BACKGROUND: Lung cancer is the leading cause of cancer-related death, of which non-small cell lung cancer (NSCLC) is the most common type. Immune checkpoint inhibitors (ICIs) have now become one of the main treatments for advanced NSCLC. This paper retrospectively investigated the effect of peripheral blood inflammatory indexes on the efficacy of immunotherapy and survival of patients with advanced non-small cell lung cancer, in order to find strategies to guide immunotherapy in NSCLC. METHODS: Patients with advanced non-small cell lung cancer who were hospitalized in The Affiliated Cancer Hospital of Nanjing Medical University from October 2018 to August 2019 were selected to receive anti-PD-1 (pembrolizumab, sintilimab or toripalimab) monotherapy or combination regimens. And were followed up until 10 December 2020, and the efficacy was evaluated according to RECIST1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were followed up for survival analysis. A clinical prediction model was constructed to analyze the predictive value of neutrophil-to-lymphocyte ratio (NLR) based on NLR data at three different time points: before treatment, 6 weeks after treatment and 12 weeks after treatment (0w, 6w and 12w), and the accuracy of the model was verified. RESULTS: 173 patients were finally included, all of whom received the above treatment regimen, were followed up for a median of 19.7 months. The objective response rate (ORR) was 27.7% (48/173), the disease control rate (DCR) was 89.6% (155/173), the median PFS was 8.3 months (7.491-9.109) and the median OS was 15.5 months (14.087-16.913). The chi-square test and logistic multi-factor analysis showed that NLR6w was associated with ORR and NLR12w was associated with ORR and DCR. Further Cox regression analysis showed that NLR6w and NLR12w affected PFS and NLR0w, NLR6w and NLR12w were associated with OS. CONCLUSIONS In patients with advanced non-small cell lung cancer, NLR values at different time points are valid predictors of response to immunotherapy, and NLR <3 is often associated with a good prognosis.
Aged ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Biomarkers/blood* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Female ; Humans ; Immunotherapy/methods* ; Inflammation/blood* ; Leukocyte Count ; Lung Neoplasms/pathology* ; Lymphocytes ; Male ; Middle Aged ; Neutrophils ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Survival Analysis ; Treatment Outcome

A highly sensitive monoclonal antibody against aflatoxin B_1(AFB_1) was prepared and an indirect competition enzyme-linked immunosorbent assay(ic-ELISA) was established based on the antibody which was used for high-throughput and rapid screening of AFB_1 contamination in Chinese herbal medicines to ensure the safety of medication. In this study, the structure of AFB_1 was modified by improved oxime method, and the carrier protein was coupled by EDC-NHS method to obtain the complete antigen of AFB_1, which was more convenient and environmental friendly. The Balb/c female mice were immunized using increasing the immunization dose and various ways of injection, and finally the AFB_1 monoclonal antibody was prepared. The AFB_1 monoclonal antibody belongs to IgG_(2 b) immunoglobulin by identifying its immunological characteristics, and its sensitivity(IC_(50)) can reach 0.15 μg·L~(-1), and the affi-nity is 2.81×10~8 L·mol~(-1). The cross-reaction rates of AFB_2, AFG_1, and AFG_2 were 35.07%, 8.75%, and 1.15%, respectively, and there was almost no cross-reactivity with other mycotoxins. Based on the high sensitivity and specificity of the antibody, an ic-ELISA method was established and applied to the determination of AFB_1 contamination in Ziziphi Spinosae Semen. According to the matrix matching standard curve, the linear concentration range for AFB_1 was 0.05-0.58 μg·L~(-1)(R~2=0.992), the recoveries were 88.00%-119.0%, and the detection limit was 1.69 μg·kg~(-1). The AFB_1 in 33 batches of Ziziphi Spinosae Semen samples was determined by ic-ELISA, and the contamination level was 3.62-206.58 μg·kg~(-1). The linear correlation coefficient between the detection results of ic-ELISA and UHPLC-MS/MS was 0.996, and there were no false positive and false negative cases. It indicates that the established ic-ELISA is accurate and reliable, and could provide a simple and effective technique for fast screening of AFB_1 contamination in Ziziphi Spinosae Semen, and also could be considered as the reference for the detection and monitoring of AFB_1 contamination in other Chinese herbal medicines.
Aflatoxin B1 ; analysis ; Animals ; Antibodies, Monoclonal ; Drug Contamination ; Enzyme-Linked Immunosorbent Assay ; Female ; Mice ; Semen ; chemistry ; Tandem Mass Spectrometry

Glycosylation is one of the common post-translational modifications of proteins to regulate the ability of tumor invasion, metastasis and tumor heterogeneity by interacting with glycan-binding proteins such as lectins and antibodies. Glycan microarray can be constructed by chemical synthesis, chemical-enzyme synthesis or natural glycan releasing. Glycan microarray is an essential analytical tool to discover the interaction between glycan and its binding proteins. Here we summarize the standard techniques to construct glycan microarray for the application in cancer vaccine, monoclonal antibody and diagnostic markers.
Antibodies, Monoclonal ; Glycosylation ; Lectins/metabolism* ; Microarray Analysis ; Neoplasms ; Polysaccharides

Conventional immunotherapy (IT) for optimal control of respiratory and food allergies has been fraught with concerns of efficacy, safety, and tolerability. The development of adjuvants to conventional IT has potentially increased the effectiveness and safety of allergen IT, which may translate into improved clinical outcomes and sustained unresponsiveness even after cessation of therapy. Novel strategies incorporating the successful use of adjuvants such as allergoids, immunostimulatory DNA sequences, monoclonal antibodies, carriers, recombinant proteins, and probiotics have now been described in clinical and murine studies. Future approaches may include fungal compounds, parasitic molecules, vitamin D, and traditional Chinese herbs. More robust comparative clinical trials are needed to evaluate the safety, clinical efficacy, and cost effectiveness of various adjuvants in order to determine ideal candidates in disease-specific and allergen-specific models. Other suggested approaches to further optimize outcomes of IT include early introduction of IT during an optimal window period. Alternative routes of administration of IT to optimize delivery and yet minimize potential side effects require further evaluation for safety and efficacy before they can be recommended.
Antibodies, Monoclonal ; Asian Continental Ancestry Group ; Base Sequence ; Cost-Benefit Analysis ; Food Hypersensitivity ; Humans ; Immunization ; Immunotherapy ; Probiotics ; Recombinant Proteins ; Treatment Outcome ; Vitamin D

BACKGROUND/AIMS: To evaluate a new monoclonal antibody for Helicobacter pylori urease in gastric tissue. METHODS: A total of 107 volunteers were enrolled. All subjects underwent a 13C-urea breath test and esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia. Six biopsy specimens in the gastric antrum and body were obtained for a rapid urease test and histology. The new monoclonal antibody-based H. pylori urease test (HPU) was performed to rapidly and qualitatively detect urease in two biopsy specimens. RESULTS: H. pylori infection was diagnosed in 73 subjects. The sensitivity and specificity of the HPU was 89% and 74%, respectively. The subjects were divided into two groups: one with true-positive and true-negative HPU results (n = 90) and the other with false-positive and false-negative HPU results (n = 17). Across all subjects, ammonia levels were 900.5 +/- 646.7 and 604.3 +/- 594.3 mumol/L (p > 0.05), and pH was 3.37 +/- 1.64 and 2.82 +/- 1.51 (p > 0.05). Sensitivity was higher in the presence of atrophic gastritis or intestinal metaplasia. CONCLUSIONS: HPU detected H. pylori in approximately 10 min. Gastric aspirate ammonia and pH levels did not affect the test results. Sensitivity was good in the presence of atrophic gastritis or intestinal metaplasia.
Adult ; Antibodies, Monoclonal/*immunology ; Bacterial Proteins/*analysis/immunology ; Biomarkers/analysis ; Biopsy ; False Negative Reactions ; False Positive Reactions ; Female ; Gastritis, Atrophic/*diagnosis/microbiology ; Helicobacter Infections/*diagnosis/microbiology ; Helicobacter pylori/*enzymology/immunology ; Humans ; *Immunologic Tests ; Male ; Metaplasia ; Middle Aged ; Predictive Value of Tests ; Pyloric Antrum/*microbiology/pathology ; Reproducibility of Results ; Time Factors ; Urease/*analysis/immunology ; Workflow

OBJECTIVETo construct and identify the monoclonal antibodies against von willebrand factor cleaving protease(ADAMTS13), and to study their biological function.

METHODSBALB/c mice were immunized by purified recombinant ADAMTS13 truncated eukaryotic protein (ADAMTS13-T7). Murine anti-human ADAMTS13 monoclonal antibodies (McAbs) were constructed by standard hybridoma technology and identified by ELISA. The recognition of McAbs with full-length recombinant ADAMTS13 protein was identified by Western blot. In function assay, the influence of McAbs on the proteolysis of vWF by ADAMTS13 was observed.

RESULTSA group of 6 murine anti-ADAMTS13 McAbs was obtained with the clone number 1G11, 2F11, 6G3, 9E1, 10A8 and 10B4. In ELISA, the highest titers of 1G11 and 2F11 were observed, both of which showed a higher affinity to ADAMTS13-T7 than full-length ADAMTS13. The Western blot demonstrated that the 6 McAbs all could recognize ADAMTS13, among which 1G11 and 2F11 showed stronger reaction with ADAMTS13. In addition, under the denatured conditions, 1G11 and 2F11 could inhibit hydrolysis of vWF by ADAMTS13, and that was stronger with the increasing of McAbs concentration.

CONCLUSIONMcAbs against ADAMTS13 have been gained, two of which are inhibitory antibodies.

ADAMTS13 Protein ; Animals ; Antibodies, Monoclonal ; analysis ; immunology ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Hybridomas ; Mice ; Mice, Inbred BALB C ; von Willebrand Factor

OBJECTIVETo investigate the prognosis value of early and interim ¹⁸F-FDG-PET/CT scan in patients with diffuse large B- cell lymphoma （DLBCL） to establish the suitable criteria for evaluating posttherapeutic lesions in scans.

METHODSFifty- six newly diagnosed DLBCL patients were enrolled in the study, and underwent baseline, early and interim ¹⁸F- FDG PET/CT scans. Five- point and % ΔSUVmax criteria were used separately to interpret ¹⁸F- FDG PET/CT images. Interobserver reproducibility was assessed with the kappa test（κ）, and thresholds of %ΔSUVmax were calculated via receiver operating characteristic curve（ROC）. Survival curves were obtained using Kaplan-Meier curves and log-rank test. Cox regression analysis was used for multi-factor analysis.

RESULTSMedian follow-up was 24 months（6 to 42 months）. The kappa value of the five- point scale was above 0.600 with the reference background set in the liver（Score≥4）. The optimal threshold of %ΔSUVmax was 81% for early PET/CT and 74% for interim PET/CT. Survival analysis showed both early and interim PET/CT scans could predict the outcome of 56 patients with DLBCL, and 3-year PFS and OS of PET-negative patients were significantly higher than those of PET-positive ones（P<0.05）. Five-score criteria were more accurate in evaluating 3- year PFS of DLBCL patients in the interim PET/CT scan（76.79%）. %ΔSUVmax criteria were better for interpreting 3-year OS（76.79% and 83.93%）. Multi-factor analysis demonstrated that early and interim PET/CT were solid predicting factors for DLBCL patients.

CONCLUSIONEarly and interim PET/CT scans could predict the outcome of patients with DLBCL, treated with R-CHOP/CHOP. Three-year OS was more accurate in early and interim PET/CT using 66 %ΔSUVmax criteria as an interpretation, while 3-year PFS was more accurate in interim PET/CT by five scores criteria.

Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Doxorubicin ; Fluorodeoxyglucose F18 ; Humans ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; drug therapy ; Positron-Emission Tomography ; Prednisone ; Prognosis ; ROC Curve ; Reproducibility of Results ; Survival Analysis ; Tomography, X-Ray Computed ; Vincristine

BACKGROUND/AIMS: Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. METHODS: Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. RESULTS: A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (> or =28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (> or =grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). CONCLUSIONS: Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.
Acute-On-Chronic Liver Failure/*diagnosis/drug therapy/etiology ; Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antiviral Agents/therapeutic use ; Cyclophosphamide/therapeutic use ; DNA, Viral/analysis ; Doxorubicin/therapeutic use ; Female ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/drug therapy ; Hospitalization ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Prednisone/therapeutic use ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Vincristine/therapeutic use ; Young Adult

The objectives of this study were to estimate the cost-of-illness (COI) and health-related quality of life (HRQOL) in patients with ankylosing spondylitis (AS) in Korea and to evaluate the effects of socio-demographic and clinical factors on the COI and the HRQOL. Face-to-face interview surveys were taken from patients with AS at the Rheumatology Clinic of Seoul National University Hospital. Direct medical and non-medical costs, indirect costs (productivity loss due to job loss and sick leave), and deterioration of HRQOL in patients with AS were measured. Factors associated with COI and HRQOL were analyzed with multiple regression and multivariate logistic regression. A total of 191 patients with AS was enrolled in the study. The COI in patients with AS amounted to 11,646,180 Korean Won (KRW) per patient, and their HRQOL was 0.62. As functional severity worsened, the total costs increased (class I, KRW 7.7 million; class II, KRW 12.9 million; classes III & IV, KRW 25.2 million) and the HRQOL scores decreased (class I, 0.72; class II, 0.61; classes III & IV, 0.24). Functional severity is the major determinant of the COI and HRQOL in patients with AS.
Adult ; Aged ; Antibodies, Monoclonal/therapeutic use ; *Cost of Illness ; Costs and Cost Analysis ; Demography ; Female ; Humans ; Interviews as Topic ; Logistic Models ; Male ; Middle Aged ; *Quality of Life ; Republic of Korea ; Severity of Illness Index ; Spondylitis, Ankylosing/drug therapy/economics/*physiopathology ; Tertiary Care Centers

Acetylcholinesterase ; analysis ; Antibodies, Monoclonal, Murine-Derived ; metabolism ; Australia ; Biopsy ; Calbindin 2 ; analysis ; Child ; Diagnosis, Differential ; Endoscopy, Gastrointestinal ; Eosinophilic Esophagitis ; pathology ; Hirschsprung Disease ; metabolism ; pathology ; Humans ; Intestinal Diseases ; pathology ; Lymphangiectasis, Intestinal ; immunology ; pathology ; Multiple Endocrine Neoplasia Type 2b ; pathology ; Nervous System Diseases ; pathology ; Quality Control