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The emergence of SARS-CoV-2 variants that threaten the efficacy of existing vaccines and therapeutic antibodies underscores the urgent need for new antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells of COVID-19 patients. The three most potent antibodies targeted distinct regions of the RBD, and all three neutralized the SARS-CoV-2 variants B.1.1.7 and B.1.351. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD, competes with the ACE2 receptor, and has limited contact with key variant residues K417, E484 and N501. We designed bispecific antibodies by combining non-overlapping specificities and identified five ultrapotent bispecific antibodies that inhibit authentic SARS-CoV-2 infection at concentrations of <1 ng/mL. Through a novel mode of action three bispecific antibodies cross-linked adjacent spike proteins using dual NTD/RBD specificities. One bispecific antibody was >100-fold more potent than a cocktail of its parent monoclonals in vitro and prevented clinical disease in a hamster model at a 2.5 mg/kg dose. Notably, six of nine bispecific antibodies neutralized B.1.1.7, B.1.351 and the wild-type virus with comparable potency, despite partial or complete loss of activity of at least one parent monoclonal antibody against B.1.351. Furthermore, a bispecific antibody that neutralized B.1.351 protected against SARS-CoV-2 expressing the crucial E484K mutation in the hamster model. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.
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Objective This study was to evaluate the relative applicability of serum cystatin C(Cys C)-based formulas and serum creatinine-based formulas for renal glomerular filtration rate(GFR) of Chinese children with chronic kidney disease(CKD).Methods Six hundred and nine Chinese CKD patients of less than 18 years old were enrolled from January 2011 to October 2016 in Shengjing Hospital of China Medical University.The value for estimated GFR (eGFR) was derived from using the 11 formulas,and 99mTc-DTPA renal dynamic imaging was the golden standard of standard GFR(sGFR).SPSS 22.0 statistical software was used to compare the accuracy of each assessment formula and the correlation between GFR markers(Cys C, β2-MG) and sGFR.Results A total of 609 children were enrolled,including 332 patients in CKD stage 1 (211 males and 121 females),165 patients in CKD stage 2(99 males and 66 females),70 patients in CKD stage 3(43 males and 27 females),22 patients in CKD stage 4(13 males and 9 females),and 20 patients in CKD stage 5(16 males and 4 females).All of the formulas either overestimate or underestimate GFR in chil-dren with CKD. In contrast with other formulas,CKD-EPI formula and Filler formula performed better regardless of gender and age difference.Serum β2-MG and serum Cys C all showed a negative relationship with sGFR(respectively r= -0.478 and r= -0.585,P<0.01).Conclusion CKD-EPI formula and Filler formula provide the better approximation to sGFR than other formulas in Chinese children with CKD.Howev-er,we need to try our best to enroll more patients to develop a more accurate GFR estimation formula in Chinese children.
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Objective To work out a flowchart for putting normal saline column by gravity drip via Groshong PICCs to guide intracavitary ECG and investigate the effect. Methods We developed the flowchart and trained the nurses to use it. Then the flowchart was used in catheteration of Groshong PICC to guide intracavitary ECG for 30 patients. Results The normal target rate was 93.3%(28/30) and the optimal tip target rate was 90.0%(27/30). The score on the flowchart by the nurses was (4.8 ± 0.4), indicating they were satisfied with it. Conclusion The flowchart for pushing normal saline column with gravity drip method via Groshong PICCs to guide intracavitary ECG provides an operational standard, enhancing the operational quality.
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s of catheter,and extend the service life of a catheter.
