Clinical evaluation of insulin resistance and β-cell function by the homeostasis model assessment in patients with systemic lupus erythematosus

The aim of this preliminary study was to evaluate insulin resistance and secretion using homeostasis model assessment (HOMA) in patients with systemic lupus erythematosus (SLE). The fasting glucose and insulin concentrations, HOMA insulin resistance (IR), HOMA -cell, antidouble-stranded DNA antibodies (anti-dsDNA), C3, C4, and SLE disease activity index (SLEDAI) were determined in a total of 58 female SLE patients. All patients were classified into subgroups according to the presence of anticardiolipin antibodies (aCL+ vs. aCL-) and SLEDAI scores (SLEDAI <3 vs. SLEDAI >3). Results showed that SLE patients with and without aCL had significantly higher fasting insulin levels, HOMA IR, and HOMA -cells than controls. Similar results were also found in SLE patients with different disease activities. Pearsons correlation analysis showed that there was a highly significant correlation of HOMA IR with fasting insulin concentration in the SLE patients and SLE subgroups overall. However, HOMA -cells were positively correlated with HOMA IR and fasting insulin level, but negatively correlated with fasting glucose concentration in SLE patients overall. In conclusion, SLE patients, regardless of the presence of aCL and different disease activities, had a higher risk of insulin resistance and abnormal insulin secretion than age-matched healthy controls, based on fasting insulin concentration, HOMA IR, and HOMA -cells.Abbreviations HOMA Homeostasis model assessment - IGT Impaired glucose tolerance - IR Insulin resistance - NGT Normal glucose tolerance - SLE Systemic lupus erythematosus - SLEDAI SLE disease activity index     

羟氯喹联合利妥昔单抗治疗系统性红斑狼疮的临床研究

目的 研究羟氯喹联合利妥昔单抗治疗系统性红斑狼疮的临床疗效。方法 选择2017年1月—2019年12月榆林市第二医院的系统性红斑狼疮患者71例作为研究对象。用抽签法随机将患者分为对照组（36例）和观察组（35例）。对照组iv利妥昔单抗注射液,100 mg/次,1次/周。观察组在对照组基础上口服硫酸羟氯喹片,0.4 g/次,2次/d。两组均治疗4周。观察两组患者的临床疗效,同时比较两组治疗前后的系统性红斑狼疮疾病活动指数（SLEDAI）评分、24 h尿蛋白、血肌酐、血清白蛋白和炎性因子水平。结果 治疗后,观察组的有效率为91.43%,明显高于对照组的69.44（P<0.05）。治疗后,两组的SLEDAI评分、血肌酐及24 h尿蛋白水平明显降低,血清白蛋白水平明显升高（P<0.05）;且观察组的SLEDAI评分、血肌酐及24 h尿蛋白水平明显低于对照组,血清白蛋白水平明显高于对照组（P<0.05）。治疗后,两组血清白细胞介素（IL）-4、IL-17和单核细胞趋化蛋白-4（MCP-4）水平明显降低（P<0.05）,且观察组的血清IL-4、IL-17和MCP-4水平明显低于对照组（P<0.05）。结论 羟氯喹联合利妥昔单抗能改善系统性红斑狼疮患者的免疫功能,降低血清IL-4、IL-17和MCP-4水平,具有一定的临床推广应用价值。     

Identification of immune-related biomarkers in adrenocortical carcinoma: Immune-related biomarkers for ACC

Emerging evidence has suggested that the tumor microenvironment, including immune infiltration, plays a crucially important role in tumor progression. Nevertheless, limited studies have been conducted on this topic in adrenocortical carcinoma. The present study aimed to explore the immune-related biomarkers in adrenocortical carcinoma. CIBERSORT was used to estimate the abundances of 22 kinds of immune cells, and univariable Cox analysis was performed to find survival-related immune cells with both Overall Survival (OS) and Progression-Free Interval (PFI). DESeq2 was applied to find differentially expressed genes between adrenocortical carcinoma and normal control samples; subsequently, weighted correlation network analysis and protein-protein interaction (PPI) network analysis were conducted to identify immune-related hub genes. xCell, TISIDB, and MsigDB were searched to validate the immune associations of hub genes. Eventually, univariable Cox and Kaplan–Meier analysis were used to assess the prognostic implications of the hub gene with the GEO database. Consequently, we identified two hub immune-related genes (ERN1, CEP55), GSEA revealed that both were mainly involved in tumor progression and immune response. ROC analysis indicated that ERN1 can accurately predict the 1-, 3-, and 5-year PFI, and CEP55 had the best performance for the prediction of both OS and PFI compared with other traits. Univariable Cox and Kaplan–Meier analysis showed that both genes have a significant effect on prognosis. Furthermore, both hub genes were validated in GEO datasets. The hub genes can provide better insights into tumor microenvironment and serve as potential biomarkers for immunotherapy in adrenocortical carcinoma.     

脑电图在肺性脑病早期诊断及评估预后中的应用效果

目的分析脑电图在肺性脑病早期诊断及评估预后中的应用效果。方法选取2017年1月-2018年8月四川省达州市中西医结合医院收治的肺性脑病患者86例,随机分为观察组和对照组各43例,观察组采用脑电图诊断,对照组采用常规诊断,比较2组患者诊断异常率及不同时间的异常率。结果观察组患者诊断总异常率为100.0%,高于对照组的81.4%(P<0.05);2组患者症状期24 h、症状消失7 d时异常率亦存在差异(P<0.05)。结论在肺性脑病的早期诊断中,脑电图可作为重要诊断依据,对于评估肺性脑病发展与预后具有一定参考作用,值得临床推广。     

Elevated antigen-specific Th2 type response is associated with the poor prognosis of hand,foot and mouth disease

The immunopathogenesis of severe hand, foot and mouth disease (HFMD) remains elusive. This study revealed that enterovirus 71 (EV71) epitope-specific CD4+ T cell responses of HFMD patients were skewed toward a Th2 cytokine profile. Patients that demonstrated higher levels of IL-4 expression in their CD4 T cells following antigen stimulation in vitro tended to have a more prolonged period of high fevers and a longer duration of illness. Thus, an increase of EV71 epitope-specific Th2 type response may portend the poor prognosis for some HFMD patients.     

Hydroxychloroquine-induced Phospholipidosis in a Case of SLE: The Wolf in Zebra Clothing

Abstract

A 30 year old lady patient of SLE on steroid and hydroxychloroquine therapy presented with lupus nephritis and later developed cardiac symptoms. Her renal biopsy revealed features of Class III lupus nephritis. Also seen was typical lamellated myelinoid material in the glomerulus. The alpha-galactosidase A activity was normal. The clinical morphological and biochemical findings were consistent with Lupus nephritis showing changes of hydroxychloroquine induced phopholipidosis. Electron microscopy along with careful clinical examination and follow up status was instrumental in the diagnosis of the latter.     

The Clinicopathologic Significance of Endothelial Tubuloreticular Inclusions in Glomerular Diseases

Abstract

Background: The presence of tubuloreticular inclusions (TRIs) in endothelial cells (ECs) always evokes suspicion of an association with underlying viral infections or autoimmune diseases. However, other underlying diseases can be associated with TRI expression. Since identification of the underlying disease is of primary consideration for management of glomerulonephritis (GN), it is important to clarify the clinical significance of TRI expression.

Methods: The authors studied 104 renal biopsy cases having TRI. They investigated their clinicopathological profiles and focused on potential connections with underlying diseases.

Results: Among 104 renal biopsy cases, 62 cases (59.6%) were associated with lupus nephritis (LN) and 20 cases (19.2%) were associated with a viral infection (hepatitis B virus (13), hepatits C virus (4), and human immunodeficiency virus (3)). Other underlying disease groups included membranous GN (MGN) (7), IgA nephropathy (7), Henoch-Schoenlein purpura (HSP) nephritis (2), and others (6). The incidence of TRIs in both LN and viral infections was significantly higher than for other diseases (p?<?0.0001). Among 7 MGN cases, 2 cases were diabetes, 1 case was associated with lung cancer, another case with antineutrophilic cytoplasmic antibody (ANCA), and the others showed no evidence of systemic disease. On immunofluorescence (IF) study, 2 MGN cases, 2 IgA nephropathy cases, and 1 HSP nephritis case showed C1q deposition, with no evidence of SLE.

Conclusions: TRIs were identified in MGN and other glomerular diseases, including IgA nephropathy and HSP nephritis. However, a diagnosis of LN should be considered because TRIs associated with a full-house IF pattern are usually found in LN.     

Derailed B cell homeostasis in patients with mixed connective tissue disease

Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder, characterized by the presence of antibodies to U1-RNP protein. We aimed to determine phenotypic abnormalities of peripheral B cell subsets in MCTD. Blood samples were obtained from 46 MCTD patients, and 20 controls. Using anti-CD19, anti-CD27, anti-IgD and anti-CD38 monoclonal antibodies, the following B cell subsets were identified by flow cytometry: (1) transitional B cells (CD19 + CD27-IgD + CD38^high); (2) naive B cells (CD19 + CD27-IgD + CD38^low); (3) non-switched memory B cells (CD19 + CD27 + IgD+); (4) switched memory B cells (CD19 + CD27 + IgD-); (5) double negative (DN) memory B cells (CD19 + CD27-IgD-) and (6) plasma cells (CD19 + CD27^highIgD-). The proportion of transitional B cells, naive B cells and DN B lymphocytes was higher in MCTD than in controls. The DN B cells were positive for CD95 surface marker. This memory B cells population showed a close correlation with disease activity. The number of plasma cells was also increased, and there was an association between the number of plasma cells and the anti-U1RNP levels. Cyclophosphamide, methotrexate, and corticosteroid treatment decreased the number of DN and CD27^high B cells. In conclusion, several abnormalities were found in the peripheral B-cell subsets in MCTD, which reinforces the role of derailed humoral autoimmune processes in the pathogenesis.