BACKGROUND & AIMS: PURPOSE OF REVIEW:Since 2016, five new programmed cell death protein 1/ligand 1 (PD-1/L1) checkpoint inhibitors have been approved for metastatic urothelial carcinoma. This review will summarize the data supporting the widespread use of these agents and highlight areas of ongoing clinical development. RECENT FINDINGS:PD-1/L1 axis inhibition has demonstrated clear superiority to chemotherapy for the treatment of metastatic urothelial cancer in the second-line setting. A multitude of ongoing studies are investigating the feasibility and efficacy of incorporating established and novel immunotherapies into earlier lines of therapy, including non-metastatic muscle-invasive bladder cancer and even non-muscle-invasive disease. Early-phase clinical trials have begun to explore the safety and activity of novel immune-oncology combinations across a range of clinical settings. Immunotherapy has a clearly defined role in the treatment of metastatic urothelial cancer both in the platinum-refractory setting and in the first-line cisplatin-ineligible setting. Ongoing clinical trials will dictate how to best incorporate immunotherapy into earlier lines of therapy and define the safety and activity of novel immunotherapy agents and combinations.

背景与目标： 审查目的：自2016年以来，已批准了五种新的程序性细胞死亡蛋白1 /配体1（PD-1 / L1）检查点抑制剂用于转移性尿路上皮癌。这篇综述将总结支持这些药物广泛使用的数据，并强调正在进行的临床开发领域。
最近的发现：在二线治疗中，PD-1 / L1轴抑制作用已显示出明显优于化疗的转移性尿路上皮癌。大量正在进行的研究正在研究将已建立的和新颖的免疫疗法纳入较早的治疗方法（包括非转移性肌肉浸润性膀胱癌，甚至非肌肉浸润性疾病）的可行性和有效性。早期临床试验已开始探索在一系列临床环境中新型免疫肿瘤组合的安全性和活性。免疫治疗在铂难治性和一线顺铂不适应性治疗中均具有明确定义的转移性尿路上皮癌治疗作用。正在进行的临床试验将决定如何将免疫疗法最佳地纳入早期疗法，并定义新型免疫疗法药物及其组合的安全性和活性。

BACKGROUND & AIMS: :The preparation and stability parameters of para-acyl-calix[4]arene based solid lipid nanoparticles (SLNs) have been investigated. Atomic force microscopy (AFM) and photon correlation spectroscopy (PCS) show a mean particle size of 130 nm. In terms of preparation parameters, using the solvent displacement method, the nature and the volume of the organic solvent, the concentration of the amphiphile and the presence of a co-surfactant in the organic phase have been shown to affect significantly the size of the produced SLNs. In contrast, the stirring speed, the viscosity and the acidity of the aqueous phase and the amphiphile hydrophobic chain length have been shown to have no effect. In terms of stability parameters, the ionic strength has been shown to affect the short-time SLN stability depending on both the anion and the cation studied, with sodium sulphate causing precipitation. Ultrasonic, ultraviolet or microwave treatments of the SLN suspensions have no effect on the size of the SLNs. The study of the effects of short time thermal treatment revealed that the SLNs are not affected by one freezing-defreezing cycle and are stable at 100 degrees C in suspension. It is difficult to reconstitute the SLN suspensions after freeze-drying. Finally, the temporal stability of these suspensions in water has been shown to be superior to 1 year. The long-term temporal stability of suspensions stored in saline solution has been investigated. It has been demonstrated that the most destabilising effects arise from the presence in the storage suspension of sulphate ions.1H NMR, X-ray powder diffraction (XPD) and AFM have also been carried out on the calix-arene based SLNs and demonstrate the presence of a semi-organised matrix structure for the SLNs.

背景与目标： ：研究了对酰基杯[4]芳烃基固体脂质纳米颗粒（SLNs）的制备和稳定性参数。原子力显微镜（AFM）和光子相关光谱（PCS）显示平均粒径为130 nm。在制备参数方面，已证明使用溶剂置换法，有机溶剂的性质和体积，两亲物的浓度以及有机相中助表面活性剂的存在会显着影响产物的大小。 SLN。相反，已显示搅拌速度，水相的粘度和酸度以及两亲性疏水链长度没有影响。就稳定性参数而言，已证明离子强度会影响短期SLN稳定性，具体取决于所研究的阴离子和阳离子，而硫酸钠会引起沉淀。 SLN悬浮液的超声波，紫外线或微波处理对SLN的大小没有影响。对短时间热处理效果的研究表明，SLN不受一个冷冻-解冻循环的影响，并且在100℃的悬浮状态下稳定。冷冻干燥后很难重新配制SLN悬浮液。最后，这些悬浮液在水中的时间稳定性已证明优于1年。已经研究了盐溶液中储存的悬浮液的长期时间稳定性。业已证明，最不稳定的作用是由硫酸根离子的储存悬浮液引起的。1HNMR，X射线粉末衍射（XPD）和AFM也在基于芳烃芳烃的SLN上进行，并证明了存在SLN的半组织矩阵结构。

BACKGROUND & AIMS: :Anal intraepitelial neoplasia (AIN) constitutes a major health problem in certain risk groups, such as patients with immunosuppression of varied origin, males who have sexual relations with other males, and females with a previous history of vaginal or cervical abnormalities in cytology. Its relationship with the human papillomavirus (HPV) infection has been well documented; however, many of the factors involved in the progression and regression of the viral infection to dysplasia and anal carcinoma are unknown. AIN can be diagnosed through cytology of the anal canal or biopsy guided by high-resolution anoscopy. However, the need for these techniques in high-risk groups remains controversial. Treatment depends on the risk factors and given the high morbidity and high recurrence rates the utility of the different local treatments is still a subject of debate. Surgical biopsy is justified only in the case of progression suggesting lesions. The role of the vaccination in high-risk patients as primary prevention has been debated by different groups. However, there is no general consensus on its use or on the need for screening this population.

背景与目标： ：在某些风险人群中，肛门上皮内瘤变（AIN）构成了主要的健康问题，例如，具有不同血统的免疫抑制的患者，与其他男性发生性关系的男性，以及在细胞学上曾有阴道或宫颈异常病史的女性。它与人乳头瘤病毒（HPV）感染的关系已有很好的文献证明。但是，涉及病毒感染发展和消退，发育不良和肛门癌的许多因素尚不清楚。可以通过肛管细胞学检查或高分辨率肛门镜检查活检来诊断AIN。但是，在高风险人群中对这些技术的需求仍然存在争议。治疗取决于风险因素，并且鉴于高发病率和高复发率，使用不同的局部治疗仍然是一个争论的话题。仅在提示病灶进展的情况下才需要进行手术活检。不同人群对疫苗接种在高危患者中作为一级预防的作用进行了辩论。但是，关于其用途或筛查该人群的需求尚无普遍共识。

BACKGROUND & AIMS: :In this study, we aimed to evaluate the antiviral effect of total flavonoids extracted from Robinia pseudoacacia cv. idaho (RPTF) in vivo and its toxicity on rats with oral gavage. RPTF was prepared by percolation with 70% ethanol for 24 h and its antiviral effect on different kinds of viruses was evaluated in vitro by MTT staining. The long-term toxicity of RPTF on rats was evaluated through the detection of general behavior, body weight, food intake and related organ tissue sections of experimental animals. We found that RPTF produced significantly inhibitory effects on HSV-1 and EV-71 viruses with the therapeutic index TI values 113.8 and 46.2, respectively. Moreover, toxicity evaluation in vivo showed no significantly adverse effects in rats, indicating that RPTF was safe in use. In conclusion, we demonstrated that RPTF, natural compounds in the Chinese traditional medicine, could act as promising and effective antiviral therapeutics with relative safety in use.

背景与目标： ：在这项研究中，我们旨在评估从刺槐中提取的总黄酮的抗病毒作用。 idaho（RPTF）体内及其对管饲大鼠的毒性。通过用70％乙醇渗滤24小时来制备RPTF，并通过MTT染色在体外评估其对不同种类病毒的抗病毒作用。通过检测实验动物的一般行为，体重，食物摄入和相关器官组织切片，评估了RPTF对大鼠的长期毒性。我们发现RPTF对HSV-1和EV-71病毒产生明显的抑制作用，治疗指数TI值分别为113.8和46.2。此外，体内毒性评估显示对大鼠没有明显的不利影响，表明RPTF使用安全。总之，我们证明了RPTF是中药中的天然化合物，可以作为有希望且有效的抗病毒治疗剂，且使用时相对安全。

BACKGROUND & AIMS: :Febrile seizures are the most common seizures of childhood. A family history of febrile seizures is common, and the disorder is genetically heterogenous. While guidelines are available for management of simple febrile seizures, the management of complex febrile seizures is individualised. After a febrile seizure, it is important to rule out CNS infection and the decision to perform a lumbar puncture should be based on the clinical condition of the child. Neuroimaging and EEG are not required immediately in workup for simple or complex febrile seizures. Recurrence of febrile seizures may be managed at home by the parents with benzodiazepines. If the recurrences are multiple or prolonged and parents are unable to give home treatment, intermittent benzodiazepine prophylaxis may be given. Continuous antiepileptic prophylaxis may be given only to the children where intermittent prophylaxis has failed. Febrile seizures are also associated with increased risk of epilepsy, but this cannot be prevented by any form of treatment. There is also an increased risk of mesial temporal sclerosis, but whether this is an effect or cause of febrile seizures is as yet unclear. There is no increase in neurological handicaps or mortality following febrile seizures.

背景与目标： ：高热惊厥是儿童最常见的惊厥。高热惊厥的家族病史很普遍，该疾病在遗传上是异质的。虽然有指导可用于管理简单的高热惊厥，但是对复杂的高热惊厥的治疗是个体化的。高热惊厥后，重要的是要排除CNS感染，应根据儿童的临床情况决定是否进行腰穿。对于简单或复杂的高热惊厥，无需立即进行神经影像检查和脑电图检查。苯二氮卓类药物的父母可在家中控制高热惊厥的复发。如果复发是多次的或延长的，并且父母无法给予家庭治疗，则可以间歇性地预防苯二氮卓类药物。持续的抗癫痫预防只能用于间歇性预防失败的儿童。高热惊厥也与癫痫风险增加有关，但这不能通过任何形式的治疗来预防。中间颞叶硬化的风险也增加了，但是，这是高热惊厥的影响还是原因尚不清楚。高热惊厥后神经障碍或死亡率没有增加。

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