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Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.
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Objective To explore the associations of non-alcoholic fatty liver disease(NAFLD)with the prevalence,severity,and prognosis of coronary heart disease(CHD). Methods A total of 512 hospitalized patients undergoing coronary angiography in our department from June 2013 to June 2015 were enrolled.Fatty liver was judged by ultrasound screening,and Gensini score was calculated according to the result of coronary angiography.Then the independent predictors of CHD were analyzed.The association between NAFLD and cardiovascular endpoints was analyzed during prospective follow-up among 276 CHD patients. Results The CHD prevalence was 76.8% in NAFLD group and 50.7% in non-NAFLD group(P=0.000),the number of target vessels was 2(1,3)and 1(1,3)(P=0.019),and the Gensini score was(29.02±27.62)and(24.04±20.18)(P=0.022),respectively.NAFLD was an independent predictor of CHD(OR=2.28,95%CI=1.54-3.56,P0.1).Cox regression analysis showed that NAFLD was not a predictor of cardiovascular endpoints in patients with CHD(HR=0.95,95%CI=0.62-1.58,P=0.691).Conclusion NAFLD is an independent predictor of CHD,and it is related to severity of coronary artery stenosis.However,it can not predict the clinical outcomes of patients with CHD.
Subject(s)
Humans , Coronary Angiography , Coronary Disease , Non-alcoholic Fatty Liver Disease , Prevalence , Prognosis , Prospective Studies , Risk FactorsABSTRACT
OBJECTIVE: To analyze studies published in journals included in PubMed in terms of randomized controlled trials (RCTs) examining the therapeutic effect of acupuncture for simple obesity, so as to provide a reference for subsequent RCT-related designs and results. METHODS: RCT literature about acupuncture treatment of simple obesity from the PubMed database and from 2000 to 2016 was retrieved by using keywords of "obesity" "fat" "acupuncture" "joint application of acupuncture and herbal medicine" or "auricular point" "electroacupuncture", "acupoint application", or "cupping", followed by screening, extraction and evaluation of the design methodology and outcomes using Consolidated Standards for Reporting of Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA). RESULTS: Fourteen articles from six countries in Asia examining the therapeutic effect of acupuncture in the treatment of simple obesity mainly by using acupoints of the Stomach Meridian were included. Generally, acupuncture was found to be more effective than sham acupuncture. However, PubMed did not include any RCTs comparing acupuncture with western medicine for weight loss and many problems (as details of needling manipulation, etc.) remained in the the research reports available in the database. CONCLUSION: All the existing RCTs generally affirm the positive efficacy of acupuncture for simple obesity, but high-quality RCTs, particularly those comparing acupuncture with western medicines for weight loss are lacking.
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Objective To explore the relationship between serum uric acid (SUA) level and coronary heart disease(CHD) in male and female patients. Methods A total of 760 hospitalized patients undergoing coronary angiography in our department from June 2013 to June 2017 were enrolled. Gensini score was calculated according to the result of coronary angiography,and SUA was tested.Patients were divided according to SUA quartiles. The relationship between SUA level and the prevalence of CHD in male and female patients was analyzed. Results Among females,there was significant difference in SUA level between patients with and without CHD (t=4.415,P=0.000). Univariate logistic regression analysis showed that SUA level was independently associated with CHD (OR=1.32,95%CI:1.12-1.58,P=0.002). The prevalence of CHD was 31.2%,52.6%,47.4%,and 59.7%,respectively,in four quartile groups (χ=13.652,P=0.003);in addition,female patients displayed significantly higher prevalence of CHD in the quartile 2 (P=0.007),3(P=0.038),and 4(P=0.000) groups than in quartile 1 group. Among female patients with CHD,there were significant differences in number of target vessels (Z=4.627,P=0.008),number of lesion vessels (χ=18.522,P=0.005),and Gensini score (Z=3.683,P=0.029) in four groups. The Gensini scores of coronary artery were significantly higher in the quartile 4 group than in quartile 1 (P=0.012) and 2 (P=0.014) groups. Multiple linear regression analysis showed that there was a dose-response relationship between SUA level and Gensini score (B=1.105,SE=0.365,P=0.003). Among males,however,there was no significant difference in SUA level between patients with and without CHD(t=1.271,P=0.205). The prevalence of CHD in four quartile groups was 77.9%,69.0%,61.7%,and 79.6%,respectively,showing no significant difference(χ=4.514,P=0.211). Conclusion sSUA is an independent risk fact for female CHD patients. High SUA level is correlated with severity of CHD only in women.
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Objective To investigate the correlation between CYP2C19 gene polymorphism and elderly cerebral infarction.Methods Two polymorphisms including rs4244285 and rs4986893 of the CYP2C19 gene were detected by gene chip technology in 72 elderly patients with acute cerebral infarction (stroke group) and 77 otherwise healthy controls. The clinical data and the polymorphism distribution of CYP2C19 were compared,and the potential association between genetic polymorphism and cerebral infarction was analyzed by Logistic regression.Results The frequencies of rs4244285 GG (45.83% vs. 63.64%,Χ =4.766,P=0.029) and rs4244285 A allele (34.03% vs. 22.73%,Χ =4.695,P=0.030) were significantly higher in stroke group than in control group. There were no significant differences in the distribution of the alleles of rs4986893 or the rs4244285 GA and AA between these two groups (all P>0.05). After the conventional cerebrovascular risk factors including gender,age,body mass index,smoking,and total cholesterol were adjusted,Logistic regression analysis showed that rs4244285 A allele significantly increased the stroke risk [the additive model AA vs. GG:OR=2.564,95%CI=1.181-5.566,P=0.017;the dominant model AA/AG vs. GG:OR=2.763,95%CI=1.343-5.685,P=0.006].Conclusion CYP2C19 genetic polymorphism may be associated with the increased risk of cerebral infarction in the elderly,although future well-designed studies with larger sample sizes are warranted.
Subject(s)
Aged , Humans , Alleles , Brain Ischemia , Genetics , Case-Control Studies , Cerebral Infarction , Genetics , Cytochrome P-450 CYP2C19 , Genetics , Gene Frequency , Genetic Predisposition to Disease , Genotype , Polymorphism, Single Nucleotide , Stroke , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To assess the diagnostic efficiency of OMOM capsule endoscopy (CE) in a group of patients with different indications.</p><p><b>METHODS</b>Data from 89 consecutive patients (49 males, 40 females) with suspected small bowel disease who underwent OMOM CE (Jinshan Science and Technology Company, Chongqing, China) examination were obtained by retrospective review. The patients' indications of the disease consisted of the following: obscure gastrointestinal bleeding (OGIB), abdominal pain or diarrhea, partial intestinal obstruction, suspected inflammatory bowel disease, tumor of unknown origin, hypoproteinemia, constipation, weight loss, and elevated tumor markers.</p><p><b>RESULTS</b>CE failed in one patient. Visualization of the entire small bowel was achieved in 75.0%. Capsules were naturally excreted by all patients. The detection rate of abnormalities was 70.5% for patients with suspected small bowel disease, and the diagnostic yield for patients with OGIB was higher than that for patients with abdominal pain or diarrhea (85.7% vs 53.3%, P<0.005). Angiodysplasia was the most common small bowel finding. Active bleeding sites were noted in the small intestine in 11 cases.</p><p><b>CONCLUSION</b>OMOM CE is a useful diagnostic tool for the diagnosis of variably suspected small bowel disease, whose diagnostic efficiency is similar to that of the Pillcam SB (small bowel) CE (Given Imaging, Yoqneam, Israel).</p>