of acetate in the intestinal environment. We established the causality of possible associations and obtained mechanical insight, through in vivo murine experiments and in silico pathway analyses. These findings serve as a reference to support the development of methods to establish optimal intestinal environment conditions for healthy lifestyles.     

p16基因和增殖细胞核抗原在胃癌组织中的表达与关系

目的　观察胃癌组织中 p16基因的表达和增殖细胞核抗原 (PCNA)染色强度指数间的关系及临床意义。方法　采用LSAB免疫组织化学法。结果　在 34例原发性胃癌组织中 ,p16基因阳性表达率4 7 0 6 % (16 / 34) ,PCNA染色指数平均为 5 9 2 8± 3 4 8,p16基因阳性率和PCNA染色指数在组织学分级Ⅰ级中明显低于组织学分级Ⅲ级 (均P <0 0 5 ) ;在无淋巴结转移者中明显低于有淋巴结转移者 (分别为P <0 0 5 ,P <0 0 1)。结论　胃癌组织中 p16基因的表达和PCNA染色指数与胃癌的发生、发展密切相关 ,可以客观反映胃癌的组织分化状态、肿瘤进展及转移潜力     

二亚硝基哌嗪对转基因小鼠TNF受体相关因子2和p16的表达

目的研究二亚硝基哌嗪(N,N′-dinitrosopi- perazine,DNP)对TgN(p53mt-LMP1)/HT小鼠鼻腔和鼻咽黏膜上皮细胞增殖与TNF受体相关因子2(TNF receptor-associated Factor 2,TRAF2)、p16基因表达的影响及两者关系。方法HE染色法观察转基因小鼠组(TC)、转基因小鼠DNP诱导组(T1)和野生小鼠组(CC)、野生小鼠DNP诱导组(CI)鼻腔和鼻咽黏膜上皮细胞增殖特征;免疫组织化学染色法检测小鼠鼻腔和鼻咽黏膜上皮组织中TRAF2、p16基因的表达水平。结果TI、TC、CI和CC组小鼠鼻腔或鼻咽黏膜上皮癌前病变率分别为90%、10%、0和0。与TC、CI和CC组相比,TI组TRAF2基因表达水平显著增高(P<0.01),而p16基因表达水平显著降低(P<0.01);TRAF2和p16基因表达水平在TC和CC组之间的差异亦有统计学意义(P<0.01)。结论TgN(p53mt-LMP1)/HT小鼠鼻腔和鼻咽黏膜上皮细胞增殖活性增加,DNP可提高其增殖活性,而细胞增殖活性增加与TRAF2基因表达水平上调和p16基因表达水平下调密切相关。     

MUC16：肿瘤治疗新靶点

黏蛋白16（mucin16, MUC16），又称癌抗原125（carbohydrate antigen 125, CA125），是1981年美国科学家Bast等从卵巢上皮癌抗原中检测出且能被单克隆抗体OC125识别的一种糖蛋白抗原。CA125在正常卵巢组织中不存在，但在卵巢上皮癌患者的血清中常见升高。CA125是卵巢上皮癌诊断和监测复发最常用的血清学生物标志物。MUC16在多种肿瘤中高表达，可以与半乳糖凝集素-1/3（galectin-1/3）、间皮素、唾液酸结合的免疫球蛋白样凝集素-9（sialic acid-binding immunoglobulin-type lectins-9, Siglec-9）等配体结合，通过多种肿瘤相关信号通路，对肿瘤发生发展、迁移侵袭及肿瘤免疫具有重要作用。靶向MUC16的治疗方式已经取得一定成效，相关临床前研究以及临床试验正在进行当中，MUC16可能是一个有潜力的肿瘤治疗新靶点。本文重点阐述MUC16在肿瘤发生发展中的作用，关注其在肿瘤治疗中的研究现状，为后续靶向MUC16的肿瘤治疗研究提供参考。     

Circulating coxsackievirus A16 identified as recombinant type A human enterovirus, China

To determine the relationship of coxsackievirus A16 (CA16) to prototype CA16-G10, we conducted a phylogenetic analysis of circulating CA16 strains in China. Complex recombinant forms of CA16-related viruses involving multiple human enteroviruses, subgroup A (CA4, CA16, and enterovirus 71), are prevalent among patients with hand, foot, and mouth disease.     

Gut Microbiota Markers and Dietary Habits Associated with Extreme Longevity in Healthy Sardinian Centenarians

This study was aimed at characterizing the gut microbiota (GM) and its functional profile in two groups of Sardinian subjects with a long healthy life expectancy, overall named Long-Lived Subjects (LLS) [17 centenarians (CENT) and 29 nonagenarians (NON)] by comparing them to 46 healthy younger controls (CTLs). In addition, the contribution of genetics and environmental factors to the GM phenotype was assessed by comparing a subgroup of seven centenarian parents (CPAR) with a paired cohort of centenarians’ offspring (COFF). The analysis was performed through Next Generation Sequencing (NGS) of the V3 and V4 hypervariable region of the 16S rRNA gene on the MiSeq Illumina platform. The Verrucomicrobia phylum was identified as the main biomarker in CENT, together with its members Verrucomicrobiaceae, Akkermansia and Akkermansia muciniphila. In NON, the strongest associations concern Actinobacteria phylum, Bifidobacteriaceae and Bifidobacterium, while in CTLs were related to the Bacteroidetes phylum, Bacteroidaceae, Bacteroides and Bacteroides spp. Intestinal microbiota of CPAR and COFF did not differ significantly from each other. Significant correlations between bacterial taxa and clinical and lifestyle data, especially with Mediterranean diet adherence, were observed. We observed a harmonically balanced intestinal community structure in which the increase in taxa associated with intestinal health would limit and counteract the action of potentially pathogenic bacterial species in centenarians. The GM of long-lived individuals showed an intrinsic ability to adapt to changing environmental conditions, as confirmed by functional analysis. The GM analysis of centenarians’ offspring suggest that genetics and environmental factors act synergistically as a multifactorial cause in the modulation of GM towards a phenotype similar to that of centenarians, although these findings need to be confirmed by larger study cohorts and by prospective studies.