Bacille Calmette-Guérin: Kev Pom Kev Pom Kev Pom Zoo Part 2
May 24, 2023
2.4. Kev txhaj tshuaj BCG hauv Covid-19
Ib txoj kev tshawb fawb loj los ntawm Brazil tsis pom muaj qhov sib txawv tseem ceeb hauv tus nqi ntawm cov xwm txheej tsis zoo nrog kev rov ua kom rov zoo li qub piv rau kev txhaj tshuaj thawj zaug35. Ib yam li ntawd, cov kev tshawb fawb los ntawm Malawi thiab Brazil pom tsis muaj pov thawj ntawm kev txhim kho kev tiv thaiv kab mob TB los ntawm kev rov ua dua 8,60. Thaum lub sijhawm sau ntawv, nees nkaum qhov kev sim tau kawm txog kev tiv thaiv ntawm kev txhaj tshuaj BCG, ntawm 11 tus neeg ua haujlwm kho mob 161. World Health Organization's Strategic Advisory Group of Experts on Immunization (SAGE) tam sim no tsis pom zoo BCG rau kev tiv thaiv; Txawm li cas los xij, qhov tshwm sim ntawm cov kev tshawb fawb saum toj no yuav cuam tshuam rau kev sib kis mus rau yav tom ntej.
Lub hom phiaj tseem ceeb ntawm kev txhaj tshuaj tiv thaiv yog ua kom lub cev tiv thaiv kab mob los ntawm kev ua kom lub cev tiv thaiv kab mob tiv thaiv kab mob tshwj xeeb. Kev tiv thaiv kab mob yog hais txog lub peev xwm ntawm tib neeg lub cev los tiv thaiv kev cuam tshuam ntawm cov kab mob, tshwj xeeb tshaj yog tshwm sim hauv kev paub txog thiab tshem tawm cov kab mob.
Thaum txhaj tshuaj tiv thaiv, cov kab mob lossis nws cov khoom hauv cov tshuaj tiv thaiv yog txhaj rau hauv tib neeg lub cev los txhawb lub cev los tsim cov tshuaj tiv thaiv kab mob, yog li tsim kev tiv thaiv kab mob tiv thaiv kab mob. Cov tshuaj tiv thaiv kab mob no suav nrog kev ua kom lub cev tiv thaiv kab mob thiab tsim cov kab mob tiv thaiv kab mob uas tshwm sim hauv lub cev. Yog hais tias tus kab mob no tau ntsib dua tom qab, lub cev tiv thaiv kab mob thiab lub cim xeeb ntawm lub hlwb yuav sai sai pib lub cev tiv thaiv kab mob, yog li sai sai exerting cov nyhuv ntawm lub cev tiv thaiv kab mob thiab tiv thaiv qhov ntxeem tau ntawm cov kab mob.
Yog li ntawd, kev txhaj tshuaj thawj zaug tuaj yeem txhim kho lub cev tiv thaiv kab mob rau cov kab mob cuam tshuam thiab ua rau lub cev tiv thaiv kab mob los ntawm cov kab mob sib xws. Nws tuaj yeem pom tias peb yuav tsum txhim kho peb txoj kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv. Cistanche yog nplua nuj nyob rau hauv ntau yam tshuaj antioxidant, xws li vitamin C, vitamin C, carotenoids, thiab lwm yam. Cov khoom xyaw no tuaj yeem tshem tawm cov dawb radicals, txo oxidative kev nyuaj siab, thiab txhim kho kev tiv thaiv. tiv thaiv kab mob.
Nyem cistanche deserticola ntxiv
3. BCG immunotherapy
William Coley suav hais tias yog leej txiv ntawm kev tiv thaiv kab mob qog noj ntshav niaj hnub no, tau piav qhia txog lub luag haujlwm ntawm cov kab mob hauv lub cev tiv thaiv kab mob tom qab pom qhov rov qab ntawm sarcoma hauv cov neeg mob erysipelas los ntawm Streptococcus pyogenes28. Ib txoj kev tshawb fawb autopsy tau tshaj tawm tias qhov tshwm sim tsawg dua ntawm cov qog nqaij hlav ntawm cov neeg uas tau txhaj tshuaj BCG88. Alvaro Morales tau piav qhia txog kev siv BCG hauv kev kho mob qog noj ntshav hauv xyoo 197692; Txawm li cas los xij, nws cov txheej txheem nthuav tawm maj mam 87. Kev siv BCG kev kho mob kom txo cov qog nqaij hlav tom qab nws qhov kev txiav tawm yog nyob ntawm lub peev xwm kom tau cov kab mob nyob ze rau qhov malignancy thiab deranged glycosaminoglycan txheej uas tso cai rau kev tiv thaiv kab mob zoo dua rau cov qog112.
Tsis tas li ntawd, antigen 85 thiab fibronectin attachment protein (FAP) qhia los ntawm BCG pab txhawb tshwj xeeb receptor-ligand-mediated txuas rau urothelium. Ib zaug txuas, BCG induces qhia ntawm MHC chav kawm II molecules ntawm urothelial hlwb ua rau lawv ua haujlwm li antigen-presenting cells (APC)107. Ntxiv mus, muaj kev tsim cov cytokines zoo li IL-6, IL-8, GMCSF, thiab TNF- 135. Cov xwm txheej no ua rau muaj kev tsim cov epithelioid thiab cov cell loj heev granulomas uas muaj cov macrophages, dendritic hlwb, lymphocytes, neutrophils, thiab fibroblasts (Fig 2 A & B) 111.
Tag nrho cov qib siab thiab qee cov qib qis uas tsis yog leeg nqaij hlav qog nqaij hlav qog nqaij hlav (NMIBC), suav nrog carcinoma hauv situ yog cov neeg sib tw rau IBCG kho; Txawm li cas los xij, kev tshuaj xyuas tsis ntev los no qhia tias tsuas yog 50 feem pua ntawm cov neeg mob uas muaj kev pheej hmoo siab tau txais nws, thiab feem ntau yog vim muaj cov xwm txheej tsis zoo, tsuas yog 16 feem pua -29 feem pua ua tiav 3- xyoo kawm ntawm immunotherapy79. Hauv lwm qhov ntawm 1316 tus neeg mob ntawm IBCG, 69.5 feem pua tau tshaj tawm cov teeb meem uas muaj xws li khaus khaus khaus mus rau qhov mob hnyav. Ntawm cov 62.8 feem pua tau muaj hauv zos thiab 30.6 feem pua tau muaj kab mob hauv lub cev 17. Raws li qee cov neeg mob tsis teb rau BCG immunotherapy, thiab vim tias muaj qee qhov kev pheej hmoo cuam tshuam nrog kev nthuav tawm cov kab mob attenuated, mycobacterial cell wall extract, thiab mycobacterial cell wall nucleic acid complex kuj tau tshawb nrhiav 71,105. Txawm hais tias cov kev tshawb fawb txog kev tiv thaiv kab mob tsis tau ua tiav, txoj hauv kev no ua rau 26.5 feem pua ntawm cov neeg mob carcinoma nyob rau hauv situ thiab 61.2 feem pua ntawm cov neeg mob uas tsis muaj kab mob papillary rau tsawg kawg yog 1 xyoo nrog rau lub zais zis 71.
Interestingly, cell phab ntsa Cheebtsam tsim ib feem ntawm ua tiav Freund adjuvant (CFA), uas muaj inactivated thiab qhuav mycobacteria thiab yog siv nrog rau emulsified velogenic antigens induce autoimmune uveitis thiab sympathetic ophthalmia22,114; Txawm li cas los xij, kev tiv thaiv kab mob tsis tshwj xeeb nrog BCG tsis muaj kev tiv thaiv tiv thaiv kab mob keratitis67,94,127.
4. BCG thiab ocular cancer immunotherapy
Rutgard thiab cov neeg ua haujlwm ua haujlwm tau ua pov thawj kev tswj hwm subconjunctival ntawm cov kab mob BCG hauv New Zealand albino luav yam tsis muaj tshuaj lom hauv zos lossis hauv qhov muag119.
Qhov no yog lub hauv paus ntawm BCG immunotherapy nyob rau hauv cov qog nqaij hlav ocular 119. Lwm cov neeg tshawb xyuas tau pom tias txo qis rov tshwm sim ntawm bovine ocular squamous cell carcinoma los ntawm kev txhaj tshuaj intralesional ntawm cov nyob hauv BCG lossis BCG cell phab ntsa piv rau cov kev tshawb fawb yav dhau los los ntawm tib pab pawg uas ib zaug txhaj tshuaj tau siv 120. Ob qho kev tshawb fawb tau pom tias qhov kev ncua sij hawm tsis txaus siab rau PPD tau mob ntev dua hauv cov tsiaj uas pom cov qog regression.
5. BCG thiab kev sim uveitis
Larson thiab cov neeg ua haujlwm yav dhau los tau ua pov thawj BCG lub luag haujlwm hauv kev tiv thaiv tus kab mob Herpes hominis hom 2 tswj los ntawm qhov chaw mos instillation, intracorneal txhaj, thiab scarification ntawm lub cornea hauv Dutch-belted thiab New Zealand rabbits67. Ua raws li qhov no, Tabbara thiab cov neeg ua haujlwm ua haujlwm tau sim BCG lub peev xwm los muab cov kev tiv thaiv tsis zoo rau cov kab mob microbial ocular (Fig. 3). Ib pawg ntawm cov luav tau txhaj tshuaj los ntawm kev txhaj tshuaj txhaj tshuaj ntawm BCG, pawg thib ob tau txais kev txhaj tshuaj unilateral retrobulbar ntawm BCG, thiab pawg thib peb, uas tau txais kev tswj hwm, tau txais kev txhaj tshuaj unilateral retrobulbar ib txwm siv tshuaj ntsev 130. Tom qab ntawd, kev sim toxoplasmic retinochoroiditis tau tshwm sim los ntawm kev txhaj tshuaj Toxoplasma kab mob hauv qhov chaw suprachoroidal. Txawm hais tias Toxoplasma raug cais tawm ntawm cov ntaub so ntswg chorioretinal hauv tag nrho peb pawg, qhov pib ntawm qhov mob ntawm qhov muag sib txawv, thiab qhov hnyav tau txo qis hauv pawg TB. Intravenous tswj tau muaj kev tiv thaiv ntau dua piv rau cov pab pawg neeg retrobulbar. Toxoplasma antibodies raug kuaj pom hauv ib tus tsiaj nkaus xwb; Txawm li cas los xij, qhov no yuav yog vim lub cev tsis muaj zog tiv thaiv kab mob yuav tshem tawm cov kab mob. Ob leeg mycobacteria thiab Toxoplasma yog intracellular pathogens thiab evoke ib Th1- hom tshuaj tiv thaiv kab mob74.
Castro thiab cov neeg ua haujlwm ua haujlwm tau tsim cov qauv luav tshiab ntawm ocular o los kuaj cov tshuaj tiv thaiv kab mob ntawm thalidomide23. Tom qab ob qhov kev txhaj tshuaj subcutaneous ntawm BCG txhawm rau txhim kho lub cev tiv thaiv kab mob, lawv tau txhaj tshuaj BCG intravitreally txhawm rau ua rau panuveitis. Lawv tau pom tias muaj kev nce hauv cov kab mob inflammatory N-acetyl-b-glucosaminidase thiab myeloperoxidase hauv cov ntaub so ntswg, uas dwindled tom qab ib qho kev txhaj tshuaj intravitreal ntawm thalidomide. Cov kws sau ntawv kuj tau lees paub cov lus teb nrog electrophysiology thiab histopathology.
6. Ocular immunology thiab retinal autoimmunity
Qee qhov xwm txheej tseem ceeb hauv kev txhim kho autoimmune uveal thiab retinal disorders yog ib qho kev tsis sib haum xeeb ntawm MHC II antigens, molecular mimicry uas muaj cov tshuaj antigen xws li retinal soluble antigen (Retinal-S Ag), interphotoreceptor retinoid-binding receptor (IRBP). ), thiab tiam ntawm ntau ntau ntawm autoreactive lymphocytes los ntawm polyclonal activation. Cov phab ntsa ntawm tes xws li lipopolysaccharides (LPS) tau koom nrog hauv qhov no. Kev qhia tsis yog kev cai lij choj ntawm MHC II antigens los ntawm cov neeg nyob hauv lub hlwb ua rau lawv ua haujlwm zoo ib yam li infiltrating hemopoietic hlwb. Retinal pigment epithelium, vascular endothelium, thiab lwm cov hlwb hauv cov neurosensory retina tuaj yeem ua haujlwm li APCs75,78. Nyob rau hauv ib rooj plaub ntawm uveitis muaj feem xyuam rau BCG, Garip, thiab cov neeg ua hauj lwm ua hauj lwm pom proliferation thiab tso tawm ntawm proinflammatory cytokines teb rau PPD, retinal-S Ag, IRBP, IRBP-peptide thiab cellular retinal-binding protein (CRALBP) 42. Qhov tseem ceeb amino acid sequence homology tau pom nyob nruab nrab ntawm cov proteins los ntawm M. tuberculosis, BCG, thiab retinal antigens, tawm tswv yim molecular mimicry raws li qhov ua rau uveitis hauv tus neeg mob no.
Cov pov thawj ntxiv ntawm autoimmunity induced los ntawm BCG los ntawm cov kev tshawb fawb ntawm cov mob reactive arthritis10. Nws yog ib qho kev tiv thaiv kab mob uas tshwm sim los ntawm autoreactive T lymphocytes induced los ntawm cov kab mob tawg xws li LPS thiab nucleic acids. Feem ntau ntawm HLA-B27 hauv kev mob caj dab reactive sib txawv ntawm 30 feem pua thiab 50 feem pua 10,154. Hla-reactivity ntawm mycobacterial antigens, tshwj xeeb tshaj yog cov 65-kD heat-shock protein, thiab HLA-B27 cov ntaub so ntswg antigen kuj tau tham txog 139. Ntawm plaub qhov xwm txheej hauv cov ntaub ntawv Askiv, peb tau tsim kev mob caj dab tom qab plaub lub voj voog ntawm BCG, thiab lwm qhov tom qab lub voj voog thib tsib 50,53,107,121. Qhov no tej zaum yuav hais txog qhov yuav tsum tau ua ua ntej ntawm cov txiaj ntsig rov tshwm sim. Ib qho ntawm cov xwm txheej no tau kuaj pom zoo rau HLA-B27 thiab HLA-DR453. HLA-DR4 yog txuam nrog kev ua haujlwm siab rau mycobacterial antigens102. Idiopathic retinal vasculitis yog lwm qhov chaw uas feem ntau xav tias muaj lub koom haum tubercular uas cuam tshuam nrog HLA-B51, HLA-DR1, thiab HLA-DR414. Txawm li cas los xij, ntau qhov chaw uveitic cuam tshuam nrog tuberculosis yog tsis muaj kab mob thiab tau tsav los ntawm qhov tshwm sim autoimmune mechanisms36.
7. Clinical spectrum of ocular ocular cuam tshuam nrog BCG
Lub spectrum ntawm qhov muag pom kev cuam tshuam nrog BCG suav nrog cov kab mob sib kis thiab tiv thaiv kab mob sib kis79. Raws li Naranjo cov qhab nia, cov koom haum no raug cais raws li qhov tseeb 80.96,97.
7.1. Cov ntaub ntawv keeb kwm ntawm BCG-kev cuam tshuam qhov muag tsis pom kev
Ntau cov ntaub ntawv keeb kwm tau tshwm sim hauv cov ntaub ntawv sai tom qab kev qhia txog kev txhaj tshuaj BCG4,39,56,76,89,132. Txawm hais tias muaj ntau yam ntawm cov kab mob no zoo ib yam li cov lus piav qhia tam sim no ntawm cov xwm txheej cuam tshuam nrog ocular tuberculosis47, qhov kev txwv ntawm cov kev tshawb fawb no yog qhov tsis zoo ntawm kev ua haujlwm tsim nyog lossis muaj cov qauv vitreous hauv "vitrectomy era". Miettinen tau piav qhia txog 149 tus neeg mob uas muaj cov kab mob ocular mob tom qab txhaj tshuaj tiv thaiv BCG thaum xyoo 1942 thiab 195689. Nws tau faib 73 qhov xwm txheej (49 feem pua) ua tubercular hauv keeb kwm thaum tus so 76 qhov xwm txheej (51 feem pua) yog cov koom haum tubercular. Nws cov kev soj ntsuam zoo suav nrog cov kab mob sib kis thiab tsis muaj kab mob (Table 1).
Raws li kev kis tus kab mob nyob hauv Europe tau xav tias siab dua, qee qhov ntawm cov mob no tuaj yeem tshwm sim los ntawm kev kis tus kab mob M. tuberculosis nws tus kheej tsis yog kev tshaj tawm ntawm M. bovis los ntawm kev txhaj tshuaj133. Qee qhov xwm txheej no tau piav qhia los ntawm Miettinen tau tsim kho sai sai tom qab txhaj tshuaj tiv thaiv, nrog rau cov ntaub ntawv tshaj tawm ntxov tshaj plaws ib hnub tom qab txhaj tshuaj tiv thaiv88. Nws niaj hnub Damato tau tshaj tawm txog 11 tus neeg mob hauv Malta hauv cov menyuam yaus hnub nyoog 4 txog 8 xyoo hauv 2 txog 6 lub lis piam tom qab txhaj tshuaj tiv thaiv32. Nws tau hais txog ob qhov xwm txheej thiab xaus lus tias qhov tshwm sim tam sim ntawd ntawm qhov chaw tsis tshua muaj qhov cuam tshuam cuam tshuam qhov cuam tshuam ntawm kev tiv thaiv kab mob los ntawm BCG. Cov menyuam yaus hauv pawg neeg no tau kuaj pom tsis zoo rau PPD ua ntej txhaj tshuaj tiv thaiv, muab kev lees paub ntxiv rau Miettinen lub koom haum putative.
Nyob rau xyoo tas los no nrog kev siv IBCG, cov koom haum tshiab tau piav qhia: Liu thiab cov neeg ua haujlwm tau hais txog 15 tus neeg mob ntawm qhov muag tom qab IBCG79. Buchs, ntawm qhov tod tes, luam tawm ntau dua ntawm qhov mob ntawm qhov muag, nrog rau ntau txog 25 feem pua ntawm cov neeg mob 16.
7.2. Conjunctivitis
Tinazzi thiab cov neeg ua haujlwm ua haujlwm tau ua qhov kev tshuaj xyuas zoo ntawm kev mob caj dab reactive tom qab IBCG instillation thiab tshaj tawm tias 24 feem pua ntawm cov neeg mob tsim kev cuam tshuam ntawm qhov muag, tsis suav nrog 2 feem pua uas muaj Sjögren syndrome132. Ng thiab cov neeg ua haujlwm tau piav qhia txog qhov xwm txheej ntawm cov zis tso zis, ob sab conjunctivitis, thiab mob nraub qaum qis tom qab lub voj voog thib plaub ntawm BCG immunotherapy99. Sib nrug los ntawm conjunctivitis txuam nrog reactive arthritis49, ib rooj plaub ntawm follicular conjunctivitis 24 teev tom qab kev sib tsoo ntawm cov tshuaj tiv thaiv BCG ntawm tus neeg ua haujlwm kho mob tau tshaj tawm 113. Thaum lub sij hawm sim txhaj tshuaj tiv thaiv kab mob BCG rau hauv lub cev tsis muaj zog sab caj npab, lub koob txhaj tshuaj tau tawm ntawm tus menyuam mos daim tawv nqaij tawm ntawm nws cov ntsiab lus mus rau hauv lub qhov muag tshuaj. Muab cov tshuaj tiv thaiv BCG yav dhau los, cov lus teb tau suav tias yog qhov tshwm sim ntawm kev qeeb qeeb. Tus kws kho mob tau kho nrog tshuaj steroids nrog rau ib lub hlis ntawm qhov ncauj isoniazid. Ib yam li ntawd, ib rooj plaub ntawm BCG reactivation nrog concurrent mucocutaneous kev koom tes nrog rau conjunctivitis tau piav nyob rau hauv ib tug me nyuam ob lub hlis tom qab txhaj tshuaj tiv thaiv BCG, thiab qhov no yog nyob rau hauv koom nrog Kawasaki kab mob40.
7.3. Kev koom tes ntawm pob txha
Chakraborty thiab cov neeg ua hauj lwm tau tshaj tawm ib rooj plaub ntawm ob sab symmetrical corneal ulceration nrog mucopurulent conjunctivitis thiab qhuav qhov muag tom qab koob thib plaub ntawm IBCG24. Cov ntaub ntawv mus rau muaj ob sab descemetocele thiab ocular perforation. Lawv tsis cais cov kab mob acid-ceev bacilli ntawm kab lis kev cai thiab suav tias yog kev tiv thaiv kab mob sib kis. Tsis muaj ntawv ceeb toom ntawm molecular mimicry los yog ib theem homology ntawm tubercular thiab corneal antigens.
7.4 ib. Endophthalmitis
Hauv kev tshawb fawb ntawm 256 cov kev kho mob nrog IBCG, 4.3 feem pua tau tshaj tawm cov kab mob sib kis 110, thiab kev koom tes hauv cheeb tsam tau pom hauv 9 feem pua ntawm cov neeg kawm. Kab lis kev cai-zoo M. bovis endophthalmitis tau tshaj tawm nyob rau hauv yim lub qhov muag ntawm tsib tus neeg mob, uas tau lees tias muaj kev cuam tshuam ncaj qha rau vitreous tom qab hematogenous nthuav tawm ntawm cov kab mob 43,48,55,68,79,138. Thawj kis, tshaj tawm los ntawm Lester thiab cov neeg ua haujlwm ua haujlwm, yog tus neeg mob muaj hnub nyoog 66- xyoo uas muaj ob tog endophthalmitis nrog cov pov thawj txo qhov loj ntawm cov kab mob retinal nrog kev kho mob antitubercular ua ntej tus neeg mob tuag 68. Ob sab retinal vasculitis thiab infiltrative retinitis yog pom hauv ib rooj plaub48. Qhov thib peb cov ntaub ntawv qhia los ntawm Gerbrandy muaj mob vitreous nyuaj los ntawm serous detachment thiab ntau choroidal granulomatous lesions43. Vadboncoeur thiab cov neeg ua haujlwm tau piav qhia lwm qhov xwm txheej tsis sib haum nrog qhov tseem ceeb ntawm cov vitreous thiab vitreous condensation nrog rau fluffy granulomatous retinal mass138. Nyob rau hauv cov ntaub ntawv no, lub real-time polymerase saw cov tshuaj tiv thaiv rau mycobacteria yog zoo. Tsis muaj acid-ceev bacilli tau pom thawj zaug, tab sis kab lis kev cai tau ua thaum lub sij hawm thib ob ntawm vitrectomy rau cov kab mob vitreous hemorrhage rov qab zoo. Tus neeg mob no tau txais IBCG peb xyoos ua ntej kev nthuav qhia ocular.
Cov ntaub ntawv tsis ntev los no tau piav qhia los ntawm Huggins thiab cov neeg ua haujlwm nrog ob tog endophthalmitis, qhov muag sab xis muaj qhov muag daj vitreous, thiab sab laug qhov muag pom tau tias muaj ntau hom focal, daj, puag ncig subretinal pigment epithelial lesions hauv macula thiab inferotemporal retina (Fig. 4) 55. Cov ntaub ntawv tau pib kuaj pom tias yog nruab nrab uveitis thiab kho nrog sub-tenon triamcinolone lwm qhov ua ntej endogenous endophthalmitis tau raug xav tias vim muaj cov catheter indwelling. Nws tsuas yog tom qab qhov thib ob kuaj mob pars plana vitrectomy uas acid-ceev bacilli tau pom ntawm histopathology. Lub sijhawm nruab nrab ntawm IBCG yav dhau los thiab endophthalmitis yog plaub lub hlis. Cov xwm txheej no qhia txog qhov teeb meem tshwm sim hauv kev tsim qhov kev kuaj mob thiab feem ntau cov txiaj ntsig tsis zoo txawm hais tias muaj kev kho mob antimycobacterial txaus. Yog li, qhov ntsuas siab ntawm qhov tsis txaus ntseeg tau qhia rau cov neeg mob uas muaj keeb kwm ntawm IBCG. Mycobacterial kab lis kev cai siv sijhawm, thiab cov txheej txheem kuaj mob molecular yog qhov tseem ceeb. Qee qhov xwm txheej uas pib tshwm sim tsis meej pem tej zaum yuav kis tau, tshwj xeeb tshaj yog nyob rau hauv vitreous haze (45.4 feem pua) thiab choroidal kev koom tes (64.4 feem pua) yog cov yam ntxwv tseem ceeb ntawm ocular tuberculosis1. Cov lus teb zoo rau cov tshuaj antitubercular yam tsis muaj cov tshuaj steroids reclassified ib co ntawm cov no yog kis46.
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