To make sure our entire project is feasible and best fit in the world of the medical field, we have always taken the IHP quite seriously through many different forms.

In order to know about the level of public awareness of Alzheimer's disease (AD) and public acceptance of clinical trials and new drugs for AD, we distributed two questionnaires in a stepwise manner.

What’s more, to have an initial understanding of AD patients, current treatments, and the current dilemmas encountered in the development phase of anti-AD drugs, we conducted two interviews with 2 medical specialists.

Also, we made a field trip to a nursing home where lives some elderly people suffer from a cognitive disability. After this visit, all of us have a deeper understanding of how suffering the AD patients are and how selfless the nursing staff are.

Last but not least, so as to better understand the process of the commercialization of the pharmaceutical industry, we made a fourth interview with a business expert, whose suggestions are really helpful for our future development.

Our activities about Integrated Human Practice are listed below:

1.Investigation-Questionnaire 1: Public awareness towards AD

Before starting our further related works, we need to have a basic understanding of public awareness to better carry out follow-up targeted publicity and science popularization. Therefore, we released an anonymous questionnaire on WeChat and other social platforms to help us collect real data.

1.1 Basic information of respondents

So far, we have received 631 valid answered samples. Most of them are teenagers and middle-aged.

1.2 The public's judgment of their own understanding of AD

From the table above, we can see that there is only 10.13% of the respondents claimed that they know about AD well. On the contrary, more than 60% admitted they do not know about AD very well, and there is even 25.16% claimed they have little or no understanding of AD. Through these data, we realized the importance to raise public awareness of AD.

1.3 Testing respondents’ understanding about AD

In order to test whether their statement about the understanding extent about AD is valid or not, we set some basic questions of AD.

Actually, the correct answer is the first two, but there are still 26.01% of people chose the wrong answer, indicating a lack of basic knowledge about AD.

1.4 The general public's preference for the treatment of AD

Moreover, we can clearly see that people are holding a positive attitude of willingness to receive corresponding treatment.

Through our first online questionnaire, it is shown that people are on the verge of a vague understanding of AD, which once again emphasizes the significance to let people get more information about AD.

2. Investigation-Questionnaire 2: public acceptance of clinical trials and new drugs for AD

Meanwhile, since our project’s goal is to find a possible remedy for AD, apart from the remedy’ feasibility, we also need to know whether people are willing to accept this new treatment or not and adjust our arrangement according to people’s willingness. Therefore, we released the second anonymous questionnaire on WeChat and other social platforms to help us collect real data.

2.1 Basic information of respondents

Since we do not know the range of potential or future users of our treatment, we released this questionnaire in a wider range on the Internet. Currently, we have 966 valid samples. Most of them are middle-aged people.

2.2 Public understanding of current available treatment of AD

Still, people’s understandings are not that high. Specifically, there more than 60% of respondents claimed that they do not know the currently available treatment of AD well. Once again, it is crucial to introduce basic information about AD treatment before we show our product.

2.3 Public sentiments toward the need for new treatment of AD

In fact, there is a significant global need for research and development of new AD drugs, because there is currently no real cure for AD, only delaying or alleviating. This indicates that public awareness of AD treatment options is limited.

2.4 The degree of public support for new drugs

Fortunately, we found that most of the respondents are holding positive sentiments about introducing new treatments for AD. This is very promising for the launch of new drugs in the future, and it also means that the pace of adoption will not be slow.

2.5 Public willingness to accept new AD treatment

According to the table above, because the number of people in each category is not very different, we can't tell whether people will accept and use it on a large scale after the actual new drug is launched.

2.6 The reason why people are reluctant to accept new AD treatment

Among the options we have given, each option has a majority of people to choose. Most of them are still due to health safety considerations and lack of relevant information, so we will popularize relevant knowledge in the future.

2.7 Public preference about different types of AD treatment

Again, this table shows people’s concern about the safety of new AD treatment. In other words, people actually hold some wait-and-see attitude towards new anti-AD drugs.

Through our second online questionnaire, the major problem of acceptance of AD treatment is its safety. While reaching our target, we should make sure people understand the validity and safety of our product.

3.1 Professor Qin Ruomeng

In the process of developing our product, of course, we also need some professional knowledge consultation. We interviewed Dr. Qin Ruomeng from Gulou Hospital (Affiliated Hospital of Nanjing Medical University). In this interview, our main purpose is to have a preliminary understanding of the situation of AD patients, current treatment methods, problems encountered, and the specific situation of medical staff.

Current Status and Symptoms of Alzheimer's Disease

We know that the number of Alzheimer's disease patients is increasing in China and worldwide. We wanted to learn more about the current status of AD, so we asked Professor Qin Ruomeng the following questions: How many Alzheimer's disease patients are diagnosed in your hospital per month or per year? What are the most significant symptoms of Alzheimer's disease?

Professor Qin Ruomeng answered as follows: The diagnosis of Alzheimer's disease can be categorized as clinical diagnosis or pathological diagnosis. Clinical diagnosis is based on typical symptoms, while pathological diagnosis requires specific biomarkers such as the measurement of amyloid protein in cerebrospinal fluid or its concentration. Pathological diagnosis is more demanding, expensive, and invasive, hence making it more difficult. Clinical diagnosis ranges from a few hundred to over a thousand cases per month, while pathological diagnosis is less than ten cases per month.

One of the earliest symptoms experienced by patients is a decline in recent memory. Although they may have clear memories of events that occurred decades ago, they may completely forget recent events, such as a visit from relatives yesterday. The difference between memory loss in AD patients and general forgetfulness is that general forgetfulness only involves forgetting specific details (the time the relatives arrived, the specific content of the conversation), while AD patients typically experience complete forgetting of the entire event. General forgetfulness can be recovered through reminders, but AD patients' memory loss is difficult to improve even with reminders.

Other symptoms include a decline in language abilities, including decreased expressive abilities, difficulty naming things, and confusion in logic. There is also a decline in executive functions, where tasks that were previously performed in the same amount of time now take longer. Spatial awareness also decreases. Emotional problems may arise, which can manifest as agitation, irritability, depression, or apathy.

Main Treatment Methods for AD

We wanted to know how many modern methods are available for treating and relieving symptoms, and specifically what those methods are. Professor Qin mentioned that there are several methods, including medication therapy and rehabilitation training.

Medication therapy includes drugs such as Donepezil, Rivastigmine, Galantamine, Memantine, and newly approved drugs like Lecanemab and Donanemab that have passed phase III clinical trials. There are also some antidepressant drugs like SSRIs, SNRIs, and NaSSAs that are used for emotional treatment.

Rehabilitation training methods involve techniques such as Transcranial Magnetic Stimulation (TMS), Direct Current Stimulation, Deep Brain Stimulation (DBS), and cognitive training, which aim to improve overall physical function.

Challenges and Perspectives in Alzheimer's Disease Research

Q1: Do you think it is feasible to target the adrenergic receptor as a potential breakthrough for drug development by proving its association with Alzheimer's disease?

A1: It is possible, but there are still many unknown factors. For example, finding drugs that target the alpha2A receptor is a challenge. Some existing drugs have effects on the 2a receptor, but they may not have the desired efficacy. Additionally, the potential adverse reactions of drugs developed through this technology would need to be considered and tested. There is still a long way to go.

Q2: What are the main challenges that Alzheimer's disease research currently faces? Are there any new research directions or developments?

A2: The main challenge lies in the fact that the exact cause of the disease is not yet fully understood. The current classic hypothesis is that abnormal deposition of amyloid proteins leads to a cascade of pathological reactions. Many drugs have been developed based on this hypothesis, but the majority of experimental results have been unsuccessful.

Hospital Care for Patients and Differences in Patients' Attitudes Before and After the Onset of the Disease

Q3: What role can hospitals play in the treatment and care of Alzheimer's disease patients?

A3: Hospitals can play a certain role in the daily care, treatment, and living conditions of Alzheimer's disease patients, but the role is limited. There are currently almost no specialized institutions in China for the recovery of Alzheimer's disease patients, so the care provided by family members is usually more meticulous.

Q4: How do the patients and their families you have interacted with perceive the treatment of Alzheimer's disease? What are the changes in patients' psychological state after diagnosis?

A4: Different patients and families have different attitudes. Since there is currently no method that can completely cure AD, and the available drugs can only delay the progression of the disease, family members' attitudes can generally be divided into two types. Some are eager to receive treatment early to delay the progression of the disease and actively try various methods. Others, especially for patients with limited financial resources and whose symptoms do not have a significant impact on daily life, prefer to continue observing and opt for conservative treatment.

How hospitals provide daily care for Alzheimer's patients and differences in patients' mentality before and after diagnosis.

Q5: What role can hospitals play in the treatment and care of Alzheimer's patients?

A5: Hospitals can play a certain role in patients' clothing, food, daily activities, and treatment, but there are limitations. There are few dedicated institutions for the care of Alzheimer's patients in China, so family members play a more crucial role in their care.

Q6: How do patients and their families typically feel about the treatment of Alzheimer's disease? What are the psychological changes in patients after diagnosis?

A6: The attitudes of patients and their families may vary. Since there is currently no cure for Alzheimer's disease and available medications can only slow down its progression, family members may have two different attitudes - some may hope to receive treatment as early as possible to delay the disease progression and actively try various methods. On the other hand, for patients with limited financial resources and whose symptoms do not significantly affect their daily lives, family members may choose to continue observing and opt for conservative treatment.

Summary: Patients' mental states also vary. As memory decline is a normal part of aging, some patients and their families may try to convince themselves that it is just normal forgetfulness and deny the disease. However, as the disease progresses and becomes more evident, patients may experience irritability, depression, and other psychological issues. Family members who bear the immense pressure of caring for the patients can also experience significant negative emotions. As the patients' memory and emotional perception abilities decline, their mentality may gradually become indifferent.

3.2 Professor Shen Xu

In order to understand the current difficulties encountered in the research and development stage of Alzheimer's drugs, and listen to professional opinions related to the project, we conducted the second interview, which is with Professor Shen Xu. Shen Xu is an expert who enjoys the special allowance of the State Council and is currently a professor and doctoral supervisor at Nanjing University of Traditional Chinese Medicine. He was awarded the National Outstanding Young Scientist Award in 2005 and has been a member of the National Committee of the Chinese Academy of Sciences for over 20 years.

Conditions for the Commercialization of Alzheimer's Disease Drug

To gain a better understanding of the commercialization of Alzheimer's disease drugs, our team posed the following questions:

Q1: Our current goal is to prove the viability of the target enzyme in Alzheimer's disease. How can we proceed with commercialization?

A1: Firstly, through our research, we need to demonstrate the specific changes in the enzyme in Alzheimer's disease patients compared to normal individuals. Then, in order to prove the efficacy of this target enzyme in combating Alzheimer's disease, further experiments and modifications will be conducted, followed by medicinal chemistry. Based on the comparison of the most effective anti-AD properties and the completeness of drug development, we can decide on potential commercial partners and negotiate related issues such as intellectual property rights to further advance drug development.

Q2: Can you provide information on the current suppliers of Alzheimer's disease treatments?

A2: There are currently many pharmaceutical manufacturers, but due to the complex pathology of AD, there is still a lack of drugs specifically targeting the disease. Most current treatments are palliative rather than curative. The first-line treatment for AD symptoms is typically donepezil hydrochloride tablets (a cholinesterase inhibitor), which has shown certain therapeutic effects for mild, moderate, and severe cognitive impairments. It has minimal side effects, good drug compliance, significant efficacy, and wide acceptance, and is being widely used.

Q3: What is the profit margin for anti-Alzheimer's disease drugs in general?

A3: It is clear that there is a high profitability in drugs for the treatment of Alzheimer's disease. With the government's renewed approval for projects related to anti-AD drugs, the stock market for companies like FDEMP has seen an increase. Naturally, if we develop an effective drug against AD, the profit margin would be significant.

Government support for Alzheimer's disease drug research and nationally recognized animal models

We also asked Prof. Shen about how greatly may government support our research.

Q4: What is the government's support policy for drug research? Are there any tax incentives?

A4: Similar to drugs for other serious diseases, the government provides support for anti-AD drugs by opening up the FDA fast track (FDA fast track is granted by the FDA to accelerate the approval process for research and development of new drugs for the treatment of serious diseases and unmet medical needs). If the drug shows good efficacy, there may be some preferential policies in place.

Q5: Besides the water maze for mice, are there any other widely recognized animal models used in screening for anti-AD drugs?

A5: Yes. One example is the "novel object recognition" test: mice are placed in a long box and allowed to freely explore. Novel objects that the mice have not seen before are placed in the box, and their interest in these objects is observed. This test is used to compare with AD patients, as they typically show reduced interest in novel objects. Another example is the Y-maze, where a mouse is placed at the bottom of a Y-shaped maze, and food is placed at the top of each arm. After the mouse retrieves the food from one arm, its ability to remember the location of the food in the other arm is tested to assess memory impairment. The elevated plus maze (EPM), which exploits mice's fear of heights, is also used to assess their anxiety state and assist in the screening of AD drugs.

Future development of Alzheimer's disease drugs

We asked Prof. Shen Xu about the trials he has conducted in the past, which were related to anti-AD drugs, in order to understand the strengths and weaknesses of past scientific research, and to use this as a reference for our research.

Q6: Have you ever had the experience of successfully developing a new drug from a targeted approach?

A6: The process from identifying a target to bringing a drug to market is quite lengthy. It takes about 8-10 years to determine whether the identified target is truly novel, and it involves a cumbersome process before it can be sold to pharmaceutical companies.

Q7: In the future of AD treatment, which has a higher probability of breakthrough, chemical drugs or biological drugs?

A7: Biological drugs are large molecule drugs. For example, Aβ, which was just discovered in Alzheimer's disease, is a large molecule drug. Currently, there are already two drugs on the market that inhibit Aβ, proving that large molecule drugs are feasible. However, simply inhibiting Aβ does not fully address the inflammation and other symptoms that affect AD. Due to the complex mechanism of Aβ, large molecule drugs are currently unable to solve all the problems, so there is a larger market for small molecule drugs, i.e. chemical drugs.

Q8: When discovering food-like drugs such as burdock or white snow tea, which have clear pharmacological activity and low or no toxicity, but are not suitable for injection or capsules, can they be developed into traditional Chinese medicine or health products?

A8: There are obstacles encountered in this regard. For example, when extracting the non-sugar component from burdock, called burdock glycoside, it cannot be absorbed orally. Although it is effective when injected, it cannot be directly injected into the vein. Therefore, it needs to be transformed into another compound that can be orally administered after being broken down in the body. As for white snow tea, it grows on rocks above 4500 meters high, making its production limited. Therefore, it cannot be used as a primary medication.

Our discussion with Professor Shen has been incredibly beneficial. He acknowledged the value of our research and emphasized its high commercial potential. Furthermore, we learned that the form of medication should prioritize convenience while ensuring its effectiveness. As a result of our conversation with Professor Shen, we have decided to exclude traditional herbal medicine and dietary supplements as potential forms for our product.

3.3 Mr. Zhang Andong

To further understand the potential commercialization of our project, we first conducted a pitch presentation to Mr. Zhang Andong, the Director of Medical Institution Risk Assessment at Powchan Financial Group Co., Ltd. (formerly COSCO Shipping Finance Leasing Co., Ltd.). We briefly introduced our current commercialization strategy through a PowerPoint presentation.

In the pitch presentation, we highlighted our plan to sell the "Report on the Experimental Process Proving the Association between α2A-AR Protein and Alzheimer's Disease" as a product in our business proposal. We also mentioned that the report would include the target identified as relevant to Alzheimer's disease and the progress made in finding this target.

After completing the pitch presentation, we conducted an interview with Mr. Zhang Andong, focusing on the commercialization of the medical industry. During the interview, he pointed out that there aren't many precedents for directly selling experimental reports in the medical field. Typically, large companies sign long-term outsourcing agreements with research institutions for R&D, making the commercialization value of selling individual experimental reports relatively low.

Specifically for our project, he mentioned that if we were to solely rely on selling experimental reports as a product in our business proposal, there might be some issues. Mr. Zhang Andong also highlighted the typical process for commercialization in the medical industry. Firstly, researchers discover target proteins related to the target disease. Secondly, this achievement is registered as an invention patent. Thirdly, an application for drug development is submitted to the China National Medical Products Administration, and approval is obtained. Lastly, phase III clinical trials are conducted to complete the market launch.

Through our interview with Mr. Zhang Andong, we gained a clearer understanding of the commercialization process in the medical industry. Additionally, he believed that our project has immense potential. With China entering an aging society and the increasing number of Alzheimer's disease patients in our country, pharmaceutical companies show high interest in Alzheimer's disease. Developing a new drug for treating Alzheimer's disease not only has significant commercial value (with a market worth at least 4 billion RMB), but also benefits humanity as a whole.

As a result, we decided to revise our original business proposal. We will now focus on developing a new drug for treating Alzheimer's disease and systematically proceed with the writing of our business proposal.

To deepen our understanding of the physical and psychological conditions of Alzheimer's disease patients, we visited and interviewed a nursing home, Lujiazui Street Comprehensive Old Service Center, in Pudong New Area, and interviewed the head of the cognitive care area there. In order to protect the privacy of the old who live in the nursing home, we will not post any pictures of them.

4.1 Current situation of the senior house

Firstly, we wanted to know about the basic information about the nursing home. The person in charge was really willing to communicate with us and provided us with detailed answers.

Q1: How many elderly people does the senior house currently serve? What is the age range of these elderly people?

A1: The senior house can accommodate up to 93 elderly people in theory, but currently has 65 residents. The average age is 85. The normal occupancy rate is 90%, but due to industry policy reasons, the current occupancy rate is 70%.

Q2: What activities does the senior house usually organize for elderly people with AD? How can the elderly sign up for these activities? Is there any fee? What if an elderly person wants to join but cannot afford it?

A2: The senior house organizes a wide range of activities, including handicrafts, puzzles, games, counting, jigsaw puzzles, calligraphy, concerts, throwing sandbags, and more. Safety is the premise of ensuring that they stay active.

4.2 The work done by the senior house for AD patients and the elderly's living and mental state

The person in charge gave a presentation on their daily activities for the elderly people with AD.

Q3: Does the nursing home provide health-related health education for elderly people with AD? If so, what is the frequency?

A3: Currently, the elderly in the senior house have not been diagnosed with AD. If there is a confirmed diagnosis of AD, a special file will be set up for the elderly. However, many elderly people with cognitive impairment have not been diagnosed in the hospital. There is no cost or registration required to participate in activities. The elderly are happy to participate.

Q4: Does the senior house have rich experience in caring for AD patients? If so, what specific measures are taken?

A4: Sometimes patients cannot eat or take care of themselves. They need care in all aspects. Patients with AD cannot express themselves, so the caregivers need to observe and protect them like infants. The senior house has installed doors with codes and locks to prevent patients from getting lost. There are also protective measures to prevent them from getting hurt. Special items can be used to help them remember things, such as beautiful objects or old items (considering space limitations, online pictures can be used, such as enamel basins and famous songs that are well-known). The caregivers are very patient.

Q5: What changes can we expect in the level of attention from family members of elderly people who are diagnosed or have symptoms similar to AD?

A5: When signs of AD are noticed, the family members will be notified. Some family members may not accept it, but most of them understand and will take the elderly to professional hospitals for examination. Family members will spend more time with the elderly, help with meals and hairstyling, and communicate with them through video calls, etc.

4.3 Heartwarming stories between caregivers and AD patients and requirements for caregivers

The person in charge said that although nursing work is truing tiring and exhausting, there are also many heart-warming stories. Because of this, they go out of their way to still love the job and never think of giving it up.

Q6: Have you encountered any heartwarming stories while interacting with AD patients, or any common challenges that staff members face?

A6: The challenges for caregivers include the exhaustion from constant communication and having to remind the patients of daily activities, such as feeding them as they may forget to eat. Caregivers need to show love and patience, as some patients may exhibit violent or abusive tendencies and even vomit. Despite facing numerous difficulties, caregivers are truly heroic.

Q7: What qualities are generally required for caregivers working in your senior care facility? What measures does the institution take if healthcare workers experience excessive mental stress?

A7: Caregivers should possess qualities such as empathy and patience. When healthcare workers experience excessive mental stress, the institution organizes team-building activities, where they can eat and have fun together, creating a sense of belonging. Additionally, they engage in physical activities like exercise routines and watch entertaining videos, providing various stress relief methods. The staff members are generally stable and well-supported.

In summary, the senior house demonstrates a commitment to elderly care, particularly for those with AD, by providing a supportive and engaging environment. Through various activities, education, and empathetic caregiving, they aim to enhance the quality of life for their residents.

· Through two rounds of surveys, we identified a significant lack of clarity in people's understanding of Alzheimer's Disease (AD). The primary concerns surrounding AD treatment drugs revolved around safety and effectiveness.

· Subsequent to three expert interviews, our research's value received recognition from experts. However, we also realized that the product's form plays a crucial role in its economic viability.

· During our visits to nursing homes, we gained firsthand insight into the complexities of caring for elderly individuals with AD. This experience has reinforced our determination to continue our research and provide solutions for families dealing with this challenging issue.

In conclusion, out team aim to test the feasibility of reducing α2A-AR on cell membrane, and therefore to find the possible remedy for AD.Once we verify the α2AAR is related to AD process, we could use it as a target to develop a drug, thereby preventing the production of protein precipitates in the patient's brain. As a result, the disease will be alleviated and medicine could be made.

In conclusion, out team aim to test the feasibility of reducing α2A-AR on cell membrane, and therefore to find the possible remedy for AD.

Once we verify the α2AAR is related to AD process, we could use it as a target to develop a drug, thereby preventing the production of protein precipitates in the patient's brain. As a result, the disease will be alleviated and medicine could be made.

Our approach to real-world implementation will focus on demonstrating the reliability and effectiveness of our product. By use advertising and cooperation with pharmaceutical companies, our product will march both To-B & To-C.