OBJECTIVES: This study aims to investigate the genome-wide DNA methylation and transcriptome expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with systemic sclerosis (SSc) with interstitial lung disease (ILD), and to analyze the effects of DNA methylation on Wnt/β-catenin and chemokine signaling pathways. METHODS: PBMCs were collected from 19 patients with SSc (SSc group) and 18 healthy persons (control group). Among SSc patients, there were 10 patients with ILD (SSc with ILD subgroup) and 9 patients without ILD (SSc without ILD subgroup). The genome-wide DNA methylation and gene expression level were analyzed by using Illumina 450K methylation chip and Illumina HT-12 v4.0 gene expression profiling chip. The effect of DNA methylation on Wnt/β-catenin and chemokine signal pathways was investigated. RESULTS: Genome-wide DNA methylation analysis identified 71 hypermethylated CpG sites and 98 hypomethylated CpG sites in the SSc with ILD subgroup compared with the SSc without ILD subgroup. Transcriptome analysis distinguished 164 upregulated genes and 191 downregulated genes in the SSc with ILD subgroup as compared with the SSc without ILD subgroup. In PBMCs of the SSc group, 35 genes in Wnt/β-catenin signaling pathway were hypomethylated, while frizzled-1 (FZD1), mitogen-activated protein kinase 9 (MAPK9), mothers against DPP homolog 2 (SMAD2), transcription factor 7-like 2 (TCF7L2), and wingless-type MMTV integration site family, member 5B (WNT5B) mRNA expressions were upregulated as compared with the control group (all P<0.05). Compared with the SSc without ILD subgroup, the mRNA expressions of dickkopf homolog 2 (DKK2), FZD1, MAPK9 were upregulated in the SSc with ILD subgroup, but the differences were not statistically significant (all P>0.05). In PBMCs of the SSc group, 38 genes in chemokine signaling pathway were hypomethylated, while β-arrestin 1 (ARRB1), C-X-C motif chemokine ligand 10 (CXCL10), C-X-C motif chemokine ligand 16 (CXCL16), FGR, and neutrophil cytosolic factor 1C (NCF1C) mRNA expressions were upregulated as compared with the control group (all P<0.05). Compared with the SSc without ILD subgroup, the mRNA expressions of ARRB1, CXCL10, CXCL16 were upregulated in the SSc with ILD subgroup, but the differences were not statistically significant (all P>0.05). CONCLUSIONS There are differences in DNA methylation and transcriptome profiles between SSc with ILD and SSc without ILD. The expression levels of multiple genes in Wnt/β- catenin and chemokine signaling pathways are upregulated, which might be associatea with the pathogenesis of SSc.
Humans ; DNA Methylation ; Transcriptome ; beta Catenin ; Leukocytes, Mononuclear ; Ligands ; DNA ; RNA, Messenger/genetics*

Objective: To improve clinical management of maternal and neonatal listeriosis through analyzing the clinical characteristics and antibiotic treatment. Methods: A retrospective analysis of 26 cases of listeriosis, including their demographic and clinical features, was conducted, involving 16 pregnant women from Civil Aviation General Hospital, Xiamen Humanity Hospital, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing Tiantan Hospital, Tangshan Maternal and Child Health Hospital, the Fourth Hospital of Tianshui City from October, 2011 to May, 2018, and 10 newborns from the Fourth Hospital of Tianshui City, Tangshan Maternal and Child Health Hospital, Zhengzhou Children's Hospital from February, 2016 to April 2018. Descriptive methods were used for data analysis. Results: (1) Among the 16 gravidas, one, five and 10 developed the infection in the 1st, 2nd and 3rd trimester of pregnancy, respectively, and eight had pregnancy complications. Furthermore, all of them developed fever [(38.9±0.5) ℃]. Symptoms such as cough, nasal congestion, runny nose, sore throat, dizziness, headache and other flu-like symptoms were observed in six cases. Gastrointestinal symptoms and flu-like symptoms were presented in four. Fetal distress, tachycardia and decreased fetal movement occurred in 11 cases. Elevated C-reactive protein and white blood cell count were detected in 16 and 14, respectively. Eight underwent placental pathological examination which shown various degrees of pathological changes, including neutrophil infiltration, acute chorioamnionitis and inflammatory necrosis. The main empirical antibiotic treatment for the 16 patients was cephalosporins and only four covered Listeria monocytogenes. Only two delivered at term, while the others (14/16) ended in miscarriage, premature delivery or stillbirth. (2) Among the 10 newborns with listeriosis, there were eight early-onset infections and two late-onset infections. All of them were febrile [(38.6±0.6)℃]. Six had cyanosis, groaning, foaming and three concave sign; five showed shortness of breath; meningitis and skin rash were found in one, respectively. All had elevated white blood cell and C-reactive protein. Six received antibiotics covering Listeria monocytogenes during the initial empirical treatment. Four were treated with cephalosporins alone, one of which died after the treatment was withdrawn. One was cured by initial treatment with meropenem alone, while eight recovered after adjustment of treatment with ampicillin, penicillin, meropenem, vancomycin alone, or meropenem combined with ampicillin or vancomycin. (3) The isolates that were susceptible to penicillin, ampicillin and meropenem accounted for 96.1% (25/26) all together and 88.5% (23/26) were susceptible to compound sulfamethoxazole. Conclusions There is no specific clinical manifestations of maternal or neonatal listeriosis. Maternal listeriosis is often characterized by acute onset and high incidence of adverse pregnancy outcomes.

Objective: To explore the occurrence, clinical characteristics, diagnosis and treatment of glomerulitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Analysis were carried out based on the clinical data of 6 patients with de novo glomerulitis following allo-HSCT hospitalized in Henan Tumor Hospital from January 2008 to December 2016, and the clinical manifestation, pathology, diagnosis, treatment and outcome were investigated. Results: The occurrence of glomerulitis was 1.26% (6/478). The median time was 447(272-1 495) d after allo-HSCT. Proteinuria and varying degrees of edema were present in all patients. Of the 6 patients, 4 patients with impaired renal function, 3 cases of hypertension, 5 cases of urine occult blood positive, 2 cases of hyperlipidemia. 5 patients underwent acute graft-versus-host disease (GVHD), 4 patients accompanied with chronic GVHD at diagnosis. Kidney pathology showed typical features of minimal change diseases in 1 patient, membranous nephropathy in 4 patients and mesangial proliferative glomerulonephritis in 1 case. Immunohistochemistry of glomerular lesions revealed that the immune complex deposition included IgG in 4 patients, C3 in 3 patients, IgM and C1q in 1 patient. Serum ANA was positive in 2 patients and serum IgG and IgM were in high level in 1 patient, respectively. Only 1 case was effective on glucocorticoid. 5 cases treated by low dose cyclophosphamide combined with mycophenolate mofetil (MMF), 2 cases achieved complete remission, and 3 cases were partial remission. Up to now, 2 cases died with lung infection, and 4 patients survived. Conclusion The predominant pathological type of glomerulitis was membranous nephropathy. Low-dose cyclophosphamide combined with MMF was an effective treatment.

Objective: To explore the occurrence, clinical characteristics, diagnosis and treatment of glomerulitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Analysis were carried out based on the clinical data of 6 patients with de novo glomerulitis following allo-HSCT hospitalized in Henan Tumor Hospital from January 2008 to December 2016, and the clinical manifestation, pathology, diagnosis, treatment and outcome were investigated. Results: The occurrence of glomerulitis was 1.26% (6/478). The median time was 447(272-1 495) d after allo-HSCT. Proteinuria and varying degrees of edema were present in all patients. Of the 6 patients, 4 patients with impaired renal function, 3 cases of hypertension, 5 cases of urine occult blood positive, 2 cases of hyperlipidemia. 5 patients underwent acute graft-versus-host disease (GVHD), 4 patients accompanied with chronic GVHD at diagnosis. Kidney pathology showed typical features of minimal change diseases in 1 patient, membranous nephropathy in 4 patients and mesangial proliferative glomerulonephritis in 1 case. Immunohistochemistry of glomerular lesions revealed that the immune complex deposition included IgG in 4 patients, C3 in 3 patients, IgM and C1q in 1 patient. Serum ANA was positive in 2 patients and serum IgG and IgM were in high level in 1 patient, respectively. Only 1 case was effective on glucocorticoid. 5 cases treated by low dose cyclophosphamide combined with mycophenolate mofetil (MMF), 2 cases achieved complete remission, and 3 cases were partial remission. Up to now, 2 cases died with lung infection, and 4 patients survived. Conclusion: The predominant pathological type of glomerulitis was membranous nephropathy. Low-dose cyclophosphamide combined with MMF was an effective treatment.
Glomerulonephritis ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Mycophenolic Acid ; Retrospective Studies

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.

Purpose To explore the expression of Toll-like receptor 4 (TLR4), PI3K, AKT and NF-κB in cervical lesions, and to in-vestigate their association with human papillomavirus ( HPV) 16 infection. Methods Immunohistochemical SP staining was performed to detect the expression of TLR4, PI3K, AKT, NF-κB in paraffin-embedded cervical tissue specimens from Uighur women with chroni-cal cervicitis, cervical intraepithelial neoplasia ( CIN) and cervical squamous cell carcinoma ( CSCC) . The HPV 16 DNA was detected by PCR. Results The positive expression rates of TLR4, PI3K, AKT, NF-κB in chronical cervicitis, CIN and cervical cancer were 32. 0%, 59. 4%, 77. 8%, 28. 0%, 56. 3%, 73. 0%, 24. 0%, 56. 3%, 79. 4%, and 8. 0%, 48. 4%, 81. 0%, respectively. The expression of them was higher in cervicitis than in CIN and cevical cancer ( P<0. 05 ) . The positive expression rates of HPV 16 in three groups were 8. 0%, 48. 4% and 81. 0% (P<0. 05). The expression of TLR4, PI3K, NF-κB and HPV 16 was related to cervi-cal cancer differentiation (P<0. 05). PI3K and AKT were significantly correlated with FIGOs’ stages (P<0. 05). NF-κB was corre-lated with lymph node metastasis. The expression of TLR4 was significantly associated with HPV 16 infection in CIN and CSCC ( r=0. 303, P=0. 015, r=0. 633, P=0. 000), and correlation with PI3K in CIN and CSCC (r=0. 254, P=0. 045, r=0. 386, P=0. 003). PI3K was associated with AKT only in CSCC (r=0. 298, P=0. 018). Conclusions The expression of TLR4 can be up-regulated by HPV 16 infection. High expression of PI3K/AKT signal pathway mediated by TLR4 may play important roles in the devel-opment and progression of CIN and CSCC, and HPV 16 infection may be a trigger factor affecting the molecular signal pathway.

Academic Health Systemis an effective mode to make a response to the change of medical pattern , and more and more aging population , and continued increasing of health care costs .By introducing the system to the field of general practice , using the systematic theory in three basic functions of high schools , combining medical schools with all levels of health-related institutions , building a systematic and continuity education system in general practice .it can resolve the problems such as lack of motivation , poor cooperation of the administrative department and education department , and lack of teachers and practice bases of general practice .

Objective To learn the management staff and funds allocation of the NRCMS in Guangxi,and come up with solution accordingly.Methods Collection of the annual report data of NRCMS in Guangxi from 2009 to 2012,and calculation of the management personnel and funds expenditure.Results The management personnel of NRCMS in Guangxi is found with a 1000-person gap between the actual staffing and approved staffing quota; the management funds rise year by year which come mostly from fiscal appropriation.Yet it accounts for less than 2.00％ and with a high rate of surplus; per-capita funds for management personnel rise significantly,along with their per-capital salaries,yet the highest fall below 25000 yuan per year per person.Conclusion Staffing quota should be fixed more rationally to ensure the number and competence of NRCMS management staff; more funds and better use of management funds are required.

Objective To understand the performance of the basic medical security system in Guangxi for decision-making support on the development planning of the system during the 12th FiveYear Plan in Guangxi.Methods Descriptive statistics were made to analyze the annual report data of Guangxi's basic medical security system during 2009 to 2011,regarding the basic medical security for urban workers and that for urban residents,as well as those of the new rural cooperative medical system.Results The survey found that the three basic medical security systems in Guangxi have almost achieved full coverage; the compensation ratio keeps rising as the inpatient expenses of urban residents was up to 62.21％,64.96％ and 66.96％ respectively from 2009 to 2011,and that for urban residents up to 34.26％,39.96％ and 49.68％ respectively; the ratio for those covered by the new rural cooperative medical system has been maintained at 45％ for the three years; the coverage of the systems keeps expanding.Conclusion Recommend to integrate pilots of the three security systems and carry out serious diseases pilot programs; encourage reform of the payment system at institutions at or above county level; reform the risk-pooling of disease management of at primary medical institutions; strengthen the information systems of basic medical insurance system,in an effort to ensure the sound development of the basic medical insurance system.

Guangxi Medical University had taken a lot of measures to construct systematic general medicine education system consisting of medical college education, post graduation education and continuing medical education. These measures included constructing the organization, modifying the personnel training program, training rural-order directional medical students, standardizing resi-dent training, providing on-the-job training and postgraduate degree education for general practitioners.