Frequency and Correlation of Common Genes Copy Number Alterations in Childhood Acute Lymphoblastic Leukemia with Prognosis

Objective: It was shown by genomic profiling that despite no detectable chromosomal abnormalities a proportion of children with pre-B acute lymphoblastic leukemia harbors copy number alterations (CNA) of genes playing role in B-cell development and function. The aim of the study was to determine the frequency of CNA in pediatric acute lymphoblastic leukemia and correlate these findings with clinical outcome. Methods: DNA extracted from peripheral blood or bone marrow at diagnosis/relapse of fifty newly diagnosed children with precursor B-cell acute lymphoblastic leukemia was analyzed for CNA with multiplex ligation-dependent probe amplification. Results: The analysis revealed 76 CNA in 24 patients most frequently found in PAR1 (17%), CDKN2A/B (15.7%) and PAX5 (14.4%) genes. There were significant CNA co-occurrences between PAX5, CDKN2A/B, BTG1, ETV6, PAR1 or XP22 genes, (p <0.020) and the high-risk group. There was a significant correlation between EBF1, RB1, and IKZF1 alterations and bone marrow relapse. Patients with CNA in screened genes are more likely to succumb to their disease except for those with PAR1 or XP22 genes (p <0.050). Conclusion: The multiplex ligation-dependent probe amplification could be considered as an independent diagnostic tool allowing prompt identification of patients at high risk of treatment failure and, subsequently, a more adequate treatment approach.     

ABCG5 基因突变致植物固醇血症1 例

目的探讨ABCG5基因突变所致的植物固醇血症的临床及基因变异特征。方法回顾分析1例ABCG5基因突变致植物固醇血症患儿的临床资料。结果 1岁3个月男性幼儿,约4月龄时腕、踝关节皮肤褶皱处开始出现线状黄瘤,后渐加重。血固醇谱检查示菜油固醇、二氢胆固醇明显升高。全外显子检测示ABCG5基因c.904+1(IVS7)GA剪切位点突变和c.-76(exonl)CT非编码区突变。经严格控制植物固醇摄入、少量限制动物固醇摄入以及口服消胆胺治疗40天后,复查患儿血固醇谱,植物固醇水平较前明显降低。结论 ABCG5变异可致植物固醇血症,及时诊断以及药物和饮食控制可改善预后。     

Ilizarov 跖骨延长治疗糖尿病足溃疡并跖骨头慢性骨髓炎

目的探讨清创后一期 Ilizarov 跖骨延长治疗糖尿病足溃疡并跖骨头慢性骨髓炎的临床疗效。方法2015 年 1 月—2018 年 10 月，应用清创后一期 Ilizarov 跖骨延长治疗糖尿病足溃疡并跖骨头慢性骨髓炎患者 8 例（9 足、11 个部位）。其中男 3 例（4 足、5 个部位），女 5 例（5 足、6 个部位）；年龄 44～65 岁，平均 57.5 岁。糖尿病足分级：Wagner 3 级 6 例（7 足）、4 级 2 例（2 足）。左足 4 例，右足 3 例；双足 1 例。慢性骨髓炎病程 1～5 年，平均 3.1 年。骨髓炎部位：第 1 跖骨头 3 足，第 3 跖骨头 1 足，第 4 跖骨头 1 足，第 5 跖骨头 6 足。其中 2 例为同一足合并 2 个部位慢性骨髓炎。记录跖骨延长长度及时间、佩戴外固定架时间，计算外固定架带架指数；观察足部溃疡及骨延长段愈合情况，记录愈合时间，计算骨延长段愈合指数。末次随访时，按照美国矫形足踝协会（AOFAS）评分标准评定足部功能。结果患者术后获随访 9～26 个月，平均 15.0 个月。除骨延长期间发生针道感染外，治疗期间均无皮肤坏死以及血管、神经损伤等并发症发生。跖骨延长长度 12～35 mm，平均 20.5 mm；跖骨延长时间 21～84 d，平均 57.8 d。佩戴外固定架时间 10.4～21.1 周，平均 14.6 周；外固定架带架指数为 42.9～59.2 d/cm，平均 54.3 d/cm。患者足部溃疡均愈合，愈合时间 19～70 d，平均 30.5 d；随访期间溃疡均无复发。X 线片复查示骨延长段均达骨性愈合，愈合指数为 37～51 d/cm，平均 42.5 d/cm。末次随访时，踝关节 AOFAS 评分为 87～95 分，平均 91.7 分；获优 5 足、良 4 足，优良率 100%。结论清创后按照 Ilizarov 张力-应力法则行一期跖骨延长，能促进糖尿病足溃疡愈合、重建跖骨长度、保留跖骨负重功能，是治疗糖尿病足溃疡并跖骨头慢性骨髓炎的一种有效方法。     

节茎石仙桃醋酸乙酯部位的化学成分研究

目的 研究节茎石仙桃Pholidota articulata全草醋酸乙酯部位的化学成分。方法 利用硅胶和Sephadex LH-20凝胶柱色谱进行分离纯化，通过NMR光谱数据分析和与标准品对比分析鉴定化合物结构。结果 从节茎石仙桃78%乙醇提取物中分离得到17个化合物，分别鉴定为2，7-二羟基-9，10-二氢-六氢菲[4，5-环]吡喃（1）、2，6-二羟基-7-甲氧基-9，10-二氢-五氢菲[4，5-环]吡喃（2）、2，7-二羟基-6-甲氧基-9，10-二氢-五氢菲[4，5-环]吡喃（3）、2，7-二羟基-4-甲氧基-9，10-二氢菲（4）、4，7-二羟基-2-甲氧基-9，10-二氢菲（5）、2，5-二羟基-4-甲氧基-9，10-二氢菲（6）、石斛酚（7）、山药素Ⅲ（8）、5，3''-二羟基-3-甲氧基联苄（9）、cirrhopetalidin（10）、β-谷甾醇（11）、豆甾醇（12）、glut-5-en-3-ol（13）、月桂酸（14）、4-（4''-羟基-苄基）苯酚（15）、3-甲氧基苯甲醛（16）、反式桂皮酸（17）。结论 化合物3～17为首次从该植物中分离得到，其中，化合物9、10、13和16为首次从石仙桃属植物中分离得到。     

羌活中的香豆素类成分及其抑制脂多糖诱导的RAW 264.7细胞NO生成活性的研究

目的研究羌活Notopterygium incisum的香豆素类成分及其抗炎活性。方法采用硅胶、HPLC等柱色谱方法进行分离纯化,通过质谱、核磁共振波谱数据鉴定化合物的结构;采用脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症反应模型,考察羌活中香豆素类成分对炎症反应模型一氧化氮(NO)生成的影响。结果从羌活甲醇提取物分离得到24个香豆素类化合物,分别鉴定为异欧前胡素(1)、川白芷素(2)、补骨脂素(3)、香柑内酯(4)、茵陈素(5)、欧芹酚(6)、5-去氢羌活醇(7)、环氧脱水羌活醇(8)、7″-O-甲基异羌活醇(9)、佛手柑素(10)、7-异戊烯氧基-6-甲氧基-香豆素(11)、栓翅芹烯醇(12)、羌活醇(13)、去甲呋喃羽叶芸香素(14)、异羌活醇(15)、蛇床夫内酯(16)、6-异戊烯氧基伞形花内酯(17)、紫花前胡苷元(18)、异虎耳草素(19)、紫花前胡苷(20)、前胡苷V(21)、前胡苷I(22)、印枳苷元-11-O-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖苷(23)、羌活苷(24)。化合物7～10、13和15抑制LPS诱导的RAW 264.7细胞NO生成活性最强,最大半数抑制浓度(IC_(50))值为8.50～35.12μmol/L。结论化合物7为新的天然产物,化合物17为首次从羌活中分离得到;C-5位上具有多烯烃结构的香豆素抑制LPS诱导的RAW 264.7细胞NO生成活性较强。     

Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.     

心血管疾病患者健康相关生命质量及其影响因素的多水平模型分析

目的 探讨心血管疾病患者的健康相关生命质量及其影响因素,为改善患者生命质量提供参考。 方法 选取2015年中国健康与养老追踪调查(CHARLS)中符合要求的心血管疾病患者1 201例,收集患者及地区信息,基于欧洲五维健康量表(EQ-5D-3L)测量健康效用值反映其健康相关生命质量。采用K-W检验对患者和地区因素进行单因素分析。以患者水平为水平1,地区水平为水平2,建立两水平回归模型,分析患者和地区因素对心血管疾病患者健康相关生命质量的影响。 结果 健康效用值平均值为0.749±0.166。单因素分析结果显示,心血管疾病患者健康相关生命质量的影响因素包括性别、受教育水平、婚姻状况、是否患有高血压、是否患有心脏病、是否患有中风、睡眠时长、吸烟状况、饮酒状况、每周中等强度体力活动时间、社交活动频率、体质量指数(BMI)、所在地区(P<0.05)。多水平模型结果显示,对心血管疾病患者健康相关生命质量有显著影响的因素有性别、受教育水平、婚姻状况、是否患有高血压病、是否患有血脂异常、是否患有心脏病、是否患有中风、吸烟状况、每周中等强度体力活动时间、社交活动频率、BMI以及地区水平的地区因素(P<0.05)。 结论 提高心血管疾病患者的健康相关生命质量既要考虑受教育水平、吸烟状况、BMI等个体因素,还应考虑不同地区患者的异质性,从而制定不同地区的针对性策略。     

综合疗法治疗4~5期慢性肾脏病31例临床观察

目的:观察综合疗法治疗慢性肾脏病(CKD)4~5期脾肾亏虚证的效果。方法:将CKD4~5期脾肾亏虚证患者62例随机分为2组,其中治疗组31例,对照组30例(剔除1例)。对照组予基础治疗合中药、骨化三醇及碳酸钙D3片治疗,治疗组予基础治疗合中药、骨化三醇及益肾泄浊汤保留灌肠治疗,观察时间为4周。比较2组血肌酐(Scr)、肾小球滤过率(e GFR)、尿素氮(BUN)、血钙、血磷、碱性磷酸酶(ALP)、甲状旁腺激素(i PTH)及中医证候疗效。结果:中医证候总有效率治疗组为83.87%(26/31),对照组为73.33%(22/30),组间比较,差异有统计学意义(P<0.05);2组Scr、e GFR、BUN、血磷治疗前后组内比较及治疗后组间比较,差异均有统计学意义(P<0.01或P<0.05);2组血钙、i PTH、ALP治疗前后组内比较,差异均有统计学意义(P<0.01),但治疗后组间比较,差异无统计学意义(P>0.05)。结论:综合疗法治疗慢性肾脏病4~5期脾肾亏虚证效果确切,安全可靠。     

MicroRNA‐375‐3p enhances chemosensitivity to 5‐fluorouracil by targeting thymidylate synthase in colorectal cancer

Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU.