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Ucwaningo oluhlukahlukene olwandulela umtholampilo lwe-stent ye-Eustachian tube (ET) ethuthukisiwe luyaqhubeka njengamanje, kodwa alukasetshenziswa emtholampilo. Ezifundweni ze-preclinical, ama-scaffolds e-ET akhawulelwe ekwandeni kwezicubu ezibangelwa yi-scaffold. Ukusebenza kwe-cobalt-chromium sirolimus-eluting stent (SES) ekuvimbeleni ukwanda kwezicubu ezibangelwa i-stent ngemva kokubekwa kwe-stent kwacwaningwa kumodeli ye-porcine ET. Izingulube eziyisithupha zahlukaniswa zaba amaqembu amabili (okungukuthi iqembu lokulawula kanye neqembu le-SES) nezingulube ezintathu eqenjini ngalinye. Iqembu lokulawula lithole i-cobalt-chromium stent engavaliwe (n = 6), futhi iqembu le-SES lithole i-cobalt-chromium stent ene-sirolimus-eluting coating (n = 6). Wonke amaqembu ahlatshwa amasonto ama-4 ngemuva kokubekwa kwe-stent. Ukubekwa kwe-Stent kube yimpumelelo kuwo wonke ama-ET ngaphandle kwezinkinga ezihlobene nokuhlinzwa. Awekho ama-stents ayekwazi ukugcina isimo sawo esiyindilinga sokuqala, futhi ukunqwabelana kwamafinyila kwabonwa ngaphakathi naseduze kwama-stents kuwo womabili amaqembu. Ukuhlaziywa kwe-Histological kubonise ukuthi indawo yokwanda kwezicubu kanye nobukhulu be-submucosal fibrosis eqenjini le-SES yayiphansi kakhulu kuneqembu lokulawula. I-SES ibonakala isebenza ngempumelelo ekuvimbeleni ukwanda kwezicubu ezibangelwa i-scaffold ezingulubeni ze-ET. Kodwa-ke, ucwaningo olwengeziwe luyadingeka ukuze kuqinisekiswe izinto ezifanele zama-stents kanye nezidakamizwa ezilwa nokuvuvukala.
Ishubhu le-Eustachian (ET) linemisebenzi ebalulekile endlebeni ephakathi (isb., ukungenisa umoya, ukuvimbela ukudluliselwa kwamagciwane kanye nezimfihlo ku-nasopharynx)1. Kuhlanganisa futhi ukuvikeleka emisindweni ye-nasopharyngeal kanye ne-regurgitation2. I-ET ivamise ukuvala, kodwa ivula ngokugwinya, ukuzamula, noma ukuhlafuna. Nokho, ukungasebenzi kahle kwe-ET kungenzeka uma ithubhu ingavuli noma ivaleke kahle3,4. I-Dilated (obstructive) ukungasebenzi kahle kwe-ET icindezela umsebenzi we-ET futhi, uma le misebenzi ingagcinwa, ingase ithuthuke ibe yi-otitis media enzima noma engapheli, esinye sezifo ezivame kakhulu ekusebenzeni kwe-ENT. Ukwelashwa kwamanje kokungasebenzi kahle kwe-ET (isb, ukuhlinzwa amakhala, ukufakwa kweshubhu lokungenisa umoya, kanye nemithi) kusetshenziswa ezigulini. Kodwa-ke, lezi zindlela zokwelapha zinokusebenza okulinganiselwe futhi zingase ziholele ekuvinjweni kwe-ET, ukutheleleka, kanye ne-tympanic membrane perforation engenakuhlehliswa3,6,7. I-Eustachian tube balloon angioplasty yethulwe njengenye indlela yokwelapha ukungasebenzi kahle kwe-ET 8 okunwetshiwe. Nakuba izifundo eziningana kusukela ku-2010 zibonise ukuthi ukulungiswa kwebhaluni ye-Eustachian kuphakeme kunokwelashwa okuvamile kokungasebenzi kahle kwe-ET, ezinye iziguli aziphenduli ekudaleni8,9,10,11. Ngakho, i-stenting ingaba yindlela yokwelapha ephumelelayo12,13. Naphezu kwezifundo eziningi eziqhubekayo eziqhubekayo ezihlola ukuthi kungenzeka yini ubuchwepheshe kanye nokuphendula kwezicubu ngemuva kokubekwa kwe-stent ku-ET, i-stent-induced tissue hyperplasia ngenxa yokulimala kwemishini ihlala iyinkinga ebalulekile ye-postoperative 14,15,16,17,18,19. izidakamizwa, ezilayishwe ama-anti-proliferative agents zithuthukisa lesi simo.
Ama-stents e-eluting drug asetshenziselwe ukuvimbela i-in-stent restenosis ebangelwa izicubu kanye ne-neointimal hyperplasia ngemva kokubekwa kwe-stent. Ngokuvamile, ama-scaffold aqinile noma ama-linings ambozwa ngezidakamizwa (isb, i-everolimus, i-paclitaxel, ne-sirolimus)20,23,24. I-Sirolimus iyisidakamizwa esivamile se-antiproliferative esivimbela izinyathelo ezimbalwa ze-restenosis cascade (isb, ukuvuvukala, i-neointimal hyperplasia, kanye ne-collagen synthesis)25. Ngakho-ke, lolu cwaningo lubonisa ukuthi ama-stents ahlanganiswe ne-sirolimus angavimbela i-hyperplasia yezicubu ezibangelwa i-stent ezingulubeni ze-ET (Umfanekiso 1). Inhloso yalolu cwaningo bekuwukuphenya ukusebenza kahle kwe-sirolimus-eluting stents (SES) ekuvimbeleni ukwanda kwezicubu ezibangelwa i-stent ngemva kokubekwa kwe-stent kumodeli ye-porcine ET.
Umfanekiso ohleliwe we-cobalt-chromium sirolimus-eluting stent (SES) yokwelapha ukungasebenzi kahle kweshubhu le-Eustachian, okubonisa ukuthi i-sirolimus-eluting stent ivimbela ukwanda kwezicubu ezibangelwa i-stent.
Ama-stents engxubevange ye-Cobalt-chromium (Co-Cr) aklanywa ngamashubhu okusika i-laser Co-Cr alloy (Genoss Co., Ltd., Suwon, Korea). Inkundla ye-stent isebenzisa isibopho esiphindwe kabili esinesakhiwo esihlanganisiwe sokuguquguquka okuphezulu okunamandla afanele we-radial, ukufinyeza nokuhambisana. Isitendi sasinobubanzi obungu-3 mm, ubude obungu-18 mm, nogqinsi lwe-strut obungu-78 µm (Fig. 2a). Ubukhulu bohlaka lwengxubevange ye-Co-Cr banqunywa ngokusekelwe ocwaningweni lwethu lwangaphambilini.
I-Cobalt-chromium (Co-Cr) i-alloy stent kanye neshethi yomhlahlandlela wensimbi yokubeka i-Eustachian tube stent. Izithombe zikhombisa (a) i-Co-Cr alloy stent kanye (b) ne-catheter yebhaluni eboshwe nge-stent. (c) I-catheter yebhaluni kanye ne-stent kusetshenziswe ngokugcwele. (d) Igobolondo lomhlahlandlela wensimbi lenzelwe imodeli yeshubhu lengulube i-Eustachian.
I-Sirolimus yafakwa phezu kwe-stent kusetshenziswa ubuchwepheshe be-ultrasonic spray. I-SES yakhelwe ukukhulula cishe u-70% womthwalo wangempela womuthi (1.15 µg/mm2) phakathi nezinsuku zokuqala ezingu-30 ngemva kokubekwa. I-ultra-thin 3 µm coating isetshenziswa kuphela ohlangothini oluseduze lwe-stent ukuze kuzuzwe iphrofayili yokukhishwa kwesidakamizwa efiselekayo kanye nokunciphisa inani le-polymer; lokhu kugcotshwa kwe-biodegradable kuqukethe i-copolymer ye-lactic ne-glycolic acid kanye nenhlanganisela yobunikazi ye-poly(1) -lactic acid)26,27. Ama-co-Cr alloy stents ayeboshelwe kuma-catheter ebhaluni angu-3 mm ububanzi nobude obungu-28 mm (Genoss Co., Ltd.; Fig. 2b). Lawa ma-stents ayatholakala eSouth Korea ukuze ekwelaphe isifo senhliziyo.
Igobolondo lensimbi elisanda kwakhiwa lemodeli yengulube ye-ET lenziwe ngensimbi engagqwali (Fig. 2c). Ububanzi bangaphakathi nangaphandle begobolondo buyi-2 mm no-2.5 ​​mm, ngokulandelana, ubude obuphelele buyi-250 mm. I-distal 30 mm sheath ibigotshwe ibe yisimo sika-J nge-engeli engu-15° ku-eksisi ukuze ivumele ukufinyelela okulula ukusuka ekhaleni kuya ku-nasopharyngeal orifice ye-ET kumodeli yengulube.
Lolu cwaningo lugunyazwe iKomidi Lesikhungo Sokunakekelwa Kwezilwane Nokusetshenziswa kwe-Asan Institute of Life Sciences (Seoul, South Korea) futhi lithobela Iziqondiso Zezikhungo Zezempilo Zikazwelonke Zokwelashwa Kwezilwane Zaselabhorethri (IACUC-2020-12-189). . Ucwaningo lwenziwe ngokuhambisana neziqondiso ze-ARRIVE. Lolu cwaningo lusebenzise ama-ET angu-12 ezingulubeni ezingu-6 ezinesisindo esingu-33.8-36.4 kg ezinyangeni ezingu-3 ubudala. Izingulube eziyisithupha zahlukaniswa zaba amaqembu amabili (okungukuthi iqembu lokulawula kanye neqembu le-SES) nezingulube ezintathu eqenjini ngalinye. Iqembu elilawulayo lithole i-stent ye-Co-Cr engahlanganisiwe, kuyilapho iqembu le-SES lathola i-Co-Cr alloy stent eluting sirolimus. Zonke izingulube zazikwazi ukufinyelela mahhala emanzini kanye nokudla futhi zazigcinwa ku-24°C ± 2°C umjikelezo wamahora angu-12 wobusuku. Kamuva, zonke izingulube zanikelwa emavikini angu-4 ngemva kokubekwa kwe-stent.
Zonke izingulube zithole ingxube ye-50mg/kg zolazepam, 50mg/kg teletamide (Zoletil 50; Virbac, Carros, France) kanye ne-10mg/kg xylazine (Rompun; Bayer HealthCare, Les Varkouzins, Germany). khona-ke ishubhu loqhoqhoqho lafakwa ngokuhogela okungu-0.5-2% isoflurane (Ifran®; Hana Pharm. Co., Seoul, Korea) kanye ne-oxygen 1:1 (510 ml/kg/min) ye-anesthesia. Izingulube zibekwe endaweni ephansi kanye ne-endoscopy eyisisekelo (i-VISERA 4K UHD rhinolaryngoscope; i-Olympus, e-Tokyo, e-Japan) yenzelwe ukuhlola i-nasopharyngeal orifice ye-ET. Igobolondo lomhlahlandlela wensimbi lathuthukiswa ngekhala laya ku-nasopharyngeal orifice ye-ET ngaphansi kokulawulwa kwe-endoscopic (Fig. 3a, b). I-catheter yebhaluni, i-stent eboshiwe, ifakwa ngelethulo ku-ET kuze kube yilapho ithiphu layo lihlangabezana nokumelana ne-osteochondral isthmus ye-ET (Fig. 3c). I-catheter ye-balloon yayigcwele ngokugcwele i-saline ku-atmospheres ye-9, njengoba kunqunywe ukuqapha kwe-manometer (Fig. 3d). I-catheter yebhaluni yasuswa ngemva kokubekwa kwe-stent (Fig. 3f), futhi ukuvuleka kwe-nasopharyngeal kwahlolwa ngokucophelela i-endoscopy yezinkinga zokuhlinzwa (Fig. 3f). Zonke izingulube zenziwa i-endoscopy ngaphambi nangemva nje kokuba i-stenting, kanye namaviki angu-4 ngemva kokugcoba, ukuhlola ubunikazi bendawo ye-stent kanye nemfihlo ezungezile.
Izinyathelo zobuchwepheshe zokubeka i-stent kushubhu ye-eustachian (ET) yengulube ngaphansi kokulawulwa kwe-endoscopic. (a) Isithombe se-Endoscopic esibonisa ukuvuleka kwe-nasopharyngeal (umcibisholo) kanye nomgodla womhlahlandlela wensimbi ofakiwe (umcibisholo). (b) Ukufakwa kwegobolondo lensimbi (umcibisholo) endaweni evulekile ye-nasopharyngeal. (c) Ikhethetha yebhaluni eline-stent-clamped (umcibisholo) yethulwa ku-ET ngesheath (umcibisholo). (d) Ikhethetha yebhaluni (umcibisholo) igcwaliswe ngokuphelele. (e) Isiphetho esiseduze se-stent siphuma ku-ET orifice ye-nasopharynx. (f) Isithombe se-Endoscopic esibonisa ukuqina kwelume eliqinile.
Zonke izingulube zagunyazwa ngokufaka i-75 mg/kg ye-potassium chloride ngomjovo wemithambo yendlebe. Izingxenye ze-sagittal ezimaphakathi zekhanda le-porcine zenziwa kusetshenziswa i-chainsaw elandelwa ukukhishwa ngokucophelela kwamasampula ezicubu ze-ET scaffold ukuhlolwa kwe-histological (I-Supplementary Fig. 1a, b). Amasampula ezicubu ze-ET alungiswe ku-10% ye-neutral buffered formalin amahora angama-24.
Amasampula ezicubu ze-ET aphelelwa amanzi ngokulandelana ngotshwala bokugxila okuhlukahlukene. Amasampuli afakwa kumabhulokhi e-resin ngokungeniswa ne-ethylene glycol methacrylate (Technovit 7200® VLC; Heraus Kulzer GMBH, Wertheim, Germany). Izigaba ze-Axial zenziwa kumasampula ezicubu ze-ET ezishunyekiwe ezigabeni eziseduze nezikude (I-Supplementary Fig. 1c). Amabhulokhi e-polymer abe esefakwa kumaslayidi engilazi e-acrylic. Amaslayidi ebhulokhi leresin ayeyi-microground futhi epholishwa ngephepha le-silicon carbide eliwugqinsi oluhlukahlukene olufika kugqinsi luka-20 µm kusetshenziswa isistimu yegridi (Apparatebau GMBH, Hamburg, Germany). Wonke amaslayidi ayengaphansi kokuhlolwa kwe-histological nge-hematoxylin kanye ne-eosin staining.
Ukuhlolwa kwe-histological kwenziwa ukuze kuhlolwe iphesenti lokusabalala kwezicubu, ukujiya kwe-submucosal fibrosis, kanye nezinga lokungena kwamangqamuzana okuvuvukala. Iphesenti le-tissue hyperplasia enendawo encane ye-ET enqamulayo ibalwe ngokuxazulula isibalo:
Ukujiya kwe-submucosal fibrosis kukalwa ngokuma kusuke ku-stent stent kuya ku-submucosa. Izinga lokungena kweseli elivuthayo lahlulelwa ngokuzimele ngokusatshalaliswa kanye nokuminyana kwamangqamuzana okuvuvukala, okungukuthi: i-1st degree (emnene) - ukungena okukodwa kwe-leukocyte; I-2nd degree (emnene kuya emaphakathi) - ukungena kwe-leukocyte okugxile; I-3rd degree (emaphakathi) - ihlanganisiwe. nama-leukocyte angakwazi ukuhlukanisa phakathi kwe-loci ngayinye; I-leukocyte yebanga lesi-4 (ephakathi kuya kokuqina) isakazeka ngokungena ngaphakathi kuyo yonke i-submucosa, futhi ibanga lesi-5 (elinzima) lisakaza ukungena nge-multiple foci ye-necrosis. Ugqinsi lwe-submucosal fibrosis kanye nezinga lokungena kweseli elivuvukalayo kutholwe ngesilinganiso samaphuzu ayisishiyagalombili azungeze isiyingi. Ukuhlaziywa kwe-Histological ye-ET kwenziwa kusetshenziswa isibonakhulu (BX51; Olympus, Tokyo, Japan). Izilinganiso zitholwe kusetshenziswa isofthiwe ye-CaseViewer (CaseViewer; 3D HISTECH Ltd., Budapest, Hungary). Ukuhlaziywa kwedatha ye-histological kwakusekelwe ekuvumelaneni kwababukeli abathathu abangazange bahlanganyele ocwaningweni.
I-Mann-Whitney U-test yasetshenziselwa ukuhlaziya umehluko phakathi kwamaqembu njengoba kudingeka. I-p <0.05 ibhekwe njengebalulekile ngokwezibalo. I-p <0.05 ibhekwe njengebalulekile ngokwezibalo. Значение p < 0,05 считалось статистически значимым. Inani elingu-p <0.05 lithathwe njengelibalulekile ngokwezibalo. 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 ibhekwe njengebalulekile ngokwezibalo. Ukuhlolwa kwe-Bonferroni-ilungiswe i-Mann–Whitney U-U-yenzelwe amanani we-p <0.05 ukuze kutholwe umehluko weqembu (p <0.008 njengebalulekile ngokwezibalo). Ukuhlolwa kwe-Bonferroni-ilungiswe i-Mann–Whitney U-yenzelwe amanani we-p <0.05 ukuze kutholwe umehluko weqembu (p <0.008 njengebalulekile ngokwezibalo). I-U-критерий Манна-Уитни с поправкой на Бонферрони был выполнен для значений p значимое). Ukuhlolwa kwe-Bonferroni-Mann-Whitney U okulungisiwe kwenzelwe amanani we-p <0.05 ukuze kutholwe umehluko weqembu (p<0.008 njengokubalulekile ngokwezibalo).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 I-U-критерий Манна-Уитни с поправкой на Бонферрони был выполнен для значений p < 0,05 kuya ku-70,05 kuya ku-2,05 kuya ku-20,05 kuya ku-20,05 kuya ku-20,05 kuya ku-1,000,00,00,10 значимым). I-Bonferroni-adjusted Mann-Whitney U-test yenzelwe p <0.05 ukuze kutholwe umehluko weqembu (p <0.008 yayibalulekile ngokwezibalo).Ukuhlaziywa kwezibalo kwenziwa kusetshenziswa isofthiwe ye-SPSS (inguqulo 27.0; SPSS, IBM, Chicago, IL, USA).
Konke ukufakwa kwama-porcine stent kube yimpumelelo ngokobuchwepheshe. I-metal guide sheath yafakwa ngempumelelo ku-nasopharyngeal orifice ye-ET ngaphansi kokulawulwa kwe-endoscopic, nakuba ukulimala kwe-mucosal nokopha kokuxhumana kwabonwa ku-4 yezibonelo ze-12 (33.3%) ngesikhathi sokufakwa kwe-metal sheath. Ngemva kwamaviki angu-4, ukopha okuzwakalayo kuyeka ngokuzenzakalelayo. Zonke izingulube zasinda kwaze kwaba sekugcineni kocwaningo ngaphandle kwezinkinga ezihlobene ne-stent.
Imiphumela ye-Endoscopy ikhonjiswe kuMfanekiso 4. Phakathi nokulandelwa kwamasonto ama-4, ama-stents ahlala endaweni yazo zonke izingulube. Ukuqoqwa kwe-Mucus ngaphakathi naseduze kwe-ET stent kwabonwa kuwo wonke (100%) ETs eqenjini lokulawula kanye nama-ET amathathu (50%) ama-ET ayisithupha eqenjini le-SES, futhi kwakungekho umehluko ezenzakalweni phakathi kwamaqembu amabili (p = 0.182). Awekho ama-stents afakiwe akwazi ukugcina umumo oyindilinga.
Izithombe ze-Endoscopic ze-Eustachian tube (ET) yengulube eqenjini elilawulayo kanye neqembu eline-cobalt-chromium stent (CXS) eluting sirolimus. (a) Isithombe esiyisisekelo se-endoscopic esithathwe ngaphambi kokubekwa kwe-stent esibonisa ukuvuleka kwe-nasopharyngeal (umcibisholo) we-ET. (b) Isithombe se-Endoscopic esithathwe ngokushesha ngemva kokubekwa kwe-stent esibonisa i-ET yokubekwa kwe-stent. Ukopha othintana naye kuye kwabonwa ngenxa yesigqoko somhlahlandlela wensimbi (umcibisholo). (c) Isithombe se-Endoscopic esithathwe amaviki angu-4 ngemva kokubekwa kwe-stent sibonisa ukunqwabelana kwamafinyila eduze kwe-stent (umcibisholo). (d) Isithombe se-Endoscopic esibonisa ukuthi i-stent ayikwazi ukuhlala iyindilinga (umcibisholo).
Okutholakele kwe-histological kuboniswa ku-Figure 5 kanye nomfanekiso ongeziwe 2. Ukwanda kwezicubu kanye nokwanda kwe-submucosal fibrous phakathi kokuthunyelwe kwe-stent ku-ET lumen yawo womabili amaqembu. Isilinganiso sephesenti yendawo ye-tissue hyperplasia yayinkulu kakhulu eqenjini lokulawula kuneqembu le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p <0.001). Isilinganiso sephesenti yendawo ye-tissue hyperplasia yayinkulu kakhulu eqenjini lokulawula kuneqembu 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 (79,68% 48,36% ± 10,06%, p <0,001). Iphesenti yendawo ye-tissue hyperplasia yayinkulu kakhulu eqenjini lokulawula kuneqembu 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). I-Средний процент площади гиперплазии тканей в контрольной группе был значительно выше, чем в группе СЭС (79,6плазии тканей в контрольной группе был значительно выше, чем в группе СЭС (79,6плазии СЭС) ± 10,06%, p <0,001). Iphesenti yendawo ye-tissue hyperplasia eqenjini lokulawula yayiphakeme kakhulu kuneqembu le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p <0.001). Ngaphezu kwalokho, ubukhulu be-submucosal fibrosis bubuye buphakeme kakhulu eqenjini lokulawula kuneqembu le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p <0.001). Ngaphezu kwalokho, ubukhulu be-submucosal fibrosis bubuye buphakeme kakhulu eqenjini lokulawula kuneqembu 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 СЭС 410, 50,± 10 ± 0,20 мм, p <0,001). Ngaphezu kwalokho, ubukhulu be-submucosal fibrosis bubuye buphakeme kakhulu eqenjini lokulawula kuneqembu 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 ±2, 510, ±2, 5,0,0 ± 0,20 мм, p <0,001). Ukwengeza, ubukhulu besilinganiso se-submucosal fibrosis eqenjini lokulawula nalo laliphakeme kakhulu kuneqembu le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p <0.001).Kodwa-ke, kwakungekho umehluko ophawulekayo ngezinga lokungena kwamaseli okuvuvukala phakathi kwamaqembu amabili (iqembu lokulawula [3.50 ± 0.55] vs. iqembu le-SES [3.00 ± 0.89], p = 0.270).
Ukuhlaziywa kokuhlolwa kwe-histological kwamaqembu amabili ama-stents abekwe ku-lumen ye-Eustachian. (a, b) Indawo ye-tissue hyperplasia (1 ka-a no-b) kanye nogqinsi lwe-submucosal fibrosis (2 ka-a no-b; imicibisholo ephindwe kabili) yayinkulu kakhulu eqenjini lokulawula kuneqembu le-SES eline-strut stenting (amachashazi amnyama), indawo yelume elimngcingo (ephuzi) kanye nendawo yestent yasekuqaleni (ebomvu). Izinga lokungena kweseli elivuvukalayo (3 ka-a kanye no-b; imicibisholo) alizange lihluke kakhulu phakathi kwamaqembu amabili. (c) Imiphumela ye-Histological yephesenti yendawo ye-tissue hyperplasia, (d) ukujiya kwe-submucosal fibrosis, kanye (e) nezinga lokungena kweseli elivuvukalayo amasonto angu-4 ngemva kokubekwa kwe-stent kuwo womabili amaqembu. I-SES, i-cobalt-chromium sirolimus eluting stent.
Ama-stents akhipha izidakamizwa asiza ukuthuthukisa amandla okuqina futhi avimbele i-stent restenosis20,21,22,23,24. Ukuqina okubangelwa i-stent kubangelwa ukwakheka kwezicubu ze-granulation kanye noshintsho lwezicubu ezine-fibrous ezingxenyeni ezihlukene ezingenayo imithambo, okuhlanganisa umphimbo, uqhoqhoqho, i-gastroduodenum, nemigudu yenyongo. Izidakamizwa ezifana ne-dexamethasone, i-paclitaxel, i-gemcitabine, i-EW-7197, ne-sirolimus zisetshenziswa ebusweni be-wire mesh noma i-stent coating ukuvimbela noma ukwelapha i-tissue hyperplasia ngemva kokubekwa kwe-stent29,30,34,35,36. Izindlela ezintsha ezisanda kwenziwa emkhakheni wama-stents asebenza ngezinto eziningi zisebenzisa ubuchwepheshe be-fusion ziphenywa ngenkuthalo ekwelapheni izifo ezingenayo i-vascular occlusive37,38,39. Esifundweni sangaphambilini kumodeli ye-porcine ET, ukwanda kwezicubu ezibangelwa i-scaffold kwabonwa. Nakuba ukuthuthukiswa kwe-stent ku-ET kungaqondakali kahle, impendulo yezicubu ngemva kokubekwa kwe-stent kutholakale ukuthi ifana nezinye izitho ze-luminal ezingenalutho19. Ocwaningweni lwamanje, i-SES isetshenziselwe ukuvimbela ukwanda kwezicubu ezibangelwa i-scaffold kumodeli ye-porcine ET. I-Sirolimus inobuthi eziqhingini ze-pancreatic kanye nemigqa yeseli ye-beta, inciphisa ukusebenza kwamaseli futhi ithuthukise i-apoptosis40,41. Lo mphumela ungase usize ukuvimbela ukwakheka kokwanda kwezicubu ngokuvuselela ukufa kwamangqamuzana. Ucwaningo lwethu lubonise ukuthi ukusetshenziswa kokuqala kwezidakamizwa-eluting stents ku-ET kuvimbele ngokuphumelelayo ukwanda kwezicubu ezibangelwa i-stent ku-ET.
I-co-Cr alloy stent enwetshwa ibhaluni esetshenziswa kulolu cwaningo itholakala kalula njengoba ijwayele ukusetshenziselwa ukwelapha isifo se-coronary artery 42. Ngaphezu kwalokho, ama-alloys e-Co-Cr anezakhiwo zemishini (isibonelo, amandla aphezulu e-radial kanye namandla anelastic) 43. Ngokusho kwe-endoscopy yocwaningo lwamanje, i-Co-Cr alloy stent esetshenziselwa i-ET yezingulube ayikwazi ukugcina isimo esiyindilinga kuzo zonke izingulube ngenxa yokunwebeka okwanele futhi ayinalo ikhono lokuzikhulisa. Ukuma kwe-stent efakiwe kungashintshwa futhi ngokuhamba eduze kwe-ET yesilwane esiphilayo (isb., ukuhlafuna nokugwinya). Izakhiwo zemishini yama-Co-Cr alloy stents seziphenduke into embi ekubekweni kwama-porcine ET stents. Ukwengeza, ukubekwa kwe-stent ku-isthmus kungase kuphumele ekuvuleni i-ET unomphela. I-ET eqhubekayo evulekile noma eyandisiwe ivumela imisindo yokukhuluma ne-nasopharyngeal, i-reflux yamathumbu, kanye nama-pathogens1 ukuthi ahambe aye endlebeni ephakathi, okubangela ukucasuka kwe-mucosal kanye nokutheleleka. Ngakho-ke, ukuvuleka okuhlala njalo kwe-nasopharyngeal kufanele kugwenywe. Ngakho-ke, uma kubhekwa uhlaka lwe-ET cartilage, ama-scaffolds angcono kakhulu enziwe kusuka kuma-alloys enkumbulo yomumo anezici ze-superelastic, njenge-nitinol. Ngokuvamile, ukukhishwa okunzima kwatholakala ngaphakathi naseduze kwe-nasopharyngeal orifice ye-stent. Njengoba ukunyakaza okujwayelekile kwe-mucociliary kwe-mucus kuvinjiwe, imfihlo kulindeleke ukuthi iqoqwe kuma-scaffolds aphuma ekuvuleni kwe-nasopharyngeal. Ukuvimbela ukukhuphuka kokutheleleka kwendlebe ephakathi kungenye yezinhloso eziyinhloko ze-ET, futhi ukubekwa kwama-stents aphuma ngaphesheya kwe-ET kufanele kugwenywe, njengoba ukuthintana okuqondile kwama-stents ane-nasopharyngeal bacterial flora kungaholela ekwandeni kwezifo ezikhuphukayo.
I-Eustachian tube balloon plasty ngokusebenzisa ukuvulwa kwe-nasopharyngeal iyindlela entsha yokwelapha ehlasela kancane yokungasebenzi kahle kwe-ET okuhloswe ngayo ukuvula nokwandisa ingxenye ye-cartilaginous ye-ET8,9,10,46. Kodwa-ke, indlela yokwelapha eyisisekelo ayizange ikhonjwe47 futhi imiphumela yayo yesikhathi eside ingase ibe yi-suboptimal8,9,11,46. Ngaphansi kwalezi zimo, ukuqina kwensimbi yesikhashana kungase kube inketho yokwelapha ephumelelayo ezigulini ezingaphenduli ekulungiseni ibhaluni ye-Eustachian, futhi ukuba nokwenzeka kwe-ET stenting kuye kwaboniswa ezifundweni eziningi zangaphambi komtholampilo. I-Poly-l-lactide scaffolds yafakwa nge-membrane ye-tympanic ku-chinchillas kanye onogwaja ukuze kuhlolwe ukubekezelelana nokuwohloka ku-vivo17,18. Ngaphezu kwalokho, imodeli yezimvu yadalwa ukuhlola iphrofayili yama-stents anwebekayo ebhaluni lensimbi ku-vivo. Esifundweni sethu sangaphambilini, imodeli ye-porcine ET yasungulwa ukuze iphenye ukuthi kungenzeka yini ubuchwepheshe kanye nokuhlolwa kwezinkinga ezibangelwa i-stent, i-19 inikeza isisekelo esiqinile salolu cwaningo ukuze kuphenywe ukusebenza kwe-SES kusetshenziswa izindlela ezisungulwe ngaphambilini. Kulolu cwaningo, i-SES yenziwe yasendaweni ngempumelelo ku-cartilage futhi yavinjelwa ngempumelelo ukwanda kwezicubu. Azikho izinkinga ezihlobene ne-stent, kodwa kube khona ukulimala kwe-mucosal okubangelwa i-metal guide sheath enokopha othintana naye okuxazululwe ngokuzenzekelayo phakathi namaviki angu-4. Njengoba kunikezwe izinkinga ezingaba khona zamashethi ensimbi, ukuthuthukisa uhlelo lokulethwa kwe-SES kuyaphuthuma futhi kubucayi.
Lolu cwaningo lunokulinganiselwa okuthile. Nakuba okutholakele kwe-histological kwahluka kakhulu phakathi kwamaqembu, inani lezilwane kulolu cwaningo lalincane kakhulu ukuhlaziya izibalo ezithembekile. Nakuba izibukeli ezintathu zaphuphuthekiswa ukuze zihlole ukuhlukahluka kwe-inter-observer, izinga lokungena kweseli yokuvuvukala kwe-submucosal lanqunywa ngokuzimele ngokusekelwe ekusabalaliseni kanye nokuminyana kwamangqamuzana okuvuvukala ngenxa yobunzima bokubala amaseli avuthayo. Njengoba isifundo sethu senziwe kusetshenziswa inani elilinganiselwe lezilwane ezinkulu, umthamo owodwa womuthi wasetshenziswa, izifundo ze-pharmacokinetic ze-vivo azizange zenziwe. Kudingeka olunye ucwaningo ukuze kuqinisekiswe umthamo ophelele womuthi kanye nokuphepha kwe-sirolimus ku-ET. Okokugcina, isikhathi sokulandela samasonto ama-4 siphinde sibe umkhawulo wocwaningo, ngakho ucwaningo lokusebenza ngempumelelo yesikhathi eside lwe-SES luyadingeka.
Imiphumela yalolu cwaningo ibonisa ukuthi i-SES ingavimbela ngokuphumelelayo ukwanda kwezicubu ezibangelwa ukulimala ngemva kokubekwa kwe-co-Cr alloy scaffolds enwebekayo ye-Co-Cr kumodeli ye-porcine ET. Emasontweni amane ngemuva kokubekwa kwe-stent, okuguquguqukayo okuhlotshaniswa nokwanda kwezicubu okubangelwa i-stent (okubandakanya indawo yokwanda kwezicubu kanye nokuqina kwe-submucosal fibrosis) bekuphansi kakhulu eqenjini le-SES kuneqembu lokulawula. I-SES ibonakala isebenza ngempumelelo ekuvimbeleni ukwanda kwezicubu ezibangelwa i-scaffold ezingulubeni ze-ET. Nakuba ucwaningo olwengeziwe ludingeka ukuze kuhlolwe izinto ezisetshenziswayo ezisezingeni eliphezulu kanye nemithamo yabantu abazokhethwa emithini, i-SES inamandla okwelapha asendaweni ekuvimbeleni i-ET tissue hyperplasia ngemva kokubekwa kwe-stent.
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