I-Groundbreaking TB kanye ne-DR-TB Diagnostic Solution nge-#Macro & Micro -Test!

Isikhali Esisha Sokuxilongwa Kwesifo Sofuba Nokutholwa Kokumelana Nezidakamizwa: Ukulandelanisa Okuhlosiwe Kwesizukulwane Esisha (tNGS) Kuhlanganiswe Nokufunda Ngomshini Kwesifo Sofuba I-hypersensitivity Diagnosis

Umbiko wezincwadi: I-CCa: imodeli yokuxilonga esekelwe ku-tNGS nokufunda komshini, elungele abantu abanesifo sofuba esinegciwane elincane kanye ne-meningitis ye-tuberculous.

Isihloko se-Thesis: Ukulandelana kwesizukulwane esilandelayo esihloselwe i-Tuberculous nokufunda komshini: isu lokuxilonga elizwela kakhulu lama-paucific pulmonary tubulars kanye ne-tubular meningitis.

Isikhathi: 《Clinica Chimica Acta》

IF:6.5

Idethi yokushicilelwa: Januwari 2024

Ihlanganiswe ne-University of Chinese Academy of Sciences kanye ne-Beijing Chest Hospital yase-Capital Medical University, i-Macro & Micro-Test isungule imodeli yokuxilongwa kwesifo sofuba esekelwe esizukulwaneni esisha sobuchwepheshe bokulandelana okuhlosiwe (tNGS) kanye nendlela yokufunda ngomshini, ehlinzeka ngokuphezulu kakhulu. ukuthola ukuzwela kwesifo sofuba esinamagciwane ambalwa kanye nemeningitis yofuba, kunikeze indlela entsha yokuxilongwa kwe-hypersensitivity yokuxilongwa emtholampilo kwezinhlobo ezimbili zesifo sofuba, futhi yasiza ekuxilongeni okunembile, ukutholwa kokumelana nezidakamizwa kanye nokwelashwa kwesifo sofuba.Ngasikhathi sinye, kutholakala ukuthi i-plasma cfDNA yesiguli ingasetshenziswa njengohlobo lwesampula olufanelekile lwesampula lomtholampilo ekuxilongweni kwe-TBM.

Kulolu cwaningo, amasampula e-plasma angama-227 kanye namasampula oketshezi lwe-cerebrospinal asetshenziselwa ukusungula amaqoqo amabili emitholampilo, lapho amasampula eqembu lokuxilonga elabhorethri asetshenziselwa ukusungula imodeli yokufunda ngomshini yokuxilongwa kwesifo sofuba, kanye namasampula eqembu lokuxilonga emtholampilo asetshenziselwa ukuqinisekisa imodeli yokuxilonga.Wonke amasampuli aqale akhonjwa iphuli yophenyo eqondiswe ngokukhethekile ye-Mycobacterium tuberculosis.Bese, ngokususelwe kudatha yokulandelana kwe-TB-tNGS, imodeli yesihlahla sesinqumo isetshenziselwa ukwenza ukuqinisekiswa okuphindwe izikhathi ezi-5 kumasethi okuqeqesha nokuqinisekisa omugqa wokuxilonga elabhorethri, kanye nomkhawulo wokuxilonga wamasampula e-plasma kanye namasampula oketshezi lwe-cerebrospinal ayatholakala.Umkhawulo otholiwe ulethwa kumasethi amabili okuhlola omugqa wokuxilongwa komtholampilo ukuze utholwe, futhi ukusebenza kokuxilonga komfundi kuhlolwa ijika le-ROC.Ekugcineni, kwatholakala imodeli yokuxilongwa kwesifo sofuba.

Umdwebo ongu-1 wohlelo lomklamo wocwaningo

Imiphumela: Ngokwemikhawulo ethile yesampula ye-CSF DNA (AUC = 0.974) kanye nesampula ye-plasma cfDNA (AUC = 0.908) enqunywe kulolu cwaningo, phakathi kwamasampuli angu-227, ukuzwela kwesampula ye-CSF kwakungu-97.01%, ukucaciswa kwakungu-95.65%, futhi ukuzwela kanye nokucaciswa kwesampula ye-plasma bekungama-82.61% kanye nama-86.36%.Ekuhlaziyweni kwamasampula abhanqiwe angama-44 e-plasma cfDNA kanye ne-cerebrospinal fluid DNA evela ezigulini ze-TBM, isu lokuxilonga lalolu cwaningo linokuqina okuphezulu okungu-90.91% (40/44) kuplasma cfDNA kanye ne-cerebrospinal fluid DNA, futhi ukuzwela kungu-95.45% (42/44).Ezinganeni ezinesifo sofuba samaphaphu, isu lokuxilonga lalolu cwaningo lizwela kakhulu kumasampula e-plasma kunemiphumela yokutholwa kwe-Xpert yamasampula ejusi yesisu ezigulini ezifanayo (28.57% VS 15.38%).

Umdwebo 2 Ukuhlaziywa kokusebenza kwemodeli yokuxilongwa kwesifo sofuba kumasampula abantu

Umdwebo 3 Imiphumela yokuxilonga yamasampuli abhanqiwe

Isiphetho: Indlela yokuxilonga ye-hypersensitive yesifo sofuba yasungulwa kulolu cwaningo, enganikeza ithuluzi lokuxilonga elinokuzwela okuphezulu kakhulu kokutholwa kweziguli zomtholampilo ezine-oligobacillary tuberculosis (isiko elibi).Ukutholwa kwesifo sofuba esibucayi esisuselwe ku-plasma cfDNA kungase kube uhlobo olufanele lwesampula lokuxilongwa kwesifo sofuba esisebenzayo kanye ne-meningitis (amasampula e-plasma kulula ukuqoqa kunoketshezi lwe-cerebrospinal ezigulini okusolwa ukuthi zinesifo sofuba ebuchosheni).

Isixhumanisi sokuqala: https://www.sciencedirect.com/science/article/pii/s0009898123004990?nge-%3Dihub

Ukwethulwa kafushane kwemikhiqizo yochungechunge lwe-Macro & Micro-Test yokuthola isifo sofuba

Ngenxa yesimo sesampula esiyinkimbinkimbi seziguli ezinesifo sofuba kanye nezidingo ezihlukahlukene, i-Macro & Micro-Test inikeza isethi ephelele yezixazululo ze-NGS zokukhipha uketshezi kumasampula esikhwehlela, ukwakhiwa komtapo wezincwadi we-Qualcomm nokulandelana kwawo, kanye nokuhlaziywa kwedatha.Imikhiqizo ihlanganisa ukuxilongwa okusheshayo kweziguli ezinesifo sofuba, ukutholwa kokumelana nezidakamizwa kwesifo sofuba, ukuthayipha kwe-mycobacterium tuberculosis kanye ne-NTM, ukuxilongwa kwe-hypersensitivity yesifo sofuba esingenalo amagciwane kanye nabantu abanesifo sofuba, njll.

Amakhithi okuthola isifo sofuba kanye ne-mycobacteria:

Into No igama lomkhiqizo okuqukethwe kokuhlola umkhiqizo uhlobo lwesampula imodeli esebenzayo
I-HWTS-3012 I-ejenti yokukhishwa kwesampula Isetshenziswe ekwelapheni ukucwiliswa kwesikhwehlela, ithole inombolo yerekhodi yezinga lokuqala, i-Sutong Machinery Equipment 20230047. isikhwehlela
HWTS-NGS-P00021 Ikhithi yokutholwa kobuningi be-Qualcomm ye-hypersensitive tuberculosis (indlela yokuthwebula i-probe) I-non-invasive (i-liquid biopsy) ukutholwa kwe-hypersensitivity ye-bacteria-negative pulmonary tuberculosis kanye namaqhuqhuva obuchopho;Amasampula abantu okusolwa ukuthi bangenwe isifo sofuba noma i-mycobacteria engesona isifo sofuba ahlaziywa nge-metagenomics elandelanayo ejulile, kanye nolwazi lokutholwa kokuthi i-mycobacteria yesifo sofuba noma engesona isifo sofuba yayingenwe yini kanye nolwazi lokuqala oluyinhloko lokumelana nomuthi lwe-mycobacterium tuberculosis. zahlinzekwa. Igazi le-peripheral, i-alveolar lavage fluid, i-hydrothorax ne-ascites, isampula yokubhoboza okugxilile, uketshezi lwe-cerebrospinal. Isizukulwane sesibili
I-HWTS-NGS-T001 Ukuthayipha kwe-Mycobacterium kanye nekhithi yokuthola ukumelana nezidakamizwa (indlela yokulandelanisa i-multiplex amplification) Ukuhlolwa kokuthayipha kwe-Mycobacterium, okuhlanganisa i-MTBC ne-187 NTM;Ukutholwa kokungazweli emishanguzweni yesifo sofuba i-Mycobacterium kuhlanganisa imithi eyi-13 kanye nezindawo ezingu-16 zokuguqula izakhi zofuzo ezimelana nezidakamizwa. Isikhwehlela, uketshezi lwe-alveolar lavage, i-hydrothorax nama-ascites, isampula yokubhoboza okugxilile, uketshezi lwe-cerebrospinal. Ipulatifomu yesizukulwane sesibili/sesithathu

Okuvelele: HWTS-NGS-T001 Mycobacterium ukuthayipha kanye nekhithi yokuthola ukumelana nezidakamizwa (indlela yokukhulisa i-multiplex)

Isingeniso somkhiqizo

Umkhiqizo usekelwe emithini eyinhloko yomugqa wokuqala nowesibili echazwe eziqondisweni zokwelashwa kwe-TB ye-WHO, ama-macrolides nama-aminoglycosides avame ukusetshenziswa eziqondisweni zokwelashwa ze-NTM, futhi iziza zokumelana nemishanguzo zihlanganisa zonke iqoqo lezindawo ezihlobene nokumelana nomuthi Ikhathalogi ye-WHO Mycobacterium tuberculosis complex mutation catalogue, kanye nezinye izakhi zofuzo ezibikiwe ezimelana nezidakamizwa kanye nezindawo eziguqukayo ngokophenyo kanye nezibalo zezincwadi ezinamagoli aphezulu ekhaya naphesheya.

Ukuhlonza ukuthayipha kusekelwe ezinhlotsheni ze-NTM ezifingqiwe kuzinkombandlela ze-NTM ezishicilelwe yi-Chinese Journal of Tuberculosis and Respiratory Diseases kanye nokuvumelana kochwepheshe.Iziqalo zokuthayipha eziklanyelwe zingakhulisa, zilandelelane futhi zichaze izinhlobo ezingaphezu kuka-190 ze-NTM.

Ngobuchwepheshe obuhlosiwe bokukhulisa i-multiplex PCR, izakhi zofuzo ze-Mycobacterium ezimelana nomuthi zakhuliswa nge-multiplex PCR, futhi kwatholakala inhlanganisela ye-amplicon yezakhi zofuzo eziqondiwe okufanele zitholwe.Imikhiqizo ekhulisiwe ingakhiwa ibe imitapo yolwazi elandelanayo yesizukulwane sesibili noma yesizukulwane sesithathu, futhi zonke izinkundla zesizukulwane sesibili nesesithathu zingase zibe ngaphansi kokulandelana okujulile ukuze kutholwe ulwazi lokulandelana kwezakhi zofuzo eziqondiwe.Ngokuqhathanisa nezinguquko ezaziwayo eziqukethwe kusizindalwazi sereferensi esakhelwe ngaphakathi (okuhlanganisa ikhathalogi ye-WHO Mycobacterium tuberculosis complex retation kanye nobudlelwano bayo nokumelana nomuthi), ukuguqulwa okuhlobene nokungazweli emthini noma ukuba sengozini kwemithi elwa nesifo sofuba kwanqunywa.Kuhlanganiswe nesixazululo sokwelashwa kwesampula sesikhwehlela esizivulayo se-Macro & Micro-Test, inkinga yokungasebenzi kahle kwe-nucleic acid yokukhulisa i-nucleic acid yamasampula esikhwehlela sasemtholampilo (iphakeme ngokuphindwe kashumi kunaleyo yezindlela zendabuko) yaxazululwa, ukuze kutholakale ukulandelana kokumelana nomuthi. isetshenziswe ngokuqondile kumasampula esikhwehlela sasemtholampilo.

Ibanga lokuthola umkhiqizo

34izakhi zofuzo ezihlobene nezidakamizwa ze18izidakamizwa ezilwa nesifo sofuba kanye6Kutholwe izidakamizwa ze-NTM, zimboza297izindawo ezimelana nezidakamizwa;Izinhlobo eziyishumi ze-Mycobacterium tuberculosis kanye nangaphezulu190izinhlobo ze-NTM zitholiwe.

Ithebula 1: Ulwazi Lwezidakamizwa Ezingu-18+6 +190+NTM

Inzuzo yomkhiqizo

Ukuguquguquka okuqinile komtholampilo: amasampula esikhwehlela angatholwa ngokuqondile nge-agent yokuzikhukhumeza ngaphandle kwesiko.

Umsebenzi wokuhlola ulula: umzuliswano wokuqala wokusebenza kwe-amplification ulula, futhi ukwakhiwa komtapo wezincwadi kuqedwa emahoreni ama-3, okuthuthukisa ukusebenza kahle komsebenzi.

Ukuthayipha okuphelele nokumelana nomuthi: ukumboza amasayithi okuthayipha nawokumelana nezidakamizwa ze-MTB ne-NTM, okungamaphuzu abalulekile okukhathazeka ngomtholampilo, ukuthayipha okunembile nokutholwa kokumelana nezidakamizwa, ukusekela isofthiwe yokuhlaziya ezimele, kanye nokukhiqiza imibiko yokuhlaziya ngokuchofoza kanye.

Ukuhambisana: ukuhambisana komkhiqizo, ukuzivumelanisa nezinkundla ze-ILM ezijwayelekile kanye ne-MGI/ONT.

Ukucaciswa komkhiqizo

Ikhodi yomkhiqizo igama lomkhiqizo Inkundla yokutholwa imininingwane
I-HWTS-NGS-T001 Ukuthayipha kwe-Mycobacterium kanye nekhithi yokuthola ukumelana nezidakamizwa (indlela yokukhulisa i-multiplex) ONT, Illumina, MGI, Salus pro 16/96rxn

Isikhathi sokuthumela: Jan-23-2024