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<b>Objective</b> To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. <b>Methods</b> The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. <b>Results</b> No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all <i>P</i><0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both <i>P</i><0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all <i>P</i><0.05). <b>Conclusions</b> The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.
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@#Objective To express the Gn protein of severe fever with thrombocytopenia syndrome virus(SFTSV) through adeno-associated virus 9(AAV9) expression system and evaluate its immunogenicity.Methods SFTSV Gn gene was inserted into viral vector pAAV-CMV-FH and the recombinant plasmid was transfected into HEK293T cells to obtain recombinant virus AAV9-Gn.The expression of Gn protein was determined by immunofluorescence and Western blot.Eighteen fernale BALB/c mice were randomly divided into three groups:Mock group(serum-free DMEM),AAV9-GFP group(1 × 10~(11) vg) and AAV9-Gn group(1 × 10~(11) vg),all of which were injected intramuscularly into the right hind limb at a dose of 100 μL per mouse.The body mass,diet,behavior and mental state of mice in each group were monitored continuously for 21 d,and the change rate of body mass was calculated;At 2,4,8 and 16 weeks after immunization,the levels of SFTSV neutralizing antibody in serum of mice in each group were detected by fluorescent reduction neutralization test(FRNT),and the levels of specific IgGl and IgG2a in serum of mice in AAV9-Gn group were detected by ELISA.Results After incubation with specific antibody,Vero cells transfected with AAV9-Gn showed specific green fluorescence under fluorescence microscope,and had specific binding to mouse anti-SFTSV Gn monoclonal antibody,and the specific binding bands were found at a relative molecular mass of about 61 000.The body mass of the three groups showed an increasing trend,there was no significant difference between the three groups(F=0.158—2.621,P> 0.05),and the diet,behavior and mental state were normal.At 2,4,8 and 16 weeks after immunization,the titer of SFTSV neutralizing antibody in serum of mice in AAV9-Gn group was significantly higher than that of Mock group and AAV9-GFP group(H=13.332—14.538,each P <0.001),and the titer peak appeared at 8 weeks;The level of specific IgG1 in serum of mice was significantly higher than that of IgG2a(F=4.373—12.975,each P <0.05) at different time points.Conclusion SFTSV Gn protein can be expressed correctly through AAV9 expression system,and has low toxicity to mice with good immunogenicity,which is expected to be a candidate component of SFTSV vaccine.
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@#Objective To explore the factors affecting the stability of high concentration variable domain of heavy-chain antibody-Fc(VHH-Fc) fusion protein.Methods Three groups of forced degradation experiments,shaking,light and 40℃ high temperature were set up.Differential scanning fluorimetry,dynamic light scattering(DLS) and ultra performance liquid chromatography-mass spectrometry(UPLC-MS) were used to detect the effects of the three forced degradation conditions on the conformational stability,colloidal stability,average hydrodynamic diameter and post-translational modifications of high concentration VHH-Fc fusion protein.Results Under the light condition,the onset temperature of unfolding(T_(onset)),melting temperature(T_m) and aggregation onset temperature(T_(agg)) of high concentration VHH-Fc fusion protein decreased the most,and the oxidation ratio of Met160 and Met266 increased significantly.Under the condition of shaking,the variation of the diffusion interaction parameter(k_D) and the average hydrodynamic diameter was the largest.Conclusion Light can significantly reduce the conformational stability of high concentration VHH-Fc fusion protein and induce methionine oxidation.Shaking has the most significant effect on its colloidal stability and promotes aggregation
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@#Objective To investigate the mechanism of anti-IL-17A monoclonal antibody(secukinumab) regulating autophagy and inflammation in gout.Methods The peripheral venous blood samples from 57 patients with acute gout(AG),57patients with intermittent gout(IG) and 82 healthy volunteers were collected and measured for the mRNA transcription levels of autophagy-related genes(ATGs) ATG4B,ATG7, A TG16L1,Beclin-1 and LC3B by RT-qPCR.The model of AG inflammation was established by adding monosodium urate(MSU) crystals into the peripheral venous blood samples of healthy volunteers,and the transcription and protein expression of IL-1β were detected by RT-qPCR and ELISA at 0,1,2,4,6 and8 h and different concentrations(0,100,200 and 400 μmol/L) of secukinumab.The peripheral blood samples of healthy volunteers were divided into control(without MSU treatment),MSU(100 μg/mL),MSU+colchicine(100 μg/mL+30 μg/mL) and MSU+secukinumab(100 μg/mL+400 μmol/L) groups,which were detected for the mRNA transcription and protein expression of IL-1 β and ATGs by RT-qPCR and Western blot,and for the expression of IL-1β,IL-12 and IL-35 by ELISA.Results The mRNA expression levels of ATG4B, Beclin-1 and LC3B in AG,IG and healthy control groups were significantly different(F=3.896,11.78 and 3.856,respectively,each P <0.05),among which the mRNA levels in AG were lower than those in IG and HC groups(t=2.692,3.234,2.231 and 2.085,4.795,2.748,respectively,each P <0.05);the expression levels of ATG16L1 mRNA were significantly different in the three groups(F=7.949,P <0.001),and was significantly lower in AG group than HC group(t=3.860,P <0.001).In AG inflammation model,the mRNA and protein expression of IL-1 β reached their peak in 2—4 h,and the anti-inflammation effect of secukinumab was the strongest at the concentration of 400 μmol/L.Compared with MSU group,the mRNA levels of ATG16L1 and LC3B(t=2.343 and 2.916,respectively,each P <0.05) as well as the expression levels of ATG4B,ATG7,Beclin-1,ATG16L1 and LC3B-Ⅱ proteins(t=28.84,11.6,8.402,4.124 and 2.458,respectively,each P <0.05) in MSU+secukinumab group decreased significantly.The expression levels of IL-12 and IL-35 in the control,MSU,MSU+colchicine and MSU+secukinumab groups showed significant difference(F=7.009 and 6.518,respectively,each P <0.01).Compared with MSU group,the expression level of IL-12 significantly decreased(t=2.604,P <0.05)in MSU+secukinumab group,and the expression level of IL-35 also decreased,while with no significant difference(t=1.928,P> 0.05).Conclusion Secukinumab can regulate the mRNA and protein expression of ATGs,reduce the levels of pro-inflammatory cytokines,and inhibit gout inflammation,which provides a reference for the treatment of gout.
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@#Objective To prepare rabbit polyclonal antibodies against pertussis toxin(PT) and develop a double antibody sandwich ELISA for quantitative determination of PT antigen,identify and apply the method.Methods The rabbit polyclonal antibody against PT was prepared by immunizing Chinchilla rabbit with PT using traditional method.The reaction conditions of ELISA system were optimized,the double antibody sandwich ELISA method for quantitative determi-nation of PT was developed,and the specificity,linearity,accuracy,precision and sensitivity were verified.The developed method was used to detect PT antigen content in fimbriae proteins(FIM) stock solution of samples during detoxification and other purification process of pertussis antigen.Results The working condition of double antibody sandwich ELISA for detection of PT antigen content was the coating concentration of PT rabbit polyclonal antibody of 1 μg/mL,and the enzyme-labeled antibody dilution of 1:8 000.This detection system showed specific reaction with PT purified protein,but had no cross reaction with filamentous hemagglutinin,diphtheria toxoid and tetanus toxoid;the linear detection range of the developed double antibody sandwich ELISA was within 25—400 ng/mL;the recovery rates of PT at high,moderate and low concentrations were 103.27%,91.48% and 103.52%,respectively;both the intra-and inter-coefficients of variation(CVs)were less than 10%;the sensitivity of the method was 20.719 ng/mL,and the detection limit was 41.438 ng/mL.Thirty-five batches of samples were detected under five different detoxification process conditions and at different sampling time points,and the changes of antigen content were all consistent with the trend of detoxification reaction.Conclusion The PT rabbit polyclonal antibody was successfully prepared,and a double antibody sandwich ELISA with high precision and accuracy was developed for the quantitative determination of PT antigen content,which can be used for the antigen content detection of chemically detoxified samples in the production process of component DPT vaccines.
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Objective To analyze the epidemiological characteristics of varicella epidemic in kindergartens and schools in Jinshan District of Shanghai from 2015 to 2022,and to understand the varicella antibody level in students aged under 30 years old,to provide evidence for developing control and prevention strategies. Methods Data of varicella epidemic situation at schools and kindergartens and varicella cases were analyzed by descriptive methods.Collect serum from healthy individuals under 30 years old to detect IgG antibody levels of varicella zoster virus.Results From 2015 to 2022, a total of 91 cases of chickenpox were reported in kindergartens and schools in Jinshan District, Shanghai, involving 412 cases.The peak incidence occurs from October to December,kindergarten childcare and primary school children were at high risk of varicella .The incidence of fever(χ2=12.93,P<0.001) and moderate to severe rash(χ2=28.79,P<0.001) in patients with varicella vaccination was lower than that in patients without varicella vaccination. A total of 227 people were surveyed,the positive rate of varicella antibody was 62. 56%,the geometric mean titer ( GMT) was 2.22±0.68(165.96mIU/ml).The difference of GMT(F=6.87,P<0.001) and positive rate (χ2=29.14,P<0.001)of antibody in different age groups was statistically significant,the positive rate was lowest in the age group of 1-3 years, and gradually increased with the increase of age. Conclusion Autumn and winter in Jinshan District are the seasons with high incidence of chickenpox in kindergartens and primary schools,two doses of chickenpox inoculation can not only reduce clinical symptoms, but also block the transmission of chickenpox epidemic,it is suggested schools and health facilities make chicken pox monitoring work, get the chickenpox vaccine on time.
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Objective:To analyze the clinical presentations and diagnostic and treatment process of one patient with autoimmune encephalitis(AE)with double positive anti-N-methyl-D-aspartate receptor(NMDAR)and anti-γ-aminobutyric acid B receptor(GABABR)secondary to herpes simplex virus encephalitis(HSVE),and to improve the clinicians'awareness of this disease.Methods:The clinical data of one AE patient with double positive anti-NMDAR and anti-GABABR secondary to HSVE were collected,the diagnostic and therapeutic processes were summarized,and the relevant literatures were reviewed.Results:The patient,a 36-year-old male,developed a headache followed by limb convulsions,and progressed to disturbed consciousness.After admission,the routine biochemistry of the cerebrospinal fluid(CSF)was abnormal,and the herpes simplex virus-1(HSV-1)IgG antibody showed positive in the CSF;both CSF and serum tests for NMDAR antibodies were positive;the head magnetic resonance imaging(MRI)results showed abnormal signals in the right occipital white matter,leading to the diagnosis of HSVE secondary to anti-NMDAR encephalitis.Several months later,the patient experienced psychiatric behavior abnormalities,cognitive dysfunction,and sleep disorders,and both the serum NMDAR and GABABR antibodies showed positive results,prompting the diagnosis of HSVE secondary anti-NMDAR encephalitis and anti-GABABR encephalitis.After treatment with steroid pulse therapy and intravenous immunoglobulin(IVIG),the patient's condition was improved and the patient was discharged.At one-year follow-up,the patient's psychiatric symptoms had completely resolved,leaving mild cognitive impairment.Conclusion:If the clinical symptoms of the patients recovering from antiviral treatment for HSVE is worsened,secondary AE should be highly suspected;it is important to complete autoimmunity antibody testing as soon as possible for the early diagnosis and treatment to improve the prognosis of the patient.
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Objective To investigate the clinical value of thyroid globulin antibody(TgAb)and thyroid peroxidase antibody(TPOAb)in the diagnosis and treatment of papillary thyroid microcarcinoma(PTMC).Methods A total of 346 patients with thyroid nodules who underwent surgical treatment in the hospital from August 2012 to October 2021 were selected as the research objects.According to the postoperative pathologi-cal results,the patients were divided into the benign nodule group,PTMC group and non-micro papillary thy-roid carcinoma(PTC)group.The general data of the patients and thyroid function indexes[free triiodothyro-nine(FT3),free tetraiodothyronine(FT4),thyroid stimulating hormone(TSH),TgAb and TPOAb]before and after operation were collected,the tumor recurrence or lymph node metastasis after operation were ob-served,and the relationship between serum TgAb and TPOAb and the risk and prognosis of PTMC was ana-lyzed.Results The positivity rate of TgAb in the PTMC and non-micro PTC groups was significantly higher than that in the benign nodule group(P<0.05).The TPOAb positivity rate was not significantly different among the three groups(P>0.05).Only the TSH level in the PTMC group was higher than that in the non-micro PTC group(P<0.05).Multivariate logistic analysis showed that younger age,higher TSH and positive TgAb were independent risk factors for PTMC and non-micro PTC(P<0.05).However,the risk of PTC didn't increase with increasing TgAb titres.The positivity rate of TgAb in the PTMC and non-micro PTC groups didn't change significantly within one month after operation,but decreased in one year after operation(P<0.05).The TPOAb positivity rate decreased after operation,but the difference was not statistically sig-nificant(P>0.05).In the PTMC group,four cases had tumor recurrence or lymph node metastasis,and the TgAb level increased by 88.4%,49.5%,5.7%and 84.0%respectively when the tumor recurred or metasta-sized.Among them,the TPOAb level increased by 51.6%,30.0%and 2.9%respectively in three cases and decreased by 53.9%in one case.In the PTMC group,there were 11 patients with cervical lymph node enlarge-ment,and there was no statistical difference in TgAb and TPOAb levels when the condition changed(P>0.05).Conclusion TgAb is a risk factor for PTMC,and can be followed up regularly during the diagnosis and treatment of PTMC.The specificity of TPOAb is not as good as that of TgAb,and appropriate follow-up can be chosen during the course of the disease.
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Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.
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Objective To explore the value of serum Irisin and thyroid peroxidase antibody(TPOAb)in the diagnosis of hypothyroidism during pregnancy.Methods A total of 107 pregnant women with hypothy-roidism during pregnancy who were diagnosed and treated in the hospital from October 2020 to October 2022 were regarded as the study group,another 107 healthy pregnant women who were examined in the hospital at the same time and whose general data matched with cases of hypothyroidism during pregnancy and 107 non pregnant healthy women were taken as the control group and health group.Pearson method was applied to an-alyze the correlation between the levels of serum Irisin and TPOAb in pregnant women with hypothyroidism during pregnancy.Logistic regression was applied to analyze the related factors affecting the occurrence of hy-pothyroidism during pregnancy.The diagnostic value of serum Irisin and TPOAb levels for hypothyroidism during pregnancy was analyzed by the receiver operating characteristic(ROC)curve.Results The levels of serum Irisin and TPOAb in the study group were significantly higher than those in the health group and con-trol group(P<0.05).The levels of serum Irisin and TPOAb in pregnant women with hypothyroidism during pregnancy were positively correlated(r=0.641,P<0.05).The proportions of pregnant women with BMI<20 kg/m2 and iodine deficiency before pregnancy in the study group were obviously higher than those in the control group(P<0.05).BMI<20 kg/m2 before pregnancy,iodine deficiency,increased levels of Irisin and TPOAb were all risk factors for hypothyroidism during pregnancy(P<0.05).The area under the curve(AUC)of serum Irisin and TPOAb in the diagnosis of hypothyroidism during pregnancy was 0.765 and 0.835,respectively,while the AUC of the combined diagnosis of the two was 0.926,the combined diagnosis of the two was better than that of serum Irisin and TPOAb alone(Zcombination-Irisin=6.105,Zcombination-TPOAb=4.951,P<0.001).Conclusion The increased levels of serum Irisin and TPOAb are closely related to the occurrence of hypothyroidism during pregnancy,and the combination of them has high diagnostic value for hypothyroid-ism during pregnancy.
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Objective To investigate the levels of serum CXC-chemokine ligand 16(CXCL16)and anti-neu-trophil cytoplasmic antibody(ANCA)in patients with allergic rhinitis and their clinical diagnostic value.Meth-ods A total of 84 patients with allergic rhinitis(allergic rhinitis group)treated in the hospital from January to December 2022 were selected as the study objects,and were divided into mild group(44 cases)and moderate and severe group(40 cases)according to the severity of their disease.Another 80 healthy subjects who had physical examination in the same period were selected as the control group.The levels of CXCL16 and ANCA in serum were determined by enzyme-linked immunosorbent assay.The correlation between serum CXCL16 and ANCA levels and inflammatory factors[interleukin(IL)-4,IL-9,IL-13]and immunoglobulin E(IgE)was analyzed by Pearson.The value of serum CXCL16 and ANCA levels in the diagnosis of moderate and severe allergic rhinitis was evaluated by receiver operating characteristic(ROC)curve.Results Compared with con-trol group,the levels of IL-4,IL-9,IL-13 and IgE in allergic rhinitis group were significantly increased,and the difference was statistically significant(P<0.05).Compared with control group,serum CXCL16 and ANCA levels in allergic rhinitis group were significantly increased,and the differences were statistically significant(P<0.05).The area under the curve(AUC)of serum CXCL16 and ANCA in patients with allergic rhinitis was 0.897 and 0.844,respectively.The AUC of combined diagnosis was 0.959,both of which were better than that of individual diagnosis(Z=2.164,3.474,P<0.05),and the specificity was 93.75%.The sensitivity was 89.29%.The levels of serum CXCL16 and ANCA in patients with allergic rhinitis increased with the se-verity of the disease(P<0.05).Pearson correlation analysis showed that serum CXCL16 and ANCA levels were positively correlated with IL-4,IL-9,IL-13 and IgE in patients with allergic rhinitis(P<0.05).ROC curve analysis results showed that the AUC of the patients diagnosed with moderate and severe allergic rhini-tis by serum CXCL16 and ANCA was 0.862 and 0.832,respectively,and the AUC of the combined diagnosis of CXCL16 and ANCA was 0.949,both of which were better than those diagnosed separately(Z=1.981,2.378,P<0.05),and the specificity was 90.91%.The sensitivity was 90.00%.Conclusion The levels of se-rum CXCL16 and ANCA in patients with allergic rhinitis increased significantly,and increased with the severi-ty of the patients'disease,both of which have certain value in the clinical diagnosis of allergic rhinitis.
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Objective To analyze the antigen recognition sites of commercial and homemade antibodies against aquaporin(AQP)9,and to identify the application effect.Methods Western blotting was used to compare the efficacy of three commercial antibodies and self-made antibody in identifying AQP9 genotypes.The antigen recognition sites of four antibodies and their specificities in practical applications were analyzed.Results Western blotting showed that protein bands of three commercial antibodies were detected in both WT and Aqp9-/-mice.The keyhole limpet hemocyanin(KLH)conjugated synthetic peptides corresponding to the three commercial antibodies were derived from rat,human and human,respectively.And The sequences of these three synthetic peptides were different from those of mice.AQP3/7 and AQP9 have similar molecular weight and were expressed in the liver with high homology.An obvious band of self-made antibody was observed at the 27 kD position in WT mice,but no band was observed at the corresponding position in Aqp9-/-mice.Conclusion Commercial antibodies 1 and 3 can be used to assist in the identification of genotypes in Aqp9-/-mice.Homemade antibodies can accurately identify genotypes at the protein level.
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Objective To investigate the correlation between HLA-DM gene polymorphism and antibody response induced by poliomyelitis vaccine.Methods 355 healthy infants aged 2 to 3 months in Guangxi Zhuang Autonomous Region were selected as the study objects,and 10 SNPs of DMA exon 3 and DMB exon 2/3 were genotyped by Sanger sequencing.The correlation between DMA and DMB genes and poliomyelitis vaccine-induced antibody response was analyzed at allele,genotype and haplotype levels.Results In the type Ⅰ antibody response induced by polio vaccine,the frequencies of DMA*01:02,DMB*01:01,DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group(P<0.05).In the polio type Ⅱ antibody response,the frequencies of DMA*01:02,DMA*01:02/DMA*01:02,DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group(P<0.05).Conclusion Alleles DMA*01:02 and DMB*01:01 may be associated with type Ⅰ and type Ⅱ antibody responses induced by poliomyelitis vaccine.
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Objective To investigate the distribution characteristics of serum sIgE antibodies against four allergenic protein components of egg white in children with egg allergy,and then clarify the clinical application value of single component-resolved diagnostics of egg allergy.Methods Serum samples from 197 children with egg allergy were collected.The levels of serum sIgE antibodies against four major allergenic protein components of egg white,including ovomucin,ovalbumin,ovotransferrin,and lysozyme,were detected by the light-excited chemiluminescence assay(LiCA),and the distribution characteristics of sIgE antibodies were analyzed.Results The positive rates of serum sIgE antibodies against ovalbumin,ovomucin,ovotransferrin,and lysozyme in 197 chlidren with egg allergy were 77.16%(152/197),70.56%(139/197),35.02%(69/197),and 18.27%(36/197),respectively.The positive rate of serum sIgE antibody against both ovomucin and ovalbumin was 30.45%.There was a weak correlation between the levels of sIgE antibodies against egg and the cumulative levels of sIgE antibodies against four allergenic protein components(r=0.266 8,P<0.05).There were signifi-cant individual differences in the levels of serum sIgE antibodies against four allergenic protein components of egg white in the children with egg allergy.Conclusion There is individual heterogeneity in the levels of serum sIgE antibodies against four components of egg white in the children with egg allergy.The detection of sIgE antibodies against egg white components can distinguish different forms of egg allergies,which is of great value for the accurate diagnosis and precise desensitization of children's egg allergy.
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Objective To investigate the clinical significance of the detection of food-specific IgE(fsIgE)and IgG4(fsIgG4)antibod-ies in the diagnosis and treatment of children's allergic diseases.Methods A total of 641 children with allergic diseases visited Hang-zhou Women's Hospital during November 2022 and November 2023 and 100 healthy children during the same period were selected,and the levels of fsIgE and fsIgG4 in their serum samples were detected.Results The total positive rates of fsIgE and fsIgG4 in children with allergic diseases were 37.44%and 90.48%,respectively,which were significantly higher than the 11.00%and 61.00%of healthy children(P<0.05).The main food allergens in children were milk and eggs.The intensity of fsIgE was concentrated in the 1-2 level and the positive result for a single food was more common.The intensity of fsIgG4 was concentrated in Grade 3 and the positive results for multiple foods were more common.The comparison of the detection results of sIgE and sIgG4 to the same food showed that the posi-tive rate of sIgG4 was significantly higher than that of sIgE(P<0.05),and the consistency between them was poor(κ<0.4).There were no significant differences in the positive rates of fsIgE and fsIgG4 between different genders(P>0.05).The highest positive rate of fsIgE was seen in the infant group and the highest positive rate of fsIgG4 was seen in the childhood group(P<0.05).The positive rates of sIgE to egg protein,shrimp,crab,and cashew were mainly seen in children with skin diseases(P<0.05).The positive rates of sIgG4 to egg and milk were mainly seen in children with respiratory diseases(P<0.05).The positive rates of sIgG4 to shrimp and wheat were mainly seen in children with skin diseases(P<0.05).Analysis of allergen components showed that the β-lactoglobulin,α-whey protein,and casein in milk and mucin in eggs were important allergenic components.Conclusion Food allergy is an important factor leading to children's allergic diseases.The combined detection of fsIgE and fsIgG4 can provide experimental basis for clinical di-agnosis and treatment as well as personalized dietary guidance of children.
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Objective To investigate the clinical manifestations of nodo-paranodopathy(NPP)with anti-neurofascin 186(NF186)antibody positive.Methods The clinical data of a NPP patient with cranial nerve damage caused by anti-NF186 antibody positive was retrospectively analyzed.Results The patient was a 70-year-old male with sudden speech disorder and dysphagia one month ago.Glucocorticoid therapy was discontinued after improvement.The patient's speech,swallowing,chewing,bristling,turning and head-up movements were laborious and progressively aggravated 5 days ago.The EMG examination of the limbs was normal,and the serum and CSF anti-NF186 antibody were positive.The curative effect of glucocorticoid treatment was not obvious,and the symptoms were significantly improved after plasma exchange treatment.Conclusions Anti-NF186 antibody-positive NPP has late onset age,severe illness and accompanied with cranial nerves damage.Conventional hormone therapy is not effective,but plasma exchange therapy is effective.
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@#Abstract: Type I interferons play an important role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Monoclonal antibody shows therapeutic potential by blocking the signaling pathway. This study used recombinant human subunit 1 of the type I interferon receptor (IFNAR1) protein to immunize New Zealand white rabbits, and applied B cell cloning technology to screen and obtain rabbit parental antibodies. After humanization modification, QX006N was obtained. In vitro biological studies showed that QX006N could specifically bind to human IFNAR1 with an affinity of 108 pmol/L, and neutralize the type I interferon signaling pathway and this pathway mediated biological effects. This study provides a solid foundation for the development of antibody drugs targeting the type I interferon signaling pathway for the treatment of SLE.
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@#Objective To compare the differences of safety and immunogenicity of DTaP-IPV-Hib-HepB hexavaccine,DTaPIPV-Hib pentavaccine plus HepB single vaccine or DTaP-IPV-HepB pentavaccine plus Hib single vaccine,so as to provide a reference for the marketing and use of hexavaccine in China.Methods Randomized controlled trials(RCTs)of DTaP-IPVHib-HepB hexavaccine,DTaP triple vaccine,Hib,IPV and HepB vaccines published at home and abroad were searched.The safety and immunogenicity of the hexavaccine were evaluated by Meta-analysis using Revman 5.4.1 software.Results A total of 7 articles,8 RCTs and 3 429 subjects were included. Meta-analysis of safety showed that there was no significant difference in the incidence of injection site and systemic adverse reactions after vaccination with hexavaccine and pentavaccine plus single vaccine(P > 0. 05)except for induration at the inoculation site and crying. Meta-analysis of immunogenicity showed no significant difference in antibody indexes after vaccination with hexavaccine and pentavaccine plus single vaccine(P > 0. 05).Conclusion The safety and immunogenicity of DTaP-IPV-Hib-HepB hexavaccine in basic immunity was comparable to that of the control vaccine,and might be applied to infants and young children to prevent related diseases. However,due to the limitations of the quantity and quality of included studies,the above conclusions still depend on the further development of larger sample,multicenter and high-quality
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Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is aggressive and prone to metastasis,and the applications of HER2 agents have improved the prognosis of patients with HER2-positive breast cancer. Among the marketed HER2 agents,macromolecular monoclonal antibodies that target the extracellular domain Ⅳ of HER2 were the cornerstone drugs of HER2-positive breast cancer,including trastuzumab,inetetamab,and margetuximab. Trastuzumab is available for the full-line treatment of breast cancer with sufficient proof of evidence-based medicine,sufficient practical experience and controllable safety. Inetetamab and trastuzumab have similar efficacy and controllable safety in HER2-positive metastatic breast cancer and neoadjuvant/ adjuvant therapy. Margetuximab focuses on patients carrying the CD16A-158F allele,and is an option of posterior line treatment for advanced breast cancer. It is necessary to select the most suitable drugs clinically according to the specific condition of the patient.
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@#Objective To evaluate the immunogenicity of prototype strain,Beta strain,Gamma strain and Delta strain of SARS-CoV-2 inactivated vaccines in rats.Methods Five female Wistar rats were immunized with SARS-CoV-2 inactivated vaccines of prototype,Beta,Gamma and Delta strains through thigh muscle twice at an interval of 14 d,with an immunization dose of 3 μg virus protein/(0.5 mL per rat).Serum samples were collected and isolated by vein 14,28 and 42 d after the first immunization.The serum IgG antibody levels were detected by indirect ELISA,the titers of serum neutralizing antibody were measured by microneutralization,and the antigenic ratios of the serum neutralizing antibody titers were calculated to evaluate the antigenicity difference between different strains.Results at 14 d after the first immunization,IgG antibodies against four strains of virus were detected in all immunized serum samples.The levels of IgG antibodies increased by more than 10 times at 28 d compared with those at 14 d,and decreased slightly at 42 d.At 14 d after the first immunization,all the neutralizing antibodies against the four strains were positive in the serum of rats immunized with prototype strain or Delta strain vaccine;In the serum samples of rats immunized with Beta and Gamma strains,all the neutralizing antibodies against Beta and Gamma strains were positive,while some neutralizing antibodies against prototype or Delta strains were positive.At 28 d after the first immunization,the neutralizing antibodies in the immune serum of the four strains were positive,and the titers of neutralizing antibodies were significantly higher than those at 14 d;The neutralizing antibody titers were slightly lower at 42 d after the first immunization than 28 d.There was small difference in the antigenicity between Beta and Gamma,prototype and Gamma,but significant difference in the antigenicity between prototype and Beta strains.Conclusion The prototype strain,Beta strain,Gamma strain and Delta strain of SARS-CoV-2 inactivated vaccines can stimulate rats to produce neutralizing antibodies with high titer,while the immunogenicity has difference.