Cov txiaj ntsig txiaj ntsig ntawm Exogenous Ketogenic Supplements Ntawm Cov Txheej Txheem Kev Laus Thiab Hnub Nyoog Txog Cov Kab Mob Neurodegenerative Part 4

Nws tau raug pom tias kev tshem tawm cov hlwb los ntawm senolytics (xws li assenolytic cocktails uas muaj quercetin thiab dasatinib) tuaj yeem ua rau txo qis cov kab mob ntsig txog kev laus, xws li Alzheimer's kab mob thiab Parkinson's kab mob, thiab txhim kho kev noj qab haus huv hauv cov neeg laus [192,203, 19219].

Nrog rau kev ncua ntawm tib neeg lub neej ncua, cov tshuaj tiv thaiv kev laus tau nyiam ntau thiab ntau dua. Ntxiv nrog rau kev ua kom cov leeg nqaij atrophy qeeb thiab txo cov kab mob ntev, cov tshuaj tiv thaiv kev laus kuj tseem tuaj yeem cuam tshuam kev nco.

Ua ntej tshaj plaws, cov tshuaj tiv thaiv kev laus feem ntau muaj cov haujlwm antioxidant. Kev puas tsuaj dawb radical yog ib qho ua rau muaj kev laus, thiab antioxidants tuaj yeem pab txo qhov kev puas tsuaj los ntawm cov dawb radicals. Qee cov kev tshawb fawb tau taw qhia tias cov tshuaj antioxidant xws li vitamin C, vitamin E, thiab lwm yam tuaj yeem tiv thaiv lub hlwb puas hlwb thiab yog li muaj txiaj ntsig zoo rau kev nco.

Qhov thib ob, qee cov tshuaj tiv thaiv kev laus kuj tuaj yeem txhawb kev loj hlob ntawm lub hlwb neurons thiab txhim kho kev kawm thiab kev nco muaj peev xwm. Piv txwv li, qee qhov kev noj haus mus sij hawm ntev, cov tshuaj cerebrovasoactive, amidases, thiab lwm yam tshuaj tau pom tias muaj txiaj ntsig zoo rau kev txhim kho kev nco.

Thaum kawg, cov kev hloov pauv ntawm cov tshuaj tiv thaiv kev laus kuj tuaj yeem pab txhim kho kev nco. Piv txwv li, qee cov tshuaj steroid tuaj yeem ua lub luag haujlwm zoo hauv kev txhim kho kev nco los ntawm kev tswj hwm qhov sib npaug ntawm cov neurotransmitters hauv lub hlwb.

Nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias cov tshuaj tiv thaiv kev laus tsuas tuaj yeem pab txo qis kev nco, tsis hloov lub txiaj ntsim ntawm kev nco. Tsis tas li ntawd, nws yog qhov zoo tshaj plaws los xaiv cov tshuaj tiv thaiv kev laus uas muaj kev nyab xeeb thiab txhim khu kev qha thiab siv lawv raws li cov lus pom zoo hauv cov lus qhia tshuaj kom tsis txhob muaj kev phiv.

Zuag qhia tag nrho, muaj kev sib raug zoo ntawm cov tshuaj tiv thaiv kev laus thiab kev nco. Los ntawm kev siv cov tshuaj tiv thaiv kev laus kom tsim nyog, tswj kev pw tsaug zog txaus, thiab noj qab haus huv, peb tuaj yeem ua kom cov txheej txheem kev laus qeeb thaum tswj kev nco zoo thiab kev txawj ntse. Peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj suav tshuaj suav nrog ntau yam tshwj xeeb, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm Cistanche deserticola los ntawm ntau yam khoom xyaw uas nws muaj, suav nrog tannic acid, polysaccharides, flavonoid glycosides, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv los ntawm ntau txoj hauv kev.

Nyem paub 10 txoj hauv kev los txhim kho kev nco

Lwm txoj hauv kev khomob khomob yog kev tswj hwm ntawm xenomorphics (xws li metformin thiab rapamycin) kom txo qis (tso tseg) cov yam ntxwv ntawm kev laus (piv txwv li, txo qis hauv kev tsim khoom thiab tso tawm ntawm SASP yam) (Daim duab 1) yam tsis tau tshem tawm cov hlwb senescent, uas yuav ncua ob qho tib si kev laus thiab kev loj hlob. Cov kab mob muaj hnub nyoog [194]. Nws tau pom tias mTOR muaj lub luag haujlwm hauv, nrog rau lwm tus, kev tswj lub neej [220].

Tseeb tiag, rapamycin (sirolimus; raws li ib qho mTOR inhibitor) (Daim duab 1cacanse qhov kev pheej hmoo ntawm kev loj hlob ntawm cov kab mob uas muaj hnub nyoog, xws li cov kab mob neurodegenerative, los txhim kho lub hnub nyoog ntsig txog kev nco qab thiab kev kawm ua haujlwm thiab txuas ntxiv mus ntev [74,220].

Rapamycin txo cov sed tsub zuj zuj ntawm A thiab Tau ua rau txo qis neurons, attenuated neuroinflammation, tion, thiab alleviated cognitivedysfunction nyob rau hauv nas qauv ntawm Alzheimer's kab mob [221]. Resveratrol kuj tseem txhawb nqa kev tshem tawm ntawm A peptides [95], zoo li los ntawm inhibition ntawm mTOR thiab ua kom AMPK [,5], thiab tiv thaiv kev puas hlwb [222] hauv cov kab sib txawv thiab cov qauv ntawm Alzheimer'sdisease.

Yog li, cov txiaj ntsig no qhia tias resveratrol thiab rapamycin tawm dag zog neuroprotective, txo cov teebmeem ntawm kev noj qab haus huv, kev ua neej nyob, thiab cov kab mob uas muaj hnub nyoog uas muaj feem cuam tshuam los ntawm kev hloov pauv ntawm autophagy thiab proteostasis (ntawm mTOR inhibition), nrog rau kev mob, ntawm lwm tus [211,212,220] (Daim duab 1) .

Rapamycin thiab metformin (ib qho tshuaj tiv thaiv kab mob ntshav qab zib, uas txo qis IGF qib, insulin tsis kam, ib zaug, thiab qib insulin) txo qis -synuclein thiab txhim kho tus cwj pwm tsis zoo hauv cov qauv ntawm Parkinson'sdisease [74,220,223].

Ntxiv mus, metformin inhibits mitochondrial electron transportchain (ETC complex I: NADH / ubiquinone oxidoreductase; yog li oxidative phosphorylation), yog li, cytoplasmic AMP / ATP thiab ADP / ATP piv tau nce ua rau gdirect activation (phosphorylation) ntawm 22, 2 AMPK. ROS theem [226].Kev ua kom AMPK (piv txwv li, los ntawm metformin) (Daim duab 1) txhim kho mitochondrial biogenesis (viaSIRT1/PGC-1 ) thiab lipid beta-oxidation (ntawm ACCs), inhibits hepatic qabzib ntau lawm thiab alleviates proteostasis (via mTOR inhibition), txhim kho autophagy (ntawm mTOR inhibition thiab ua kom ULK1), evokes hypoglycemia (txo qis cov piam thaj hauv plasma, piv txwv li, los ntawm kev txhim kho cov tshuaj insulin hauv siab ua rau txo qis hauv cov piam thaj hauv siab), txhim kho cov txiaj ntsig zoo (ntawm IIS / mTOR / SIRT1. txoj hauv kev), inhibits NF-κB, txhim kho DNA kho thiab txo cov qib ntawm proinflammatory cytokines (piv txwv li, los ntawm kev ua kom muaj SIRT1) [6,12,225–228] ua rau alleviating teebmeem ntawm kev laus-txheej txheem thiab muaj feem xyuam rau cov kab mob neurodegenerative.

Raws li AMPK-kev ywj pheej cuam tshuam, metformin tuaj yeem inhibitROS ntau lawm (piv txwv li, inhibition ntawm mitochondrial ETC thiab ua kom muaj cov tshuaj tiv thaiv kab mob antioxidant nuclear erythroid 2-txog yam 2/Nrf2) (Daim duab 1), txhim kho autophagy (los ntawm kev cuam tshuam ncaj qha ntawm mTOR. ), txhim kho SIRT1 kev ua haujlwm (tshwj xeeb tshaj yog thaum NAD + qib txo qis), qhib DNA-kev puas tsuaj zoo li cov lus teb (thiab pab txhawb DNArepair zoo li ntawm p53), txo qis NF-κB teeb liab thiab synthesis (tso tawm) ntawm proinflammatorycytokines, inhibit SASP yam ntawm Nrf2 thiab txo qis. theem ntawm insulin thiab IGF{12}} theem ua ke los ntawm insulin / IGF{13}} qhia (los ntawm qhov txo qis mTOR kev ua haujlwm) [66,{15}},225,229–232].

Tag nrho cov txheej txheem no tuaj yeem ua rau kom muaj sia nyob thiab ua rau muaj kev cuam tshuam rau kev laus thiab cov kab mob uas muaj hnub nyoog, xws li Alzheimer's kab mob thiab Parkinson's kab mob [224,225,233]. Tsis tas li ntawd, metformicanto inhibits qia cell laus (ntawm Nrf2), txhim kho stemcell rejuvenation (los ntawm ) [234], cuam tshuam cov kev hloov kho histone (piv txwv li, los ntawm kev ua haujlwm ntawm SIRT1, inhibition ntawm Class II HDACs thiab HAT phosphorylation) los ntawm AMPK-dependentand ywj siab txoj hauv kev [235], nce qib ntawm ntau miRNAs, uas cuam tshuam rau kev tswj kev laus thiab cellular senescence, yuav dhau los ntawm AMPK [236] thiab txo cov telomere luv (piv txwv li, ntawm AMKP / PGC-1 / telomeric rov muaj RNA / TERRApathway; TERRA tau sau los ntawm telomeres thiab muaj lub luag haujlwm tseem ceeb hauv kev tiv thaiv oftelomere kev ncaj ncees) [225,237,238 ] (Daim duab 1).

Qhov tseeb, nws tau pom tias kev ua kom muaj zog ntawm AMPK tuaj yeem txhim kho cov noob qhia (piv txwv li, los ntawm phosphorylation / inactivation ntawm HDACsand ua kom HAT1-evoked acetylation ntawm histones) thiab inhibit gene transcription (piv txwv li, los ntawm kev txhim kho cellular NAD + qib, thiab Raws li qhov tshwm sim, nce SIRT1 deacetylation kev ua haujlwm) [235]. Ntxiv mus, resveratrol kuj tseem tuaj yeem ua rau lub neej ntev thiab tiv thaiv cov kab mob neurodegenerative [239].

Piv txwv li, resveratrol tuaj yeem tsim cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv oxidative (piv txwv li, txo qis ROS, p53, NF-κB thiab proinflammatory cytokines, xws li TNF- thiab IL-1) [5] thiab nce lub neej expectancy. thiab lub neej ntev tshaj plaws hauv cov qauv ntawm Alzheimer's disease [240]. Ntxiv mus, resveratrol txhim kho lub cev muaj zog neuron muaj nuj nqi thiab txuas ntxiv lub neej nyob rau hauv tus qauv nas ntawm amyotrophic lateral sclerosis [241].

Nws tau pom zoo tias resveratrol tuaj yeem ua rau nws cuam tshuam los ntawm kev ua kom AMPK/SIRT1-modulatedpathways [242] (Daim duab 1) uas cov tshuaj no tuaj yeem deacetylate ob peb substrates, xws li asp53, PGC-1 , FOXOs (xws li, FOXO3) thiab SREBP1 ua rau induction ntawm cell voj voog ntes, mitochondrial biogenesis, kho DNA, oxidative kev nyuaj siab teb, autophagy thiab kev tswj ntawm lipid metabolism [6,101,243]. Piv txwv li, SIRT1 tuaj yeem txo ROS thiab NF-κB-evokedeffects (piv txwv li, neuroinflammation) ntawm Nrf2 [5] (Daim duab 1).

Txawm li cas los xij, nws kuj tau hais tias tsis yog SIRT nkaus xwb tab sis kuj PGC 1- tuaj yeem nce qhov kev qhia ntawm Nrf2 [244,245] thiab AMPK txhim kho kev hloov pauv nuclear ntawm Nrf2 [246]. Raws li cov txiaj ntsig no, cov tshuaj sirtuin-activating compounds tau tsim muaj txiaj ntsig zoo dua, xws li SRT2104, uas cov tshuaj tej zaum yuav muaj txiaj ntsig zoo los tiv thaiv kev laus (xws li, nws nce lifespan thiab txo cov txheej txheem inflammatory) [247].

Lwm yam khoom ntuj tsim, xws li curcumin, beriberi, ne, thiab quercetin [6] tuaj yeem tsim cov txiaj ntsig zoo ntawm kev ua neej nyob (los ntawm kev laus qeeb), hnub nyoog thiab cov kab mob uas muaj hnub nyoog, piv txwv li, los ntawm AMPK activation thiab mTOR inhibition (xws li, induce autophagy), ua kom SIRT1 (los txhawb mitochondrial biogenesis) thiab cov tshuaj tiv thaiv kab mob [74,248–250].

Thuthe s, kev tswj hwm ntawm cov tshuaj chemotherapeutic qhia tias cov cuab yeej kho mob thiab cov tshuaj, hloov cov txheej txheem kev laus los ntawm kev ua kom lossis inhibition ntawm qee yam kev taw qhia thiab tseem tuaj yeem tshem tawm txoj kev loj hlob (lossis txhim kho cov tsos mob) ntawm cov kab mob neurodegenerative (xws li Alzheimer's disease, thiab Parkinson's side thiab amyotrophic lateralsclerosis) , txhim kho kev nco thiab kev kawm ua haujlwm, nrog rau kev ua kom lub neej ntev.

3. Alleviating Effects of Ketosis on Lifespan, Aging and Age-RelatedNeurodegenerative Diseases

3.1. Ketosis-Evoked Neuroprotective Effects thiab Downstream Signaling Pathways

Nws tau raug pom tias ketosis thiab kev tswj hwm ntawm HB (raws li lwm cov roj hluav taws xob rau cov piam thaj) tuaj yeem nce mitochondrial ATP ntau lawm thiab ATP tso tawm ua rau muaj zog ntxiv ntawm cellulalevelsel ntawm purine nucleoside adenosine (ntawm cov metabolism ntawm ATP) [251-253].

Adenosine tuaj yeem qhib nws cov receptors ua rau txo qis oxidative kev nyuaj siab (ROS qib) [254] thiab txo cov txheej txheem inflammatory [255]. Tseeb, ib qho kev txhim kho ntawm ROS tuaj yeem qhib (qhib) mPTporese yog li uncoupling lub tshuab thauj khoom hluav taws xob los ntawm ATP ntau lawm, HB-evoked txo qis hauv ROS ntau lawm [94] tuaj yeem txhim kho mitochondrial ua pa thiab ATP ntau lawm [49].

Nws kuj tau pom tias kev kho mob ketosis tuaj yeem ua rau nce qhov inhibitory GABAergic teebmeem [22,256], txo glutamate tso tawm thiab glutamate-induced neuronal excitability [256,25,7], thiab modulate (nce) qib ofdopamine, adrenaline, noradrenaline, ne, thiab serotonin. 258, 259] ib.

Raws li kev tswj hwm ntawm cov noob caj noob ces, HB tuaj yeem cuam tshuam cov haujlwm ntawm HDACfamily classical (Class I thiab Class IIa HDACs) ua rau kev txhim kho acetylation ntawm histone residue s, yog li DNA tuaj yeem nkag mus rau cov ntsiab lus hloov pauv, xws li FOXO3A [53,132,260].

FOXO3A generates enhanced qhia ntawm ntau yam antioxidant noob, txhim khu mitochondrial homeostasis (xws li, los ntawm kev tswj ntawm mitochondrial biogenesis thiab ATP synthesis), thiab txo oxidative kev nyuaj siab [260,261]. Ntxiv mus, qhov txo qis hauv oxidative kev nyuaj siab kuj tuaj yeem tsim los ntawm HB-evoked inhibition ntawm HDACs ntawm attenuation ntawm ER kev nyuaj siab [262].

Nws kuj tseem tau pom, tias qhov kev qhia ntawm lub hlwb-derived neurotrophic yam (BDNF) tuaj yeem nce ntxiv los ntawm HB-evoked inhibition ntawm HDACs [263] los ntawm HB evokesanti-inflammatory teebmeem (ntawm inhibition ntawm NLRP3, NF-, κB thiab proinflammatorycytokine. qib) [264,265], nce mitochondrial respiration thiab ATP qib [266], txhim khu kev ua haujlwm ntawm antioxidant enzymes (xws li SOD), thiab tiv thaiv cov ntaub so ntswg tiv thaiv glutamate-induced excitotoxicity [267,268].

Nws kuj tau pom tias HB tuaj yeem hloov pauv cov noob qhia los ntawm kev nce qib ntawm histone thiab non-histone acetylation byHATs [266,269]. Ntxiv mus, tuaj yeem khi ncaj qha rau RNA-binding protein hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1), uas cov protein tswj, piv txwv li, RNA ua thiab ua haujlwm, nrog rau kev ruaj khov ntawm mRNA [59,270,271].

Cov kev tshawb fawb yav dhau los tau pom tias HB, dhau los ntawm HCAR2, ua kom AMPK ua rau NAD+- tiam, uas ua rau muaj kev ua haujlwm ntawm SIRTs (xws li SIRT1 thiab SIRT3; HB/HCAR2/NAD+/SIRTs pathways) [272] (Daim duab 1) thiab yog li no evoke cov teebmeem neuroprotective [53,83,273,274]. Los ntawm ob qho tib si HB / HCAR2 / AMPK / SIRT1 / NF-κB txoj hauv kev thiab HB / HCAR2 / AMPK / mTORpathway, HB tuaj yeem tsim cov tshuaj tiv thaiv kab mob los ntawm, piv txwv li, inhibition ntawm proinflammatory transcription factor NF-κB thiab kev txhim kho ntawm autophagy, raws li [55,272,275], ua rau txo qis ntawm cov tshuaj proinflammatory (xws li, TNF- , IL-1 ) [50,55,57,276]. HB / HCAR2 / AMPK / SIRT1 / FOXO3A txoj hauv kev tuaj yeem ua rau muaj kev cuam tshuam antioxidant, txo oxidative kev nyuaj siab los ntawm kev nthuav tawm cov noob ntawm cov tshuaj antioxidants (xws li manganese superoxide dismutase / MnSOD: HB / HCAR2 / AMPK / SIRT1 / FOXO3A / MnSODpathway) [164, . Ketone lub cev nce kev qhia tsis yog HCAR2 nkaus xwb [278,279] tab sis kuj SIRTs (xws li SIRT1 thiab SIRT3) thiab PGC1- [164,278,280].

Cov txiaj ntsig no qhia tias ob qho tib si HB/HCAR2/AMPK/SIRT1/PGC1- thiab HB/HCAR2/AMPK/SIRT3/PGC1- txoj hauv kev tuaj yeem ua haujlwm hauv CNS. Tseeb tiag, neuroprotective influences ntawm PGC1- (xws li, tshuaj tiv thaiv kab mob thiab txhawb kev ua haujlwm ntawm mitochondrial) tuaj yeem hloov kho tsis yog SRT1 nkaus xwb tab sis kuj SIRT3 [278,281–283]. Nws kuj tau qhia tias HBevoked cov teebmeem ntawm kev ua haujlwm mitochondrial (xws li, mitochondrial biogenesis) yuav raug tsim los ntawm HB/HDAC/BDNF/PGC1- txoj kev [284].

Tsis tas li ntawd, ketosis tuaj yeem txhim kho qhov kev qhia ntawm PPARs thiab kev ua haujlwm ntawm Nrf2 hauv lub hlwb zoo li HB / HCAR2 / AMPK / Nrf2 lossis HB / HCAR2 / AMPK / SIRTs / PGC 1- / Nrf2 txoj hauv kev [285–287].

Nws tau raug qhia tias ketosis tuaj yeem txhim kho kev qhia ntawm UCPs, yog li txo qis ntawm ROS [23,288,289] thiab tiv thaiv mitochondria thiab mitochondrial zog (xws li, los ntawm kev txo qis ntawm oxidative kev nyuaj siab) los ntawm kev ua kom HB/HCAR2/AMPK/SIRT3/PGC{{5 } } /UCP1 txoj kev [283] thiab/los yog HB/HCAR2/AMPK/SIRT3/PGC{10}} /UCP2pathway [278].

Ntxiv mus, tsis tsuas yog ketosis (HB, tab sis kuj txo qis hauv cov piam thaj hauv cov ntshav tuaj yeem txo cov txheej txheem inflammatory los ntawm kev txo qis NLRP3 inflammasome. IL-1 receptor)/NF-κB txoj hauv kev, qhov nce qib qabzib tuaj yeem txhim kho cov haujlwm ntawm NLRP3 thiab cov txheej txheem inflammatory.

Tsis tas li ntawd, cov qib qabzib txhim kho feem ntau nce insulevelsevel ua rau txo qis hauv ketone lub cev synthesis [290–292]. EKSs tau raug pov thawj los txo qis cov piam thaj [21,26,28,36,293], yog li lawv tuaj yeem ua rau muaj kev ua haujlwm ntawm AMPK/SIRTs qhia txoj hauv kev thiab inhibit mTOR-evoked teebmeem (Daim duab 1).

Yog li, raws li cov kev tshawb fawb yav dhau los, HB/HCAR2/AMPK/SIRT1/NF-κB, HB/HCAR2/AMPK/mTOR, thiab HB/NLRP3/IL-1R/NF-κB pathways (anti-inflammatory teebmeem) , HB/HCAR2/AMPK/SIRT1/FOXO3A txoj kev (txhim kho mitochondrial functions, anti-oxidant influences), HB/HCAR2/AMPK/SIRT1/PGC1- /Nrf2, HCAR2/AMPK/SIRT3/PGC{18} } / Nrf2 thiab HCAR2 / AMPK / Nrf2 txoj hauv kev (txhim kho mitochondrial functions, anti-oxidant thiab anti-inflammatory teebmeem), HB / HDAC / BDNF / PGC 1- txoj kev (txhim kho mitochondrial functions; anti-oxidant thiab anti-inflammatory influences), HB/HCAR2/AMPK/SIRT3/PGC1- /UCP1 thiab/los yog HB/HCAR2/AMPK/SIRT3/PGC1- /UCP2 txoj kev (anti-oxidant thiab anti-inflammatory teebmeem, kev txhim kho mitochondrial functions) thiab modulatory los ntawm HB ntawm neurotransmission (piv txwv li, purinergic, GABAergic, dopaminergic, noradrenergic thiab glutamatergic systems), gene qhia (xws li, txhim kho acetylation ntawm histone residues ntawm HB / HDACs, nce histone thiab non-histone acetylation HATs thiab hydroxybutyrylation ntawm histones) thiab RNA kev ua haujlwm (piv txwv li, ntawm RNA-biding proteins) tuaj yeem ua rau lub sijhawm ketosis (Daim duab 2).

Yog li ntawd, EKSs-evoked ketosis (nce hauv cov ntshav HB qib) tuaj yeem cuam tshuam tag nrho cov lus hais saum toj no (piv txwv li, mTOR-, AMPK- thiab SIRTs-evoked) downstream signaling pathways thiab modulatory teebmeem, uas tuaj yeem ua rau muaj kev cuam tshuam ntawm cov teebmeem (xws li, anti-inflammatory teebmeem) ntawm cov txheej txheem muaj hnub nyoog (cov cim kev laus) (Daim duab 1 thiab 2).

Ntxiv mus, theoretically, EKSs-tsim kev hloov kho ntawm cov kev taw qhia txoj hauv kev thiab cov txiaj ntsig tuaj yeem txhim kho cov tsos mob thiab / lossis ncua kev loj hlob tsis nyob rau ntawm cov cim kev laus (xws li kev hloov pauv hauv txoj hauv kev ua kom muaj txiaj ntsig zoo, ua kom luv ntawm telomere, genomic instability, epigenetic. Kev hloov pauv, mitochondrial tsis ua haujlwm, hloov pauv kev sib txuas lus ntawm tes, cellular senescence, poob ntawm proteostasis thiab qia cell qaug zog), tab sis kuj muaj hnub nyoog-txog cov kab mob neurodegenerative thiab kom ntev lifespan (los ntawm ob qho tib si nce qib HB- thiab txo cov piam thaj hauv qib-evoked hloov pauv hauv kev ua ntawm ntau txoj hauv kev. ) (Daim duab 1 thiab 2).

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