Coexistence of Subcutaneous Panniculitis-Like T-Cell Lymphoma and Dermatomyositis in a 12-Year-Old Boy.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is an extremely rare, indolent skin malignancy that can be difficult to distinguish from autoimmune disease-associated panniculitides. Here, we describe a 12-year-old boy who was diagnosed at age 7 years with dermatomyositis with classical manifestations, including poikiloderma, Gottron's sign, and symmetric muscle weakness. Recently, the boy presented multiple subcutaneous nodules and fever. Histopathological examination and immunohistochemical staining revealed coexistence of SPTL. To our knowledge, this is the first case of dermatomyositis accompanied with SPTL. This case alert clinical physicians of the possibility of SPTL should be considered when a patient with dermatomyositis has new lesions presenting as nodules and unknown fever.

Genetic and phenotypic diversities of nevus spilus phenotypes: Case series and a proposed diagnostic algorithm.

Nevus spilus (NS) is composed of multiple types that characterized by a congenital hyperpigmented patch within variable even superimposed lesions originating from melanocytic lineage cells. The molecular mechanism and classification of diverse NS phenotypes remain unclear. Five children with a phenotype of NS were genotyped by the panel based on next-generation sequencing in this study. DNA from biopsies, blood samples and hair follicle were sequenced to confirm the presence of a somatic mutation. Sequencing results indicated somatic mutation in the gene of NRAS or HRAS in all biopsies from the nevi, and the pathogenic variants were not detected in the samples of blood and hair follicle. This study successfully identified the somatic mutation in five unrelated children with diverse NS phenotypes. Moreover, it provided typical images and differential diagnoses between variable NS phenotypes in clinical, pathological, and genetic features, and first proposed a clinical diagnostic algorithm that contributed to simplifying and optimizing the diagnoses and management of these overlapped diseases.

Constructed a self-powered sensing platform based on nitrogen-doped hollow carbon nanospheres for ultra-sensitive detection and real-time tracking of double markers.

Acute myocardial infarction (AMI) is acute necrosis of a portion of the myocardium caused by myocardial ischemia, which seriously threatens people's health and life safety. Its early diagnosis is a difficult problem in clinical medicine. Research has found that the abnormal expression of microRNA-199a (miR-199a) and microRNA-499 (miR-499) was closely related to AMI disease. In this work, we took advantage of the structural advantages of nitrogen-doped hollow carbon nanospheres (N-HCNSs) to design an ultra-sensitive, portable real-time monitoring visual self-powered biosensor system, which based on dual-target miRNAs triggered catalytic hairpin assembly (CHA) for sensitive detection of miR-199a and miR-499. In addition, the capacitor and the smartphone are introduced into the system to realize the secondary improvement of system sensitivity and portable real-time visual monitoring. Under optimized conditions, in the linear range of 0.1-100000 aM, the detection limits of miR-199a and miR-499 are 0.031 and 0.027 aM, respectively. At the same time, the ultra-sensitive detection of miRNAs is realized in the serum sample, and the recovery rate of miR-199a and miR-499 are 98.0-106.0% (RSD: 0.6-8.1%) and 94.0-109.7% (RSD: 1.8-7.7%), respectively. The method is simple, sensitive and can be used for real-time tracking and portable monitoring of related diseases.

Lidocaine alleviates inflammation and pruritus in atopic dermatitis by blocking different population of sensory neurons.

BACKGROUND AND PURPOSE: Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro-immune communication. Neuronal mechanism-based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro-immune mechanism. EXPERIMENTAL APPROACH: Pharmacological intervention, immunofluorescence, RNA-sequencing, genetic modification and immunoassay were performed to dissect the neuro-immune basis of itch and inflammation in atopic dermatitis-like mouse model and in patients. KEY RESULTS: Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)-induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX-314, a charged NaV blocker that enters through pathologically activated large-pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV 1.8-expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1-positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model. CONCLUSION AND IMPLICATIONS: NaV 1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti-inflammatory and anti-pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis.

Centrifugal lipodystrophy on a spectrum with lupus erythematosus panniculitis in children and efficacy and safety of hydroxychloroquine: A clinicopathological study.

This study aimed to investigate the relationship between centrifugal lipodystrophy (CLD) and lupus erythematosus panniculitis (LEP), and the efficacy and safety of hydroxychloroquine (HCQ) for treating CLD in children. A total of 29 cases clinically diagnosed as CLD (n = 24) and CLD/LEP overlap (n = 5) were enrolled and all were confirmed by skin biopsies of CLD and LEP. The clinicopathological findings, clinical outcomes, and prognosis with the treatment of HCQ between CLD and LEP were compared. All 29 cases (male: female = 1:1.6; median age at onset: 3 years) had cutaneous lesions of centrifugally expanding lipoatrophy, of which five cases overlapped with LEP lesions presented as erythematous indurated plaque (n = 2), subcutaneous nodules (n = 2) and alopecia along Blaschko's lines (n = 1). Antinuclear antibodies were found in six (25.0%) CLD and two (40.0%) overlapped patients (p = 0.597). Histopathologically, of the 24 cases of CLD, 14 (58.5%) exhibited subcutis loss or mild lobular inflammation. Ten (41.7%) cases displayed lobular panniculitis with moderate to dense lymphohistiocytic infiltrate and plasma cells, similar to the five cases of overlap. Small clusters of CD123 positive plasmacytoid dendritic cells were found in 62.5% (5/8) of CLD and 66.7% (2/3) of overlap cases (p > 0.99). HCQ (5 mg/kg/d) treatment showed improvement in 91.3% (21/23) of CLD and all overlap cases, including four cases unresponsive to previous oral glucocorticosteroid treatment. Our findings suggested that CLD and LEP represent a spectrum within the same disease. HCQ (5 mg/kg/d) was effective and safe for treating CLD (age >1.5 years), and early treatment and a regular long-term follow-up are essential.

Progress in Antibacterial Hydrogel Dressing.

Antibacterial hydrogel has excellent antibacterial property and good biocompatibility, water absorption and water retention, swelling, high oxygen permeability, etc.; therefore, it widely applied in biomedicine, intelligent textiles, cosmetics, and other fields, especially for medical dressing. As a wound dressing, the antibacterial hydrogel has the characteristics of absorbing wound liquid, controlling drug release, being non-toxic, being without side effects, and not causing secondary injury to the wound. Its preparation method is simple, and can crosslink via covalent or non-covalent bond, such as γ-radiation croFsslinking, free radical polymerization, graft copolymerization, etc. The raw materials are easy to obtain; usually these include chondroitin sulfate, sodium alginate, polyvinyl alcohol, etc., with different raw materials being used for different antibacterial modes. According to the hydrogel matrix and antibacterial mode, the preparation method, performance, antibacterial mechanism, and classification of antibacterial hydrogels are summarized in this paper, and the future development direction of the antibacterial hydrogel as wound dressing is proposed.

Perinatal outcomes in pregnancies complicated by type 1 diabetes mellitus.

The aim of this study was to explore the risk of perinatal outcomes in pre-gestational type 1 diabetes mellitus (T1DM) compared to gestational diabetes mellitus (GDM) and pregnancy without diabetes and to examine the association of glycemic level of third-trimester gestation with perinatal outcomes in T1DM. We included 69 pre-gestational T1DM, 1398 cases of GDM, and 1304 control pregnancies and collected data regarding demographics, obstetric, and perinatal outcomes from the hospital discharge database. Relative to the pregnancies without diabetes, women with T1DM encountered increasing risk of polyhydramnios, preterm delivery, and cesarean section. These adverse outcomes were also common in GDM, although with relatively lower adjusted ORs. The weights of babies delivered by women with T1DM were more intend to be large for gestational age, as well as to be less than 2.5 kg relative to those without diabetes. Poorly controlled hemoglobin A1c in late pregnancy was significantly associated with an increased risk of preterm birth in T1DM (adjusted odds ratio 2.01, 95%confidence interval 1.1-3.6). Women with T1DM have considerably increased risks of adverse perinatal outcomes, which appear more prevalent than the perinatal outcomes in women with GDM. Thus, a specific routine is required for pregnancy in T1DM to improve the glycemic control and obstetric care.

Influence of fetal sex on perinatal outcomes in women with gestational diabetes mellitus.

BACKGROUND: Fetal sex has recently been considered to be related to maternal glucose homeostasis and perinatal outcomes during pregnancy. Here, we investigated the effects of fetal sex on the perinatal outcomes of pregnancies with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM). METHODS: This was a retrospective cohort study of 1292 women with NGT and 1155 women with GDM. Pregnant women were divided into four groups according to the maternal glucose level and fetal sex. Logistic regression was used to evaluate the risks for adverse perinatal outcomes among NGT-males, NGT-females, GDM-males and GDM-females. RESULTS: NGT-males had higher risks for macrosomia and large for gestational age (LGA) than NGT-females with an odds ratio (OR) of 1.9 (95% CI 1.2-2.9). Additionally, GDM-males had higher risks for neonatal infection (OR, 3.0; 95% CI, 1.3-6.9), acute respiratory disorders (OR, 3.9; 95% CI, 1.1-13.7) and abnormal neonatal central nervous system development (OR, 3.1; 95% CI, 1.1-8.4) than GDM-females. Furthermore, there was a significantly higher risk for newborn infection (OR, 8.5; 95% CI, 1.1-66.8) in the GDM-male group than in the GDM-female group with a glycosylated hemoglobin A1c (HbA1c) level ≥5.5% in the late trimester of pregnancy, which was not observed with an HbA1c level of <5.5%. CONCLUSIONS: Male fetuses have worse perinatal outcomes than female fetuses, and the difference is more pronounced in GDM pregnancies. More postpartum care is needed for male fetuses, especially in GDM pregnancies with substandard glycemic control.

THE ASSOCIATION OF GESTATIONAL WEIGHT GAIN AND ADVERSE PREGNANCY OUTCOMES IN WOMEN WITH GESTATIONAL DIABETES MELLITUS.

Objective: To explore the association of excessive gestational weight gain (GWG) defined by the Institute of Medicine (IOM) targets and adverse perinatal outcomes in gestational diabetes mellitus (GDM) pregnancies, and whether a modified target might be related to a lower rate of adverse perinatal outcomes for GDM. Methods: This retrospective cohort study involved 1,138 women of normal glucose tolerance (NGT) and 1,200 women with GDM. Based on the IOM target, pregnancies were classified to appropriate GWG (aGWG), inadequate GWG, and excessive GWG (eGWG). Modified GWG targets included: upper limit of IOM target minus 1 kg (IOM-1) or 2 kg (IOM-2), both upper and lower targets minus 1 kg (IOM-1-1) or 2 kg (IOM-2-2). Results: The proportions of women achieving eGWG were 26.3% in NGT and 31.2% in GDM (P = .036); in comparison, for aGWG NGT, the risks of large for gestational age (LGA) were significantly higher in eGWG NGT (adjusted odds ratio [OR] 1.47; 95% confidence interval [CI] 1.02 to 2.13), aGWG GDM (adjusted OR 1.42; 95% CI 1.03 to 1.95), and eGWG GDM (adjusted OR 2.70; 95% CI 1.92 to 3.70). GDM pregnancies gaining aGWG based on the modified GWG targets (IOM-2, IOM-1-1, and IOM-2-2) had a lower prevalence of LGA and macrosomia delivery than that for similar pregnancies using the original IOM target (all P<.05). Conclusion: For aGWG GDM according to the IOM target, adhering to a more stringent weight control was associated with decreased adverse outcomes. A tighter IOM target might help to reduce the prevalence of adverse pregnancy outcomes. Abbreviations: aGWG = appropriate gestational weight gain; BG = blood glucose; BMI = body mass index; CI = confidence interval; eGWG = excessive gestational weight gain; GDM = gestational diabetes mellitus; GW = gestational weeks; GWG = gestational weight gain; HbA1c = hemoglobin A1c; iGWG = inadequate gestational weight gain; IOM = Institute of Medicine; LGA = large for gestational age; NGT = normal glucose tolerance; NICU = neonatal intensive care unit; OGTT = oral glucose tolerance test; OR = odds ratio; PARp = partial population attributable risks; SGA = small for gestational age.

Efficacy and Safety of Basal Analog Regimens in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: This study compared basal analog (BA: glargine U100/mL and detemir) and premix (PM: human, lispro and aspart biphasic) insulin regimens in terms of their efficacy and safety in type 2 diabetes mellitus patients. METHODS: Searches of MEDLINE, Embase, and CENTRAL identified primary randomized controlled trials (RCTs) ≥ 12 weeks in duration that compared BA or PM insulin regimens in adults with T2DM, with ≥ 30 patients per arm. A systematic literature review and a pairwise meta-analysis were performed using a random effects model adjusted for between-study variability. Analyses were conducted based on frequency of bolus insulin and PM injections, PM ratio and type, BA type, race, follow-up period, and baseline glycosylated hemoglobin (HbA1c). RESULTS: Twenty-two primary RCTs with 9691 patients were included. The BA and PM regimens yielded similar changes in HbA1c and postprandial glucose levels, with a statistically significant reduction in fasting glucose [mean difference (MD) - 0.61 mmol/L (95% confidence interval (CI) - 0.90, - 0.32), I2 = 89.6%]. The BA regimens showed significantly reduced rates of total hypoglycemia [odds ratio (OR) 0.77 (95% CI 0.64, 0.92), I2 = 65.3%] and changes in body weight [MD - 0.48 kg (95% CI - 0.86, - 0.11), I2 = 75.7%] compared to PM regimens. Stratification by PM type and dosing ratio demonstrated statistically significant reductions in HbA1c favoring BA compared to human [MD - 0.39% (95% CI - 0.60, - 0.18), I2 = 61.8%] or 50/50-ratio [MD - 0.22% (95% CI - 0.40, - 0.04), I2 = 0.0%] PM regimens. Other subgroup analyses found no difference in HbA1c change between the BA and PM regimens. CONCLUSION: When compared to PM regimens, BA regimens yielded similar efficacies and better safety profiles in patients with type 2 diabetes mellitus. FUNDING: Sanofi (Shanghai, China).

Risk of beta-cell autoimmunity presence for progression to type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND: Islet autoantibodies have been applied for diagnosis of type 1 diabetes mellitus (T1DM) at an asymptomatic stage in individuals with high-risk genotypes. Evidence is insufficient to support a broad application of islet autoantibody screening for T1DM in clinical practice. The aim of this study was to assess the evidence of an association between islet autoantibodies and the development of T1DM in a pooled population of both genetically at-risk individuals and general people without definite genetic background. METHODS: A comprehensive literature search was performed of Pubmed, Web of knowledge and Cochrane library. Prospective cohort studies evaluating the role of islet autoantibodies in prediction of T1DM progression were included. Risk ratios (RRs) were calculated and pooled to arrive at summary estimate. χ2 and I2-values were calculated as measures of heterogeneity and subgroup analyses were performed to explore sources of heterogeneity. RESULTS: Twenty-one studies matched the inclusion criteria. A total of 71,482 nondiabetic participants who were genetically at-risk individuals or from the general population were included, and 926 cases of T1DM were reported during a median follow-up of 7 years. Compared with people free of islet autoantibody, those positive for any type or number of islet autoantibody showed a significantly increased risk of developing T1DM (RR 150.42 [95% CI 87.34, 259.04]). Moreover, the risk for people with multiple islet autoantibodies was 8.59-fold higher than the risk for those with single islet autoantibody, although a moderate heterogeneity existed between studies. The subgroup analysis further revealed that RRs of multiple islet autoantibodies in at-risk population and general population were 7.17 and 13.72, respectively. CONCLUSION: This study established the association between the seroconversion of islet autoantibodies and T1DM progression in nondiabetic people with or without definite genetic susceptibility, providing further evidence for an extensive application in routine clinical practice to identify individuals at risk of T1DM.

Generalized eruptive keratoacanthoma with vitiligo followed by the development of prurigo nodularis: A case report and published work review.

Herein, we report a unique case of generalized eruptive keratoacanthoma (GEKA) in a 47-year-old Chinese man presenting with extensive pruritic papules and nodules accompanied by oral lesions. He also had a 2-year history of vitiligo and long-term experience of working outdoors. Biopsies were consistent with keratoacanthoma . Interestingly, prurigo nodularis (PN) was found in histopathology at 1-year follow up. To our knowledge, this is the first report describing a case of GEKA with oral lesions complicated with vitiligo and developed with PN.

Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves ß-cell Function in Patients and Non-obese Mice with Severe Diabetes.

Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for type 1 diabetes (T1D). However, little is known on whether MSC transplantation can benefit T1D patients with ketoacidosis and its potential actions. Here, we show that infusion with bone marrow MSCs preserves ß-cell function in some T1D patients with ketoacidosis by decreasing exogenous insulin requirement and increasing plasma C-peptide levels up to 1-2 years. MSC transplantation increased plasma and islet insulin contents in non-obese diabetic (NOD) mice with severe diabetes. In comparison with severe diabetes controls, MSC infusion reduced insulitis, decreased pancreatic TNF-α, and increased IL-10 and TGF-ß1 expression in NOD mice. MSC infusion increased the percentages of splenic Tregs and levels of plasma IL-4, IL-10 and TGF-ß1, but reduced the percentages of splenic CD8+ T and levels of plasma IFN-γ, TNF-α and IL-17A in NOD mice. Finally, infused MSCs predominantly accumulated in pancreatic tissues at 28 days post infusion. The effects of MSCs on preserving ß-cell function and modulating inflammation tended to be dose-dependent and multiple doses of MSCs held longer effects in NOD mice. Hence, MSC transplantation preserved ß-cell function in T1D patients and NOD mice with severe diabetes by enhancing Treg responses.

Liraglutide Enhances the Efficacy of Human Mesenchymal Stem Cells in Preserving Islet ß-cell Function in Severe Non-obese Diabetic Mice.

Glucagon-like peptide 1 (GLP-1) can promote islet ß-cell replication and function, and mesenchymal stem cells (MSCs) can inhibit T cell autoimmunity. This study aimed at testing the dynamic distribution of infused human MSCs and therapeutic effect of combined MSCs and Liraglutide, a long-acting GLP-1 analogue, on preserving ß-cell function in severe non-obese diabetic (NOD) mice. We found that infused MSCs accumulated in the pancreas at 4 weeks post infusion, which was not affected by Liraglutide treatment. Liraglutide significantly enhanced the function of MSCs to preserve islet ß-cells by reducing glucose level at 30 minutes post glucose challenge and increasing the contents and secretion of insulin by islet ß-cells in severe diabetic NOD mice. Infusion with MSCs significantly reduced insulitis scores, but increased the frequency of splenic Tregs, accompanied by reducing the levels of plasma IFN-γ and TNF-α and elevating the levels of plasma IL-10 and transforming growth factor-ß1 (TGF-ß1) in NOD mice. Although Liraglutide mitigated MSC-mediated changes in the frequency of Tregs and the levels of plasma IL-10, Liraglutide significantly increased the levels of plasma TGF-ß1 in severe diabetic NOD mice. Therefore, our findings suggest that Liraglutide may enhance the therapeutic efficacy of MSCs in treatment of severe type 1 diabetes.

Comparative efficacy of anti-diabetic agents on nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized and non-randomized studies.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in patients with type 2 diabetes mellitus (T2DM). In this study, we sought to provide a comprehensive assessment regarding the effects of anti-diabetic agents on NAFLD in patients with T2DM. METHODS: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) with different anti-diabetic agents in T2DM. Observational trials were also recruited to expand our population. Hepatic fat content and liver histology were evaluated as primary outcomes. Pooled estimates were calculated using a fixed effect model. RESULTS: One thousand one hundred ninety-six participants in 19 RCTs and 14 non-randomized studies were included. Evidence from RCTs and observational studies suggested that greater hepatic fat content reduction and improved liver histology were seen in thiazolidinediones for 12-72 weeks; glucagon-like peptide-1 receptor agonists had beneficial effects on hepatic fat content after 26-50 weeks intervention, and insulin/metformin combination with 3-7 months improved hepatic fat content. Initiating metformin or dapagliflozin showed no benefit on hepatic fat content or liver histology in 16-48 weeks. Besides, nateglinide for 18 months was reported in a small sample-size RCT to improve hepatic fat content and liver histology. Sitagliptin therapy of 1 year also provided benefit on nonalcoholic steatohepatitis score in an observational study. CONCLUSIONS: For T2DM with NAFLD, administrating thiazolidinediones and glucagon-like peptide-1 receptor agonists seems to provide more identified advances in attenuating hepatic fat content. Further RCTs are warranted to assess the efficacy of various hypoglycemic agents on clinical outcomes associated with NAFLD in T2DM. Copyright © 2015 John Wiley & Sons, Ltd.