ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Humans ; Thymoma/surgery* ; Thyroid Neoplasms ; Thymus Neoplasms/surgery* ; Neoplasms, Glandular and Epithelial

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
Adult ; Aged ; Animals ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/genetics* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Kinesins/metabolism* ; Liver Neoplasms/pathology* ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein Binding ; RNA, Small Interfering/metabolism* ; Survival Analysis ; Tumor Burden ; Wnt Signaling Pathway ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism*

Objective To explore the correlation and diagnostic value of serum visfatin (visfatin),high sensitive C reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) in patients with different types of angina pectoris.Methods Eighty-four patients with angina pectoris who were treated in the Eighth hospital of Wuhan from January 2013 to December 2016 were selected as the research subjects,the patients were divided into stable angina pectoris (SAP) group with 39 cases and unstable angina pectoris (UAP) group with 45 cases according to the classification criteria of angina pectoris,Thirty-seven healthy volunteers in the outpatient department of the same period were selected as the control group.To compare the levels of serum visfatin,hs-CRP and TNF-alpha in three groups,analyze the correlation between the levels of serum visfatin and hs-CRP and TNF-alpha levels in patients with angina pectoris,and analyze the diagnostic value of the levels of serum visfatin,hs-CRP,TNF-α and plasma oxidized low density lipoprotein (Ox-LDL) by ROC curve.Results There were no significant differences in fasting blood glucose,uric acid,creatinine,total cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) among the three groups (all P＞0.05).The systolic pressure (SBP) was (134.27± 11.96) mmHg and diastolic pressure (DBP) was (84.23 ± 7.15) mmHg in SAP group,the SBP was (135.98±12.33) mmHg and DBP was (84.47±7.22) mmHg in UAP group,which were all higher than SBP ((121.49±9.97)mmHg)and DBP ((77.38±6.94)mmHg) in the control group (all P＜0.05),but there was no significant differences between the SAP group and the UAP group (all P＞0.05).The level of visfatin in UAP group was (6.57± 1.36) μg/L,which was higher than that in SAP group ((4.62 ± 1.08) μg/L) and in control group((4.27± 1.03)μg/L) (all P＜0.05),but there was no significant differences between the SAP group and the control group (P＞0.05).The level of serum hs-CRP,TNF-α and plasma Ox-LDL were (12.38±2.63) mg/L,(4.35±0.28) ng/L and (617.32±53.48) μg/L in UAP group,and the level of serum hs-CRP,TNF-α and plasma Ox-LDL were (8.29 ± 1.74) mg/L,(1.82 ± 0.34) ng/L and (418.57±43.85) μg/L in SAP group,which were higher than hs-CRP (4.06±1.52) mg/L,TNF-α (0.98 ±0.13) ng/L,Ox-LDL (213.64±32.83) μg/L in control group(all P＜0.05),and the UAP group was higher than that in the SAP group (all P＜0.05).The level of serum visfatin in group SAP and group UAP had no significant correlation with age,body mass index,SBP,DBP,fasting blood glucose,uric acid,creatinine,total cholesterol,triglyceride,HDL cholesterol,low density lipoprotein cholesterol (all P ＞ 0.05).The serum visfatin level was positively correlated with serum hs-CRP,TNF-alpha level and plasma Ox-LDL level in SAP group.(r=0.687,0.634,0.656,all P＜0.05).The serum visfatin level was positively correlated with the serum hs-CRP,TNF-a level and Ox-LDL level in UAP group (r =0.721,0.652,0.673,all P＜ 0.05).ROC curve analysis showed that the levels of serum visfatin,hs-CRP,TNF-α and plasma Ox-LDL were all near 0.7,and the sensitivity and specificity were all above 0.6 identification of different types of angina pectoris.Conclusion The level of serum visfatin in patients with UAP was significantly higher than that of SAP patients,its level is related to serum hs-CRP,TNF-alpha and plasma Ox-LDL levels,the four indexes have a certain predictive value for different types of angina pectoris,and can provide reference for different types of angina.

Objective To study the levels of antibodies against bordetella pertussis among pregnant women and neonates in Beijing. Method From December 2016 to March 2017, pregnant women and their newborns from three women and children′s hospitals in Beijing were enrolled in this study. 3 ml of venous blood from the mothers and 3 ml of umbilical cord blood from neonates were drawn.Pertussis bacillus IgG antibody (PER-IgG) and pertussis toxin IgG antibody (PT-IgG) were tested using enzyme-linked immunosorbent assay. &chi;2 test was used to compare the positive rate of pertussis IgG antibodies in maternal and cord blood in the three hospitals. Correlational analyses of the antibodies levels in each hospital were conducted. The demographic characteristics, history of cough during pregnancy and history of DTaP vaccination of the mothers were collected via questionnaires. Result A total of 612 pairs of venous blood and cord blood samples were collected, including 4 mothers delivered twins and 616 cases of cord blood sample were collected. No history of pertussis were found in the 612 mothers. Among the 616 cases of umbilical cord blood, positive rate of PER-IgG was 13.3％ (82/616), positive rate of PT-IgG was 0.5％ (3/616). Among 612 cases of venous blood from the mothers, positive rate of PER-IgG was 7.7％ (47/612), positive rate of PT-IgG was 0.3％ (2/612). Positive rates of PER-IgG and PT-IgG in the mothers′ venous blood were not correlated with their residences (P=0.676 and 0.544). Positive rates of PER-IgG (r=0.842, P<0.001) and PT-IgG (r=0.619, P<0.001) in the mothers′ blood were positively correlated with the positive rate in umbilical cord blood. Conclusion This study shows that the positive rate of PER-IgG is very low in the maternal and umbilical cord blood in Beijing. Positive correlations of PER-IgG and PT-IgG between mother and umbilical cord blood were existed. Most mothers and their newborns do not have enough protection against pertussis.

Objective: To assess the trend of lifestyle changing instruction for acute myocardial infarction (AMI) patients at discharge in China from 2001-2011. Methods: Based on national representative data of China PEACE retrospective AMI study and the number of instructions AMI patients received at discharge, our research was classified into 3 groups: no instruction group, (1-2) instructions group and (3-5) instructions group. We described the instruction rates in different groups with 10-year trend and no instruction status in 5 regions of eastern urban, central/western urban, eastern rural, central rural, and western rural. In addition, we reported the instruction rates of diet consulting, exercise consulting, blood lipid evaluation, smoking cessation, and weight control with 10-year trend. Results: A total of 16100 medical records of AMI from 162 hospitals were enrolled. No instruction rates at discharge were 76.6%, 65.7% and 54.4% in 2001, 2006 and 2011, respectively, Ptrend<0.001. The proportion for receiving (1-2) instruction(s) at discharge increased from 23.2% in 2001 to 42.9% in 2011, Ptrend<0.001; the rate for receiving (3-5) instructions was 2.7% in 2011.No instruction rates in 5 regions were from 47.1% to 69.5%; no instruction rates in central and western rural regions had little changes during the 10-year period, Ptrend=0.11 and Ptrend=0.10, respectively; no instruction rates in the rest 3 regions showed decreasing trend, all Ptrend<0.001. Most of the single instruction rates for lifestyle changing increased from 2001 to 2011, diet consulting were 16.6%, 27.8%, and 38.3% respectively, Ptrend<0.001; exercise consulting were 9.2%, 10.9% and 14.3% respectively, Ptrend<0.001; from 2001 to 2011, blood lipids evaluation was increased from 0.9% to 11.9%; smoking cessation increased from 2.2% to 8.8%, both Ptrend<0.001; however the weight control rate was 1.3% in 2011, which was had little change within 10 years, Ptrend=0.32.

AIM:To assess the changes in higher order aberrations after wavefront guided femtosecond laser assisted laser in situ keratomileusis ( FS-LASIK ) for moderate to high astigmatism.?METHODS: Eighty-eight eyes of 50 myopia patients with moderate to high astigmatism were included in this prospective study. There were 51 eyes with moderate astigmatism (≥-1. 50D and <-3. 00D) and 37 eyes with high astigmatism (≥-3. 00D). All patients underwent wavefront guided FS-LASIK. Uncorrected distance visual acuity ( UDVA ) , corrected distance visual acuity (CDVA), keratometry, central corneal thickness ( CCT)and higher order aberrations ( HOAs ) were evaluated before operation and 3mo postoperatively.?RESULTS:At the 3mo after operation, the mean UDVA of all eyes was above 20/20, better than before operation (P<0. 05), but CDVA remained unchanged (P=0. 36) and no eyes lost ≥2 lines of CDVA. Mean astigmstism of 85 eyes ( 97％) was reduced below - 1. 00D, mean astigmatism of 70 eyes ( 80％) was reduced below-0.50D(P<0. 05). The average corneal curvature was flatter by 3. 81 ± 1. 97D and CCT was reduced by 78. 66 ± 37. 22μm, postoperatively (P<0. 05). Coma and trefoil aberrations remained unchanged(P=0. 078, 0. 065). The spherical aberration, secondary astigmatism and the HOA root mean square ( RMS ) increased from 0. 19 ± 0. 06, 0.05±0. 02 and 0. 42±0. 12, preoperatively to 0. 32± 0. 17, 0. 26 ± 0. 08 and 0. 78 ± 0. 28 ( P < 0. 05 ), postoperatively.?CONCLUSION: Wavefront-guided FS-LASIK is a safe and effective option for the patients with moderate to high astigmstism although parts of HOAs increased.

Object To verify and evaluate the performances of Sysmex XN-9000 hematology analyzer under body fluid mode when used for peritoneal and pleural fluids detection.Methods According to the guidance of ICSH, Sysmex XN-9000 hematology analyzer under body fluid mode had its performances verified on background counting, carryover, precision, linear range and etc of RBC-BF and TC-BF, and then was compared with microscopy on RBC-BF, TC-BF, PMN％, MN％, N％, L％, M％and E％.Results The RBC-BF and TC-BF had the background counting being 0.00, carryover being 0.00％and 0.07％ respectively, coefficients of variation (CV) of within-run precision being from 0.96％to 17.89％as well as from 2.19％to 10.33％respectively, CV of between-run precision being from 3.34％to 4.73％as well as from 8.33％to 10.75％resptctively, and the linear ranges being (0～5) ×1012/L and (0～20) ×109/L respectively. There was a high correlation between Sysmex XN-9000 hematology analyzer and microscopy when detecting RBC-BF, TC-BF, PMN％, MN％, N％, L％, M％and E％. The Spearman rank correlation coefficients (rs) were 0.977, 0.995, 0.863, 0.929, 0.926, 0.949, 0.965 and 0.816 (P<0.05), and there were statistical significances between the correlations. Bland-Altman bias analysis on the analyzer and microscopy showed that RBC-BF had the bias (4.6％) lower than that (5.6％) of TC-BF;MN％had the bias (-2.0％) lower than that (4.2％) of PMN％;L％, N％, M％and E％had the bias being-0.5％, 4.4％,-5.9％and-1.6％respectively, which were all met the requirements of the manufacturer.Conclusion Sysmex XN-9000 hematology analyzer under body fluid mode proves its performances for routine detection of peritoneal and pleural fluids.