The earth land area is heterogeneous in terms of elevation; about 45% of its land area belongs to higher elevation with altitude above 500 meters compared to sea level. In most cases, oxygen concentration decreases as altitude increases. Thus, high-altitude hypoxic stress is commonly faced by residents in areas with an average elevation exceeding 2500 meters and those who have just entered the plateau. High-altitude hypoxia significantly affects advanced neurobehaviors including learning and memory (L&M). Hippocampus, the integration center of L&M, could be the most crucial target affected by high-altitude hypoxia exposure. Based on these points, this review thoroughly discussed the relationship between high-altitude hypoxia and L&M impairment, in terms of hippocampal neuron apoptosis and dysfunction, neuronal oxidative stress disorder, neurotransmitters and related receptors, and nerve cell energy metabolism disorder, which is of great significance to find potential targets for medical intervention. Studies illustrate that the mechanism of L&M damaged by high-altitude hypoxia should be further investigated based on the entire review of issues related to this topic.
Neurological disorders are often progressive and lead to disabilities with limited available therapies. Epidemiological evidence implicated that prolonged exposure to hypoxia leads to neurological damage and a plethora of complications. Neural stem cells (NSCs) are a promising tool for neurological damage therapy in terms of their unique properties. However, the literature on the outcome of NSCs exposed to severe hypoxia is scarce. In this study, we identified a responsive gene that reacts to multiple cellular stresses, marked cold-inducible RNA-binding protein (CIRBP), which could attenuate NSC apoptosis under hypoxic pressure. Interestingly, ISRIB, a small-molecule modulator of the PERK-ATF4 signaling pathway, could prevent the reduction and apoptosis of NSCs in two steps: enhancing the expression of CIRBP through the protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) axis. Taken together, CIRBP was found to be a critical factor that could protect NSCs against apoptosis induced by hypoxia, and ISRIB could be acted upstream of the axis and may be recruited as an open potential therapeutic strategy to prevent or treat hypoxia-induced brain hazards.
Background: The use of the term “rare disease” in China dated back to the 1960s, while clinical research on this disease category began in late 80s. In recent times, continuous release of policies and investment of funding were made on perspective of rare disease treatments and healthcare coverage, which positively encouraged the social understanding of this disease topic. Despite of the attention, it is limited to see studies describing the status of rare disease clinical research in Chinese population, not to say those originally organized and conducted by Chinese investigators. A clear understanding of the status and trend of clinical research in the field of rare disease gives supportive evidence for future political assessment and project management in a practical manner. Objective: The object of this study is to clarify the clinical research status and trend of rare diseases categorized in the “1st Catalogue of Rare Diseases (2018)” (“Catalogue” for short) in China. Based on analysis of the contents, we address the weaknesses presented in recent studies and explore the way for improvements. Methods: Entities of 121 rare diseases listed in the “Catalogue” were extracted from cross-references of paper manuals and network resources, and contextual association and mapping of the entities were made to constructed the terminology system of rare diseases. Registrations from ClinicalTrials.gov were retrieved based on both the diseases entities and the terminology system to ensure the formation of the original datasets was fairly accurate. Recorded programs were then organized in line with the list order of the “Catalogue”. Studies initiated by investigators outside of the People’s Republic of China were filter out and the cleaned dataset was used for analysis of research status and trends. Results: From January 1st 2001 to December 31st 2021, 848 rare disease clinical researches that categorized in the list of 121 rare diseases were found, and 43.63% of the total registrations were initiated and conducted by Chinese investigators. 47.93% of the disease types listed in the “Catalogue” were covered, making Hemophilia, Amyotrophic Latera Sclerosis, and Idiopathic Pulmonary Arterial Hypertension the frequently researched diseases. Interventional, single-centered and single-disease are predominant types of studies, and the spatial distributions were unevenly accumulated in 5 areas, including Beijing, Tianjin, Shanghai, Guangdong and Taiwan. 24.05% of records completed patients recruitment without delays and the result post rate was only 4.29% . Continuous rise in the number of rare disease clinical studies was seen, but more types of rare diseases, quality control of the registrations and innovative research strategies still needs to be promoted. Conclusion: This study describes the status and trends of rare disease clinical researches initiated in China and presents the characteristics of Chinese population in perspective of the “Catalogue”. The results can serve to support the adjustment of healthcare policy focus, rearrangement of medical resources, improvements of registered quality control, and development of innovative strategies for recruitment in the context of China.
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