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@#Objective To compare the immunogenicity of varicella-zoster virus(VZV)Oka-7S strain and VZV Oka strain.Methods Female BALB/c mice were subcutaneously immunized with VZV Oka-7S and Oka strains at high,medium and low doses(1 000,250 and 62.5 PFU/dose)for total two doses at an interval of 14 d,separately,with 12 mice in each group.The VZV-specific humoral immunity was evaluated based on fluorescent antibody to membrane antigen assay(FAMA),and the VZV-specific cellular immunity was evaluated by enzyme-linked immunospot assay(ELISPOT).Results Both VZV Oka-7S and VZV Oka strains induced specific humoral and cellular immune responses,and showed considerable immune effects;The level of anti-VZV specific IgG in serum of mice in Oka-7S-2.2 group increased significantly with the increase of immunization times and immunization doses.Conclusion The VZV Oka-7S strain had comparative immunogenicity with VZV Oka strain.
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@#Objective To select and optimize the process parameters of SARS-CoV-2 F61 affinity chromatography by the screening and optimization experiment of Design of Experiment(DoE),in order to obtain the optimal process conditions.Methods Eight process parameters that may affect the experimental response results in affinity chromatography were selected and their level ranges were determined.DoE screening test was used to perform 8 factor 2 level screening tests on the selected process parameters.The response values were detected and the mathematical model was fitted by statistical software.Three key process parameters significantly affecting the key quality attributes were obtained by Pareto diagram analysis(P < 0.05).Then DoE response surface method(RSM)was selected to optimize the key process parameters.First,the full factorial experiment design was completed,the response results were detected to fit the mathematical model,and the bending term P value was analyzed to judge the range of significant factors in the optimal range(bending P < 0.05),then according to the sequential complement of the central composite face-centered design(CCF)experiment,through the detection of the response results to fit the response surface model,the range of optimal conditions was obtained,and the stability of the optimal parameters was finally verified by repeated experiments.Results In the screening experiment,it was found that the significant factors affecting F61 in the affinity chromatography stage were elution buffer pH,elution buffer salt concentration,leaching buffer salt concentration and equilibrium buffer salt concentration.The optimal conditions of key process parameters in affinity chromatography were obtained by CCF.When the pH of elution buffer was 3.2,the elution buffer salt concentration was 0.07 mol/L NaCl,and the leaching buffer salt concentration was 0.31 mol/L NaCl,the yield of F61 reached 95.25%,the residual amount of host cell protein(HCP)was 97.33 ppm,and the monomer purity of the sample was98.51% at the affinity chromatography stage.Conclusion Different types of DoE methods were used to screen and optimize the process parameters of F61 affinity chromatography stage,and the optimal process conditions were obtained,which lays a foundation for the esta-blishment of F61 purification process.
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The World Health Organization has declared that the outbreak of coronavirus disease 2019(COVID-19) is a global pandemic. As mutations occurred in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the global epidemic still needs further concern. Worryingly, the effectiveness and neutralizing activity of existing antibodies and vaccines against SARS-CoV-2 variants is declining. There is an urgent need to find an effective antiviral medication with broad-spectrum inhibitory effects on novel coronavirus mutant strains against the SARS-CoV-2 infection. Neutralizing antibodies play an important role in the prevention and treatment of COVID-19. The interaction of spike-receptor-binding domain (Spike-RBD) of SARS-CoV-2 and human angiotensin-converting enzyme 2 (ACE2) is the first and critical step of SARS-CoV-2 infection. Hence, the SARS-CoV-2 Spike-RBD is a hot target for neutralizing antibodies development. Evusheld, the combination of Tixagevimab and Cilgavimab monoclonal antibodies (mAbs) targeting Spike-RBD exhibits neutralizing activity against BA.2.12.1, BA.4 and BA.5, which could be used as pre-exposure prophylaxis against SARS-CoV-2 infection. The nucleocapsid (N) protein is a conservative and high-abundance structural protein of SARS-CoV-2. The nCoV396 monoclonal antibody, isolated from the blood of convalescent COVID-19 patients against the N protein of SARS-CoV-2. This mAb not only showed neutralizing activity but also inhibits hyperactivation of complement and lung injury induced by N protein. The mAb 3E8 targeting ACE2 showed broadly neutralizing activity against SARS-CoV-2 and D614G, B.1.1.7, B.1.351, B.1.617.1 and P.1 variants in vitro and in vivo, but did not impact the biological activity of ACE2. Compared with neutralizing antibodies, small molecule inhibitors have several advantages, such as broad-spectrum inhibitory effect, low cost, and simple administration methods. Several small-molecule inhibitors disrupt viral binding by targeting the ACE2 and N-terminal domain (NTD) of SARS-CoV-2 spike protein. Known drugs such as chloroquine and hydroxychloroquine could also block the infection of SARS-CoV-2 by interacting with residue Lys353 in the peptidase domain of ACE2. The transmembrane protease serine 2 (TMPRSS2) inhibitors Camostat mesylate and Proxalutamide inhibit infection by blocking TMPRSS2 mediates viral membrane fusion. The main protease inhibitor Paxlovid and RNA-dependent RNA polymerase inhibitor Azvudine have been approved for treatment of COVID-19 patients. This review summarizes the current research status of neutralizing antibodies and small molecule inhibitors and prospects for their application. We expect to provide more valuable information for further studies in this field.
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ObjectiveRecent successful restoration of the native conformation and function of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs) demonstrates that the era of molecular conformational engineering is dawning. Basically, molecular conformational engineering aims to precisely tune flexible non-functional molecules into special conformations to carry out novel functions, in the same way as protein folding. In order to explore the general applicability of molecular conformational engineering, as well as to reveal the mechanism of protein structure-function relationship, the objective of this work is to restore the native conformation and function of the CDRs of an antibody on platinum nanoparticles (PtNPs). MethodsThe CDR fragment of the anti-lysozyme antibody cAB-lys3, which has no stable conformation or function in free state, was conjugated onto the surface of PtNPs through two Pt-S bonds. The original antigen-recognizing function of the CDR restored on PtNPs was assessed by the specific inhibition of the enzymatic activity of lysozyme by the PtNP-CDR conjugates. ResultsAfter optimization of the peptide density on the surface of PtNPs and modification of PtNPs with polyethylene glycol (PEG), the resulted PtNP-based hybrid artificial antibody (PtNP-10PEG-30P1), dubbed Platinumbody, could bind specifically to lysozyme and significantly inhibit the activity of lysozyme. ConclusionThis is the first time that the fragment of a protein could refold on PtNPs. Together with the previous Goldbody and Silverbody, current work demonstrates that artificial proteins could be generally created by restoration of the native conformation of natural proteins fragments on NPs.
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Approximately 50% of patients with non-small-cell lung cancer (NSCLC) are diagnosed at advanced stages and face a challenging prognosis despite the integration of targeted therapies, immunotherapy, and systemic chemotherapy into current standard care. A key factor in this context is trophoblast cell-surface antigen 2 (TROP2), which is widely expressed in NSCLC and strongly associated with poor patient outcomes. This article examines the latest developments in the application of datopotamab deruxtecan (Dato-DXd, DS-1062), a novel antibody-drug conjugate targeting TROP2, in the treatment of NSCLC. It provides a detailed assessment of Dato-DXd’s technical design, evaluates its efficacy by using recent clinical trial data, and discusses its safety profile.
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Currently, breast cancer is a common malignancy in female, and previous guidelines recommended that one of the key biomarkers for breast cancer, human epidermal growth factor receptor 2 (HER2), is classified as either positive or negative to guide clinicians’ treatment decisions. While nearly half of breast cancer patients have low HER2 expression (IHC expression is 1+ or 2+ and ISH detection is negative), such patients are insensitive to traditional anti-HER2 targeted therapy. However, novel antibody-drug conjugates (ADCs) provide new targeted therapy options for breast cancer patients with low HER2 expression, challenging the traditional binary concept and arousing research enthusiasm. In the latest ASCO/CAP guidelines for HER2 detection in breast cancer, HER2-low breast cancer has been included as a clinical treatment subgroup. This article will review the definition of HER2-low breast cancer, the progress of drug therapy such as ADC, and the current challenges faced by this subgroup.
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Since the approval of gemtuzumab ozogamicin, an antibody–drug conjugate (ADC) targeting CD33 in 2000, 13 ADC drugs have been approved by the FDA. Although these drugs have clearly improved the survival of patients with various types of advanced cancers, their significant toxicity has compromised their therapeutic benefits. The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities, where the payload drug is a determining factor. Antibody and linker may also affect the degree of toxicity. Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency, but treatment-related adverse reactions also increase accordingly. This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies, including but not limited to optimizing linker molecules, upgrading antibody design, and changing drug administration strategies, to improve the overall safety profile of ADC drugs.
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@#Objective To express and purify the protein of variable region of adeno-associated virus 9(AAV9) capsid in prokaryotic cells,and prepare rabbit polyclonal antibody against it.Methods DNA sequence encoding variable region of AAV9 capsid protein was designed,synthesized and inserted into prokaryotic expression vector pET-30a. The obtained plasmid pET-30a-AAV-VR was transformed to E.coli BL21(DE3),induced by IPTG to express the multivalent antigenic peptide and purified by Ni-NTA resin under denaturation conditions. Male Japanese large-eared white rabbits were immunized with the AAV9 variable region protein after dialysis and renaturation to prepare polyclonal antibody,which was determined for the antibody potency by indirect ELISA,and for the specificity by Western blot and cellular immunofluorescence.Results The recombinant prokaryotic expression plasmid pET-30a-AAV-VR expressing the variable region of AAV9 capsid was constructed correctly as identified by XhoⅠ and BglⅡ digestion. The expressed protein was recognized by His tag antibody after purification with a relative molecular mass of about 20 000. The potency of rabbit polyclonal antibody was 1∶10 240 000,which specifically recognize AAV9 capsid protein.Conclusion The capsid variable region protein of AAV9 was successfully expressed and rabbit polyclonal antibody with high potency was prepared,which laid a foundation of the subsequent development of AAV vector and the research of AAV biological function.
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@#Objective To develop and verify a reporter gene assay for the determination of antibody dependent cellular phagocytosis(ADCP)potency of Ig G2 monoclonal antibody(m Ab)against epidermal growth factor receptor(EGFR)by combining Design of Experiment(DOE)and one factor at a time(OFAT).Methods The Jurkat/NFAT-Re/FcγRⅡa stably transformed cell line was used as effector cells,while the A431 cell line as the target cells.The JMP software was used to optimize the seven key factors in the experiment by combining DOE and OFAT analysis,while the ratio of upper and lower asymptotes(D/A)was used as the statistic,and the reporter gene method was developed to evaluate the ADCP potency of Ig G2 anti-EGFR m Ab.The method was verified according to the general chapter<9401>of Chinese Pharmaco-poeia（Ⅲ/Ⅳvolume,2020 edition)and used to determine the biological potency of Ig G2 anti-EGFR m Ab injection.Results After three rounds of experiments,the reporter gene method to evaluate the ADCP potency of Ig G2 anti-EGFR m Ab was developed.The method showed a dose-response relationship and was consistent with the four-parameter regression equa-tion y=(A-D）/[1+(x/C)~B]+D.The range of seven key conditions was determined:the density of effector cells was(1.25-3.75）×10~4 cells/well,the density ratio of effector cells to target cells was 1.0-2.0,the incubation time of target cells was 20-40 min,the incubation time of administration was 15-30 min,the total time was 5.5-6.5 h,and the color time was 5-30 min with luciferase detection system(Bright-Glo)as the color agent.The method had good specificity.Six independent tests were run for the five potency levels,with the correlation coefficient r of 0.994 5 and the linear regression equation slope of 1.02.The relative potency of five potency levels respectively was(62.15±1.38)%,(78.53±2.82)%,(99.12±3.95)%,(123.27±4.59)%and(155.22±7.04)%,the range of relative biases was-2.9%-0.2%,and the range of generalized cross-validation(GCV)was 2.2%-4.6%.The method had good linearity,relative accuracy and precision in the range of 64%-156%.The mean value of the potency of IgG2 anti-EGFR m Ab in three tests was(101.5±2.8)%.Conclusion The reporter gene assay developed in this study can be used to evaluate the ADCP potency of IgG2 anti-EGFR mAb
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【Objective】 To explore the distribution and types of platelet antibodies in children with positive platelet antibody in initial screening. 【Methods】 Blood samples of 80 pediatric patients who applied for platelet transfusion in our hospital from September 2021 to May 2022 and tested positive for platelet antibodies were identified using the PAKPLUS kit for antibody identification, and the distribution of HLA and HPA antibodies were analyzed. 【Results】 Among the 80 reactive samples in initial screening, 9 were negative, 71 were positive. Among the 71 positive cases, 1 was HLA-Ⅰantibody positive(1.41%, 1/71), 21 were HPA antibody positive (29.58%, 21/71), and 49 were both HLA-Ⅰ antibody and HPA antibody positive(69.01%, 49/71). Among the 70 HPA positive cases, 23.95% (17/71) had a single HPA antibody, with 18.31% (13/71) of anti GP Ⅱb/Ⅲa, 2.82% (2/71) of anti GP Ⅰa/Ⅱa, 2.82% (2/71) of anti GP Ⅳ and 0% (0/71) of anti GP Ⅰb/Ⅸ, while 74.65% (53/71) presented multiple HPA antibodies. No statistically significant difference was found in antibody distribution among age, gender, transfusion history and disease types. 【Conclusion】 HLA-Ⅰ antibody combined with HPA antibody are the main types of platelet antibodies among children with positive platelet antibodies. Anti-GPⅡb/Ⅲa accounted for the largest proportion of HPA antibodies. Antibody distribution is not releted to age, gender, history of blood transfusion and disease types.
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【Objective】 To report the antibody specific identification process of a pregnant woman who had no history of blood transfusion but presented high-frequency anti-Jra antibodies. 【Methods】 Antibody screening and identification were performed by saline and indirect Coomb’s technique (microcolumn gel card, PEG). ABO, Rh and other blood group antigens were identified by saline. Further antibody identification tests were performed by the reaction between cells treated with various enzymes and patient plasma. Jra antigen was identified by human anti-Jra antibody. JR blood type genotyping was performed by MALDI-TOF mass spectrometry detection system. Antibody titer in serum was tested. 【Results】 The patient′s blood type was O with RhD(+ ) and CcDEe. The plasma reacted negatively with antibody screening and identification cells by saline, but positively by indirect globulin test. The self-control was negative. The patient′s Jra antigen was negative in serological tests and mass spectrometry blood type genotyping. Mass spectrometry revealed a homozygous nonsense mutation (c.376C>T) in exon 4. The anti-Jra antibody titer was 1∶2. 【Conclusion】 The patient developed high-frequency anti-Jra antibodies during pregnancy.
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【Objective】 To identify antibody specificity in an elderly patient with hydronephrosis accompanied by ureteral stones and shock who had multiple antibodies. 【Methods】 Microcolumn gel method was used to screen unexpected antibodies of red blood cells and identify antibodies. Enzyme method and antibody absorption method were used to help judge the specificity of antibodies in patients.The ABO blood type, Rh blood type and MNS blood type of patient were determined by saline tube method. 【Results】 The patient′s blood types were O, CCDee, NNss, and a combination of anti-E, anti-c, anti-M and anti-S antibodies was detected. 【Conclusion】 Repeated blood transfusion may lead to the presence of one or more unexpected antibodies in patients. Patients with multiple or high-frequency antibodies may experience difficulties in identification and delayed blood use.
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【Objective】 To statistically analyze the perioperative results of patients with ABO-incompatible kidney transplantation (ABOi-KT), in order to explore the changes in blood group antibody of type-A/B recipients. 【Methods】 A total of 33 cases of blood group A/B ABOi-KT recipients in our hospital from January 2021 to October 2023 were recruited and divided into two groups of group A(n=18) and group B(n=15) according to the different blood types of recipient. The effects of preoperative plasmapheresis on antibody titer, antibody rebound and renal function after operation(serum urea nitrogen, creatinine and estimated glomerular filtration rate on the 1st, 3rd, 7th and 14th day) were analyzed between the two groups. According to the postoperative rebound of blood type antibodies, 33 recipients were divided into antibody rebound group(n=7) and non rebound group(n=26), and the differences in initial blood type antibody titers between the two groups were analyzed. 【Results】 There was no significant difference in the clearance rate of IgM with preoperative plasma exchange between the two groups (Z=-0.26, P>0.05); Levels of serum urea nitrogen and creatinine on the 1st, 3rd, 7th and 14th day after operation between group A and group B were not statistically significant(P>0.05), the same as eGFR. Group B was more prone to rebound antibody compared with group A (P0.05) between the two groups was found. 【Conclusion】 The patients type B receiving type AB kidney donors are more prone to rebound antibody after ABOi-KT operation compared to the the patients type A receiving type AB.
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【Objective】 To analyze the antibody types of autoimmune hemolytic anemia(AIHA) patients in Panyu district, Guangzhou and track the therapeutic effect of blood transfusion, so as to provide reference for clinical transfusion treatment strategy of AIHA patients. 【Methods】 From January 2021 to October 2023, 96 ambiguous cross-matching blood samples from Blood Transfusion Departments of local hospitals sent to Panyu Central Blood Station were analyzed, and 25 samples of AIHA patients were identified. Then blood group identification, Rh system antigen phenotyping, antibody screening and cross-matching were further performed to analyze the correlation between antibody types and transfusion efficacy in AIHA patients. 【Results】 Among the 25 samples of AIHA patients, 17 showed consistency between forward and reverse blood grouping and 8 showed discrepancy. There were 19 (19/25, 76%) samples incompatible in cross match on the major side, of which 18 (18/19, 94.7%) were positive for direct Coombs test, autoantibodies and non-specific antibodies, and 1 (1/19, 5.3%)was positive for autoantibody and alloantibody.There were 6 (6/25, 24%) samples compatible in cross match on the major side, of which 3 (3/6, 50%) were positive for autoantibodies, 3 (3/6, 50%) were positive for autoantibody and alloantibody. Of the 25 AIHA patients, 20 received blood transfusion treatment and could be traced, and 5 patients did not receive blood transfusion treatment or transferred to other hospitals and could not be traced. Blood transfusion was effective in 11 (11/20, 55%) cases, partially effective in 6 (6/20, 30%) cases, and ineffective in 3 (3/20, 15%) cases. Among the ABO blood group incompatibility samples, transfusion was effective or partially effective in 17 (17/20, 85%) cases. 【Conclusion】 The transfusion efficacy of AIHA patients is not directly related to the results of cross-matching. Under the premise of regulating the autoimmune environment and eliminating the ABO blood group incompatibility caused by unexpected alloantibodies, AIHA patients with incompatible cross-matching can be transfused when necessary, and transfusion of ABO and Rh system antigen homologous blood can improve the safety and efficiency of transfusion.
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Unexpected red blood cell antibodies refer to antibodies except for anti-A and anti-B in normal ABO blood group, and are widely present in patients with pregnancy, transfusion, transplantation, injection of immunogenic substances, or autoimmune diseases, leading to difficulties in blood type identification and cross matching test, which seriously affect transfusion safety and efficacy. This consensus aims to further standardize the requirements, operating procedures and clinical significance of antibody screening, thus improving the safety and efficacy of blood transfusion.
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【Objective】 To perform pre-transfusion examination and major crossmatch test using CD47 anti-idiotypic antibody (CD47 AID) (method 1) and reagent lack of anti-IgG4 anti-human globulin(method 2) in patients treated with CD47 monoclonal antibodies, and evaluate the feasibility of method 1 by comparing the transfusion efficacy of patients after cross matching with two methods. 【Methods】 Post-drug samples were collected from 18 clinical subjects treated with CD47 monoclonal antibody in our hospital. Antibody screening and major crossmatch test were performed using method 1 and method 2, and the difference of ΔHb (post-transfusion Hb minus pre-transfusion Hb) was compared after transfusion. The differences in ΔHb after transfusion were analyzed between the test group using method 1 and the control group without CD47 monoclonal antibody using ordinary microcolumn gel method. 【Results】 There was no significant difference in ΔHb between the test group using method 1 and test group using method 2 (8.40±0.71 vs 7.36±0.94, P>0.05). No significant difference was noticed in ΔHb between the test group using method 1 and the control group without CD47 monoclonal antibody (8.40±0.71 vs 6.59±0.77, P>0.05). 【Conclusion】 In the test group, major crossmatch test with method 1 has the same transfusion efficacy as the test with method 2. Method 1 is simple and easy to operate, and the results are objective and accurate. It is recommended to use method 1 for pre-transfusion antibody screening and major crossmatch tests for patients using CD47 monoclonal antibody.
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Objective Based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,data mining was conducted on hematological adverse events related to antibody drug conjugates(ADC),providing reference for the safe use of ADC drugs in clinical practice.Methods The report data from the third quarter of 2011 to the fourth quarter of 2022 were retrieved from the FAERS database.After data cleaning such as deduplication and name standardization,extract hematological adverse events related to ADC,and use report odds ratio method and the information component method for signal detection.Results A total of 101 610 adverse event reports were extracted,with 8 ADC drugs as the primary suspected drugs,and 5 768 ADC related hematological adverse event reports.Among them,3 423 cases of agranulocytosis were involved,and the signal intensity from strong to weak were sacituzumab govitecan(SG),gemtuzumab ozogamicin(GO),brentuximab vedotin(BV),polatuzumab vedotin(PV),enfortumab vedotin(EV),trastuzumab deruxtecan(TD),inotuzumab ozogamicin(IO)and ado-trastuzumab emtansine(TDM-1).There were 2 327 cases hematopoietic cell deficiency,with signals ranging from strong to weak were IO,SG,BV,EV,PV,TD,TDM-1,and GO.Report with clinical outcome of death of ADC drug related hematological adverse events included BV 179(16.84％),TDM-1 102(13.01％),TD 88(27.08％),GO 12(16.90％),IO 8(11.59％),EV 54(24.32％),PV 22(27.16％),and SG 84(21.05％).Adverse event time analysis showed that the number of events on the first day of TD,IO,and SG medication accounts for ≥ 40％of the total number of cases.The median time of hematological adverse events in TD,GO,IO,EV,PV,and SG was within one treatment course(21 days).Conclusion Attention should be paid to the risk of ADC drug-related hematological adverse event,during the clinical medication process,blood cell count changes should be closely monitored,and any abnormalities should be promptly diagnosed and treated.
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Objective To analyze the global research status,hotspots,and frontiers of proprotein convertase subtilisin/Kexin type 9(PCSK9)monoclonal antibodies,and to provide a reference for related scientific research and the rational drug use in clinical practice in China.Methods The research literature related to PCSK9 monoclonal antibody included in the Web of Science database was searched for the period from January 2011 to February 2022,and the literature included in the study was visually analyzed by the CiteSpace software.Results A total of 723 articles were included,and the annual number of publica-tions showed an overall upward trend.The top three countries were the United States,France,and the United Kingdom.Sanofi was the organization with the largest number of articles,and the organization with the highest citation of articles was Brigham and Women's Hospital.The hotspots of research mainly included the use of PCSK9 monoclonal antibody in the treatment of patients with hypercholesterolemia,patients who do not tolerate statins,patients with high cardiovascular risk,and the efficacy and safety of PCSK9 monoclonal antibody in lipid-lowering therapy combined statins;The frontiers of research in recent two years is the appli-cation of PCSK9 monoclonal antibodies in patients with acute coronary syndrome and the clinical benefits after reducing the level of lipoprotein(a).Conclusion A large number of studies have confirmed the efficacy and safety of PCSK9 monoclonal anti-bodies in reducing blood lipids,but there is still a lack of research on its economics and application in special populations,which should be the focus of future research.
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Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.
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Objective:To investigate the effectiveness and safety of plasma exchange for thrombotic microangiopathy and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which require renal replacement therapy.Methods:This is a retrospective study. The clinical data of four patients who underwent plasma exchange at the Blood Purification Center, North Branch of the First Affiliated Hospital of Anhui Medical University, from June 2021 to February 2022 were collected and analyzed. The records included a total of 19 treatments performed, including 15 treatments with a single plasma exchange regimen used in 3 patients and 4 treatments with double filtration plasmapheresis used in 1 patient. Changes in condition before and after treatment, as well as corresponding biochemical test results, were recorded.Results:In four patients, clinical symptoms and biochemical indicators improved. Three patients required maintenance hemodialysis, while one patient showed remarkable clinical efficacy. After treatment, hemoglobin level increased from 76 g/L to 83 g/L, blood creatinine level decreased from 703.6 μmol/L to 526.2 μmol/L, anti-SM antibody decreased from > 400 RU/mL to < 2 RU/mL, anti-myeloperoxidase antibody decreased from 255.49 RU/mL to 15.64 RU/mL, and perinuclear anti-neutrophil cytoplasmic antibody turned negative. During treatment, there were two cases of allergic reactions, which were significantly alleviated after treatment.Conclusion:Plasma exchange is safe and effective against thrombotic microangiopathy and anti-neutrophil cytoplasmic antibody-associated vasculitis, which require renal replacement therapy.