Programmed Cell Death-One Inhibition Therapy in Classical Hodgkin Lymphoma

The majority of patients with classical Hodgkin lymphoma (cHL) may be cured, but for patients with relapsed or refractory (R/R) cHL, the prognosis is unfavorable. Immune dysfunction is a significant contributor of relapse and a hallmark of cHL; in particular, the immune system is unable to eradicate lymphoma cells that overexpress immune checkpoint proteins. The blocking of this mechanism used by lymphoma cells to evade the immune system has resulted in clinical benefits. Use of checkpoint inhibitors (CPIs) in R/R cHL is associated with high response rates and an acceptable adverse effects profile. There is growing interest in combining chemotherapy with CPIs in frontline therapy of cHL treatment to improve relapse rates without significant additive toxicity. In this review, we discuss the current evidence supporting CPI use in R/R cHL and maintenance therapy. We present emerging CPI data in frontline adult cHL and assess its role in the elderly. In addition, we discuss critical immune-related toxicities and their management, and elaborate on the challenges of monitoring response and minimal residual disease as tools for maximizing efficacy by limiting toxicity.     

新生儿苯丙酮尿症两种实验室筛查方法的质量评价

目的比较筛查新生儿苯丙酮尿症(PKU)的2种检测苯丙氨酸(Phe)的方法——细菌抑制法(B IA)和荧光法。方法参加美国疾病控制中心(CDC)质量评价,分析B IA和荧光法的批内、批间误差及相对偏差,比较2种方法的结果。结果用CDC质控品测得BIA批内变异系数(CV)为14.29%,荧光法为5.85%;用不同浓度质控品测得B IA批间CV分别为25.34%、20.86%、34.78%和25.72%,荧光法为16.46%、13.22%、19.53%和15.41%;B IA的PKU阳性检出率为5.04/10万,荧光法为7.79/10万。结论荧光法较B IA具有更灵敏、准确、可定量、费时少的优点,国内今后应顺应其发展趋势,普及推广运用荧光法筛查新生儿PKU。     

Thyroid hormone concentrations and inhibition of thyroid stimulating hormone secretion in euthyroid subjects with autonomous thyroid nodules

Abstract. Sixty-four euthyroid patients with autonomous thyroid nodules and normal thyroxine (T₄) concentrations and tri-iodothyronine resin uptake have been studied. The serum tri-iodothyronine (T₃) concentration of the patients was 2.24 (±0.67) ng/ml, significantly higher than in a group of fifty-seven euthyroid control subjects (1.58 ± 0.30 ng/ml). When no extranodular tissue was visible on the basal thyroid scan, the T₃ was 2.31 (±0.63) ng/ml, significantly higher than in patients with some extranodular uptake on the basal scan (1.91 ± 0.42 ng/ml). There was no significant difference in the serum T₄ concentrations of the patients (7.37 ± 2.10 μg/100 ml) compared to the control group (6.88 ± 1.89 μg/100 ml). The T₄ concentrations were not correlated with total or partial inhibition of the extranodular tissue. The thyroid hormone concentrations were not directly correlated to the size of the nodule assessed by scan imaging. The thyroid stimulating hormone (TSH) concentration of the patients (1.52 ± 0.38 μU/ml) was significantly lower than in normals (2.49 ± 0.96 μU/ml). No significant difference was found in the TSH concentrations of patients with partial or total inhibition of extranodular tissue irrespective of the T₃ concentration. A thyrotrophin releasing hormone stimulation test in twelve patients did not increase the serum TSH, irrespectively of the T₃ concentration.
These data show the high frequency of elevated serum T₃ concentrations despite normal serum T₄ concentration in euthyroid patients with autonomous thyroid nodules. They confirm that inhibition of TSH secretion can occur when thyroid hormone concentrations are in the normal range.     

一种卷烟用抗菌接装纸抑菌效果及毒性试验观察

为了解卷烟用抗菌接装纸抗菌效果及卫生质量,进行了细菌污染检测和抑菌试验及皮肤刺激性试验。结果,此种卷烟用抗菌接装纸细菌污染检测全部合格,抑菌试验作用2 m in,对大肠杆菌、金黄色葡萄球菌抑菌率达到93%以上。该接装纸对家兔皮肤无刺激性,亦无皮肤变态反应。结论,新型卷烟用抗菌接装纸抑菌效果好,对皮肤无刺激,无致变态反应作用。     

Effects of differential blockade of the renin-angiotensin system in postinfarcted rats

The present study compared short-term effects of the AT(1)-receptor antagonist, irbesartan with the angiotensin-converting enzyme (ACE) inhibitor, enalapril on systemic haemodynamics and cardiac remodelling in post-myocardia-infarcted (MI) rats. MI Sprague-Dawley rats were orally treated for 4 weeks with irbesartan (50 mg/kg/day) or enalapril (10 mg/kg/day). Then, cardiac and systemic haemodynamics were measured. Compared with the sham-operated group, left ventricular end-diastolic pressure (LVEDP), diastolic pressure (LVDP), heart weight to body weight ratio were all significantly increased in the MI group while the LV contractility (dP/dt) and pulsatile arterial pressure were significantly reduced. Both drugs reduced the elevated LVEDP and LVDP and prevented cardiac hypertrophy. Furthermore, irbesartan attenuated the right shift of the pressure-volume curves, prevented postinfarction-induced increase in urinary cyclic guanosine monophosphate and reduced urinary aldosterone excretion. Although both drugs were able to prevent further cardiac hypertrophy and improved cardiac filling pressure, only irbesartan limited LV dilatation. These data indicate that blockade of the renin-angiotensin system at the level of AT1 receptors may have a better cardioprotective benefit than reducing angiotensin II levels by ACE inhibition.     

Nitric oxide donor,NOC7, reveals dose dependently and cGMP pathway independently biphasic effects on contractile force of isolated rat heart after global ischemia

Purpose: Our purpose was to investigate whether the 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), an ideal NO donor was dose dependently and cGMP-independent in restored cardiac function after global ischemia in an isolated rat heart model. Methods: Langendorff preparations of an isolated rat heart model were established. Isolated rat hearts (n = 40) were randomly divided into 5 groups (ischemic control group, NOC7 groups and NOC7+NS2028 groups). All groups were subjected to 35 min global ischemia, followed by 30 min reperfusion with Krebs-Henseleit bicarbonate buffer (KHB), and NOC7, NOC7+NS2028 at 2 and 200 μM, respectively. Left ventricular developed pressure (LVDP), the maximum and the minimal rate of rise in LVP (±dP/dt), and coronary flows were measured continuously. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were measured in myocardium homogenate, using enzyme immunoassay (EIA). Results: 30 min of global ischemia increased LVDP to 121.9±11.5% at 35 min of reperfusion of 2 μM NOC7 group and 2 μM NOC7 associated with NS2028 group from the ischemic control group (P < 0.05). While in 200 μM NOC7 group and 200 μM NOC7 associated with NS2028 group, the LVDP value only slightly reduced, resulting in a value of only 45.3±10.4% and 35.3±6.0% of baseline (P > 0.05). Conclusion: NOC7 has biphasic effect on isolated rat heart after ischemia and reperfusion myocardial contractility. This biphasic effect shows neither concentration-dependent nor the cGMP-dependent characteristics.     

Reliability of single and paired‐pulse transcranial magnetic stimulation in the vastus lateralis muscle

Introduction: Transcranial magnetic stimulation (TMS) is an important tool to examine neurological pathologies, movement disorders, and central nervous system responses to exercise, fatigue, and training. The reliability has not been examined in a functional locomotor knee extensor muscle. Methods: Within‐ (n = 10) and between‐day (n = 16) reliability of single and paired‐paired pulse TMS was examined from the active vastus lateralis. Results: Motor evoked potential amplitude and cortical silent period duration showed good within‐ and between‐day reliability (intraclass correlation coefficient [ICC] ≥ 0.82). Short‐ and long‐interval intracortical inhibition (SICI and LICI, respectively) demonstrated good within‐day reliability (ICC ≥ 0.84). SICI had moderate to good between‐day reliability (ICC ≥ 0.67), but LICI was not repeatable (ICC = 0.47). Intracortical facilitation showed moderate to good within‐day reliability (ICC ≥ 0.73) but poor to moderate reliability between days (ICC ≥ 0.51). Conclusions: TMS can reliably assess cortical function in a knee extensor muscle. This may be useful to examine neurological disorders that affect locomotion. Muscle Nerve 52: 605–615, 2015     

Right prefrontal and ventral striatum interactions underlying impulsive choice and impulsive responding

Although a multifaceted concept, many forms of impulsivity may originate from interactions between prefrontally‐mediated cognitive control mechanisms and limbic, reward or incentive salience approach processes. We describe a novel task that combines reward and control processes to probe this putative interaction. The task involves elements of the monetary incentive delay task (Knutson et al., [2000]: Neuroimage 12:20–27) and the Go/No‐Go task (Garavan et al., [1999]: Neuroimage 17:1820–1829) and requires human subjects to make fast responses to targets for financial reward but to occasionally inhibit responding when a NoGo signal rather than a target is presented. In elucidating the dynamic between reward anticipation and control we observed that successful inhibitions on monetary trials, relative to unsuccessful inhibitions, were associated, during the anticipation phase, with increased activation in the right inferior frontal gyrus (rIFG), decreased activity in the ventral striatum (VS), and altered functional connectivity between the two. Notably, this rIFG area had a small overlap but was largely distinct from an adjacent rIFG region that was active for the subsequent motor response inhibitions. Combined, the results suggest a role for adjacent regions of the rIFG in impulsive choice and in impulsive responding and identify a functional coupling between the rIFG and the VS. Hum Brain Mapp, 36:187–198, 2015. © 2014 Wiley Periodicals, Inc .