Evaluation of CHIP (iproplatin) in recurrent pediatric malignant solid tumors

CHIP (325 mg/M²), a second generation cisplatin derivative, was administered intravenously every 3 weeks to 85 pediatric patients with recurrent sarcomas (19), osteosarcomas (20), neuroblastoma (23), germ cell tumors (10), and other malignant tumors (7). Thirty-eight of them had been previously exposed to cisplatin. Partial remissions were only observed in 3 of 23 (13% SE=7%) patients having neuroblastoma. Severe thrombocytopenia (65%) and neutropenia (35%) were the dose limiting factors.     

Evidence for a glycerol pathway through aquaporin 1 (CHIP28) channels

Permeabilities to glycerol and small non-electrolytes of three Aquaporin 1 CHIP (AQP1) water channels were measured in AQP1 cRNA-injected Xenopus laevis oocytes and in human AQP1 channels reconstituted in proteoliposomes. By an osmotic swelling assay, significant increases of ethylene glycol, glycerol and 1,3-propanediol apparent permeability coefficients (P_solutes) were found in oocytes expressing human, rat and frog AQP1. p-Chloromercuribenzene sulphonate (PCMBS) and CuSO₄ inhibited, by 95% and 58% respectively, apparent glycerol permeability (P _gly) in oocytes expressing human AQP1. pCMBS inhibition was reversed by -mercaptoethanol and CuSO₄ inhibition was partly reversed by the Cu²⁺-binding peptide Gly-Gly-His. Tritiated glycerol uptakes confirmed the augmented P _gly value of AQP1 cRNA-injected oocytes. In contrast, no increases of urea, meso-erythritol, D- or L-threitol, xylitol and mannitol uptakes were detected. Stopped-flow light scattering experiments performed with human AQP1 proteoliposomes also revealed a much greater increase of P _gly than did those with protein-free liposomes; the initial rate of proteoliposomes also swelling was inhibited by 96.2% with HgCl₂ and by 72.5% with CuSO₄. In AQP1 cRNA-injected oocytes and in proteoliposomes, the value of the glycerol reflection coefficient was 0.74–0.80, indicating that water and glycerol share the same pathway. All these results provide strong evidence that water and certain small solutes permeate the AQP1 channels expressed at the surface of X. laevis oocytes or reconstituted in proteoliposomes. The urea exclusion suggests that the selectivity of the AQP1 channels not only depends on the size of the solutes but probably also on their flexibility and their ability to form H-bonds.     

Clinical Implications of Clonal Hematopoiesis

Clonal hematopoiesis (CH)—an expansion of blood cells derived from a single hematopoietic stem cell—is a defining feature of hematologic cancers, but recently CH was also found to be a frequent consequence of aging. When aging-associated CH results from acquisition of a somatic mutation in a driver gene associated with leukemia, and this mutation is present at a variant allele frequency of at least 0.02 (2%) yet the patient does not meet World Health Organization diagnostic criteria for a hematologic neoplasm, this state is termed clonal hematopoiesis of indeterminate potential (CHIP). CHIP is present in approximately 10% to 15% of people older than 70 years and more than 30% by age 85 years and represents a precursor state for neoplasia akin to monoclonal gammopathy of undetermined significance. Recently, CHIP was unexpectedly found to be an important risk factor for cardiovascular events, with accumulating evidence supporting a mechanism of accelerated atherogenesis as a result of vascular inflammation driven by clonally derived monocytes/macrophages. Risk factors for CHIP include aging, male sex, cigarette smoking, and a common germline variant in the telomere-associated gene TERT. Clonal hematopoiesis can also occur after cytotoxic chemotherapy or radiotherapy for a solid tumor, after hematopoietic stem cell transplant, in the context of aplastic anemia, or after induction chemotherapy for acute leukemia; in each setting, CH has distinct clinical implications. This review summarizes recent studies of CH and CHIP and outlines challenges in clinical management of affected patients.     

UBXN2A regulates nicotinic receptor degradation by modulating the E3 ligase activity of CHIP

Neuronal nicotinic acetylcholine receptors (nAChRs) containing the α3 subunit are known for their prominent role in normal ganglionic transmission while their involvement in the mechanisms underlying nicotine addiction and smoking-related disease has been emerging only in recent years. The amount of information available on the maturation and trafficking of α3-containing nAChRs is limited. We previously showed that UBXN2A is a p97 adaptor protein that facilitates the maturation and trafficking of α3-containing nAChRs. Further investigation of the mechanisms of UBXN2A actions revealed that the protein interacts with CHIP (carboxyl terminus of Hsc70 interacting protein), whose ubiquitin E3 ligase activity regulates the degradation of several disease-related proteins. We show that CHIP displays E3 ligase activity toward the α3 nAChR subunit and contributes to its ubiquitination and subsequent degradation. UBXN2A interferes with CHIP-mediated ubiquitination of α3 and protects the nicotinic receptor subunit from endoplasmic reticulum associated degradation (ERAD). UBXN2A also cross-talks with VCP/p97 and HSC70/HSP70 proteins in a complex where α3 is likely to be targeted by CHIP. Overall,we identify CHIP as an E3 ligase for α3 and UBXN2A as a protein that may efficiently regulate the stability of CHIP’s client substrates.     

An ultra-low-profile 0.85 mm Nano Hydro balloon to treat wire-crossable balloon-uncrossable lesions: A useful tool in CTO armamentarium

Balloon uncrossable lesions are commonly encountered during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). A sequential strategy and planning are required to tackle such lesions. We present a case series of severely calcified, device uncrossable lesions where the traditional strategies failed and an ultra-low-profile (0.85 mm) balloon was crucial to successful PCI. To our best knowledge, this is the first case series describing the use of this balloon in real world.     

CHIP 2021评测任务1概述:医学对话临床发现阴阳性判别任务

介绍基于医学对话的信息抽取相关研究现状,结合第七届中国健康信息处理会议组织的基于医学对话的临床发现阴阳性判别评测任务,阐述该任务评测数据集、评估指标,对比介绍前4名参赛者的方法并进行总结,以推进医疗人工智能领域的发展。     

医疗多模态信息抽取技术评测数据集概述

阐述医疗多模态信息抽取技术评测数据集的结构、构建方法、应用情况等,包括面向“基因-疾病”的关联语义挖掘数据集、中文医疗因果关系抽取数据集、医疗文本诊疗决策树抽取数据集、医疗材料要素提取数据集、临床诊断编码数据集,提出上述数据集有望为各种技术、算法以及系统的评估和实施提供有力支撑和参考。     

The state Children's Health Insurance Program (CHIP)

PURPOSE: To provide an overview of the Children's Health Insurance Program (CHIP), along with implications for practice as it applies to nurse practitioners. DATA SOURCES: Extensive review of the on-line and published literature on CHIP. CONCLUSIONS: Congress established CHIP in an effort to reduce the high number of uninsured children in America. Each state administers its own program and children who are under age 19, 200% below federal poverty levels, and ineligible for Medicaid may qualify. Even though CHIP has made health care possible for over 3 million children, there are still many obstacles that need to be overcome to ensure that access to healthcare is a reality for America's children. IMPLICATIONS FOR PRACTICE: Although CHIP has made healthcare accessible for many low income children, there are still hundreds of children left without health insurance. Many children who could qualify for CHIP remain without access to healthcare. Nurse practitioners have the opportunity to make healthcare a reality for children by becoming knowledgeable about this plan in order to refer patients to the program who are eligible and by advocating for future legislation that will ensure its long term success.