DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal and tumor growth of cancer stem-like cells derived from non-small cell lung cancer.

BACKGROUND: CSLCs(Cancer stem cell-like cells), which are central to tumorigenesis, are intrinsically influenced by epigenetic modifications. This study aimed to elucidate the underlying mechanism involving the DNMT1/miR-152-3p/SOS1 axis in regulating the self-renewal and tumor growth of LCSLCs (lung cancer stem-like cells). MATERIALS AND METHODS: Target genes of miR-152-3p were predicted using TargetScan Human 8.0. Self-renewal and tumor growth of LCSLC were compared in suspension-cultured non-small cell lung cancer (NSCLC) cell lines H460 and A549 cell-derived globe cells. Functional effects of the DNMT1/miR-152-3p/SOS1 axis were assessed through gain-of-function experiments in vitro and in vivo. Additionally, luciferase reporter assays were employed to analyze the interaction among DNMT1, miR-152-3p, and SOS1. RESULTS: Our findings highlight a negative interaction between DNMT1 and miR-152-3p, resulting in reduced miR-152-3p level. This, in turn, leads to the alleviation of the inhibitory effect of miR-152-3p on the target gene SOS1, ultimately activating SOS1 and playing an essential role in self-renewal and tumor growth of LCSLC. However, the alteration of SOS1 does not affect DNMT1/miR-152-3p regulation. Therefore, it is reasonable to infer that the DNMT1/miR-152-3p negative feedback loop critically sustains self-renewal and tumor growth of LCSLC through SOS1. CONCLUSIONS: This study reveals a novel mechanism underpinning self-renewal and tumor growth of CSLC (cancer stem cell) in NSCLC and identifies potential therapeutic targets for NSCLC treatment.

Key takeaways from China's success in eliminating malaria: leveraging existing evidence for a malaria-free world.

Although the total number of malaria cases and fatalities have declined globally since 2010, there were still 241 million malaria cases identified across 85 countries and territories in 2020. As the global malaria eradication process accelerates, more countries have launched their own initiatives of elimination. Notably, China achieved this goal by 2021, ending thousands of years of endemic. Undoubtedly, tremendous experience and vital lessons have been accrued en route to the malaria-free goal in malaria-eliminated countries including China. To enhance prospects of a malaria-free world by bridging the key evidence from a malaria-eliminated country to the contexts of affected, this personal view highlights concerted commitments and universal investment in healthcare, improved surveillance and response system, constant capacity building, demand-oriented scientific research, and multiway cooperation, which have helped China to eliminate this ancient scourge. We discuss how these key takeaways could be leveraged to different contexts. We also argue the long-term challenges and barriers on the pathway to malaria elimination and underline the needs for consistent efforts to maintain zero indigenous cases and prevent re-introduction of malaria. Through concerted efforts from global collaboration, a malaria-free world can become a reality.

Seventy years' achievements of international cooperation by the National Institute of Parasitic Diseases at the Chinese Center for Disease Control and Prevention.

BACKGROUND: With the promotion of national control programs on parasitic and tropical diseases in China, the National Institute of Parasitic Diseases (NIPD), Chinese Center for Disease Control and Prevention has gained significant experience in the global health arena through international cooperation over the last seven decades allowing a multilateral impact in the elimination of major endemic diseases. METHODS: The achievements of NIPD since 1950 has been analyzed with emphasis on the various stages that started with research and control of the endemic parasitic and other tropical diseases at the national level and progressed via international cooperation into a global presence. RESULTS: The major achievements contributed by NIPD consist of (i) improving technical capability; (ii) promoting control and elimination of parasitic and tropical diseases; (iii) participating in global health governance and cooperation; and (iv) developing a cooperation model for technical assistance and global public health development. It is expected that NIPD's experience of international cooperation will be essential for the dissemination of China's successful experience in global health governance, emergency response and development, with focus on malaria and neglected tropical diseases such as schistosomiasis, soil-borne and food-borne helminthiases and echinococcosis. CONCLUSIONS: NIPD's new tasks will not only continue to promote national control of endemic parasitic infections and disease elimination programs in China, but also play a leading role in global health and disease elimination programs in the future.

From parasitic disease control to global health: New orientation of the National Institute of Parasitic Diseases, China CDC.

As the only specialized institution for research and control of parasitic diseases at the national level in China for almost 70 years, the National Institute of Parasitic Diseases (NIPD) at the Chinese Center for Disease Control and Prevention (China CDC) has been instrumental in supporting the remarkable progress from high prevalence to transmission interruption or low endemicity of several diseases, lymphatic filariasis, malaria and schistosomiasis in particular. This has taken place through technical guidance, emergency response and scientific research as well as providing technical service, education, training, health promotion and international cooperation. With China's increasing involvement in international cooperation and the increased risk for (re)emerging tropical diseases in mind, the Chinese Government designated in 2017 a new Chinese Center for Tropical Disease Research to NIPD. Responding to the expanded responsibilities, the institute is scaling up its activities in several ways: from parasitic diseases to the wider area of tropical diseases; from disease control to disease elimination; from biological research to policy evidences accumulation; and from public health to global health. Based on this new vision and China's previous accomplishments in the areas mentioned, the institute is in a position to move forward with respect to global health and equitable development according to the central principles of the United Nations' Sustainable Development Goals.

Malaria in China, 2011-2015: an observational study.

OBJECTIVE: To ascertain the trends and burden of malaria in China and the costs of interventions for 2011-2015. METHODS: We analysed the spatiotemporal and demographic features of locally transmitted and imported malaria cases using disaggregated surveillance data on malaria from 2011 to 2015, covering the range of dominant malaria vectors in China. The total and mean costs for malaria elimination were calculated by funding sources, interventions and population at risk. FINDINGS: A total of 17 745 malaria cases, including 123 deaths (0.7%), were reported in mainland China, with 15 840 (89%) being imported cases, mainly from Africa and south-east Asia. Almost all counties of China (2855/2858) had achieved their elimination goals by 2015, and locally transmitted cases dropped from 1469 cases in 2011 to 43 cases in 2015, mainly occurring in the regions bordering Myanmar where Anopheles minimus and An. dirus are the dominant vector species. A total of United States dollars (US$) 134.6 million was spent in efforts to eliminate malaria during 2011-2015, with US$ 57.2 million (43%) from the Global Fund to Fight AIDS, Tuberculosis and Malaria and US$ 77.3 million (57%) from the Chinese central government. The mean annual investment (US$ 27 million) per person at risk (574 million) was US$ 0.05 (standard deviation: 0.03). CONCLUSION: The locally transmitted malaria burden in China has decreased. The key challenge is to address the remaining local transmission, as well as to reduce imported cases from Africa and south-east Asia. Continued efforts and appropriate levels of investment are needed in the 2016-2020 period to achieve elimination.

Lessons on malaria control in the ethnic minority regions in Northern Myanmar along the China border, 2007-2014.

BACKGROUND: For many countries where malaria is endemic, the burden of malaria is high in border regions. In ethnic minority areas along the Myanmar-China border, residents have poor access to medical care for diagnosis and treatment, and there have been many malaria outbreaks in such areas. Since 2007, with the support of the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), a malaria control project was introduced to reduce the malaria burden in several ethnic minority regions. METHODS: A malaria control network was established during the period from 2007 to 2014. Multiple malaria interventions, including diagnosis, treatment, distribution of LLINs and health education, were conducted to improve the accessibility and quality of malaria control services for local residents. Annual cross-sectional surveys were conducted to evaluate intervention coverage and indicators of malaria transmission. RESULTS: In ethnic minority regions where a malaria control network was established, both the annual malaria incidence (19.1 per thousand per year, in 2009; 8.7, in 2014) and malaria prevalence (13.6 % in 2008; 0.43 % in 2014) decreased dramatically during the past 5-6 years. A total of 851 393 febrile patients were detected, 202 598 malaria cases (including confirmed cases and suspected cases) were treated, and 759 574 LLINs were delivered to populations at risk. Of households in 2012, 73.9 % had at least one ITNs/LLINs (vs. 28.3 %, in 2008), and 50.7 % of children less than 5 years and 50.3 % of pregnant women slept under LLINs the night prior to their visit. Additionally, malaria knowledge was improved in 68.4 % of residents. CONCLUSION: There has been great success in improving malaria control in these regions from 2007 to 2014. Malaria burdens have decreased, especially in KOK and WA. The continued maintenance of sustainable malaria control networks in these regions may be a long-term process, due to regional conflicts and the lack of funds, technology, and health workers. Furthermore, information and scientific support from the international community should be offered to these ethnic minority regions to uphold recent achievements.

Risk Assessment of Malaria Prevalence in Ludian, Yongshan, and Jinggu Counties, Yunnan Province, After 2014 Earthquake Disaster.

The objective of this study was to investigate malaria prevalence after the 2014 earthquakes in Ludian, Yongshan, and Jinggu counties, Yunnan Province, China. We collected and analyzed epidemiological data and made a risk assessment of transmission probability. From January 2005 to July 2015, 87 malaria cases were reported in the three counties, most of which (81.6%) occurred between 2005 and 2009, with five cases reported in Jinggu County between January 2014 and July 2015, of which one case was reported after the earthquake. In addition, no local transmission occurred in the three counties from 2010, and 95.5% of imported malaria occurred in patients who had returned from Myanmar. The townships of Lehong, Qingsheng, and Weiyuan were the main endemic areas in the three counties. The probability of malaria transmission in the three counties was low, but Jinggu County had a higher risk due to the existence of infected patients and an appropriate vector. With sporadic cases reported annually, close monitoring should continue to enhance early detection of a possible malaria outbreak.

Public awareness of malaria at the beginning of a national malaria elimination program in China.

INTRODUCTION: This study aimed to investigate the baseline level of malaria awareness in residents in 20 malaria-endemic provinces from October 2010 to January 2011 at the beginning of the implementation of the China National Malaria Elimination Programme (NMEP). METHODOLOGY: A structured questionnaire about basic malaria knowledge was administrated to residents in rural areas from 20 provinces, municipalities, and autonomous regions. RESULTS: A total of 182,085 residents no younger than 15 years of age took part in the cross-sectional investigation; 3,232 were excluded because of incomplete survey responses. Of the respondents, 56.86% were aware of malaria, 18.03% responded correctly to all five questions, and 5.57% answered all the questions incorrectly. Malaria awareness among different age groups was statistically significant (p < 0.001), males had a better understanding of malaria than did females (p < 0.001), and Type I counties had a better understanding than did Type II counties (p < 0.001). CONCLUSIONS: The level of malaria awareness was low among residents at the beginning of the NMEP, especially about malaria pathogenicity and preventive methods. Health education campaigns should be developed and implemented to increase the public perceptions about malaria prevention and treatment, and to promote malaria elimination in China.

Historical patterns of malaria transmission in China.

The historical patterns of malaria transmission in the People's Republic of China from 1949 to 2010 are presented in this chapter to illustrate the changes in epidemiological features and malaria burden during five decades. A significant reduction of malaria incidence has resulted in initiation of a national malaria elimination programme. However, challenges in malaria elimination have been identified. Foci (or hot spots) have occurred in unstable transmission areas, indicating an urgent need for strengthened surveillance and response in the transition stage from control to elimination.

Feasibility and roadmap analysis for malaria elimination in China.

To understand the current status of the malaria control programme at the county level in accordance with the criteria of the World Health Organisation, the gaps and feasibility of malaria elimination at the county and national levels were analysed based on three kinds of indicators: transmission capacity, capacity of the professional team, and the intensity of intervention. Finally, a roadmap for national malaria elimination in the People's Republic of China is proposed based on the results of a feasibility assessment at the national level.

Transition from control to elimination: impact of the 10-year global fund project on malaria control and elimination in China.

The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) supported a project on the control and elimination of malaria in People's Republic of China which was one of the biggest-scale international cooperation programmes to control malaria in the country during the past 10 years. The project promoted the effective implementation of the Chinese national malaria control programme. On the basis of epidemiologic data, an overview of the project activities and key performance indicators, the overall impact of the GFATM project was evaluated. We also reviewed relevant programme features including technological and management approaches, with a focus on best practice, innovations in implementation and the introduction of international standards. Last, we summarised the multi-stakeholder cooperation mechanism and comments on its sustainability in the post-GFATM period. Recommendations for the future management of the Chinese national malaria elimination programme are put forward after considering the challenges, shortcomings and lessons learnt during the implementation of the GFATM project in China to sustain past achievements and foster the attainment of the ultimate goal of malaria elimination for the country.

China-Africa cooperation initiatives in malaria control and elimination.

Malaria has affected human health globally with a significant burden of disease, and also has impeded social and economic development in the areas where it is present. In Africa, many countries have faced serious challenges in controlling malaria, in part due to major limitations in public health systems and primary health care infrastructure. Although China is a developing country, a set of control strategies and measures in different local settings have been implemented successfully by the National Malaria Control Programme over the last 60 years, with a low cost of investment. It is expected that Chinese experience may benefit malaria control in Africa. This review will address the importance and possibility of China-Africa collaboration in control of malaria in targeted African countries, as well as how to proceed toward the goal of elimination where this is technically feasible.

Malaria baseline survey in four special regions of northern Myanmar near China: a cross-sectional study.

BACKGROUND: Epidemiological data in the border area of the northern Myanmar near China are either of little accuracy or sparse of information, due to the poor public health system in these areas, and malaria cases may be severely underestimated. This study aimed to investigate malaria prevalence and health facilities for malaria services, and to provide the baseline information for malaria control in these areas. METHODS: A cluster, randomized, cross-sectional survey was conducted in four special regions of northern Myanmar, near China: 5,585 people were selected for a malaria prevalence survey and 1,618 households were selected for a mosquito net-owning survey. Meanwhile, a total of 97 health facilities were surveyed on their malaria services. The data were analysed and descriptive statistics were used. RESULTS: A total of 761 people were found positive through microscopy test, including 290 people for Plasmodium falciparum, 460 for Plasmodium vivax, two for Plasmodium malariae, and nine for mixed infection. The average prevalence of malaria infection was 13.6% (95% CI: 12.7-14.6%). There were significant differences of prevalence of malaria infection among the different regions (P < 0.01); 38.1% (95% CI: 28.3-48.0%) of health facilities had malaria microscope examination service, and 35.1% (95% CI: 25.4-44.7%) of these had malaria treatment services, 23.7% (95% CI: 15.1-32.3%) had malaria outreach services. 28.3% (95% CI: 26.1-30.6%) of households owned one or more long-lasting insecticidal bed nets (LLINs). CONCLUSION: The prevalence of malaria infection was high in the four special regions of northern Myanmar, near China. Malaria services in health facilities in these areas were weak. ITNs/LLINs owning rate was also low. The cross-border cooperation mechanism should be further strengthened to share the epidemical data about malaria, support technical assistance, and conduct joint malaria control or elimination activities.

[Risk assessment for malaria elimination in P. R. China].

OBJECTIVE: To identify the risk area in China during the malaria elimination process, and provide the evidence for promotion of the national malaria elimination programme and implementation of elimination strategy. METHODS: Data collection was conducted in 24 endemic provinces in 2010, including data of transmission capacity, potential risk of malaria transmission and the capacity of health professional team at county level. Quantitative assessment of the malaria transmission risk as well as the capacity of health facilities were conducted based on the calculation of malaria transmission risk index (MTI) and health facilities capacity index (CI). ArcGIS 10.0 was used to develop the risk map based on the outcome of quantitative assessment. RESULTS: The data of transmission capacity, potential risk of transmission and the capacity of health professional team were collected from 2147 counties in 24 provinces. Based on MTI and CI calculated for each county, statistic results showed that about 40% of the counties were under the average level of both MTI and CI. The relationship among potential risk of transmission, the capacity of health professional team and malaria incidence were analyzed in three dimensions, and four types were categorized among 2147 counties. Type I (super-high risk area) counties (20) distributed in Yunnan (9), Guangxi (5), Henan (1), Hunan (1), Hebei (1), Sichuan (1), Chongqing (1), and Tibet (1). 17 counties were classified into type II (high risk area) area, distributed in Yunnan (3), Guangxi (2), Guizhou (2), Shaanxi (2), Guangdong (1), Jiangxi (1), Hubei (1), Sichuan (1), Gansu (1), Hebei (1), Fujian (1) and Tibet (1). A total of 170 type III (moderate risk area) counties distributed in 19 provinces including Yunnan (15), Guizhou (14), Hebei (14), Sichuan (13), Shanxi (10), Guangxi (9), Hunan (9), Anhui (9), Jiangsu (9), Shaanxi (9), Shandong (9), Chongqing (8), Gansu (8), Jiangxi (7), Henan (7), Fujian (6), Guangdong (5), Hubei (5), and Zhejiang (4). 1940 type IV (low risk area) counties distributed in 24 provinces. CONCLUSION: The distribution of four types of risk area for malaria elimination is identified in China.

[Determination of key interventions for the transition from control to elimination of malaria in China].

OBJECTIVE: To determine the key interventions transferring from the control to elimination of malaria in China so as to provide the basic information for achieving malaria elimination. METHODS: Based on the data collected from the document entitled of The National Annual Report on Schistosomiasis, Malaria and Echinococcosis, published by the National Institute of Parasitic Diseases of Chinese Center for Disease Control and Prevention, the malaria incidence and intervention data were selected only in the typical endemic provinces during the period of 2004-2010. The correlation between the incidence and interventions in the target provinces was analyzed based on the Panel Data Regression Model, and the key interventions were determined. RESULTS: Four provinces namely Anhui, Yunnan, Hainan and Henan were targeted with 87.56% of the national malaria figures from 2004 to 2010. When Y was given as vivax malaria incidence, X1 as the log of the number of historical cases receiving radical treatment in the pre-transmission stage (RTPT) (F = 14.53, P < 0.01, R2 = 0.72), X2 as the log of risk population receiving RTPR (F = 15.90, P < 0.01, R2 = 0.71) and X3 as the number of technicians trained in microscopy (F = 11.53, P < 0.01, R2 = 0.61), three space-fixed effect models were established respectively, and X1, X2, as well as X3 had negative effects on Y value. When Y was given as falciparum malaria incidence, X1 as the accumulated technicians trained in microscopy (F = 11.06, P < 0.01, R2 = 0.87), X2 as the log of technicians trained in entomology (F = 15.28, P < 0.01, R2 = 0.89) , two two-way (space and time) fixed effect models were established respectively, and both X1 and X2 had negative effects on Y value. CONCLUSION: RTPT among historical patients and at-risk populations as well as microscopy training influences the variation of vivax malaria incidence, while the significant interventions of microscopy training and vector control training indicate that the integrated measures with strengthened capacity in diagnosis and vector control are of importance in the control of falciparum malaria transmission.

Students' awareness of malaria at the beginning of national malaria elimination programme in China.

BACKGROUND: In the battle against malaria in China, the rate of elementary and high school students' awareness on malaria knowledge is an important index for malaria elimination, but only rare data is available. This study aimed to investigate the level of malaria awareness in students at elementary and high schools in malaria endemic areas of China, and to provide the baseline information for the malaria elimination. METHODS: This cross-sectional survey was conducted in 20 different malaria-endemic provinces in the first year of China's National Malaria Elimination Programme (NMEP). A structured questionnaire was administrated to students at elementary and high schools enrolled. A total of 44,519 questionnaires were effective while 1,220 were excluded because of incomplete survey responses. RESULTS: More than 60% of students were aware of malaria, but only 9,013 of them answered correctly to all five questions, and there were still 1,862 students unaware of malaria. There were significant differences of the awareness of malaria among different age groups, between male and female, between two different education levels. DISCUSSION: The study reveals that students at elementary and high school levels did not have adequate knowledge of malaria about biology, pathogenicity, transmitting vectors and preventive methods and so on at the beginning of NMEP in China. Further emphasis should be paid on health education campaigns in China to increase students' public awareness of malaria about vector control, treatment, prevention.

A potential threat to malaria elimination: extensive deltamethrin and DDT resistance to Anopheles sinensis from the malaria-endemic areas in China.

BACKGROUND: Insecticide resistance in malaria vectors is a growing concern in many countries and requires immediate attention because of the limited chemical arsenal available for vector control. There is lack of systematic and standard monitoring data of malaria vector resistance in the endemic areas, which is essential for the ambitious goal of malaria elimination programme of China. METHODS: In 2010, eight provinces from different malaria endemic region were selected for study areas. Bioassays were performed on F1 progeny of Anopheles sinensis reared from wild-caught females using the standard WHO susceptibility test with diagnostic concentrations of 0.25% deltamethrin and 4% DDT. RESULTS: For An. sinensis, the results indicated that exposure to 0.25% deltamethrin of F1 families with mortalities ranging from 5.96% to 64.54% and less than 80% mortality to DDT at the diagnostic concentration of 4% across the study areas. CONCLUSIONS: Anopheles sinensis was completely resistant to both deltamethrin and DDT, and resistance to pyrethroid has risen strikingly compared to that recorded during 1990s. The results highlight the importance of longitudinal insecticide resistance monitoring and the urgent need for a better understanding of the status of insecticide resistance in this region.

[Schistosomiasis transmission in areas where inhabitants migrated from outside embankment to new settlement].

OBJECTIVE: To observe the impact on the transmission of schistosomiasis in areas where the local inhabitants migrated from outside embankment to new settlements. METHODS: Two villages (Chenqiao and Qingjie) where the inhabitants had moved out and another 2 villages (Jiangzhou and Xiaohuang) disused for both inhabitants and cultivated land were selected for the investigation. Data on prevalence in human and domestic animals, and Oncomelania snail habitats, were collected. RESULTS: After moving from outside embankment to new settlements, the density of infested snails in Chenqiao and Qingjie decreased by 79.1% and 45.2% in 2005 compared with that in 2002, and the infection rate of snails decreased by 75.5% and 84.9%, respectively (P < 001). In Jiangzhou and Xiauhuang, the density of infested snails decreased by 100% and 74.9% in 2005 compared with that in 2002, and the infection rate of snails decreased by 100% and 40.0%, respectively (P > 0.05). In villages that only disused for inhabitants, the density and egg-positive rate of feces collected from the wild were higher than the other 2 villages. However, in villages disused for both inhabitants and cultivated land, the density and egg-positive rate of wild feces decreased gradually and no egg-positive feces was found in 2005. The prevalence of schistosomiasis in humans in villages disused only for inhabitants changed slightly from 2002 to 2005, but decreased gradually in villages disused for both inhabitants and cultivated land. Higher prevalence in cattle was found in villages disused only for inhabitants. Number of cattle reduced yearly and no cattle left in villages disused for both inhabitants and cultivated land in 2005. CONCLUSION: No significant change on the factors of schistosomiasis transmission has been found in villages disused only for inhabitants, but the transmission has been effectively controlled in villages disused for both inhabitants and cultivated land.