Using the Lorenz curve to assess the feasibility of targeted screening for esophageal adenocarcinoma

Swedish Research CouncilSwedish Cancer SocietyAccepte

A possible link between famine exposure in early life and future risk of gastrointestinal cancers : implications from age-period-cohort analysis

The Chinese famine in 1958-1962 was one of the worst in human history, but its potential influence on cancer risks is uncertain. Using cancer incidence data in Shanghai, China, during 1983-2007, we calculated age-specific incidence rates of gastrointestinal cancers in birth cohorts exposed to the Chinese famine in different periods of life and a non-exposed reference cohort. Age-period-cohort regressions estimated the overall relative risks of gastrointestinal cancers in each birth cohort. A total of 212,098 new cases of gastrointestinal cancer were identified during the study period (129,233 males and 82,865 females), among whom 18,146 had esophageal cancer, 71 ,011 gastric cancer, 55,864 colorectal cancer, 42,751 liver cancer, 9,382 gallbladder cancer, and 14,944 had pancreatic cancer. The risk of esophageal, gastric, colorectal, and liver cancers was higher in cohorts exposed to the Chinese famine in early life than in the reference cohort, except for esophageal cancer in women. The risk of esophageal, liver, and colorectal cancers was particularly high in men exposed to famine during early childhood (0-9 years). There were no clear associations between famine exposure and the risk of pancreatic or gallbladder cancer. This study suggests an increased risk of esophageal, gastric, liver, and colorectal cancers associated with childhood exposure to the Chinese famine. These findings indicate a need for further investigations confirming the results and identifying the underlying mechanisms.Swedish Research Council, Swedish Cancer SocietyAccepte

Global time trends in the incidence of esophageal squamous cell carcinoma

Background & Aims: Esophageal squamous cell carcinoma (ESCC) is the dominant histological type of esophageal cancer worldwide (90%). We aimed to provide an update of the global temporal trends in the incidence of ESCC. Methods: Incidence data for ESCC were collected from 30 well-established cancer registries from 20 countries in Europe, Northern America, Australia, or Asia in 1970-2015. Time trends in annual age-standardized incidence rates of ESCC were assessed using joinpoint analysis and log-linear regression. Age-period-cohort analysis was used to estimate the influence of age, calendar-period, and birth-cohort on the observed time trends in incidence. Results: The age-standardized incidence rates of ESCC varied more than 8-fold in men and 7-fold in women across populations. In 2012, the highest rate in men was observed in Japan, Nagasaki (9.7/100 000 person-years) and women in Scotland (2.7/100 000 person-years). In men, the incidence decreased globally during the study period, as well as during the last few years. In women, the incidence increased in Japan (3 regions), the Netherlands, New Zealand, Norway, and Switzerland, while it was stable or decreased in other populations. Among ethnical groups in the United States, black men and women had more pronounced decreases in incidence than other groups. Generally, birth-cohort effects were stronger determinants of incidence trends than calendar-period effects. Conclusions: In men, the global ESCC incidence has decreased over time. In women, the incidence trends vary across populations, and the rates have increased in some countries. Changes in the prevalence of tobacco smoking and alcohol consumption may have contributed to these time trends.The Swedish Research Council (521-2014-2536)The Swedish Cancer Society (CAN 2015/460)Publishe

Smoking cessation and risk of esophageal cancer by histological type : systematic review and meta-analysis

Background Tobacco smoking strongly increases risk of esophageal squamous cell carcinoma and moderately increases risk of esophageal adenocarcinoma. How smoking cessation influences esophageal cancer risk across histological subtypes, time latencies, and geographic regions is not clear. Methods Studies were systematically searched on Medline, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. Pooled estimates of risk ratios (RRs) were derived using a random effects model. Cochran’s Q test and I2 statistic were used to detect heterogeneity. Results Among 15 009 studies, 52 fulfilled the inclusion criteria. Using nonsmokers as a reference, risk of esophageal squamous cell carcinoma was lower among former smokers (RR = 2.05, 95% confidence interval [CI] = 1.71 to 2.45) than among current smokers (RR = 4.18, 95% CI = 3.42 to 5.12). Compared with current smokers, a strong risk reduction was evident after five or more years (RR = 0.59, 95% CI = 0.47 to 0.75), and became stronger after 10 or more years (RR = 0.42, 95% CI = 0.34 to 0.51) and 20 or more years (RR = 0.34, 95% CI = 0.25 to 0.47) following smoking cessation. The risk reduction was strong in Western populations, while weak in Asian populations. Using nonsmokers as reference, the risk of esophageal adenocarcinoma was only slightly lower among former smokers (RR = 1.66, 95% CI = 1.48 to 1.85) than among current smokers (RR = 2.34, 95% CI = 2.04 to 2.69). The risk of esophageal adenocarcinoma did not show any clear reduction over time after smoking cessation, with a risk ratio of 0.72 (95% CI = 0.52 to 1.01) 20 or more years after smoking cessation, compared with current smokers. Conclusions Smoking cessation time-dependently decreases risk of esophageal squamous cell carcinoma, particularly in Western populations, while it has limited influence on the risk of esophageal adenocarcinoma.Swedish Cancer SocietySwedish Research CouncilAccepte

Association between metformin use and risk of esophageal squamous cell carcinoma in a population-based cohort study

Objectives: Esophageal cancer is a highly fatal malignant neoplasm, with two etiologically different histological types. A large prospective study is expected to elucidate the specific risk of the 90% subtype of esophageal cancer, esophageal squamous cell carcinoma, with metformin therapy. This study aims to determine the association between metformin use and incident esophageal squamous cell carcinoma risk. Methods: This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015. Among 8.4 million participants identified in the cohort, 411,603 (5%) were metformin users. The users were compared with 10 times as many frequency-matched non-users of metformin (n=4,116,030) by age and sex. Metformin use was treated as a time-varying variate and multivariable cause-specific proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for esophageal squamous cell carcinoma, adjusted for age, sex, calendar year, residence area, tobacco smoking, alcohol overconsumption, and use of non-steroidal anti-inflammatory drugs or statins. Results: The incidence rates of esophageal squamous cell carcinoma were 3.5 per 100,000 person-years among the metformin users and 5.3 per 100,000 person-years in the non-users. Metformin users overall were at a decreased risk of esophageal squamous cell carcinoma compared with non-users (HR 0.68, 95% CI 0.54-0.85). The decrease in risk was more pronounced in new metformin users (HR 0.44, 95% CI 0.28-0.64) and participants aged 60-69 years (HR 0.45, 95% CI 0.31-0.66). Conclusions: Metformin use decreases the risk of developing esophageal squamous cell carcinoma.Swedish Research CouncilSwedish Cancer SocietyUnited European Research PrizeManuscrip

Family caregiver’s willingness to care from the perspective of altruism

ObjectivesThe willingness of family members to take care of older relatives directly affects the quality of life of disabled older adults, so it is necessary to understand the status quo of willingness to care and its influencing factors. This has been extensively studied in other countries, but, it is rarely studied in China. Based on the theory of altruism, employing a unique sample from Shanghai, China in 2017 and 2022, we attempt to reveal the influencing factors of the care willingness of family caregivers during the transition period.MethodsTo measure caregiver burden and functional disability of the care recipient, we employ the Zarit Burden Interview (ZBI) and the Barthel Index, respectively. Then we utilized the ordinary least squares (OLS) methodology and estimated four regression models. Models 1, 2, and 3 examined the impact of the variables of the caregiver burden, responsibility and love, and the quality of the caregiver-caregiver recipient relationship, respectively, on family caregivers’ willingness to care. Model 4 was the full model. To testify whether the caregiver burden is likely to act as a mediator, path analysis was used, and the path was adjusted and verified.ResultsAccording to the survey, in Shanghai, only half of the caregivers had a very high care willingness to care for disabled older relatives, while nearly one-tenth of the caregivers had a low willingness. It was the caregiver burden rather than the functional disability of older adults that harms family caregivers’ willingness to care. Responsibility and caring out of love were positively related to care willingness. Relationship quality was the most important influencing factor, explaining 10.2% of the variance in care willingness. Path analysis demonstrated that responsibility, caring out of love, and relationship quality directly and through the mediation of caregiver burden indirectly affected care willingness.ConclusionOur results revealed that reciprocal altruism presented by the quality of the caregiver-care recipient relationship had a significantly positive impact on family caregivers’ willingness to care. In addition, the caregiver burden was found not only directly affected care willingness, but also acted as a mediator. To promote the perfection of laws and policies, comprehensive samples of different types of cities should be included and the measurement of key variables could be further improved in future studies

Mechanism of supply chain coordination based on price discount with privacy protection in one-supplier-one-buyer system

It is of great economic significance to optimize the total cost and improve the performance of the supply chain. In this paper, we assume that the market demand is random, and the seller and the buyer share information and make decisions together. We analyze the optimal joint order quantity under probabilistic demand and design the quantity discount model and profit distribution mechanism. Under a certain quantity discount mechanism and profit distribution strategy, both the seller and the buyer can reduce costs. The quantity discount model and profit distribution mechanism designed require supply chain members to share information. In order to protect the privacy of members and improve the willingness of supply chain members to share information, we designed a privacy protection joint ordering policy protocol and privacy protection quantity discount policy based on Secure multiparty computation technology. Then, the joint ordering strategy, the privacy-preserving joint ordering strategy, and quantity discount protocol are numerically simulated. The numerical simulation results show that the privacy-preserving quantity discount coordination mechanism designed by us can reduce the cost of supply chain members to varying degrees and effectively protect the shared information of supply chain members. This work is helpful to the research of cost optimization of the system in complex supply chain systems

Modulation of polymorphonuclear neutrophil functions by astrocytes

<p>Abstract</p> <p>Background</p> <p>Neuroinflammation is a complex process involving cells from the immune system and the central nerve system (CNS). Polymorphonuclear neutrophils (PMN) are the most abundant class of white blood cells, and typically the first type of leukocyte recruited to sites of inflammation. In the CNS, astrocytes are the most abundant glial cell population and participate in the local innate immune response triggered by a variety of insults. In the present study, we investigated the impacts of astrocytes on PMN function.</p> <p>Methods</p> <p>Primary astrocyte cultures were derived from postnatal C57BL/6 mice and primary neutrophils were isolated from 8 to 12 weeks old C57BL/6 mice. PMNs respiratory burst was analyzed by H2DCFDA assay. For phagocytosis assay, neutrophils were incubated with FITC-labeled E. coli and the phagocytosis of E coli was determined by flow cytometer. PMNs degranulation was determined by myeloperoxidase assay. Cytokine expression was determined by real-time PCR. To determine the involvement of different signaling pathway, protein lysates were prepared and western blots were conducted to assess the activation of Akt, Erk1/2, and p38.</p> <p>Results</p> <p>Using ex vivo neutrophils and primary astrocyte cultures, our study demonstrated that astrocytes differentially regulate neutrophil functions, depending upon whether the interactions between the two cell types are direct or indirect. Upon direct cell-cell contact, astrocytes attenuate neutrophil apoptosis, respiratory bust, and degranulation, while enhancing neutrophil phagocytic capability and pro-inflammatory cytokine expression. Through indirect interaction with neutrophils, astrocytes attenuate apoptosis and enhance necrosis in neutrophils, augment neutrophil phagocytosis and respiratory burst, and inhibit neutrophil degranulation. In addition, astrocytes could augment Akt, Erk1/2, and p38 activation in neutrophils.</p> <p>Conclusions</p> <p>Astrocytes differentially regulate neutrophil functions through direct or indirect interactions between the two cell types. The diversified actions of astrocytes on neutrophils might provide protection against potential microbial infections given compromised blood-brain barrier integrity under certain neuropathological conditions. The complex actions of astrocytes on neutrophils could provide further insight to harness the inflammatory response to promote CNS repair.</p