Predictive model for epileptogenic tubers from all tubers in patients with tuberous sclerosis complex based on 18F-FDG PET: an 8-year single-centre study.

BACKGROUND: More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. METHODS: Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. RESULTS: PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70-0.83) than the LDA (AUC = 0.7506; 95% CI 0.68-0.82) and ANN models (AUC = 0.7425; 95% CI 0.67-0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71-0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71-0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74-0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75-0.87). CONCLUSIONS: The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.

LncRNA ENST00000370438 promotes cell proliferation by upregulating DHCR24 in breast cancer.

Long noncoding RNAs (lncRNAs) are critically involved in the occurrence and development of breast cancer (BC). In this study, we performed RNA sequencing, and the results revealed an increase in the expression level of novel lncRNA ENST00000370438 in tissues of patients with BC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) results showed an increase in lncRNA ENST00000370438 expression level in 23 pairs of BC tissues. Next, we determined the effect of ENST00000370438 on BC cell proliferation, and the results showed that ENST00000370438 promotes cell proliferation in BC. The proteomic analysis showed a decrease in DHCR24 expression level in BC cells transfected with ENST00000370438 small interfering RNA. Western blot and qRT-PCR assay results showed that ENST00000370438 regulated DHCR24 expression. Furthermore, the rescue experiment showed that the interference with ENST00000370438 expression could restore the effect of DHCR24 overexpression on BC cell proliferation, demonstrating that ENST00000370438 could promote cell proliferation by upregulating DHCR24. Finally, we showed that lncRNA ENST000000370438 could promote tumor growth by overexpressing DHCR24 in nude mice. Our results demonstrated that lncRNA ENST00000370438 promotes BC cell proliferation by upregulating DHCR24 expression.

Inflammation-related genes and immune infiltration landscape identified in kainite-induced temporal lobe epilepsy based on integrated bioinformatics analysis.

Background: Temporal lobe epilepsy (TLE) is a common brain disease. However, the pathogenesis of TLE and its relationship with immune infiltration remains unclear. We attempted to identify inflammation-related genes (IRGs) and the immune cell infiltration pattern involved in the pathological process of TLE via bioinformatics analysis. Materials and methods: The GSE88992 dataset was downloaded from the Gene Expression Omnibus (GEO) database to perform differentially expressed genes screening and weighted gene co-expression network analysis (WGCNA). Subsequently, the functional enrichment analysis was performed to explore the biological function of the differentially expressed IRGs (DEIRGs). The hub genes were further identified by the CytoHubba algorithm and validated by an external dataset (GSE60772). Furthermore, the CIBERSORT algorithm was applied to assess the differential immune cell infiltration between control and TLE groups. Finally, we used the DGIbd database to screen the candidate drugs for TLE. Results: 34 DEIRGs (33 up-regulated and 1 down-regulated gene) were identified, and they were significantly enriched in inflammation- and immune-related pathways. Subsequently, 4 hub DEIRGs (Ptgs2, Jun, Icam1, Il6) were further identified. Immune cell infiltration analysis revealed that T cells CD4 memory resting, NK cells activated, Monocytes and Dendritic cells activated were involved in the TLE development. Besides, there was a significant correlation between hub DEIRGs and some of the specific immune cells. Conclusion: 4 hub DEIRGs (Ptgs2, Jun, Icam1, Il6) were associated with the pathogenesis of TLE via regulation of immune cell functions, which provided a novel perspective for the understanding of TLE.

Distribution of lean mass and mortality risk in patients with type 2 diabetes.

AIMS: The aim of the study is to evaluate the association of distribution of lean mass with the risk of all-cause mortality among patients with type 2 diabetes. METHODS: The present cohort study included 2 335 patients with type 2 diabetes. Lean mass was assessed by dual energy X-ray absorptiometry. Cox proportional hazards regressions were used to estimate the association of lean mass distribution on the risk of mortality. RESULTS: The average age of the patients was 58 years at baseline and 51.4% of patients were women. During a median follow-up of 4.31 years, 128 patients died. The multivariable-adjusted hazards ratios for all-cause mortality were 1.00, 1.63 (0.89-2.99), and 2.68(1.51-4.76) across the tertiles of android-to-gynoid lean mass ratio (P for trend < 0.001), respectively. The positive association of android-to-gynoid lean mass ratio with the risk of all-cause mortality was present among patients of different ages, body mass index ≥ 24 kg/m2, hemoglobin A1c ≥ 7.0%, nonsmokers, men, patients using insulin, and patients with diabetes durations of more than 10 years. CONCLUSIONS: Higher android-to-gynoid lean mass ratio, assessed by dual energy X-ray absorptiometry, was significantly associated with increased risk of all-cause mortality among patients with type 2 diabetes.

Lance Adams syndrome: two cases report and literature review.

Hypoxic myoclonus, also known as Lance Adams syndrome, is a rare syndrome that results from the serious brain damage caused by cerebral hypoxia that often follows cardiopulmonary resuscitation. This current case report describes two patients with post-hypoxic myoclonus, both of whom received cardiopulmonary resuscitation. The neurological symptoms of these two patients were significantly improved by the administration of clonazepam and sodium valproate sustained-release tablets. The report presents a literature review detailing the pathogenesis, diagnosis and treatment of Lance Adams syndrome. The timely diagnosis and treatment of Lance Adams syndrome can significantly improve the quality of life of patients. Valproic acid, clonazepam and other antiepileptic drugs can be used. Whether levetiracetam is effective for cortical myoclonus requires further clinical study.

Cardiovascular Risk Factor Status in Hospitalized Patients With Type 2 Diabetes in China.

Background: Controlling blood glucose, blood pressure, and blood lipid is of great importance for patients with type 2 diabetes, not only for cardiovascular disease, but also for other complications. Previous studies mainly focused on the control rate of outpatients, and the results were suboptimal, but few studies aimed at the inpatients. Method: The present study involved 3,245 hospitalized patients with type 2 diabetes from 2013 to 2017 in the Department of Endocrinology and Metabolism of Tianjin Medical University General Hospital. The percentages of inpatients who attained the goals of the China Diabetes Society and the American Diabetes Association were calculated for major cardiovascular risk factors (HbA1c, blood pressure, and blood lipid). The prevalence of microvascular and macrovascular complications was also assessed. Result: The percentages of patients who met the Chinese Diabetes Society goals-HbA1c <7%, blood pressure <130/80 mmHg, normal lipids, and all three goals-were 26.7, 14.8, 10.4, and 0.2% in 2013 and 30.5, 16.2, 8.0, and 0.9% in 2017, respectively. The percentage of patients who met all three American Diabetes Association goals (HbA1c<7%, blood pressure <140/90 mmHg, low-density lipoprotein cholesterol <2.6 mmol/L) increased from 4.3% in 2013 to 9.0% in 2017. The prevalence of major diabetes complications including coronary heart disease (31.7 vs. 31.9%), stroke (16.7 vs. 14.8%), diabetic kidney disease (37.9 vs. 35.8%), diabetic retinopathy (48.0 vs. 46.5%), neuropathy (63.1 vs. 61.9%), and diabetic foot (0.8 vs. 1.2%) were stable from 2013 to 2017. Conclusion: During 2013 to 2017, control rates of major cardiovascular risk factors including HbA1c, blood pressure, and low-density lipoprotein cholesterol were improved among hospitalized patients in Tianjin, China.

Different Indicators of Adiposity and Fat Distribution and Cardiometabolic Risk Factors in Patients with Type 2 Diabetes.

OBJECTIVE: This study aimed to evaluate the effect of adiposity and fat distribution on the odds of elevated cardiovascular risk factors among adults with type 2 diabetes mellitus. METHODS: The present cross-sectional study included 2,427 adults with type 2 diabetes mellitus. Body fat was assessed by dual-energy x-ray absorptiometry. Multivariate-adjusted logistic regression was used to estimate effects of adiposity parameters on elevated hemoglobin A1c (HbA1c , ≥7.0%), hypertension (blood pressure ≥140/90 mmHg), and elevated low-density lipoprotein (LDL) cholesterol (≥2.6 mmol/L). RESULTS: The multivariable-adjusted odds ratio (OR) for elevated HbA1c was 0.82 (95% CI: 0.70-0.96) for each SD increase in leg fat mass. The multivariable-adjusted OR for hypertension was 1.15 (95% CI: 1.00-1.32) for each SD increase in android fat mass. Multivariable-adjusted ORs for elevated LDL cholesterol ranged from 1.16 (95% CI: 1.00-1.35) to 1.27 (95% CI: 1.06-1.51) for each SD increase in arm and android fat mass and percentage of total, truncal, arm, and android fat. Each SD increase in BMI, truncal-to-leg fat ratio, and android-to-gynoid fat ratio was significantly associated with increased risks of elevated HbA1c , hypertension, and elevated LDL cholesterol. CONCLUSIONS: Subcutaneous fat in the lower body was associated with a more favorable glycemic profile, but not blood pressure or lipid profile, whereas central adiposity was associated with poor control of cardiovascular risk factors among patients with type 2 diabetes mellitus.

Biological behaviors of mutant proinsulin contribute to the phenotypic spectrum of diabetes associated with insulin gene mutations.

Insulin gene mutation is the second most common cause of neonatal diabetes (NDM). It is also one of the genes involved in maturity-onset diabetes of the young (MODY). We aim to investigate molecular behaviors of different INS gene variants that may correlate with the clinical spectrum of diabetes phenotypes. In this study, we concentrated on two previously uncharacterized MODY-causing mutants, proinsulin-p.Gly44Arg [G(B20)R] and p.Pro52Leu [P(B28)L] (a novel mutant identified in one French family), and an NDM causing proinsulin-p.(Cys96Tyr) [C(A7)Y]. We find that these proinsulin mutants exhibit impaired oxidative folding in the endoplasmic reticulum (ER) with blocked ER export, ER stress, and apoptosis. Importantly, the proinsulin mutants formed abnormal intermolecular disulfide bonds that not only involved the mutant proinsulin, but also the co-expressed WT-proinsulin, forming misfolded disulfide-linked proinsulin complexes. This impaired the intracellular trafficking of WT-proinsulin and limited the production of bioactive mature insulin. Notably, although all three mutants presented with similar defects in folding, trafficking, and dominant negative behavior, the degrees of these defects appeared to be different. Specifically, compared to MODY mutants G(B20)R and P(B28)L that partially affected folding and trafficking of co-expressed WT-proinsulin, the NDM mutant C(A7)Y resulted in an almost complete blockade of the ER export of WT-proinsulin, decreasing insulin production, inducing more severe ER stress and apoptosis. We thus demonstrate that differences in cell biological behaviors among different proinsulin mutants correlate with the spectrum of diabetes phenotypes caused by the different INS gene mutations.

Waist Circumference and its Changes Are More Strongly Associated with the Risk of Type 2 Diabetes than Body Mass Index and Changes in Body Weight in Chinese Adults.

BACKGROUND: The associations of different adiposity indicators and short-term adiposity change with diabetes risk are not fully elucidated. OBJECTIVE: We aimed to assess the independent and joint effects of different baseline adiposity indicators and short-term body adiposity change on the risk of type 2 diabetes. METHODS: We prospectively followed 10,419 Chinese adults aged 20-80 y in 2008-2012. Incident diabetes was diagnosed based on fasting glucose, 2-h glucose, or glycated hemoglobin (HbA1c) after an oral glucose tolerance test using the American Diabetes Association standard. Cox proportional hazard regression models were used to assess the associations of adiposity indicators and adiposity change with diabetes risk. RESULTS: During a mean follow-up of 2.8 y, we identified 805 type 2 diabetes cases. Baseline BMI, waist circumference, and waist-height ratio (WHtR) were all positively associated with diabetes risk. The area under the curve was significantly greater for waist circumference (0.624) and WHtR (0.627) than for BMI (0.608) (P <0.05). Compared with subjects with stable adiposity levels (±2 kg or ± 3 cm in changes in body weight or waist circumference) from baseline to Year 1, those subjects with the most weight gain or the most waist circumference gain had a 1.53-fold or 1.37-fold greater risk of diabetes; those with the most weight loss had a 46% lower risk of diabetes. Furthermore, regardless of baseline weight status, weight or waist circumference change in the first year was associated with diabetes risk. CONCLUSION: Abdominal adiposity indicators, waist circumference and its change, are more strongly associated with the risk of type 2 diabetes than general adiposity indicators, BMI, and changes in body weight among Chinese adults.

Testing of diagnosis criteria of tension-type headache: A multicenter clinical study.

Objective Tension-type headache is *These authors contributed equally to this work. usually manifested as head pain without associated symptoms, and the validation of diagnostic criteria presented are lacking and highly required in the International Classification of Headache Disorders. The aim of the present study was to explore the diagnosis criteria of tension-type headache in a multicenter-based sample from Chongqing, China. Methods Clinical characteristics and demographics were systematically and prospectively collected between March 2014 and December 2015 from 15 participating hospitals in Chongqing, using a semi-structured face-to-face interview. All patients were asked to complete a headache diary for at least 4 weeks. Results Out of 1832 patients with headache, 150 patients (97 female/53 male, 44.56 ± 11.9 years old) were diagnosed with tension-type headache based on the standard International Classification of Headache Disorders, 3rd edition beta version, and interestingly, 114 (76%) patients were diagnosed with tension-type headache based on the alternative criteria. One patient was excluded because only two of the four characteristics were fulfilled. Thirty-five (23.3%) patients did not meet the alternative criteria because of associated symptoms, including mild nausea (n = 6), photophobia (n = 1), and phonophobia (n = 28). All patients with TTH had mild or moderate headaches, 98.0% of patients suffered from non-pulsating headaches, 99.3% of patients said their headaches were not aggravated by routine physical activity, and 77.3% of patients had bilateral headache. Conclusions Non-pulsating headaches and headaches that are not aggravated by routine physical activity may represent core criteria for screening patients with tension-type headache. Nausea might not be an exclusion feature for diagnosis of TTH, but an important criterion for screening. Further studies are needed.

A polymorphism (-455G>A) in the ß-fibrinogen gene is associated with an increased risk of cerebral infarction in the Chinese population: A meta-analysis.

BACKGROUND: Previous studies have investigated the association between a polymorphism (-455 G>A) in the ß-fibrinogen gene and the risk of cerebral infarction. However, these results are controversial. To shed light on these inconclusive findings, we performed a meta-analysis of studies relating the ß-fibrinogen genetic polymorphism (-455 G>A) to the risk of cerebral infarction. METHODS: We identified literature published before July 2013 by searching PubMed, EMBASE, ISI Web of Science, the Chinese National Knowledge Infrastructure database (CNKI) and the Wanfang database in China and by reviewing the references of retrieved articles. We included studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between the ß-fibrinogen genetic polymorphism and cerebral infarction risk. Publication bias was tested by a funnel plot, and the OR of all studies were combined dependent on the results of the heterogeneity tests among the individual studies. The software Review Manager (Version 5.2) was used for meta-analysis. RESULTS: Twenty independent case-control studies containing 9477 subjects were included. Our results showed that the -455 G>A polymorphism in the ß-fibrinogen gene was associated with the increased risk of cerebral infarction [(AA+GA) vs. GG, OR=1.17, 95%CI: 1.04-1.31, p=0.008; A vs. G, OR=1.12, 95%CI: 1.01-1.23, p=0.03] in the Chinese population by a meta-analysis. However, we did not find this association in the Caucasian population [(AA+GA) vs. GG, OR=0.99, 95%CI: 0.87-1.11, p=0.84; A vs. G, OR=0.97, 95%CI: 0.84-1.13, p=0.73, respectively]. CONCLUSION: The results of our meta-analysis indicate that the -455 G>A polymorphism in the ß-fibrinogen gene is a susceptibility marker of ischemic cerebral infarction in the Chinese population.

Serum Brain-derived neurotrophic factor levels in post-stroke depression.

BACKGROUND: Depression is a frequent mood disorder that affects around a third of stroke patients and has been associated with poorer outcome. Our aim was to determine whether there is a relationship between serum Brain-derived neurotrophic factor (BDNF) levels and post-stroke depression (PSD). METHODS: Two hundred and sixteen ischemic stroke patients admitted to the hospital within the first 24h after stroke onset were consecutively recruited and followed up for 3 months. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for post-stroke depression at day 90. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of BDNF at admission. Multivariate analyses were performed using logistic regression models. RESULTS: In our study, 59 patients (27.3%) were diagnosed as having major depression at 3 months. Patients with major depression showed lower levels of serum BDNF [8.1 (5.6-9.4) vs. 13.7 (10.4-16.5)ng/ml, P<0.0001] at admission. In multivariate analyses, serum BDNF was an independent predictor of PSD at 3 months [odds ratio (OR): 0.79(0.72-0.87), P=0.003]. Serum levels of BDNF≤10.2ng/ml were independently associated with post-stroke (OR, 11.5; 95% CI, 5.6-23.4, P<0.0001), after adjustment for possible variables. CONCLUSION: The present study demonstrates a strong relationship between serum BDNF levels at admission and the development of PSD within 3 months. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options.

Plasma levels of glutamate during stroke is associated with development of post-stroke depression.

BACKGROUND: Depression is a frequent mood disorder that affects around 33% of stroke patient. Our aim was to test the possible association between plasma glutamate and the development of post-stroke depression (PSD) in Chinese patients. METHODS: The subjects were first-ever acute ischemic stroke (AIS) patients who were hospitalized during the period from November 2011 to September 2013. Clinical information and stroke severity was collected at admission. Neurological and neuropsychological evaluations were conducted at the 3-month follow-up. Plasma glutamate levels were analyzed at baseline using liquid chromatography followed by tandem mass spectrometry. Glutamate oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and blood markers were also tested. Multivariate analyses were performed using logistic regression models. RESULTS: During the study period, 209 patients were included in the analysis. Seventy patients (33.5%) were diagnosed as having major depression at 3 month. Patients with major depression showed higher levels of plasma glutamate [299 (235-353) vs. 157 (108-206) µM, P<0.0001] and lower GOT [14 (11-20) vs. 21 (15-32)U/L, P<0.0001] at admission. In multivariate analyses, plasma glutamate and GOT were independent predictors of PSD at 3 months [odds ratio (OR): 1.03 (1.02-1.04), P<0.0001; 0.84 (0.75-0.97), P=0.003]. Plasma levels of glutamate >205 µM were independently associated with PSD (OR, 21.3; 95% CI, 8.28-67.36, P<0.0001), after adjustment for possible variables. CONCLUSION: The present study demonstrates a strong relationship between plasma glutamate and GOT levels at admission and the development of PSD within 3 months. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options.