1.Establishment and stress analysis of a finite element model for adolescent cervical disc herniation
Yuxin ZHAO ; Liang LIANG ; Feng JIN ; Yangyang XU ; Zhijie KANG ; Yuan FANG ; Yujie HE ; Xing WANG ; Haiyan WANG ; Xiaohe LI
Chinese Journal of Tissue Engineering Research 2025;29(3):448-454
BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.
2.Mechanism of in Vitro and in vivo Models of Osteoporosis Regulation by Active Ingredients of Traditional Chinese Medicine: A Review
Ming YANG ; Jinji WANG ; Xuefeng ZHUANG ; Xiaolei FANG ; Zhijie ZHU ; Huiwei BAO ; Lijing LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):281-289
Osteoporosis is a common bone disease, whose incidence is still on the rise, posing great challenges to patients and society. This review mainly studies the pathogenesis of osteoporosis from the aspects of oxidative stress, inflammatory response, and glucolipotoxicity-induced injury and clarifies the efficacy and mechanism of some active ingredients of traditional Chinese medicine against osteoporosis through the integration of in vitro and in vivo experiments. The experimental results suggest that some active ingredients can improve bone resorption markers and maintain bone homeostasis by modulating inflammation, oxidative stress, etc. These active ingredients regulate osteoporosis through the receptor activator of nuclear transcription factor-κB (NF-κB) ligand (RANKL) pathway, osteoprotegerin (OPG) pathway, Wnt/β-catenin pathway, NF-κB pathway, mitogen-activated protein kinase (MAPK) pathway, adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, and oxidative stress pathway. This review provides ideas for the progress of the prevention and treatment of osteoporosis with the active ingredients of traditional Chinese medicine, aiming to provide new potential lead compounds and reference for the development of innovative drugs and clinical therapy for the treatment of osteoporosis.
3.A Retrospective Analysis of Sangmei Pingfeng Granules for Allergic Asthma in Chronic Persistent Stage
Jiaqi LI ; Hongsheng CUI ; Zhijie ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):98-105
ObjectiveTo observe the efficacy of Sangmei Pingfeng granules combined with western medicine in the treatment of patients with allergic asthma in the chronic persistent stage, diagnosed with lung-spleen Qi deficiency syndrome in traditional Chinese medicine (TCM). MethodsA retrospective analysis was conducted on 420 patients with allergic asthma in the chronic persistent stage and TCM-diagnosed lung-spleen Qi deficiency syndrome, treated at the Third Affiliated Hospital of Beijing University of Chinese Medicine from January 2017 to September 2024. Patients were divided into an exposed group (320 cases) and a non-exposed group (100 cases) based on whether they used Sangmei Pingfeng granules. The non-exposed group received conventional western medicine treatment, while the exposed group took Sangmei Pingfeng Granules in addition to conventional western medicine. The following indicators were observed: recurrence rate per 100 patients per year, pulmonary function tests, fractional exhaled nitric oxide (FeNO) and fractional nasal nitric oxide (FnNO) tests, serum total IgE (TIgE) detection, TCM syndrome score, and changes in asthma control test (ACT) scores between the two groups. ResultsThe annual recurrence rate per 100 people was 8.4 times/100 person-years in the exposed group, lower than the 13 times/100 person-years in the unexposed group. After treatment, the exposed group showed increases in forced vital capacity percentage predicted (FVC%pred), forced expiratory volume in one second percentage predicted (FEV1%pred), the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC), and peak expiratory flow percentage predicted (PEF%pred) (P0.05). Lung function indicators in the non-exposed group showed no statistically significant differences after treatment. Residual volume as a percentage of total lung capacity (RV%TLC) showed no statistically significant difference after treatment in either group. Compared with the non-exposed group, the exposed group had increased FVC%pred, FEV1%pred, FEV1/FVC, and PEF%pred, without statistically significant differences. After treatment, fractional exhaled nitric oxide (FeNO), fractional nasal nitric oxide (FnNO), and total immunoglobulin E (TIgE) decreased in the exposed group. FeNO decreased in the non-exposed group (P0.05). FnNO decreased, and TIgE increased in the non-exposed group, without statistically significant differences. After treatment, compared with the non-exposed group, the treatment group had decreased FeNO (P0.05). After treatment, traditional Chinese medicine (TCM) syndrome scores decreased, and asthma control test (ACT) scores increased in both groups (P0.01). After treatment, compared with the non-exposed group, the exposed group had decreased TCM syndrome scores and increased ACT scores (P0.01). ConclusionCombining Sangmei Pingfeng granules with Western medicine significantly reduces recurrence rates, enhances clinical efficacy, improves lung function, lowers serum TIgE and FeNO levels, and reduces reliance on Western medications in patients with allergic asthma. This integrated approach is worthy of clinical promotion and application.
4.Evaluation of perioperative nutritional status and body composition in patients with stomach neoplasms
Hong WANG ; Zhijie DING ; Yafang YE ; Lihui LIN ; Dandan KANG ; Yanping YUAN ; Lei LI
Chinese Journal of Practical Nursing 2024;40(10):772-779
Objective:To investigate the nutritional risk, incidence of malnutrition, and intake of three major energy-supplying nutrients, analyze changes in their body composition and the possible influencing factors in patients with stomach neoplasms during perioperative period in order to provide a theoretical basis for the nutritional management of patients with stomach neoplasms during perioperative period.Methods:This was a cross-sectional study. A total of 105 patients who underwent gastric cancer radical surgery in the Gastrointestinal Department of Zhongshan Hospital Affiliated to Xiamen University from June 2021 to May 2023 were taken as the research subjects using fixed-point continuous sampling method. They were recruited for screening and assessment using Nutritional Risk Screening 2002 (NRS 2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Nutrients intake during the perioperative period were investigated using the 24-h recall method and dietary diary method, etc. Body compositions were measured using the bioelectrical resistance method.Results:Among the 105 patients, there were 78 males and 27 females, with an average age of (61.5 ± 10.3) years. About 83.8% (88/105) gastric cancer patients were at nutritional risk and 82.9% (87/105) were malnourished. The preoperative and postoperative energy intake were (1 646.1 ± 321.5) and (1 317.2 ± 365.8) kcal (1 kcal=4.184 kJ), respectively, which were significantly lower than the target amount of (1 896.7 ± 262.9) kcal, the difference was statistically significant ( t=6.23, 8.29, both P<0.05).The preoperative body mass, muscle mass, skeletal muscle, fat mass, and skeletal muscle index were (51.5 ± 9.6), (40.8 ± 6.0), (23.6 ± 4.0), (8.3 ± 4.9) kg, and 6.7 ± 0.8 respectively, while the postoperative values were (50.0 ± 9.1), (39.8 ± 6.0), (22.8 ± 3.6), (7.8 ± 5.2) kg, and 6.5 ± 0.8 respectively, with statistically significant differences between the two groups ( t values were 2.89-10.61, all P<0.05). Logistic multivariate regression analysis showed that the operation time ( OR=3.984, 95% CI 1.433-11.080, P<0.05) and energy satisfaction ( OR=0.053, 95% CI 0.005-0.610, P<0.05) were independent influencing factors for the degree of skeletal muscle loss. Conclusions:During perioperative period, the gastric cancer patients had poor nutritional status with insufficient nutrient intake and accelerated loss of body muscle and fat. Therefore, it was necessary to conduct a comprehensive nutritional evaluation for patients with stomach neoplasms during perioperative period in time and take steps to promote recovery by providing individualized nutritional therapy.
5.Effect of overexpression of protein phosphatase 2Cm on transcriptome of human renal tubular epithelial cells
Li ZHANG ; Wenjun YANG ; Xiaohong SANG ; Yuanyuan HAN ; Zhijie MAO ; Shun WANG ; Chen LU
Chinese Journal of Tissue Engineering Research 2024;28(1):68-73
BACKGROUND:A previous study by our group found that protein phosphatase 2Cm(PP2Cm)null mice developed significantly fewer symptoms of renal failure relative to wild-type mice,and thus it was speculated that PP2Cm may play an important protective role in the development of renal fibrosis,however,the molecular mechanisms remain undefined. OBJECTIVE:To investigate the effect of the PP2Cm gene on the transcriptome of human renal tubular epithelial cells. METHODS:Cultured human renal tubular epithelial cells were transfected with the PP2Cm gene into human renal tubular epithelial cells using plasmids.The expression of PP2Cm in the cells was detected by fluorescence quantitative PCR assay and western blot assay,and subsequently,cell RNA was separately extracted for transcriptome sequencing to look for differentially expressed genes between transfected and control groups.The resulting differential genes were further subjected to GO analysis and KEGG analysis using bioinformatics methods. RESULTS AND CONCLUSION:There were 796 differentially expressed genes,553 of which were downregulated genes and 243 upregulated genes,in human renal tubular epithelial cells transfected with the PP2Cm gene compared with untransfected blank cells by sequencing analysis.GO analysis results showed that the upregulated genes were significantly enriched in cellular biosynthetic processes,protein translation,intrinsic apoptotic signaling pathways,and so on.The downregulated expressed genes were significantly enriched in endothelial cell proliferation,cell adhesion and other signaling pathways.KEGG analysis results showed that the significantly up-regulated genes were enriched in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.The downregulated expressed genes were significantly enriched in signaling pathways such as pantothenate and coenzyme A biosynthesis.Our results show that PP2Cm overexpression can affect a number of signaling pathways related to a range of biological processes in renal tubular epithelial cells,which may be important in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.
6.Finite element model establishment and stress analysis of lumbar-sacral intervertebral disc in ankylosing spondylitis
Zhijie KANG ; Zhenhua CAO ; Yangyang XU ; Yunfeng ZHANG ; Feng JIN ; Baoke SU ; Lidong WANG ; Ling TONG ; Qinghua LIU ; Yuan FANG ; Lirong SHA ; Liang LIANG ; Mengmeng LI ; Yifei DU ; Lin LIN ; Haiyan WANG ; Xiaohe LI ; Zhijun LI
Chinese Journal of Tissue Engineering Research 2024;28(6):840-846
BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.
7.Strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates ameliorate bone loss in ovariectomized mice
Zhi ZHOU ; Zhijie CHEN ; Shicheng HUO ; Zhanchun LI
Chinese Journal of Tissue Engineering Research 2024;28(17):2653-2658
BACKGROUND:Inhibition of osteoclast activity by bisphosphonates slows the progression of osteoporosis.However,serious complications of bisphosphonates,such as osteonecrosis of the jaw and atypical femur fracture,limit the clinical application of bisphosphonates.Effective alternative therapies need to be sought to improve existing clinical dilemmas. OBJECTIVE:To prepare strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates(BPS@Sr-MBG)and analyze its activity against bone loss. METHODS:Strontium-containing mesoporous bioactive glass nanoparticles(Sr-MBG)were prepared by sol-gel method and added to alendronate saturated solution for the preparation of BPS@Sr-MBG.(1)Cell experiment:Mouse bone marrow macrophages were inoculated in 96-well plates and supplemented with ɑ-MEM complete culture medium containing macrophage colony stimulating factor and activator-ligand of nuclear factor κB receptor for osteoclast induced differentiation experiment.Meanwhile,they were cultured in three groups.The blank group was added with PBS.The control group was added with bisphosphonate,and the experimental group was added with BPS@Sr-MBG.After 5 days of culture,the differentiation of osteoclasts was observed by F-actin ring staining.(2)Animal experiments:Twenty-four female C57/BL mice were randomly divided into four groups with six mice in each group.Except sham operation group,ovariectomy group,BPS group and BPS@Sr-MBG group were used to construct osteoporosis model.One week after model establishment,mice in BPS group and BPS@Sr-MBG group were intraperitoneally injected with bisphosphonate solution and BPS@Sr-MBG solution,respectively.Mice in the sham operation group and ovariectomy group were intraperitoneally injected with PBS once a week.After 8 weeks of continuous injection,mouse femurs were taken for Micro-CT scanning and hematoxylin-eosin staining. RESULTS AND CONCLUSION:(1)Cell experiment:F-actin ring-formation staining demonstrated that compared with blank group,the area proportion and number of osteoclasts in the control group were decreased(P<0.01).Compared with the control group,the area proportion of osteoclasts and the number of osteoclasts in the experimental group were decreased(P<0.01).(2)Animal experiments:Micro-CT scanning results of femur showed that compared with the sham operation group,bone density,trabecular bone volume fraction,trabecular thickness and trabecular number of mice in the ovariectomy group were decreased(P<0.05,P<0.01),while trabecular distance and structural model index were increased(P<0.01).Compared with the ovariectomy group,the above bone parameters in the BPS group and BPS@Sr-MBG group were significantly improved(P<0.01),and the improvement in the BPS@Sr-MBG group was more obvious.The Micro-CT scanning results were further confirmed by hematoxylin-eosin staining of the femur.(3)The results show that BPS@Sr-MBG can exert anti-osteoporosis activity through anti-osteoclastic effect and promoting bone formation.
8.Visualization analysis of vascular stimulating scaffolds in bone tissue engineering
Yuan FANG ; Zhijie KANG ; Haiyan WANG ; Xiaohe LI ; Kai ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(17):2708-2715
BACKGROUND:The study of the physical properties of scaffolds has always been a hot topic in the field of tissue engineering research.However,for vascular stimulating scaffolds,in addition to meeting the basic performance of the scaffold,other methods are also needed to promote the regeneration of blood vessels within the scaffold,in order to achieve the ultimate goal of repairing bone tissue. OBJECTIVE:A visualization analysis was carried out on the literature published in and outside China on scaffold stimulation for bone tissue engineering,to explore the research hotspots and research status in this field,and to provide a reference for subsequent studies. METHODS:Using the CNKI database and Web of Science core database as retrieval databases,the relevant literature on vascular scaffolds for bone tissue engineering was retrieved.The literature that did not conform to the research object was removed.The obtained data were imported into CiteSpace 6.1.R2 software.Visualization analysis was performed on authors,national institutions,and keywords in the research field. RESULTS AND CONCLUSION:(1)China,the United States,and Germany were the top three countries with the most articles on scaffold stimulation for bone tissue engineering.(2)The top 3 institutions in the CNKI database were Southern Medical University,Huazhong University of Science and Technology,and Donghua University.In the core database of Web of Science,Shanghai Jiao Tong University,Sichuan University and Chinese Academy of Sciences ranked the top 3 in terms of the number of institutional publications.(3)The top 3 keywords in the CNKI database were"tissue engineering,vascularization,angiogenesis".The top 3 keywords in the Web of Science core database were"mesenchymal stem cell,scaffold,vascularization".(4)Through the analysis of co-citation and highly cited references,the main concerns were as follows:vascularization strategies:scaffold design,angiogenic factor delivery,in vitro co-culture,and in vivo pre-vascularization.Technology:3D printing,electrospinning,vascular transplantation,vascular fusion.Mechanisms:immune regulation and macrophages,drug/growth factor delivery,the relationship between endothelial cells and osteoblasts,the paracrine relationship between bone cells and endothelial cells,signaling molecular pathways,angiogenesis,and anti-angiogenesis molecules.(5)The researches concerning vascular stimulating scaffolds in bone tissue engineering in and outside China attach great importance to the application of stem cells and 3D printing technology.Current research focuses on biological 3D printing technology,scaffold modification methods,and the development and application of intelligent biomaterials based on bone repair mechanisms.
9.Puerarin inhibits the differentiation of Raw264.7 cells into osteoclasts through the Notch signaling pathway
Chunli LIU ; Yujuan YAN ; Liwen MO ; Zhijie WU ; Li ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(35):5636-5641
BACKGROUND:Previous studies have shown that puerarin can inhibit the differentiation of osteoclasts,and the expression of Notch signaling pathway-related proteins such as Notch1,HES1,and Jagged1 is decreased.However,the specific mechanism of the Notch1 signaling pathway for the inhibition of osteoclast differentiation by puerarin is not clear. OBJECTIVE:To explore the effect of Notch signaling pathway on puerarin inhibiting the differentiation of mouse macrophage Raw264.7 into osteoclasts. METHODS:Raw264.7 cells were divided into seven groups for intervention culture.Blank control group was cultured in high-sugar DMEM medium;the osteoclast induction group was cultured in osteoclast induction medium;the puerarin intervention group was cultured with 50 μmol/L puerarin at the same time of osteoclast induction;Notch1 siRNA control group,Notch1 siRNA group,Notch1 overexpression control group and Notch1 overexpression group were transfected with Notch1 siRNA control sequence,Notch1 siRNA,Notch1 overexpression control plasmid and Notch1 overexpression plasmid,respectively,and then cultured with osteoclast induction medium and puerarin.The number and size of osteoclasts were observed by tartrate-resistant acid phosphatase staining,the skeleton formation of osteoclasts was observed by F-actin staining,and the gene expression level of osteoclast formation markers was detected by RT-PCR. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining results showed that puerarin intervention could inhibit the generation of osteoclasts,Notch1 silencing could further reduce the number of osteoclasts,while the number of osteoclasts in the osteoclast-induced group increased significantly after Notch1 overexpression.The results of F-actin showed that Raw264.7 cells could form a well-defined F-actin ring after osteoclast induction.Puerarin intervention would inhibit the formation of cytoskeleton,and Notch1 silencing could aggravate the inhibitory effect of cytoskeleton formation,while Notch1 overexpression could alleviate this inhibitory effect of puerarin.RT-PCR results showed that puerarin could inhibit the mRNA expression levels of tartrate-resistant acid phosphatase,Cathepsin K and c-Fos,the expression of the above-mentioned three factors decreased significantly after Notch1 gene silencing,and Notch1 overexpression could upregulate the expression of these factors.These finding indicate that puerarin inhibits the differentiation of Raw264.7 cells into osteoclasts through the Notch signaling pathway.
10.Transcriptomic analysis of SR8278 improving lacrimal gland dysfunction in-duced by jet lag in mice
Shenzhen HUANG ; Di QI ; Xiaoting PEI ; Dingli LU ; Hongli SI ; Duliurui HUANG ; Wenxiao ZHANG ; Mengru BA ; Shuting XUAN ; Zhijie LI
Recent Advances in Ophthalmology 2024;44(4):264-269
Objective To investigate the role and mechanism of SR8278,a synthetic antagonist of nuclear receptor subfamily 1 group D member 1(NR1D1),in alleviating the structural and functional impairment of the extraorbital lacrimal glands induced by jet lag in mice.Methods Totally 36 healthy wild C57BL/6J mice aged 8-10 weeks were randomly divid-ed into 3 groups(normal group,jet-lag group,and jet-lag+SR8278 group)after adapting to a circadian rhythm chamber under the 12 h light/12 h dark(12 h/12 h LD)cycle for 2 weeks,with 12 mice in each group.Mice in the normal group were fed in a circadian rhythm chamber in a 12 h LD cycle,mice in the jet-lag group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule,and mice in the jet lag+SR8278 group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule and received 25 mg·kg-1 SR8278.At the end of 5 days of intervention,locomotor activity,core body temperature and tear secretion of mice in each group were collected,and the weight of lacrimal gland tissues and size of lacrimal gland cells were measured.Immunohistochemical methods were used for histological evaluation of the extraor-bital lacrimal glands in mice.Lacrimal ribonucleic acid(RNA)was extracted for high-throughput RNA-sequencing analysis containing NR1D1,and the obtained transcriptomic data were used for KEGG and GO functional enrichment analysis.Re-sults Compared with the normal group,the jet-lag group had higher daytime activity,lower nighttime activity,higher daytime core body temperature,and lower nighttime core body temperature,with statistically significant differences(all P<0.05).Compared with the jet-lag group,the jet-lag+SR8278 group had lower daytime activity,higher nighttime activi-ty,lower daytime core body temperature,and higher nighttime core body temperature,with statistically significant differ-ences(all P<0.05).Compared with the normal group,the jet-lag group showed a decrease in lacrimal gland weight and tear secretion and an increase in size of lacrimal gland cells,with statistical significance(all P<0.05);compared with the jet-lag group,the jet-lag+SR8278 group had an increase in lacrimal gland weight and tear secretion and a decrease in size of lacrimal gland cells,with statistical significance(all P<0.05).Compared with the normal group,the jet-lag group showed a higher expression of NR1D1 in the lacrimal gland at night;compared with the jet-lag group,the jet-lag+SR8278 group showed a lower expression of NR1 D1 in the lacrimal gland at night(both P<0.05).Bioinformatics analysis showed 947 significantly different genes in the jet-lag group and the jet-lag+SR8278 group,of which 43 are significantly upregulated genes,and 904 are significantly downregulated genes.The Notch signaling pathway has the most significant difference.Conclusion SR8278 effectively enhances the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition.This process may be completed through the Notch signaling pathway.

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