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Ntau yam kev tshawb fawb preclinical ntawm tsim Eustachian raj (ET) stent yog tam sim no tab tom ua, tab sis nws tseem tsis tau siv hauv kev kho mob. Hauv kev tshawb fawb preclinical, ET scaffolds tau txwv rau scaffold-induced cov ntaub so ntswg proliferation. Kev ua tau zoo ntawm cobalt-chromium sirolimus-eluting stent (SES) hauv inhibiting stent-induced cov ntaub so ntswg proliferation tom qab stent tso kawm nyob rau hauv ib tug porcine ET qauv. Rau npua tau muab faib ua ob pawg (piv txwv li pab pawg tswj hwm thiab SES pawg) nrog peb tus npua hauv txhua pab pawg. Pab pawg tswj hwm tau txais ib qho tsis muaj cobalt-chromium stent (n = 6), thiab pawg SES tau txais ib qho cobalt-chromium stent nrog sirolimus-eluting txheej (n = 6). Txhua pab pawg tau txi 4 lub lis piam tom qab tso stent. Kev tso stent tau ua tiav hauv txhua qhov ETs yam tsis muaj teeb meem cuam tshuam nrog kev phais. Tsis muaj ib qho ntawm cov stents tuaj yeem khaws lawv cov qauv puag ncig, thiab cov hnoos qeev tau pom nyob rau hauv thiab ib ncig ntawm cov stents hauv ob pawg. Histological tsom xam pom tias thaj tsam ntawm cov nqaij mos proliferation thiab thickness ntawm submucosal fibrosis nyob rau hauv SES pab pawg neeg yog ho txo ​​qis tshaj nyob rau hauv pawg tswj. SES zoo li muaj txiaj ntsig zoo hauv inhibiting scaffold-induced cov ntaub so ntswg proliferation hauv ET npua. Txawm li cas los xij, kev tshawb fawb ntxiv yog xav tau kom paub meej cov ntaub ntawv zoo tshaj plaws rau stents thiab tshuaj tiv thaiv kab mob.
Eustachian tube (ET) muaj lub luag haujlwm tseem ceeb hauv pob ntseg nruab nrab (xws li kev ua pa, tiv thaiv kev hloov pauv ntawm cov kab mob thiab cov zais zis mus rau nasopharynx) 1. Kuj muaj xws li kev tiv thaiv nasopharyngeal suab thiab regurgitation2. ET feem ntau yog kaw, tab sis qhib nrog nqos, yawning, lossis zom. Txawm li cas los xij, ET tsis ua haujlwm tuaj yeem tshwm sim yog tias lub raj tsis qhib lossis kaw kom zoo3,4. Dilated (obstructive) dysfunction ntawm ET depresses ET kev ua haujlwm thiab, yog tias cov haujlwm no tsis tau khaws cia, tuaj yeem txhim kho mus rau qhov mob otitis media, ib qho ntawm cov kab mob feem ntau hauv ENT xyaum. Cov kev kho mob tam sim no rau ET dysfunction (xws li, phais qhov ntswg, tso pa tso pa, thiab siv tshuaj) yog siv rau cov neeg mob. Txawm li cas los xij, cov kev kho mob no muaj kev txwv tsis pub siv thiab tuaj yeem ua rau muaj kev cuam tshuam ET, kev kis kab mob, thiab tsis tuaj yeem rov qab tympanic membrane perforation3,6,7. Eustachian tube balloon angioplasty tau qhia ua lwm txoj kev kho mob rau dilated ET 8 tsis ua haujlwm. Txawm hais tias ntau qhov kev tshawb fawb txij li xyoo 2010 tau pom tias Eustachian tube balloon kho yog qhov zoo tshaj rau kev kho mob rau ET dysfunction, qee cov neeg mob tsis teb rau dilatation8,9,10,11. Yog li, stenting tej zaum yuav yog ib txoj kev kho mob zoo 12,13. Txawm hais tias muaj ntau qhov kev tshawb fawb tsis tu ncua ntsuas qhov ua tau zoo thiab cov ntaub so ntswg teb tom qab stent tso rau hauv ET, stent-induced cov nqaij mos hyperplasia vim kev puas tsuaj rau cov khoom siv tseem ceeb yog qhov teeb meem tom qab 14,15,16,17,18,19. tshuaj-coated, loaded nrog cov tshuaj tiv thaiv proliferative txhim kho qhov teeb meem no.
Drug-eluting stents tau siv los inhibit in-stent restenosis los ntawm cov ntaub so ntswg thiab neointimal hyperplasia tom qab tso stent. Feem ntau, stent scaffolds los yog hauv ob sab phlu yog coated nrog tshuaj (xws li, everolimus, paclitaxel, thiab sirolimus) 20,23,24. Sirolimus yog ib qho tshuaj tiv thaiv kab mob uas tiv thaiv ntau cov kauj ruam ntawm qhov restenosis cascade (xws li, o, neointimal hyperplasia, thiab collagen synthesis) 25. Yog li, qhov kev tshawb fawb no tau pom tias sirolimus-coated stents tuaj yeem tiv thaiv stent-induced nqaij hyperplasia hauv ET npua (Daim duab 1). Lub hom phiaj ntawm txoj kev tshawb no yog los tshawb xyuas qhov ua tau zoo ntawm sirolimus-eluting stents (SES) hauv inhibiting stent-induced cov ntaub so ntswg proliferation tom qab stent tso rau hauv porcine ET qauv.
Schematic illustration ntawm cobalt-chromium sirolimus-eluting stent (SES) rau kev kho mob ntawm Eustachian raj dysfunction, qhia hais tias lub sirolimus-eluting stent inhibits stent-induced cov ntaub so ntswg proliferation.
Cobalt-chromium (Co-Cr) alloy stents tau tsim los ntawm laser txiav Co-Cr alloy tubes (Genoss Co., Ltd., Suwon, Kauslim). Lub stent platform siv qhib ob daim ntawv cog lus nrog kev sib koom ua ke rau kev ua haujlwm siab nrog kev pom zoo radial quab yuam, luv luv thiab ua raws. Lub stent muaj ib txoj kab uas hla ntawm 3 hli, ntev ntawm 18 hli, thiab strut thickness ntawm 78 µm (Fig. 2a). Qhov ntev ntawm Co-Cr alloy ncej tau txiav txim siab raws li peb txoj kev tshawb fawb dhau los.
Cobalt-chromium (Co-Cr) alloy stent thiab hlau qhia sheath rau Eustachian raj stent tso. Cov duab qhia (a) Co-Cr alloy stent thiab (b) stent-clamped balloon catheter. (c) Lub zais pa catheter thiab stent tau siv tag nrho. (d) Ib daim ntawv qhia hlau yog tsim los rau porcine Eustachian raj qauv.
Sirolimus tau siv rau saum npoo ntawm stent siv ultrasonic spray technology. SES yog tsim los tso tawm yuav luag 70% ntawm thawj cov tshuaj thauj khoom (1.15 µg / mm2) hauv thawj 30 hnub tom qab tso. Ib txheej txheej ultra-nyias 3 µm tsuas yog siv rau sab ze ntawm lub stent kom ua tiav cov yeeb yaj kiab uas xav tau thiab txo cov nyiaj polymer; no biodegradable txheej muaj ib copolymer ntawm lactic thiab glycolic acids thiab ib tug proprietary blend ntawm poly(1)-lactic acid)26,27. Co-Cr alloy stents tau crimped mus rau balloon catheters 3 mm nyob rau hauv txoj kab uas hla thiab 28 mm ntev (Genoss Co., Ltd.; Fig. 2b). Cov stents no muaj nyob rau hauv Kaus Lim Qab Teb rau kev kho mob plawv.
Cov txheej txheem tshiab tsim hlau qhia plhaub rau npua ET qauv yog ua los ntawm stainless hlau (Fig. 2c). Sab hauv thiab sab nraud ntawm lub plhaub yog 2 hli thiab 2.5 hli, feem, qhov ntev yog 250 hli. Lub distal 30 mm sheath tau khoov rau hauv J-puab ntawm 15 ° lub kaum sab xis rau lub axis kom yooj yim nkag los ntawm lub qhov ntswg mus rau nasopharyngeal orifice ntawm ET hauv tus qauv npua.
Txoj kev tshawb no tau pom zoo los ntawm Pawg Saib Xyuas Tsiaj Tsiaj thiab Siv Pawg ntawm Asan Institute of Life Sciences (Seoul, South Kauslim) thiab ua raws li National Institutes of Health Guidelines for the Humane Treatment of Laboratory Animals (IACUC-2020-12-189). . Txoj kev tshawb no tau ua raws li ARRIVE cov lus qhia. Txoj kev tshawb no siv 12 ETs hauv 6 tus npua uas hnyav 33.8-36.4 kg thaum muaj hnub nyoog 3 hlis. Rau npua tau muab faib ua ob pawg (piv txwv li pab pawg tswj hwm thiab SES pawg) nrog peb tus npua hauv txhua pab pawg. Pab pawg tswj hwm tau txais ib qho tsis muaj co-Cr alloy stent, thaum pawg SES tau txais Co-Cr alloy stent eluting sirolimus. Txhua tus npua tau nkag mus rau dej thiab pub dawb thiab tau khaws cia ntawm 24 ° C ± 2 ° C rau 12-teev nruab hnub hmo ntuj. Tom qab ntawd, tag nrho cov npua tau txi 4 lub lis piam tom qab tso stent.
Txhua tus npua tau txais kev sib xyaw ntawm 50mg / kg zolazepam, 50mg / kg teletamide (Zoletil 50; Virbac, Carros, Fabkis) thiab 10mg / kg xylazine (Rompun; Bayer HealthCare, Les Varkouzins, Lub teb chaws Yelemees). Tom qab ntawd lub raj tracheal tau muab tso rau hauv qhov nqus ntawm 0.5-2% isoflurane (Ifran®; Hana Pharm. Co., Seoul, Kauslim) thiab oxygen 1: 1 (510 ml / kg / min) rau tshuaj loog. Npua tau muab tso rau hauv txoj hauj lwm supine thiab lub hauv paus endoscopy (VISERA 4K UHD rhinolaryngoscope; Olympus, Tokyo, Nyiv) tau ua los tshuaj xyuas lub nasopharyngeal orifice ntawm ET. Ib daim hlau qhia sheath tau dhau los ntawm lub qhov ntswg mus rau nasopharyngeal orifice ntawm ET nyob rau hauv endoscopic tswj (Daim duab 3a, b). Lub zais pa catheter, ib lub corrugated stent, yog ntxig los ntawm tus neeg qhia rau hauv ET kom txog thaum nws cov lus taw qhia raws li kev tiv thaiv hauv osteochondral isthmus ntawm ET (Daim duab 3c). Lub zais pa catheter tau ua kom puv nrog ntsev rau 9 qhov chaw, raws li kev txiav txim siab los ntawm tus saib xyuas manometer (Daim duab 3d). Lub zais pa catheter raug tshem tawm tom qab tso stent (Fig. 3f), thiab qhov qhib qhov ntswg tau ua tib zoo soj ntsuam endoscopy rau kev phais mob (Daim duab 3f). Txhua tus npua tau kuaj xyuas ua ntej thiab tam sim ntawd tom qab stenting, nrog rau 4 lub lis piam tom qab stenting, txhawm rau txheeb xyuas qhov patency ntawm qhov chaw stent thiab ib puag ncig cov zais zis.
Cov kauj ruam kev ua haujlwm rau kev tso ib lub stent rau hauv eustachian raj (ET) ntawm tus npua nyob rau hauv kev tswj endoscopic. (a) Endoscopic duab qhia lub nasopharyngeal qhib ( xub xub) thiab ntxig hlau qhia sheath ( xub). (b) Ntxig ib tug hlau sheath ( xub) rau hauv lub nasopharyngeal qhib. (c) Ib qho stent-clamped balloon catheter ( xub) yog nkag rau hauv ET los ntawm ib lub hnab ( xub xub). (d) Lub zais pa catheter ( xub xub) yog tag nrho inflated. (e) Qhov kawg ntawm qhov stent protrudes los ntawm ET orifice ntawm nasopharynx. (f) Endoscopic duab qhia stent lumen patency.
Txhua tus npua tau euthanized los ntawm kev tswj hwm 75 mg / kg poov tshuaj chloride los ntawm kev txhaj tshuaj hauv pob ntseg. Qhov nruab nrab sagittal ntawm lub taub hau porcine tau ua los ntawm kev siv lub saw saw txuas ntxiv los ntawm kev ua tib zoo rho tawm ntawm ET scaffold cov ntaub so ntswg kuaj rau kev kuaj mob histological (Ntxiv daim duab 1a,b). ET cov ntaub so ntswg kuaj tau kho nyob rau hauv 10% nruab nrab buffered formalin rau 24 teev.
ET cov ntaub so ntswg kuaj tau ua kom lub cev qhuav dej nrog cawv ntawm ntau qhov ntau. Cov qauv raug muab tso rau hauv cov blocks resin los ntawm kev nkag mus nrog ethylene glycol methacrylate (Technovit 7200® VLC; Heraus Kulzer GMBH, Wertheim, Lub teb chaws Yelemees). Axial seem tau ua nyob rau hauv embedded ntaub so ntswg specimens nyob rau hauv lub proximal thiab distal seem (Ntxiv daim duab 1c). Tom qab ntawd cov polymer blocks tau muab tso rau ntawm acrylic iav slides. Resin block slides yog microground thiab polished nrog silicon carbide ntawv ntawm ntau yam thicknesses mus txog ib tug tuab ntawm 20 µm siv ib daim phiaj system (Apparatebau GMBH, Hamburg, lub teb chaws Yelemees). Tag nrho cov slides tau raug soj ntsuam histological nrog hematoxylin thiab eosin staining.
Kev ntsuam xyuas histological tau ua los ntsuas qhov feem pua ​​​​ntawm cov nqaij mos proliferation, thickness ntawm submucosal fibrosis, thiab qib ntawm inflammatory cell infiltration. Qhov feem pua ​​​​ntawm cov nqaij mos hyperplasia nrog qhov nqaim ET qhov chaw hla ntu tau suav los ntawm kev daws qhov sib npaug:
Lub thickness ntawm submucosal fibrosis tau ntsuas vertically los ntawm stent struts mus rau submucosa. Lub degree ntawm inflammatory cell infiltration yog subjectively txiav txim los ntawm kev faib thiab ceev ntawm inflammatory cells, namely: 1st degree (mob) - ib tug tib leukocyte infiltration; 2nd degree (mob rau nruab nrab) - focal leukocyte infiltration; 3rd degree (nruab nrab) - ua ke. nrog leukocytes tsis tuaj yeem paub qhov txawv ntawm tus kheej loci; Qib 4 (nruab nrab mus rau hnyav) leukocytes diffusely infiltrating tag nrho submucosa, thiab qib 5 (hnyav) diffuse infiltration nrog ntau foci ntawm necrosis. Lub thickness ntawm submucosal fibrosis thiab qib ntawm inflammatory cell infiltration tau los ntawm nruab nrab yim lub ntsiab lus nyob ib ncig ntawm lub ncig. Kev soj ntsuam histological ntawm ET tau ua tiav siv lub tshuab ntsuas (BX51; Olympus, Tokyo, Nyiv). Cov kev ntsuas tau txais los ntawm CaseViewer software (CaseViewer; 3D HISTECH Ltd., Budapest, Hungary). Kev soj ntsuam ntawm cov ntaub ntawv histological tau ua raws li kev pom zoo ntawm peb tus neeg soj ntsuam uas tsis koom nrog hauv txoj kev tshawb no.
Mann-Whitney U-test tau siv los txheeb xyuas qhov sib txawv ntawm pawg raws li xav tau. A p <0.05 tau suav tias yog qhov tseem ceeb. A p <0.05 tau suav tias yog qhov tseem ceeb. Значение p < 0,05 считалось статистически значимым. Tus nqi p <0.05 tau suav tias yog qhov tseem ceeb. p <0.05 被认为具有统计学意义. p <0.05 p <0,05 считали статистически значимым. p <0.05 tau suav tias yog qhov tseem ceeb. Bonferroni-kho Mann-Whitney U-test tau ua rau p qhov tseem ceeb < 0.05 txhawm rau txheeb xyuas pab pawg sib txawv (p < 0.008 raws li kev txheeb cais tseem ceeb). Bonferroni-kho Mann-Whitney U-test tau ua rau p qhov tseem ceeb < 0.05 txhawm rau txheeb xyuas pab pawg sib txawv (p <0.008 raws li qhov tseem ceeb). U-критерий Манна-Уитни с поправкой на Бонферрони был выполнен для значений p <0,05 для выявления <0,05 для выявления груполнен груполнен как статистически значимое). Bonferroni-adjusted Mann-Whitney U kuaj tau ua rau p qhov tseem ceeb <0.05 txhawm rau txheeb xyuas pab pawg sib txawv (p <0.008 raws li qhov tseem ceeb).对p 值< 0.05 进行Bonferroni 校正的Mann-Whitney U 检验以检测组差异 (p < 0.008 具有统计学意义).对p 值< 0.05 进行Bonferroni 校正的Mann-Whitney U U-критерий Манна-Уитни с поправкой на Бонферрони был выполнен для значений p < 0.05 для выявления груполнен 0,008 был статистически значимым). Bonferroni-adjusted Mann-Whitney U-test tau ua rau p <0.05 txhawm rau txheeb xyuas cov pab pawg sib txawv (p <0.008 yog qhov tseem ceeb).Kev txheeb cais tau ua tiav siv SPSS software (version 27.0; SPSS, IBM, Chicago, IL, USA).
Txhua qhov chaw porcine stent tau ua tiav kev ua tiav. Ib daim ntawv qhia hlau tau ua tiav nyob rau hauv lub nasopharyngeal orifice ntawm ET nyob rau hauv endoscopic tswj, txawm hais tias mucosal raug mob nrog los ntshav tau pom nyob rau hauv 4 ntawm 12 tus qauv (33.3%) thaum lub sij hawm hlau sheath insertion. Tom qab 4 lub lis piam, palpable los ntshav spontaneously nres. Txhua tus npua ciaj sia mus txog qhov kawg ntawm txoj kev tshawb no yam tsis muaj teeb meem nrog stent.
Endoscopy cov txiaj ntsig tau pom nyob rau hauv daim duab 4. Thaum lub sij hawm 4-lub lim tiam tom qab, cov stents tseem nyob hauv txhua tus npua. Mucus tsub zuj zuj hauv thiab ib ncig ntawm ET stent tau pom nyob rau hauv tag nrho (100%) ETs hauv pawg tswj hwm thiab peb (50%) ntawm rau ETs hauv pawg SES, thiab tsis muaj qhov sib txawv ntawm ob pawg (p = 0.182). Tsis muaj ib qho ntawm cov stents ntsia tau tuaj yeem tuav ib puag ncig.
Endoscopic dluab ntawm Eustachian raj (ET) ntawm ib tug npua hauv pawg tswj thiab pab pawg nrog cobalt-chromium stent (CXS) eluting sirolimus. (a) Baseline endoscopic duab coj ua ntej stent qhov chaw uas qhia lub nasopharyngeal qhib ( xub xub) ntawm ET. (b) Endoscopic duab coj tam sim ntawd tom qab tso stent qhia ET ntawm stent tso. Kev sib cuag los ntshav tau raug pom vim yog cov ntawv qhia hlau (xub xub). (c) Daim duab Endoscopic coj 4 lub lis piam tom qab tso stent qhia pom cov hnoos qeev nyob ib ncig ntawm lub stent ( xub xub). (d) Endoscopic duab qhia tias lub stent tsis tuaj yeem nyob puag ncig ( xub xub).
Cov kev tshawb pom histological tau pom nyob rau hauv daim duab 5 thiab daim duab ntxiv 2. Cov ntaub so ntswg proliferation thiab submucosal fibrous proliferation ntawm stent posts hauv ET lumen ntawm ob pawg. Qhov feem pua ​​​​ntawm cov ntaub so ntswg hyperplasia yog qhov loj dua hauv pawg tswj hwm ntau dua li hauv pawg SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001). Qhov feem pua ​​​​ntawm cov ntaub so ntswg hyperplasia yog qhov loj dua hauv pawg tswj hwm ntau dua li hauv pawg SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001). Средний процент площади гиперплазии тканей был значительно больше в контрольной группе, чем в 7 ± 4 групе 6,82% против 48,36% ± 10,06%, p < 0,001). Qhov nruab nrab thaj tsam feem pua ​​​​ntawm cov ntaub so ntswg hyperplasia tau loj dua hauv pawg tswj hwm ntau dua li hauv pawg SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001).SES 组 (79.48% ± 6.82% vs.48.36% ± 10.06%, p <0.001). 48.36% ± 10.06%, p <0.001). Средний процент площади гиперплазии тканей в контрольной группе был значительно выше, чем в 6 груС, 7% пе против 48,36% ± 10,06%, p <0,001). Qhov nruab nrab thaj tsam feem pua ​​​​ntawm cov nqaij mos hyperplasia hauv pawg tswj tau ntau dua li hauv pawg SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001). Ntxiv mus, qhov nruab nrab thickness ntawm submucosal fibrosis kuj tseem ceeb heev nyob rau hauv cov tswj pawg tshaj li nyob rau hauv SES pawg (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001). Ntxiv mus, qhov nruab nrab thickness ntawm submucosal fibrosis kuj tseem ceeb heev nyob rau hauv cov tswj pawg tshaj li nyob rau hauv SES pawg (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001). Более того, средняя толщина подслизистого фиброза также была значительно выше в контрольной , груга СЭС (1,41 ± 0,25 против 0,56 ± 0,20 мм, p < 0,001). Ntxiv mus, qhov nruab nrab thickness ntawm submucosal fibrosis kuj tseem ceeb heev nyob rau hauv cov tswj pawg tshaj li nyob rau hauv SES pawg (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001).SES 组 (1.41 ± 0.25 vs.0.56 ± 0.20 hli, p <0.001). 0.56 ± 0.20mm, p <0.001). Кроме того, средняя толщина подслизистого фиброза в контрольной группе также была значительно чруппе была значительно (1,41 ± 0,25 против 0,56 ± 0,20 мм, p < 0,001). Tsis tas li ntawd, qhov nruab nrab thickness ntawm submucosal fibrosis nyob rau hauv pawg tswj kuj tseem ho siab tshaj nyob rau hauv SES pawg (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001).Txawm li cas los xij, tsis muaj qhov sib txawv tseem ceeb hauv qib ntawm inflammatory cell infiltration ntawm ob pawg (tswj pab pawg [3.50 ± 0.55] vs. SES pawg [3.00 ± 0.89], p = 0.270).
Kev soj ntsuam ntawm histological ntawm ob pawg ntawm stents tso rau hauv Eustachian lumen. (a, b) thaj tsam ntawm cov nqaij mos hyperplasia (1 ntawm a thiab b) thiab cov tuab ntawm submucosal fibrosis (2 ntawm a thiab b; ob lub xub) tau loj dua hauv pawg tswj hwm ntau dua li hauv pawg SES nrog strut stenting (dub dots), thaj tsam ntawm cov lumen nqaim (daj) thiab thaj tsam qub (daj)). Qhov degree ntawm inflammatory cell infiltration (3 ntawm a thiab b; xub) tsis txawv ntawm ob pawg. (c) Cov txiaj ntsig histological ntawm feem pua ​​​​ntawm cov ntaub so ntswg hyperplasia, (d) thickness ntawm submucosal fibrosis, thiab (e) degree ntawm inflammatory cell infiltration 4 lub lis piam tom qab stent tso rau hauv ob pawg. SES, cobalt-chromium sirolimus eluting stent.
Drug-eluting stents pab txhim kho stent patency thiab tiv thaiv stent restenosis20,21,22,23,24. Stent-induced strictures tshwm sim los ntawm granulation cov ntaub so ntswg tsim thiab fibrous cov ntaub so ntswg hloov nyob rau hauv ntau yam uas tsis yog-vascular kab mob, nrog rau txoj hlab pas, trachea, gastroduodenum, thiab bile ducts. Cov tshuaj xws li dexamethasone, paclitaxel, gemcitabine, EW-7197, thiab sirolimus yog siv rau saum npoo ntawm cov hlau mesh lossis stent txheej los tiv thaiv lossis kho cov ntaub so ntswg hyperplasia tom qab stent tso 29,30,34,35,36. Cov kev hloov tshiab tsis ntev los no hauv kev ua haujlwm ntawm ntau lub tshuab stents siv fusion technology tau raug tshawb xyuas rau kev kho mob ntawm cov kab mob uas tsis yog vascular occlusive37,38,39. Hauv kev tshawb fawb yav dhau los hauv tus qauv porcine ET, scaffold-induced cov ntaub so ntswg proliferation tau pom. Txawm hais tias kev txhim kho stent hauv ET tsis to taub zoo, cov ntaub so ntswg teb tom qab tso stent tau pom tias zoo ib yam li lwm cov kab mob uas tsis yog vascular luminal19. Hauv kev tshawb fawb tam sim no, SES tau siv los tiv thaiv scaffold-induced cov ntaub so ntswg proliferation hauv porcine ET qauv. Sirolimus yog tshuaj lom rau pancreatic islets thiab beta cell kab, txo cov cell viability thiab txhim kho apoptosis40,41. Cov nyhuv no yuav pab kom inhibit qhov tsim ntawm cov ntaub so ntswg proliferation los ntawm stimulating cell tuag. Peb txoj kev tshawb fawb tau pom tias thawj zaug siv cov tshuaj eluting stents hauv ET tau zoo inhibited stent-induced cov nqaij mos proliferation hauv ET.
Lub balloon-expandable Co-Cr alloy stent siv nyob rau hauv txoj kev tshawb no yog yooj yim muaj raws li nws yog feem ntau siv los kho tus kab mob coronary artery 42. Tsis tas li ntawd, Co-Cr alloys muaj cov khoom siv kho tshuab (piv txwv li, lub zog radial siab thiab inelastic rog) 43 . Raws li kev tshawb fawb endoscopy ntawm txoj kev tshawb fawb tam sim no, Co-Cr alloy stent siv rau ET ntawm npua tsis tuaj yeem tuav ib puag ncig zoo hauv txhua tus npua vim tsis txaus elasticity thiab tsis muaj peev xwm los nthuav nws tus kheej. Cov duab ntawm qhov ntxig stent tuaj yeem hloov pauv los ntawm kev txav mus los ntawm ET ntawm cov tsiaj muaj sia (xws li zom thiab nqos). Cov khoom siv hluav taws xob ntawm Co-Cr alloy stents tau dhau los ua qhov tsis zoo nyob rau hauv qhov chaw ntawm porcine ET stents. Tsis tas li ntawd, qhov chaw ntawm stent nyob rau hauv lub isthmus yuav ua rau qhib ET mus tas li. Kev qhib tsis tu ncua lossis ncua ET tso cai rau kev hais lus thiab nasopharyngeal suab, gastrointestinal reflux, thiab pathogens1 mus rau hauv nruab nrab pob ntseg, ua rau mucosal irritation thiab kis kab mob. Yog li ntawd, yuav tsum zam qhov qhib qhov ntswg mus tas li. Yog li ntawd, muab cov qauv ntawm ET pob txha mos, scaffolds yog nyiam dua los ntawm cov duab nco alloys nrog superelastic zog, xws li nitinol. Feem ntau, hnyav tawm tau pom nyob rau hauv thiab ib ncig ntawm lub nasopharyngeal orifice ntawm stent. Txij li thaum lub cev mucociliary txav ntawm cov hnoos qeev raug thaiv, qhov zais cia yuav tsum khaws cia rau hauv scaffolds protruding los ntawm qhov qhib nasopharyngeal. Kev tiv thaiv kab mob hauv pob ntseg nruab nrab yog ib lub hom phiaj tseem ceeb ntawm ET, thiab kev tso cov stents uas protrude tshaj ET yuav tsum raug zam, txij li kev sib cuag ncaj qha ntawm stents nrog nasopharyngeal kab mob tuaj yeem ua rau muaj kab mob nce ntxiv.
Eustachian tube balloon plasty los ntawm qhov qhib nasopharyngeal yog ib qho kev kho mob tsawg kawg nkaus rau ET dysfunction aimed ntawm qhib thiab nthuav cov cartilaginous feem ntawm ET8,9,10,46. Txawm li cas los xij, cov txheej txheem kho mob hauv qab no tsis tau txheeb xyuas 47 thiab nws cov txiaj ntsig mus ntev yuav yog qhov zoo tshaj 8,9,11,46. Nyob rau hauv cov xwm txheej no, ib ntus hlau stenting yuav yog ib qho kev kho mob zoo rau cov neeg mob uas tsis teb rau Eustachian tube balloon kho, thiab qhov ua tau ntawm ET stenting tau pom nyob rau hauv ntau cov kev tshawb fawb preclinical. Poly-l-lactide scaffolds tau muab cog los ntawm tympanic membrane hauv chinchillas thiab luav los ntsuas kev kam rau siab thiab degradation hauv vivo17,18. Tsis tas li ntawd, tus qauv yaj tau tsim los ntsuas qhov profile ntawm cov hlau balloon expandable stents hauv vivo. Hauv peb txoj kev tshawb fawb yav dhau los, tus qauv porcine ET tau tsim los tshawb xyuas qhov ua tau zoo thiab kev soj ntsuam ntawm cov teeb meem tshwm sim los ntawm stent, 19 muab lub hauv paus ruaj khov rau txoj kev tshawb no los tshawb xyuas qhov ua tau zoo ntawm SES siv cov txheej txheem yav dhau los. Nyob rau hauv txoj kev tshawb no, SES tau ua tiav nyob rau hauv cov pob txha mos thiab zoo inhibited cov ntaub so ntswg proliferation. Tsis muaj cov teeb meem cuam tshuam nrog stent, tab sis muaj kev raug mob los ntawm cov hlau qhia sheath nrog kev sib cuag los ntshav uas daws tau tus kheej li ntawm 4 lub lis piam. Muab cov teeb meem muaj peev xwm ntawm cov hlau sheaths, kev txhim kho SES kev xa khoom yog ceev thiab tseem ceeb.
Txoj kev tshawb no muaj qee qhov kev txwv. Txawm hais tias kev tshawb pom histological sib txawv ntawm cov pab pawg, cov tsiaj hauv qhov kev tshawb fawb no tsawg dhau rau kev txheeb xyuas kev txheeb xyuas kev ntseeg tau. Txawm hais tias peb tus neeg soj ntsuam tau ua qhov muag tsis pom kev los ntsuas qhov sib txawv ntawm cov neeg soj ntsuam, qhov degree ntawm submucosal inflammatory cell infiltration tau txiav txim siab raws li kev faib tawm thiab qhov ntom ntawm cov kab mob inflammatory vim qhov nyuaj ntawm enumerating inflammatory cells. Txij li thaum peb txoj kev tshawb fawb tau ua los ntawm kev siv qee tus tsiaj loj, ib koob tshuaj tau siv, hauv vivo pharmacokinetic kev tshawb fawb tsis tau ua. Cov kev tshawb fawb ntxiv yog xav tau kom paub meej tias qhov kev pom zoo ntawm cov tshuaj thiab kev nyab xeeb ntawm sirolimus hauv ET. Thaum kawg, 4-lub lim tiam kev soj ntsuam kuj yog ib qho kev txwv ntawm txoj kev tshawb no, yog li kev tshawb fawb txog kev ua haujlwm ntev ntawm SES yog xav tau.
Cov txiaj ntsig ntawm txoj kev tshawb no qhia tau hais tias SES tuaj yeem cuam tshuam cov neeg kho tshuab raug mob-vim cov ntaub so ntswg proliferation tom qab muab tso rau ntawm balloon-expandable Co-Cr alloy scaffolds nyob rau hauv ib tug porcine ET qauv. Plaub lub lis piam tom qab tso stent, cov kev hloov pauv uas cuam tshuam nrog cov ntaub so ntswg tshwm sim (nrog rau thaj tsam ntawm cov nqaij mos proliferation thiab thickness ntawm submucosal fibrosis) tau qis dua hauv pawg SES dua li hauv pawg tswj hwm. SES zoo li muaj txiaj ntsig zoo hauv inhibiting scaffold-induced cov ntaub so ntswg proliferation hauv ET npua. Txawm hais tias xav tau kev tshawb fawb ntxiv los ntsuas cov khoom siv stent zoo thiab ntau npaum li cas ntawm cov neeg sib tw tshuaj, SES muaj peev xwm kho tau hauv zos hauv kev tiv thaiv ET cov ntaub so ntswg hyperplasia tom qab tso stent.
Di Martino, EF Eustachian tube kev ua haujlwm kuaj: qhov hloov tshiab. Nitric acid 61, 467–476. https://doi.org/10.1007/s00106-013-2692-5 (2013).
Adil, E. & Poe, D. Dab tsi yog tag nrho cov kev kho mob thiab phais kev kho mob muaj rau cov neeg mob uas muaj Eustachian tube dysfunction?. Adil, E. & Poe, D. Dab tsi yog tag nrho cov kev kho mob thiab phais kev kho mob muaj rau cov neeg mob uas muaj Eustachian tube dysfunction?.Adil, E. thiab Poe, D. Dab tsi yog tag nrho cov kev kho mob thiab kev phais kev kho mob rau cov neeg mob uas muaj Eustachian raj tsis ua haujlwm? Adil, E. & Poe, D. Adil, E. & Poe, D.Adil, E. thiab Poe, D. Dab tsi yog tag nrho cov kev kho mob thiab kev phais kho mob muaj rau cov neeg mob uas muaj Eustachian tube dysfunction?Tam sim no. Kev xav. Otolaryngology. Kev phais ntawm lub taub hau thiab caj dab. 22:8-15. https://doi.org/10.1097/moo.00000000000000020 (2014).
Llewellyn, A. et al. Kev cuam tshuam rau eustachian raj tsis ua haujlwm hauv cov neeg laus: kev tshuaj xyuas zoo. kev noj qab haus huv technology. Ntsuas. 18 (1-180), v-vi. https://doi.org/10.3310/hta18460 (2014).
Schilder, AG et al. Eustachian tube dysfunction: kev pom zoo ntawm cov ntsiab lus, hom, kev kho mob tshwm sim, thiab kev kuaj mob. kho mob. Otolaryngology. 40, 407–411. https://doi.org/10.1111/coa.12475 (2015).
Bluestone, CD Lub pathogenesis ntawm otitis media: lub luag hauj lwm ntawm Eustachian raj. Pediatrics. Kab mob. Dis. J. 15, 281–291. https://doi.org/10.1097/00006454-199604000-00002 (1996).
McCoul, ED, Singh, A., Anand, VK & Tabaee, A. Balloon dilation of the Eustachian tube in a cadaver model: Technical considerations, learning curve, and potential barriers. McCoul, ED, Singh, A., Anand, VK & Tabaee, A. Balloon dilation of the Eustachian tube in a cadaver model: Technical considerations, learning curve, and potential barriers.McCole, ED, Singh, A., Anand, VK thiab Tabai, A. Balloon dilatation of the eustachian tube in a trophoblastic model: technical considerations, learning curve, and potential obstacles. McCoul, ED, Singh, A., Anand, VK & Tabaee, A. McCoul, ED, Singh, A., Anand, VK & Tabaee, A. 尸体model中少鼓管的气球 Expansion: technical considerations, learning curve and potential obstacles.McCole, ED, Singh, A., Anand, VK thiab Tabai, A. Balloon dilatation of the eustachian tube in a trophoblastic model: technical considerations, learning curve, and potential obstacles.Laryngoscope 122, 718–723. https://doi.org/10.1002/lary.23181 (2012).
Norman, G. et al. Kev tshuaj xyuas cov ntaub ntawv pov thawj tsawg rau kev kho mob ntawm eustachian tube dysfunction: kev ntsuas kev kho mob. kho mob. Otolaryngology. Sab 39, 6–21. https://doi.org/10.1111/coa.12220 (2014).
Ockermann, T., Reineke, U., Upile, T., Ebmeyer, J. & Sudhoff, HH Balloon dilation Eustachian tuboplasty: Kev tshawb fawb txog qhov ua tau. Ockermann, T., Reineke, U., Upile, T., Ebmeyer, J. & Sudhoff, HH Balloon dilation Eustachian tuboplasty: Kev tshawb fawb txog qhov ua tau.Okkermann, T., Reineke, U., Upile, T., Ebmeyer, J. and Sudhoff, HH Balloon dilatation of the Eustachian tuboplasty: feasibility study. Ockermann, T., Reineke, U., Upile, T., Ebmeyer, J. & Sudhoff, HH 球囊扩张咽鼓管成形术：可行性研究. Ockermann, T., Reineke, U., Upile, T., Ebmeyer, J. & Sudhoff, HH.Okkermann T., Reineke U., Upile T., Ebmeyer J. thiab Sudhoff HH Balloon dilatation of Eustachian tube angioplasty: kev kawm ua tau.Tus sau. neuron. 31, 11:00–11:03 dr hab. https://doi.org/10.1097/MAO.0b013e3181e8cc6d (2010).
Randrup, TS & Ovesen, T. Balloon Eustachian tuboplasty: Kev tshuaj xyuas zoo. Randrup, TS & Ovesen, T. Balloon Eustachian tuboplasty: Kev tshuaj xyuas zoo.Randrup, TS thiab Ovesen, T. Ballon, Eustachian tuboplasty: kev tshuaj xyuas zoo. Randrup, TS & Ovesen, T. Balloon Eustachian tuboplasty: 系统评价. Randrup, TS & Ovesen, T. Balloon Eustachian tuboplasty: 系统评价.Randrup, TS thiab Ovesen, T. Ballon, Eustachian tuboplasty: kev tshuaj xyuas zoo.Otolaryngology. Kev phais ntawm lub taub hau thiab caj dab. 152, 383–392, ib. https://doi.org/10.1177/0194599814567105 (2015).
Song, HY et al. Fluoroscopic balloon dilatation siv ib tug hloov tau yooj yim guidewire rau obstructive Eustachian raj tsis ua hauj lwm. J. Vaske. xam phaj. hluav taws xob. 30 Ib., 1562-1566. https://doi.org/10.1016/j.jvir.2019.04.041 (2019).
Silvola, J., Kivekäs, I. & Poe, DS Balloon dilation ntawm cartilaginous feem ntawm Eustachian raj. Silvola, J., Kivekäs, I. & Poe, DS Balloon dilation ntawm cartilaginous feem ntawm Eustachian raj. Silvola, J., Kivekäs, I. & Poe, DS Баллонная дилатация хрящевой части евстахиевой трубы. Silvola, J., Kivekäs, I. & Poe, DS Balloon dilatation of the cartilaginous part of the Eustachian tube. Silvola, J., Kivekäs, I. & Poe, DS 咽鼓管软骨部分的气球扩张. Silvola, J., Kivekäs, I. & Poe, DS Silvola, J., Kivekäs, I. & Poe, DS Баллонная дилатация хрящевой части евстахиевой трубы. Silvola, J., Kivekäs, I. & Poe, DS Balloon dilatation of the cartilaginous part of the Eustachian tube.Otolaryngology. Shea Journal of Surgery. 151, 125–130. https://doi.org/10.1177/0194599814529538 (2014).
Song, HY et al. Retrievable nitinol-coated stent: kev paub txog kev kho mob ntawm 108 tus neeg mob uas muaj cov kab mob esophageal strictures. J. Wask. xam phaj. hluav taws xob. 13, 285-293, ib. https://doi.org/10.1016/s1051-0443(07)61722-9 (2002).
Song, HY et al. Self-expanding hlau stents nyob rau hauv high-risk benign prostatic hyperplasia cov neeg mob: ib tug mus sij hawm ntev soj ntsuam. Radiology 195, 655–660. https://doi.org/10.1148/radiology.195.3.7538681 (1995).
Schnabl, J. et al. Yaj raws li tus qauv tsiaj loj rau cov khoom siv hnov ​​​​lus cog rau hauv nruab nrab thiab sab hauv pob ntseg: kev kawm cadaveric feasibility. Tus sau. neurons. 33, 481–489, ib. https://doi.org/10.1097/MAO.0b013e318248ee3a (2012).
Pohl, F. et al. Eustachian tube stent nyob rau hauv kev kho mob ntawm otitis media - ib qho kev kawm ua tau nyob rau hauv yaj. Tshuaj ntawm lub taub hau thiab lub ntsej muag. 14, 8. https://doi.org/10.1186/s13005-018-0165-5 (2018).
Park, JH et al. Qhov ntswg tso ntawm balloon-expandable hlau stents: kev kawm ntawm Eustachian raj hauv tib neeg cadaver. J. Vaske. xam phaj. hluav taws xob. 29 Ib., 1187-1193. https://doi.org/10.1016/j.jvir.2018.03.029 (2018).
Litner, JA et al. Tolerability thiab kev nyab xeeb ntawm poly-l-lactide eustachian raj stents siv tus qauv chinchilla tsiaj. J. Intern. Advanced. Tus sau. 5, 290–293 (2009).
Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. Lub poly-l-lactide Eustachian raj stent: Tolerability, kev nyab xeeb thiab resorption nyob rau hauv ib tug luav qauv. Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. Lub poly-l-lactide Eustachian raj stent: Tolerability, kev nyab xeeb thiab resorption nyob rau hauv ib tug luav qauv. Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. Стент для евстахиевой трубы из поли-l-лактида: переносимость, безопа сно модели кролика. Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. Poly-l-lactide eustachian tube stent: tolerability, kev nyab xeeb, thiab resorption hauv tus qauv luav. Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. 聚-l-丙交酯咽鼓管支架：兔模型的耐受性、安全性和吸收. Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. 聚-l-丙交阿师鼓管板入：兔注册的耐受性、safety and absorption.Presti, P., Linstrom, SJ, Silverman, KA thiab Littner, J. Poly-1-lactide eustachian tube stent: kam rau ua, kev nyab xeeb, thiab nqus hauv tus qauv luav.J. Nruab nrab ntawm lawv. Tom ntej. Tus sau. 7, 1-3 (2011).
Kim, Y. et al. Technical feasibility thiab histological tsom xam ntawm balloon-expandable hlau stents muab tso rau hauv porcine Eustachian raj. nqe lus. kev kawm. 11, 1359 (2021).
Shen, JH et al. Tissue hyperplasia: kev tshawb nrhiav ntawm paclitaxel-coated stents hauv tus qauv canine urethra. Xov tooj cua 234, 438–444. https://doi.org/10.1148/radiol.2342040006 (2005).
Shen, JH et al. Cov nyhuv ntawm dexamethasone-coated stent grafts ntawm cov ntaub so ntswg teb: kev sim kawm hauv tus qauv canine bronchial. EURO. hluav taws xob. 15 Ib., 1241–1249. https://doi.org/10.1007/s00330-004-2564-1 (2005).
Kim, E.Yu. IN-1233 Coated Hlau Stent Tiv Thaiv Hyperplasia: Kev Tshawb Fawb Kev Tshawb Fawb hauv Rabbit Esophagus Model. Xov tooj cua 267, 396–404. https://doi.org/10.1148/radiol.12120361 (2013).
Bunger, KM et al. Sirolimus-eluting poly-1-lactide stents biodegradable rau siv nyob rau hauv peripheral vasculature: kev kawm ua ntej ntawm porcine carotid hlab ntsha. J. Surgical Journal. cia tank. 139, 77-82, ib. https://doi.org/10.1016/j.jss.2006.07.035 (2007).