Targeted therapies in the treatment of pancreatic carcinoma

Pancreatic carcinoma is the fifth leading cause of cancer deaths in the western world. Although some progress has been made in the clinical management of pancreatic cancer, surgical resection remains the only potentially curative treatment. New strategies are urgently needed for the treatment of this disease. Advances in knowledge in genetics and molecular biology have led to the development of novel treatments targeting specific molecules. Todate, the results obtained with these new drugs have not been superior to those observed with conventional chemotherapy. In the present article we review some of the new therapies for pancreatic cancer such as the use of inhibitors of epidermal growth factor receptors, the inhibitors of metalloproteases of the extracellular matrix, the inhibitors of farnesyltransferase, and the use of anti-angiogenic treatment. MLA is supported by grant 01/9563 from the Instituto de Salud Carlos III, Madrid, Spain.     

磁性二氧化硅纳米微球对人源脐带间充质干细胞活性的影响

目的 探究磁性二氧化硅纳米微球作为一种干细胞表面的潜在标记物,对人脐带间充质干细胞(umbilical cord mesenchymal stem cells,UCMSCs)的表面干性标志物表达、细胞增殖和迁移能力等生物学活性的影响.方法 先采用溶剂热法和St?ber方法制备一种生物相容性高的磁性二氧化硅纳米微球,再通...     

慢性乙型肝炎患者肝再生酶变化与肝纤维化的相关研究

目的 探讨慢性乙型肝炎（下称乙肝）患者血清中β-N-乙酰氨基葡萄糖苷酶（NAG）、单胺氧化酶（MAO）、胆碱酯酶（CHE）的活性变化与肝纤维化的相关性。方法 采用速率法对健康对照组和慢性乙肝疾病组的NAG、MAO、CHE活性进行测定,应用肝穿刺活检对慢性乙肝患者肝组织的纤维化活动度进行观测。结果 慢性乙肝组各种酶的活性与健康对照组比较,差异有统计学意义（P〈0．01）。NAG、MAO与肝纤维化程度呈正相关,CHE与肝纤维化程度呈负相关。结论 NAG、MAO、CHE与肝纤维化程度相关性显著,可以作为检测肝纤维化程度的良好指标。     

CO2 Adsorption over 3d Transition-Metal Nanoclusters Supported on Pyridinic N3-Doped Graphene: A DFT Investigation

CO₂ adsorption on bare 3d transition-metal nanoclusters and 3d transition-metal nanoclusters supported on pyridinic N₃-doped graphene (PNG) was investigated by employing the density functional theory. First, the interaction of Co₁₃ and Cu₁₃ with PNG was analyzed by spin densities, interaction energies, charge transfers, and HUMO-LUMO gaps. According to the interaction energies, the Co₁₃ nanocluster was adsorbed more efficiently than Cu₁₃ on the PNG. The charge transfer indicated that the Co₁₃ nanocluster donated more charges to the PNG nanoflake than the Cu₁₃ nanocluster. The HUMO-LUMO gap calculations showed that the PNG improved the chemical reactivity of both Co₁₃ and Cu₁₃ nanoclusters. When the CO₂ was adsorbed on the bare 3d transition-metal nanoclusters and 3d transition-metal nanoclusters supported on the PNG, it experienced a bond elongation and angle bending in both systems. In addition, the charge transfer from the nanoclusters to the CO₂ molecule was observed. This study proved that Co₁₃/PNG and Cu₁₃/PNG composites are adequate candidates for CO₂ adsorption and activation.     

Endoplasmic Stress Affects the Coinfection of Leishmania Amazonensis and the Phlebovirus (Bunyaviridae) Icoaraci

Viral coinfections can modulate the severity of parasitic diseases, such as human cutaneous leishmaniasis. Leishmania parasites infect thousands of people worldwide and cause from single cutaneous self-healing lesions to massive mucosal destructive lesions. The transmission to vertebrates requires the bite of Phlebotomine sandflies, which can also transmit Phlebovirus. We have demonstrated that Leishmania infection requires and triggers the Endoplasmic stress (ER stress) response in infected macrophages. In the present paper, we tested the hypothesis that ER stress is increased and required for the aggravation of Leishmania infection due to coinfection with Phlebovirus. We demonstrated that Phlebovirus Icoaraci induces the ER stress program in macrophages mediated by the branches IRE/XBP1 and PERK/ATF4. The coinfection with L. amazonensis potentiates and sustains the ER stress, and the inhibition of IRE1α or PERK results in poor viral replication and decreased parasite load in macrophages. Importantly, we observed an increase in viral replication during the coinfection with Leishmania. Our results demonstrated the role of ER stress branches IRE1/XBP1 and PERK/ATF4 in the synergic effect on the Leishmania increased load during Phlebovirus coinfection and suggests that Leishmania infection can also increase the replication of Phlebovirus in macrophages.     

HIV screening and linkage to care in a health department in Valencia,Spain: Lessons learned from a healthcare quality improvement project

Spain’s rate of new human immunodeficiency virus (HIV) diagnoses exceeds that of the European Economic Area average (8.6 vs 5.6:100,000 in 2018). The country has failed to meet the first of United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV control by 2020, with 87.0% of people living with HIV knowing their status, and late presentation rates of 47.6% and 51.5% country-wide and in the Valencian autonomous community, respectively. Advancing screening and linkage to care (SLTC) practices is necessary to effectively control the epidemic. The Valencia Viral Screening (CRIVALVIR) project adopted the TEST model for opportunistic and systematic HIV SLTC in individuals aged 18 to 80 who required blood work for any purpose, as of February 2019. SLTC was integrated into routine clinical workflow across primary care centers serving a population of 360,000 people in Valencia, Spain. Our project successfully upscaled total HIV testing by 194% to over 32,000 patients tested in 14 months. We found an overall prevalence of 0.13% (0.08–0.21) among those screened per protocol (n = 13,061), with foreign-born citizens presenting a 12.5 times significantly higher likelihood of acquiring HIV (95% confidence interval 4.63–33.96, P < .0001). We improved late presentation by 18.2 percentage points and prevented an estimated 58 to 70 new secondary infections. HIV screening of the general population in primary care is an effective strategy for achieving timely diagnosis and preventing new infections. Opportunistic, systematic, opt-out approaches are essential to control the HIV epidemic.     

蕲蛇抗栓酶注射液稳定性的研究

为获取对蕲蛇抗栓酶(acutobin)注射液的酶活有保护作用且使制剂稳定的保护剂配方，本实验设计了7个单方及四组正交实验共16个保护剂处方．以加入保护剂的蕲蛇抗栓酶为样品，未加保护剂的为空白对照．在37℃温度加速实验下，间隔一定时间观测蕲蛇抗栓酶制剂的酶活及澄明度的变化。结果，单方氨基酸和小肽类的加入使酶活力保存率提高，而多元醇类的加入使澄明度得到改善；复方保护剂的加入对蕲蛇抗栓酶的保护作用不明显。     

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??OBJECTIVE To investigate the influencing mechanism of the particle size of hydroxypropyl methylcellulose (HPMC) on the release behavior of nifedipine from a sustained-release tablet system based on the compaction properties of HPMC. METHODS The compaction properties of HPMC K4M of different particle sizes were determined. Hydrophilic matrix sustained-release tablets were prepared using nifedipine as the active ingredient and HPMC K4M as a hydrophilic matrix former. The effect of compaction properties of HPMC K4M on the porosity, release, and other properties of nifedipine hydrophilic matrix sustained-release tablets were also studied. RESULTS The decrease of the particle size of HPMC K4M resulted in higher bulk density, tap density, compressibility index, and tensile strength and smaller elastic recovery of HPMC K4M, which all led to the decrease of thickness and porosity and the increase of HPMC concentration per unit volume of nifedipine hydrophilic matrix sustained-release tablets. These factors resulted in faster gelation rate of nifedipine sustained-release tablets and decreased water ingress and polymer swelling, so the release of nifedipine from the delivery system was prolonged. CONCLUSION The obviously different compaction properties of HPMC of different particle sizes influence the porosity and gelation rate and then the release of hydrophilic matrix nifedipine sustained-release tablets.     

桂枝饮片标准汤剂质量标准研究

目的制备桂枝饮片标准汤剂,并进行质量标准研究。方法依照标准汤剂的制备要求,制备15批桂枝饮片标准汤剂,以肉桂酸作为定量检测指标,计算转移率与出膏率,并建立其HPLC指纹图谱分析方法。结果通过对15批桂枝标准汤剂进行测定,肉桂酸转移率为56.93%~94.06%,出膏率为3.30%~9.40%;并用中药色谱指纹图谱相似度评价系统(2012A)软件进行指纹图谱分析,标定了9个共有峰,确认4个,分别为原茶儿酸(1号峰)、香豆素(4号峰)、肉桂酸(6号峰)、桂皮醛(7号峰)。对15批桂枝饮片标准汤剂分别进行了相似度评价,其相似度均高于0.95。结论建立了桂枝饮片标准汤剂指纹图谱,该方法精密度、稳定性和重复性良好,具有一定的鉴别意义,可为桂枝配方颗粒的质量控制提供参考。