Trans-Ethnic Mendelian-randomization Study Qhia Txog Kev Sib Raug Zoo Ntawm Cov Txheej Txheem Cardiometabolic Thiab Kab Mob Raum Ⅰ
Nov 28, 2023
Abstract
Keeb kwm: Txoj kev tshawb no yog los ntsuam xyuas seb puas tau tshaj tawm yav dhau los muaj feem cuam tshuam raumob raum mob(CKD) muaj feem cuam tshuam nrog CKD hauv European thiab East Asian poj koob yawm txwv siv Mendelian randomization. Txoj Kev: Tag nrho ntawm 45 yam muaj feem cuam tshuam nrog cov ntaub ntawv caj ces hauv European caj ces thiab 17 qhov kev pheej hmoo ntawm cov neeg Esxias sab hnub tuaj raug txheeb xyuas raws li raug pom los ntawm PubMed. Peb txhaisCKDlos ntawm kev kuaj mob lossis los ntawm kwv yees glomerular pom tus nqi ntawm<60ml/min/1.73 m2. Thaum kawg, 51 672 CKD rooj plaub thiab 958 102 kev tswj hwm ntawm European caj ces los ntawm CKDGen, UK Biobank, thiab HUNT, thiab 13 093 CKD rooj plaub thiab 238 118 kev tswj hwm ntawm East Asian caj ces los ntawm Biobank Nyiv , Tuam Tshoj Kadoorie Biobank thiab Nyiv-Kidney-Biobank/ToMMo tau suav nrog. Cov txiaj ntsig: Yim yam txaus ntshai tau pom cov pov thawj ntseeg tau ntawmua rau muaj teebmeem ntawm CKDnyob rau hauv cov teb chaws Europe, suav nrog genetic kwv yees lub cev lojQhov ntsuas (BMI), ntshav siab,systolic ntshav siab, high-density lipoprotein cov roj cholesterol, apolipoprotein AI, lipoprotein (a), ntshav qab zib hom 2 (T2D) thiab nephrolithiasis. Hauv East Asians, BMI, T2D, thiab nephrolithiasis tau pom cov pov thawj ntawm causality ntawm CKD. Hauv ob qhov kev tshuaj ntsuam xyuas kev ywj pheej, peb tau pom tias muaj kev pheej hmoo siab kub siab tau pom cov pov thawj txhim khu kev qha ntawm qhov ua rau muaj kev pheej hmoo ntawm CKD hauv cov neeg nyob sab Europe tab sis qhov sib txawv, pom qhov cuam tshuam tsis zoo hauv East Asians. Txawm hais tias kev lav phib xaub rau T2D pomcov teebmeem zoo ib yam ntawm CKD, the effects of glycaemic phenotypes on CKD were weak. Non-linear Mendelian randomization indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI of >25 kg / m2.
Cov ntsiab lus xaus: Yim yam kev pheej hmoo cardiometabolic pom qhov ua rau muaj kev cuam tshuam rau CKD hauv cov neeg European thiab peb ntawm lawv tau pom tias muaj kev phom sij hauv East Asians, muab kev nkag siab txog kev tsim cov kev cuam tshuam yav tom ntej los txo lub nra ntawm CKD.
Ntsiab lus:mob raum mob, cardiometabolic txaus ntshai yam, Mendelian randomization, kev ua txhaum, kev kawm trans-ethnic
CISTANCHE EXTRACT nrog 25% ECHINACOSIDE thiab 9% ACTEOSIDE rau raum kab mob
Cov lus tseem ceeb
• Qhov kev tshawb nrhiav caj ces loj no tau pom cov pov thawj muaj txiaj ntsig los txhawb lub luag haujlwm ua rau muaj yim yam kab mob cardiometabolic txaus ntshai ntawm cov kab mob raum ntev (CKD) ntawm cov neeg European thiab peb ntawm cov kev pheej hmoo no tau ua rau cov neeg Esxias sab hnub tuaj. • Kev sib piv ntawm haiv neeg txawv teb chaws qhia tias kev kub ntxhov tau pom muaj lub luag haujlwm tseem ceeb ntawm CKD hauv cov neeg European tab sis tsis muaj lub luag haujlwm tseem ceeb hauv East Asians.
• Cov pov thawj caj ces tau qhia tias mob ntshav qab zib hom 2 tuaj yeem muaj cov piam thaj tsis txaus ntseeg los cuam tshuam CKD.
• Txoj kev tshawb no qhia txog qhov tseem ceeb ntawm kev tswj cov kab mob plawv thiab CKD uas yog ib qho kev cuam tshuam los txo lub nra ntawm ob yam kab mob.
Taw qhia
Mob raum mob(CKD) cuam tshuam txog 10-15% ntawm cov pejxeem thoob ntiaj teb. Nws muaj kev cuam tshuam loj rau kev noj qab haus huv thoob ntiaj teb, ob qho tib si ua rau muaj kev mob tshwm sim thiab kev tuag thiab ua ib qho teeb meem tseem ceeb rau cov kab mob cardiometabolic.1-3 Txij xyoo 1990 txog 2017, lub ntiaj teb hnub nyoog-tus qauv kev tuag rau ntau yam kab mob tseem ceeb tsis sib kis tau poob qis. . Piv txwv li, cov kab mob plawv tuag tau raug txo los ntawm 30.4%. Txawm li cas los xij, kev tuag poob rau CKD tsuas yog 2.8% xwb 4 Feem ntau ntawm cov kev sim cuam tshuam tau tsom mus rau kev kho mob ntau dua li kev tiv thaiv thawj. Hauv cov ntaub ntawv, cov piam thaj tsis txaus, ntshav siab thiab siab lub cev qhov ntsuas (BMI) yog ib qho ntawm cov kev pheej hmoo ua rau CKD. Txawm li cas los xij, txawm tias muaj kev cuam tshuam uas twb muaj lawm rau cov kev pheej hmoo no, lub nra ntawmCKDtseem tsis tau poob qis raws li qhov xav tau.4 Ntxiv mus, kev paub txog CKD tsuas yog txwv rau cov pej xeem thiab cov neeg saib xyuas kev noj qab haus huv. Yog li, ib qho kev ntsuam xyuas zoo ntawm qhov kev txiav txim siab ntawm CKD yog qhov xav tau sai sai los txhawb kev hloov pauv ntawm kev kho mob.CKDcov neeg mob rau kev tiv thaiv kab mob hauv cov pab pawg muaj kev pheej hmoo siab.
Kev tsim qauv zoo-tswj kev sim (RCTs) feem ntau yog txoj hauv kev zoo tshaj plaws rau kev kwv yees kev sib raug zoo ntawm qhov muaj feem pheej hmoo thiab kab mob. Txawm li cas los xij, ntau qhov kev tshawb fawb tau txheeb xyuas qhov muaj feem cuam tshuam rau kev nce qib ntawm CKD, tsis muaj pov thawj ntseeg tau los txhawb lawv lub luag haujlwm ua rau ntawm CKD tshwm sim. Mendelian randomization (MR) yog ib txoj hauv kev sib kis uas tuaj yeem siv tau kom tau txais cov pov thawj txog qhov tshwm sim ntawm kev hloov pauv kev cuam tshuam cov hom phiaj.5 MR siv cov kev faib tawm ntawm cov noob caj noob ces ntawm kev xeeb tub thiab yog li ntawd, tsis tshua muaj kev cuam tshuam rau kev ntxhov siab thiab thim rov qab causality dua li ib txwm muaj. kev soj ntsuam kev tshawb fawb. Kev muaj peev xwm nce ntxiv ntawm cov khoom siv caj ces-kev koom ua ke muab lub sijhawm rau kev sim cov txiaj ntsig ntawm ntau yam kev pheej hmoo ntawm CKD.6,7
In this study, we aimed to investigate the causal effects of 45 previously reported risk factors on CKD using twosample linear and non-linear MR approaches. We used the largest available genome-wide association studies (GWASs) for risk factors in European and East Asian ancestries. Summary data for CKD and estimated glomerular filtration rate (eGFR) were obtained from >1 lab tus neeg tuaj koom los ntawm CKDGen consortium, 8 UK Biobank, 9 Trøndelag Health (HUNT) Txoj Kev Kawm, 10 Biobank Nyiv, 11 Tuam Tshoj Kadoorie Biobank12 thiab Nyiv-Kidney Biobank/ToMMo consortium.
Cov txheej txheem
Cov ntaub ntawv, cov txheej txheem tshuaj xyuas, thiab cov ntaub ntawv kawm yuav muab rau lwm tus kws tshawb fawb rau lub hom phiaj ntawm kev tsim cov txiaj ntsig. Yog xav paub ntxiv, cov ntaub ntawv kev sib txuas ntawm caj ces ntawm cov kev pheej hmoo raug xaiv muaj nyob rau hauv Cov Lus Qhia Ntxiv (muaj raws li cov ntaub ntawv ntxiv ntawm IJE online). GWAS cov ntaub ntawv sau tseg rau CKD thiab eGFR uas tau tsim los siv UK Biobank thiab CKDGen cov ntaub ntawv muaj los ntawm MRC-IEU OpenGWAS database (https://gwas.mrcieu.ac.uk/) thiab CKDGen lub vev xaib (http://ckdgen. imbi.uni-freiburg.de/) raws. GWAS tau los ntawm HUNT, Biobank Nyiv, Tuam Tshoj Kadoorie Biobank thiab Nyiv-Kidney Biobank/ToMMo tuaj yeem nkag mus tau los ntawm kev thov rau cov ntaub ntawv tuav. Cov ntawv analytical ntawm MR tsom xam ua nyob rau hauv txoj kev tshawb no muaj nyob rau ntawm GitHub repository ntawm 'TwoSampleMR' R pob (https://github.com/ MRCIEU/TwoSampleMR/).
Daim duab 1 Kev kawm tsim ntawm trans-ethnic Mendelian-randomization kawm txog kab mob raum ntev
Kawm tsim qauv
Peb txoj kev tshawb fawb muaj plaub yam (Daim duab 1). Ua ntej, peb tau txheeb xyuas 45 yam muaj feem cuam tshuam rau CKD los ntawm kev tsuas PubMed. Thib ob, peb tau kwv yees qhov tshwm sim ntawm cov teeb meem kev pheej hmoo ntawm CKD thiab eGFR hauv CKDGen, 8 UK Biobank, 9 HUNT Study, 10 Biobank Nyiv, 11 Tuam Tshoj Kadoorie Biobank12 thiab Nyiv-Kidney-Biobank/ToMMo consortium cais. Thib peb, peb tau soj ntsuam cov kev tshawb pom raws li lub zog thiab qhov sib xws ntawm cov pov thawj thoob plaws MR txoj hauv kev thiab thoob plaws cov kev tshawb fawb ntawm tus kheej. Thaum kawg, peb tau ua cov kev soj ntsuam xyuas kom paub tseeb tias qhov kev tshawb pom ntawm cov ntshav siab, glycemic, thiab ntshav lipid phenotypes ntawm CKD. Thaum kawg, tsis yog-linear MR tau ua los kwv yees qhov pom zoo BMI thiab ceev cov piam thaj kom txo qis CKD kev pheej hmoo hauv UK Biobank thiab HUNT Study.
Kev xaiv cov xwm txheej pheej hmoo CKD raug txheeb xyuas los ntawm kev tshuaj xyuas cov ntaub ntawv siv MELODI-Presto13,14 los tshawb nrhiav PubMed database (Cov Lus Qhia Ntxiv S1, muaj nyob rau hauv cov ntaub ntawv ntxiv ntawm IJE online). Peb tau txheeb xyuas 45 yam kev pheej hmoo rau CKD, suav nrog cov ntshav siab phenotypes, glycemic phenotypes, lipid phenotypes, rog rog, haus luam yeeb, haus dej cawv, pw tsaug zog tsis zoo, nephrolithiasis, serum uric acid, kab mob plawv, cov pob txha pob txha pob txha ntom ntom, homocysteine , C- , micro-nutrient phenotypes (serum hlau thiab vitamins), lub cev qhuav dej thiab cov thyroid phenotypes. Los ntawm kev tshawb nrhiav qhov loj tshaj plaws muaj GWASs (kom paub meej qhov tsawg kawg nkaus tus qauv sib tshooj nrog cov txiaj ntsig cov qauv), peb tau rho tawm cov noob caj noob ces cuam tshuam nrog tag nrho 45 qhov muaj feem cuam tshuam los ntawm European kev tshawb fawb poj koob yawm txwv thiab muab rho tawm 17 ntawm 45 qhov muaj feem cuam tshuam los ntawm East Asian cov kev tshawb fawb txog poj koob yawm txwv (Table Ntxiv S1 thiab Ntxiv. Nco tseg S1, muaj raws li cov ntaub ntawv ntxiv ntawm IJE online). Txhawm rau xaiv cov noob caj noob ces ywj pheej, cov genome-wide tseem ceeb ib leeg-nucleotide polymorphism (SNPs) tau muab faib ua pawg los ntawm kev sib txuas tsis sib xws (LD) (r 2.<0.001 for SNPs within 1 Mb genomic region) and the SNP with the lowest P-value per group was retained (Supplementary Tables S2 and S3, available as Supplementary data at IJE online).
Kev sib koom ua ke ntawm cov noob caj noob ces nrog CKD thiab eGFR
Hauv UK Biobank, 9 HUNT Study10, thiab Tuam Tshoj Kadoorie Biobank, 12 CKD tau txhais raws li International Classification of Diseases (ICD) 10th Revision. Cov xwm txheej CKD tau txhais tias yog cov neeg koom nrog ICD 10 code N18. Cov neeg koom nrog txhua yam mob raum (N00 rau N29) raug tshem tawm los ntawm kev tswj hwm kom txo tau qhov muaj peev xwm suav nrog CKD cov teeb meem hauv pawg tswj hwm. Hauv Nyiv-Kidney-Biobank/ToMMo consortium, CKD tau txhais tias yog eGFR ntawm<60 ml/min/ 1.73 m2 and/or the presence of urine abnormality, which is similar to the clinical diagnosis for CKD. In CKDGen8 and Biobank Japan,11 CKD was defined as eGFR of <60 ml/min/1.73 m2 . In all studies, eGFR was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.15 The genetic associations with CKD and eGFR were reported in three studies of European ancestry (CKDGen: 41 395 cases, 439 303 controls, 8.7% diabetes patients; UK Biobank: 6985 cases, 454 323 controls, 5.2% with diabetes; and HUNT Study: 3292 cases, 64 476 controls, 4.9% with diabetes). The genetic associations with CKD were reported in three East Asian studies (Biobank Japan: 8586 cases, 133 808 controls, 10.2% with diabetes; China Kadoorie Biobank: 461 cases, 94 887 controls, 6.7% with diabetes; Japan-Kidney-Biobank/ToMMo consortium: 4046 cases, 9423 controls, 7.3% with diabetes) and eGFR genetic associations were reported in Biobank Japan (Supplementary Table S4 and Supplementary Note S2, available as Supplementary data at IJE online). All participants included in the CKDGen,8 UK Biobank,9 HUNT,10 Biobank Japan,11 China Kadoorie Biobank12 and Japan-Kidney-Biobank/ToMMo provided written informed consent and studies were approved by their local research ethics committees and institutional review boards as applicable.
Kev txheeb cais
MR yog ib txoj hauv kev sib txawv uas siv cov noob caj noob ces ua cov cuab yeej los ntsuas qhov kev sib raug zoo ntawm qhov raug (piv txwv li BMI) thiab qhov tshwm sim (xws li CKD) thiab yuav tsum muaj peb qhov kev xav kom txaus siab (Cov Duab Ntxiv S1 thiab Cov Lus Qhia Ntxiv S3, muaj raws li Cov ntaub ntawv ntxiv ntawm IJE online). Rau binary exposures [xws li hom 2 mob ntshav qab zib mellitus (T2D)], peb hloov qhov sib txawv ntawm qhov sib txawv (ORs) [multiplying log(ORs) los ntawm log (2) (sib npaug rau 0.693) thiab ces exponentiating] thiaj li sawv cev LOSSIS ntawm qhov tshwm sim ib ob npaug ntawm qhov sib txawv ntawm qhov raug rau qhov raug.16,17
Qhov kev kwv yees MR rau txhua qhov kev pheej hmoo raug txiav txim siab siv qhov ntsuas qhov sib txawv ntawm qhov sib txawv (MR-IVW), uas siv cov txiaj ntsig ntawm qhov ntsuas qhov ntsuas qhov sib txawv los ua ke ntawm Wald piv kwv yees 18 ntawm cov txiaj ntsig tau los ntawm txhua qhov kev sim SNPs. Cov txheej txheem ntawm kev tshuaj ntsuam rhiab heev, suav nrog MR-Egger, 19 MR qhov hnyav nruab nrab, 20 MR hom kwv yees 21 thiab kev xeem heterogeneity, 22 tau ua los ntsuas cov kev xav hauv MR. Peb kuj tau tshuaj xyuas qhov muaj peev xwm rov qab los ntawm kev siv bidirectional MR23 thiab siv ntau qhov sib txawv MR kev tshuaj ntsuam ntawm cov phenotypes sib raug zoo (Cov Lus Qhia Ntxiv S4, muaj raws li cov ntaub ntawv ntxiv ntawm IJE online). Ib tug conservative Bonferroni-kho qhov pib (a ¼ 1.11 10–3, raws li 45 qhov kev pheej hmoo raug soj ntsuam) tau siv los suav rau ntau qhov kev xeem. Cov Lus Qhia Ntxiv S5 (muaj raws li cov ntaub ntawv ntxiv ntawm IJE online) qhia txog qhov ntsuas lub zog kwv yees20 thiab kev suav lub zog.24,25 Cov MR thiab kev soj ntsuam rhiab heev tau ua los ntawm TwoSampleMR pob.26
Ua raws li
MR tshuaj ntsuam xyuas txhawm rau txheeb xyuas cov qauv sib txawv ntawm cov ntshav siab thoob plaws cov poj koob yawm txwv, peb tau ua cov txheej txheem kev soj ntsuam raws li nram no: (i) los kwv yees qhov muaj peev xwm cuam tshuam ntawm ntsuas qhov loj me thiab qhov tshwm sim lub zog ntawm MR kev tshuaj ntsuam, peb tau ua tshiab East Asian GWASs ntawm ntshav siab (N mob ¼ 40 318, N tswj¼ 60 323),systolic ntshav siab(SIB),diastolic ntshav siab(DBP) thiabmem tes siab(PP) hauv 100 641 Tuam Tshoj Kadoorie Biobank koom. Los ntawm kev rho tawm cov cuab yeej tshuaj caj ces los ntawm GWASs uas muaj zog, peb ntxiv dag zog lub zog ntsuas (F-statistics) ntawm kev kub siab los ntawm 275.19 txog 330.85 (Table Ntxiv S3, muaj nyob rau hauv cov ntaub ntawv ntxiv ntawm IJE online). Siv cov ntaub ntawv no ua cov cuab yeej, peb tau ua qhov kev lees paub MR ntawm cov ntshav siab phenotypes thiab CKD hauv peb qhov kev tshawb fawb East Asian; (ii) rau European SBP thiab DBP cov cuab yeej, peb tau tshuaj xyuas seb lawv cov kev sib txuas caj ces puas tau rov ua dua hauv East Asian GWASs.27 Peb mam li siv cov SNPs ntawm SBP thiab DBP (Supplementary Table S5, muaj raws li cov ntaub ntawv ntxiv ntawm IJE online) rau ua qhov thib ob validation MR (saib raws li European variant þ East Asian nyhuv tsom xam); (iii) peb piv cov kev taw qhia ntawm cov nyhuv thiab cov heterogeneity ntawm cov noob caj noob ces los ntawm kev kub siab nyob rau hauv cov Europeans thiab East Asians siv khub-wise Z xeem thiab khiav rhiab heev MR tsom xam kom tshem tawm cov cuab yeej nrog heterogeneity.
Txhawm rau kom nkag siab zoo dua cov txheej txheem kev sib txuas ntawm T2D nrog CKD, plaub qhov kev tshuaj ntsuam MR ntxiv tau ua: (i) peb tau lees paub qhov cuam tshuam ntawm yim glycemic phenotypes ntawm CKD siv Steiger filtering28 thiab radial MR; 29 (ii) peb tau txiav txim siab qhov cuam tshuam ntawm caj ces lub luag haujlwm. rau hom 1 mob ntshav qab zib mellitus (T1D)30 (Table Ntxiv S2, muaj raws li cov ntaub ntawv ntxiv ntawm IJE online) ntawm CKD; (iii) cov neeg koom nrog kev ntsuas eGFR tau stratified rau cov neeg mob ntshav qab zib (N ¼ 11 529) thiab cov neeg tsis muaj ntshav qab zib (N ¼ 118 460) 31 thiab peb tau ua MR tshuaj ntsuam xyuas ntawm T2D thiab tsib glycemic phenotypes ntawm eGFR hauv cov no. ob subpopulation; (iv) mob ntshav qab zib retinopathy tau suav nrog ua qhov txiaj ntsig zoo los tswj xyuas qhov kev tshuaj ntsuam xyuas. Cov cuab yeej siv rau T2D thiab glycemic phenotypes tau siv los ua qhov tshwm sim, thaum CKD cov ntaub ntawv los ntawm CKDGen, UK Biobank, thiab HUNT nrog rau cov ntaub ntawv mob ntshav qab zib retinopathy los ntawm UK Biobank SAIGE tso tawm 32 tau siv los ua cov txiaj ntsig (Table Ntxiv S4, muaj raws li cov ntaub ntawv ntxiv ntawm IB online).
Txhawm rau txheeb xyuas qhov kev tshawb pom MR ntawm lipids ntawm CKD, cov kev soj ntsuam hauv qab no tau ua: (i) txhawm rau txheeb xyuas cov qib siab lipoprotein cholesterol (HDL-C) MR cov txiaj ntsig hauv East Asians, peb tau ua tib yam European sib txawv þ East Asian nyhuv tsom xam txhawm rau txhawb lub zog ntawm MR kev tshawb pom (HDL-C cov ntaub ntawv los ntawm Spracklen li al.33) (Cov Lus Qhia Ntxiv S5, muaj raws li cov ntaub ntawv ntxiv ntawm IJE online); (ii) peb tau sim cov nyhuv independent ntawm HDL-C thiab apolipoprotein AI ntawm CKD siv ntau tus qauv MR (Cov Lus Qhia Ntxiv S4, muaj raws li cov ntaub ntawv ntxiv ntawm IJE online); (iii) peb kwv yees cov txiaj ntsig ntawm kev ncig cov roj cholesterol hloov pauv cov protein ntau theem 34 ntawm CKD (Table Ntxiv S2, muaj raws li cov ntaub ntawv ntxiv ntawm IJE online); (iv) muab cov lipoprotein(a) qib rau qhov ruaj khov apolipopro tein(a) isoform loj yuav txawv, peb kwv yees cov nyhuv ntawm apolipoprotein(a) isoform loj ntawm CKD [lipoprotein(a) KIV2 rov ua dua thiab apolipoprotein(a) protein isoform cov ntaub ntawv loj los ntawm Saleheen li al.35] (Table Ntxiv S2, muaj raws li cov ntaub ntawv ntxiv ntawm IJE online).
Thaum kawg, rau BMI thiab yoo mov qabzib, ib txoj hauv kev feem ntau polynomial 36-38 tau siv los kwv yees cov duab tsis zoo ntawm kev sib koom ntawm cov kev pheej hmoo thiabCKDsiv cov ntaub ntawv los ntawm UK Biobank thiab HUNT (Cov Lus Qhia Ntxiv S6, muaj raws li cov ntaub ntawv ntxiv ntawm IJE online).
Kev soj ntsuam ntawm MR pov thawj
Cov kev tshawb fawb yav dhau los tau qhia tias P-value thresholds yuav tsum tsis yog tib txoj hauv kev los txhais 'qhov tseem ceeb'.39,40,41 Peb, yog li ntawd, ntsuas MR pov thawj siv peb yam: (i) MR pov thawj lub zog: seb qhov kev kwv yees MR-IVW ntawm txhua qhov kev pheej hmoo dhau ntawm Bonferroni-kho P-tus nqi pib (P < 1.1 10–3) hauv tsawg kawg ib txoj kev tshawb fawb thiab dhau qhov kev hloov pauv (P < 0.05) hauv tsawg kawg ib qho kev kawm; (ii) haum ntawm MR kev xav: seb qhov MR kwv yees rau txhua qhov kev pheej hmoo pom tau zoo ib yam ntawm cov kev cuam tshuam thoob plaws MR rhiab heev tsom xam thiab pom qhov txwv tsis pub muaj kev cuam tshuam ntawm kab rov tav pleiotropy siv MR-Egger cuam tshuam lub sij hawm thiab heterogeneity test; (iii) seb qhov kev taw qhia ntawm MR cuam tshuam ntawm txhua qhov kev pheej hmoo ntawm CKD tau zoo ib yam nyob rau ntau qhov kev tshawb fawb. Daim duab 1 qhia tau hais tias yuav ua li cas cov pov thawj MR raug soj ntsuam hauv cov neeg European thiab cov neeg Esxias sab hnub tuaj sib cais: 'cov pov thawj ntseeg tau' yog hais txog cov xwm txheej txaus ntshai uas ua tiav tag nrho peb cov qauv, qhov 'Cov pov thawj tsis muaj zog' yog hais txog cov xwm txheej pheej hmoo uas tsis ua tiav tag nrho cov qauv (xws li MR. kwv yees nrog cov ntaub ntawv pov thawj MR muaj zog tab sis nrog cov kev taw qhia tsis sib xws).
Supportive Service Ntawm Wecistanche-Qhov loj tshaj plaws cistanche exporter nyob rau hauv Tuam Tshoj:
Email: wallence.suen@wecistanche.com
Whatsapp / Tel: +86 15292862950
Khw Muag Khoom Kom Paub Ntxiv Specifications:
https://www.xjcistanche.com/cistanche-shop
