基于倾向性评分匹配的聚乙二醇化重组人粒细胞刺激因子预防宫颈癌同步放化疗中性粒细胞减少症效果分析

目的 探讨聚乙二醇化重组人粒细胞刺激因子（PEG-rhG-CSF）在宫颈癌同步放化疗中预防中性粒细胞减少的疗效及安全性。方法 按单中心单臂历史对照研究,选取2019年6月—2021年1月32例符合入排条件,拟行同步放化疗的宫颈癌患者组成试验组,同时搜集2017年1月—2019年6月行同步放化疗且符合对照组治疗方案的宫颈癌患者病历资料,按1∶1倾向性评分匹配法组成对照组。试验组为前瞻性入组,患者第1次化疗给药结束24 h后sc聚乙二醇化重组人粒细胞刺激因子注射液,每次6 mg,每化疗周期1次,共给药2次。若使用PEG-rhG-CSF预防后,中性粒细胞计数（ANC）仍＜1.0×109·L^-1,可给予短效重组人粒细胞刺激因子注射液5 μg·kg^-1,sc给药,直至ANC≥2.0×109·L^-1。对照组患者采用倾向性评分匹配既往同步放化疗的宫颈癌患者,初始不给予PEG-rhG-CSF,当患者出现ANC＜1.0×109·L^-1后sc给予重组人粒细胞刺激因子注射液,5 μg·kg^-1,持续使用,每日1次,直至ANC≥2.0×109·L^-1。记录两组患者3、4度中性粒细胞减少症发生率及持续时间;粒细胞减少性发热（FN）发生率;中性粒细胞减少导致化疗延迟和放疗中断发生率;评价两组不良反应情况,包括乏力、骨关节痛、发热、皮肤黏膜反应、恶心及呕吐等。结果 试验组与对照组各32例,两组基线均衡。试验组中性粒细胞减少症发生率59.4%,对照组为84.3%,试验组显著低于对照组（P＜0.05）;3、4度中性粒细胞减少症发生率试验组为31.3%（10/32）,对照组为56.3%（18/32）,试验组显著低于对照组（P＜0.05）。3度中性粒细胞减少持续时间,试验组中位时间为0 d（0～29 d）,显著低于对照组2 d（0～38 d）;4度中性粒细胞减少持续时间,试验组中位时间为0 d（0～22 d）,显著低于对照组1 d（0～38 d）。两组FN发生率比较无明显差异,但试验组有降低趋势。试验组放疗中断1例,对照组2例,两组比较无显著统计学差异（P＞0.05）;试验组延迟化疗出现4例（12.5%）,对照组出现12例（37.5%）,两组比较差异显著（P＜0.05）。两组不良反应主要包括乏力、骨关节痛、发热、皮肤黏膜反应、恶心及呕吐等,组间比较,差异不显著（P＞0.05）。结论 宫颈癌同步放化疗过程中预防性应用PEG-rhG-CSF具有安全性、有效性,可以降低中性粒细胞减少症发生率,减少FN和不良反应,避免治疗延迟。     

Nano-hydroxyapatite modulates osteoblast lineage commitment by stimulation of DNA methylation and regulation of gene expression

Hydroxyapatite (HA) is the primary structural component of the skeleton and dentition. Under biological conditions, HA does not occur spontaneously and therefore must be actively synthesized by mineralizing cells such as osteoblasts. The mechanism(s) by which HA is actively synthesized by cells and deposited to create a mineralized matrix are not fully understood and the consequences of mineralization on cell function are even less well understood. HA can be chemically synthesized (HAp) and is therefore currently being investigated as a promising therapeutic biomaterial for use as a functional scaffold and implant coating for skeletal repair and dental applications. Here we investigated the biological effects of nano-HAp (10 × 100 nm) on the lineage commitment and differentiation of bone forming osteoblasts. Exposure of early stage differentiating osteoblasts resulted in dramatic and sustained changes in gene expression, both increased and decreased, whereas later stage osteoblasts were much less responsive. Analysis of the promoter region one of the most responsive genes, alkaline phosphatase, identified the stimulation of DNA methylation following cell exposure to nano-HAp. Collectively, the results reveal the novel epigenetic regulation of cell function by nano-HAp which has significant implication on lineage determination as well as identifying a novel potential therapeutic use of nanomaterials.     

卡培他滨片联合奥沙利铂注射剂治疗晚期结肠癌患者的临床研究

目的观察卡培他滨片联合奥沙利铂注射剂治疗晚期结肠癌患者的临床疗效及安全性。方法将97例晚期结肠癌患者随机分为对照组49例和试验组48例。对照组给予130 mg·m^-2奥沙利铂,静脉滴注,于2~3 h内滴完,第1天;试验组在对照组治疗的基础上,给予1 250 mg·m^-2卡培他滨,bid,口服,第1~14天。2组患者均治疗6个疗程,每个疗程21 d。比较2组患者的临床疗效,血清癌基因ras产物P21蛋白(rasP21)和环氧化酶-2(COX-2)的水平,以及药物不良反应的发生情况。方法治疗后,试验组和对照组的总有效率分别为60.42%(29例/48例)和36.73%(18例/49例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的rasP21分别为(10.03±2.11)和(19.90±3.02)ng·mL^-1,COX-2分别为(3.11±1.10)和(6.70±2.01)ng·mL^-1,差异均有统计学意义(均P<0.05)。2组患者的药物不良反应均以恶心呕吐、白细胞减少、血小板减少、手足综合征、神经毒性和皮炎为主。试验组和对照组的总药物不良反应发生率分别为66.67%(32例/48例)和73.47%(36例/49例),差异无统计学意义(P>0.05)。结论卡培他滨片联合奥沙利铂注射剂治疗晚期结肠癌患者的临床疗效确切,其能明显降低血清rasP21和COX-2水平,且不增加药物不良反应的发生率。     

应用HPV和液基细胞筛查内蒙古杭锦旗宫颈病变的研究

评估宫颈癌筛查方法,探讨少数民族地区宫颈病变发病情况。方法:2010年3月24日～2010年3月30日,在当地政府大力支持下,由当地妇幼保健院组织常住鄂尔多斯杭锦旗2013名年龄在25-65岁已婚有户籍的妇女进行宫颈癌筛查。采用第二代杂交捕获人乳头瘤病毒(HC-Ⅱ)和宫颈薄层液基细胞学(TCT)检测,对宫颈细胞异常和HC-Ⅱ阳性者进行阴道镜检查,阴道镜异常者行多点活检或宫颈管诊刮术,以病理学诊断为金标准。比较3种方法的检出率,评价TCT,HPV的诊断价值。结果:2013例受检者中,TCT异常患者258例,占12.82%;HPV-DNA阳性者,481例,占23.89%,在阴道镜下行多点活检,病理结果 CINⅠ以上者191例,占9.49%.TCT和HPV均阴性者,属于无病理改变。TCT(-),HPV(+)者中≥CINⅡ的检出率13.33%(2/15),TCT(+)和HPV(+)同时存在的病例中,CINⅡ的检出率最高占39.32%(46∕117),仅TCT(+)而HPV(-)者,占13.60%(8/59),8例均为CINⅡ,无原位癌和浸润癌发生。P<0.05差异有统计学意义。结论:持续的HR-HPV感染与宫颈病变的演进有关,TCT联合HC-Ⅱ是宫颈癌筛查最有效的方法,尤其对宫颈高度病变,可以有效的预防宫颈癌的发生。     

A nomenclature for sequence-based forensic DNA analysis

Forensic DNA analysis of casework samples using massively parallel sequencing (MPS) technology requires a system of nomenclature for uniquely labeling sequence-based alleles and artifacts. The DNA Commission of the ISFG has published considerations concerning a nomenclature format that addresses the requirement for unique labeling of sequences. Nomenclatures based on this format can be used in databasing, or communicating sequence types, but the format is lengthy for software interfaces. The sequence identifier (SID) nomenclature addresses this gap by generating short labels able to uniquely identify all sequences (allelic and artifactual) in single-source or casework profiles. Sequences in casework profiles can be uniquely labeled with only two or three SID characters, making the format compact. SID labels can be used in algorithms for identifying and filtering artifacts, and for expressing associations between artifacts and their likely parent alleles. The nomenclature is suitable for use in downstream mixture analysis by any software able to accept character values rather than numeral values. The SID nomenclature is described, and its ability to discriminate sequence-based alleles and artifacts is demonstrated, and its applicability to forensic mixture analysis is demonstrated.