AbstractBackground In recent years, headache diseases have spread throughout the world, causing great suffering and even severe disability to patients, and increasing the burden on health care systems. However, studies of specific regions are rare. The purpose of our study is to comprehensively analyze the current situation and trends of headache diseases in Asia between 1990 and 2021, to provide details of headache diseases in Asia, and to provide scientific data to support health development strategies. Methods Data from the Global Burden of Disease (GBD) 2021 database were used to calculate the incidence, prevalence and disability-adjusted life years (DALYs) of headache disorders in Asia from 1990 to 2021. Differences between years, ages, sexes and countries were also assessed, and we evaluated the correlation between epidemiological and sociodemographic indices (SDIs). Result In 2021, there were approximately 11,584,32824 cases of migraine in Asia. Meanwhile, there are now 2011612877 cases associated with tension-type headache (TTH) in Asia. Specifically, the age-standardized DALYs (ASDR) [607 cases per 100,000 people (95% UI: 70-1363)] for migraine were highest in East Asia, and the ASDR [422 cases per 100,000 people (95% UI: 86-938)] was lowest in high-income countries of the Asia-Pacific region. ASDR [67 cases per 100,000 people (95% UI: 18-236)] was highest for TTH in Central Asia and lowest for ASDR [43 cases per 100,000 people (95% UI: 13-141)] in East Asia. In addition, women are the key population for migraine and TTH prevalence. In Asia, there were negative and positive correlations between migraine and TTH and SDI, respectively. Conclusions Headache disorders pose a serious threat to the quality of life and safety of patients in Asia, increasing the burden on society, and this impact will continue to grow. Our findings suggest that active public awareness, improved guidelines, and better disease management are necessary to expand the public and healthcare system's attention to headache disorders, and thereby gain a greater advantage in combating the burden of headache disorders in the future.
A palladium-catalyzed domino cyclization/cycloisomerization reaction of alkyne-tethered carbamoyl chlorides with (E)-β-chloroenones is reported. This reaction proceeds via a syn-carbopalladation of the alkyne, followed by a vinyl-PdII-catalyzed cycloisomerization of the (E)-β-chloroenone cascade, which provides an efficient method to synthesize furan-linked methylene oxindoles. The reaction features stereodefined vinyl-PdII species, high to excellent 5-exo/6-endo selectivity, excellent Z/E selectivity, and the sequential formation of three bonds and bis-heterocycles. The strategy for the synthesis of furan-containing benzofurans has also been demonstrated.
Esophageal cancer (EC) is the sixth cause of cancer-related deaths and still is a significant public health problem globally. Nitrosamines exposure represents a major health concern increasing EC risks. Exploring the mechanisms induced by nitrosamines may contribute to the prevention and early detection of EC. However, the mechanism of nitrosamine carcinogenesis remains unclear. Ribonucleic acid export 1 (RAE1), has an important role in mediating diverse cancer types, but, to date, there has been no study for any functional role of RAE1 in esophageal carcinogenesis. Here, we successfully verified the nitrosamine-induced malignant transformation cell (MNNG-M) by xenograft tumor model, based on which it was found that RAE1 was upregulation in the early stage of nitrosamine-induced esophageal carcinogenesis and EC tissues. RAE1 knockdown led to severe blockade in G2/M phase and significant inhibition of proliferation of MNNG-M cells, whereas RAE1 overexpression had the opposite effect. In addition, peroxisome proliferator-activated receptor-alpha (PPARα), was demonstrated as a downstream target gene of RAE1, and its down-regulation reduced lipid accumulation, resulting in causing cells accumulation in the G2/M phase. Mechanistically, we found that RAE1 regulates the lipid metabolism by maintaining the stability of PPARα mRNA. Taken together, our study reveals that RAE1 promotes malignant transformation of human esophageal epithelial cells (Het-1A) by regulating PPARα-mediated lipid metabolism to affect cell cycle progression, and offers a new explanation of the mechanisms underlying esophageal carcinogenesis.
Herein, a palladium-catalyzed diastereoselective dearomatization/cross-coupling cyclization reaction between N-arylacyl indoles and (E)-β-chlorovinyl ketones is reported. Through this cyclization/cycloisomerization cascade, a series of furan-containing indolines were obtained in yields up to 95%. The reaction features readily accessible starting materials, benzyl Pd(II)-catalyzed cycloisomerization of (E)-β-chlorovinyl ketones, the sequential formation of three bonds and bis-heterocycles, and excellent diastereoselectivity. More importantly, the carbene–secondary benzyl migratory insertion is proven to be a critical process in the sequential cyclizations.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)