Topical tacrolimus therapy in the management of lower extremity ulcers due to prolidase deficiency

Prolidase deficiency is a rare autosomal recessive disorder characterized by cutaneous ulcers, facial dysmorphism, recurrent infections, and intellectual disability. We report a unique case of a 6‐year‐old boy with prolidase deficiency and Crohn's disease who presented with lower extremity ulcers. Cutaneous ulcers due to prolidase deficiency are historically resistant to treatment, and we report success with the novel use of topical tacrolimus.     

Glutamate hypothesis in schizophrenia

Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d ‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.     

Gd-EOB-DTPA增强MRI评估功能性肝体积与肝功能Child-Pugh分级的相关性

目的：对比解剖性肝脏体积（ALV）和功能性肝脏体积（FLV）与肝功能Child-Pugh分级的相关性。方法：选择温州医科大学附属第二医院育英儿童医院2014年1月至2019年4月同时行增强CT和Gd-EOB-DTPA增强MRI扫描的肝硬化患者25例。对所有患者进行肝功能Child-Pugh评分，检测所有入组患者每个肝段的Gd-EOB-DTPA增强MRI平扫期和肝胆特异期的信号对比增强率（CER），以CT扫描的数据为基础利用MI-3DVS计算每个肝段的ALV和全肝的FLV。分析ALV和FLV与肝功能Child-Pugh分级的相关性。结果：肝功能Child-Pugh分级与ALV呈负相关（r=-0.792，P＜0.001），曲线拟合的决定系数（R2）=0.63；肝功能Child-Pugh分级与FLV亦呈负相关（r=-0.911，P＜0.001），曲线拟合的R2=0.80。FLV与肝功能Child-Pugh分级有更显著的负相关性。结论：结合Gd-EOB-DTPA增强MRI平扫期和肝胆特异期的信号CER和ALV计算所得的FLV较ALV能更好地反映肝脏的功能状态。     

基于虚实辨证的补泻平衡手法治疗膝骨关节炎临床研究

目的观察补泻平衡手法治疗膝骨关节炎的疗效及对患者临床症状、体征的影响。方法采用随机数字表法将220例单膝骨关节炎患者分为治疗组和对照组各110例。治疗组予补泻平衡手法,对照组予常规推拿手法,均每次20 min,每日2次,1周为1个疗程,连续治疗2个疗程。观察2组治疗前后及治疗后3、6个月全身临床症状、体征及中医证候评分,比较2组临床疗效及不良反应。结果与本组治疗前比较,2组治疗后全身临床症状、体征评分明显降低(P<0.05),治疗组中医证候评分明显降低(P<0.05);2组治疗后比较,治疗组全身临床症状、体征改善程度优于对照组(P<0.05);与本组治疗后比较,2组治疗后3、6个月全身临床症状、体征评分升高。治疗组治疗后3、6个月中医证候评分升高,仍低于治疗前(P<0.05)。治疗组总有效率为91.8%(101/110),对照组为78.2%(86/110),2组比较差异有统计学意义(P<0.05)。2组均未见不良反应。结论补泻平衡手法与常规推拿手法治疗膝骨关节炎均有效,前者疗效优于后者,且中远期疗效更佳。     

2‐deoxy D‐glucose treatment does not elicit a hair growth response in alopecia areata

2‐deoxy D‐glucose (2DG) was tested for efficacy in treating alopecia areata using the C3H/HeJ skin graft model. 2DG has proven to be efficacious in treatment of various mouse models of autoimmunity with minimal serious side effects noted. This agent has been shown to normalize abnormally activated T‐cell populations while also preventing cell surface expression of NKG2D; key factors defining alopecia areata disease progression. Daily oral ingestion of 2DG via drinking water to mice with patchy or diffuse alopecia areata for 16 weeks failed to prevent expansion of alopecia or cause regrowth of hair in treated mice. Histologically, there were no differences between treated and control groups. These results indicate that, while 2DG is effective for some autoimmune diseases, it was not efficacious for the cell‐mediated autoimmune mouse disease, alopecia areata.     

Cyclin D1启动子在养精胶囊促进小鼠精原干细胞增殖中的作用※

目的 研究养精胶囊促进小鼠精原干细胞（SSCs）增殖的分子机制。方法 将不同浓度的养精胶囊提取物加入SSCs中培养48 h，CCK-8检测细胞的增殖活性，流式细胞仪检测细胞周期，荧光素酶报告基因检测Cyclin D1启动子的活性，qRT-PCR以及免疫荧光检测Cyclin D1的表达。之后进行阻断实验，在加入养精胶囊前预先加入siRNA-Cyclin D1，同样的方法检测细胞的增殖活性、细胞周期、Cyclin D1启动子的活性以及Cyclin D1的表达情况。结果 低、中、高浓度的养精胶囊可以促进SSCs的增殖，提高S期细胞的比例，增强Cyclin D1启动子的活性，促进Cyclin D1的表达。阻断Cyclin D1后，SSCs的增殖活性降低，S期细胞比例减少，Cyclin D1启动子的活性降低，Cyclin D1的表达减少。结论 养精胶囊通过增强Cyclin D1启动子的活性提高Cyclin D1的转录和翻译水平，进而促进SSCs增殖。     

Bishonokiol A Induces Multiple Cell Death in Human Breast Cancer MCF-7 Cells

Objective: A dimeric neolignan, bishonokiol A (BHNKA) isolated from Magnolia grandiflora, significantly inhibits the proliferation of human breast cancer cells. However, the exact mechanism of BHNKA induced breast cancer cell death is unknown. In this study, we investigated the pharmacological mechanism underlying BHNKA induced MCF-7 cell death. Methods: Cell viability measurement was performed by the MTT assay. Flow cytometry with PI staining, DAPI staining, and electron microscopy were used to analyze cellular death modes. In addition, western blotting, siRNA transfection, ATP assay, and fluorescence microscopy were used to determine the mechanism of BHNKA induced MCF-7 cell death. Results: BHNKA induced cell death by apoptosis, necroptosis and autophagy at the same concentration and time in MCF-7 cells, and electron microscopy confirmed these results. The mechanism of BHNKA triggered apoptosis and autophagy in MCF-7 cells was primarily due to an increase in the Bax/Bcl-2 ratio and simultaneous up-regulation of LC3-II protein expression, respectively. BHNKA induced necroptosis by activation of the RIP1-RIP3-MLKL necroptosis cascade, up-regulation of cyclophilin D (CypD) protein expression to stimulate ROS generation. We further demonstrated that siRNA-mediated down-regulation of CypD protected against BHNKA induced cell death. Conclusions: These results suggest that BHNKA may be a potential lead compound for development as an anti-breast cancer agent for induction of multiple cell death pathways.     

Using structural equation modelling to understand the contributors to anaemia among young Burkinabe children

Anaemia is a persistent problem among young Burkinabe children, yet population‐specific information on its determinants is scant. We used baseline data from an evaluation of Helen Keller International's Enhanced Homestead Food Production Program (n=1210 children) to quantify household‐, mother‐, and child‐level factors associated with anaemia in Burkinabe children aged 6‐12 months. We used structural equation modelling to assess a theoretical model, which tested four categories of factors: (a) household food security and dietary diversity, (b) household sanitation and hygiene (latrine and poultry access and bednet ownership), (c) maternal factors (anaemia, stress, cleanliness, and health, hygiene and feeding knowledge and practices), and (d) child nutrition and health (iron deficiency (ID), retinol binding protein (RBP), malaria, and inflammation). The model also included household socio‐economic status, size, and polygamy; maternal age and education; and child age and sex. Results showed that ID, malaria, and inflammation were the primary direct determinants of anaemia, contributing 15%, 10%, and 10%, respectively. Maternal knowledge directly explained improved child feeding practices and household bednet ownership. Household dietary diversity directly explained 18% of child feeding practices. Additionally, RBP, child age and sex, and maternal anaemia directly predicted child haemoglobin. Our findings suggest that program effectiveness could be increased by addressing the multiple, context‐specific contributors of child anaemia. For young Burkinabe children, anaemia control programs that include interventions to reduce ID, malaria, and inflammation should be tested. Other potential intervention entry points suggested by our model include improving maternal knowledge of optimal health, hygiene, and nutrition practices and household dietary diversity.