Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

Objective:To analyze the epidemiological and clinical characteristics of respiratory syncytial virus (RSV) infection in children in Jiangsu Province from 2014 to 2023.Methods:The acute respiratory infection cases in children aged 0-14 years were selected from outpatient/emergency or inpatient departments in 2 surveillance sentinel hospitals, respectively, in Nanjing, Suzhou and Taizhou of Jiangsu from 1 July 2014 to 31 December 2023, and RSV nucleic acid test was conducted and the intensity of the RSV infection was accessed by WHO influenza epidemiological threshold method, and case information and clinical data were collected. χ2 test was used to compare the differences between groups, and the Bonferroni method was used for pairwise comparisons between groups. Results:In 4 946 cases of acute respiratory infections, the RSV positive rate was 8.21% (406/4 946), and the age M( Q1, Q3) of the cases was 1 (0, 3) years. The RSV positive rate was 10.92% (258/2 362) during 2014-2019 and 6.06% (118/1 948) during 2019-2023, the difference was significant ( χ2=31.74, P<0.001). RSV infection mainly occurred from October to March during 2014-2019, with the incidence peak in December and moderate or higher intensity. The seasonality of RSV infection was not obvious during 2019-2023, with low intensity. The RSV positive rate was highest in children in age group 0- years (17.85%, 151/846), and the positive rate declined gradually with age ( χ2=184.51, P<0.001). The RSV positive rate was higher in inpatient cases (9.84%, 244/2 480) than in outpatient/emergency cases (6.57%, 162/2 466) ( χ2=17.54, P<0.001). In the 155 RSV infection cases with complete clinical data, the clinical symptoms mainly included cough (99.35%, 154/155), fever (55.48%, 86/155), and shortness of breath (45.16%, 70/155). In the cases aged <6 months, the proportion of those with fever was low, but the proportion of those with shortness of breath, transferred to intensive care units, and receiving oxygen therapy were higher (all P<0.05). Children aged <6 months and those with underlying diseases were more likely to have severe RSV infection (all P<0.05). Conclusions:RSV infection in children in Jiangsu Province showed seasonal prevalence in winter from 2014 to 2019. Since 2020, the seasonal characteristics of the epidemic have changed, the epidemic period has been dispersed and the epidemic intensity has decreased. Infants <1 year old were at high risk for RSV infection, and those <6 months old and with underlying diseases might have severe infection.

Patients with diabetic retinopathy often experience diabetes distress when facing the challenges of the disease, which has adverse effects on their health outcomes. This paper summarizes the current situation of diabetes distress in patients with diabetic retinopathy, and the assessment tools, influencing factors, and intervention measures, aiming to provide a reference for healthcare professionals to conduct intervention studies.

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.

Based on the characteristics of forensic pathology, this paper explains the concept, connotation and advantages of holistic medicine and integrated medicine in the teaching of forensic pathology. Then, through the introduction of the specific teaching process design and effect analysis of the death cause analysis practical cases, it clarifies the necessity and effectiveness of integrated medicine and holistic medicine in the teaching of forensic pathology, and provides new ideas for the reform of the overall teaching of forensic pathology.

Abstract The prevalence of overweight and obesity among children in China has entered a new phase of pandemic, with substantial regional differences. There are diverse and complex determinants for overweight and obesity in school age children, it is necessary to take targeted measures towards children of different ages and regions, comprehensively consider the effects of physiological, social, household and behavioral factors and simultaneously strengthen connections between schools, medical institutions and families, so as to actively respond to the severe situation of childhood obesity epidemic.

Objective: To compare the difference of cognitive fusion, empirical avoidance between patients with obsessive-compulsive disorder and healthy control group, and to explore the relationship between obsessive-compulsive score and cognitive fusion, empirical avoidance. Methods: The cognitive fusion questionnaire(CFQ), acceptance and action questionnaire-2nd edition(AAQ-II) and Yale-Brown scale for obsessive-compulsive symptoms (Y-BOCS) were used to investigate 100 subjects with obsessive-compulsive disorder (OCD) and 166 healthy controls.And the differences in cognitive fusion and empirical avoidance scores were compared between the two groups.The relationship of obsessive-compulsive symptoms and cognitive fusion, empirical avoidance was analyzed using multiple linear regression analysis. Results: The scores of cognitive fusion ((49.89±10.62) vs (33.88±11.44), t=-11.345, P<0.01)and empirical avoidance ((29.75±9.53) vs (21.59±7.03), t=-7.995, P<0.01) in obsessive-compulsive disorder group were significantly higher than those in healthy control group.There were significant differences in cognitive fusion and empirical avoidance in age variables (F=8.63, P<0.01). In AAQ-Ⅱ, item 2 (r=0.246, P<0.05), item 6 (r=0.223, P<0.05) and total score (r=0.240, P<0.05) were positively correlated with the total score of Y-BOCS.Item 2 (r=0.311, P<0.01), item 3 (r=0.286, P<0.05), item 6 (r=0.248, P<0.05) and total score (r=0.229, P<0.05) were positively correlated with the scores of obsessive-thinking.In CFQ, item 2 (r=0.231, P<0.0) 5), item 4 (r=0.242, P<0.05), item 7 (r=0.308, P<0.05), item 8 (r=0.277, P<0.05) and item 9 (r=0.249, P<0.05) were positively correlated with the total score of Y-BOCS.Item 8 (r=0.261, P<0.05) was positively correlated with the scores of obsessive-thinking, item 7 (r=0.237, P<0.05) and item 9 (r=0.238, P<0.05) were positively correlated with scores of obsessive-compulsive behavior.When predicting total obsessive-compulsive scores, only CF item 7 of Q (B=1.827, P<0.01), item 3 (B=0.956, P<0.05), and item 6 of AAQ-Ⅱ (B=0.584, P<0.05) entered the equation with a joint explanatory variation of 19%.When predicting the score of obsessive-thinking, only item 2 of AAQ-Ⅱ (B=0.446, P<0.01) entered the equation, explaining the variance was 9.7%.In the prediction of obsessive-compulsive behavior, only item 9 (B=0.815, P<0.05) of CFQ entered the equation, and the explanatory variation was 5.6%. Conclusion Cognitive fusion in the patients with obsessive-compulsive disorder and the high level of empirical avoidance may be an important factor for the maintenance of the symptoms.

Monoclonal antibody (mAb)-based therapeutics are playing an increasingly important role in the treatment or prevention of many important diseases such as cancers, autoimmune disorders, and infectious diseases. Multi-domain mAbs are far more complex than small molecule drugs with intrinsic heterogeneities. The critical quality attributes of a given mAb, including structure, post-translational modifications, and functions at biomolecular and cellular levels, need to be defined and profiled in details during the developmental phases of a biologics. These critical quality attributes, outlined in this review, serve an important database for defining the drug properties during commercial production phase as well as post licensure life cycle management. Specially, the molecular characterization, functional assessment, and effector function analysis of mAbs, are reviewed with respect to the critical parameters and the methods used for obtaining them. The three groups of analytical methods are three essential and integral facets making up the whole analytical package for a mAb-based drug. Such a package is critically important for the licensure and the post-licensure life cycle management of a therapeutic or prophylactic biologics. In addition, the basic principles on the evaluation of biosimilar mAbs were discussed briefly based on the recommendations by the World Health Organization.
Animals ; Antibodies, Monoclonal ; chemistry ; therapeutic use ; Biological Products ; therapeutic use ; Glycosylation ; Humans ; Kinetics ; Ligands

Animals ; Antibodies, Monoclonal ; pharmacokinetics ; therapeutic use ; Antibodies, Viral ; therapeutic use ; Hepatitis B virus ; immunology ; Histocompatibility Antigens Class I ; metabolism ; Humans ; Macaca fascicularis ; Mice ; Protein Binding ; Protein Engineering ; Receptors, Fc ; metabolism

Bispecific antibodies can target two different targets simultaneously with a wide application prospect and rapid development in tumor treatment. The main function is to recruit effector cells selectively in order to kill tumor cells or bind tumor-associated growth factor receptor to inhibit cell proliferation. This paper reviews the current situation of bispecific antibodies in design, mechanism of action and the research progress in the clinical cancer treatment.