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Moreover, Yang Yifeng is recognized as a genius by the hospital. If he won the bid, no one would suspect that there was a fake in it, but today's incident can be regarded as bad luck for eight lifetimes.
What's more, the ones that contradict his subject were also published in top journals like science. If this is not handled well, it will really be impossible to finish the question, and it will be difficult to finish.
Even in the end, the management personnel of the National Natural Science Foundation of China would come to trouble Yang Yifeng, saying that when he applied for the project, he had insufficient reserves in the early stage.
Of course, even if it was such a reason, Ding Changle had to find a way to make Yang Yifeng go around.
Yang Yifeng is now holding his tender, the ppt he has already prepared.
At this moment, his face was full of sternness: "Master, Professor Jiang Hong, fellow seniors, thank you for your hard work. This time, the topic I plan to apply for is nerve healing."
"The details are as follows, you can read my ppt content, I don't gossip..."
"Nerve repair is currently a very popular research direction in many departments such as hand surgery and neurosurgery. The significance of the existence of this topic is that after the nerve is broken, even if it is stitched together."
"Even with the best nerve suture technology and the best suture objective conditions, there will be loss of function after nerve healing, or even non-union. This is the background and role of the research significance."
"And the small background of my choice of topic has the following aspects."
While talking, Yang Yifeng clicked on the ppt to introduce everyone.
In fact, at Yang Yifeng's level, the topics he researches are not only the top group of people in the world, but also, in the field of his research, there are not many people who can compare with him in depth and knowledge reserve. He compares.
Because the direction was deliberated by Yang Yifeng himself, and he did a lot of collecting work, so if he wants to find a solution now, he must also present the basic research background.
It is equivalent to explaining all the research mechanisms and ideas of this topic, so that everyone can help to find a solution, instead of asking everyone to find or collect information by themselves, wasting time.
"The concept of neural healing is the process by which damaged parts of the nervous system are restored to normal function."
"In recent years, not only in China, but also more and more research teams all over the world have begun to study the mechanism of nerve healing and explore related popular targets and healing mechanisms. The following are some of the more popular mechanisms. And some of their simple action processes."
"The first, and currently the most popular understanding is that all healing is inflammatory healing, so nerve healing is no exception."
"So?"
"Applications of the inflammatory response and modulation of the immune system to the nervous system are --
"After the nervous system is damaged, the regulation of local inflammatory response and immune system plays a key role in nerve regeneration and repair. Therefore, regulating the inflammatory response and immune system of the nervous system may be an important target to promote nerve healing."
"Nerve growth factors and neurotransmitters: Nerve growth factors and neurotransmitters are important molecules that affect neuronal growth and regeneration to promote nerve regeneration and repair.
"Extracellular Matrix: The extracellular matrix is the supportive tissue surrounding cells that plays an important role in nerve regeneration and repair."
"Gangliosides and other molecules: Gangliosides and other molecules are signaling molecules between neurons and their surroundings, and they can affect neuronal growth and regeneration."
"The above are the popular directions of research, and these directions are covered in the articles published this time. The published articles are the conclusions of a very comprehensive topic and the cooperation of multiple researchers. "
"Regarding the research on inflammatory response and immune system regulation in nerve healing, some studies have shown that local inflammatory response can play a positive role in nerve regeneration and repair, but excessive inflammatory response may negatively affect nerve regeneration. Therefore, Finding molecules and drugs that modulate the inflammatory response and the immune system is a current research hotspot."
"In recent years, some drugs that regulate the immune system have been confirmed to promote nerve healing, such as some antirheumatic drugs, glucocorticoids, neuropeptides, etc. In addition, some cytokines such as interleukin-10 (IL-10), transformation Growth factor-beta (TGF-beta), among others, has also been found to regulate inflammation and the immune system, thereby promoting nerve healing."
"In the paper published this time, it happened to cover the role of interleukin-10, a cytokine, in nerve healing."
"Then if we want to go deeper, we must either do the parallel pathway of IL-10, or do the role of the upstream and downstream pathways of IL-10."
"And when I checked the literature before, I found that the upstream and downstream pathways are basically perfect at present, and there is no groundbreaking significance, so it is a redundant, or exclusionary, tentative research."
When Yang Yifeng said this, he only explained the background of one of the research pathways.
Seeing that no one responded, Yang Yifeng continued to dig deeper:
"And in terms of nerve growth factor and neurotransmitters!"
"The role of nerve growth factor and neurotransmitters in nerve healing has been widely recognized. Nerve growth factor is a class of proteins that promote the growth, differentiation and regeneration of neurons."
“Among them, neurotrophic factor (NGF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and nerve growth inhibitory factor (GDNF) have been shown to promote nerve healing. In addition, neurotransmitters are a A class of chemicals that transmit signals between neurons, of which acetylcholine and norepinephrine are common neurotransmitters."
"Corresponding drugs such as clonidine and lidocaine have also been found to promote the release of neurotransmitters, thereby promoting nerve healing."
"However, there is a certain intersection between neurotrophic factors and inflammation in promoting nerve healing, so this research also covers this aspect of research."
"The drug can also promote nerve healing by promoting the secretion of nerve growth factor."
"The third is the new application of the recognized extracellular matrix."
"The extracellular matrix plays an important role in nerve regeneration and repair. In recent years, many studies have developed some materials with extracellular matrix components that support nerve regeneration, such as nerve regeneration bioscaffolds. These bioscaffolds can provide neurons with Provide a suitable physical and chemical environment to promote the growth and connection of neurons. At the same time, some inhibitors of extracellular matrix degrading enzymes have also been shown to promote nerve healing."
"In this study, it is also applied to this aspect, and they also used this material as a medium to obtain preliminary data in the animal test."
"Then there are neural stem cells and stem cell factors. Neural stem cells are a type of pluripotent stem cells that have the ability to self-renew and differentiate into neurons and glial cells. Some studies have shown that neural regeneration and repair can be promoted by implanting neural stem cells, thereby Improving the recovery of neurological function…”
As Yang Yifeng went deeper, everyone was caught in a brainstorm, and at the same time, almost everyone cast pitiful eyes on Yang Yifeng.
What the fuck is wrong with you that you stumbled into this project?
This person has basically introduced you and done everything that should be done, so what else do you have to do?
This is purely unlucky, because when Yang Yifeng applied, other people's results had not yet been released, and it was impossible to publish half of the results, and then as soon as Yang Yifeng applied for the project, others had already published the article.
The difficulty now is not entirely that Yang Yifeng cannot continue to go deeper, but how to go deeper and how to find the best quality direction with limited funds.
Of course, it will be quite difficult to achieve similar results or go further. Moreover, if we want to go deeper, we will spend according to the temporary funds provided by Yang Yifeng.
At least 500 million or more.
As for the projects Yang Yifeng applied for, the total funding was less than 30 yuan, a gap of more than N times, and this gap could not even be filled by Yang Yifeng himself with his salary.
Ding Changle looked at Jiang Hong.
Jiang Hong sniffed, shrugged his eyelids, and said in a helpless tone, "Yi Feng, are you stabbing a hornet's nest?"
"When you applied for the project, what was the expected result?"
"The expectations are not high, just publish three SCI papers, train a Ph.D. and three master students."
"If the 30 yuan is used, if it is only used to publish articles, to find loopholes and fill in vacancies, it is enough. But if it is used as the basis for subsequent research directions, it is obviously not enough."
"I thought so." Yang Yifeng hesitated to speak.
He is unwilling to waste the country's money on things that don't make much sense, not just because of his pride.
What's more, Zhou Cheng's project and clinical project are going smoothly now, but he turned over the car just now, how will he cooperate in the future, people who don't know think that Yang Yifeng followed Zhou Cheng, just licking the dog.
So, this time, he wanted to brainstorm a discussion, hoping to find a relatively novel angle.
At this moment, Zhou Cheng just finished reading that article. To be honest, the research level of this article is relatively broad and in-depth, and it almost blocks Yang Yifeng's current research direction!
However, Zhou Cheng had seen other things when he was simulating nerve suturing before.
"Yi Feng, if the nerves heal, there should be some pathways besides these pathways, right? Have you ever understood it?" After Zhou Cheng finished reading the article, he opened his mouth without waiting for others to speak.
Now he doesn't need to be too modest to save face for Ding Changle and others.
Big articles, big topics, innovative topics, and global topics, Zhou Chengcheng has a resume, what qualifications do you still talk to me about?
Zhou Cheng was blunt. He believed that Ding Changle would not be offended. If he didn't have such a heart, Ding Changle would not be able to sit as the chief director of orthopedics.
However, it is clear that Ding Changle is more concerned about the progress of this project than Yang Yifeng: "Does Xiao Zhou have a better idea?"
Zhou Cheng shook his head first, thinking to himself, I can understand so deeply beyond Yang Yifeng, isn't it fake?
"I seem to have seen it when I checked the literature. Professor Ding."
These things are not within Yang Yifeng's knowledge threshold, so he needs to search for a while.
Then, Yang Yifeng nodded, unhurriedly showing his strong knowledge and knowledge control ability: "Yes, there are mainly three aspects."
"First, brain-derived neurotrophic factor, brain-derived neurotrophic factor (BDNF) is a nerve growth factor that plays an important role in the growth, differentiation, maturation and survival of neurons. Studies have shown that BDNF can not only promote Neuronal growth and connection, but also improved neuronal metabolism and reduced apoptosis."
"Therefore, by increasing the level of BDNF or enhancing its function, nerve regeneration and repair can be promoted. Some studies have shown that the use of BDNF or its mimics can promote nerve regeneration and repair, and achieved certain clinical effects."
"Second, gene therapy. Ethics fail!"
"Third, optical neuromodulation technology."
"This is a technology that uses light-sensitive proteins or compounds to stimulate and regulate neurons. This technology can precisely control the activity of neurons in space and time, so as to achieve the effect of nerve regeneration and repair..."
"These three aspects are not common because they cost more money to carry out, and the expected effect is very limited."
"Then you have no solution? I think you can spend more money, transfer the funds in the research group, write a few articles and finish the problem." Jiang Hong said.
Nerve healing belongs to relatively basic research, and it is not new. Basic means that the research is extensive and lasts for a long time. After such a large article is published this time, no one will touch it for at least ten years.
Why does Yang Yifeng need to be entangled and persistent?
Ding Changle looked at Yang Yifeng, almost convinced that Yang Yifeng could only use Shui Wenwen to finish the question, and asked, "Yifeng, writing a few articles, you should be fine, right?"
Yang Yifeng did too much homework, and the things he expressed were too detailed, basically there was not much space for others to drill, so stop thinking about big topics and big articles.
Chapter 464 New Ideas
"Have you ever learned about the specific mechanism of action of brain-derived neural factors? It is not as popular as the other pathways?" Zhou Cheng asked more precisely and deeply, from a purely academic point of view.
Modern scholarship can be divided into pure scholarship and pandering scholarship. For real academic issues, if you want to go very deep, the depth will reach a very precise angle. Every step you take, there are too many complicated possibilities.
Basically, it is difficult to exhaust them in a short period of time. This is because a Ph.D. or research team who really knows how to be an academic will not be afraid of not being able to publish articles, but only to see how meaningful the published articles are.
But in fact, many articles are just to promote the development of the discipline, and will not directly touch the threshold of the next stage of the development of the discipline. From the overall point of view, it needs a process of accumulating and accumulating to break through in one fell swoop!
Yang Yifeng looked at Zhou Cheng, and knew that Zhou Cheng would not target indiscriminately.
But Zhou Cheng's question, he couldn't answer for a while, so he said: "Just wait for me."
After finishing speaking, Yang Yifeng closed his eyes a little bit and began to meditate, as if he was extracting something.
In reality, Yang Yifeng has never really shown his true strength and original complete talent.
But in the simulated world, Zhou Cheng knew that Yang Yifeng seemed unreliable, but he actually had a strong knowledge reserve and knowledge system. Moreover, Yang Yifeng's reserve and system were different from others. For storage, it is necessary to temporarily organize and extract the corresponding key ingredients——
Yang Yifeng often browses articles and memorizes them, but he doesn’t analyze them in depth. Being able to remember them with a photographic memory doesn’t mean that everything he memorizes will be refined into his own.
Zhou Cheng didn't bother Yang Yifeng either!
Ding Changle and others were even more afraid to speak, because the background listed by Yang Yifeng just now exceeded the in-depth research content of most general fund projects.
Huaguo's current general research projects are basically problems involving simple pathways, which are already considered very in-depth!
For each disease, there will be many pathways, including popular and non-popular pathways, and then start to play marginal cards, use effective drugs to act on cells, and see if the drugs can increase the level of expression of the corresponding pathways, so as to verify Whether the drug has a promoting or negative effect on a certain disease.
This is very in-depth, and it can be regarded as a top-level research project.
However, the rebound that Yang Yifeng touched this time is obviously not such a simple matter.
However, Yang Yifeng did not keep everyone waiting for a long time, and said: "BDNF's mechanism of action on nerve repair, or the promotion of neuronal connections, mainly has the following aspects."
"Promotes the growth and connection of neurons
"BDNF can stimulate the growth cones of neurons and promote the growth and connection of neurons. After BDNF binds to its high-affinity receptor TrkB, it can activate a variety of signaling pathways, such as Akt, ERK, CREB and other pathways, and then promote the growth of neurons. Growth and synapse formation. In addition, another mechanism of BDNF is to promote neuronal connections by regulating synaptic plasticity. BDNF can strengthen synaptic connections, thereby promoting the maturation and survival of neurons.
"Promote the metabolism of neurons
"BDNF can promote the metabolism of neurons, improve the level of energy metabolism, enhance the stability of cell membranes and prevent oxidative stress. BDNF can promote the energy metabolism of neurons and improve the metabolism of cells by activating the AMPK signaling pathway. In addition, BDNF also It can enhance the stability of neuron cell membrane and prevent the occurrence of oxidative stress by activating NF-κB signaling pathway.
"Reduce apoptosis
"BDNF can reduce the apoptosis of neurons, and enhance the anti-apoptotic ability of cells by activating Akt and other signaling pathways. BDNF can regulate cell apoptosis through two receptors, TrkB and p75NTR, and the activation of TrkB receptors can be activated through Akt Signaling pathway to inhibit cell apoptosis, p75NTR receptor activation can promote cell apoptosis.
"The regulatory pathways mainly include TrkB receptor, p75NTR receptor, CREB signaling pathway, ERK signaling pathway, and Akt signaling pathway. The current level of research on cell experiments is roughly the same."
"You mean, I want to find a suitable point by exploring the role of BDNF in these pathways?"
Hearing this, Zhou Cheng nodded and shook his head, ignoring the addition of other people's eyes: "TrkB is a receptor, a high-affinity receptor for BDNF. Activating TrkB will promote the growth and connection of neurons, promote cell metabolism and reduce cell apoptosis." Death."
"To sum up, promote metabolism and reduce apoptosis."
"p75NTR is a low-affinity receptor for BDNF. It binds to TrkB to enhance TrkB signaling and enhance neuronal growth and connection. However, the activation of p75NTR can also promote cell apoptosis, so its regulation is very important .”
"To sum up, regulation."
"CREB is a transcription factor that can promote the expression and release of BDNF by activating the CREB signaling pathway. BDNF can activate the CREB signaling pathway by activating the TrkB receptor, forming a positive feedback regulatory loop."
"It's positive feedback."
"ERK signaling pathway is an important signaling pathway for BDNF to promote neuron growth and connection. The activation of ERK can promote neuron growth and connection, and also plays an important role in synaptic plasticity and learning and memory. BDNF can activate TrkB to stimulate body to activate the ERK signaling pathway."
"This is equivalent to a bypass."
"Akt signaling pathway is an important signaling pathway for BDNF to regulate apoptosis. The activation of Akt can inhibit cell apoptosis and enhance the ability of cells to resist apoptosis. BDNF can activate Akt signaling pathway by activating TrkB receptor." Zhou Chengkan And talking.
But after Zhou Cheng almost repeated the main mechanism of action of the several pathways mentioned by Yang Yifeng, Yang Yifeng said in amazement: "How many articles have you memorized? How many years have you memorized the front?"
Yang Yifeng's words drew Ding Changle's cough, which seemed to be a signal to tell Yang Yifeng not to speak too bluntly, otherwise it would be too monstrous, and the wind would destroy it.
After all, there is still Jiang Hong in person.
Jiang Hong is a little stupid.