1.Three-dimensional human-robot mechanics modeling for dual-arm nursing-care robot transfer based on individualized musculoskeletal multibody dynamics.
Zhiqiang YANG ; Funing HOU ; Qiang LIN ; Jiexin XIE ; Hao LU ; Shijie GUO
Journal of Biomedical Engineering 2025;42(1):96-104
During transfer tasks, the dual-arm nursing-care robot require a human-robot mechanics model to determine the balance region to support the patient safely and stably. Previous studies utilized human-robot two-dimensional static equilibrium models, ignoring the human body volume and muscle torques, which decreased model accuracy and confined the robot ability to adjust the patient's posture in three-dimensional spatial. Therefore, this study proposes a three-dimensional spatial mechanics modeling method based on individualized human musculoskeletal multibody dynamics. Firstly, based on the mechanical features of dual-arm support, this study constructed a foundational three-dimensional human-robot mechanics model including body posture, contact position and body force. With the computed tomography data from subjects, a three-dimensional femur-pelvis-sacrum model was reconstructed, and the individualized musculoskeletal dynamics was analyzed using the ergonomics software, which derived the human joint forces and completed the mechanic model. Then, this study established a dual-arm robot transfer platform to conduct subject transfer experiments, showing that the constructed mechanics model possessed higher accuracy than previous methods. In summary, this study provides a three-dimensional human-robot mechanics model adapting to individual transfers, which has potential application in various scenarios such as nursing-care and rehabilitating robots.
Humans
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Robotics
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Biomechanical Phenomena
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Posture
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Imaging, Three-Dimensional
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Nursing Care
2.BRD4 regulates m6A of ESPL1 mRNA via interaction with ALKBH5 to modulate breast cancer progression.
Haisheng ZHANG ; Linlin LU ; Cheng YI ; Tao JIANG ; Yunqing LU ; Xianyuan YANG ; Ke ZHONG ; Jiawang ZHOU ; Jiexin LI ; Guoyou XIE ; Zhuojia CHEN ; Zongpei JIANG ; Gholamreza ASADIKARAM ; Yanxi PENG ; Dan ZHOU ; Hongsheng WANG
Acta Pharmaceutica Sinica B 2025;15(3):1552-1570
The interaction between m6A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m6A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m6A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.
3.Denatonium benzoate promotes MrgprB2-mediated rat mast cell degranulation
Huaping XU ; Xiaoyun SHI ; Jiexin ZOU ; Xin LI ; Mengting XIE ; Shiyu XIAO ; Linbo SHI
Chinese Journal of Immunology 2024;40(10):2037-2041
Objective:To explore the potent effects of denatonium benzoate(DB)on Mas-related G protein-coupled receptor-B2(MrgprB2)-mediated rat mast cell degranulation.Methods:RBL-2H3 cells were treated with DB overnight,before challenged with MrgprB2 ligands substance P(SP).The release of β-hex from MrgprB2-activated RBL-2H3 was detected by substrate method.Detec-tion of LTC4,IL-6,TNF-α and cPLA2 activity were performed by ELISA.The Ca2+influx and the expression of RBL-2H3 MrgprB2 re-ceptors were measured by fluorescence assay.Results:The results showed 10 μmol/L,50 μmol/L,80 μmol/L,100 μmol/L DB treat-ments promoted β-hex and LTC4 releases from activated RBL-2H3,accompanied by increased Ca2+mobilization and cPLA2 activa-tion.DB treatments did not affect IL-6 and TNF-α LTC4 releases in MrgprB2-activated RBL-2H3,as well as the levels of MrgprB2 ex-pression in mast cells.Conclusion:Taken together,DB enhanced the MrgprB2-mediated RBL-2H3 degranulation in vitro,probably by up-regulating Ca2+mobilization in activated cells.
4.A novel inhibitor of N 6-methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities.
Guoyou XIE ; Xu-Nian WU ; Yuyi LING ; Yalan RUI ; Deyan WU ; Jiawang ZHOU ; Jiexin LI ; Shuibin LIN ; Qin PENG ; Zigang LI ; Hongsheng WANG ; Hai-Bin LUO
Acta Pharmaceutica Sinica B 2022;12(2):853-866
N 6-methyladenosine (m6A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m6A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m6A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.
5.The effects of multi-disciplinary team management on the outcome in neonates with omphalocele
Haiqing ZHENG ; Suting XU ; Zijun HUANG ; Shanshan MEI ; Bin YAN ; Qiuming HE ; Zhe WANG ; Junjian LYU ; Xiaoli XIE ; Jiexin ZHANG ; Wei ZHONG
Chinese Journal of Neonatology 2020;35(1):25-28
Objective To study the effect of multi-disciplinary team (MDT) management on the outcome in neonates with omphalocele.Method A retrospective non-randomized controlled clinical study was conducted.Neonates who were diagnosed as omphalocele and admitted to the surgical neonatal intensive care unit of the Guangzhou Women and Children Medical Center from December 2010 to December 2017 were collected.Because MDT was established in December 2014,infants were assigned into non-MDT group and MDT group according to their dates of admission.The characteristics and outcomes between non-MDT group and MDT group were compared using x2,t-test or rank-sum test.Multivariate analysis was performed by Logistic regression.Result A total of 91 neonates were included in the study,50 were in non-MDT group and 41 were in MDT group.The mortality in MDT group (2.4%,1/41) was lower than that in non-MDT group (18.0%,9/50),the difference was statistically significant (P < 0.05).The median time of mechanical ventilation of giant omphalocele in non-MDT group (18.3 hours) was longer than that in MDT group (41.7 hours),the difference was also statistically significant (P < 0.05).After adjusting for the associated confounding risk factors,the risk of death in non-MDT group was 54 times higher than that in MDTgroup (OR=54.19,95%CI2.64 ~1 113.49,P<0.05).Conclusion There was significant association between the MDT management and the decreased risk of death of omphalocele.
6.Clinical value of combining indocyanine green fluorescence navigation with blue dye in sentinel lymph node biopsy in patients with breast cancer
Zechun ZHANG ; Paize XIE ; Jiexin CHEN ; Jianhao HUANG ; Yanghang FAN ; Xuyuan LI ; Zhiyong WU
Chinese Journal of Clinical Oncology 2016;43(17):757-760
Objective:To examine the clinical value of combining indocyanine green (ICG) fluorescence navigation with blue dye in sen-tinel lymph node biopsy (SLNB) for patients with breast cancer. Methods:A total of 89 patients with early-stage breast cancer who met the inclusion criteria were admitted at Shantou Central Hospital, Guangdong from May 2013 to April 2014. In phase one, ICG and blue dye were applied in all 53 patients, and then SLNB and axillary lymph node dissection (ALND) were performed based on fluores-cence signal or visual sense of the lymph nodes. In phase two, 36 patients with early-stage breast cancer were included. ALND was omitted when sentinel lymph nodes were frozen showing negative result. Rates of detection, accuracy, and false-negative were calcu-lated. Results:A total of 89 patients were monitored, of which the total rate of SLNB detection was 96.6%(86/89). In the validation pe-riod, the rates of detection, accuracy, and false-negative were 94.3%(50/53) 98.0%(49/50), and 2.6%(1/38), respectively. In the alter-ative period, the rates of detection reached 100%. Of the 196 sentinel lymph nodes, 179 showed fluorescence signal, 142 exhibited blue dying, 54 only demonstrated fluorescence signals, and 45 demonstrated metastasis with five signaling fluorescence. About 24.7%of patients were diagnosed with SLN metastasis (22/89), where SLNB in two patients showed fluorescence signal but without blue dye. No ipsilateral lymph node relapsed were observed during a median follow up of 25 months. Conclusion:Combination of ICG fluores-cence navigation with blue dye in SLNB is safe for patients with breast cancer.

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