1.Multidimensional Analysis of Mechanisms of Nuciferine Against Cerebral Ischemia Based on Transcriptomic Data
Yingying QIN ; Peng LI ; Sha CHEN ; Yan LIU ; Jintang CHENG ; Qingxia XU ; Guohua WANG ; Jing ZHOU ; An LIU ; Chang CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):184-191
ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect, but the specific mechanism of action has not been elaborated. Based on the transcriptome results, the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue, cell, pathological process, biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group, model group and nuciferine group(40 mg·kg-1) according to weight. Except for the sham group, the model of middle cerebral artery occlusion(MCAO) was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery, transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue, and gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue, cell, pathological process, biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform(TMNP). ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response, ion transport, cell proliferation and differentiation, and synaptic function. TMNP research found that at the tissue level, nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels, nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells, mobilizing immune cells, regulating inflammation. And at the level of biological processes and signaling pathways, nuciferine mainly acted on the processes such as vascular remodeling, inflammation-related signaling pathways, and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing, gene quantitative analysis and TMNP, the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation, affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.
2.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.
3.Biomechanical features of posterior"Y"osteotomy and fixation in treatment of ankylosing spondylitis based on finite element simulation analysis
Le ZHANG ; Zhenhua CAO ; Yunfeng ZHANG ; Yangyang XU ; Feng JIN ; Baoke SU ; Lidong WANG ; Xing WANG ; Ling TONG ; Qinghua LIU ; Yuan FANG ; Lirong SHA ; Haiyan WANG ; Xiaohe LI ; Zhijun LI
Chinese Journal of Tissue Engineering Research 2024;28(12):1842-1848
BACKGROUND:Ankylosing spondylitis is a progressive inflammation of spinal stiffness deformity caused by tissue ossification and fibrosis.The posture of ankylosing spondylitis patients is abnormal and their activities are limited that minor injuries can lead to thoracolumbar fractures.Traditional medical image observation limits doctors'preoperative decision planning and postoperative disease prevention for ankylosing spondylitis treatment. OBJECTIVE:Based on the spinal model of ankylosing spondylitis patients before and after posterior spinal cancellous ossification osteotomy("Y"osteotomy for short),to explore the biomechanical changes of"Y"osteotomy and fixation in the treatment of ankylosing spondylitis. METHODS:Based on the preoperative and postoperative CT images of an ankylosing spondylitis patient who went to the Second Affiliated Hospital of Inner Mongolia Medical University,a three-dimensional spine model(T11-S1)before and after"Y"osteotomy(L3 osteotomy)was reconstructed in Mimics 19.0 software.A 7.5 Nm torque was applied to the top of T11 vertebral body to simulate the movement of the spine under six conditions:flexion,extension,left bending,right bending,left rotation and right rotation.Finally,the range of motion of each vertebral body,the stress of each intervertebral disc,and the stress of the screw rod system were simulated. RESULTS AND CONCLUSION:(1)After"Y"type osteotomy and posterior fixation,the range of motion of all vertebrae in the spine decreased,and the loss rate of upper vertebrae was large(L1:77.95%).(2)The maximum stress of the spinal intervertebral disc before operation occurred at the L1-L2 segment(0.55 MPa),and the maximum stress of the spinal intervertebral disc after operation occurred at the T11-T12 segment(0.50 MPa),and the stress of intervertebral disc below T12 was far less than that before operation.(3)The maximum stress of the screw rod system(166.67 MPa)occurred in the upper and middle segments of the rod body and the root of the pedicle screw.(4)In conclusion,the"Y"type posterior fixation operation enhances the stability of the spine and reduces the range of motion of the spine.The vertebral body decompression of the fixed segment is great and the stress-shielding phenomenon of the lower vertebral body is significant.The stiffness of the rod body and the stress concentration area of the pedicle screw should be strengthened to avoid the fracture of the rod caused by stress fatigue.
4.Perspective of Calcium Imaging Technology Applied to Acupuncture Research.
Sha LI ; Yun LIU ; Nan ZHANG ; Wang LI ; Wen-Jie XU ; Yi-Qian XU ; Yi-Yuan CHEN ; Xiang CUI ; Bing ZHU ; Xin-Yan GAO
Chinese journal of integrative medicine 2024;30(1):3-9
Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.
Calcium
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Acupuncture Therapy
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Acupuncture
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Acupuncture Analgesia/methods*
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Acupuncture Points
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Technology
5. Targeted biotherapy for chronic obstructive pulmonary disease
Haodong BAI ; Bingxian SHA ; Ambedkar Kumar YADAV ; Xianghuai XU ; Li YU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(4):377-382
Chronic obstructive pulmonary disease (COPD) is the most common chronic airway disease. The current status of treatment based mainly on bronchodilators and ICS is not sufficient for all of COPD patients. Various studies have attempted to use biologics targeting specific cytokines and their receptors in COPD patients to alleviate respiratory symptoms or reduce the risk of acute exacerbations. However, they failed to bring significant clinical benefits. More studies are needed to further determine the efficacy of targeted biotherapy for COPD.
6. Use of central neuromodulators in chronic cough
Bingxian SHA ; Haodong BAI ; Wanzhen LI ; Li YU ; Xianghuai XU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(4):432-439
Chronic cough is a common condition that imposes significant physical, psychological, and social burdens on patients. Although chronic cough is often associated with underlying conditions such as asthma, gastroesophageal reflux disease, and eosinophilic bronchitis, some patients experience uncontrollable coughing that is difficult to attribute to a specific cause. Many of these patients exhibit clinical features of cough hypersensitivity syndrome, providing new directions for research into the treatment of chronic cough. As the pathophysiological mechanisms of chronic cough are further elucidated, treatment approaches for chronic cough are entering a new stage of development. This article summarizes and discusses the mechanisms and clinical evidence of central neuromodulators used in the treatment of chronic cough, suggesting promising clinical applications for these drugs in the future.
7.Targeted biotherapy for chronic obstructive pulmonary disease
Haodong BAI ; Bingxian SHA ; Yadav Kumar AMBEDKAR ; Xianghuai XU ; Li YU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(4):377-382
Chronic obstructive pulmonary dis-ease(COPD)is the most common chronic airway disease.The current status of treatment based mainly on bronchodilators and ICS is not sufficient for all of COPD patients.Various studies have at-tempted to use biologics targeting specific cyto-kines and their receptors in COPD patients to allevi-ate respiratory symptoms or reduce the risk of acute exacerbations.However,they failed to bring significant clinical benefits.More studies are need-ed to further determine the efficacy of targeted biotherapy for COPD.
8.Use of central neuromodulators in chronic cough
Bingxian SHA ; Haodong BAI ; Wanzhen LI ; Li YU ; Xianghuai XU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(4):432-439
Chronic cough is a common condition that imposes significant physical,psychological,and social burdens on patients.Although chronic cough is often associated with underlying condi-tions such as asthma,gastroesophageal reflux dis-ease,and eosinophilic bronchitis,some patients ex-perience uncontrollable coughing that is difficult to attribute to a specific cause.Many of these pa-tients exhibit clinical features of cough hypersensi-tivity syndrome,providing new directions for re-search into the treatment of chronic cough.As the pathophysiological mechanisms of chronic cough are further elucidated,treatment approaches for chronic cough are entering a new stage of develop-ment.This article summarizes and discusses the mechanisms and clinical evidence of central neuro-modulators used in the treatment of chronic cough,suggesting promising clinical applications for these drugs in the future.
9.Analysis of pathogenic bacteria distribution,laboratory indicators and prognosis in patients with bacterial ascites
Xipeng SHANG ; Sha LI ; Xu LIU ; Jinghui DU
China Modern Doctor 2024;62(4):43-46
Objective To investigate the clinical features,laboratory indicators and prognosis of patients with bacterial ascites,and to provide evidence for early clinical diagnosis and treatmen.Methods Clinical data of patients diagnosed with cirrhosis ascites from First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from January 2019 to January 2022 were retrospectively analyzed.According to diagnostic criteria,they were divided into bacterial ascites group(n=24),spontaneous bacterial peritonitis group(n=20)and control group(n=26).The clinical features,laboratory indicators and prognosis of three groups were compared.Results Cirrhosis ascites caused by hepatitis B accounted for the highest proportion.The white blood cell count,neutrophil percentage,ascites white blood cell and polymorphonuclear leukocyte count of patients in bacterial ascites group were significantly higher than those in control group(P<0.05).Gram-positive bacteria was the main pathogens causing bacterial ascites,among which staphylococcus accounts for the highest proportion.Ten cases of bacterial ascites with symptoms of infection were treated with ascites culture and anti-infection therapy.The 14 patients without symptoms of infection were given different treatment according to the development of the disease,one patient died,and the other patients improved.Conclusion The number of patients with bacterial ascites was large,and the main pathogenic bacteria was Gram-positive coccus.The combination of clinical symptoms and laboratory indicators is beneficial to the early diagnosis of bacterial ascites and the decision of treatment.
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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