Antibodies currently comprise the predominant treatment modality for a variety of diseases; therefore, optimizing their properties rapidly and efficiently is an indispensable step in antibody-based drug development. Inspired by the great success of artificial intelligence-based algorithms, especially deep learning-based methods in the field of biology, various computational methods have been introduced into antibody optimization to reduce costs and increase the success rate of lead candidate generation and optimization. Herein, we briefly review recent progress in deep learning-based antibody optimization, focusing on the available datasets and algorithm input data types that are crucial for constructing appropriate deep learning models. Furthermore, we discuss the current challenges and potential solutions for the future development of general-purpose deep learning algorithms in antibody optimization.
Deep Learning ; Humans ; Antibodies/chemistry* ; Algorithms ; Artificial Intelligence ; Drug Development

Objective To investigate the expression and clinical significance of B7-H5 in patients with chro-nic hepatitis B and hepatitis B virus(HBV)-related hepatocellular carcinoma.Methods Enzyme-linked immu-nosorbent assay(ELISA)was used to detect the serum levels of B7-H5 in 104 patients with chronic hepatitis B,28 patients with HBV-related hepatocellular carcinoma and 35 healthy controls.And statistical methods were used to analyze the difference,correlation and diagnostic value of the results.Results The serum levels of B7-H5 in patients with HBV-related hepatocellular carcinoma,patients with chronic hepatitis B and healthy subjects were statistically different(P＜0.05),and the level from high to low was HBV-related liver cancer patients,chronic hepatitis B patients,healthy subjects.The serum level of B7-H5 in chronic hepatitis B pa-tients with negative HBV-DNA was significantly higher than that in healthy subjects(P＜0.01).The level of B7-H5 in patients with chronic hepatitis B was positively correlated with HBV-DNA load(P＜0.05).And the level of B7-H5 in patients with HBV-related hepatocellular carcinoma was positively correlated with HBsAg,HBeAg and AFP levels(P＜0.05).In addition,B7-H5 had diagnostic value for chronic hepatitis B and HBV-related hepatocellular carcinoma(P＜0.01),and the diagnostic value for HBV-related hepatocellular carcino-ma was higher than that for chronic hepatitis B.The level of B7-H5 in patients with HBV-related hepatocellu-lar carcinoma after surgery was significantly lower than that before surgery(P＜0.05).Conclusion Serum levels of B7-H5 is related to the progression of CHB and HBV-related hepatocellular carcinoma,and can be considered as an effective detection index for the auxiliary diagnosis and the judgment of postoperative condi-tion of CHB and HBV-related hepatocellular carcinoma.

Objective: To investigate the effect and safety of ultra-thin oblique posterosuperior auricular fascial flap in the second stage of ear reconstruction. Methods: Fifty-six cases with congenital microtia treated in The Second Affiliated Hospital of Zhengzhou University Medical Cosmetology Department from November 2015 to November 2018 were selected as the research objects. In the first stage, the costal cartilage ear stent was implanted, and in the second stage. The ultra-thin posterior oblique fascia flap was used to cover the stent. And the cranioauricular angle was reconstructed by free skin grafting. Results: 48 cases of the 54 cases completely survived, and 8 cases had hemorrhage after operation. The wounds were healed after dressing change. The postoperative cranioauricular angle was close to the healthy side. Conclusions In the second stage of ear reconstruction, the retroauricular ultra-thin fascial flap method has reliable blood supply, small wound, unswollen reconstructed ears, and good outcome. It is a good choice for covering the ear framework.

Objective:To investigate the value of dynamic contrast-enhanced(DCE)-MRI based textural analysis in differentiating IDH mutated high-grade gliomas from IDH gene wild types.Methods:Twenty-nine patients with high grade gliomas collected from April 2016 to December 2019 in First People's Hospital of Changzhou were assessed retrospectively, including 10 patients with IDH mutation and 19 patients with IDH gene wild type. All patients underwent DCE, conventional plain and enhanced MR scanning. Omni Kinetics software was used to perform DCE-MRI data processing, volume transfer constant (K trans), ratio constant of tracer refluxing from tissue to plasma (Kep), extravascular extracellular space per unit volume of tissue (Ve), blood plasma volume (Vp) and area under the gadolinium concentration-time curve (AUC) were obtained. Five commonly used textural features, including Energy, Entropy, Inertia, Correlation, and Inver Difference Moment (IDM), were generated based on gray-level co-occurrence matrices. The independent samples t test (normal distributionand equal variance) or Mann-Whitney rank sum test (abnormal distribution or unequal variance) was used to compare the differences in textural features of DCE-MRI parameters between IDH mutated group and IDH gene wild type group. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of textural features of DCE-MRI parameters in differentiating IDH mutated high-grade gliomas from IDH gene wild types for statistically significant textural features. Results:Entropy of K trans and Ve for IDH mutated group were 5.368±1.458 and 6.698±1.081, respectively; while the corresponding values were 7.334±1.385 and 8.213±1.320 for IDH gene wild type group, respectively. The difference between the two groups was statistically significant ( t values were-3.570, -3.113, P values were 0.001, 0.004, respectively). Inverse difference moment of K trans and Ve for IDH mutated group were 0.567±0.147 and 0.417±0.106, respectively; while for IDH gene wild type group, the values were 0.393±0.119 and 0.296±0.101, respectively. The difference between the two groups was statistically significant ( t values were 3.452, 3.014, P values were 0.002, 0.006, respectively). In all textural features, the area under the ROC curve of entropy of K trans was the largest (0.874), and the sensitivity was the highest (100%), and the specificity of IDM of Ve was the highest (94.7%). Conclusion:Textural analysis of DCE-MRI can help to differentiate IDH mutated high-grade gliomas from IDH gene wild types.

Objective: To observe the conditions of the eighth costal cartilage in ear reconstructed patients, and accomplish individualized aesthetic helix fabrication according to the texture and features of the cartilage. Methods: From May 2013 to May 2016, the conditions of the eighth costal cartilages in 415 patients who received ear reconstruction with autogenous costal cartilage in our hospital were analyzed, during which, the length, width, flexibility, and plasticity that were closely related with the reconstruction of the helix attracted predominant attentions. During the surgery, based on the features of the above-mentioned aspects, 4 different methods were used to achieve reasonable length and strength of the helix as well as natural jointing between the helix and ear lobe. Results: Four possible methods of using the eighth costal cartilage to reconstruct the helix were summarized and an autogenous costal cartilage framework that was individualized and with natural appearance was obtained. Conclutions According to the conditions of the eighth costal cartilage, a more satisfactory appearance of the reconstructed ear than ever before is obtained by choosing relevant helix fabrication programs.

Objective To investigate the association of polymorphisms in the filaggrin (FLG)gene with the occurrence and clinical phenotypes of atopic dermatitis (AD).Methods A questionnaire survey was carried out to collect data from 261 patients with AD,including the diagnosis of allergic rhinitis and asthma,and the severity of AD.Mixed food allergen screening test and mixed inhaled allergen screening test were performed in a part of patients,so was the detection of total serum IgE and eosinophil cationic protein (ECP).Among the above AD patients and 276 healthy controls,17 polymorphic sites in exon 3 of the FLG gene,including R444G,T454A,P478S,H519N,D836D,S1482Y,A1805V,R1891Q,1961Q,S2166S,Y2194H,H2330H,D2339N,S2366T,E2398Q,K2444E and E2652D,were genotyped by overlapping PCR and DNA sequencing.Results Binary logistic regression analysis and chi-square test showed no correlations between the 17 polymorphic sites in the FLG gene and the occurrence of AD (all P ＞ 0.05).However,the H519N polymorphic site was associated with AD complicated by asthma (x2 =8.680,P =0.011),and the AA genotype of H519N could increase the risk of asthma in the AD patients (P =0.004,OR =1.061,95％ CI:1.016-1.109).The S2366T and K2444E polymorphic sites were associated with food sensitization in the AD patients (x2 =6.520,6.121,P =0.038,0.047,respectively),and the GG + CG genotype of S2366T (P =0.012,OR =1.396,95％ CI:1.054-1.849)and its G allele (P =0.037,OR =1.350,95％ CI:1.008-1.807) both could increase the risk of food sensitization in the AD patients.Similarly,the AA + GA genotype of K2444E (P =0.013,OR =1.393,95％ CI:1.049-1.850)and its G allele (P =0.028,OR =1.380,95％ CI:1.025-1.857) could increase the risk of food sensitization in the AD patients.Conclusions The FLG polymorphisms may be predisposing factors for some AD-related clinical phenotypes in Chinese Han population.The H519N gene may be associated with AD complicated by asthma,and the S2366T and K2444E genes may be related to food sensitization in AD patients.

ObjectiveTo understand the difference in characteristics between juvenile dermatomyositis (JDM) and adult dermatomyositis (ADM).Methods Sixty-one cases of JDM were retrospectively analyzed and compared with 30 cases of ADM. Results The rashes were presented as the initial symptom in all expect one JDM patients. Gottron’s papules were presented in 90% JDM patients and 67% ADM patients. Calcium deposition was presented in 7% JDM patients and none of the ADM patients. The cardiovascular system was involved in 7 % JDM patients and 23% ADM patients. Cancer occurred in none of JDM patients and 13% ADM patients. In JDM and ADM patients, the ratio of elevated muscle enzymes from highest to lowest was LDH, hy-droxybutyric acid enzyme, CK-MB, AST, and CK. The positive ratio of magnetic resonance (MRI) all exceeded 80% in JDM and ADM groups. Two cases died in each group.Conclusions The clinical presentation of JDM is basically the same as that of ADM. The most common initial symptoms in JDM are skin rashes and Gottron's papules. Cardiovascular disease and cancer are less in JDM than in ADM. MRI is valuable in the diagnosis of DM.

Objective To investigate the prevalence and progression process of atopic diseases in adolescents, and to assess their relationship with filaggrin(FLG)mutations. Methods Totally, 334 adolescents aged from 11 to 19 years in a middle school in shanghai were enrolled into this study. A clinical interview was carried out to determine the prevalence of atopic diseases (such as ichthyosis, atopic dermatitis (AD), asthma, rhinitis, etc)in these subjects. Peripheral blood samples were collected from 285 out of the 334 adolescents for screening for common FLG mutations, including 3321delA and K4671X. Five years later, these adolescents were followed up for reevaluation of clinical presentations of atopic diseases. Statistical analysis was carried out by the chi-square test with the SPSS 20.0 software. Results As the baseline survey showed, 19 (5.69%)of the 334 adolescents had AD, 14 (4.19%)had ichthyosis vulgaris, 36(10.78%)had allergic rhinitis, and 4(1.20%)had asthma. FLG mutations were observed in 24(8.42%) of the 285 adolescents. Five years later, 265 adoscents completed the follow-up, and 69 (20.66%)were lost to follow-up. Of the 265 adolescents reevaluated, 13(4.89%)had AD, 15(5.64%)had ichthyosis vulgaris, 27(10.15%)had allergic rhinitis, and 1 (0.38%)had asthma. By the time the second survey was performed, 6 out of the 19 patients initially diagnosed with AD had achieved complete regression, 13 had experienced a marked decrease in SCORing atopic dermatitis (SCORAD)score, and symptoms had disappeared in 9 of the 36 patients initially diagnosed with allergic rhinitis. The frequency of FLG mutations was 10.0%in patients with AD, 55.6%in those with ichthyosis, and 40.0%in those with both AD and ichthyosis, and the development of ichthyosis was associated with FLG mutations(P<0.001). Conclusions The frequency of common FLG mutations was 8.42%in these adolescents. FLG gene may be a semidominant gene associated with ichthyosis vulgaris, and multiple factors influence its expression.

Objective Previous literatures have reported favorable results in ear reconstruction.Many details in fabricating cartilage framework have been paid much attention.Whereas,many patients still complain about unnatural contours.This article is to provide a new technique to solve some of the problems.Methods A total of 253 patients underwent reconstruction using the modified technique from 2011 to 2014.In fabricating the complex of antihelix,the authors modified the prior method.Instead of sculpting a sharp Y-shaped cartilage graft for projecting the prominent structures,the authors increased the width of the superior crura,sculpted a gentle slope in the both sides of superior crura,simultaneously carved a groove in the base frame to join with the carved attachment smoothly.The width of inferior crura was about one third of the superior crura width,and the iuferior crura was narrow and prominent.A gentle slope was carved on the antihelix and a groove was carved on the base frame for the antihelix to sit on.Results Four cases have been selected to illustrate the favorable results of this technique.Due to the modified details,the superior crura,inferior crura,antihelix and the structures around them,in these cases,show natural contours,and provide a coordinated figure to the integrity of reconstructed ear.Conclusions Antihelix complex is one of the most important structures for creating a natural auricle.The natural superior and inferior crura and antihelix can enhance theimpression of a harmonious shape,and acquire an increased satisfaction for both patients and surgeons.

To investigate the relationship among serum vascular endothelial cells(VE) -cadherin, advanced glycation end-products( AGE), and atherosclerotic lesion. 20 healthy subjects and 60 patients with diabetes mellitus,including 30 patients with carotid atherosclerosis (CI), were enrolled.Soluble VE-cadherin and AGE were determined using the enzyme-linked immunosorbent method (ELISA). The relationships among the concentration of soluble VE-cadherin, AGE, and the course of the disease, blood glucose, and blood lipid levels were analyzed with multivariant stepwise regression analysis. The levels of serum VE-cadherin and AGE in the patients with diabetes and CI were higher than those in control group( P＜0. 05 ). There was a significant difference in VE-cadherin between the diabetes group and the CI group( P＜0. 05 ). Serum VE-cadherin levels were positively correlated with serum AGE levels(r = 0. 69, P＜0. 01 ). AGE levels were positively correlated with the diabetes duration ( r = 0. 31, P =0. 02 ). The levels of serum VE-cadherin in diabetic patients are positively correlated with their serum AGE levels. The VE-cadherin seems to play an important role in the development of atherosclerosis caused by AGE.