AKR7A3在肺腺癌中异常表达及临床意义

目的:探讨醛-酮还原酶家族7成员A3（AKR7A3）在肺腺癌中的异常表达及与临床病理特征的关系，并探究其临床意义。方法:采用生物信息学数据库分析、免疫组化、Western Blot、Real-time PCR等方法对肺腺癌组织及不同细胞中AKR7A3的表达进行检测与分析。结果:Oncomine数据库分析结果显示，在肺腺癌中，AKR7A3的表达普遍高于正常肺组织，分别为正常肺组织的1.811倍（P=0.022）、1.356倍（P<0.01）、1.413倍（P=0.002）。Kaplan-Meier Plotter数据库分析结果显示，AKR7A3高表达的患者较低表达的患者生存时间缩短，差异具有统计学意义（P=0.003 7）。免疫组化染色显示肺腺癌组织中AKR7A3的表达较癌旁增高，在与临床病理特征的相关性分析中，发现其与肿瘤分化程度（P<0.01）、淋巴结转移情况（P=0.029）以及TNM分期（P<0.01）相关，且会造成患者生存时间缩短（P=0.031）。Cox多因素分析表明AKR7A3可能是影响肺腺癌患者预后的独立危险因素(P=0.012)。Western Blot及Real-time PCR实验提示不同肺腺癌细胞中AKR7A3蛋白及mRNA表达普遍增高。结论:AKR7A3在肺腺癌中表达增高，对预后有不良影响，有促进肿瘤发生发展的作用。     

B7-H3 and its role in bone cancers

Most bone cancers have a high risk of metastasis, recurrence, and poor prognosis. Although conventional treatments are still the most important therapy, disadvantages still exist. Therefore, there is an unmet need to develop effective strategies. Immunotherapy is a promising therapy. Immunotherapies targeting checkpoints have proven to be successful, but B7-H3 (CD276, clusters of differentiation protein 276), a member of the B7-family of co-stimulatory molecules, is not being widely studied in bone cancers. This review summarized the studies on B7-H3 in bone cancers. 4 studies investigated B7-H3 expression in osteosarcoma, but there is no study on B7-H3 expression in chondrosarcoma. Two studies investigated the possibility to treat Ewing`s sarcoma through targeting the B7-H3 CAR (chimeric antigen receptors) T-cells or using anti-B7-H3 antibody. A study observed the growth of myeloma in B7-H3-deficient mice and the therapeutic effect of B7-H3 antibody and a study invested B7-H3 expression in myeloma patients. One study reported B7-H3 expression in osteoclastomas and one study investigated B7-H3 expression in chordoma tumor tissues. Two clinical trials are conducting on the therapy of osteosarcoma and myeloma using B7-H3 as a target. In conclusion, B7-H3 could be a target of bone cancers.     

椎弓回植与椎板切除治疗轻中度峡部裂性腰椎滑脱症疗效比较

目的比较椎弓回植与椎板切除治疗单节段峡部裂性腰椎滑脱症的临床疗效。方法回顾分析 2014 年 3 月—2016 年 7 月采用椎弓回植或椎板切除治疗的 66 例单节段峡部裂性腰椎滑脱症患者临床资料，根据手术方式不同分为试验组（34 例，采用椎弓完整回植固定椎间融合内固定术）和对照组（32 例，采用椎板切除并椎间融合内固定术）。两组患者性别、年龄、病程、病变节段、Meyerding 分度及术前疼痛视觉模拟评分（VAS）、Oswestry 功能障碍指数（ODI）、日本骨科协会（JOA）评分等一般资料比较差异，均无统计学意义（P>0.05），具有可比性。记录并比较两组患者手术时间、术中出血量、并发症情况、术后试验组回植椎弓融合情况及两组硬膜外瘢痕形成情况。术前及术后 3、6、12 个月和末次随访时行腰痛 VAS 评分、JOA 评分及 ODI 评分，并参照侯树勋等提出的标准进行临床疗效评价。 结果所有患者均顺利完成手术，无神经损伤加重、硬脊膜撕裂、感染等并发症发生。试验组手术时间与对照组比较差异无统计学意义（t=0.583，P=0.562），但术中出血量显著低于对照组（t=2.134，P=0.037）。66 例患者均获随访，随访时间 13～18 个月，平均 16.2 个月。所有患者术后临床症状明显改善。对照组 7 例于术后 3 个月发现体位变动时椎管狭窄症状，5 例于术后 18 个月出现轻度双下肢麻木症状；其余患者未发生感染、神经损伤等并发症。试验组 34 例硬膜外瘢痕组织均被完全阻滞于回植椎弓以外，对照组有 11 例硬膜外瘢痕组织侵入椎管内。末次随访时试验组椎间植骨及椎弓回植融合率均为 100%，对照组椎间植骨融合率亦为 100%。两组术后各时间点 VAS 评分、ODI 评分、JOA 评分均较术前显著改善（P<0.01）；试验组术后 3 个月和末次随访时 ODI 评分、JOA 评分显著优于对照组（P<0.05），其余时间点两组间各评分比较差异无统计学意义（P>0.05）。参照侯树勋等提出的标准进行临床疗效评价，试验组优良率为 91.2%，与对照组优良率 84.4%比较差异无统计学意义（χ²=1.092，P=0.573）。 结论与椎板切除相比，椎弓回植能更好地改善术后神经症状，最大程度重建了骨性椎管，恢复了椎管内环境稳定性，对于峡部裂性腰椎滑脱是一种较好的手术方式。     

SDF-1α/CXCR4 信号通路在轴向应力刺激促进骨再生中的作用研究

目的通过轴向应力刺激促进骨再生，观察基质细胞衍生因子 1α/趋化因子 CXC 亚族受体 4（stromal cell-derived factor 1α/cysteine X cysteine receptor 4，SDF-1α/CXCR4）信号通路变化，探讨轴向应力刺激促进骨再生的机制。方法取 72 只雄性新西兰大白兔，于右后肢胫骨近端内侧制备直径 8 mm 圆形皮质骨缺损并脱蛋白松质骨支架修复模型，随机分为 3 组（n=24）。A 组腹腔注射 PBS，B 组术肢给予应力刺激治疗+腹腔注射 PBS，C 组术肢给予应力刺激治疗+腹腔注射 CXCR4 拮抗剂（AMD3100）。术后 2、4、8、12 周，摄 X 线片并采用 Lane-Sandhu X 线评分标准评价骨愈合情况，取标本行 HE 染色观察新生骨组织及支架降解，免疫组织化学染色观察 VEGF、CXCR4 表达水平；4、8 周取标本 Western blot 检测 SDF-1α 及 CXCR4 蛋白表达水平；12 周行 Micro-CT 检查，计算新生骨体积及新生骨密度。 结果X 线片检查示，除术后 2 周各组骨缺损区及支架无明显变化外，4、8 及 12 周时 B 组骨愈合评分均高于 A、C 组（P<0.05）。12 周时 Micro-CT 扫描可见 B 组骨缺损修复、髓腔再通，新生骨体积及骨密度均高于 A、C 组（P<0.05）。HE 染色显示，术后 4 周开始 B 组骨再生及支架降解均明显快于 A、C 组。免疫组织化学染色示，各组 VEGF 及 CXCR4 阳性表达均在 4 周达峰值；各时间点 B 组 VEGF 及 CXCR4 表达量均显著高于 A、C 组（P<0.05）。Western blot 检测显示，4、8 周时 B 组 SDF-1α 与 CXCR4 表达量均显著高于 A、C 组（P<0.05）。 结论轴向应力刺激促进骨再生可能与其促进骨缺损区组织高表达 SDF-1α，激活与其下游调控 BMSCs 募集的 CXCR4 信号有关。     

Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents

Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4’-dimethyl-2,2’-dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass spectrometry, and elemental analyses were utilized for chemical characterizations. Cell viability, cancer cell colony formation, endothelial tube formation, and cytoskeleton staining assays were performed using A549 lung adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1-Pt) was the most promising complex, and has similar activity with the approved chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for BPA-L1-Pt were 9.15 µM on A549s and 16.61 µM on HUVECs; the values for cis-platinum were 5.24 µM on A549s and 23.14 µM on HUVECs. Consequently, further synthesis studies should be performed to boost the cancer cell selectivity feature of BPA by varying metal and ligand types.     

Comparison of Time to Next Treatment,Health Care Resource Utilization,and Costs in Patients with Chronic Lymphocytic Leukemia Initiated on Front-line Ibrutinib or Chemoimmunotherapy

BackgroundStudies assessing ibrutinib’s economic burden versus chemoimmunotherapy (CIT) focused on pharmacy costs but not medical costs. This study compared time to next treatment (TTNT), health care resource utilization (HRU), and total direct costs among patients with chronic lymphocytic leukemia (CLL) initiating front-line ibrutinib single agent (Ibr) or CIT.Materials and MethodsOptum Clinformatics Extended DataMart De-Identified Databases were used to identify adults with ≥ 2 claims with a CLL diagnosis initiating front-line Ibr or CIT from February 12, 2014 to June 30, 2017. Inverse probability of treatment weighting was used to control for potential differences in baseline characteristics between the Ibr and CIT cohorts. Two periods were considered: entire front-line therapy (until initiation of second-line therapy) and first 6 months of front-line therapy. Comparisons with a subgroup of CIT patients initiating bendamustine/rituximab (BR) were also conducted.ResultsTTNT was significantly longer for Ibr (N = 322) relative to CIT (N = 839; hazard ratio, 0.54; P = .0163; Kaplan-Meier rates [24 months]: Ibr = 88.6%, CIT = 75.9%) and the subset of CIT patients treated with BR (N = 455; hazard ratio, 0.54; P = .0208; Kaplan-Meier rates [24 months]: Ibr = 89.0%, BR = 79.0%). During the entire front-line therapy, Ibr patients had significantly fewer monthly days with outpatient visits (rate ratio = 0.75; P = .0200). Ibrutinib’s higher pharmacy costs (mean monthly cost difference [MMCD] = $6,849; P < .0001) were offset by lower medical costs (MMCD = ?$10,615; P < .0001), yielding net savings (MMCD = ?$3,766; P < .0001) versus CIT. Ibr was associated with net savings (MMCD = ?$5,569; P < .0001) versus BR. Cost savings and reductions in HRU were more pronounced during the first 6 months of front-line therapy.ConclusionDuring front-line CLL treatment, Ibr was associated with longer TTNT, fewer monthly days with outpatient visits, and net monthly total cost reduction versus CIT and BR.     

Echocardiographic features of interventricular septal dissection in patients with Behçet's disease

Involvement of the heart in Behçet's disease (BD) is rare. We retrospectively analyzed these three patients with interventricular septal (IVS) dissection in BD and discussed the echocardiographic manifestations of IVS dissections. In our patients, the echocardiographic characteristics of IVS dissection were echo‐free space in the IVS basal segment or basal to middle segment, dilatation in the diastole and contraction in systole, and abnormal turbulent blood flow in the heart.     

Antibody persistence and booster response following MenACWY-CRM vaccination in children as assessed by two different assay methods

BackgroundThe quadrivalent meningococcal conjugate vaccine MenACWY-CRM has been shown to be immunogenic and well-tolerated in infants and toddlers. We evaluated antibody persistence for up to 4 years after vaccination with MenACWY-CRM in the first years of life and response to a booster dose administered at 60 months of age.MethodsThis was phase 3b, open-label, multicenter extension trial (NCT01148017). We assessed by hSBA and rSBA the persistence of antibody responses to serogroups ACWY in 203 healthy 60-month-olds receiving 4 doses of MenACWY-CRM during infancy (ACWY-4 group), or 2 doses at 12/13 and 15 months or 1 dose at 18 months of age (ACWY-2 group). We administered a MenACWY-CRM dose to 224 primed and 45 naïve 60-month-olds and evaluated safety and antibody response 1 month later.ResultsAntibody persistence measured by both assays was higher in primed than naïve 60-month-olds. The percentages of primed children with hSBA titers ≥8 was low for serogroup A (6–25%) and moderate for serogroups C (27–43%), Y (69–74%) and W (56–69%). For all serogroups, hSBA antibody geometric mean titers (GMTs) tended to be higher in the ACWY-2 than the ACWY-4 group. Post-booster/single dose, ≥96% of primed and ≥73% of naïve children had hSBA titers ≥8 against each serogroup, and hSBA GMTs were higher in primed children. The booster dose was well-tolerated and no safety concern was identified. We further assessed persistence using rSBA across different age groups and detected no overall correlation between rSBA and hSBA titers.ConclusionsPrimary vaccination of infants/toddlers with MenACWY-CRM resulted in moderate antibody persistence against serogroups C, W and Y for up to 4 years after the last priming dose. Regardless of priming schedule, a MenACWY-CRM booster dose at 60 months of age induced a robust immune response against all serogroups and was well-tolerated in all children.