Except through gene therapy, there is no way for doctors to directly intervene in the amount of AQP4 protein expressed. That is, there is no direct treatment for AQP4 protein underexpression. But...... That doesn't stop doctors from doing some bold, experimental brainstorming.

Just like the early coronary artery bypass grafting, when doctors deal with the lack of certain tissues in the body, one is a "loan maniac". They have been tearing down the east wall and repairing the west wall for hundreds of years - it has been widely used by doctors since the first black slave teeth were transplanted to the president of the United States.

However, when the method of tearing down the east wall and replacing the west wall does not work, doctors will consider some means to stimulate the human body so that the fallen west wall can be re...... It is re-"ridged" and used as a wall to a minimum.

After all, the human body is a living system, not like industrially produced equipment – once it fails, there is no choice but to replace it. If the original organ can be kept functioning, it is likely that the fault can be eliminated by repairing at the cellular level.

For other enzyme or protein deficiencies, it is often difficult for doctors to intervene. For example, Chen Tianyi, who was previously diagnosed with ornithine formyltransferase deficiency (OTCD). The reason why treatment is done by liver transplantation, rather than simply supplementing with ornithine formyltransferase, is that there is no reliable means of delivering the drug, which is essentially a protein. Due to the protein-digesting effect of the digestive tract, it cannot be administered orally. Ornithine formyltransferases given intravenously are also of no value – the main location of these transferases is in the mitochondria of hepatocytes, and no amount of transferases floating in the blood can enter the mitochondria of hepatocytes to play a role.

Therefore, in the treatment of OTCD, doctors mainly use various means to remove and reduce ammonia from the human body that cannot be converted by ornithine formyltransferase.

When dealing with underexpression of AQP4 protein, doctors can take similar measures to intervene in OTCD. Supplementing the body directly with AQP4 protein will have no effect – these proteins may be digested and stored in the body as excess proteins. For the AQP4 protein to function, it must be present on the cell membrane.

But the study of AQP4 gave Sun Lien a new idea. If the current amount of AQP4 protein is insufficient, it will be difficult to complete the set task...... Then stimulate them and let them play a bigger role than before.

As a highly specific protein, AQP4 itself is a very efficient water channel. However, the lack of quantity led to severe mesenchymal cell edema in Tang Min. Numbers cannot be intervened, at least not by current medical means. Then, protein phosphorylation has become the most likely effective means that Sun Lien can take now.

Protein phosphorylation is the most basic, ubiquitous, and important mechanism for regulating and controlling protein viability and function. According to the current research results, PKA (protein kinase A) and PKC (protein kinase C) are both potentially effective substances to phosphorylate AQP4 and greatly improve water permeability.

Although the exact mechanism and flow of action cannot be determined, in some cases, PKA can catalyze serine phosphorylation on aquaporins. PCK, on the other hand, is a regulator of AQP4 expression. As an activator of PKC, Phobol Diphosphate Sodium can act on AQP4 and regulate AQP4 activity by catalyzing the phosphorylation of AQP4 protein.

Sun Lien aimed at the beginning of the "Phobolol Diphosphate Sodium Diphosphate", which was a strange name. But...... In the few minutes he waited for his comrades to reply, he painfully found ...... I'm afraid this path won't work.

Although I have never heard of this drug, from the information found by Sun Lien, phorbolol, also known as phorbol ester, is a T lymphocyte activator and is highly carcinogenic. Its main use is to act on HL-60 cells and to induce TNF-α (tumor necrosis factor α).

HL-60 cells are an important cell line for basic medical research, and like the famous HeLa cells, they were isolated from a human with cancer. The patient had acute promyelocytic leukemia, and the isolated cells were spontaneously pollinated and differentiated by certain substances. And phorbolol is one such substance.

In other words, Sodium Phobolol Diphosphate is a highly carcinogenic chemical agent used to induce TNF-α secretion in HL-60 cells that can only be used in experiments on a specific cell in the human body. It is a dangerous tool in the field of medical research. This means that it is unlikely that Sun will be able to modulate Tang's AQP4 activity with phorbol diphosphate – unless he intends to risk being convicted of murder and practicing medicine illegally, and causing Tang Min to develop cancer.

The paper doesn't stop there, though. Probably because of the close association between AQP4 protein and hydrocephalus, there is no shortage of research on the stimulation of AQP4. While Sun Lien vetoed the sodium diphosphate of phorbol, he found a path that seemed to be much safer.

AQP4 potency in brain cells may be activated by arginine vasopressin (AVP). AVP activates two types of receptors, V1 and V2, while V1 activates PLC (phospholipase C) and V2 receptor activates AC (adenylyl cyclase). Subsequently, phosphatase C and adenylyl cyclase activated protein kinase A and protein kinase C, respectively, to achieve phosphorylation of AQP4 protein.

Arginine vasopressin is much more familiar to Sun Lien.

Arginine vasopressin, also known as vasopressin, is an antidiuretic hormone. Clinically, doctors often use this injection to treat central diabetes insipidus and transient diabetes insipidus caused by cranial trauma or surgery. It can also be used to differentially diagnose diabetes insipidus, treat nocturnal enuresis in patients aged six years or older, and more.

And the best thing is that, as a hormone, it can easily cross the brain-blood barrier, and the safety is dozens of orders of magnitude stronger than the highly carcinogenic sodium phorbol diphosphate. With the exception of isolated cases of skin allergies and anaphylaxis, there are few serious side effects and adverse effects of this drug.

There are only two main points that Sun Lien deserves to think about again.

As an antidiuretic drug, arginine vasopressin inherently increases intracranial fluid and may lead to water intoxication due to fluid overdose. Therefore, caution should be exercised in patients at risk of increased intracranial pressure. Secondly, it is assumed that arginine vasopressin successfully entered Tang Min's body and crossed the brain-blood barrier into her brain tissue. To successfully achieve phosphorylation of AQP4 protein, it also needs to undergo a conversion process of V1V2 receptor and PCL and AC. It is not known what effect this conversion process will have on the body, and how much arginine vasopressin is needed to achieve the desired level of phosphorylation.

But at least that's the direction.

Sun Lien had just straightened out his thoughts and was about to share his "unique and bold ideas" with Yuan Ping'an, when Yuan Ping'an suddenly jumped up from his seat.

He waved the mobile phone in his hand towards Sun Lien, and Sun Lien could only roughly recognize the WeChat chat interface displayed on the mobile phone screen. But he couldn't even make out a single word of what was written on it.

"Tongxie still has samples on hand, and they are starting to perform mRNA measurements!" After being excited for a while, Yuan Ping'an realized that Sun Lien didn't know what he was excited about. So he hurriedly stuffed his mobile phone into Sun Lien's hand and said, "The paraffin sample is stored in a freezer at minus 80 degrees, so we don't need to do another biopsy!"