Fulminant Type 1 Diabetes Mellitus Associated With Drug Hypersensitivity and Epstein-Barr Virus Infection: A Case Report.

Background: Fulminant type 1 diabetes mellitus (FT1DM) is a new subtype of type 1 diabetes, first proposed by Japanese scholars in 2000. Herein, the functions of the islets are rapidly destroyed. Its pathogenesis is related to viral infection. Most people have been infected with Epstein-Barr virus (EBV), and many people have also suffered from drug hypersensitivity, however, few cases of FT1DM which were caused by both of the two conditions have been reported. Thus, below, we describe one such valuable case. Case Summary: The plasma glucose levels of a 73-year-old man diagnosed with drug-induced dermatitis showed a sudden increase (42 mmol/L) during methylprednisolone therapy. The urine ketone test was positive. The glycated hemoglobin level was 7%, endogenous insulin secretion decreased significantly, and the islet-related autoantibodies were negative. The patient was diagnosed with FT1DM. The lymphocyte EBV-DNA showed high copies numbers. The general condition of the patient improved after symptomatic treatment with insulin. However, the systemic allergic reaction aggravated after the use of iodinated contrast agents, prednisone, and thymic pentapeptide. The re-test for EBV-DNA showed significantly high relative levels, thus indicating the presence of EBV infection. We think that drug hypersensitivity and EBV infection together led to FT1DM in this case. After an indication for multiple daily insulin therapy, the patient's blood glucose was quickly controlled and he was discharged on the 38th-day post-admission. Conclusion: FT1DM is a rare case, however, drug hypersensitivity and EBV infection are not rare in the population. This is a rare case of FT1DM caused by drug hypersensitivity reaction and EBV infection. Through this case report, we emphasize the importance of the relationship between drug hypersensitivity, EBV infection and FT1DM and vigilance for the occurrence of FT1DM among hypersensitive individuals in clinical practice.

Comparative Study of Damage Detection Methods Based on Long-Gauge FBG for Highway Bridges.

Damage detection of highway bridges is a significant part of structural heath monitoring. Conventional accelerometers or strain gauges utilized for damage detection have many shortcomings, especially their monitoring gauge length being too short, which would result in poor damage detection results. Under this circumstance, long-gauge FBG sensors as a novel optical sensor were developed to measure the macro-strain response of the structure. Based on this sensor, many derived damage detection methods were proposed. These methods exhibit various characteristics and have not been systematically compared. As a result, it is difficult to evaluate the state of the art and also leads to confusion for users to select. Therefore, a strict comparative study on three representative methods using long-gauge FBG was carried out. First, these methods' theoretical backgrounds and formats were reformulated and unified for better comparison. Then, based on validated vehicle-bridge coupling simulation, these methods' performances were tested through a series of parametric studies including various damage scenarios, vehicle types, speeds, road roughness and noise levels. The precision and reliability of three methods have been thoroughly studied and compared.

The ratio of superoxide dismutase to standard deviation of erythrocyte distribution width as a predictor of systemic lupus erythematosus.

BACKGROUND: To explore the clinical value of the serum superoxide dismutase-to-standard deviation of erythrocyte distribution width ratio (SRSR) in systemic lupus erythematosus (SLE). METHODS: A total of 222 SLE patients from the Rheumatology and Immunology Department in the Second Affiliated Hospital of Chongqing Medical University from January 2017 to April 2019 were collected as the experimental group, and a total of 202 healthy physical examiners were extracted as the control group. Neutrophil-to-lymphocyte ratio (NLR), superoxide dismutase-to-standard deviation of erythrocyte distribution width ratio (SRSR), and platelet-to-lymphocyte ratio (PLR) were calculated from the collected data and then compared the level of the above three indexes between the two groups. In addition, we analyzed the association between SRSR and clinically relevant indicators. RESULTS: We found that the SRSR of SLE patients was significantly lower than healthy control group, by analyzing the receiver operating characteristic (ROC) curve; it revealed that the SRSR had higher specificity and sensitivity than either superoxide dismutase (SOD) or standard deviation of erythrocyte distribution width (RDW-SD) alone. The area under the curve (AUC) for SRSR was significantly larger than either SOD or RDW-SD alone, and the AUC for SRSR was also larger than NLR and PLR. And it was found that SRSR was independently correlated with SLE disease activity through multiple linear regression analysis. CONCLUSION: SRSR is a useful biomarker for the diagnosis of SLE, and it is of great significance in the clinical application.

Association between the insulin-like growth factor 1 gene rs2195239 and rs2162679 polymorphisms and cancer risk: a meta-analysis.

BACKGROUND: Many epidemiological studies have suggested that insulin-like growth factor1 (IGF1) gene single-nucleotide polymorphisms (SNPs) may be associated with cancer risk. Among several commonly studied polymorphisms in IGF1 gene, rs2195239 and rs2162679 attracted many attentions. So we perform a meta-analysis to determine potential associations between IGF1 rs2195239 and rs2162679 polymorphisms and cancer risk. METHODS: We retrieved relevant articles from the PubMed, Embase, and Web of Science databases up to April 30, 2018. Ultimately, thirteen studies were included in the present meta-analysis, which involved 12,515 cases and 19,651 controls. The odd ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the strength of the associations. RESULTS: rs2195239 reduces the overall cancer risk in homozygote model, as well as reducing cancer risk in Asian populations in allele, homozygote, and recessive models. No significant relationship was found between rs2195239 and breast or pancreatic cancer risk. rs2162679 reduces the overall cancer risk in allele, homozygote, dominant, and recessive models, as well as reducing cancer risk in Asian populations in allele, homozygote, and recessive models. CONCLUSIONS: IGF1 rs2195239 and rs2162679 were associated with overall cancer risk based on present studies.

The association between BRCA1 gene polymorphism and cancer risk: a meta-analysis.

Many studies have reported that BRCA1 polymorphisms are associated with cancer risk, but the results remain controversial. The purpose of this meta-analysis is to evaluate the relationship between BRCA1 polymorphisms (rs799917, rs1799950, rs1799966, or rs16941) and cancer risk. Relevant studies were identified via a systematic search of the PubMed, Embase, and Web of Science databases up to July 31, 2017. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to examine the strength of the associations. Thirty-five studies published in 19 publications involving 28,094 cases and 50,657 controls were included in this meta-analysis. There was no obvious association between rs799917, rs1799966, or rs16941 polymorphisms and overall cancer risk in any genetic models. However, subgroup analyses revealed that the rs799917 polymorphism could decrease the risk of cervical cancer, esophageal squamous cell carcinoma (ESCC), gastric cancer, and non-Hodgkin lymphoma (NHL) among Asian populations in one or more genetic models and that rs16941 could increase overall cancer risk among Caucasian populations in the homozygote and recessive models. Our meta-analysis also indicated that rs1799950 could decrease the breast cancer (BC) risk among Caucasian populations in the homozygote and recessive models. In summary, our results suggest that BRCA1 polymorphisms may play an important role in the etiology of cancer. However, due to the limited number of studies, these findings should be confirmed by new studies with larger sample sizes that address various types of cancer.

Effect of MTHFR A1298C and MTRR A66G Genetic Mutations on Homocysteine Levels in the Chinese Population: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: The Chinese population typically has inadequate folate intake and no mandatory folic acid fortification. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are the two key regulatory enzymes in the folate/homocysteine (Hcy) metabolism. Hcy has been implicated in the pathogenesis of cardiovascular disease. We conducted a meta-analysis to assess whether the MTHFR gene A1298C and the MTRR gene A66G polymorphisms affect Hcy levels in the Chinese population. METHODS: This analysis included 13 studies with Hcy levels reported as one of the study measurements. Summary estimates of weighted mean differences and 95% confidence intervals (CIs) were obtained using random-effect models. RESULTS: Overall, there were no significant differences in Hcy concentrations between participants with the MTHFR 1298 CC (12 trials, n = 129), AA (n = 2166; ß, -0.51 µmol/L; 95%CI: -2.14, 1.11; P = 0.53), or AC genotype (n = 958; ß, 0.55 µmol/L; 95%CI: -0.72, 1.82; P = 0.40). Consistently, compared to those with the MTRR 66 GG genotype (6 trials, n = 156), similar Hcy concentrations were found in participants with the AA (n = 832; ß, -0.43 µmol/L; 95%CI: -1.04, 0.17; P = 0.16) or AG (n =743; ß, -0.57 µmol/L; 95%CI: -1.46, 0.31; P = 0.21) genotype. Similar results were observed for the dominant and recessive models. CONCLUSIONS: Neither the MTHFR A1298C polymorphism nor the MTRR A66G polymorphism affects Hcy levels in the Chinese population.

Anti-neutrophil cytoplasmic antibodies in cholesterol embolism: A case report and literature review.

Cholesterol embolism is a multisystemic disorder with clinical manifestations that resemble vasculitis. Anti-neutrophil cytoplasmic antibodies (ANCA) are a defining feature of ANCA-associated vasculitis, and the presence of ANCA in cholesterol embolism complicates its differential diagnosis and treatment. At present, the role of ANCA in cholesterol embolism remains unclear and no effective treatment is currently available. The present study reports the case of an Asian male who presented with spontaneous cholesterol embolism with proteinase 3 (PR3)-specific ANCA, subacute interstitial nephritis and late-developing skin lesions. The 69-year-old patient was admitted to The First Affiliated Hospital of Xiamen University (Xiamen, China) complaining of chest tightness, fatigue, progressive renal failure and refractory hypertension. In addition, transient eosinophilia was detected. Following immunosuppressive therapy with steroids and cyclophosphamide for 6 months, hemodialysis treatment was initiated. Skin lesions appeared at >1 month following hemodialysis initiation; however, they were gradually improved following treatment with atorvastatin and anti-platelet aggregation therapy for 5 months. The patient was maintained on hemodialysis for ~2 years and exhibited general good health at the most recent follow-up. In addition, 11 cases of cholesterol embolism associated with ANCA reported in the literature were discussed in the present study.

[Tripartite-motif protein 25 and pyruvate kinase M2 protein expression in non-small cell lung cancer].

OBJECTIVE: To investigate the expression of tripartite-motif protein 25 (TRIM25) and pyruvate kinase M2 (PKM2) protein in non-small cell lung cancer (NSCLC) and explore their role in the occurrence and progression of NSCLC. METHODS: The expressions of TRIM25 and PKM2 protein were detected in 60 NSCLC specimens and 20 adjacent normal lung tissue (>5 cm from the lesions) with immunofluorescence histochemical method and in 10 fresh specimens of NSCLC with Western blotting. The results were analyzed in relation with the clinicopathological features of the patients. RESULTS: The positivity rates of TRIM25 expression was 45% in the 60 lung carcinoma specimens, significantly higher than that in the 20 normal lung tissues (10%, P=0.005). TRIM25 protein was expressed in 28.6% of lung adenocarcinoma tissues and in 59.4% of squamous carcinoma tissues (P=0.017). TRIM25 protein expression was positively correlated with the TNM stages and lymph node metastasis of NSCLC (P<0.05). The expressions of PKM2 protein in 60 cases of lung carcinoma was 73.3%,while in 20 cases of normal lung tissues the expressions was 30%(P=0.001). The positivity rates of PKM2 expression differed significantly between lung adenocarcinoma and squamous carcinoma (57.1% vs 87.5%, P=0.008). An inverse correlation was noted between TRIM25 and PKM2 expressions (P=0.026). CONCLUSION: TRIM25 and PKM2 protein may participate in the occurrence and progression of NSCLC, and their expressions are inversely correlated.

Discriminative Hierarchical K-Means Tree for Large-Scale Image Classification.

A key challenge in large-scale image classification is how to achieve efficiency in terms of both computation and memory without compromising classification accuracy. The learning-based classifiers achieve the state-of-the-art accuracies, but have been criticized for the computational complexity that grows linearly with the number of classes. The nonparametric nearest neighbor (NN)-based classifiers naturally handle large numbers of categories, but incur prohibitively expensive computation and memory costs. In this brief, we present a novel classification scheme, i.e., discriminative hierarchical K-means tree (D-HKTree), which combines the advantages of both learning-based and NN-based classifiers. The complexity of the D-HKTree only grows sublinearly with the number of categories, which is much better than the recent hierarchical support vector machines-based methods. The memory requirement is the order of magnitude less than the recent Naïve Bayesian NN-based approaches. The proposed D-HKTree classification scheme is evaluated on several challenging benchmark databases and achieves the state-of-the-art accuracies, while with significantly lower computation cost and memory requirement.

Proteomic analysis of ubiquitination-associated proteins in a cisplatin-resistant human lung adenocarcinoma cell line.

The objective of this study was to screen for ubiquitination-associated proteins involved in cisplatin resistance in a human lung adenocarcinoma cell strain using a comparative proteomic strategy. We employed 1D SDS-PAGE to separate ubiquitinated proteins isolated and enriched from A549 and A549/CDDP lysates via affinity chromatography. The differentially expressed bands between 45-85 kDa were subsequently hydrolyzed by trypsin and subjected to HPLC-CHIP-MS/MS analysis. Of the 11 proteins identified, 7 proteins were monoubiquitinated or polyubiquitinated substrates and 4 proteins were E3 ubiquitin ligase-associated proteins. The results of western blotting and confocal laser scanning microscopy indicated that the expression levels of the E3 ubiquitin ligases RNF6, LRSAM1 and TRIM25 in A549 cells were significantly lower than those in the A549/CDDP cell line. The expression levels of the above three ubiquitin ligases in both cell lines were significantly decreased upon treatment with cis-diamminedichloroplatinum (CDDP), and the expression in the A549/CDDP cell after the treatment with CDDP decreased to a lesser extent. The expression of the substrate PKM2 in the A549 cell was higher than that in the A549/CDDP cells. Moreover, the expression of PKM2 increased in the A549 cell line and decreased in the A549/CDDP cell line upon CDDP treatment. This study suggests that drug resistance is closely correlated with changes in the ubiquitination process at the protein level in a human lung adenocarcinoma cell line.

Asymmetric total synthesis of (-)-saframycin A from L-tyrosine.

The asymmetric total synthesis of (-)-saframycin A, a natural antitumor product of the tetrahydroisoquinoline antitumor antibiotics family, has been accomplished by employing L-tyrosine as the starting chiral building block in 24 steps for the longest linear sequence in an overall yield of 9.7%. The key steps in the synthesis involve stereoselective intermolecular and intramolecular Pictet-Spengler reactions, which induced the correct stereochemistry at C-1 and C-11, respectively. The selective protection-deprotection protocol of an amino group in the two-step transformation from intermediate 10 to 12 and a hydroxyl group in the first two steps resulted in both high selectivity and efficiency of the synthetic route.

Synthesis and antitumor activity of simplified ecteinascidin-saframycin analogs.

Two series of simplified analogs of the ecteinascidin-saframycin type alkaloids were prepared from l-DOPA. Their in vitro antitumor activity was tested against three human cancer cell lines (HCT-8 colon carcinoma, Bel-7402 liver carcinoma, and BGC-823 gastric carcinoma). Among these compounds, the ester analogs have stronger activities than those of amide analogs in general. Among them, 1-naphthalene carboxylate ester analog 31 has the strongest activity against BGC-823 cells.

[Progress in the studies on antitumor natural product ecteinascidin-743].

The alkaloid ecteinascidin-743, isolated from the marine tunicate Ecteinascidia turbinata, binds to DNA and induces cytotoxic effects in several tumors. The drug is being codeveloped by Pharma Mar and Ortho Biotech. In May 2001 and October 2003, it was granted orphan drug status by the European Commission for soft tissue sarcoma and ovarian cancer, respectively. This paper reviews its research progress, including chemical synthesis, in vitro studies and mechanism of action, antitumor activity in vivo, toxicity, pharmacokinetics, and clinical studies.