1.Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1 -mutated oral squamous cell carcinoma.
Yumeng LIN ; Yibo HUANG ; Bowen YANG ; You ZHANG ; Ning JI ; Jing LI ; Yu ZHOU ; Ying-Qiang SHEN ; Qianming CHEN
Chinese Medical Journal 2025;138(15):1853-1865
BACKGROUND:
Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy.
METHODS:
To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated.
RESULTS:
OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression.
CONCLUSION
Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans
;
ErbB Receptors/metabolism*
;
Mouth Neoplasms/metabolism*
;
Cell Line, Tumor
;
Animals
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Drug Resistance, Neoplasm/genetics*
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Cadherins/metabolism*
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Carcinoma, Squamous Cell/metabolism*
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Mice
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Mutation/genetics*
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Mice, Nude
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Protein Kinase Inhibitors/therapeutic use*
;
Cetuximab/pharmacology*
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Afatinib/therapeutic use*
;
Cell Proliferation/drug effects*
;
Signal Transduction/drug effects*
2.Multi-Node Data Fusion Method of Home Health Monitoring Equipment for Assisting TCM Diagnosis
Qicheng YANG ; Chuanbiao WEN ; Yibo ZHOU ; Tao YANG ; Junying ZHU ; Ji LUO ; Ju CHEN
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(5):1344-1353
Objective To solve the problem of large data volume,multiple dimensions and low value for assisting traditional Chinese medicine clinical diagnosis in home health perception layer devices.Methods Based on the principles of traditional Chinese medicine diagnosis,this paper divides home health data into three types:complementary,redundant,and collaborative,and proposes a solution for data fusion at the levels of device data,home events,and traditional Chinese medicine symptoms.Results The proposed data fusion solution in this paper enables the data collected by various devices in the home environment to work together,extracts home data that is more valuable for traditional Chinese medicine diagnosis,and reduces the real-time pressure on the home network bandwidth caused by the sensors on the home side.Conclusion The construction of an open IoT ecosystem for home health based on multiple devices is a huge project,which includes the construction of perception layer hardware,data cleaning,fusion,normalization,labeling,modeling,and other aspects.This paper focuses on the idea of home health data fusion,which can provide directions for cleaning up heterogeneous data from multiple sources at home and also provide ideas for subsequent data labeling and modeling with traditional Chinese medicine characteristics,thus providing more valuable decision-making assistance for traditional Chinese medicine clinical practice.
3.Application of 3D printing technology combined with locking plate fixation in femoral shaft fracture of patients with femoral deformity
Yu SU ; Teng MA ; Qian WANG ; Ming LI ; Yibo XU ; Yao LU ; Bing DU ; Shuai JI ; Dongchen LI ; Yu CUI ; Yanling YANG ; Cheng REN ; Kun ZHANG ; Zhong LI
International Journal of Surgery 2023;50(11):731-737
Objective:To analyze the therapeutic effect of 3D printing technology combined with locking plate fixation on femoral shaft fracture in patients with femoral deformity.Methods:The clinical data of 33 patients with femoral shaft fracture with femoral deformity who met the inclusion criteria and underwent locking plate fixation in the Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from June 2014 to December 2020 were retrospectively analyzed. The patients were divided into 3D printing group ( n=18) and control group ( n=15) according to whether 3D printing was performed before operation. The 3D printing group including 11 males and 7 females with an age of (46.78±13.76) years.The control group including 9 males and 6 females with an age of (48.20±14.27) years.The operation time, intraoperative blood loss, fracture healing time and complications of the two groups were recorded. Visual analogue scale (VAS) scores of pain were evaluated before and 6, 12, 24, 48 and 72 h after operation. According to the Harris hip score, the Hospital for Special Surgery (HSS) knee score and The MOS 36-item short-from Health Survey (SF-36), the hip and knee function and quality of life of the patients before and 12 months after injury were evaluated. The measurement data were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data between groups was conducted by Chi-square test or Fisher exact probability. Results:The operation time, intraoperative blood loss, and incidence of complications in the 3D printing group were (91.50±9.07) min, (191.11±16.01) mL, and 0(0/18), respectively, and those in the control group were (118.07±14.19) min, (270.27±17.59) mL, and 26.7% (4/15), the differences between the two groups were statistically significant ( P <0.05). The pain VAS scores of the 3D printing group were significantly better than those of the control group at 6, 12, 24, 48, and 72 h after operation ( P<0.05). There were no differences in fracture healing time and preoperative pain VAS between the two groups( P>0.05). There were no significant differences in hip function, knee function and quality of life scores between the two groups before injury and 12 months after injury( P>0.05). Conclusion:In the treatment of femoral shaft fractures in patients with femoral deformity with locking plate fixation, the application of 3D printing technology can be used for preoperative design and plate preshaping, which can shorten the operation time, reduce the amount of intraoperative blood loss, reduce the VAS of pain and the incidence of complications, improve the satisfaction of surgery, and provide a new option for the treatment of femoral shaft fractures in patients with femoral deformity.
4.Changes in serum C3d and C5b-9 levels in elderly patients with idiopathic membranous nephropathy and their clinical significance
Lu WEN ; Fengping JI ; Yibo WEN ; Xiaoyang WANG ; Zhanzheng ZHAO
Chinese Journal of Geriatrics 2021;40(10):1245-1249
Objective:To investigate changes in serum C3d and C5b-9 levels in elderly patients with idiopathic membranous nephropathy(IMN)and their correlations with prognosis.Methods:Two hundred thirty-one elderly patients with IMN and 96 non-elderly patients with IMN confirmed by kidney biopsy at the First Affiliated Hospital of Zhengzhou University from January 2015 to May 2017 were enrolled.During the same period, 118 healthy individuals receiving health checkups were included as controls.Patients were divided into the low C3d group( n=112)and the high C3d group( n=113)according to the median level of serum C3d.Serum C3d and C5b-9 levels were measured by enzyme-linked immunosorbent assays. Results:Serum C3d and C5b-9 levels in elderly IMN patients were 0.23(0.15, 0.45)mg/L and 0.28(0.20, 1.23)mg/L, respectively, which were higher than those in healthy controls[0.18(0.13, 0.22)mg/L, 0.22(0.16, 0.26)mg/L, respectively]( Z=-4.261 and -6.213, P<0.001). Serum C3d levels in elderly and non-elderly IMN patients were correlated negatively with the estimated glomerular filtration rate( r=-0.155 and -0.426, P=0.019 and 0.000), but positively with serum creatinine, anti-phospholipase A2 receptor(PLA2R)antibody levels and 24 h urinary protein( r=0.184, 0.326, 0.407, 0.321 and 0.145, P=0.005, 0.001, 0.000, 0.001 and 0.027). Kaplan-Meier survival analysis showed that the cumulative renal survival rate in elderly IMN patients was lower in the high C3d group than in the low C3d group(47.8% vs.70.8%, Log Rank χ2=7.399, P=0.007). Multivariate Cox regression analysis showed that high C3d levels were an independent risk factor for poor renal outcomes in elderly IMN patients( HR=2.288, 95% CI: 1.082-4.839, P=0.030). Conclusions:High serum C3d levels are associated with increases in urinary protein excretion and anti-PLA2R antibody levels, renal function decline, and poor renal outcomes in elderly IMN patients.
5.The change of serum complement factor B and its clinical implication in children with primary IgA nephropathy
Lu WEN ; Fengping JI ; Yibo WEN ; Xiaoyang WANG ; Zhanzheng ZHAO
Chinese Journal of Applied Clinical Pediatrics 2021;36(24):1882-1886
Objective:To detect serum level of complement factor B (CFB), and to explore its correlations with clinical parameters and prognosis in children with primary IgA nephropathy (IgAN).Methods:A total of 204 children with primary IgAN confirmed by kidney biopsy in the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from December 2014 to April 2017 were included in IgAN group.During the same period, 84 healthy children were included in healthy control group.Their mean age was (11.0±3.5) years and (10.9±3.2) years, respectively.Patients in IgAN group were divided into low CFB group (102 cases) and high CFB group (102 cases) according to the medium serum level of CFB measured by enzyme-linked immunosorbent assay. Spearman′ s coefficient was employed to analyze correlation amongst various parameters.Multivariable-adjusted Cox proportional ha-zards models were used to evaluate the relationship between serum CFB level and prognosis in children with IgAN. Results:Serum CFB levels were significantly higher in IgAN group than that in healthy control group [290.9 (186.2-453.9) mg/L vs.218.9 (155.0-321.3) mg/L, Z=-3.372, P=0.001]. Serum levels of CFB were negatively correlated with serum albumin ( r=-0.388, P<0.001) and estimated glomerular filtration rate ( r=-0.416, P<0.001), but positively correlated with serum creatinine ( r=0.305, P<0.001) and 24 h urinary protein ( r=0.456, P<0.001) in IgAN group.The incidences of crescents (C1-2) (70.6% vs.29.4%, χ2=34.588, P<0.001) and C 3 deposition (+ + -+ + + ) (63.7% vs.44.1%, χ2=7.892, P=0.005) were significantly higher in high CFB group than those in low CFB group. Kaplan- Meier analysis showed that high CFB levels predicted worse renal outcome in pediatric IgAN patients ( χ2=17.509, P<0.001). Multivariate Cox regression analysis showed that the high CFB level was the independent risk factor for the poor renal outcome ( HR=2.517, 95% CI: 1.284-4.932, P=0.007). Conclusions:High serum levels of CFB are associated with decreased renal function, increased urinary protein excretion, crescentic formation and poor renal outcome in pediatric IgAN patients.
6.Construction of the curriculum for developing the ability to solving complex engineering problems in the field of biotechnology industry.
Yibo ZHU ; Lingtian WU ; Jinnan WU ; Hong JI
Chinese Journal of Biotechnology 2021;37(9):3383-3396
Accurately understanding the features and connotations of complex engineering problems is an important prerequisite for setting graduation requirements, constructing curriculum and designing teaching contents. By discussing the characteristics of complex engineering problems in the biological industry, this paper explored the demands for undergraduates in Yangtze river delta region, summarized the typical jobs and their requirements, and expounded the connotation of complex engineering problems contained in various typical tasks. On this basis, a gradual curriculum system was constructed, which included multiple stages of conceiving, formation and application, to cultivate the ability to solve complex engineering problems in the major of bioengineering. The curriculum coordinated the implementation of deep integration of industry and education, research feed back course construction, course team and advanced courses building up, professional associations covered all crews and students, supporting the ability training of solving complex engineering problems.
Biotechnology
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Curriculum
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Engineering
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Humans
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Industry
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Problem Solving
7.Development of a practical innovation course for biological engineering major under the background of Engineering Education Certification.
Lingtian WU ; Jinnan WU ; Yibo ZHU ; Delei XU ; Meilin ZHAO ; Luye YAO ; Hong JI
Chinese Journal of Biotechnology 2021;37(12):4455-4464
According to the teaching philosophy of the outcome-based education, this study elaborates the development of a practical innovation course for biological engineering major after five runs of teaching practice and continuous improvement. It mainly includes the methods for selection of teaching subjects, implementation of teaching process, process assessment, evaluation and improvement. Based on the performance and achievements of three grades of students majored in bioengineering, we found that the logic and methods of the practical innovation course could greatly stimulate the motivation of students for learning, as well as their scores. Therefore, the logic and methods described in this study may serve as a reference for the reforms of practical training courses of engineering major under the background of Engineering Education Certification.
Bioengineering
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Certification
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Curriculum
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Humans
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Learning
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Students
8. A mid-term clinical analysis of the treatment of ossification of the posterior longitudinal ligament with C1,2 single-door laminoplasty
Yibo ZHAO ; Xiaofeng ZHAO ; Xiangdong LU ; Zhonghua ZHANG ; Detai QI ; Xiaonan WANG ; Runtian ZHOU ; Yuanzhang JI ; Bin ZHAO
Chinese Journal of Orthopaedics 2019;39(22):1365-1372
Objective:
To analyze the mid-term clinical efficacy of extended to C1, 2 posterior single-door laminoplasty for the treatment of ossification of the posterior longitudinal ligament combined the upper cervical spine.
Methods:
From February 2013 to December 2015, 32 patients with cervical OPLL who were extended to C1, 2 posterior open-door laminoplasty were enrolled in our hospital (complete follow-up of 25 patients). There were 19 males and 6 females, aged 48-76 years (mean 60.1±7.0 years). Cervical spinal cord function was assessed using the Japanese Orthopaedic Association (JOA) spinal cord function score, and the rate of improvement in neurological function was calculated. The quality of life of patients was assessed using the neck disability index (NDI). Axial symptoms were assessed and indexed using the visual analog scale (VAS). The C0-2 angle of the cervical spine was measured by X-ray preoperative and at the last follow-up. The cervical curvature was evaluated by the C2-7 angle, and the cervical vertebra activity was observed by the dynamic X-ray of the cervical spine.
Results:
25 patients were followed up for a period of 26-64 months (mean 35.9±8.1 months). At the last follow-up, the JOA score was 14.32±3.24, the NDI score was 7.61±1.23, and the VAS score was 1.42±0.78. The differences between the three scores were statistically significant compared with the preoperative scores. The neurological improvement rate at the last follow-up was 79.61%±13.23%. The preoperative C0-2 angle was 26.04°±6.28°, and the last follow-up was 24.92°±5.51°; the C2-7 angle was 19.55°±9.42° before surgery, and the C2-7 angle at last follow-up was 17.97°±8.80°. The C2-7 angle at last follow-up was slightly reduced compared with that preoperative, but the difference was not statistically significant. The preoperative cervical vertebra ROM was 35.31°±12.24°, and at the last follow-up it was 32.23°±9.65°. The ROM of cervical vertebrae at the last follow-up was slightly lower than that before surgery, but the difference was not statistically significant. Among them, the reduction of the ROM of overflexion was greater than that of the over-extension, which was the main reason for the decrease of ROM. The OPLL bone mass continued to grow at the last follow-up of 11 patients.
Conclusion
The extended to C1, 2 posterior single-door laminoplasty for the treatment of ossification of the posterior longitudinal ligament combined the upper cervical spine can achieve adequate spinal cord decompression, satisfactory neurological improvement, and improve the postoperative cervical curvature and activity. There was no obvious change in the curvature and activity of the cervical spine, and the axial symptoms did not increase significantly, and the clinical efficacy was positive.
9.Investigation of the Problems and Solutions for CO2 Laser Treatment Apparatus in Hospital
Yibo JI ; Ming HAN ; Bingzhen WEI ; Fengping CHEN
Chinese Journal of Medical Instrumentation 2016;40(2):131-133
The current situation of the CO2 laser treatment apparatus in hospital was evaluated through actual investigation and testing data in this paper. The existing problems have been analyzed and the solutions are proposed, which wil play a role in maintenance, testing and drafting standards for this kind of medical devices being used in hospital.
10.The present situation and future development of research on new algorithms of gait recognition with multi-angles.
Yibo LI ; Kun LI ; Xiaofei JI
Journal of Biomedical Engineering 2014;31(1):205-209
Gait recognition is a new technology in biometric recognition and medical treatment which has advantages such as long-distance and non-invasiveness. Depending on the differences between different people's walking pos tures, we can recognize individuals by characteristics extracted from the images of walking movement. A complete gait recognition process usually includes gait sequence acquisition, gait detection, feature extracting and recognition. In this paper, the commonly used methods of these four processes are introduced, and feature extraction methods are classified from different multi-angle views. And then the new algorithm of multi-view emerged in recent years is highlighted. In addition, this paper summarizes the existing difficulties of gait recognition, and looks into the future development trends of it.
Algorithms
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Biometry
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Gait
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Humans
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Image Interpretation, Computer-Assisted
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Walking

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