1.Vascular endothelial growth factor 165/bone morphogenetic protein improves osteoblast injury under hypoxic and reoxygenated conditions
Yiting ZHAO ; Yuxiang ZHANG ; Jie MA ; Xuejiao HE
Chinese Journal of Tissue Engineering Research 2024;28(35):5669-5674
BACKGROUND:It has been found that vascular endothelial growth factor 165 and bone morphogenetic proteins interact with each other during hypoxia-reoxygenation and are involved in the repair process of osteoblast injury by regulating the activation of intracellular signaling pathways. OBJECTIVE:To further investigate the relationship between vascular endothelial growth factor 165/bone morphogenetic protein and hypoxic-reoxygenated osteoblast injury. METHODS:Osteoblasts were selected and the hypoxic-reoxygenated injury model was established.Vascular endothelial growth factor 165 and bone morphogenetic protein expressions at mRNA and protein levels were detected by real-time PCR and western blot before and after modeling.After modeling,osteoblasts were given different concentrations of vascular endothelial growth factor 165 and bone morphogenetic protein 2(10,20,40 ng/mL).Cell proliferation was detected by cell counting kit-8 method and apoptosis was detected by DAPI at 12,24,36,48,and 72 hours after treatment. RESULTS AND CONCLUSION:Compared with before modeling,the mRNA and protein expressions of vascular endothelial growth factor 165 and bone morphogenetic protein 2 in osteoblasts after modeling were significantly decreased(P<0.05).The proliferation rate of osteoblasts was significantly increased with the increase of vascular endothelial growth factor 165 concentration(P<0.05),while the apoptosis rate of osteoblasts decreased significantly with the increase of vascular endothelial growth factor 165 concentration(P<0.05).The proliferation rate of osteoblast was significantly increased with the increase of bone morphogenetic protein 2 concentration(P<0.05),while the apoptosis rate of osteoblast decreased significantly with the increase of bone morphogenetic protein 2 concentration(P<0.05).To conclude,vascular endothelial growth factor 165 and bone morphogenetic protein are lowly expressed in hypoxic-reoxygenated osteoblast injury,and treatment with vascular endothelial growth factor 165 and bone morphogenetic protein can reduce the injury of hypoxic-reoxygenated osteoblast in a concentration-dependent manner,suggesting that vascular endothelial growth factor 165 and bone morphogenetic protein have a significant protective effect against the injury of hypoxic-reoxygenated osteoblasts.
2.Effects of Aβ42 oligomers on expression of synaptic and extrasynaptic glutamate receptors
Qiuxuan CHEN ; Yani HE ; Yuxiang LIU ; Yi FENG ; Keke ZHANG ; Wei WEI
Chinese Journal of Pathophysiology 2024;40(6):1025-1032
AIM:To explore the expression and distribution of synaptic and extrasynaptic glutamate receptors under the action of amyloid β-protein 42 oligomers(Aβ42Os)in Alzheimer disease.METHODS:In vitro,primary neu-rons from neonatal mice were treated with different concentrations of Aβ42Os.In vivo,Aβ42Os were stereotaxically injected into the lateral ventricle of C57BL/6 mice.Western blot was used to detect the protein levels of metabotropic gultamate re-ceptor 5(mGluR5)and N-methyl-D-aspartate receptor(NMDAR)subunits(NR2A,NR2B and NR1)in mouse primary neurons and mice.Immunofluorescence staining was performed to observe the distribution of mGluR5 and NMDAR.Addi-tionally,Western blot was employed to examine the expression of mGluR5 downstream phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway-related proteins,calcium signaling pathway-related proteins and synapse-related proteins in mouse hippocampal tissues.RESULTS:(1)High concentrations of Aβ42Os increased mGluR5 expression in mouse primary neurons,but reduced the expression of NR2A,NR2B and NR1(P<0.01).Treatment of pri-mary neurons with high concentration of Aβ42Os resulted in aggregation of mGluR5 on the membrane surface,and re-duced the expression of NR2A,NR2B and NR1 on the membrane surface.(2)High concentration of Aβ42Os increased the expression of synaptic mGluR5 in mouse hippocampal tissues(P<0.01),but reduced the expression of synaptic NR2A(P<0.05)and NR2B(P<0.01)and increased the expression of extrasynaptic NR2B(P<0.01).High concentration of Aβ42Os inhibited the expression of PI3K and the phosphorylation of AKT and extracellular signal-regulated kinase(ERK),and overactivated calcium/calmodulin-dependent protein kinase IIα(CaMKIIα).High concentration of Aβ42 decreased the expression of postsynaptic density protein 95,spinophilin,synaptophysin and microtubule-associated protein 2(P<0.01).CONCLUSION:(1)High concentrations of Aβ42Os increase mGluR5 expression and decrease NR2A,NR2B and NR1 expression in synapse,along with an increase in extrasynaptic NR2B.(2)High concentrations of Aβ42Os inhibit the PI3K/AKT and ERK signaling pathways,overactivated the CaMKIIα pathway,and destroyed the synaptic structures.
3.iTRAQ-based proteomics reveals the mechanism of action of Yinlai decoction in treating pneumonia in mice consuming a high-calorie diet
Qianqian Li ; Tiegang Liu ; Chen Bai ; Xueyan Ma ; Hui Liu ; Zi ; an Zheng ; Yuxiang Wan ; He Yu ; Yuling Ma ; Xiaohong Gu
Journal of Traditional Chinese Medical Sciences 2024;11(1):21-32
Objective:
To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie diet-induced pneumonia through proteomics analysis.
Methods:
Based on the Gene Expression Omnibus (GEO) database, lung tissue samples from normal and high-fat diet (HFD) fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses. In the animal experiments, mice were randomly divided into the control (N), high-calorie diet pneumonia (M), and Yinlai decoction treatment (Y) groups. Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d. The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d. Pathological evaluation of the lung tissue was performed. Differentially expressed proteins (DEPs) in the lung tissue were identified using quantitative proteomics and bioinformatics analyses. The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory (MGL) Tools. DEPs were verified by western blot.
Results:
GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue. The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet. A total of 47 DEPs were identified between the Y and M groups. Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle (TCA) and oxidative phosphorylation. The protein-protein interaction network revealed that Atp5a1, Pdha1, and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction. Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide, praeruptorin B, chrysoeriol, and other components in Yinlai decoction to Atp5a1.
Conclusion
The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation. Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.
4.Clinical efficacy and safety of extended debridement combined with BAM bone-induced artificial bone repair in treating Cierny-Mader type IV osteomyelitis
Keye LI ; Daqiang LIN ; Xu ZHANG ; Yuxiang LIANG ; Dong HE ; Qiang GUO ; Zhigang LANG
Clinical Medicine of China 2024;40(5):328-334
Objective:To explore the clinical effect and safety of extended debridement combined with BAM bone-induced artificial bone repair in the treatment of Cierny-Mader type IV osteomyelitis.Methods:From January 2021 to December 2022, 106 patients with Cierny-Mader type IV osteomyelitis who were treated with allogeneic bone mixed with autologous bone in department of orthopedics of Sichuan Orthopedic Hospital were retrospectively selected as the study subjects. Among them, 54 patients who were combined with BAM bone-induced artificial bone mixed with autologous bone repair were included in observation group, and 52 patients who only received allogeneic bone mixed with autologous bone repair were enrolled as control group. The clinical related indicators (bone healing time, fracture healing time), clinical efficacy (Johner-Wruh tibial shaft fracture evaluation standard) at 1 year after surgery, inflammatory factors (white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin), limb function (American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AH)) and bone healing degree before surgery and at 1 year after surgery were compared between both groups. Chi-square test was used to compare the enumeration data between groups, and the independent sample t test was performed to compare the measurement data with normal distribution between groups.Results:At 1 year after surgery, the clinical healing indicators of bone healing time and fracture healing time and inflammatory factors such as WBC, ESR, CRP and procalcitonin with (21.19±2.16) weeks, (11.35±1.01) weeks, (6.15±0.73)×10 9/L, (9.10±1.05) mm/h, (8.09±1.11) mg/L and (0.05±0.01) μg/L in observation group were significantly shorter or lower than (24.32±2.39) weeks, (12.29±1.27) weeks, (7.86±0.89)×10 9/L, (10.10±1.32) mm/h, (9.26±1.23) mg/L and (0.08±0.01) μg/L in control group,and the differences were statistically significant ( t values were 7.08, 4.23, 10.83, 4.33, 5.15, and 15.44, respectively; all P<0.001). The clinical effective rate (85.19%(46/54)), AOFAS-AH score((84.83±12.17) points) and bone healing probability (94.44%(51/54)) were higher than (67.31%(35/52)), (79.17±11.25) points and 80.77% (42/52) in control group,with statistically significant differences (statistical values were χ2=4.70, t=2.48, and χ2=4.60, respectively; P values were 0.030, 0.015, and 0.032, respectively). Conclusion:Expanded debridement combined with BAM bone-induced artificial bone repair can effectively promote the bone tissue healing in patients with Cierny-Mader type IV osteomyelitis, relieve the inflammatory response, and improve the limb function, and it has good clinical efficacy and high safety.
5.Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway.
Hongqi ZHANG ; Gang XIANG ; Jiong LI ; Sihan HE ; Yunjia WANG ; Ang DENG ; Yuxiang WANG ; Chaofeng GUO
Chinese Medical Journal 2023;136(12):1468-1477
BACKGROUND:
Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23.
METHODS:
We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined.
RESULTS:
DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown.
CONCLUSIONS
Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.
Humans
;
Osteopontin/genetics*
;
Alkaline Phosphatase/metabolism*
;
Receptor, Fibroblast Growth Factor, Type 3/metabolism*
;
Scoliosis/genetics*
;
Osteoblasts/metabolism*
;
Calcinosis
;
RNA, Messenger/metabolism*
;
Bone Diseases, Metabolic/metabolism*
;
Fibroblast Growth Factors/genetics*
6.Research on a portable shielding-free ultra-low field magnetic resonance imaging system.
Yuxiang ZHANG ; Wei HE ; Lei YANG ; Yucheng HE ; Jiamin WU ; Zheng XU
Journal of Biomedical Engineering 2023;40(5):829-836
The portable light-weight magnetic resonance imaging system can be deployed in special occasions such as Intensive Care Unit (ICU) and ambulances, making it possible to implement bedside monitoring imaging systems, mobile stroke units and magnetic resonance platforms in remote areas. Compared with medium and high field imaging systems, ultra-low-field magnetic resonance imaging equipment utilizes light-weight permanent magnets, which are compact and easy to move. However, the image quality is highly susceptible to external electromagnetic interference without a shielded room and there are still many key technical problems in hardware design to be solved. In this paper, the system hardware design and environmental electromagnetic interference elimination algorithm were studied. Consequently, some research results were obtained and a prototype of portable shielding-free 50 mT magnetic resonance imaging system was built. The light-weight magnet and its uniformity, coil system and noise elimination algorithm and human brain imaging were verified. Finally, high-quality images of the healthy human brain were obtained. The results of this study would provide reference for the development and application of ultra-low-field magnetic resonance imaging technology.
Humans
;
Magnetic Resonance Imaging/methods*
;
Magnetic Resonance Spectroscopy/methods*
;
Head
;
Equipment Design
;
Magnets
7.Effect of rhythmic auditory stimulation on gait of patients with cerebral palsy: a systematic review
Hongying MA ; Jianjun LIU ; Xuejin HE ; Yuxiang WANG
Chinese Journal of Rehabilitation Theory and Practice 2023;29(12):1386-1394
ObjectiveTo systematically review the effect of rhythmic auditory stimulation on gait of patients with cerebral palsy. MethodsRelevant literature on gait improvement of patient with cerebral palsy by rhythmic auditory stimulation were retrieved from Web of Science, PubMed, EBSCO, CNKI and Wanfang database from establishment to December, 2022. Physiotherapy Evidence Database (PEDro) scale was used to evaluate the methodological quality of the articles, and the relevant data was extracted. A systematic review was conducted. ResultsA total of 1 339 literatures were retrieved, and ten were finally included. The patients mainly came from America, Egypt, Israel, South Korea and Greece. The intervention sites were mainly in hospitals and communities, and some patients received home-based intervention. The publication date was mainly after 2010. Adding rhythmic auditory stimulation on the basis of conventional rehabilitation training increased the range of motion of the joints of patients with cerebral palsy; improved the walking speed, step length and stride length; improved the movement mode, and enhanced the intervention effect of gait training. ConclusionRhythmic auditory stimulation is effective on the range of motion, walking speed, step length and stride length of patient with spastic cerebral palsy, which can improve gait.
8.Clinical Investigation of Key Parameter Range of AMG Muscle Relaxant Monitor.
Jian CEN ; Zuming YAO ; Yuxiang HE ; Hua TAO ; Qiling LIU ; Qiu YUAN
Chinese Journal of Medical Instrumentation 2022;46(4):464-468
The accelerometry(AMG) muscle relaxant monitor is the most widely used quantitative muscle relaxant monitor to assess the degree of neuromuscular at present. In this study, the ulnar nerve was stimulated by using train of four stimulation(TOF) mode of the AMG muscle relaxant monitor, and the movement of the adductor pollicis muscle was monitored. In this way, the distribution range of key parameters (acceleration peak value, response time, and TOF ratio) of the adductor pollicis muscle during the use of muscle relaxant in clinical practice is analyzed and will provide a practical basis for the development and improvement of the muscle relaxant monitor.
Electric Stimulation
;
Muscle, Skeletal
;
Neuromuscular Blockade
;
Neuromuscular Nondepolarizing Agents
;
Ulnar Nerve/physiology*
9.Structural and functional characteristics of microbiota in oropharynx of sub-healthy children with gastrointestinal heat retention syndrome differentiated by traditional Chinese medicine
Zhen JIANHUA ; Yu HE ; Li XIAOFEI ; Dong FEI ; Zheng ZI'AN ; Ma XUEYAN ; Wan YUXIANG ; Liu TIEGANG ; Fan LU ; Gu XIAOHONG
Journal of Traditional Chinese Medical Sciences 2022;9(3):230-236
Objective:To explore the structural and functional characteristics of microbiota in oropharynx of sub-healthy children with gastrointestinal heat retention syndrome(GHRS)differentiated by traditional Chinese medicine,and screen the biometric operational taxonomic units(OTUs)to assist the clinical diagnosis.Methods:We recruited children according to the"GHRS diagnostic scale",collected their oropharyngeal swabs,and sequenced the 16S rDNA V4 region.We described the bacterial structure with alpha-indexes,beta-distances,and relative abundances;moreover,we screened the differential genera/OTUs with Wilcoxon rank-sum test,MetagenomeSeq analysis,and linear discriminant analysis effect size(LEfSe)analysis,in which biometric OTUs were selected to construct the receiver operating characteristic curve to verify the diagnostic value.The bacterial function was predicted with Kyoto Encyclopedia of Genes and Genomes pathways according to 16S rDNA gene by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.Results:The study population was composed of 10 children with GHRS and 10 healthy control children.GHRS children were more likely to overeat(gluttony,P=.033).Alpha-indexes,such as Sobs,abundance-based coverage estimator,Bootstrap,and Qstat,were significantly higher in the GHRS group,while beta-distances did not exhibit any significant intergroup differences.There were 9 differently distributed non-predominant genera between the groups in Wilcoxon rank-sum test,as well as 13 non-predominant genera in MetagenomeSeq analysis and 3 non-predominant OTUs in LEfSe analysis.OTU44 and OTU196 were used to construct the receiver operating characteristic curve,and the area under curve was 0.92.Predicted functions showed that pathways related to oxidative phosphorylation and carbon metabolism were enriched in healthy control samples,while the pathway related to renin secretion was remarkably enriched in GHRS samples.Conclusion:Unique oropharyngeal microbial structure and function were identified in GHRS children.OTU44 and OTU196 were specific OTUs,which could be used as biomarkers of GHRS to assist clinical diagnosis.
10.Bibliometric analysis of domestic enhanced recovery after surgery studies based on Web of Science
Liping HE ; Yuxiang LIU ; Jinwen HE
Chinese Journal of Modern Nursing 2022;28(22):2981-2987
Objective:To explore the research status and hotspots of enhanced recovery after surgery (ERAS) in China by means of bibliometrics.Methods:Based on the Web of Science, the original researches related to ERAS published by Chinese scholars from January 1, 2000 to December 31, 2020 were retrieved and screened. The annual number of publications and citations, distribution of authors, institutions, provinces, journals published and cited, operations and keywords applied, study design, and level of evidence were analyzed.Results:A total of 297 articles were included, and the number of annual publications and citations showed a significant upward trend. Wang was a high-volume author, and Jiang was a high-volume corresponding author, and Kehlet was a highly cited author in the bibliography. Zhejiang University, Sichuan University, and Nanjing University were high-volume institutions, and Jiangsu, Zhejiang, and Sichuan were high-volume provinces. British Journal of Surgery was a highly cited journal. ERAS was most commonly used in colorectal surgery, the most frequently occurring keywords were colorectal surgery, gastric cancer and laparoscopy. Key words that frequently appeared in recent years included total knee arthroplasty, lung cancer, length of stay, postoperative complications, nursing, elderly and quality of life. The most common study designs were randomized controlled trials, followed by retrospective case-control studies. Among the published studies, the second-level evidence and the fourth-level evidence were the most, and the number of citations of the second-level evidence was significantly higher than that of the fourth-level evidence, and the difference was statistically significant ( P<0.01) . Conclusions:Knee replacement, lung surgery, length of stay, postoperative complications, nursing, elderly, quality of life and so on are the contents of high concern in the original research of ERAS in China in recent years. Prospective, high-level studies should be carried out in the future.


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