Tshooj Ob Transgelin-2 hauv Ntau Myeloma: Tus Cim Tshiab Ntawm Lub Raum Tsis Zoo

Cov txiaj ntsig

1. Cov yam ntxwv ntawm Pawg Kawm

Peb txoj kev tshawb fawb soj ntsuam yav tom ntej suav nrog 126 tus neeg mob nrog MM, raug xaiv thaum lub sijhawm thauj mus los tswj xyuas ntawm Lub Tsev Haujlwm ntawm Hematology ntawm Tsev Kho Mob University hauv Kraków, Poland. Tag nrho ntawm 73 tus poj niam thiab 53 tus txiv neej tau suav nrog, hnub nyoog 29 txog 90 xyoo (Table 1). Cov tsos mob MM tau kuaj pom hauv 119 tus neeg mob, feem ntau ntawm lawv nyob hauv ISS theem I. Cov neeg mob uas tseem tshuav xya tus neeg mob MM. Cov neeg mob feem ntau tau txais tsawg kawg ib kab ntawm kev kho mob ua ntej pib txoj kev tshawb fawb thiab kwv yees li ib nrab ntawm cov pab pawg tau txais kev kho mob ntawm lub hauv paus (Table 1). Cov keeb kwm ntawm mob raum raug mob tau zoo hauv yim (6 feem pua) cov neeg mob.

Qhov nruab nrab qhov nruab nrab eGFR (CKD-EPICr) yog 74 (SD: 24) mL / min / 1.73 m2 thiab 29 (23 feem pua) cov neeg mob muaj eGFR<60 mL/min/1.73 m2 (Table 2). eGFR was above 60 mL/min/1.73 m2 in 97 patients (77%), between 30 and 60 mL/min/1.73 m2 in 18 patients (14%) and below 30 mL/min/1.73 m2 in 11 patients (9%). The selected laboratory test results in the studied group are shown in Table 2. As compared to a control group of 32 healthy volunteers (16 men and 16 women aged 29–74 years), the studied MM patients presented with significantly higher serum concentrations of transgelin and interleukin 6 and higher urinary concentrations of IGFBP-7 and TIMP-2 (Table 2). Although the age range of healthy controls was matched with the age range of patients, the mean age was lower in the control group (50 versus 67 years, p < 0.001). However, serum transgelin remained higher in patients than in controls after adjustment for the age difference (p = 0.034). The sex distribution in the study and control groups was similar (p = 0.4).

2. Kev sib txawv ntawm cov tshuaj Serum Transgelin ntawm Baseline

Qhov nruab nrab serum transgelin nyob rau hauv tag nrho cov kev tshawb fawb pawg yog 84.1 ng / mL (Table 2). Transgelin concentrations ntau dua nyob rau hauv cov txiv neej (qhov nruab nrab 96.2 piv rau 78.8 ng / mL; Daim duab 1A), nyob rau hauv cov neeg mob smoldering MM ( nruab nrab 149.2 piv rau 82.4 ng / mL; p=0.003; Daim duab 1B), thiab kev kho mob tsis zoo. cov neeg mob (qhov nruab nrab 145.2 piv rau 82.5 ng/mL; p=0.014; Daim duab 1C); Txawm li cas los xij, feem ntau ntawm cov neeg mob uas muaj MM (5 tawm ntawm 7) thiab cov neeg mob kho tsis zoo (6 ntawm 8) yog txiv neej. Ntawm kev txaus siab, ntshav transgelin tau siab dua hauv cov poj niam noj qab haus huv dua li cov txiv neej (tswj pawg; nruab nrab 83.4 vs 60.5 ng / mL, raws li; p=0.011).

Rau cov neeg mob uas tau txais kev kho mob MM ua ntej nkag mus rau txoj kev tshawb no, tsis muaj kev sib raug zoo ntawm cov ntshav transgelin thiab cov kab mob ua ntej (R {{0}}} −{{10}}. 10; p=0.3). Cov neeg mob ntawm kev kho mob tsis muaj qhov tseem ceeb hauv cov ntshav transgelin qis dua li qhov kev kho mob-naïve (qhov nruab nrab 77.4 piv rau 91.0 ng / mL; p=0.051). Cov kev kho mob suav nrog lenalidomide hauv 25 tus neeg mob (20 feem pua), bortezomib hauv 21 (17 feem pua), thalidomide hauv 15 (12 feem pua), cyclophosphamide hauv 8 (6 feem pua), thiab melphalan hauv 3 (2 feem pua); steroids tau siv hauv 58 (46 feem pua) ntawm cov neeg mob. Peb tsis tau soj ntsuam qhov sib txawv tseem ceeb hauv cov ntshav transgelin concentration ntawm cov neeg mob kho thiab tsis kho nrog cov tshuaj tshwj xeeb (p > 0.05 rau txhua qhov kev sib piv). Qib Transgelin tsis txawv raws li ISS theem (p=0.3; Daim duab 1B) lossis kab mob (ua tiav lossis ib nrab teb, tus kab mob ruaj khov, lossis kab mob loj tuaj; p=0.2). Serum transgelin hauv cov neeg mob nrog eGFR<60 mL/min/1.73 m2 did not differ significantly from the levels observed in those with higher eGFR (median 106.6 versus 79.7 ng/mL; p = 0.057; Figure 1D). The presence of proteinuria was not associated with serum transgelin (p = 0.3).

Kev sib raug zoo tseem ceeb tau raug kuaj pom ntawm transgelin thiab serum creatinine (R {{0}}}.29; p=0.001), eGFR (CKD-EPICr) ( R=−0.25; p=0.007), uric acid (R=0.19; p=0.036), alanine (R=0.18; p=0.048) thiab aspartate (R=0.26; p=0.003) aminotransferases, ferritin (R=−0.22) ; p=0.049), hepcidin (R =} −0.25; p=0.033), thiab zis cystatin C (R=0.19; p {{34}). }.042 ib.). Tsis tas li ntawd, tom qab kev cais tawm ntawm cov neeg mob smoldering MM, transgelin cuam tshuam nrog cov ntshav FLC lambda (R=0.18; p=0.047)) thiab ntshav periostin (R=−0.22; p=0.013). Hauv ntau qhov kev hloov pauv mus tom ntej, uric acid tau txheeb xyuas tias tsuas yog tus kws tshaj lij ywj pheej ntawm cov ntshav transgelin (beta=0.31; tus qauv yuam kev=0.13; p=0.023).

3. Lub koom haum ntawm Serum Transgelin thiab lub raum ua haujlwm tom qab lub sijhawm ua raws

Cov ntaub ntawv taug qab tau sau tseg rau 27 lub hlis txij li pib txoj kev tshawb fawb. Tag nrho ntawm 23 tus neeg mob (18 feem pua) tau tuag thaum lub sijhawm kawm, suav nrog 12 vim yog MM, 7 vim yog kis kab mob, thiab 3 vim tsis muaj laj thawj. Lub sijhawm soj ntsuam nruab nrab yog 21 (15; 24) lub hlis. Thaum kawg ntawm lub sijhawm ua raws, eGFR qis dua hauv 47 (37 feem pua) ntawm cov neeg mob thiab nce lossis tseem tsis hloov pauv hauv 71 (56 feem pua) cov neeg mob. Tsis muaj cov ntaub ntawv rov qab tau muaj rau yim tus neeg mob (6 feem pua). Cov neeg mob uas eGFR poob qis dua tuaj yeem nthuav qhia ntau dua hauv paus transgelin piv rau cov uas tsis muaj kev hloov pauv lossis nce hauv eGFR qhov tseem ceeb (qhov nruab nrab 106.6 piv rau 83.9 ng / mL; p=0.051; Daim duab 2).

Txawm li cas los xij, lub hauv paus transgelin muaj kev sib raug zoo nrog cov ntshav creatinine tom qab ua raws (R=0.37; p < 0.001) thiab tsis zoo cuam tshuam nrog eGFR tom qab ua raws. -up (R=−{20}}.33; p < 0.001; Daim duab 2). Ntxiv mus, lub hauv paus siab dua cov ntshav transgelin tau kwv yees qis dua eGFR qhov tseem ceeb tom qab lub sijhawm ua raws, ntawm nws tus kheej ntawm lub hauv paus eGFR, tso zis ntau ntawm cov cim raug mob (NGAL monomer thiab IGFBP-7), poj niam txiv neej, hnub nyoog, kev kho mob ua ntej, kev kho mob. thiab lub sijhawm soj ntsuam (Table 3). Ntxiv mus, qhov tseem ceeb ntawm cov transgelin nyob rau sab sauv tertile (piv txwv li, saum toj no 110.6 ng / mL) nws tus kheej cuam tshuam nrog qis eGFR thaum kawg ntawm kev soj ntsuam (Daim duab 2; Table 3). Txawm hais tias lub hauv paus ntawm uNGAL (R=−0.31; p < 0.001) thiab uIGFBP-7 (R=−0.35; p < 0.001) kuj tseem cuam tshuam nrog qhov kawg eGFR, cov koom haum no tsis tau ua pov thawj tias muaj kev ywj pheej ntawm lwm qhov kev kwv yees, suav nrog cov kab hauv qab eGFR (Table 3).

Los ntawm kev siv yooj yim Cox regression, peb tsis tau soj ntsuam ib qho kev koom tes ntawm cov ntshav transgelin thiab zuag qhia tag nrho- los yog MM-specific ciaj sia taus, tsis yog nyob rau hauv tag nrho cov kev tshawb fawb pab pawg neeg los yog tom qab cais cov neeg mob nrog smoldering MM (p > 0.5 nyob rau hauv txhua rooj plaub).

Cov ntaub ntawv thiab cov txheej txheem

Kawm Tsim thiab Cov Neeg Mob

Qhov no yog ib txoj kev tshawb nrhiav yav tom ntej. Cov neeg mob tau raug xaiv thaum lub sijhawm thauj neeg mob mus ntsib ntawm Lub Tsev Haujlwm ntawm Hematology ntawm Tsev Kho Mob University hauv Kraków, Poland. Hnub nyoog siab dua lossis sib npaug li 18 xyoo thiab kev kuaj mob ntawm SMM lossis MM raws li International Myeloma Working Group sawv cev rau cov txheej txheem suav nrog. Cov txheej txheem cais tawm yog cov hauv qab no: (1) kab mob tsis ntev los no, (2) keeb kwm ntawm kab mob siab B, C, lossis kab mob tib neeg tiv thaiv kab mob (HIV), thiab (3) mob qog noj ntshav uas tsis yog myeloma. Rau txhua tus neeg mob, cov ncauj lus ntxaws ntxaws ntawm tus kab mob tau sau los ntawm cov ntaub ntawv kho mob muaj. Cov ntaub ntawv khaws cia ntawm qhov kev mus ntsib thawj zaug suav nrog tus neeg mob lub hnub nyoog thiab poj niam txiv neej, hnub kuaj pom thawj zaug ntawm SMM lossis MM, kev kuaj mob tam sim no, muaj cov pob txha raug mob ntawm X-ray, thiab cov ntaub ntawv hais txog kev kho mob yav dhau los thiab tam sim no suav nrog cov lus teb rau Kev kho mob: ua kom tiav cov lus teb (CR), ib nrab teb (PR), kab mob ruaj khov (SD), lossis kab mob hnyav (PD). Cov ntaub ntawv rov qab tau raug sau tom qab 27 lub hlis tom qab pib txoj kev tshawb fawb thiab suav nrog (1) hnub thiab qhov ua rau tuag, thiab (2) cov txiaj ntsig ntawm kev kuaj sim, suav nrog ntshav creatinine thiab eGFR tau txais ntawm qhov kawg ua raws- mus xyuas.

Pawg tswj hwm tau raug xaiv kom tau txais cov txiaj ntsig ntawm kev kuaj tsis yog qauv thiab suav nrog 32 tus neeg ua haujlwm noj qab haus huv (16 tus poj niam, 16 tus txiv neej) hnub nyoog 29 txog 74 xyoo.

Nyem qhov no kom tau txais cov teebmeem ntawm Cistanche

2. Nqe lus hais txog Ethics

Txoj kev tshawb no tau ua raws li cov hauv paus ntsiab lus ntawm Kev Tshaj Tawm ntawm Helsinki thiab ua raws li International Conference on Harmonization / Good Clinical Practice rules. Txoj kev tshawb no tau pom zoo los ntawm Bioethics Committee ntawm Jagiellonian University thiab txhua tus neeg mob tau kos npe rau kev pom zoo rau lawv txoj kev koom tes. Txhua tus neeg mob tau raug kho ntawm Lub Tsev Haujlwm Saib Xyuas Hematology, Tsev Kho Mob University hauv Krakow.

3. Kev kuaj ntshav thiab kuaj ntshav

Thaum sawv ntxov ntawm hnub sau ntshav tom qab kev yoo mov ib hmos thiab so, kev kuaj mob niaj hnub ntawm ob tus neeg mob thiab cov kev tswj hwm tau ua, uas suav nrog cov ntshav suav tag nrho, cov ntshav ntshav ntau ntawm creatinine, cov dej ntshiab ntawm lactate dehydrogenase, tag nrho cov protein, albumin, { {0}}microglobulin, dawb lub teeb chains, tso zis ntau ntawm lub teeb chains, alanine thiab aspartate aminotransferases, thiab ferritin.

Cov ntshav tau sau raws li Kev Ntsuas Zoo (GLP) thiab Cov Cai Kho Mob Zoo (GCP) los ntawm cov neeg ua haujlwm tsim nyog. Cov ntshav tau sau rau hauv cov raj kaw nrog lub tshuab ua kom ntshav khov. Cov qauv tau muab sib xyaw thiab khaws cia ntawm qhov kub thiab txias nyob rau hauv txoj hauj lwm ntsug rau 30 feeb, ces centrifuged ntawm 1300 × g rau 15 min. Tom qab centrifugation, cov ntshav tau aliquoted thiab khaws cia ntawm -70 ◦C kom txog thaum kev soj ntsuam. Peb tsis tau siv hemolyzed los yog lipemic kuaj.

Cov qauv kuaj ntshav rau lwm qhov kev sim kuaj tau raug aliquoted thiab khaws cia ntawm qhov kub ntawm -70◦C. Cov kev kuaj tsis niaj hnub no suav nrog cov zis NGAL monomer, zis IGFBP-7 thiab TIMP-2, zis cystatin-C, transgelin, periostin, hepcidin, thiab interleukin 6 (IL-6).

Tsis siv neeg biochemical analyzers tau siv, Hitachi 917 (Hitachi, Ibaraki, Nyiv) thiab Modular P (Roche Diagnostics, Mannheim, Lub teb chaws Yelemees). Hematological parameters raug ntsuas siv Sysmex XE 2100 analyzer (Sysmex, Kobe, Nyiv). Qhov concentration ntawm cov ntshav FLC, zis LC (κ thiab λ hom), thiab 2-microglobulin tau ntsuas los ntawm immunonephelometric method ntawm BN II analyzer (Siemens GmbH, Goerlitz, Lub teb chaws Yelemees). Kev txiav txim siab ntawm cov saw dawb dawb (FLC κ, FLC λ) tau ua los ntawm kev siv Freelite reagents (Binding Site, Birmingham, UK) nrog rau kev siv ntau yam: 1.7–3.7 g / L thiab 0.9–2.1 g / L feem. Lub immunophenotype ntawm monoclonal protein tau txiav txim los ntawm cov tshuaj tiv thaiv kab mob ntshav (IFE) ntawm agarose gel (EasyFix G26, Interlab, Ltalis).

Tus nqi eGFR raug xam raws li cov ntshav creatinine siv cov kab mob hauv lub raum-kab mob sib kis (CKD-EPI) 2009 cov mis raws li cov ntshav creatinine thiab cystatin C.

Cistanche hmoovthiabCistanche extract

Cov kev ntsuam xyuas tsis tu ncua tau ua nyob rau hauv series, siv cov khoom siv tshuaj immunoenzymatic muaj muag. Serum IL-6 tau ntsuas los ntawm Quantikine ELISA Tib Neeg IL-6 Immunoassay (R&D Systems, Inc., Minneapolis, MN, USA), nrog qhov ntsuas pom tsawg kawg ntawm 0.7{{7 }} pg/mL, thiab intra- thiab interassay precision ntawm 2.0 feem pua ​​thiab 3.8 feem pua, raws li. Kev siv ntau yam rau IL{{10}} yog 3.13–12,5 pg/mL. Serum transgelin tau ntsuas siv tib neeg TAGLN (Transgelin) ELISA Cov Khoom Siv (Wuhan Fine Biotech Co, Wuhan, Tuam Tshoj), nrog rau kev kuaj pom ntau ntawm 0.625–40 ng/mL, thiab cov intra- thiab interassay precision ntawm 8 feem pua ​​​​thiab 10 feem pua, raws li qhia los ntawm cov chaw tsim khoom ntawm qhov ntsuas. Serum periostin tau ntsuas siv Periostin Enzyme Immunoassay Kit (Biomedica Medizinprodukte GmbH &Co KG, Wien, Austria), nrog rau kev kuaj pom ntau ntawm 0–4000 pmol/L; txwv kev kuaj pom ntawm 20 pmol / L thiab intra- thiab interassay precision ntawm 3.0 feem pua ​​thiab 6.0 feem pua. Ntshav siab hepcidin 25 qib tau ntsuas siv Hepcidin 25 human Cet. No. S-1337 cov khoom siv (Peninsula Laboratories International, Inc., San Carlos, CA, USA). Kev kuaj pom ntau rau hepcidin 25 yog 0.02-25 ng / mL. Cov zis NGAL monomer tau raug soj ntsuam siv Human NGAL monomer-specific ELISA Kit (BioPorto Diagnostics A/S, Hellerup, Denmark), nrog rau qhov tsawg kawg nkaus kuaj tau koob tshuaj ntawm 10 pg/mL thiab kuaj pom ntau yam rau NGAL ntawm 10–1000 pg/mL. Cov zis IGFBP-7 tau ntsuas siv IBP-7 ELISA Kit (EIAab Science Inc, Wuhan, Suav). Kev kuaj pom ntau rau IGFBP7 yog 0.312–20 ng / mL. Cov zis TIMP-2 qib tau ntsuas los ntawm Human Metalloproteinase Inhibitor 2 ELISA Kit (EIAab Science Inc, Wuhan, Tuam Tshoj), nrog rau kev kuaj pom ntau ntawm 0.312–20 ng/mL. Cystatin C concentrations hauv cov zis thiab cov ntshav tau ntsuas los ntawm Human Cystatin C ELISA- IVD (BioVendor Research thiab Diagnostic Products, Brno, Czech Republic), nrog rau kev tshawb pom ntau ntawm 0.25–25 ng / mL, thiab Intra thiab interassay precision ntawm 3.5 feem pua. thiab 10.4 feem pua.

4. Kev txheeb xyuas qhov tseeb

ntsuas normality. Raws li cov txiaj ntsig ntawm cov ntshav transgelin tsis nquag faib, lawv tau muab piv nrog cov pab pawg nrog Mann-Whitney's lossis Kruskal-Wallis 'kev xeem. Lub hnub nyoog-hloov kho logistic regression tau siv los txheeb xyuas cov ntshav transgelin qib sib txawv ntawm cov neeg mob thiab kev tswj hwm. Spearman rank correlation coefficient tau siv los ntsuas qhov sib raug yooj yim. Ib kauj ruam rov qab ntau txoj kab rov ua dua tau siv los nrhiav kev ywj pheej kwv yees ntawm qib ntshav transgelin. Cov qauv suav nrog cov kev hloov pauv loj heev (p < 0.05) cuam tshuam nrog cov ntshav transgelin hauv kev tshuaj xyuas yooj yim. Ntau txoj kab rov tav kuj tau siv los ntsuas kev sib koom ua ke ntawm cov hauv paus ntshav ntshav transgelin thiab eGFR qhov tseem ceeb ntawm qhov kawg ntawm kev ua raws. Serum transgelin tau suav nrog hauv cov qauv xws li qhov sib txawv tsis tu ncua lossis tom qab categorization rau hauv cov tertiles. Cov qauv tau hloov kho rau cov kev hloov pauv uas cuam tshuam nrog qhov kawg ntawm eGFR qhov tseem ceeb hauv kev txheeb xyuas yooj yim thiab cov kws kho mob tshwj xeeb ua ntej (hnub nyoog, poj niam txiv neej, kev kho mob yav dhau los, kev kho mob, kev soj ntsuam ntev). Txoj cai-skewed variables tau log-hloov ua ntej suav nrog rau cov qauv linear regression. Qhov yooj yim proportional hazard Cox regression tau siv los kuaj xyuas qhov sib koom ntawm cov ntshav transgelin concentrations thiab tag nrho thiab MM tshwj xeeb ciaj sia taus. Lub sij hawm muaj sia nyob tau suav txij thaum pib ntawm txoj kev tshawb fawb mus txog rau tus neeg mob tuag los yog hnub ntawm nws qhov kev soj ntsuam zaum kawg. Cov kev ntsuam xyuas kev txheeb xyuas tau ob-tailed thiab p < 0.05 qhia txog qhov tseem ceeb. Statistica 12.0 (StatSoft, Tulsa, OK, USA) tau siv rau kev suav.

Cistanche tubulosa

Cov lus xaus

Peb txoj kev tshawb fawb pom thawj zaug uas nce cov ntshav transgelin tsis zoo cuam tshuam nrog glomerular filtration rate hauv MM thiab kwv yees qhov txo qis hauv lub raum ua haujlwm dhau mus ntev. Txawm li cas los xij, kev nce ntshav siab transgelin hauv MM tuaj yeem cuam tshuam nrog lwm cov txheej txheem pathological, piv txwv li, malignancy, lossis o, nrog rau kev kho MM. Xav txog cov kev txwv ntawm peb txoj kev tshawb fawb, kev ua haujlwm ntxiv yog xav tau los ntsuas cov kev qhia transgelin hauv ntau hom kev koom tes hauv lub raum hauv MM. Txawm li cas los xij, peb qhov kev tshawb pom txhawb nqa cov ntaub ntawv dhau los uas txuas transgelin rau lub raum fibrosis.

Cov txiaj ntsig Cistanche

Cov ntaub ntawv

1. Cowan, AJ; Allen, C.; ib. Barac, UA; Basaleem, H.; Bensenor, ib.; Curado, MP; Thawj Tswj Hwm, K.; Gupta, R.; Harvey, J.; Hosgood, HD; ua al. Ntiaj teb no Burden of Multiple Myeloma: Kev Tshawb Fawb Txog Kev Tshawb Fawb Txog Kev Tshawb Fawb Ntiaj Teb ntawm Kab Mob 2016. JAMA Oncol. 2018, 4, 1221–1227.

2. Rajkumar, SV; Dimopoulos, MA; Palumbo, UA; Blade, J.; Merlini, G.; Mateos, M.-V.; Kumar, S.; Hillengass, J.; Kastritis, E.; Richardson, P.; ua al. International Myeloma Working Group tau hloov kho cov txheej txheem rau kev kuaj mob ntau yam myeloma: nthuav qhia cov yam ntxwv thiab kev kwv yees ntawm cov txiaj ntsig hauv 94 tus neeg mob los ntawm ib lub tsev kawm ntawv. Lancet Oncol. Xyoo 2014, 15, e538–e548.

3. Bladé, J.; Fernández-Llama, P.; Bosch, F.; ib. Montolíu, J. Lens, XM; Montoto, S.; Cas, A.; Darnell, UA; Rozman, C.; Montserrat, E. Lub raum Failure hauv Ntau Myeloma. Arch. Intern. Med. Xyoo 1998, 158, 1889–1893.

4. Gertz, MA; Lacy, MQ; Dispenzieri, A.; Hayman, SR; Kumar, S.; Leung, N.; Gastineau, DA Kev cuam tshuam ntawm lub hnub nyoog thiab cov ntshav creatinine tus nqi ntawm qhov tshwm sim tom qab autologous ntshav qia cell hloov rau cov neeg mob uas muaj ntau yam myeloma. Pob txha pob txha Transplant. 2007, 39, 605–611.

5. Kyle, RA; Gertz, MA; Witzig, TE; Lust, JA; Lacy, MQ; Dispenzieri, A.; Fonseca, R.; Rajkumar, SV; Kev, JR; Larson, DR; ua al. Kev tshuaj xyuas ntawm 1027 Cov Neeg Mob nrog Kev Tshawb Fawb Tshiab Ntau Yam Myeloma. Mayo Clin. Proc. 2003, 78, 21–33.

6. Augustson, BM; Pib, G.; Dunn, JA; Barth, NJ; Davies, F.; Morgan, G.; Behrens, J.; ib. Smith, UA; Me nyuam, JA; Drayson, MT Kev tuag ntxov tom qab kuaj pom ntau yam myeloma: Kev tshuaj xyuas ntawm cov neeg mob nkag mus rau hauv lub tebchaws United Kingdom kev tshawb fawb pawg thawj coj saib xyuas kev sim ntawm xyoo 1980 thiab 2002—Kev tshawb fawb kev kho mob pawg neeg laus leukemia ua haujlwm tog. J. Clin. Oncol. 2005, 23, 9219–9226.

7. Dimopoulos, M.; Delimpasi, S.; Katodritou, E.; Vaus, A.; Kyrtsonis, MC; Repousis, P.; Kartasis, Z.; Parcharidou, UA; Michael, M.; Michalis, E.; ua al. Kev txhim kho tseem ceeb hauv kev ciaj sia ntawm cov neeg mob uas muaj ntau yam myeloma tshwm sim nrog lub raum tsis zoo tom qab qhia cov neeg ua haujlwm tshiab. Ann. Oncol. 2014, 25, 195–200.

8. Bernstein, SP; Humes, HD Reversible raum insufficiency nyob rau hauv ntau yam myeloma. Arch. Intern. Med. 1982, 142, 2083–2086.

9. Knudsen, LM; Hjorth, M.; Hippe, E. Nordic Myeloma Study Group Lub raum tsis ua haujlwm nyob rau hauv ntau yam myeloma: Reversibility thiab cuam tshuam rau qhov kev tshwm sim. Eur. J. Haematol. 2000, 65, 175–181.

10. Sakhuja, V.; Yaj, V.; Vaum, S.; Joshi, K.; Gupta, KL; Sud, K.; Kohli, H. Lub raum kev koom tes hauv ntau yam myeloma: A 10- xyoo kawm. Ren. Ua tsis tiav. 2000, 22, 465–477.

11. Gonsalves, WI; Leung, N.; Rajkumar, SV; Dispenzieri, A.; Lacy, MQ; Hayman, SR; Buadi, FK; Dingli, D.; Kapoor, P.; Mus, RS; ua al. Kev txhim kho ntawm lub raum ua haujlwm thiab nws qhov cuam tshuam rau kev muaj sia nyob hauv cov neeg mob uas tau kuaj pom ntau yam myeloma tshiab. Ntshav Cancer J. 2015, 5, e296.

12. Bernard, RS; Chodirker, L.; Masih-Khan, E.; Jiang, H.; Franke, N.; Kukreti, V.; Tiedemann, R.; Trudel, S.; Reece, D.; Chen, CI Efficacy, toxicity thiab kev tuag ntawm autologous SCT nyob rau hauv ntau tus neeg mob myeloma nrog dialysis-dependent raum tsis ua haujlwm. Pob txha pob txha Transplant. Xyoo 2015, 50, 95–99.

13. Tosi, P.; Zamagni, E.; Tacchetti, P.; Ceccolini, M. Perrone, G.; Brioli, UA; Pallotti, MC; Pantani, L.; Petrucci, UA; Baccarani, M.; ua al. Thalidomide-Dexamethasone li Induction Therapy ua ntej Autologous Stem Cell Transplantation nyob rau hauv cov neeg mob uas tau kuaj pom ntau yam myeloma thiab lub raum tsis txaus. Biol. Ntshav Marrow Transplant. 2010, 16, 1115–1121.

14. Uttervall, K.; Duru, A.; Lus, J.; Liing, J.; Gahrton, G.; ib. Holmberg, E.; Aschan, J.; Alici, E.; Nahi, H. Kev siv cov tshuaj Novel tuaj yeem txhim kho cov lus teb zoo, ncua sij hawm rov qab los, thiab txhim kho kev ciaj sia nyob hauv ntau tus neeg mob Myeloma nrog raum tsis zoo. PLoS IB 2014, 9, e101819.

15. Woziwodzka, K.; Vesole, DH; Małyszko, J.; Batko, K.; Jurczyszyn, A.; Koc-˙Zórawska, E.; Krzanovski, M.; Małyszko, J.; ˙Zórawski, M.; Waszczuk-Gajda, A.; ua al. Cov cim tshiab ntawm lub raum tsis ua haujlwm hauv Ntau Myeloma thiab Monoclonal Gammopathies. J. Clin. Med. Peb Hlis 2020, 9, 1652.

16. Woziwodzka, K.; Małyszko, J.; Koc-˙Zórawska, E.; ˙Zórawski, M.; Dumnicka, P.; Jurczyszyn, A.; Batko, K.; Masur, P.; Banaszkiewicz, M.; Krzanovski, M.; ua al. Lub raum Impairment Detectors: IGFBP-7 thiab NGAL li Tubular Injury Markers nyob rau ntau tus neeg mob Myeloma. Medicina 2021, 57, 1348.

17. Herrera, GA; Joseph, L.; Gu, X.; Hoob, A.; Barlogie, B. Lub raum Pathology Spectrum nyob rau hauv ib qho Kev Txiav Txim Siab ntawm Cov Neeg Mob Plasma Cell Dyscrasia. Arch. Pathol. Lab. Med. Xyoo 2004, 128, 875–879.

18. Kim, H.R.; Park, J.-S.; Karabulut, H.; Yasmin, F.; Jun, C.-D. Transgelin-2: Ib rab ntaj ob sab hauv kev tiv thaiv kab mob thiab mob qog noj ntshav. Pem hauv ntej. Cell Dev. Biol. 2021, 9, 606149 ib.

19. Zatula, A.; Dikic, UA; Mulder, C.; Sharma, UA; Vågbø, CB; Sousa, MML; Vaaj, A.; Slupphaug, G. Proteome alterations cuam tshuam nrog kev hloov pauv ntawm ntau yam myeloma mus rau theem nrab plasma cell leukemia. Oncotarget 2016, 8, 19427–19442.

20. Meng, T.; Li, L.; Hao, R.; Chen, S.; Dong, Y. Transgelin-2: Muaj peev xwm oncogenic yam. Tumor Biol. Xyoo 2017, 39, 1010428317702650.

21. Shimada, S.; Hiros, T.; Takahashi, C.; Saib, E.; Kinugasa, S.; Awsaki, Y.; Kisu, K.; Saib, H.; Ib, S.; Mori, T. Pathphysiological thiab molecular mechanisms koom nrog raum congestion nyob rau hauv ib tug tshiab nas qauv. Sci. Rep. 2018, 8, 1–15.

22. Gerolymos, M.; Karagianni, F.; Papasotiriou, M.; Kalliakmani, P.; Sotsiou, F.; Charonis, UA; Goumenos, D. Kev nthuav qhia ntawm Transgelin hauv tib neeg Glomerulonephritis ntawm Ntau Etiology. Nephron 2011, 119, c74–c82.

23. Hauser, PV; Perco, P.; Mühlberger, ib.; Pib, J.; Blonski, M.; Mayer, IB; Alpers, CE; Oberbauer, R.; Shankland, SJ Microarray thiab Bioinformatics Analysis of Gene Expression in Experimental Membranous Nephropathy. Nephron 2009, 112, e43–e58.

24. Inomata, S.; Sakatsume, M.; Sakamaki, Y.; Wang, X.; Goto, S.; Yamamoto, T.; Gejyo, F.; Narita, I. Kev nthuav qhia ntawm SM22 (Transgelin) hauv Glomerular thiab Interstitial Renal Injury. Nephron 2011, 117, e104–e113.

25. Miao, J.; Fan, Q.; caw, q.; Zhang, H. Chen, L.; Vang, S.; Guan, N.; Guan, Y.; Ding, J. Kev txheeb xyuas cytoskeletal Cheebtsam tshiab tau cuam tshuam nrog kev hloov pauv ntawm cov txheej txheem podocyte ko taw. Nephrol. Hu rau. Hloov. 2009, 24, 3297–3305.

26. Ogawa, A.; Sakatsume, M.; Wang, X.; Sakamaki, Y.; Tsubata, Y.; Alchi, IB; Kuroda, T.; Kev, H.; Narita, ib.; Shimizu, F.; ua al. SM22 : Novel Phenotype Marker of Injured Glomerular Epithelial Cells in Anti-Glomerular Basement Membrane Nephritis. Nephron 2007, 106, e77–e87.

27. Sakamaki, Y.; Sakatsume, M.; Wang, X.; Inomata, S.; Yamamoto, T.; Gejyo, F.; Narita, I. Lub raum mob hlwb nthuav qhia SM22 (transgelin): Cov yam ntxwv tshwj xeeb txawv ntawm -smooth leeg actin (SMA). Nephrology 2011, 16, 211–218.

28. Karagianni, F.; Prakoura, N.; Kaltsa, G.; Politis, P.; Arvaniti, E.; Kaltezioti, V.; Psarras, S.; Pagakis, S.; Katsimpoulas, M.; Ab, A.; ua al. Transgelin Up-Regulation hauv Obstructive Nephropathy. PLoS ONE 2013, 8, e66887.

29. Upadhyay, R.; Ying, W.-Z.; Nasrin, Z.; Safah, H.; Jaimes, EA; Feng, W.; Sanders, PW; Batuman, V. Free light chains injure proximal tubule cells through the STAT1/HMGB1/TLR axis. JCI Insight 2020, 5, 137191.

30. Ying, W.-Z.; Li, X.; Rangarajan, S.; Feng, W.; Curtis, LWM; Sanders, PW Immunoglobulin lub teeb chains ua rau muaj kev mob thiab profibrotic raum raug mob. J. Clin. Tshawb xyuas. 2019, 129, 2792–2806.

31. Hutchison, CA; Cockwell, P.; Stringer, S.; Bradwell, UA; Cook, M.; Gertz, MA; Dispenzieri, A.; Lub caij ntuj no, JL; Kumar, S.; Rajkumar, SV; ua al. Kev txo qis thaum ntxov ntawm Serum-Free Light Chains Associates with Renal Recovery in Myeloma raum. J. Am. Soc. Nephrol. 2011, 22, 1129–1136.

32. Montseny, JJ; Kleinknecht, D.; Meyrier, UA; Vanhille, P. Simon, P.; Pluas, A.; Eladari, D. Cov txiaj ntsig ntev raws li cov kab mob raum histological hauv 118 tus neeg mob uas muaj cov kab mob monoclonal gammopathies. Nephrol. Hu rau. Hloov. Xyoo 1998, 13, 1438–1445.

33. Royal, V.; Leung, N.; Troyanov, S.; Nasr, SH; Écotière, L.; Leblanc, R.; Adas, B.; Angioi, A.; Alexander, MP; Asunis, AM; ua al. Clinicopathologic predictors ntawm lub raum tshwm sim nyob rau hauv lub teeb saw cam khwb cia nephropathy: Ib tug multicenter retrospective kawm. Ntshav 2020, 135, 1833–1846.

34. Eadon, MT; Schwantes-An, T.-H.; Phillips, CL; Roberts, AW; Greene, CV; Hallab, A.; Hart, KJ; Lip, S.; Perez-Ledezma, C.; Omar, KO; ua al. Lub raum Histopathology thiab Prediction ntawm lub raum tsis ua haujlwm: Kev Tshawb Fawb Txog Kev Tshawb Fawb. Am. J. Raum Dis. 2020, 76, 350–360.

35. Silliman, CC; Dzieciatkowska, M.; Moore, EE; Kelher, MR. Banerjee, A.; Liang, X.; Av, KJ; Hansen, KC Proteomic tsom xam ntawm tib neeg plasma: Venus piv rau Mars. Translation 2012, 52, 417–424.

36. Ortega, FJ; Moreno-Navarrete, JM; Mercader, JM; Gómez-Serrano, M.; García-Santos, E.; Latorre, J.; Lus, A.; Sabater, M.; Caballano-Infantes, E.; Guzman, R.; ua al. Cytoskeletal transgelin 2 pab txhawb rau poj niam txiv neej-dependent adipose cov ntaub so ntswg expandability thiab tiv thaiv kab mob. FASEB J. 2019, 33, 9656–9671.

37. Zeidan, A.; Swärd, K.; Nordström, ib.; Ekblad, E.; Zhang, JC; Parmacek, MS; Hellstrand, P. Ablation ntawm SM22 txo qis contractility thiab actin cov ntsiab lus ntawm nas vascular du nqaij. PEB Lett. 2004, 562, 141–146.

38. Shapland, C.; Xu, JJ; Totty, NF; Lawson, D. Purification thiab cov khoom ntawm transgelin: Ib qho kev hloov pauv thiab cov duab hloov pauv rhiab heev actin-gelling protein. J. Cell Biol. Xyoo 1993, 121, 1065–1073.

39. Yamamura, H.; Masuda, H.; Ikeda, W.; Tokuyama, T.; Takagi, M.; Shibata, N.; Taus, M.; Takahashi, K. Cov qauv thiab kev nthuav qhia ntawm tib neeg SM22 Gene, Kev Ua Haujlwm ntawm Gene rau Chromosome 11, thiab Kev Ruaj Ntseg ntawm Kev Txhawb Kev Ua Haujlwm los ntawm Cytosine DNA Methylation. J. Biochem. 1997, 122, 157–167.

40. Yin, L.-M.; Ua, L.; Yang, Y.-Q. Transgelin-2: Biochemical thiab Clinical Implications in Cancer thiab Asthma. Trends Biochem. Sci. Xyoo 2019, 44, 885–896.

41. Field-Smith, A.; Morgan, G.; Davies, F. Bortezomib (Velcade?) nyob rau hauv kev kho mob ntawm ntau yam myeloma. Ther. Clin. Risk Manag. 2006, 2, 271–279.

42. Bolomsky, A.; Hub, W.; Spada, S.; Müldür, E.; Schlangen, K.; Heintel, D.; ib. Rocci, UA; Weißmann, UA; Fritz, V.; Willheim, M.; ua al. IKAROS qhia nyob rau hauv cov pob txha hlwb sib txawv raws li tus neeg sib tw biomarker rau cov txiaj ntsig nrog kev kho lenalidomide dexamethasone hauv ntau yam myeloma. Am. J. Hematol. 2017, 92, 269–278.

43. Brunskill, EW; Sequeira-Lopez, MLS; Pentz, ES; Lin, E.; Yog, J.; Aronow, BJ; Potter, SS; Gomez, RA Genes uas lees paub tus kheej ntawm Renin Cell. J. Am. Soc. Nephrol. 2011, 22, 2213–2225.

44. Kotla, V.; Goel, S.; Nias, S.; Hais, C.; Vivek, K.; Das, B.; Verma, A. Mechanism ntawm kev txiav txim ntawm lenalidomide hauv hematological malignancies. J. Hematol. Oncol. Xyoo 2009, 2, 36.

45. Dai, X.; Thiagarajan, D.; Fang, J.; Shen, J.; Annam, NP; Yaj, Z.; Jiang, H.; Ju, D.; Xie, Y.; Zhang, K.; ua al. SM22 suppresses cytokine-induced o thiab transcription ntawm NF-κB inducing kinase (Nik) los ntawm modulating SRF transcriptional kev ua si nyob rau hauv vascular du leeg hlwb. PLoS IB 2017, 12, e0190191.

Karolina Woziwodzka 1 , Jolanta Małyszko 2 , Ewa Koc-˙Zórawska 3 , Marcin ˙Zórawski 4 , Paulina Dumnicka 5 , Artur Jurczyszyn 6 , Krzysztof Batko 1 , 5 Paulina Mazur nowski 1, Paulina Gołasa 1, Jacek A . Małyszko 7 , Ryszard Dro˙zd˙z 5 and Katarzyna Krzanowska 1,