Polygenic risk-stratified screening for nasopharyngeal carcinoma in high-risk endemic areas of China: a cost-effectiveness study.

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization. Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79. Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women. Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China.

Application of Clustering Algorithm in Corporate Strategy and Risk.

With the increasing rise of market mechanism and corporate strategic management theory, many companies, especially listed companies, take diversification as their basic strategy. As the main source of power to promote the rapid development of China's economy, listed companies have also changed the way of China's economic development. It increases the speed of economic development, improves the level of economic technology, and accelerates the process of economic internationalization. Any economic behavior of an enterprise involves risks. As the development plan to mobilize the overall interests of the enterprise, the strategy will definitely involve the long-term development direction of the enterprise. Enterprise strategic deployments to strategic managements are affected by risk control elements. Strategic risk, as an unavoidable practical problem for enterprises, must be managed. Managing strategic risk is the key to effectively evaluate the management and control system. In order to solve this problem, this paper introduces a clustering algorithm, classifies the strategic risk of diversification, and analyzes its causes. For an in-depth analysis of the risks that diversification will face, this paper selects the case of the enterprise's diversification development to carry out the research. It conducts in-depth analysis and research on its basic situation, diversification strategy, dilemma, and behavior. The experimental results show that the financial leverage coefficients of the company in the four quarters are 24.64, 3.93, 104.71, and 6.59 respectively. From the numerical value, it can be concluded that the enterprise is in a high-risk state and the strategic risk status of the company can be accurately judged.

Burden, trends, and risk factors for breast cancer in China from 1990 to 2019 and its predictions until 2034: an up-to-date overview and comparison with those in Japan and South Korea.

BACKGROUND: The difference in epidemiological characteristics of breast cancer (BC) across countries is valuable for BC management and prevention. The study evaluated the up-to-date burden, trends, and risk factors of BC in China, Japan and South Korea during 1990-2019 and predicted the BC burden until 2034. METHODS: Data on incident cases, deaths, disability-adjusted life-years (DALYs) and age-standardized rate (ASR) of BC were extracted from the Global Burden of Disease Study 2019. Trend analysis and prediction until 2034 were conducted by estimated annual percentage change and a Bayesian age-period-cohort model, respectively. Besides, the attributable burden to BC risk factors was also estimated. RESULTS: In 2019, the number of BC incident cases, deaths and DALYs in China were 375,484, 96,306 and 2,957,453, respectively. The ASR of incidence increased, while that of death and DALYs decreased for Chinese females and Japanese and South Korean males during 1990-2019. High body-mass-index (BMI) was the largest contributor to Chinese female BC deaths and DALYs, while alcohol use was the greatest risk factor for Japanese and South Korean as well as Chinese males. The incident cases and deaths were expected to continue increase during 2020-2034 (except for Japanese female incident cases). CONCLUSIONS: China had the greatest burden of BC among the three countries. Incident cases and deaths of BC were projected to increase over the next 15 years in China, particularly among Chinese males. Effective prevention and management strategies are urgently necessary for BC control in China.

IL-27 signalling promotes adipocyte thermogenesis and energy expenditure.

Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3-6. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.

Global trends in incidence and mortality of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a rare malignancy with an extraordinarily skewed geographic distribution worldwide. Although decreasing trends in incidence and mortality of NPC have been sporadically reported in some high-risk areas, no comprehensive description of the global trends has ever been made. We accessed incidence (1970-2007) and mortality (1970-2013) data from multiple sources, with the main ones being the Cancer Incidence in Five Continents (CI5) series and the World Health Organization (WHO) cancer mortality database. During the entire period studied, age-standardized incidence rates (ASIRs) of NPC decreased significantly in southern and eastern Asia, north America and Nordic countries with average annual percent changes (AAPCs) of -0.9% to -5.4% in males and -1.1% to -4.1% in females. Declines in age-standardized mortality rates (ASMRs) are even more remarkable and extensive, with AAPCs varying from -0.9% and -0.8% to -3.7% and -6.5% in males and females, respectively. Decreasing trends in NPC incidence are probably due to tobacco control, changes in diets and economic development. Declines in mortality rates are the results of advancements in diagnostic and radiotherapy techniques, as well as decreased incidence rates.