godfather of surgery

Chapter 1317 Uncontrolled Fever

Yang Ping replied to Dr. Chen's email, pointing out that his research was outdated and suggesting that he take some time to visit the digital medicine laboratory at Nandu Medical University.

Looking back now, under Yang Ping's leadership, the research level of the entire Nandu Group has risen several levels. For example, the Digital Medicine Laboratory is already at the world's top level, and they are the leaders in the application of digital medicine and artificial intelligence in medicine.

It is precisely because of the establishment of these research foundations that Yang Ping is now able to put his ideas into practice at will.

Yang calmed down and carefully reviewed the entire research process of his regulation theory, feeling a mix of emotions.

The inspiration for the theory of system regulation came entirely from an accident.

The regulatory theory stems from in-depth research on K therapy, which in turn originated from the accidental discovery of the K factor in Sisi's tumor cells.

When Sisi's tumor cells were extracted for experimental research, a large number of tumor cells suddenly died one day during in vitro culture.

Normally, such death would seem meaningless to the average person. Tumor cells are cultured in vitro, and if the conditions are not suitable, the tumor cells may die. Other tumor researchers would not pay attention to such a common occurrence. However, Yang Ping did not overlook this issue. After a rigorous scientific analysis of the causes of tumor cell death, he discovered that the cause of death was not related to external conditions, but rather that the tumor cells had initiated the apoptosis process themselves.

This result surprised Yang Ping and aroused his strong curiosity.

He decided to explore the reasons behind this, so he conducted further research and discovered that there was a special protein factor in the culture medium and inside the tumor cells. He had never seen this protein factor before. He extracted this protein factor for research, and it turned out that this thing was the "hero" that killed the tumor cells.

So Yang Ping seized upon this achievement and conducted further research, eventually developing K therapy.

At that time, research on factor K appeared to be very in-depth, having been analyzed at the biochemical microscopic level. Then, adenovirus was used as a vector to carry factor K to infect tumor cells. After the adenovirus carrying factor K entered the tumor cells, factor K took effect and initiated the apoptosis program to eliminate the tumor cells.

Yang Ping thought the research had ended there, but the results did not satisfy his strong curiosity. He continued to investigate why factor K could initiate the apoptosis program in tumor cells, and he tried to design a new factor K.

Later, as the research deepened, Yang Ping discovered that the truth was far more complex than that.

All previous research only scratched the surface; it seemed to have answered what it was, but in reality, it was still only at the level of "what it is".

This greatly displeased Yang Ping. After going around in circles, thinking he had reached the top of the mountain, he looked up and found himself still at the foot of the mountain.

So he continued his research. He had money and time to spare, and since he was just idling around anyway, he was determined to figure this out. Finally, he discovered that Factor K was able to initiate the apoptosis process because it could restore the body's system's ability to re-recognize and identify tumor cells.

Subsequently, Yang Ping proposed the system regulation hypothesis, and his team launched a massive research project around this hypothesis.

Since Yang Ping published his "system regulation" theory hypothesis, his team has seen a surge in publications. Some core papers have been published in their own journal, Medicine, and others have been published in other top international journals to increase the exposure of the theory.

A team led by Tang Shun published a paper titled "TIM conformational dynamics as a core regulatory switch for cellular identity: single-molecule real-time imaging evidence" in *Nature*. Using super-resolution fluorescence lifetime imaging, they observed for the first time in living cells that when the K factor binds, the TIM protein cluster undergoes a conformational transition from loose dynamics to ordered locking. This transition is precisely coupled in time with downstream mitochondrial membrane potential fluctuations and changes in chromatin accessibility. More importantly, they found that the synchronization rate of this conformational transition is high in normal cells with stable identity states, decreases in precancerous cells, and almost disappears in aggressive cancer cells. This directly confirms the function of the TIM system as a fidelity amplifier for identity signals and its gradual detuning during carcinogenesis.

A collaborative paper by Song Ziming, Xu Zhiliang, and Professor He from the Digital Medicine Laboratory of Nandu Medical University, titled "Exferring the State Attractor Landscape of a System from Single-Cell Multi-Omic Time-Series Data: A Case Study of Precancerous Intervention in Lynch Syndrome," was published in *Cell*. Based on high-density data from Elena and five other early participants, the paper constructed a personalized system dynamics model and successfully simulated how regulatory intervention reshaped the system's potential landscape from multiple shallow and chaotic disease depressions into a deep and broad health basin. The model's predicted post-intervention state trajectory closely matched the actual observational data. This research provides the first computational-level quantitative evidence for the hypothesis that regulation alters the system's topography.

The third paper, from Lu Xiaolu's team, found that the expression patterns and conformational stability of TIM homologous proteins in the intestinal stem cells of aged mice exhibited noise-induced increases similar to those seen in precancerous cells. Treatment with a mild modulator targeting aged TIM variants not only improved the homeostasis of the intestinal epithelium but also reduced systemic mild inflammation and improved exercise endurance in the mice. The paper cautiously hypothesizes that age-related functional decline may be partly due to signal attrition and decreased error-correction capabilities of the cell identity maintenance system, and that targeted, mild modulation may partially restore this intrinsic maintenance capacity. This paper was published in the journal *Science*.

These three papers, like three solid foundation stones, firmly support the core theory of system regulation.

The initial skepticism and wait-and-see attitude in academia quickly transformed into enthusiasm for following up, verifying, and expanding upon these developments. A news feature in the journal *Nature*, titled "From Attack to Dialogue: The Data Cornerstone of a New Model of Medicine," detailed these advancements.

The article quotes several previously critical and authoritative scholars who have changed their tune: "I must admit, the data is compelling. They not only put forward a beautiful hypothesis, but also transformed it into a measurable and predictable model with a series of brilliant experiments."

This was followed by a second wave of fervor surrounding the "Huangdi Neijing" (Yellow Emperor's Inner Classic).

The first surge of interest stemmed from Yang Ping's casual mention of "shared ideas," tinged with curiosity and symbolism. This time, however, with the system regulation theory repeatedly supported by hard data from top journals, the comment about "shared ideas with the *Huangdi Neijing*" carried a completely different weight. It was no longer merely a scientist's personal cultural preference, but rather a startling discovery—an ancient wisdom validated by modern science. The *Huangdi Neijing* began to appear frequently in high society salons, club chats, and case discussions at top business schools. It became a new form of "social currency" and a symbol of "cultural significance."

In a private members-only club in London's Mayfair district, a hedge fund manager pointed to an antique-style thread-bound copy of the *Huangdi Neijing* (which he had hardly ever opened) prominently displayed in his study and said to his guests, "Did you know that Professor Yang Ping's breakthrough was hinted at in this book? Balance, regulation, preventive medicine... When we invest in biotechnology, we should not only look at the technology, but also understand the philosophy behind it. This is the mindset for the next wave."

In a luxurious mansion on the shores of Lake Zurich, the wife of a tech tycoon hosted a luncheon themed "Eastern Wisdom and Healthy Living." The hired "Traditional Chinese Medicine cultural consultant" (actually a local student who had studied Chinese for half a year) was stumbling over her explanations of "Yin and Yang, the Five Elements, and the Holistic View." The guests listened with a mixture of understanding and confusion, nodding frequently as if they had touched upon some key to a healthy future.

A more tangible impact is occurring in the high-end medical and health management sectors. Traditional Chinese medicine clinics in Europe and America, previously confined to Chinese communities or alternative therapy corners, are suddenly receiving a surge in inquiries from non-Asian clients, including wealthy individuals, celebrities, and executives. Their needs are clear: they desire treatment based on ancient theories of systems regulation.

Dr. Xu, a traditional Chinese medicine practitioner in Munich, said with a wry smile: "Recently, some German businessmen have come with German abstracts of Professor Yang's papers, asking me if I can perform 'systemic state diagnosis' for them, to regulate their 'TIM' or 'yin-yang balance.' I explained that the syndrome differentiation and treatment in traditional Chinese medicine is not the same as modern molecular biology, but they thought I was being conservative. Some even asked me to combine their gene testing reports and gut microbiota analysis to prescribe medicine... This is completely impossible."

This demand has given rise to a new hybrid service: "integrated systems health management." Some astute institutions are combining traditional Chinese medicine's diagnostic methods of observation, auscultation, inquiry, and palpation, along with constitution identification, with modern functional medicine testing and lifestyle analysis and management, packaging them into exorbitantly priced annual health management plans. Although the scientific rigor varies, these plans precisely target the desire of high-end individuals for "systemic regulatory treatment."

After all, Yang Ping's theory and practice of system regulation are still in the experimental stage, while ancient Chinese medicine has already used the simple tool of herbs for regulation.

This trend has even reverberated within China. Some urban elites who were previously skeptical of Traditional Chinese Medicine (TCM) have begun to re-examine traditional medicine because Yang Ping's theories "proved the advanced nature of TCM concepts." The stock prices of leading Chinese medicine companies have risen, TCM universities have gained more attention, and there has been a significant increase in appointments at high-end TCM hospitals.

What troubles Yang Ping's team the most is that many members of the public, and even some industry insiders, simply equate the theory of "system regulation" with "traditional Chinese medicine," and further simplify "traditional Chinese medicine" into "taking herbal medicine" and "acupuncture."

"This is a serious conceptual confusion."

Yang Ping sat at the conference table and rubbed his temples.

"What inspires us is the holistic and dynamic balance-based philosophical thinking inherent in Traditional Chinese Medicine (TCM). As for specific techniques, Chinese herbal medicine and acupuncture are tools developed by the ancients based on their knowledge and available resources at the time. In contrast, we use precise regulatory molecules designed based on modern molecular biology, structural biology, and computational science. The two can engage in dialogue in terms of concepts, but they are completely different in terms of methodology."

Song Ziming added: "What's even more dangerous is that this confusion could be exploited. There are now so-called health products on the market that are based on the Yellow Emperor's Inner Canon and the TIM regulation theory. The ingredients are just ordinary plant extracts, but they claim to regulate cell identity and prevent cancer. This is completely fraudulent and will ruin the entire research direction. These health products have already been launched at home and abroad, and their sales on e-commerce platforms are astonishing."

Tang Shun was also very distressed because his American and Japanese friends had been frequently calling him to ask for recommendations for traditional Chinese medicine, but he knew nothing about it. Many of his female friends even hoped to come to China to see him for "hormonal regulation," claiming it would make them younger and more energetic.

It seems the second wave of enthusiasm has gotten out of control, and the team has decided to conduct another public science education campaign.

They produced a series of short videos featuring Song Ziming, Tang Shun, Lu Xiaolu, and others, using simple language and animation to explain the difference between "shared ideas" and "different technologies." In one video, Tang Shun, holding the *Huangdi Neijing* (Yellow Emperor's Inner Classic) and a molecular biology textbook, said: "This book (Neijing) teaches us 'which direction to think in,' while this book (textbook) and our laboratory are exploring how to achieve this kind of thinking using modern tools. Respecting traditional wisdom while adhering to modern scientific standards are not contradictory, and both are indispensable."

However, their voices were drowned out by the surging tide of public opinion, and people no longer cared about their explanations.

Yang Ping's team has launched a new research project. The team members are all newcomers to the lab, and the project doesn't directly involve patients. Instead, it's conducted using computer models and in vitro cultured immune cell lines donated by APECED patients. After screening dozens of known surface molecules involved in inducing immune cell tolerance, the team focused on a protein complex called "T-SEED." This complex is highly expressed on the surface of thymic epithelial cells and is believed to play a supporting role in presenting self-antigens to developing T cells and teaching them "self-tolerance."

Computational model simulations show that enhancing a certain conformational state of the T-SEED complex may improve its efficiency and stability in presenting self-antigen peptides, thereby potentially “enhancing” the negative selection of self-reactive T cells, i.e., eliminating or inactivating those T cells that attack the body.

“This is just a theoretical regulatory target,” the young researcher in charge of the project reported rigorously. “We are still far from actual intervention. Moreover, in APECED patients, due to the AIRE gene defect, the thymic autoantigen profile is incomplete, and simply regulating the presenting complex may have limited effect.”

But this discovery, along with previous unexpected gains in aging research, has shown Yang Ping the potential boundaries of the systemic regulation approach.

It may not only apply to diseases like cancer that involve "identity fraud," but may also provide new perspectives for autoimmune diseases ("identity misjudgment") and even some age-related functional declines ("identity signal wear-off").

Of course, with each step forward, the unknown risks increase. Applying regulatory approaches to the immune system is far more complex and dangerous than oncology. The team is extremely cautious about this, strictly limiting its research to basic research.

The research on system regulation theory is becoming increasingly extensive, and Yang Ping must conduct in-depth thinking on it in order to ensure that he can master it.

(End of this chapter)