1.The Icarian flight of antibody-drug conjugates: target selection amidst complexity and tackling adverse impacts.
Han LIU ; Hongye ZENG ; Xiaojing QIN ; Wenjing NING ; Lin XU ; Shiting YANG ; Xue LIU ; Wenxin LUO ; Ningshao XIA
Protein & Cell 2025;16(7):532-556
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
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Immunoconjugates/adverse effects*
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Neoplasms/immunology*
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Animals
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Antibodies, Monoclonal/therapeutic use*
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Antineoplastic Agents/therapeutic use*
2.Isokinetic muscle strength of knee for patients with chondromalacia patellae
Jiaman ZHONG ; Jingjie HUANG ; Fuyifei LIU ; Shiting ZHAO ; Wenxia XU ; Junxing YANG
Chinese Journal of Rehabilitation Theory and Practice 2022;28(4):379-383
Objective To analyze the characteristics of the muscle strength around the knee joint of chondromalacia patellae patients, and to explore the difference with normal people.Methods In March, 2021, 70 knee-onset chondromalacia patellae patients (experimental group) and 35 normal people (control group) were measured isokinetic muscle strength of flexion and extension of knee in angular velocities of 60°/s and 180°/s.Results At 60°/s and 180°/s, the peak torque, the peak torque-to-weight ratio and the total work of the flexor and extensor muscles on the affected side in the experimental group were lower than that of the control group (U > 1097.0, P<0.001). The peak torque, the peak torque-to-weight ratio and the total work of the flexor and extensor muscles at 60°/s and extensor muscles at 180°/s were lower on the affected side than on the healthy side in the experimental group (|Z| > 2.121, P<0.05). The peak torque ratios at 60°/s and 180°/s were more in the affected knees than in the healthy knees of experimental group and in the control group (U > 1810.0, |Z| >3.691, P<0.01).Conclusion The explosive force and endurance of the knee flexor and extensor has weakened in patients with chondromalacia patellae, and there is imbalance in knee joint muscle strength.
3.Anatomic and clinical application of lateral-perineal approach for inferior ramus of pubis-ischium ramus
Wei LIU ; Jianwen CHENG ; Shiting TANG ; Jinmin ZHAO ; Zhi YANG ; Feng HU ; Muwen LI ; Peng LIU ; Hongrong YU ; Zhen TAN
Chinese Journal of Orthopaedics 2022;42(13):823-830
Objective:To explore the anatomical and clinical effects of lateral-perineal approach in treating the fracture of inferior ramus of pubis-ischium ramus.Methods:The lateral approach of the perineum was simulated on 10 side of 5 intact wet adult cadavers to determine the surface symbols of incision design and to expose the operative field of the approach and to observe the anatomical characteristics of the perineal branch of the posterior femoral cutaneous nerve and the incision of the surgical approach. Five points were selected at the incision of the approach. The distance (L 1-L 5) between each point and the body surface projection of the perineal branch of the posterior femoral cutaneous nerve was measured. A total of 11 patients, including 5 males and 6 females with an average age of 41.55±14.32 years, ranging from 18 to 62 years, were treated by this approach in clinical practice. All patients had a reduction and fixation to the fracture of inferior ramus of pubis-ischium ramus. The operation duration, incision length, intraoperative blood loss and surgical complications were recorded. The quality of fracture reduction was evaluated according to Matta radiographic criteria. The strength of the adductor was measured. The pelvic function was evaluated according to Majeed Pelvic Score at the last follow-up. Results:Anatomical studies shown that the line between the two points. One point was 4 cm lateral to the level of the apex of the pubic arch. Another point was 4 cm from the ischial tubercle on the line from the ischial tuberosity to the point that 4 cm lateral to the level of the apex of the pubic arch was the axis of the approach lateral of the perineum. Anatomical studies showed that the lateral-perineal approach could expose the range from pubic symphysis to sciatic tuberculum. The distance between the points selected at the incision of the approach and the body surface projection of the perineal branch of the posterior femoral cutaneous nerve: L 1 was 19.40±1.17 mm, ranging from 18 to 21 mm; L 2 was 16.60±2.76 mm, ranging from 10 to 20 mm; L 3 was 18.30±1.89 mm, ranging from 16 to 21 mm; L 4 was 19.20±1.93 mm, ranging from 16 to 22 mm; L 5 was 14.70±1.83 mm, ranging from 13 to 18 mm. All patients were followed up for 17.91±4.09 months, ranging from 13 to 26 months. The incision length was 8.18±0.98 cm, ranging from 7 to 10 cm. The operation duration was 59.64±12.17 min, ranging from 43 to 85 min. The intraoperative blood loss was 100 ml, ranging from 50 to 130 ml. All incisions were healed in all patients. The fractures were healed in 13.36±2.06 weeks, ranging from 10 to 16 weeks. According to Matta radiographic criteria, the quality of fracture reduction was excellent in 6 cases, good in 4 cases and fair in 1 case. At the last follow-up, the adductor muscle strength reached grade 4 in 4 patients and grade 5 in 7 patients. Furthermore, according to the Majeed Pelvic Score, the score of every patient was 86.55±9.59, ranging from 66 to 100, and 8 cases were excellent, 3 cases were good at the last follow-up. The heterotopic ossification occurred in 2 patients, the pain during intercourse occurred in 2 patients. No patient had sensory disturbance or pain in the perineal area. Conclusion:A certain safe distance is between the lateral to the perineum and the perineal branch of the posterior femoral cutaneous nerve with limited risk of injuring posterior femoral cutaneous nerve via the lateral approach of the perineum. The advantages in treating the fracture of inferior ramus of pubis-ischium ramus by this approach have concealed incision, short operation duration and less bleeding with satisfied short-term clinical effects.
4.Development of a mouse model of stellate ganglion block and subsequent effects on cerebral cortical blood flow
Jiahua WANG ; Wei ZHOU ; Xiaohong WANG ; Shiting YAN ; Shunping TIAN ; Ying WANG ; Le-Yang YU ; Hu LI ; Dongsheng ZHANG ; Zhuan ZHANG ; Weili LIU
Chinese Journal of Anesthesiology 2022;42(4):430-434
Objective:To develop a model of stellate ganglion block (SGB) in mice and investigate the effect of SGB on cerebral cortical blood flow.Methods:Thirty clean-grade healthy male C57BL/6 mice, aged 8-9 weeks, weighing 23-27 g, were divided into 5 groups ( n=6 each) using a random number table method: control group (group C), left SGB group (group L), left normal saline group (group SL), right SGB group (group R) and right normal saline group (group SR). Group C received no intervention.SGB was performed with 0.25% ropivacaine 0.08 ml via percutaneous posterior approach in L and R groups, while the equal volume of normal saline 0.08 ml was given instead at the location of left and right stellate ganglion in SL and SR groups, respectively.The cerebral cortical blood flow was determined using laser speckle contrast imaging system before SGB (T 0) and at 10, 30, 60, 90 and 120 min after SGB (T 1-5). Results:Mice developed ptosis on the block side, indicating that the model of SGB was successfully developed in L and R groups.There was no significant difference in cerebral cortical blood flow at each time point among C, SL and SR groups ( P>0.05), and cerebral cortical blood flow on the block side decreased at T 1, began to increase at T 2, peaked at T 3, and decreased at T 5 which was still higher than that at T 0 in group L and group R ( P<0.01). Compared with C and SL groups, the left cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group L ( P<0.01). Compared with C and SR groups, the right cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group R ( P<0.01). There were no significant differences in cerebral cortical blood flow at each time point between group C and group SL and between group C and group RL ( P>0.05). Conclusions:The mouse model of SGB via percutaneous posterior approach is successfully developed.Unilateral SGB can affect cerebral cortical blood flow on the block side, which shows a transitory decrease followed by a sustained significant increase.
5.Proteomics investigation on periosteum of children with tibia congenital pseudarthrosis
Yaoxi LIU ; Yan CHEN ; Yu ZHENG ; Guanghui ZHU ; Ge YANG ; Shiting XIANG ; Qian TAN ; Jiangyan WU ; Kun LIU ; Shasha MO ; Haibo MEI
Chinese Journal of Orthopaedics 2021;41(2):92-102
Objective:To identify and analyze different proteins expression in the periosteum of congenital pseudarthrosis of the tibia (CPT) using tandem mass tags (TMT) proteomics.Methods:The samples were divided into three groups, namely CPT with neurofibromatosis type 1 (NF1) group (NF1-CPT group), CPT without NF1 group (nonNF1-CPT group) and control group (patients with open tibial fracture). A fold change ≥1.5 or ≤0.66 and P-value <0.05 was regarded as the threshold to screen differentially expressed proteins (DEPs). Subsequently, bioinformatics resources such as online tools DAVID and STRING were used to conduct GO annotation, KEGG pathways enrichment and protein-protein interaction (PPI) network with DEPs. Results:A total of 347 proteins differentially expressed in NF1-CPT group, 212 of which were up-regulated and 135 down-regulated. We identified 467 DEPs in nonNF1-CPT group, including 281 up-regulated and 186 down-regulated. Among of them, NF1-CPT group and nonNF1-CPT group shared 231 DEPs, except for HLA-DRB1 which increased in NF1-CPT group but decreased in nonNF1-CPT group. The remaining 230 DEPs showed the same expression trend in the two positive groups, including 117 up-regulated and 113 down-regulated. In particular, a total of 116 proteins were altered only in NF1-CPT group, including 94 up-regulated and 22 down-regulated. However, there were 236 proteins altered only in nonNF1-CPT group, including 164 up-regulated and 72 down-regulated. The results indicated that the pathogenesis of NF1-CPT was similar as nonNF1-CPT largely with a few differences. Finally, compared with nonNF1-CPT, there were 47 proteins changed 1.5-fold and P-value <0.05 in NF1-CPT group. Conclusion:The proteins expression in the periosteum of CPT is different from that of normal tibia. The expression of periosteal protein is also different between NF1-CPT and nonNF1-CPT. The present study will deepen our understanding of the pathogenesis of CPT in the protein level.
6.Anterior approach combined with blocking plates and screws in the management of acetabular fracture involving the quadrilateral area
Wei LIU ; Jianwen CHENG ; Shiting TANG ; Zhi YANG ; Zhen TAN ; Xiaorong SHI ; Yuquan LI ; Donglei WEI ; Feng HU ; Jinmin ZHAO
Chinese Journal of Trauma 2021;37(10):919-925
Objective:To investigate the clinical efficacy of anterior approach combined with blocking plates and screws in the management of acetabular fracture involving the quadrilateral area.Methods:A retrospective case series analysis was performed for 16 patients with acetabular fracture involving the quadrilateral area admitted to First and Second Affiliated Hospital of Guangxi Medical University from January 2017 to January 2019. There were 12 males and 4 females,with the age of 21-66 years[(45.3±10.6)years]. According to Letournel-Judet classification,there were 9 patients with bi-column fracture,6 with anterior and posterior traverse fracture and 1 with anterior column fracture. A total of 9 patients were operated via the ilioinguinal approach and 7 via the lateral-rectus approach. Reduction and fixation of the pelvis and acetabulum were performed,using 3.5 mm cortical bone screws or plates to block the internal displacement of fracture in the quadrilateral body. The incision length,operation time and intraoperative blood loss were recorded. The quality of fracture reduction was assessed according to the Matta reduction criteria at postoperative 2 days and hip function by the modified Merle D'Aubigne-Postel score at postoperative 3 months and 12 months. Postoperative complications were observed.Results:All patients were followed up for 13-24 months[(16.1±2.9)months]. The ilioinguinal approach and lateral-rectus approach showed surgical incision of 12-26 cm[(18.6±4.0)cm]and 8-15 cm[(10.7±2.3)cm],respectively. The operation time was 107-215 minutes[(159.2±27.8)minutes]and the intraoperative blood loss was 200-2,300 ml[(853.1±489.7)ml]. According to Matta reduction criteria,the results were excellent in 9 patients and good in 7. Three months after operation,the modified Merle D'Aubigne-Postel score was 11-18 points[(15.2±2.2)points],which showed the results were excellent in 4 patients,good in 7,fair in 4 and poor in 1,with the excellent and good rate of 69%. Twelve months after operation,the modified Merle D'Aubigne-Postel score was 13-18 points[(16.9±1.4)points],which showed the results were excellent in 7 patients,good in 8 and fair in 1,with the excellent and good rate of 94%. The liquefaction of post-surgical incision was seen in a patient,bladder injury in a patient,lateral femoral cutaneous nerve injury in a patient,and heterotopic ossification in a patient. There was no loosening or breakage of the internal fixation.Conclusion:For acetabular fracture involving the quadrilateral area,anterior approach combined with blocking plates and screws can prevent the displacement of quadrilateral fracture and attain satisfactory reductiongood hip function recovery and few complications.
7.The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)
Wenming WU ; Jie CHEN ; Chunmei BAI ; Yihebali CHI ; Yiqi DU ; Shiting FENG ; Li HUO ; Yuxin JIANG ; Jingnan LI ; Wenhui LOU ; Jie LUO ; Chenghao SHAO ; Lin SHEN ; Feng WANG ; Liwei WANG ; Ou WANG ; Yu WANG ; Huanwen WU ; Xiaoping XING ; Jianming XU ; Huadan XUE ; Ling XUE ; Yang YANG ; Xianjun YU ; Chunhui YUAN ; Hong ZHAO ; Xiongzeng ZHU ; Yupei ZHAO
Chinese Journal of Digestive Surgery 2021;20(6):579-599
Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
8.The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)
Wenming WU ; Jie CHEN ; Chunmei BAI ; Yihebali CHI ; Yiqi DU ; Shiting FENG ; Li HUO ; Yuxin JIANG ; Jingnan LI ; Wenhui LOU ; Jie LUO ; Chenghao SHAO ; Lin SHEN ; Feng WANG ; Liwei WANG ; Ou WANG ; Yu WANG ; Huanwen WU ; Xiaoping XING ; Jianming XU ; Huadan XUE ; Ling XUE ; Yang YANG ; Xianjun YU ; Chunhui YUAN ; Hong ZHAO ; Xiongzeng ZHU ; Yupei ZHAO
Chinese Journal of Surgery 2021;59(6):401-421
Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
9.The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)
Wenming WU ; Jie CHEN ; Chunmei BAI ; Yihebali CHI ; Yiqi DU ; Shiting FENG ; Li HUO ; Yuxin JIANG ; Jingnan LI ; Wenhui LOU ; Jie LUO ; Chenghao SHAO ; Lin SHEN ; Feng WANG ; Liwei WANG ; Ou WANG ; Yu WANG ; Huanwen WU ; Xiaoping XING ; Jianming XU ; Huadan XUE ; Ling XUE ; Yang YANG ; Xianjun YU ; Chunhui YUAN ; Hong ZHAO ; Xiongzeng ZHU ; Yupei ZHAO
Chinese Journal of Surgery 2021;59(6):401-421
Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
10.Evidence based practice for the application of feeding management after spinal operation
Jingjing LIU ; Xiaoling ZHANG ; Zhengxiang CHEN ; Yang XIAO ; Jinfeng ZHENG ; Shiting FAN ; Yan SUN ; Zheng ZHOU ; Qiaomei FU
Chinese Journal of Practical Nursing 2018;34(22):1701-1706
Objective To analyze the effect of evidence based practice on feeding after spinal operation. Methods To formulate an answerable question, find the best available evidence, appraise the evidence and formulate the recommendations by using the method of evidence-based medicine. A total of 60 postoperative patients who received spinal operation were divided into observation group and control group (30 cases in each group). Those patients in control group received the routine diet guidance and the guidelines for the standardization of intake and consumption after spinal cord surgery were used for patients in observation group. The outcomes were evaluated by postoperative recovery and complications of patients after spinal operation. Results There were no significant difference in the incidence of nausea, vomiting , bloating and celialgia in the 5 hours after surgery and 2 hours after feeding between the two groups (P>0.05). The incidence of thirst and hunger in the 5 hours after surgery in observation group were 3.33%(1/30) and 13.33%(4/30).The incidence of thirst and hunger in the 5 hours after surgery in control group were 80.00%(24/30) and 83.33%(25/30). There were statistically significant in the incidence of thirst and hunger in the 5 hours after surgery between the two groups (χ2=36.27, 24.09, P<0.05). There were not statistically significant in the time of anal exsufflation and first defecation time between the two groups(P>0.05). Conclusions Evidence-based practice in the use of guidelines for the standardization of intake and consumption after spinal cord surgery can guide clinical practice.

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