Improvement of native pulmonary alveolar proteinosis after contralateral single living‐donor lobar lung transplantation: A case report

PAP is a rare disease characterized by the accumulation of surfactant materials in the alveolar spaces due to the imbalance of surfactant homeostasis (production and clearance). We herein report a case of an 8‐year‐old girl who developed PAP after BMT from her mother for the treatment of DBA. The anemia was improved by BMT; however, respiratory dysfunction due to graft‐versus‐host disease gradually progressed. She eventually underwent right single LDLLT from her mother when she was 14 years old. A pathological examination of the excised lung confirmed the finding of diffuse bronchiolitis obliterans and unexpectedly revealed widespread alveolar proteinosis. Interestingly, the GGO of her native left lung on chest X‐ray was improved after LDLLT. We present the very unique clinical course of this patient and discuss the mechanisms underlying the development of PAP after BMT and its improvement after LDLLT from the same donor.     

Metabolism of MMB022 and identification of dihydrodiol formation in vitro using synthesized standards

MMB022 (methyl 3‐methyl‐2‐[1‐(pent‐4‐en‐1‐yl)‐1H‐indole‐3‐carboxamido]butanoate) is a new synthetic cannabinoid with an alkene at the pentenyl side chain, a rare functional group for synthetic cannabinoids. Metabolite identification is an important step for the detection of synthetic cannabinoids in humans, since they are generally extensively metabolized. The aims of the study were to tentatively identify in vitro phase I metabolites, to confirm major metabolites using synthesized metabolites, to examine metabolic pathways thoroughly, to study metabolic stability and to suggest metabolites appropriate for urine screening. MMB022 and its synthesized metabolites were incubated with human liver microsomes (HLM) and the supernatants were analyzed by liquid chromatography‐quadrupole time‐of‐flight mass spectrometry. Sixteen metabolites were identified, which were generated via dehydrogenation, dihydrodiol formation, ester hydrolysis, hydroxylation, and combinations thereof. A major biotransformation of the alkene at the pentenyl side chain was confirmed to be dihydrodiol formation. The major metabolites were ester hydrolysis (M15) and dihydrodiol (M8) metabolites, whereas the metabolite derived from the combination of ester hydrolysis and dihydrodiol (M5) was the fourth most abundant metabolite. The metabolic pathways were investigated using synthesized metabolites and revealed that M5 is an end product of the pathways, indicating that it might become a more abundant metabolite in vivo depending on the rate of metabolism in humans. The major pathway of MMB022 to M5 was determined to be via M8 formation. Intrinsic clearance of MMB022 was determined to be 296 mL/min/kg and t_1/2 was 2.1 min, indicating a low metabolic stability. M15, M8, and potentially M5 are suggested as suitable urinary targets.     

L‐Leucine improves the anaemia in models of Diamond Blackfan anaemia and the 5q‐ syndrome in a TP53‐independent way

Haploinsufficiency of ribosomal proteins (RPs) and upregulation of the tumour suppressor TP53 have been shown to be the common basis for the anaemia observed in Diamond Blackfan anaemia and 5q‐ myelodysplastic syndrome. We previously demonstrated that treatment with L‐Leucine resulted in a marked improvement in anaemia in disease models. To determine if the L‐Leucine effect was Tp53‐dependent, we used antisense MOs to rps19 and rps14 in zebrafish; expression of tp53 and its downstream target cdkn1a remained elevated following L‐leucine treatment. We confirmed this observation in human CD34+ cells. L‐Leucine thus alleviates anaemia in RP‐deficient cells in a TP53‐independent manner.     

Synthesis and antitumor activity evaluation of novel ursolic acid derivatives

Eleven novel ursolic acid (UA) derivatives were designed and synthesized with modification at positions of C-2, C-3, and C-28 of UA. Their structures were confirmed by MS, ¹H NMR, and elemental analysis. Their in vitro cytotoxicities against various cancer cell lines (HeLa, HepG2, and BGC-823) were evaluated by MTT assay. The results indicated that all compounds could inhibit cell proliferation of HeLa, HepG2, and BGC-823 cells. Among them, compounds I₃ and I₄ showed more potent cytotoxicity on these three tumor cells than gefitinib (positive control), worthy to be studied further.     

化学合成多肽体外抗HBV复制的研究

目的 观察人工设计并化学合成的多肽在体外乙型肝炎病毒（HBV）复制模型中对HBV-DNA复制、病毒标志物表达的影响,及其细胞毒性强弱,筛选高HBV抑制且低细胞毒性的多肽,探索多肽作为新型HBV抗病毒药物分子的潜力。方法 采用传统的甲基丙烯酸聚合物平台设计并合成的7种多肽（KBDT-1、2、3……7,以疏水性及阳离子电亲和力大小为依据）,将7种化学合成多肽（10 mg/mL）、拉米夫定（1 mg/mL,阳性对照）、空白溶剂（阴性对照）作用于HepG 2.2.15细胞系,检测化学合成多肽对HBV的抑制作用,采用结晶紫染色法检测细胞存活率,比较各组药物对细胞毒性的强弱。选取HBV抑制作用最强的多肽,设置10、1、0.1 mg/mL浓度梯度,分别处理HepG 2.2.15细胞3、6、9 d后,收集细胞上清液,采用实时荧光定量聚合酶链反应（RT-PCR）检测病毒DNA拷贝量,化学发光微粒子免疫分析法检测HBsAg及HBeAg的变化。结果 从7种化学合成多肽中筛选出多肽KBDT-2,RT-PCR结果显示,KBDT-2具有体外抗HBV复制作用,且药物浓度越高,抑制效果越好;化学发光微粒子免疫分析法检测显示,KBDT-2对HBV生物学标志物HBsAg及HBeAg有抑制作用;结晶紫染色检测结果显示,KBDT-2对HepG 2.2.15无明显毒性作用。结论 KBDT-2具有抑制HBV复制作用,且无明显细胞毒性,可以有效降低HBsAg、HBeAg表达,为探索抗HBV新型药物提供了实验数据支持。     

An interview-informed synthesized contingency analysis to inform the treatment of challenging behavior in a young child with autism

ABSTRACT

Purpose: Experimental Functional analysis (EFA) is considered the “gold standard” of behavioural assessment and its use is predictive of treatment success. However, EFA has a number of limitations including its lengthy nature, the high level of expertise required, and the reinforcement of challenging behaviour. This study aimed to further validate a novel interview-informed synthesised contingency analysis (IISCA).

Methods: An open-ended interview and brief direct observation informed an IISCA for a young boy with autism who engaged in challenging behaviour. Resulting data supported the hypothesis that the target behaviour was multiply controlled by escape from demands and access to tangible items. An intervention comprised of most-to-least prompting, escape extinction, differential reinforcement and a high-probability instruction sequence was evaluated using a reversal design.

Results: This intervention reduced challenging behaviour to low levels and resulted in increased compliance.

Conclusions: Findings support the status of the IISCA as a valid, practical, and effective process for designing function-based interventions.     

抗菌肽对抗肿瘤细胞的机制：选择性膜破坏和非膜溶解

文题释义：爪蟾素Ⅱ：是一种从非洲爪蛙的皮肤中分离出来的抗菌肽,在严重造血和实体恶性肿瘤中显示出有效的抗癌作用。作为一种具有螺旋结构的离子载体肽,爪蟾素Ⅱ已被证明能够穿透癌细胞膜,起到离子通道的作用,导致癌细胞的细胞溶解,显著增强了细胞毒性化疗药物的抗肿瘤作用。乳铁蛋白：是一种分子质量80 kD的铁隔离糖蛋白,存在于乳汁等外分泌液和多形核白细胞颗粒中。乳铁蛋白B具有一定的抗肿瘤作用,因为它能够对肿瘤细胞的胞质膜和线粒体膜产生致命的、选择性的失稳作用,并且已被证明对结直肠癌、神经母细胞瘤和黑色素瘤癌细胞有效。背景：抗菌肽作为一种可从自然中提取并且对快速增殖的细胞产生毒性的宿主免疫基本成分,引起了科学家们广泛关注。熟悉抗菌肽的抗肿瘤机制才能更好的将其应用于临床实践中。目的：综述近年来抗菌肽抗肿瘤机制的研究进展。方法：由第一作者应用计算机检索PubMed、Springerlink、Web of Science、ScienceDirect等数据库2015年1 月至2019年5月发表的文献,检索词为“antimicrobial,peptide,antitumor mechanisms,antitumor activity,anti-neoplastic”,选择与抗菌肽抗肿瘤机制及其研究进展相关的文献。结果与结论：核糖体合成的阳离子抗菌肽或宿主防御肽通过与细菌表面带负电荷脂质的静电相互作用显示出了广谱抗菌活性。与正常细胞相比,由于癌细胞表面的磷脂酰丝氨酸(带负电荷)比例增加,因此阳离子双亲肽可能是抗肿瘤药物的一个有效治疗方法,并且具有高选择性。抗菌肽的抗肿瘤机制从作用模式上可以分为2类：选择性膜破坏和非膜溶解作用机制,其代表性的抗肿瘤肽包括α防御素1、乳铁蛋白B等。抗菌肽抗肿瘤的临床应用主要制约在其稳定性及给药途径,通过对其进行结构优化,开发创新配方和药物输送系统,使这些抗菌肽在未来肿瘤治疗过程中发挥更大的作用。ORCID: 0000-0001-7405-1386(弓磊)中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

不同玷污层对4种树脂粘接系统粘接强度及粘接耐久性的影响

文题释义：玷污层：牙体预备时由于车针的高速切割和挤压,牙本质表面形成厚1-5 μm的玷污层,它由无机物碎屑和凝固的胶原纤维碎屑组成。切割碎屑深入牙本质小管口形成管塞。磷酸酸蚀处理能够去除牙本质表面的玷污层及污物,而自酸蚀粘接剂则因为酸性较弱仅能对牙本质表面的玷污层及杂质进行部分溶解,并最终将剩余的玷污层包含在内形成混合粘接层。甲基丙烯酰癸氧基二氢磷酸酯(10-MDP)：是一种性能优良的酸性功能单体,与羟基磷灰石反应生成的难溶性钙盐形成“纳米层状结构”,强烈吸附于牙本质表面,这一特点被认为能够增强粘接性能,并且对胶原纤维有保护作用,长期观察发现其可以提高粘接剂的耐久性。背景：当用旋转式或手动器械处理牙表面时,在牙釉质和牙本质上由切割和磨损产生的碎片形成了玷污层。玷污层是影响牙和修复材料之间粘接的重要因素,明确玷污层对不同种类粘接剂的影响对口腔医生的临床选择与正确使用具有重要的临床意义。目的：评价使用不同金刚砂车针预备的试件在人工唾液中存储24 h与100 d后,对4种粘接剂与牙本质粘接强度的影响。方法：获取离体人磨牙80颗,分别进行600号碳化硅砂纸(对照)、中细粒度金刚砂车针、标准粒度金刚砂车针、粗粒度金刚砂车针4种牙本质表面处理,每种处理20颗;每种处理方法内分4个亚组,分别以两步法自酸蚀粘接剂Optibond Versa(VSA组)、一步法自酸蚀粘接剂Optibond All in One(AIO组)、通用型粘接剂Single Bond Universal(SBU组)及全酸蚀粘接剂Bond 5(GLU组)进行树脂粘接。粘接完成后,将试件置于人工唾液中37 ℃储存24 h及100 d,随后进行微拉伸强度测试,使用扫描电镜观察牙本质端断裂面,并对断裂模式进行分析。结果与结论：①储存24 h：使用两步法粘接剂或全酸蚀粘接剂的情况下,不同表面处理组间的粘接强度比较差异无显著性意义(P > 0.05);使用一步法粘接剂或通用型粘接剂的情况下,仅粗粒度车针组粘接强度低于砂纸组(P < 0.05)。使用砂纸或中细粒度车针的情况下,仅AIO组与VSA组粘接强度比较无差异;使用标准粒度车针的情况下,仅AIO组与VSA组、GLU组与SBU组粘接强度比较无差异(P > 0.05);使用粗粒度车针的情况下,VSA组与AIO组、GLU组、SBU组粘接强度比较差异均有显著性意义(P < 0.05),其余组间比较无差异(P > 0.05);②储存100 d：使用两步法粘接剂或全酸蚀粘接剂的情况下,不同表面处理组间的粘接强度比较差异无显著性意义(P > 0.05);使用一步法粘接剂的情况下,仅粗粒度车针组粘接强度低于砂纸组(P < 0.05);使用通用型粘接剂的情况下,仅标准粒度车针组、粗粒度车针组粘接强度低于砂纸组(P < 0.05)。使用砂纸或中细粒度车针的情况下,仅VSA组与SBU组粘接强度无差异(P > 0.05);使用标准粒度车针的情况下,仅SBU组与VSA组、GLU组与SBU组、GLU组与VSA组粘接强度无差异(P > 0.05);使用粗粒度车针的情况下,仅VSA组与AIO组粘接强度无差异(P > 0.05);③仅在使用两步法粘接剂的情况下,不同表面处理组100 d后的粘接强度与24 h比较差异有显著性意义(P < 0.05);④与浸泡24 h相比,VSA组、SBU组、GLU组浸泡100 d后的粘接界面断裂和混合断裂比例略有增加,其中VSA组变化最大;与其他组比较,GLU组浸泡24 h与100 d的粘接界面断裂和混合断裂模式比例均超过50%;⑤结果表明,使用不同粒度车针预备产生了不同的玷污层,对一步法自酸蚀粘接剂粘接强度产生了显著影响,对两步法自酸蚀粘接剂和全酸蚀粘接剂未产生显著影响;存储时间对不同粘接剂产生了显著影响。ORCID: 0000-0002-1639-6498(郑适泽)中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Robot-Assisted Retroperitoneoscopic Diamond Bypass Pyeloplasty

AimRobot (da Vinci Si; Intuitive Surgical, Sunnyvale, CA) assisted retroperitoneoscopic diamond bypass pyeloplasty (R-RDBP) performed for ureteropelvic junction (UPJ) obstruction (n = 5) is presented.MethodsPatients were placed affected side up and the retroperitoneal space accessed conventionally using 3–4 trocars. The diamond-shaped anastomosis involved incising the lowest part of the renal pelvis 12–15 mm transversely and the ureter distal to the obstruction 10–12 mm longitudinally. The first two sutures were placed retroperitoneoscopically; one from the mid-caudal line of the renal pelvis to the apex of the ureteric incision (the apex of the diamond) and the other from the corner of the incision in the renal pelvis to halfway along the ureteric incision. Trocars were replaced and the robot system docked. The first robot suture was placed between these two sutures, and the anastomosis completed by suturing from posterior to ventral applying minimal tension to keep the anastomosis close to the renal pelvis. All sutures were interrupted absorbable 5-0 monofilament.ResultsMean age at R-RDBP was 4.3 (range: 1–14) years old. Height/weight were average. Preoperative Society for Fetal Urology (SFU) grading was 4.0 in all cases. All repairs were primary and progressed smoothly without perioperative complications; 3/5 had improved appetite postoperatively. Mean SFU grades 1–3 months postoperatively were 2.8, 2.2, and 1.6, respectively. Diuretic renography that was obstructive in all cases preoperatively was normal in four and delayed in one case, postoperatively.ConclusionR-RDBP prevented rotation/kinking of the ureter, enhanced precision of suturing, and maximized the diameter at the anastomosis, facilitating smooth urine flow.Level of EvidenceLEVEL IV.     

Utilization of respondent-driven sampling among a population of child workers in the diamond-mining sector of Sierra Leone

Abstract

This article describes the implementation of respondent driven sampling (RDS) in a study conducted in Kono District, Sierra Leone. RDS was used to identify children, under the age of 18 years old, working in the diamond sector of Sierra Leone. This includes children working directly as diamond miners as well as children working in the informal sector connected to the diamond field. The article seeks to postulate that RDS is a suitable method for a rapid approach to a population that is unidentified in size and demonstrate how RDS can reach a study population within a limited period.