Siyabonga ngokuvakashela i-Nature.com. Inguqulo yesiphequluli oyisebenzisayo inokusekelwa okulinganiselwe kwe-CSS. Ukuze uthole ulwazi olungcono kakhulu, sincoma ukuthi usebenzise isiphequluli esibuyekeziwe (noma ukhubaze i-Compatibility Mode ku-Internet Explorer). Okwamanje, ukuqinisekisa ukwesekwa okuqhubekayo, sizonikeza isayithi ngaphandle kwezitayela kanye ne-JavaScript.
Izifundo ezahlukahlukene zangaphambi kokwelashwa ze-stent ye-Eustachian tube (ET) ethuthukisiwe ziyaqhubeka okwamanje, kodwa ayikasetshenziswa emtholampilo. Ezifundweni zangaphambi kokwelashwa, ama-scaffolds e-ET anqunyelwe ekukhuleni kwezicubu ezibangelwa yi-scaffold. Ukusebenza kahle kwe-stent ye-cobalt-chromium sirolimus-eluting (SES) ekuvimbeleni ukwanda kwezicubu ezibangelwa yi-stent ngemva kokubekwa kwe-stent kwafundwa kumodeli ye-ET yengulube. Izingulube eziyisithupha zahlukaniswa ngamaqembu amabili (okungukuthi iqembu lokulawula kanye neqembu le-SES) nezingulube ezintathu eqenjini ngalinye. Iqembu lokulawula lathola i-stent ye-cobalt-chromium engagqokwanga (n = 6), kanti iqembu le-SES lathola i-stent ye-cobalt-chromium ene-sirolimus-eluting coating (n = 6). Wonke amaqembu ahlatshwa amasonto ama-4 ngemva kokubekwa kwe-stent. Ukubekwa kwe-stent kwaphumelela kuwo wonke ama-ET ngaphandle kwezinkinga ezihlobene nokuhlinzwa. Awekho ama-stent ayengagcina isimo sawo sokuqala esiyindilinga, futhi ukuqongelela kwe-mucus kwabonwa ngaphakathi naseduze kwama-stent kuwo womabili amaqembu. Ukuhlaziywa kwe-histological kubonise ukuthi indawo yokwanda kwezicubu kanye nobukhulu be-submucosal fibrosis eqenjini le-SES yayiphansi kakhulu kunaseqenjini lokulawula. I-SES ibonakala isebenza kahle ekuvimbeleni ukwanda kwezicubu ezibangelwa yi-scaffold ezingulubeni ze-ET. Kodwa-ke, kudingeka izifundo ezengeziwe ukuqinisekisa izinto ezifanele kakhulu ze-stent kanye nemithi yokulwa nokwanda kwezicubu.
I-Eustachian tube (ET) inemisebenzi ebalulekile endlebeni ephakathi (isb., ukuphefumula, ukuvimbela ukudluliselwa kwamagciwane kanye nokuphuma koketshezi e-nasopharynx)1. Kuhlanganisa nokuvikela imisindo ye-nasopharyngeal kanye nokubuyela emuva kwe-2. I-ET ivame ukuvalwa, kodwa ivuleka ngokugwinya, ukukhafula, noma ukuhlafuna. Kodwa-ke, ukungasebenzi kahle kwe-ET kungenzeka uma i-tube ingavuli noma ingavali kahle3,4. Ukungasebenzi kahle kwe-ET okuvulekile (okuvimbe) kunciphisa ukusebenza kwe-ET futhi, uma le misebenzi ingagcinwanga, ingase ikhule ibe yi-otitis media ebukhali noma engamahlalakhona, esinye sezifo ezivame kakhulu emtholampilo we-ENT. Ukwelashwa kwamanje kokungasebenzi kahle kwe-ET (isb., ukuhlinzwa kwekhala, ukufakwa kwe-ventilation tube, kanye nemithi) kusetshenziswa ezigulini. Kodwa-ke, lokhu kwelashwa kunamandla amancane futhi kungaholela ekuvinjweni kwe-ET, ekuthelelekeni, kanye nokubhoboka kwe-tympanic membrane okungaguquki3,6,7. I-Eustachian tube balloon angioplasty yethulwe njengendlela yokwelapha ehlukile yokungasebenzi kahle kwe-ET 8 okuvulekile. Nakuba izifundo eziningana kusukela ngo-2010 zikhombisile ukuthi ukulungiswa kwebhaluni le-Eustachian tube kungcono kunokwelashwa okuvamile kokungasebenzi kahle kwe-ET, ezinye iziguli aziphenduli ekukhuleni8,9,10,11. Ngakho-ke, ukufaka i-stenting kungaba yindlela yokwelapha ephumelelayo12,13. Naphezu kwezifundo eziningi eziqhubekayo zangaphambi kokwelashwa ezihlola ukusebenziseka kobuchwepheshe kanye nokusabela kwezicubu ngemva kokufakwa kwe-stent ku-ET, i-hyperplasia yezicubu ezibangelwa yi-stent ngenxa yomonakalo womshini isalokhu iyinkinga ebalulekile ngemva kokuhlinzwa14,15,16,17,18,19. I-embozwe ngemithi, egcwele ama-anti-proliferative agents ithuthukisa lesi simo.
Ama-stent asusa izidakamizwa asetshenziswe ukuvimbela i-in-stent restenosis ebangelwa yizicubu kanye ne-neointimal hyperplasia ngemva kokufakwa kwe-stent. Ngokuvamile, ama-stent scaffolds noma ama-linings ambozwe ngemithi (isb., i-everolimus, i-paclitaxel, kanye ne-sirolimus)20,23,24. I-Sirolimus umuthi ojwayelekile wokulwa nokwanda kwezicubu ovimbela izinyathelo eziningana ze-restenosis cascade (isb., ukuvuvukala, i-neointimal hyperplasia, kanye nokwakheka kwe-collagen)25. Ngakho-ke, lolu cwaningo lucabange ukuthi ama-stent afakwe i-sirolimus angavimbela i-stent-induced tissue hyperplasia ezingulubeni ze-ET (Isithombe 1). Inhloso yalolu cwaningo kwakuwukuphenya ukusebenza kahle kwama-stent asusa izicubu (i-SES) ekuvimbeleni ukwanda kwezicubu ezisusa izicubu ngemva kokufakwa kwe-stent kumodeli ye-ET yengulube.
Umfanekiso ohleliwe we-stent ye-cobalt-chromium sirolimus-eluting (SES) yokwelapha ukungasebenzi kahle kwe-Eustachian tube, okubonisa ukuthi i-stent ye-sirolimus-eluting ivimbela ukwanda kwezicubu ezibangelwa yi-stent.
Ama-stents e-alloy e-Cobalt-chromium (Co-Cr) enziwe ngamashubhu e-alloy e-Co-Cr okusika nge-laser (Genoss Co., Ltd., Suwon, Korea). Ipulatifomu ye-stent isebenzisa isibopho esivulekile esiphindwe kabili esinomklamo ohlanganisiwe wokuguquguquka okuphezulu ngamandla e-radial afanele, ukufinyeza kanye nokuhambisana. I-stent yayinobubanzi obungu-3 mm, ubude obungu-18 mm, kanye nobukhulu be-strut obungu-78 µm (Isithombe 2a). Ubukhulu bohlaka lwe-alloy ye-Co-Cr bunqunywe ngokusekelwe ocwaningweni lwethu lwangaphambilini.
I-stent ye-alloy ye-Cobalt-chromium (Co-Cr) kanye ne-sheath yesiqondiso sensimbi yokubeka i-stent ye-tube ye-Eustachian. Izithombe zibonisa (a) i-stent ye-alloy ye-Co-Cr kanye (b) ne-catheter ye-balloon eboshwe nge-stent. (c) I-catheter ye-balloon kanye ne-stent zifakwe ngokugcwele. (d) I-sheath yesiqondiso sensimbi yakhelwe imodeli ye-tube ye-porcine Eustachian.
I-Sirolimus yafakwa ebusweni be-stent kusetshenziswa ubuchwepheshe be-ultrasonic spray. I-SES yenzelwe ukukhulula cishe u-70% womthwalo wokuqala wemithi (1.15 µg/mm2) zingakapheli izinsuku ezingu-30 zokuqala ngemuva kokufakwa. Isembozo esincane kakhulu esingu-3 µm sisetshenziswa kuphela ohlangothini oluseduze lwe-stent ukuze kufezwe iphrofayili yokukhululwa kwemithi oyifunayo futhi kuncishiswe inani le-polymer; lesi sembozo esibolayo siqukethe i-copolymer yama-lactic acid nama-glycolic kanye nenhlanganisela ekhethekile ye-poly(1)-lactic acid)26,27. Ama-Co-Cr alloy stents afakwe kuma-catheter ebhaluni angu-3 mm ububanzi kanye no-28 mm ubude (Genoss Co., Ltd.; Umfanekiso 2b). Lawa ma-stents atholakala eNingizimu Korea ekwelapheni isifo senhliziyo.
Igobolondo eliqondisa insimbi elisha elithuthukisiwe lemodeli ye-ET yengulube lenziwe ngensimbi engagqwali (Isithombe 2c). Ububanzi bangaphakathi nangaphandle begobolondo bungu-2 mm no-2.5 ​​mm, ngokulandelana, ubude obuphelele bungu-250 mm. Igobolondo elikude elingama-30 mm lagotshwa laba yisimo se-J nge-engeli engu-15° kuya ku-axis ukuze kuvunyelwe ukufinyelela kalula kusuka ekhaleni kuya endaweni yokungena ye-nasopharyngeal ye-ET kumodeli yengulube.
Lolu cwaningo luvunyiwe yiKomidi Lokunakekelwa Kwezilwane Nokusetshenziswa Kwezikhungo le-Asan Institute of Life Sciences (eSeoul, eNingizimu Korea) futhi luhambisana ne-National Institutes of Health Guidelines for the Humane Treatment of Laboratory Animals (IACUC-2020-12-189). . Ucwaningo lwenziwe ngokuhambisana neziqondiso ze-ARRIVE. Lolu cwaningo lusebenzise ama-ET angu-12 ezingulubeni eziyisithupha ezinesisindo esingu-33.8-36.4 kg ezinyangeni ezintathu ubudala. Izingulube eziyisithupha zahlukaniswa ngamaqembu amabili (okungukuthi iqembu lokulawula kanye neqembu le-SES) nezingulube ezintathu eqenjini ngalinye. Iqembu lokulawula lathola i-stent ye-Co-Cr alloy engagqokwanga, kanti iqembu le-SES lathola i-stent ye-Co-Cr alloy eluting sirolimus. Zonke izingulube zazinokufinyelela mahhala emanzini nasekudleni futhi zagcinwa ku-24°C ± 2°C umjikelezo wamahora angu-12 emini nobusuku. Ngemva kwalokho, zonke izingulube zahlatshwa ngemva kwamasonto ama-4 ngemuva kokufakwa kwe-stent.
Zonke izingulube zathola ingxube ye-50mg/kg zolazepam, 50mg/kg teletamide (Zoletil 50; Virbac, Carros, France) kanye ne-10mg/kg xylazine (Rompun; Bayer HealthCare, Les Varkouzins, Germany). kwabe sekufakwa ithubhu le-tracheal ngokuphefumula i-isoflurane engu-0.5-2% (Ifran®; Hana Pharm. Co., Seoul, Korea) kanye ne-oxygen 1:1 (510 ml/kg/min) ukuze kutholakale i-anesthesia. Izingulube zabekwa endaweni yokulala phansi kwathi kwenziwa i-baseline endoscopy (VISERA 4K UHD rhinolaryngoscope; Olympus, Tokyo, Japan) ukuze kuhlolwe i-nasopharyngeal orifice ye-ET. I-sheath yensimbi eqondisayo yadluliselwa ekhaleni yaya e-nasopharyngeal orifice ye-ET ngaphansi kokulawulwa kwe-endoscopic (Isithombe 3a, b). I-catheter yebhaluni, i-stent ehlanganisiwe, ifakwa ngesiqalisi ku-ET kuze kube yilapho isihloko sayo sihlangana nokumelana ku-isthmus ye-osteochondral ye-ET (Isithombe 3c). I-catheter yebhaluni yagcwala ngokuphelele nge-saline kuma-atmospheres angu-9, njengoba kunqunywe yi-monitor ye-manometer (Isithombe 3d). I-catheter yebhaluni yasuswa ngemuva kokufakwa kwe-stent (Isithombe 3f), kwathi ukuvulwa kwe-nasopharyngeal kwahlolwa ngokucophelela i-endoscopy ukuze kutholakale izinkinga zokuhlinzwa (Isithombe 3f). Zonke izingulube zahlolwa i-endoscopy ngaphambi nangemva kokukhishwa kwe-stent, kanye namasonto ama-4 ngemva kokukhishwa kwe-stent, ukuze kuhlolwe ukuqina kwendawo ye-stent kanye nokuphuma okuzungezile.
Izinyathelo zobuchwepheshe zokubeka i-stent ku-eustachian tube (ET) yengulube ngaphansi kokulawulwa kwe-endoscopic. (a) Isithombe se-Endoscopic esibonisa ukuvulwa kwe-nasopharyngeal (umcibisholo) kanye ne-metal guide sheath (umcibisholo) efakiwe. (b) Ukufakwa kwe-metal sheath (umcibisholo) embobeni ye-nasopharyngeal. (c) I-catheter yebhaluni eboshwe nge-stent (umcibisholo) ifakwa ku-ET nge-sheath (umcibisholo). (d) I-balloon catheter (umcibisholo) igcwele umoya. (e) Ukuphela kwe-stent kuphuma ku-ET orifice ye-nasopharynx. (f) Isithombe se-Endoscopic esibonisa i-stent lumen patency.
Zonke izingulube zabulawa ngokubulala ngokufaka i-potassium chloride engu-75 mg/kg ngomjovo wemithambo yendlebe. Izingxenye eziphakathi ze-sagittal zekhanda lezingulube zenziwa kusetshenziswa i-chainsaw kwalandela ukukhishwa ngokucophelela kwamasampula ezicubu ze-ET scaffold ukuze kuhlolwe ngokwesayensi (Isithombe Esingeziwe 1a,b). Amasampula ezicubu ze-ET aqiniswe ku-formalin engu-10% engathathi hlangothi amahora angama-24.
Amasampula ezicubu ze-ET ahlanzwa ngokulandelana ngotshwala obuhlukahlukene. Amasampula afakwa kumabhulokhi e-resin ngokufaka i-ethylene glycol methacrylate (Technovit 7200® VLC; Heraus Kulzer GMBH, Wertheim, Germany). Izingxenye ze-axial zenziwa kumasampula ezicubu ze-ET ezifakiwe ezingxenyeni eziseduze nezikude (Isithombe Esingeziwe 1c). Amabhulokhi e-polymer abe esefakwa kumaslayidi engilazi ye-acrylic. Amaslayidi e-resin block agcotshwa nge-microground futhi apholishwa ngephepha le-silicon carbide elinobukhulu obuhlukahlukene obufika ku-20 µm kusetshenziswa uhlelo lwegridi (Apparatebau GMBH, Hamburg, Germany). Wonke amaslayidi ahlolwa nge-histological nge-hematoxylin kanye ne-eosin staining.
Ukuhlolwa kwe-histological kwenziwa ukuhlola iphesenti lokwanda kwezicubu, ukujiya kwe-submucosal fibrosis, kanye nezinga lokungena kwamaseli okuvuvukala. Iphesenti le-tissue hyperplasia enendawo encane ye-ET cross-sectional labalwa ngokuxazulula lesi sibalo:
Ubukhulu be-submucosal fibrosis bulinganiswe ngokuqondile kusukela kuma-stent struts kuya ku-submucosa. Izinga lokungena kwamaseli okuvuvukala lahlulelwa ngokwehlukana ngokwalo ngokusatshalaliswa kanye nobuningi bamaseli okuvuvukala, okungukuthi: izinga loku-1 (elincane) - ukungena kwe-leukocyte eyodwa; izinga lesi-2 (elincane kuya kweliphakathi) - ukungena kwe-leukocyte egxile; izinga lesi-3 (eliphakathi) - lihlanganiswe. nama-leukocyte angakwazi ukuhlukanisa phakathi kwendawo ngayinye; ama-leukocyte ebanga lesi-4 (eliphakathi kuya kwelinzima) angena ngokusabalala kuyo yonke i-submucosa, kanye nokungena kwe-diffuse yebanga lesi-5 (elinzima) okune-foci eminingi ye-necrosis. Ubukhulu be-submucosal fibrosis kanye nezinga lokungena kwamaseli okuvuvukala kutholakale ngokwesilinganiso samaphuzu ayisishiyagalombili azungeze umjikelezo. Ukuhlaziywa kwe-histological kwe-ET kwenziwa kusetshenziswa i-microscope (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.
Ukuhlolwa kwe-Mann-Whitney U kwasetshenziswa 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 le-p < 0.05 libhekwe 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 kwabhekwa njengokubalulekile ngokwezibalo. Ukuhlolwa kwe-Mann-Whitney U okulungiswe yi-Bonferroni kwenziwa ngamanani e-p < 0.05 ukuthola umehluko wamaqembu (p < 0.008 njengobalulekile ngokwezibalo). Ukuhlolwa kwe-Mann-Whitney U okulungiswe yi-Bonferroni kwenziwa ngamanani e-p < 0.05 ukuthola umehluko wamaqembu (p < 0.008 njengobalulekile ngokwezibalo). I-U-критерий Манна-Уитни с поправкой на Бонферрони был выполнен для значений p значимое). Ukuhlolwa kwe-Mann-Whitney U okulungiswe yi-Bonferroni kwenziwe ngamanani e-p <0.05 ukuthola umehluko wamaqembu (p<0.008 njengobalulekile 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). Ukuhlolwa kwe-Mann-Whitney U okulungiswe yi-Bonferroni kwenziwe ku-p < 0.05 ukuthola umehluko wamaqembu (p < 0.008 kwakubalulekile ngokwezibalo).Ukuhlaziywa kwezibalo kwenziwe kusetshenziswa isofthiwe ye-SPSS (inguqulo 27.0; SPSS, IBM, Chicago, IL, USA).
Zonke izindawo zokubeka i-stent yezingulube ziphumelele ngokobuchwepheshe. I-sheath yensimbi eqondisayo ibekwe ngempumelelo emgodini we-nasopharyngeal we-ET ngaphansi kokulawulwa kwe-endoscopic, yize ukulimala kwe-mucosal kanye nokopha kokuthintana kwabonwa ezibonelweni ezine kweziyi-12 (33.3%) ngesikhathi sokufakwa kwe-sheath yensimbi. Ngemva kwamasonto ama-4, ukopha okuzwakalayo kwaphela ngokuzenzekelayo. Zonke izingulube zasinda kwaze kwaba sekupheleni kocwaningo ngaphandle kwezinkinga ezihlobene ne-stent.
Imiphumela ye-Endoscopy iboniswe kuMfanekiso 4. Ngesikhathi sokulandelela kwamasonto amane, ama-stents ahlala endaweni yawo wonke amangulube. Ukuqongelela kwama-mucus ngaphakathi naseduze kwe-stent ye-ET kwabonwa kuwo wonke ama-ET (100%) eqenjini lokulawula kanye nama-ET amathathu (50%) kwayisithupha eqenjini le-SES, futhi akukho mehluko ekutholakaleni phakathi kwamaqembu amabili (p = 0.182). Awekho ama-stents afakiwe angagcina isimo esiyindilinga.
Izithombe ze-endoscopic ze-Eustachian tube (ET) yengulube eqenjini lokulawula kanye neqembu eline-cobalt-chromium stent (CXS) elisusa i-sirolimus. (a) Isithombe se-endoscopic esithathwe ngaphambi kokufakwa kwe-stent esibonisa ukuvulwa kwe-nasopharyngeal (umcibisholo) we-ET. (b) Isithombe se-endoscopic esithathwe ngokushesha ngemva kokufakwa kwe-stent esibonisa i-ET yokufakwa kwe-stent. Ukopha kokuthintana kuye kwabonwa ngenxa ye-sheath yesiqondiso sensimbi (umcibisholo). (c) Isithombe se-endoscopic esithathwe emavikini ama-4 ngemuva kokufakwa kwe-stent sibonisa ukunqwabelana kwe-mucus ezungeze i-stent (umcibisholo). (d) Isithombe se-endoscopic esibonisa ukuthi i-stent ayikwazi ukuhlala iyindilinga (umcibisholo).
Okutholakele kwe-histological kuboniswe ku-Figure 5 kanye ne-Supplementary Figure 2. Ukwanda kwezicubu kanye nokwanda kwe-submucosal fibrous phakathi kwezikhala ze-stent ku-ET lumen yamaqembu womabili. Iphesenti elimaphakathi lendawo ye-tissue hyperplasia lalilikhulu kakhulu eqenjini lokulawula kunaseqenjini le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001). Iphesenti elimaphakathi lendawo ye-tissue hyperplasia lalilikhulu kakhulu eqenjini lokulawula kunaseqenjini 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 elimaphakathi lendawo ye-tissue hyperplasia lalilikhulu kakhulu eqenjini lokulawula kunaseqenjini 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 elimaphakathi lendawo ye-tissue hyperplasia eqenjini lokulawula laliphezulu kakhulu kunaseqenjini le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001). Ngaphezu kwalokho, ubukhulu obuphakathi be-submucosal fibrosis nabo babuphakeme kakhulu eqenjini lokulawula kunaseqenjini le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001). Ngaphezu kwalokho, ubukhulu obuphakathi be-submucosal fibrosis nabo babuphakeme kakhulu eqenjini lokulawula kunaseqenjini 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 obuphakathi be-submucosal fibrosis nabo babuphakeme kakhulu eqenjini lokulawula kunaseqenjini 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). Ngaphezu kwalokho, ubukhulu obuphakathi be-submucosal fibrosis eqenjini lokulawula nabo babuphakeme kakhulu kunaseqenjini le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001).Kodwa-ke, bekungekho mehluko obalulekile ezingeni lokungena kwamaseli okuvuvukala phakathi kwamaqembu amabili (iqembu lokulawula [3.50 ± 0.55] uma kuqhathaniswa neqembu 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 nobukhulu be-submucosal fibrosis (2 ka-a no-b; imicibisholo ephindwe kabili) yayinkulu kakhulu eqenjini lokulawula kunaseqenjini le-SES eline-strut stenting (amachashazi amnyama), indawo ye-lumen emincane (ophuzi) kanye nendawo ye-stent yokuqala (obomvu). Izinga lokungena kwamaseli okuvuvukala (3 ka-a no-b; imicibisholo) alizange lihluke kakhulu phakathi kwamaqembu amabili. (c) Imiphumela ye-histological yendawo yephesenti le-tissue hyperplasia, (d) ubukhulu be-submucosal fibrosis, kanye (e) izinga lokungena kwamaseli okuvuvukala emavikini ama-4 ngemuva kokufakwa kwe-stent kuwo womabili amaqembu. I-SES, i-cobalt-chromium sirolimus eluting stent.
Ama-stent asusa izidakamizwa asiza ekuthuthukiseni i-stent patency futhi avimbele i-stent restenosis20,21,22,23,24. Ama-stricture abangelwa yi-stent avela ekwakhekeni kwezicubu ze-granulation kanye noshintsho lwezicubu ze-fibrous ezithweni ezahlukene ezingezona ezemithambo yegazi, kufaka phakathi i-esophagus, i-trachea, i-gastroduodenum, kanye ne-bile ducts. Izidakamizwa ezifana ne-dexamethasone, i-paclitaxel, i-gemcitabine, i-EW-7197, kanye ne-sirolimus zifakwa ebusweni be-wire mesh noma i-stent coating ukuvimbela noma ukwelapha i-hyperplasia yezicubu ngemuva kokufakwa kwe-stent29,30,34,35,36. Izinto ezintsha zakamuva emkhakheni wama-stent amaningi asebenzisa ubuchwepheshe be-fusion ziyaphenywa ngenkuthalo ekwelapheni izifo ezingezona ezemithambo yegazi37,38,39. Esifundweni sangaphambilini kumodeli ye-porcine ET, ukwanda kwezicubu okubangelwa yi-scaffold kwabonwa. Nakuba ukuthuthukiswa kwe-stent ku-ET kungaqondakali kahle, impendulo yezicubu ngemva kokufakwa kwe-stent itholakale ifana neyezinye izitho zokukhanya ezingezona imithambo yegazi19. Kulesi sifundo samanje, i-SES yasetshenziswa ukuvimbela ukwanda kwezicubu okubangelwa yi-scaffold kumodeli ye-ET yengulube. I-Sirolimus inobuthi eziqhingini ze-pancreatic kanye nemigqa yamaseli e-beta, inciphisa ukusebenza kwamaseli futhi ithuthukisa i-apoptosis40,41. Lo mphumela ungasiza ekuvimbeleni ukwakheka kokwanda kwezicubu ngokukhuthaza ukufa kwamaseli. Ucwaningo lwethu lukhombisile ukuthi ukusetshenziswa kokuqala kwama-stent asusa izidakamizwa ku-ET kuvimbele ngempumelelo ukwanda kwezicubu okubangelwa yi-stent ku-ET.
I-stent ye-Co-Cr alloy enwebekayo esetshenziswa kulolu cwaningo itholakala kalula njengoba ivame ukusetshenziswa ukwelapha isifo semithambo yenhliziyo 42. Ngaphezu kwalokho, ama-Co-Cr alloys anezakhiwo zomshini (isibonelo, amandla aphezulu emisebe kanye namandla anganwebeki) 43. Ngokusho kwe-endoscopy yocwaningo lwamanje, i-stent ye-Co-Cr alloy esetshenziselwa i-ET yezingulube ayikwazi ukugcina isimo esiyindilinga kuzo zonke izingulube ngenxa yokunganwebeki ngokwanele futhi ayinalo ikhono lokuzikhulisa. Isimo se-stent efakiwe singashintshwa nangokunyakaza okuzungeze i-ET yesilwane esiphilayo (isb., ukuhlafuna nokugwinya). Izakhiwo zomshini zama-stent e-Co-Cr alloy ziye zaba yiphutha ekubekweni kwama-stent e-ET ezingulube. Ngaphezu kwalokho, ukufakwa kwe-stent kulesi siqhingi kungabangela i-ET evulekile unomphela. I-ET evulekile noma enwetshiwe eqhubekayo ivumela imisindo yokukhuluma kanye ne-nasopharyngeal, i-reflux yesisu, kanye namagciwane1 ukuthi akhuphuke aye endlebeni ephakathi, okubangela ukucasuka kwe-mucosal kanye nokutheleleka. Ngakho-ke, kufanele kugwenywe ukuvuleka kwamazinyo okuhlala njalo. Ngakho-ke, uma ubheka isakhiwo se-cartilage ye-ET, ama-scaffolds angcono enziwe ngama-alloys enkumbulo yesimo anezakhiwo ze-superelastic, njenge-nitinol. Ngokuvamile, kutholakale ukukhishwa okukhulu ngaphakathi naseduze kwe-nasopharyngeal orifice ye-stent. Njengoba ukunyakaza okuvamile kwe-mucus kuvinjiwe, imfihlo kulindeleke ukuthi iqoqeke kuma-scaffolds avela ekuvulekeni kwe-nasopharyngeal. Ukuvimbela ukutheleleka kwendlebe ephakathi okukhuphukayo kungenye yezinhloso eziyinhloko ze-ET, futhi ukubekwa kwama-stents avela ngale kwe-ET kufanele kugwenywe, ngoba ukuxhumana ngqo kwama-stents nezitshalo zamagciwane e-nasopharyngeal kungaholela ekwandeni kokutheleleka okukhuphukayo.
I-Eustachian tube balloon plasty ngokusebenzisa ukuvulwa kwe-nasopharyngeal iyindlela entsha yokwelapha engavamile yokungasebenzi kahle kwe-ET okuhloswe ngayo ukuvula nokwandisa ingxenye ye-cartilaginous ye-ET8,9,10,46. Kodwa-ke, indlela yokwelapha eyisisekelo ayikakatholakali47 futhi imiphumela yayo yesikhathi eside ingase ibe ngaphansi kakhulu8,9,11,46. Ngaphansi kwalezi zimo, i-metal stenting yesikhashana ingaba yindlela yokwelapha ephumelelayo yeziguli ezingaphenduli ekulungisweni kwe-Eustachian tube balloon, futhi kungenzeka ukuthi i-ET stenting iboniswe ezifundweni eziningi zangaphambi kokwelashwa. Ama-scaffolds e-Poly-l-lactide afakwe nge-membrane ye-tympanic kuma-chinchillas nakonogwaja ukuze kuhlolwe ukubekezeleleka kanye nokuwohloka kwe-vivo17,18. Ngaphezu kwalokho, kwadalwa imodeli yezimvu ukuze kuhlolwe iphrofayili yama-stents anwebekayo ebhaluni lensimbi emzimbeni. Esifundweni sethu sangaphambilini, kwasungulwa imodeli ye-ET yengulube ukuze kuhlolwe ukuthi kungenzeka yini ubuchwepheshe kanye nokuhlolwa kwezinkinga ezibangelwa yi-stent,19 okuhlinzeka ngesisekelo esiqinile salolu cwaningo ukuze kuhlolwe ukusebenza kahle kwe-SES kusetshenziswa izindlela ezisungulwe ngaphambilini. Kulesi sifundo, i-SES yatholakala ngempumelelo ku-cartilage futhi yavimbela ngempumelelo ukwanda kwezicubu. Azikho izinkinga ezihlobene ne-stent, kodwa kwakukhona ukulimala kwe-mucosal okubangelwe yi-metal guide sheath kanye nokopha kokuxhumana okwaxazululeka ngokuzenzakalelayo zingakapheli amasonto ama-4. Njengoba kunikezwe izinkinga ezingaba khona ze-metal sheaths, ukuthuthukisa uhlelo lokulethwa kwe-SES kuyaphuthuma futhi kubalulekile.
Lolu cwaningo lunemikhawulo ethile. Nakuba okutholakele kwe-histological kwahlukahluka kakhulu phakathi kwamaqembu, inani lezilwane kulolu cwaningo lalilincane kakhulu ukuze kuhlaziywe izibalo okuthembekile. Nakuba ababukeli abathathu babephuphuthekiswe ukuhlola ukuguquguquka kwababukeli, izinga lokungena kwamaseli okuvuvukala ngaphansi kwe-mucosal lanqunywa ngokwehlukile ngokusekelwe ekusatshalalisweni nasekubuneni kwamaseli okuvuvukala ngenxa yobunzima bokubala amaseli okuvuvukala. Njengoba ucwaningo lwethu lwenziwe kusetshenziswa inani elilinganiselwe lezilwane ezinkulu, kwasetshenziswa umthamo owodwa womuthi, izifundo ze-pharmacokinetic ze-in vivo azange zenziwe. Kudingeka izifundo ezengeziwe ukuqinisekisa umthamo ofanele womuthi kanye nokuphepha kwe-sirolimus ku-ET. Okokugcina, isikhathi sokulandelela samaviki ama-4 naso siwumkhawulo wocwaningo, ngakho-ke izifundo mayelana nokusebenza kahle kwesikhathi eside kwe-SES ziyadingeka.
Imiphumela yalolu cwaningo ikhombisa ukuthi i-SES ingavimbela ngempumelelo ukwanda kwezicubu ezibangelwa ukulimala komshini ngemuva kokubekwa kwezicafu ze-Co-Cr alloy ezinwebekayo ngebhaluni kumodeli ye-ET yengulube. Emasontweni amane ngemuva kokubekwa kwe-stent, iziguquguquko ezihlotshaniswa nokwanda kwezicubu ezibangelwa yi-stent (kufaka phakathi indawo yokwanda kwezicubu kanye nobukhulu be-submucosal fibrosis) zaziphansi kakhulu eqenjini le-SES kunaseqenjini lokulawula. I-SES ibonakala isebenza kahle ekuvimbeleni ukwanda kwezicubu ezibangelwa yi-scaffold ezingulubeni ze-ET. Nakuba kudingeka ucwaningo olwengeziwe ukuze kuhlolwe izinto ezifanele ze-stent kanye nemithamo yabantu abazongenela imithi, i-SES inamandla okwelapha endawo ekuvimbeleni i-ET tissue hyperplasia ngemva kokubekwa kwe-stent.
UDi Martino, EF Ukuhlolwa komsebenzi we-Eustachian tube: isibuyekezo. I-Nitric acid 61, 467–476. https://doi.org/10.1007/s00106-013-2692-5 (2013).
U-Adil, E. kanye no-Poe, D. Yiluphi uhla oluphelele lwezokwelapha nokuhlinzwa olutholakalayo ezigulini ezine-Eustachian tube dysfunction? U-Adil, E. kanye no-Poe, D. Yiluphi uhla oluphelele lwezokwelapha nokuhlinzwa olutholakalayo ezigulini ezine-Eustachian tube dysfunction?U-Adil, E. no-Poe, D. Yiluphi uhla oluphelele lwezokwelapha nokuhlinzwa olutholakalayo ezigulini ezine-Eustachian tube dysfunction? Adil, E. & Poe, D. 咽鼓管功能障碍患者可使用的全方位内科和外科治疗方法是什么? U-Adil, E. kanye no-Poe, D.U-Adil, E. no-Poe, D. Yiluphi uhla oluphelele lwezokwelapha nokuhlinzwa olutholakalayo ezigulini ezine-Eustachian tube dysfunction?Okwamanje. Umbono. I-Otolaryngology. Ukuhlinzwa kwekhanda nentamo. 22:8-15. https://doi.org/10.1097/moo.000000000000020 (2014).
ULlewellyn, A. nabanye. Ukungenelela kokungasebenzi kahle kwe-eustachian tube kubantu abadala: isibuyekezo esihlelekile. ubuchwepheshe bezempilo. Hlola. 18 (1-180), v-vi. https://doi.org/10.3310/hta18460 (2014).
USchilder, AG nabanye. Ukungasebenzi kahle kwe-Eustachian tube: ukuvumelana ngezincazelo, izinhlobo, ukubonakaliswa kwemitholampilo, kanye nokuxilongwa. imitholampilo. I-Otolaryngology. 40, 407–411. https://doi.org/10.1111/coa.12475 (2015).
I-Bluestone, i-CD I-pathogenesis ye-otitis media: indima ye-Eustachian tube. Pediatrics. Infect. Dis. J. 15, 281–291. https://doi.org/10.1097/00006454-199604000-00002 (1996).
UMcCoul, ED, Singh, A., Anand, VK & Tabaee, A. Ukwandiswa kwebhaluni le-Eustachian tube kumodeli yesidumbu: Izinto ezicatshangelwayo zobuchwepheshe, ijika lokufunda, kanye nezithiyo ezingaba khona. UMcCoul, ED, Singh, A., Anand, VK & Tabaee, A. Ukwandiswa kwebhaluni le-Eustachian tube kumodeli yesidumbu: Izinto ezicatshangelwayo zobuchwepheshe, ijika lokufunda, kanye nezithiyo ezingaba khona.UMcCole, ED, Singh, A., Anand, VK kanye noTabai, A. Ukwanda kwebhaluni le-eustachian kumodeli ye-trophoblastic: izinto ezicatshangelwayo zobuchwepheshe, ijika lokufunda, kanye nezithiyo ezingaba khona. McCoul, ED, Singh, A., Anand, VK & Tabaee, A. 尸体模型中咽鼓管的气球扩张：技术考虑、学习曲线和潜在障碍。 McCoul, ED, Singh, A., Anand, VK & Tabaee, A. 尸体model中少鼓管的气球ukunwetshwa: ukucatshangelwa kobuchwepheshe, ijika lokufunda nezithiyo ezingaba khona.UMcCole, ED, Singh, A., Anand, VK kanye noTabai, A. Ukwanda kwebhaluni le-eustachian kumodeli ye-trophoblastic: izinto ezicatshangelwayo zobuchwepheshe, ijika lokufunda, kanye nezithiyo ezingaba khona.I-Laryngoscope 122, 718–723. https://doi.org/10.1002/lary.23181 (2012).
UNorman, G. nabanye. Ukubuyekezwa okuhlelekile kwesisekelo sobufakazi obulinganiselwe bokwelashwa kokungasebenzi kahle kwe-eustachian tube: ukuhlolwa kobuchwepheshe bezokwelapha. ukwelashwa. I-Otolaryngology. Amakhasi 39, 6-21. https://doi.org/10.1111/coa.12220 (2014).
U-Ockermann, T., uReineke, U., u-Upile, T., u-Ebmeyer, J. no-Sudhoff, HH Ukwandiswa kwebhaluni I-Eustachian tuboplasty: Ucwaningo lokubona ukuthi kungenzeka yini. U-Ockermann, T., uReineke, U., u-Upile, T., u-Ebmeyer, J. no-Sudhoff, HH Ukwandiswa kwebhaluni I-Eustachian tuboplasty: Ucwaningo lokubona ukuthi kungenzeka yini.U-Okkermann, T., uReineke, U., u-Upile, T., u-Ebmeyer, J. no-Sudhoff, HH Ukwandiswa kwebhaluni kwe-tuboplasty yase-Eustachian: ucwaningo lokufezwa. 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.U-Okkermann T., uReineke U., u-Upile T., u-Ebmeyer J. kanye no-Sudhoff HH Ukwandiswa kwebhaluni kwe-Eustachian tube angioplasty: ucwaningo lokufezwa.Umbhali. neuron. 31, 11:00–11:03. https://doi.org/10.1097/MAO.0b013e3181e8cc6d (2010).
Randrup, TS & Ovesen, T. Ibhaluni i-Eustachian tuboplasty: Ukubuyekezwa okuhlelekile. Randrup, TS & Ovesen, T. Ibhaluni i-Eustachian tuboplasty: Ukubuyekezwa okuhlelekile.URandrup, TS no-Ovesen, T. Ballon, i-Eustachian tuboplasty: isibuyekezo esihlelekile. Randrup, TS & Ovesen, T. Balloon Eustachian tuboplasty：系统评价。 Randrup, TS & Ovesen, T. Balloon Eustachian tuboplasty：系统评价。URandrup, TS no-Ovesen, T. Ballon, i-Eustachian tuboplasty: isibuyekezo esihlelekile.I-Otolaryngology. Ukuhlinzwa kwekhanda nentamo. 152, 383–392. https://doi.org/10.1177/0194599814567105 (2015).
Song, HY nabanye. Ukwanda kwebhaluni le-fluoroscopic kusetshenziswa ucingo oluqondisayo oluguquguqukayo lokungasebenzi kahle kwepayipi le-Eustachian elivimbayo. J. Vaske. interview. radiation. 30, 1562-1566. https://doi.org/10.1016/j.jvir.2019.04.041 (2019).
USilvola, J., Kivekäs, I. & Poe, DS Ukwandiswa kwebhaluni kwengxenye ye-cartilaginous ye-Eustachian tube. USilvola, J., Kivekäs, I. & Poe, DS Ukwandiswa kwebhaluni kwengxenye ye-cartilaginous ye-Eustachian tube. 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.I-Otolaryngology. Ijenali Yokuhlinzwa ye-shea. 151, 125–130. https://doi.org/10.1177/0194599814529538 (2014).
I-Song, HY nabanye. I-stent egcotshwe yi-nitinol: isipiliyoni ekwelapheni iziguli ezingu-108 ezine-malignant emphinjeni. J. Wask. interview. radiation. 13, 285-293. https://doi.org/10.1016/s1051-0443(07)61722-9 (2002).
I-Song, HY nabanye. Ama-stents ensimbi akhulisayo ezigulini ezine-benign prostatic hyperplasia ezisengozini enkulu: ukulandelwa kwesikhathi eside. I-Radiology 195, 655–660. https://doi.org/10.1148/radiology.195.3.7538681 (1995).
USchnabl, J. et al. Imvu njengemodeli yesilwane esikhulu sezinsiza zokuzwa ezifakwe endlebeni ephakathi nangaphakathi: ucwaningo lokufezwa kwesidumbu. Umbhali. ama-neurons. 33, 481–489. https://doi.org/10.1097/MAO.0b013e318248ee3a (2012).
Pohl, F. nabanye. I-stent ye-Eustachian tube ekwelapheni i-otitis media engapheli - ucwaningo lokungenzeka kwezimvu. Umuthi wekhanda nobuso. 14, 8. https://doi.org/10.1186/s13005-018-0165-5 (2018).
UPark, JH nabanye. Ukubekwa kwe-stent yensimbi enwebekayo ekhaleni: ucwaningo lwe-Eustachian tube esidunjini somuntu. J. Vaske. interview. radiation. 29, 1187-1193. https://doi.org/10.1016/j.jvir.2018.03.029 (2018).
ULitner, JA nabanye. Ukubekezeleleka nokuphepha kwama-stents e-poly-l-lactide eustachian tube kusetshenziswa imodeli yesilwane se-chinchilla. J. Intern. Advanced. Author. 5, 290–293 (2009).
Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. I-poly-l-lactide Eustachian tube stent: Ukubekezeleleka, ukuphepha kanye nokumuncwa kabusha kumodeli yonogwaja. Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. I-poly-l-lactide Eustachian tube stent: Ukubekezeleleka, ukuphepha kanye nokumuncwa kabusha kumodeli yonogwaja. Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. Стент для евстахиевой трубы из поли-l-лактида: переносимость, безопасность и резорблиевой трубы Presti, P., Linstrom, CJ, Silverman, CA & Litner, J. I-Poly-l-lactide eustachian tube stent: ukubekezeleleka, ukuphepha, kanye nokumuncwa kabusha kumodeli yonogwaja. 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、ukuphepha nokumuncwa.Presti, P., Linstrom, SJ, Silverman, KA kanye noLittner, J. I-stent ye-Poly-1-lactide eustachian tube: ukubekezeleleka, ukuphepha, kanye nokumuncwa kwimodeli yonogwaja.J. Phakathi kwabo. Phambili. Umbhali. 7, 1-3 (2011).
UKim, Y. nabanye. Ukusebenziseka kobuchwepheshe kanye nokuhlaziywa kwe-histological kwama-stents ensimbi anganwebeka ebhaluni abekwe ku-porcine Eustachian tube. isitatimende. isayensi. 11, 1359 (2021).
UShen, JH nabanye. I-Tissue hyperplasia: ucwaningo lokuhlola ama-stents ambozwe nge-paclitaxel kumodeli we-canine urethra. I-Radiology 234, 438–444. https://doi.org/10.1148/radiol.2342040006 (2005).
UShen, JH nabanye. Umphumela we-dexamethasone-coated stent grafts empendulweni yezicubu: ucwaningo lokuhlola kumodeli ye-bronchial yenja. I-EURO. imisebe. 15, 1241–1249. https://doi.org/10.1007/s00330-004-2564-1 (2005).
UKim, E.Yu. IN-1233 I-Stent Yensimbi Embozwe Ivimbela I-Hyperplasia: Ucwaningo Lokuhlola Kumodeli Ye-Rabbit Esophagus. I-Radiology 267, 396–404. https://doi.org/10.1148/radiol.12120361 (2013).
UBunger, KM nabanye. Ama-Sirolimus-eluting poly-1-lactide stents abolakala kalula ukuze asetshenziswe emithanjeni yegazi engaphandle: ucwaningo lokuqala lwemithambo yegazi ye-porcine carotid. J. Surgical journal. ithangi lokugcina. 139, 77-82. https://doi.org/10.1016/j.jss.2006.07.035 (2007).