BACKGROUND:Ferroptosis-related genes have been found to play an important role in the pathogenesis of rheumatoid arthritis.However,there is currently a lack of immune expression of ferroptosis-related signature genes in rheumatoid arthritis and the construction of competing endogenous RNA(CeRNA)interaction networks.Machine learning,as a powerful signature gene selection algorithm based on bioinformatics,can more accurately identify ferroptosis-related signature genes that dominate the pathogenesis of rheumatoid arthritis. OBJECTIVE:To screen ferroptosis-related signature genes in rheumatoid arthritis using bioinformatics and machine learning methods,and to analyze the correlation between ferroptosis-related signature genes and immune infiltration and the construction of CeRNA network of ferroptosis-related signature genes. METHODS:Rheumatoid arthritis-related microarrays were obtained from the GEO database,and ferroptosis-related genes and their differential gene expression were extracted using R language.The differentially expressed genes were screened using machine learning methods.The LASSO regression and SVM-RFE methods were used for signature gene screening,and the genes filtered by both were re-intersected to finally obtain the signature genes in rheumatoid arthritis.Receiver operating characteristic curves were used to assess the accuracy of the screened signature genes for disease diagnosis.Immune infiltration of rheumatoid arthritis and normal synovial tissues was analyzed using the CIBERSORT algorithm,and the correlation between the signature genes and immune cells was analyzed.Finally,the CeRNA network of ferroptosis-related signature genes for rheumatoid arthritis was constructed and the disease signature genes were validated. RESULTS AND CONCLUSION:A total of 150 ferroptosis-related genes in rheumatoid arthritis were obtained,including 55 up-regulated genes and 95 down-regulated genes.GO and KEGG enrichment analyses identified 18 GO significantly correlated entries and 30 KEGG entries respectively,mainly involving metal ion homeostasis,ferric ion homeostasis and oxidative stress response.Machine learning analysis finally identified disease signature genes GABARAPL1 and SAT1.GSEA analysis found that adipocytokine signaling pathway,drug metabolism cytochrome P450,fatty acid metabolism,PPAR signaling pathway,tyrosine metabolism were mainly concentrated when GABARAPL1 was highly expressed,and chemokine signaling pathway,intestinal immune network on IGA production were mainly concentrated when SAT1 was highly expressed.Immune infiltration analysis found that nine immune cells were significantly different in rheumatoid arthritis and normal synovial tissues,in which plasma cells,T-cell CD8,and T-cell follicular helper were highly expressed and the rest were lowly expressed in the disease group.Single gene and immune cell correlation analysis found that GABARAPL1 was positively correlated with dendritic resting cells,activated NK cells,and macrophage M1,with the most significant correlation with dendritic resting cells,while SAT1 was positively correlated with T cell CD4 and γδ T cells and negatively correlated with NK resting cells.GSVA analysis found that SAT1 was upregulated in ascorbic acid and aldehyde metabolism,while downregulated in B-cell receptor signaling pathway,Toll-like receptor signaling pathway,T-cell receptor signaling pathway,and natural killer cell-mediated cytotoxicity.GABARAPL1 showed a down-regulation trend in PPAR signaling pathway,metabolism of nicotinate and nicotinamide,tryptophan metabolism,fatty acid metabolism,and steroid biosynthesis.Sixty long non-code RNAs may play a key role in the development of rheumatoid arthritis.To conclude,the occurrence of rheumatoid arthritis is significantly correlated with the abnormal expression of rheumatoid arthritis-induced ferroptosis-related signature genes,and the signature genes induce disease development via relevant signaling pathways.By analyzing rheumatoid arthritis-related long non-code RNAs-mediated ceRNA networks,potential therapeutic targets and signaling pathways can be identified to further elucidate its pathogenesis and provide a reference basis for subsequent experimental studies.

Objective:To explore the effect of rapamycin on 1-methyl-4-phenylpyridinium iodide (MPP+ )-induced activation of Nod-like receptor protein 3 (NLRP3) inflammasome in microglia.Methods:The BV2 microglia cells were divided into control group, model group and rapamycin group.The model group and rapamycin group were treated by MPP+ to activate NLRP3 inflammasome, and rapamycin group was pretreated with rapamycin.Quantitative real-time PCR (RT-qPCR) was used to detect the mRNA levels of NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1.Immunofluorescence was used to detect the protein expression of NLRP3 and interleukin-1β (IL-1β). Western blot was carried out to assess the protein expression of NLRP3, ASC, caspase-1, beclin1 and microtubule-associated protein 1 light chain 3 (LC3).Results:The mRNA levels of NLRP3, ASC and caspase-1 in model group were higher than those in control group ( t=4.825, 3.015, 5.853, all P<0.05). The mRNA levels of NLRP3 and caspase-1 in rapamycin group were lower than those in model group ( t=2.75, 2.89, both P<0.05). In model group, the protein expressions of NLRP3 (1.54±0.22), ASC (1.02±0.13) and caspase-1 (1.42±0.30) were higher than NLRP3 (0.66±0.15), ASC (0.41±0.14) and caspase-1 (0.70±0.10) in control group ( t=5.653, 5.602, 3.964, all P<0.01), while the protein expression of beclin1 (0.28±0.09) and LC3II/LC3I ratio(0.69±0.14) were lower than beclin1 (0.60±0.11) and LC3II/LC3I (1.29±0.23) in control group ( t=4.010, 3.982, both P<0.01). The protein expressions of NLRP3 (0.80±0.18) and ASC (0.68±0.14) in rapamycin group were lower than those in model group ( t=4.413, 3.077, both P<0.05), while the protein expression of beclin1 (0.65±0.20) and LC3II/LC3I ratio(1.42±0.36) were higher than those in model group ( t=2.965, 3.278, both P<0.05). Conclusion:MPP+ activates NLRP3 inflammasome and impairs autophagic function in microglia.Rapamycin inhibits MPP+ -induced activation of NLRP3 inflammasome by restoring autophagic impairment in microglia.

Systemic sclerosis (SSc) is a rare, chronic connective tissue disease with internal organ fibrosis, and interstitial lung disease (ILD) is the leading cause of death in patients with SSc. The onset of SSc-associated ILD is usually latent, and delayed treatment may lead to rapid progression, and markedly decrease the quality of life and survival rate of patients. This review summarizes approaches to the early diagnosis of SSc-associated ILD and the time-to-treatment, and provides an overview of its treatment, including traditional immunosuppressive agents, newly emerging targeted therapies, hematopoietic stem cell transplantation, lung transplantation, and so on.

Objective To investigate the effects and regulating mechanisms of matrix metalloproteinase 9 (MMP-9) gene silencing on aquaporin 4(AQP4) expression in astrocytes induced by oxygen-glucose deprivation.Methods Cerebral cortical astrocytes from 2 days newborn SD rats were undergone the primary culture.The ischemic cell model was established by oxygen-glucose deprivation.This experiment were divided into control group,negative control group and MMP-9 gene silencing group.The leakage rate of lactated dehydrogenase (LDH)was detected by chromatoptometry.The MMP-9 gene silencing was carried out by Lentivirus transfection.Real-time fluorescence quantitative PCR and Western blot were used to detect the expression levels of AQP4 and MMP-9.The expressions of PKA,PKC,PKG and CaMK Ⅱ were determined by Western blot.Results Compared with control group,LDH leakage rate was significantly higher in astrocytes induced by oxygen-glucose deprivation(t=13.35,P＜0.01).The expression of MMP-9 mRNA in astrocytes in MMP-9 gene silencing group(0.412±0.297) decreased significantly compared with that in negative control group(1.118 ± 0.240) (t =-4.964,P＜ 0.05).The expression of AQP4 mRNA in astrocytes in MMP-9 gene silencing group(1.002±0.082) decreased significantly compared with that in negative control group(1.442±0.066) (t=-9.886,P＜0.01).The expression of AQP4 protein in astrocytes in MMP-9 gene silencing group(0.643±0.036)decreased significantly compared with that in negative control group(1.000± 0.069)(t=-11.073,P＜0.01).The expression of PKC protein in astrocytes in MMP-9 gene silencing group (0.198±0.110)decreased significantly compared with that in negative control group (0.980± 0.232) (t =-7.218,P＜0.01).The expressions of PKA(t=0.875),PKG(t=0.818) and CaMK Ⅱ (t=0.933) protein had no statistically significant difference between negative control group and MMP-9 gene silencing group(all P＞0.05).Conclusion The permeability of astrocytes is increased by oxygen-glucose deprivation.Gene silencing MMP-9 could induce expression of AQP4 mRNA and protein decreased,and MMP-9 may regulate AQP4 expression by regulating PKC activity.

Objective To study the relation between alcohol-induced osteonecrosis of femoral head (AIONFH) related with high morbidity TCM constitution type with CYP2C8 gene polymorphisms.Methods Totally 152 Han nationality NONFH cases from Feburary 2014 to September 2015 from outpatient and the inpatient departments in Gansu Province Hospital of TCM were collected. 50 AIONFH cases were set as medical case group; meanwhile, 45 healthy volunteers were enrolled as control group. Database for medical materials of all patients and volunteers was established. TCM distribution for AIONFH patients was determined. Solution DNA extraction kit was used to extract DNA, and detect the concentration and purity of DNA. The target gene was amplified by PCR and the target gene was amplified by gel electrophoresis. The length of the fragment was confirmed to conduct target gene sequencing. With the results of sequencing and gel electrophoresis, the relation of AIONFH with CYP2C8 gene polymorphism in AIONFH patients with phlegm-dampness syndrome and the control group.ResultsThe CYP2C8 gene loci rs17110453 gene polymorphism was not statistically significant between the two groups (χ2=0.253,P>0.05). There was no significant difference in allele between the two groups (χ2=0.077,P>0.05). The risk of disease in CC genotype was 1.37 times higher than the AA genotype (95%CI: 0.339-5.540), without statistical significance (P>0.05). There was no significant difference in genotype and allele distribution between AIONFH patients with phlegm-dampness and non-phlegm-dampness and the control group (P>0.05).Conclusion CYP2C8 gene loci rs17110453 gene polymorphism A/C mutation has no obvious relation with AIONFH risk. There is no clear relationship between CYP2C8 gene loci rs17110453 gene polymorphism with AIONFH.

Objective To investigate the perioperative complications of stenting with symptomatic intracra-nial artery stenosis and study the mechanism and prevention of complications. Methods 63 patients were collect-ed from Stroke Center of Guangxi. They were proved intracranial artery stenosis and performed intracranial stents. Patients′ age,with hypertension,diabetes and hyperlipidemia or not,smoking or not,types and occurrence time of complications were registered. Results 63 patients were registered and 2 patients terminated operation due to blood vessels circuity or serious vessel spasm. Operation success rate reached 96.83％. 5 patients had complications among 63 cases,with complication incidence of 8.20％. 3 patients experienced cerebral hemorrhage and two cere-bral infarction in peri-operation period. 2 patients died of complications and mortality rate was 3.28％. Conclu-sions The incidence rate of complications of intracranial stenting with symptomatic intracranial artery stenosis is relatively high and it can be reduced by preoperative sufficient assessment and prudent selection ,careful operation and strict management after operation.

Objective To explore the risk factors of poststroke infection after cerebral infarction. Methods We consecutively included 283 patients with acute ischemic infarcts confirmed by diffusion-weighted imaging (DWI) within 72 hours from Guangxi stroke center. Based on infection status, patients were divided into Not infection group(n=198) and infection group (n=85). The serum cortisol and plasma IL-4 were assessed using chemiluminescent system and double antibody sandwich enzyme linked immunosorbent assay at admission and seventh day later,respectively. Results Compare to no infection group, smoking, mechanical ventilation, diabetes mellitus, dysphagia, COPD,level of consciousness, cortisol and IL-4 at admission, NIHSS, middle area and large area infarction, large atherosclerosis and cardiogenic infarction, left side,both side and subtentorial infarction are more liable to infection(P<0.05);After a Single-factor and Multivariate analysis,we found that cortisol(OR 3.26)and IL-4(OR 2.83)at admission,large area infarction(OR 2.67),left side(OR 3.78)and subtentorial infarction(OR 3.12)were significant correlated with infection, suggesting that they might be the independent risk factors for infection after cerebral infarction. Conclusion Immunological factors and different regional cerebral infarction may increase susceptibility to infection after stroke.

Objective To assess the test-retest reliability of pressure biofeedback in measuring intra abdominal pressure in the lumbar region for normal subjects .Methods We choosed 33 subjects (20 to 27 years old) and asked them to do four movements (movement A :prone position ;movement B :supine position with flexion hip and knee joint ;movement C :supine position with single flexion hip and knee joint ;movement D :prone position with flexion shoulder joint ;) by using pressure biofeedback twice totally ,and the last measurement should be done after 24 h .The indicator of test-retest reliability of joint position was intraclass correlation co-efficient (ICC) .Results The test-retest reliability of intra abdominal pressure was modest in the four movements in the lumbar re-gion ,and the values of ICC were from 0 .786 - 0 .848 .The test-retest reliability of intra abdominal pressure was good in Movement A [ICC(95% CI)= 0 .817(0 .630 - 0 .910)] ,Movement B [ICC(95% CI)= 0 .848 (0 .692 - 0 .925)] ,Movement D [ICC(95% CI)= 0 .841(0 .678 - 0 .921)] .And the test-retest reliability of intra abdominal pressure was good in Movement C [ICC (95% CI) =0 .786(0 .566 - 0 .894)] .Conclusion The test-retest reliability of intra abdominal pressure was modest and good in the lumbar re-gion ,and pressure biofeedback could be useful to assess intra abdominal pressure .

Chronic low back pain is a common type of pain which is related to the dysfunction of low back muscles. In recent years, the pressure biofeedback has been widely used for the assessment and treatment of chronic low back pain. This paper reviewed the reliability and validity of pressure biofeedback unit in the evaluation of lumbar and abdominal muscles activity, as well as its application on the rehabil-itation of chronic low back pain, which mainly related to the assessment and treatment of lumbar muscle activity and lumbar spine stability.

Objective To analyze lesion patterns of lacunae-sized infarctions in the perforating arterial territory in terms of shape and determine whether the lesion patterns associate with their prognosis. Methods We consecutively included patients with confirmed lacunae-sized acute ischemic infarcts in the penetrating arterial territories on diffu?sion-weighted imaging(DWI)from Guangxi stroke center between June 2012 to September 2013. Based on diffu?sion-weighted MRI, the shape of ischemic infarcts were divided into oval or conglomerated beads shape. Demographics, risk factors and NIH Stroke Scale (NIHSS) score at admission and discharge, Ranking score after three months and stroke mechanisms were analyzed. Results Among 189 patients, the conglomerated beads shape and oval shape of infarcts were detected in 69(36.5%)and 120(63.5%)patients, respectively. There were not difference between these two groups in de?mographics, risk factors and NIH Stroke Scale (NIHSS) score at admission. However, the maximal diameter of the lesion was significantly larger in the conglomerated beads shape group than in the oval shape (13.8±2.3 mm vs. 10.6±3.2 mm, P=0.006). Early neurologic deterioration was also more commonly detected in the conglomerated beads shape group than in the oval shape group (24.6% vs. 5.0%,P=0.009). Early neurologic rehabilitation was slower in the conglomerated beads shape group than in the oval shape group(30.5% vs. 10.8%,P=0.018). Multiple logistic regression analysis showed that the conglomerated beads shape was significantly associated with early neurologic deterioration (OR=7.55, 95%CI:1.73~33.25,P=0.010) and was negatively related to early neurologic rehabilitation(OR=5.75, 95%CI:1.53~28.70,P=0.030). Conclusions The conglomerated beads shape of lacunae infarction is significantly associated with ear?ly neurologic deterioration and is negatively related to early neurologic rehabilitation.