Nuclear-targeted EGF receptor enhances proliferation and migration of human anaplastic thyroid cancer cells

Introduction: Epidermal growth factor (EGF) has various important physiological functions, which it exerts by binding to  the epidermal growth factor receptor (EGFR). Reports show that EGF expression is strongly correlated with the occurrence and development of many types of tumour. To date, however, the relationship between EGF/EGFR and the occurrence and development of thyroid carcinoma remains unclear. Material and methods: In the current study, we investigated this phenomenon using human anaplastic thyroid carcinoma cell lines (SUN-80). Results: The results indicated that EGF triggered the EGFR-mediated intracellular signalling pathway, including signal transducers and activators of transcription 1/3/5 (STAT1/3/5) and protein kinase B (AKT) in a time- and dose-dependent manner. In addition, results from EGF-induced EGFR internalization and co-localization analyses showed that clathrin, Rab5/7, and EEA1 play critical roles in the intracellular trafficking of EGF/EGFR. Interestingly, EGF triggered EGFR translocation into the nucleus, while nuclear-localized EGFR affected cell cycle distribution, thereby significantly promoting the ration of S phase. Overall, these findings indicated that nuclear EGFR exerts biological activity and physiological functions, including changing cell cycle, which in turn promotes proliferation and migration of SUN-80 cells. Conclusion: These findings lay a foundation for further explorations seeking to understand the biological effects of the EGF/EGFR system on the occurrence and development of thyroid cancer

Chicken IFI6 inhibits avian reovirus replication and affects related innate immune signaling pathways

Interferon-alpha inducible protein 6 (IFI6) is an important interferon-stimulated gene. To date, research on IFI6 has mainly focused on human malignant tumors, virus-related diseases and autoimmune diseases. Previous studies have shown that IFI6 plays an important role in antiviral, antiapoptotic and tumor-promoting cellular functions, but few studies have focused on the structure or function of avian IFI6. Avian reovirus (ARV) is an important virus that can exert immunosuppressive effects on poultry. Preliminary studies have shown that IFI6 expression is upregulated in various tissues and organs of specific-pathogen-free chickens infected with ARV, suggesting that IFI6 plays an important role in ARV infection. To analyze the function of avian IFI6, particularly in ARV infection, the chicken IFI6 gene was cloned, a bioinformatics analysis was conducted, and the roles of IFI6 in ARV replication and the innate immune response were investigated after the overexpression or knockdown of IFI6 in vitro. The results indicated that the molecular weight of the chicken IFI6 protein was approximately 11 kDa and that its structure was similar to that of the human IFI27L1 protein. A phylogenetic tree analysis of the IFI6 amino acid sequence revealed that the evolution of mammals and birds was clearly divided into two branches. The evolutionary history and homology of chickens are similar to those of other birds. Avian IFI6 localized to the cytoplasm and was abundantly expressed in the chicken lung, intestine, pancreas, liver, spleen, glandular stomach, thymus, bursa of Fabricius and trachea. Further studies demonstrated that IFI6 overexpression in DF-1 cells inhibited ARV replication and that the inhibition of IFI6 expression promoted ARV replication. After ARV infection, IFI6 modulated the expression of various innate immunity-related factors. Notably, the expression patterns of MAVS and IFI6 were similar, and the expression patterns of IRF1 and IFN-β were opposite to those of IFI6. The results of this study further advance the research on avian IFI6 and provide a theoretical basis for further research on the role of IFI6 in avian virus infection and innate immunity

Can Health Disparity Be Eliminated? The Role of Family Doctor Played in Shanghai, China

Background: Globally, the elimination of health disparity is a significant policy target. Primary health care has been implemented as a strategy to achieve this target in China for almost 10 years. This study examined whether family doctor (FD) policy in Shanghai contributed to eliminating health disparity as expected. Methods: System dynamics modeling was performed to construct and simulate a system of health disparity formation (business-as-usual (BAU) scenario, without any interventions), a system with FD intervention (FD scenario), and three other systems with supporting policies (Policy 1/Policy 2/Policy hybrid scenario) from 2013 to 2050. Health disparities were simulated in different scenarios, making it possible to compare the BAU results with those of FD intervention and with other policy interventions. Findings: System dynamics models showed that the FD policy would play a positive role in reducing health disparities in the initial stage, and medical price control—rather than health management—was the dominant mechanism. However, in this model, the health gap was projected to expand again around 2039. The model examined the introduction of two intervention policies, with findings showing that the policy focused on socioeconomic status improvement would be more effective in reducing health disparities, suggesting that socioeconomic status is the fundamental cause of these disparities. Conclusions: The results indicate that health disparities could be optimized, but not eliminated, as long as differences in socioeconomic status persists

Which Matters for Medical Utilization Equity under Universal Coverage: Insurance System, Region or SES

Background: China has achieved universal coverage, with a higher rate of 95% medical insurance. However, huge inequalities are concealed under universal coverage. This article aims to explore the medical insurance utilization disparities over different insurance schemes, regions, and socioeconomic statuses (SES). Methods: This study was based on an open-access dataset in 2010, 2012, 2014, and 2016. A longitudinal analysis and separate logistic models were performed. Results: Urban Employee Basic Medical Insurance (UEBMI) members had an outstanding advantage in specialist visiting over those on the Urban Resident Basic Medical Insurance Scheme (URBMI) (OR = 0.607, p < 0.001) and New Cooperative Medical System (NCMS) (OR = 0.262, p < 0.001). However, in terms of a doctor visiting if a person is sick, the odds of patients in the NCMS receiving a visit were 55.1% ((OR = 1.551; p < 0.05) higher than those on the UEBMI. Compared with west China, the odds of those in the north-east and east were 2.1% (p > 0.05) and 97.2% (OR = 1.972; p < 0.001) higher for seeking medical treatment if sick, and 10.8% (OR = 0.892; p < 0.01) and 42.7% lower (OR = 0.573; p < 0.001) for a specialist visiting. In terms of SES, for each unit of increase in the Standard International Occupational Prestige Scale (SIOPS), the odds of seeking medical treatment decreased by 4.3% (OR = 0.958; p < 0.05), and the odds of a specialist visiting increased by 17.1% (OR = 1.171; p < 0.001) for each unit of the annual income logarithm. Conclusions: NCMS members and residents in west China were in a disadvantage status in terms of access to specialists, though had a higher probability of medical care if sick. SES variables were positively correlated with a specialist visiting consistently. We suggest a further focus on healthcare quality in the west and rural areas

Factors associated with residents' contract behavior with family doctors in community health service centers: A longitudinal survey from China.

BackgroundChina adopted family doctor (FD) to help achieve "Healthy China 2030" through providing continuous, comprehensive, and life-cycle contract services. However, there is a disparity between actual and targeted FD use, as residents continue to visit specialists in large hospitals. The government implemented initiatives to improve residents' willingness to sign up with and visit their FDs. Factors that influence contract behavior are therefore significant for frontier policy research.MethodsTwo survey waves were conducted in Shanghai (2013 and 2016). The first wave included 2754 people and the second 1995 people. Exploratory factor analysis was used to synthesize "satisfaction" as a predictor of contract behavior. Pearson's chi-square, pooled and logistic regression models were used to estimate associations between influencing factors and contract behavior, and clarify variations in factors across the two waves.ResultsFour factors were extracted from 15 satisfaction items: "Treatment Environment," "Medical Technology," "Service Specification" and "Service Attitude". Consistent with descriptive analysis, longitudinal analysis showed sociodemographic characteristics (age, education, marital status, and hukou) were significant predictors of contract behavior. The odds ratio of non-communicable diseases (NCD) patients for contract behavior was 2.218 times that of residents without NCD. Contract behavior was positively correlated with awareness of FD services (OR = 21.674, 95%CI = 15.043-31.229), satisfaction with Service Attitude (OR = 1.210, 95%CI = 1.009-1.451), and visit compliance (OR = 1.959, 95%CI = 1.564-2.452). Over time, the odds ratios of the married, Shanghai hukou, NCD, and awareness of FD services declined from 0.456, 1.795, 2.492, 28.690 to 0.443, 1.678, 1.910 and 14.031 respectively, while those of age, and visit compliance increased from 1.027, 1.521 to 1.041 and 2.305 respectively. In 2016, an education-contract gradient had formed (the higher the education level, the higher probability of signing with a FD), whereas high school education had the highest odds ratio (OR = 1.163,95%CI = 0.740-1.827) in 2013. Service Attitude was the only significant satisfaction-related predictor (OR = 1.358, 95%CI = 1.001-1.842) in 2016, compared with "Treatment Environment" (OR = 1.224, 95%CI = 1.001-1.496) and "Service Specification" in 2013(OR = 1.270, 95%CI = 1.040-1.552).ConclusionsExcept for the socio-demographic variables, NCD, awareness of FD services, satisfaction and visit compliance were significant predictors of contract behavior with FDs. The effect of visit compliance had increased over time while NCD and awareness of FD services were losing impact over time. Significant satisfaction factors had also changed from "Treatment Environment" and "Service Specification" to "Service Attitude"

The Construction of an Evaluation Index System for Operation of Fever Alertness Clinics Based on Grounded Theory

Background In March 2020, the Shanghai Municipal Health Commission proposed that fever alertness clinics should be set up in primary healthcare institutions (community health service centers) to deal with multi-site sporadic outbreaks by the principle of local emergency disposal combined with standardized and regular outbreak control. Objective To explore and construct a comprehensive and standardized evaluation index system for the operation of fever alertness clinics. Methods Two rounds of semi-structured in-depth interviews were conducted with 10 staff from three fever alertness clinics in downtown, suburban, and peri urban locations of Shanghai, respectively, using a purposive sampling method from January to April 2021. Raw data were obtained, interview materials were collated with the aid of the ROST CM6 software, and paradigm analyses were conducted using the Charmaz constructing grounded theory. Using a purposive sampling method, 12 experts familiar with the operating characteristics of fever alertness clinics (fever alertness clinics managers, researchers from universities, scholars from related associations, health development institutes, etc.) were invited as consulting objects to answer the correspondence questionnaire for 2 rounds from May to June 2021, and the weighting of indicators at each level was determined by hierarchical analysis to check the logical consistency of indicators at all levels, the evaluation index system of operation of fever alertness clinics was finally formed. Results The evaluation index system for operation of fever alertness clinics, which was constructed based on the grounded theory, consisted of 5 primary indicators, 13 secondary indicators and 29 tertiary indicators. The effective recoveries rate of the two rounds of expert consultation questionnaires was 100.0%, the expert authority coefficient of the two rounds was all 0.81, Kendall's W coefficients were 0.265 (χ2=163.768, P<0.001) and 0.320 (χ2=130.323, P<0.001) , respectively. The final developed evaluation index system for operation of fever alertness clinics consisted of 5 primary indexes (functions and responsibilities, consulting room setting requirements, staffing, workflow and work specifications) , 13 secondary indexes and 25 tertiary indexes. The weights of the five primary indexes were 0.033 7, 0.056 4, 0.392 6, 0.377 8 and 0.139 5, respectively. The consistency ratio (CR) of indicators at all levels was 0.056 5、0.032 5、0.042 4 (<0.100 0) . Conclusion The application of grounded theory to the construction of evaluation index system for fever alertness clinics is highly operable, and the constructed evaluation index system has a certain scientific validity and application value. Follow up with the policy iterations, the evaluation index system can be further supplemented and improved with the aid of grounded theory

Comparing Regional Distribution Equity among Doctors in China before and after the 2009 Medical Reform Policy: A Data Analysis from 2002 to 2017

Background: Although China began implementing medical reforms in 2009 aimed at fair allocation of the regional distribution of doctors, little is known of their impact. This study analyzed the geographic distribution of doctors from 2002 to 2017. Methods: This study calculated the Gini coefficient and Theil index among doctors in the eastern, central, and western regions (Category 1) of China, and in urban and rural areas (Category 2). The statistical significance of fairness changes was analyzed using the Mann–Whitney U test. Results: The annual growth rates of the number of doctors for the periods from 2002 to 2009 and 2010 to 2017 were 2.38% and 4.44%. The Gini coefficients among Category 1 were lower than those in Category 2, and statistically decreased after the medical reforms (P < 0.01) but continued to increase in Category 2 (P = 0.463). In 2017, the Theil decomposition result of Category 1 was 74.33% for the between-group, and in Category 2, it was 95.22% for the within-group. Conclusions: The fairness among the regional distribution of doctors in Category 1 is now at a high level and is better than that before the reforms. While the fairness in Category 2 is worse than that before the reforms, it causes moderate inequality and is continually decreasing. Overall unfairness was found to be derived from the between-group

Prevalence of Met Needs for Contracted Family Doctor Services and Associated Factors in Young and Middle-aged Office Building Occupants

Background Shanghai is gradually expanding the supply of family doctor contract service to building functional communities, but the prevalence of met needs of such services in young and middle-aged office building occupants is still unknown, and relevant studies on the prevalence and associated factors could inform the development and improvement of policies regarding building-based family doctor services. Objective To explore the prevalence of met needs for contracted family doctor services and associated factors in young and middle-aged office building occupants. Methods A questionnaire survey was implemented from December 2019 to December 2020 in the setting of office buildings selected by typical sampling from Hongkou District, Pudong New District and Jing'an District of Shanghai. Among the young and middle-aged occupants (n=2 272, 18-59 years old) selected from the buildings by use of cluster random sampling to attend the survey, 1 137 with an experience of using contracted family doctor services were determined as the participants. The survey involved four aspects, including sociodemographic and economic characteristics, health status, understanding level of contracted family doctor services, and met needs of these services (containing essential and personalized service needs assessed using a 5-point Likert scale). Multinomial and ordinal Logistic regression was used to analyze factors associated with met needs of contracted family doctor services. Results The prevalence of having needs of essential family doctor services considerably/completely met was 39.61% (425/1 073). And that of having needs of personalized family doctor services considerably/completely met was 39.01% (419/1 074). Multinomial and ordinal Logistic regression analysis revealed that registered place of household (Shanghai or not), occupation, annual income, self-rated health, understanding of the "1+1+1" type of contracted family doctor services, level of trust in family doctors, and evaluation of family doctors' service capabilities were associated with met needs of essential family doctor services (P<0.05). Sex, annual income, chronic disease prevalence, understanding of the "1+1+1" type of contracted family doctor services and the composition of a family doctor team, as well as evaluation of family doctors' service capabilities were associated with met needs of personalized family doctor services (P<0.05) . Conclusion The prevalence of self-reported met needs of essential or personalized family doctor services in the young and middle-aged office building occupants was about 40%, which was associated with sociodemographic and economic characteristics, health status, understanding level of contracted family doctor services, and self-assessed family doctors' service capabilities. It is recommended to improve the publicity of the system of contracting family doctor services, customize personalized service plans according to the characteristics and differentiated needs of the population, improve the family doctor's service capabilities and enrich the services

Visual Analysis of Hotspots and Cutting-edge Trends of Community TCM Service Research in China in the Context of Healthy China

Background Community traditional Chinese medicine (TCM) service is an important step in promoting the construction of Healthy China. There are abundant academic research results in the field of community TCM service in China, but there is a lack of collation of these research results. Systematically sorting out the relevant literature in the field of community TCM service by using the method of bibliometrics can provide a macroscopic understanding of the research progress and hotspots in this field and reference for future research. Objective To sort out the hotspots and development trends of community TCM service research in China by using bibliometric methods. Methods On May 2 in 2022, CNKI, Wanfang Data Knowledge Service Platform and VIP were searched for relevant research literature on community TCM service research in China from January 2000 to April 2022. By using CiteSpace software, the visual analysis of the co-occurrence of authors included in the literature, keywords co-occurrence, clustering, timeline distribution, and burst terms were performed and the relevant graphs were plotted. Results A total of 1 440 papers were included, and the publication volume of community TCM services in China showed an overall increasing trend, with 75 papers (5.2%) published in 2000—2005, 382 papers (26.5%) in 2006—2011, and 983 papers (68.3%) in 2012—2022. The top three authors in the publication volume were Shi Yongxing (25 articles), Bao Yong (16 articles), and Liu Deng (14 articles). The top 5 high-frequency keywords in terms of centrality were "TCM" "Chinese medicine" "community" "general practitioner" and "general practice". The keyword clustering analysis formed 12 cluster labels, and the top three clusters by scale were "community" "TCM" and "general practitioner". The timeline distribution suggested that clusters such as "community" "TCM" "general practitioner" and "TCM nursing" were research hotspots in this field. From the perspective of burst terms, "family doctor" has the highest burst value (8.07), and "elderly people" "diabetes" "family doctor" "medical consortium" "general practice of TCM" and the "integrated medical care and elderly services" are future research directions. Conclusion The current status of community TCM service in China, development of TCM general practitioners and community TCM nurses, and the improvement of TCM service capabilities of community health care institutions are research hotspots. In the future, more attention will be paid to the digital compact TCM medical consortium based on the Internet platform and the contracted family doctor service model with the participation of TCM general practitioners, so as to better utilize the characteristics and advantages of community TCM services in integrated medical care and elderly services