Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

Development of donor specific antibodies after SARS-CoV-2 vaccination:What do we know so far?

Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.

An ELISA Based on a Truncated Soluble ORF2 Protein for the Detection of PCV2 Antibodies in Domestic Pigs

Postweaning multisystemic wasting syndrome (PMWS) is an important swine disease that is closely associated with porcine circovirus type 2 (PCV2). The capsid protein (Cap protein) is a major structural protein that has at least three immunoreactive regions, and it can be a suitable candidate antigen for detecting the specific antibodies of a PCV2 infection. In the present study, an indirect enzyme-linked immunosorbent assay (TcELISA) based on a truncated soluble Cap protein produced in Escherichia coli (E.coli) was established and validated for the diagnostic PCV2 antibodies in swine. The TcELISA was validated by comparison with an indirect immunofluorescence assay (IIFA). The diagnostic sensitivity (DSN), specificity (DSP), and accuracy of the TcELISA were 88.6%, 90.7% and 89.4%, respectively. The agreement rate was 89.38% between results obtained with TcELISA and IIFA on 113 field sera. A cross-reactivity assay showed that the method was PCV2-specific by comparison with other sera of viral disease. Therefore ,the TcELISA will be helpful for the development of a reliable serology diagnostic test for large scale detection of PCV2 antibodies and for the evaluation of vaccine against PCV2 in swine.

Tumoricidal activation of murine resident peritoneal macrophages on pancreatic carcinoma by interleukin-2 and monoclonal antibodies

INTRODUCTIONMacrophages play an important role in tumor lysisand growth inhibition.They can be activated to atumoricidal state by a variety of agents such asIFNr,TNFα or IL2.The killing machanisms ofactivated macrophages have been extensivelyinvestigated.Recently,it has been proved thatantibody dependent cellular cytotoxicity (ADCC) isone of the potent arms to lyse tumor cells

Relationship and significance between anti-b2-glycoproteinⅠantibodies and platelet activation state in patients with ulcerative colitis

AIM： To study the relationship between anti-β2- glycoprotein Ⅰ （aβ2GPⅠ） antibodies and platelet activation state in patients with ulcerative colitis （UC） and its significance. METHODS： Peripheral blood samples were collected from 56 UC patients （34 males and 22 females, aged 43.5 years, range 21-66 years）, including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of aβ2GP Ⅰ was measured by ELISA. The platelet activation markers, platelet activation complex- Ⅰ （PAC- Ⅰ ） and P-selectin （CD62P） were detected by flow cytometry. RESULTS： The A value for IgG aβ2GP Ⅰ in the active UC group was 0.61 ± 0.13, significantly higher than that in the remittent UC and control groups （0.50 ± 0.13 and 0.22 ± 0.14, P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. The A value for IgM aβ2GP Ⅰ in the active and remittent UC groups was 0.43 ± 0.13 and 0.38 ± 0.12, significantly higher than that in the control group （0.20 ± 0.12, P 〈 0.01）. However, there was no significant difference between the two groups （P 〉 0.05）. The PAC- Ⅰ positive rate for the active and remittent UC groups was 30.6% ± 7.6% and 19.6% ± 7.8% respectively, significantly higher than that for the control group （6.3% ± 1.7%,P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. The CD62P positive rate for the active and remittent UC groups was 45.0% ± 8.8% and 31.9% ± 7.8% respectively, significantly higher than that for the control group （9.2% ± 2.7%, P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. In the active UC group, the more severe the state of illness was, the higher the A value for IgG aβ2GP Ⅰ was, and the positive rate for PAC-Ⅰ and CD62P was positively correlated with the state of illness （Faβ2GP Ⅰ = 3.679, P 〈 0.05; FPAC-Ⅰ （%） = 5.346, P 〈 0.01; and FCD62P （%） = 5. 418, P 〈 0.01）. Meanwhile, in the same state of illness, the A value for IgG aβ2GP Ⅰ was positively correlated to the positive rates for PAC-Ⅰ and CD62P. CONCLUSION： aβ2GP Ⅰ level, platelet activation state and their relationship of them are closely correlated with the pathogenesis and development of UC.

Epitope Analysis of Anti-SARS-CoV-2 Neutralizing Antibodies

Coronavirus disease 2019 is threatening thousands of millions of people around the world.In the absence of specific and highly effective medicines,the treatment of infected persons is still very challenging.As therapeutics,neutralizing antibodies(NAbs)have great potential.Many NAbs have been reported,and most target various regions on the receptor-binding domain of the spike(S)protein,or the N-terminal domain.Several NAbs and NAb cocktails have been authorized for emergency use,and more arc in clinical trials or are under development.In this review,considering the angle of binding epitopes on the S protein,we summarize the functions and the underlying mechanisms of a set of well-recognized NAbs and provide guidance for vaccine design and the combinatorial use of these antibodies.In addition,we review the NAbs and NAb cocktails that have been approved for emergency use and discuss the effectiveness of these NAbs for combating severe acute respiratory syndrome coronavirus 2 mutants.

Cross-species recognition of bat coronavirus RsYN04 and cross-reaction of SARS-CoV-2 antibodies against the virus

Following the outbreak of coronavirus disease 2019(COVID-19),several severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-related coronaviruses have been discovered.Previous research has identified a novel lineage of SARS-CoV-2-related CoVs in bats,including RsYN04,which recognizes human angiotensin-converting enzyme 2(ACE2)and thus poses a potential threat to humans.Here,we screened the binding of the RsYN04receptor-binding domain(RBD)to ACE2 orthologs from 52animal species and found that the virus showed a narrower ACE2-binding spectrum than SARS-CoV-2.However,the presence of the T484W mutation in the RsYN04 RBD broadened its range.We also evaluated 44 SARS-CoV-2antibodies targeting seven epitope communities in the SARS-CoV-2 RBD,together with serum obtained from COVID-19 convalescents and vaccinees,to determine their cross-reaction against RsYN04.Results showed that no antibodies,except for the RBD-6 and RBD-7 classes,bound to the RsYN04 RBD,indicating substantial immune differences from SARS-CoV-2.Furthermore,the structure of the RsYN04 RBD in complex with cross-reactive antibody S43 in RBD-7 revealed a potently broad epitope for the development of therapeutics and vaccines.Our findings suggest RsYN04 and other viruses belonging to the same clade have the potential to infect several species,including humans,highlighting the necessity for viral surveillance and development of broad anticoronavirus countermeasures.

Effect of bovine pellucid zone 3 monoclonal antibodies on B cell lymphoma 2 expressions of granulosa cell and mice (Mus musculus) follicle diameter

Objective:To evaluate the effects of pellucid zone 3 monoclonal antibodies against B-cell lymphoma 2 (BCL-2) expression and mice follicle diameter at various time periods.Methods:The animal model of this study was 36 Balb/c mice (Mus musculus). A true experimental design was used with a post-test only control group approach. BCL-2 expression was observed using immunohistochemistry, while the follicle diameter was observed by haematoxylin-eosin staining. The data was analyzed using nested ANOVA to compare the results of the mean expression of BCL-2 on the 5th and 20th day of observation in the pre-antral and antral follicle between the control and treatment groups.Results:No significant differences were found in BCL-2 gene expression. There were also no significant differences in BCL-2 expression on the 10th day of pre-antral follicle analysis. Moreover, there were no significant differences between the mean follicle diameter on the 5th, 10th, and 20th day of pre-antral and antral follicle development between the control and treatment groups. The addition of bovine pellucid zone 3 (bZP3) monoclonal antibodies on the 5th and 20th day of observation did not decrease the expression of BCL-2 gene in the pre-antral and antral follicle of mice. Administering bZP3 monoclonal antibodies on the 10th day of observation did not affect BCL-2 expression in the pre-antral follicle but did decrease BCL-2 expression in the antral follicle. Supplying bZP3 monoclonal antibodies on the 5th, 10th and 20th day did not affect the diameter of pre-antral and antral follicles of the mice.Conclusion: The monoclonal antibodies bovine zona pelusida 3 has the potential to be developed as a safe immunocontraception preparation.

Analysis of Specific Th1/Th2 Helper Cell Responses and IgG Subtype Antibodies in Anti-CD4 Monoclonal Antibody Treated Mice with Autoimmune Cardiomyopathy

The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice （6–8 weeks old） were randomized into 3 groups： dilated cardiomyopathy （DCM） group, DCM-tolerance （Tol） group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were moni- tored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group （P〈0.01）. On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group （P〈0.01）, and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.

SARS-CoV-2 in inflammatory bowel disease population:Antibodies,disease and correlation with therapy

BACKGROUND Guidelines recommend to cease inflammatory bowel disease(IBD)biologic therapy during coronavirus disease 2019(COVID-19).AIM To investigate severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)antibody positivity in an IBD cohort,COVID-19 disease severity and to evaluate the correlation with clinical/therapeutic variables.METHODS Prospective observational cohort study.IBD patients were tested for SARS-CoV-2 IgG.Data on COVID-19 disease,demographics/therapeutics and clinical features of the IBD population were collected.IgG≥7 was set for SARS-CoV-2 antibody positivity.Throat swab was performed in cases of IgG positivity.Correlations between antibody positivity or COVID-19 symptoms and therapeutic/clinical data were assessed.RESULTS In total,103 IBD patients were enrolled.Among them,18.4%had IgG≥7.Multivariate analysis of antibody positivity correlated only with IBD treatment.For IgG≥7,the odds ratio was 1.44 and 0.16 for azathioprine and mesalazine,respectively,vs biologic drugs(P=0.0157 between them).COVID-19 related symptoms were reported in 63%of patients with IgG positivity.All but one patient with COVID-19 symptoms did not require ceasing IBD treatment or hospitalization. IBDtreatment and body mass index correlated with COVID-19 disease development with symptoms.CONCLUSIONThe IBD population does not have a higher risk of severe COVID-19. The relative risk of havingSARS-CoV-2 antibodies and symptoms was higher for patients taking azathioprine, then biologictherapy and lastly mesalazine. None of the patients under biologic therapy developed severeCOVID-19.

Prevalence of Anti-Cardiolipin and Anti-β2 Glycoprotein Antibodies in Indian Systemic Lupus Erythematosus Patients

Anti-phospholipid antibodies (APA) like anti-cardiolipin antibodies (ACA) and anti-β2glycoprotien (anti-β2GP) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. The prevalence of these antibodies in SLE patients at the time of diagnosis is not known in Indian SLE patients. This study was conducted to evaluate the prevalence of ACA and anti-β2GP autoantibodies in SLE patients and to correlate them with disease activity and immune parameters such as C3, C4 and CRP levels. where 85 SLE patients referred from Rheumatology Department, KEM hospital, Mumbai were studied. SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI) score at the time of evaluation. All patients studied were in an active stage of disease of which 37.6% patients had renal disorders, which were categorized as Lupus Nephritis (LN) and 62.3% patients did not show any renal manifestations (non-LN). ACA and anti-β2GP autoantibodies, to IgG and IgM subclasses were tested by ELISA. C3, C4 and CRP levels were detected by nephelometer. It was observed that 12.9% patients were IgG-ACA and IgM-ACA positive and ACA positivity was noted more among LN group Anti-β2GP autoantibody positivity was 27.1% for IgG and 31.8% for IgM., IgG-anti-β2GP antibodies were slightly higher in non-LN patients, whereas a higher incidence of IgM-anti-β2GP antibodies were detected in LN patients. Hence detection both ACA and anti-β2GP antibodies along with associated immune parameters were helpful to evaluate their possible association with disease severity in SLE patients. A long term follow up of patients having ACA and anti-β2GP antibodies without thrombotic event is also needed to detect their possible thrombotic event in future along with their clinical presentation.

Maternal-derived antibodies hinder the antibody response to H9N2 AIV inactivated vaccine in the field

The H9N2 subtype avian influenza virus(AIV)inactivated vaccine has been used extensively in poultry farms,but it often fails to stimulate a sufficiently high immune response in poultry in the field,although it works well in laboratory experiments;hence,the virus still causes economic damage every year and poses a potential threat to public health.Based on surveillance data collected in the field,we found that broilers with high levels of maternal-derived antibodies(MDAs)against H9N2 virus did not produce high levels of antibodies after vaccination with a commercial H9N2 inactivated vaccine.In contrast,specific pathogen-free(SPF)chickens without MDAs responded efficiently to that vaccination.When MDAs were mimicked by administering passively transferred antibodies(PTAs)into SPF chickens in the laboratory,similar results were observed:H9N2-specific PTAs inhibited humoral immunity against the H9N2 inactivated vaccine,suggesting that H9N2-specific MDAs might hinder the generation of antibodies when H9N2 inactivated vaccine was used.After challenge with homologous H9N2 virus,the virus was detected in oropharyngeal swabs of the vaccinated and unvaccinated chickens with PTAs but not in the vaccinated chickens without PTAs,indicating that H9N2-specific MDAs were indeed one of the reasons for H9N2 inactivated vaccine failure in the field.When different titers of PTAs were used to mimic MDAs in SPF chickens,high(HI=12 log2)and medium(HI=log 9 log2)titers of PTAs reduced the generation of H9N2-specific antibodies after the first vaccination,but a booster dose would induce a high and faster humoral immune response even of PTA interference.This study strongly suggested that high or medium titers of MDAs might explain H9N2 inactivated vaccine failure in the field.

Role of M₃Muscarinic Acethylcholine Receptor Antibodies as a New Marker in Primary Sjögren Syndrome

Aims: This paper investigates the presence of M3 muscarinic acetylcholine receptor autoantibody present in the serum of patients with primary Sj?gren syndrome (pSS). Main methods: We detected the levels of M3mAChR peptide IgG, PGE2, IL-1β in serum of SS patients using the enzyme-linked immune sorbent assay (ELISA). To measure the quantity of nitrite/nitrate, we used Griess reagent system. Key findings: Titres of M3mAChR antibody in sera from SS patients are significantly enhanced compared to healthy subjects (control). The enhancement of these autoantibodies is accompanied by the increase of the levels of PGE2, IL-1β and nitrite/nitrate in serum. Under in vitro conditions, the synthetic human M3 peptide impaires the increment of M3mAChR antibody but not that of nati-Ro/SSA antibody. In positive anti-Ro/SSA antibody patients, the increment of M3mAChR peptide IgG and the measured pro-inflammatory substances is related. Significance: On this basis, anti M3mAChR peptide IgG can be said to act as a modulator of the immune system and to play a role in the host-chronic increment of proinflammatory substances in SS patients with positive Ro/SSA antibody. This association between the antibody and the pathogenesis of SS disease may result in useful predicting SS.

Neutralizing Antibodies Bloek COVID-19 Virus Binding to Its Reeeptor ACE2

As revealed in a research published lately in Science,two human-origin monoclonal antibodies identified and reproduced by Chinese scientists were able to protect mice from COVID-19.These virus-neutralizing antibodies,acting to block the virus binding to its victim cells,were harvested from the blood of a convedescent donor once infected with COVID-19.

Relationship Between the Efficacy of Low-Dose Glucocorticoids Combined with Tacrolimus in the Treatment of Adult Idiopathic Membranous Nephropathy and the Level of Serum Anti-PLA2R Antibodies

Objective:To further evaluate the efficacy and safety of low-dose glucocorticoids combined with tacrolimus in the treatment of adult idiopathic membranous nephropathy(IMN)in a clinical setting.Methods:We carried out a single-center prospective study of 88 patients with IMN who were admitted into the Affiliated Hospital of Hebei University from January 2019 to December 2021,and the participants were divided into two groups based on their serum anti-PLA2R antibody levels:the negative group and the positive group.46 patients were positive for anti-PLA2R antibodies and 42 were negative.Results:After 6 months of treatment,the serum albumin,cholesterol,and 24h urine protein quantification in the anti-PLA2R negative group improved more significantly compared to the positive group(P<0.05);after 6 months of treatment,the remission rate of the positive group was significantly lower than that of the negative group,and(P<0.05);Conclusion:After treatment with tacrolimus combined with low-dose glucocorticoids,patients with idiopathic membranous nephropathy who were tested positive for anti-PLA2R antibodies had a higher overall remission rate compared those who were tested negative for serum anti-PLA2R antibodies.

Anticardiolipin antibodies do not mediate macrovascular complications of type 2 diabetes

The relationship of anticardiolipin antibodies (ACA), markers of the antiphospholipid syndrome, with vascular complications of diabetes mellitus is polemic. This cross-sectional study assessed the frequency of IgG, IgM, and IgA ACA in type 2 diabetics with and without history of vascular events for the last 5 years, and in healthy controls. ACA were detected by enzyme immunoassay. A total of 73 type 2 diabetics (33 with history of vascular events) and 54 healthy controls were tested. Most diabetics were female (p = 0.003), and older than controls (p 0.09). ACA positivity rates were also similar when diabetics with and without history of vasculopathy were compared (p > 0.47). After adjusting for gender, age, hypertension, and smoking status, a weak but statistically insignificant association between IgM ACA and diabetics with vasculopathy was found (adjusted OR 2.7;95% CI 0.2 - 34.2;p = 0.441). Overall, levels of IgG (r = 0.25;p = 0.005) and IgM (r = 0.23;p = 0.010) ACA were associated with increasing age. In short, the frequency of a positive ACA test in type 2 diabetics (with or without previous macrovasculopathy) was not significant as compared to healthy controls. There was no association of ACA with vascular events in patients with type 2 diabetes.

CLINICAL SIGNIFICANCE OF DETECTING SERUM ANTIBODIES TO NUCLEOPROTEIN AND GLYCOPROTEIN G_2 OF HANTAAN VIRUS IN PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

Antibody blocking enzyme linked immunosorbent assays, respectively detecting antibodies to Hantaan virus nucleoprotein (NPAb) and glycoprotein GZ (G,Ab), were developed using monoclonal antibody L133, L13r3, LV48A and LVZB28B NPAb and GZAb in 291 serum samples from 65 patientswith kemorrkagic fever with renal syudrome (HFRS) were detfrmlned by these methods. The positive rates or NPAb were 90N on day 2-3 and 100 % on day 8-9 arter onset of disease, respectively.NPAb titers Increased during fever period and reached Peak levels during kypotensive and oliguric periods of HFRS. It was suggested that NPAb might be an important component Involved in the immunopathogenlc lin'alrmeut of HFRS and the detection of NPAb might be useful for the early diagnosis or HFRS. The I,osltlve rates and titers of GZAh were very low during the rirst three periods,namely rever, hypoteuslve and ollgurlc periods, and reached high levels during the convalescent period. GRAb titers were negatively related to the I,rotelnurla levels during the course of HFRS. It wasIndicated that GZAb might be the main component or neutralizing autlhodles to Hantaan virus Infection and the efrlclent production or GZAb was a good marker ror predicting the recovery and betterprognosis of HFRS.

^(124)I标记抗体及抗体片段用于胃癌动物模型表皮生长因子受体表达水平

西妥昔单抗(Cetuximab)常用于晚期胃癌肿瘤患者的治疗,获得患者肿瘤表皮生长因子受体(Epidermal growth factor receptor,EGFR)的整体表达水平对于预测西妥昔单抗的疗效尤为重要。本研究拟通过对比研究的方式筛选最符合临床需求的靶向EGFR的探针。本研究基于西妥昔单抗通过酶切法制备了Cet-F(ab')_(2)和Cet-Fab,并偶联CY3-NHS酯(Cyanine 3 NHS ester)得CY3-Cetuximab、CY3-Cet-F(ab')_(2)和CY3-Cet-Fab进行细胞荧光实验以验证亲和力。通过Iodogen(1,3,4,6-四氯-3α,6α-二苯基甘脲)法制备得到3种^(124)I标记的分子探针:^(124)I-Cetuximab、^(124)I-Cet-F(ab')_(2)和^(124)I-Cet-Fab,使用micro-PET/CT分别在探针注射后1 h、3 h、6 h、12 h显像进行对比研究。最后,通过生物学分布实验探究3种探针在各时间点在体内的分布情况,采用两独立样本t检验进行组间比较。西妥昔单抗经过片段化后,亲和力无显著降低。Cetuximab、Cet-F(ab')_(2)和Cet-Fab分子量分别约为150 kDa、100 kDa和50 kDa。经^(124)I标记并纯化后,^(124)I-Cetuximab、^(124)I-Cet-F(ab')_(2)和^(124)I-Cet-Fab放射化学纯度均大于94%,比活度均约为2×10^(4) MBq/μmol。^(124)I-Cetuximab、^(124)I-Cet-F(ab')_(2)和^(124)I-Cet-Fab在生理盐水和胎牛血清(FBS)中稳定性好,体外放置24 h放射化学纯度仍高于90%。Micro-PET/CT显像显示在^(124)I-Cet-Fab尾静脉注射后3 h肿瘤部位明显浓聚,^(124)I-Cet-F(ab')_(2)尾静脉注射后12 h肿瘤部位明显浓聚,而^(124)I-Cetuximab尾静脉注射后12 h肿瘤部位仍无明显显像剂分布。生物学分布结果与micro-PET/CT结果一致。3种正电子探针中,^(124)I-Cet-Fab代谢速度最快,肿瘤最早显象的同时有最少的累积辐射剂量,有一定的临床转化潜力。

乳腺癌患者病理特征与Bcl-2、CXCL13、PAX8表达情况的关系分析

目的分析乳腺癌患者病理特征与B细胞淋巴瘤/白血病-2基因(Bcl-2)、趋化因子配体13(CXCL13)、配对盒基因8抗体(PAX8)表达情况的关系。方法收集2021年1月至2023年1月该院收治的160例乳腺癌患者临床资料。采用免疫组化法对其癌组织与癌旁组织Bcl-2、CXCL13、PAX8表达情况进行检测,并分析3项指标与患者病理特征的关系。结果与癌旁组织比较,癌组织Bcl-2、CXCL13、PAX8阳性率更高,差异有统计学意义(P<0.05)。与雌激素受体(ER)阴性、肿瘤最大径≥3 cm、孕激素受体(PR)阴性患者比较,ER阳性、肿瘤最大径<3 cm、PR阳性患者中Bcl-2高表达占比更高,差异有统计学意义(P<0.05);与无淋巴结转移、Ⅰ~Ⅱ期患者比较,淋巴结转移、Ⅲ~Ⅳ期患者中CXCL13高表达占比更高,差异有统计学意义(P<0.05);与Ⅰ~Ⅱ期、高/中分化、无淋巴结转移患者比较,Ⅲ~Ⅳ期、低分化、有淋巴结转移患者中PAX8高表达占比更高,差异有统计学意义(P<0.05)。ER、PR表达情况与Bcl-2表达情况呈正相关(P<0.05),肿瘤最大径与Bcl-2表达情况呈负相关(P<0.05);临床分期、淋巴结转移情况与CXCL13、PAX8表达情况呈正相关(P<0.05);分化程度与PAX8表达情况呈负相关(P<0.05)。结论乳腺癌患者Bcl-2、CXCL13、PAX8表达情况对疾病的发生和发展具有明显影响,有望成为评估乳腺癌患者病情严重程度的标志物。

2型糖尿病患者维生素D水平与血清CRP、自身免疫抗体及甲状腺功能的相关性

目的研究2型糖尿病患者维生素D水平与血清C反应蛋白(CRP)、自身免疫抗体及甲状腺功能的相关性。方法选取2018年1月至2019年1月于信阳职业技术学院附属医院就诊的150例2型糖尿病患者为研究组,同期选取50例健康体检者作为对照组。检测血清CRP、血清25-羟维生素D[25(OH)D]、胰岛自身免疫抗体和甲状腺功能指标水平并比较两组差异;按血清25(OH)D水平将研究组分为正常组(34例)、不足组(37例)、缺乏组(39例)和严重缺乏组(40例)4个亚组,比较组间血清CRP、胰岛自身免疫抗体阳性率和甲状腺功能指标水平差异;对血清25(OH)D与CRP、胰岛自身免疫抗体阳性率及甲状腺功能指标水平的相关性进行Pearson和Spearman相关性分析;随访3 a,统计甲状腺功能障碍发生率,并绘制受试者工作特征(ROC)曲线分析2型糖尿病患者血清25(OH)D对甲状腺功能障碍的预测效能。结果与对照组比较,研究组血清25(OH)D、TSH水平较低,CRP水平和胰岛自身免疫抗体阳性率较高(P<0.05)。正常组、不足组、缺乏组和严重缺乏组的血清CRP、胰岛自身免疫抗体阳性率和TSH水平比较差异有统计学意义,其中血清CRP、TSH水平逐渐上升(P<0.05)。2型糖尿病患者血清25(OH)D水平与CRP(r=-0.714)、胰岛自身免疫抗体阳性率(r=-0.397)和TSH(r=-0.410)水平均呈负相关(P<0.001)。2型糖尿病患者甲状腺功能障碍发生率为25.33%(38/150),绘制ROC曲线分析血清25(OH)D预测甲状腺功能障碍发生的AUC为0.916。结论2型糖尿病患者血清维生素D与CRP、自身免疫抗体阳性率以及甲状腺功能指标水平存在负相关关系,且对甲状腺功能障碍的发生有一定预测价值。