1.Resistance to antibody-drug conjugates: A review.
Sijia LI ; Xinyu ZHAO ; Kai FU ; Shuangli ZHU ; Can PAN ; Chuan YANG ; Fang WANG ; Kenneth K W TO ; Liwu FU
Acta Pharmaceutica Sinica B 2025;15(2):737-756
Antibody-drug conjugates (ADCs) are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker. Currently, 15 ADCs have been clinically approved worldwide. More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs. ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development. It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells, thereby producing promising antitumor efficacy and favorable adverse effect profiles. However, emergence of drug resistance has severely hindered the clinical efficacy of ADCs. In this review, we introduce the structure and mechanism of ADCs, describe the development of ADCs, summarized the latest research about the mechanisms of ADC resistance, discussed the strategies to overcome ADCs resistance, and predicted biomarkers for treatment response to ADC, aiming to contribute to the development of ADCs in the future.
2.Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.
Sijia ZHAO ; Yanyan YANG ; Hong LI ; Pin SUN ; Xiangqin HE ; Chao WANG ; Jingjing ZHANG ; Yu TIAN ; Tao YU ; Zhirong JIANG
Acta Pharmaceutica Sinica B 2025;15(10):5127-5144
Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.
3.Current status and influencing factors of delirium among patients of advanced age hospitalized in internal medicine departments
Xueyan FAN ; Liu HAN ; Qiushuang YU ; Sijia YANG ; Dahua ZHANG ; Jingjing LI ; Xueling MA ; Li YU
Chinese Journal of Modern Nursing 2025;31(29):3984-3989
Objective:To explore the incidence of delirium in patients of advanced age hospitalized in internal medicine departments and analyze its influencing factors.Methods:A retrospective analysis was conducted on the medical records of 586 patients of advanced age hospitalized in internal medicine departments at the Beijing University of Chinese Medicine Third Affiliated Hospital from May 2023 to May 2024. Patients were divided into a delirium group and a non-delirium group based on whether delirium occurred. Univariate analysis and binary Logistic regression analysis were used to explore the factors influencing delirium in patients of advanced age hospitalized in internal medicine departments.Results:Among 586 patients of advanced age hospitalized in internal medicine departments, the incidence of delirium was 21.2% (124/586). Binary Logistic regression analysis showed that age, activities of daily living (Barthel Index), folate deficiency, sleep disorders, and indwelling catheters were factors influencing delirium in patients of advanced age hospitalized in internal medicine departments ( P<0.05) . Conclusions:The incidence of delirium is high among patients of advanced age hospitalized in internal medicine departments. Healthcare professionals should pay particular attention to elderly patients with advanced age, limited activities of daily living, folate deficiency, sleep disorders, and indwelling catheters, and should implement targeted preventive strategies as early as possible.
4.Mechanism of action of cholangiocyte senescence in cholestatic liver disease and retated targeted therapies
Huaming XU ; Liu YANG ; Wuling YAN ; Sijia ZHENG ; Nian YANG ; Yanxin LIU
Journal of Clinical Hepatology 2025;41(8):1708-1714
Cholestatic liver disease(CLD)is a liver condition caused by disorders in bile acid secretion and metabolism due to various reasons,and it has the common pathological features of various chronic liver diseases.In recent years,the role of cholangiocyte senescence(CS)in the pathogenesis of CLD has attracted more and more attention,and CS not only participates in the development and progression of CLD,but it is also significantly associated with the course and prognosis of the disease.Targeted clearance of senescent cholangiocytes or blocking senescence-related pathways can improve CLD.This article summarizes the role of CS in CLD,related influencing factors,and the research advances in CLD,in order to provide a theoretical reference for subsequent studies on CLD.
5.Analysis of the Application Effect of 3D Technology Combined with Smartphone in Neuroendoscopy PBL
Yang LI ; Sijia ZHANG ; Chuanlu JIANG ; Haicheng YANG ; Jinquan CAI ; Xiangqi MENG ; Xuesong HU ; Jiawei DONG
Chinese Hospital Management 2025;45(2):87-89
Objective To investigate the effect of 3D technology combined with smartphones in problem-based learning(PBL)for neuroendoscopy.Methods 82 trainees who were enrolled from January 2021 to January 2023 were selected as the research subjects.A randomized controlled trial was conducted,and the subjects were divided into a control group and an experimental group.PBL and 3D technology combined with smartphone-assisted PBL were implemented respectively for two groups of students.The data were analyzed using t-test.Teaching satisfac-tion is evaluated by 2 test.Results The results of the in-operation examination and theoretical examination of the ex-perimental group students were found to be higher than those of the control group students(t=8.630,6.087,P<0.001),the satisfaction scores of students and teachers showing that the satisfaction of the experimental group was higher than that of the control group(x2=4.213,6.301,7.026,P<0.01).Conclusion In the PBL of neuroendosco-py,the use of 3D technology combined with smart phones as an auxiliary teaching system can effectively improve students'sense of participation,reduce the difficulty of skull base anatomy learning,and improve students'theo-retical and surgical assessment scores and teaching satisfaction.
6.Research on Optimization Path of Neurosurgery Clinical Teaching Management Mode Integrating Artificial Intelligence and PBL Teaching Method
Yang LI ; Sijia ZHANG ; Lihan ZHANG ; Haicheng YANG ; Jinquan CAI ; Xiangqi MENG ; Chuanlu JIANG
Chinese Hospital Management 2025;45(8):70-72,76
Objective In the clinical teaching of neurosurgery,the traditional Problem-Based Learning(PBL)teaching model faces systematic challenges such as the disconnection between the training cycle of specialized talents and technological iteration,the limitation of practical opportunities due to hospital infections,and the inefficient allocation of teaching resources.It provides a new path for teaching reform based on the deep integration of Artificial Intelligence and PBL,but it still needs to address issues such as differences in intern participation,insufficient technical adaptability of instructors,and fragmented resource allocation.Based on these problems,a collaborative mechanism of"technology development-talent cultivation"and a multi-dimensional optimization path of"intern participation-instructor training-hospital resource input"are proposed.On this basis,through collaborative strategies such as strengthening the incentive mechanism for autonomous learning,establishing a standardized instructor training system,and building a dynamic resource allocation platform,the management of neurosurgery clinical teaching is promoted towards intelligence,personalization,and systematization.
7.Molecular Identification of Cremastra appendiculata and Other Original Medicinal Materials of Cremastrae Pseudobulbus and Confusing Products Based on ITS Sequences in DNA Barcodes
Jinling ZHANG ; Qiuxiao XIAO ; Qian WANG ; Sijia ZHOU ; Yali LONG ; Yong HUANG ; Lin ZHENG ; Zipeng GONG ; Yang JIN ; Yueting LI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):142-146
Objective To distinguish Cremastra appendiculata(D.Don)Makino,Pleione yunnanensis Rolfe and Pleione bulbocodioides,and its easily confusing products Oreorchis patens and Iphigenia indica Kunth using the ITS sequence in DNA barcodes;To explore the genetic diversity of Cremastra appendiculata germplasm resources.Methods Three different original Cremastra appendiculata,Pleione yunnanensis Rolfe and Pleione bulbocodioides,and their easily confusing products Cremastrae Pseudobulbus of Oreorchis patens and Iphigenia indica Kunth were selected as the research objects,and the genomic DNA of the above samples were extracted by the modified CTAB method,and then the ITS sequences were amplified,sequenced and spliced by PCR technology.The Kimura 2-Parameter(K2P)model was used to calculate the genetic distance,and the phylogenetic tree was constructed with the help of neighbour joining method(NJ)for genetic relationship analysis.Results Except for the Iphigenia indica Kunth species that were not found during the BLAST search,the BLAST comparison results of the other samples were higher than 95%.At the same time,the results of phylogenetic tree showed that Cremastra appendiculata,Pleione yunnanensis Rolfe and Pleione bulbocodioides were clustered into one branch,respectively,and the easily confusing products were also respectively clustered into one branch.Conclusion The ITS sequence in DNA barcodes can be used to accurately distinguish Cremastra appendiculata,Pleione yunnanensis Rolfe and Pleione bulbocodioides,and its easily confusing products Oreorchis patens and Iphigenia indica Kunth.
8.Analysis of the Institutional Flow and Trend of Changes in the Total Cost of Grassroots Traditional Chinese Medicine in China
Zi YANG ; Xiaowei MAN ; Sijia QI
Chinese Health Economics 2025;44(5):49-52
Objective:To analyze the total amount,institutional flow and development trend of total Traditional Chinese Medicine(TCM)costs in China from 2018 to 2022,and to study the changes of total TCM costs in different primary healthcare institutions.Methods:The total TCM costs were accounted for using the institutional flow method and the case-base aggregation method.Results:From 2018 to 2022,the total TCM costs of primary healthcare organizations in China accounted for a rising proportion,with a stable growth trend,in which the total flow to community and township health centers accounted for a higher proportion,the proportion of total TCM costs of primary institutions in rural areas declined,and there was a negative growth in the village clinics;the growth rate of primary drug costs slowed down,and the growth rate of medical costs showed a wave-like change,with an overall increase in the amount of financial subsidies and subsidies from the higher level.Conclusion:The TCM service capacity of primary healthcare institutions nationwide has been developing steadily,and should continue to expand the existing advantages and build up a solid position for grassroots TCM service in China;the TCM service capacity of China's rural areas still needs to be improved;it is needed to continue to enhance the capacity of primary technical services of Chinese medicine practitioners and rationalizing the role of pharmaceutical services,and the percentage of financial and higher-level subsidies for primary healthcare institutions has been rising fluctuatingly.
9.Characteristics of injury cases among the elderly in Ningbo City from 2014 to 2023
SUN Qiang ; HUANG Ying ; LI Xiaoyong ; YANG Chenying ; WANG Sijia
Journal of Preventive Medicine 2025;37(8):822-826,831
Objective:
To analyze the characteristics of injury surveillance cases among the elderly in Ningbo City, Zhejiang Province from 2014 to 2023, so as to provide the basis for formulating targeted injury intervention measures.
Methods:
Injury surveillance cases aged ≥60 years were collected from seven injury sentinel hospitals in Ningbo City through the Zhejiang Provincial Chronic Disease Surveillance Information Management System from 2014 to 2023. Population distribution, temporal distribution, injury circumstances, and clinical characteristics were described.
Results:
A total of 67 259 injury surveillance cases among the elderly were reported in Ningbo City from 2014 to 2023, including 32 159 males (47.81%) and 35 100 females (52.19%). The median age was 68.00 (interquartile range, 14.00) years. The three months with a higher number of cases were December (6 271 cases, 9.32%), August (6 226 cases, 9.26%) and October (6 221 cases, 9.25%). The primary causes of injury were falls (25 276 cases, 37.58%), stabs (12 250 cases, 18.21%), and sprains (11 815 cases, 17.57%). The injury occurred mainly in homes (44 975 cases, 66.87%) and streets/urban areas (16 174 cases, 24.05%). The predominant activities at the time of injury were leisure activities (28 801 cases, 42.82%) and household chores (23 647 cases, 35.16%). The proportions of falls as the cause of injury and injuries occurring at home among females and people aged 80 years and above were relatively high. The predominant sites of injury were upper limbs (23 354 cases, 34.72%) and lower limbs (20 343 cases, 30.25%). The predominant nature of injury were soft tissue injuries (43 345 cases, 64.44%) and bone and joint injuries (22 042 cases, 32.77%). Injuries were primarily mild and moderate in severity, with 46 391 cases (68.97%) and 20 205 cases (30.04%), respectively. The proportion of bone and joint injuries, moderate in injuries among females and people aged 80 years and above was relatively high.
Conclusions
The main causes of injury surveillance cases among the elderly in Ningbo City from 2014 to 2023 were falls and stabs, and the injuries occurred mainly in homes and streets/urban areas. Female and elderly people have a higher risk of injury.
10.Prognostic model of ferroptosis-related genes in gastric cancer and experimental validation
Zhao Zhang ; Hongjun Tian ; Keshuo Ding ; Yong Zhu ; Feng Lin ; Sijia Yang ; Wenbin Wang
Acta Universitatis Medicinalis Anhui 2025;60(12):2215-2226
Objective:
To identify ferroptosis-related genes associated with gastric cancer prognosis and investigate their potential molecular functions.
Methods:
Gene expression profiles and clinical information of gastric cancer tissues and adjacent normal tissues were obtained from TCGA database. Differential expression analysis of ferroptosis-related genes was performed using the "DESeq2" package in R software. Key genes were identified and a prognostic model for gastric cancer was constructed through Cox regression analysis based on the LASSO algorithm. Patients were stratified into high-risk and low-risk groups according to the median risk score. The accuracy of the model was evaluated using Kaplan-Meier survival analysis and ROC curve analysis. Immune cell infiltration in gastric cancer patients was assessed with the "CIBERSORT" package. The mRNA expression of differentially expressed genes(DEGs) with prognostic significance was examined in both gastric cancer and adjacent normal tissue samples. In vitro experiments were conducted to validate the impact of hydroxycarboxylic acid receptor 1(HCAR1) on the malignant biological behavior of gastric cancer.
Results:
Based on ferroptosis-related genes from the TCGA database, a novel prognostic model was constructed. It demonstrated robust predictive power for survival in both training and validation cohorts. RT-qPCR analysis of 8 pairs of gastric cancer and normal tissues revealed that the expression patterns of 6 prognostic DEGs in cancer tissues were consistent with those predicted by the model. In vitro experiments confirmed that downregulation of the key gene HCAR1 could inhibit the proliferation, invasion, and metastasis of gastric cancer cells.
Conclusion
The ferroptosis-related gene based prognostic model exhibits robust predictive capability, allowing for accurate determination of prognosis and survival in individuals with gastric cancer.


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