Weakly Supervised Breast Lesion Detection in Dynamic Contrast-Enhanced MRI

Journal of Digital Imaging - Currently, obtaining accurate medical annotations requires high labor and time effort, which largely limits the development of supervised learning-based tumor detection...     

Single-cell profiling of ineffective erythropoiesis in a mouse model of β-thalassaemia intermedia

Beta-thalassaemia is an inherited haemoglobin disorder characterised by ineffective erythropoiesis (IE). The detailed pathogenesis of IE remains unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to examine IE in Th3/+ β-thalassaemic mice. The results showed that the erythroid group was remarkably expanded, and genes involved in biological processes such as iron metabolism, haeme synthesis, protein folding, and response to heat were significantly upregulated from erythroid progenitors to reticulocytes in β-thalassaemic mice. In particular, we identified a unique cell population close to reticulocytes, named ThReticulocytes, characterised by a high level of heat shock protein 70 (Hsp70) expression and dysregulation of iron metabolism and haeme synthesis signalling. Treatment of β-thalassaemic mice with the haeme oxygenase inhibitor tin-mesoporphyrin effectively improved the iron disorder and IE, and the ThReticulocyte population and Hsp70 expression were significantly suppressed. This study revealed in detail the progression of IE at the single-cell level and possibly provided clues to find therapeutic targets in thalassaemia.     

增强型体外反搏对69例冠心病患者的血清炎性因子的影响探讨

目的 分析增强型体外反搏冠心病患者的血清炎性因子的影响,探讨冠心病治疗的新靶点。方法 将69例冠心病采用数字表法将患者随机分为观察组和对照组,观察组35例,对照组34例,对照组患者接受常规药物治疗;观察组在对照组治疗基础上接受反搏治疗,两组治疗时间均为6周,比较两组患者疗效;采集患者治疗前后外周血,采用ELISA法对患者血清中炎性因子CRP、hsCRP、TNFα以及IL-6水平进行检测。结果 观察组患者治疗总有效显著高于对照组 (P<0.05),对照组患者治疗前后血清炎性因子水平变化差异无统计学意义(P>0.05),观察组患者治疗后血清炎性因子水平显著低于治疗前(P<0.05)。结论 体外反搏治疗冠心病患者临床疗效显著,治疗后患者血清炎性因子降低显著,值得临床进一步推广应用。     

金纳米颗粒在肿瘤放射增敏中的研究进展

金纳米颗粒(AuNPs)以其独特的理化性质及良好的生物相容性在生物医药方面广泛应用,其中金纳米颗粒肿瘤放射增敏作用是目前研究热点。大量体、内外研究证实AuNPs具有放射增敏效果,但AuNPs放射增敏相关机制仍有待进一步研究,目前普遍认为增敏主要由AuNPs促进肿瘤细胞由放疗不敏感期(G₀+G₁期)转为放疗敏感期(G₂+M期)所致。影响AuNPs放射增敏效果的因素有很多,其中包括AuNPs粒径大小及其表面修饰和微观分布、放射线能量及剂量大小和肿瘤细胞类别等。此外值得注意的是,AuNPs用于肿瘤放射增敏的同时也要关注它的安全性。目前已开展了AuNPs有关临床试验,尚需继续进行AuNPs放射增敏的研究才能实现真正的临床转化。     

Diffusion MRI detects early brain microstructure abnormalities in 2‐month‐old 3×Tg‐AD mice

The 3×Tg‐AD mouse is one of the most studied animal models of Alzheimer's disease (AD), and develops both amyloid beta deposits and neurofibrillary tangles in a temporal and spatial pattern that is similar to human AD pathology. Additionally, abnormal myelination patterns with changes in oligodendrocyte and myelin marker expression are reported to be an early pathological feature in this model. Only few diffusion MRI (dMRI) studies have investigated white matter abnormalities in 3×Tg‐AD mice, with inconsistent results. Thus, the goal of this study was to investigate the sensitivity of dMRI to capture brain microstructural alterations in 2‐month‐old 3×Tg‐AD mice. In the fimbria, the fractional anisotropy (FA), kurtosis fractional anisotropy (KFA), and radial kurtosis (K_┴) were found to be significantly lower in 3×Tg‐AD mice than in controls, while the mean diffusivity (MD) and radial diffusivity (D_┴) were found to be elevated. In the fornix, K_┴ was lower for 3×Tg‐AD mice; in the dorsal hippocampus MD and D_┴ were elevated, as were FA, MD, and D_┴ in the ventral hippocampus. These results indicate, for the first time, dMRI changes associated with myelin abnormalities in young 3×Tg‐AD mice, before they develop AD pathology. Morphological quantification of myelin basic protein immunoreactivity in the fimbria was significantly lower in the 3×Tg‐AD mice compared with the age‐matched controls. Our results demonstrate that dMRI is able to detect widespread, significant early brain morphological abnormalities in 2‐month‐old 3×Tg‐AD mice.     

The effect of acetylation on the protein stability of BmApoLp‐III in the silkworm,Bombyx mori

Acetylation is an important, reversible posttranslational modification to a protein. In a previous study, we found that there were a large number of acetylated sites in various nutrient storage proteins of the silkworm haemolymph. In this study, we confirmed that acetylation can affect the stability of nutrient storage protein Bombyx mori apolipophorin‐III (BmApoLp‐III). First, the expression of BmApoLp‐III could be upregulated when BmN cells were treated with the deacetylase inhibitor panobinostat (LBH589); similarly, the expression was downregulated when the cells were treated with the acetylase inhibitor C646. Furthermore, the increase in acetylation by LBH589 could inhibit the degradation and improve the accumulation of BmApoLp‐III in BmN cells treated with cycloheximide and MG132 respectively. Moreover, we found that an increase in acetylation could decrease the ubiquitination of BmApoLp‐III and vice versa; therefore, we predicted that acetylation could improve the stability of BmApoLp‐III by competing for ubiquitination and inhibiting the protein degradation pathway mediated by ubiquitin. Additionally, BmApoLp‐III had an antiapoptosis function that increased after LBH589 treatment, which might have been due to the improved protein stability after acetylation. These results have laid the foundation for further study on the mechanism of acetylation in regulating the storage and utilization of silkworm nutrition.     

Aldehyde dehydrogenase 2 deficiency significantly exacerbates tert-butyl alcohol-induced toxicity in mice

Owing to the use of ethyl tert-butyl ether (ETBE) as a fuel additive, the possible adverse effects of ETBE exposure have become a public concern. Our previous study showed that ETBE-induced toxicity in aldehyde dehydrogenase 2 (Aldh2) gene knockout (KO) mice was caused by its primary metabolite acetaldehyde, which was toxic. However, it is unclear whether tert-butyl alcohol (TBA), another main metabolite of ETBE, plays a role in ETBE-induced toxicity. To investigate this relationship, we analyzed the changes of TBA concentrations in tissues after ETBE exposure, and then evaluated the toxicity after direct TBA treatment in both KO and wild-type (WT) mice. An exposure to 500 ppm ETBE via inhalation resulted in the formation of its three metabolites, TBA, 2-methyl-1,2-propanediol and ethanol, whose concentrations in the liver, brain, fat and testis of male KO mice were significantly higher than the corresponding concentrations observed in male WT mice. Direct treatment to TBA (20 mg/mL of drinking water) caused significant changes in relative organ weights and histopathology, and increased levels of genetic damages in both types of mice. These toxic effects were also seen in KO mice exposed to a lower concentration of TBA (5 mg/mL), which was associated with increased oxidative stress in serum (reduced glutathione and reduced glutathione/oxidized glutathione ratio decreased). Our findings indicate that ALDH2 is involved in the metabolism of ETBE and TBA, and ALDH2 deficiency could greatly increase the sensitivity to TBA-induced toxicity.     

Clinical characteristics and prognosis of postpartum acute kidney injury

ObjectiveTo investigate the clinical characteristics and prognoses of patients with postpartum acute kidney injury (PPAKI).MethodsWe retrospectively reviewed the clinical presentations, laboratory examinations, treatments, and outcomes of patients with PPAKI admitted to our hospital from January 2013 to December 2017. We then analyzed the clinical characteristics and prognoses of the mothers and their infants.ResultsOf 37 patients diagnosed with PPAKI, 26 (70.3%) received treatment in the intensive care unit, mainly for hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome (28/37, 75.7%), pre-eclampsia (26/37, 70.3%), and postpartum hemorrhage (22/37, 59.5%). Twenty patients required renal replacement treatment (RRT), but renal recovery times were similar in the RRT and non-RRT groups. Renal function recovered completely in 30 patients (81.1%) and partially in one patient (2.7%), and was not re-examined in two patients (5.4%). Three patients (8.1%) were lost to follow-up. Only one patient (2.7%) remained dialysis-dependent, and no maternal deaths occurred. The preterm birth, low birth weight, and infant survival rates were 70.7% (29/41), 68.3% (28/41), and 78.0% (32/41), respectively.ConclusionRRT does not reduce renal recovery time compared with non-RRT. Overall, the prognoses of both mothers and their fetuses are good following treatment for PPAKI.