At this moment, Fang Ziye was also a little nervous, but he didn't expect that the inhuman question raised by Jiehan was really raised.

At this moment, Fang Ziye immediately recited the absolute mantra of the defense in his heart.

Defense. Only answer, not defense. Point out the problem, admit it first and then argue. Thanks for making suggestions......

The defense link is not child's play, that is, the question is answered, as long as the question is asked, it has already arrived in the camera, and it must not be interrupted or stuck, therefore, Fang Ziye can only think hard to find a solution.

Yuan Weihong is Fang Ziye's mentor, and it is not his turn to speak at this time, so he can only be in a hurry.

At the same time, I felt a little hatred in my heart, if it was Professor Deng Yong who was sitting here now, Professor Zheng Tonghui from the Third People's Hospital of Hubei Province, would dare to ask such a question?

Is this pathway of practical significance, are you questioning the topic I applied for or questioning my student's answer essay, are you TM full of support?

Professor Zhang Fangping Zhang of the Department of Spine Surgery of Zhongnan Hospital stretched his neck at this moment, which seemed to be moving his muscles and bones, but in fact he was alleviating an embarrassment in the current situation.

This kind of problem may lead to disputes in the future.

Indeed, this time, you may be able to prepare a second argument for the students of our hospital, yes. If you ask a question, and the student can't answer it, you can argue twice, no problem, go through this procedure.

But TM's I obviously told you in advance, this student's workload, as a doctoral dissertation defense is no problem, you still ask, are you brain-dead or what?

Let's just say that all the students in your future school, when they defend their master's degree, do they have to benchmark the workload and difficulty of the problem?

Naturally, as the proposer of the question, Professor Zheng Tonghui was also secretly bitter in his heart at the moment, he just cared about the consideration of the thesis, and forgot that this was the master's thesis defense.

And it is precisely because Fang Ziye's workload and the depth of basic scientific research are not small that he directly forgot the occasion at that time, and threw this question out of the scene of peer communication, which is equivalent to pulling calves from each other.

Finally, after being silent for nearly half a minute, Fang Ziye gave an answer: "Thank you, Professor Zheng, for your question, I would like to explain this question as follows. ”

"As early as the 30s of the 20th century, the Warburg team observed that cancer cells undergo glycolysis even in a hyperaerobic environment, resulting in high lactate levels, a phenomenon known as aerobic glycolysis or the 'Warburg' effect."

"The aerobic glycolysis process, while producing less ATP than oxidative phosphorylation, can rapidly provide sufficient energy for cell proliferation and precursors for biosynthesis. Thus, aerobic glycolysis has been identified as the seventh feature of cancer. ”

Fang Ziye is explaining that various behaviors of tumor cells require energy, and the energy source of tumor cells is mainly glycolysis, not oxidative phosphorylation of normal cells.

Most of the energy source for normal cells is aerobic respiration!

This is fundamentally, first to answer why the team is looking for HK2 as a target as a node to study tumor cells.

It's hard to answer, but it's only a question that can be answered.

Fang 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 control of glucose flux is most dependent on the upregulation of glucose transporters and hexokinase (HK). ”

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

In this sentence, Fang Ziye is explaining that since most of the energy sources of tumor cells come from glycolysis, it is most appropriate to find a more critical one-step metabolic regulation target.

If the process of glycolysis is compared to a person's meal, then if you eat more and eat less, you may have to pay attention to the seasoning of the side dishes.

Fang continued: "In humans, HK is divided into four subtypes: HK1, HK2, HK3, and HK4. HK2 is highly expressed in a variety of tumor cells. HK3 will be inhibited at physiological blood glucose concentration; HK4 is mostly expressed only in the liver and pancreas. ”

"Other studies have proved that HK2 is overexpressed in a variety of solid tumors such as colorectal cancer, liver cancer, ovarian cancer and pancreatic cancer, suggesting that HK2 plays an important role in the occurrence and development of tumors. Further studies have found that in most tumors in our body, the main hexokinase is HK2, and HK2 is a key component in promoting tumor cell survival and energy production pathways. ”

In this sentence, Fang Ziye is expounding, if HK2 is a delicious condiment, then the condiment suitable for people must be our common food.

For example, if it is the same food, cats will think that it is good to eat raw mice, dogs will also feel very fragrant when they eat feces, and feces shells and maggots will feel that the dung pit is a paradise.

There are many subtypes of HK in the human body, and generally speaking, HK2 is a delicious condiment that is suitable for people. This is to bring the topic to HK2.

"In addition, many scholars have found that the overexpression of HK2 is also positively correlated with the stage, differentiation and lymphadenopathy of tumors, and will reduce the survival rate of patients. In recent years, it has also been found that the level of HK2 in vigorous osteosarcoma cells is also increased. In addition, some studies have confirmed that the expression level of HK2 in osteosarcoma affects the prognosis of osteosarcoma patients. ”

This is also a kind of foreshadowing, although the target of HK2 has a regulatory effect on most tumors, but in some tumors, it does not have much regulatory significance.

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

Naturally, the question is answered here, still not enough, just quotes.

Fang Ziye continued: "If you want to further confirm whether HK2 also has an absolute negative effect on normal cells, you need to first construct the survival rate and survival rate of nude mice after the HK2 gene is knocked out, and then start to verify the survival state of humanoid monkeys, apes and other organisms after knocking out. ”

"Naturally, if we want to go this step first, we may also need to knock out or silence the normal state of many organs and cells in the human body, and observe their activity and efficiency. That's a lot of work. ”

"At present, there are no papers and studies to support it worldwide. However, by reading the previously published literature, it can be seen that the glycolytic pathway, which can be advanced step by step, means that the corresponding cells can still survive after silencing with each step of the rate-limiting enzyme. ”

"Perhaps, the next step of our group's research, for example, to find the upstream and downstream elements that can regulate the level of HK2 but not in normal cells, and to inhibit the expression of HK2 in osteosarcoma by targeting and regulating the level of these elements, but not affecting the expression of HK2 in normal cells, is a key step to solve the problem you raised."

"It's a lot of work, and if the opportunity is right, I have the opportunity to further my education, and I will work hard and forge ahead in this direction."

"At present, all the evidence cannot confirm whether the side effects of this target will exceed the range of side effects of chemotherapy drugs currently known to mankind if it is knocked out."

"Thank you, teacher."

After Fang Ziye finished speaking, there was a faint sweat on his back.

This question is too sharp, so sharp that he may not be able to answer it if his foundation is a little worse.

But even now, Fang Ziye's answer is still not particularly good. But this is all that Fang Ziye can answer.

Naturally, Fang Ziye also knows that if this question is put in any oncology medical research research group in the world, it will be difficult for the other party to answer.

Who can be sure that even if a targeted drug with this target is found, it will be able to guarantee its safety and efficacy?

If it can, then this research group has long been famous in the industry and belongs to the top bulls. Because they may have solved all the problems of a tumor line.

When Fang Ziye returned here, Associate Professor Xie Jinyuan, as the secretary of the defense, looked at Professor Zheng Tonghui.

Zheng Tonghui nodded, and hurriedly found a reason to make up for it: "This aspect is indeed an aspect that we need to pay attention to when doing scientific research, of course, the scope of this topic is a bit too wide." ”

"As a professional master's student, you can do so much work during your master's degree, and your reading volume is also very extensive."

"The workload as a graduation thesis must be completely sufficient, but I know that an excellent person like you, classmate, will definitely go to society in the future......"

When Fang Ziye heard Zheng Tonghui say this, he breathed a sigh of relief, he was really afraid that the other party would deliberately find fault, but fortunately, the other party stopped halfway and talked about the problem in the direction of nonsense.

Because once a person just doesn't pass you, the second argument definitely needs to be prepared, and it takes a cooling-off period of about half a year, which is embarrassing.

Although I defended in July, it will not affect my normal doctoral studies, but I also encountered a stunned person in case of a moment.

If you don't have a graduate degree certificate or a master's degree certificate before the start of your doctorate, then you have nothing to do with yourself to study for a doctorate.

Even if in the Third People's Hospital of Hubei Province in the future, basically all the masters will not be able to graduate, but this is not what Fang Ziye needs.

At this point, Zheng Tonghui symbolically asked a small question, and quickly skipped it.

You can't go too deep into the question, and treat this master's thesis defense as the kind of question that is a peer exchange, which will ask questions.

Professor Du from the Provincial People's Hospital, who also belongs to the Affiliated Hospital of Han University, was not embarrassed, but just chose a question of medium difficulty.

The difficulty of this question is almost the same as that of the doctoral defense, but Professor Du has obviously thought about it.

Fang Ziye's answer was not bad.

……

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

But when he arrived at Professor Wu from the Third Affiliated Hospital of Central South University, Professor Wu looked at Fang Ziye's paper left and right, and then asked: "Classmate, I see that in your paper, the workload of the basic cell experiment part is not small, but in the animal experiment part, only the size comparison of the tumor carrier experiment was done, why didn't you think about doing a slice typing treatment?" ”

When Fang Ziye heard this, his back immediately tightened slightly.

The difficulty of this question is a bit high, although it is not as sharp as the previous question raised by Professor Zheng Tonghui, but in fact, it is to examine the depth of Fang Ziye's animal experiment technology.

And it just so happens that Fang Ziye is in a relatively weak link in this aspect, and Fang Ziye can almost understand the corresponding meaning.

However, fortunately, Fang Ziye has spare knowledge.

I thought silently in my heart, I'm sorry, knowledgeable people, I can't keep you.

Some!

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

All of Fang Ziye's knowledge points have been emptied.

No matter how slow the accumulation of knowledge points in the back is, let's graduate and defend first.

Some parts about simple animal basic experiments appeared in Fang Ziye's mind, so Fang Ziye was more transparent about what the angle of Professor Wu's question was.

It's a bit tricky, but it's not hard.

"Professor Wu, the current research perspective of this research group is about the effect of HK2 on osteosarcoma cells, mainly to observe the growth rate of osteosarcoma cells after the molecular overexpression of HK2 and silencing."

"It's the shallowest part of the HK2 study."

"Before the experiment, the cell lines of osteosarcoma had been classified, and MG63, U2OS, Saos-2, and HOS were all purchased from the Cell Resource Center of the Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, so the classification of osteosarcoma cell lines by slicing is of little reference significance."

"It is not very meaningful to study the mortality of tissue cells such as viscera, bone and brain tissue in experimental mice."

"If there is a drug intervention, sectioning these tissues is to observe the corresponding toxicity of the drug or the inner plant. In this research group, only the treatment at the cellular level is involved, and there are no other interfering substances entering the body of nude mice, and there are no long-term retained exogenous substances. ”

"Therefore, it doesn't make much sense to do a slicing study, we mainly look at their growth rate."

Fang Ziye replied relatively easily, this is Fang Ziye's answer, the purpose and significance of the operation of slicing, and has nothing to do with the operation of this research group.

Of course, the answer to this question does not stop there.

Professor Wu still asked again, if you want to slice the tumor, what other operations can be done.

Therefore, Fang Ziye continued to answer: "If you want to perform post-sectional studies of the internal angiogenesis of the tumor, you may need to use the specific maker of vascular endothelial cells. ”

"However, this is the pathway and topic corresponding to HK2 and pro-tumor intracellular angiogenesis, and there is a certain directional deviation from the experiments and topics being done by this research group, so it is not within the scope of the current topic of this research group."

"It belongs to the theoretical research category of growth promoters of HK2 in the growth process of osteosarcoma cells, which may be the scope of our next discussion."

"And if you want to determine the source of the tumor organ, this experiment ......"

After Fang Ziye answered, he finally breathed a sigh of relief.

Set your eyes on your master, Master, I've survived here, and then it's time for you to fight your tongues, these professors are too old and slippery, I really can't hold on.

In the defense stage, the teacher can help to supplement, if Yuan Weihong's level is high enough, he can even add one or two when Zheng Tonghui raised a question, but in order to give the professor face, Yuan Weihong did not speak.

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

Yuan Weihong, since Professor Chu passed away, he became a postdoctoral fellow without a teacher in the department, he knew that he had to rely on his own efforts, therefore, Yuan Weihong's theoretical reserves, scientific research and operation reserve capabilities, that is not bragging.

Those who dare to apply for thousands of young people, with this ambition, are definitely not incompetent.

With the teacher's participation in the war, Fang Ziye found that after hearing Yuan Weihong's words, several other professors hid all kinds of emotions on their faces, and their gaze at Yuan Weihong also changed slightly.

This inconspicuous young mentor should definitely not be underestimated, maybe in a few years, he will be able to represent the professor senior title group of Zhongnan Hospital to show his style across the country.

The workload, the quality of work, the level of technology, the depth of scientific research, and the essence of clinical operation are all whether you can be truly valued in the eyes of others, or the greatest guarantee of human sophistication.

……

The end of the sentence.

Fang Ziye finally left the classroom with Yuan Weihong, leaving only the defense secretary and others for a meeting.

The meeting was not long, only a dozen minutes.

After the defense, Professor Deng Yong immediately catered to him and engaged in a small PY transaction with the professors, that is, business blowing.

Naturally, the matter of eating and drinking will not be left behind, but before that, Professor Deng Yong still took them to his office, and the hardship and labor expenses had to be paid......

And after Xie Jinyuan came out, he just nodded to Yuan Weihong.

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

"Master, Master, brother, come and take a picture." At this moment, Jiehan was holding the camera, Lan Tianluo was moving the stool, and after Yuan Weihong sat down, Fang Ziye stood next to him and took a group photo of the tutor and the student in a proper manner.

The two just waited for the defense committee to come out, and then took a group photo with Fang Ziye and Yuan Weihong with a red background banner for the defense, and the defense procedure came to an end.

Next, it is a simple thank-you banquet.

This thank-you banquet is very simple, paid by Fang Ziye and Sun Shaoqing, thanks to the grace of the teacher, thanks to the care of the teacher, thanks to the past master-apprentice relationship, and the friendship between master and apprentice for a lifetime.

It's a bit expensive, and he and his brother cost about 6-8k each.

But this money is far from making up for the teacher's usual expenses for dinner, and it is not deliberately embarrassing.

(End of chapter)