1.Effect of removing microglia from spinal cord on nerve repair after spinal cord injury in mice.
Qi JIANG ; Chao QI ; Yuerong SUN ; Shiyuan XUE ; Xinyi WEI ; Haitao FU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(6):754-761
OBJECTIVE:
To investigate the effects of removing microglia from spinal cord on nerve repair and functional recovery after spinal cord injury (SCI) in mice.
METHODS:
Thirty-nine 6-week-old female C57BL/6 mice were randomly divided into control group ( n=12), SCI group ( n=12), and PLX3397+SCI group ( n=15). The PLX3397+SCI group received continuous feeding of PLX3397, a colony-stimulating factor 1 receptor inhibitor, while the other two groups were fed a standard diet. After 14 days, both the SCI group and the PLX3397+SCI group were tested for ionized calcium binding adapter molecule 1 (Iba1) to confirm that the PLX3397+SCI group had completely depleted the spinal cord microglia. The SCI model was then prepared by clamping the spinal cord in both the SCI group and the PLX3397+SCI group, while the control group underwent laminectomy. Preoperatively and at 1, 3, 7, 14, 21, and 28 days postoperatively, the Basso Mouse Scale (BMS) was used to assess the hind limb function of mice in each group. At 28 days, a footprint test was conducted to observe the gait of the mice. After SCI, spinal cord tissue from the injury site was taken, and Iba1 immunofluorescence staining was performed at 7 days to observe the aggregation and proliferation of microglia in the spinal cord. HE staining was used to observe the formation of glial scars at the injury site at 28 days; glial fibrillary acidic protein (GFAP) immunofluorescence staining was applied to astrocytes to assess the extent of the injured area; neuronal nuclei antigen (NeuN) immunofluorescence staining was used to evaluate neuronal survival. And 5-hydroxytryptamine (5-HT) immunofluorescence staining was performed to assess axonal survival at 60 days.
RESULTS:
All mice survived until the end of the experiment. Immunofluorescence staining revealed that the microglia in the spinal cord of the PLX3397+SCI group decreased by more than 95% compared to the control group after 14 days of continuous feeding with PLX3397 ( P<0.05). Compared to the control group, the BMS scores in the PLX3397+SCI group and the SCI group significantly decreased at different time points after SCI ( P<0.05). Moreover, the PLX3397+SCI group showed a further decrease in BMS scores compared to the SCI group, and exhibited a dragging gait. The differences between the two groups were significant at 14, 21, and 28 days ( P<0.05). HE staining at 28 days revealed that the SCI group had formed a well-defined and dense gliotic scar, while the PLX3397+SCI group also developed a gliotic scar, but with a more blurred and loose boundary. Immunofluorescence staining revealed that the number of microglia near the injury center at 7 days increased in the SCI group than in the control group, but the difference between groups was not significant ( P>0.05). In contrast, the PLX3397+SCI group showed a significant reduction in microglia compared to both the control and SCI groups ( P<0.05). At 28 days after SCI, the area of spinal cord injury in the PLX3397+SCI group was significantly larger than that in SCI group ( P<0.05); the surviving neurons significantly reduced compared with the control group and SCI group ( P<0.05). The axonal necrosis and retraction at 60 days after SCI were more obvious.
CONCLUSION
The removal of microglia in the spinal cord aggravate the tissue damage after SCI and affecte the recovery of motor function in mice, suggesting that microglia played a neuroprotective role in SCI.
Animals
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Spinal Cord Injuries/surgery*
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Microglia/pathology*
;
Female
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Mice
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Mice, Inbred C57BL
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Nerve Regeneration/drug effects*
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Spinal Cord/pathology*
;
Pyrroles/administration & dosage*
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Aminopyridines/administration & dosage*
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Recovery of Function
;
Disease Models, Animal
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Calcium-Binding Proteins/metabolism*
;
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors*
;
Microfilament Proteins/metabolism*
;
Glial Fibrillary Acidic Protein/metabolism*
2.The correlation between dietary nutrition and skeletal muscle mass in the elderly with advanced age
Xiaoxiao LIANG ; Shiyuan CAI ; Huijuan RUAN ; Jiaoyan HUANG ; Youyang HUANG ; Hanping SHI ; Dawei CHEN ; Xue LI
Shanghai Journal of Preventive Medicine 2024;36(6):589-595
ObjectiveThis research focused on examining the distinctive characteristics of nutrient intake and dietary patterns among long-lived elderly individuals. Additionally, the study was aimed to explore the specific dietary components that may impact the skeletal muscle mass in this particular group. MethodsThis study was conducted in the Chongming area of Shanghai, China. A total of 206 long-lived elderly individuals aged 90 or above were recruited. The 3-day 24-hour dietary recall method was used to collect dietary information and general demographic data through face-to-face interviews with professional nutritionists. The skeletal muscle mass index(SMI) was measured by bioelectrical impedance analysis(BIA), and low skeletal muscle mass was diagnosed based on the 2019 Asian Working Group for Sarcopenia criteria. T-test analysis, chi-square test, and logistic regression were used to analyze the relationship between dietary nutrient intake and skeletal muscle mass. ResultsIn terms of food intake categories, compared with the long-lived elderly people with normal muscle mass, the intake of cereals containing miscellaneous beans and vegetables in the long-lived elderly people with low muscle mass was significantly lower(P<0.05). In terms of the nutrient intake, compared with the long-lived elderly people with normal muscle mass, the intake of total energy, carbohydrate, dietary fiber, vitamin D, folic acid, phosphorus, potassium, magnesium, iron, and manganese in the long-lived elderly people with low muscle mass was significantly lower(P<0.05). After continuous adjustment for the covariates, multivariate logistic regression analysis found that the intake levels of folic acid and dietary fiber were important factors influencing skeletal muscle mass, Individuals with lower intake levels of folic acid and dietary fiber are at a higher risk of low muscle mass in long-lived elderly individuals [ORfolic acid T1, dietary fiber T1 (95%CI): 2.90 (1.11‒7.61); 4.09 (1.53‒10.91)]. ConclusionThe consumption of cereals that include a variety of beans and vegetables was noticeably lower in the long-lived elderly individuals with lower muscle mass when compared to those with normal muscle mass. Furthermore, low levels of folic acid and dietary fiber intake are associated with an increased risk of low skeletal muscle mass.
3.Causal relationship between branched-chain amino acids and peripheral atherosclerosis: a Mendelian randomization study
Yuanyuan FU ; Jie CHEN ; Shiyuan CAI ; Xue LI
Shanghai Journal of Preventive Medicine 2023;35(6):536-541
ObjectiveWe conducted a two-sample Mendelian randomization (MR) study to assess the causal relationship between circulating isoleucine, leucine and valine levels and the risk of peripheral atherosclerosis. MethodsBased on the large-scale genome-wide association study (GWAS) database, single nucleotide polymorphisms (SNPs) closely related to the circulating levels of isoleucine, leucine and valine were identified as instrumental variables (IVs). Two-sample MR analysis applying the inverse variance weighted (IVW) method and the weighted median estimator (WME) method were performed to estimate the causal relationship between the risk of peripheral atherosclerosis and the exposure with more than three SNPs that were available as IVs. The pleiotropy was evaluated by using the MR-Egger regression and MR-PRESSO method, and the leave-one-out method was used in sensitivity analysis. ResultsFour, one and one SNPs were identified as IVs for circulating isoleucine, leucine and valine levels, respectively. For isoleucine, the IVW model demonstrated there was no evidence of heterogeneity among the IVs (P=0.715), and there was a significant causal relationship between the increase of circulating isoleucine level and a higher risk of peripheral atherosclerosis risk. Per every 1 elevated standard deviation (SD) of circulating isoleucine level resulted in increasing 31% of peripheral atherosclerosis risk (OR=1.31, 95%CI: 1.07‒1.61). Similarly, the OR(95%CI) was 1.33 (1.04‒1.71) in the WME model. The MR-Egger regression and MR-PRESSO analysis indicated no evidence of pleiotropy in IVs (all P>0.05). The result of the leave-one-out sensitivity analysis was stable. The Wald ratio model displayed that the causal relationship between circulating leucine and valine levels and the risk of peripheral atherosclerosis was not statistically significant. The OR (95%CI) for leucine and valine was 1.13 (0.78‒1.63) and 1.11 (0.82‒1.50), respectively. ConclusionThere is a significant causal relationship between the increase of circulating isoleucine level and a higher peripheral atherosclerosis risk. The causal relationships between circulating leucine and valine levels and the risk of peripheral atherosclerosis need to be further confirmed in future studies.
4.A survey report on the application status of artificial intelligence in medical imaging in China
Junlin ZHOU ; Yi XIAO ; Xuejun ZHANG ; Caiqiang XUE ; Lin JIANG ; Qi YANG ; Huimao ZHANG ; Shiyuan LIU
Chinese Journal of Radiology 2022;56(11):1248-1253
Objective:To explore the current status of the artificial intelligence (AI) developments in medical imaging in China, and to provide data for the development of AI.Methods:In May 2022, the Radiology Branch of the Chinese Medical Association and the China Medical Imaging AI Industry-University-Research Innovation Alliance jointly launched a nationwide survey on the application status and development needs of medical imaging AI in China in the form of a questionnaire. This survey was carried out for different groups of people, focusing on the clinical applications of medical imaging AI, enterprise development, and educational needs in colleges and universities, with the descriptive statistical analysis performed.Results:China′s medical imaging AI has made great progress in clinical applications, in enterprise developments, as well as in the education and teaching areas. In terms of clinical application, 90.8% (5 765/6 347) of the survey respondents had a preliminary understanding of AI. There were 62.1% (3 798/6 119) doctors confirmed the applications medical imaging AI products in their departments. AI products were applied in the whole process of medical imaging examination, especially in assistance of the diagnosis. The application of pulmonary nodules screening accounted for 89.5% (3 401/3 798) of all medical imaging AIs. The main factors restricting the rapid development of medical imaging AI included lack of experts [47.3% (3 002/6 347)], poor data quality [45.7% (2 898/6 347)] and imperfect function of the products [40.4% (2 566/6 347)]; in terms of enterprises, there were 65.4% enterprises with a scale of less than 100 employees (17/26), and 34.6% with a scale of more than 100 employees (9/26). The main group of the customers were the hospitals above the second level, accounting for about 92.3% (24/26); in terms of education, the number and quality of AI courses, practical operations and lectures currently carried out by schools vary between different levels. The AI courses for graduated students accounted for about 22.5% (86/381), which were the largest in number; while the proportion of AI courses for junior college students, undergraduates and regular trainees were less than 15%. More than 60% of the students thought it necessary for schools to establish AI courses. Among all the students, the master′s and doctoral candidates had the greatest demand for additional AI courses [84.8% (323/381)].Conclusions:The development and popularization of medical imaging AI in China continues to prosper, with opportunities and challenges coexisting. It is necessary to adhere to the orientation of clinical needs, and to realize the coordinated development of clinical application, enterprise development, as well as education and teaching.
5.Long-term safety and activity of humanized CD19 chimeric antigen receptor T cells for children and young adults with relapsed/refractory acute lymphoblastic leukemia
Shiyuan WANG ; Li’na ZHAO ; Hai CHENG ; Ming SHI ; Wei CHEN ; Kunming QI ; Cai SUN ; Xue WANG ; Jiang CAO ; Kailin XU
Chinese Journal of Hematology 2022;43(7):557-561
Objective:To investigate the efficacy and safety of humanized CD19-specific chimeric antigen receptor T cells (hCART19s) in treating children and young adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) and to analyze relevant factors affecting its curative effect and prognosis.Methods:We conducted a single-center clinical trial involving 31 children and young adult patients with R/R B-ALL who were treated with humanized CD19-specific CAR-T cells (hCART19s) from May 2016 to September 2021.Results:Results showed that 27 (87.1%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) one month after CAR-T cell infusion. During treatment, 20 (64.5%) patients developed grade 1-2 cytokine release syndrome (CRS) , and 4 (12.9%) developed grade 3 CRS. Additionally, two patients had grade 1 neurological events. During the follow-up with a median time of 19.3 months, the median event-free survival (EFS) was 15.7 months (95% CI 8.7-22.5) , and the median overall survival (OS) was 32.2 months (95% CI 10.6-53.9) . EFS and OS rates were higher in patients who have undergone hemopoietic stem cell transplantation (HSCT) than in those without [EFS: (75.0 ± 12.5) % vs (21.1 ± 9.4) %, P=0.012; OS: (75.0 ± 12.5) % vs (24.6 ± 10.2) %, P=0.035]. The EFS and OS rates were significantly lower in patients with >3 treatment lines than in those with <3 treatment lines [EFS: 0 vs (49.5±10.4) %, P<0.001; OS: 0 vs (52.0±10.8) %, P<0.001]. To the cutoff date, 12 patients presented with CD19 + relapse, and 1 had CD19 - relapse. Conclusion:hCART19s are effective in treating pediatric and young adult R/R ALL patients, with a low incidence of severe adverse events and reversible symptoms. Following HSCT, the number of treatment lines can affect the long-term efficacy and prognosis of pediatric and young adult R/R ALL patients.
6.Electrical stimulation relieves muscle atrophy induced by chronic hypoxia-hypercapnia through the PTEN/Akt/FoxO1 pathway
Jie SHEN ; Xiaotong WANG ; Yanqing QIN ; Shiyuan HUANG ; Xianxun JIANG ; Xue NIE
Chinese Journal of Physical Medicine and Rehabilitation 2021;43(8):680-685
Objective:1. To detect any change in the PTEN/Akt/FoxO1 signaling pathway in the muscles of rats with chronic hypoxia-hypercapnia treated using neuromuscular electrical stimulation (NMES), and 2. To document the role of chronic hypoxia-hypercapnia in inducing muscle atrophy.Methods:Thirty-two male Sprague-Dawley rats were randomly divided into a control group, a model group, a mock stimulation group, and an NMES group, each of eight. All of the rats in the model group, the mock stimulation group and the NMES group were placed in a hypoxia-hypercapnia chamber with a 9-11% O 2 and 5.5-6.5% CO 2 atmosphere for 8h per day and 7d per week, lasting 4 weeks. The control group were placed in a similar chamber with normal air. In the last 2 weeks, after the 8h in the chamber, the NMES group were given 30min of electrical stimulation at 100Hz to the calf muscles of their bound lower limbs. The mock stimulation group were only bound without any electrical stimulation. After the 4-week intervention, the gastrocnemius muscles were resected and their cross-sectional areas (CSAs) were observed using hematoxylin-eosin staining. Immunohistochemistry and western blotting were employed to detect the protein expression of phosphatase and tensin (PTEN), p-Akt, Akt and FoxO1. Results:Compared with the control group, a significant decrease was observed in the average CSA and in the expression of p-Akt and Akt in the model group, while a significant increase was found in the average protein expression of PTEN and FoxO1. Compared with the model group, there was a significant increase in the average CSA, as well as the average expression of p-Akt and Akt in the NMES group, but a significant decrease in the average expression of PTEN and FoxO1.Conclusion:Neuromuscular electrical stimulation can relieve muscle atrophy from chronic hypoxia-hypercapnia by inducing skeletal muscle protein synthesis through regulating the PTEN/Akt/FoxO1 signaling pathway, at least in rats.
7.The prognostic value of combined detection of serum indicators in elderly patients with community acquired pneumonia
Chunyan ZHAO ; Shumin TU ; Bing XUE ; Lei RUI ; Shiyuan SONG ; Jianguo HOU
Chinese Journal of Geriatrics 2020;39(11):1283-1286
Objective:To evaluate the prognostic value of combined detection of serum C-reactive protein(CRP), procalcitonin and lactic acid in elderly patients with community acquired pneumonia(CAP).Methods:Ninety-five elderly CAP patients in the emergency department of Shangqiu First People's Hospital were included as the case group, and 45 elderly healthy people in the emergency department of Shangqiu First People's Hospital were enrolled as the control group.Levels of blood lactic acid, procalcitonin and CRP were compared between the two groups.Meanwhile, blood levels of lactic acid, procalcitonin and CRP were compared between patients with different outcomes in the case group.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic value of CRP, procalcitonin and blood lactic acid in elderly patients with CAP.Results:Compared with the control group, blood levels of lactic acid, procalcitonin and CRP were increased in the case group( t=20.77, 26.03 and 31.27, all P<0.01). During a 12-month follow-up, 13 cases(13.68%, 13/95)died and 82 cases(86.32%, 82/95)survived in the case group.Blood levels of lactic acid, procalcitonin and CRP were higher in the death group than in the survival group( t=25.56, 8.30 and 13.56, all P<0.01). ROC curve analysis showed that the sensitivity and specificity of serum lactic acid, procalcitonin and CRP in predicting the prognosis of elderly CAP patients were 76.92% and 73.17%, 84.62% and 78.05%, and 69.23% and 70.73%, respectively.The sensitivity and specificity of combined detection of the three indicators were 92.31% and 89.02%, respectively, higher than those of the individual indicators. Conclusions:Serum levels of lactic acid, procalcitonin and CRP are increased in elderly patients with CAP.Combined detection of the three indicators can improve the prognostic value and therefore has important clinical significance.
8.Fungus infection in immunocompromised rabbits:correlation of thin-section CT findings and histopathology
Feng XUE ; Shiyuan LIU ; Kai LIU ; Lixuan XIE ; Yousan CHEN ; Jian ZHANG ; Huimin LI ; Jin HE
Chinese Journal of Radiology 2009;43(1):71-77
Objective To compare the thin-section CT findings of pulmonary candidiasis,aspergillosis and eryptococcosis wim histopathology in immunoeomprimised rabbits and impmve the diagnostic accuracy of fungus infection. Methods Heathy New Zealand white rabbits were used for immunoeompromised animal models.Thin-section CT scan was performed before and 2,4,6,8,10,12,14 d after inoculation.The pattern and distribution of the pulmonary abnormalities were retrospectively assessed by two thomeic radiologists and compared with histopathology.The granulocyte count was compared before and after administration of immunosuppressive agents.The pmred t test,chi square test and the Fisher's exact test were used for the statistics.Results Fourteen rabbits had candidiasis.16 rabbits had cryptocoecosis,15 rabbits had aspergillosis.The granulocyte counts before and after administration of immunosuppressive agents were(2.91±0.92)and(0.35±0.19)×109/L respectively in eandidiasis group,there was a significant difference(t=12.484,P<0.05);(2.51±0.82)and(0.76±0.71)×109/L in aspergillosis group,there was a significant difference(t=5.792,P<0.05);(2.10±0.65)and (0.48±0.22)×109/L in cryptococcosis group,there was a significant difference(t=8.199,P<0.05).The onaet time of infections on CT were not significantly different in three groups (P>0.05).Ground glass opacity (GGO) and consolidation were the two most colnlnon findings in immunocompromised rabbits with three fungus infections,areas of GGO was correlated with the congestion,hemorrhage,inflammatory cell infiltration and interstitial hyperplasia in pathology. Consolidation was correlated with the severe congestion,hemorrhage, inflammatory cell infiltration, interstitial hyperplasia, necrosis and vascular embolism in pathology. Conclusion GGO and consolidation are the two most common findings of fungus infections in immunocompromised animal models and thin-section CT findings can reflect the pathological changes.
9.Pulmonary infections after kidney transplantation:analysis of CT findings
Feng XUE ; Shiyuan LIU ; Li LI ; Xin GAO ; Kai LIU ; Huimin LI
Chinese Journal of Radiology 2009;43(1):12-16
Objective To review the CT findings in patients with pulmonary infection after kidney transplantation and to determine the characteristic features in different infections.Methods The medical records were reviewed in 446 patients with pulmonary infection after kidney transplantation and 121 patients who had pulmonary thin-section CT were included in this study.The pattern and distribution of the pulmonary abnormalities were interpreted independently by two thoracic radiologists.Statistical analysis was performed using the X2 test and the Fisher's exact teat.Results (1)Time course:65(14.6/) patients initially had pulmonary infection in the first 30 days,147(32.9/)between 1 and 3 months,91(20.4/)between 3 and 6 months,23(5.2/)between 6 and 12 months,120(26.9/)afler 12 months of transplantation.In the first month after procedure,bacterial infection(4/5,80.0/)was the most common infection,bacterial(34/41,82.9/)、mixed(19/41,46.3/)and virus infections(11/41.26.8/)were seen commonly 1 to 6 months following transplant,the incidence of fungal(14/38,36.8/)and myeobaeterial(5/38,1 3.2/)infections was increased after 1 2 months of transplantation.(2)Pathogens:Baeterial(34,28/)and mixed infections(34,28/)were the most common,followed by fungus infeetion(9.7/),TB(7,6/)and eytomegalovirus(5,4/).(3)CT findings:Ground-galss attenuations(69,57.0/)was the most common findings of pneumonia,followed by reticular or linear opacities(68,56.2/),nodules (66,54.5/),pleural thickening(41,33.9/),consolidations(31,25.6/),tree-in-bud patterns(24,19.8/),pleural effusion(22,18.2/),and bronchovascular bundle thickening(16,13.2/).Ground-glass attenuation was commonly seen in cytomegalovirus pneumonia (4,80.0/),and nodule was commonly observed in bacterial infection(23.67.6/),tree-in-bud pattern was the most common finding in pulmonary tuberculosis (4.P=0.049).There were no statistically significant difierences in the prevalence of other CT paRerns (P>0.05).Conclusions The peak incidence of pulmonary infection is in the 3 month after renal transplantation and bacterial infection is the most common.The CT diagnosis of infeetion can be made by combining the time course of infection,clinical laboratory data and lesion distribution.

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