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Kev Tshawb Fawb Tom Qab NMN—Ib qho ruaj khov, ntseeg tau NAD ntxiv rau Activator Thiab Anti-Aging MoleculeThe Science Tom Qab NMN—Ib qho ruaj khov, ntseeg tau NAD ntxiv rau Activator Thiab Anti-Aging Molecule

Jul 20, 2023

Christopher Shade, Ph.D., tus tsim thiab CEO ntawm Quicksilver Scientific, tseem yog tus tsav tsheb ntawm kev txhim kho thiab kev tsim kho tshiab. Dr. Shade qhov tob thiab dav ntawm kev paub, mob siab rau kev kho mob, thiab kev nkag siab zoo ntawm chemistry thiab biology tau tshwm sim nyob rau hauv Quicksilver Scientific cov txheej txheem tsim kom tshem tawm cov co toxins, cov khoom siv tshwj xeeb ntxiv, thiab patented mercury speciation test. Dr. Shade tau txais nws PhD los ntawm University of Illinois Urbana-Champaign thiab nws kawm tiav qib siab hauv Environmental Chemistry yog los ntawm Lehigh University.

Glycoside ntawm cistanche tuaj yeem ua rau muaj kev ua haujlwm ntawm SOD hauv plawv thiab daim siab cov ntaub so ntswg, thiab txo cov ntsiab lus ntawm lipofuscin thiab MDA hauv txhua cov ntaub so ntswg, tshem tawm ntau yam reactive oxygen radicals (OH-, H₂O₂, thiab lwm yam) thiab tiv thaiv DNA puas. los ntawm OH-radicals. Cistanche phenylethanoid glycosides muaj peev xwm tshem tawm cov dawb radicals, muaj peev xwm txo tau ntau dua li cov vitamin C, txhim kho cov haujlwm ntawm SOD hauv cov phev ncua, txo cov ntsiab lus ntawm MDA, thiab muaj qee yam kev tiv thaiv ntawm cov phev ua haujlwm. Cistanche polysaccharides tuaj yeem txhim kho kev ua haujlwm ntawm SOD thiab GSH-Px hauv erythrocytes thiab ntsws cov ntaub so ntswg ntawm cov nas senescent sim los ntawm D-galactose, nrog rau txo cov ntsiab lus ntawm MDA thiab collagen hauv lub ntsws thiab ntshav, thiab nce cov ntsiab lus ntawm elastin, muaj Cov nyhuv scavenging zoo ntawm DPPH, ncua lub sijhawm ntawm hypoxia hauv cov nas senescent, txhim kho cov haujlwm ntawm SOD hauv cov ntshav, thiab ncua lub physiological degeneration ntawm lub ntsws hauv kev sim cov nas nrog cellular morphological degeneration, kev sim tau pom tias Cistanche muaj peev xwm antioxidant zoo. thiab muaj peev xwm los ua ib qho tshuaj tiv thaiv thiab kho cov kab mob ntawm daim tawv nqaij laus. Nyob rau tib lub sijhawm, echinacoside hauv Cistanche muaj lub peev xwm tseem ceeb txhawm rau txhawm rau DPPH dawb radicals thiab muaj peev xwm tshem tawm cov pa oxygen reactive thiab tiv thaiv dawb radical-induced collagen degradation, thiab kuj muaj kev kho zoo ntawm thymine dawb radical anion puas.

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Dr. Shade yog ib tug kws paub txog mercury thiab liposomal delivery systems. Nws tau qhuab qhia thiab cob qhia cov kws kho mob hauv Tebchaws Meskas thiab thoob ntiaj teb txog cov tshuaj mercury, cov hlau hnyav, thiab tib neeg cov tshuaj tua kab mob. Dr. Shade lub hom phiaj tam sim no yog nyob rau ntawm kev txhim kho ntawm kev txiav-ntug, lipid-raws li kev xa khoom rau nutraceuticals, xws li liposomes thiab micro-emulsion systems, los hais txog qhov kev xav tau loj hlob rau cov khoom lag luam zoo, pheej yig detoxification daws teeb meem.

Thaum Lub Rau Hli 2018, Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Ntiaj Teb (WHO) tau tshaj tawm 11th tsab ntawm nws International Classification of Diseases, thiab thawj zaug ntxiv kev laus.1 Kev faib tawm ntawm kev laus raws li tus kab mob ua rau txoj kev tshawb fawb tshiab rau kev kho tshiab kom ncua lossis Cov kab mob rov qab muaj hnub nyoog xws li mob qog noj ntshav, kab mob plawv thiab kab mob metabolic, thiab neurodegeneration.2,3 Cov khoom noj muaj txiaj ntsig tau ua rau muaj kev tshawb fawb hnyav, suav nrog mTOR (lub hom phiaj mammalian ntawm rapamycin) rau kev tswj cov protein synthesis thiab cell loj hlob; AMPK (activated protein kinase) rau kev hnov ​​​​mob qis zog; thiab sirtuins, ib tsev neeg ntawm xya proteins tseem ceeb rau DNA qhia thiab kev laus, uas tuaj yeem ua haujlwm nrog NAD ntxiv (nicotinamide adenine dinucleotide), coenzyme tam sim no hauv txhua lub hlwb.4

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Thoob plaws hauv lub nceeg vaj ntawm lub neej, kev nce qib hauv cov cell ntawm NAD ntxiv rau kev hloov pauv uas txhim kho kev muaj sia nyob, suav nrog kev txhawb nqa lub zog thiab txhim kho cellular kho.5 Qhov tseeb, cov txheej txheem qeeb, tsis muaj peev xwm ntawm kev laus tau piav qhia tias yog "cascade ntawm robustness tawg. tshwm sim los ntawm kev txo qis hauv NAD ntxiv rau biosynthesis thiab qhov tshwm sim ua haujlwm tsis zoo hauv lub cev thiab cov ntaub so ntswg. " thiab dysregulated intercellular kev sib txuas lus.7,8

Los ntawm cov hnub nyoog nruab nrab, peb cov qib NAD ntxiv tau poob mus rau ib nrab ntawm peb cov hluas.9 Ntau qhov kev tshawb fawb tau pom tias kev txhawb nqa NAD ntxiv rau qib nce insulin rhiab heev, thim rov qab mitochondrial tsis ua haujlwm, thiab txuas ntxiv lifespan.10,11 NAD ntxiv rau qib tuaj yeem nce ntxiv los ntawm kev ua kom muaj zog. enzymes uas txhawb cov synthesis ntawm NAD ntxiv, los ntawm inhibiting ib qho enzyme (CD38) uas degrades NAD ntxiv, thiab los ntawm supplementing nrog NAD precursors, xws li nicotinamide riboside (NR) thiab nicotinamide mononucleotide (NMN).12,13 Lub tswvyim hu ua NAD World. , tsim nyob rau hauv lub xyoo caum dhau los los ntawm kev loj hlob biologist Shin-ichiro Imai, MD, Ph.D., ntawm Washington University School of Medicine, posits NMN raws li ib tug tseem ceeb, systemic signaling molecule uas tuav lub lom robustness ntawm kev sib txuas lus network txhawb NAD ntxiv. 6

Noj hauv qhov ncauj, NMN tau nqus sai sai thiab hloov mus rau NAD ntxiv .14 Hauv ntau cov kev tshawb fawb, kev ntxiv nrog NMN tau nce NAD ntxiv rau biosynthesis, txo qis hnub nyoog ntsig txog cov ntaub so ntswg adipose, txhim kho insulin secretion thiab insulin ua haujlwm, txhim kho mitochondrial muaj nuj nqi, txhim kho neuronal muaj nuj nqi hauv lub hlwb, thiab lwm yam. Ntawm no, peb saib cov kev tshawb fawb tom qab NMN, nws txoj kev ruaj ntseg, muaj peev xwm pharmacokinetics, kev thauj mus los, kev ua haujlwm, thiab muaj peev xwm ua kom muaj biosynthesis ntawm NAD ntxiv rau .15 Ntxiv NMN tuaj yeem yog ib qho txiaj ntsig zoo rau kev tiv thaiv kev laus, nrog cov txiaj ntsig zoo ntawm ntau qhov sib txawv. physiological functions.16

Txoj kev mus rau NMN hauv tib neeg lub cev

Ib qho kev sib raug zoo ntawm kev sib cuam tshuam kev hloov pauv tso cai rau NAD ntxiv rau ob qho tib si synthesized thiab tswj hauv lub cev. Nws paub zoo tias vitamin B3 yog lub tsev thaiv rau Nicotinamide adenine dinucleotide (NAD ntxiv). Nws kuj tau lees paub dav dav tias NMN yog qhov muaj peev xwm ua ntej rau NAD ntxiv. Txawm hais tias NMN ib txwm pom muaj me me hauv cov txiv hmab txiv ntoo thiab zaub xws li avocados, broccoli, zaub qhwv, edamame, thiab cucumbers17, hauv cov tsiaj txhu feem ntau NMN yog tsim los ntawm vitamin B3 hauv daim ntawv ntawm nicotinamide. Ntawm qhov chaw yog nicotinamide phosphoribosyltransferase (NAMPT), ib qho tseem ceeb tus nqi-txheej enzyme uas catalyzes hloov los ntawm nicotinamide rau NMN, uas muaj nyob rau hauv ob qho tib si ib tug intracellular (iNAMPT) thiab extracellular daim ntawv (eNAMPT). daim ntawv intracellular thiab tau pom nyob rau hauv cov ntshav plasma, seminal plasma, thiab cerebrospinal kua nyob rau hauv tib neeg.19,20 Tsis tas li ntawd, eNAMPT zoo nkaus li tsim los ntawm ntau hom cell-xws li roj (adipocytes), siab (hepatocytes), Cov qe ntshav dawb (leukocytes thiab monocytes), thiab lub plawv thiab lub hlwb hlwb (cardiomyocytes thiab glia cells).21 Zoo li NAD ntxiv thiab NMN, eNAMPT poob qis nrog lub hnub nyoog. Ob leeg dawb thiab xim av adipocytes nquag zais eNAMPT, tawm tswv yim tias cov ntaub so ntswg rog tuaj yeem yog qhov hloov pauv ntawm NAD ntxiv rau biosynthesis.6 Adipose cov ntaub so ntswg nquag zais cov hlwv extracellular (EVs) uas muaj txiaj ntsig nrog NMN thiab tuaj yeem ncig los ntawm cov ntshav. EVs yog cov khoom siv los ntawm daim nyias nyias uas nyob ib puag ncig los ntawm phospholipid bilayer uas tau tso tawm los ntawm cov hlwb hauv tib neeg lub cev.22 Cov EVs no tsis tsuas yog tiv thaiv lawv cov khoom thauj, tab sis lawv tuaj yeem tso lawv cov load rau qhov xav tau.23

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NMN thiab NR dance ua ke. NMN tuaj yeem hloov los ntawm lub cev mus rau NR, uas tom qab ntawd nkag mus rau hauv cov hlwb, thiab hloov mus rau NMN los ntawm ib qho enzyme hu ua nicotinamide riboside kinase (NRK). Tsis ntev los no, ib qho "elusive' transporter tau tshawb pom, uas tuaj yeem thauj NMN ncaj qha mus rau hauv cov hlwb.24 NMN yog thauj mus los ntawm cov cell membranes ncaj qha mus rau cytoplasm ntawm lub cell, los ntawm ib qho enzyme hu ua Slc12a8. Uptake pathways ntawm NMN txawv nrog cov ntaub so ntswg, thiab interestingly, Slc12a8 qhia yog hais txog 100-fold zaus siab dua nyob rau hauv cov hnyuv me ntawm nas tshaj nyob rau hauv lub hlwb los yog cov ntaub so ntswg adipose. Cov kws tshawb fawb xav tias lub plab microbiome, thiab qee cov kab mob nyob hauv nws, tuaj yeem tsim NMN.25.

NMN qib poob nrog lub hnub nyoog, thiab kev laus nws tus kheej kuj tau pom tias muaj kev cuam tshuam rau lub cev hloov pauv ntawm NMN rau NAD ntxiv rau .26.

Cov pov thawj ntau rau Kev Tiv Thaiv Kev Laus thiab Kev Noj Qab Haus Huv Txhim Kho Cov teebmeem ntawm NMN

Hauv ntau tus nas qauv ntawm tus kab mob thiab kev laus, NMN tau nthuav tawm ntau yam ntawm cov txiaj ntsig zoo kawg li, muaj txiaj ntsig zoo xws li ntshav qab zib rau Alzheimer's kab mob mus rau ischemia.27

Hais lusKev tswj hwm NMN tau nrawm nrawm rau hauv NAD ntxiv rau hauv cov ntaub so ntswg hauv nas. NMN muaj peev xwm txo tau cov hnub nyoog txuam nrog qhov hnyav nce, txhim kho lub zog metabolism thiab kev ua haujlwm ntawm lub cev, txhim kho insulin rhiab heev, txhim kho qhov muag ua haujlwm, txhim kho mitochondrial metabolism, thiab tiv thaiv hnub nyoog-txuas kev hloov pauv hauv cov noob qhia. , NMN tau txhim kho ob qho tib si kev ua thiab kev tso tawm ntawm insulin.29 NMN kuj tiv thaiv nas lub plawv los ntawm ischemia thiab/los yog reperfusion raug mob.30 Nws tau rov qab kho cov leeg pob txha hauv cov nas muaj hnub nyoog 31, thiab ua rau kev txawj ntse poob qis hauv nas qauv ntawm Alzheimer's disease, los ntawm kev txhim kho. Kev muaj sia nyob ntawm cov neurons, txhim kho cov metabolism hauv lub zog, thiab txo qis cov pa oxygen reactive.32 Nws tuaj yeem pab tswj kev ncaj ncees ntawm cov ntshav-hlwb barrier.33 NMN yuav yog ib tus neeg sib tw zoo los tiv thaiv qhov mob-qhov nce hauv qhov mob cuam tshuam nrog kev laus-txij li kev tshawb fawb. qhia tias nws txo qis cov ntaub so ntswg adipose nrog rau hnub nyoog. Cov nas laus zoo li teb tau ntau dua rau NMN, piv nrog cov nas me.

NMN zoo li ruaj khov hauv dej; nyob rau hauv ib txoj kev tshawb no 93 feem pua ​​-99 feem pua ​​​​ntawm NMN tau khaws cia nyob rau hauv cov dej haus ntawm chav tsev kub rau 7-10 hnub. NMN kuj zoo li yuav nqus tau sai. Thaum muab rau nas los ntawm qhov ncauj gavage, muaj qhov nce siab ntawm plasma NMN hauv ib ob thiab ib nrab feeb xwb, nrog kev nce ntxiv ntawm 5-10 feeb. Plasma qib tom qab ntawd tsis kam mus rau hauv paus, qhia txog kev nqus sai hauv lub plab.29 Lub sijhawm ntev (1-} xyoo) NMN tau muab rau hauv qhov ncauj, hauv cov koob tshuaj txog li 300 mg / kg, tau pom tias muaj kev nyab xeeb thiab tiv taus zoo hauv qhov qub. mus. 29

Saib rau pem hauv ntej: NMN thiab Human Health

NMN yog ib tug murine fountain ntawm cov hluas. Tab sis li cas txog tib neeg? Shin-ichiro Imai tau hais tias NMN tuaj yeem txhim kho cov neeg laus cov metabolism hauv cov neeg laus, ua rau nws zoo ib yam li ntawm kaum lossis nees nkaum xyoo yau dua.34 Nws pab neeg tam sim no tab tom kawm NMN hauv tib neeg. David Sinclair, Harvard University tus kws tshawb fawb los tiv thaiv kev laus, uas nws cov kev tshawb fawb txog resveratrol, NAD ntxiv, thiab sirtuins yog lub ntiaj teb nto moo, tseem ua rau tib neeg sim. Nws tab tom noj NMN nws tus kheej; nws tau hais tias nws cov lipid profile tau txhim kho zoo heev thiab nws xav tias muaj zog dua thiab nws cov ntshav cov cim, ntawm ze li ntawm 60 xyoo, yog ze rau cov neeg ntawm 31-xyoo-laus.35,36

Cov lus nug nthuav yog kev xa khoom rau qhov ncauj NMN: EVs uas thauj cov molecule los ntawm cov ntshav hauv lub cev yog liposomes. Ib qho liposomal version ntawm NMN tuaj yeem ua tib zoo ua raws li lub cev kev thauj mus los, txhim kho kev noj qab haus huv thiab kev xa khoom, raws li kev tshawb fawb tau ua tiav nws txoj kev nkag siab ntawm qhov dawb huv grail ntawm thim rov qab kev laus.

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Cov ntaub ntawv

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  2. Blagosklonny MV. Kab mob los yog tsis, kev laus yog kho tau yooj yim. Aging (Albany NY). 2018 Nov 17;10(11):3067-3078

  3. Editorial. Qhib qhov rooj los kho kev laus raws li tus kab mob. Lancet Diabetes Endocrinol. 2018 Aug; 6(8):587

  4. López-Otín C et al. Cov cim ntawm kev laus. Cell 2013; 153(6):1194-1217

  5. Schultz MB et al. Yog vim li cas NAD ntxiv rau Kev Txom Nyem Thaum Laus: Nws Raug Kev Puas Tsuaj. Cell Metab. 2016 Lub Rau Hli 14; 23(6): 965–966

  6. Imai S. NAD Ntiaj Teb 2.0: qhov tseem ceeb ntawm kev sib txuas lus ntawm cov ntaub so ntswg sib kho los ntawm NAMPT/NAD ntxiv /SIRT1 hauv cov tsiaj txhu kev laus thiab kev tswj kav ntev. NPJ Syst Biol Appl. 2016 Aug 18; 2:16018

  7. Conboy IM et al. Rejuvenation ntawm cov laus progenitor hlwb los ntawm raug rau ib tug hluas systemic ib puag ncig. Xwm 2005; 433: 760–764 : kuv.

  8. de Magalha˜ es JP et al. Meta-kev tshuaj xyuas ntawm cov hnub nyoog muaj feem cuam tshuam cov noob qhia profiles qhia pom cov npe kos npe ntawm kev laus. Bioinformatics 2009: 25: 875–881.

  9. Zhu XH et al. Hauv vivo, NAD kev soj ntsuam qhia txog cov ntsiab lus ntawm NAD intracellular thiab redox lub xeev hauv tib neeg lub hlwb noj qab haus huv thiab lawv lub hnub nyoog dependences. Proc. Natl. Acad. Sci. 2015; 112:2876–2881 : kuv

  10. Suav AA. NAD ntxiv thiab vitamin B3: los ntawm cov metabolism mus rau kev kho mob. J Pharmacol Exp Ther. Peb Hlis 2008; 324(3):883-93

  11. Li CF et al. Targeting NAD ntxiv rau Metabolism ua Kev cuam tshuam rau Mitochondrial Kab Mob. Sci Rep. 2019 Lub Ob Hlis 28; 9(1): 3073

  12. Camacho-Pereira J et al. CD38 Dictates Age-Related NAD Kev Txom Nyem thiab Mitochondrial Dysfunction los ntawm SIRT3-Dependent Mechanism. Cell Metab. 2016 Jun 14; 23(6):1127-1139

  13. Longo VD et al. Kev cuam tshuam rau kev laus qeeb hauv tib neeg: Puas yog peb npaj txhij? Hnub nyoog Cell 14 (4): 497-510.

  14. Poljsak B. NAMPT-Mediated NAD biosynthesis raws li cov txheej txheem sab hauv: hauv NAD ntxiv rau ntiaj teb, lub sijhawm tab tom khiav hauv nws txoj kev. Rejuvenation Res. Lub Rau Hli 21, 2018 (3): 210-224

  15. Johnson S et al. NAD ntxiv rau biosynthesis, kev laus, thiab kab mob. F1000 Res. Peb 1, 2018, 7:132

  16. Yoshino J et al. NAD ntxiv rau Cov Neeg Nruab Nrab: Biology thiab Kev Kho Mob Muaj Peev Xwm ntawm NMN thiab NR. Cell Metab. 2018 Mar 6;27(3):513-528

  17. Revollo JR et al. NAD biosynthesis txoj kev kho los ntawm nicotinamide phosphoribosyltransferase tswj Sir2 kev ua haujlwm hauv cov tsiaj txhu. J Biol Chem. 2004; 279: 50754–50763

  18. Mills KF et al. Kev Tswj Lub Sij Hawm Ntev ntawm Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline nyob rau hauv nas. Cell Metab. 2016; 24: 795–806

  19. Hallschmid M et al. Kev sib raug zoo ntawm cerebrospinal kua visfatin (PBEF / Nampt) qib thiab adiposity hauv tib neeg. Mob ntshav qab zib. 2009; 58:637–640

  20. Friebe D et al. Leucocytes yog lub hauv paus loj ntawm nicotinamide phosphoribosyltransferase (NAMPT) / pre-B cell colony (PBEF) / visfatin txuas kev rog thiab mob rau tib neeg. Diabetologia. 2011; 54:1200–1211 : kuv

  21. Yoshino J et al. NAD ntxiv rau Cov Neeg Nruab Nrab: Cov kab mob biology thiab kho muaj peev xwm ntawm NMN thiab NR. Cell Metab. 2018 Mar 6;27(3):513-528

  22. Van der Meel R et al. Extracellular vesicles raws li kev xa cov tshuaj: cov lus qhia los ntawm liposome teb. J Tswj Tso Tawm. 2014 Kaum Ob Hlis 10; 195:72-85

  23. Yoshida M. Extracellular vesicle-contained eNAMPT ncua kev laus thiab ncua kev ua neej nyob hauv cov nas. Cell Metab. 2019 Aug 6;30(2):329-342.e5

  24. Wu LE et al. NMN thauj khoom tsis pom muaj. Hnub Tim 2019;1(1):8-9

  25. Grozio A et al. Slc12a8 yog nicotinamide mononucleotide transporter. Nat Metab. 2019; 1(1):47–57.

  26. Imai, S. Diagnostic and therapeutic applications of a novel plasma metabolite, Nicotinamide Mononucleotide (NMN), rau hnub nyoog-kev cuam tshuam cov teeb meem metabolic hauv tib neeg. Longer Life Foundation 2011.

  27. Keisuke Okabe et al. Kev cuam tshuam ntawm kev hloov pauv NAD metabolism hauv cov teeb meem metabolic. Phau ntawv Journal of Biomedical Science 2019; 26:34

  28. Mills KF et al. Kev tswj hwm mus sij hawm ntev ntawm nicotinamide mononucleotide mitigates lub hnub nyoog cuam tshuam ntawm lub cev poob qis hauv cov nas. Cell Metab. 2016 Dec 13; 24(6):795-806

  29. Caton PW et al. Nicotinamide mononucleotide tiv thaiv proinflammatory cytokine-mediated impairment ntawm nas islet muaj nuj nqi. Diabetologia. 2011 Dec; 54(12):3083-92

  30. Yamamoto T. Nicotinamide mononucleotide, ib qho nruab nrab ntawm NAD ntxiv synthesis, tiv thaiv lub plawv ntawm ischemia thiab reperfusion. PLoS Ib. 2014 Lub Xya hli ntuj 6; 9(6):e98972.

  31. Mendelsohn AR et al. Kev thim rov qab ib nrab ntawm cov leeg pob txha laus los ntawm kev kho dua qub NAD ntxiv rau qib. Rejuvenation Res. 2014 Feb; 17(1):62-9.

  32. Wang X et al. Nicotinamide mononucleotide tiv thaiv -amyloid oligomer-induced cognitive impairment thiab neuronal tuag. Lub hlwb Res. 2016 Jul 15; 1643:1-9

  33. Wei CC et al. NAD ntxiv nrog nicotinamide mononucleotide tiv thaiv cov ntshav-hlwb barrier kev ncaj ncees thiab attenuates qeeb cov ntaub so ntswg plasminogen activator-induced hemorrhagic transformation tom qab cerebral ischemia. Br J Pharmacol. Nov 2017; 174(21):3823-3836

  34. Kev tiv thaiv kev laus hauv kev sim tshuaj tib neeg: puas yuav txhawb nqa NMN qeeb?

  35. Bolotnikova MN. Anti-aging txoj kev. Harvard Magazine. Sept-Oct 2017.

  36. Taylor M. Cov kws tshawb fawb tej zaum yuav nyob ze dua li qhov koj xav tias yog tshuaj tiv thaiv kev laus. Tab sis ceev faj ntawm hype. Kaiser Health Xov Xwm.

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