top student at medical school

Chapter 111 Thrilling (Please Subscribe)

At this moment, Fang Ziye was also a little nervous. He hadn't expected that the inhuman question raised by Jie Han would actually be brought up.

At that moment, Fang Ziye immediately recited the absolute key to the defense in his mind.

The defense, the response. Just answer, no defense. Point out the problems, acknowledge them first, then argue. Offer suggestions, and keep thanking them…

The defense session is no joke; it's a question-and-answer session. Once a question is asked, it's already on camera and cannot be interrupted or paused. Therefore, Fang Ziye could only rack his brains to find a solution.

Yuan Weihong is Fang Ziye's mentor, and it's not his turn to speak yet, so he can only watch anxiously.

At the same time, he felt a little resentful. If it were Professor Deng Yong sitting here now, would Professor Zheng Tonghui from the Third People's Hospital of Hubei Province dare to ask such a question?

Does this pathway have any practical significance? Are you questioning the research topic I applied for or my student's dissertation? Are you out of your mind?
Professor Zhang Fangping of the Department of Spinal Surgery at Zhongnan Hospital stretched his neck, seemingly to loosen his muscles, but actually to alleviate the awkwardness of the current situation.

This kind of problem could easily lead to disputes later on.

Indeed, this time, you might be able to let our hospital's students prepare for the second round of debates. Yes. You raised a question, and the students couldn't answer it, so a second round of debates is possible. No problem, let's proceed with this procedure.

But damn it, I already told you beforehand that this student's workload is more than enough for a doctoral dissertation defense, and you still ask this question? Are you brain-dead or what?
So, when all students in your school defend their master's theses, will they all have to benchmark against Fang Ziye's workload and the difficulty of his questions?
Naturally, Professor Zheng Tonghui, who raised the question, was secretly groaning. He had been so focused on his thesis that he had forgotten he was defending his master's thesis.

And precisely because Fang Ziye's workload and the depth of his basic research were not small, he completely forgot the occasion and brought up the issue in a scenario where peers were exchanging ideas, which was essentially just joking around.

Finally, after nearly half a minute of silence, Fang Ziye gave his answer: "Thank you for your question, Professor Zheng. I would like to offer the following explanation."

"As early as the 1930s, the Warburg team observed that cancer cells would undergo glycolysis even in a high-oxygen environment, resulting in high lactate levels. This phenomenon is known as aerobic glycolysis or the 'Warburg effect'."

"Although aerobic glycolysis produces less ATP than oxidative phosphorylation, it can rapidly provide sufficient energy and precursors for cell proliferation and biosynthesis. Therefore, aerobic glycolysis has been identified as the seventh characteristic of cancer."

Fang Ziye is explaining that tumor cells require energy for all their behaviors, and that the energy source for tumor cells is mainly glycolysis, rather than oxidative phosphorylation in normal cells.

The majority of energy for normal cells comes from aerobic respiration!

This is fundamentally about answering why the team chose HK2 as a target for studying tumor cells.

Although the question is difficult to answer, it's the only thing I can do.

Fang Ziye continued, "Although the rate of glycolysis can be regulated by a variety of metabolic enzymes in the glycolytic pathway, most studies have shown that in glycolysis, the flux control of glucose depends primarily on the upregulation of glucose transporters and hexokinase (HK)."

"Moreover, HK-catalyzed glucose phosphorylation, as a key irreversible step in the glycolysis pathway, plays a crucial role in aerobic glycolysis."

In this sentence, Fang Ziye is explaining that since most of the energy for tumor cells comes from glycolysis, it would be most appropriate to find a key metabolic regulatory target.

If we compare the process of glycolysis to eating, then how much one eats depends on the seasoning of the side dishes. If the seasoning is good, one can eat more rice; if the seasoning is bad, like eating rice with pig feed, most people probably can't eat it.

方子业继续说：“在人体中，HK共分为四个亚型：HK1、HK2、HK3、HK4，四个亚型中，尚未有文献报道 HK1与恶性肿瘤的相关性；HK2在多种肿瘤细胞中，都有高表达；HK3会在生理的血糖浓度就受到抑制；而 HK4大多只在肝脏和胰腺中有表达。”

"Further studies have shown that HK2 is overexpressed in various solid tumors, including colorectal cancer, liver cancer, ovarian cancer, and pancreatic cancer, suggesting that HK2 plays an important role in the development and progression of tumors. Further research has found that HK2 is the main hexokinase in most tumors in the human body, and that HK2 is a key component in promoting tumor cell survival and energy production pathways."

In this sentence, Fang Ziye is explaining that if HK2 is a delicious condiment, then the condiments that are suitable for people must be the foods we commonly eat.

For example, when it comes to food, cats might think eating raw mice is good, dogs might think eating feces is delicious, and dung beetles and maggots might think that a cesspool is a paradise.

Within the human body, there are several subtypes of HK, but generally speaking, HK2 is the most suitable and delicious seasoning for humans. This brings us to the topic of HK2.

"Furthermore, many studies have found that HK2 overexpression is positively correlated with tumor stage, differentiation, and lymph node enlargement, and it reduces patient survival. In recent years, similar studies have found that HK2 levels are also increased in rapidly growing osteosarcoma cells. Moreover, studies have confirmed that the expression level of HK2 in osteosarcoma affects the prognosis of osteosarcoma patients."

This is also a kind of groundwork. Although the target HK2 has a regulatory effect on most tumors, it has little regulatory significance in some tumors.

Moreover, HK2 overexpression does indeed affect the survival rate of osteosarcoma patients.

Of course, this is still not enough to answer the question; it's just a quote.

Fang Ziye continued, "If we want to further confirm whether HK2 also has an absolutely negative effect on normal cells, we need to first construct the survival rate and survival rate correlation of nude mice after the HK2 gene is knocked out, and then the survival status of humanoid monkeys, apes and other organisms after the knockout, and then begin to verify it."

"Of course, if we want to get to this point, we may also need to knock out or silence HK2 in the normal state of many organ cells in the human body and observe their activity efficiency. This is a very large workload."

"Currently, there are no corresponding papers or research to support this worldwide. However, by reading the previously published literature, we know that the reason why the glycolysis pathway can proceed step by step means that even after the rate-limiting enzyme at each step is silenced, the corresponding cell still has the possibility of survival."

"Perhaps, the next step in our research group's work, such as finding osteosarcoma-specific upstream and downstream elements that can regulate HK2 levels but are not present in normal cells, and then targeting and regulating the levels of these elements to inhibit HK2 expression in osteosarcoma without affecting HK2 expression in normal cells, would be a key step in solving the problem you raised, Professor."

"This requires a tremendous amount of work. If the opportunity is right, I will have the chance to pursue further studies and will work hard and strive in that direction."

"Current evidence is insufficient to confirm whether knocking out this target would cause side effects exceeding the range of side effects currently known to humankind of chemotherapy drugs."

"Thank you, teacher."

After Fang Ziye finished speaking, a thin layer of sweat began to trickle down his back.

This question is far too pointed; it's so pointed that anyone with even a slightly weaker foundation in the subject might not be able to answer it.

Even now, Fang Ziye's answer wasn't particularly well-reasoned. But that was all the answer he could give.

Naturally, Fang Ziye also knew that if this question were asked to any cancer medical research group in the world, they would find it difficult to answer.

Who can guarantee the safety and efficacy of a drug that targets this specific target even if it is found?

If possible, this research group would already be renowned in the industry, considered among the top experts. Because they might have solved all the problems within an oncology department.

When Fang Ziye returned, Associate Professor Xie Jinyuan, who was serving as the defense secretary, looked at Professor Zheng Tonghui.

Zheng Tonghui nodded, quickly finding a reason to cover it up: "This is indeed an aspect we need to pay attention to when doing scientific research. Of course, the scope of this topic is a bit too broad."

"As a professional master's student, you have been able to produce such a large amount of work during your master's studies, and your reading volume is also very extensive."

"The workload for a graduation thesis is definitely more than enough. However, I know that someone as outstanding as you will eventually enter the workforce..."

Fang Ziye breathed a slight sigh of relief when he heard Zheng Tonghui say that. He was really afraid that the other party would deliberately cause trouble. Fortunately, the other party stopped halfway and changed the subject to nonsense.

Because if someone just won't let you pass, you definitely need to prepare for the second debate, and there's also a cooling-off period of about six months, which is really awkward.

Although I will defend my dissertation in July and it won't affect my doctoral studies, I'm just worried about encountering another idiot next time.

If one does not have a graduate diploma and master's degree certificate before starting doctoral studies, then pursuing a doctorate is completely out of the question.

Even if, in the future, most master's students at the Third People's Hospital of Hubei Province will not be able to graduate, that's not what Fang Ziye needs.

At this point in the conversation, Zheng Tonghui asked one more perfunctory question before quickly moving on.

We can't go too deep into the topic, treating this master's thesis defense like a peer interview with interrogation questions; that would lead to problems. Professor Du from the Provincial People's Hospital, also affiliated with Wuhan University Hospital, didn't make things difficult, simply choosing a question of moderate difficulty.

This is a question that would typically arise during a doctoral dissertation defense, but Professor Du had clearly given it considerable thought.

Fang Ziye's answer was also quite good.

……

Then Professor Li and Professor Wu from Peking Union Medical College Hospital, and Professor Qi from Tongji Hospital, each asked a standard question.

But when Fang Ziye arrived at the Third Affiliated Hospital of Central South University, Professor Wu looked through his paper and asked, "Student, I see that the workload of the basic cell experiments in your paper is quite large, but in the animal experiments, you only did a size comparison of the tumor-bearing experiments. Why didn't you think of doing a tissue typing process?"

Upon hearing this, Fang Ziye immediately tensed up slightly.

This question is a bit too difficult. Although it's not as pointed as the question Professor Zheng Tonghui asked earlier, it's actually designed to test Fang Ziye's depth of knowledge in animal experimentation techniques.

Fortunately, Fang Ziye was relatively weak in this area, and he could roughly understand the meaning behind it.

Fortunately, Fang Ziye had spare knowledge points.

I silently apologized to myself, "I'm sorry, my students, I can't keep you here."

add a bit!

As a result, Fang Ziye's proficiency in the basic animal experiment section immediately increased from level 1 to level 3 200/500!

All of Fang Ziye's knowledge points were cleared.

No matter how slowly you accumulate knowledge later, let's focus on the graduation defense first.

Some ideas about basic animal experiments came to Fang Ziye's mind, and he gained a clearer understanding of Professor Wu's perspective on the question.

It's a bit tricky, but not difficult.

"Professor Wu, our research group is currently studying the effects of HK2 on osteosarcoma cells. We are mainly observing the growth rate of osteosarcoma cells after HK2 is overexpressed and then silenced."

"It belongs to the most superficial part of the HK2 study."

"Before the experiment, the osteosarcoma cell lines had already been classified as MG63, U2OS, Saos-2, and HOS, all of which were purchased from the Cell Resource Center of the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. Therefore, the classification of osteosarcoma cell lines by sectioning them is not very meaningful."

"If we were to conduct a section study on the mortality rate of cells in the internal organs, bones, and brain tissue of laboratory mice, it wouldn't be very meaningful."

"If there is drug intervention, these tissue sections are used to observe the corresponding toxicity of the drug or endophyte. Our research group only involves cellular-level treatments, and does not involve any other interfering substances entering the nude mice, nor any exogenous substances that remain for a long time."

"Therefore, conducting section studies is not very meaningful; we mainly observe their growth rate."

Fang Ziye replied quite easily, stating that the purpose and significance of the slicing operation were unrelated to the operations performed by their research group.

Of course, there are other angles to answer this question.

Professor Wu asked again what other procedures could be performed if a tumor biopsy were to be taken.

Therefore, Fang Ziye continued, "If we want to study the internal angiogenesis of tumors by cutting them into sections, we may need to use a specific marker for vascular endothelial cells."

"However, this is about the pathway and topic related to HK2 and the promotion of angiogenesis in tumor cells, which is somewhat different from the direction of our research group's experiments and research. Therefore, it is not within the scope of our current research group."

"This falls under the category of more in-depth research, specifically the theoretical study of growth-promoting factors of HK2 in the growth process of osteosarcoma cells. This may be the scope of our next exploration."

"And if the goal is to determine the organ origin of the tumor, this experiment..."

Fang Ziye finally breathed a sigh of relief after answering.

He turned his gaze to his master. "Master, I've made it this far. Now it's your turn to debate with the scholars. These professors are all too cunning. I really can't hold on any longer."

During the defense, the professors could have provided supplementary information. If Yuan Weihong were of a higher rank, he could have even offered some additional information when Zheng Tonghui raised the question. However, to save face for the professor, Yuan Weihong refrained from speaking.

So, in the next ten minutes or so, Yuan Weihong demonstrated his solid skills to everyone.

Since Professor Chu passed away, Yuan Weihong has become the only postdoctoral fellow in the department without a mentor. He knew that he had to rely on his own efforts. Therefore, Yuan Weihong's theoretical knowledge and scientific research skills were not something he boasted about.

Those who dare to apply for the Young Thousand Talents Program and harbor such ambition are definitely not incompetent.

With the teachers' involvement, Fang Ziye noticed that after hearing Yuan Weihong's statement, the other professors concealed their various emotions and their gazes towards Yuan Weihong changed slightly.

This unassuming young mentor is not to be underestimated. Perhaps in a few years, he will be able to represent the senior professors of Zhongnan Hospital and showcase his talents nationwide.

Once you reach the level of senior professional, your national standing in the academic world depends entirely on your own efforts. Your workload, work quality, technical skills, the depth of your scientific research, and the sophistication of your clinical procedures are all factors that determine whether you are truly valued by others and are the biggest guarantee of your interpersonal relationships.

……

After he finished speaking...

Fang Ziye and Yuan Weihong finally left the demonstration room, leaving only the defense secretary and others to hold a meeting.

The meeting was short, only about ten minutes long.

After the defense, Professor Deng Yong immediately went to curry favor with the other professors and engaged in a small-scale "business deal," which was essentially mutual flattery.

Of course, dinner and drinks were included, but before that, Professor Deng Yong took them to his office to pay them their trouble fees and service fees...

After Xie Jinyuan came out, he simply nodded to Yuan Weihong.

Yuan Weihong and Fang Ziye both breathed a sigh of relief.

"Master, Master, Senior Brother, come over and take a picture." At this moment, Jie Han held up the camera, while Lan Tianluo moved the stool so that Yuan Weihong could sit down. Fang Ziye stood next to him and took a proper photo of the mentor and student.

The two of them simply waited for the defense committee members to come out, and then took a group photo with Fang Ziye and Yuan Weihong, with the red banner of the defense on it. The defense process was then over.

Next was a simple thank-you banquet for the teachers.

This teacher appreciation banquet was very simple. Fang Ziye and Sun Shaoqing paid the bill to express their gratitude to their teacher for his guidance and care, to express their gratitude for the past teacher-student relationship, and to continue the teacher-student relationship for a lifetime.

It's a bit expensive; he and his senior each need to spend around 6 to 8 yuan.

But this amount of money is far from enough to cover the teacher's usual expenses for treating people to meals, so it's not that the teacher is deliberately making things difficult for the teacher.

(End of this chapter)