Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.

The dynamic tracking of antibody‒drug conjugates (ADCs) in serum is crucial. However, a versatile bioanalytical platform is lacking due to serious matrix interferences, the heterogeneity and complex biotransformation of ADCs, and the recognition deficiencies of traditional affinity technologies. To overcome this, a multiepitope recognition technology (MERT) was developed by simultaneously immobilizing CDR and non-CDR ligands onto MOF@AuNPs. MERT's excellent specificity, ultrahigh ligand density, and potential synergistic recognition ability enable it to target the different key regions of ADCs to overcome the deficiencies of traditional technologies. The binding capacity of MERT for antibodies is ten to hundred times higher than that of the mono-epitope or Fc-specific affinity technologies. Since MERT can efficiently capture target ADCs from serum, a novel bioanalytical platform based on MERT and RPLC‒QTOF-MS has been developed to monitor the dynamic changes of ADCs in serum, including the fast changes of drug-to-antibody ratio from 3.67 to 0.22, the loss of payloads (maytansinol), and the unexpected hydrolysis of the succinimide ring of the linker, which will contribute to clarify the fate of ADCs and provide a theoretical basis for future design. In summary, the MERT-based versatile platform will open a new avenue for in-depth studies of ADCs in biological fluids.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Dynamic tracking analysis of monoclonal antibodies(mAbs)biotransformation in vivo is crucial,as certain modifications could inactivate the protein and reduce drug efficacy.However,a particular chal-lenge(i.e.immune recognition deficiencies)in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen.To address this limitation,a multi-epitope affinity technology utilizing the metal organic framework(MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region(CDR)mimotope peptide(HH24)and non-CDR mimotope aptamer(CH1S-6T)onto the surface of MOF@Au nanocomposite.Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited signifi-cantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope af-finity technology.Moreover,the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry(LC-QTOF-MS).Therefore,multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb.Particularly,the novel bioanalytical platform can be suc-cessfully used for the tracking analysis of trastuzumab modifications in different biological fluids.Compared to the spiked phosphate buffer(PB)model,faster modification trends were monitored in the spiked serum and patients'sera due to the catalytic effect of plasma proteins and relevant proteases.Differences in peptide modification levels of trastuzumab in patients'sera were also monitored.In summary,the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb,contributing to improved understanding and paving the way for future research and clinical applications.

In this research,a new phospholipid based monolith was fabricated by in situ co-polymerization of 1-dodecanoyl-2-(11-methacrylamidoundecanoyl)-sn-glycero-3-phosphoethanolamine and ethylene dimethacrylate to mimick bio-membrane environment.Excellent physicochemical properties of this novel monolith that were achieved included column efficiency,stability,and permeability.Moreover,the biomimetic monolith showed outstanding separation capability for a series of intact proteins and small molecules.In particular,it exhibited good potential as an alternative to the commercial immobilized artificial membrane(IAM)column(IAM.PC.DD2)for studying drug-membrane interactions.This study not only enriched the types of IAM stationary phases,but also provided a simple model for the prediction of phosphatidylethanolamine related properties of drug candidates.

Zwitterionic sulfobetaine-based monolithic stationary phases have attracted increasing attention for their use in hydrophilic interaction chromatography.In this study,a novel hydrophilic polymeric monolith was fabricated through photo-initiated copolymerization of 3-(3-vinyl-1-imidazolio)-l-propanesulfonate(SBVI)with pentaerythritol triacrylate using methanol and tetrahydrofuran as the porogenic system.Notably,the duration for the preparation of this novel monolith was as little as 5 min,which was significantly shorter than that required for previously reported sulfobetaine-based monoliths prepared via conventional thermally initiated copolymerization.Moreover,these monoliths showed good morphology,permeability,porosity(62.4％),mechanical strength(over 15 MPa),column efficiency(51,230 plates/m),and reproducibility(relative standard deviations for all analytes were lower than 4.6％).Mechanistic studies indicated that strong hydrophilic and negative electrostatic interactions might be responsible for the retention of polar analytes on the zwitterionic SBVI-based monolith.In particular,the resulting monolith exhibited good anti-protein adhesion ability and low nonspecific protein adsorption.These excellent features seem to favor its application in bioanalysis.Therefore,the novel zwitterionic sulfobetaine-based monolith was successfully employed for the highly selective separation of small bioactive compounds and the efficient enrichment of N-glycopeptides from complex samples.In this study,we prepared a novel zwitterionic sulfobetaine-based monolith with good performance and developed a simpler and faster method for preparation of zwitterionic monoliths.

An analytical methodology based on an O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine (MQD)-silica hybrid monolithic column was developed for the enantioseparation of 9-fluorenylmethoxycarbonyl (FMOC) derivatized amino acids by nano-liquid chromatography. The mo-bile phase was optimized including the apparent pH, content of ACN, and concentration of the buffer to obtain a satisfactory enantioresolution performance. 27 FMOC derivatized amino acids including 19 protein and 8 non-protein amino acids were tested, and 19 out of them were enantiomerically discriminated obtaining baseline separation for 11 of them. Analytical characteristics of the method were evaluated for norvaline and tryptophan in terms of linearity, precision, accuracy, limits of detection (LOD) and quantitation (LOQ) showing good performance to be applied to the enantiomeric determination of these amino acids in dietary supplements. LOD and LOQ values were 9.3 and 31μM for norvaline en-antiomers and 7.5 and 25μM for tryptophan enantiomers, respectively. The contents of D-norvaline and D-tryptophan were below their respective LODs in all the analyzed samples. Quantitation of L-tryptophan and L-norvaline showed good agreement with the labeled contents except for one sample which did not show presence of L-norvaline, contrary to the label indication.

Objective To investigate the teaching effects of flipped class model on the Surgery Intensive Care Unit (SICU) nurses' ability of autonomic learning. Methods From July to December 2015, a total of 38 nurses who worked in SICU of Zhejiang Cancer Hospital were selected as the research objects by convenience sampling method. The nurses were trained in postoperative pain management knowledge by flipped class model, and were evaluated before and after the training by rating scale of self-directed learning competence for nurses. Results The total score of rating scale of self-directed learning competence for nurses, self motivation belief, task analysis, self monitoring and regulation, self evaluation were (128.26±18.69), (54.50±7.65), (22.05±3.66), (37.57±5.82) and (14.13±2.67) after the training, which all improved than (108.89±15.71), (47.18±6.61), (18.03±3.33), (31.37±5.24) and (12.32±2.14) respectively before training. The differences were statistically significant (t=-4.889, -4.460, -5.013, -4.883, -3.266; P<0.05). Conclusions Flipped class teaching model improves nurses' autonomous learning ability comprehensively and provide a new teaching mode for nurses' training.

ObjectiveTo investigate clinical symptoms and influencing factors of food intolerance and to identify susceptibility of food intolerance among adults with various Traditional Chinese Medicine (TCM) constitutions.MethodsA total of 411 individuals were recruited by using simple sampling method.ELISA was used to test serum levels of food intolerance specific IgG antibody.TCM constitution,food intake habit,lifestyle,and biochemical data were collected.Results ( 1 ) The prevalence of food intolerace was 60.1％ (247/411).(2) The most commonly seen food intolerance specific IgG were those against egg (44.9％ ),crab ( 37.7％ ),or cod ( 23.1％ ).Intolerance to 1 to 5 kinds of food could be found in single individual.Subhealthy people were more likely to suffer from food intolerance ( P＜0.05 ).( 3 ) Those with food intolerance always presented with various symptoms,mainly respiratory system symptoms.(4) The most common types of TCM constitution of the participants were gentleness constitution,qi-insufficiency constitution,yang-deficiencyconstitution,anddampness-heatconstitution.Thoseofnon-bloodstasis constitution were more likely to suffer from crab intolerance ( P＜0.05 ).Conclusion The prevalence of food intolerance is relatively high in Fuzhou areas.Subhealthy status,obesity women,and pathological constitutions may be risk factors of food intolerance.

Objective To investigate the symptoms and affecting factors of food intolerance among 903 adults.Methods Food special antibody(IgG)in human serum were examined by ELISA.Food Intolerance Health Assessment Questionnaire was used to assess positive rate of food intolerance and food intake habits.Chi-square test and Mann-Whitney test were used for data analysis.Results The ratio of food intolerance was 0.33％ to 28.13％.Intolerant foods include crab(28.13％),yolk(27.02％),milk (13.07％),soybean(11.96％),shrimp,tomato,corn,beef,rice,chicken,mushroom,wheat,and pork.The symptoms of nervous system(55.89％),digestive system(45.69％)and respiratory system(15.64％)were commonly seen.Prevalence of food intolerance in mental labors was lower than manual labors.Conclusion The most common intolerant food includes crab,yolk and milk.The symptoms of food intolerance are different.Manual labors are more susceptible to food intolerance.