Ntxiv Cheebtsam C1q Raws li Lub Taub Hau Kev Ntsuas Cov Cuab Yeej Rau Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Subtyping

Abstract:Keeb Kwm: Kev ntsuas ntshav niaj hnub yog siv hauv tsev kho mob los kuaj mobkab mob los yog paub meej tias tib neeg txoj kev noj qab haus huv. Rau myalgic encephalomyelitis / mob nkeesSyndrome (ME/CFS), ib tus kab mob tsuas yog nyob ntawm cov tsos mob ntawm kev kuaj mob rau nws qhov kev kuaj mob, ntshavanalytics tsuas yog ua haujlwm los txiav txim rau cov xwm txheej hauv qab uas ua rauexerting qaug zog. Txawm li cas los xij, kev tshawb fawbntsuam xyuas cov ntaub ntawv ntshav ua kom tiav thiab loj los ntawm cov txheej txheem sib xyaw ua ke los ua pov thawj ME / CFStej yam xwm txheej los yog ntes/ txheeb xyuas cov pab pawg pawg tseem tsawg.

Txoj kev:Txoj kev tshawb no tau siv tsis muaj kev ncaj nceeshierarchical pawg tsom xam ntawm ib pawg loj ntawm 250 ua tib zoo phenotyped poj niam ME / CFS mob

mus tshawb nrhiav qhov muaj peev xwm no. Cov txiaj ntsig: Cov txiaj ntsig tau qhia peb cov tsos mob raws li pawg, caisraws li qhov hnyav, nruab nrab, thiab me me, nthuav tawm qhov sib txawv tseem ceeb (p < 0.05)="" in="" five="" blood="">

Kev npaj txhij txog txoj kev tshawb fawb kuj tau qhia txog qib siab ntawm kev sib txuas ntxiv C1q hauv 107/250(43 feem pua) ntawm cov neeg koom, muab C1q ua ib qho tseem ceeb molecule los txheeb xyuas ME / CFS subtype / subgroupnrog cov tsos mob tshwm sim tshwm sim.

Cov lus xaus:Cov txiaj ntsig tau txais muaj qhov cuam tshuam tseem ceebrau kev tshawb fawb ntawm ME / CFS etiology thiab, feem ntau yuav, rau kev siv cov kev kuaj mob yav tom ntejcov txheej txheem thiab kev kho mob ntawm ME / CFS hauv tsev kho mob.

Ntsiab lus:myalgic encephalomyelitis;chronic fatigue syndrome; c1q; ib. complement system; ntshavkev tsom xam; kuaj mob; cov tsos mob; kev txheeb xyuas pawg

Nyem qhov no kom paub ntau ntxiv txog CFS thiab kev tiv thaiv kev qaug zog

1. Taw qhiaMyalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS) yog ib qho mob hnyav.teeb meem kev noj qab haus huv uas truncates lub neej ntawm lab tus tib neeg thiab lawv tsev neeg nyob ib ncig ntawm lubntiaj teb. ME / CFS yog ib qho mob ntev uas tshwm sim los ntawm kev qaug zog heev uasyog exacerbated los ntawm lub cev / lub hlwb thiab kev xav (tseem hu ua PEM; post-exertionalmalaise), tsis muaj kev pw tsaug zog thiab dysautonomia, thiab ntau yam ntxivcomorbidities; nws qhov kev kuaj mob tseem tsuas yog nyob ntawm kev soj ntsuam cov tsos mobtom qabtxiav txim tawm tej yam mob uas yuav piav tau rau tus neeg mob´s cov tsos mob.Txawm hais tias muaj ntau cov kev tshawb fawb tsom los ua pov thawj cov kev kuaj mob niaj hnub uas tuaj yeem ua taumuaj txiaj ntsig, yam tsawg kawg rau qhov kev tsis txaus siab ntawm ME / CFS rooj plaub, ob peb qhov sib txawv muajtau qhia. Piv txwv li, Nacul et al. pom tau qhov tseem ceeb qis nruab nrab ntawmSerum creatine kinase (CK) hauv cov neeg mob hnyav piv rau kev noj qab haus huv tswj (HCs)thiab tsis hnyav ME/CFS (qhov nruab nrab=54, 101.5, thiab 84 U/L, feem) [9], kev nrhiavtau lees paub los ntawm ob qhov kev tshawb fawb ntxiv. Thaum CK qhov sib txawv tuaj yeem muab tau los ntawmtus neeg mob sedentarism nws tus kheej, qee qhov muaj peev xwm sib txawv, suav nrog qib alkalinephosphatase, dawb T4 qib, lossis eosinophil suav, raug kuaj pom ntawm qhov tseem ceeb (p < 0.1)="" in="">pawg me me (n = 15/pab)tsim nyog tshawb nrhiav ntxiv hauv cov pab pawg loj dua, tus kheejlos yog ua ke nrog lwm tus.Cov ntshav yam hloov pauv hloov pauv hauv ME / CFS cov pab pawg yuav ua rau muaj txiaj ntsigcov cuab yeej hauv tsev kho mob kom ua tiav cov kev kho mob zoo dua qub, tshwj xeeb tshaj yog rau qhov tseebcov hom phiaj tshuaj, thaum lawv kuj tseem tuaj yeem pab txo tus neeg mob heterogeneity hauv kev tshawb fawbkev kawm. Kev nthuav tawm qhov xwm txheej ntawm ME / CFS, qhov tseeb, yuav zoo nyob ntawm homogeneousKev ntsuam xyuas tus neeg mob subset, boosting statistical robustness ntawm cov ntaub ntawv.Yog li ntawd, nyob rau hauv txoj kev tshawb no tam sim no, peb tsom rau kev txheeb xyuas cov kev kho mob uasSib txawv ME / CFS cov ntaub ntawv pab pawg los ntawm lawv tus kheej lossis cuam tshuam rau cov tsos mob hnyav,nyob rau hauv ib pawg loj ntawm poj niam ME / CFS cov ntaub ntawv (n = 250), muaj peev xwm kho tau thiab/los yoglub hom phiaj tshawb fawb.

2. Cov ntaub ntawv thiab cov txheej txheem

2.1. Cov neeg koom nrog

Nyob rau hauv qhov kev soj ntsuam no, ib-center, cross-sectional cohort kawm, tag nrho ntawm 250 poj niamnrog ME/CFS tau raug xa mus rau lub chaw saib xyuas tertiary rau kev soj ntsuam kuaj moblos ntawm ME / CFS tus kws kho mob tshwj xeeb (Vall d'Hebron University Tsev Kho Mob, Barcelona,Spain) thaum lub Peb Hlis 2017 thiab Kaum Ob Hlis 2019. Cov neeg koom nrog tau raug caw tom qab tsim nyogtau lees paub. Cov txheej txheem suav nrog suav nrog cov poj niam laus neeg ua tiav xyoo 1994CDC/Fukuda txhaisthiab 2003 Canadian Consensus Criteria for ME/CFS. 

Cov neeg koom nrograug cais tawm yog tias lawv tau kuaj pom yav dhau los muaj mob hnyav lossiscomorbid kab mob uas tuaj yeem cuam tshuam nrog lawv cov tsos mob. Cov neeg koom pub dawb acov ntshav kuaj rau niaj hnub kuaj ntshav, ua tiav cov lus nug uas tau lees paub,thiab muab cov ntaub ntawv pej xeem thiab cov yam ntxwv kho mob thaum lub sijhawm lawv suav nrog hauvtxoj kev kawm.Cov txheej txheem kawm tau raug tshuaj xyuas thiab pom zoo raws li cov lus pom zoolos ntawm Pawg Neeg Saib Xyuas Kev Tshawb Fawb Hauv Nroog (Vall d'Hebron UniversityTsev Kho Mob, Barcelona, ​​Spain; IRB raws tu qauv: CEIC/PR-AG-VITAE-2015, pom zoonyob rau lub Rau Hli 2015).

Txhua tus neeg mob tau txais kev tso cai sau ntawv kos npe rau kev pom zoo ua ntejlos kawm txog kev koom tes, raws li cov lus qhia ntawm Kev Tshaj Tawm ntawm Helsinki thiab hauvua raws li cov kev cai Spanish tam sim no ntawm kev tshawb fawb soj ntsuam thiab cov qauv ntawm EUkev kho mob zoo.

2.2. Kev ntsuas

Cov neeg koom nrog tau hais kom ua tiav qhov kev ntsuas tus kheej tau tshaj tawm cov txiaj ntsig raws li cov tsos mobcov cuab yeej ntsuas. Cov kev ntsuas tau piav qhia hauv qab no yog siv los ntsuas txhua tus neeg koomnyob rau hauv kev saib xyuas ntawm ob tug kws tshawb fawb (JC-M. thiab JA), uas saib xyuas cov neeg koomkev ua raws cai.

2.2.1. Fatigue Impact Scale

Fatigue Impact Scale (FIS-40) yog 40- daim ntawv nug uas tsim los ntsuas kev qaug zogcov tsos mob raws li ib feem ntawm tus mob nyob rau hauv lub mob. Nws suav nrog peb tus thawj saib xyuaskev xav ntawm qaug zog: lub cev (10 yam), kev txawj ntse (10 yam), thiab kev puas siab puas ntswskev ua haujlwm (20 yam khoom). Txhua yam khoom tau qhab nia ntawm xoom (tsis muaj kev qaug zog) mus rau plaub (kev qaug zog hnyav). Covtag nrho cov qhab nia yog xam los ntawm kev ntxiv ua ke cov lus teb rau 40 cov lus nug (nrog raulos ntawm 0 mus rau 160 ntsiab lus). Cov qhab nia siab dua qhia tias muaj kev txwv ntau dua vim kev qaug zog.

2.2.2. Composite Autonomic Symptom Score

Rau kev ntsuas kev ua haujlwm tsis raug cai, txhua tus neeg koom tau raug tshuaj xyuas siv CompositeAutonomic Symptom Score (COMPASS-31), ib yam khoom 31-refined thiab abbreviateddaim ntawv nug tsim los ntsuas qhov zaus thiab qhov hnyav ntawm kev ua haujlwm autonomicCov tsos mob, muab faib ua rau lub npe: orthostatic intolerance (plaub yam), vasomotor (peb.khoom), secretomotor (plaub yam), plab hnyuv (12 yam), zais zis (3 yam), thiabpupillomotor cov tsos mob (tsib yam khoom). Ntxiv ua ke, rau cov qhab nia sau npe muab atag nrho COMPASS{{0}} qhab nia xws li 0 txog 100 cov ntsiab lus. Cov qhab nias siab dua qhia tias hnyav duaautonomic kev tsis txaus siab.

2.2.3. Pittsburgh Pw tsaug zog zoo Index

Pittsburgh Pw tsaug zog zoo Index (PSQI) yog ib qho 19- daim ntawv nug tus kheejFeem ntau siv los ntsuas kev pw tsaug zog tsis zoo nyob rau hauv ib lub sijhawm 1- hli. Cov qhab nias yogtau txais ntawm txhua ntawm xya lub ntsiab ntawm kev pw tsaug zog zoo: kev pw tsaug zog zoo, pw tsaug zoglatency, pw tsaug zog ntev, ib txwm pw tsaug zog efficiency, pw tsaug zog cuam tshuam, siv tshuaj tsaug zog, thiab kev ua haujlwm ntev ntev. Txhua tus sau tau qhab nia ntawm xoom mus rau peb (zero=tsisteeb meem thiab peb {{0}} teeb meem loj). Tag nrho PSQI cov qhab nia nyob ntawm 0 txog 21 cov ntsiab lus,nrog cov qhab niaNtau dua lossis sib npaug5 qhia tias pw tsaug zog tsis zoo.

2.2.4. Short-Form-36 Kev Tshawb Fawb Txog Kev Noj Qab Haus Huv

SF-36 Daim Ntawv Tshawb Fawb Txog Kev Noj Qab Haus Huv, ib qho kev ntsuas dav dav uas qhia txog kev noj qab haus huvprofile, tau siv los ntsuas lub neej zoo. SF-36 muaj 36 nqe lus nug uas tshawb nrhiavyim qhov ntev ntawm kev noj qab haus huv (lub cev ua haujlwm, lub luag haujlwm txwv vim kev noj qab haus huv ntawm lub cev,mob lub cev, kev noj qab haus huv, kev loj hlob, kev ua haujlwm hauv zej zog, lub luag haujlwm ntawm kev xav, thiab kev mob hlwb),nrog rau ob lub subscales dav dav npog lub cev thiab lub hlwb noj qab haus huv. 

2.3. Kev sau ntshav thiab ua tiav

Cov ntshav kuaj tau sau los ntawm venipuncture tom qab 12 teev yoo mov tam sim ntawdCov kev kuaj sim niaj hnub los ntawm ib tus kws saib xyuas kev tshawb fawb txog kev paub dhau los ntawm ME / CFS qhov chaw kho mob sab nraud(Vall d'Hebron University Tsev Kho Mob, Barcelona, ​​Spain). Cov ntshav tau xa mus raucov tub ntxhais kawm hauv zos hauv tsev kho mob hauv 2 teev ntawm kev sau thiab tshuaj xyuas txuas ntxiv.Standard HUVH (Vall d'Hebron University Tsev Kho Mob Core Lab, Barcelona, ​​Spain) kuajCov txheej txheem tau siv rau kev sau, thauj thiab ua, thiab kuaj ntshav niaj hnubua raws li cov txheej txheem kev khiav hauj lwm (SOPs).

2.4. Ntshav Analytics

Cov kev sim hauv paus hauv paus tau siv feem ntau kom tsis suav cov tsos mob ntawm ME / CFSntawm lwm yam mob ntsig txog qaug zog. Cov kev kuaj ntshav yoo mov no suav nrog cov ntshav suav tag nrho,erythrocyte sedimentation tus nqi (ESR), platelets, ntshav biochemistry tsis, creatinine,yoo mov qabzib, urea, uric acid, bilirubin, kuaj electrolyte (sodium, potassium, calcium),Kev kuaj lub siab ua haujlwm (AST, ALT, ALP, GGT), lipid profile (cholesterol, triglycerides, LDL,HDL), cov thyroid ua haujlwm, vitamin D, immunoglobulin (IgA, IgM, IgG, thiab lawv cov isohom), ntxiv cov proteins (C1 inhibitor, C1q, C3, C4), thiab tshuaj tiv thaiv phospholipid antibodies(cardiolipin, beta{0}}glycoprotein I). Cov qib ntxiv tau ntsuas los ntawm nephelometrysiv BN II System (Siemens Healthcare Headquarters, Erlangen, Lub teb chaws Yelemees). Ib txwmNtau qhov kev siv qib muab los ntawm Vall d'Hebron University Tsev Kho Mob, Barcelona, ​​Spainrau txhua qhov kev kawm sib txawv yog qhia nyob rau hauv Cov Lus Qhia Ntxiv S1.

2.5. Cluster Analysis

Hierarchical pawg tsom xam tau pib siv Ward txoj kevrautxheeb xyuas tus naj npawb ntawm pawg xaiv los ntawm kev txhais lus thiab kev siv tau zoo. Ak-txhais tau hais tias pawg soj ntsuam tau raug coj mus rau muab cov neeg koom rau pawg. Welch covANOVA tau siv rau ntawm qhov sib txawv ntawm kev txaus siab los txheeb xyuas qhov sib txawv ntawm pawg, ua rawslos ntawm kev sib piv sib piv ntawm cov pawg thaum cov kev txheeb xyuas tsis sib xws yog qhov tseem ceeb(p <>

2.6. Statistical Analysis thiab Plotting

Cov ntaub ntawv txuas ntxiv tau pom tias yog txhais tau tias± SD (tus qauv sib txawv). Kev txheeb cais sib txawvtau txiav txim siab siv ob-tailed unpaired Welcht- kuaj. Kev faib tawm ib txwm raug soj ntsuamlos ntawm Shapiro-Wilk normality test. Categorical variables tau nthuav tawm raws lin (%), ib txwmfaib variables tau nthuav tawm raws li qhov txhais tau tias± SD, thiab tsis yog ib txwm faib cov hloov pauvtau nthuav tawm raws li qhov nruab nrab (interquartile range). Qhov sib txawv ntawm pawg tau txiav txim siabtseem ceeb ntawmp Tsawg dua los yog sib npaug0.05. Kev sib txawv tsis sib xws tau raug ntsuas los ntawm qhov yooj yim linear regressiontxoj kev (tsawg-squares mus kom ze). Kev txheeb cais tau ua nrog R 3.6.3, thiabcov duab tau tsim los siv lub pob ggplot2. 

3. Cov txiaj ntsig

3.1. Demographics thiab Clinical yam ntxwv ntawm cov neeg koom

Txoj kev tshawb nrhiav yav tom ntej no suav nrog 250 tus poj niam laus tau kuaj pomME/CFS los ntawm 1994 CDC/Fukuda thiab 2003 CCC, kev soj ntsuam ntawm 69 kuaj ntshavcov kev xeem, cov kev sib txawv ntawm cov pej xeem, thiab plaub daim ntawv nug uas tau lees paub tus kheej tau tshaj tawm los ntsuaskab mob hnyav thiab comorbidities. Tsis tas li ntawd, lub plawv hloov pauv thiab tshuajCov tshuaj tau sau tseg (Table Ntxiv S1). Rooj1 qhia piavparameters ntawm cov neeg koom kev kawm. Qhov nruab nrab hnub nyoog ntawm cov neeg koom yog 45.9± 7,02 y os.11.6 feem pua ​​(29/250) qhia kev rog (BMINtau dua lossis sib npaug30), haum nrog 13 feem pua ​​​​ntawm kev ntsuas rau cov dav davpej xeem, nruab nrab lub plawv dhia yog 78.5± 10.3 bpm, thiab systolic thiab diastolic ntshavsiab yog 125.8± 2.5 thiab 76.3± 1.6, feem, ntawm cov neeg koom. Zuag qhia tag nrhoFIS-40 cov qhab nia ntau tau cuam tshuam txog qhov muaj cov neeg koom nrog qhov sib txawv ntawm kev qaug zoghnyav. Feem coob ntawm cov neeg tuaj koom muaj qhov ua rau qaug zog hnyav (98.8 feem pua) thaum tsuas yog1.2 feem pua ​​​​tau qaug zog me ntsis / nruab nrab, raws li kev soj ntsuam los ntawm FIS-40 daim ntawv nug uas tau muab raucov neeg koom kev kawm. Tsis tas li ntawd, ntau tshaj 50 feem pua ​​​​ntawm cov kev kawm tau txais tsawg kawg yog ntau tshaj ib qhotshuaj raws li ib txwm muaj / kev kho mob niaj hnub (Table1). 

Table 1.Cov pej xeem thiab cov yam ntxwv ntawm kev kho mob ntawm cov neeg koom hauv lub hauv paus. Cov ntaub ntawv raug nthuav tawmraws li lub ntsiab lus± standard deviation (SD) rau qhov sib txawv tsis tu ncua thiab muab piv los ntawm Tub Kawm Ntawvt-test,whereas categorical variables yog muab raws li tus lej nrog feem pua ​​(%) thiab piv los ntawm Fisher'skuaj xyuas.

Cov ntawv luv:BMI, lub cev hnyav index; DPB, diastolic ntshav siab; SBP, systolic ntshav siab; FIS-40, 40- khoomFatigue Impact Scale; COMPASS-31, 31- khoom Composite Autonomic Symptom Score; PSQI, Pittsburgh Pw tsaug zogQhov Performance index; SF-36, 36-Khoom Short-Form Health Survey; NSAIDs, nonsteroidal anti-inflammatory tshuaj.Covbody-mass index (BMI) yog qhov hnyav hauv kilograms muab faib los ntawm square ntawm qhov siab hauv meters.

3.2. Kev Tshawb Fawb Case Cluster Analysis Raws li cov tsos mob

Tom qab siv unbiased hierarchical pawg thiab pom kev pab pawg raws li ktxhais tau hais tias kev tshuaj ntsuam xyuas los txheeb xyuas cov xwm txheej, raws li tau piav qhia hauv Tshooj2, ib pawg ntawm peb pawgqhia qhov sib txawv tseem ceeb hauv lawv tag nrho FIS-40, tag nrho COMPASS-31, tag nrho PSQI, lub cevkev ua haujlwm, thiab cov qhab nia mob ntawm lub cev tau txais (Table2). Plotting ntawm qhov khoomCov qhab-nees sib txawv ntawm tus qauv qhia meej qhia qhov sib txawv ntawm qhov ntsuas ntawmtag nrho FIS-40, tag nrho COMPASS-31, thiab tag nrho PSQI uas ntaus qhab nia siab dua rau qhov hnyav duacov tsos mob thiab SF-36 subscales uas ua qhov opposite. Raws li qhov tshwm sim, peb pawg ntawm 250 tus neeg mobtau muab faib ua pawg 1, suav nrog cov neeg mob uas pom cov tsos mob hnyav dua hauv tag nrho tsibxaiv parameter (n = 94), pawg 2 nrog cov xwm txheej nthuav tawm kev hlub me ntsis (n = 107), thiab ib pawg me ntawm tsuas yog 49 tus neeg uas muaj cov tsos mob me me (pawg 3) (Daim duab1). Qhov no qhia tau hais tias pawg neeg tshawb fawb feem ntau muaj mob hnyav mus rau nruab nrab, nrog<20%>ntawm cov mob me me. Lub ntsiab lus ntawm qhov hnyav hauv pawg 1 suav nrog tag nrho cov qhab nia FIS dhau145 ntawm qhov nruab nrab, cov qhab nia tshaj 65 rau tag nrho COMPASS-31, cov qhab nia tshaj 15 qhov nruab nrab rau PSQI,thiab cov qhab nia qis tshaj plaws rau kev ua haujlwm ntawm lub cev thiab mob lub cev, uas tuaj yeem txhais ua aKev qaug zog hnyav dua phenotype, nrog rau dysautonomia thiab teeb meem pw tsaug zog thaumntsib kev mob ntau dua thiab cuam tshuam lub cev ua haujlwm ntau dua li lwm tusob pawg (Table2, Daim duab1). 

Rooj 2.Clustering ntawm ME / CFS cov ntaub ntawv raws li cov tsos mob sib txawv, raws li kev txhawb nqa los ntawm k-txhais tau tiastsom xam. Cov ntaub ntawv raug nthuav tawm raws li qhov nruab nrab± SD rau txhua yam khoom. Lub cev ua haujlwm thiab mob lub cevraug soj ntsuam los ntawm ob yam khoom ntawm 36- yam luv luv-Form Health Survey (SF-36)

3.3. Cluster-Based Differential Analysis of Blood ParametersTom ntej no, peb ntsuas qhov sib txawv ntawm cov ntshav analytical variables ntawm pebpawg ntawm cov xwm txheej (pawg 1, 2, thiab 3, raws li tau hais tseg saum toj no) siv cov kev txheeb xyuas tsis sib xws (saibTshooj2 kom paub meej). Cov kev ntsuam xyuas tau npaj los txheeb xyuas cov ntshav tsis nyob hauv qhov qubKev siv ntau qhov txiaj ntsig tau nthuav tawm qhov sib txawv tseem ceeb thoob plaws pawg neeg (pawg) thiabYog li ntawd, tej zaum yuav txuam nrog cov tsos mob. Kev txheeb xyuas txheeb xyuas pom tsibntshav tsis ua kom tiav cov kev xav tau, nrogp-values ​​< 0.05 (Table3).

Table 3.Ntshav analytic sib txawv ntawm cov tsos mob raws li cov kab mob. Cov ntaub ntawv tau nthuav tawm raws litxhais tau tias± (SD) rau txhua qhov sib txawv biochemical.

Txawm li cas los xij, thaum saib qhov sib txawv ntawm qhov sib txawv ntawm ib tus khub, pebpom tias tsis muaj ib qho ntawm tsib qhov tsis tuaj yeem sib txawv ntawm pawg 1, 2, thiab3. Rau qib hemoglobin (Hb), tsuas yog pab pawg nruab nrab (cluster 2) sib txawv ntawmLwm qhov ob, kev soj ntsuam nrog kev txhais tsis meej ntawm lub cev. Rau neutrophilsuav (NT), qhov sib txawv ntawm cov mob hnyav (pawg 1) thiab mob me (cluster 3),tab sis tsis muaj leej twg raug kuaj pom rau cov pab pawg nruab nrab. Rau qib roj cholesterol (COL), hnyav heevrooj plaub (pawg 1) nthuav tawm qhov sib txawv nrog nruab nrab thiab me me (pawg 2 thiab 3), tsis muajQhov sib txawv ntawm ob qhov kawg, qhov sib txawv ntawm cov lipoproteins siab (HDL)tshwm sim ntawm pawg 1 thiab 2, tab sis tsis nrog pawg 3. Thaum kawg, cov theem ntawm kev sib ntxivyam 3(C3) nthuav tawm qhov sib txawv ntawm cov pawg hnyav thiab me me, nrog rau ntawmqhov mob me thiab nruab nrab, tab sis tsis muaj qhov sib txawv ntawm qhov hnyav thiab qhovnruab nrab pawg, qhia tias muaj peev xwm muaj nuj nqis raws li tus cim rau qhov sib txawv me me los ntawmtus so (Daim duab2). 

Ntshav analytic sib txawv boxplots ntawm ME / CFS cov tsos mob raws li pawg. Cov ntawv luv: Hb, hemoglobin;NT, suav neutrophil; COL, cholesterol; HDL, high-density lipoprotein; C3, ntxiv 3. Cov theem tseem ceeb tau teeb tsantawmp< 0.05.="" cov="" ntaub="" ntawv="" tshaj="" 1.5="" inter-quartile="" ntau="" qhov="" tseem="" ceeb,="" sawv="" cev="" rau="" qhov="" muaj="" peev="" xwm="" outliers,="" yog="" npaj="" ua="" ib="" tus="" neeg="">

Hauv kev xaus, cov tsos mob-raws li cov ntaub ntawv pawg ua raws li kev ntsuas ntshav sib txawvics tsis muaj txiaj ntsig rau kev txheeb xyuas cov ntshav ib leeg hloov pauv muaj feem cuam tshuam nrog kev noj qab haus huvqhov hnyav, raws li tau hais tseg hauv peb pawg no. Txawm li cas los xij, nws yog qhov nthuav tias qee qhov ntawm nocov ntshav tsis tuaj yeem, rau qee qhov, sib txawv ntawm pawg, qhov tseem ceeb ntawmuas tsis to taub tam sim no.

3.4.1. Cov ntshav tsis zoo nrog cov txiaj ntsig txawv txavSab saum toj analytic variable qhov tseem ceeb deviating los ntawm tsim cov pej xeem noj qab haus huv sivQhov ntau yog vit D (60.4 feem pua) feem ntau sawv cev los ntawm qhov tsis txaus, LDL (55.6 feem pua), ntxivC1q (42.8 feem pua), thiab cov roj (cholesterol) (26.4 feem pua), txhua qhov qhia tau tias muaj txiaj ntsig ntau ntxiv. Platelettxhais tau hais tias qhov ntim qhov tseem ceeb tshwm sim rau ob qho tib si nce thiab txo qis (Table4 thiab ntxivDaim duab S1).

Rooj 4.Cov ntshav analytic variables saum toj kawg nkaus tau pom qhov txawv txav nrog rau qhov kev siv qhov tseem ceeb hauvpeb pawg (n = 250). Tus naj npawb ntawm cov xwm txheej uas muaj qhov txawv txav nrog rau kev siv cov txiaj ntsig thiabfeem pua ​​(%) yog qhia.

Kev sib xyaw ua ke ntawm tsib cov ntshav analytical variables uas suav nrog tsawg kawg 20 feem pua ​​​​ntawmCov xwm txheej hauv peb pawg neeg tau pom tias vitamin D thiab LDL yog ob qho tib si txawv txav hauv 32.4 feem puacov neeg koom. Lwm qhov sib xyaw ua ke, xws li vitamin D tsis txaus thiab nce ntawm C1q,or increased LDL with C1q or cholesterol involved over 20% of the participants (>50 cas).Txij li thaum vitamin D siv qhov tseem ceeb yog dav cuam tshuam los ntawm caj ces thiab ib puag ncigyam, thiab cov kev ntsuam xyuas kom quantitate nws theem feem ntau qhia variability tshaj±10 feem pua, ua rau tsis muaj kev pom zoo rau cov txiaj ntsig siv thoob ntiaj teb, peb txiav txim siab tshem tawm qhov nosib txawv ntawm peb stratified downstream tsom xam.Ib yam li ntawd, vim qhov sib txawv ntawm LDL thiab cov roj (cholesterol) tsis muaj feem cuam tshuam tshwj xeebnrog cov kab mob, qee zaum tshwm sim nrog vitamin D tsis txaus, lawvtsis txuas ntxiv mus, txhais tau hais tias lawv tsis tau siv los teeb tsa cov xwm txheej stratification ntawm pebpawg. Qhov kev pom tsis tau pom ntawm qhov feem tseem ceeb ntawm ME / CFS cov xwm txheej qhiance qib ntawm C1q thiab txo C1 inhibitor (42.8 feem pua ​​​​thiab 8.8 feem pua, raws li) (NtxivTable S1), ua ke nrog C1q tsis muaj peev xwm cuam tshuam nrog autoimmunekab mob xws li systemic lupus erythematosus, txhawb peb txoj kev txaus siab rau kev xavC1q ua lub peev xwm biomarker rau ME / CFS subtyping.

3.4.2. Cov tsos mob sib txawv thoob plaws C1q Case Clusters

Kev soj ntsuam qis tom qab kev saib xyuas 5 feem pua ​​​​ntawm kev txiav tawm saum toj C1q qhov siab tshaj plawstus nqi stratification (cov qauv nrog C1q> 26.05 mg / dL, pawg 1, nrog raun = 90; cov qauv nrogC1q < 26.05 mg/dL, pawg 2, nrogn = 160), Txawm li cas los xij, tsis muaj qhov sib txawv tseem ceebnyob rau hauv txhua tus qhab nia cov tsos mob, tsuas yog kev zam ntawm kev nyiam rau lub cev mob (p = 0.09), qhia tias tej zaum muaj mob ntau ntxiv hauv pab pawg nrog qib C1q siab (txhais tau tias qhov tseem ceeb yog14.24 vs. 17.33, ntsig.) (Table5)

3.4.3. Ntshav analytic Qhov txawv ntawm C1q Case ClustersTxhawm rau soj ntsuam seb cov pab pawg ntawm cov xwm txheej nthuav tawm nce qib C1q (pawg 1,n = 90) tuaj yeem, tib lub sijhawm, nthuav tawm nrog cov ntshav ntxiv qhov sib txawv, txawm tiasthaum nyob rau hauv ib txwm siv qhov tseem ceeb rau cov pab pawg uas qhia C1q qhov tseem ceeb(Cluster 2,n = 160), peb tau siv qhov kev xeem txheeb cais tom qab kev sib koom ua ke, raws li tau piav qhia hauvTshooj2. Cov txiaj ntsig tau pom qhov sib txawv tseem ceeb hauv xya qhov ntsuas ntshav (p < 0.05),="">raws li qhia hauv Table6. 

Table 6.Ntshav analytic sib txawv ntawm C1q cov ntaub ntawv pawg. Pab pawg txhais tau tias thiab tus qauv sib txawvtau qhia.

Zuag qhia tag nrho, pawg nrog nce qib C1q nthuav tawm nrog cov ntshav liab ntau duasuav, nrog rau tag nrho cov protein, C3, thiab C4 qib, thiab qis dua IgG3, IgG4, thiab C1ua inhconcentrations, qhia txog txoj hauv kev uas muaj feem cuam tshuam nrog qib siab C1q thiab,Yog li, muaj feem cuam tshuam rau kev kho mob ntawm ib qho tseem ceeb ntawm cov neeg mob ME/CFS.

4. Kev sib tham

Raws li tau hais dhau los, kev siv cov qauv kuaj ntshav kom tsawg kawg yog txhawb nqa lub peev xwmrooj plaub ntawm ME/CFS ("triage" diagnosis method) thiab/los yog sib txawv cov pab pawg rauKev kho mob thiab kev tshawb fawb lub hom phiaj yuav muab qhov zoo meej. Qhov tseeb, nws yuav zooua tus yuam sij rau kev nthuav tawm ME / CFS pawg etiology thiab evolution.Txawm hais tias kev sib koom ua ke raws li cov tsos mob tshwm sim tau muaj txiaj ntsig zoo hauv kev txheeb xyuasautonomic phenotypes hauv CFS [25], lawv ua tsis tiav ntawm kev txheeb xyuas cov ntshav sib raug zoonruab nrab ntawm cov tsos mob thiab tus kheej cov ntshav tsis nyob hauv peb pawg (Daim duab2). Txoj kev mus kom zetau, txawm li cas los xij, qhia tau tias muaj peev xwm sib txawv ntawm cov mob hnyav, nruab nrab, lossis mob mekev hlub raws li tau hais tseg los ntawm tsib cov tsos mob uas tau siv rau kev sib koom ua ke (Tables2 thiab3). Covphysiological qhov tseem ceeb ntawm qhov kev tshawb pom, suav nrog kev nce qib ntawm C3 hauv qhov hnyav thiabnruab nrab nrog rau cov teeb meem me me los yog nce neutrophil suav hauv qhov hnyavME / CFS los ntawm nws tus kheej lossis ua ke nrog LDL thiab cov roj cholesterol, nrog rau lawv txoj kev koom tesnyob rau hauv cov tsos mob kev loj hlob los yog txij nkawm, tseem yuav elucidated.Txawm li cas los xij, qhov muaj feem ntau ntawm ME / CFS (42.8 feem pua ​​lossis 107/250) tus neeg mobnrog kev nthuav qhia ntau ntxiv ntawm C1q, thawj zaug, yuav tseem ceeb rau lub hauv paus rau yav tom ntejME / CFS subtyping.

C1q ua raws li thawj feem hauv txoj hauv kev ntxiv rau classical. Qhov ntxivsystem yog lub hauv paus ntawm kev tiv thaiv innate nrog ob lub luag haujlwm tseem ceeb: kev pabcuamraws li ib tug tiv thaiv system tiv thaiv invading pathogens thiab tshem tawm cov tuag hlwb los yog khib nyiab. C1q lees paub PAMPs (cov kab mob cuam tshuam nrog cov qauv molecular), suav nrogLPS (lipopolysaccharide) thiab cov kab mob porins, ntxiv rau kev paub txog cov moleculesxws li phosphatidylserine thiab dsDNA nthuav tawm ntawm qhov chaw ntawm cov hlwb tuag. Yog li, qhov kuaj pom tau nce qib ntawm C1q thiab lwm cov khoom ntxiv hauv apawg pawg ntawm ME/CFS cov neeg mob yuav qhia tau hais tias lub xeev ntawm active efferocytosis mus rau kev sib ntaus sib tuaib tug kab mob subjacent los yog thaum tshem cov ntaub so ntswg puas. Tsis tas li ntawd, cov mob uas muaj mob ntevkev ua kom txoj hauv kev ntxiv tuaj yeem, vim li no, ua rau muaj kev cuam tshuam tshwj xeebto PEM, muaj peev xwm uas yuav tsim nyog tshawb nrhiav.Nws tau zoo sau tseg tias, ob qho tib si tsis muaj txiaj ntsig thiab overstimulation ntawm qhov ntxivqhov system tuaj yeem ua rau muaj kev puas tsuaj rau tus tswv tsev, thiab cuam tshuam nrog kev nce siab raukab mob, autoimmunity, mob o, thiab thrombotic microangiopathy, ntawmlwm tus. Qee cov txheej txheem no tau cuam tshuam nrog ME / CFS. Txawm li cas los xij, peb tsuas pom qee qhov xwm txheej ntawm kev tiv thaiv tus kheej tiv thaiv tus kheej zoo nyob thoob plaws 10- kuajkhiav thov rau 250 tus neeg koom nrog (Table Ntxiv S1).Kev soj ntsuam uas, ntawm ntau cov ntshav ntsuas ntsuas, cov uas paub tias yogntsig txog C1q muaj nuj nqi, piv txwv li, C1 inhibitors C3 thiab C4 pom qhov sib txawv tseem ceeb ntawmpab pawg (Table6) ntxiv txhawb nqa qhov teeb meem kev ua haujlwm ntawm qhov kev sib txuas ntxiv hauv qhov nopab pawg ntawm cov neeg mob, tej zaum nrog rau qhov tshwm sim hauv cov txheej txheem ntawm coagulation. Ib tug yav tom ntejKev soj ntsuam ntawm coagulopathies nyob rau hauv pab pawg neeg no ntawm cov neeg mob, yog li, tshwm sim.Tsis ntev los no, Benavente et al. pom tias C1q ua raws li ligand uas tuaj yeem khi ncaj qhaib tug series ntawm receptors yav tas los tsis paub tias yog cov koom tes ntawm no molecule, nrog rau covcov proteins hauv qab no: CD44, GPR62, BAI1, c-MET, thiab ADCY5, uas ua rau muaj kev ua haujlwm ntawmdownstream signaling txoj kevthiab, yog li, cuam tshuam ntau yam ntawm neuroepithelialstem cell biology. Qhov kev tshawb pom los ntawm cov kws sau ntawv no tias C1q tau nce siab thaum cov hlab ntsha raug mob thiab cov kev sib txuas tshiab ntawm C1q nrog cov kab mob neurodegenerativeqhibQhov muaj peev xwm txaus siab uas nce qib ntawm C1q tuaj yeem ua rau ME / CFS kev txawj ntseteeb meem. C1q hloov kho cov kab mob prion, tswj cov neuron pruning, thiabmodulates cov txheej txheem ntawm phagocytosis los ntawm microglia thaum teb rau amyloid plaquetsim. Hmoov tsis zoo, tsis muaj cov cuab yeej tshwj xeeb rau kev ntsuas kev paub meejntawm cov neeg koom lossis cov cuab yeej neuroimaging tau siv hauv txoj kev tshawb no.Thaum kawg, qhov tseeb tias ob lub strata nthuav tawm ib txwm thiab nce qib ntawm C1q pomQhov sib txawv ntawm qhov mob yuav qhia tau tias muaj kev koom tes ncaj qha ntawm C1q hauv cov tsos mob. Nws yuavmuaj feem cuam tshuam nrog rau kev soj ntsuam ntxaws ntxiv ntawm cov tsos mob no los ntawm kev siv qhov mob tsomCov lus nug, xws li FIQ (Fibromyalgia Impact Questionnaire) thiab/los yog lwm tus, hauv kev tshawb fawb yav tom ntej ntawm C1q lub luag haujlwm hauv ME/CFS. Txawm tias tsis ua hauj lwm ntawm cov lus nugtshaj SF-36 txhawm rau txheeb xyuas cov tsos mob ntsig txog qhov sib txawv nrog C1q qib (Table5) coj peb musxav tias tsis muaj kev koom tes loj ntawm C1q hauv qhov nam ntawm tus kab mob no, nws zoo li xav paub tiaslub phiaj xwm ntawm ob pawg pom qhov sib txawv ntawm txhua tsib cov tsos mob xaiv los ntawmk-txhais tau tias kev tshuaj ntsuam xyuas los teeb tsa cov tsos mob raws li pawg ntawm pawg (Figures1 thiab3). Tsis tas li ntawd, nyob rau hauv 94 tus neeg mob hauv pawg "mob hnyav" (pawg 1) ntawm peb cov tsos mob-raws likev txheeb xyuas pawg (Table2), kwv yees li 39 feem pua ​​(37/94) nthuav qhia nce qib C1q thaum 61 feem pua(57/94) pom cov qib ib txwm muaj; nyob rau hauv 107 qhov xwm txheej ntawm pawg "nruab nrab" (cluster 2),35 feem pua ​​(37/107) tau nce C1q thiab 65 feem pua ​​(70/107) ib txwm C1q theem; hauv 49 casentawm pawg "mob" (cluster 3), 33 feem pua ​​(16/49) pom tau tias nce qib C1q thiab 67 feem pua ​​(33/49)muaj C1q qib nyob rau hauv ib txwm siv qhov tseem ceeb. Qhov no qhia txog qhov ntxhib 1: 2 tag nrho qhov piv ntawmCov neeg mob uas muaj C1q nce qib hauv pab pawg "mob", nrog qhov nce me ntsis hauv qhov piv nonyob rau hauv "nruab nrab" thiab ib tug ntau dua piv (1: 1.5) nyob rau hauv lub "hnyav" pawg, qhia ib tugKev nce ntxiv ntawm qib siab C1q nrog cov kab mob hnyav, txawm tias tsis muajKev sib raug zoo ntawm tus neeg mob cov qhab nia thiab qib C1q. Ib qho kev sib raug zoontawm C1q qib nrog cov xwm txheej ntev ntawm cov xwm txheej tsis tuaj yeem tsim los yog.

Cov ntshav tsis ntxiv uas pom qhov txawv txav ntawm qhov loj ntawmCov tib neeg hauv peb pawg, xws li vitamin D tsis txaus, qib LDL, cholesterol, C3 qib,los yog platelet txhais tau tias tus nqi, tej zaum yuav muab cov ntaub ntawv tseem ceeb rau kev kho mob, ib yamtsis nkag siab zoo tam sim no, uas yuav tsum tau saib xyuas ntxiv rau yav tom ntej.Nws yuav tsum tau hais tias, txawm hais tias sib txawv siv qhov tseem ceeb tau tsimrau vitamin D tsis txaus, piv txwv li, cov lus pom zoo los ntawm 2011 US Institute ofTshuaj (IOM) tau tshaj tawm qhov tsawg kawg nkaus ntawm 52 nmol / L, thaum US EndocrineCov txheej txheem hauv zej zog tau hais tias qhov tsawg kawg nkaus ntawm 78 nmol / L, siv ntau yamNyob rau hauv txoj kev tshawb no yog nyob rau hauv qis dua qhov qis tshaj (50 nmol / L, Supplementary Table S1), thiabyet a large proportion of cases (>60 feem pua) pom tias tsis muaj vitamin D (Table4). Kev txwv ntxivTxawm hais tias pawg neeg nyob hauv kev kawm suav nrog ntau yam kev kawm(n = 250), sab nraud validity ntawm cov ntaub ntawv tseem txwv rau cov poj niam. Random xaiv cov neeg koomtuaj yeem ua rau ntau tus neeg sawv cev cov txiaj ntsig pej xeem-ntseeg; Txawm li cas los xij, kev kawm heterogeneitytxhais rau hauv kev txhim kho kev hloov pauv, cuam tshuam rau kev tsim kho kom muaj zogQhov sib txawv, tej zaum muaj feem cuam tshuam rau kev kuaj mob ntawm ME / CFS. Qhov tsis muaj qhov cuam tshuam ntxivQhov sib txawv ntawm ME / CFS cov teeb meem tsis tuaj yeem txiav txim siab los ntawm kev ua haujlwm hnyav, tseem tsis tau txiav txim siabntawm no ua.

5. Cov lus xausHauv kev xaus, txoj kev tshawb no tau txheeb xyuas tus neeg muaj peev xwm tshiab hauv ME / CFS pathology,cov C1q tivthaiv ntawm cov khoom siv ntxiv, cuam tshuam ntau dua 40 feem pua ​​​​ntawm cov neeg mob. Qhov kev tshawb pom nopave txoj hauv kev rau kev tshawb nrhiav C1q-raws li tus qauv kuaj kuaj kom pom ME / CFS subtypesnrog rau kev soj ntsuam thiab kev tshawb fawb cuam tshuam. Kev nkag siab ntawm lub hauv pauspathomechanisms tom qab qhov kev tshawb pom no txwv tam sim no, muab kev tshawb nrhiav ntxivkev soj ntsuam.

Cov khoom siv ntxiv:Daim duab S1: Lub thawv ntawv ntawm cov ntshav analytic sib txawv saum toj kawg nkaus uas qhia tawm qhov qubcov ntaub ntawv pov thawj hauv peb pawg (n = 250). Cov kab liab qhia qhov muaj nuj nqis ib txwm muaj. Blackline nyob rau hauvlub thawv yog qhov nruab nrab ntawm cov nqi quartile. Cov nqi ib txwm muaj nyob rau hauv ntsuab thaum cov nqi txawv txavmuaj nyob rau hauv liab. Table S1: Cohort dataset.

Tus sau kev koom tes:Conceptualization, JC-M. thiab EO; Kev sau cov ntaub ntawv, JC-M. thiab JA-M.;Cov ntaub ntawv tsom xam thiab txhais lus, JC-M., MZ, EA-P. thiab EO; sau ntawv-kev npaj ua ntej,JC-M., MZ thiab EO; sau ntawv- tshuaj xyuas thiab kho, txhua tus sau; Kev nrhiav nyiaj txiag, JC-M., JA-M.thiab EO Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau..

Nyiaj txiag:Qhov kev tshawb fawb no yog ib feem nyiaj los ntawm Lub Koom Haum ntawm Cov Neeg Mob nrog ME / CFS thiabFibromyalgia hauv Catalonia, Spain (ACAF;( nkag mus rau 23 Lub Peb Hlis 2019) rauJC-M. thiab JA-M., thiab los ntawm UCV 2020-270-001 pub rau EO

Institutional Review Board Statement:Txoj kev tshawb fawb tau ua raws li cov lus qhiantawm tsab ntawv tshaj tawm ntawm Helsinki thiab pom zoo los ntawm Pawg Neeg Saib Xyuas Kev Tshawb Fawb Hauv Nroog (Valld'Hebron University Tsev Kho Mob, Barcelona, ​​Spain; IRB siv tus lej: CEIC/PR-AG-VITAE-2015,pom zoo nyob rau lub Rau Hli 2015).

Cov Lus Qhia Txog Kev Pom Zoo:Sau ntawv tso cai tau txais los ntawm txhua tus neeg koom nrogtxoj kev kawm.

Cov ntaub ntawv muaj nyob:Cov ntaub ntawv muaj nyob rau hauv Cov Lus Qhia Ntxiv S1.

Kev lees paub:Cov kws sau ntawv ua tsaug rau txhua tus neeg mob ME / CFS (Association of ME / CFS thiab Fibromyalgiahauv Catalonia, Spain) uas tau koom nrog txhawb txoj kev tshawb fawb no. Cov kws sau ntawv kuj yogtshwj xeeb ua tsaug rau Ramon Sanmartin thiab Marta Yuav tsumé rau lawv txoj kev tswj hwm thiab kev txhawb nqahauv kev yooj yim kom tau txais cov ntaub ntawv los ntawm cov neeg koom nrog kev kawm. Vall d'Hebron Lub Tsev Kho Mob Tshawb Fawb(VHIR) yog ib tug tswv cuab ntawm CERCA program (Network of Excellence Research Centers of Catalonia,Spain).

Kev tsis sib haum xeeb ntawm kev txaus siab:Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab. Tus neeg nrhiav nyiaj txiag tsis muaj lub luag haujlwm hauv kev tsimntawm kev kawm; hauv kev sau, txheeb xyuas, lossis txhais cov ntaub ntawv, hauv kev sau cov ntawv sau, lossishauv kev txiav txim siab tshaj tawm cov txiaj ntsig.

Nrhiav qhov zoo tshaj plaws BOTANICAL HOLISTIC CARE FOR RELIVE PHYSICAL FATIGUE IN DAYLIFE

Peb ua tib zoo xuas tes ua Neuro Regen mis muaj xws li tshuaj ntsuab tshawb fawb zoo tshaj plaws. Txhua qhov qhia tau hais tias muaj peev xwm zoo rau kev txo qis kev qaug zog mob ntev, ntxiv rau cov paj hlwb thiab cov neuron txhawb nqa tag nrho.

Xws li:

Cistanche Extract #5-

Cistancheyog cov tshuaj ntsuab uas siv ntau tshaj plaws nyob rau hauv cov tshuaj suav tshuaj suav tshuaj rau kev txo lub cev qaug zog. Qhov tseeb,Cistancheyog ib hom khoom noj khoom haus. Raws li theoretical hauv paus ntawm cov tshuaj tsoos, cov tshuaj niaj hnub no kuj tau tshawb fawb ntau ntawm covtiv thaiv qaug zognyhuv ntawmCistanche. Cov kev sim tau ua pov thawj tias covtiv thaiv qaug zognyhuv ntawmCistancheyog vim kev txhim kho ntawm lub cev ntawm lub cev ntawm Cistanche. Cistanche tuaj yeem txhim kho cov haujlwm ntawm lub raum thiab lub siab, yog li ua tiav ib qhotiv thaiv qaug zognyhuv. Cov hauv qab no yog cov ntsiab lus ntawm yuav ua li cas Cistanche tuaj yeem txo qhov qaug zog.