I can extract side effects.
Chapter 634 The Dawn of Treatment for ALS
Chapter 634 The Dawn of Treatment for ALS
"Sure enough, the rat's spinal cord injury recovered."
Chen Yiqing looked at the squeaking rats in the cage with infinite vitality, his eyes were a little lost, and he muttered to himself.
A week ago, he received a neural stem cell transplant from Ding Mian.
In fact, this thing is not as easy to handle as he imagined. It took Ding Mian a lot of effort to cultivate a jar of rat neural stem cell suspension and hand it over.
The next preclinical animal research is very simple.
In Chen Yiqing's laboratory, there are no other animals. There are all kinds of rats suffering from Alzheimer's disease, Parkinson's disease, ALS and other neurodegenerative diseases.
There are even quite a few mice with broken legs, crooked necks, and all kinds of high paraplegia.
So he quickly gathered 30 rats with very fresh spinal cord injuries, and divided them into control, injury and transplantation groups, 10 in each group.
At the beginning, the rats screamed, their limbs were weak, and they could only lie on the bottom of the cage, which looked quite miserable.
Then, the experimenters waved the thick needles in their hands and injected the neural stem cell suspension into the injured spinal cords of the rats in the transplantation group one by one.
As for the rats in the injury group, they also received in-depth greetings from the needle, but they were injected with the same amount of normal saline.
Soon, things changed significantly.
The rats in the injury group and the control group were still depressed, but the damaged spinal nerves began to repair spontaneously.
Pure natural, without human intervention, but it is slow, and the effect is not satisfactory.
In the spinal cord of animals, there are actually a small number of endogenous neural stem cells, which usually do not move, as if they do not exist, but once the spinal cord is damaged, they can be quickly triggered.
These neural stem cells in the spinal cord continue to proliferate, migrate all the way to the lesion site, and then differentiate into a large number of astrocytes and a small number of oligodendrocytes, thereby forming a glial scar.
During spinal cord recovery, these neural stem cells will also regulate the inflammatory and immune microenvironment, and secrete neurotrophic molecules such as growth factors.
In short, it is both money and effort, and strives to repair the damaged nerves and create a nutritious recuperation environment.
It looks pretty good, and if it keeps going, there will be nothing wrong with humans.
Unfortunately, the number of these endogenous neural stem cells is very limited.
If humans do not intervene, these pitiful neural stem cells will basically not be able to do much work, and will be exhausted.
Therefore, according to the basic law of development in nature, the iron-blooded principle of biological evolution over hundreds of millions of years-just make do with it.
These rare neural stem cells, as expected, all differentiated into glial cells, forming massive scars, causing cavities and ruptures in the spinal cord tracts.
The natural world may think so, with a click, you fall from a high place, and your neck is crooked.
The first reaction must be to stop the bleeding, let the bones and muscles grow back, and get out of danger as soon as possible.
As for the broken nerve, it can't be connected, and there are scars on the spinal cord, that's not a big deal.
Not every animal dies like this and breaks its neck.
What?You said that some animals have broken their spinal cords and their limbs are paralyzed.
Live it!
Get knocked out now!
Basically, most organisms evolve according to such a set of laws.
Therefore, making do with it has become the first rule of biological evolution.
As long as you can survive, it doesn't matter so much.
Anyway, those who didn't adapt were eliminated.
As for optimization and reorganization, that is impossible, not possible in this lifetime.
Therefore, when human beings start to study biology, seeing the traces of stitches on these chromosomes and embryos is exactly the same as the mood of programmers when they see the code of shit mountain.
But there is no way, I can only pinch the nose, hold a microscope and a needle, poke here, look there, and see if the functional failure can be rescued.
Right now, Chen Yiqing is doing just that.
The neural stem cells in rats cannot be allowed to let themselves go, grow wantonly, and become disconnected scars on the nerve bundles.
It must be like a parent interfering with a child's learning, enter the market forcefully, and control the differentiation direction of neural stem cells in the spinal cord.
The child goes the wrong way, the parents suffer, and the wallet suffers heavy damage.
If the cells go the wrong way, the patient will suffer, but the KPI of the researcher will also suffer a lot.
This also gives the two powerful driving forces to wield the whip/needle.
Since neural stem cells are allowed to develop by themselves, they can only differentiate into astrocytes, not neurons and oligodendrocytes, which greatly limits its regenerative effect.
He will cultivate neural stem cells in vitro, and then add immune T cells and various cytokines to control its differentiation direction.
It not only makes it accurately differentiate into neuron cells, but also repairs myelin sheath formation, supports the growth of axons and blood vessels, and achieves the purpose of repairing spinal cord injuries.
A large number of differentiated neuron cells can be used as a cell source for damage repair, replenish damaged nerve cells, and also greatly reduce the formation of glial scars.
Of course, during the differentiation process of neural stem cells, various neurotrophic factors will also be secreted.
Growth factors, for example, support the growth of motor and sensory axons.
Vascular endothelial growth factor, which can promote the growth of damaged blood vessels.
The neural stem cells that grow wildly will only become a group of glial cells, just like the ice floes on the river surface, which do not have normal connection functions at all.
After a long time, when the river dries up, the broken riverbed will be exposed, completely blocking the signal transmission of the nervous system.
Under the control of humans, neuron cells grow axons one by one, like the steel bars of a bridge, connecting the two ends of the river bank, and the surrounding area is filled with glial cells. This is a normal healthy nerve cell tissue.
The transplanted rats were in stark contrast to the lesion and control rats who were left alone.
The neural stem cell suspension injected into the body first effectively fills the lesion.
Then differentiate into a large number of neuronal cells and glial cells, replacing the missing cellular components.
These neuronal cells, including a variety of intermotor neurons and sensory neurons, send axons into normal spinal cord tissue to establish synaptic connections with downstream neurons.
The axon continued to grow, headed into the brainstem, and the growth distance to the tail also exceeded 14 spinal cord segments, extending to the tail of the rat body.
At the same time, neural stem cells secreted a large number of nutrient molecules, which greatly promoted the regeneration of descending motor axons (such as CST and 5-HT energy axons) and ascending sensory axons of the spinal cord.
The regenerated axons establish functional synaptic connections with newly differentiated neurons, thereby reestablishing the continuity of spinal nerve signaling pathways.
In addition to neurons, neural stem cells also differentiate into non-neural cells, such as oligodendrocytes, which participate in the formation of myelin and maintain the stability of nerve conduction.
In addition, with the nutritional environment created by the neural stem cells.
A large number of corticospinal tracts also spontaneously entered the lesion, and gathered in clusters, forming layers of spatial distribution similar to the normal spinal cord gray matter lamellar structure.
In these spaces, regenerated neurons and densely grown axons are connected layer by layer, spreading throughout the space, establishing a neural network that spreads around.
At this point, the nerve damage to the spinal cord is completely filled and repaired.
This series of experiments is enough to prove that neural stem cell transplantation can repair spinal cord injury to the greatest extent, making it close to a physiologically healthy state.
Chen Yiqing was not as cold-blooded and ruthless as Ding Mian. After observing signs of recovery from the spinal cord injury, he did not immediately terminate the experiment and kill the lives of 30 rats, but continued the experiment.
In the past, after neural stem cells were transplanted into animals, it took a long time to differentiate into mature cells, lasting up to 1 year.
But accelerated by additional growth factors, the number and distance of axon regrowth peaked in the spinal cords of rats 1 month after stem cell transplantation.
By 3 months after transplantation, the number of axons had almost halved again.
"Sure enough, the differentiation process of the transplanted neural stem cells is very similar to the development of the mammalian nervous system."
During these three months, Chen Yiqing almost forgot to sleep and eat in the laboratory, and plunged into the arms of the rats.
Even though he had been prepared for the effect of stem cell transplantation to repair the spinal cord, when this discovery appeared in front of him, his pupils still trembled.
"It can be speculated that the process of axon regeneration also undergoes functional selection and elimination."
"The nervous system performs delicate pruning on the regenerated mass of axons, removing all unnecessary axons, just like a gardener prunes the branches and weeds of trees."
"Such a regenerative remodeling mechanism lays the foundation for the establishment of functional neural circuits after neural stem cell transplantation and the reduction of side effects."
Chen Yiqing got up from the microscope and paced back and forth in the laboratory, still unable to restrain the excitement in his heart.
The corners of his eyebrows and eyes couldn't stop exuding joy.
"Great, I finally figured out the whole process of neural stem cell transplantation."
"I can't wait to use it on patients."
He was so excited, but still did not lose his mind, but immediately thought of some key information about stem cell clinical trials.
"Stem cell therapy is not uncommon at present. There are related products on the market both at home and abroad, and the relevant review regulations are relatively complete."
"So in terms of safety, there is no big problem, and there are a lot of clinical studies to prove it."
"It shouldn't be too difficult to pass the review. I just need to design a rigorous experimental plan based on the characteristics of the product."
"After years of research on ALS, I have also accumulated a lot of cases. After the review is approved, clinical trials should be able to proceed immediately."
Thinking of this, he was eager to try, but also a little emotional.
"It took so long, and it turned out that after the breakthrough of stem cell therapy, we could find the ray of hope for the treatment of ALS."
"It's a trick of good fortune. I wish I knew it earlier. I will definitely keep an eye on Ding Mian every day and complete the research in this area as soon as possible."
Chen Yiqing wanted to do it, and acted immediately.
Due to the particularity of stem cell research, it involves a lot of ethical considerations, and domestic supervision on it is very strict.
According to the requirements of "double filing", not only must apply for approval from the Food and Drug Administration, but also jointly file with the National Health Commission.
At the same time, the qualification review of stem cell clinical research institutions is also very strict.
It can only be a tertiary first-class hospital, and it has to undertake major provincial scientific research projects. The most rare thing is that the person in charge of the project must have a senior professional title.
This requirement is not generally high. Ordinary CRO outsourcing medical institutions are not qualified to do clinical research in this area.
In short, it fully reflects the high, precise and cutting-edge scientific research requirements.
Fortunately, Sanqing's cooperative scientific research institutions are mostly tertiary hospitals, and quite a few can meet the standards.
Especially the No.1 Minority Hospital in Kunming City, since Jian Yunyun was promoted to the director of neurosurgery with the brain-computer interface, a national key project.
The research on neuroscience between the two sides has become closer than ever before.
Chen Yiqing called Jian Lianyun immediately, and wanted to file the project with the hospital.
"Director Jian, I am old Chen, by the way, I have something to tell you."
"There is a new stem cell project in our laboratory, mainly for clinical research on ALS."
"Yes, the current experiments on rats have confirmed that the joint transplantation of neural stem cells and immune T cells can repair spinal cord injuries, especially motor nerve injuries."
"So I want to start the phase I clinical trial as soon as possible. As you know, the clinical research of stem cells is quite special..."
"Old Chen, it seems that you have a deep love for ALS. Hahaha~"
Jian Lianyun's crisp voice came over, with a hint of playfulness in the excitement.
"Walking around, experiencing so much in the middle, and finally turning back to the same place, you really paid too much for ALS."
"Okay, you send me the information, I will immediately set up an expert group and an ethics committee, and then submit the declaration."
"Don't worry, if everything goes well, it will be done within three days."
She was originally capable of doing things, and her execution ability was even more outstanding. After becoming a director, she was in control of the power and her style became more vigorous, which made Chen Yiqing very satisfied.
"Director Jian, just laugh at me. In order to treat ALS, I really put in a lot of effort. I even created a brain-computer interface in the middle, and the effect is not bad."
Chen Yiqing laughed cheerfully: "Now that I have finally found a cure for ALS, it can be said that I will not forget my original intention, and it will last forever."
"Okay, congratulations, you've got what you wanted. I'm going to have an operation later. I'll talk to you after reading the information."
As the director of the department and an academic leader in the field of neuromedicine in China, Jian Jianyun is so busy that he keeps his feet on the ground, and he is also very streamlined when making phone calls, without a word of nonsense.
After the exchange of information was completed, they immediately hung up the phone and rushed to the next target.
Chen Yiqing has worked with her for many years and is used to this style.
"The hospital is still busy. Compared with her, we are much more leisurely."
He thought to himself, came to the office and prepared the filing materials.
(End of this chapter)
"Sure enough, the rat's spinal cord injury recovered."
Chen Yiqing looked at the squeaking rats in the cage with infinite vitality, his eyes were a little lost, and he muttered to himself.
A week ago, he received a neural stem cell transplant from Ding Mian.
In fact, this thing is not as easy to handle as he imagined. It took Ding Mian a lot of effort to cultivate a jar of rat neural stem cell suspension and hand it over.
The next preclinical animal research is very simple.
In Chen Yiqing's laboratory, there are no other animals. There are all kinds of rats suffering from Alzheimer's disease, Parkinson's disease, ALS and other neurodegenerative diseases.
There are even quite a few mice with broken legs, crooked necks, and all kinds of high paraplegia.
So he quickly gathered 30 rats with very fresh spinal cord injuries, and divided them into control, injury and transplantation groups, 10 in each group.
At the beginning, the rats screamed, their limbs were weak, and they could only lie on the bottom of the cage, which looked quite miserable.
Then, the experimenters waved the thick needles in their hands and injected the neural stem cell suspension into the injured spinal cords of the rats in the transplantation group one by one.
As for the rats in the injury group, they also received in-depth greetings from the needle, but they were injected with the same amount of normal saline.
Soon, things changed significantly.
The rats in the injury group and the control group were still depressed, but the damaged spinal nerves began to repair spontaneously.
Pure natural, without human intervention, but it is slow, and the effect is not satisfactory.
In the spinal cord of animals, there are actually a small number of endogenous neural stem cells, which usually do not move, as if they do not exist, but once the spinal cord is damaged, they can be quickly triggered.
These neural stem cells in the spinal cord continue to proliferate, migrate all the way to the lesion site, and then differentiate into a large number of astrocytes and a small number of oligodendrocytes, thereby forming a glial scar.
During spinal cord recovery, these neural stem cells will also regulate the inflammatory and immune microenvironment, and secrete neurotrophic molecules such as growth factors.
In short, it is both money and effort, and strives to repair the damaged nerves and create a nutritious recuperation environment.
It looks pretty good, and if it keeps going, there will be nothing wrong with humans.
Unfortunately, the number of these endogenous neural stem cells is very limited.
If humans do not intervene, these pitiful neural stem cells will basically not be able to do much work, and will be exhausted.
Therefore, according to the basic law of development in nature, the iron-blooded principle of biological evolution over hundreds of millions of years-just make do with it.
These rare neural stem cells, as expected, all differentiated into glial cells, forming massive scars, causing cavities and ruptures in the spinal cord tracts.
The natural world may think so, with a click, you fall from a high place, and your neck is crooked.
The first reaction must be to stop the bleeding, let the bones and muscles grow back, and get out of danger as soon as possible.
As for the broken nerve, it can't be connected, and there are scars on the spinal cord, that's not a big deal.
Not every animal dies like this and breaks its neck.
What?You said that some animals have broken their spinal cords and their limbs are paralyzed.
Live it!
Get knocked out now!
Basically, most organisms evolve according to such a set of laws.
Therefore, making do with it has become the first rule of biological evolution.
As long as you can survive, it doesn't matter so much.
Anyway, those who didn't adapt were eliminated.
As for optimization and reorganization, that is impossible, not possible in this lifetime.
Therefore, when human beings start to study biology, seeing the traces of stitches on these chromosomes and embryos is exactly the same as the mood of programmers when they see the code of shit mountain.
But there is no way, I can only pinch the nose, hold a microscope and a needle, poke here, look there, and see if the functional failure can be rescued.
Right now, Chen Yiqing is doing just that.
The neural stem cells in rats cannot be allowed to let themselves go, grow wantonly, and become disconnected scars on the nerve bundles.
It must be like a parent interfering with a child's learning, enter the market forcefully, and control the differentiation direction of neural stem cells in the spinal cord.
The child goes the wrong way, the parents suffer, and the wallet suffers heavy damage.
If the cells go the wrong way, the patient will suffer, but the KPI of the researcher will also suffer a lot.
This also gives the two powerful driving forces to wield the whip/needle.
Since neural stem cells are allowed to develop by themselves, they can only differentiate into astrocytes, not neurons and oligodendrocytes, which greatly limits its regenerative effect.
He will cultivate neural stem cells in vitro, and then add immune T cells and various cytokines to control its differentiation direction.
It not only makes it accurately differentiate into neuron cells, but also repairs myelin sheath formation, supports the growth of axons and blood vessels, and achieves the purpose of repairing spinal cord injuries.
A large number of differentiated neuron cells can be used as a cell source for damage repair, replenish damaged nerve cells, and also greatly reduce the formation of glial scars.
Of course, during the differentiation process of neural stem cells, various neurotrophic factors will also be secreted.
Growth factors, for example, support the growth of motor and sensory axons.
Vascular endothelial growth factor, which can promote the growth of damaged blood vessels.
The neural stem cells that grow wildly will only become a group of glial cells, just like the ice floes on the river surface, which do not have normal connection functions at all.
After a long time, when the river dries up, the broken riverbed will be exposed, completely blocking the signal transmission of the nervous system.
Under the control of humans, neuron cells grow axons one by one, like the steel bars of a bridge, connecting the two ends of the river bank, and the surrounding area is filled with glial cells. This is a normal healthy nerve cell tissue.
The transplanted rats were in stark contrast to the lesion and control rats who were left alone.
The neural stem cell suspension injected into the body first effectively fills the lesion.
Then differentiate into a large number of neuronal cells and glial cells, replacing the missing cellular components.
These neuronal cells, including a variety of intermotor neurons and sensory neurons, send axons into normal spinal cord tissue to establish synaptic connections with downstream neurons.
The axon continued to grow, headed into the brainstem, and the growth distance to the tail also exceeded 14 spinal cord segments, extending to the tail of the rat body.
At the same time, neural stem cells secreted a large number of nutrient molecules, which greatly promoted the regeneration of descending motor axons (such as CST and 5-HT energy axons) and ascending sensory axons of the spinal cord.
The regenerated axons establish functional synaptic connections with newly differentiated neurons, thereby reestablishing the continuity of spinal nerve signaling pathways.
In addition to neurons, neural stem cells also differentiate into non-neural cells, such as oligodendrocytes, which participate in the formation of myelin and maintain the stability of nerve conduction.
In addition, with the nutritional environment created by the neural stem cells.
A large number of corticospinal tracts also spontaneously entered the lesion, and gathered in clusters, forming layers of spatial distribution similar to the normal spinal cord gray matter lamellar structure.
In these spaces, regenerated neurons and densely grown axons are connected layer by layer, spreading throughout the space, establishing a neural network that spreads around.
At this point, the nerve damage to the spinal cord is completely filled and repaired.
This series of experiments is enough to prove that neural stem cell transplantation can repair spinal cord injury to the greatest extent, making it close to a physiologically healthy state.
Chen Yiqing was not as cold-blooded and ruthless as Ding Mian. After observing signs of recovery from the spinal cord injury, he did not immediately terminate the experiment and kill the lives of 30 rats, but continued the experiment.
In the past, after neural stem cells were transplanted into animals, it took a long time to differentiate into mature cells, lasting up to 1 year.
But accelerated by additional growth factors, the number and distance of axon regrowth peaked in the spinal cords of rats 1 month after stem cell transplantation.
By 3 months after transplantation, the number of axons had almost halved again.
"Sure enough, the differentiation process of the transplanted neural stem cells is very similar to the development of the mammalian nervous system."
During these three months, Chen Yiqing almost forgot to sleep and eat in the laboratory, and plunged into the arms of the rats.
Even though he had been prepared for the effect of stem cell transplantation to repair the spinal cord, when this discovery appeared in front of him, his pupils still trembled.
"It can be speculated that the process of axon regeneration also undergoes functional selection and elimination."
"The nervous system performs delicate pruning on the regenerated mass of axons, removing all unnecessary axons, just like a gardener prunes the branches and weeds of trees."
"Such a regenerative remodeling mechanism lays the foundation for the establishment of functional neural circuits after neural stem cell transplantation and the reduction of side effects."
Chen Yiqing got up from the microscope and paced back and forth in the laboratory, still unable to restrain the excitement in his heart.
The corners of his eyebrows and eyes couldn't stop exuding joy.
"Great, I finally figured out the whole process of neural stem cell transplantation."
"I can't wait to use it on patients."
He was so excited, but still did not lose his mind, but immediately thought of some key information about stem cell clinical trials.
"Stem cell therapy is not uncommon at present. There are related products on the market both at home and abroad, and the relevant review regulations are relatively complete."
"So in terms of safety, there is no big problem, and there are a lot of clinical studies to prove it."
"It shouldn't be too difficult to pass the review. I just need to design a rigorous experimental plan based on the characteristics of the product."
"After years of research on ALS, I have also accumulated a lot of cases. After the review is approved, clinical trials should be able to proceed immediately."
Thinking of this, he was eager to try, but also a little emotional.
"It took so long, and it turned out that after the breakthrough of stem cell therapy, we could find the ray of hope for the treatment of ALS."
"It's a trick of good fortune. I wish I knew it earlier. I will definitely keep an eye on Ding Mian every day and complete the research in this area as soon as possible."
Chen Yiqing wanted to do it, and acted immediately.
Due to the particularity of stem cell research, it involves a lot of ethical considerations, and domestic supervision on it is very strict.
According to the requirements of "double filing", not only must apply for approval from the Food and Drug Administration, but also jointly file with the National Health Commission.
At the same time, the qualification review of stem cell clinical research institutions is also very strict.
It can only be a tertiary first-class hospital, and it has to undertake major provincial scientific research projects. The most rare thing is that the person in charge of the project must have a senior professional title.
This requirement is not generally high. Ordinary CRO outsourcing medical institutions are not qualified to do clinical research in this area.
In short, it fully reflects the high, precise and cutting-edge scientific research requirements.
Fortunately, Sanqing's cooperative scientific research institutions are mostly tertiary hospitals, and quite a few can meet the standards.
Especially the No.1 Minority Hospital in Kunming City, since Jian Yunyun was promoted to the director of neurosurgery with the brain-computer interface, a national key project.
The research on neuroscience between the two sides has become closer than ever before.
Chen Yiqing called Jian Lianyun immediately, and wanted to file the project with the hospital.
"Director Jian, I am old Chen, by the way, I have something to tell you."
"There is a new stem cell project in our laboratory, mainly for clinical research on ALS."
"Yes, the current experiments on rats have confirmed that the joint transplantation of neural stem cells and immune T cells can repair spinal cord injuries, especially motor nerve injuries."
"So I want to start the phase I clinical trial as soon as possible. As you know, the clinical research of stem cells is quite special..."
"Old Chen, it seems that you have a deep love for ALS. Hahaha~"
Jian Lianyun's crisp voice came over, with a hint of playfulness in the excitement.
"Walking around, experiencing so much in the middle, and finally turning back to the same place, you really paid too much for ALS."
"Okay, you send me the information, I will immediately set up an expert group and an ethics committee, and then submit the declaration."
"Don't worry, if everything goes well, it will be done within three days."
She was originally capable of doing things, and her execution ability was even more outstanding. After becoming a director, she was in control of the power and her style became more vigorous, which made Chen Yiqing very satisfied.
"Director Jian, just laugh at me. In order to treat ALS, I really put in a lot of effort. I even created a brain-computer interface in the middle, and the effect is not bad."
Chen Yiqing laughed cheerfully: "Now that I have finally found a cure for ALS, it can be said that I will not forget my original intention, and it will last forever."
"Okay, congratulations, you've got what you wanted. I'm going to have an operation later. I'll talk to you after reading the information."
As the director of the department and an academic leader in the field of neuromedicine in China, Jian Jianyun is so busy that he keeps his feet on the ground, and he is also very streamlined when making phone calls, without a word of nonsense.
After the exchange of information was completed, they immediately hung up the phone and rushed to the next target.
Chen Yiqing has worked with her for many years and is used to this style.
"The hospital is still busy. Compared with her, we are much more leisurely."
He thought to himself, came to the office and prepared the filing materials.
(End of this chapter)
You'll Also Like
-
Zongman: The Traveler In Our Dreams
Chapter 83 12 hours ago -
Cyberpunk Starts With Signing In The Legendary Mantis Knife
Chapter 83 12 hours ago -
Pokemon: A Review Of Ash’s World Championship Moments
Chapter 117 12 hours ago -
Demon Slayer: Add friends to become stronger! Zenitsu is my best friend
Chapter 150 12 hours ago -
Zombie Contract: After the doomsday crisis, the strongest zombie is born
Chapter 171 12 hours ago -
People in Naruto: Many Children Bring Blessings to Revitalize Uchiha
Chapter 62 12 hours ago -
Transformed into the Mother Tree of Desire, it's not too much to give birth to gods
Chapter 98 12 hours ago -
The field increases by 1 ghost per second. I am the ghost king in Tokyo.
Chapter 156 12 hours ago -
Supreme Beauty, I summon the heroes to establish the Supreme Divine Dynasty
Chapter 177 12 hours ago -
Yuan Beng Tie: A list of 30 popular characters at the beginning
Chapter 98 12 hours ago