1.Identification of core genes of osteoarthritis by bioinformatics
Xuekun ZHU ; Heng LIU ; Hui FENG ; Yunlong GAO ; Lei WEN ; Xiaosong CAI ; Ben ZHAO ; Min ZHONG
Chinese Journal of Tissue Engineering Research 2025;29(3):637-644
BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.
2.IDH3A Inhibits Cardiomyocyte Hypertrophy via Elevating α-Ketoglutarate Level
Huayan WU ; Yihong WEN ; Hengli ZHAO ; Yuan GAO ; Chuanmeng ZHOU ; Ya WANG ; Jiening ZHU ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):275-283
ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A (IDH3A) on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers (n=10) and patients with heart failure (HF) (n=10), and in the myocardium of mice subjected to transverse aortic constriction (TAC) surgery and sham operation, as well as in phenylephrine (PE)-induced neonatal rat ventricular cardiomyocytes (NRVCs), was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity, IDH3A_D208A, was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype, ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid (AKG) on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay, respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients, in the myocardium of TAC-operated mice, and in PE-induced NRVCs (P = 0.005 2,P = 0.026 6,P = 0.041 3 and P = 0.006 6, respectively). Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs (P < 0.000 1, P = 0.000 1 and P = 0.000 2, respectively). The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs (P = 0.001 2 and P<0.000 1, respectively), whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could, but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level, providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.
3.Clinical and Laboratory Characteristics of Streptococcus mitis Causing Bloodstream Infection in Children with Hematological Disease.
Yu-Long FAN ; Guo-Qing ZHU ; Zhi-Ying TIAN ; Yan-Xia LYU ; Zhao WANG ; Ye GUO ; Wen-Yu YANG ; Qing-Song LIN ; Xiao-Juan CHEN
Journal of Experimental Hematology 2025;33(1):286-291
OBJECTIVE:
To investigate the risk factors, clinical characteristics, and bacterial resistance of bloodstream infections caused by Streptococcus mitis in children with hematological disease, so as to provide a reference for infection control.
METHODS:
The clinical information and laboratory findings of pediatric patients complicated with blood cultures positive for Streptococcus mitis from January 2018 to December 2020 in the Institute of Hematology & Blood Diseases Hospital were searched and collected. The clinical characteristics, susceptibility factors, and antibiotic resistance of the children were retrospectively analyzed.
RESULTS:
Data analysis from 2018 to 2020 showed that the proportion of Streptococcus mitis isolated from bloodstream infections in children (≤14 years old) with hematological diseases was the highest (19.91%) and significantly higher than other bacteria, accounting for 38.64% of Gram-positive cocci, and presented as an increasing trend year by year. A total of 427 children tested positive blood cultures, including 85 children with bloodstream infections caused by Streptococcus mitis who tested after fever. Most children experienced a recurrent high fever in the early and middle stages (≤6 d) of neutropenia and persistent fever for more than 3 days. After adjusting the antibiotics according to the preliminary drug susceptibility results, the body temperature of most children (63.5%) returned to normal within 4 days. The 85 children were mainly diagnosed with acute myeloid leukemia (AML), accounting for 84.7%. The proportion of children in the neutropenia stage was 97.7%. The incidence of oral mucosal damage, lung infection, and gastrointestinal injury symptoms was 40%, 31.8%, and 27.1%, respectively. The ratio of elevated C-reactive protein (CRP) and procalcitonin was 65.9% and 9.4%, respectively. All isolated strains of Streptococcus mitis were not resistant to vancomycin and linezolid, and the resistance rate to penicillin, cefotaxime, levofloxacin, and quinupristin-dalfopristin was 10.6%, 8.2%, 9.4%, and 14.1%, respectively. None of children died due to bloodstream infection caused by Streptococcus mitis.
CONCLUSION
The infection rate of Streptococcus mitis is increasing year by year in children with hematological diseases, especially in children with AML. Among them, neutropenia and oral mucosal damage after chemotherapy are high-risk infection factors. The common clinical symptoms include persistent high fever, oral mucosal damage, and elevated CRP. Penicillin and cephalosporins have good sensitivity. Linezolid, as a highly sensitive antibiotic, can effectively control infection and shorten the course of disease.
Humans
;
Child
;
Streptococcal Infections/microbiology*
;
Retrospective Studies
;
Hematologic Diseases/complications*
;
Streptococcus mitis
;
Drug Resistance, Bacterial
;
Risk Factors
;
Microbial Sensitivity Tests
;
Anti-Bacterial Agents
;
Female
;
Male
;
Bacteremia/microbiology*
;
Child, Preschool
;
Adolescent
4.Deep learning algorithms for intelligent construction of a three-dimensional maxillofacial symmetry reference plane.
Yujia ZHU ; Hua SHEN ; Aonan WEN ; Zixiang GAO ; Qingzhao QIN ; Shenyao SHAN ; Wenbo LI ; Xiangling FU ; Yijiao ZHAO ; Yong WANG
Journal of Peking University(Health Sciences) 2025;57(1):113-120
OBJECTIVE:
To develop an original-mirror alignment associated deep learning algorithm for intelligent registration of three-dimensional maxillofacial point cloud data, by utilizing a dynamic graph-based registration network model (maxillofacial dynamic graph registration network, MDGR-Net), and to provide a valuable reference for digital design and analysis in clinical dental applications.
METHODS:
Four hundred clinical patients without significant deformities were recruited from Peking University School of Stomatology from October 2018 to October 2022. Through data augmentation, a total of 2 000 three-dimensional maxillofacial datasets were generated for training and testing the MDGR-Net algorithm. These were divided into a training set (1 400 cases), a validation set (200 cases), and an internal test set (200 cases). The MDGR-Net model constructed feature vectors for key points in both original and mirror point clouds (X, Y), established correspondences between key points in the X and Y point clouds based on these feature vectors, and calculated rotation and translation matrices using singular value decomposition (SVD). Utilizing the MDGR-Net model, intelligent registration of the original and mirror point clouds were achieved, resulting in a combined point cloud. The principal component analysis (PCA) algorithm was applied to this combined point cloud to obtain the symmetry reference plane associated with the MDGR-Net methodology. Model evaluation for the translation and rotation matrices on the test set was performed using the coefficient of determination (R2). Angle error evaluations for the three-dimensional maxillofacial symmetry reference planes were constructed using the MDGR-Net-associated method and the "ground truth" iterative closest point (ICP)-associated method were conducted on 200 cases in the internal test set and 40 cases in an external test set.
RESULTS:
Based on testing with the three-dimensional maxillofacial data from the 200-case internal test set, the MDGR-Net model achieved an R2 value of 0.91 for the rotation matrix and 0.98 for the translation matrix. The average angle error on the internal and external test sets were 0.84°±0.55° and 0.58°±0.43°, respectively. The construction of the three-dimensional maxillofacial symmetry reference plane for 40 clinical cases took only 3 seconds, with the model performing optimally in the patients with skeletal Class Ⅲ malocclusion, high angle cases, and Angle Class Ⅲ orthodontic patients.
CONCLUSION
This study proposed the MDGR-Net association method based on intelligent point cloud registration as a novel solution for constructing three-dimensional maxillofacial symmetry reference planes in clinical dental applications, which can significantly enhance diagnostic and therapeutic efficiency and outcomes, while reduce expert dependence.
Humans
;
Deep Learning
;
Algorithms
;
Imaging, Three-Dimensional/methods*
;
Male
;
Female
;
Maxilla/diagnostic imaging*
;
Adult
5.Erratum: Author correction to "SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade" Acta Pharm Sin B 9 (2019) 304-315.
Mingxia ZHAO ; Wenjie GUO ; Yuanyuan WU ; Chenxi YANG ; Liang ZHONG ; Guoliang DENG ; Yuyu ZHU ; Wen LIU ; Yanhong GU ; Yin LU ; Lingdong KONG ; Xiangbao MENG ; Qiang XU ; Yang SUN
Acta Pharmaceutica Sinica B 2025;15(5):2810-2812
[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].
6.Effect of regional crosstalk between sympathetic nerves and sensory nerves on temporomandibular joint osteoarthritic pain.
Zhangyu MA ; Qianqian WAN ; Wenpin QIN ; Wen QIN ; Janfei YAN ; Yina ZHU ; Yuzhu WANG ; Yuxuan MA ; Meichen WAN ; Xiaoxiao HAN ; Haoyan ZHAO ; Yuxuan HOU ; Franklin R TAY ; Lina NIU ; Kai JIAO
International Journal of Oral Science 2025;17(1):3-3
Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals
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Osteoarthritis/physiopathology*
;
Mice
;
Sympathetic Nervous System/physiopathology*
;
Temporomandibular Joint Disorders/physiopathology*
;
Arthralgia
;
Sensory Receptor Cells
;
Disease Models, Animal
;
Norepinephrine
;
Male
;
Temporomandibular Joint/physiopathology*
;
Pain Measurement
7.Evaluation of the function and activity of masticatory muscles using a self-developed wireless surface electromyography system.
Wenbo LI ; Yujia ZHU ; Qingzhao QIN ; Shenyao SHAN ; Zixiang GAO ; Aonan WEN ; Yong WANG ; Yijiao ZHAO
West China Journal of Stomatology 2025;43(3):346-353
OBJECTIVES:
This study aimed to evaluate the repeatability and reliability of a self-developed domestic wireless surface electromyography (sEMG) system (Oralmetry) in assessing the activity of the temporalis and masseter muscles to provide theoretical support for its clinical application.
METHODS:
Twenty-two volunteers were recruited. Through multiple repeated measurements, the sEMG signals of bilateral anterior temporalis and masseter muscles during maximum voluntary clenching were collected using the self-developed sEMG device, Oralmetry, and two commercial sEMG devices (Zebris and Teethan), filtered, screened, and standardized. Seven sEMG indicators for assessing masticatory muscle function were calculated. The intraclass correlation coefficient (ICC) was used to evaluate the repeatability of the measurements from the three sEMG devices, and statistical analysis was conducted to compare the consistency of the seven sEMG indicators obtained from the devices.
RESULTS:
Among the 22 participants, the ICC values of the repeated measurements from the three sEMG devices ranged from 0.88 to 0.99. The measurements of three sEMG indicators (antero-posterior coeffificient, percentage overlapping coeffificient_MM, and percentage overlapping coeffificient_TA) obtained by Zebris were significantly different from those obtained by Oralmetry and Teethan (P<0.05). No significant differences in the measurements of the seven sEMG indicators were found between Oralmetry and Teethan.
CONCLUSIONS
Oralmetry and the two commercial sEMG devices demonstrated good repeatability in capturing sEMG indicators for evaluating masticatory muscle function. In particular, Oralmetry showed the highest ICC values. All three devices also exhibited good consistency in measuring sEMG indicators, and a high agreement was observed between the two wireless sEMG devices (Oralmetry and Teethan). These findings provide theoretical support for the clinical application of Oralmetry.
Humans
;
Electromyography/methods*
;
Masseter Muscle/physiology*
;
Masticatory Muscles/physiology*
;
Wireless Technology
;
Reproducibility of Results
;
Temporal Muscle/physiology*
;
Male
;
Adult
;
Female
;
Young Adult
8.Application of two different methods of visual acuity assessment for myopia screening among lower grade elementary school students
LIANG Li, XU Shaojun, ZHU Yi, XU Xing, ZHAO Mengya, WEN Yuechun, TAO Fangbiao
Chinese Journal of School Health 2024;45(2):273-276
Objective:
To explore two visual acuity standards for examining uncorrected visual acuity (UCVA) to define poor vision in lower grade elementary school students, and to compare the difference of screening myopia rates when combined with non cycloplegic auto refraction (NCAR), so as to provide a scientific basis for standardizing UCVA examination methods using CAR as the gold standard of authenticity and reliability.
Methods:
From March 22nd to April 9th, 2023, a total of 549 first and second grade students aged 7-8 years from a primary school in Hefei City were selected for the study by convenient cluster sampling method. Two methods were employed for UCVA examination:the first method involved charts where the student could not make mistakes in identifying at least half of the characters per line (V1), and the second method used charts with character sizes ranging from 4.0 -4.5, 4.6-5.0 and 5.1-5.3, without allowing 1, 2 and 3 errors per line (V2). While NCAR was performed, then 187 students underwent CAR examination. Paired Wilcoxon rank-sum test and McNemar test were used to compare the differences between V1 and V2 methods in defining poor vision and screening myopia rates. Using CAR as the gold standard, the authenticity and reliability of defining screening myopia rates through the combination of V1 and V2 methods along with NCAR were evaluated.
Results:
The UCVA examination results for V1 and V2 showed statistically significant differences in both the right eye [5.0(4.9,5.0), 4.9(4.8,5.0)] and the left eye [ 5.0 (4.9,5.0), 4.9(4.8,5.0)] ( Z=-13.95, -13.34, P <0.01). The detection rates of poor vision for the right eye were 43.53% for V1 and 63.21% for V2, and the left eye with 44.08% for V1 and 62.11% for V2, with statistically significant differences ( χ 2= 106.01 , 95.09, P <0.01). When screening myopia rates were assessed for UCNA methods combined with NCAR, the right eye rates were 21.49% for V1 and 24.59% for V2, and the left eye rates were 21.31% for V1 and 23.13% for V2, with statistically significant differences ( χ 2=15.06, 8.10, P <0.01). Using CAR as the gold standard, the detection rates in the right eye and left eye were 16.58 % and 17.11%, respectively. The Youden indices for defining screening myopia in the right eye were 0.80 for V1 and 0.79 for V2, and the left eye with 0.85 for V1 and 0.83 for V2. The agreement rates for the right eye were 91.98 % for V1 and 89.30% for V2, and the left eye with 94.12% for V1 and 91.98% for V2. The Kappa values for the right eye were 0.73 for V1 and 0.67 for V2, and the left eye with 0.81 for V1 and 0.75 for V2.
Conclusions
Authenticity and reliability of two UCVA examination methods combined with NCAR in defining screening myopia are higher in V1 than V2 methods. It is recommended to unify the visual acuity examination methods by requiring the correct identification of more than half of the total number of visual markers in a row.
9.A Case Report of Multidisciplinary Management of a Patient with Schimke Immuno-Osseous Dysplasia
Juan DING ; Wei WANG ; Juan XIAO ; Yan ZHANG ; Huijuan ZHU ; Wen ZHANG ; Peng GAO ; Limeng CHEN ; Wei LYU ; Xuan ZOU ; Xiaoyi ZHAO ; Hongmei SONG ; Mingsheng MA
JOURNAL OF RARE DISEASES 2024;3(4):465-470
Schimke immuno-osseous dysplasia (SIOD)caused by
10.Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants
Sha ZHU ; Jing XU ; Ranran SHI ; Xiaokang WANG ; Maomao SUN ; Shina LI ; Lingling GAO ; Yuanyuan LI ; Huimin WEN ; Changliang ZHAO ; Shuai LI ; Juan JI ; Cuihong YANG ; Yonghui YU
Chinese Journal of Pediatrics 2024;62(1):29-35
Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.


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