Community-associated methicillin-resistant Staphylococcus aureus infection of diabetic foot ulcers in an eastern diabetic foot center in a tertiary hospital in China: a retrospective study.

BACKGROUND: Diabetic foot concerns are a major public health problem. Methicillin-resistant Staphylococcus aureus (MRSA) plays a significant role in diabetic foot ulcers. Community-associated MRSA has become notorious for skin and skin soft tissue infections over the last two decades. This study investigated MRSA infection in diabetic foot patients at a tertiary hospital, focusing on the epidemiology and characteristics of community-associated MRSA. METHODS: A total of 149 patients with diabetic foot infection whose culture results indicated Staphylococcus aureus as the source were selected. Epidemiological investigations, clinical characteristics, laboratory index records, antibiotic susceptibility analysis, and clinical outcome tracking were performed in all cases. Based on oxacillin resistance using the Vitek Compact 2 system, cases were divided into methicillin-sensitive Staphylococcus aureus and MRSA groups. Subgroup analysis of the MRSA group was performed in accordance with the Centers for Disease Control definition: community-associated MRSA and hospital-associated MRSA. RESULTS: The MRSA group (n = 41, 27.5%) had a longer duration of ulcers and hospital stay and higher hospitalization costs than the methicillin-sensitive Staphylococcus aureus group (n = 108, 72.5%). According to the classification criteria of Infectious Diseases Society of America, the severity of infection in the community-associated MRSA group was higher than that in the hospital-associated MRSA group. The analysis of antimicrobial susceptibility of 41 MRSA isolates showed that the resistance rates to erythromycin, clindamycin, quinolone, gentamicin, tetracycline, and rifampicin were 78.0%, 68.3%, 31.7%, 17.1%, 9.8%, and 2.4%, respectively. All the MRSA strains were sensitive to linezolid, tigecycline, and vancomycin. The resistance rates to quinolones and gentamycin in the community-associated MRSA group (both 0%) were lower than those in the hospital-associated MRSA group. CONCLUSION: Emergence of MRSA in diabetic foot ulcer was associated with a prolonged wound duration and increased consumption of medical resources. Community-associated MRSA strains predominated among MRSA isolates from diabetic foot wounds and caused more severe infections.

Maternal undernutrition modulates hepatic MicroRNAs expression in the early life of offspring.

Emerging studies revealed that a poor intrauterine environment elicited by maternal nutrient restriction (MNR) is associated with an increased risk of metabolic diseases in adulthood. Previous research has shown that microRNAs (miRNAs) exert pivotal roles in modulating molecular pathways involved in disease pathogenesis and progression. In this respect, we herein examined miRNA profiles in samples of liver from offspring whose mothers were fed either with a 50% food-restricted diet or standard laboratory chow during pregnancy. Our findings enumerated that miR-181a, involved in lipid metabolism, was found to be downregulated in the liver of MNR offspring at 1 day of age when compared to that of control offspring. We also noted that overexpression of miR-181a reduced the lipid droplets after treatment with oleic acid for 48 h, which suppressed the expressions levels of SIRT1, FOXO1, KLF6 and PPARγ in BRL-3A cells, while the opposite results were observed with decreased expression of miR-181a. Furthermore, the luciferase reporter assay confirmed the direct interactions between miR-181a with KLF6 and SIRT1. In adults, the MNR offspring elucidated increased TG content, decreased expression of miR-181a, and increased expressions levels of SIRT1, FOXO1, KLF6, and PPARγ in liver tissues. Collectively, these findings provided novel evidence that MNR could regulate miRNAs expression, which might be related to lipid metabolism in MNR offspring.

[Correlation between serum free fatty acid level and estimated glomerular filtration rate in type 2 diabetic patients].

OBJECTIVE: To investigate the relationship between serum free fatty acid (FFA) level and glomerular filtration rate (GFR) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 442 T2DM patients treated in Sir Run Run Shaw Hospital from January 2013 to June 2015 were retrospectively analyzed and divided into three groups according to estimated glomerular filtration rate (eGFR) levels using modified modification of diet in renal disease (MDRD) formula: eGFR≥90 ml·min(-1)·1.73 m(-2)group (group A, 227 cases), 60 ml·min(-1)·1.73 m(-2)≤eGFR<90 ml·min(-1)·1.73 m(-2)group (group B, 118 cases), and eGFR<60 ml·min(-1)·1.73 m(-2)group (group C, 97 cases). In addition, 50 body mass index (BMI)-matched non-diabetic subjects were selected as control group. Fasting serum FFA level was measured in each group, and its relationship with eGFR was analyzed. RESULTS: FFA level in group C[(450±203)µmol/L]was significantly higher than that in group A[(326±167)µmol/L], group B[(394±184)µmol/L]and control group[(320±90)µmol/L](all P<0.05). Meanwhile, FFA level in group B was higher compared with that in group A (P<0.05). However, no statistical difference was found in FFA level between group A and Control group (P>0.05). Multiple linear regression analysis using eGFR as the dependent variable demonstrated that uric acid (UA), FFA, triglyceride (TG), total cholesterol (TC), albuminuria, hypertension, smoking and duration of diabetes were all independent risk factors for decreased eGFR (all P<0.05). CONCLUSION: The present results suggest that increased FFA level might be involved in the development of diabetic nephropathy.

[Effects of intrauterine growth restriction and high-fat diet on serum lipid and transcriptional levels of related hepatic genes in rats].

OBJECTIVE: To study the effects of intrauterine growth restriction (IUGR) and high-fat diet on the growth, lipid metabolism, and related hepatic genes in rat offspring. METHODS: The rat model of IUGR was established by food restriction during the entire pregnancy. After weaning, 32 normal rats and 24 offspring rats with IUGR were randomly allocated to standard diet group or high-fat diet group. At the age of 10 weeks, fasting plasma glucose and blood lipid were examined. Additionally, pathological sections for hepatic tissues were observed, and the transcriptional levels of related hepatic genes were measured. RESULTS: At the age of 10 weeks, there was a significant difference in body weight between IUGR rats and normal rats on standard diets, but no significant difference in body weight was observed between the two groups on high-fat diets. Compared with the normal rats, IUGR rats showed increased energy intake and increased levels of fasting plasma glucose, total cholesterol, and triglyceride on both standard and high-fat diets. High-fat diets reduced the concentration of serum triglyceride in both normal rats and IUGR rats. IUGR and high-fat diets aggravated the fat accumulation in the liver. Two-factor analysis of variance showed that at the age of 10 weeks, the expression of genes related to lipid metabolism in the liver, PGC-1α, CPT-1, SREBF-2, HMGR, LDLR and SREBF-1, differed significantly between IUGR and normal rats. Compared with standard diets, high-fat diets increased the expression of PPARα, SREBF-1, SREBF-2, ABCG5, and CYP7A1 in both normal rats and IUGR rats. IUGR and high-fat diets had an interactive effect on LDLR expression. CONCLUSIONS: Hyperlipidemia and fat accumulation in the liver observed in IUGR rats may be related to increased appetite and regulation disorder in genes related to fatty acid oxidation at the transcriptional level. High-fat diets may aggravate fat accumulation in the liver in rats, which may be related to increased expression of genes related to regulation of fatty acid synthesis at the transcriptional level and reduction in secretion of triglyceride.

Triglyceride-raising APOA5 genetic variants are associated with obesity and non-HDL-C in Chinese children and adolescents.

BACKGROUND: Although the association between the apolipoprotein A5 (APOA5) genetic variants and hypertriglyceridemia has been extensively studied, there have been few studies, particularly in children and adolescents, on the association between APOA5 genetic variants and obesity or non-high-density lipoprotein cholesterol (non-HDL-C) levels. The objective of this study was to examine whether APOA5 gene polymorphisms affect body mass index (BMI) or plasma non-HDL-C levels in Chinese child population. METHODS: This was a case-control study. Single nucleotide polymorphisms (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for an association study in 569 obese or overweight and 194 healthy Chinese children and adolescents. RESULTS: Genotype distributions for all polymorphisms in both cohorts were in accordance with the Hardy-Weinberg distribution. The frequencies of the risk alleles in rs662799 and rs651821 SNPs in APOA5 gene were all increased in obese or overweight patients compared to the controls. After adjusted for age and sex, C carriers in rs662799 had a 1.496-fold [95% confidence interval (CI): 1.074-2.084, P = 0.017] higher risk for developing obesity or overweight than subjects with TT genotype, while C carriers in rs651821 had a 1.515-fold higher risk than subjects with TT genotype (95% CI: 1.088-2.100, P = 0.014). Triglyceride (TG) and non-HDL-C concentrations were significantly different among rs662799 variants and both were higher in carriers of minor allele than in noncarriers for TG (1.64 ± 0.96 vs. 1.33 ± 0.67 mmol/L) (P < 0.001), and for non-HDL-C (3.23 ± 0.92 vs. 3.02 ± 0.80 mmol/L) (P = 0.005), respectively. There was also a trend towards increased TG and non-high-density lipoprotein cholesterol levels for rs651821 C carriers (P < 0.001 and P = 0.002, respectively). Furthermore, to confirm the independence of the associations between APOA5 gene and TG or non-HDL-C levels, multiple linear regression analysis was performed and the relationships were not eliminated by adjustment for age, sex and BMI. CONCLUSIONS: These findings suggest the TG-raising genetic variants in the APOA5 gene may influence the susceptibility of the individual to obesity, which may also contribute to an increased risk of high non-HDL-C levels in Chinese obese children and adolescents.

[Comparison of clinical application of two definitions of metabolic syndrome in children and adolescents].

OBJECTIVE: To compare and evaluate clinical applications of two definitions of metabolic syndrome in children and adolescents, which was developed by Pediatric Academy of Chinese Medical Association in 2012 (Chinese definition) and by International Diabetes Federation in 2007 (IDF definition), respectively. METHODS: 593 obese children and adolescents aged 10 ≊16 y from July 2006 to December 2012 were enrolled in the study. The diagnostic concordance of two definitions for metabolic syndrome and individual components was estimated, and their sensitivity and specificity for detecting insulin resistance and early macrovascular complications were compared. RESULTS: The concordance between two definitions for diagnosing metabolic syndrome was good (kappa=0.626); as for detecting the individual components, the Kappa concordance index were 1.000, 0.803, 0.780, 0.734 and 0.594 for hypertriglyceridemia, hyperglycemia, cholesterol abnormality and hypertension, respectively. The incidence of insulin resistance and early macrovascular complications, detected by the two definitions, were both increased with increasing number of abnormal components. The sensitivity and specificity for detecting insulin resistance in children with metabolic syndrome were 54.5% and 65.7% by Chinese definition, and 36.1% and 83.1% by IDF definition; while the sensitivity and specificity for detecting early macrovascular complications were 58.3% and 55.8% by Chinese definition, and 37.3% and 70.8% by IDF definition. After adjusting for age and sex, compared to the obese children and adolescents without metabolic syndrome, the odds ratios of insulin resistance and early macrovascular complications were 2.166 (P<0.001) and 1.771(P=0.008) for children with metabolic syndrome diagnosed by Chinese definition, and the odds ratio of insulin resistance and early macrovascular complications were 2.618 (P<0.001) and 1.357 (P=0.190) by IDF definition. CONCLUSION: The concordance between Chinese and IDF definitions for diagnosing metabolic syndrome in Chinese obese children and adolescents is good. Compared to IDF definition, Chinese definition is more sensitive for hypertension, hyperglycemia and hypercholesterolemia, thus it can more effectively detect insulin resistance and early macrovascular complication.

[Non-high-density-cholesterol as a predictor of non-lipid cardiovascular disease risk factors in obese children].

OBJECTIVE: To investigate the role of non-high density lipoprotein cholesterol (non-HDL-C) in the assessment of cardiovascular disease (CVD) risk factors such as hypertension, pre-diabetes and diabetes in obese children. METHODS: According to the presence of complications (hypertension, pre-diabetes and diabetes), 810 children with central obesity were divided into two groups: one group with complications (n=499) and one group without complications (n=311). One hundred and sixty-four age- and sex-matched children served as the control group. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to analyze the detection of non-lipid CVD risk factors by seven lipid markers. RESULTS: The prevalence rates of hypertension and pre-diabetes were significantly higher in obese children with high non-HDL-C concentrations (≥3.76 mmol/L). After adjusting for waist circumference Z-scores, the area under the ROC curve for non-HDL-C was 0.680 to detect non-lipid CVD risk factors, while the areas for low-density lipoprotein cholesterol, total cholesterol and apoprotein B were 0.659, 0.669 and 0.647 respectively. CONCLUSIONS: Compared with the other lipid markers, non-HDL-C is a better predictor for non-lipid CVD risk factors in obese children. Measurement of non-HDL-C concentations is recommended for obese children.

A Bibliometric Analysis of the Top-Cited Articles on Diabetic Foot Ulcers.

The aim of this study was to determine the top-cited articles in the field of diabetic foot ulcer (DFU) research. A cross-sectional bibliometric analysis was conducted in January 2021 by using Boolean search terms in the Scopus and the Web of Science databases. The 50 top-cited articles that met the inclusion criteria were ranked and evaluated for several characteristics, including year of publication, country of origin, authorship, publishing journal, topic categories, publishing type, and level of evidence. The median number of citations per article in the list was 442 (interquartile range [IQR], 320-520), with a median of 21.8 citations (IQR, 16.5-34.5) per year since publication. The publication years ranged from 1986 to 2017, with 1998 accounting for the greatest number of studies (n = 7). The citation classics were published in 20 journals and originated from institutions in 9 countries. The majority of the studies were clinical, of which expert opinion/review with Level V evidence and clinical studies with Levels I and II evidence comprised the greater proportion in the list. This study provides useful insights into the history and development of DFU research. The top-cited list may serve as a quick reference for education curriculums and clinical practice, in addition to providing a foundation for further studies on this topic.

Analysis of Gene Expression Profiles in the Liver of Rats With Intrauterine Growth Retardation.

Background: Intrauterine growth restriction (IUGR) is highly associated with fetal as well as neonatal morbidity, mortality, and an increased risk metabolic disease development later in life. The mechanism involved in the increased risk has not been established. We compared differentially expressed genes between the liver of appropriate for gestational age (AGA) and IUGR rat models and identified their effects on molecular pathways involved in the metabolic syndrome. Methods: We extracted RNA from the liver of IUGR and AGA rats and profiled gene expression by microarray analysis. GO function and KEGG pathway enrichment analyses were conducted using the Search Tool for the Retrieval of Interacting Genes database. Then, the Cytoscape software was used to visualize regulatory interaction networks of IUGR-related genes. The results were further verified via quantitative reverse transcriptase PCR analysis. Results: In this study, 815 genes were found to be markedly differentially expressed (fold-change >1.5, p < 0.05) between IUGR and AGA, with 347 genes elevated and 468 suppressed in IUGR, relative to AGA. Enrichment and protein-protein interaction network analyses of target genes revealed that core genes including Ppargc1a, Prkaa2, Slc2a1, Rxrg, and Gcgr, and pathways, including the PPAR signaling pathway and FoxO signaling pathway, had a potential association with metabolic syndrome development in IUGR. We also confirmed that at the mRNA level, five genes involved in glycometabolism were differentially expressed between IUGR and AGA. Conclusion: Our findings elucidate on differential gene expression profiles in IUGR and AGA. Moreover, they elucidate on the pathogenesis of IUGR-associated metabolic syndromes. The suggested candidates are potential biomarkers and eventually intended to treat them appropriately.

Association of continuous glucose monitoring-derived time in range with major amputation risk in diabetic foot osteomyelitis patients undergoing amputation.

Objective: The metrics generated from continuous glucose monitoring (CGM), such as time in range (TIR), are strongly correlated with diabetes complications. This study explored the association of perioperative CGM-derived metrics with major amputation risk in patients with diabetic foot osteomyelitis (DFO). Methods: This study recruited 55 DFO patients with grade 3-4 wounds according to the Wagner Diabetic Foot Ulcer Classification System, all of whom underwent CGM for 5 days during the perioperative period. The CGM-derived metrics were defined in accordance with the most recent international consensus recommendations. Results: Patients with major amputation had significantly less TIR and higher time below range (TBR) (all p < 0.05). In binary logistic regression analyses, a lower TIR was associated with the risk of major amputation (odds ratio: 0.83 (95% confidence interval: 0.71-0.99), p = 0.039). This association remained statistically significant after adjustments for age, sex, body mass index, type of diabetes, smoking, drinking, durations of diabetes and DFU, ankle-brachial index, albumin, estimated-glomerular filtration rate, Society for Vascular Surgery wound, ischemia, and foot infection (WIfi) stage, multidrug-resistant organisms, and hemoglobin A1c. Further adjustment for the mean amplitude of glycemic excursion (MAGE) reduced this association. TBR was also independently associated with the risk of major amputation (odds ratio: 1.60 (95% confidence interval: 1.17-2.18), p = 0.003); this association persisted after adjustment for MAGE. Conclusion: Perioperative TIR (3.9-10.0 mmol/L) and TBR (<3.9 mmol/L) were significantly associated with major amputation in hospitalized patients with DFO.

Identification of the Key Pathways and Genes in Hypoxia Pulmonary Arterial Hypertension Following Intrauterine Growth Retardation.

High-throughput sequencing and weighted gene co-expression network analysis (WGCNA) were used to identify susceptibility modules and genes in liver tissue for the hypoxic pulmonary arterial hypertension (PAH) animal model following intrauterine growth retardation (IUGR). A total of 5,000 genes were clustered into eight co-expression modules via WGCNA. Module blue was mostly significantly correlated with the IUGR-hypoxia group. Gene Ontology analysis showed that genes in the module blue were mainly enriched in the fatty acid metabolic process, lipid modification, and fatty acid catabolic process. The Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the genes in module blue were mainly associated with fatty acid metabolism, PPAR signaling pathway, and biosynthesis of unsaturated fatty acids. In addition, the maximal clique centrality method was used to identify the hub genes in the subnetworks, and the obtained results were verified using real-time quantitative PCR. Finally, we identified that four genes including Cyp2f4, Lipc, Acadl, and Hacl1 were significantly associated with IUGR-hypoxia. Our study identified a module and several key genes that acted as essential components in the etiology of the long-term metabolic consequences in hypoxia PAH following IUGR.

Combining CRISPR-Cas12a-Based Technology and Metagenomics Next Generation Sequencing: A New Paradigm for Rapid and Full-Scale Detection of Microbes in Infectious Diabetic Foot Samples.

Introduction: Diabetic foot infections (DFIs) pose a huge challenge for clinicians. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is one of the most significant pathogens of DFI. Early pathogen identification will greatly benefit the diagnosis and treatment of the disease. However, existing diagnostic methods are not effective in early detection. Methods: We developed an assay that coupled loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) techniques to enable quick and specific detection of Staphylococcus aureus and differentiate MRSA in samples from patients with DFI. Furthermore, the results were compared using a reference culture, quantitative real-time polymerase chain reaction (qRT-PCR), and metagenomics next generation sequencing (mNGS). Results: The CRISPR-LAMP assay targeting nuc and mecA successfully detected S. aureus strains and differentiated MRSA. The limit of detection (LoD) of the real-time LAMP for nuc and mecA was 20 copies per microliter reaction in comparison to two copies per µL reaction for the qRT-PCR assay. The specificity of the LAMP-CRISPR assay for nuc was 100%, without cross-reactions with non-S. aureus strains. Evaluating assay performance with 18 samples from DFI patients showed that the assay had 94.4% agreement (17/18 samples) with clinical culture results. The results of mNGS for 8/18 samples were consistent with those of the reference culture and LAMP-CRISPR assay. Conclusion: The findings suggest that the LAMP-CRISPR assay could be promising for the point-of-care detection of S. aureus and the differentiation of MRSA in clinical samples. Furthermore, combining the LAMP-CRISPR assay and mNGS provides an advanced platform for molecular pathogen diagnosis of DFI.

Knockdown of insulin-like growth factor 2 gene disrupts mitochondrial functions in the liver.

Even though insulin-like growth factor 2 (IGF2) has been reported to be overexpressed in nonalcoholic fatty liver disease (NAFLD), its role in the progression of NAFLD and the potential mechanism remain largely unclear. Using in vitro models, we found that IGF2 was the key overexpressed gene in steatosis, suggesting a possible association between IGF2 and NAFLD. Interestingly, loss-of-function experiments revealed that inhibition of IGF2 protein impaired mitochondrial biogenesis and respiration. It additionally disrupted the expression changes of mitochondrial fusion and fission-related proteins necessary in maintaining mitochondrial homeostasis. Consistently, IGF2 knockdown reduced the mitochondrial membrane potential and increased the production of reactive oxygen species. Mechanistically, IGF2 regulates mitochondrial functions by modulating the expression of SIRT1 and its downstream gene PGC1α. This research opens a new frontier on the role of IGF2 in energy metabolism, which potentially participates in the development of NAFLD. As such, IGF2 is a potential therapeutic target against NAFLD.

Early Growth Hormone Intervention Improves Glucose Metabolism in Adult Rats Born Small for Gestational Age.

BACKGROUND: Small for gestational age (SGA) due to intrauterine malnourishment is closely related to metabolic syndrome and type 2 diabetes mellitus. Growth Hormone (GH) treatment has been demonstrated to influence metabolic parameters and islet function of SGA individuals. The present study demonstrates the effects of early GH treatment on glucose tolerance and expression of pancreatic duodenal homeobox 1 (Pdx1) of SGA rats during adulthood. METHODS: SGA rat model was induced by restricting food intake during pregnancy. GH or normal saline was administered during postnatal days 21-35 of SGA rats and appropriate for gestational age (AGA) rats, respectively. RESULTS: In early adulthood (postnatal day 70), as compared to AGA rats, SGA rats showed: (1) decreased body weight; (2) increased postprandial blood glucose; and (3) down-regulated Pdx1 with increased histone deacetylase (HDAC) and down-regulated histone H3-lysine 4 methyltransferase SET7/9. Exogenous GH administration led to a restoration of body weight and normalized glucose tolerance due to an enhanced Pdx1 expression, accompanied by decreased HDAC and up-regulated SET7/9 in SGA rats in early adulthood. CONCLUSION: Our results demonstrate positive effects on glucose metabolism by an early and short GH treatment in SGA adulthood.

The Long Noncoding RNA Blnc1 Protects Against Diet-Induced Obesity by Promoting Mitochondrial Function in White Fat.

INTRODUCTION: Long noncoding RNAs (lncRNAs) play critical regulatory roles in metabolic disorder. Whereas, the regulatory role of lncRNAs in mitochondrial function of white adipose tissue (WAT) is unknown. MATERIALS AND METHODS: We investigated the role of Blnc1 in metabolic homeostasis and mitochondrial function of C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks, followed by multi-point injection of adenovirus carrying Blnc1 into epididymal fat (eWAT). In vitro, mitochondrial biogenesis and function were analyzed in 3T3-L1 pre-adipocytes with Blnc1 overexpression or knockdown. Mechanically, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) were used to highlight the molecular mechanism of Blnc1 in pre-adipocytes. RESULTS: Gross eWAT weight was significantly decreased and insulin resistance was improved in HFD-Ad-Blnc1 mice. Mitochondrial biosynthesis was induced by Blnc1 in eWAT, as evidenced by an increased mitochondrial DNA and enhanced Mito-tracker staining. The expression of mitochondria-related genes was increased in eWAT, hepatic fatty acid oxidation was upregulated, and lipid deposition was reduced in HFD-Ad-Blnc1 mice. Knockdown of Blnc1 in 3T3-L1 pre-adipocytes resulted in mitochondrial dysfunction. The mechanistic investigation indicated that Blnc1 stimulated the transcription of Pgc1ß via decoying hnRNPA1. CONCLUSION: Therefore, eWAT-specific overexpression of Blnc1 improves hepatic steatosis and systemic insulin sensitivity, likely by enhancing mitochondrial biogenesis and function.

Development and validation of a prognostic nomogram to predict overall survival and cancer-specific survival for patients with anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare malignant tumor with a poor prognosis. However, there is no useful clinical prognostic predictive tool for ATC so far. Our study identified risk factors for survival of ATC and created a reliable nomogram to predict overall survival (OS) and cancer-specific survival (CSS) of patients with ATC. METHODS: A total of 1,404 cases of ATC diagnosed between 1983 and 2013 were extracted from on the Surveillance, Epidemiology and End Results database based on our inclusion criteria. OS and CSS were compared among patients between each variable by Kaplan-Meier methods. The Cox proportional hazards model was used to evaluate multiple prognostic factors and obtain independent predictors. All independent risk factors were included to build nomograms, whose accuracy and practicability were tested by concordance index (C-index), calibration curves, ROC curves, DCA, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: Historic stage, tumor size, surgery and radiotherapy were independent risk factors associated with ATC according to multivariate Cox regression analysis of OS. However, gender was also an important prognostic predictor in CSS besides the factors mentioned above. These characteristics were included in the nomograms predicting OS and CSS of patients with ATC. The nomograms predicting OS and CSS performed well with a C-index of 0.765 and 0.773. ROC curves, DCA, NRI and IDI suggested that the nomogram was superior to TNM staging and age. CONCLUSION: The proposed nomogram is a reliable tool based on the prediction of OS and CSS for patients with ATC. Such a predictive tool can help to predict the survival of the patients.

Effect of Induced Membrane Formation Followed by Polymethylmethacrylate Implantation on Diabetic Foot Ulcer Healing When Revascularization Is Not Feasible.

No study has investigated the role of induced membrane (IM) formation in treating diabetic foot ulcer (DFU). This retrospective study was aimed (1) at evaluating the potential role of a two-staged surgical approach, comprising polymethylmethacrylate (PMMA) implantation and IM formation, in the treatment of DFU and (2) at comparing the results of those with routine wound debridement in patients with DFUs and nonrevascularized peripheral arterial disease (PAD). Fifty patients with infected DFUs who were not candidates for vascular interventions were enrolled between February 2016 and April 2018 and assigned to the PMMA group (n = 28) and conventional group (n = 22). The healing rate, major amputation rate, duration of healing, frequency of debridement procedures, patient survival rate, and reulceration of DFUs were determined. The Mann-Whitney U test, independent sample t-test, and χ 2 or Fisher exact test were used in statistical analysis. Overall clinical outcomes were statistically different between the groups (Z = -2.495, P = 0.013). In the PMMA group, 16 patients (57.1%) with intact IM formation achieved ulceration healing at 13.1 ± 3.7 weeks with a mean number of debridements of 1.3 ± 0.4, which were significantly different compared to those values in 5 patients of the conventional group (22.7%, P = 0.014; healing duration: 26.4 ± 7.8 weeks, P = 0.016; mean number of debridements: 3.6 ± 0.5, P ≤ 0.001). At a mean 16.8 ± 4.3-month follow-up, patient survival rates were 92.9% and 68.2% in the PMMA and conventional groups, respectively (P = 0.032). The major amputation rate and reulceration of DFUs were similar between the groups. The two-staged surgical approach is an available, effective modality for improving healing of DFUs. This study provides preliminary information of IM formation followed by PMMA implantation in the management of DFUs in PAD when revascularization is not feasible.

Growth hormone reverses dyslipidemia in adult offspring after maternal undernutrition.

The abnormal intrauterine milieu of fetal growth retardation could lead to dyslipidemia in adulthood. Studies have shown that growth hormone (GH) therapy in small for gestational age (SGA) children would be beneficial for metabolic parameters. Here we investigated whether GH treatment introduced at adolescent period in SGA could reverse dyslipidemia during later life. SGA rat model was established by using semi-starvation treatment during the whole pregnancy. SGA or appropriate for gestational age (AGA) offspring were assigned to receive GH or normal saline (NS). Once-daily subcutaneous injections of GH were administered between 21-35 days of age. In adulthood, as compared to AGA, SGA showed: (1) decreased body weight and length; (2) increased serum triglycerides; (3) down-regulated hepatic AMPK-α1 but up-regulated SREBP-1c and ACC-1; (4) a significant reduction in histone H3 acetylation at the promoter of AMPK-α1. Exogenous GH administration led to a restoration of body weight and length and normalized serum triglycerides by reversing expression of AMPK-α1 and its targeted genes SREBP-1c and ACC-1, through increasing H3 acetylation at the promoter of AMPK-α1 in SGA in adult period. These results demonstrated positive effects on lipid metabolism by a short treatment course of GH in SGA adult period.

Fish oil improves lipid profile in juvenile rats with intrauterine growth retardation by altering the transcriptional expression of lipid-related hepatic genes.

OBJECTIVE: To determine whether maternal intrauterine undernutrition and post-weaning fish oil intake influence lipid profile in juvenile offspring, and explore the possible mechanisms at transcriptional levels. METHODS: After weaning, 32 control offspring and 24 intrauterine growth retardation (IUGR) offspring were randomly allocated to standard chow or fish oil diet. At 10 weeks, fasting plasma glucose, triglycerides, total cholesterol and expressions of related hepatic genes were examined. RESULTS: IUGR offspring without catch-up growth tended to develop hyperglycemia, dyslipidemia and hepatic steatosis. Down-regulation of CPT-1 and LDLR at transcriptional levels were found in IUGR offspring. Early short-term fish oil intervention reversed these unfavorable changes in juvenile rats with IUGR. The mechanisms might be mediated by decreased expression of ACC-1, increased expression of CPT-1, LDLR and ABCG5. CONCLUSION: These data suggest that IUGR offspring already present lipid abnormality in juvenile stage, and early short-term fish oil consumption is beneficial to prevent these unfavorable changes.

Maternal undernutrition leads to elevated hepatic triglycerides in male rat offspring due to increased expression of lipoprotein lipase.

Small for gestational age (SGA) at birth increases the risk of developing metabolic syndrome, which encompasses various symptoms including hypertriglyceridemia. The aim of the present study was to determine whether maternal undernutrition during pregnancy may lead to alterations in hepatic triglyceride content and the gene expression levels of hepatic lipoprotein lipase (LPL) in SGA male offspring. The present study focused on the male offspring in order to prevent confounding factors, such as estrus cycle and hormone profile. Female Sprague Dawley rats were arbitrarily assigned to receive an ad libitum chow diet or 50% food restricted diet from pregnancy day 1 until parturition. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to measure the gene expression levels of hepatic LPL at day 1 and upon completion of the third week of age. Chromatin immunoprecipitation quantified the binding activity of liver X receptor­α (LXR­α) gene to the LXR response elements (LXRE) on LPL promoter and LPL epigenetic characteristics. At 3 weeks of age, SGA male offspring exhibited significantly elevated levels of hepatic triglycerides, which was concomitant with increased expression levels of LPL. Since LPL is regulated by LXR­α, the expression levels of LXR­α were detected in appropriate for gestational age and SGA male offspring. Maternal undernutrition during pregnancy led to an increase in the hepatic expression levels of LXR­α, and enriched binding to the putative LXR response elements in the LPL promoter regions in 3­week­old male offspring. In addition, enhanced acetylation of histone H3 [H3 lysine (K)9 and H3K14] was detected surrounding the LPL promoter. The results of the present study indicated that maternal undernutrition during pregnancy may lead to an increase in hepatic triglycerides, via alterations in the transcriptional and epigenetic regulation of the LPL gene.