I Am Diagnosed as a Medical Titan

Through deduction and theoretical analysis of the biochemical properties of local amino acid residues, this paper proposes that the cysteine residue (Cys12), created by the mutation at position 12, exhibits extremely strong nucleophilicity in its side-chain sulfhydryl group within a specific local microenvironment.

This sulfhydryl group possesses immense potential to act as a Covalent Anchor...

1. KRAS mutations are extremely common in pancreatic cancer, non-small cell lung cancer (NSCLC), and colorectal cancer. The physiological function of wild-type KRAS relies on its cyclical binding with GTP and GDP...

2. The significant shift in local side-chain chemical properties induced by the G12C mutation...

3. Potential regulation of the sulfhydryl group and amplification of its nucleophilicity by the local microenvironment...

4. The kinetic feasibility of a covalent targeting strategy...

5. Conclusion and Future Strategy Recommendations: KRAS G12C is not undruggable.

Future research in structural biology and computer-aided drug design must completely shift its paradigm.

Stop searching for deep pockets on wild-type KRAS.

Concentrate computing power on simulating the surface of the G12C mutant, especially the region immediately adjacent to the Cys12 residue (within a 5-10 angstrom range).

Focus on finding dynamic and shallow allosteric sites capable of accommodating small-molecule scaffolds.

Delivering molecules carrying electrophilic warheads to the vicinity of Cys12 will surely become the greatest breakthrough in conquering KRAS...

...

...

「At Yang Xu’s home.」

The moment Wang Xiaoqing walked in the door, she turned and hammered Yang Xu’s shoulder twice.

Yang Xu said, "Hey, what was that for? Starting with the domestic abuse the second you get home?"

Wang Xiaoqing rolled her eyes. "You tell your student everything, don’t you? Huh? Something like trying for a baby... couldn’t you just discuss it with me in private? But you had to go and tell Jiang He? Why don’t you just go live with your student then, you have no shame!"

Yang Xu scratched his head, chuckling as he explained, "I was just thinking that Jiang He’s sharp, you know? A quick thinker. Since he’s the head of the project and a researcher, I figured he might have some good ideas to get you situated nicely."

"You have the nerve to say that! He’s a twenty-one-year-old kid. You start talking to him about us trying for a baby—how is he supposed to respond to that? You should take a few lessons from your student. He’s way more mature than you are."

Yang Xu sidled up to her.

His hands weren’t exactly clean, but he wrapped an arm around her waist. "Right, right, he’s mature, he’s mature. But didn’t things work out perfectly? You’ll be handling administration, and it won’t get in the way of our own ’big project’."

Wang Xiaoqing shot him a look. "Open your mouth."

Yang Xu obediently opened his mouth. "Ahhh—"

Wang Xiaoqing leaned in for a sniff, then nodded in satisfaction. "Alright. Not bad."

Trying for a baby was a two-person affair.

Yang Xu, a chain-smoker for over a decade, had been making a serious effort to quit recently.

He had replaced all the cigarettes in his pockets with chewing gum, which certainly showed his commitment.

Suddenly, Wang Xiaoqing felt her bra being unhooked.

Annoyed, she slapped him soundly. "Go take a shower first!"

Yang Xu feigned a pained expression. "See? I told you. When it comes to domestic abuse, it’s either zero times or countless times..."

Wang Xiaoqing couldn’t help but laugh. "You’re really asking for it!"

After they fooled around for a bit,

Wang Xiaoqing received a text message.

It was from Li Jianping.

Li Jianping wanted to ask someone about Jiang He’s performance at Affiliated Hospital No. 1, and the first person who came to mind was, of course, Wang Xiaoqing.

After all, Wang Xiaoqing was the admin of their group chat.

Wang Xiaoqing opened the text, scanned it, and turned to Yang Xu.

"Old Yang, it’s a message from Professor Li Jianping at Ruijin."

"What’s he say?"

"He said that Jiang He, Elder Zhi’s friend, is coming to Ruijin for an exchange program soon. They’re planning a multi-hospital live-streamed surgery—a very complex Whipple procedure for cancer of the pancreatic head. Apparently, Jiang He is quite interested in the procedure, so Wen Xuyang suggested letting him join as the third assistant to get a close-up view."

Yang Xu rubbed his chin. "Jiang He mentioned this to me. He’s definitely interested in the Whipple procedure."

"Li Jianping is asking me about Jiang He’s performance in the OR here at Affiliated Hospital No. 1. He says this surgery is a huge deal, with a nationwide broadcast, so he wants to confirm whether he can safely let Jiang He be the third assistant. He’s worried he might mess up during the operation."

After all, Yang Xu was the hospital’s deputy dean and Jiang He’s direct supervising teacher. He would know best.

That’s why Wang Xiaoqing was asking him.

Yang Xu’s immediate reaction was, "That’s a no-brainer! Jiang He’s surgical skills are incredible! Who at Affiliated Hospital No. 1 isn’t impressed? Even Wang Zhengchu next door is a believer! We can all vouch for him!"

Wang Xiaoqing nodded. "Okay, I’ll tell him that then..."

"Whoa, wait! Not so fast!"

Yang Xu said suddenly, "Let me think... No, that’s not the right way to reply."

Wang Xiaoqing looked at him quizzically. "Why not?"

Yang Xu explained his reasoning. "I know this guy, Old Li. He’s the top surgeon at Ruijin, a real master. Jiang He is only twenty-one, after all. If you tell him right now that Jiang He’s surgical skills are god-tier, his first reaction will be total disbelief. And even if he does believe you, his expectations for Jiang He will be sky-high."

Wang Xiaoqing thought about it and had to admit he had a point.

Yang Xu continued, "Think about it. A nationwide, multi-hospital live stream? The pressure is immense. Jiang He’s new there, it’s an away game for him. If we hype him up to the moon, then if he does even one little thing wrong during the surgery, Old Li’s gonna feel let down."

"So what do you suggest?"

"Let’s be conservative. Play it safe. Just tell him: ’Jiang He’s clinical skills are pretty good, and he’s a very fast learner. However, his license to practice is currently restricted to our Affiliated Hospital No. 1. If you want him to perform surgery at Ruijin, our two hospitals will have to go through the paperwork for special approval to grant him visiting surgeon privileges.’"

Wang Xiaoqing typed as she listened. "Anything else?"

"And say: ’He’s never actually performed a major Level 4 surgery this complex, so it’s a bit of a stretch. But just being a third assistant and holding retractors? That’s definitely not a problem. When the time comes, we hope Professor Li Jianping, as a senior surgeon, will be able to guide him and give him some pointers during the procedure.’"

After Wang Xiaoqing finished typing, she showed it to Yang Xu for confirmation and then hit send.

She looked up at Yang Xu’s cunning expression and couldn’t help but laugh. "You’re so devious. Aren’t you deliberately misleading him?"

Yang Xu replied with a straight face, "How is that devious? It’s called managing expectations, you see? That way, the shock will be even greater."

Wang Xiaoqing thought about it and figured Yang Xu’s logic was sound.

She didn’t say any more about it and got up to take a shower.

She purposefully left the door unlocked.

Hearing no click of the lock, Yang Xu was over the moon. It was simply... *ahem*, scratch that, scratch that.

How should one put it?

Boss Yang’s maneuver was, in all fairness, well-intentioned.

𝚏𝗿𝗲𝐞𝚠𝕖𝐛𝗻𝗼𝐯𝕖𝚕.𝚌𝗼𝗺

But he had, in fact, well and truly duped Li Jianping.

...

「Hushang.」

Li Jianping said to Wen Xuyang,

"See? It’s a good thing I’m so thorough. I sent a message to Professor Wang to ask ahead of time."

"Professor, what did they say?"

"The reply came from Dean Yang of Affiliated Hospital No. 1 himself. He said Jiang He has never actually performed such a major, complex surgery and asked me to take him under my wing."

Wen Xuyang nodded. "That makes sense. He’s only twenty-one, after all."

"So, you see, in medicine, research and clinical practice really are two different things."

"So, Professor, the third assistant position..."

"We’ll hold it for him for now. I think, after Jiang He gets here, I’ll need to give him some personal instruction first."

Li Jianping rubbed his chin, already formulating a teaching plan in his mind.

Even though a third assistant just holds retractors, there’s a proper way to do it.

Where to stand so you don’t block the light, how to apply force without your hands trembling—all these details needed to be taught beforehand.

’This is for his own protection, too.’

’After all, it’s a nationwide multi-hospital live stream. So many eyes will be watching. If he lets a retractor slip, it won’t just be embarrassing for him; Ruijin would lose face, too.’

The more he thought about it, the more Li Jianping felt he had handled the situation perfectly.

He had shown Jiang He (Elder Zhi’s friend) the utmost courtesy while also fulfilling his duty as a senior to mentor a junior.

"Xuyang, go coordinate with the medical affairs department on the paperwork for a temporary consultation by an outside expert. Get it processed as quickly as possible," Li Jianping instructed.

"Yes, Professor."

After Wen Xuyang left,

Li Jianping sat alone in his office, a gentle and benevolent smile gracing his lips.

He had even prepared the lines he would use to comfort Jiang He on the operating table.

’Jiang He, don’t be nervous. Keep your hands steady and just follow my lead.’

Li Jianping thought to himself, ’Such magnanimity, such grace... Tsk, tsk. That’s me, all right.’