Kev Tshawb Fawb Txog Kev Tiv Thaiv Kab Mob Nephritis Hauv 2023 Ⅱ

Membranous nephropathy (MN)

(1) MN neoantigens

Thaum lub Tsib Hlis 2023, "Kidney International" tau tshaj tawm Mayo Clinic qhov kev pom zoo ntawm MN, hais txog kev faib ob theem ntawm MN. Tsawg kawg yog 14 MN lub hom phiaj antigens tau pom, suav txog 80% txog 90% ntawm MN kis. Ntau tus MNs cuam tshuam nrog cov hom phiaj tshiab no muaj cov tshuaj kho mob tshwj xeeb thiab kab mob phenotypes, uas cuam tshuam cov txheej txheem kev faib tawm ntawm thawj thiab theem nrab MNs. Nws tsis yog feem ntau ua tau los txheeb xyuas tag nrho cov hom phiaj antigens nyob rau theem no, tab sis lub rooj sib tham tau pom zoo tias lub sijhawm tshiab ntawm antigen-based MN kev faib tawm tau nkag mus. Hauv thawj kauj ruam, qhov ua tau, lub hom phiaj antigen yog txiav txim siab los ntawm staining lub raum biopsy cov ntaub so ntswg thiab / lossis loj spectrometry ua ke nrog serology, immunofluorescence, los yog immunohistochemistry. Qhov thib ob yog mus nrhiav cov kab mob hauv qab. Peb lub hom phiaj antigens saum toj kawg nkaus ntawm MN yog antiphospholipase A2 receptor (PLA2R) (55%), NELL1 (10%), thiab EXT1/2 (7%). Yog li, qhov kev pom zoo pom zoo tias cov neeg mob MN yuav tsum tau kuaj PLA2R thiab NELL1 ua ntej, thiab yog tias tsis zoo, lwm cov hom phiaj antigens yuav tsum tau kuaj ntxiv. Thaum kawg, ua ke nrog tus neeg mob lub pathology (lub raum pathological yam ntxwv, lub hom phiaj antigens txheeb xyuas los ntawm immunofluorescence, immunohistochemistry lossis huab hwm coj spectrometry), serology (MN autoantibodies, serological hloov hauv lwm yam kab mob autoimmune, serological hloov hauv kab mob), thiab cov ntaub ntawv pej xeem thiab keeb kwm tshuaj, kev kho mob. manifestations (comorbidities, imaging manifestations), los txiav txim qhov kev kuaj zaum kawg thiab kev faib tawm ntawm MN.

Nyem rau Cistanche rau mob raum

Thaum lub Tsib Hlis 2023, "Kidney International" tau tshaj tawm cov kev tshawb fawb ntawm Casa li al. Pab neeg no pom 7 lub cev tiv thaiv kab mob tso rau hauv glomeruli ntawm PLA2R, THSD7A, exostosin, thiab NELL1-cov neeg mob tsis zoo MN thiab cov neeg mob SLE membranous lesions. Ntau cov neoantigens muaj xws li FCN3, CD206, EEA1, SEZ6L2, NPR3, MST1 thiab VASN. Qhov saum toj no xya antigens yog tag nrho qhia los ntawm podocytes. Ib tsab xov xwm tshuaj xyuas nyob rau tib lub sijhawm tau taw qhia tias txawm hais tias qhov kev tshawb pom ntawm qee cov antigens tshiab tsis pom cov tshuaj tiv thaiv kab mob sib xws hauv kev ncig, thiab kev sib raug zoo ntawm antigen tshwj xeeb thiab cov tshuaj phenotypes yog qhov nyuaj los piav qhia hauv ob peb kis, txoj kev tshawb fawb tsim nyog. kev tshuaj xyuas.

Thaum Lub Yim Hli 2023, "Kidney International" tau tshaj tawm txoj kev tshawb fawb los ntawm Sethi thiab lwm tus, uas pom tias cov protein convertase subtilisin 6 protein (PCSK6) tuaj yeem yog lub hom phiaj antigen ntawm nonsteroidal anti-inflammatory tshuaj (NSAIDs) ntsig txog MN. Cov kws tshawb fawb tau ua glomerular laser microdissection thiab kev tsom xam loj ntawm 250 PLA2R-negative MN cov neeg mob. PCSK6 tau kuaj pom nyob rau hauv 5 tus neeg mob, thiab 8 PCSK6-cov neeg mob tau pom zoo nyob rau hauv pawg validation. Tag nrho 13 tus neeg mob tsis zoo rau lwm tus paub MN antigens. IgG elution thiab Western Blot tsom xam ntawm eluates los ntawm cov ntaub so ntswg khov kho tau txheeb xyuas qhov muaj cov tshuaj tiv thaiv PSCK6 hauv cov ntshav. Immunohistochemistry tau nthuav tawm ntxiv granular deposition ntawm PCSK6 protein raws GBM, thiab subepithelial electron-dense deposition tau pom nyob rau hauv electron microscopy. Kaum ntawm 13 tus neeg mob tau muaj keeb kwm ntawm kev siv NSAID hnyav. Yog li, cov kws tshawb fawb ntseeg tias PCSK6 yuav yog lub hom phiaj tshiab antigen cuam tshuam nrog kev siv NSAIDs hauv MN. Yog tias PCSK6 raug kuaj pom hauv immunohistochemistry, immunofluorescence, lossis kev tshawb fawb loj ntawm MN, nws yuav tsum tau xav txog tag nrho cov kev sib raug zoo ntawm MN thiab NSAIDs. kev sib raug zoo.

(2) Novel anti-CD20 monoclonal antibody rau kev kho mob ntawm thawj MN (PMN)

Thaum lub Cuaj Hlis 2023, American Journal of Nephrology tau luam tawm txoj kev tshawb fawb rov qab los ntsuas seb ofatumumab tuaj yeem siv los kho MN cov neeg mob uas tiv taus lossis tsis kam rau rituximab. Ofatumumab yog tib neeg thib ob tiam anti-CD20 antibody. Nyob rau hauv txoj kev tshawb no, 7 cov neeg mob uas intolerant rau rituximab tag nrho tau pom tag nrho los yog ib feem ntawm kev kho mob, thaum 10 cov neeg mob tau resistant rau rituximab. Peb ntawm cov neeg mob uas tsis muaj tshuaj tiv thaiv tau pom tias ua tiav lossis ib nrab kev kho mob. Txhua tus neeg mob nrog PLA2R-txuas nrog MN tau txo cov tshuaj tiv thaiv kab mob. Cov kev tshawb fawb tau pom tias ofatumumab tuaj yeem txo qis proteinuria thiab nce qib albumin thiab IgG hauv MN cov neeg mob. Ofatumumab tuaj yeem yog qhov kev xaiv pheej hmoo rau MN cov neeg mob uas tsis kam ua rau rituximab.

MIL62 yog ib qho tshiab glycoengineered hom II anti-CD20 antibody thiab thawj lub tsev thib peb tiam CD20 antibody. Piv nrog rau thawj tiam anti-CD20 antibody rituximab, nws qhia tau hais tias muaj zog ADCC kev ua ub no thiab clearance nyob rau hauv lub cev tsis muaj peev xwm mus qhib B hlwb. Thaum Lub Rau Hli 2023, theem II cov ntaub ntawv kho mob ntawm MIL62 hauv kev kho mob ntawm MN tau tshaj tawm nyob rau hauv daim ntawv qhia qhov ncauj thaum lub sij hawm 60th European raum Association Congress. Tag nrho ntawm 86 MN cov neeg mob uas muaj proteinuria Ntau dua lossis sib npaug li 3.5 g / d tau suav nrog hauv txoj kev tshawb no, thiab 60 tus neeg mob tau txais tsawg kawg 12 lub lis piam tom qab, 24/40 (60%) cov neeg mob hauv lub MIL62 pawg thiab 7/20 (35%) cov neeg mob hauv pawg cyclosporine tau ua tiav lossis ib nrab cov lus teb; 26 tus neeg mob tau txais tsawg kawg 24 lub lis piam tom qab. Ntawm lawv, 11/18 cov neeg mob (61.1%) hauv pawg MIL62 thiab 2/8 (25%) cov neeg mob hauv pawg cyclosporine tau txais cov lus teb ib nrab. Txoj kev tshawb no ntseeg tias MIL62 muaj qhov pib ua sai dua li rituximab, nrog 62.9% (22/35) ntawm cov neeg mob tau ua tiav lossis ib nrab tso tawm ntawm 24 lub lis piam, thaum lub hli 6- cov lus teb rau rituximab tau tshaj tawm hauv Kev Tshawb Fawb Kev Tshawb Fawb. tus nqi yog 35% (23/65). Cov xwm txheej tshwm sim ntawm kev kho mob ntsig txog cov xwm txheej tsis zoo hauv MIL62 600 mg pawg, MIL62 1000 mg pawg, thiab pawg cyclosporine yog 73.3%, 77.1%, thiab 88.5% raws li, thiab tsis muaj kev kho mob ntsig txog kev tuag. tshwm sim. Cov ntaub ntawv qhia tau hais tias MIL62 muaj qhov pom tseeb hauv kev kho mob zoo tshaj li thawj tiam CD20 antibody rituximab thiab calcineurin inhibitors hais txog kev nyab xeeb, kev ua tau zoo, kev tiv thaiv lub raum ua haujlwm, thiab ua raws.

(3) Anti-CD38 monoclonal antibody (Felzartamab, Felzartamab) rau kev kho mob PMN

Thaum Lub Kaum Ib Hlis 2023, cov txiaj ntsig ntawm M-PLACE txoj kev tshawb fawb tau tshaj tawm hauv tsab ntawv ceeb toom ntawm qhov ncauj ntawm American Society of Nephrology Lub Rooj Sib Tham Txhua Xyoo. Qhov no yog Phase Ib/IIa pov thawj-ntawm-lub tswv yim, qhib-daim ntawv sau npe, kev tshawb fawb thoob ntiaj teb tsim los ntsuas kev nyab xeeb thiab kev ua tau zoo ntawm felzartamab hauv cov neeg laus nrog PLA2R antibody (aPLA2R)-zoo PMN. Txoj kev tshawb no suav nrog ob pawg ntawm aPLA2R-zoo PMN cov neeg mob, uas yog cov neeg mob tshiab los yog rov qab los (C1, 18 tus neeg mob) thiab cov neeg mob refractory (C2, 13 kis). Cov neeg mob tau txais cuaj infusions ntawm Felzartamab tshaj li 5 lub hlis, nrog rau tag nrho lub sij hawm soj ntsuam ntawm 12 lub hlis. Cov txiaj ntsig ntawm kev tshawb fawb tau pom tias ntawm 31 tus neeg mob, 23 (74%) tau ua tiav cov lus teb tiv thaiv kab mob uas txo qis aPLA2R ntau dua 50%, thiab 8 (26%) ntawm lawv tau ua tiav kev tiv thaiv kab mob. Tsis pub dhau 12 lub hlis, 47% ntawm cov neeg mob hauv C1 caj npab thiab 18% ntawm cov neeg mob hauv C2 caj npab tau ua tiav ib feem ntawm kev tshem tawm cov proteinuria, tab sis tsis muaj cov neeg mob ua tiav kev tshem tawm. Cov tshuaj tiv thaiv infusion (29.0%) yog cov xwm txheej tshwm sim feem ntau cuam tshuam txog tshuaj.

Cistanche kho mob raum li cas?

Cistanche yog cov tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho ntau yam mob, suav nrograumkab mob. Nws yog muab los ntawm qhuav stems ntawmCistanchedeserticola, ib tsob nroj nyob rau hauv cov suab puam ntawm Tuam Tshoj thiab Mongolia. Lub ntsiab active Cheebtsam ntawm cistanche yogphenylethanoidglycosides, echinacoside cov tshuaj, thiabacteoside, uas tau pom tias muaj txiaj ntsig zoo rau lub raum kev noj qab haus huv.

Kab mob raum, tseem hu ua kab mob raum, hais txog ib yam mob uas lub raum ua haujlwm tsis zoo. Qhov no tuaj yeem ua rau muaj cov khoom pov tseg thiab cov co toxins hauv lub cev, ua rau muaj ntau yam tsos mob thiab teeb meem. Cistanche tuaj yeem pab kho mob raum ase los ntawm ntau lub tswv yim.

Ua ntej, cistanche tau pom tias muaj cov nyhuv diuretic, txhais tau tias nws tuaj yeem ua rau cov zis ntau ntxiv thiab pab tshem tawm cov khoom pov tseg ntawm lub cev. Qhov no tuaj yeem pab txo lub nra ntawm lub raum thiab tiv thaiv kev tsim cov co toxins. Los ntawm kev txhawb nqa diuresis, cistanche kuj tseem tuaj yeem pab txo qis ntshav siab, ib qho teeb meem ntawm cov kab mob raum.

Ntxiv mus, cistanche tau pom tias muaj cov teebmeem antioxidant. Kev ntxhov siab oxidative, tshwm sim los ntawm qhov tsis sib xws ntawm kev tsim cov dawb radicals thiab lub cev tiv thaiv antioxidant, ua lub luag haujlwm tseem ceeb hauv kev mob raum. ies pab neutralize dawb radicals thiab txo Oxidative kev nyuaj siab, yog li tiv thaiv lub raum los ntawm kev puas tsuaj. Cov phenylethanoid glycosides pom hauv cistanche tau tshwj xeeb hauv kev tshem tawm cov dawb radicals thiab inhibiting lipid peroxidation.

Tsis tas li ntawd, cistanche tau pom tias muaj cov nyhuv anti-inflammatory. Kev mob yog lwm yam tseem ceeb hauv kev loj hlob thiab kev loj hlob ntawm cov kab mob raum. Cistanche's anti-inflammatory zog pab txo cov zus tau tej cov pro-inflammatory cytokines thiab inhibit qhov ua kom o yuav tsum tau txoj kev, yog li alleviating o nyob rau hauv lub raum.

Tsis tas li ntawd, cistanche tau pom tias muaj cov teebmeem immunomodulatory. Hauv kab mob raum, lub cev tiv thaiv kab mob tuaj yeem ua rau tsis zoo, ua rau muaj kev mob ntau dhau thiab cov ntaub so ntswg puas. Cistanche pab tswj lub cev tiv thaiv kab mob los ntawm kev hloov kho kev tsim khoom thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob, xws li T hlwb thiab macrophages. Txoj cai tiv thaiv kab mob no pab txo qhov mob thiab tiv thaiv kev puas tsuaj ntxiv rau lub raum.

Ntxiv mus, cistanche tau pom los txhim kho lub raum kev ua haujlwm los ntawm kev txhawb nqa kev tsim kho ntawm lub raum hlab nrog cov hlwb. Lub raum tubular epithelial hlwb ua lub luag haujlwm tseem ceeb hauv kev pom thiab rov nqus cov khoom pov tseg thiab electrolytes. Hauv kab mob raum, cov hlwb no tuaj yeem raug puas tsuaj, ua rau lub raum ua haujlwm puas. Cistanche lub peev xwm los txhawb kev tsim kho ntawm cov hlwb no pab kho lub raum kom zoo thiab txhim kho lub raum tag nrho.

Ntxiv nrog rau cov kev cuam tshuam ncaj qha rau lub raum, cistanche tau pom tias muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev hauv lub cev. Txoj hauv kev zoo rau kev noj qab haus huv no tseem ceeb tshwj xeeb hauv cov kab mob raum, vim tias tus mob feem ntau cuam tshuam rau ntau lub cev thiab lub cev. che tau pom tias muaj kev tiv thaiv rau lub siab, lub plawv, thiab cov hlab ntsha, uas feem ntau cuam tshuam los ntawm kab mob raum. Los ntawm kev txhawb nqa kev noj qab haus huv ntawm cov kabmob no, cistanche pab txhim kho lub raum tag nrho thiab tiv thaiv kev mob ntxiv.

Hauv kev xaus, cistanche yog cov tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho mob raum. Nws cov active Cheebtsam muaj diuretic, antioxidant, anti-inflammatory, immunomodulatory, thiab regenerative teebmeem, uas pab txhim kho lub raum ua haujlwm thiab tiv thaiv ob lub raum los ntawm kev puas tsuaj ntxiv. , cistanche muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev, ua rau nws txoj hauv kev zoo rau kev kho mob raum.