Immunotherapy in biliary tract cancers: Current evidence and future perspectives

Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder tumors. These are aggressive tumors and chemotherapy is still the main treatment for advanced-stage disease and most of these cases have a poor overall survival. Strategies are aimed at treatments with better outcomes and less toxicity which makes immunotherapy an area of ​​significant importance. Recent Food and Drug Administration approvals of immune checkpoint inhibitors (ICI) for agnostic tumors based on biomarkers such as microsatellite instability-high and tumor mutation burden-high are important steps in the treatment of patients with advanced bile duct tumors. Despite limited responses with isolated checkpoint inhibitors in later lines of systemic treatment in advanced disease, drug combination strategies have been demonstrating encouraging results to enhance ICI efficacy.     

Prolonged migraine aura without headache arrested by sumatriptan. A case report with further considerations

The case of a 42-year-old woman with prolonged migraine visual aura without headache, whose long-lasting episodes of visual aura were successfully controlled by oral sumatriptan, is reported. Effectiveness of sumatriptan was unequivocal, since, after taking sumatriptan, duration of aura would drop from 1.5 h to approximately 20 min. This case suggests that sumatriptan may cross the blood-brain barrier and block spreading depression.     

Misdiagnosis of tuberculosis and the clinical relevance of non—tuberculous mycobacteria in Zambia

ObjectiveTo determine the accuracy of TB diagnosis of TB in Zambia in the era of increasing HIV prevalence.MethodsSputum of the clinically diagnosed TB cases was additionally subjected to liquid culture and molecular identification. This study distinguished between TB cases confirmed by positive Mycobacterium tuberculosis (M. tuberculosis) cultures and mycobacterial disease caused by non-tuberculous mycobacteria (NTM).ResultsOnly 49% of the 173 presumptively diagnosed TB cases was M. tuberculosis cultured, while in 13% (22) cases, a combination of M. tuberculosis and NTM was found. In 18% of the patients only NTM were cultured. In 28%, no mycobacteria was cultivable. HIV positive status was correlated with the isolation of NTM (P <0.05).ConclusionsThe diagnosis of tuberculosis based on symptoms, sputum smear and/or chest X-ray leads to significant numbers of false-positive TB cases in Zambia, most likely due to the increased prevalence of HIV. The role of NTM in tuberculosis-like disease also seems relevant to the false diagnosis of TB in Zambia.     

组织工程技术仿生构建颅颌骨组织的研究

目的:探索构建组织工程化仿生骨种植体的方法流程,并制备成骨细胞-可吸收载体种植体样品,同时尝试建立组织工程化非承载骨种植体的评价方法。方法:实验于2001-05/2005-12分别在天津市口腔医院组织工程实验室和天津大学材料学院高分子材料研究所完成。①通过相分离技术制备壳聚糖/明胶三维网络多孔支架,在支架材料表面原位沉积纳米级的羟基磷灰石晶体,构筑纳米羟基磷灰石/壳聚糖/明胶仿生骨组织工程支架材料,并进行表征和性能检测。②用酶消化法和条件培养法分离、诱导培养中国小型猪成骨细胞作为组织工程种子细胞。③用静态复合共培养法体外构建2种骨组织工程种植体样品:成骨细胞-纳米羟基磷灰石/壳聚糖/明胶仿生骨种植体,成骨细胞-纳米羟基磷灰石/胶原种植体。④采用扫描电镜、透射电镜、FDA荧光、LDH、MTT等定期观测仿生骨样品中细胞形态、细胞增殖速率、碱性磷酸酶活性、矿化结节形成等指标,以比较样品的细胞增殖活性和成骨活性。结果:①成功构筑了具有良好的生物相容性和力学相容性的纳米羟基磷灰石/壳聚糖/明胶,这种材料具有适于细胞黏附与生长的(90±1)%的孔隙率,孔径为100￣300μm的微孔结构,且原位沉积的纳米羟基磷灰石晶体的粒径为50nm左右,接近与天然骨的组成。②自中国小型猪腿骨成功分离培养了成骨细胞,并在诱导培养条件下,表现出很强的增殖活力和成骨活性,适合作为实验用骨组织工程的种子细胞。③成功构建了两种成骨细胞-可吸收载体种植体样品:经检验仿生构建的小型猪成骨细胞-纳米羟基磷灰石/壳聚糖/明胶种植体具有细胞亲和性和体外成骨活性。结论:①在体外成功仿生构建了结构与活性接近天然骨的骨组织工程种植体--纳米羟基磷灰石/壳聚糖/明胶种植体。②初步建立了仿生组织工程化非承载骨种植体的评价方法,为其进一步用于体内修复颅颌骨组织损伤的深化研究提供了实验数据和科学依据。     

Immunohistochemical study on gastroenteric nervous system in trisomy 16 mice:an animal model of Down syndrome

AIM:To study the development of gastroenteric nervous system in trisomy 16 mouse embryos.The gastroenteric nervous system in trisomy 16 mice and their normal littermates, serving as controls from embryonic days 13 to 18 (ED13-18) was identified by using primary antibody against protein gene product (PGP) 9.5.METHODS:Trisomy 16 mouse breeding and trisomy 16 mouse embryos were identified from their normal littermates by chromosome examination; PGP 9.5 immunohistochemical stainning.RESULTS:In normal littermates embryos, the precursor cells from the neural crest migrated into stomach and intestine at ED 13 and ED 14 respectively.Numerous nervous processes connected to each other and formed early nervous networks at ED 14 stomach and ED 15 intestine. Original ganglia in the muscular nervous plexus of the stomach appeared at ED15 with very simple arrangement. At ED 16 the early developed myenteric nervous plexuses were regularly found in the stomach and intestine respectively. In both stomach and intestine, the development of submucosal nervous plexuses were finished at ED17. However, the myenteric nervous plexus and the internal and external submucosal nervous plexuses were differentiated only in the stomach at ED 18.In comparison with the normal littermates, stomach and intestine nervous system developed much slower in trisomy 16 mice. Their immature neurons did not appear in the stomach and intestine until ED 14 and ED 15. Between ED 14 and ED 16, the gastroenteric nervous system was composed of only some scattered neurons with different distribution density and size. The development and differentiation of the gastroenteric nervous system were delayed and the myenteric nervous plexus did not appear until ED 18. There was no submucosal nervous plexus in all stomach and intestine specimens. A semiquantitative analysis and rank sum test of the data showed that the trisomy 16 mouse embryos were markedly retarded in the gastroenteric nervous development compared with their normal littermates.CONCLUSION:Trisomy 16 mice, as an animal model for Down syndrome, has abnormality not only in several systems and organs but also in gastroenteric innervation. This report describes for the first time that the development of the gastroenteric nervous system was not only delayed but also pathological.     

A mortality cost of virginity at older ages in female Mediterranean fruit flies

Mortality rates were measured over the lifetime of 65,000 female Mediterranean fruit flies, Ceratitis capitata, maintained in either all-female (virgin) cages or cages with equal initial numbers of males, to determine the effect of sexual activity and mating on the mortality trajectory of females at older ages. Although a greater fraction of females maintained in all-female (virgin) cages survived to older ages, the life expectancy of the surviving virgins was less than the life expectancy of surviving non-virgins at older ages. This was due to a mortality crossover where virgin flies experience lower mortality than mated flies from eclosion to Day 20 but higher mortality thereafter. These results suggest that there are two consequences of mating--a short-term mortality increase (cost) and a longer term mortality decrease (benefit).