Quantification of myocardial fibrosis using noninvasive T2-mapping magnetic resonance imaging: Preclinical models of aging and pressure overload

Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T₂-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T₂-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T₂-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T₂ relaxation times (25.3 ± 0.6 in aged vs. 29.9 ± 0.7 ms in young mice, p = 0.002; and 24.3 ± 1.7 in PO vs. 28.7 ± 0.7 ms in shams, p = 0.05). However, no significant difference in T₂ was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T₂ relaxation time was derived (R² = 0.98): T₂ (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T₂-map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T₂-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis.     

Effect of compression stockings on overnight rostral fluid shift and obstructive sleep apnea: A meta-analysis

ObjectiveThe overnight rostral fluid shift from the lower limbs is one of the causes of obstructive sleep apnea (OSA). Compression stockings (CS) prevent lower limb fluid retention and have been reported to decrease nighttime fluid shift. The aim of this study is to evaluate the effect of CS on fluid shift and the severity of OSA.MethodsA systematic literature search was performed in the PubMed, EMBASE and Cochrane Library databases. The data were analyzed using Comprehensive Meta-Analysis software (Version 3; Biostat, Englewood, NJ). Studies evaluating the effect of CS on the overnight fluid shift and OSA severity were included in the analysis.ResultsA total of 4 studies were included in this meta-analysis. The pooled analysis showed that the apnea-hypopnea index (AHI) of the overall study group was significantly lower after using CS (SMD, -1.08; 95% CI, -1.49 to -0.67). Decreases in the AHI were also observed in the normal fluid status (SMD, -1.05; 95% CI, -1.73 to -0.37) and fluid overload status (SMD, -1.17; 95% CI, -1.76 to -0.58) populations. The overall study group had significant decreases in overnight changes in neck circumference (SMD, -1.05; 95% CI, -2.06 to -0.03) and leg fluid volume (SMD, -1.14; 95% CI, -1.88 to -0.41) after using CS. However, no significant differences in overnight changes in neck circumference and leg fluid volume were observed in normal fluid status patients.ConclusionCS may help decrease overnight fluid shift and could be a treatment option for OSA.     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Endothelial C3a receptor mediates vascular inflammation and blood-brain barrier permeability during aging

Dysfunction of immune and vascular systems has been implicated in aging and Alzheimer disease; however, their interrelatedness remains poorly understood. The complement pathway is a well-established regulator of innate immunity in the brain. Here, we report robust age-dependent increases in vascular inflammation, peripheral lymphocyte infiltration, and blood-brain barrier (BBB) permeability. These phenotypes were subdued by global inactivation and by endothelial cell–specific ablation of C3ar1. Using an in vitro model of the BBB, we identified intracellular Ca²⁺ as a downstream effector of C3a/C3aR signaling and a functional mediator of vascular endothelial cadherin junction and barrier integrity. Endothelial C3ar1 inactivation also dampened microglia reactivity and improved hippocampal and cortical volumes in the aging brain, demonstrating a crosstalk between brain vasculature dysfunction and immune cell activation and neurodegeneration. Further, prominent C3aR-dependent vascular inflammation was also observed in a tau-transgenic mouse model. Our studies suggest that heightened C3a/C3aR signaling through endothelial cells promotes vascular inflammation and BBB dysfunction and contributes to overall neuroinflammation in aging and neurodegenerative disease.     

Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73–0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.     

Aging attenuates the ovarian circadian rhythm

ObjectiveTo study the effect of aging on ovarian circadian rhythm.DesignHuman and animal study.SettingUniversity hospital and research laboratory.Patients/animalsHuman granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice.Intervention(s)None.Main outcome measure(s)Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice.Result(s)All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice.Conclusion(s)Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01943-y) contains supplementary material, which is available to authorized users.     

妇产科专科特色处方前置审核系统的建设与应用

目的 建立适应妇产科专科特色的处方前置审核系统。方法 引进处方前置审核软件,经后台运行收集基于商业知识库规则的审方数据,建立妇产科用药规则维护分级依据,进行规则优化并形成妇产科合理用药知识库,疏通处方前置审核流程并加以实施。结果 通过抽样数据对比发现,药师审方上线后,系统预审问题数及比例、医师提交问题数及比例明显下降、医师主动返回修改问题数及比例相应上升,人员疏忽所致的严重用药错误可被拦截,药师干预处方/医嘱成功率达93.81%。结论 建立妇产科专科特色处方前置审核系统,能有效保证审方准确性,能减少临床医师和审方药师不必要的工作量,有利于处方前置审核工作的推进,进一步保障患者用药的安全性和合理性。     

针刺治疗慢性疼痛的功能磁共振研究述评＊

目的基于针刺治疗慢性疼痛的功能磁共振(Functional magnetic resonance imaging,fMRI)文献进行述评,为针刺治疗慢性疼痛的机制研究提供思路和借鉴。方法对近10年针刺治疗慢性疼痛的fMRI研究进行回顾,依据病种选择、样本量计算、试验设计、研究结果四方面内容进行述评,分析并总结当前研究现状。结果偏头痛、膝骨关节炎和下腰痛是目前研究中涉及频次最高的3个病种。受试者的疾病亚型、年龄段、利手习惯及fMRI禁忌症在研究中基本都保证了一致性和规范性。但多数研究仍存在样本量计算方式不明确的问题。对照组设置主要包括标准对照、无效对照和安慰对照。针刺效应因素在各研究间存在较大差异。研究中结局指标包括疾病特异性量表、疼痛评分及心理、精神状态的评估。fMRI设计以静息态和单一任务态设计为主,多任务fMRI研究相对较少。研究证实针刺可调节疼痛处理网络的功能连接,有效建立心理物理疼痛稳态。结论运用fMRI探讨针刺治疗慢性疼痛作用机制的研究成果丰硕,未来可通过扩大病种的选择,完善质量控制,关注针刺效应影响因素,丰富数据处理手段,借鉴多学科任务设计方式等方式,促进针刺疗慢性疼痛机制研究的进一步发展。