{Sketchy micro} 药理学 | 双语精校

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P1 · {Sketchy micro} 药理学 | 双语精校 p01 A5.1 - 两性霉素 B、氟胞嘧啶 (P1)

{Sketchy micro} 药理学 | 双语精校 p01 A5.1 - 两性霉素 B、氟胞嘧啶 (P1)

发布于 2026-02-22 · 时长 10:00

字幕摘录

时间	英文	中文
0:00	Hey everyone!	大家好! 大家好! 你们好!
0:01	Surprised you're back.	惊讶你回来了
0:01	Honestly, it got a little awkward during that antibiotics unit.	老实说,在抗生素组里有点尴尬
0:06	Well, I apologize.	对不起
0:08	Welcome to the first video in our unit on antifungal drugs.	欢迎收看本单位首部关于抗风药的视频.
0:11	Let's start with Amphotericin.	先说安普陀利金.
0:14	You know what?	你知道吗?
0:15	Amphotericin gets a pretty bad rap, doesn't it?	安非他明的说唱很烂 不是吗?
0:18	I've heard them all.	我全都听过了
0:20	Amphoterrable.	阴阳之气.

展开字幕全文（144 条）

序号	英文	中文
1	Hey everyone!	大家好! 大家好! 你们好!
2	Surprised you're back.	惊讶你回来了
3	Honestly, it got a little awkward during that antibiotics unit.	老实说,在抗生素组里有点尴尬
4	Well, I apologize.	对不起
5	Welcome to the first video in our unit on antifungal drugs.	欢迎收看本单位首部关于抗风药的视频.
6	Let's start with Amphotericin.	先说安普陀利金.
7	You know what?	你知道吗?
8	Amphotericin gets a pretty bad rap, doesn't it?	安非他明的说唱很烂 不是吗?
9	I've heard them all.	我全都听过了
10	Amphoterrable.	阴阳之气.
11	Amphoterrorofterror.	阿弥陀佛.
12	pho(原变种).
13	I mean, how terrible could it really be?	我的意思是,这到底有多可怕?
14	When I think of Amphotericin, you know what comes to mind?	当我想到安非他明时 你知道想些什么吗?
15	Amphibians, of course.	当然是两栖动物
16	Our recurring sketchy symbol for this toxic drug.	我们反复出现的这个有毒药物的象征
17	Our scene takes place in a community college science classroom, where some lab amphibians	我们的场景发生在一个社区大学科学教室里 一些实验室的两栖动物
18	are making a daring escape.	正在做一个大胆的逃跑。
19	Let's see if Amphotericin is really as terrible as everyone says.	让我们看看安非他明是否和大家说的一样可怕
20	First of all, see the terrarium?	首先,看到地球仪了吗?
21	Every science classroom has one.	每个科学教室都有一个
22	At least the cool ones do.	至少那些酷的会
23	And we're going to sketch some fungus in it to remind you that we are talking antifungals	我们要画一些真菌在里面 提醒你我们是在谈论反佛贡
24	here.	在这里。
25	Ergosterol is found in the cell membrane of fungi, while the dominant sterile of human	Ergosterol在真菌的细胞膜中被发现,而人类的主要无菌
26	and bacterial cells is cholesterol.	细菌细胞是胆固醇
27	So the glass of our fungal terrarium will represent the fungal cell membrane.	因此,我们的真菌腺体的玻璃将代表真菌细胞膜.
28	This is where Amphotericin acts.	这是阿姆菲特林的行为。
29	We'll sketch in this sign on the wall above the terrarium, non-sterile, not only to remind	我们在上面的墙上画个图,不消毒,不只是为了提醒
30	kids to wash their hands after handling amphibians, but that the fungal cell membrane is not your	孩子们处理两栖动物后洗手 但真菌细胞膜不是你的
31	usual sterile.	通常无菌。
32	它由ergosterol而不是胆固醇组成.
33	Amphotericin binds to ergosterol and forms pores in the cell membrane, allowing leakage	安非他明与ergosterol结合,形成细胞膜中的毛孔,允许渗漏
34	of electrolytes and macromolecules and eventually cell death.	电解质和大分子 最后细胞死亡
35	We'll convey this mechanism of action here at the wall of the terrarium, where amphibians	我们把这一行动机制 传达到地球圈的墙上 两栖动物
36	are making their escape.	他们正在逃跑
37	These frogs of NIM are breaking through holes in the glass, just like pores in an ergosterol	这些NIM的青蛙正在破碎 玻璃的孔, 就像毛孔在ergosterol
38	膜ne.
39	And also, notice water is leaking through these holes just like leakage of electrolytes.	还有,注意水就像电解质的渗漏一样从这些孔漏出。
40	If an exam question mentions resistance to amphotericin, it will involve changing the	如果一个考试问题提到对阿姆斐特林的抗药性,将涉及改变
41	molecular components of the fungal cell membrane.	球菌细胞膜的分子成分。
42	If a fungal pathogen decreases the amount of ergosterol in its membrane, amphotericin	如果真菌病原体会降低细胞膜中的ergosterol量,则酰胺
43	can't insert pores to kill the cell.	无法插入毛孔来杀死细胞。
44	Amphotericin B is the antifungal with the broadest spectrum of action.	亚麻黄素 B是具有最广泛行动的反风剂.
45	It has activity against pretty much any serious fungal infection you throw at it.	它的活性 几乎可以防止任何严重的真菌感染
46	This includes yeasts like candida and cryptococcus, endemic mycosis like histo, blasto, coccidio,	包括果冻和冰毒等酵母, 地方性肌病,如肝脏、肝脏、肝脏、心肌炎,
47	and molds like aspergillosis and mucor.	以及像麻痹和黏液一样的模具
48	Think of amphotericin as your antifungal used in severe systemic or life-threatening fungal	把安非他明当做你的抗风剂 用于严重的系统化或危及生命的真菌
49	infections.	传染病。
50	This will be represented by the anatomical model, a biology classroom fixture, next to	解剖模型 生物课堂固定器 旁边
51	the amphotericin terrarium.	氨基酸盐
52	All these organs exposed should remind you of infections such as severe fungal pneumonia,	所有这些器官都会让你想起 严重的真菌肺炎之类的感染
53	severe cryptococcal meningitis, just look at that brain, or disseminated infection with	严重的密码性脑膜炎, 看看大脑,或传播感染
54	one of the endemic mycosis such as histo or coccidio.	一种地方性肌炎,如骨科或骨科。
55	Amphotericin is given IV in order to treat systemic infections.	为了治疗系统性感染,安非他明被授予IV.
56	And to highlight IV administration, notice the IV at the top of the terrarium.	并突出IV管理,注意IV位于地标顶部.
57	Notice too, that frog inside is doing that big neck croak thing that frogs do.	注意 里面的青蛙在做 青蛙做的大项圈的事情
58	This is to evoke the image of a round liposome.	这是用来唤起圆润的画面。
59	Because of amphotericin's severe toxicities, liposomal drug formulations have been developed.	由于麻黄素的剧毒,脂质药物配方得到发展.
60	This permits packaging of the drug in lipid delivery vehicles, which decreases drug binding	这允许在脂质运载工具中包装药物,从而减少药物绑定
61	to human cholesterol membranes, thus lowering toxicity.	至人类胆固醇膜,从而降低毒性。
62	This chubby frog isn't going to wreak any havoc today.	这个肥胖的青蛙今天不会造成任何破坏
63	Let's talk about those toxicities.	我们来谈谈这些毒物
64	Because there are a lot of them, and they can be separated into two categories.	因为有很多种,它们可以分为两类.
65	Infusion-related immediate reactions, and slow cumulative toxicity.	与输液相关的即时反应,且累积毒性缓慢.
66	First of all, these toxicities result from amphotericin non-selectively binding to mammalian	首先,这些有毒物质 是由无选择性地对哺乳动物产生
67	cholesterol membranes instead of ergosterol membranes, so one of our frogs is clinging	胆固醇膜代替了ergosterol膜, 所以我们的一只青蛙在粘着
68	onto a teacher's necktie, which is decorated with the structure of mammalian cholesterol.	在老师的领带上, 它与哺乳动物胆固醇的结构装饰。
69	Infusion-related reactions are nearly universal, and consist of fever, chills, muscle spasm,	与输液相关的反应几乎是普遍的,由发烧,寒冷,肌肉痉挛组成.
70	vomiting, headache, and hypotension.	呕吐,头痛,下焦.
71	The headache and hypotension will be represented by the teacher who is grabbing his hat and	头痛和体弱的老师 将代表他拿起帽子
72	fainting as an immediate reaction to the frog suddenly jumping onto his tie.	晕倒作为对青蛙的即时反应,突然跳上他的领带.
73	He's knocked over a Bunsen burner, and this red, sweaty frog who is shaking in fear next	他撞倒了一辆邦森燃烧机 和这只红色的汗水青蛙
74	to the flame depicts the classic shake and bake fever and chills.	对火焰的描述是 经典的摇晃 烤热和寒冷。
75	Amphotericin is still sometimes used to treat fungal CNS infections, and must be administered	Amphotericin仍然有时用于治疗真菌CNS感染,必须服用
76	intrathecally.	在剧场里
77	We'll sketch in a frog here who is latched onto the model brain with his tongue, kind	我们用青蛙画画 他用他的舌头 和善良的
78	of like an intrathecal line.	就像一个内线。
79	This kind of administration can cause major CNS side effects, including seizures and neurological	这种管理可造成重大的CNS副作用,包括缉获和神经病
80	damage.	损害。
81	Notice, we've added our sketchy seizure action lines to this frog in order to convey this.	注意,我们已经增加了 我们的粗略的查封行动线 这只青蛙 为了传达这一点。
82	Also, during systemic administration, thrombophlebitis can occur at the injection site, and this	此外,在系统治疗期间,血栓性血栓炎可能在注射地点出现,而这种血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性血栓性
83	will be highlighted by the blue, veiny pattern on the frogs in the scene.	将会被现场青蛙身上的蓝色,静脉图案突出.
84	Next, let's highlight the more cumulative toxicities.	接下来,让我们强调更多的累积毒性.
85	Renal damage is the most significant toxic reaction.	肾损伤是最大的毒性反应.
86	In fact, renal impairment occurs in nearly all patients.	事实上,几乎所有患者都患有肾功能障碍。
87	Amphotericin can lead to reversible pre-renal azotemia or irreversible renal tubular injury,	安非他明会导致肾上腺素前的可逆性贫血或不可逆性肾小管损伤,
88	leading to a type 1 renal tubular acidosis.	导致1型肾管酸化.
89	We usually convey a tubular acidosis with a test tube of acid, and in this classroom	我们通常用酸的试验管 来传递输卵管酸化
90	we have a budding chemist holding a graduated cylinder full of acid.	我们有一个萌芽的化学家 持有一个毕业的圆柱 充满酸。
91	Notice, the graduated cylinder is shaped like the number 1 in order to emphasize a	注意 毕业的圆柱形状像1号 为了强调一个
92	type 1 renal tubular acidosis.	1型肾小管酸化。
93	RTA type 1 is associated with hypokalemia, so that's why he's sipping on this potassium	RTA 1型与低血压有关 所以他吸食这种钾
94	depleted banana peel.	香蕉皮耗尽了
95	Amphotericin toxicity also leads to renal magnesium wasting, represented by the magnesium	氨酸毒性还会导致肾上腺镁的浪费,以镁为代表。
96	magnet he was using to stir the kidney beaker contents falling into the sink.	他用磁铁搅动掉进水槽的肾泡子
97	Volume expansion with IV normal saline is usually initiated before drug administration	通常在服药前先用IV正常盐碱进行体积扩张
98	in order to ameliorate the initial decline in GFR and prevent ensuing renal damage.	目的是改善GFR的最初下降,并防止随之而来的肾脏损伤。
99	To represent this, we have emergency saline shower next to our chemist, who is embodying	为了代表这个 我们的化学家旁边有紧急盐水淋浴 他代表着
100	all that is nephrotoxic about amphotericin.	所有关于安非他明的肾上腺素都有毒
101	Now would probably be a good time to use it.	现在可能是一个好时机使用它。
102	All this damage to renal tubular cells leads to anemia, because the kidney can no longer	肾脏输卵管细胞的这些损伤 会导致贫血,因为肾脏无法继续
103	produce adequate amounts of EPO.	生产足够的EPO。
104	Take a look at the kidney shaped beaker that is knocked over and shattered.	看看被撞倒和粉碎的 肾脏形状的烧杯
105	Its red contents are now draining down the sink, while a frightened pale frog hops to	它的红色内装物正在水槽中排水, 而一个害怕的苍白青蛙跳到
106	safety.	保证安全
107	Let this remind you of decreased EPO production by the kidney, leading to anemia.	这提醒你肾脏的EPO产量下降,导致贫血。
108	See that falling rack of test tubes?	看到那个坠落的试验管架了吗?
109	I just want to emphasize that damage to renal tubular cells can cause anemia, because the	我只想强调肾脏输卵管细胞的损伤 会导致贫血,因为...
110	kidney is an important organ of EPO production.	肾是EPO生产的重要器官.
111	Remember that anemia does not have to originate in the bone marrow.	记住贫血症不必起源于骨髓.
112	Amphotericin B is one of the primary drugs used to treat cryptococcal meningitis, and	亚麻黄素 B是治疗密码球菌脑膜炎的主要药物之一,
113	it is often used in combination with the antifungal agent flucidazine to rapidly sterilize the	它常与抗风剂氟丙胺结合使用,以迅速消毒。
114	CSF.	(原始内容存档于2018-09-26). CSF.
115	Flucidazine will be highlighted in the music classroom across the hall, where a student	在大厅对面的音乐教室里 将突出Flucidazine, 一个学生
116	is practicing flute.	正在练习长笛。
117	Take a look at the sheet music in front of our flucidazine flute player, which will convey	看看我们的风笛演奏者面前的床单音乐 它将传达
118	this mechanism of action.	这种行动机制。
119	As one of the escaped frogs hops across the music stand, keep an eye on the notes we've	当一个逃出来的青蛙跳过音乐台时, 注意我们的音符
120	highlighted.	重点突出。
121	We have F and C next to each other, representing how flucidazine starts like a fluorinated	我们有F和C 相邻,代表氟西丁是如何开始像氟的
122	cytosine.	细胞素.
123	Then, as the frog hops off the page, the C has tipped over and turned into a U, depicting	然后,随着青蛙跳出页面, C已经向上倾斜,变成一个U,描绘
124	how cytosine deaminase converts flucidazine into 5-fluorouracil.	细胞氨酸脱氨酶如何将氟丙胺转化为5-氟磺酰胺.
125	From here, it's converted into a few more forms before being incorporated into growing	从这里,它被转换成几种形式,然后被融入成长
126	strands of DNA and RNA and halting their synthesis.	DNA和RNA链 停止它们的合成
127	The bars of music drawn on the chalkboard spiral into DNA and RNA strands, and a frog	粉笔板上的音乐条 螺旋状的DNA和RNA线 和一只青蛙
128	has smeared them, depicting this halt in DNA and RNA synthesis.	在DNA和RNA合成中描绘了这种停顿。
129	A question on an exam might word this mechanism as fungal DNA replication and fungal protein	测试中的问题可能把这个机制说成是真菌DNA复制和真菌蛋白
130	synthesis being inhibited.	合成受到抑制。
131	To emphasize that the flucidazine and amphotericin combo is often used for cryptococcus specifically,	为了强调氟丙胺和氨基苯丙胺组合常被具体用于密码学,
132	we'll sketch in the name of the opera for which our fungal flutist is practicing, Anthony	我们以歌剧的名义来画 我们的真菌笛手正在练习的歌剧 安东尼
133	和Cleopatra, 与Cleopatra的密码草图 在粉笔板上,
134	our cryptococcus sketchy microsketch.	我们的密码 粗略的微秒。
135	One more drug to cover in this sketch, and that's ni-statin.	还有一种药物要用这个草图来覆盖, 那就是Ni -statin.
136	Ni-statin has the same mechanism of action as amphotericin, in other words, it binds	Ni-statin与阿片胺具有相同的作用机制,换句话说,它绑定了
137	their gosterol and fungal cell membranes, creating pores and causing cell lysis.	产生毛孔 引起细胞解析
138	So it will be depicted right outside the amphibian-ridden lab room in the hallway.	因此,它将被描绘在走廊上两栖的实验室房间外。
139	Notice the be nice sign to emphasize the name ni-statin.	注意注意,好兆头 以强调ni -statin这个名字。
140	Ni-statin is active against most Canada species, as symbolized by our Canada Canadian flag,	Ni-statin积极对抗大多数加拿大物种,象征着我们的加拿大加拿大国旗,
141	with numerous patches of snow outside, just like the easily scraped patches of Canada.	外面有无数的积雪 就像加拿大容易刮伤的积雪
142	Ni-statin is available for topical use to treat mucocutaneous candidiasis, including	Ni-Statin可用于治疗皮肤三丁基苯丙胺,包括:
143	vaginal candidiasis, as depicted by the student outside getting pelted in the crotch.	阴道排骨, 由学生描绘 外面被打入喉咙。
144	Typical Canadian	典型的加拿大人

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P2 · {Sketchy micro} 药理学 | 双语精校 p02 A5.2 - 唑类抗真菌药 (P2)

{Sketchy micro} 药理学 | 双语精校 p02 A5.2 - 唑类抗真菌药 (P2)

发布于 2026-02-22 · 时长 10:00

字幕摘录

时间	英文	中文
0:00	The Wizard of Oz.	绿野仙踪
0:01	It's a timeless children's story.	无时童子说法.
0:04	But some see L. Frank Baum's original	但有些人看到L. Frank Baum的原创作品
0:07	story as a social satire.	故事作为一个社交讽刺。
0:09	Dorothy, your typical American.	桃乐西,你典型的美国人
0:12	A brainless scarecrow?	无脑稻草人?
0:14	Farmers.	农民。
0:15	A tin man with no heart?	无心的锡人?
0:16	Industry.	工业.
0:18	A cowardly lion?	一只懦弱的狮子?

展开字幕全文（177 条）

序号	英文	中文
1	The Wizard of Oz.	绿野仙踪
2	It's a timeless children's story.	无时童子说法.
3	But some see L. Frank Baum's original	但有些人看到L. Frank Baum的原创作品
4	story as a social satire.	故事作为一个社交讽刺。
5	Dorothy, your typical American.	桃乐西,你典型的美国人
6	A brainless scarecrow?	无脑稻草人?
7	Farmers.	农民。
8	A tin man with no heart?	无心的锡人?
9	Industry.	工业.
10	A cowardly lion?	一只懦弱的狮子?
11	Politicians.	政治家们.
12	You know what I see, though.	你知道我看见了什么
13	I mean, it's obvious.	我的意思是,这是明显的。
14	It's an allegory of antifungals.	反佛法喻义.
15	Don't believe me?	不相信我吗?
16	Get out that old Dark Side of the Moon record,	拿出月球纪录的黑暗面
17	wait for the third lion roar, and follow me.	等着第三只狮子咆哮 跟着我
18	We're off to see the Wizard, the wonderful	我们要去见巫师 美妙的
19	Wizard of Azols.	阿索尔的巫师。
20	Azols include the imidazoles, ketoconazole, myconazole, and clotrimazole,	亚速尔族包括伊米达佐尔族、凯托康纳佐尔族、我的康纳佐尔族和血红素族。
21	以及三亚ole,二亚az,氟con,和五亚ole.
22	The spectrum	频谱
23	of action of the azole drugs is broad, so we'll cover important clinical indications as we go	zo类药物的作用是广泛的, 所以我们会覆盖重要的临床征兆 当我们去
24	through each individual drug.	通过每种药物。
25	Let's cover mechanism of action first.	让我们先讨论行动机制
26	Like we mentioned	就像我们提到的
27	in the Amphotericin sketch, the cell membrane of fungi is composed of ergosterol, not cholesterol,	在安非他明草图中,真菌的细胞膜由ergosterol组成,而不是胆固醇,
28	and antifungal drugs often exploit this difference.	和抗风药 经常利用这种差异。
29	Ergosterol将出席大会
30	by the building blocks comprising the perimeter of the emerald city.	由翡翠城周边的构件组成
31	想想翡翠 ergosterol,
32	just like the fungal cell membrane.	就像真菌细胞膜一样
33	Notice, too, that the emerald city even has a postmodern	注意,翡翠城甚至有后现代
34	fungal architectural design.	真菌建筑设计.
35	The antifungal activity of azol drugs results from the	zo类药物的抗风活性源于
36	从拉诺斯特醇抑制ergosterol合成.
37	So we'll sketch in some munchkin builders bringing	所以,我们画一些 曼奇金建筑工带来
38	ergosterol材料到翡翠城墙.
39	And we all know the story from there.	我们都知道这个故事
40	Dorothy,	多萝西
41	after her house is picked up by the tornado, murders the first person she meets in the land	在她的房子被龙卷风抢走后 谋杀了她在陆地上遇到的第一个人
42	of azols.	动物园。
43	Notice, her house has landed right in the middle of the yellow brick road, crushing	注意,她的房子已经落在 黄砖路中间,粉碎
44	one of the emerald city workers, probably unionized in some kind of workers guild, too.	一个翡翠城的工人, 可能工会 某种工人盾,太。
45	The yellow brick road is closed, as indicated by this lane closed sign.	如本车道封闭标志所示,黄砖路封闭.
46	Think of lane closed	想想关闭的车道
47	as lanosterol unable to turn into ergosterol.	作为拉诺斯特醇 无法转化为ergosterol。
48	Specifically, azols hold the enzyme that turns	具体地说,动物园持有着转动的酶
49	lanosterol into ergosterol, fungal cytochrome P450.	拉诺斯特醇转化为ergosterol,真菌细胞色素P450.
50	And if you take a look under the house,	如果你看看这房子下面
51	it's none other than our recurring cytochrome chrome bumper with CYP450 license plate,	我们的细胞色素铬保险杠 上面有CYP450的车牌
52	attached to the back of a carriage, destroyed by yet another unreported workplace accident	车厢后部被另一起未报告的工作场所事故摧毁
53	at the emerald city.	在翡翠城。
54	So, azols halt the production of ergosterol from lanosterol	因此,阿佐尔斯停止生产 ergosterol 从拉诺斯特尔
55	by inhibiting cytochrome enzymes.	通过抑制细胞色素酶.
56	While azols exhibit higher affinity for fungal rather than	动物园对真菌的亲和度更高
57	human cytochrome P450 enzymes, all azol drugs are prone to drug interactions because they affect	人类细胞色素P450酶,所有 a类药物都容易发生药物相互作用,因为它们影响
58	mammalian cytochrome enzymes to some extent.	哺乳动物细胞色素酶在一定程度上.
59	So, remember these drug interactions for all the	所以,记住这些药物的相互作用
60	azols covered in this scene.	这个场景覆盖着动物园
61	Voriconazole, especially, is a clinically relevant inhibitor	特别是Voriconazole是一种临床相关的抑制剂
62	of mammalian cytochrome P450.	哺乳动物细胞色素P450。
63	This makes sense in our scene because voriconazole is symbolized	在我们的场景中,这是有道理的 因为Voriconazole是象征
64	by a vortex, or tornado, that same tornado that dropped Dorothy's house on the cytochrome carriage	由漩涡,或龙卷风, 同样的龙卷风 扔多萝西的房子 在细胞色素的马车
65	in the first place.	最初.
66	So, when voriconazole therapy is started, dose reduction of a number of	因此,当高丽烯醇疗法开始后,剂量会减少一些
67	is required, including the cytochrome P450 substrates cyclosporine, tacrolimus, and statins.	需要,包括细胞色素P450底物环鱼、塔克罗利穆斯和静脉管。
68	A unique adverse reaction to voriconazole is visual disturbances.	对磷酸 v的一种独特的不良反应是视觉扰动.
69	Blurry vision or	透视或
70	flashes of light are a common but transient reaction and are represented here by these	光的闪光是一种常见但短暂的反应,由这些反应来代表。
71	blurry flashes of light within the tornado.	龙卷风内部光线模糊
72	Changes in color vision can also occur.	颜色视觉的变化也可能发生.
73	And that's why the tornado is traveling through a completely sepia-toned rural landscape.	这就是为什么龙卷风正在穿越 一个完全塞普亚式的乡村景观。
74	Voriconazole是入侵性麻痹症的首选药物.
75	We'll sketch in the Scarecrow	我们在稻草地上画画
76	guy to remind you of the Scarecrow in our sketchy micro aspergillus sketch.	让你想起稻草人 草草草图里的草草
77	Let his	让他
78	hyphae-like strands remind you of the invasive hyphae of aspergillosis.	类似血栓的线条 让你想起了麻痹的入侵性血栓
79	And he's coughing because	他咳嗽是因为
80	he aspirated dust from the vortex.	他从漩涡里吹出尘埃
81	The hay bursting from his lungs represents systemic	肺部的干草 代表着系统
82	aspergillosis.	麻痹症
83	If he only had a brain, he would probably have a brain aspergilloma as well.	如果他只有大脑,他可能也会有脑瘤。
84	This rural scene does not take place in Kansas this time, but Canada, because Canada is our	这次不发生在堪萨斯州 而是加拿大 因为加拿大是我们的
85	recurring sketchy theme for Candida.	Candida 反复出现的粗略主题。
86	Voriconazole对坎迪达物种有出色的活动
87	and is useful for treating Candida esophagitis in patients with AIDS.	并且对治疗艾滋病患者的坎迪达肝炎有用。
88	Well, as you can see,	嗯,如你所见,
89	we're not in Canada anymore, so let's move on to Fluconazole, the agent most commonly used for	我们不在加拿大了,所以让我们去Fluconazole, 最常用的剂
90	treatment of mucocutaneous candidiasis.	治疗手足肌动脉瘤。
91	Fluconazole will be represented by flying monkeys.	花椰子将由飞猴代表.
92	Again,	再说一遍
93	we have the Canada flag.	我们有加拿大国旗。
94	But now that we're in the land of Azoles, it's in stunning technicolor.	但是现在我们在阿佐尔斯的土地上, 它在惊人的技术色彩。
95	Unusual weather we're having, ain't it?	天气很不寻常,不是吗?
96	Think of these patches of snow as the easily	把这些雪片当做容易
97	scraped-off patches of Candida yeast infection on mucous membranes.	在粘膜上刮掉Candida酵母感染的补丁.
98	Fluconazole对Candida物种的活性极佳,用作一次性剂量
99	to treat vaginal candidiasis, as shown by this flying monkey getting pelted in the nether regions.	治疗阴道性肉瘤, 这只飞行的猴子在网状区域被打
100	Just one dose necessary there.	只需要一剂
101	Fluconazole也用于治疗坎迪达结膜炎
102	and, when given IV, esophagitis in AIDS patients, as represented here by the snow collecting in	并且,当给IV时,艾滋病病人患上食道炎,这代表了这里的积雪。
103	these esophagus-like gutters.	这些类似食道的沟渠。
104	记住,Candida sophagitis需要系统性的抗风治疗.
105	It should never be managed with local agents.	绝不应与当地人员管理。
106	These statues are adorning the top of a crypt.	这些雕像装饰着一个墓穴的顶部.
107	My guess is for the Wicked Witch of the East to remind you that Fluconazole is the agent of	我猜是东方的邪恶女巫 提醒你 Fluconazole是特工
108	for treatment and prophylaxis of cryptococcal meningitis.	治疗和预防密码性脑膜炎。
109	事实上,Fluconazole用于
110	lifelong maintenance therapy and that's why it's represented by these statues,	终身维持疗法 这就是为什么它的代表 这些雕像,
111	permanent fixtures guarding the crypt.	守卫地窖的永久固定装置
112	I really want to emphasize its high levels of CNS penetration,	我真的想强调它高水平的CNS渗透,
113	so the flying monkeys will be wearing the recurring red meningitis mohawk helmets.	所以飞猴会戴着 反复出现的红色脑膜炎莫霍克头盔
114	Fluconazole has some activity against the dimorphic fungi, but mainly against coccidioidal	氟丙烯对异形真菌具有一定的活性,但主要针对共效真菌
115	meningitis.	脑膜炎
116	So let's move on to the drug of choice for treating dimorphic fungi,	因此,让我们继续 选择药物 治疗畸形真菌,
117	(原始内容存档于2018-10-03). Itriconazole.
118	Itriconazole由"好女巫"Reconazole代表.
119	Notice that the Good Witch	注意那个好女巫
120	has butterfly wings.	有蝴蝶的翅膀。
121	This is because in Sketchy Micro, our dimorphic fungi, the ones that change	这是因为在Sketchy Micro, 我们的异形真菌, 那些改变的真菌
122	from yeast to mold when causing systemic infection, are associated with a butterfly,	从酵母到模具 当引起系统感染, 与蝴蝶,
123	which is a dimorphic creature that morphs from a caterpillar.	它是一种异形生物 它从毛虫身上变形
124	The Good Witch is seen here casting	好巫婆在这里表演
125	butterflies to cure Dorothy's systemic mycosis, namely histoplasmosis, blastomycosis, and	蝴蝶可以治好多萝西的全身性肌萎缩, 即组织性骨质硬化, 发光性硬化,
126	coccidioidomycosis.	脑膜炎
127	And don't forget sporothricks, probably something she picked up at the farm.	别忘了斯波罗特里克夫妇 可能是她在农场捡到的东西
128	Remember, Itriconazole for those fungi with two iterations, in other words, dimorphic fungi.	记住,Itriconazole 对于那些真菌 有两个迭代,换句话说, 异形真菌。
129	She's also touching her cone wand to the toes of Dorothy's ruby slippers,	她还在摸她的圆锥棒 摸桃乐西的红宝石拖鞋的脚趾
130	well not really ruby this time, but kind of black, to remind you of Itriconazole's	这次不是红宝石 而是黑色的 为了提醒你伊特里科纳佐尔
131	extensive use in the treatment of onychomycosis.	广泛用于治疗内膜炎。
132	It's also used to treat dermatophytes.	也用于治疗脱马生虫.
133	In fact,	事实上,
134	many azoles have activity against those pesky dermatophytes that cause the tinny infections	许多阿佐尔人对导致小感染的 麻风脱氧核糖核酸有活动
135	such as tinea corporis.	比如公司
136	We'll highlight some of the topical agents here, next to our tin man.	我们会强调一些时事特务 在这里,旁边我们的锡人。
137	When you see the tin man, think tinea.	当你看到锡人的时候,想想锡亚
138	See the characteristic ring-like rust rash?	看见典型的环状锈疹了吗?
139	Topical	专题
140	毒剂包括clutrimazole和 myconazole,常作为奶油服用.
141	So next to our	所以在我们身边
142	tinea tin man, we have our cowardly lion getting a nice close trim, clotrimazole, and hugging onto	铁锡人,我们有胆小的狮子 得到一个漂亮的近端的修饰,clutrimazole, 并拥抱在
143	his pine cone metal he was duped into thinking gives him courage.	他的松果金属 被骗到脑海里 给了他勇气
144	It's my cone, he says, my	这是我的锥子,他说,我的
145	锥az.
146	Remember, myconazole and clotrimazole are topical agents for treating tinea.	记住,我的冷却剂和血红素 是治疗Tinea的热门药剂
147	They are	他们是
148	also topical agents used to treat vaginal candidiasis.	也用于治疗阴道排尿症的热门药剂.
149	What?	你说什么?
150	Okay, that just happened I guess.	好吧,那只是发生了,我想。
151	Again, getting pelted in the groin to represent treatment of vaginal yeast infection, uncalled	再一次,被打进腹股沟 以代表治疗阴道酵母感染,无谓
152	for.	为.
153	这幅草图中包含的最后的azole是ketoconazole.
154	It's available as a cream to treat	它可以做奶油来治疗
155	cutaneous dermatophytosis, such as tinea corporis.	皮革脱氧基,如天麻科。
156	And that's why our tinea tin man is holding this	所以我们的锡人拿着这个
157	key with the pine cone keychain.	键与松锥键链。
158	Ketoconazole 通常不用作系统剂,因为
159	other azoles have a much better safety profile.	其他动物园的安全情况要好得多。
160	Ketoconazole有更大的抑制倾向
161	mammalian cytochrome P450, for example.	例如哺乳动物细胞色素P450.
162	One important adverse effect we will highlight is	我们将强调的一个重要不利影响是:
163	the inhibition of adrenal steroid production, as well as gonadal synthesis of androgens and	抑制肾上腺类固醇的生产,以及淋病合成和
164	estrogens.	雌激素(原变种).
165	Notice this key is fitting into a lock that looks like a kidney with the bolt at the top	注意这把钥匙装进一个锁上 看起来像肾脏的锁上
166	representing the triangle adrenal gland.	代表三角肾上腺.
167	将ketoconanazole 视为将肾上腺锁上.
168	Specifically, it inhibits the first step of steroid synthesis from cholesterol,	具体来说,它抑制了胆固醇合成的第一步,
169	1720 desmolase.	1720 脱摩洛酶.
170	If you look behind the locked vents, it's none other than the Wicked Witch of	如果你看看被锁住的通风口后面 那只不过是个邪恶的女巫
171	the West, of course.	当然是西方
172	She is at her cauldron synthesizing steroid hormones.	她正在肠道合成类固醇激素
173	She's throwing	她在扔东西
174	in a basic cholesterol structure and is hoping to create some androgens and estrogens represented	在基本的胆固醇结构中 并且希望创造一些 蛋白质和雌激素
175	by the male and female symbols.	以男女的象征发誓,
176	Also, the moon face should evoke an image of the moon facies	而且,月亮的面貌应该能唤起月亮的影像
177	当ketoconanazole可以用来 帮助抑制其他疾病时

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P4 · {Sketchy micro} 药理学 | 双语精校 p04 A6.1 - 核苷类逆转录酶抑制剂（NRTIs） (P4)

{Sketchy micro} 药理学 | 双语精校 p04 A6.1 - 核苷类逆转录酶抑制剂（NRTIs） (P4)

发布于 2026-02-22 · 时长 10:00

字幕摘录

时间	英文	中文
0:00	Substantial advances have been made	已取得重大进展
0:02	in antiretroviral therapy since the introduction	抗逆转录病毒疗法
0:04	1987年,第一个毒剂Cytovidine。
0:08	Six classes of antiretrovirals	六类抗逆转录病毒药物
0:10	are currently available for use,	目前可供使用,
0:12	and these classes we'll cover over the next few sketches.	接下来的几段草图中我们再讨论一下
0:15	In order to reach adequate reduction of viral load	为了适当减少病毒负荷
0:18	and reduce the risk of resistance,	并降低抵抗风险,
0:20	antiretrovirals are chosen in combination,	抗逆转录病毒药物是混合选择的,
0:23	tailored to the patient.	适应病人需要

展开字幕全文（250 条）

序号	英文	中文
1	Substantial advances have been made	已取得重大进展
2	in antiretroviral therapy since the introduction	抗逆转录病毒疗法
3	1987年,第一个毒剂Cytovidine。
4	Six classes of antiretrovirals	六类抗逆转录病毒药物
5	are currently available for use,	目前可供使用,
6	and these classes we'll cover over the next few sketches.	接下来的几段草图中我们再讨论一下
7	In order to reach adequate reduction of viral load	为了适当减少病毒负荷
8	and reduce the risk of resistance,	并降低抵抗风险,
9	antiretrovirals are chosen in combination,	抗逆转录病毒药物是混合选择的,
10	tailored to the patient.	适应病人需要
11	And as you'll see soon,	你很快就会看到
12	these drugs each inhibit HIV replication	这些药物都抑制了艾滋病毒的复制
13	at a different part of the cycle.	在循环的不同部分。
14	For our first antiretroviral drug, though,	但是,对于我们的第一种抗逆转录病毒药物,
15	let's enter the Arthurian cycle.	让我们进入亚瑟的循环。
16	This sketch is going to cover nucleoside	这个草图会覆盖核侧
17	and nucleotide reverse transcriptase inhibitors, or NRTIs.	和核苷酸反转录酶抑制剂,或NRTIs.
18	And in this scene, NRTI stands for none other	而在这个场景中, NRTI 代表没有其他
19	than the legendary Knights of the Round Table.	胜过传说中的圆桌骑士
20	Get ready for tales of chivalry, magic, adultery,	准备好讲讲骑士、魔法、通奸
21	lactic acidosis.	乳酸化.
22	NRTIs are the backbone of antiretroviral therapy.	NRTI是抗逆转录病毒疗法的支柱。
23	Treatment regimens usually consist of a pair of NRTIs,	治疗方法通常包括一对NRTI,
24	along with a third agent from another drug class.	还有另一个毒品类的第三个毒剂
25	Here's how NRTIs work.	这是NRTIs的工作原理
26	They act by competitive inhibition	他们通过竞争抑制
27	of HIV reverse transcriptase.	艾滋病毒反向记录器。
28	If you recall our evil HIV human immunodeficiency wizard	如果你记得我们邪恶的HIV人体免疫机能丧失术士
29	从Sketchy Micro, 他有一个咒语书
30	to magically convert RNA back to DNA	以神奇地将 RNA 转换回DNA
31	called reverseotranscriptam.	称为反转图兰刻录。
32	And as you can see, our brave knights have gotten ahold	正如你所见 我们勇敢的骑士们得到了支持
33	of one of the wizard's books,	是巫师的一本经典,
34	which now lies open on the table in front of them.	现在放在他们面前的桌子上
35	Because NRTIs are nucleotides and nucleosides,	因为NRTIs是核苷酸和核苷酸,
36	they incorporate into growing viral DNA strands.	它们融入了不断增长的病毒DNA链.
37	However, they lack a hydroxyl group important	然而,它们缺乏一个重要的羟基组
38	for phosphodiester bond formation,	磷化物债券形成,
39	so this causes premature chain termination.	因此,这导致过早的链断。
40	To show this, enter King Arthur	为了展示这个,请进入亚瑟王
41	at the center of the round table.	在圆桌会议的中心。
42	He's rallying his men, slamming his mace on the table.	他正在召集他的部下 把他的磁盘砸在桌子上
43	Notice his mace looks like a nucleoside,	注意他的乳头看起来像个核糖体
44	a sugar bound to a nitrogenous base,	糖与氮基结合,
45	and one of the spikes is missing.	其中一个钉子不见了
46	Yep, it's the hydroxyl at the three prime end,	是的,这是羟基 在三个质端,
47	which is why DNA elongation is terminated.	这就是为什么DNA延长终止。
48	Let's add in the page numbers three prime and five prime	加上三档和五档
49	to emphasize that it is three to five prime	以强调三至五金
50	phosphodiester bond formation that's inhibited,	磷化物的结合 抑制,
51	and a bookmark that looks like a halted DNA strand.	和一个书签 看起来像一个停止的DNA链。
52	As King Arthur rallies his men,	当亚瑟国王召集手下时
53	readying his attack on the evil retroviral wizard,	准备攻击邪恶的抗反转录病毒术士
54	notice that he presents a scroll,	你应当记取他所降示的经典,
55	a scroll sealed with a P.	卷轴封着一个P
56	This is because his NRTI knights,	这是因为他的NRTI骑士,
57	except for one who you'll meet later,	除了你以后会遇到的人
58	are not nucleotides, but nucleosides,	不是核苷酸,而是核苷酸,
59	and need phosphorylation by cellular enzymes	需要细胞酶的磷化作用
60	in order to be activated.	为了被激活。
61	Well, this scroll cell signal	这个滚动的手机信号
62	is officially activating his men, calling them to action.	正式启动他的部下 要求他们采取行动
63	Take a close look at the round table.	仔细观察圆通.
64	Looks kinda sister-nay, eh?	看起来有点像妹妹,是吗?
65	Yep, it's designed to evoke the image of a mitochondrion.	是的,它是用来唤起 线粒体的形象。
66	This is because all NRTIs are associated	这是因为所有NRTI都是关联的
67	with mitochondrial toxicity.	与线粒体毒性。
68	Oh, you're thirsty.	哦,你渴吗?
69	How about a nice curdling bottle of sour milk?	来瓶酸奶怎么样?
70	The perfect beverage before any crusade,	任何十字军之前的完美饮料,
71	and our recurring sketchy symbol for lactic acidosis,	以及我们反复出现的乳酸化符号
72	an adverse effect associated with all NRTIs.	与所有非关税壁垒相关的一种不利影响。
73	Oh, no, no.	哦,没有,没有。
74	You first, I insist.	你先来,我坚持
75	And you know what?	你知道吗?
76	We all know that the knights of the round table	我们都知道 圆桌骑士
77	eat ham and jam and spam a lot.	吃火腿、果酱和垃圾邮件
78	So they've prepared a hearty feast.	所以他们准备了盛宴
79	The suffix dyne is attached to a few of the NRTIs,	后缀是附着在少数NRTI上,
80	a useful tip for recognizing them on the exam.	一个有用的小费 在考试中认出他们。
81	So in this scene, they will be dining at the round table.	因此,在这个场景中,他们会在圆桌会议上吃饭。
82	见见Lamivudine, 由餐厅代表。
83	Lamivudine is associated with peripheral neuropathy,	拉米武丁与边缘神经病有关
84	and that's why he's wearing our recurring symbol,	这就是为什么他穿着我们反复出现的标志,
85	the old stockings and gloves,	旧的袜子和手套,
86	like the stocking and glove pattern	就像袜子和手套一样
87	of peripheral sensory loss.	外围感官损失
88	If you ask me, it looks like he's a little bored	如果你问我,看起来他有点无聊
89	of this whole affair.	这整个事情。
90	Wait, did somebody say affair?	等等 有人说有外遇吗?
91	Lancelot?	兰斯洛特?
92	No.	没有
93	Wait, really?	等等,真的吗?
94	You can tell me.	你可以告诉我。
95	He has another secret, though.	不过他还有一个秘密
96	He's part of a medieval secret society	他是中世纪秘密社团的成员
97	whose crest is a hippo,	他的峰顶是河马,
98	the noblest creature of the animal kingdom.	动物王国最崇高的生物
99	This is to remind you that lamivudine specifically	这是提醒你,拉米武丁特别
100	is used to treat hep B,	用于治疗乙肝,
101	because the hippo is our sketchy symbol	因为河马是我们的小符号
102	for hepatitis treatment.	治疗肝炎。
103	As a little extra reminder,	作为一点额外的提醒,
104	we've included our recurring peace sign theme	我们已经加入了我们反复出现的和平标志主题
105	to remind you of our sketchy micro hep B hippies sketch.	为了提醒你 我们的微小母鸡 B嬉皮士草图。
106	Because lamivudine inhibits DNA replication,	因为拉米武丁抑制DNA复制,
107	if patients are co-infected with HIV and HBV,	如果患者同时感染艾滋病毒和HBV,
108	discontinuing this agent can result	终止此代理可导致
109	in a flare of hepatitis.	在肝炎的发作中
110	Also part of the secret hep B society	也是秘密乙肝社会的一部分
111	is Sir Tristan, who will represent tenofovir.	特里斯坦爵士将代表杰诺弗维尔
112	Tenofovir从T开始,
113	so remember that this is a nucleotide,	记住,这是核苷酸,
114	not a nucleoside.	不是核侧。
115	Therefore, it does not need to be phosphorylated	因此,它不需要被磷化
116	to become active.	变得活跃。
117	Think of nafa-tenofovir,	想想纳法 -特诺菲尔
118	as in na-phosphorylation needed to become active.	纳磷酸盐需要活化
119	And as you can see,	如你所见,
120	Sir Tristan is not waiting for that phosphorylation scroll.	特里斯坦爵士没有等待 磷酸盐卷轴。
121	He's already active,	他已经很活跃了
122	and sailing off because the Tide is right,	并且因为潮汐是正确的而离开,
123	that's nucleotide,	这是核苷酸,
124	while the others must wait inside.	其他人必须在里面等
125	Think nucleoside,	想想核侧,
126	because they need phosphorylation signal.	因为他们需要磷酸盐信号
127	Remember that he also has activity	记住他也有活动
128	against hepatitis B,	乙型肝炎,
129	just like lamivudine.	就像拉米武丁一样
130	So he's adjacent to the sigil of the hippo's templar.	所以他与河马的天线的西吉尔相邻.
131	But Tristan shares another quality with Lancelot.	但特里斯坦与兰斯洛特分享了另一种品质.
132	He also has a secret lover, of course,	他当然还有个秘密情人
133	Isolde.	伊索尔德
134	And if I remember the story correctly,	如果我记的没错的话
135	the king finds out.	国王发现。
136	Which is probably why Tristan is sneaking out early.	所以崔斯坦才会提前溜出去
137	Isolde is dining at the table,	伊索德在餐桌上吃饭
138	and she'll represent zadovudine.	她会代表扎多武丁
139	Remember that dine suffix,	记得那个晚饭后缀,
140	often associated with these nucleoside analogs.	常与这些核边模拟物相关.
141	Isolde's crest also incorporates a dove	伊索尔德的山峰上还有一只鸽子
142	for zadovudine.	为了扎多武丁
143	Anyway, as Isolde awaits for her lover's return,	总之 伊索尔德在等她的情人回来时
144	notice that she's looking a little pregnant.	她看起来有点怀孕了
145	Yep, she's carrying Tristan's child.	是的 她怀着崔斯坦的孩子
146	A little surprise for him when he returns home.	回家后给他一个小惊喜
147	Zadovudine is one of the first line agents	扎多武丁是最早的线人之一
148	for use in pregnant women.	用于孕妇。
149	It's used during pregnancy,	在怀孕期间使用
150	and postpartum during breastfeeding	产后哺乳期
151	to reduce vertical transmission.	以减少垂直传输。
152	Infants usually receive several weeks	婴儿通常得到数周
153	使用 zadovudine 的剖面访问。
154	Remember that all pregnant women	记住所有孕妇
155	should take antiretroviral therapy,	应接受抗逆转录病毒治疗,
156	regardless of viral load and CD4 count.	不管病毒载荷和CD4计数
157	The most common side effect of zadovudine	扎多武丁最常见的副作用
158	is myelosuppression,	是我的催眠,
159	and that's why Isolde is dining on this dish	所以伊索尔德就在这盘菜上吃饭
160	that evokes an image of bone marrow.	唤起骨髓的影像
161	I have to admit,	我必须承认,
162	those erythroblasts look quite delectable.	那些红外线弹看起来很迷人
163	This can lead to anemia and neutropenia,	这会导致贫血和中微肺炎,
164	which will be embodied	将包含
165	in her white anemic-looking dress.	穿着白色的麻醉衣
166	And to emphasize neutropenia and granulocytopenia,	为了强调中子肺病和小颗粒细胞原虫,
167	she's holding our recurring sand timer	她拿着我们反复出现的沙子计时器
168	of falling granules	掉落颗粒
169	as she awaits her lover's return.	她正等着她情人回来
170	Lipodystrophy is another side effect,	利波迪精神是另一个副作用
171	which involves the redistribution of fat	包括脂肪的再分配
172	from the extremities to the trunk.	从极限到后备箱
173	Patients may describe their legs looking like sticks	病人的腿看起来像棍子
174	while their central adiposity increases.	而他们的中心消化能力增加。
175	This side effect is clearly seen	这个副作用是显而易见的
176	in the majestic steed behind her,	在她身后的马队中,
177	whose gracefully thin legs look like	优雅的瘦腿看起来像
178	they're about to collapse	他们就要崩溃了
179	under its more centralized adiposity.	在更集中的消化能力下
180	This is the trusty steed of Sir Steve,	这是史蒂夫爵士的忠实战马
181	who represents zadovudine.	他们代表扎多武丁
182	He's dining next to Isolde,	他在伊索德旁边吃饭
183	so remember the dyne suffix.	记得戴恩的后缀
184	Lipodystrophy is another common side effect of stavudine.	利波狄斯营养是Stavudine的另一个常见副作用.
185	This NRTI's major toxicity, though,	但NRTI的主要毒性
186	is peripheral neuropathy.	是边缘神经病
187	So remember those stockings and gloves	所以记住那些袜子和手套
188	we highlighted with lamivudine in the center.	我们用拉米武丁在中央突出。
189	Our next knight is Sir Dan,	下一个骑士是丹爵士
190	who will represent didanosine.	他将代表德兰诺辛。
191	Though he doesn't have quite the same dyne suffix,	虽然他的后缀不太一样
192	the word dyne is hidden in there somewhere,	戴恩这个词藏在某个地方
193	so we've made him at the feast as well.	所以我们也让他在宴会上。
194	Sir Dan is the newest member of the group,	丹爵士是这个组织的最新成员
195	so it's his job to think of a cooler knight name	所以他的工作就是想一个更酷的骑士名字
196	than Sir Dan.	胜过丹爵士
197	Sir Danodine?	达诺丁爵士?
198	And to do the cleaning.	并作净业.
199	Didanosine的主要毒性
200	is dose-dependent pancreatitis,	是依赖剂量的胰腺炎,
201	and notice his sponge looks like a pancreas,	注意他的海绵看起来像胰腺
202	squeezing out some digestive secretions.	挤出一些消化分泌物。
203	The risk of peripheral neuropathy	边缘神经病的风险
204	is also increased when didanosine	当二氨基苯丙胺发生时也会增加
205	以Stavudine为单位。
206	So again, keep in mind	再说一遍,记住
207	those luxurious medieval stockings and gloves	那些奢华的中世纪长袜和手套
208	worn by Lancelot.	被兰斯洛特穿。
209	No Knights of the Round Table sketch	没有圆桌骑士素描
210	would be complete without Merlin, of course,	当然,没有梅林是完整的,
211	and we're going to associate him with abacavir,	我们要把他和阿巴卡维尔联系起来
212	因为abracadabra, 需要我说更多吗?
213	Abacavir 可以引起超敏反应
214	这与HLA-B5701 ALELE密切相关。
215	So he's opened his spellbook to a spell titled HLA-B	因此,他打开了他的咒语书 一种名为HLA -B的咒语
216	and he's turned to verse 57, line 01.	他转至第57行第01行
217	This spell results in the presentation of self-peptides	此咒语导致自我佩戴的呈现
218	to the immune system	对免疫系统的影响
219	and a delayed type 4 hypersensitivity	和延迟型号 4 超敏感
220	characterized by a delayed rash,	有缓缓的疹子,
221	which is represented by his spotted rash	以他的斑疹为代表
222	appearing on the arm of our absent-minded sorcerer.	出现在我们心不在焉的巫师的手臂上
223	He looks a little distracted as usual,	他看起来有点分心 像往常一样
224	so he'll most likely have a delayed reaction.	所以他很可能会延迟反应
225	最后但并非最不重要的是, NRTI M. tricitabine,
226	represented here as Arthur's trusty	作为亚瑟的忠实代表
227	和刺激的刀锋 Excalibur。
228	One unique minor side effect	一个独特的次要副作用
229	is hyperpigmentation of palms and soles,	是手掌和脚掌的夸张,
230	represented by King Arthur's bad ass	以亚瑟王的坏屁股为代表
231	leather sword handling gloves.	皮剑处理手套。
232	All right, let's sum up these NRTI	好吧,让我们总结一下这些NRTI
233	Knights of the Round Table, shall we?	圆桌骑士,可以吗?
234	Nucleoside and nucleotide reverse transcriptase inhibitors	核苷酸和核苷酸反转录酶抑制剂
235	comprise the backbone of antiretroviral therapy.	构成抗逆转录病毒疗法的支柱。
236	And like King Arthur's antagonizing mace,	就像亚瑟国王对马斯的敌意一样
237	they work by competitive inhibition	他们通过竞争抑制工作
238	of HIV reverse transcriptase,	艾滋病毒反向记录器,
239	以我们的 reversotranscriptum 拼写本为代表。
240	This halts DNA synthesis,	这停止了DNA的合成,
241	like the chain-terminated DNA bookmark.	就像链断的DNA书签
242	Arthur holds up the P scroll to remind you	亚瑟举起P卷轴提醒你
243	that these nucleoside analogues	这些核边类比
244	need to be phosphorylated to get activated.	需要磷化才能启动。
245	At the table are Lamivudine Lancelot,	在桌子上是拉米武丁兰斯洛特,
246	(原始内容存档于2019-10-29). Zadovudine Isolde, Stavudine Steve,.
247	and Adanasine Dan,	阿达纳辛丹,
248	who all kind of incorporate that dine suffix,	任何一种 包含该 晚餐后缀,
249	hence their dining.	他们的晚餐。
250	Important side effects to record-	重要的副作用 记录 -

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P7 · {Sketchy micro} 药理学 | 双语精校 p07 A6.4 - 马拉韦罗、融合抑制剂、整合酶抑制剂 (P7)

{Sketchy micro} 药理学 | 双语精校 p07 A6.4 - 马拉韦罗、融合抑制剂、整合酶抑制剂 (P7)

发布于 2026-02-22 · 时长 10:00

字幕摘录

时间	英文	中文
0:00	This marks the last chapter in our unit on antiretroviral therapy, and we have three	这是本单位关于抗逆转录病毒疗法的最后一章,我们有三个
0:05	more classes of drugs to cover, entry inhibitors, fusion inhibitors, and integrase inhibitors.	更多种类的药物可以覆盖, 进入抑制剂,聚变抑制剂, 和无心抑制剂。
0:11	So as the battle unfolds, let's highlight these stages of the viral life cycle and illustrate	因此,随着战斗的展开,让我们强调病毒生命周期的这些阶段,并举例说明
0:17	how King Arthur and the rest of the antiretrovirals defend against HIV at every turn.	亚瑟国王和其他抗反转录病毒药物如何在每一个转弯时防御艾滋病毒。
0:24	First, the history of this conflict.	第一,这一冲突的历史。
0:26	HIV infects host immune cells such as macrophages, dendritic cells, and CD4 T cells.	感染HIV的人会接受免疫细胞,如巨噬细胞,腺细胞,以及CD4 T细胞.
0:33	And so, our evil retroviral wizard has seized the neighboring castle.	所以,我们的邪恶的抗反转录病毒术士 已经夺取了邻近的城堡。
0:39	Let the crusade cross theme represent the letter T as in T cell.	让十字路口主题代表T单元格中的字母T。
0:44	Once incorporated into host DNA, it commandeers the host's machinery to transcribe viral	一旦并入宿主DNA,它就要求宿主的机器来转录病毒
0:49	genes.	遗传学

展开字幕全文（128 条）

序号	英文	中文
1	This marks the last chapter in our unit on antiretroviral therapy, and we have three	这是本单位关于抗逆转录病毒疗法的最后一章,我们有三个
2	more classes of drugs to cover, entry inhibitors, fusion inhibitors, and integrase inhibitors.	更多种类的药物可以覆盖, 进入抑制剂,聚变抑制剂, 和无心抑制剂。
3	So as the battle unfolds, let's highlight these stages of the viral life cycle and illustrate	因此,随着战斗的展开,让我们强调病毒生命周期的这些阶段,并举例说明
4	how King Arthur and the rest of the antiretrovirals defend against HIV at every turn.	亚瑟国王和其他抗反转录病毒药物如何在每一个转弯时防御艾滋病毒。
5	First, the history of this conflict.	第一,这一冲突的历史。
6	HIV infects host immune cells such as macrophages, dendritic cells, and CD4 T cells.	感染HIV的人会接受免疫细胞,如巨噬细胞,腺细胞,以及CD4 T细胞.
7	And so, our evil retroviral wizard has seized the neighboring castle.	所以,我们的邪恶的抗反转录病毒术士 已经夺取了邻近的城堡。
8	Let the crusade cross theme represent the letter T as in T cell.	让十字路口主题代表T单元格中的字母T。
9	Once incorporated into host DNA, it commandeers the host's machinery to transcribe viral	一旦并入宿主DNA,它就要求宿主的机器来转录病毒
10	genes.	遗传学
11	The HIV structural genes GAG, PAL, and ENV specifically code for polyprotein precursors	艾滋病毒结构基因GAG、PAL和ENV专门编码多蛋白前体
12	which incorporate into a new virion.	包含在新的病毒中
13	And so, after seizing the T castle, the HIV wizard commandeers the castle's workers to	因此,在夺取了T城堡后,HIV巫师征用了城堡的工人
14	assemble an invading ship, much like the HIV virus assembles a virion to butt off and invade	组装一艘入侵的飞船, 很像HIV病毒 组装一个病毒 来挡住和入侵
15	the next cell.	下一个囚室。
16	As this brand new invading virion ship heads for Camelot, notice it has prisoners on board	当这个全新的入侵维利翁船 前往卡美洛特时 请注意船上有囚犯
17	in the center of the ship, gagged.	在船的中央,堵住。
18	This is because the GAG structural gene has coded for virion core proteins, P7 and P24.	这是因为GAG结构基因已经编码了病毒核蛋白,P7和P24.
19	And that's also why the gagged prisoners are tied around a sundial.	也正因为如此,被困的囚犯们被绑在日落周围.
20	Remember, 24 hours a day, 7 days a week for the core proteins, just like the guard here	记住 每周七天、每天24小时 做核蛋白 就像这里的警卫一样
21	watching these prisoners 24-7.	24 -7监视这些囚犯
22	The ship has sent out a small landing party, their boat labeled Envoy.	舰只派出了一个小型登陆队 他们的船标记为特使
23	This is because the ENV structural gene codes for virion envelope proteins such as GP41	这是因为GP41等Virion信封蛋白的ENV结构基因编码.
24	and GP120.	(原始内容存档于2018-09-31). and GP120.
25	So while it might look like a harmless diplomatic envoy, these outer troops represent the viral	所以,虽然它可能看起来像一个无害的外交特使, 这些外围部队代表病毒
26	envelope proteins crucial for infiltrating the membrane of the next host cell.	信封蛋白对渗透下一个宿主细胞的膜至关重要。
27	Here's where two important antiviral drugs come into play, entry inhibitors and fusion	这里有两种重要的抗病毒药物 进入抑制剂和聚变
28	inhibitors.	抑制剂。
29	The outer wall of Camelot will represent our defending host cell membrane.	卡美洛的外墙将代表我们捍卫的宿主细胞膜.
30	And let's first focus on the main gate and highlight the activity of entry inhibitors.	让我们首先关注正门,突出进入抑制剂的活动.
31	For HIV to infect a cell, its surface glycoprotein, GP120, must bind to the host cell CD4 molecule	艾滋病毒感染细胞时,其表面的甘油蛋白GP120必须附着在宿主细胞CD4分子上
32	和化金受体,CXCR4或CCR5.
33	This GP120 is like HIV's army battering ram, and notice that we've incorporated	这GP120就像HIV的军队打公羊, 并且注意到我们已经融入
34	the number 120 into its design.	120号进入它的设计。
35	Well, these invaders can only gain entry by making contact with CD4 and the chemokine	这些入侵者只能通过接触CD4和化疗 才能进入
36	receptor.	受药者.
37	At Skechie, we depict a CD4 helper T-cell as a little helper squire man with four feathers,	在斯基奇,我们描绘一个CD4帮手T细胞 是一个小帮手侍从 四个羽毛,
38	usually going around and helping out other T-cell knights.	通常四处转转 帮助其他T细胞骑士
39	Remember that T-shaped crusader cross as well.	记得那个T形十字架吗?
40	These are T-cells we're talking about here.	这些是T细胞 我们在这里谈论。
41	除了与CD4接触,HIV Vireon的GP120分子还结合了CCR5受体.
42	on the host cell, which is depicted by the cool CCR banner he carries, as well as the	在主机手机上, 由他携带的 酷酷的CCR 旗帜以及
43	banners at the entrance of the castle.	城堡入口处的旗帜
44	However, before the 120 battering ram makes contact, in comes Mare Avarok, the entry inhibitor,	然而,在120 击打公羊接触之前, 进入抑制器Mare Avarok来了,
45	a brave knight rearing up on his mare.	勇敢的骑士在母马身上长大
46	Mare Avarok binds to the CCR5 receptor, so we've drawn him brandishing the CCR5 banner	Mare Avarok绑在CCR5受体上 所以我们把他画成了CCR5的旗帜
47	as well.	临Τ
48	Since Mare Avarok binds exclusively to CCR5, not the CXCR4 receptor, the strain of HIV	由于Mare Avarok只与CCR5结合,而不是CXCR4受体,艾滋病毒的菌株
49	virus should be determined before starting therapy.	在开始治疗之前,应先确定病毒。
50	If the Vireon had attached successfully, the next step would be membrane fusion.	如果Vireon号成功附着,下一步将是膜聚变.
51	And this is where fusion inhibitors join the fray.	这就是核聚变抑制剂加入火花的地方。
52	While the GP120 battering ram was for HIV entry, the GP41 surface protein is for HIV	虽然GP120击打公羊是用于HIV的,GP41表面蛋白是用于HIV的
53	fusion.	核聚变。
54	So enemy troops are seen here at the castle wall trying to adhere with these GP41 hookshots.	因此在城堡墙上可以看到敌军试图坚持这些GP41钩枪.
55	But before fusion can occur, in comes Enfuvertide.	但是在核聚变发生之前,Enfuvertide来了。
56	记住核聚变听起来像Enfuvertide.
57	And it works by binding these GP41 viral surface proteins, just like our cell membrane defender	它通过捆绑这些GP41病毒表面蛋白, 就像我们的细胞膜维护者一样。
58	who is deflecting the invader's GP41 hookshots.	他正在转移入侵者的GP41钩枪
59	I want to reiterate where these GP120 and GP41 surface proteins came from.	我想重申这些GP120和GP41表面蛋白质的来源。
60	The ENV gene coded for them, and that's why these viral attachment weapons are unloaded	这些病毒附着武器被卸载的原因
61	从ENVOY。
62	Resistance to entry inhibitors and fusion inhibitors can result from mutations of the	对进入抑制剂和聚变抑制剂的耐受性可能来自
63	HIV ENV基因,可以使GP120和GP41改变.
64	Also, a test question may involve the initial processing of these viral surface proteins	另外,一个测试问题可能涉及这些病毒表面蛋白的初始处理.
65	in the host cell's endoplasmic reticulum.	在宿主细胞的内质还原。
66	So remember, the ENV gene encodes for these surface attachment proteins, which are first	记住,ENV基因 编码这些表层附着蛋白质, 这是第一个
67	sent to the host cell ER for processing, because they have to be sent to the cell membrane,	被送到主机细胞ER处理, 因为他们必须送到细胞膜,
68	thus incorporating into surface of a budding Vireon.	从而将萌芽的维里翁融入表面.
69	Notice the reef around the ENV boat kind of looks like the ER, the processing center for	注意ENV船周围的礁石 看起来像ER,处理中心
70	virus surface proteins.	病毒表面蛋白质。
71	If HIV successfully enters a host cell, viral RNA is released from the nucleocapsid and	如果HIV成功进入宿主细胞,病毒RNA会从核糖体释放出来,
72	transcribed into double-stranded DNA by reverse transcriptase.	通过反转录酶转录成双弦DNA.
73	And so our evil retroviral wizard has penetrated the castle wall.	我们邪恶的抗反转录病毒术士 已经深入城堡墙壁了
74	He's using his reverseotranscriptum spellbook, that's reverse transcriptase, to turn his	他正在使用他的反转图文拼写本, 即反转的笔录,
75	single-file RNA army into a double-file DNA army.	单档案RNA军队变成双档案DNA军队.
76	正是在这一步,NRTIs和NNRITIs开始行动.
77	So we've brought back King Arthur and Queen Elphavir from our NRTI and NNRTI sketches,	我们从NRTI和NNRTI的草图中 带回了亚瑟国王和埃尔法维尔王后
78	respectively.	页:1
79	They take action by inhibiting reverse transcriptase.	他们采取行动,抑制反向记录器。
80	Resistance to NRTIs and NNRTIs is due to mutations in the viral PAL gene.	对NRTIs和NNRTIs的抗药性是由于病毒PAL基因的突变所致.
81	The PAL structural gene is responsible for making enzymes such as reverse transcriptase.	PAL结构基因负责制造反转录酶等酶.
82	If altered, it can produce enzymes resistant to binding.	如果改变,可以产生耐捆绑的酶.
83	Enter Paul the blacksmith, a blacksmith of enzymes.	进入铁匠保罗,一个酶的铁匠.
84	He's here representing the PAL gene coding for proteases, the blades, reverse transcriptases,	他在这里代表PAL基因编码 蛋白质,刀片,反转录
85	the spellbooks, and integrases.	咒语书,和整齐。
86	Integrase will be represented by the keys he produces to unlock the nucleus of the host	由他制作的解锁主机核心的密钥来代表Integrase
87	cell, so that the double-stranded DNA army can infiltrate the host DNA.	细胞,这样双弦DNA军团就可以渗入宿主DNA.
88	The double-helix staircase at the center of the castle represents the host DNA.	城堡中心的双螺旋楼梯代表宿主DNA.
89	Don't worry though, it's locked and guarded by the integrase inhibitors that work by binding	不过别担心,它被锁住了 并被用捆绑的抑制剂控制
90	viral integrase.	病毒内脏
91	Roltegravir is an integrase inhibitor that disrupts the ability of double-stranded HIV	Roltegravir是一种整形抑制剂,会干扰双弦HIV的能力.
92	DNA to integrate into host chromosomes.	DNA可以融入宿主染色体.
93	An exam question may also word this as preventing the transcription of HIV mRNA, because if the	考试问题也可以说这是防止艾滋病毒mRNA的复制,因为如果
94	host cell RNA polymerase to produce some viral mRNAs to code for protein production.	宿主细胞RNA聚合酶生成一些病毒mRNA以编码蛋白质生产.
95	Remember where all these enzymes came from, because it's key to understanding resistance.	记住所有这些酶的来源,因为它是理解阻力的关键.
96	Paul the blacksmith represents the PAL gene, which encoded for reverse transcriptases,	铁匠保罗代表PAL基因, 编码为反转录酶,
97	proteases, and integrases.	蛋白质,和内脏。
98	If the PAL gene is mutated, resistance develops to NRTIs, NNRTIs, protease inhibitors, and	如果PAL基因发生变异,则对NRTIs,NNRTIs,蛋白质抑制剂,以及
99	integrase inhibitors.	整形抑制剂。
100	Alas, the double-stranded army has unlocked another passage to the DNA staircase with	唉,双弦军队又打开了一条通往DNA楼梯的通道
101	a mutated key, and it looks like the integrase inhibitor at the door was slacking off a bit.	一个变异的钥匙, 看起来门前的整形抑制剂 有点松动。
102	Notice that he's not paying attention, instead shamelessly devouring a crispy chicken value	发现他没注意 反而无耻地吞噬了鸡肉
103	meal, you know, from the local butcher shop.	吃餐,你知道, 从当地的屠夫店。
104	A bite out of the chicken leg is our recurring symbol for rhabdomyolysis, a rare side effect	从鸡腿上咬出来就是我们反复出现的 rhadomyolyo解症的象征 一种罕见的副作用
105	caused by integrase inhibitors.	由胰腺抑制剂引起
106	Alright kids, we've finally reached the end of this Arthurian cycle.	好了,孩子们,我们终于完成了亚瑟循环
107	Let's sum up this timeless legend into a few important points.	让我们把这个无时无刻的传说归纳为几个重要点.
108	The gagged prisoners on the invading ship represent the gag structural gene that codes	被困在入侵船上的俘虏 代表着编码的堵塞结构基因
109	for core proteins at the core of the ship.	对于核心蛋白质 在飞船的核心。
110	Think of P7 and P24, because those gagged prisoners are guarded 24 hours a day, 7 days	想想P7和P24 因为那些被蒙住的囚犯 一天24小时被看守7天
111	a week.	一个星期
112	Virion信封蛋白的ENV结构基因编码,如GP41和GP120.
113	These will be unloaded by the ENV envoy, which releases the first wave of viral proteins,	这些会由ENV特使卸下, 释放第一波病毒蛋白,
114	crucial for infiltrating the membrane of the host cell.	对渗入主细胞膜至关重要。
115	Because they are envelope proteins, they are processed in the host cell ER before being	由于它们是信封蛋白质,所以在寄主细胞ER进行处理后,才会被
116	sent to the surface of the budding virion.	送入萌芽的病毒表面
117	One of these viral envelope proteins is GP120, the battering ram.	这些病毒信封蛋白质中的一个是GP120,即击打公羊.
118	It must make contact with CD4, our helper T-cell Squire, and CCR5, the banner he carries.	它必须接触CD4,我们的帮手T细胞Squire,和CR5,他携带的横幅.
119	Enter Mare-Avroch, the entry inhibitor, which binds CCR5 to prevent virus entry.	输入Mare-Avroch,即输入抑制剂,将CCR5绑定以防止病毒进入.
120	The other envelope protein is GP41, the hookshot, important for virus fusion.	另一个信封蛋白是GP41,钩射,对病毒聚变很重要.
121	这被聚变抑制剂Enfuvertide所阻断.
122	Once HIV enters the cell, viral RNA is turned into double-stranded DNA by reverse transcriptase,	一旦HIV进入细胞,病毒RNA通过反转录酶转化为双弦DNA,
123	our evil retroviral wizard's spellbook.	我们邪恶的抗反转录病毒魔法师的咒语书。
124	Reverse transcriptase is inhibited by King Arthur and his NRTIs, as well as Queen Elphavir	反转记录器被亚瑟国王和他的 NRTIs 以及埃尔法维尔王后抑制
125	还有她的NRTIs
126	Reverse transcriptase is encoded by the viral Paul gene.	反转录酶由病毒保罗基因编码.
127	Paul, the blacksmith, is also responsible for making proteases and integrases.	铁匠保罗(Paul)也负责制作蛋白质和整粒.
128	Integrases are the keys that can unlock the nucleus of the cell.	integrass是能够解锁细胞核的键.

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