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Uphononongo olwahlukeneyo lwangaphambili lwetyhubhu ephuhlisiwe ye-Eustachian (ET) stent luyaqhubeka ngoku, kodwa ayikasetyenziswa kunyango lwezonyango.Kwizifundo zangaphambi kweklinikhi, i-ET scaffolds ziye zanqunyulwa kwi-scaffold-induced tissue proliferation.Ukusebenza kwe-cobalt-chromium sirolimus-eluting stent (SES) ekuvimbeleni ukwanda kwezicubu ezibangelwa yi-stent emva kokubekwa kwe-stent kufundwe kwimodeli ye-porcine ET.Iihagu ezintandathu zohlulwa zangamaqela amabini (okt iqela lolawulo kunye neqela leSES) neehagu ezintathu kwiqela ngalinye.Iqela lolawulo lifumene i-cobalt-chromium stent engafakwanga (n = 6), kwaye iqela le-SES lifumene i-cobalt-chromium stent kunye ne-sirolimus-eluting coating (n = 6).Onke amaqela abingelelwa kwiiveki ezi-4 emva kokubekwa kwestent.Ukubekwa kwe-Stent kuphumelele kuzo zonke ii-ET ngaphandle kweengxaki ezinxulumene nokuhlinzwa.Akukho nasinye sezitenti ezikwaziyo ukugcina imilo yazo engqukuva, kwaye ukuqokelelana kwe-mucus kwabonwa ngaphakathi nangaphandle kwee-stents kuwo omabini amaqela.Uhlalutyo lwe-Histological lubonise ukuba indawo yokwanda kwezicubu kunye nobukhulu be-submucosal fibrosis kwiqela le-SES yayisezantsi kakhulu kuneqela lolawulo.I-SES ibonakala isebenza kakuhle ekunqandeni ukwanda kwezicubu ezibangelwa yi-scaffold kwiihagu ze-ET.Nangona kunjalo, uphando olongezelelweyo luyafuneka ukuze kuqinisekiswe izixhobo ezifanelekileyo ze-stents kunye neziyobisi ezichasayo.
I-tube ye-Eustachian (ET) inemisebenzi ebalulekileyo kwindlebe ephakathi (umzekelo, ukukhupha umoya, ukuthintela ukuhanjiswa kwe-pathogens kunye neemfihlo kwi-nasopharynx)1.Kwakhona kubandakanya ukukhuselwa kwizandi ze-nasopharyngeal kunye ne-regurgitation2.I-ET idla ngokuvalwa, kodwa ivula ngokuginya, ukuzamla, okanye ukuhlafuna.Nangona kunjalo, ukungasebenzi kwe-ET kunokwenzeka ukuba ityhubhu ayivuli okanye ivale ngokufanelekileyo3,4.I-Dilated (obstructive) i-dysfunction ye-ET depresses ET umsebenzi kwaye, ukuba le misebenzi ayigcinwanga, inokuphuhlisa i-otitis media ebukhali okanye engapheliyo, esinye sezifo eziqhelekileyo kwi-ENT practice.Unyango lwangoku lwe-ET ukungasebenzi (umzekelo, utyando ngeempumlo, ukufakwa kwetyhubhu yokuphefumla, kunye namayeza) zisetyenziswa kwizigulana.Nangona kunjalo, olu nyango lunokusebenza okulinganiselweyo kwaye lunokukhokelela ekuthinteleni kwe-ET, ukusuleleka, kunye ne-membrane ye-tympanic engenakuguquleka ye-perforation3,6,7.I-Eustachian tube balloon angioplasty iye yaziswa njengonyango olulolunye lokungasebenzi kakuhle kwe-ET 8.Nangona izifundo ezininzi ukususela kwi-2010 zibonise ukuba ukulungiswa kwebhaluni ye-Eustachian iphezulu kunonyango oluqhelekileyo lwe-ET ukungasebenzi, ezinye izigulane aziphenduli kwi-dilatation8,9,10,11.Ngaloo ndlela, i-stenting ingaba yindlela yonyango esebenzayo12,13.Nangona uphando oluninzi oluqhubekayo oluvavanya ukuba nokwenzeka kobugcisa kunye nokuphendula kwezicubu emva kokubekwa kwe-stent kwi-ET, i-stent-induced tissue hyperplasia ngenxa yomonakalo womatshini ihlala iyingxaki ebalulekileyo emva kokuhlinzwa 14,15,16,17,18,19.iziyobisi, zilayishwe ii-anti-proliferative agents ziphucula le meko.
I-stent-eluting stents isetyenziselwe ukuthintela i-in-stent restenosis ebangelwa yi-tissue kunye ne-neointimal hyperplasia emva kokubekwa kwe-stent.Ngokuqhelekileyo, i-stent scaffolds okanye i-linings igqunywe ngamachiza (umzekelo, i-everolimus, i-paclitaxel, kunye ne-sirolimus) i-20,23,24.I-Sirolimus liyeza eliqhelekileyo le-antiproliferative elithintela amanyathelo amaninzi e-restenosis cascade (umzekelo, ukuvutha, i-neointimal hyperplasia, kunye ne-collagen synthesis)25.Ke ngoko, olu phononongo lubonisa ukuba i-sirolimus-coated stents inokuthintela i-hyperplasia yezicubu ezibangelwa yi-stent kwiihagu ze-ET (Umfanekiso 1).Injongo yolu phononongo yayikukuphanda ukusebenza kwe-sirolimus-eluting stents (SES) ekuvimbeleni ukwanda kwezicubu ezenziwe nge-stent emva kokubekwa kwe-stent kwimodeli ye-porcine ET.
Umzobo weSchematic we-cobalt-chromium sirolimus-eluting stent (SES) yonyango lwe-Eustachian tube dysfunction, ebonisa ukuba i-sirolimus-eluting stent inqanda ukwanda kwezicubu ezibangelwa yi-stent.
I-Cobalt-chromium (Co-Cr) i-alloy stents yenziwe nge-laser cutting Co-Cr alloy tubes (Genoss Co., Ltd., Suwon, Korea).Iqonga le-stent lisebenzisa i-double bond evulekileyo kunye nesakhiwo esidityanisiweyo sokuguquguquka okuphezulu kunye ne-radial force ephezulu, ukunciphisa kunye nokuthotyelwa.I-stent yayinobubanzi obuyi-3 mm, ubude be-18 mm, kunye nobukhulu be-strut obuyi-78 µm (Fig. 2a).Imilinganiselo yesakhelo se-alloy ye-Co-Cr yamiselwa ngokusekelwe kuphononongo lwethu lwangaphambili.
I-Cobalt-chromium (i-Co-Cr) i-alloy stent kunye ne-sheath yesikhokelo sesinyithi sokubeka i-Eustachian tube stent.Iifoto zibonisa (a) i-stent ye-Co-Cr ialloy kunye (b) ne-stent-clamped balloon catheter.(c) I-catheter yebhaluni kunye ne-stent zisasazwe ngokupheleleyo.(d) Isingxobo sesikhokelo sesinyithi saphuhliswa imodeli yetyhubhu ye-Eustachian.
I-Sirolimus isetyenziswe kumphezulu we-stent usebenzisa iteknoloji yokutshiza ye-ultrasonic.I-SES yenzelwe ukukhulula phantse i-70% yomthwalo wokuqala wamachiza (1.15 µg/mm2) phakathi kweentsuku zokuqala ezingama-30 emva kokubekwa.I-3 µm ebhityileyo kakhulu yokwambathisa igalelwa kuphela kwicala elisecaleni le-stent ukuphumeza iprofayili efunwayo yokukhupha ichiza kunye nokunciphisa ubungakanani bepolima;le ngubo ye-biodegradable iqulethe i-copolymer ye-lactic kunye ne-glycolic acid kunye ne-proprietary blend ye-poly(1) -lactic acid)26,27.Ico-Cr ialloy stents zaxilwa kwiicathetha zebhaluni eziyi-3 mm ububanzi kunye ne-28 mm ubude (Genoss Co., Ltd.; Fig. 2b).Ezi stents ziyafumaneka eMzantsi Korea ukunyanga isifo sentliziyo.
Igobolondo elisanda kuveliswa lesikhokelo sentsimbi yemodeli ye-ET yehagu yenziwe ngentsimbi engenasici (Umfanekiso 2c).I-diameter yangaphakathi nangaphandle yegobolondo yi-2 mm kunye ne-2.5 mm, ngokulandelanayo, ubude obupheleleyo buyi-250 mm.I-distal 30 mm sheath yayigotywe kwi-J-shape kwi-angle ye-15 ° ukuya kwi-axis ukuvumela ukufikelela lula ukusuka empumlweni ukuya kwi-nasopharyngeal orifice ye-ET kwimodeli yehagu.
Olu pho nonongo luvunyiwe yi-Institutional Animal Care and Use Committee ye-Asan Institute of Life Sciences (Seoul, South Korea) kwaye ihambelana neZiko leSizwe leZikhokelo zezeMpilo kwi-Humane Treatment of Laboratory Animals (IACUC-2020-12-189)..Uphononongo luqhutywe ngokuhambelana nezikhokelo ze-ARRIVE.Olu pho nonongo lusebenzise i-12 ETs kwiingulube ze-6 ezinobunzima be-33.8-36.4 kg kwiinyanga ezi-3 ubudala.Iihagu ezintandathu zohlulwa zangamaqela amabini (okt iqela lolawulo kunye neqela leSES) neehagu ezintathu kwiqela ngalinye.Iqela lolawulo lifumene i-stent ye-Co-Cr engafakwanga, ngelixa iqela le-SES lifumene i-Co-Cr i-alloy stent eluting sirolimus.Zonke iihagu zazingena simahla emanzini kunye nokutya kwaye zazigcinwa ku 24°C ± 2°C umjikelo weyure eziyi-12 ebusuku.Emva koko, zonke iihagu zabingelelwa kwiiveki ezi-4 emva kokubekwa kwezibaya.
Zonke iihagu zafumana umxube we 50mg/kg zolazepam, 50mg/kg teletamide (Zoletil 50; Virbac, Carros, France) kunye ne 10mg/kg xylazine (Rompun; Bayer HealthCare, Les Varkouzins, Germany).ke ityhubhu ye-tracheal ibekwe nge-inhalation ye-0.5-2% isoflurane (Ifran®; Hana Pharm. Co., Seoul, Korea) kunye ne-oxygen 1: 1 (510 ml / kg / min) ye-anesthesia.Iihagu zibekwe kwindawo ye-supine kunye ne-endoscopy esisiseko (i-VISERA 4K UHD rhinolaryngoscope; i-Olympus, i-Tokyo, eJapan) yenziwa ukuhlola i-nasopharyngeal orifice ye-ET.I-sheath yesikhokelo yesinyithi yaqhutyelwa phambili nge-nostril ukuya kwi-nasopharyngeal orifice ye-ET phantsi kolawulo lwe-endoscopic (Umfanekiso 3a, b).I-balloon catheter, i-stent corrugated, ifakwe nge-introducer kwi-ET de i-tip yayo ihlangabezane nokuchasana kwi-osteochondral isthmus ye-ET (Fig. 3c).I-catheter yebhaluni ifakwe ngokupheleleyo nge-saline ukuya kwi-9 atmospheres, njengoko inqunywe yi-monitor monitor (umzobo 3d).I-catheter yebhaluni yasuswa emva kokubekwa kwe-stent (Umfanekiso we-3f), kwaye ukuvulwa kwe-nasopharyngeal kuhlolwe ngokucophelela i-endoscopy yeengxaki zokuhlinzwa (umzobo 3f).Zonke iihagu ziye zafumana i-endoscopy ngaphambi nangemva kokuba i-stenting, kunye neeveki ezi-4 emva kokunyuka, ukuvavanya i-patency yendawo ye-stent kunye ne-secretions ejikelezileyo.
Amanyathelo obugcisa bokubeka i-stent kwi-tube ye-eustachian (ET) yehagu phantsi kolawulo lwe-endoscopic.(a) Umfanekiso we-Endoscopic obonisa ukuvuleka kwe-nasopharyngeal (utolo) kunye ne-sheath yesikhokelo sesinyithi esifakiwe (utolo).(b) Ukufakwa kwesingxobo sentsimbi (utolo) kwintunja yomkhala.(c) I-stent-clamped ibhaluni catheter (utolo) yaziswa kwi-ET ngesingxobo (utolo).(d) Ikhathetha yebhaluni (utolo) ivuthelwe ngokupheleleyo.(e) Isiphelo esiphezulu se-stent siphuma kwi-ET orifice ye-nasopharynx.(f) Umfanekiso we-Endoscopic obonisa ukuqina kwelumen eqinileyo.
Zonke iihagu zaye zabulawa ngokufaka i-75 mg / kg ye-potassium chloride ngenaliti ye-ear vein.Amacandelo e-Median sagittal entloko ye-porcine ayenziwe kusetyenziswa i-chainsaw elandelwa ukukhutshwa ngokucokisekileyo kweesampuli ze-ET ze-scaffold ze-tissue ukuhlolwa kwe-histological (i-Supplementary Fig. 1a, b).Iisampulu zezicubu ze-ET zilungiswe kwi-10% ye-neutral buffered formalin kwiiyure ze-24.
Iisampulu ze-ET ze-tissue zahlanjululwa ngokulandelelana ngotywala bezinto ezahlukeneyo.Iisampulu zifakwe kwiibhloko ze-resin ngokungena nge-ethylene glycol methacrylate (Technovit 7200® VLC; Heraus Kulzer GMBH, Wertheim, Germany).Amacandelo e-Axial ayenziwe kwiisampuli ze-ET ezifakwe kwi-ET kumacandelo asondeleyo kunye ne-distal (i-Supplementary Fig. 1c).Iibhloko zepolymer zaye zaxhonywa kwi-acrylic glass slides.Izilayidi zebhlokhi yeresin beziyimicroground kwaye zapolishwa ngesilicon carbide iphepha lobunzima obahlukeneyo ukuya kubukhulu obuyi-20 µm kusetyenziswa inkqubo yegridi (Apparatebau GMBH, Hamburg, Germany).Zonke izilayidi zaziphantsi kovavanyo lwe-histological kunye ne-hematoxylin kunye ne-eosin staining.
Uvavanyo lwe-Histological lwenziwa ukuvavanya ipesenti yokunyuka kwezicubu, ubukhulu be-submucosal fibrosis, kunye neqondo lokungena kweeseli ezivuthayo.Ipesenti ye-tissue hyperplasia ene-ET emxinwa yendawo enqamlezileyo ibalwa ngokusombulula i-equation:
Ubunzima be-submucosal fibrosis bulinganiswa ngokuthe nkqo ukusuka kwi-stent struts ukuya kwi-submucosa.Iqondo lokungena kweeseli ezivuthayo ligwetywa ngokuzimeleyo ngokusasazwa kunye nokuxinana kweeseli ezivuthayo, ezizezi: i-degree ye-1 (i-mild) - i-leukocyte eyodwa yokungena;I-2nd degree (i-mild to moderate) - i-focal leukocyte infiltration;I-3rd degree (imodareyitha) - idibene.kunye ne-leukocyte engakwazi ukwahlula phakathi kwe-loci yomntu;ibakala lesi-4 (eliphakathi ukuya kubunzima) i-leukocytes isasazeka ngokungena kwi-submucosa yonke, kunye ne-5 (enzima) i-infiltration infiltration kunye ne-multiple foci ye-necrosis.Ubukhulu be-submucosal fibrosis kunye neqondo lokungena kweeseli ezivuthayo zifunyenwe ngomlinganiselo wamanqaku asibhozo ajikeleze i-circumference.Uhlalutyo lwe-Histological ye-ET lwenziwa ngokusebenzisa i-microscope (BX51; Olympus, Tokyo, Japan).Imilinganiselo ifunyenwe kusetyenziswa isoftware yeCaseViewer (CaseViewer; 3D HISTECH Ltd., Budapest, Hungary).Uhlalutyo lwedatha ye-histological lusekelwe kwimvumelwano yababukeli abathathu abangazange bathathe inxaxheba kwisifundo.
Uvavanyo lwe-Mann-Whitney U-uvavanyo lwasetyenziselwa ukuhlalutya umahluko phakathi kwamaqela njengoko kufuneka. I-p <0.05 yayithathwa njengebalulekileyo ngokwezibalo. I-p <0.05 yayithathwa njengebalulekileyo ngokwezibalo. Значение p < 0,05 считалось статистически значимым. Ixabiso le-p <0.05 lithathwa njengelibalulekileyo ngokweenkcukacha-manani. 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 ithathwa njengebaluleke kakhulu ngokwezibalo. Uvavanyo lwe-Bonferroni-ukulungiswa kwe-Mann-Whitney U-U-yenzelwe amaxabiso e-p <0.05 ukufumanisa ukungafani kweqela (p <0.008 njengezibalo ezibalulekileyo). Uvavanyo lwe-Bonferroni-ukulungiswa kwe-Mann-Whitney U lwenzelwe amaxabiso e-p <0.05 ukubona umahluko weqela (p <0.008 njengokubaluleka kwezibalo). U-критерий Манна-Уитни с поправкой на Бонферрони был выполнен для значений p <0,05 для выявления групповых различи00 (p0,058, p. Uvavanyo lwe-Bonferroni-uhlengahlengiso lwe-Mann-Whitney U lwenzelwe amaxabiso e-p <0.05 ukubona umahluko weqela (p <0.008 njengokubaluleka kwezibalo).对p 棄umfanekiso weskrini < 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 ukuya 3/05/2014 10 ). Uvavanyo lwe-Bonferroni-uhlengahlengiso lwe-Mann-Whitney lwenziwa kwi-p <0.05 ukubona ukuhlukana kweqela (p <0.008 yayibaluleke kakhulu).Uhlalutyo lwamanani lwenziwa kusetyenziswa isoftware ye-SPSS (uhlobo 27.0; SPSS, IBM, Chicago, IL, USA).
Konke ukufakwa kwestent yehagu kube yimpumelelo ngokobugcisa.I-sheath yesikhokelo yensimbi ifakwe ngempumelelo kwi-nasopharyngeal orifice ye-ET phantsi kolawulo lwe-endoscopic, nangona ukulimala kwe-mucosal kunye nokuphuma kwegazi kwabonwa kwi-4 yemifanekiso ye-12 (33.3%) ngexesha lokufakwa kwe-metal sheath.Emva kweeveki ezi-4, ukopha okuphuphumayo kuye kwaphela.Zonke iihagu zasinda de kwagqitywa uphononongo ngaphandle kweengxaki ezinxulumene nestent.
Iziphumo ze-Endoscopy ziboniswe kuMzobo 4. Ngethuba lokulandelelana kweeveki ezi-4, ii-stents zahlala kwindawo yazo zonke iihagu.Ukuqokelela kwe-Mucus kunye nokujikeleza i-ET stent kwabonwa kuzo zonke (100%) ii-ETs kwiqela lolawulo kunye nezintathu (50%) ze-ET ezintandathu kwiqela le-SES, kwaye akukho mmahluko kwiziganeko phakathi kwamaqela amabini (p = 0.182).Akukho nanye kwi-stents efakiweyo enokugcina imilo engqukuva.
Imifanekiso ye-Endoscopic ye-Eustachian tube (ET) yehagu kwiqela lolawulo kunye neqela eline-cobalt-chromium stent (CXS) eluting sirolimus.(a) Umfanekiso osisiseko we-endoscopic othathwe phambi kokubekwa kwe-stent ebonisa ukuvuleka kwe-nasopharyngeal (utolo) lwe-ET.(b) Umfanekiso we-Endoscopic othathwe ngokukhawuleza emva kokubekwa kwestent ebonisa iET yokubekwa kwestent.Ukopha koqhagamshelwano kuye kwabonwa ngenxa ye-sheath yesikhokelo sesinyithi (utolo).(c) Umfanekiso we-Endoscopic othathwe kwiiveki ezi-4 emva kokubekwa kwe-stent ubonisa ukufumba kwe-mucus ejikeleze i-stent (utolo).(d) Umfanekiso we-Endoscopic obonisa ukuba i-stent ayikwazi ukuhlala ingqukuva (utolo).
Iziphumo ze-Histological ziboniswe kwi-Figure 5 kunye ne-Supplementary Figure 2. Ukunyuka kwezicubu kunye ne-submucosal fibrous proliferation phakathi kwezithuba ze-stent kwi-ET lumen yamaqela omabini. Ipesenti yepesenti yendawo ye-tissue hyperplasia yayinkulu kakhulu kwiqela lolawulo kuneqela le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p <0.001). Ipesenti yepesenti yendawo ye-tissue hyperplasia yayinkulu kakhulu kwiqela lolawulo kuneqela le-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 группе СЭС (79,6,8% 0,06%, p <0,001). Ipesenteji yendawo ye-tissue hyperplasia yayinkulu kakhulu kwiqela lolawulo kuneqela le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p <0.001).I-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 группе СЭС (79,6,40,6%2% 06%, p <0,001). Ipesenteji yendawo ye-tissue hyperplasia kwiqela lolawulo laliphezulu kakhulu kuneqela le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p <0.001). Ngaphezu koko, ubukhulu becala le-fibrosis ye-submucosal nayo yayiphezulu kakhulu kwiqela lolawulo kuneqela le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p <0.001). Ngaphezu koko, ubukhulu becala le-fibrosis ye-submucosal nayo yayiphezulu kakhulu kwiqela lolawulo kuneqela le-SES (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 группе, чем в группе, 410, ± 60,± 10 20 мм, p <0,001). Ngaphezu koko, ubukhulu becala le-fibrosis ye-submucosal nayo yayiphezulu kakhulu kwiqela lolawulo kuneqela le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p <0.001).I-SES 组（1.41 ± 0.25 vs.0.56 ± 0.20 mm, p <0.001). 0.56±0.20mm, p <0.001). Кроме того, средняя толщина подслизистого фиброза в контрольной группе также была значительно выше, чем в группе СЭ0, ±20,±20,±20,20,±1,60 0 мм, p <0,001). Ukongezelela, ubukhulu becala le-submucosal fibrosis kwiqela lolawulo laliphezulu kakhulu kuneqela le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p <0.001).Nangona kunjalo, kwakungekho mmahluko obalulekileyo kwiqondo lokungena kweeseli ezivuthayo phakathi kwamaqela amabini (iqela lokulawula [3.50 ± 0.55] vs iqela le-SES [3.00 ± 0.89], p = 0.270).
Uhlalutyo lovavanyo lwe-histological lwamaqela amabini e-stents abekwe kwi-lumen ye-Eustachian.(a, b) Indawo ye-tissue hyperplasia (1 ye-a kunye ne-b) kunye nobukhulu be-submucosal fibrosis (2 ye-a kunye ne-b; iintolo eziphindwe kabini) zazinkulu kakhulu kwiqela lolawulo kuneqela le-SES eline-strut stenting (amachaphaza amnyama), indawo ye-lumen emxinwa (etyheli) kunye nendawo yestent yokuqala (ebomvu).Iqondo lokungena kweeseli ezivuthayo (i-3 ye-a kunye ne-b; iintolo) ayizange ihluke kakhulu phakathi kwamaqela amabini.CI-SES, i-cobalt-chromium sirolimus eluting stent.
I-stent-eluting stents inceda ukuphucula i-stent patency kunye nokukhusela i-stent restenosis20,21,22,23,24.Ukuqina okubangelwa yi-stent kubangelwa ukubunjwa kwezicubu ze-granulation kunye notshintsho lwezicubu ze-fibrous kumalungu ahlukeneyo angenayo i-vascular, kubandakanywa ummizo, uqhoqhoqho, i-gastroduodenum, kunye ne-bile ducts.Iziyobisi ezifana ne-dexamethasone, i-paclitaxel, i-gemcitabine, i-EW-7197, kunye ne-sirolimus isetyenziswe kumphezulu we-wire mesh okanye i-stent coating ukukhusela okanye ukunyanga i-tissue hyperplasia emva kokubekwa kwe-stent29,30,34,35,36.Izinto ezintsha zamva nje kwintsimi ye-stents esebenzayo usebenzisa iteknoloji ye-fusion iphandwa ngenkuthalo yonyango lwezifo ezingenayo i-vascular occlusive37,38,39.Kuphononongo lwangaphambili kwimodeli ye-porcine ET, ukwanda kwezicubu ezibangelwa yi-scaffold kwabonwa.Nangona uphuhliso lwe-stent kwi-ET aluqondwa kakuhle, impendulo ye-tissue emva kokubekwa kwe-stent ifunyenwe ifana neyezinye izitho ze-luminal ze-nonvascular19.Kuphononongo lwangoku, i-SES yayisetyenziselwa ukuthintela ukwanda kwezicubu ezibangelwa yi-scaffold kwimodeli ye-porcine ET.I-Sirolimus inetyhefu kwi-pancreatic islets kunye nemigca yeeseli ze-beta, iyanciphisa ukusebenza kweeseli kunye nokwandisa i-apoptosis40,41.Esi siphumo sinokunceda ukuthintela ukwakheka kokwanda kwezicubu ngokukhuthaza ukufa kweeseli.Uphononongo lwethu lubonise ukuba ukusetyenziswa kokuqala kweziyobisi-eluting stents kwi-ET kwanqanda ngokufanelekileyo ukwanda kwezicubu ezibangelwa yi-ET.
I-balloon-expandable Co-Cr alloy stent esetyenziswe kolu phando ifumaneka lula njengoko isetyenziswa ngokuqhelekileyo ukunyanga isifo se-coronary artery 42.Ukongezelela, ii-alloys ze-Co-Cr zinempahla yomatshini (umzekelo, amandla aphezulu e-radial kunye ne-inelastic forces) 43.Ngokutsho kwe-endoscopy yophando lwangoku, i-stent ye-Co-Cr ye-alloy esetyenziselwa i-ET yeehagu ayikwazi ukugcina imilo ejikelezayo kuzo zonke iihagu ngenxa yokungonelanga kwe-elasticity kwaye ayinakho ukukwazi ukuzikhulisa.Ukumila kwe-stent efakiweyo kunokutshintshwa ngokujikeleza kwe-ET yesilwanyana esiphilayo (umzekelo, ukuhlafuna kunye nokuginya).Iimpawu zemishini ye-Co-Cr i-alloy stents ibe yinto engafanelekanga ekubekweni kwe-porcine ET stents.Ukongezelela, ukufakwa kwe-stent kwi-isthmus kunokubangela ukuvula ngokusisigxina i-ET.I-ET eqhubekayo evulekile okanye eyandisiweyo ivumela intetho kunye nezandi ze-nasopharyngeal, i-reflux ye-gastrointestinal, kunye ne-pathogens1 ukuba ihambe ifike kwindlebe ephakathi, ibangele ukucaphuka kwe-mucosal kunye nokusuleleka.Ngoko ke, ukuvuleka okusisigxina kwe-nasopharyngeal kufuneka kugwenywe.Ngoko ke, ukunikezelwa kwesakhiwo se-ET cartilage, i-scaffolds ikhethwa ngokufanelekileyo kwi-alloys yememori ye-shape kunye neempawu ze-superelastic, ezifana ne-nitinol.Ngokuqhelekileyo, ukukhutshwa okunzima kufunyenwe ngaphakathi kunye nakwi-orifice ye-nasopharyngeal ye-stent.Ekubeni ukunyakaza okuqhelekileyo kwe-mucociliary ye-mucus ivaliwe, imfihlo ilindeleke ukuba iqokelele kwi-scaffolds ephuma kwi-nasopharyngeal opening.Ukuthintela ukunyuka kwentsholongwane yendlebe ephakathi ngenye yeenjongo eziphambili ze-ET, kunye nokubekwa kwee-stents eziphuma ngaphandle kwe-ET kufuneka kugwenywe, ekubeni ukudibana ngokuthe ngqo kwe-stents kunye ne-nasopharyngeal bacterial flora kunokukhokelela ekunyukeni kwezifo ezikhulayo.
I-Eustachian tube balloon plasty ngokuvula i-nasopharyngeal yonyango olutsha oluncinci lwe-ET ukungasebenzi okujoliswe ekuvuleni kunye nokwandisa inxalenye ye-cartilaginous ye-ET8,9,10,46.Nangona kunjalo, indlela yonyango engaphantsi kwayo ayichongwanga47 kwaye iziphumo zayo zexesha elide zinokuba yi-suboptimal8,9,11,46.Ngaphantsi kwezi meko, i-metal stenting yesikhashana ingaba yindlela yonyango esebenzayo kwizigulane ezingaphenduliyo ukulungiswa kwebhaluni ye-Eustachian, kwaye ukuba nokwenzeka kwe-ET stenting kubonakaliswe kwizifundo ezininzi zangaphambili.I-Poly-l-lactide scaffolds ifakwe kwi-membrane ye-tympanic kwi-chinchillas kunye noonogwaja ukuvavanya ukunyamezela kunye nokuthotywa kwe-vivo17,18.Ukongeza, imodeli yegusha yenzelwe ukuvavanya iprofayili yentsimbi yentsimbi enwebekayo i-stents kwi-vivo.Kuphononongo lwethu lwangaphambili, imodeli ye-porcine ET yaphuhliswa ukuphanda ukuba nokwenzeka kobugcisa kunye nokuvavanywa kweengxaki ezibangelwa yi-stent, i-19 inika isiseko esiqinileyo solu phando ukuphanda ukusebenza kwe-SES usebenzisa iindlela ezisekelwe ngaphambili.Kule sifundo, i-SES yafakwa ngempumelelo kwi-cartilage kwaye yathintela ngokufanelekileyo ukwanda kwezicubu.Kwakungekho zingxaki ezinxulumene ne-stent, kodwa kwakukho ukulimala kwe-mucosal okubangelwa i-sheath yesikhokelo sesinyithi kunye nokopha koqhagamshelwano olusombululwe ngokuzenzekelayo kwiiveki ze-4.Ukunikezelwa kweengxaki ezinokuthi zenzeke kwiishethi zetsimbi, ukuphucula inkqubo yokuhanjiswa kwe-SES ingxamisekile kwaye ibalulekile.
Olu phononongo lunemida ethile.Nangona iziphumo ze-histological zahluka kakhulu phakathi kwamaqela, inani lezilwanyana kolu phononongo lalincinci kakhulu kuhlalutyo oluthembekileyo lwamanani.Nangona ababukeli abathathu baphuphuthekiswa ukuba bahlole ukuguquguquka kwe-inter-observer, i-degree of submucosal inflammatory infiltration inqunywe ngokuzimeleyo ngokusekelwe ekusasazeni kunye nobuninzi beeseli ezivuthayo ngenxa yobunzima bokubala iiseli ezivuthayo.Ekubeni isifundo sethu siqhutywe kusetyenziswa inani elincinci lezilwanyana ezinkulu, i-dose enye yeyeza yayisetyenzisiwe, kwi-vivo izifundo ze-pharmacokinetic azizange zenziwe.Uphononongo olongezelelweyo luyafuneka ukuze kuqinisekiswe idosi efanelekileyo yechiza kunye nokhuseleko lwe-sirolimus kwi-ET.Ekugqibeleni, ixesha lokulandelelana kweeveki ezi-4 likwangumlinganiselo wokufunda, ngoko ke izifundo malunga nokusebenza kwexesha elide le-SES ziyafuneka.
Iziphumo zolu pho nonongo zibonisa ukuba i-SES inokuthintela ngokufanelekileyo ukwanda kwezicubu ezibangelwa ngumatshini emva kokubekwa kwe-Balloon-expandable Co-Cr alloy scaffolds kwimodeli ye-porcine ET.Kwiiveki ezine emva kokubekwa kwe-stent, izinto eziguquguqukayo ezinxulumene nokunyuka kwezicubu ezibangelwa yi-stent (kubandakanya indawo yokwanda kwezicubu kunye nobukhulu be-submucosal fibrosis) zazisezantsi kakhulu kwiqela le-SES kuneqela lolawulo.I-SES ibonakala isebenza kakuhle ekunqandeni ukwanda kwezicubu ezibangelwa yi-scaffold kwiihagu ze-ET.Nangona uphando olongezelelweyo lufuneka ukuvavanya ezona zinto zilungileyo ze-stent kunye needosi zabaviwa bamachiza, i-SES inamandla onyango asekhaya ekuthinteleni i-ET tissue hyperplasia emva kokubekwa kwe-stent.
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