Andres Lozano: Parkinson's, depression and the switch that might turn them off

Translator: Joseph Geni Reviewer: Morton Bast

翻译人员: Alex Ho 校对人员: Julia Xu

One of the things I want to establish right from the start

演讲开始之前我想先说明一件事，

is that not all neurosurgeons wear cowboy boots.

那就是并不是所有的精神科医生都穿马丁靴。

I just wanted you to know that.

就是想让你们知道而已。

So I am indeed a neurosurgeon,

所以我确实是一位神经外科医生，

and I follow a long tradition of neurosurgery,

而我从事的神经外科学历史也十分悠久，

and what I'm going to tell you about today

今天我要和大家说的是

is adjusting the dials in the circuits in the brain,

现在神经外科学让我们能够到达人脑中的任意位置，

being able to go anywhere in the brain

将任意部分激活或休眠，

and turning areas of the brain up or down

并以此来调整在大脑回路中的“调节控制器”，

to help our patients.

最终达到治疗的目的。

So as I said, neurosurgery comes from a long tradition.

我刚刚讲过，神经外科学由来已久，

It's been around for about 7,000 years.

大约在7000年前就已经兴起了。

In Mesoamerica, there used to be neurosurgery,

在中美洲文化发源的地方，神经外科学就有所发展，

and there were these neurosurgeons that used to treat patients.

那时就有治疗病痛的神经外科医生。

And they were trying to -- they knew that the brain was involved

那些医生想要——他们知道

in neurological and psychiatric disease.

神经系统疾病和精神病都与大脑有关。

They didn't know exactly what they were doing.

他们并不完全知道自己在做什么。

Not much has changed, by the way. (Laughter)

其实现在状况也没有多大变化。（笑声）

But they thought that,

但他们觉得，

if you had a neurologic or psychiatric disease,

如果你患有神经系统或者精神方面的疾病，

it must be because you are possessed

那一定是因为

by an evil spirit.

你被邪神控制住了。

So if you are possessed by an evil spirit

所以，如果你因为被邪神所控

causing neurologic or psychiatric problems,

患上了神经系统或者精神方面的疾病，

then the way to treat this is, of course,

那治疗的方法当然就是

to make a hole in your skull and let the evil spirit escape.

在你的脑壳上打一个孔，把邪神放出来。

So this was the thinking back then,

所以，这就是过去的理解方式

and these individuals made these holes.

他们在病人的脑壳上打洞。

Sometimes the patients were a little bit reluctant

有时候病人会有点不情愿接受打洞

to go through this because, you can tell that

因为你可以看得出来

the holes are made partially and then, I think,

洞并没有完全打完。

there was some trepanation, and then they left very quickly

我觉得当时的医生可能在脑壳上钻了几，下病人就飞快逃走了

and it was only a partial hole,

所以洞并没有完全打好，

and we know they survived these procedures.

但我们知道病人还是都活了下来。

But this was common.

但这样的开颅手术在那时是很常见的。

There were some sites where one percent

在一处遗址所发掘出的头骨中

of all the skulls have these holes, and so you can see

大约有百分之一有这样的洞，

that neurologic and psychiatric disease is quite common,

所以神经系统和精神疾病是很普遍的，

and it was also quite common about 7,000 years ago.

在7000年前也是一样的。

Now, in the course of time,

到了目前，随着时间的推移，

we've come to realize that

我们逐渐认识到

different parts of the brain do different things.

大脑的不同区域有不同功能。

So there are areas of the brain that are dedicated

有特定的区域

to controlling your movement or your vision

用来控制你的运动或者视野

or your memory or your appetite, and so on.

或者记忆力或者你的食欲等。

And when things work well, then the nervous system

如果一切正常，神经系统

works well, and everything functions.

也就正常，每个功能也就正常。

But once in a while, things don't go so well,

但偶尔也会出现问题，

and there's trouble in these circuits,

回路会出现故障，

and there are some rogue neurons that are misfiring

一些异常的神经细胞就就会失效，造成问题，

and causing trouble, or sometimes they're underactive

或者有的时候，神经细胞不够活跃，

and they're not quite working as they should.

没有达到预期功能，

Now, the manifestation of this

出现这样的症状

depends on where in the brain these neurons are.

与大脑的神经细胞所在的位置有关。

So when these neurons are in the motor circuit,

当神经细胞在驱动回路时，

you get dysfunction in the movement system,

运动系统就不能正常工作，

and you get things like Parkinson's disease.

会产生类似于帕金森氏综合症一样的疾病，

When the malfunction is in a circuit that regulates your mood,

当负责情绪的回路出现问题时，

you get things like depression,

会产生像抑郁症一样的疾病，

and when it is in a circuit that controls your memory and cognitive function,

当负责记忆和认知功能的回路出现故障时，

then you get things like Alzheimer's disease.

会产生像阿兹海默症一样的疾病。

So what we've been able to do is to pinpoint

因而我们能做的就是定位

where these disturbances are in the brain,

大脑中的异常区域，

and we've been able to intervene within these circuits

并且介入大脑中的这些回路

in the brain to either turn them up or turn them down.

或调整回路中信号的强弱。

So this is very much like choosing the correct station

就像使用收音机的调台旋钮，

on the radio dial.

选择想听的频道。

Once you choose the right station, whether it be jazz or opera,

一旦选择了，无论是爵士或者歌剧，

in our case whether it be movement or mood,

就像选择运动神经或情绪神经，

we can put the dial there,

我们就把调节器的旋钮放在那儿，

and then we can use a second button to adjust the volume,

然后用另一个旋钮来调整音量，

to turn it up or turn it down.

调高或者调低。

So what I'm going to tell you about

所以，我要说的是

is using the circuitry of the brain to implant electrodes

借由植入大脑回路中的电极

and turning areas of the brain up and down

来调整大脑中某些区域的信号强弱

to see if we can help our patients.

来看我们是否能帮助病人。

And this is accomplished using this kind of device,

使用这种装置就能完成，

and this is called deep brain stimulation.

这被称为大脑深部电击术。

So what we're doing is placing these electrodes throughout the brain.

我们将电极置入大脑的各个区域

Again, we are making holes in the skull about the size of a dime,

同样，在脑壳上打个硬币大小的洞，

putting an electrode in, and then this electrode

置入电极

is completely underneath the skin

使其完全在皮肤下

down to a pacemaker in the chest,

就像是胸腔内的心律调节器，

and with a remote control very much like a television remote control,

就像电视机的遥控器一样

we can adjust how much electricity we deliver

我们能够调整电流强度

to these areas of the brain.

以及刺激相应的脑部区域。

We can turn it up or down, on or off.

我们可以调强，调弱，开关。

Now, about a hundred thousand patients in the world

现在，全球约有10万病人

have received deep brain stimulation,

已接受了大脑深部电击术，

and I'm going to show you some examples

接下来我将给大家你们展示几个案列

of using deep brain stimulation to treat disorders of movement,

通过大脑深部电击术来治疗运动失调,

disorders of mood and disorders of cognition.

情绪失调和认知失调。

So this looks something like this when it's in the brain.

它在脑中看起来就像这样。

You see the electrode going through the skull into the brain

你可以看到电极穿过脑壳进入脑部

and resting there, and we can place this really anywhere in the brain.

停留在那里，我们可以把它放到大脑的任何位置。

I tell my friends that no neuron is safe

我告诉我的朋友，没有任何神经细胞，

from a neurosurgeon, because we can really reach

是神经外科医生碰不到的，我们现在可以

just about anywhere in the brain quite safely now.

安全的对大脑任何部位做手术了。

Now the first example I'm going to show you is a patient

我要给大家展示的第一个案列

with Parkinson's disease,

是位帕金森氏综合症的病人。

and this lady has Parkinson's disease,

这位女士患有帕金森氏综合症，

and she has these electrodes in her brain,

她的脑部有这些电极，

and I'm going to show you what she's like

我要给你们展示的是

when the electrodes are turned off and she has her Parkinson's symptoms,

当电源关闭时，她的帕金森病症表现，

and then we're going to turn it on.

然后我们打开电源。

So this looks something like this.

就会变成这样。

The electrodes are turned off now, and you can see that she has tremor.

现在电源关闭了，你们看到，她在颤抖。

(Video) Man: Okay. Woman: I can't. Man: Can you try to touch my finger?

（视频）男：好的。女：我做不到。男：你能试着碰下我的手指吗？

(Video) Man: That's a little better. Woman: That side is better.

（视频）男：有好一点。女：那边比较好。

We're now going to turn it on.

现在要把电源打开。

It's on. Just turned it on.

打开了。

And this works like that, instantly.

只要打开，就立即见效。

And the difference between shaking in this way and not --

抖动和稳定的区别

(Applause)

（掌声）

The difference between shaking in this way and not is related to the misbehavior

抖动和稳定的区别

of 25,000 neurons in her subthalamic nucleus.

和她的丘脑下核的25000个神经细胞有关。

So we now know how to find these troublemakers

我们已知道怎么找出这些问题细胞

and tell them, "Gentlemen, that's enough.

并告诉它们“嘿，玩够了。

We want you to stop doing that."

我们想让你们停止。”

And we do that with electricity.

我们可以用电流。

So we use electricity to dictate how they fire,

所以我们想使用电流来控制神经细胞的反应，

and we try to block their misbehavior using electricity.

并且通过电流阻断异常行为。

So in this case, we are suppressing the activity of abnormal neurons.

此例是抑制不正常细胞的反应。

We started using this technique in other problems,

我们将这种技术用在其他问题上，

and I'm going to tell you about a fascinating problem

下面是我们遇到的一个很棒问题的案例，

that we encountered, a case of dystonia.

称为肌张力障碍。

So dystonia is a disorder affecting children.

肌张力障碍是影响儿童的病变，

It's a genetic disorder, and it involves a twisting motion,

它是遗传疾病，会有扭曲的动作，

and these children get progressively more and more twisting

这些儿童会越来越扭曲

until they can't breathe, until they get sores,

直到不能呼吸，直到觉得病痛，

urinary infections, and then they die.

泌尿系统感染，最终走向死亡。

So back in 1997, I was asked to see this young boy,

回到1997年，我应要求去看望这个小男孩，

perfectly normal. He has this genetic form of dystonia.

他看起来很正常，但他有肌张力障碍的基因。

There are eight children in the family.

一家有8个孩子，

Five of them have dystonia.

5个有肌张力障碍。

So here he is.

这就是他。

This boy is nine years old, perfectly normal until the age six,

这个男孩9岁，6岁前完全正常，

and then he started twisting his body, first the right foot,

然后他身体开始扭曲，先是右腿，

then the left foot, then the right arm, then the left arm,

然后是左腿、右臂、左臂，

then the trunk, and then by the time he arrived,

然后是躯干，等他来的时候，

within the course of one or two years of the disease onset,

距离病发有1～2年的时间，

he could no longer walk, he could no longer stand.

他已经不能行走和站立。

He was crippled, and indeed the natural progression

他的腿跛了，事实上随着病情恶化，

as this gets worse is for them to become progressively twisted,

肢体扭曲的情形会加重，

progressively disabled, and many of these children do not survive.

残障日益加重，许多孩子无法存活。

So he is one of five kids.

他是五个孩子之一。

The only way he could get around was crawling on his belly like this.

他想行动时，只能趴在地上爬行。

He did not respond to any drugs.

药物已不起任何作用。

We did not know what to do with this boy.

我们对他的病症无计可施。

We did not know what operation to do,

我们不知道，

where to go in the brain,

该对他脑部的哪个区域进行什么手术，

but on the basis of our results in Parkinson's disease,

但从帕金森氏综合症的的经验，

we reasoned, why don't we try to suppress

我们推论，何不尝试抑制

the same area in the brain that we suppressed

造成帕金森氏综合症的同一区域，

in Parkinson's disease, and let's see what happens?

看看会发生什么？

So here he was. We operated on him

于是我们对他进行了手术

hoping that he would get better. We did not know.

希望他能好转。我们当时没有把握。

So here he is now, back in Israel where he lives,

这是现在的他，回到了以色列的家，

three months after the procedure, and here he is.

这是他手术过后3个月的样子。

(Applause)

（掌声）

On the basis of this result, this is now a procedure

借由这次经验，这项手术

that's done throughout the world,

已在全世界施行，

and there have been hundreds of children

已有数百名儿童

that have been helped with this kind of surgery.

受惠于这项手术。

This boy is now in university

这个男孩现在已上大学

and leads quite a normal life.

过着正常的生活。

This has been one of the most satisfying cases

这是我从医多年来

that I have ever done in my entire career,

最满意的一个案例。

to restore movement and walking to this kind of child.

使这类病童恢复运动和行走能力。

(Applause)

（掌声）

We realized that perhaps we could use this technology

我们认识到也许这项科技

not only in circuits that control your movement

不仅可以控制运动

but also circuits that control other things,

还能控制于其他方面，

and the next thing that we took on

我们研究的下一个课题

was circuits that control your mood.

是控制情绪的回路。

And we decided to take on depression,

我们决定治疗抑郁症，

and the reason we took on depression is because it's so prevalent,

我们之所以选择它是因为它很普遍，

and as you know, there are many treatments for depression,

而且你们也知道，治疗抑郁症的方法有多种，

with medication and psychotherapy,

有药物治疗和心理治疗，

even electroconvulsive therapy,

甚至有电休克疗法，

but there are millions of people,

但在数百万人中，

and there are still 10 or 20 percent of patients with depression

仍然有百分之十到二十的患者

that do not respond, and it is these patients that we want to help.

无法治愈，就是这些患者需要我们的帮助。

And let's see if we can use this technique

让我们来看看这项科技

to help these patients with depression.

能否改善抑郁症患者的病情。

So the first thing we did was, we compared,

我们做的第一件事情是，比较

what's different in the brain of someone with depression

抑郁症患者的脑部

and someone who is normal,

和正常人脑部的不同之处，

and what we did was PET scans to look at the blood flow of the brain,

我们通过正电子发射层析扫描来查看脑部血流的流向，

and what we noticed is that in patients with depression

我们注意到抑郁症患者

compared to normals,

与正常人相比较，

areas of the brain are shut down,

脑部某些地方停工了，

and those are the areas in blue.

这些地方呈现蓝色。

So here you really have the blues,

所以你就感到抑郁了，

and the areas in blue are areas that are involved

这些蓝色区域和

in motivation, in drive and decision-making,

动机，驱动力和决策有关，

and indeed, if you're severely depressed as these patients were,

如果你的抑郁和这些病人一样严重，

those are impaired. You lack motivation and drive.

你会缺乏动机和驱动力。

The other thing we discovered

我们发现的另一件事是

was an area that was overactive, area 25,

有个区域过于活跃，

seen there in red,

就是呈现红色的25号区域，

and area 25 is the sadness center of the brain.

25号区域是大脑的悲伤中心。

If I make any of you sad, for example, I make you remember

如果我让你悲伤，比如，我让你回想起

the last time you saw your parent before they died

亲人或朋友

or a friend before they died,

去世前的最后一面，

this area of the brain lights up.

脑部的这个区域就会启动。

It is the sadness center of the brain.

这是大脑的悲伤中心。

And so patients with depression have hyperactivity.

抑郁症患者发病时，

The area of the brain for sadness is on red hot.

大脑的悲伤中心运作到最高峰。

The thermostat is set at 100 degrees,

好像调节器的温度被设定在100度，

and the other areas of the brain, involved in drive and motivation, are shut down.

动机和驱动力等区域完全停工。

So we wondered, can we place electrodes in this area of sadness

我们想，如果把电极置于悲伤中心，

and see if we can turn down the thermostat,

降低温度，

can we turn down the activity,

以降低这个区域的活跃性，

and what will be the consequence of that?

结果又会是怎样的呢？

So we went ahead and implanted electrodes in patients with depression.

我们将电极植入抑郁症患者的脑部。

This is work done with my colleague Helen Mayberg from Emory.

我和在Emory大学的同事Helen Mayberg一起合作。

And we placed electrodes in area 25,

我们将电极置入25号区域，

and in the top scan you see before the operation,

最上面那张是手术前扫描

area 25, the sadness area is red hot,

的25号区域，即悲伤中心，呈现红色，

and the frontal lobes are shut down in blue,

脑前额叶部完全停工，呈现蓝色，

and then, after three months of continuous stimulation,

每天24小时连续刺激，连续3个月，

24 hours a day, or six months of continuous stimulation,

6个月后

we have a complete reversal of this.

情况完全逆转。

We're able to drive down area 25,

25号区域的活跃程度，

down to a more normal level,

已降低到正常水准，

and we're able to turn back online

脑前额叶，

the frontal lobes of the brain,

则重新上线，

and indeed we're seeing very striking results

我们从这些重度抑郁症患者的身上

in these patients with severe depression.

看到了惊人的结果。

So now we are in clinical trials, and are in Phase III clinical trials,

我们正进行3期临床试验，

and this may become a new procedure,

这有可能成为新的治疗方式，

if it's safe and we find that it's effective,

只要证实是否能安全，有效的

to treat patients with severe depression.

治疗重度抑郁症患者。

I've shown you that we can use deep brain stimulation

刚才向大家展示的是使用大脑深部刺激电击术

to treat the motor system

治疗动力系统的相关疾病

in cases of Parkinson's disease and dystonia.

比如帕金森氏综合症和肌张力障碍。

I've shown you that we can use it to treat a mood circuit

大家看到了它能够治疗情绪回路的疾病，

in cases of depression.

比如抑郁症。

Can we use deep brain stimulation to make you smarter?

那能否用大脑深部电击术让你变得更聪明呢？

(Laughter)

（笑声）

Anybody interested in that?

有人有兴趣吗？

(Applause)

（掌声）

Of course we can, right?

当然可以对吧？

So what we've decided to do is

我们决定

we're going to try to turbocharge

要试着

the memory circuits in the brain.

给大脑中的记忆回路充电。

We're going to place electrodes within the circuits

将电极置入

that regulate your memory and cognitive function

控制记忆和认知的回路，

to see if we can turn up their activity.

来看能够增强它们的活跃性。

Now we're not going to do this in normal people.

我们不会拿正常人做实验。

We're going to do this in people that have cognitive deficits,

而是用在有认知缺陷的患者身上，

and we've chosen to treat patients with Alzheimer's disease

我们尝试治疗老年痴呆症

who have cognitive and memory deficits.

他们的认知和记忆有缺陷。

As you know, this is the main symptom

如各位所知，这是

of early onset Alzheimer's disease.

早期老年痴呆症的主要症状。

So we've placed electrodes within this circuit

我们放置电极的位置

in an area of the brain called the fornix,

称为穹窿，

which is the highway in and out of this memory circuit,

它是进出记忆回路的高速公路，

with the idea to see if we can turn on this memory circuit,

看看是否能够开启记忆回路，

and whether that can, in turn, help these patients

进而是否可以帮助

with Alzheimer's disease.

老年痴呆症的患者。

Now it turns out that in Alzheimer's disease,

结果发现老年痴呆症患者的脑部，

there's a huge deficit in glucose utilization in the brain.

对葡萄糖的利用有严重的缺陷。

The brain is a bit of a hog when it comes to using glucose.

脑部是大量消耗葡萄糖的地方。

It uses 20 percent of all your --

尽管只占体重的百分之二

even though it only weighs two percent --

却消耗人体总量的百分之二十

it uses 10 times more glucose than it should based on its weight.

脑部葡萄糖的消耗量是其本身质量的10倍

Twenty percent of all the glucose in your body is used by the brain,

人体总量百分之二十的葡萄糖用在脑部，

and as you go from being normal

从正常的脑部

to having mild cognitive impairment,

到轻微的认知损伤，

which is a precursor for Alzheimer's, all the way to Alzheimer's disease,

再发展成为老年痴呆症，

then there are areas of the brain that stop using glucose.

脑部有些区域停止利用葡萄糖。

They shut down. They turn off.

停工了。关机了。

And indeed, what we see is that these areas in red

事实上，我们可以看到

around the outside ribbon of the brain

脑中央带状区的外圈

are progressively getting more and more blue

由红色逐渐变蓝

until they shut down completely.

直到完全停工。

This is analogous to having a power failure

好像是大脑停电了

in an area of the brain, a regional power failure.

形成区域性供电异常。

So the lights are out in parts of the brain

老年痴呆症的患者的部分大脑，

in patients with Alzheimer's disease,

好像因停工而陷入异常，

and the question is, are the lights out forever,

问题是，电力中断是永久性的呢，

or can we turn the lights back on?

还是我们有办法恢复？

Can we get those areas of the brain to use glucose once again?

可以让这些区域再利用葡萄糖吗？

So this is what we did. We implanted electrodes in the fornix

我们把电极植入穹窿

of patients with Alzheimer's disease, we turned it on,

以激活老年痴呆症患者的这一区域，

and we looked at what happens to glucose use in the brain.

并观察大脑利用葡萄糖的情况。

And indeed, at the top, you'll see before the surgery,

上面那张是手术前，

the areas in blue are the areas that use less glucose than normal,

蓝色区域葡萄糖的用量比正常的少，

predominantly the parietal and temporal lobes.

主要是在顶骨和大脑的颞叶。

These areas of the brain are shut down.

大脑的这些区域停工了。

The lights are out in these areas of the brain.

这些区域停电了。

We then put in the DBS electrodes and we wait for a month

我们放入大脑深部电击电极并等待一个月

or a year, and the areas in red

或一年，红色区域

represent the areas where we increase glucose utilization.

代表葡萄糖的利用率在增加。

And indeed, we are able to get these areas of the brain

所以，我们确实可以让大脑中

that were not using glucose to use glucose once again.

本该不使用葡萄糖的区域重新恢复使用。

So the message here is that, in Alzheimer's disease,

结果显示，老年痴呆症的患者，

the lights are out, but there is someone home,

虽然停电了，但仍有人在家

and we're able to turn the power back on

我们可以

to these areas of the brain, and as we do so,

让这些区域的电力恢复，

we expect that their functions will return.

我们预期它们的功能也会恢复。

So this is now in clinical trials.

这正在临床试验阶段，

We are going to operate on 50 patients

我们对50位

with early Alzheimer's disease

早期老年痴呆症患者做了手术，

to see whether this is safe and effective,

确认是否安全有效

whether we can improve their neurologic function.

是否能改善他们神经的功能。

(Applause)

（掌声）

So the message I want to leave you with today is that,

我要传给各位的讯息是，

indeed, there are several circuits in the brain

脑部不同回路的异常

that are malfunctioning across various disease states,

和不同的疾病有关，

whether we're talking about Parkinson's disease,

我们讨论了帕金森氏综合症，

depression, schizophrenia, Alzheimer's.

抑郁症，精神分裂症，老年痴呆症。

We are now learning to understand what are the circuits,

我们现在在学习了解这些回路，

what are the areas of the brain that are responsible for

还有对应的脑部区域

the clinical signs and the symptoms of those diseases.

以及对应的临床症状。

We can now reach those circuits.

我们现在可以碰触这些回路。

We can introduce electrodes within those circuits.

并在其中中放入电极。

We can graduate the activity of those circuits.

我们可以控制它们的活动，

We can turn them down if they are overactive,

如果它们太活跃

if they're causing trouble, trouble that is felt throughout the brain,

引发问题，影响大脑运转，我们可以将它们调低，

or we can turn them up if they are underperforming,

如果它们不太活跃，则可调高，

and in so doing, we think that we may be able to help

我们认为由此可以帮助

the overall function of the brain.

整个大脑的功能。

The implications of this, of course, is that we may be able

这意味着我们能够

to modify the symptoms of the disease,

缓和疾病的症状，

but I haven't told you but there's also some evidence

但我还没有告诉大家，有迹象表明

that we might be able to help the repair of damaged areas of the brain using electricity,

电流可以帮助修复大脑受损区域，

and this is something for the future, to see if, indeed,

这些都是未来的愿景，

we not only change the activity but also

我们不仅可以调整脑部活动，

some of the reparative functions of the brain

还能实现大脑受损功能

can be harvested.

得到修复。

So I envision that we're going to see a great expansion

我预期这项技术在未来

of indications of this technique.

将会得到广泛的应用。

We're going to see electrodes being placed for many disorders of the brain.

我们将看到电极被用于修复多种脑部问题，

One of the most exciting things about this is that, indeed,

而其中最令人振奋的是，

it involves multidisciplinary work.

它还涉及跨领域的合作。

It involves the work of engineers, of imaging scientists,

包括工程师，影像科学家，

of basic scientists, of neurologists,

基础科家学，神经病学家，

psychiatrists, neurosurgeons, and certainly at the interface

精神医师，神经外科医师通力合作，

of these multiple disciplines that there's the excitement.

这样的跨领域合作是最令人兴奋的。

And I think that we will see that

我想将来有一天

we will be able to chase more of these evil spirits

随着时间的推移

out from the brain as time goes on,

越来越多的邪恶将被赶出脑袋，

and the consequence of that, of course, will be

结果当然是，

that we will be able to help many more patients.

更多的病人能够得到救治。

Thank you very much.

非常感谢。