藏药绿萝花中1个新的香豆素

目的研究结香属藏药绿萝花(滇结香Edgeworthia gardneri干燥花蕾)的化学成分。方法利用硅胶、AB-8大孔树脂、sephadex LH-20、pre-HPLC等色谱方法对绿萝花进行分离纯化,根据理化常数测定及波谱数据分析鉴定化合物结构。结果从绿萝花70%乙醇提取物中分离得到4个化合物,分别鉴定为绿萝花苷C(1)、西瑞香素-5-O-β-D-吡喃葡萄糖基-(1→2)-β-D-吡喃葡萄糖苷(2)、(3S)-1,2,3,4-四氢-β-咔啉-3-羧酸(3)、二氢山柰酚(4)。结论化合物1为新化合物,化合物4为首次从该属植物中分离得到。     

Apatinib Monotherapy or Combination Therapy for Non-Small Cell Lung Cancer Patients With Brain Metastases

Apatinib, an oral small molecular receptor tyrosine kinase inhibitor (TKI) developed first in China, exerts antiangiogenic and antineoplastic function through selectively binding and inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we aimed to explore the efficacy and safety profile of apatinib monotherapy, or combined with chemotherapy or endothelial growth factor receptor (EGFR)-TKI in heavily pretreated non-small cell lung cancer (NSCLC) patients with brain metastases. We performed a retrospective analysis for relapsed NSCLC patients with brain metastases from our institute, who received apatinib (250 mg or 500 mg p.o. qd) monotherapy, or combination with EGFR-TKI or chemotherapy as second or more line systemic therapy until disease progression or unacceptable toxicity occurred. The objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and safety were analyzed. A total of 26 eligible patients were included: 24 patients diagnosed with adenocarcinoma, 2 with squamous carcinoma, and 14 patients harboring EGFR sensitizing mutations. The mPFS and mOS were 4.93 (range, 0.27−32.91; 95% CI 3.64−6.22) and 14.70 (range, 0.27−32.91; 95% CI 0.27−43.60) months for the whole group. The ORR and DCR were 7.7% (2/26) and 69.2% (18/26) for the entire lesions, and 7.7% (2/26) and 79.6% (20/26) for brain metastases, respectively. Compared with patients who received apatinib monotherapy, patients who received apatinib combination treatment had more favorable mPFS (11.77 vs. 2.27 months, p<0.05) and mOS (24.03 vs. 6.07 months, p<0.05). Treatment-related toxicities were tolerable including grade 1/2 hypertension, hand-and-foot syndrome, fatigue, nausea, liver dysfunction, myelosuppression, skin rash, and palpitation. In conclusion, apatinib exhibited high activity and good tolerance for NSCLC patients with brain metastasis, and it might become a potential choice for metastatic brain tumors in NSCLC patients.     

HIFα Regulates Developmental Myelination Independent of Autocrine Wnt Signaling

The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα–Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα–Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury.     

Molecular profiling of Chinese R-CHOP treated DLBCL patients: Identifying a high-risk subgroup

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.     

Burden of illness among patients with severe aplastic anemia who have had insufficient response to immunosuppressive therapy: a multicenter retrospective chart review study

Annals of Hematology - This study assessed treatment patterns and healthcare resource utilization (HRU) of patients with severe aplastic anemia (SAA) with insufficient response to immunosuppressive...     

珠海地区NRXN1和NLGN1基因多态性与儿童孤独症的关联性研究

目的 探索珠海地区NRXN1和NLGN1基因多态性与儿童孤独症易感性的关系,为孤独症的防治提供科学依据。方法 采用病例对照的研究方法,选取2011－2016年就诊于珠海市妇幼保健院的123例珠海地区的孤独症患儿和506例健康对照。采用口腔拭子采集口腔上皮细胞以提取DNA,采用Sequenom Mass Array platform分型技术对NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544进行基因分型。结果 NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因型分布在孤独症组和健康对照组比较,差异无统计学意义;但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824存在基因与基因间的交互作用(预测准确率为0.480,交叉验证一致性为10/10,P=0.040)。结论 NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因多态性可能与孤独症易感性没有关联,但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824之间的交互作用可能是孤独症易感性的影响因素。     

我国类鼻疽病的流行病学特征及诊疗的研究进展

类鼻疽病是由类鼻疽伯克霍尔德菌(Burkholderia pseudomallei)感染引起的一类人畜共患病,主要流行于全球热带及亚热带地区。在我国主要流行于南部地区,疫源地为海南、广东、广西、台湾等。伴随着旅游业和贸易业的发展,我国其他非疫区出现了输入性病例。类鼻疽病的感染途径主要为经伤口、粘膜、呼吸道、消化道等,其病变可涉及机体所有器官,易造成较高的误诊率和病死率。然而我国目前类鼻疽病的流行病筛查技术存在一定的局限性,在防控方面未实行有效的疾病监测和疾病报告制度,对基层医师和民众疾病知识普及的力度不够。因此,本文旨在提高我国医务工作者对类鼻疽病的重视程度,从类鼻疽病的病原学特征、流行病学特征、临床特征、诊断与治疗、防控措施这五个方面进行详细综述。     

紫杉醇联合卡铂化疗治疗卵巢癌的效果分析

目的探讨紫杉醇联合卡铂化疗治疗卵巢癌的效果分析。方法选自2018年5月-2019年5月132名符合入组以及排除标准的患者,随后研究人员将患者分为对照组以及研究组,分组应按照科学、合理、随机的标准,两组患者分别均有67例,对照组患者按照研究要求,接受卡铂化疗治疗,研究组患者按照研究要求,接受紫杉醇联合卡铂化疗治疗,两组患者分别接受不同的治疗,评估患者的临床效果,对比两组患者的观察指标,如:T细胞亚群、临床疗效。结果治疗后,CD8、CD4、CD3、CD4/CD8,研究组高于对照组;研究组中,CR+PR+SD人数多于对照组患者,且治疗总有效率高于对照组患者(P<0.05)。结论紫杉醇联合卡铂化疗治疗卵巢癌,能够提升患者自身的免疫功能,促进疾病的好转。     

学龄期儿童前房深度发育状况分析

目的了解7~14岁学龄期儿童前房深度发育情况。探索其与屈光度数间的关系。方法收集2012年6月至2014年6月眼科门诊7~14岁儿童为研究对象，共计521例（1042只眼）。采用IOLMaster人工晶状体生物测量仪测量各屈光参数，同时测量身高、体重。散瞳后验光测得静态屈光度。分析前房深度发育情况及不同屈光状态的学龄期儿童前房深度发育情况。结果（1）随着年龄的增长，7~14岁学龄期的儿童前房深度随之增长，差异具有统计学意义（P＜0.01）。同一年龄段儿童的左右眼之间的均值相近，且生长发育趋势相近（均P＞0.05）。（2）随着年龄的增长，男女的前房深度均逐渐增大，同一年龄段男性前房深度大于女性前房深度（均P＜0.01）。（3）儿童前房深度与身高正相关（P＜0.01）。（4）前房深度随近视度数增高而增大，低度近视组与中度近视组及高度近视组差异有统计学意义（P＜0.05）。结论学龄期儿童的前房深度的发育受到身高、性别及屈光度数的影响，与身高呈正相关，同一年龄段，男性前房深度大于女性。双眼前房深度发育同步。低中度近视的儿童前房深度增大。