【Objective】 To explore the differential expression and functional analysis of circRNA from myocardial mitochondria in diabetes cardiomyopathy (DCM) mice. 【Methods】 The DCM mice model was established in 16-week-old db/db mice, and C57BL/KsJ mice were used as controls. RNA was extracted from the myocardium of two groups of mice, high-throughput sequencing was used to screen mitochondrial circRNA differentially expressed in the two groups, RT-qPCR was used to verify the sequencing results of the first 10 circRNAs with significant differential expression, and functional enrichment analysis was performed on the differentially expressed circRNA target genes, and miRNA target prediction software was used to analyze the circRNA-miRNA co-expression network. 【Results】 There were 147 mitochondrial circRNAs differentially expressed in the myocardium of DCM mice, including 89 highly expressed and 58 low expressed. The expression pattern of differentially expressed circRNAs in tissues was consistent with those of sequencing results. The enrichment analysis of GO and KEGG showed that the differentially expressed circRNA target genes were mainly enriched in cGMP/PKG, glucagon pathways, which were related to mitochondrial energy metabolism and cardiac hypertrophy. circRNA-miRNA co-expression analysis found that the most significantly up-regulated circRNA, chrM:1207-1536+, was associated with miR-491-3p, miR-99a-3p, and miR-99b-3p, and the most significantly down-regulated circRNA, chrM:1453-3205+, was associated with miR-181b-1-3p, miR-181b-2-3p, and miR-672-5p. 【Conclusion】 Compared to the control mice, there is differential expression of circRNAs in myocardial mitochondria of DCM mice. The differentially expressed circRNAs may interact with the corresponding miRNA to affect myocardial fibrosis and hypertrophy through regulation of energy metabolism, apoptosis and other pathways, thus participating in the pathogenesis of DCM.

【Objective】 To make bioinformatics analysis of inflammatory cardiomyopathy so as to screen out hub genes related to etiology and therapeutic targets. 【Methods】 Differential expression analysis of inflammatory cardiomyopathy gene chip data from Gene Expression Omnibus （GEO） Database was carried out via GEO2R tool. Protein-protein interaction（PPI）network and hub genes identification were realized by String database and CytoHubba. GO and KEGG enrichment analysis for functional annotation and pathway analysis of hub genes were conducted by R language. Web-based enrichment analysis platform Enrichr and Drug Signatures database were applied to screen out candidate drugs targeting hub genes for inflammatory cardiomyopathy. 【Results】 The 149 DEGs were statistically significant， among which 44 were upregulated and 105 were downregulated. To identify hub genes， PPI network consisting of 37 nodes and 116 edges was constructed， and 16 hub genes were NDUFB7， POLR2L， NDUFS7， UQCR11， NDUFA13， NDUFA2， PHPT1， NDUFB10， UBA52， ATP5D， NDUFA3， COX6B1， POLR2J， COX4I2， AURKAIP1 and MRPL41. Hub genes were enriched to 113 different GO terms， and the most significant terms were mitochondrial ATP synthesis coupled electron transport， respiratory electron transport chain， oxidative phosphorylation， respiratory chain， mitochondrial inner membrane， NADH dehydrogenase activity and oxidoreductase activity. DEGs were enriched to 13 different signal pathways， including oxidative phosphorylation， non-alcoholic fatty liver disease， diabetic cardiomyopathy， and cardiac muscle contraction. We screened out candidate drugs targeting hub genes， namely， metformin hydrochloride， clindamycin， and hydralazine. 【Conclusion】 Hub genes screened out by decoding the expression profiles are convolved in the etiology and mechanism of inflammatory cardiomyopathy， which might serve as latent therapeutic targets and benefit patients with inflammatory cardiomyopathy.

OBJECTIVE: To evaluate the effect of rosmarinic acid (RA) on mitophagy and hypertrophy of cardiomyocytes exposed to high glucose (HG). METHODS: Rat cardiomyocytes (H9c2) exposed to HG (25 mmol/L) were treated with 50 μmol/L RA or with both RA treatment and Parkin siRNA transfection, with the cells cultured in normal glucose (5.5 mmol/L) and HG as the controls. The expressions of PINK1, Parkin and LC3II/LC3I in the cells were detected by Western blotting. The formation of mitochondrial autophagosomes was observed by transmission electron microscope. Flow cytometry was employed to detect the level of reactive oxygen species (ROS) and apoptotic rate of the cells. The activities of respiratory chain complex enzymes were measured by spectrophotometry. Fluorescence enzyme labeling and RESULTS: RA treatment significantly increased the expression levels of PINK1, Parkin and LC3-II/I ( CONCLUSIONS RA can protect rat cardiomyocytes against oxidative stress injury and cardiomyocyte hypertrophy induced by HG by activating Parkin-mediated mitophagy.
Animals ; Cinnamates ; Depsides ; Glucose ; Hypertrophy ; Mitophagy ; Myocytes, Cardiac ; Protein Kinases ; Rats ; Reactive Oxygen Species ; Ubiquitin-Protein Ligases/genetics*

Objective To investigate the protective effect and mechanism of serum containing Euonymus fortunei on the rat pancreatic islet cells. Methods Forty male SD rats were randomly divided into 5 groups (n=8 in each group), including the control group (normal rat islet cells were cultured with normal rat serum), ischemic preconditioning group (abdominal aorta was blocked first and then re-opened before the pancreas was obtained, and the pancreatic islet cells were cultured with normal rat serum), Euonymus fortunei treatment group (normal rat islet cells were cultured with rat serum containing Euonymus fortunei), Euonymus fortunei group and blank group (normal rats were administered orally with Euonymus fortunei extract or distilled water for the preparation of rat serum). Diphenylthiocarbazone (DTZ) staining was utilized to observe and calculate the quantity of islets. Acridine orange (AO)/propidium iodide (PI) staining was adopted to calculate the survival rate of islet cells. The insulin release experiment was performed to calculate the stimulation index (SI) and evaluate islet cell function. The concentration of glutathione (GSH) and nitric oxide (NO) in islet cells was detected using GSH and NO kits. The expression level of inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) was quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). Results Islet cells were observed in specifically scarlet color after DTZ staining. The quantity of islet cells did not significantly differ among different groups (all P>0.05). Along with the prolongation of culture time, the activity of islet cells in each group was gradually decreased. At 72 h after isolation and culture, compared with the control group, the survival rate of the cells was significantly higher in the Euonymus fortunei treatment group (P<0.05). The insulin release test results demonstrated that compared with the control group, the SI of the ischemic preconditioning and Euonymus fortunei treatment groups was significantly increased (both P<0.05). Compared with the control group, the GSH contents of pancreatic islet cells in the ischemic preconditioning and Euonymus fortunei treatment groups were considerably enhanced, the NO content was significantly decreased, and the expression level of iNOS mRNA was significantly down-regulated (all P<0.05). Conclusions Euonymus fortunei can increase the survival rate of islet cells and enhance the function of pancreatic islets by increasing the level of GSH, down-regulating the expression of iNOS and decreasing the NO production.

Objective To investigate the expression and antibacterial function of Neutrophil extracellular traps (NETs) in systemic lupus erythematosus (SLE) patients.Methods Thirty stable SLE patients and thirty normal controls (NC) were recruited to this study.The acitivity of SLE was assessed by SLE Disease Activity Index (SLEDAI).Density gradient centrifugation was uesd to isolate neutrophilic granulocytes.Picogreen assay was used to quantify NETs formation.Colony counting method was used to compare the antibacterial rate of NETs between two groups.Variation of quantity and activities of neutrophil elastase (NE) and myeloperoxidase (MPO) on induced NETs was tested by enzyme linked immunosorbent assay (ELISA).Results There was no significant difference in the number of NETs between SLE and NC.Compared to the control group,more NETs were induced from neutrophils in SLE,the antibacterial rate of induced NETs was significantly lower,with the activities of antibacterial protein MPO decreased.Conclusions Stable SLE patients are more easily to induce NETs,and the antibacterial function of induced NETs are truly defective,may be related to the decreased activity of the antibacterial protein MPO.

Objective:To analyze the trend relevant factors leading to death and their patterns over a 10-year period in inpatients with connective tissue diseases (CTDs).Methods:All clinical data about death in inpatients with CTDs were retrospectively reviewed between 2005 and 2014 at the Department of Rheumatology and Immunology in Xiangya Hospital of Central South University.Results:In the 10-year time period,the overall hospital mortality was 15.689‰.The disease itself accounted for 44.71% of the total causes of death,infection accounted for 42.94%,and comorbidities accounted for 12.35%.The constituent ratio of deaths and the average hospital mortality caused by the disease itself declined gradually year by year,and the constituent ratio of deaths caused by infection and comorbidities increased gradually year by year (P<0.05).In 2013-2014,infection was the leading cause of death,which accounted for 51.06%.The survival time for CTDs inpatients with interstitial lung disease (ILD) was shorter than that of CTDs inpatients without ILD,and even the risk of death was 1.722 times of the latter.The proportion of deaths caused by the disease itself was the highest in systemic sclerosis and systemic lupus erythematosus,that by infection was the highest in idiopathic inflammatory myopathy (IIM),and that by comorbidities was the highest in rheumatoid arthritis.Conclusion:The proportion of deaths and the hospital mortality in CTDs inpatients caused by the disease itself show a declining trend,while the proportion of deaths caused by infection and comorbidities increase.CTDs patients with ILD have shorter survival time and an increase in risk of death.

Objective To investigate the clinical effect of repairing soft tissue defects of foot and ankle by sural neurovascular adipofascial flap.Methods Application of sural neurovascular adipofascial flap to repaire soft tissue defects of foot and ankle in 19 patients,inclouding 3 csaes with the soft tissue defects of medial malleolus and 16 cases of dorsum pedis from May,2006 to May,2013.The size of soft tissue defects was 3 cm ×3 cm-7 cm ×9 cm.The skin of the donor site was sutured directly.The recipient area was reshaped granulation and underwent free skin graft after the adipofascial flap survived.Results After followed up of 3-18 months,the adipofascial flaps were all survived,the recipient area was almost flat with the surrounding tissue,the donor area only leaving linear scar,the appearance and function of donor area and adopt area were satisfactory.The sensation of lateral dorsal region of foot decreased to S3,and the sensation of recipient site recovered to S2.There were some changes in pigmentation with the skin graft region.Conclusion Sural neurovascular adipofascial flap can be effectively repaired soft tissue defects of foot and ankle,and it can avoid irregularity of donor area and enlargement of adopt area,the appearance and function were satisfactory.

Objective To investigate the efficacy and safety of low-dose prednisone combined with methotrexate (MTX) and hydroxychloroquine (HCQ) in the treatment of rheumatoid arthritis (RA).Methods In this 12-week study,150 patients with active rheumatoid arthritis were randomly divided into two groups:prednisone group (70 cases who were received prednisone 5 ～ 10 mg/d + MTX 10 mg/w +HCQ 0.2 g/d) and control group (80 cases who were treated by Meloxicam 7.5 mg/d + MTX 10 mg/w +Leflunomide (LEF) 20 mg/d).The primary end-points were tender and swollen joint counts,visual analogue scales (VAS),and global physician and patients assessments of disease.The secondary end-points were morning stiffness time,C-reactive protein,erythrocyte sedimentation rate,the Health Assessment Questionnaire (HAQ),DAS28 and ACR20,ACR50.Results After 12 weeks,in terms of primary endpoints,tender and swollen joint counts,VAS and global physician assessments in the prednisone group were improved significantly [(4.5 ± 2.5),(3.2 ± 3.36),(21 ± 15),(24.2 ± 16.4),(20.2 ± 10.4) vs (6.4 ±5.84),(6.6±5.5),(46±14),(37.9±19.7),(34.1±12.4),P ＜0.05orP ＜0.01].In terms of secondary end-points,the prednisone group produced higher response rates [HAQ score (0.93 ± 0.52),CRP(10.2 ± 5.8) mg/L,ESR(30 ± 14) mm/h,morning stiffness time (32.0 ± 32.3) min,DAS 28 score (3.1±0.9) vs (1.22 ±0.81),(16.3±10.1)mg/L,(33±29)mm/h,(54.7±45.4)min,(4.9±1.9),P ＜0.05 orP ＜0.01].The incidence of adverse events was similar between two groups (43％ vs 49％,P ＞ 0.05).Conclusions Low-dose prednisone combined with MTX and HCQ produced rapid and relevant improvements in RA signs and symptoms.

OBJECTIVE: To study the clinical characteristics of invasive fungal infection secondary to systemic lupus erythematosus (SLE). METHODS: We observed the clinical features and experimental examination in 91 patients treated in Xiangya Hospital in recent years, of which 48 patients with invasive fungal infection and 41 patients without invasive fungal infection. RESULTS: The invasive fungal infection secondary to SLE mainly occurred in the lungs, nervous system, and urinary system. The fungi were mainly Candida albins and Aspergillus. The rate of invasive fungal infection in SLE patients and the level of CRP and TNF-α in these patients were significantly increased. The occurrence of invasive fungal infection was positively correlated with the prolonged course of disease, long-term use of immunosuppressants and antibiotics, and occurrence of complications, such as hypoproteinemia, leukocytopenia, and so on. The levels of C-reactive protein (CRP) and tumor necrosis factor-α(TNF-α) were increased in SLE patients with invasive fungal infection. CONCLUSION The clinical features of SLE patients with invasive fungal infections are long course of disease, long-time use of immunosuppressants or antibiotics, and occurrence of complications, such as hypoproteinemia or leukopenia. The level of CRP and TNF-α can be used as an important reference index for diagnosing invasive fungal infections.
Adolescent ; Adult ; Aspergillus ; isolation & purification ; C-Reactive Protein ; metabolism ; Candida albicans ; isolation & purification ; Central Nervous System Fungal Infections ; epidemiology ; Child ; China ; Female ; Humans ; Lung Diseases, Fungal ; epidemiology ; Lupus Erythematosus, Systemic ; microbiology ; Male ; Middle Aged ; Mycoses ; complications ; Tumor Necrosis Factor-alpha ; blood ; Young Adult

Objective To investigate the feedback of eight-year program students to problem-based learning ( PBL ),and find out the existing problems and solutions.MethodsThe questionnaire survey was made in the eight-year program students.ResultsApplication of PBL could achieve good feedback.It helped to enhance the self-directed learning,expressing ability,accessing resource skill,and team spirit.ConclusionAlthough there are some problems in the practice of PBL,PBL is a good teaching method in eight-year program education.