Overview
Figure 1. Map of interviewers
In 2024, our Integrated Human Practices (IHP) initiated exploration in the emerging field of Reverse Cardio-oncology through the "Heartecho" project. IHP is integrated with the project throughout the entire process, promoting and enhancing each other. In the selection of the research domain , the proposition of cardiovascular diseases and tumors by cardiologists led us into the interdisciplinary realm. Literature review focused our attention on Reverse Cardio-oncology. Oncologists provided both empirical medical affirmation and evidence-based medical proof supported by the database. In the initial design stage of the project , through exchanges with clinical experts, we went through a transformation from coronary heart disease to the pathological process of atherosclerosis and then back to coronary heart disease. Through bioinformatics analysis, myocardial infarction was determined as the choice. During the project refinement phase, we discussed with professors and designed a two-arm AND gate LIRA detection system. In the implementation of the project , suggestions from scientific research experts aided in optimizing the technical points of experiments and models, facilitating the project's realization. Significantly, ethics was considered throughout the entire process. We consulted experts and lawyers to obtain approvals, enabling close communication with patient groups. For the final implementation of the project, we have embraced full-scale commercialization. Through extensive and meaningful interaction with all stakeholders, we have successfully achieved the closed loops. This not only showcases our commitment to the best IHP but also paves the way for a sustainable and impactful future in the field of Reverse Cardio-oncology (Figure 1).
Inspiration
Tune in to the world:
The World Health Organization's (WHO) 2024 World Health Statistics report highlights that Ischaemic heart disease remained the leading cause of global mortality in 2000, 2019, 2020, and 2021, which prompted us to focus on cardiovascular diseases (Figure 2). Through extensive literature reading, we are shocked to find that approximately 17.9 million people die from cardiovascular diseases annually, as reported by the WHO.
Figure 2. WHO 2024 World Health Statistics report
To better understand the real dilemma of cardiovascular disease patients, we decided to interview front-line clinicians working in this field. We consulted Prof. Huan Sun from the Department of Cardiology at the China-Japan Union Hospital of Jilin University (Figure 3). Professor Sun highlighted several high-risk factors for cardiovascular diseases, including smoking, diabetes, hyperlipidemia, and family history. Since our team is from the cancer biology laboratory, when we heard about smoking and family history, we associated it with cancer. Thus, Professor Sun put forward that cancer and its treatment can accelerate the progression of cardiovascular diseases, a phenomenon that has evolved into a mature research field known as Cardio-Oncology. Additionally, He mentioned that some patients with a previous history of cardiovascular diseases were found to have cancer during follow-up visits, and this situation deserves our attention. Armed with this information, we began to explore the potential link between cardiovascular diseases and the cancer.
Figure 3. Interview with Dr. Huan Sun
Through extensive literature review, we focused on the emerging field of Reverse Cardio-oncology, which reveals that cardiovascular diseases can indeed facilitate the onset and progression of cancer. By tracing relevant literature, we drew out the development of this field in a timeline manner (Figure 4). This discovery led us to turn our attention to oncology departments for further investigation to assess whether cancer patients have a history of cardiovascular diseases.
Figure 4. Development of Reverse Cardio-Oncology
We then interviewed Dr. Linlin Liu, Director of the Oncology Department at the China-Japan Union Hospital of Jilin University, and learned that many cancer patients have a history of cardiovascular disease (Figure 5). The affirmation of this fact sparked our interest in conducting further research in the intersection of these two health issues. In our in-depth discussion with Dr. Liu, we gained valuable insights, particularly regarding the investigation of the prevalence of cardiovascular diseases among cancer patients.
Next, Dr. Liu introduced us to the hospital's specialized disease databases, which contain detailed records of patients' treatment histories and provide valuable data support for conducting retrospective and prospective studies . These data resources not only can helped us identify more effective treatment methods but were also crucial in understanding the interaction between cancer and heart health. By leveraging these rich data resources, our project can explore the link between cancer and cardiovascular disease more deeply, ultimately providing scientific evidence for developing more targeted and effective interventions.
Figure 5. Interview with Dr. Linlin Liu
This interview not only deepened our understanding of the clinical realities faced by patients with both cancer and cardiovascular disease but also emphasized the key areas we should focus on as we advance the project. Dr. Liu's insights and recommendations have inspired us to further refine our project to better serve this vulnerable patient population and to contribute to the development of Reverse Cardio-oncology.
After selecting Reverse Cardio-oncology as our research focus, to spread the concepts of cardiac health to a broader group, including both students and faculty, our team participated in the Health Run event organized by Jilin University (Figure 6). During the event, we conducted interviews on campus to gain insights into the diverse forms of physical exercise among students and to explore the strong connection between physical activity and cardiac health. Through these interviews, we found that most students believed physical exercise could enhance various aspects of heart function. However, we also discovered that their knowledge of emergency measures and the prognosis of cardiovascular diseases was limited. This lack of awareness among college students highlights the importance of incorporating heart health education into our future outreach efforts, with the aim of raising public awareness of cardiovascular health.
Figure 6. The Heart Health Run interview
Subsequently, in order to obtain a reliable public sample and analyze public awareness of Reverse Cardio-oncology through specific survey data, we conducted the "Listening to the Heart - Heart Disease Survey" (Figure 7). Within one week, we collected 236 results. Among them, participants aged 18-25 and 36-55 accounted for about 90% and they were mainly students and office workers. Among all the participants, more than 90% were unaware of the potential link between cardiovascular diseases and cancer. This lack of awareness, combined with the fact that 34% of people think about the high costs of cancer screening and 37% of people consider the painful procedures of cancer screening, often led to cancer being detected only in its late stages. This survey result indicates that it is very necessary to raise the awareness of patients with cardiovascular diseases on early cancer screening. More importantly, this detection system should be less invasive and reasonably priced.
Figure 7. Listening to the Heart - Heart Disease Survey
At the Elderly Care and Health Expo, we had the opportunity to interview a lot of salesmen in pharmaceutical companies that specialized in various health-related products and services. During these interviews, we gained valuable insights into the current market trends and demands. They affirmed that there existed a notable market gap for cancer early screening kits of patients with cardiovascular diseases. This discovery highlighted the potential for innovation and development in this specific area of healthcare, presenting an opportunity for companies to fill this gap and make a positive impact on cancer prevention and early diagnosis (Figure 8).
Figure 8. The Elderly Care and Health Expo interview
After conducting detailed surveys and thorough considerations among university students, the public, and companies, we were inspired to create an early cancer screening kit to identify high-risk cancer patients among those who used to have cardiovascular diseases.
SWOT analysis for stakeholders
Understanding and addressing the interests of stakeholders is crucial to the success of our project. Stakeholders play a pivotal role in shaping the project's direction, influencing outcomes, and determining its overall impact. Their perspectives, needs, and concerns can significantly affect the project's success, making it essential to engage with them thoughtfully and strategically. By conducting a thorough analysis of the strengths, weaknesses, opportunities, and threats associated with each stakeholder group, the Heartecho project is better equipped to anticipate and address potential challenges, thereby optimizing the use of available resources to achieve its objectives. This comprehensive approach not only enhances our understanding of the project but also supports informed decision-making throughout its various phases (Figure 9).
Figure 9. Stakeholders SWOT analysis
Our SWOT analysis of stakeholders, including the public, experts, doctors, and corporations, revealed complementary relationships that help balance the limitations of individual groups. Recognizing this synergy, our next step is to engage with a broader range of stakeholders through interviews to gather more detailed feedback and additional insights. This approach will allow us to effectively meet the diverse needs of all involved and further optimize our project.
Consideration of ethics
Since our project is deeply intertwined with clinical practice, it is crucial that we prioritize ethical considerations. Understanding the critical role that ethics play in ensuring the well-being and rights of patients, we sought guidance from Prof. Yunsheng Dong, an expert in ethics from the School of Philosophy and Social Sciences at Jilin University (Figure 10). Prof. Dong stressed that ethical vigilance should be maintained at every stage of the project, from initial planning through to implementation and beyond. He reminded us that when working with vulnerable populations, such as specific patient groups, it is essential to prioritize ethical principles like respect for autonomy, non-maleficence, beneficence, and justice. These principles are not just theoretical but must be actively upheld in all interactions with patients and in every aspect of our research design.
Figure 10. Interview with Dr. Yunsheng Dong
Taking these insights to heart, we meticulously incorporated these ethical considerations into our project design. Our aim is to create a framework that not only advances scientific knowledge but also protects and respects the dignity and rights of every participant. By integrating these ethical guidelines, we hope to set a standard for responsible research that others can follow.
Expertise boosts project
Project Initial Design:
We aim to identify cardiovascular diseases and cancers that show a relatively strong correlation as indicated by epidemiological research. To deepen our understanding of the latest advancements in these fields, we actively participated in Cardio-Oncology Day and the 5th National Tumor Cardiology Publicity Week (Figure 11). During this academic conference, we learned that coronary heart disease is one of the most prevalent cardiovascular diseases. Coronary heart disease is caused by structural or functional abnormalities of the coronary arteries, leading to coronary artery stenosis or occlusion, with atherosclerosis being the most common cause of coronary heart disease[1]. Atherosclerosis, being an important fundamental pathological change in cardiovascular diseases, prompts us to shift from the exploration of clinical diseases to a focus on pathology. Atherosclerosis association with cancer still needs to be confirmed through literature review.
Figure 11. Cardio-Oncology Day and the 5th National Tumor Cardiology Publicity Week
Subsequently, we conducted an extensive literature review on the epidemiological studies of the association between atherosclerosis and cancer. An epidemiological study on cardiovascular diseases and cancer risks published in August 2023, JACC (J Am Coll Cardiol CardioOnc) showed that the cancer risk in patients with atherosclerotic cardiovascular disease (aCVD) is significantly higher than in those without cardiovascular disease (no CVD) and in those with non-atherosclerotic cardiovascular disease (na CVD). This study further analyzed the risk ratios of different cancer sub-types between aCVD and na CVD, and the results showed that, when directly comparing aCVD with na CVD, the risk of lung cancer, bladder cancer, colon cancer, and other cancers in aCVD was significantly higher than that in naCVD, with lung cancer risk being the highest[2]. Therefore, we began to focus on the association between atherosclerosis and lung cancer.
Not only is there macroscopic epidemiological evidence, but there is also collateral evidence in the literature on the common target of the relationship between atherosclerosis and lung cancer on a microscopic level. A study published in 2017 in The New England Journal of Medicine indicated that canakinumab, an IL-1βinhibitor, significantly reduced the recurrence of cardiovascular diseases, particularly those associated with atherosclerosis, in patients with cardiovascular diseases. This trial was known as the CANTOS trial[3]. However, researchers discovered that the incidence of lung cancer also decreased during the CANTOS trial. The researchers analyzed the effect of canakinumab on the incidence of lung cancer in patients with atherosclerosis, and the results showed that IL-1β inhibition significantly reduced the incidence of lung cancer in patients with atherosclerosis[4]. These two studies further demonstrate that atherosclerosis may promote the development and progression of lung cancer through certain mechanisms, providing deeper confirmation of the association between the two.
To gain a deeper understanding of the clinical front-line situation of atherosclerosis and to determine the feasibility of our project selection, we interviewed Dr. Beibei Du, the Associate Chief Physician of Cardiology at the China-Japan Union Hospital of Jilin University. Dr. Du is an expert member of the American College of Cardiology (FACC) and the International Cardio-Oncology Society (IC-OS) (Figure 12). He has made significant contributions to the field of Cardio-Oncology, specializing in the interventional treatment of complex coronary artery disease and the management of myocardial damage caused by targeted anti-cancer drugs.
Figure 12. Interview with Dr. Du
We consulted Dr. Du in detail about the clinical situation of atherosclerosis. Dr. Du pointed out that atherosclerosis is a stage in the development of vascular lesions. The process begins with endothelial dysfunction in the blood vessels, followed by the formation of atherosclerotic plaques. As these plaques grow, they can cause vascular blockages and narrowing, leading to various diseases. The most commonly affected target organs by atherosclerosis are the heart, brain, kidneys, and peripheral arteries, potentially leading to conditions such as myocardial infarction, cerebral infarction, renal insufficiency, and peripheral arterial occlusion or stenosis, which are categorized as specific diseases. From a scientific research perspective, focusing on pathological processes is conducive to the exploration of specific mechanisms. However, it is not practical enough if one wants to develop a screening kit that can be applied in clinical practice. Simply referring to "atherosclerosis" is too broad, and it's challenging to find patients categorized solely under this term.
Dr. Du also mentioned that cardiology departments focus more on coronary atherosclerotic heart disease because the symptoms in such patients are more pronounced, such as chest tightness, chest pain, shortness of breath, and cognitive disturbances, which are the symptoms that drive patients to seek medical attention . On the other hand, in cases of lower limb artery involvement, the presence of collateral circulation may mean that plaque formation does not affect mobility, so patients generally do not seek medical care.
The interview with Dr. Du has led us to narrow our research focus from the broad scope of atherosclerosis back to coronary atherosclerotic heart disease, and we were now ready to begin the next steps in our project design.
After deciding to use LIRA as a tool to detect miRNA as biomarker, we interviewed Dr. Daoyuan Si, Associate Chief Physician of Cardiology at the China-Japan Union Hospital of Jilin University, to seek his opinions on our project. Dr. Si is a member of the Heart Rhythm Society, with his primary research focus on post-myocardial infarction ventricular remodeling, arrhythmia, and endothelial dysfunction. He has been invited multiple times to deliver a lecture at the American Heart Association (AHA), American College of Cardiology (ACC), and Heart Rhythm Society (HRS) conferences.
We presented the preliminary design of our project to Dr. Si in detail. He suggested that while epidemiological surveys are a useful starting point, they are not sufficient for establishing the connection between heart disease and cancer. We should also conduct bioinformatic analyses to screen the biomarker miRNA we intend to detect, thereby better establishing the link between cardiovascular diseases and cancer.
During our bioinformatic analysis, we focused on both cardiovascular diseases (CVD) using GEO dataset and cancer using the TCGA dataset. Initially, we identified 294 different microRNAs from the TCGA database (Figure 13). Our goal was to determine the microRNAs were present in both CVD and cancer datasets, aiming to find biomarkers that could indicate cancer risk in patients already diagnosed with CVD.
Figure 13. Bioinformatic analysis
In the data analysis of coronary heart disease, there are relatively few databases to choose from. Moreover, the screened hsa-miR-187/185-3p is involved in fewer cancer types, while hsa-miR-16-2-3p is involved in more cancer types, but its expression fold is not at the forefront. The less-than-ideal data structure cannot sufficiently support us in selecting miRNAs with strong specificity. Therefore, we have shifted our thinking to other cardiovascular diseases in the field of Reverse Cardio-oncology. During our comparisons, we discovered that in the Myocardial Infarction (MI) dataset, miR-210-3p demonstrated better performance. Specifically, miR-210-3p showed a fold change of 73 and also found in datasets for 13 different types of cancer. Based on these findings, we concluded that miR-210-3p is particularly promising biomarkers. It not only effectively identifies patients with Myocardial Infarction but also show strong correlations with various cancers.
We further validated these results by revisiting the raw data in GEO and conducting additional analyses, including ROC curves and literature review. This confirmed that the detection of miR-210-3 shows the best diagnostic outcomes.
Our findings consistently showed that miR-210-3p performed better across these aspects, reinforcing their potential as biomarkers for myocardial infarction and cancers.
We then communicated to Dr. Si that our screening led us to choose myocardial infarction over coronary atherosclerotic heart disease (Figure 14). Dr. Si agreed with our screening method and mentioned that he would pay special attention to the occurrence of cancer in the follow-up of patients with myocardial infarction in future clinical work, and relay this information to the oncology department.
Figure 14. Communication with Dr. Si
After extensively seeking expert advice and continuously refining our project, we have completed the background research and preliminary design, and are now moving into the detailed design phase.
Project Refinement:
After deciding to focus on myocardial infarction as the cardiovascular disease for our project, we sought to deepen our understanding of the condition to refine our project design. Coincidentally, the Department of Cardiology at China-Japan Union Hospital of Jilin University, where we are based, hosted the First Spring City Cardiology Conference (Figure 15). We volunteered at this academic event, assisting the attending physicians with the registration process and providing guidance throughout the venue. By contributing our efforts to the event, we aimed not only to give back to the community but also to seize this valuable opportunity to seek more in-depth expert opinions.
Figure 15. The First Spring City Cardiology Conference
Taking advantage of our participation in the conference, we attentively attended Dr. Yunzeng Zou's presentation on "Myocardial Injury and Protection" on the first day ( Figure 16). Following the presentation, we interviewed Dr. Zou to seek his insights and suggestions for our project. Dr. Zou is a leading figure in the field of cardiovascular medicine in China, serving as the Director of the Shanghai Institute of Cardiovascular Diseases. His primary research focuses on the pathogenesis of hypertensive myocardial hypertrophy, heart failure, and miRNA-mediated cardiac hypertrophy.
Figure 16. Interview with Dr. Zou
Dr. Zou directly pointed out potential issues with the sensitivity and specificity of our proposed detection system. He noted that, compared to the traditional tumor screening methods currently used in clinical practice, relying on the detection of a single miRNA could lead to instability in the system, potentially resulting in a high rate of false positives. After thorough discussion and reconsideration of our design, we ultimately decided to modify the structure of the single-arm LIRA system and develop a dual-arm AND-gate LIRA detection system.
After revisiting the miRNA screening results, we discovered that miR-142-3p, which ranked second both in fold change values in the myocardial infarction dataset and in occurrence frequency in cancer, also stands out as a promising biomarker. Numerous studies have indicated that the up-regulation of miR-142-3p expression promotes the progression of various cancers. Following the advice of our Principal Investigator, Professor Xin Hu, we conducted functional validation experiments for both miR-210-3p and miR-142-3p in cancer cell lines. The results from Transwell, Wound Healing, and CCK-8 assays consistently demonstrated that elevated expression of miR-210-3p and miR-142-3p promotes the progression of renal cancer.
After carefully considering the valuable advice from several experts, along with our bioinformatic analysis, literature review, and functional validation, we have ultimately identified miR-210-3p and miR-142-3p as the two biomarkers we aim to detect. Additionally, we have chosen renal cancer as the specific type of cancer for our detection focus. We then proceeded to redesign the LIRA system using a dual-arm AND-gate structure. After extensive consideration and discussion, we decided to construct the LIRA system with one short arm and one long arm, forming an AND-gate. The long arm was deliberately designed to be thermodynamically stable, such that it can only be opened when the short arm is activated, weakening the stability of the long arm. We incorporated the sequences of miR-210-3p and miR-142-3p into the recognition domains of the LIRA dual-arm structure, enabling the simultaneous detection of both miRNAs.
On the second day of the conference, we attended Dr. Jian Wu's presentation on "Mechanisms of Myocardial Remodeling Due to Volume Overload and Precision Treatment Approaches." This lecture expanded our understanding of myocardial infarction from a macro level to a more detailed consideration of the underlying micro-mechanisms of its prognosis and recovery. Dr. Jian Wu, who is affiliated with the Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University , focuses his research on cardiac remodeling and heart failure. After the presentation, we shared our project with Dr. Wu and conducted an interview to gain insights into the prognosis of myocardial infarction patients, aiming to ensure that our diagnostic kit aligns closely with the core needs of these patients (Figure 17). Dr. Wu highlighted that myocardial infarction is a leading cause of cardiac remodeling and heart failure, with a poor prognosis, particularly among patients who also have cancer. He encouraged us to develop our diagnostic kit into a viable product but also cautioned that there could be discrepancies between in vivo and in vitro experimental results. Additionally, he advised us to carefully consider the cost of testing.
Figure 17. Interview with Dr. Wu
The interview with Dr. Wu deepened our understanding of the critical challenges faced by myocardial infarction patients and strengthened our resolve to improve our project to better support them. His encouragement also inspired us to consider the commercial potential of our work, with the goal of developing a low-cost early cancer screening kit.
After numerous revisions and refinements, our project design has taken shape. To seek further opportunities for exchange and collaboration, we traveled to Shanghai to participate in the 18th Oriental Cardio-Oncology Conference , where we submitted our project as an abstract. The submission was under the theme of Cardio-Oncology, titled "A Dual-Arm RNA AND-Gate Detection System Based on Reverse Cardio-oncology" (Figure 18). We hope that our project can contribute even a small spark to the ongoing research in Reverse Cardio-oncology. At the conference, we engaged in discussions with experts from both domestic and international institutions, fully immersing ourselves in the rich academic atmosphere and experiencing the unique blend of cardiology research with intangible cultural heritage. In the conference, our project was affirmed, and the abstract we submitted attracted an amount of attention.
Figure 18. The 18th Oriental Cardio-Oncology Conference
Project Implement:
With a comprehensive project design in place, we proceeded to the implementation phase, initiating both wet and dry lab experiments.
During the design of the parts, we sought to ensure that there were no design flaws by consulting a paper that utilized LIRA technology for RNA detection. We reached out to the corresponding author, Dr. Alex Green, and the first author, Dr. Duo Ma. Dr. Ma provided us with valuable feedback on our design, particularly emphasizing the importance of ensuring that the input RNA is in sufficient excess (Figure 19). He recommended using the high-copy plasmid backbone pET-15b for the input RNA, while the plasmid for LIRA transcription should utilize the low-copy plasmid backbone pCOLA. Following his advice, we swapped the backbones of these two plasmids to ensure that the input RNA was present in excess within the reaction system. Dr. Ma also suggested that even without including the Lac Operator in the plasmid, IPTG could still be used to induce the transcription of both LIRA and the input RNA. This is because IPTG induces the production of T7 RNA polymerase in bacteria, which initiates transcription. To avoid unnecessary complexity and waste, Dr. Ma advised us to remove the Lac Operator from the plasmid, a suggestion we followed successfully in our experimental validation.
With a comprehensive project design in place, we proceeded to the implementation phase, initiating both wet and dry lab experiments.
Figure 19. Emails with Dr. Ma
During the design of the parts, we sought to ensure that there were no design flaws by consulting a paper that utilized LIRA technology for RNA detection. We reached out to the corresponding author, Dr. Alex Green, and the first author, Dr. Duo Ma. Dr. Ma provided us with valuable feedback on our design, particularly emphasizing the importance of ensuring that the input RNA is in sufficient excess (Figure 19). He recommended using the high-copy plasmid backbone pET-15b for the input RNA, while the plasmid for LIRA transcription should utilize the low-copy plasmid backbone pCOLA. Following his advice, we swapped the backbones of these two plasmids to ensure that the input RNA was present in excess within the reaction system. Dr. Ma also suggested that even without including the Lac Operator in the plasmid, IPTG could still be used to induce the transcription of both LIRA and the input RNA. This is because IPTG induces the production of T7 RNA polymerase in bacteria, which initiates transcription. To avoid unnecessary complexity and waste, Dr. Ma advised us to remove the Lac Operator from the plasmid, a suggestion we followed successfully in our experimental validation.
During the wet lab experiments, we encountered some challenges. In the proof-of-concept stage, we aimed to co-transform the plasmid capable of transcribing LIRA and the plasmid transcribing the input RNA into the same host to validate the functionality of the single-arm LIRA system. Given our lack of experience with co-transformation of two plasmids, we sought to avoid technical setbacks. Dr. Ma explained two co-transformation strategies: the first involved simultaneously introducing the plasmid for LIRA transcription and the plasmid for input RNA transcription into the same host; the second involved preparing a competent cell with the LIRA transcription plasmid, followed by introducing the input RNA transcription plasmid. We experimented with both co-transformation methods and achieved initial success with each.
During the development of our LIRA optimization model based on logistic regression, we encountered performance bottlenecks, particularly due to the inadequacies in data processing, which led to suboptimal model performance. To address this issue, we consulted Professor Lina Jin, a renowned expert from the School of Public Health at Jilin University. Professor Jin suggested that we consider incorporating more advanced machine learning models, such as Random Forest or Gradient Boosting Trees, to capture the nonlinear relationships in the data (Figure 20). She also emphasized the importance of expanding the sample size and refining variable selection.
Figure 20. Interview with Dr. Jin
After adopting Professor Jin's recommendations, we took immediate action by significantly expanding our dataset and optimizing our variable set through feature engineering. These improvements notably enhanced the model's predictive accuracy and generalization ability, leading to significant progress in our LIRA optimization project.
Close to clinical practice:
To understand clinical doctors' opinions on our Heartecho project and its practical application, we interviewed Dr. Weihua Zhang from the First Hospital of Jilin University (Figure 21). Dr. Zhang pointed out that currently, the world has limited medical resources. If all patients were to seek treatment at first-tired hospitals, it would inevitably lead to overcrowding. However, our project aims to simplify and optimize the diagnosis and treatment processes for cancer, enabling these medical services to be extended to community hospitals. This approach would make medical services more convenient. Meanwhile, a more crucial duty of community hospitals is to improve and monitor the disease prognosis of the extensive community population. And our project fits this need perfectly. Dr. Zhang's endorsement of our testing kit concept provided us with great confidence and encouragement.
Figure 21. Interview with Dr. Zhang
Additionally, during our interview with Dr. Wenqi Zhang from the China-Japan Union Hospital of Jilin University, he emphasized the importance of considering both clinical doctors' opinions and patients' perspectives. Taking his advice to heart, we began conducting interviews with patients to gather their views and insights (Figure 22).
Figure 22. Interview with Dr. Zhang
References
[1] Shaw, Leslee J., et al. "Sex differences in mortality associated with computed tomographic angiographic measurements of obstructive and nonobstructive coronary artery disease: an exploratory analysis." Circulation: Cardiovascular Imaging 3.4 (2010): 473-481.
[2] Bell CF, Lei X, Haas A, et al. Risk of Cancer After Diagnosis of Cardiovascular Disease. JACC CardioOncol. 2023;5(4):431-440. Published 2023 Apr 11.
[3] Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377(12):1119-1131.
[4] Ridker PM, MacFadyen JG, Thuren T, et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10105):1833-1842.
Patient-focused care
Preparation of ethics and legal advice
Patient interviews play a crucial role in our project, as they ensure that our efforts remain patient-centered, ethically sound, and practically viable. By engaging with patients, we gain valuable insights into their experiences, needs, and perspectives, allowing us to tailor our project to better serve their interests. These interviews help us understand the real-world implications of our work, ensuring that our project is not only theoretically robust but also grounded in the practical realities of patient care.
To obtain ethical guidance for interviewing patients and to understand the considerations during the patient interview process, we consulted with Professor Songli Mei, a doctoral advisor in medical ethics at the School of Public Health, Jilin University (Figure 23). Prof. Mei brought to our attention the issue of "labeling," a concept that arises frequently in both sociology and medicine. He explained that labeling can have profound psychological and social impacts on patients, potentially leading to stigma or unintended consequences. Therefore, we must be particularly careful in how we classify and describe patients within our project, ensuring that our language and methodologies do not inadvertently cause harm or perpetuate biases.
Figure 23. Interview with Prof. Mei
As for the legal field, we consulted with lawyer Jiuhui Feng. Our discussions covered patient informed consent, considerations for vulnerable patients, privacy policies, data security, communication of results, follow-up recommendations, product liability, and handling disputes. Her guidance has been crucial in shaping our approach to patient interactions and ensuring alignment with legal and ethical standards (Figure 24).
Figure 24. Interview with lawyer Feng
Ethical material preparation
Our project is based at the China-Japan Union Hospital of Jilin University, and we aim to interview the hospital's patients to understand their views and willingness to use our early cancer screening kit, particularly among those who have experienced myocardial infarction. To clarify the hospital's ethics committee requirements for patient interviews, understand the proper procedures for communicating with patients, and ensure the protection of patient privacy and rights, we interviewed Professor Jun Wei, the Director of the Ethics Committee at the China-Japan Union Hospital of Jilin University (Figure 25).
Figure 25. Interview with Dr. Wei
Professor Wei first explained the process for conducting patient interviews. He emphasized that interviews should take place in a private, secure setting, such as a conference room or a doctor's office. He also reminded us that, unlike standard interviews, psychological interviews should use post-interview informed consent to avoid influencing the results. However, since our interviews with patients do not involve psychological analysis, we decided, after discussion with Professor Wei, to proceed with pre-interview informed consent, with a registered physician from the hospital serving as a witness. During the consent process, the patient should sign the informed consent form first, followed by the interviewer and the witness, to avoid causing any unnecessary psychological pressure on the patient. The exact time of signing should be recorded, down to the minute. At the beginning of the interview, the interviewer should clearly and thoroughly explain the project plan to the patient to ensure that their genuine thoughts and opinions are obtained.
Subsequently, we prepared the informed consent form and submitted it to Professor Wei for review, hoping to receive his feedback. He noted that our consent form was too simplistic and suggested that it should at least include details about the potential impact on patients, compensation for those who agree to participate, and information on how to withdraw consent. He offered to provide us with a framework outlining the necessary content to help us make the required revisions (Figure 26).
Figure 26. The first edition of consent form
Following Professor Wei's advice and using the informed consent framework that he provided, we revised the consent form and presented it to him again for review. Professor Wei indicated that the content of the consent form was now relatively complete. He reminded us to strictly adhere to ethical guidelines during the interviews and to ensure the protection of patient privacy. He also pointed out that patients might be more focused on their personal cancer risk rather than the project itself, so we should be prepared to respond to unexpected questions and concerns (Figure 27).
Figure 27. The final edition of consent form
Patient interviews
After extensive preparation, we were finally able to move forward with confidence into the patient interview phase, where we aimed to understand their real-life situations and gather their views on our early cancer screening kit. Through direct conversations with patients, we gained deeper insights into the health challenges that they faced in daily life, their concerns about cancer and cardiovascular diseases, their experiences with current medical practices, and their hopes for the future of healthcare. Unlike previous interviews, no photos or video recordings were taken throughout this session to ensure the privacy and safety of the patients. The interviews were conducted in a private and quiet environment, and informed consent was signed by the patients, their families, and the attending physicians on the day of the interview, with the signing time recorded to the minute.
We first contacted Dr. Ming Yu from the Department of Cardiovascular Medicine at the China-Japan Union Hospital of Jilin University (Figure 28). We gave her a brief overview of the project, explained our intention to interview heart attack patients, and submitted the project' s ethical approval and informed consent forms. After obtaining consent from both the patients and their families, Dr. Yu provided us with an overview of the patients' conditions and highlighted key details to consider when communicating with them.
Figure 28. Interview with Dr. Yu
At the start of the interviews, we clearly and thoroughly explained the background and objectives of the Heartecho project to each of the two patients. We then conducted individual interviews, carefully listening to their thoughts and feedback. This approach ensured transparency and independence in communication while allowing us to gain a more comprehensive understanding of each patient's unique perspective and needs regarding the project.
The patient is a 68-year-old woman who was admitted to the hospital after experiencing intermittent chest tightness for one month, which worsened over the course of a day. A coronary CTA revealed triple-vessel coronary artery disease, and she was diagnosed with acute myocardial infarction. Dr. Yu advised that when communicating with the patient, it is important to use simple and easy-to-understand language, approach the conversation from the patient's perspective, and minimize psychological stress for her.
We are attentive to the cognitive differences between genders and are also interested in understanding the perspectives of male patients. To gain more insight, we reached out to Dr. Zhongfan Zhang from the Department of Cardiovascular Medicine at the China-Japan Union Hospital of Jilin University to learn more about the patients' basic conditions (Figure 29).
Figure 29. Interview with Dr. Zhang
The patient is a 58-year-old man who has experienced episodic chest pain for three years and persistent chest pain for two hours. Based on the findings from an electrocardiogram and other diagnostic tests, he was diagnosed with acute ST-segment elevation myocardial infarction (STEMI).
The feedback from patients has highlighted that many individuals with cardiovascular disease are unaware of their potential cancer risk and often neglect the importance of early screening. Through our conversations with them, we have become even more convinced of the urgency and importance of developing this screening tool. This project is not just about scientific research, but more about directly improving the quality of life and health of patients. By offering earlier intervention, particularly for those who with a history of cardiovascular disease, we could improve their survival rates and overall quality of life.
Additionally, the participation of patients has provided us with a clear understanding of the key features that our test kit must have—rapid results, affordability, and ease of use. These characteristics are essential for ensuring Heartecho is widely accepted and accessible to a broader population. The contribution of patients goes beyond the technical aspects of the project; they are a driving force in moving the project toward practical application. Their feedback not only helps us evaluate the convenience and effectiveness of the kit in real-world use, but it also provides valuable suggestions for improvement. This ensures the test kit will be not only effective in the lab but also a true asset in clinical practice, delivering meaningful benefits to patients.
Entrepreneurship
Unmet needs
In the face of the significant health burden posed by myocardial infarction globally, coupled with the even more severe prognosis when patients subsequently develop cancer, there is a pressing need for effective solutions. Recognizing this urgent market demand, Heartecho presents a revolutionary breakthrough. Our innovative Loop-Initiated RNA Activator (LIRA)-based AND logic gate system detects the biomarker microRNA (miRNA) and integrates with a cell-free system to show results. With Heartecho, we aim to achieve cancer screening for post-myocardial infarction patients, providing unparalleled benefits for both patients and healthcare providers .
This diagram outlines the core elements driving the business plan of Heartecho. We began with a identification of unmet needs within the diagnostics landscape. After that we proposed innovative solutions. Finally, it culminates in the outlining of a sustainable business model designed to ensure market success through strategic positioning and partnerships, thereby bridging the gap from need identification to commercial viability (Figure 30).
Figure 30. The core elements driving the business plan of Heartecho
The "China Cardiovascular Health and Disease Report 2023" highlighted that the prevalence of cardiovascular disease (CVD) in China is continuing to rise, with an estimated 330 million CVD patients. According to data from the Global Burden of Disease Study (GBD), the age-standardized incidence of CVD among people aged 1-79 years in China was 646.2 per 100,000 between 1990 and 2019. In 2022, a total of 1.034 million inpatients with AMI were treated, with 47.4% were ST-segment elevation myocardial infarction (STEMI), 41.1% were non-ST-segment elevation myocardial infarction (NSTEMI), and 11.5% were unclassified acute myocardial infarction. The above data indicates that the health burden of cardiovascular diseases is enormous and the number of patients with myocardial infarction is large.
We have also conducted relevant research on microRNAs (miRNAs) as biomarkers. According to Data Bridge Market Research, the global miRNA sequencing and detection market is valued at $381.39 million in 2023 and could reach $916.55 million by 2031, with a projected compound annual growth rate (CAGR) of 11.6% over the forecast period. Growing awareness of proper medication use has positioned hospitals as the dominant segment in the miRNA sequencing and testing market. Increasing functional genomics research, rising incidence of chronic diseases, and advancements in next-generation sequencing (NGS) technology are the growth drivers for the miRNA detection market.
From this, it is clear that Heartecho is not only an innovative solution targeting unmet needs but also demonstrates strong potential and promising prospects in the market.
Heartecho will be priced at $22 per unit. This affordable price point ensures accessibility to a wider range of patients. The kit's key advantages lie in its cost-effectiveness, ease of use, and the precision it offers in identifying miRNA cancer biomarkers within this specific patient population.
Stakeholders & Potential Customers
As we embark on the journey of Heartecho's commercialization, crafting a comprehensive Stakeholder Map becomes a pivotal step. It not only aids in clearly identifying and understanding all stakeholders vital to the project's success , but also guides us in effectively managing and communicating with them. This ensures that Heartecho's commercialization strategy advances smoothly towards a mutually beneficial outcome. The following is an introduction to our carefully crafted Stakeholder Map, which outlines the core value and vision of this blueprint (Figure 31).
Figure 31. Stakeholder map
Presented as a three-dimensional jigsaw puzzle, our Stakeholder Map vividly illustrates the multifaceted interactions and connections among stakeholders in the Heartecho commercialization journey. Each stakeholder has their own distinct role and influence, contributing to the overall success and sustainability of our commercialization strategy. Just like piecing together a puzzle, successful commercialization requires careful consideration, strategic alignment, and seamless integration of all stakeholder perspectives. It signifies our commitment to working together, leveraging the strengths and insights of each stakeholder to create a cohesive and effective commercialization plan.
At the heart of effective stakeholder management lies a deep understanding of each stakeholder's power and interest. The Power-Interest Matrix is a valuable tool for mapping out these dynamics, enabling us to identify key stakeholders, assess their level of influence, and gauge their vested interest in our success(Figure 32) .
Figure 32. Power-Interest Matrix
By analyzing this matrix, we can strategically prioritize our stakeholder engagement efforts, ensuring that we foster collaborative relationships, address concerns proactively, and harness the collective power of our stakeholders to drive successful commercialization outcomes.
For the different quadrants of stakeholders in the Power-Interest Matrix, tailored strategies are essential to ensure effective engagement and collaboration.
High Power, High Interest:
These stakeholders have significant influence and a vested interest in the commercialization of Heartecho. To engage them effectively, we will establish regular communication channels, actively seek their input in decision-making processes, and work closely to align our strategies with their interests. Given their high interest and power, they are ideal candidates for becoming our customers, as they are likely to be actively involved in the adoption and promotion of our solutions.
High Power, Low Interest:
While these stakeholders possess considerable influence, their direct interest in our commercialization may be limited. To manage this group, we will focus on providing clear and concise information about our progress and goals, demonstrating the value of their support, and exploring opportunities for mutual benefit. Although they may not initially show strong interest, by highlighting the benefits and aligning our offerings with their broader objectives, we can potentially convert them into customers.
Low Power, High Interest:
These stakeholders may have limited influence but are highly invested in our success. To harness their enthusiasm, we will actively listen to their perspectives, keep them informed about project developments, and seek ways to empower them through collaboration or representation. While they may not possess significant power, their high interest indicates potential as customers. By nurturing these relationships and addressing their specific needs, we can encourage their involvement and support.
Low Power, Low Interest:
Although their influence and direct interest may be minimal, maintaining positive relationships with these stakeholders is still important. We will ensure transparent communication, address any concerns they may have, and explore potential areas of synergy where their interests can align with our commercialization objectives. Although they may not be immediate customers, by fostering positive relationships and demonstrating the value of our offerings, we can lay the groundwork for future engagement and customer conversion.
Product Feasibility
To ensure the feasibility of our Heartecho, we embarked on a comprehensive process involving interviews with experts from various domains.
We started by receiving valuable academic insights from Professor Ling Ren , a respected expert at the Business School of Jilin University. Professor Ren's expertise in business strategy and innovation management provided us with a unique perspective on navigating the complex landscape of commercializing cutting-edge technology.
During our interview, Professor Ren emphasized the importance of understanding market dynamics and aligning Heartecho with evolving customer needs. She highlighted the significance of conducting thorough market research to identify key segments, assess competitor positions, and uncover untapped opportunities for growth.
Furthermore, Professor Ren stressed the role of strategic partnerships. She suggested seeking collaborations with industry leaders, research institutions, and government entities to leverage their resources, expertise, and networks. By forging these alliances, Heartecho can enhance its technological capabilities, expand its market reach, and gain a competitive edge (Figure 33).
Figure 33. Interview with Prof. Ren
On the commercial side, we consulted a business expert who helped us assess the market potential of our product. Kunyang Xue, the Vice General Manager of Dongguan Binhaiwan Industry Investment Co., Ltd, provided valuable insights about pricing strategies, target demographics, and potential competitors, allowing us to refine our marketing and sales approach.
With his extensive experience in the investment of innovative technologies, Xue provided us with a unique perspective on navigating the complexities of bringing Heartecho to market. He recommended conducting thorough market research to assess market demand, analyze the competitive landscape, and develop pricing strategies, enabling us to position Heartecho effectively in the market.
Furthermore, Xue highlighted the importance of a robust business model that aligns with market realities. He advised us to consider various revenue streams, pricing models, and distribution channels to ensure sustainable growth and profitability. Additionally, he emphasized the need for a clear value proposition that differentiates Heartecho from competitors and resonates with customers (Figure 34).
Figure 34. Interview with manager Xue
Next, we engaged a legal expert, Junling Bai to received legal and intellectual property (IP) insights, ensuring our product complied with all relevant laws and regulations governing medical devices.
With her expertise in technology law and IP management, Bai offered essential guidance on navigating the legal landscape and protecting Heartecho's intellectual assets. She suggested conducting a thorough IP audit to identify and assess existing patents, trademarks, copyrights, and other IP assets. This will enable us to safeguard Heartecho's unique technologies and brand identity.
During our interview, Bai emphasized the need for comprehensive legal framework to support Heartecho's commercialization efforts, including contracts, agreements, and compliance policies. This will ensure that all business activities are conducted in accordance with applicable laws and regulations.
Bai also called our attention to considering potential legal risks and challenges. She advised us to conduct a thorough legal due diligence to identify any potential legal issues or liabilities that may arise from Heartecho's technology, partnerships, or market entry strategies. By addressing these risks proactively, we can mitigate potential legal disputes and protect our business interests (Figure 35).
Figure 35. Interview with lawyer Bai
We also sought input from industry experts who offered insights into manufacturing, distribution, and supply chain management. Hongyu Li, the Secretary of Board of Changchun High-Tech Industry (Group) Co.,Ltd , provided us with a comprehensive understanding of the key factors driving Heartecho's success. They offered insightful suggestions for the company's development (Figure 36).
Figure 36. Interview with Li
Collaborative partnerships were considered essential for Heartecho's success. Establishing partnerships with healthcare providers, insurance companies, and government agencies will facilitate widespread adoption and create a strong network of support. Maintaining product integrity and patient safety is paramount, and obtaining necessary certifications and approvals will enhance Heartecho's market credibility.
Scalability and sustainability were seen as important considerations for Heartecho's long-term success. Planning for scalability to accommodate growing demand and implementing sustainable business models that support long-term growth and profitability will ensure the company's stability and continued growth.Utilizing digital marketing channels and engaging in industry events can expand Heartecho's reach and visibility.
Lastly, the experts stressed the importance of ongoing customer support and feedback. Establishing customer support systems to address inquiries, concerns, and provide technical assistance is vital. Actively seeking customer feedback for continuous improvement and product enhancement will allow Heartecho to adapt to market needs and stay ahead of the competition.
After interviewing several experts, we are confident in moving forward with the development and commercialization of our Heartecho, assured that it meets the needs of the target audience and shows strong potential in the marketplace.
When we completed the initial draft of our business plan and established the business model, we embarked on the process of seeking validation for our product's feasibility from the pharmaceutical company, Johnson & Johnson Medical Devices Companies China .
We approached representatives of this company with a comprehensive presentation outlining our Heartecho, its unique features, and the market potential it holds. The Senior Clinical Specialist Junming Yan expressed recognition of the feasibility of our product. His positive feedback was based on a thorough evaluation of our business plan, which outlined the scientific foundation, technical specifications, and market potential of our product. They appreciated the comprehensive approach we had taken, considering not only the technical aspects but also the regulatory, commercial, and operational challenges. This recognition from industry experts underscores the strong potential of our Heartecho and its alignment with the needs and expectations of the pharmaceutical sector (Figure 37).
Figure 37. Interview with Johnson & Johnson Medical Devices Companies China.
SWOT Analysis
To comprehensively understand the strengths, weaknesses, opportunities, and threats associated with our Heartecho, we conducted a thorough SWOT analysis. This strategic planning tool allowed us to assess our internal capabilities and external environment, providing a clear road-map for our entrepreneurial journey. By identifying and leveraging our strengths, addressing our weaknesses, capitalizing on opportunities, and mitigating potential threats, we are confident in the viability and success of Heartecho in the market (Figure 38).
Figure 38. SWOT analysis of Heartecho in the market
Development Plans
As part of our development plans, we have crafted a comprehensive Business Canvas for Heartecho. This canvas serves as a strategic roadmap, outlining the key elements and intricacies of our Heartecho. It encapsulates our unique value proposition, target market insights, revenue streams, and strategic partnerships, providing a holistic view of our business model. The Heartecho Business Canvas not only guides our development efforts but also illustrates the potential and viability of our solution in addressing unmet needs in the healthcare industry. With this strategic blueprint in place, we are poised to bring Heartecho to market (Figure 39).
Figure 39. Business Canvas for Heartecho
We have also developed a milestone-driven plan to guide the future growth and development of Heartecho. This plan outlines key milestones and targets that will steer our efforts towards establishing Heartecho. Each milestone, from product development to market expansion, represents a critical step forward in realizing our vision. This comprehensive roadmap keeps us focused , adaptable, and aligned with our strategic objectives, ultimately positioning Heartecho for long-term success and impact in the healthcare industry (Figure 40).
Figure 40. Development Plan for Heartecho
Bussiness Plan
A business plan is a document that outlines our new venture goals, operations, industry position, commercialization strategy, marketing objectives, risk analysis, and financial projections . We have crafted a business plan for Heartecho. It encompasses a thorough analysis of the market, a clear definition of our unique value proposition, and a strategic blueprint for executing our vision. The business plan also details our marketing strategies, revenue projections, and key performance indicators, ensuring that we have a solid foundation for growth and scalability. The pdf of our business plan shows all entrepreneurial efforts undertaken by CJUH-JLU-China.
Responsible for the world
This year, we are deeply grateful to the many doctors, professors, and patients whose support and guidance have continuously improved our Heartecho project. Their contributions have inspired us to promote our project to the broader society, raising awareness about Reverse Cardio-oncology. By focusing on publications, ethical responsibility and public engagement, we ensure that our work positively impacts the world. Grounded in ethical theories, public health principles, and social cognitive frameworks, we are dedicated to making our project responsible on both moral and social levels (Figure 41).
Figure 41 Responsible for the world
Public participation
Numerous scientific studies have supported the benefits of regular exercise for the prevention and management of cardiovascular disease (CVD)[1] and cancer[2]. Despite this evidence, physical inactivity remains highly prevalent worldwide, largely due to a lack of awareness, as these topics are not typically covered in educational curriculum or workplace health programs. Inspired by the spirit of the Paris 2024 Olympic Games, we initiated a series of innovative sport activities aimed at raising public awareness about cardiac health and cancer prevention through practical engagement to address this issue.
Our activities are designed based on the triple interaction theory model , proposed by psychologist Albert Bandura. This interactive approach fosters a cognitive cycle where participants learn about heart disease and cancer prevention in a dynamic and engaging environment. Through these activities, we aim to enhance public awareness and promote healthier lifestyles, ultimately contributing to the reduction of CVD and cancer rates. Our team believes that by integrating educational content with physical activity, we can create a more profound and lasting impact on public health (Figure 42).
Figure 42. The triple interaction theory model
Frisbee activity
We had the pleasure of organizing a truly meaningful event at Jilin University's South Campus, which we called "Synthetic Journey: 'Fly' with You." This event creatively combined frisbee, synthetic biology, cardiac health, and cancer prevention, aiming to leave a lasting impression on participants and the wider community. We provided each participant with a free frisbee and offered them our custom-designed stickers to help them understand what Reverse Cardio-oncology is. Through this engaging activity, we helped participants understand the vital importance of cardiovascular health and shared practical tips for incorporating heart-healthy habits into their daily lives. This innovative approach ignited curiosity and made complex subjects accessible and enjoyable in a way that traditional methods might not have achieved.The impact of our event went beyond the participants themselves. We demonstrated how an interdisciplinary approach can effectively engage the broader public, using simple and enjoyable activities to communicate complex scientific and health-related ideas (Figure 43).
Figure 43. "Synthesis Journey: Let Your Frisbee Fly" activity
Ultimately, "Synthesis Journey: Let Your Frisbee Fly" became more than just an educational event—it was a celebration of creativity, health, and community. The enthusiastic feedback we received from participants confirmed that innovative, interdisciplinary approaches like this can effectively bridge the gap between science, health, and society.
Additionally, through analyzing participant feedback, we discovered that many attendees expressed a desire for more authoritative theories or guidance from experts in future activities. In response, we made improvements in our subsequent events to incorporate expert-led sessions. This event inspired many to explore and appreciate the critical importance of scientific discovery and heart health, and we are excited to continue this journey in future initiatives (Figure 44).
Figure 44. Feedback from participators
Campus tennis teaching activity
We had the pleasure of hosting a tennis event at Song Zhiping Gymnasium, Jilin University, titled "One Net Forward, Endless Heart Joy". This event was a collaborative effort between our team and the Jilin University Tennis Club. Twenty-eight students from 12 different faculties, including Law, Economics, and Physics, came together for an afternoon that combined the excitement of tennis with a focus on heart health awareness.The impact of this event on the public was both multifaceted and significant. It successfully raised awareness about the importance of cardiovascular health, particularly by highlighting the benefits of regular physical activity. By combining tennis—a sport that is both accessible and enjoyable for many—with heart health education, we were able to engage a diverse group of students who might not otherwise have been involved in such discussions (Figure 45).
Figure 45. "One Net Forward, Endless Heart Joy"activity
The event also demonstrated the effectiveness of community-driven initiatives in promoting health and well-being. Participants not only gained practical knowledge about heart health but also experienced the immediate benefits of physical exercise. This hands-on approach reinforced the importance of maintaining an active lifestyle for long-term health. Moreover, the collaboration between our team and the Tennis Club underscored the power of interdisciplinary efforts in addressing public health challenges. By integrating scientific research with sports, we showcased how different fields can come together to create impactful and meaningful programs. After considering feedback from participants in the frisbee activity, we enlisted the expertise of Professor Xiaogang Ma from the School of Physical Education at Jilin University to provide professional guidance for our tennis event. His guidance played a crucial role in enhancing the quality and enjoyment of the event, further amplifying its positive impact.
After the event concluded, we received feedback from participants who highly recognized and praised our efforts. They expressed that we provided them with a valuable opportunity to learn about the sport of tennis and gain knowledge about heart health. However, they also suggested that if we could create videos of our activities for wider promotion, the impact would be even greater. We took this feedback into account and made improvements in our subsequent activities (Figure 46).
Figure 46. Feedback from participators
Cardiac Health Excercises
The cardiac health exercise is a simple yet effective way to stay active, with its lively rhythm attracting participants of all ages. We designed the movements by incorporating elements of Tai Chi, using gentle actions such as tapping and stretching to promote overall blood circulation and protect heart health. We believe that regular exercise is vital for maintaining overall well-being, especially for the heart.This exercise routine has been implemented across campus through various sports activities, such as tennis and frisbee events, making it an integral part of our health initiatives (Figure 47).
Figure 47. Students doing the Cardiac Health Excercises
We've also extended its reach beyond the university by promoting it in elderly care homes, where it has been warmly received by the senior community. For older adults, this gentle routine improves flexibility and endurance, significantly enhancing their quality of life. Recognizing its potential impact and in order to improve our activity, we further called upon several iGEM teams across China to collaborate on creating a cardiac health exercise video. This collective effort involved nearly 200 participants and reached a wide audience, demonstrating the routine's broad appeal and effectiveness. As a practice that encourages widespread participation, the cardiac health exercise not only aids in the recovery of cardiovascular patients but also strengthens the body and plays a crucial role in preventing cardiovascular diseases (Figure 48).
Figure 48. Doing the Cardiac Health Excercises with the old
By organizing a series of sports activities, we effectively showcased the importance of exercise in preventing cardio vascular disease and cancer, while also raising public awareness about Reverse Cardio-oncology. These events not only boosted public awareness for doing regular exercise but also effectively disseminated crucial knowledge about cardiac health and cancer prevention. The activities saw widespread participation on campus and were then shared on social platforms like Bilibili, TikTok, and WeChat, further amplifying their positive impact on public awareness.
7th Chinese Doctor's Day
August 19 is the Chinese Doctor's Day, a special occasion dedicated to honoring and appreciating healthcare professionals. To celebrate this important day, we prepared some thoughtfully designed mementos—badges featuring our team logo and refrigerator magnets—as gifts for the cardiologists working tirelessly on the front-lines of clinical practice. These doctors dedicate themselves to providing high-quality treatment and care to patients in their daily work, and their professionalism and dedication have deeply moved us. Through these gifts, we hope to express our deep gratitude and wish them a day filled with care and blessings, making this Doctor's Day a joyful and memorable one (Figure 49).
Figure 49. Giving gifts to doctors we have interviewed
In addition, we provided a brief update on our project's latest progress to several doctors we previously interviewed, including Dr. Yuquan He, Dr. Daoyuan Si, and Dr. Huan Sun. During this exchange, we specifically mentioned the valuable advice they had given us before, detailing how this advice played a crucial role in helping us overcome various challenges during the project's advancement. We sincerely appreciate the time they took from their busy schedules to offer us guidance and support, and we hope to continue receiving their help and direction in the future. On this special day, we once again extend our heartfelt respect and gratitude to them and wish them success in their careers and happiness in their lives.
We plan to continue these activities with a focus on analyzing their long-term effects on participants' health and well-being. By gathering and assessing data from these initiatives, we aim to better understand how regular physical activity can impact the prevention of cardiovascular disease and cancer. Additionally, we will actively seek collaboration with experts in the fields of cardiology, oncology, and public health, as well as with educational institutions, to broaden our reach and influence. We are confident that with sustained effort, continued research, and strong community involvement, the Heartecho project will not only maintain its momentum but also achieve even greater success in promoting health and raising awareness on a larger scale.
Inking our duty
In order to offers new insights for the prognosis assessment of cardiovascular disease (CVD) patients and the development of precise, personalized treatment plans, and aiming to enhance overall societal well-being. Our PI, Professor Xin Hu, Professor Yuquan He, and Yutong Yao, have published a review article titled "Research Progress in Reverse Cardio-oncology" in the Chinese Journal of Heart Failure and Cardiomyopathy. This article is the first of its kind to be included in the Chinese Medical Journal, focusing on the field of Reverse Cardio-oncology. The article systematically explains the research advancements in Reverse Cardio-oncology and points out directions for future development (Figure 50).
Figure 50. What could cause tumor growth
To safeguard the rights and welfare of all the participants involved in our project, ensuring that every step of our project meets the highest ethical standards. We adhere to the three fundamental ethical principles outlined in the Belmont Report: Respect for Persons, Beneficence, and Justice , which have been a source of inspiration from Prof. Yunsheng Dong. Guided by these principles, we have made the "Ethics of Synthetic Biology" handbook. Under the principle of Respect for Persons, we emphasize the importance of safeguarding the autonomy and dignity of all participants. Our project includes a detailed informed consent process, ensuring that each participant fully understands the procedures, risks, and potential benefits involved, and can make autonomous decisions accordingly. Additionally, we pay special attention to providing extra protections for groups with limited autonomy, such as minors, the elderly, and individuals with cognitive impairments, to ensure their rights are fully protected. Secondly, the principle of Beneficence, we aim to maximize benefits while minimizing harm for participants. We conduct thorough risk assessments and implement safety measures, with continuous monitoring to ensure the project remains beneficial and safe. And Finally, guided by the principle of Justice, we ensure that the benefits and risks of the project are fairly distributed. Our participant selection is inclusive and unbiased, with specific strategies to protect vulnerable groups. We are also committed to the equitable global distribution of the project's benefits, ensuring all groups can share in its outcomes.
Further, the handbook serves as a valuable resource for the general public, aiming to share knowledge about synthetic biology, raise awareness of its ethical issues, and foster public acceptance and support for this technology. Through this comprehensive and multi-faceted ethical guidance, our handbook will be an essential tool in advancing the field of synthetic biology responsibly, balancing technological progress with social responsibility.
References
[1] Fiuza-Luces C, Santos-Lozano A, Joyner M, et al. Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors. Nat Rev Cardiol. 2018;15(12):731-743.
[2] Fiuza-Luces C, Valenzuela PL, Gálvez BG, et al. The effect of physical exercise on anticancer immunity [published correction appears in Nat Rev Immunol. 2024 Mar;24(3):229.