Children with Steroid-resistant Nephrotic Syndrome:Long-term Outcomes of Sequential Steroid Therapy

Objective This study aimed to investigate the long-term outcomes in children with steroid-resistant nephrotic syndrome （SRNS）, who received methylprednisolone pulse therapy （MPT）-based sequential steroid therapy. In particular, we aimed to observe whether these patients had a high risk of adverse events. Methods We conducted a retrospective study over a 5-year period. The long-term outcomes for children with SRNS receiving sequential therapy were observed. Results Sixty-three children were diagnosed with SRNS and underwent MPT-based sequential steroid therapy. Thirty-five （55.6%） achieved complete or partial remission, 19 （30.2%） of whom were in remission even after treatment cessation at last review. The mean time to initial remission after MPT was 24.3±13.1 days. Forty-nine children （77.8%） experienced relapses, of whom 31 （49.2%） demonstrated a frequent relapsing course. Adverse effects relevant to MPT were generally mild and infrequent. Five patients （7.9%） complained of vomiting or nausea during MPT infusion; 25 （39.7%） experienced excessive weight gain and developed an obvious Cushingoid appearance; and 26 （41.3%） had poor growth associated with long-term steroid use. Twenty-eight patients （44.4%） failed to respond to MPT, of whom 21 （33.3%） achieved complete or partial remission with immunosuppressive agents. Conclusion MPT-based sequential steroid therapy appears to be a safe and effective method for inducing rapid remission in childhood SRNS. Further clinical studies are needed to comprehensively evaluate this therapy.

镰刀状红细胞贫血患儿的右心室异常改变:进展性肺循环血管阻力增高的临床证据

Objective:To assess the effects of sickle cell anemia (SCA)-on the right ventricle (RV). Study design:Echocardiograms of 32 children with SCA were compared with age-matched healthy controls. RV measurements included diastolic area index,fractional area change,free-wall mass index,ejection time corrected for heart rate (ETc),and tricuspid regurgitation(TR) gradient. Results:SCA subjects had elevated RV ETc(mean ±standard deviation,0.369 ±0.030 sec vs 0.351 ±0.022 sec; P < 0.01),diastolic area index (19.9 ±2.4 cm2/m2 vs13.2 ±2.1 cm2/m2; P < 0.01) and free-wall mass index (33.2 ±4.4 g/m2 vs 23.9 ±4.3 g/m2; P < 0.01),whereas RV fractional area change (37 ±8%vs 36 ±4%) was not different from controls. Although RV diastolic area index in SCA paralleled the normal range over time,RV free-wall mass index continued to gradually rise throughout childhood (r = 0.42; P < 0.05). TR gradients>2.5m/sec,consistent with pulmonary hypertension,were found in 5 (16%) of SCA subjects,all older than 9 years.Conclusions:RV preload and systolic function do not worsen during childhood in SCA; however,RV mass index and the prevalence of pulmonary hypertension increase consistent with rising pulmonary vascular resistance.

A novel in vitro angiogenesis model based on a microfluidic device

Angiogenesis is very important for many physiological and pathological processes. However, the molecular mechanisms of angiogenesis are unclear. To elucidate the molecular mechanisms of angiogenesis and to develop treatments for "angiogenesis-dependent" diseases, it is essential to establish a suitable in vitro angiogenesis model. In this study, we created a novel in vitro angiogenesis model based on a microfluidic device. Our model provides an in vivo-like microenvironment for endothelial cells (ECs) cultures and monitors the response of ECs to changes in their microenvironment in real time. To evaluate the potential of this microfluidic device for researching angiogenesis, the effects of pro-angiogenic factors on ECs proliferation, migration and tube-like structure formation were investigated. Our results showed the proliferation rate of ECs in 3D matrix was significantly promoted by the pro-angiogenic factors (with an increase of 59.12%). With the stimulation of pro-angiogenic factors gradients, ECs directionally migrated into the Matrigel from low concentrations to high concentrations and consequently formed multi-cell chords and tube-like structures. These results suggest that the device can provide a suitable platform for elucidating the mechanisms of angiogenesis and for screening pro-angiogenic or anti-angiogenic drugs for "angiogenesis-dependent" diseases.

Zinc homeostasis in the metabolic syndrome and diabetes

Zinc(Zn)is an essential mineral that is required for various cellular functions.Zn dyshomeostasis always is related to certain disorders such as metabolic syndrome,diabetes and diabetic complications.The associations of Zn with metabolic syndrome,diabetes and diabetic complications,thus,stem from the multiple roles of Zn:(1)a constructive component of many important enzymes or proteins,(2)a requirement for insulin storage and secretion,(3)a direct or indirect antioxidant action,and(4)an insulin-like action.However,whether there is a clear cause-and-effect relationship of Zn with metabolic syndrome,diabetes,or diabetic complications remains unclear.In fact,it is known that Zn deficiency is a common phenomenon in diabetic patients.Chronic low intake of Zn was associated with the increased risk of diabetes and diabetes also impairs Zn metabolism.Theoretically Zn supplementation should prevent the metabolic syndrome,diabetes,and diabetic complications;however,limited available data are not always supportive of the above notion.Therefore,this review has tried to summarize these pieces of available information,possible mechanisms by which Zn prevents the metabolic syndrome,diabetes,and diabetic complications.In the final part,what are the current issues for Zn supplementation were also discussed.

IL-6/gp130 signaling:a key unlocking regeneration

Liver is an organ with notable capacity of regeneration.Reprogramming of hepatocytes towards an immature state is one of the important mechanisms for hepatocyte replenishment.Inflammatory response mediated by IL-6 and its family cytokines has been widely reported closely related with tissue regeneration in myriads of organs.Recently Hui and colleagues reported that the dedifferentiation of hepatocytes depends upon IL-6 signaling from Kupffer cells and the reprogramming of gene expression under the inflammatory condition is different from the regulation of gene expression during embryo hepatocyte specification,highlighting a tight linkage between extracellular microenvironment and parenchymal cell plasticity during tissue regenerative repair.

基于微流控芯片构建一种新的体外血管生成模型

血管生成在许多生理和病理过程中发挥着重要作用,但血管生成的机理仍不清楚.因此,为探明血管生成机理及开发"血管生成相关"疾病的治疗方法,在体外构建一个合适的血管生成模型是十分必要的.基于微流控系统构建了一种新型体外血管生成模型,该系统不仅能为内皮细胞生长提供一种近似于在体的微环境,并能实时监测内皮细胞对其微环境所发生变化的响应.为评价该系统用于血管生成模型建立的可行性和优越性,考察了促血管生长因子对内皮细胞增殖、迁移和管样结构形成能力的影响.研究结果表明,在促血管生长因子的诱导作用下,内皮细胞在三维基质材料中的增殖能力大大提高(提高了59.12%);在促血管生长因子浓度梯度的诱导作用下,内皮细胞定向从低浓度往高浓度侵入基质胶且形成管腔样结构.以上结果表明,该系统不仅能为血管生成机理的阐明提供一个良好的研究平台,还能为促血管生成药物或者抗血管生成药物的筛选提供一个合适的筛选平台.