BACKGROUND:Indolepropionic acid has been shown to reduce diabetes-induced central nervous system inflammation.However,there is a lack of research on whether to inhibit microglia M1 polarization for the treatment of spinal cord injury. OBJECTIVE:To investigate the mechanism of indolepropionic acid inhibition of microglial cell M1 polarization for the treatment of spinal cord injury through cell and animal experiments. METHODS:(1)In vitro experiments:BV2 cell viability was assessed using the CCK-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,BV2 cells were categorized into control group,administration group(50 μmol/L indolepropionic acid),lipopolysaccharide group(100 ng/mL lipopolysaccharide),and treatment group(100 ng/mL lipopolysaccharide + 50 μmol/L indolepropionic acid).Nitric oxide content was quantified using the Griess method.Real-time quantitative PCR and western blot assay were employed to measure mRNA and protein levels of pro-inflammatory factors.Cell immunofluorescence staining was conducted to assess inducible nitric oxide synthase expression.The Seahorse assay was employed to assess glycolytic stress levels in BV2 cells.(2)In vivo experiments:30 SD rats were randomly divided into three groups:sham surgery group,spinal cord injury group,and indolepropionic acid group.Motor function recovery in rats after spinal cord injury was assessed using BBB scoring and the inclined plane test.Immunofluorescence staining of spinal cord tissue was conducted to evaluate the expression of inducible nitric oxide synthase in microglial cells.ELISA was employed to measure protein expression levels of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in spinal cord tissue. RESULTS AND CONCLUSION:(1)In vitro experiments:Indolepropionic acid exhibited significant suppression of BV2 cell viability when its concentration exceeded 50 μmol/L.Indolepropionic acid achieved this by inhibiting the activation of the nuclear factor κB signaling pathway,thereby suppressing the mRNA and protein expression levels of pro-inflammatory cytokines(interleukin-1β and tumor necrosis factor-α),as well as the M1 polarization marker,inducible nitric oxide synthase,in BV2 cells.Additionally,indolepropionic acid notably reduced the glycolytic level in BV2 cells induced by lipopolysaccharides.(2)In vivo experiments:Following indolepropionic acid intervention in spinal cord injury rats,there was a noticeable increase in BBB scores and the inclined plane test angle.There was also a significant decrease in the number of M1-polarized microglial cells in spinal cord tissue,accompanied by a marked reduction in the protein expression levels of pro-inflammatory cytokines(interleukin-1β and tumor necrosis factor-α).(3)These results conclude that indolepropionic acid promotes functional recovery after spinal cord injury by improving the inflammatory microenvironment through inhibition of microglia M1 polarization.

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17⁺ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17⁺ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.
Animals ; Rats ; Interleukin-17 ; Rats, Sprague-Dawley ; Recovery of Function ; Spinal Cord Injuries/drug therapy* ; T-Lymphocytes, Regulatory ; Receptors, Antigen, T-Cell, gamma-delta/immunology*

BACKGROUND: Osteoporosis (OP) has become a major public health issue, threatening the bone health of middle-aged and elderly people from all around the world. Changes in the gut microbiota (GM) are correlated with the maintenance of bone mass and bone quality. However, research results in this field remain highly controversial, and no systematic review or meta-analysis of the relationship between GM and OP has been conducted. This paper addresses this shortcoming, focusing on the difference in the GM abundance between OP patients and healthy controls based on previous 16S ribosomal RNA (rRNA) gene sequencing results, in order to provide new clinical reference information for future customized prevention and treatment options of OP. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, sensitivity analysis, Egger's test, and Begg's test to assess the risk of bias. RESULTS: This research ultimately considered 12 studies, which included the fecal GM data of 2033 people (604 with OP and 1429 healthy controls). In the included research papers, it was observed that the relative abundance of Lactobacillus and Ruminococcus increased in the OP group, while the relative abundance for Bacteroides of Bacteroidetes increased (except for Ireland). Meanwhile, Firmicutes, Blautia, Alistipes, Megamonas, and Anaerostipes showed reduced relative abundance in Chinese studies. In the linear discriminant analysis Effect Size (LEfSe) analysis, certain bacteria showed statistically significant results consistently across different studies. CONCLUSIONS: This observational meta-analysis revealed that changes in the GM were correlated with OP, and variations in some advantageous GM might involve regional differences.
Middle Aged ; Aged ; Humans ; Gastrointestinal Microbiome/genetics* ; RNA, Ribosomal, 16S/genetics* ; Genes, rRNA ; Osteoporosis ; Feces

OBJECTIVES: To explore and analyze the epidemic features of coronavirus disease 2019 (COVID-19) in Hunan Province from January 21, 2020 to March 14, 2020, as well as to investigate the COVID-19 epidemics in each city of Hunan Province. METHODS: The epidemic data was obtained from the official website of Hunan Province's Health Commission. The data of each city of Hunan Province was analyzed separately. Spatial distribution of cumulative confirmed COVID-19 patients and the cumulative occurrence rate was drawn by ArcGIS software for each city in Hunan Province. Some regional indexes were also compared with that in the whole country. RESULTS: The first patient was diagnosed in January 21, sustained patient growth reached its plateau in around February 17. Up to March 14, the cumulative confirmed COVID-19 patients stopped at 1 018. The cumulative occurrence rate of COVID-19 patients was 0.48 per 0.1 million person. The number of cumulative severe patients was 150 and the number of cumulative dead patients was 4. The mortality rate (0.39%) and the cure rate (99.6%) in Hunan Province was significantly lower and higher respectively than the corresponding average rate in the whole country (0.90% and 96.2%, Hubei excluded). The first 3 cities in numbers of the confirmed patients were Changsha, Yueyang, and Shaoyang. While sorted by the cumulative occurrence rate, the first 3 cities in incidence were Changsha, Yueyang, and Zhuzhou. CONCLUSIONS The epidemic of COVID-19 spread out smoothly in Hunan Province. The cities in Hunan Province implement anti-disease strategies based on specific situations on their own and keep the epidemic in the range of controllable.
Betacoronavirus ; China ; epidemiology ; Cities ; epidemiology ; Coronavirus Infections ; epidemiology ; mortality ; Humans ; Pandemics ; Pneumonia, Viral ; epidemiology ; mortality

BACKGROUND: miRNA-136-5 p plays a crucial regulatory role in pathological changes, inflammatory response and regeneration after spinal cord injury. OBJECTIVE: To investigate the effect of miRNA-136-5 p on the expression of cytokines in serum and NF-κB protein in spinal cord in rats with spinal cord injury and to explore the molecular mechanism. METHODS: Thirty-six male Sprague-Dawley rats, of SPF grade were provided by Laboratory Animal Center of Guangxi Medical University. The lentiviral vector system was prepared and transfected into spinal cord injured rats. Thirty-six rat models of spinal cord injury were established by modified Allen's method. Basso Beattie Bresnahan scores were performed. Rats were randomly divided into normal control, modeling (LV-ctrl plus spinal cord injury), overexpression (spinal cord injury plus LV-miRNA-136-5 p), and inhibition (spinal cord injury plus LV-sponge) groups (n=9/group). Seven days before surgery and the day of surgery, the overexpression and inhibition groups were continuously injected with the lentivirus suspension into the injured area, and the normal control and modeling groups were injected with the same amount of normal saline. Three rats were sacrificed at 1, 3 and 7 days, and blood and spinal cord tissues were taken. The levels of interleukin-1β, interleukion-6 and interferon-α in rat serum were determined by ELISA. The expression of NF-κB protein was detected by western blot assay and double immunofluorescence. RESULTS AND CONCLUSION: (1) There was no significant difference in preoperative Basso Beattie Bresnahan scores (P＞ 0.05). In the modeling group, the rats showed prone walking, vary degrees of urinary retention, and spinal shock, with complete loss of function of both hind limbs and muscle strength of 0. (2) Compared with the normal control group, the levels of inflammatory factors in the other groups were increased significantly (P ＜ 0.05). The expression levels of inflammatory factors were highest in the overexpression group, followed by modeling group, and lowest in the inhibition group. (3) Results of western blot assay and double immunofluorescence showed that the expression level of NF-κB protein in the modeling, overexpression and inhibition groups was significantly higher than that in the normal control group (P ＜ 0.05), and the level was highest in the overexpression group. (4) In summary, miRNA-136-5 p can affect inflammatory factors and NF-κB in rats with acute spinal cord injury.

BACKGROUND: Change of microenvironment after acute spinal cord injury is the main factor causing secondary injury, so it is of great significance to investigate the changes of microenvironment after acute spinal cord injury for clinical diagnosis and treatment. OBJECTIVE: To investigate the expression levels and clinical significance of interleukin-6, brain derived neurotrophic factor, basic fibroblast growth factor, neurotrophin-3 and neurotrophin-4 in peripheral blood within 48 hours after acute spinal cord injury. METHODS: Twenty-nine patients with acute spinal cord injury admitted at the Department of Spinal Osteopathia, the First Affiliated Hospital of Guangxi Medical University from October 2016 to June 2018 were enrolled, and were divided into two groups according to American Spinal Injury Association impairment scale: complete spinal cord injury (n=11) and incomplete spinal cord injury (n=18). Thirteen patients with avascular necrosis of the femoral head were selected as controls. The expression levels of interleukin-6, brain derived neurotrophic factor, basic fibroblast growth factor, neurotrophin-3 and neurotrophin-4 in peripheral blood of 42 patients were determined by ELISA and compared. RESULTS AND CONCLUSION: The ELISA results showed that the expression levels of interleukin-6, brain derived neurotrophic factor, basic fibroblast growth factor, neurotrophin-3 and neurotrophin-4 in peripheral blood in the spinal cord injury group were significantly higher than those in the control group (P ＜ 0.05). The expression levels of all above cytokines in the complete spinal cord injury group were significantly higher than those in the incomplete spinal cord injury group (P ＜ 0.05). In summary, increased expression of interleukin-6, brain derived neurotrophic factor, basic fibroblast growth factor, neurotrophin-3, neurotrophin-4 after acute spinal cord injury indicates that it may participate in the important pathophysiological process after acute spinal cord injury.

OBJECTIVE: To establish a cone beam computed tomography (ECBCT) system for high-resolution imaging of the extremities. METHODS: Based on three-dimensional X-Ray CT imaging and high-resolution flat plate detector technique, we constructed a physical model and a geometric model for ECBCT imaging, optimized the geometric calibration and image reconstruction methods, and established the scanner system. In the experiments, the pencil vase phantom, image quality (IQ) phantom and a swine feet were scanned using this imaging system to evaluate its effectiveness and stability. RESULTS: On the reconstructed image of the pencil vase phantom, the edges were well preserved with geometric calibrated parameters and no aliasing artifacts were observed. The reconstructed images of the IQ phantom showed a uniform distribution of the CT number, and the noise power spectra were stable in multiple scanning under the same condition. The reconstructed images of the swine feet had clearly displayed the bones with a good resolution. CONCLUSIONS The ECBCT system can be used for highresolution imaging of the extremities to provide important imaging information to assist in the diagnosis of bone diseases.
Algorithms ; Animals ; Artifacts ; Calibration ; Cone-Beam Computed Tomography ; instrumentation ; methods ; Equipment Design ; Extremities ; diagnostic imaging ; Image Processing, Computer-Assisted ; methods ; Phantoms, Imaging ; Radiographic Image Enhancement ; instrumentation ; methods ; Swine

As a dioxygenase, Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities.
5-Methylcytosine ; analogs & derivatives ; chemistry ; metabolism ; Animals ; Cell Differentiation ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; DNA-Binding Proteins ; physiology ; Genome ; Genomics ; Mice ; Mice, Knockout ; Osteoclasts ; cytology ; metabolism ; Proto-Oncogene Proteins ; physiology

Objective: To assess the clinical characteristics and identify the risk factors in the acute myocardial infarction (AMI) patients complicating with ventricular septal rupture (VSR). Methods: A retrospective study was performed on 96 AMI patients complicating with VSR, who were hospitalized in the Second Xiangya Hospital of Central South University, Hunan Provincial Peoples′ Hospital, the First Affiliated Hospital of University of South China, the Second Affiliated hospital of University of south China, Xiangtan Central Hospital from December 2007 to May 2017. There were 46 females and the age was (66.2±10.7) years (from 43 to 90 years). Patients were divided into in-hospital survival group (n=64) and in-hospital death group (n=32). The 96 patients were also divided into the early death group (survived ≤2 weeks after admission, n=50) and non-early death group (survived>2 weeks after admission, n=46). Multivariate logistic regression was used to analyze the independent risk factors of the early death. Results: Location of VSR was available in 71 patients, VSR was located at the apical or anterior septum near the apical region in 64.0% (32/50) patients with the anterior AMI, VSR was located at the posterior wall and basal inferior segment in 57.1% (12/21) patients with non-anterior AMI. Compared to the in-hospital survival group, patients in the in-hospital death group were older ((69.6±11.3) years vs. (64.6±10.1) years, P=0.031), incidence of non-ventricular aneurysm (71.9% (23/32) vs. 37.5% (24/64), P=0.001) and anterior AMI (84.4%(27/32) vs. 62.5%(40/64), P=0.028) was significantly higher in the in-hospital death group than in the in-hospital survival group. The comparison between the early death group and non-early death group showed that older age, female, no history of angina or myocardial infarction, Killip grade>Ⅲ, and non-ventricular aneurysm were related to increased risk of the early mortality in this patient cohort. Logistic regression analysis revealed that female (OR=5.109,95%CI 1.19-22.00, P=0.012), no history of angina or myocardial infarction (OR=23.34, 95%CI 3.44-158.37, P=0.001), Killip grade>Ⅲ(OR=5.35, 95%CI 1.26-22.66, P=0.019) and non-ventricular aneurysm (OR=6.30,95%CI 1.67-23.73, P=0.005) were independent risk factors for early death in this patient cohort. Conclusion The risk factors of in-hospital death include older age, non-ventricular aneurysm and anterior AMI. Female, no history of angina or myocardial infarction, Killip grade>Ⅲ and non-ventricular aneurysm are independent risk factors for the early death of AMI patients complicating VSR.

Objective To evaluate the effect of electroacupuncture (EA) preconditioning on inositol-requiring kinase 1 (IRE1)-X-box binding protein 1 (XBP1) signaling pathway in endoplasmic reticulum in the cortex in a rat model of cerebral ischemia-reperfusion (I/R).Methods One hundred and eight pathogen-free healthy male Sprague-Dawley rats,aged 8-12 weeks,weighing 200-250 g,were assigned into 3 groups (n =36 each) using a random number table:sham operation group (group S),group I/R and EA preconditioning group (group EA).Focal cerebral I/R was induced by occlusion of right middle cerebral arteries for 2 h followed by reperfusion in rats anesthetized with chloral hydrate.In group EA,Baihui acupoints were stimulated with an electric stimulator for 30 min once a day for 5 consecutive days starting from 5 days before ischemia,and the model was established at 24 h after the last preconditioning.Rats were sacrificed after neurological deficit was scored at 6,12 and 24 h of reperfusion,brains were removed,and the ischemic area in cerebral cortex was isolated for examination of the cell ultrastructure (with an electronic microscope) and for determination of the expression of IRE1 and XBP1 (by Western blot).Results Compared with group S,the neurological deficit scores were significantly increased,and the expression of IRE1 and XBP1 in the ischemic area was up-regulated at each time point in I/R and EA groups (P＜0.01).Compared with group I/R,the neurological deficit scores were significantly decreased,and the expression of IRE1 and XBP1 was up-regulated at each time point in group EA (P＜0.05).The cell damage in the ischemic area in cerebral cortex was significantly attenuated in group EA when compared with group I/R.Conclusion The mechanism by which EA preconditioning attenuates cerebral I/R injury is related to activating IRE1-XBP 1 signaling pathway and relieving endoplasmic reticulum stress in rats.