Stakeholder Profile

These stakeholders in our Human Practices are closely related to the development of our experimental topic.

Before conducting the Human Practices survey, we thought about the groups that would be relevant to our topic. Through interviews and surveys we found that all people can be both providers and demanders.They contributed to the conduct and development of our experiments. Please scroll down to learn more about our story.

Stage 1: Entering the World of Patients with Chronic Hepatitis

1. Discovering It

In the early stages of the project, a video about a young man whose chronic alcohol abuse had led to decompensated cirrhosis was brought to our attention. The story, adapted from a real-life incident, tells of a 27-year-old man who had been drinking an average of three bottles of rum a day since he was a teenager, and was eventually admitted to hospital with a sudden episode of vomiting blood. Medical examination revealed that the cause of his hypovolemic shock was his decompensated cirrhosis.

Although this patient was fortunate to have a liver donor to save his young life when his hepatitis had reached a serious stage, it is alarming that bad habits like alcohol abuse are at the cost of health. So, we began to attach importance to chronic diseases, including chronic hepatitis.

2. Understanding It

a. Literature

With regard to the causes of alcoholic liver disease in the previous article, we initially understood that it is a form of chronic hepatitis. When alcohol is consumed, it is broken down in human body into acetaldehyde, which is harmless in small doses and is quickly broken down into acetic acid. However, excessive alcohol consumption will lead to incomplete decomposition of ethanol and thus accumulation of acetaldehyde. Acetaldehyde is toxic, and it damages the DNA in the liver cells. Acetaldehyde also causes immune cells to attack the liver. The final stage of liver damage is cirrhosis, which can lead to more serious metabolic problems, such as inability to metabolise bilirubin, hepatic encephalopathy, lack of blood clotting factors and stomach bleeding, etc.

After reviewing the literature, we continued to understand that chronic hepatitis is an inflammation of liver that lasts for more than 6 months. Chronic hepatitis is less common than acute viral hepatitis (hepatitis A, hepatitis B, etc.), but it can last for several years or even a decade. The causes of chronic hepatitis are also varied, such as obesity, substance abuse, non-alcoholic fatty liver disease, heavy alcohol consumption, hepatitis B or C infection, etc. We are also concerned about the recent increase in hepatitis among a younger age and the worsening of the disease.

The onset of chronic hepatitis seems to be around the corner.

References

Aiping Tian,Yongfeng Yang."A comparative analysis of pathological grading and staging systems for chronic hepatitis." Journal of Clinical Hepatology 34.11(2018):2271-2277.

Yan Jia, et al."Research progress of alcoholic fatty liver disease in China." Chinese Journal of Gastroenterology and Hepatology 23.04(2014):376-379.

b.Prevalence Survey in China

China is a country plagued by hepatitis.

According to relevant statistics, the number of patients with chronic liver disease in China, including chronic hepatitis, fatty liver and cirrhosis, may exceed 447 million in 2020. In terms of viral hepatitis, there are currently about 86 million people infected with chronic hepatitis B in China, including 20-30 million cases of chronic hepatitis B and 5.6 million infected with hepatitis C.

One third of the world's 240 million patients with chronic hepatitis B, more than half of the world’s new liver cancer patients, and about 7% of the world’s 130-150 million patients with hepatitis C are in China.

Summary：

Our investigations revealed that chronic hepatitis is caused by diverse factors, and many of these factors are related to poor lifestyle habits. Recent advances show that the Chinese government has made impressive efforts to curb hepatitis B and C infections, and viral hepatitis is largely under control in China, especially in urban areas. However, metabolic liver disease has become a major threat to the health and quality of life of people in China and the world. We predicted that there would be a growing demand for research into liver disease.

3. Outreaching to Explore the Needs of the Public’s Needs

Experimental and project design will be of value, if it is closely related to practical problems concerning people's livelihoods. We decided to start with our project from connecting people.

How much does the general public know about chronic hepatitis? Does the actual situation match what we hpothesized? We conducted questionnaire surveys and interviews in different communities in Nanjing in order to find out more about the perceptions and needs of the community in relation to chronic hepatitis. We gave due considerations to the contents of the consultation prior to the interview to ensure that it was a survey of perceptions and needs without targeted and pointed questions, and that it did not involve privacy of the interviewees with their informed consent. Respondents gave us informed and voluntary feedback.

Community Survey - Nanjing Map

Questionnaire results

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Our interviews revealed that most citizens have little knowledge of chronic hepatitis, and some have not even heard of it. Though the general public is unfamiliar with the disease, factors that may contribute to the development of chronic hepatitis, such as extreme dietary preferences, alcoholism and mental health problems, are a constant part of people's routine lives.

Of the few people who know a bit about chronic hepatitis, some had shared the troubles of people with chronic hepatitis. Patients with chronic hepatitis have basically no obvious clinical manifestations in the early stages of the disease. When it progresses, symptoms such as insomnia, high fever, nausea and pain in the liver area may appear, and in the later stages, liver fibrosis and liver dysfunction may occur, threatening the life of the patient. It is the lack of obvious symptoms in the early stages and the lack of awareness and access to medical check-ups for most of the potentially affected population that leads to the development of chronic hepatitis.

In addition, a Ms. Li specifically mentioned that patients with chronic hepatitis will be obsessed with the disease for a long time, greatly reducing their capabilities, and consequently leading to a significant lack of energy in their daily work. Patients with severe disease will be completely incapacitated and unable to lead a normal life. Meanwhile, the long-term treatment required for chronic liver disease will add to the financial stress of the family. Many patients therefore become depressed and pessimistic, making it more difficult to treat the disease. Patients with viral hepatitis, in particular, are often burdened with greater psychological stress because of the infectious disease.

At this stage we have conducted not only a survey on the public's understanding of chronic hepatitis, but also a survey on the level of understanding of synthetic biology and the reasons for this. This provides us with an important basis for our subsequent choices and activities in the education and dissemination of synthetic biology.

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Summary:

In conclusion, we have found that education and awareness of chronic hepatitis in China is inferior at present, but the prevalence of the disease and the number of people suffering from it are increasing year after year. People often failed to notice the changes in their bodies in the early stage of the disease, which leads to the development of chronic hepatitis. Patients who suffer from chronic hepatitis are also subjected to enormous physical, psychological and financial stress.

But at the same time, we also noticed that only 6% of the 841 questionnaires we collected and the 108 people we interviewed were aware of chronic hepatitis, which is far less than we thought. Is chronic hepatitis really a problem that needs to be addressed? This question prompted us to think about whether our choice to conduct research in the area of chronic hepatitis would have a broad impact in China or even globally. Through our project, can we advance the cause of human and world health?

4. Figuring out Solutions through Communication with Doctors：A Talk with Dr. Ji

In order to determine whether it is valuable to address chronic hepatitis-related issues and to acquire more advice from experts, we decided to continue the investigation. We planned to engage with clinicians and medical professors to understand the epidemiology and pathological characteristics, as well as treatment plans and caring guidelines of chronic hepatitis. So, we interviewed Dr. Ji Guangxin from Peixian People's Hospital.

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Dr. Ji answered our questions. He commented that our previous survey was not wrong or meaningless. Causes of our biased result was that we mainly chose community groups as respondents, ignoring the fact that most people in the general community are healthy. In fact, the field of chronic hepatitis has still great research value, and people urgently need a revolution in the field of liver diseases.

He also told us that liver diseases had the characteristics of high disease incidence, long disease course, high curing difficulty, and frequent recurrence. Nowadays, diseases caused by bad living habits are becoming a major obstacle to health.

Finally, Dr. Ji shared his thoughts about the treatment and testing methods for chronic hepatitis. He suggested that we should assess not only the application value of our project, but also its feasibility. We learned that the treatment of hepatitis is very complex and there are so many relevant factors, so we eventually decided to focus on the detection of chronic hepatitis. Currently, the diagnostic procedures for hepatitis are complex, requiring great time and economic costs. From the perspective of the ordinary people, if the disease could be detected as early as possible through testing, the follow-up treatment will be much simpler and less stressful in all aspects.

We gained a lot in this interview and started thinking to design a simple and quick hepatitis test kit to help people detect chronic hepatitis on their own. Inspired by doctors, we decided to take advantage of bile acids and attempted to devise such kind of quick-reaction kit for hepatitis problems.

5. Interviewing with Prof. Liu

After having a general idea, we turned to Prof. Liu Jiaguo from Nanjing Agricultural University. According to the preliminary survey we conducted, in addition to viral hepatitis, people were actually more concerned about alcoholic hepatitis. Relevant data also indicated that chronic alcoholic hepatitis patients accounted for the largest proportion of the patients with hepatitis, up to nearly 60%. So alcohol drinking was a factor that cannot be ignored. To discuss with this phenomenon, we started a discussion on alcoholic hepatitis.

Prof. Liu explained the interaction between drinking alcohol and hepatitis from a TCM theory perspective.

According to TCM, Qi is one of the basic substances that make up the human body and maintain human activities. While alcohol, the essence of the crop, is regarded as fierce and toxic. Long-term inordinate alcoholic life tends to hurt the internal organs, leading to damage and weakness of the liver. After the long-time imbalanced body situation, the stagnation of Qi will result in poor blood flow and meridians paralysis. Therefore, to handle this health issue, TCM recommends the treatment principle of regulating and detoxifying relevant organs.

Generally, it is very interesting to discuss chronic hepatitis from the perspective of TCM. In a nutshell, TCM believes that alcohol breaks the balance of Qi in the body, causing weaker liver function. So it is important to apply reasonable regulation to ameliorate chronic hepatitis. What’s more, Prof. Liu especially emphasized the importance of decent medical care for patients with chronic hepatitis, which is critical to the quality of life but easy to be overlooked. Care services for such chronic diseases encompass many aspects, such as mobility, diet, psychology and so on. So in the health-caring industry, the care of chronic diseases requires considerable resources. However, due to the insufficient nursing workers and doctors in China, it is much more difficult for them to give patients adequate education and dietary guidance. What’s worse, most patients with alcoholic hepatitis lack a proper understanding of their disease. To help mitigate this problem, dietary management is regarded as a key factor, as different dietary combinations contribute differently to health to a very large degree. For example, relevant studies have shown that a diet featuring a preference for fresh milk and fruit has a significant positive effect on reducing the risk of the development of non-alcoholic fatty liver hepatitis.

Summary：

Through this interview, we recognized the nursing needs of patients with chronic hepatitis. We realized that it is not enough to construct only one test for chronic hepatitis. People's needs lie in all aspects. They have both awareness gaps and testing needs, as well as a wide range of difficulties in treatment and care. We wanted to exert our efforts on solving more of their difficulties for the well-being of humanity. Therefore, the initial aim of our project expanded from the construction of a hepatitis test to a dual application of detection and ancillary care. We started with a background analysis and thought about the appropriate strategy at a later stage.

6. From China to the World

In our conversations with doctors and professors we also learned about the hepatitis situation abroad. What can we contribute to the world? Can we advance the cause of human and world health? We began to learn more about the global situation of hepatitis.

According to data released by the World Health Organization in 2021, one person dies from a hepatitis-related disease every 30 seconds globally. Commonly known as hepatitis B and C, it causes 1.1 million deaths and 3 million new infections each year. Notably, since March of 2022, several countries and regions around the world have reported severe acute hepatitis in children of unknown origin, the cause of which is not yet clear and the situation is not promising.

In 2016, the World Health Organization (WHO) set the goal of eliminating hepatitis by 2030, which has become the "No. 1 issue" in the field of liver disease prevention and control worldwide. As a region with a high prevalence of liver disease, China plays a pivotal role in achieving prevention and control of liver disease.

Mark Bartlett, head of the World Health Organization's Global Liver Programme, emphasized: "To fight liver disease, firstly we must identify those infected, and the current situation is that a large number of infected people do not know they are infected. The second difficulty is to further eliminate discrimination against people with liver disease. And the third is the issue of treatment. There are still irregularities in treatment, and here it involves re-education of doctors, elimination of regional disparities, patient education and popularization of science. It is not the responsibility of medical professionals alone to achieve this wonderful vision, but requires the joint efforts of the government, NGOs, the medical profession, society and individual patients."

With this in mind, we believe the project design we envisage has global significance.

The emphasis on the field of hepatitis in China is a strong backing for our approach to chronic hepatitis testing. And the World Health Organization's analysis the hepatitis situation, which is similar to our background and findings. This may be a special time for the field of hepatitis research.

Using synthetic biology, we hope to remedy the shortcomings of chronic hepatitis detection methods, significantly reduce the development of chronic hepatitis and contribute to human health.

Summary：

The investigations conducted in this phase is significant in that it is the first time for us to confront a problem on human health and well-being. We aspired to help people test chronic hepatitis by experimentally providing a simple and quick testing method. We were seeking ways to assist patients in their later care through communication and collaboration, and to raise awareness of chronic hepatitis and synthetic biology through education.

With this in mind, we began to construct the framework for our experiments.

Stage2: Interviews of Stakeholders and Solution Design

1. Brainstorming with iGEMers

After the investigation above, we started our brainstorming. At present, the level of bile acid is an effective indicator of diversified liver diseases detection worldwide. Moreover, the level of bile acids varies little between normal individuals, which makes it suitable for index monitoring. Generally speaking, the method of detecting bile salts mainly includes the detection of serum total bile acid and urine total bile acid content. Serum bile acid content is inconvenient to sample, and is often affected by diet, so it is only suitable for accurate detection in hospital environment. By contrast, with the convenient sampling and stability against diet, the content of urinary bile acids is more suitable for routine detection. So, we chose urinary bile acid as the detection indicator of chronic hepatitis. In our design, we proposed to take advantage of synthetic biology to develop a fast-reaction test kit that can be applied to the homely detection of liver hepatitis.

It is worth mentioning that during the brainstorming stage, we came up with three ideas in total, from which we need to choose one as our final project. We contacted the iGEM team from Nanjing Medical University (NJMU-China). They discussed with our Wet lab and eventually we finalized our project – Liver Monitor: Rapid cell-free detection of liver disease based on bile acids level.

They also reminded us of confirming the changes of bile acid content in urine before and after contracting liver disease. We accepted their advice and verified this question. Meanwhile, we also offered some suggestions for their project and gave them some assistance.

In the later stage of our experiment, we attached importance to communication and cooperation with other iGEMers. Throughout the whole season, NJMU-China and BIT-China played an important role in the progressing of our project, especially for the Wet Lab. We also gave them some valuable suggestions.

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2. Prof. Yan: Using ddRFP

We invited Dr. Yan Xin, a microbiology expert, to participate in the development of the protocol of our project. After discussions, Dr. Yan Xin approved our current project idea, and suggested that ddRFP could be used instead of turning on the downstream promoter pathway. By simplifying the gene pathway, we were able to avoid the side effects of complex reactions.

Summary：

We had improved our overall design of the project as follows.

Firstly, BSS removed the sulfate group in urine bile acids, generating desulfonated bile acids that could be recognized by our receptor. Then, after being activated by bile acids, FXR would dimerize with RXR, driving the downstream ddRFP to dimerize, subsequently emitting red fluorescence. Finally, the fluorescence would provide a warning signal for potential patients with chronic hepatitis. We hoped that our project could be used as a reference for testing other diseases.

3. Discussing the Feasibility and Significance of the Kit with Dr. Xiao

After designing the general framework, we immediately started a new investigation to verify the feasibility of our assay. We learned that some products on the market were using bile acids for hepatitis testing. Was our assay sufficiently superior to them? We consulted Dr. Xiao, who works in the laboratory department of the Jilin University Hospital. He has extensive theoretical knowledge and operational experience in medical chemistry testing methods.

Dr. Xiao showed great interest in our project and agreed with our choice of urine bile acid testing. He talked about the existing methods in the medical industry for urine bile acid testing, but they all have certain disadvantages. For example, high performance liquid chromatography and mass spectrometry, which are commonly used in hospitals, are complicated to handle at home, and the instruments are expensive. There are also monoclonal antibody-based enzyme-linked immunosorbent assays and electrospray ionisation mass spectrometry, which need to be further optimised. In addition, there is more primitive bile acid sulphate enzyme method, which has expensive reagents and enzymes. He hoped that our team could attempt actively to improve this situation. He also mentioned that we need to firstly investigate the public's acceptance of this testing method and whether they have corresponding requirements or needs, such as reasonable price and degree of security.

Summary:

Dr. Xiao explained the limitations of the current urinary bile acid testing in medical industry, and was supportive of our experimental prospects. Harboring connecting people as our prime principle, we were more motivated by Dr. Xiao's encouragement to rethink about its application among people.

4. Public Survey: Connecting People and Applying It to People

Encouraged by Dr. Xiao, we set about preparing a targeted survey to continue to explore their ideas and intentions. The focus of the survey was understanding the public’s acceptance and approval of this type of testing, and finding out whether they had any corresponding requests or needs.

We conducted a self-check prior to the survey, taking the lessons of the last public survey into consideration when selecting our target population.

Q: Who were selected as our target population? Why? Are they representative?

A: The general population were chosen, because a random selection of people in a community is in line with the purpose of this survey to find out ordinary people’s needs toward a testing kit, and the results were representative.

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After feeling assured that we had got a right starting point, we conducted random interviews and questionnaires respectively.

We had specifically stressed to people that this is only an intention survey about using the kit. We were not currently using it for clinical trials. And it is a test on urine, so the experimental substance will not enter the human body directly.The questionnaire survey showed that the public was interested in a new kit for home use, and there were 96% of them willing to try it.

The interviews revealed that people were more concerned about the following questions.

1. Is the accuracy of testing guaranteed?

2. Is it safe? Will it affect the environment?

3. Is there any other services other than testing?

From the questionnaires, we knew that people had high expectations on the new type of kit. They easily associated hepatitis test kits with those devices like home blood glucose testers and oximeters, which pioneered the introduction of modern medical equipment into home, and then facilitated their acceptance of the new kit for hepatitis. We felt happy about this finding because from it we saw the prospects of applying the kit to people once it was brought to market.

Summary:

Feedback from the public survey had inspired us greatly in the subsequent progress of our project. We had incorporated the three areas of concern and need from the public into our project, and continued to think about the ways to address these issues as we proceeded with the experimental design.

At every stage of our activities, we were committed to connecting and serving people.

This public survey was conducted when we were providing voluntary medical consultation for pets in a community together with students from College of Veterinary Medicine in Nanjing Agricultural University. Welcome to find out more about that.

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Stage 3: Problem Solving

1. Consulting Dr. Chen: Helping Our Wet Lab to Solve the Problem of Low Brightness of Fluorescent Protein

The Wet Lab met some difficulties during the experiment.

We chose dimerization-dependent fluorescent protein (ddRFP) as the reporter. Theoretically, FXR would dimerize with RXR after being bound with bile acids and activate the promoter. After the dimerization of these two parts, they would emit red fluorescence signal. However, some problems beyond expectation occurred, including the low brightness of the fluorescent protein, and obvious fluorescence difference whereas invisible to naked eyes. To solve this problem, we contacted Dr. Xi Chen.

After being informed of our project, Dr. Chen analyzed the factors that might affect the brightness of fluorescent proteins. At first, he suggested that we tried to link the two proteins without receptors. But after verification, we did not get the ideal result.

So, Dr. Chen suggested us to use the linker to connect these two fluorescent proteins and test their binding ability as well as color-rendering ability.

We adopted his suggestion. The results showed that the two proteins emit fluorescence after linking, while the color was pink instead of showing bright red.

Given our feedback, he suggested us to use the T7 promoter to increase the expression level. Finally, after the replacement with the T7 promoter, a bright red fluorescence was observed.

2. Consulting Prof. Josef: Obtaining Strains that Emit Visible Fluorescence

We conducted the experiments while exploring. Using ddRFP, we found that the fluorescence intensity was lower than expected. We attempted to find a certain explanation in previous studies. Then,according to the literature, the structure of ddRFP was different from what we simulated, and there were minor differences between its original sequence and the sequence we used. We believed that these sequence differences affected the folding of the protein and made the fluorescence intensity weaker. Fortunately, FXR and RXR had been well studied and characterized, and the gene sequences and expression conditions obtained by our sequencing were not inconsistent with the literature and were correctly-folded structures.

Dr. Xi Chen learnt the problem we were having and introduced us to Professor Josef Voglmeir, who is experienced in ddRFP research, and recommended us to ask him for advice on related issues.

After an in-depth conversation with us, Professor Josef Voglmeir provided us with strains he was working on that fluoresced with the naked eyes to help us run our project more smoothly.

With the help of Professor Josef Voglmeir, our problem was solved quickly. We could almost see the light of victory.

3. Consulting Professor Wang: Solving the Problem of Inclusion Body

In September, our experiment was near the dawn; however, it was suspended at the last stage. The Wet Lab members found that according to SDS-PAGE electrophoresis, our target protein was in the precipitation, which meant that we failed to purify the target protein. We suspected that this phenomenon was caused by unwanted inclusion body.

To solve this problem, we consulted Professor Weiwu Wang .

Professor Wang speculated that the concentration of IPTG we used was too high to lead to the formulation of considerable inclusion body. We followed his guide and tried to reduce the concentration of IPTG to a lower level.

After the shift, we expressed the target protein successfully.

4.Respond to People's Concern about the Accuracy of the Test：

a.Bile Acid Test with the Kit in A Simulated Urine Environment Confirmed the Good Detection Ability of Our Research Results

The experimental results showed that our system could effectively detect the concertration of CDCA (Fig. 4). The bile acid sulfate sulfatase could also function at room temperature(Fig. 5). For optimal performance, we performed a simulation of the urine environment by integrating the experimental data. Therefore, we predict that the best way to use our product is to dilute 5 times urine at 25 ° C. This provides a convenient and low-cost home testing method for patients with potential liver disease.

b.Interviewing with Mr. Li Mingxing, R&D Staff of Getein Biotechnology Co.,Ltd: Gaining Commitment from the Company

Getein Biotechnology Co.,Ltd. is a major supplier in the field of in vitro diagnostics, especially POCT in China. It is dedicated to the research, development, production and sales of professional medical devices and diagnostic reagents. Their products mainly cover cardiovascular diseases, kidney injury, infectious diseases and other major diseases, and are widely used in hospitals, community outpatient clinics, health centers, laboratories, etc. at all levels. Getein Biotechnology Co., Ltd. is one of the top companies in China in its field.

We were honored to contact Mr. Li Mingxing, the R&D staff of Getein Biotechnology Co., Ltd.

Mr. Li Mingxing gave us a realistic and professional evaluation after learning about our project design. He also shared with us his experience on the development of assay kits and the related technology.

He commented that our project is in line with the current concept of POCT testing. Our test is non-invasive and is in line with the application scenario. He thought highly of our project and regarded it as a good, meaningful and valuable topic. For POCT home self-test, the ultimate goal to pursue is accuracy of the test results. He suggested us to work on quantitative testing in the future, continuing to determine the minimum detection limit, precision, and accuracy, to analyze the specificity, to conduct interference experiments, and to study the negative and positive compliance rate, so as to increase the accuracy of product results and the credibility of new method. Convenient and fast operation is an unchanging concept in our design.

He also introduced some domestic and international supervision and management agencies to us, for example, the State Food and Drug Administration (CFDA) in China and FDA in the United States.

He also would like to help us optimize our testing protocols and improve our testing rates. In the future, if possible, he would provide us with the protocols and procedures to establish clinical reference intervals, guide us to mitigate matrix effects in clinical sample dilution, and provide us with some experiences in clinical testing.

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Summary:

By talking with Mr. Li, we learned about the new development of the test kit technology, and learned about the domestic and international legal regulations, management supervision standards. The direction of our future improvement was thus clarified.

We realized that the world has a huge demand for the development of home testing methods for various diseases, and we had a long way to go to change the dilemma of chronic hepatitis testing. We hoped that our results would be of interest in related testing.

Responding to people's concerns about detection accuracy：

With the help of our experts and teachers, our experiment progressed smoothly, and the data measured from our experiment showed the effectiveness of the kit, which can solve the public's concern about the accuracy rate to a certain extent. Moreover, Mr. Li Mingxing affirmed our current experimental results and would like to provide us with better technical support in the future, which makes us believe that the detection rate of the kit will be improved in the future.

5. Responding to People's Concerns about Security：Discussing Safety Issues with Professor Yan

After getting a successful result, we contacted again Dr. Yan Xin, the microbiologist who once helped us with the topic. Dr. Yan Xin firstly praised what we had achieved, and then accepted our interview.

We discussed the safety of the assay kit. The final product we designed would be a cell-free system, which can only perform biological activities under certain quantitative conditions. The system will not contain substances that are harmful or toxic to organisms and the environment. Therefore, it will not cause harm to the environment if released outside the containment area.

We clearly responded to the public's concern about safety here. Our final product is non-toxic and non-harmful to organisms and the environment.

Stage 4: Focus on People's Need for Care

Our experimental design has come to a successful ending, but we are still on the move.

1. Discussing with the iDEC Team

During the pre-interview survey, we noticed the contradiction between the huge demand for care for people with chronic hepatitis, and the imbalanced and insufficient development in the healthcare sector. In the post-survey, people were also keen to know more about our project than just testing.

Sticking to the original idea, we still bore in mind to develop a dual application product for hepatitis test kit and complementary care.

We have been talking to many teams and students to get inspirations on the ways to take care of the problem.

The International Directed Evolution Competition (iDEC) is an international research competition on the theme of directed evolution. iDEC and iGEM share similar research interests and we often communicate with iDEC teams. We seek common ground and work together to promote each other's progress.

The iDEC team suggested that we could design a program for hepatitis test users to solve some of their problems when necessary. The development of a program would greatly facilitate the correct use of the kit, as well as provide other medical guidance on chronic hepatitis or a personalized service.

The idea of developing a dedicated user program sounded good, and members of the Wiki group said they could try to develop one. But we did not know enough about it. “Is it feasible? What kind of program would it be? What kind of efforts shall we put in?” We immediately took actions.

2. Interviewing with Programmer Mr. Qi

Since we knew very little about the design and post-programming process, we needed to fill in the gaps in our knowledge. We contacted a programmer, Mr. Qi. His job is to develop software and programs.

After learning our objectives, he first shared the differences, advantages and disadvantages of APP and WeChat applet based on our ideas. WeChat is the most dominant communication platform in China and most citizens use it. WeChat applets are applications that can be used without downloading and installation, using WeChat as the backing platform.

We had summarized the points：

Mr. Qi emphasised that there is no absolute good or bad app or program. Everything starts from needs of the product, and the budget. We had analyzed our needs and the WeChat applet can meet them in terms of audience and functionality, and has a higher feasibility in the short term.

After identifying our medium, Mr. Qi briefed us on the way and process of program development and the Wiki group acquired some tips from him on creating web pages and programs. These tips not only helped the development of the applet, but may also be useful in the building of our webpage.

Summary:

After talking to Mr. Qi we realized that we need to consider the audience, functional requirements, development costs, feasibility, etc. The most important thing was the question "what kind of program do I want to make?" Combined with the preliminary research, we had much clearer thoughts.

3. Envisioning WeChat Applet for Liver Care

The goal of building up a functional WeChat applet for liver care is based on the results of our Human Practices. We had organized various activities to spread the knowledge about chronic hepatitis and synthetic biology to the public. During these interacting activities, we had benefited greatly. Eventually, based on extensive investigations and interviews, we implemented the idea of establishing a WeChat applet of liver care for our potential users.

Firstly, we listed several principal needs of the users with chronic hepatitis:

1. Nursing needs: Chronic liver diseases require long-term treatment, reasonable diet and lifestyle management. Unfortunately, most patients lack recordings and management of their life.

2. Psychological needs: Some patients may suffer from greater psychological pressure after contracting diseases. Studies have shown that reasonable psychological nursing intervention for patients with chronic hepatitis is of great value to their psychological state and disease recovery.

3. Educational needs: Most families have little knowledge about chronic hepatitis. Raising their awareness would be of great significance to improve their situation from changing their living habits and to play a preventive role.

Profile of our target customers and our design concept:

Target customers: Individuals requiring fast-reaction liver test kits, including healthy ones.

Design concept: Sharing short videos and articles about liver health could raise people's awareness of liver disease. By the recording function we offer, customers may take advantage of our products to record and improve their lifestyle. What’s more, establishing a good collaboration with hospital network could offer psychological service to meet customers’ needs.

For the customers using test kits, they can become users of the Liver Nursing WeChat Mini Applet by providing their information to registrate. We offered the following functions on the platform:

1. Life Diary

To help customers better manage their lifestyle, this section is used to record their diet, sleep, mood, and exercises. There were 4 corresponding recording areas. After the selection of this module, one can write down his/her life in these four dimensions and the corresponding data will be compared with our preset healthy lifestyles. Then it will be evaluated, and corresponding personalized health advice would be formulated and provided to customers automatically.

2. Mini Class on Hepatitis

To improve people's awareness of hepatitis, this section provides short video lessons and related articles on hepatitis. During the early-stage investigation, it was found that the general public generally lacked the understanding of the occurrence and development of hepatitis, and the current level of knowledge and education about hepatitis in China was not sufficient either. Thus, we intended to help people make the most of their fragmented time to learn about liver health through portable knowledge education short videos. We will keep on uploading high-quality videos and articles so that people can gain more information about liver health in this module in the future.

3. One-to-one Oriented Psychological Service Community

To meet people's communication needs regarding liver disease and relieve the psychological pressure of patients with chronic hepatitis, this module aimed to provide special communication services to our customers. Studies have shown that reasonable nursing intervention for patients with chronic hepatitis is of great value to their mental state and recovery. So, we decided to provide psychological counseling services. We realized that although the resources of professional doctors are in short supply, the huge network of customer service resources in hospitals is currently in a state of oversupply. Most of those staff in medical network services are well-trained and have sufficient knowledge of many diseases. They mainly provide disease consultation and online communication services. Actually, they can fully meet the needs of patients instead of turning to doctors in business. Plus, the hospital network customer service is not equal to the hospital hotline customer service, it will not occupy the hospital's hotline at all. Based on this discovery, we integrated the hospital network customer service into our applet. Patients could initiate an online discussion in this section, and they could be automatically connected to the hospital network customer service for communication.

It is worth mentioning that our prototype of this communication module was to create an open and threshold-free sharing community that was similar to YouTube. In other words, users could upload relevant posts and communicate freely. However, after further investigation, we found that there had already been communication software or communities for some special groups in use. Designers of these applications tried to achieve a communication society between special groups by directly forming a large community to meet patients’ psychological needs. However, these communities were not significantly different from ordinary ones. Considering the occurrence of irrelevant topics or detrimental information to our platform in a free communication atmosphere. We eventually decided to set the one-to-one communication style, which limits the free communication between users and avoids problems such as the leakage of privacy. If feasible, the one-to-one oriented psychological customer service community will become a new link between users and medical staff.

Summary：

We did our best to meet all the needs of patients with chronic hepatitis. The above are our preliminary planning assumptions, and we sincerely hope that our attempts will be beneficial. For these three functional modules, we conducted a questionnaire survey in the public.

4. Feedback from the Questionnaire Survey on the Functional Design of the WeChat Applet for Liver Care

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We received 70 pieces of feedback in total. The results indicated that people have a high expectation for our health applet, and one of the reasons was that our WeChat applet was very convenient to use. We speculated that for most healthy people, it was "redundant" to download a specific software to pay attention to their liver health, but our applet did not occupy the resources in their cellphones. So, it is a sensible choice for us to choose to develop a WeChat applet. For the functions of the applet, most people found it very useful. They could use their fragmented time to record lifestyle data and understand relevant knowledge about liver health, especially the "one-to-one oriented psychological customer service community", which earned a high evaluation. Compared with the community where users could give their opinions freely, communicating with the hospital's service online could not only meet people's communication needs with experienced experts, but also avoid some privacy leakage problems or detrimental statements.

We are glad that our design idea has been recognized by the public. We have designed the prototype of the app under the guidance of Mr. Qi. Although it has not yet been vetted and put into use, it qualifies as an exciting experiment. We have stepped into an unfamiliar territory and made a little progress, which proves that our potential is unlimited if we imagine and practice. We hope that both our test kits and Liver Nursing WeChat Mini Applet will become reality in the future. In the meantime, Apart from recognition and appreciation, we also received some suggestions for our WeChat applet. These will serve as our inspiration and we are planning to turn these ideas into reality.

5. Interviewing with Start-up Teams

As inexperienced developers of test kits, we bothered to realize that people's approval does not mean the final application and commercial benefits. How should we make people use and understand our test kits and applets better? We were lucky to have a great opportunity to exchange ideas with some start-up teams.

"The 8th China International Internet+ Student Innovation and Entrepreneurship Competition” is one of the large-scale competitions for university students in China. The competition aims to promote social progress by encouraging exchange, cooperation and integration among young people in innovation and entrepreneurship in various schools, as well as the achievements in the construction of new engineering, new medicine, new agriculture and new arts, taking into account the real needs of various economic and social fields. The Jiangsu provincial selection competition was hosted by Nanjing Agricultural University, with a total of nearly 700 teams from different universities and disciplines, all of whom have outstanding achievements and contributions in various fields. During this period, we seized the opportunity to conduct random interviews with these teams who have rich experience in creation, hoping to receive further innovative, commercialized experiences and suggestions.

In response to our desire to have the opportunity to apply the products to humans in the future, the Nanjing Agricultural University team suggested that the kit could be used in a small-scale pilot project to observe the market demand through a small-scale rollout in order to make improvements. In response to our desire to build a liver care micro-application, they made a more far-reaching suggestion. They suggested us to build more sections with different functions according to the needs, and to confirm if we should seek direct collaboration with companies and medical professionals. We also want to think about how to promote the kit and the liver care micro-app.

The exchange with start-up teams broadened our horizons and gave us a reminder and a new direction to explore. First of all, the project needs to meet the test of national requirements and legal procedures, and be able to stand the test of the public. In addition to our efforts to get the project implemented, we need to focus on publicity to raise public awareness of the disease and the project.

6. Chronic Hepatitis from a Global Perspective

We had surveyed people's willingness and confirmed that they would like to try the kits. We had designed an additional service, the Liver Care WeChat app, based on people's needs. We expected more people to pay attention to chronic hepatitis as a disease and build human health and wellbeing together. We also expected more people to understand and evaluate our program to promote us to improve it.

We tried to seek cooperation to promote our results with others. We contacted OHIA and had an online meeting with them.

OHIA is the only student organization in China that is registered with ISOHA (International Student One Health Alliance, ISOHA). We were introduced to the One Health concept through a conversation with the OHIA Club at Nanjing Agricultural University. "One Health’is about global health, which integrates multidisciplinary knowledge to address regional, national and global health issues and improves human, animal and environmental health. The concept of "One Health" provides us with some insights. We recognized that the WHO concept is closely related to One Health, namely, the idea of health globalization.

Bad habits behind chronic hepatitis can actually be extended to the more far-reaching effects of globalization. For example, the epidemic of viral hepatitis, unhealthy habits such as alcohol consumption and late nights represent the pollution of the brewing industry and urban light pollution. Effects of these negative factors can finally be better understood in terms of the cycle of relationships between humans, animals and the environment. This exchange not only answered the meaning of our work from another perspective, but also provided us with a new idea to persuade people to detect and prevent chronic hepatitis early.

The exchange allowed us to understand each other, promote each other, and expand the influence of iGEM and One Health.

Summary and Future Research

At present, the need for treatment and care of chronic hepatitis in China remains enormous, and public awareness of the disease is yet to be spread. Chronic hepatitis is a complex disease, and although there is now a greater understanding of the mechanisms of its development and the identification of appropriate targets for drug therapy, there are no specific drugs available for clinical use. Active detection of chronic hepatitis at an early stage is particularly important, as aggressive treatment of early disease can achieve significant results and slow the progression of the disease, while reversing advanced liver fibrosis or cirrhosis once the disease has progressed can be a major challenge.

The research and interviews we conducted above helped us to refine our project and make it more mature and meaningful. We have been able to guide the progress of the experiment and understand people's needs through extensive communication. Connecting people is at the heart of our work.

In terms of experiments, our home test kits are designed to provide a good reference for the detection of chronic hepatitis and offer more hope for an early cure, given that there is no particularly prominent method for detecting chronic hepatitis. In terms of connecting people, we have made many efforts to respond the health needs of people, not just those with hepatitis. The functional vision of the Liver Care WeChat app provides a new solution to meet the practical needs of the population.

In the future, we would further optimize our product, making it a practical and feasible solution that is no longer on paper.