尼索地平对单硝酸异山梨酯在小鼠体内组织分布的影响

目的考察尼索地平对单硝酸异山梨酯在小鼠体内组织分布的影响。方法 30只健康昆明种小鼠,♂,随机分成2组,分别为单独给药组和联合给药组,HPLC测定组织中单硝酸异山梨酯的浓度。结果小鼠组织中单硝酸异山梨酯浓度在给药后0.083 h为小肠>胃>心>肝>肾,给药后0.5 h为胃>小肠>肾>心>肝。胃中最大浓度出现时间因给药方案不同而异:单独给药组在给药后0.5 h单硝酸异山梨酯浓度最大,联合给药组在给药后0.083 h浓度最大。胃中单硝酸异山梨酯最大浓度,2组具有显著性差异(P<0.05)。结论尼索地平对单硝酸异山梨酯在小鼠组织中的分布具有一定影响。     

A 65-year-old Woman With Persistent Dyspnea,Arthritis, and Raynaud's Phenomenon

Antisynthetase syndrome (AS) is a rare disease that affects patients with inflammatory myopathies such as polymyositis (PM) and dermatomyositis (DM). In patients with AS, up to 95% of patients develop antisynthetase syndrome-associated interstitial lung disease (AS-ILD). Although AS-ILD commonly occurs in patients with a well-established diagnosis of AS, it can be the first or only manifestation of an occult AS. The frequency of interstitial lung disease (ILD), myopathy, and skin involvement are often dependent on the type of myositis-specific antibodies present. AS-ILD patients who are positive for both anti-Jo-1 and anti-SSA/RO-52 autoantibodies often present with a severe degree of lung restriction on pulmonary function tests and radiologic imaging with an inadequate response toward immunosuppressive therapies. We describe a 65-year-old woman who presents with chronic dyspnea. She was initially diagnosed with corticosteroid-resistant cryptogenic organizing pneumonia based on the radiological findings on her CT chest. Her symptoms did not improve, and she suffered from intolerable corticosteroid-related side effects. Reviews of systems were positive for arthritis and Raynaud's phenomenon. She was found to have elevated inflammatory markers and autoantibodies such as anti-Jo-1, anti-RO-52, and anti-SSA. A diagnosis of AS-ILD resistant to corticosteroid therapy was made. Her lung function improved with combination therapy of mycophenolate and rituximab. Our case highlights that a detailed history and physical exam, compatible radiologic imaging, and autoantibodies are essential for the diagnosis of AS-ILD.     

Two cases of rt-PA with dual antiplatelet therapies with capsular warning syndrome

Rationale:Capsular warning syndrome (CWS) is a term to describe stereotyped lacunar transient ischemic attacks (TIAs). Patients with CWS are at high risk of developing completed stroke. However, the exact pathophysiology of CWS is still unclear, and there is no conclusive clinical strategy for CWS patients.Patient symptoms:Two cases of middle-aged men with hypertension, hyperlipidemia, and diabetes mellitus presented with fluctuating right-sided weakness, numbness, and dysarthria.Diagnoses:These two patients were diagnosed with CWS.Interventions:Recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis (0.9 mg/kg) was administered first and treated with aspirin (100 mg) and clopidogrel (75 mg) after 24 h of rt-PA for 21 days following by aspirin (100 mg) alone.Outcomes:Both cases got favorable clinical outcomes of somatic symptoms. In addition, diffusion-weighted imaging (DWI or DW-MRI) showed that ischemic injury disappeared in case 1 while maintained within a reasonable range in case 2.Lessons:Early recognition and rt-PA/dual antiplatelet treatment may be an effective strategy for patients with CWS.     

静脉给予两次低剂量重组人脑利钠肽治疗顽固性心衰的疗效及安全性

目的:观察冻干重组人脑利钠肽(新活素,recombinant human brain natriuretic peptide,rhBNP)治疗顽固性心衰(refractory heart failure,RHF)的疗效与安全性.方法:2013年2月至2014年5月第二军医大学长海医院心血管内科收治的RHF病人78例,随机分为对照组和rhBNP组,每组39例.在常规抗心衰治疗的基础上,rhBNP组给予rhBNP治疗,先在10 min内匀速静脉注射负荷剂量1.5 μg/kg,随后以0.01μg·kg-1·min-1维持静脉泵入(至少10h泵入),每次总量0.5 mg,隔3d再重复给药1次.第2次用药后7d,比较两组病人的心功能分级、脑利钠肽(BNP)和肌酐水平、左室射血分数(LVEF)、左室舒张末内径(LVEDD),并记录不良反应.结果:rhBNP组心功能改善36例,总有效率为92.31％,显著高于对照组的28例(71.79％,P＜0.05).两组病人用药后心率减慢,舒张压、肌酐和BNP降低,LVEF提高,LVEDD减小,与用药前比较差异有极显著意义(P＜0.001),且rhBNP组心率、舒张压、LVEDD、血肌酐和BNP水平的降低,和LVEF的提高比对照组更明显(P＜0.001).rhBNP组发生1例低血压和1例低血钾,对照组发生2例低血压和1例室性心律失常,两者不良事件无显著差异(P＞0.05).结论:在常规抗心衰治疗基础上再静脉给予两次rhBNP(间隔3d),可以进一步改善RHF病人的心功能和血流动力学,降低血浆BNP和血清肌酐水平,使疗效提高,但并不增加不良反应.     

A study of the sequential treatment of acute heart failure with sacubitril/valsartan by recombinant human brain natriuretic peptide: A randomized controlled trial

This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated.Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, β receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment.The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance.Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.     

Triclosan exhibits a tendency to accumulate in the epididymis and shows sperm toxicity in male sprague‐dawley rats

Triclosan (TCS) is considered a potent endocrine disruptor that causes reproductive toxicity in non‐mammals, but it is still unclear exactly whether TCS has adverse effects on the sperm or reproductive organs in mammals. In this study, we aimed to evaluate the distribution status of TCS in male reproductive organs of rats, and seek the correlation with the TCS‐induced sperm toxicity or reproductive organ damage. Male rats were intragastrically administered with TCS at a dose of 50 mg/kg, the kinetics of TCS in the plasma and reproductive organs were investigated. TCS in testes and prostates both showed a lower‐level distritbution compared to that in the plasma, which indicates it has no tendency to accumulate in those organs. However, TCS in the epididymides showed a longer elimination half‐life (t_1/2z), a longer the mean retention time (MRT), and a lower clearance (CL_Z/F) compared with those in the plasma. Besides, the ratios of mean area under the concentration‐time curve (AUC)_{0–96h(epididymides/plasma)} and AUC_{0–∞(epididymides/plasma)} were 1.13 and 1.51, respectively. These kinetic parameters suggest TCS has an accumulation tendency in the epididymides. Based on this, we investigated the TCS‐induced sperm toxicity and histopathological changes of reproductive organs in rats. TCS was given intragastrically at doses of 10, 50, and 200 mg/kg for 8 weeks. Rats treated with the high dose (200 mg/kg) of TCS showed a significant decrease in daily sperm production (DSP), changes in sperm morphology and epididymal histopathology. Considering the histopathological change in the epididymides, TCS may induce the epididymal damage due to the epididymal accumulation of that. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 83–91, 2015.     

Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers

B cell-activating factor of the TNF family (BAFF) is an essential B cell survival factor. However, high levels of BAFF promote systemic lupus erythematosus (SLE) in mice and humans. Belimumab (anti-human BAFF) limits B cell survival and is approved for use in patients with SLE. Surprisingly, the efficacy of rituximab (anti-human CD20) in SLE remains controversial, despite depleting B cells more potently than belimumab. This raises the question of whether B cell depletion is really the mechanism of action of belimumab. In BAFF transgenic mice, SLE development is T cell-independent but relies on innate activation of B cells via TLRs, and TLR expression is modulated by the BAFF receptor TACI. Here, we show that loss of TACI on B cells protected against BAFF-mediated autoimmune manifestations while preserving B cells, suggesting that loss of BAFF signaling through TACI rather than loss of B cells may underpin the effect of belimumab in the clinic. Therefore, B cell-sparing blockade of TACI may offer a more specific and safer therapeutic alternative to broad B cell depletion in SLE.     

Breast Density Analysis Using an Automatic Density Segmentation Algorithm

Breast density is a strong risk factor for breast cancer. In this paper, we present an automated approach for breast density segmentation in mammographic images based on a supervised pixel-based classification and using textural and morphological features. The objective of the paper is not only to show the feasibility of an automatic algorithm for breast density segmentation but also to prove its potential application to the study of breast density evolution in longitudinal studies. The database used here contains three complete screening examinations, acquired 2 years apart, of 130 different patients. The approach was validated by comparing manual expert annotations with automatically obtained estimations. Transversal analysis of the breast density analysis of craniocaudal (CC) and mediolateral oblique (MLO) views of both breasts acquired in the same study showed a correlation coefficient of ρ = 0.96 between the mammographic density percentage for left and right breasts, whereas a comparison of both mammographic views showed a correlation of ρ = 0.95. A longitudinal study of breast density confirmed the trend that dense tissue percentage decreases over time, although we noticed that the decrease in the ratio depends on the initial amount of breast density.     

明胶微冰胶支架有利于脂肪来源间充质干细胞体外干性维持并提高其体内应用价值

目的研究人脂肪来源间充质干细胞(ADSCs)与明胶微冰胶材料体外联合培养时,材料是否能维持间充质干细胞的生物学特性。方法 ADSCs种植于明胶微冰胶材料后进行Calcein-AM和PI活细胞染色检测细胞活力,细胞滴度蓝法检测细胞增殖能力,定量PCR检测干性基因OCT4、Nanog、SOX2表达情况,以及在成脂成骨诱导过程比较ADSCs在二维环境和种植于明胶微冰胶材料后的分化潜能。结果 ADSCs在三维明胶微冰胶支架材料中能保持较高活性,增殖能力不受影响,干性基因表达上调,成脂成骨分化相关基因表达水平比二维诱导环境低。结论明胶微冰胶可以为ADSCs提供一个较二维培养更好的微环境,有利于ADSCs体外干性维持,从而在干细胞移植法治疗相关疾病时以非侵入性的细胞传递方式发挥更长期的应用价值。     

胃癌中VEGF、NRP1和干细胞标志物CD44的表达及相关性

目的探讨VEGF、NRP1和干细胞标志物CD44在胃癌组织中的表达及三者间的相关性。方法应用高通量组织芯片技术和免疫组化SP法检测72例胃癌和52例正常胃组织中VEGF、NRP1和CD44蛋白的表达,并分析三者之间的相关性以及与胃癌临床病理特征的关系。结果 (1)胃癌组织中VEGF、NRP1和CD44蛋白阳性率分别为76.4%、66.7%、83.3%,三者在胃癌组织中的表达显著高于正常胃组织,差异均具有统计学意义(P均<0.01)。(2)VEGF、NRP1蛋白表达与胃癌浸润深度、淋巴结转移、临床分期有关(P均<0.05);CD44表达与Lauren分型、分化程度、淋巴结转移、临床分期有关(P均<0.05)。(3)胃癌组织中VEGF、NRP1和CD44蛋白的表达均呈正相关(rs=0.578,rs=0.278,rs=0.316,P均<0.05)。结论 VEGF、NRP1和干细胞标志物CD44在胃癌中均呈高表达,且与胃癌的恶性生物学行为密切相关。VEGF与NRP1之间可能存在协同作用,二者均与干细胞标志物CD44的表达密切相关,其具体机制有待进一步研究。