Management of paroxysmal ectopic atrial tachycardia with long sinus pauses in a teenager

Sinus pauses in the setting of supraventricular tachycardia is rare in children. We describe an asymptomatic teen with irregular heart rate detected during an incidental exam who was found to have short runs of a slow ectopic atrial tachycardia on electrocardiogram and prolonged sinus pauses on routine ambulatory ECG. Successful catheter ablation of the ectopic atrial tachycardia led to resolution of the sinus pauses.     

Growth‐associated protein 43 promotes thyroid cancer cell lines progression via epithelial‐mesenchymal transition

Thyroid cancer is maintaining at a high incidence level and its carcinogenesis is mainly affected by a complex gene interaction. By analysis of the next‐generation resequencing of paired papillary thyroid cancer (PTC) and adjacent thyroid tissues, we found that Growth Associated Protein 43 (GAP43), a phosphoprotein activated by protein kinase C, might be novel markers associated with PTC. However, its function in thyroid carcinoma has been poorly understood. We discovered that GAP43 was significantly overexpressed in thyroid carcinoma and these results were consistent with that in The Cancer Genome Atlas (TCGA) cohort. In addition, some clinicopathological features of GAP43 in TCGA database showed that up‐regulated GAP43 is significantly connected to lymph node metastasis (P < 0.001) and tumour size (P = 0.038). In vitro experiments, loss of function experiments was performed to investigate GAP43 in PTC cell lines (TPC‐1 and BCPAP). The results proved that GAP43 knockdown in PTC cell significantly decreased the function of cell proliferation, colony formation, migration, and invasion and induced cell apoptosis. Furthermore, we also indicated that GAP43 could modulate the expression of epithelial‐mesenchymal transition‐related proteins, which could influence invasion and migration. Put those results together, GAP43 is a gene which was associated with PTC and might be a potential therapeutic target.     

Revealing the Short‐Circuiting Mechanism of Garnet‐Based Solid‐State Electrolyte

Garnet‐type solid‐state electrolytes (SSEs) have been widely studied as a promising candidate for Li metal batteries. Despite the common belief that inorganic SSEs can prevent dendrite propagation, garnet SSEs suffer from relatively low critical current density (CCD) at which the SSEs are abruptly short‐circuited by Li dendrites. In this study, the short‐circuiting mechanism of garnet Li₇La_2.75Ca_0.25Zr_1.75Nb_0.25O₁₂ (LLCZN) is investigated. It is found that instead of propagating uniaxially from one electrode to other in a dendritic form, metallic lithium is formed within the SSE. This can be attributed to the fact that electrons combine with Li ions at the grain boundary, which exhibits relatively high electronic conductivity, and then reduce Li⁺ to Li⁰ to cause short circuits. In order to reduce the electronic conductivity at the grain boundary, a thin layer of LiAlO₂ is coated on the grain surface of LLCZN, which results in an improved CCD value. It is also found that under higher external voltages, the electronic conductivity of SSE becomes more significant, which is believed to be the origin of CCD. These findings not only shed light on the short‐circuiting mechanism of garnet‐type SSEs but also offer a novel perspective and useful guidance on their designs and modifications.     

桥本氏病合并甲状腺乳头状癌患者血清甲状腺相关激素水平的变化及意义

目的:探究桥本氏病(HT)合并甲状腺乳头状癌(PTC)患者血清甲状腺相关激素水平的变化及意义。方法:对我院148例HT患者的临床资料进行回顾性分析,根据其是否合并PTC分为HT合并PTC组(n=68)和单纯HT组(n=80)。比较两组患者性别、年龄及血清促甲状腺激素(TSH)、甲状腺功能指标[游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)]、抗甲状腺抗体[甲状腺球蛋白抗体(TGAb)、甲状腺过氧物酶抗体(TPOAb)]水平等临床资料差异,分析血清TSH水平变化及意义。结果:HT合并PTC组患者男性比例、年龄、病程及血清TSH水平均大于单纯HT组,血清TGAb、TPOAb水平则均小于单纯HT组(P0.05);血清FT3、FT4水平比较差异无统计学意义(P0.05)。HT合并PTC患者组血清TSH4.2 m IU/L患者占比高于血清TSH正常组(P0.05)。血清TSH4.2 m IU/L患者中HT合并PTC患者的占比大于血清TSH水平正常的患者(P0.05)。HT合并PTC患者中,血清TSH水平4.2 m IU/L患者中央区淋巴结转移发生率高于血清TSH水平正常患者(P0.05);血清TSH4.2 m IU/L与血清TSH正常患者多灶癌发生率比较差异无统计学意义(P0.05)。结论:HT患者血清TSH水平升高可能促进其甲状腺组织癌变,HT合并PTC患者血清TSH水平升高可能促进其中央区淋巴结转移。     

Contemporary trends of pelvic lymph node dissection at radical cystectomy for urothelial carcinoma of urinary bladder and associated cancer specific mortality and complications: comparison between octogenarian versus younger patients

BackgroundWe analysed contemporary pelvic lymph node dissection (PLND) trend during radical cystectomy (RC) for urothelial carcinoma of urinary bladder (UCUB), as well as PLND association with cancer specific mortality (CSM) and complications after stratification according to octogenarian vs. younger age.Materials and methodsWithin the SEER and NIS databases, respectively 10,427 (T2 and T3 stages) and 19,203 (all T-stages) RC patients (2004–2015) for UCUB were identified. Univariable and multivariable analyses focused on PLND rates, CSM after inverse probability of treatment weighting (IPTW) adjustment, complication rates, length of stay (LOS) and total hospital charge (THC).ResultsWithin the SEER database, RC and PLND was performed in 9,406 patients (87.4%), 981 (10.4%) octogenarians and 8,227 younger patients (at, respectively, 83 and 89% PLND). PLND rates increased over time in both patients groups (p < 0.05). PLND was independently associated with lower CSM in both age groups (octogenarians: hazard ratio [HR] 0.51, p < 0.001; younger patients: HR 0.56, p < 0.001). Within the NIS database, PLND was marginally higher associated with overall complications in octogenarians than in younger patients (odd ratio [OR]: 1.32 vs. 1.23, both p < 0.001), with longer LOS (OR: 1.20 vs. 1.08, both p < 0.001), higher THC (relative increase: 6933 vs. 4484, both p < 0.001), but not with higher in-hospital mortality.ConclusionsPLND is associated with lower CSM, but its rate lags in octogenarian vs. younger patients. In both age groups, PLND leads to marginally higher complications, longer LOS and higher THC, but not to higher in-hospital mortality.     

Charge variants characterization and release assay development for co-formulated antibodies as a combination therapy

Combination therapy is a fast-growing strategy to maximize therapeutic benefits to patients. Co-formulation of two or more therapeutic proteins has advantages over the administration of multiple medications, including reduced medication errors and convenience for patients. Characterization of co-formulated biologics can be challenging due to the high degree of similarity in the physicochemical properties of co-formulated proteins, especially at different concentrations of individual components. We present the results of a deamidation study of one monoclonal antibody component (mAb-B) in co-formulated combination antibodies (referred to as COMBO) that contain various ratios of mAb-A and mAb-B. A single deamidation site in the complementarity-determining region of mAb-B was identified as a critical quality attribute (CQA) due to its impact on biological activity. A conventional charge-based method of monitoring mAb-B deamidation presented specificity and robustness challenges, especially when mAb-B was a minor component in the COMBO, making it unsuitable for lot release and stability testing. We developed and qualified a new, quality-control-friendly, single quadrupole Dalton mass detector (QDa)–based method to monitor site-specific deamidation. Our approach can be also used as a multi-attribute method for monitoring other quality attributes in COMBO. This analytical paradigm is applicable to the identification of CQAs in combination therapeutic molecules, and to the subsequent development of a highly specific, highly sensitive, and sufficiently robust method for routine monitoring CQAs for lot release test and during stability studies.     

Contrasting responses of steppe Stipa ssp. to warming and precipitation variability

Climate change, characterized by warming and precipitation variability, restricted the growth of plants in arid and semiarid areas, and various functional traits are impacted differently. Comparing responses of functional traits to warming and precipitation variability and determining critical water threshold of dominate steppe grasses from Inner Mongolia facilitates the identification and monitoring of water stress effects. A combination of warming (ambient temperature, +1.5°C and +2.0°C) and varying precipitation (?30%, ?15%, ambient, +15%, and +30%) manipulation experiments were performed on four Stipa species (S. baicalensis, S. bungeana, S. grandis, and S. breviflora) from Inner Mongolia steppe. The results showed that the functional traits of the four grasses differed in their responses to precipitation, but they shared common sensitive traits (root/shoot ratio, R/S, and specific leaf area; SLA) under ambient temperature condition. Warming increased the response of the four grasses to changing precipitation, and these differences in functional traits resulted in changes to their total biomass, with leaf area, SLA, and R/S making the largest contributions. Critical water thresholds of the four grasses were identified, and warming led to their higher optimum precipitation requirements. The four steppe grasses were able to adapt better to mild drought (summer precipitation decreased by 12%–28%) when warming 1.5°C rather than 2.0°C. These results indicated that if the Paris Agreement to limit global warming to 1.5°C will be accomplished, this will increase the probability for sustained viability of the Stipa steppes in the next 50–100 years.     

食物网关键种的判定及其对稳健性的影响

食物网关键种的定量判定方法不仅有助于揭示食物网中的物种关系, 而且有利于对关键物种进行优先保护。本研究以包含49个物种的河流生态系统食物网为对象, 计算网络中表征度性质的指标(点度中心度、中介中心度、紧密中心度), 并根据指标对物种进行聚类, 分析不同类物种影响食物网连接稳健性程度的差异, 探讨不同节点去除方式下节点数量对食物网连接稳健性的影响。结果发现, 聚类将食物网中物种分成三类。I类物种具有相对较高的点度中心度、中介中心度、紧密中心度; II类物种具有相对更低的点度中心度、中介中心度、紧密中心度; III类物种的点度中心度、中介中心度、紧密中心度介于前两者之间。I类物种处于更为重要的地位, 可认为是关键种。本研究为如何判定关键种贡献了新的思路。另外, 升序去除方式下, 连接稳健性呈降低趋势; 降序去除与随机去除方式下, 连接稳健性在持续降低后又有小幅度增加, 这表明去除方式对食物网连接稳健性有影响。三种去除方式下, 食物网连接稳健性发生显著变化对应着几乎相同的去除节点数量, 表明关键种在维持食物网稳健性方面发挥着重要作用。