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*

ObjectiveTo compare the difference in adverse reactions after oxaliplatin-containing chemotherapy between colorectal cancer patients with or without spleen-kidney yang deficiency syndrome. MethodsA retrospective study was conducted using the electronic medical records of Beijing Hospital of Traditional Chinese Medicine， Capital Medical University. A total of 483 colorectal cancer patients from January 1， 2009 to December 31， 2022 were selected. Patients were divided into two groups based on their syndrome types， that was spleen-kidney yang deficiency syndrome （SKYDS） group （130 cases） and non-SKYDS group （353 cases）. The incidence of adverse reactions including gastrointestinal reactions， liver damage， bone marrow suppression， and peripheral neurotoxicity after completing 2， 4， 6， and more than 6 cycles of chemotherapy was compared between the two groups. Univariate and multivariate logistic regression analyses were used to analyze the associations of age， gender， alcohol history， primary tumor location， tumor differentiation， tumor staging， chemotherapy courses， and syndrome types with the occurrence of gastrointestinal adverse reactions， liver function damage， bone marrow suppression and peripheral neurotoxicity in colorectal cancer patients who have completed 2， 4， 6 and more than 6 cycles of oxaliplatin-containing chemotherapy. ResultsThere were significant differences in the occurrence of gastrointestinal reactions after completing 2， 4， 6 and more than 6 cycles of chemotherapy between the two groups （P＜0.01）， with much more severe conditions in SKYDS group than non-SKYDS group （P＜0.01）. There was no significant difference in liver function damage and bone marrow suppression between groups （P＞0.05）. There were statistically significant differences in the occurrence of peripheral neurotoxicity after completion of 2 cycles （P=0.044）， 4 cycles （P=0.002） and more than 6 cycles （P＜0.001） of chemothe-rapy， with higher rate in SKYDS group than the non-SKYDS group （P＜0.05）. Univariate analysis showed that female， patients with stage Ⅲ tumors and patients having completed ≥ 6 cycles of chemotherapy had a higher incidence of bone marrow suppression （P＜0.05）， and patients with SKYDS had a higher incidence of gastrointestinal reactions （P＜0.001）. Patients with a history of drinking， stage Ⅳ cancer， and ≥6 cycles of chemotherapy had a higher incidence of liver function injury （P＜0.05）. Patients with stage Ⅲ cancer， ≥6 cycles of chemotherapy， and SKYDS had a higher incidence of peripheral neurotoxicity （P＜0.05）. Multivariate analysis showed that the risk factor for bone marrow suppression was chemotherapy ≥6 cycles （P=0.001）， and SKYDS was the risk factor for gastrointestinal reaction （P＜0.001）. The risk factor for liver function damage was tumor stage Ⅳ （P=0.001） and SKYDS （P=0.039）. All variables had no significant correlation with the occurrence of peripheral neurotoxicity. ConclusionFor colorectal cancer patients， being diagnosed with SKYDS is a risk factor for developing gastrointestinal adverse reactions and peripheral neurotoxicity following chemotherapy with an oxaliplatin-based regimen.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

Objective To analyze the therapeutic effect of anti-programmed death receptor 1(PD-1)/pro-grammed death ligand 1(PD-L1)and the characteristics of intestinal flora in patients with non-small cell lung cancer(NSCLC).Methods A total of 81 NSCLC patients admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from January 2020 to January 2022 were taken as the research object.According to the patients'immunotherapy response,the patients were divided into non-response group and response group.The differences in clinical data and intestinal flora distribution between the two groups were compared,and the correlation between PFS and intestinal flora a diversity index was analyzed by Spearman correlation.Results The proportion of smoking patients in response group was significantly lower than that in non-re-sponse group,and the difference was statistically significant(x2=4.648,P=0.031).Chao1 index,ACE index and shannon wiener index patients in non-response group were lower than those in response group,while Simpson diversity index was higher than that in response group,with statistical significance(P＜0.05).Chao1 index,ACE index and shannon wiener index were positively correlated with PFS(r=0.526,0.579 and 0.539,all P＜0.05),while Simpson diversity index was negatively correlated with PFS(r=-0.867,P＜0.001).The principal coordinate analysis was used to analyze the β diversity structure of intestinal flora.The first principal component contribution rate was 70.36％,and the second principal component contribution rate was 16.63％.Conclusion The diversity and distribution of intestinal flora in NSCLC patients are related to anti-PD-1/PD-L1 therapy.The higher the diversity of intestinal flora,the more sensitive the anti-PD-1/PD-L1 therapy.

Objective To analyze the current state,research hotspots,and development trends of electroencephalography(EEG)applied in the field of autism spectrum disorder(ASD). Methods Relevant literature from the Web of Science core collection database from January,2014 to January,2024 were retrieved and analyzed using CiteSpace 6.2.R4. Results A total of 1 509 articles were included,with an increasing trend in publication volume over the years.The United States ranked highest in both publication volume and node centrality.The primary journals in this field were concentrated in clinical medicine,immunology and psychology.Keyword co-occurrence and clustering indicated that research primarily focused on the correlation between core symptoms of ASD and EEG indicators,differential diagnosis of ASD and its comorbidities,brain functional connectivity,and assessment of rehabilitation efficacy.Keywords bursted in the past three years mainly included artificial intelligence and machine learning. Conclusion The researches in EEG technology in the field of ASD is generally increasing.Future researches may focus on exploring the brain network mechanisms of ASD using EEG combined with multimodal neuroimaging,and machine learning technologies.

Objective:To investigate the effect of a visual walking training based on wearable cueing devices on ground reaction force of Parkinson's disease patients with freezing of gait. Method:Twenty-three PD with FOG(PD+FOG)were selected and twenty healthy controls(HC)were tested in gait laboratory.The experimental group was trained with wearable walking guide devices for 20 minutes,twice a day for one week.The Vicon 3D gait analysis system was used to collect the spatiotemporal parame-ters and the ground reaction force parameters of the non-dominant side and the dominant side including front-back peak,medial-lateral peak and the first vertical peak)of the experimental group and the control group be-fore and after training. Result:①After the intervention,the bilateral step length and velocity of patients in the experimental group in-creased signi ficantly(P＜0.05),while cadence,double stance phase decreased significantly(P＜0.05).After train-ing,there was no significant difference in the dominant step length,cadence and double stance phase between experimental group and control group(P＞0.05).②After the training,bilateral parameters(landing angles of hip joints,the maximum angles of ankle dorsiflexion and plantar flexion,and the ranges of motion of lower limb joints)in the experimental group increased significantly,while the landing angles of knee joints de-creased,and the stage of the first peak of ankle joints was delayed,with statistical significance(P＜0.05).Af-ter the training,knee joint landing angle,maximum ankle dorsiflexion angle,the first peak stage of ankle joint,lower limb joint range of motion had no significant difference between the experimental group and the control group in both sides(P＞0.05).③After the intervention,the front-back peak value and the first vertical peak of the bilateral ground reaction force in the experimental group were significantly increased(P＜0.05),while the medial-lateral peak value of the ground reaction force was significantly decreased(P＜0.05).Compared with the control group,there was no significant difference in the backward peak,medial peak of non-domi-nant side and parameters of the dominant side(P＞0.05). Conclusion:The visual walking training based on wearable walking guide devices improve the stability and consistency of gait of PD+FOG.

Objective:To analyze and explain the influences of the professional background of the directors of public hospitals on the economic operation of the hospital,and to provide research support for training compound hospital management talents and improving the relevant policies of public hospital director management.Methods:The fixed effect model was used to conduct a quantitative analysis based on the data of individual directors and hospital economic performance of public hospitals in Guangdong from 2005 to 2018.Results:Compared with hospitals whose directors without clinical medical backgrounds,the medical income,the number of admissions and medical expenditure of the hospitals whose directors with clinical medical backgrounds were lower,and turnover of bed rate was higher,the differences were statistically significant(P＜0.05).Compared with hospitals where the directors had not obtained a degree related to management and did not participate in management training,the asset-liability ratio and management cost of the hospital where the directors had obtained a degree or participated in the training were lower,and the liquidity ratio was higher,with statistical significance(P＜0.05).Conclusion:For the economic operation indicators closely related to clinical work,directors with clinical medical background have a more significant impact because of their advantages in clinical front-line learning and work experience.For the economic operation indicators closely related to asset management,administration and cost management,directors with management learning experience can better reveal and exert their advantages in applying advanced management concepts,methods and tools,and have a more significant impact.

Objective:To explore the application value of real-time shear wave elastography(SWE)and ultrafast pulse wave velocity(UFPWV)techniques in assessing carotid artery stiffness of patients with gouty arthritis(GA).Methods:A total of 80 GA patients admitted to the First People's Hospital of Yibin from August 2022 to July 2023 were selected as GA group.Among of them,24 cases combined with bone erosion who were confirmed by imaging examination,and 56 cases did not combine with bone erosion.In addition,a total of 40 healthy individuals,who underwent physical examinations in our hospital during the same period,were selected as the healthy control group.SWE and UFPWV were used to detect the maximum,minimum and mean values of Young's modulus values of the vessel wall of common carotid artery,and the pulse wave velocity at the beginning of systole(PWVBS)and pulse wave velocity at the end of systole(PWVES)of the vessel wall of common carotid artery of all subjects,and to assess the hardness of circumferential and longitudinal vessel wall of common carotid artery of them.The differences in Young's modulus values,PWVBS and PWVES between two groups were compared.And then,the correlations between bone erosion and Young's modulus values,PWVBS,PWVES of GA patients were further analyzed.Results:The maximum,minimum,mean values,PWVBS and PWVES in the GA group were respectively(78.80±12.38)kPa,(57.83±7.42)kPa,(67.67±8.38)kPa,(7.06±0.59)m/s and(9.50±0.63)m/s,which were significantly higher than those in the healthy control group(t=11.066,8.216,11.751,14.159,19.118,P＜0.05).The maximum,minimum,mean values,PWVBS and PWVES of GA patients with bone erosion were respectively(82.95±6.37)kPa,(59.59±5.29)kPa,(72.18±7.62)kPa,(7.37±0.43)m/s,(10.43±0.47)m/s,which were significantly higher than those[(77.01±5.32)kPa,(57.08±4.73)kPa,(65.73±4.54)kPa,(6.92±0.39)m/s and(9.10±0.41)m/s]of GA patients without bone erosion,the differences were significant(t=4.309,2.099,4.699,4.586,12.720,P＜0.05).Spearman correlation analysis showed that there was significant correlations between maximum,minimum,mean values,PWVBS,PWVES and the combined bone erosion in GA patients(r=0.602,0.421,0.682,0.647,0.732,P＜0.05).Conclusion:SWE and UFPEV techniques can evaluate the hardness of vascular wall of GA patients,and the hardness of circumferential and longitudinal vessel wall of common carotid artery of GA patient is higher than that of healthy person,and the hardness of circumferential and longitudinal vessel wall of common carotid artery of GA patient with bone erosion is higher.

Restricted repetitive behaviors (RRBs) are the most characteristic behaviors of autism spectrum disorder. The clinical diagnosis and treatment of RRBs are extremely difficult resulting from its complex and variable etiology, highly heterogeneous clinical manifestations influenced by multiple factors (sleep quality, gastrointestinal health, age and gender), lack of precise diagnostic criteria and low effectiveness of current clinical interventions. This article mainly reviews the recent related studies on RRBs and discusses the challenges and progress in clinical diagnosis and treatment of RRBs so as to provide new ideas for future clinical diagnosis and treatment.

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.