The status,limitation and improvement of adoptive cellular immunotherapy in advanced urologic malignancies

In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved understanding of theoretical basis, such as molecular biology and immunology. Thereinto, adoptive cellular immunotherapy (ACI) has become one of the hotspots, which comprises a variety of treatment approaches, such as TIL, CIK cell, γδ T cell, CAR-engineered T cell and Allogeneic stem cell transplantation (alloSCT). Although preclinical efficacy has been demonstrated remarkably, clinical trials could not consistently show the benefit due to multi-factors in complex immunosuppressive microenvironment in vivo compared to that of in vitro. Here we review some timely aspects of ACI for advanced urologic malignancies, and describe the current status and limitation of immunotherapy from the cellular level. It’s our expectation to provide prompting consideration of novel combinatorial ACI strategies and a resurgence of interest in ACI for advanced urologic malignancies.     

中西医结合治疗急性脑梗死伴抑郁70例

目的:观察中西医结合治疗急性脑梗死伴抑郁(气虚血瘀证)的临床疗效.方法:选取急性脑梗死伴抑郁(气虚血瘀证)患者140例,按照随机数字表法分为观察组和对照组各70例.对照组给予阿司匹林和盐酸舍曲林口服治疗,观察组在对照组治疗的基础上加用自拟安神汤治疗,两组疗程均为30 d.结果:治疗后两组患者HAMD-17评分均较治疗前明显改善,且观察组明显优于对照组(P＜0.05);治疗后观察组患者睡眠不深、早醒、抑郁情绪和胃肠道症状评分均明显优于对照组(P均＜0.05);观察组患者使用盐酸舍曲林的剂量明显低于对照组(P＜0.05);观察组NIHSS评分、mRS残障评级(0～2级)和Barthel指数评分≥85分改善情况均明显优于对照组(P均＜0.05).结论:中西医结合治疗急性脑梗死伴抑郁(气虚血瘀证)可显著改善抑郁症状,减少盐酸舍曲林的使用剂量,促进神经功能恢复,降低残障评级,提高日常生活活动能力.     

溶栓治疗老年人急性脑梗死的临床研究

目的 :探讨老年人急性脑梗死 (ACI)溶栓治疗的疗效及安全性。方法 :将 5 5例病人分为≥ 70岁组和 <70岁组 ,均在发病 72h内用尿激酶 2 0万U ,连用 7d。结果 :≥ 70岁组与 <70岁组在疗效和出血等副作用上无明显差异。结论 :溶栓治疗急性脑梗死其疗效和安全性与年龄无明显相关 ,不应把高龄作为限制溶栓治疗的独立指标 ,其效益大于治疗风险。     

关节软骨创伤早期关节腔内注射透明质酸对软骨细胞凋亡的影响

目的 研究关节软骨创伤（Articular cartilage injury,ACI）后早期行关节腔（Joint cavity,JC）内注射透明质酸（Hyaluronate acid,HA）对软骨细胞（Cartilage cells,CC）凋亡的影响.方法 将2010年3月～2013年3月被确诊为ACI的78例患者,以数字法随机分成观察组与对照组各39例,对照组仅以ACI常规抗感染以及手术等方案治疗,观察组在ACI早期缝合皮肤前行JC内注射HA.对比两组经流式细胞仪以及TUNEL法测定的CC凋亡情况,分析两组CC细胞周期情况.结果 观察组以流式细胞仪测定的CC凋亡率为（3.63±0.46）％,显著低于对照组的（6.87±0.85）％.差异有统计学意义（P＜0.05）.观察组以TUNEL法测定的CC凋亡率为2.98±0.23,显著低于对照组的6.54±0.17.差异有统计学意义（P＜0.05）.观察组G0/G1为82.21±2.02,显著低于对照组的91.32±3.65;S、G2/M、PI分别为8.74±2.65、9.08士1.65和17.81±1.65,均显著高于对照组的3.65±0.27、5.05±0.54和8.71±1.05,差异均有统计学意义（均P＜0.05）.结论 ACI后早期患者行JC内注射HA,可明显减少CC凋亡,促进患者康复,效果较为显著,值得临床推广应用.     

Shear Strength of Externally U-Bonded Carbon Fiber-Reinforced Polymer High-Strength Reinforced Concrete

In this paper, we investigate the contribution of Fiber-Reinforced Polymer (FRP) to the load-carrying capacity of shear-strengthened Reinforced Concrete (RC) beams. Specifically, the investigation is focused on the FRP’s contribution in the presence and absence of shear stirrups. To this end, two sets of full-scale RC beam specimens were tested to failure in a simply supported setup. Set 1 consisted of specimens without shear stirrups whereas Set 2 included steel stirrups spaced at 170 mm. One and two layers of FRP discrete strips were bonded to the beams in a U-jacketing configuration. To investigate the contribution of FRP and its interaction with the stirrups, two different locations were considered when bonding the FRP strips: between the stirrups (referred to as Off-beams) and at the same level of the stirrups (referred to as On). Results of the experimental program showed that strengthening the beams with two layers of FRP does not necessarily translate to improved capacity. Furthermore, the location of FRP strips with respect to the location of shear stirrups has an influence on the beam’s overall behavior, especially its displacement ductility. This is an important parameter to consider to avoid premature failure of RC members. Test results were then used to assess the performance and accuracy of the predictions of ACI PRC-440.2-17 and fib-TG9.3. Both design codes were found to be conservative with an average prediction-to-test ratio of 0.7.     

Characterization of Phenytoin-Resistant Kindled Rats, a New Model of Drug-Resistant Partial Epilepsy: Comparison of Inbred Strains

Summary: Purpose: Previous work from our laboratory showed that amygdala-kindled Wistar outbred rats can be selected according to the increase of afterdischarge threshold (ADT) after phenytoin application. Animals that consistently do not respond to phenytoin (PHT) with an ADT increase (non-responders) are the first animal model of pharmacoresistant complex partial seizures. In this study, we determined the ability to respond to PHT in male kindled rats of different inbred strains.
Methods: The experiments were performed in fully kindled rats of five different inbred strains, Wistar-Kyoto, Lewis, Fischer 344, ACI, and Brown Norway. The response type of each rat was revealed by four consecutive PHT applications (75 mg/kg, i.p.) in fully kindled rats.
Results: PHT application resulted in plasma concentrations ranging from some 16 μg/ml in Lewis rats to 35 μg/ml in Fischer 344 rats, and in slight ataxia, most strongly in Fischer 344 rats. The rats of each strain did not show a homogeneous response to PHT. A significant increase of ADT was found after 86–97% of applications in Lewis, Wistar-Kyoto, and Fischer 344 rats. In contrast, Brown Norway rats responded in only 34% of experiments. This led to a considerable number of responders (i.e., consistent ADT increase by >20%) in Fischer 344, Wistar-Kyoto, and Lewis rats. The only strain revealing nonresponders (i.e., consistent lack of ADT increase by >20% with PHT treatment) was Brown Norway.
Conclusions: Inbred strains, although genetically more homogenous than outbred strains, differ in their response to PHT. Brown Norway rats can offer advantages for further detailed investigation of the resistance to PHT in the kindling model of complex partial seizures.     

Nodular Development of Spontaneous Epithelial Thymoma in (ACI/NMs × BUF/Mna)F1 Rats

The BUF/Mna strain is a high thymoma line of rats, and virtually all rats develop overt thymomas by the age of 40 weeks. To reveal the early morphologic changes in this thymomagenesis, thymuses and thyraomas were studied in (ACI/NMs × BUF/Mna)Fl (ABF1) rats, which inherit a thymoma susceptibility gene ( Tsr-1 ) from the BUF/Mna strain. At 50 weeks of age, 18% of ABF1 rats had developed medium to large thymomas, 54% had just began to develop multiple, small round nodules in their involuted thymuses, and the remaining 29% had involuted thymus only. The nodules were, microscopically, composed of cortex-like tissues with a starry-sky pattern, showing a quite similar structure to that of the large macroscopic thymomas of predominantly lymphocytic type seen in 104-week-old ABF1 or BUF-Mna rats. Thus, the nodule was actually a small thymoma. In fact, their epithelial cells often had larger atypical nuclei than those in the adjacent involuted thymus cortex. At 104 weeks of age, the incidences of the medium to large thymomas and the small thymoma nodules in ABF1 rats were 64 and 19%, respectively. These results suggest that the thymoma of ABF1 rats occurs initially as multiple small nodules which develop further into medium to large overt thymomas as a result of growth and fusion.     

Announcement

Histologic specimens of ventral and dorsolateral prostate from ACI male rats of varying ages (3, 6, 12, 18, 24, and 29–32 months) were examined to identify changes associated with the development of adenocarcinoma. The same specimens were examined immunohistochemically for their distribution of prolactin binding sites. At 3 months of age ventral lobes of these ACI rats exhibited normal histology and prolactin binding patterns. At 6 and 12 months of age most ventral prostate alveoli showed epithelial cell atrophy, along with occasional acini containing normal-looking epithelial cells. Prolactin binding activity was present in most epithelial cells at 6 months of age but disappeared from atrophied cells at 12 months of age. At 18 months of age epithelial atrophy was more advanced and devoid of prolactin binding activity while zones of epithelial cell proliferation were expanded containing populations of normal-looking cells, and cells that were either hyperplastic or dysplastic (abnormal looking), all of which were capable of binding prolactin. Older rats, 24–32 months of age, also showed prostatic adenocarcinoma in ventral prostate and these cancerous cells bound prolactin. A continuum was frequently seen between areas of normal epithelial cells, hyperplasia, dysplasia, and adenocarcinoma of ventral prostate. Morphology and prolactin binding patterns in dorsal and lateral prostates of old ACI rats were similar to young adult rats and did not contain adenocarcinoma. In conclusion, age-dependent atrophy of the ventral prostate gland of ACI rats occurs early in life and precedes adenocarcinoma. Precancerous dysplastic changes appear to arise from normal and hyperplastic epithelial cells that are capable of binding prolactin rather than those that undergo precocious atrophy and lose their prolactin binding activity. Although atrophic epithelial cells do not appear to be progenitors of prostatic cancer, the possible relationship between precocious senescence (atrophy) and adenocarcinoma in ventral prostates of ACI rats is discussed.     

D-D、Fb和AT-Ⅲ在脑梗死不同时期的变化及相关性分析

目的：探讨血浆D-二聚体（D-D）、纤维蛋白原（Fb）和抗凝血酶Ⅲ（AT-Ⅲ）在脑梗死（CI）不同时期的变化及其临床意义。方法：根据临床特征,对260例CI患者进行分组,其中CI急性期组80例、进展期组41例、非进展期组65例、康复期组74例;90例体检健康者为正常对照组。采用SYSMEX CA7000血凝仪分别检测其血浆D-D、Fb和AT-Ⅲ水平。结果：CI急性期、进展期、非进展期患者D-D、Fb含量均明显高于正常对照组（P〈0.01）,AT-Ⅲ低于正常对照组（P〈0.01）;脑梗死组中,D-D与AT-Ⅲ呈负相关（P〈0.01）,D-D与Fb呈正相关（P〈0.01）,AT-Ⅲ与Fb无相关性。结论：CI患者D-D、Fb、AT-Ⅲ变化显著,D-D升高伴随AT-Ⅲ含量降低,提示D-D、Fb、AT-Ⅲ共同参与了梗死发生发展的病理生理过程,可作为CI临床危险分级和病情监测的指标。