Global, Regional, and National Burdens of Otitis Media From 1990 to 2019: A Population Based Study.

OBJECTIVES: Otitis media is one of the most important causes of hearing loss at an early age. Effective vaccination with the routine 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in 2000. It has been gradually replaced by the pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine or the higher-valent 13-valent PCV (PCV-13) since 2010. Data on the change in otitis media burden in recent years are sparse at the global, regional, and national levels. DESIGN: The Global Burden of Disease 2019 study was used to evaluate the prevalence, incidence, mortality, disability-adjusted life year (DALY) rates, and the average annual percentage changes (AAPCs) in otitis media in geographic populations worldwide from 1990 to 2019. These global trends were further analyzed by subgroup (age, sex, and sociodemographic index [SDI]). RESULTS: Globally, the all-age rate of prevalence (AAPC = -0.7, 95% confidence interval [CI] = -0.7 to -0.8), DALYs (AAPC = -1.0, 95% CI = -1.1 to -1.0), and mortality (AAPC = -6.8, 95% CI = -7.3 to -6.4) from otitis media decreased constantly between 1990 and 2019. The all-age rate of incidence decreased sharply between 2000 and 2009 with an AAPC of -1.2 (95% CI = -1.4 to -0.9) and continued the downward trend between 2010 and 2019 (AAPC = -0.2, 95% CI = -0.3 to -0.1). In 2019, children aged 1 to 4 years old had the highest incidence at 29,127.3 per 100,000 population, while young adults under 30 years old accounted for 91.3% of the incident cases. Individuals living in middle-SDI countries had the largest increase in the incidence of otitis media, with an AAPC of 0.3 (95% CI = 0.3 to 0.3) between 1990 and 2019. The incidence and DALYs from otitis media decreased with increasing SDI. Regionally, the largest increase in incidence was observed in high-income Asia Pacific, Eastern Europe, and Western Sub-Saharan Africa between 1990 and 2019. Nationally, the largest increase in the incidence of otitis media was observed in the Republic of Korea, with an AAPC of 0.8 (95% CI = 0.6 to 1.1) in the same time period. CONCLUSIONS: There have been successful previous endeavors to reduce DALYs and mortality attributed to otitis media on a global scale. The worldwide incidence of otitis media experienced a sharp decline following the introduction of PCV-7 in 2000, and this downward trend persisted in subsequent years with the adoption of PCV-13/pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine. Continual epidemiological surveillance of otitis media's global trends, pathogen distribution, and resistance patterns remains imperative.

BZW2 promotes the malignant progression of colorectal cancer via activating the ERK/MAPK pathway.

Colorectal cancer (CRC) is one of the most prevalent malignant solid cancers worldwide involving the dysregulation of multiple signaling molecules. However, the role and corresponding mechanism of basic leucine zipper and W2 domains 2 (BZW2) in CRC development, to our knowledge, has not been reported. We found BZW2 was overexpressed in human CRC tissues compared with that in paired adjacent colorectal samples. BZW2 overexpression was closely associated with tumor T stage (p = .030), metastatic lymph nodes (p = .037), TNM stage (p = .018) and the worse prognosis of CRC patients (p = .009). Moreover, BZW2 was an independent disadvantage prognostic factor (p = .031). BZW2 also showed an increased expression in different invasive CRC cell lines. Its silencing and overexpression diminished and increased cell proliferation, invasion, and migration in Colo205 and HCT116 cells via specifically activating of extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling. Moreover, ERK/MAPK inhibitor PD98059 reverse the enhancement of cell proliferation, invasion, and migration in BZW2 overexpressing HCT116 cells. BZW2 silencing also inhibited subcutaneous tumors growth and p-ERK expression in vivo. BZW2 promotes the malignant progression of CRC via activating ERK/MAPK signaling, which provided a promising gene target therapy for CRC.

The impact of global, regional, and national population ageing on disability-adjusted life years and deaths associated with diabetes during 1990-2019: A global decomposition analysis.

AIMS: To understanding the net regional, national, and economic effect of global population ageing on diabetes and its trends during 1990 and 2019 worldwide. METHODS: We employed a decomposition method to estimate the impact of population ageing on diabetes-related disability-adjusted life years (DALYs) and total deaths in 204 countries from 1990 to 2019 at the global, regional, and national level. This method separated the net effect of population ageing from population growth and changes in mortality. RESULTS: Globally, population ageing has become the major contributor to diabetes-related deaths since 2013. The increases in diabetes-related deaths attributed to population ageing exceeding the decreases in mortality change. Population ageing produced an additional 0.42 million diabetes-related deaths and 14.95 million DALYs from 1990 to 2019. At the regional level, population ageing is associated with the increases in diabetes-related deaths in 18 out of 22 regions. The highest increase in diabetes-related deaths attributed to population ageing occurred in men in East Asia (136.31%) and women in Central Latin America (118.58%). The proportion of diabetes-related deaths and DALYs attributable to population ageing showed a bell-shaped relationship with sociodemographic index (SDI) and peaked at high-middle-SDI countries. CONCLUSIONS: The decreases in diabetes-related deaths attributed to mortality change exceeded the increases attributed to population ageing between 1990 and 2019 globally and regionally. The diabetes-related deaths in high-middle-SDI countries were most impacted by population ageing.

GINS2 promotes EMT in pancreatic cancer via specifically stimulating ERK/MAPK signaling.

Go-Ichi-Ni-San 2 (GINS2), as a newly discovered oncogene, is overexpressed in several cancers. However, the specific role of GINS2 in the development of pancreatic cancer (PC), to our knowledge, is poorly understood. We systematically explored the potential role of GINS2 in epithelial-mesenchymal-transition (EMT)-stimulated PC in vitro and vivo. GINS2 was overexpressed in human PC specimens, which was positively associated with tumor size (P = 0.010), T stage (P = 0.006), vascular invasion (P = 0.037), and the poor prognosis (P = 0.004). Interestingly, a close correlation between GINS2, E-cadherin, and Vimentin (P = 0.014) was found in human PC specimens and cell lines that coordinately promoted the worse survival of PC patients (P = 0.009). GINS2 overexpression stimulated EMT in vitro, including promoting EMT-like cellular morphology, enhancing cell motility, and activating EMT and ERK/MAPK signal pathways. However, PD98059, a specific MEK1 inhibitor, reversed GINS2 overexpression-stimulated EMT in vitro. Conversely, GINS2 silencing inhibited EMT in PANC-1 cells, which was also rescued by GINS2-GFP. Moreover, GINS2 was colocalized and co-immunoprecipitated with ERK in GINS2 high-expression Miapaca-2 and PANC-1 cells, implying a tight interaction of GINS2 with ERK/MAPK signaling. Meanwhile, GINS2 overexpression inhibited distant liver metastases in vivo, following a tight association with EMT and ERK/MAPK signaling, which was reversed by MEK inhibitor. Overexpression of GINS2 contributes to advanced clinical stage of PC patient and promotes EMT in vitro and vivo via specifically activating ERK/MAPK signal pathway.

Angiopoietin-like protein 1 inhibits epithelial to mesenchymal transition in colorectal cancer cells via suppress Slug expression.

The role of ANGPTL1 in cancer development is still little known, especially in colorectal cancer (CRC). We investigated the clinical significance of ANGPTL1 expression in CRC tissues and its potential role in the progression of epithelial to mesenchymal transition (EMT) in CRC cells, which has not been reported to our knowledge. ANGPTL1 expression in CRC tissues was much lower that than in paired adjacent normal tissues by IHC, WB and qRT-PCR assays. ANGPTL1 positive expression was negatively associated with tumor size (P = 0.034), T stage (P = 0.015), lymph nodes metastasis (P = 0.045) and TNM stage (P = 0.009) and poor prognosis of CRC patients (P = 0.003). In vitro, ANGPTL1 showed decreasing expression in CRC cell lines from primary tumor to ascites metastasis. Meanwhile, ANGPTL1 silencing enhanced EMT in HCT116 cells followed with the increase of Slug, Fibronectin and Vimentin, the decrease of E-cad, and the enhancement of EMT-like cell morphology and cell invasion and migration. Low ANGPTL1 expression is closely associated with multiple clinical significance and prognosis of CRC patients. ANGPTL1 inhibits EMT of CRC cells via inhibiting E-cad suppressor Slug expression.

Roles of Carbonic Anhydrase IX in Development of Pancreatic Cancer.

The aim of this study was to study the effects of carbonic anhydrase IX (CA IX) towards the invasion and metastasis of pancreatic cancer. The expressions of CA IX in 58 cases of pancreatic cancer and paired paracancerous normal tissues, obtained from 2005 to 2012 in the first Affiliated Hospital of China Medical University, were detected, as well as its expressions in different pancreatic cancer cell lines, aiming to detect the impacts of CA IX silencing towards the invasion and metastasis of pancreatic cancer cells. The CA IX expressions in 58 pancreatic cancer cases were higher than those in the paired paracancerous normal tissues (P < 0.01), and positively correlated with the tumor size and the UICC staging UICC (P < 0.05), the multivariate analysis showed that the high expression of CA IX was the independent risk factor towards the prognosis of pancreatic cancer (P < 0.05). The CA IX was highly expressed in AxPC-1 and Miapaca-2, and the interference effects were significant. CA IX silencing could significantly inhibit the invasion and metastasis of AxPC-1 and Miapaca. We support a pro-tumor role of CA IX in the development and progression of pancreatic cancer.