国医大师禤国维应用酸敛法治疗小儿特应性皮炎经验

介绍禤国维教授应用酸敛法治疗小儿特应性皮炎的临床经验。认为表虚兼有表燥是本病的基本病机特点,酸敛法可调理肺气、收敛心神、收敛肝气;治疗上注重散收并用,乌梅、五味子、白芍为其最常用的酸敛药,可调理肺、心、肝三脏的功能,并通过与辛散类药物(紫苏叶、防风、蝉蜕等)的配合,达到敛阴而不留邪、祛邪而不伤正的效果。并附验案1则。     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis

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Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

Guidelines of the French Society of Otorhinolaryngology-Head and Neck Surgery (SFORL) and the French Society of Audiology (SFA) for Speech-in-Noise Testing in Adults

ObjectivesThis document presents the fundamentals of speech audiometry in noise, general requirements for implementation and criteria for choice among the tests available in French according to the health-professional's needs.Material and methodsThe recommendations are based on a systematic analysis of the literature carried out by a multidisciplinary group of doctors, audiologists and audioprosthetists from all over France. They are graded A, B, C or expert opinion according to decreasing level of scientific evidence.ResultsEight tests of speech audiometry in noise can be used in France.ConclusionTo be complete, evaluation of hearing status requires testing understanding of speech in noise. The examination must begin with a minimum of two measurements familiarizing the subject with the test procedure. For initial diagnosis, adaptive procedures establishing the 50% speech reception threshold (SRT50) in noise are to be preferred in order to obtain a rapid and standardized measurement of perception of speech in noise. When the aim is to measure real-life speech comprehension, tests based on sentences, cocktail-party noise and free-field stimulation are to be preferred. Prosthetic gain is evaluated exclusively in free field. This is the only way to evaluate the contribution of binaurality and to measure perception in noise in an environment as close as possible to real life. In order to avoid acoustic interference in free field, at least five loudspeakers should be used, in particular for evaluating the effectiveness of directional microphones, CROS devices enabling sounds picked up in the damaged ear to be rerouted to the functional ear, or bimodal fitting (i.e., when hearing is enabled by two modalities: for example, hearing aid for one ear, cochlear implant for the other).