1.Structure and Function of GPR126/ADGRG6
Ting-Ting WU ; Si-Qi JIA ; Shu-Zhu CAO ; De-Xin ZHU ; Guo-Chao TANG ; Zhi-Hua SUN ; Xing-Mei DENG ; Hui ZHANG
Progress in Biochemistry and Biophysics 2025;52(2):299-309
GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.
2.Expert consensus on the positioning of the "Three-in-One" Registration and Evaluation Evidence System and the value of orientation of the "personal experience"
Qi WANG ; Yongyan WANG ; Wei XIAO ; Jinzhou TIAN ; Shilin CHEN ; Liguo ZHU ; Guangrong SUN ; Daning ZHANG ; Daihan ZHOU ; Guoqiang MEI ; Baofan SHEN ; Qingguo WANG ; Xixing WANG ; Zheng NAN ; Mingxiang HAN ; Yue GAO ; Xiaohe XIAO ; Xiaobo SUN ; Kaiwen HU ; Liqun JIA ; Li FENG ; Chengyu WU ; Xia DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):445-450
Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.
3.Exploring mechanism of action and validation of key regulatory pathways of selenshenzhi prescription in treatment of esophageal cancer based on network pharmacology
Ke-Yi JI ; Su-Hui WU ; Jia-Yao YUAN ; Han-Bing LI ; Shun-Cai WANG ; Long-Jie WANG ; Lin-Lin WANG ; Qi-Long GAO
Chinese Pharmacological Bulletin 2024;40(11):2174-2184
Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.
4.Single mini-incision combined with honeycomb titanium plate in treatment of acute acromioclavicular joint disloca-tion
Yu-Chen WANG ; Wei-Zhong YU ; Yun-Feng LI ; Wen-Ke ZHU ; Chuan JIA ; Jun-Qi WU ; Hua GAO ; Lin JI
China Journal of Orthopaedics and Traumatology 2024;37(6):576-582
Objective To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation.Methods The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods.Among them,20 patients were fixed with single small incision with honeycomb titanium plate(titanium plate group),including 11 males and 9 females,aged from 23 to 65 years old with an average of(47.40±12.58)years old;12 patients on the left side,8 patients on the right side;11 patients with type Ⅲ,3 patients with type Ⅳ,and 6 patients with type Ⅴ according to Rockwood classification.Twenty patients were fixed with clavicular hook plate(clavicular hook group),including 8 males and 12 females,aged from 24 to 65 years old with an average of(48.40±12.08)years old;12 patients on the left side,8 patients on the right side;10 patients with type Ⅲ,2 patients with type Ⅳ,and 8 patients with type V according to Rockwood classifica-tion.Operative time,incision length,intraoperative blood loss,hospital stay,visual analogue scale(VAS)and Constant-Murley score of shoulder joint function were compared between two groups.Anteroposterior radiographs of the affected shoulder joint were recorded before,immediately and 6 months after surgery,and the coracoclavicular distance was measured and compared.Results Both groups of patients were successfully completed operation without serious complications.All patients were fol-lowed up for 6 to 15 months with an average of(11.9±4.8)months.There were no incisional infection,internal plant fracture or failure,bone tunnel fracture and other complications occurred.The incision length of titanium plate group(35.90±3.14)mm was significantly shorter than that of clavicular hook group(49.30±3.79)mm(P<0.05).There were no significant difference in operative time,intraoperative blood loss and hospital stay between two groups(P>0.05).At 1 and 3 months after operation,VAS of titanium plate group was lower than that of clavicular hook group(P<0.05).Connstant-Murley scores in titanium plate group at 1,3 and 6 months after operation were(86.80±1.36),(91.60±2.32)and(94.90±2.22),respectively;and in clavicular hook group were(78.45±5.47),(85.55±2.01)and(90.25±1.92),which were higher than that of clavicular hook group(P<0.05).There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after op-eration(P>0.05).Conclusion For the treatment of acute acromioclavicular joint dislocation,single small incision combined with honeycomb titanium plate have advantages of shorter incision,fast recovery of shoulder joint function without the second operation,and has good satisfaction of patient.
5.Establishment and evaluation of animal model of filum terminale traction tethered cord syndrome
Qing-Yu JIANG ; Ai-Jia SHANG ; Xu-Dong SHI ; Hao-Feng CHENG ; Tian-Qi SU ; Yan WU
Journal of Regional Anatomy and Operative Surgery 2024;33(11):985-990
Objective To establish a new animal model of filum terminale traction tethered cord syndrome to explore its pathogenesis.Methods Sixteen New Zealand white rabbits were randomly divided into the traction group and the sham group,with 8 rabbits in each group.The traction group used silk thread to establish a model of filum terminale traction tethered cord syndrome,while the sham group only cut the filum terminale without traction.After 8 weeks,the behavioral Talov score,lumbosacral MRI examination,somatosensory evoked potential detection,urodynamic index test and pathological analysis were completed.Results At the 8th week after surgery,the hindlimb injury was obvious in the traction group,and the Talov scores at the 4th and 8th weeks after operation were lower than those in the sham group(P<0.001).The lumbosacral MRI results at 8 weeks after surgery showed that the distal filum terminale was pulled by silk thread,with bladder abnormal enlargement in sagital MRI in the traction group,while axial MRI showed the spinal cord within the spinal canal was subjected to mechanical forces in the downward and dorsal directions;the sagittal and axial MRI of the sham group showed that the spinal cord was located in the middle of the spinal canal and the bladder size was normal.At the 8th week after surgery,the amplitude in the traction group was significantly lower than that in the sham group(P<0.001),and the amplitude decreased by more than 50% .The overall latency period in the traction group was slightly longer than that in the sham group(P<0.05).The results of urodynamic examination showed that the maximum bladder capacity in the traction group was significantly higher than that in the sham group(Z=-3.361,P<0.001),the bladder pressure was significantly lower than that in the sham group(Z=-3.361,P<0.001),and the bladder compliance was significantly higher than that in the sham group(P<0.001).Pathological staining showed that the traction of the filum terminale on the spinal cord led to nerve tissue damage and degeneration of bladder epithelial cells.Conclusion This study successfully established a model of filum terminale traction tethered cord syndrome of New Zealand white rabbits,which can provide reference for exploring the pathogenesis of tethered cord and understanding the pathological process of spinal cord injury.
6.Background, design, and preliminary implementation of China prospective multicenter birth cohort
Si ZHOU ; Liping GUAN ; Hanbo ZHANG ; Wenzhi YANG ; Qiaoling GENG ; Niya ZHOU ; Wenrui ZHAO ; Jia LI ; Zhiguang ZHAO ; Xi PU ; Dan ZHENG ; Hua JIN ; Fei HOU ; Jie GAO ; Wendi WANG ; Xiaohua WANG ; Aiju LIU ; Luming SUN ; Jing YI ; Zhang MAO ; Zhixu QIU ; Shuzhen WU ; Dongqun HUANG ; Xiaohang CHEN ; Fengxiang WEI ; Lianshuai ZHENG ; Xiao YANG ; Jianguo ZHANG ; Zhongjun LI ; Qingsong LIU ; Leilei WANG ; Lijian ZHAO ; Hongbo QI
Chinese Journal of Perinatal Medicine 2024;27(9):750-755
China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.
7.Effect and Mechanism of Qixian Tongluo Formula on Contralateral Corticospinal Tract Remodeling and Motor Functional Recovery in Rats with Cerebral Infarction
Shengqiang ZHOU ; Dahua WU ; Bo LI ; Yanjun CHEN ; Jia HUANG ; Qi WANG ; Wen ZENG ; Lingjuan TAN ; Yihui DENG ; Fang LIU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1319-1328
Objective To observe the effect of Qixian Tongluo Formula on contralateral corticospinal tract(CST)remodeling and motor functional recovery in rats with cerebral infarction,and to explore its potential molecular mechanism from the perspective of regulating factors related to never remodeling.Methods The rat middle cerebral artery occlusion(MCAO)model was established by silk thread ligation.Fifty model rats were randomly divided into model group,citicoline group(0.054 g·kg-1),Qixian Tongluo Formula low-,medium-and high-dose(7.83,15.66,31.32 g·kg-1)groups,and sham operation group,with 10 rats in each group.The intervention administration was started on the 3rd day after operation once a day for 26 consecutive days.On the 3rd,14th and 28th day after operation,the gross motor function was evaluated by Longa score,and the fine motor function was evaluated by beam-walking test(BWT)score.The contralateral motor cortex was injected with the nerve tracer biotin dextran amine(BDA)on the 14 th day after operation to anterogradely trace the CST.On the 28th day after operation,the expression of axonal growth associated protein-43(GAP-43)and BDA positive fibers in the contralateral motor cortex and cervical spinal cord were detected by immunohistochemistry.The co-localization areas of BDA positive fibers and presynaptic marker protein vesicular glutamate transporter 1(VGLUT1)in the cervical spinal cord gray matter were detected by immunofluorescence.The expressions of brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and nerve remodeling-associated inhibitory factor[Nogo-A,oligodendrocyte myelin glycoprotein(OMgp)and myelin-associated glycoprotein(MAG)]in the contralateral motor cortex were detected by Western Blot.Pearson correlation analysis was used to analyze the correlation between Longa score or BWT score and BDA/VGLUT1 co-localization area,respectively.Results Compared with the sham operation group,rats in the model group had obvious symptoms of motor function deficits,and the Longa scores were significantly increased(P<0.01)and the BWT scores were significantly decreased(P<0.05,P<0.01)at each time point.The expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was up-regulated(P<0.05),the number of edge-crossing fibers from the posterior funiculus in cervical cord was increased(P<0.05),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was increased(P<0.05),the expressions of BDNF,GDNF and NGF in the contralateral motor cortex were up-regulated(P<0.05),while the expressions of Nogo-A,OMgp and MAG were down-regulated(P<0.05).Compared with the model group,the Longa scores in each administration group on the 14th and 28th day after MCAO operation were significantly decreased(P<0.01),the BWT scores were significantly increased(P<0.01),the expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was significantly up-regulated(P<0.01).The number of edge-crossing fibers from the posterior funiculus in cervical cord was significantly increased(P<0.01),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was significantly increased(P<0.01).The expressions of BDNF,GDNF and NGF in the contralateral motor cortex were significantly up-regulated(P<0.01,P<0.05),while the expressions of Nogo-A,OMgp and MAG were significantly down-regulated(P<0.05),and the most significant effect was observed in the high dose group.The Longa score was negatively correlated with the co-localization area of BDA/VGLUT1(r=-0.89,P<0.01),and the BWT score was positively correlated with the co-localization area of BDA/VGLUT1(r=0.84,P<0.01).Conclusion Qixian Tongluo Formula can improve motor function through promoting contralateral CST remodeling in MCAO rats after cerebral infarction,and the molecular mechanism may be related to the regulation of the expression of nerve remodeling-associated factor in the contralateral motor cortex.
8.Curriculum system of graduation internship for undergraduate students majoring in biomedical engineering
Xiao-Li LIU ; Huan-Shu LIU ; Lu JIA ; Qi-Bo MA ; Zhao ZHANG ; Wen-Fang WU
Chinese Medical Equipment Journal 2024;45(9):89-94
Objective To construct a set of graduation internship curriculum system suitable for undergraduate students majoring in biomedical engineering to facilitate standardizing the curriculum system of biomedical engineering major.Methods An initial version of the curriculum system was established with the way of letter and the methods of questionnaire survey,Delphi,expert interview and expert brainstorming;then the initial version was adjusted and refined using 2 rounds of expert consultation to form a set of curriculum system for graduation internship for undergraduate students majoring in biomedical engineering,and the curriculum system was validated.Results The curriculum system included 5 first-level catalogs,11 second-level catalogs and 39 third-level catalogs;the 36 third-level catalogs had a curriculum compliance rate of 0.85 to 0.97.Conclusion The curriculum system constructed can be used for graduation internship of biomedical engineering undergraduates,and references are provided for developing standardized and generally applicable graduation internship curriculum system for biomedical engineering undergraduates.[Chinese Medical Equipment Journal,2024,45(9):89-94]
9.Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor
Jia QI ; Zhou YINYIN ; Song LI ; Shi XIMENG ; Jiang XUAN ; Tao RUIZHI ; Wang AIYUN ; Wu YUANYUAN ; Wei ZHONGHONG ; Zhang YINAN ; Li XIAOMAN ; Lu YIN
Journal of Pharmaceutical Analysis 2024;14(7):1047-1062
Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.
10.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.


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