GLP-1 10 mg

▎ GLP-1 Structure

▎ GLP-1 Kev Tshawb Fawb

Kev tshawb fawb keeb kwm ntawm GLP-1 yog dab tsi?

GLP-1 yog tib neeg glucagon-zoo li peptide-1 (GLP-1) analog, cais raws li GLP-1 receptor agonist. GLP-1 yog cov tshuaj hormones tsim los ntawm cov hnyuv tom qab noj mov. Nws ua lub luag haujlwm hauv kev txhawb nqa insulin secretion thiab inhibiting glucagon secretion, yog li tswj cov ntshav qabzib. Txoj kev loj hlob ntawm GLP-1 pib los ntawm kev tshawb fawb tob txog kev ua haujlwm ntawm lub cev ntawm GLP-1. Txawm li cas los xij, GLP-1 muaj ib nrab ntawm lub neej luv luv hauv lub cev, kav ntev li ntawm 1 mus rau 2 feeb, uas yog vim nws qhov cuam tshuam rau degradation los ntawm dipeptidyl peptidase-4 (DPP-4) enzymes hauv lub cev. Txhawm rau kov yeej qhov kev txwv no, cov kws tshawb fawb tau hloov kho cov qauv ntawm GLP-1 los ntawm kev hloov pauv amino acid tshwj xeeb thiab ntxiv cov pab pawg tiv thaiv, txhim kho nws qhov tsis kam rau DPP-4 enzymes thiab yog li ncua nws lub sijhawm ua haujlwm ^[1] . Hauv cov qauv ntawm GLP-1, alanine ntawm 8 txoj haujlwm yog hloov los ntawm α-aminoisobutyric acid (Aib). Qhov kev hloov no tsis tsuas yog txhim kho kev ruaj ntseg ntawm cov tshuaj tab sis kuj ntxiv dag zog rau nws txoj kev khi rau GLP-1 receptor (Ma H, 2020). Tsis tas li ntawd, ib qho tshwj xeeb fatty acid sab saw txuas nrog nws C-terminus, txuas ntawm γ-glutamine rau lysine residues, txuas ntxiv mus rau ib nrab-lub neej, ua kom muaj kev txhaj tshuaj ib zaug ib lim tiam lossis kev tswj hwm qhov ncauj ib hnub ^[1] . Thaum pib raws li kev tshawb fawb thiab kev hloov kho ntawm ntuj GLP-1, GLP-1 lub hom phiaj los muab kev kho mob zoo dua rau cov neeg mob ntshav qab zib hom 2 ^{[1, 2]} . Tom qab kev txhim kho cov txheej txheem, nws khaws cov kev ua haujlwm ntawm lub cev ntawm GLP-1 thaum txhim kho nws cov tshuaj pharmacokinetic, dhau los ua qhov tseem ceeb ntawm kev ua haujlwm ntev GLP-1 receptor agonist. Kev tshawb fawb thiab kev loj hlob ntawm GLP-1 yog qhov tseem ceeb heev rau kev kho mob ntshav qab zib hom 2, muab cov kev xaiv tshiab rau cov neeg mob. Los ntawm kev txhim kho cov qauv, nws kov yeej qhov teeb meem ntawm lub neej luv luv ntawm GLP-1, txhim kho cov tshuaj ruaj khov thiab lub sijhawm ua haujlwm.

GLP-1 mechanism ntawm kev txiav txim yog dab tsi?

GLP-1 yog qhov ua haujlwm ntev glucagon-zoo li peptide-1 (GLP-1) receptor agonist, thiab nws cov txheej txheem ntawm kev ua haujlwm yog raws li hauv qab no:

Kev tswj hwm ntshav qabzib: Raws li qhov tshiab glucagon-zoo li peptide-1 receptor agonist (GLP-1RA), GLP-1 feem ntau txo cov neeg mob 'kev xav tau zaub mov thiab txo lawv txoj kev nyiam rau cov zaub mov muaj roj ntau los ntawm kev txo qis qab los noj mov. Nws tswj cov chaw pub mis hauv hypothalamus, txo cov khoom noj kom tsawg, ua kom satiety, inhibiting gastric emptying, thiab txo cov plab hnyuv motility, yog li ua tiav lub hom phiaj ntawm kev poob phaus. Kev poob phaus pab txhim kho insulin tsis kam thiab tswj cov ntshav qabzib ntxiv ^[3] (Kim HS, 2021). GLP-1 induces poob ceeb thawj nyob rau hauv nas los ntawm kev faib neural pathways. Cov kev tshawb fawb tau pom tias GLP-1 ua ncaj qha rau thaj chaw xws li lub paj hlwb, septal nucleus, thiab hypothalamus. Txawm hais tias nws tsis hla cov ntshav-hlwb teeb meem, nws cuam tshuam nrog lub hlwb los ntawm cov kab mob hauv lub cev thiab cov cheeb tsam tshwj xeeb ze ntawm lub ventricles. Nws induces central c-Fos activation nyob rau hauv 10 lub paj hlwb cheeb tsam, nrog rau cov hindbrain cheeb tsam ncaj qha tsom los ntawm GLP-1 thiab theem nrab cheeb tsam yam tsis muaj kev cuam tshuam ncaj qha GLP-1R, xws li lub lateral parabrachial nucleus. Kev tshuaj xyuas tsis siv neeg qhia tau hais tias qhov ua kom muaj feem cuam tshuam nrog kev txiav tawm ntawm cov zaub mov tswj hwm los ntawm cov neurons nyob rau sab nraud parabrachial nucleus, yog li tswj cov ntshav qabzib qib ^[4].

GLP-1 receptors nyob rau hauv lub plab zom mov. Los ntawm txoj kev afferent ntawm cov hlab ntsha vagus, nws ua rau thaj chaw hauv lub hlwb xws li cov nucleus ntawm cov leeg ib leeg thiab cov dorsal motor nucleus ntawm cov hlab ntsha vagus kom tswj cov plab hnyuv motility. Nws tuaj yeem cuam tshuam qhov contraction ntawm lub plab antrum, txhim kho qhov nro ntawm pyloric sphincter, ncua lub sijhawm nyob ntawm cov zaub mov hauv plab, thiab ncua nws nkag mus rau hauv duodenum, tiv thaiv kev nce sai hauv cov ntshav qabzib thiab ua rau cov ntshav qabzib hloov ntau ruaj khov ^[5] (Katsurada K, 2016). Tsis tas li ntawd, GLP-1 ua rau GLP-1 receptors nyob rau hauv lub hauv paus paj hlwb, feem ntau nyob rau hauv cov cheeb tsam xws li arcuate nucleus thiab paraventricular nucleus ntawm lub hypothalamus. Nws inhibits kev tso tawm ntawm qab los noj mov-stimulating yam xws li neuropeptide Y (NPY) thiab agouti-related protein (AgRP), thiab nyob rau tib lub sij hawm activates pro-opiomelanocortin (POMC) neurons, txhawb lub secretion ntawm α-melanocyte-stimulating hormone (α-MSH) ^[5] . Cov teebmeem no ua rau muaj kev xav ntawm satiety, txo kev tshaib kev nqhis, thiab txo cov zaub mov kom tsawg, ua rau muaj kev cuam tshuam zoo rau kev tswj ntshav qabzib.

Kev tiv thaiv kab mob plawv: GLP-1 tuaj yeem txhawb nqa vascular endothelial hlwb kom tso tawm vasodilatory yam xws li nitric oxide (NO), txhim kho vascular dilation muaj peev xwm thiab txhim kho cov ntshav ntws perfusion. Nyob rau tib lub sijhawm, nws inhibits inflammatory teb thiab oxidative kev nyuaj siab, txo kev puas tsuaj rau vascular endothelial hlwb, thiab txo cov kev pheej hmoo ntawm atherosclerosis. Ntxiv mus, los ntawm kev txo qis qab los noj mov, GLP-1 pab kom poob phaus, txhim kho cov kab mob ntshav qab zib mellitus, txo cov qib triglycerides thiab qis lipoprotein cholesterol (LDL-C), thiab nce qib ntawm high-density lipoprotein cholesterol (HDL-C). Nws kuj tseem tuaj yeem muaj txiaj ntsig zoo rau ntshav siab los ntawm kev tswj hwm lub raum hemodynamics thiab cov haujlwm neuroendocrine, txo qhov kev pheej hmoo ntawm kub siab thiab kab mob plawv ^[6].

GLP-1 thiab kev tswj hwm kev hloov pauv ntawm WAT rau BAT hloov pauv thiab ua kom BAT.

Source: PubMed ^[12]

Cov kev sim thiab kev tshawb fawb tseem ceeb yog dab tsi?

Kev tsim thiab kev ua kom zoo ntawm cov qauv tshuaj: Thaum tsim GLP-1, ib txoj hauv kev ntawm kev thim rov qab khi rau albumin tau txais yuav los txuas ntxiv cov tshuaj lub sijhawm ua haujlwm. Los ntawm kev txiav txim siab kev sib xyaw ua ke ntawm fatty acids thiab linkers, thaum tswj kev ua tau zoo ntawm GLP-1 receptor (GLP-1R), lub peev xwm khi rau albumin tau nce siab ^[7].

Kev Siv Tshuaj: GLP-1 yog glucagon-zoo li peptide-1 receptor agonist (GLP-1 RA) nrog kev tshem tawm ntev ib nrab-lub neej, tso cai rau kev txhaj tshuaj subcutaneous ib zaug. Hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus (T2DM), qhov hnyav poob ntawm kev txhaj tshuaj subcutaneous ib zaug hauv ib lub lis piam ntawm GLP-1 yog qhov zoo dua li ntawm lwm lub lim tiam GLP-1RAs. Hauv theem II tshuaj-kev tshawb nrhiav rau cov neeg mob rog rog yam tsis muaj T2DM, ib zaug ib hnub subcutaneous txhaj tshuaj ntawm GLP-1 tau pom tias muaj txiaj ntsig zoo dua li cov placebo thiab ib hnub ib zaug 3.0 mg liraglutide. Cov qib kev poob phaus los ntawm GLP-1 hauv txoj kev tshawb no tau tshaj cov qauv rau cov tshuaj poob phaus uas tau teev tseg los ntawm European Medicines Agency (EMA) thiab US Food and Drug Administration (FDA), thiab nws muaj kev nyab xeeb, qhia tias kev txhaj tshuaj subcutaneous ib hnub ntawm GLP-1 muaj peev xwm dhau los ua tshuaj yuag yav tom ntej ^[8].

Kev kho cov kab mob plawv los ntawm Kev Txhim Kho Kev Ua Haujlwm Zoo: Cov txiaj ntsig ntawm STEP-HFpEF kev sim tau pom tias cov tshuaj tiv thaiv kab mob ntshav qab zib zoo li glucagon-zoo li peptide 1 agonist GLP-1 tau txhim kho cov tsos mob cuam tshuam nrog lub plawv tsis ua haujlwm nrog kev khaws cia ejection feem (HFpEF) thiab txo cov qib ntawm cov tshuaj tiv thaiv-N-P-F. (NT-proBNP). Kev tshawb fawb soj ntsuam tau pom tias kev kho mob hnyav nrog GLP-1 tuaj yeem ua rau muaj kev ntxhov siab ntawm tib neeg atrial trabeculae los ntawm ntau dua peb zaug hauv kev siv tshuaj, yam tsis muaj kev xav ntau ntxiv rau arrhythmia. Cov txiaj ntsig no tuaj yeem yog vim qhov nce ntxiv ntawm Ca2 + los ntawm sarcoplasmic reticulum. Kev kho mob nrog koob tshuaj GLP-1 hauv cov neeg mob uas muaj lub plawv tsis ua haujlwm tuaj yeem txhim kho atrial muaj nuj nqi, yog li txo cov tsos mob ^[9].

GLP-1 tab tom tshawb nrhiav rau kev kho mob tsis muaj dej cawv steatohepatitis (NASH): Kev tsim qauv tsim nyog ntawm GLP-1 tau ua haujlwm zoo rau kev txhim kho cov ntshav qabzib, lub cev hnyav, ntshav siab, ntshav lipids, β-cell ua haujlwm, thiab cov hlab plawv hauv cov neeg mob ntshav qab zib hom 2. Tsis tas li ntawd, kev tsim kho qhov ncauj ntawm GLP-1 tuaj yeem muab qhov txiaj ntsig ntxiv rau cov neeg mob kev ua raws li kev kho mob ^[7].

Dab tsi yog qhov txawv ntawm qhov poob phaus los ntawm GLP-1 ntawm cov neeg sib txawv?

Cov neeg laus uas muaj cov kab mob plawv ua ntej, rog dhau lossis rog tab sis tsis muaj ntshav qab zib: Hauv SELECT cov txiaj ntsig ntawm cov hlab plawv, GLP-1 txo cov xwm txheej loj ntawm cov hlab plawv los ntawm 20% hauv 17,604 cov neeg laus uas muaj cov kab mob plawv ua ntej, rog dhau lossis rog, thiab tsis muaj ntshav qab zib ^[10 , 20] (R). Hauv qhov kev ntsuam xyuas ua ntej no, cov kws tshawb fawb tau tshuaj xyuas qhov cuam tshuam ntawm GLP-1 ntawm lub cev qhov hnyav, qhov tshwm sim anthropometric, kev nyab xeeb, thiab kev ua siab ntev raws li qhov ntsuas lub cev qhov hnyav (BMI). Cov neeg mob tau txais GLP-1 tau ntsib kev poob qis hauv lub cev tsis tu ncua hauv 65 lub lis piam, kav ntev txog 4 xyoos. Ntawm 208 lub lis piam, piv nrog cov placebo pab pawg, GLP-1 ua rau qhov nruab nrab qhov hnyav ntawm lub cev (-10.2%), lub duav ncig (-7.7 cm), thiab lub duav-rau-qhov siab (-6.9%), thaum cov placebo pab pawg tau txo qis ntawm (-1.5%, -1.3 cm, thiab -1.0%) raws li qhov sib piv, thiab txhua qhov chaw sib piv tseem ceeb. Clinically lub ntsiab lus poob phaus tshwm sim nyob rau hauv cov txiv neej thiab cov poj niam, tag nrho cov haiv neeg, hom ntawm lub cev, thiab cheeb tsam. GLP-1 tau cuam tshuam nrog tsawg dua cov xwm txheej tsis zoo. Rau txhua pawg BMI (<30, 30 txog <35, 35 txog <40, thiab ≥40 kg / m²), qhov tshwm sim ntawm cov xwm txheej tsis zoo ntawm GLP-1 (tus naj npawb ntawm cov xwm txheej pom ib 100 tus neeg-xyoo) qis dua (43.23, 43.54, 51.070, thiab, rau GLP-4, thiab 43.23. 49.66, 52.73, thiab 60.85 rau cov placebo). GLP-1 tau cuam tshuam nrog kev nce ntxiv ntawm kev txiav tawm ntawm cov khoom sim. Raws li BMI qeb txo qis, qhov kev txiav tawm tau nce ntxiv. Hauv kev sim SELECT, ntawm 208 lub lis piam, GLP-1 tau tsim cov kev kho mob hnyav thiab kev txhim kho hauv cov txiaj ntsig anthropometric piv nrog cov placebo, thiab qhov hnyav poob mus rau 4 xyoo.

Cov tib neeg uas rog dhau lossis rog tab sis tsis muaj ntshav qab zib: Kev tshuaj xyuas zoo tau soj ntsuam qhov ua tau zoo thiab kev nyab xeeb ntawm GLP-1 hauv cov tib neeg uas rog lossis rog tab sis tsis muaj ntshav qab zib ^[11] . Qhov kev tshuaj xyuas no tau tsim cov txiaj ntsig ntawm ntau qhov kev sim tshuaj ntsuam xyuas, hais txog qhov cuam tshuam ntawm GLP-1 ntawm kev poob phaus, metabolic tsis, thiab tag nrho cov txiaj ntsig kev noj qab haus huv. Cov txiaj ntsig tau pom tias GLP-1 muaj feem cuam tshuam nrog kev poob phaus thiab txhim kho kev noj qab haus huv ntsig txog kev rog, thiab nws yuav yog qhov kev xaiv zoo rau cov neeg mob rog.

Cov neeg mob uas tsis muaj ntshav qab zib (cov ntaub ntawv pov thawj los ntawm ntau RCTs): Hauv 4 qhov kev sim tshuaj ntsuam xyuas, cov neeg mob uas muaj lub cev hnyav ntawm 96 txog 105 kg tau txais kev txhaj tshuaj subcutaneous txhua lub lim tiam ntawm 2.4 mg ntawm GLP-1 thiab kev pabcuam kev ua neej (kev tawm tswv yim, kev noj haus, thiab kev ua si lub cev) rau kev kho mob yuag. Ib qho randomized tswj kev sim rau cov neeg mob uas tsis muaj ntshav qab zib (N = 1961) tau pom tias tom qab 68 lub lis piam, qhov nruab nrab qhov hnyav poob yog 15% (15 kg), uas yog qhov sib txawv ntawm 2% (3 kg) hauv pawg placebo. Qhov feem pua ​​​​ntawm cov neeg mob poob ceeb thawj ≥5% yog 86% piv nrog 32% hauv cov placebo pab pawg, thiab tus lej yuav tsum tau kho (NNT) = 2; qhov feem pua ​​​​ntawm cov neeg mob poob ceeb thawj ntawm ≥10% yog 69% piv nrog 12% hauv cov placebo pab pawg, thiab NNT = 2. Qhov hnyav poob qis ntawm li 60 lub lis piam. Qhov tshwm sim ntawm kev mob plab hnyuv (AEs) yog 74% piv nrog 48% hauv pawg placebo, thiab tus naj npawb xav tau los ua phem (NNH) = 3. Qhov feem pua ​​ntawm cov neeg mob txiav tawm kev kho mob vim yog cov xwm txheej tsis zoo yog 7% piv nrog 3% hauv pawg placebo, thiab NNH = 25. Nyob rau hauv lwm qhov kev sib tw randomized hauv kev noj qab haus huv = 6 txoj kev ua neej nrog kev sib tw. Hauv pawg GLP-1 yog 16% (17 kg), uas yog qhov sib txawv ntawm 6% (6 kg) hauv pawg placebo. Hauv kev tshawb nrhiav tshuaj randomized tswj kev sim rau cov neeg mob ntshav qab zib (N = 1210), cov neeg mob tau muab 2.4 mg ntawm GLP-1 txhua lub lim tiam, 1.0 mg ntawm GLP-1, lossis placebo. Tom qab 68 lub lis piam, qhov hnyav poob qis yog 10% (2.4 mg), 7% (1.0 mg), thiab 3% (placebo) feem. Qhov feem pua ​​​​ntawm cov neeg mob poob ceeb thawj ntawm ≥5% yog 69% (2.4 mg), 57% (1.0 mg) piv nrog 29% hauv cov placebo pawg. Rau cov koob tshuaj 2.4 mg thiab 1.0 mg, NNT = 9. Cov xwm txheej tsis zoo tau zoo ib yam ntawm cov koob tshuaj sib txawv. Hauv kev saib xyuas qhov hnyav randomized tswj kev sim (N = 803), cov neeg uas tsis yog mob ntshav qab zib tau txais kev kho mob txhua lub lim tiam nrog 2.4 mg ntawm GLP-1 rau 20 lub lis piam, thiab tom qab ntawd tau muab faib ua pawg txuas ntxiv GLP-1 kev kho mob lossis pab pawg placebo. Tom qab 48 lub lis piam, cov pab pawg txuas ntxiv kho GLP-1 poob 8% ntawm lawv lub cev hnyav, thaum pab pawg placebo nce 7% ntawm lawv lub cev hnyav.

Hauv kev xaus, GLP-1 yog GLP-1 receptor agonist tshuaj nrog daim ntawv thov tus nqi hauv ntau qhov chaw. Hauv kev kho mob ntshav qab zib mellitus, nws muaj txiaj ntsig zoo tswj cov ntshav qabzib los ntawm kev khi rau GLP-1 receptors, txhawb nqa insulin secretion, thiab inhibiting glucagon tso tawm, muab kev kho mob tseem ceeb rau cov neeg mob ntshav qab zib hom 2. Nyob rau hauv nam ntawm kev kho mob rog rog, GLP-1 txo qis lub zog noj los ntawm cov txheej txheem xws li kev noj qab haus huv hauv nruab nrab thiab ua rau lub plab zom mov qeeb, pab cov neeg mob rog rog thiab txhim kho lawv cov txheej txheem metabolic. Tsis tas li ntawd, GLP-1 kuj qhia tau hais tias muaj peev xwm thov kev cia siab rau hauv kev tiv thaiv thiab kho cov kab mob plawv. Nws txoj kev txhim kho ntawm cov teeb meem plawv plawv muab ib txoj hauv kev tshiab los txo cov xwm txheej ntawm cov hlab plawv.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Hegner P yog tus kws tshawb fawb ntawm University of Regensburg. Nws txoj haujlwm nthuav dav Chemistry, Cardiovascular System, thiab Cardiology. Hauv Chemistry, nws tshawb nrhiav cov kev cuam tshuam cuam tshuam rau kev mob plawv. Hauv kev tshawb fawb Cardiovascular System, nws soj ntsuam lub plawv thiab hlab ntsha, nrhiav kev kho mob kev pom. Nws txoj kev tshawb fawb Cardiology tsom rau kev tiv thaiv kab mob plawv, kev kuaj mob, thiab kev kho mob.

Hegner qhov kev koom tes tseem ceeb heev. Nws cov kev pom tshuaj lom neeg tau txhawb nqa cov tshuaj kho mob plawv tshiab. Nws txoj haujlwm ntawm lub plawv thiab cov hlab ntsha mechanisms tau txhim kho kev nkag siab ntawm cov kab mob plawv. Clinically, nws txoj kev tshawb fawb tau txhim kho kev tswj kab mob plawv, txhim kho cov qauv ntawm kev saib xyuas neeg mob. Zuag qhia tag nrho, Hegner txoj kev qhuab qhia ntau txoj hauv kev txhawb nqa cov tshuaj mob plawv, muab kev cia siab rau txo cov kab mob thiab cov txiaj ntsig zoo ntawm tus neeg mob. Hegner P tau teev nyob rau hauv kev siv ntawm cov ntaub ntawv pov thawj ^[9].

▎ Cov Lus Qhia Tseem Ceeb

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[2] Ma H, Huang W, Wang X, et al. Cov qauv kev pom zoo rau kev ua kom GLP-1R los ntawm ib qho me me molecule agonist [J]. Cell Research, 2020,30(12):1140-1142.DOI:10.1038/s41422-020-0384-8.

[3] Kim HS, Jung C H. Oral GLP-1, Thawj Qhov Ncauj Glucagon-zoo li Peptide-1 Receptor Agonist: Nws Puas Yuav Ua Tau Khawv koob rau Hom 2 Ntshav Qab Zib?[J]. International Journal of Molecular Sciences, 2021,22(18).DOI:10.3390/ijms22189936.

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[5] Katsurada K, Yada T. Neural teebmeem ntawm plab- thiab lub hlwb-derived glucagon-zoo li peptide-1 thiab nws cov receptor agonist [J]. Phau ntawv Journal of diabetes Investigation, 2016,7:64-69.DOI:10.1111/jdi.12464.

[6] Ryan DH, Lingvay I, Colhoun HM, et al. GLP-1 cuam tshuam rau cov txiaj ntsig ntawm cov hlab plawv hauv cov neeg muaj rog lossis rog (SELECT) qhov laj thawj thiab tsim [J]. American Heart Journal, 2020,229:61-69.DOI:10.1016/j.ahj.2020.07.008.

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[11] Alanazi M, Alshahrani JA, Aljaberi AS, et al. Qhov cuam tshuam ntawm GLP-1 hauv cov tib neeg uas muaj rog lossis rog dhau yam tsis muaj ntshav qab zib [J]. Cureus Journal of Medical Science, 2024,16(8).DOI:10.7759/cureus.67889.

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Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.