[Establishing and verifying the threshold value of HLA mixed antigen reagent screening test results].

Objective: To establish the threshold value of human leukocyte antigen (HLA) mixed antigen reagent screening test results, and to verify it by HLA single antigen reagent confirmation test results. Methods: The results of 2 255 serum samples tested for HLA antibodies by HLA mixed antigen reagent in the department of HLA Laboratory, the First Affiliated Hospital of Soochow University from October 2017 to December 2021 were retrospectively analyzed. Among them, 1 139 samples were also tested by single antigen HLA Class-Ⅰ reagent and 1 116 samples were also tested by single antigen HLA Class-Ⅱ reagent. Based on the same antigens coated with both reagents, the Mean Fluorescence Intensity (MFI) and Nomalized Background ratio (NBG ratio) of 12 HLA Class-Ⅰ beads and 5 HLA Class-Ⅱ beads in the HLA mixed antigen reagent and the MFI of 77 anti-HLA class-Ⅰ antibodies and 35 anti-HLA class-Ⅱ antibodies detected by HLA single antigen reagent were recorded. The MFI and NBG ratio of HLA mixed antigen reagent beads in 1 139 or 1 116 samples were segmented according to the positive rate of antibodyies detected by the single antigen reagent corresponding to the antigens coated with each HLA mixed antigen reagent bead, and the results of the HLA mixed antigen screening test were verified by the HLA single antigen reagent confirmation test. Results: The threshold values of MFI and NBG ratio of HLA mixed antigen reagent's 17 beads were established. The MFI of No. 1 to No. 17 beads of HLA mixed antigen reagent ranged from 26.86 to 21 925.58, and the NBG ratio ranged from 0 to 434.65. According to the positive detection rate of HLA single antigen reagent corresponding to the coated antigens, the MFI and NBG ratio of the beads of HLA mixed antigen reagent were divided into positive interval, suspicious positive interval, suspicious negative interval and negative interval. The positive rates of anti-HLA class-Ⅰ antibodies by HLA mixed antigen reagent and single antigen HLA Class-Ⅰ reagent were 87.5% (997/1 139) and 66.3% (755/1 139). The positive rates of anti-HLA class-Ⅱ antibodies were 63.4% (707/1 116) and 44.9% (501/1 116). In the samples with suspicious negative, suspicious positive and positive results of HLA class-Ⅰ、Ⅱ antibodies detected by HLA mixed antigen reagent, the positive detection rates of single antigen HLA Class-Ⅰ reagent were 14.9% (17/114), 41.3% (145/351) and 91.3% (590/646), respectively. The positive detection rates of single antigen HLA Class-Ⅱ reagent were 15.5% (58/375), 26.5% (81/306) and 88.8% (356/401), respectively. Conclusions: In this study, the threshold values of MFI and NBG ratio of HLA mixed antigen reagent screening test are established, and the threshold values are verified by the results of HLA single antigen reagent confirmation test. HLA mixed reagent screening test can be used for screening of HLA antibodies, and if necessary, it should be combined with HLA single antigen confirmatory test for clinical detection of HLA antibodies.

[Comparative analysis of population distribution, severity, emotional, and cognitive characteristics among different side idiopathic tinnitus patients].

To provide basis for prevention and treatment by analyzing the clinical features, emotional and cognitive states and their correlations of idiopathic tinnitus. Cross-sectional study was used. Thirty-six right, 44 left, and 46 bilateral idiopathic tinnitus patients diagnosed in Beijing Tongren Hospital were prospectively enrolled from October, 2020 to February, 2022. The clinical data was recorded and the THI, DBI, STAI, and MoCA were evaluated. The clinical features and the incidence of severe tinnitus, hearing lose, anxiety, and cognitive impairment were compared by one-way ANOVA, Kruskal-Wallis H, and chi-square test. The correlation between tinnitus or hearing and emotional and cognitive states were evaluated by multivariable correlation analysis. There was no significant difference in age, BMI, years of education, tinnitus duration, and the incidence of hearing loss among groups (F=0.730,P=0.484;F=1.535,P=0.219;F=1.506,P=0.226;χ²=4.242,P=0.120;χ²=6.672,P=0.083). In right, left, and bilateral tinnitus patients, the number of severe tinnitus was 12, 7, and 20 cases and the incidence was 33.3%, 15.9%, and 43.5%; the number of depression was 13, 14, and 26 cases and incidence was 36.1%, 31.8%, and 53.5%; the number of trait anxiety was 3, 2, and 10 cases and the incidence was 8.3%, 4.5%, and 21.7%. Compared with left tinnitus patients, the incidence of severe tinnitus, depression, and trait anxiety was higher in bilateral tinnitus patients (χ²=8.139,P=0.004;χ²=5.558,P=0.018;χ²=5.753,P=0.007). The incidence of state anxiety and cognitive impairment were no significant difference among groups (χ²=0.142,P=0.931;χ²=1.338,P=0.512). The overall incidence of state anxiety and cognitive impairment were 16.7%(21/126) and 37.3%(47/126) respectively. There was positive correlation between THI score and BDI, S-AI, and T-AI scores (r=0.529,P=0.001; r=0.649,P<0.001; r=0.483,P=0.003) and negative correlation between THI and MoCA scores (r=-0.364,P=0.029) in right tinnitus group. The positive correlation was found between THI score and BDI, S-AI, and T-AI scores in left tinnitus group (r=0.508,P<0.001; r=0.506,P<0.001; r=0.357,P=0.017). The positive correlation between THI score and BDI, S-AI, and T-AI scores (r=0.753,P<0.001; r=0.527,P<0.001; r=0.536,P<0.001) and the positive correlation between tinnitus duration and MoCA score(r=0.334,P=0.023) were also found in bilateral tinnitus group.

[Clinicopathological features of NTRK3 gene rearrangement papillary thyroid carcinoma].

Objective: To investigate the clinicopathological features and differential diagnosis of NTRK3 gene rearrangement thyroid papillary carcinoma (PTC). Methods: The PTC cases without BRAF V600E mutation were collected at Fujian Provincial Hospital South Branch from January 2015 to January 2020. The cases of NTRK3 gene rearrangement PTC were examined using immunohistochemistry and fluorescence in situ hybridization (FISH). The clinical data, histopathological characteristics, immunohistochemical features and molecular pathological changes were retrospectively analyzed. Data from the TCGA PTC dataset and the literature were also studied. Results: A total of 3 PTC cases harboring NTRK3 gene rearrangement were confirmed. All the patients were female, aged from 26,49,34 years. Histologically, two of them demonstrated a multinodular growth pattern. Only one case showed prominent follicular growth pattern; the other two tumors showed a mixture of follicular, papillary and solid growth patterns. All tumors showed a typical PTC nuclear manifestation, with some nuclear pleomorphism, vacuolated foci and oncocytic features. The characteristic formation of glomeruloid follicular foci was present in two cases which also showed psammoma bodies, and tumoral capsular or angiolymphatic invasion. The background thyroid parenchyma showed chronic lymphocytic thyroiditis. Mitotic rates were low, and no cases had any tumor necrosis. The pan-TRK and TTF1 testing was both positive in 3 cases, while S-100 and mammaglobin were both negative in them. FISH studies confirmed the NTRK3 gene rearrangement in all 3 cases. Studies on the TCGA datasets and literature revealed similar findings. Conclusions: NTRK3 gene rearrangement PTC is rare. It may be easily misdiagnosed due to the lack of histological and clinicopathological characteristics. Molecular studies such as pan-TRK immunostaining, FISH and even next-generation sequencing are needed to confirm the diagnosis. Immunohistochemistry of pan-TRK performed in the PTC cases without BRAF V600E mutation can be used as a good rapid-screening tool. With the emergence of pan-cancer tyrosine receptor kinase inhibitors, proper diagnosis of these tumors can help determine appropriate treatments and improve their outcomes.

[Complexities and challenges in the management of portal vein thrombosis in cirrhosis].

Portal vein thrombosis is a common complication of liver cirrhosis. Based on the recent "Expert Consensus on the Management of Portal Vein Thrombosis in Liver Cirrhosis (2020, Shanghai)", we analyzed a series of differences in the field of portal vein thrombosis in liver cirrhosis and point out the complexities and challenges faced by clinical anticoagulation treatment, so as to provide a reference for further clinical exploration of the standardized management of portal vein thrombosis in liver cirrhosis.

[Clinical significance of CTP combined with ABIC score in predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure].

Objective: To investigate the risk factors affecting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and establish a new scoring model to predict the short-term prognosis of patients. Methods: This study enrolled 222 patients with HBV-ACLF. According to their clinical outcomes during hospitalization and 90 days after discharge, they were divided into survival and death group. Clinical data were collected to calculate the Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), albumin-bilirubin (ALBI), and age-bilirubin-international normalized ratio-creatinine (ABIC) scores for prognosis. Multivariate logistic regression analysis was used to analyze the independent risk factors affecting 90-day mortality in HBV-ACLF patients. Cox regression model was used to establish a new prediction model. Area under the receiver operating characteristic curve was used to calculate short-term prognostic value of the models. K-M survival curve was used to predict the prognosis of patients. Results: CTP and ABIC scores were independent risk factors for 90-day mortality in HBV-ACLF patients, and the risk of death from liver failure had increased with increase of score. Cox regression model established a new predictive model CTP-ABIC = 0.551 × CTP + 0.297 × ABIC. Area under the receiver operating characteristic curve of all three scoring models (CTP, ABIC and CTP-ABIC) were 0.878, 0.829, 0.927, respectively. CTP-ABIC score was superior to the CTP and ABIC score (P value < 0.001). Patients with CTP-ABIC score ≥9.08 had higher mortality rate than patients with CTP-ABIC score < 9.08, and the difference was statistically significant (P < 0.001). Conclusion: All three scoring systems can predict short-term prognosis in patients with HBV-ACLF, but the accuracy of CTP-ABIC is superior.

Activation of AMPK-SIRT3 signaling is chondroprotective by preserving mitochondrial DNA integrity and function.

OBJECTIVE: In osteoarthritis (OA), articular chondrocytes manifest mitochondrial damage, including mitochondrial DNA 4977-bp (mtDNA4977) deletion that impairs mitochondrial function. OA chondrocytes have decreased activity of AMPK, an energy biosensor that promotes mitochondrial biogenesis. Here, we tested if pharmacologic AMPK activation, via downstream activation of predominately mitochondrially localized sirtuin 3 (SIRT3), reverses existing decreases in mitochondrial DNA (mtDNA) integrity and function in human OA chondrocytes and limits mouse knee OA development. DESIGN: We assessed mtDNA integrity and function including the common mtDNA4977 deletion and mtDNA content, mitochondrial reactive oxygen species (mtROS) generation, oxygen consumption and intracellular ATP levels. Phosphorylation of AMPKα, expression and activity of SIRT3, acetylation and expression of the mitochondrial antioxidant enzyme SOD2 and DNA repair enzyme 8-oxoguanine glycosylase (OGG1), and expression of subunits of mitochondrial respiratory complexes were examined. We assessed effect of pharmacologic activation of AMPK on age-related spontaneous mouse knee OA. RESULTS: The mtDNA4977 deletion was detected in both OA chondrocytes and menadione-treated normal chondrocytes, associated with increased mtROS, decreased SIRT3, and increased acetylation of SOD2 and OGG1. AMPKα1 deficient chondrocytes exhibited significantly reduced SIRT3 activity. AMPK pharmacologic activation attenuated existing mtDNA4977 deletion and improved mitochondrial functions in OA chondrocytes via SIRT3 by reducing acetylation and increasing expression of SOD2 and OGG1, and limited aging-associated mouse knee OA development and progression. CONCLUSIONS: AMPK activation, via SIRT3, limits oxidative stress and improves mtDNA integrity and function in OA chondrocytes. These effects likely contribute to chondroprotective effects of AMPK activity.

Tunable quad-band transmission response, based on single-layer metamaterials.

We investigated the electromagnetically induced transparency (EIT)-like effects in planar metamaterials (MMs) at microwave (GHz) frequencies. The specific MMs that were used in this study consist of cut-wire resonator/ring resonator, which achieved the dual EIT-like effects in a single-layer through the bright- and quasi-dark-mode coupling and the lattice mode coupling. In addition, by varying the distance between the two resonators, the quad-band EIT spectral response in the microwave region was obtained, and the group refractive index at the EIT-like resonance of proposed design reached up to 4,000. This study provides the design approach to the multispectral EIT-like effects and might suggest potential applications in a variety of fields, for example, low-loss slow-light device, multiple switching sensor, and other sensing devices.

Conditional ablation of neuroligin-1 in CA1 pyramidal neurons blocks LTP by a cell-autonomous NMDA receptor-independent mechanism.

Neuroligins are postsynaptic cell-adhesion molecules implicated in autism and other neuropsychiatric disorders. Despite extensive work, the role of neuroligins in synapse function and plasticity, especially N-methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent long-term potentiation (LTP), remains unclear. To establish which synaptic functions unequivocally require neuroligins, we analyzed single and triple conditional knockout (cKO) mice for all three major neuroligin isoforms (NL1-NL3). We inactivated neuroligins by stereotactic viral expression of Cre-recombinase in hippocampal CA1 region pyramidal neurons at postnatal day 0 (P0) or day 21 (P21) and measured synaptic function, synaptic plasticity and spine numbers in acute hippocampal slices 2-3 weeks later. Surprisingly, we find that ablation of neuroligins in newborn or juvenile mice only modestly impaired basal synaptic function in hippocampus and caused no alteration in postsynaptic spine numbers. However, triple cKO of NL1-NL3 or single cKO of NL1 impaired NMDAR-mediated excitatory postsynaptic currents and abolished NMDAR-dependent LTP. Strikingly, the NL1 cKO also abolished LTP elicited by activation of L-type Ca2+-channels during blockade of NMDARs. These findings demonstrate that neuroligins are generally not essential for synapse formation in CA1 pyramidal neurons but shape synaptic properties and that NL1 specifically is required for LTP induced by postsynaptic Ca2+-elevations, a function which may contribute to the pathophysiological role of neuroligins in brain disorders.

Systemic lupus erythematosus with and without a family history: a meta-analysis.

Objective The objective of this paper is to investigate the association of clinical manifestations and laboratory parameters between familial systemic lupus erythematosus (SLE) and sporadic SLE. Methods All relevant literature was retrieved from the PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) databases. The qualities of these studies were evaluated using a modified version of the Newcastle-Ottawa scale. The characteristics and clinical manifestations of involved individuals were extracted from each study. Pooled odds ratio (OR) was calculated using the random effects-method, and the heterogeneity between studies was quantified using the I2 statistic. Results Of 330 studies identified by the search strategy, six were included in this review. In total, 733 cases were familial SLE and 1405 were sporadic SLE. Analysis revealed that photosensitivity, nephritis and thrombocytopenia were negatively associated with familial SLE, with OR (95% CI) values of 0.73 (0.60-0.89), 0.72 (0.59-0.88) and 0.75 (0.57-0.98), respectively. Conclusions Photosensitivity, thrombocytopenia and renal involvement could be more common in non-familial SLE, which should be further confirmed by well-designed studies with large populations.

A first-principles study of the electrically tunable band gap in few-layer penta-graphene.

The structural and electronic properties of bilayer (AA- and AB-stacked) and tri-layer (AAA-, ABA- and AAB-stacked) penta-graphene (PG) have been investigated in the framework of density functional theory. The present results demonstrate that the ground state energy in AB stacking is lower than that in AA stacking, whereas ABA stacking is found to be the most energetically favorable, followed by AAB and AAA stackings. All considered model configurations are found to be semiconducting, independent of the stacking sequence. In the presence of a perpendicular electric field, their band gaps can be significantly reduced and completely closed at a specific critical electric field strength, demonstrating a Stark effect. These findings show that few-layer PG will have tremendous opportunities to be applied in nanoscale electronic and optoelectronic devices owing to its tunable band gap.

Structural signature and transition dynamics of Sb2Te3 melt upon fast cooling.

Crystalline Sb2Te3 is widely studied due to its important applications in memory materials and topological insulators. The liquid and amorphous structures of this compound as well as the dynamics upon quenching, however, are yet to be fully understood. In this work, we have systematically studied the dynamical properties and local structure of Sb2Te3 at different temperatures using ab initio molecular dynamics simulations. The calculated structure factors agree well with the experimental results. The atomic number density and mean-squared displacement as a function of temperature clearly indicate three states as the temperature decreases, namely, melt, undercooled liquid and glass state, respectively. By analyzing the chemical environments and bond-angle distribution functions, we demonstrate that the most probable short-range motifs in the Sb2Te3 system are defective octahedrons, and they are connected with each other via four-fold rings. This interesting structural feature may be responsible for the high fragility and easy phase transition upon glass forming that is applied in memory devices.

[A study on genotype of 271 mycobacterium tuberculosis isolates in 6 prefectures in Yunnan Province].

Objective: To understand the characteristics of genotypes of Mycobacterium tuberculosis isolates in Yunnan province, and provide the molecular epidemiological evidence for prevention and control of tuberculosis in Yunnan Province. Methods: Mycobacterium Tuberculosis isolates were collected from 6 prefectures of Yunnan province in 2014 and their Genetypes of Mycobacterium tuberculosis isolates were obtained using spoligotyping and multiple locus variable numbers of tandem repeats analysis (MLVA). The results of spoligotyping were entered into the SITVITWEB database to obtain the Spoligotyping International Type (SIT) patterns and the sublineages of MTB isolates. The genoyping patterns were clustered with BioNumerics (version 5.0). Results: A total of 271 MTB isolates represented patients were collected from six prefectures in Yunnan province. Out of these patients, 196 (72.3%) were male. The mean age of the patients was (41.9±15.1) years. The most MTB isolates were from Puer, totally 94 iusolates(34.69%). Spoligotyping analysis revealed that 151 (55.72%) MTB isolates belonged to the Beijing genotype, while the other 120 (44.28%) were from non-Beijing genotype; 40 genotypes were consisted of 24 unique genotypes and 16 clusters. The 271 isolates were differentiated into 30 clusters (2 to 17 isolates per cluster) and 177 unique genotypes, showing a clustering rate of 23.62%. Beijing genotype strains showed higher clustering rate than non-Beijing genotype strains (29.14% vs 16.67%). The HGI of 12-locus VNTR in total MTB strains, Beijing genotype strains and non-Beijing genotype was 0.993, 0.982 and 0.995 respectively. Conclusion: The Beijing genotype was the predominant genotype in Yunnan Province, the characteristics of Mycobacterium tuberculosis showed high genetic diversity. The genotyping data reflect the potential recent ongoing transmission in some area, which highlights the urgent need for early diagnosis and treatment of the infectious TB cases, to cut off the transmission and avoid a large TB outbreak.

[Association between the accumulation of metabolic syndrome abnormal components and arterial pulse wave velocity among adult individuals undergoing routine health examination].

Objective: To explore the association between the accumulation of metabolic syndrome (MS) components and abnormal brachial ankle pulse wave velocity (baPWV), and to investigate the effect of accumulation of abnormal metabolic components on abnormal baPWV among adult individuals undergoing routine health examination. Methods: It's a cross-sectional study. Data from 9 201 stratified sampled subjects, aged between 25 to 75 years old, who took part in the annual health checkups in 11 cities of Zhejiang Province from January to December 2016, were analyzed. Blood pressure(BP), fasting plasma glucose(FPG), waist circumference(WC), triglyceride(TG), high-density lipoprotein cholesterols(HDL-C) were defined as MS components. The baPWV was measured by VP-1000 (BP-203RPE Ⅲ) and ΔbaPWV (measured baPWV-reference baPWV/reference baPWV) ×100 (%)> 10% was defined as abnormal. The relationship between MS components and ΔbaPWV was analyzed by linear regression, and impact of accumulation of MS components on ΔbaPWV was analyzed by logistic regression, and the ΔbaPWV in subjects with different levels of MS components were analyzed by analysis of variance. Results: (1) The linear regression analysis demonstrated a positive correlation between ΔbaPWV and MS components including systolic blood pressure, diastolic blood pressure, WC, FPG, TG, while ΔbaPWV was negatively correlated with HDL-C. The ß values were 0.518, 0.616, 0.208, 2.778, 1.862, -1.339, respectively (all P<0.001), indicating a strong association between ΔbaPWV and systolic blood pressure, diastolic blood pressure, and FPG. (2) The logistic regression analysis showed that the proportion of abnormal ΔbaPWV was 2.595 times higher in MS individuals than in non-MS individuals (P<0.001). Abnormal ΔbaPWV increased in proportion with increase in numbers of the metabolic components (OR=1.913, 2.884, 3.833, 6.161, 11.176 in individuals with 1,2,3,4,5 metabolic components, respectively, all P<0.001). (3) The logistic analysis suggested that each component of MS could affect baPWV,and OR was 4.68, 2.45 for systolic blood pressure and/or diastolic blood pressure and FPG. All combinations of 2 components of MS also significantly affected baPWV,and OR value was the highest (5.104(95%CI 4.281-6.085), P<0.001) for FPG+BP. All combinations of 3 components of MS significantly affected baPWV,and OR value was the highest(5.385(95%CI 4.245-6.831), P<0.001) for BP+FPG+TG. All combinations of 4 components of MS affected baPWV,and OR value was the highest (6.519(95%CI 4.731-8.984), P<0.001) for BP+FPG+WC+TG. (4) Finally, every component of MS was divided into 3 levels, their impact on abnormal ΔbaPWV was analyzed. Prevalence of abnormal ΔbaPWV significantly increased with the increasing levels of the metabolic components expect for HDL-C, the F values were 1 224.66, 832.89, 192.72, 112.79 and 56.22, respectively (all P<0.001), indicating that higher levels of metabolic components significantly affected the ΔbaPWV. Conclusions: MS and accumulation of abnormal MS components are closely related with abnormal ΔbaPWV, and the combination of BP and FPG have the greatest impact on the abnormal ΔbaPWV. Analysis on the accumulation of MS components might serve as an early indicator of arteriosclerosis.

Deficiency of filaggrin regulates endogenous cysteine protease activity, leading to impaired skin barrier function.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disorder, characterized by skin barrier defects and enhanced allergen priming. Null mutations in the filaggrin gene (FLG) are strongly associated with moderate to severe AD, but the pathways linking barrier dysfunction and cutaneous inflammation are still largely unknown. AIM: To assess alteration of endogenous cysteine protease activity in FLG-deficient keratinocytes, and to determine whether the alteration in cysteine protease activity affects epidermal barrier function and associated gene and protein expression. METHODS: We established a stable FLG knockdown cell line, and reconstructed epidermal equivalents in vitro. Barrier function of the reconstructed epidermis, the barrier-associated genes and proteins, and the activity of endogenous cysteine proteases were tested. Inhibitors of cysteine proteases were used to further evaluate the role of endogenous cysteine proteases in epidermal barrier function. RESULTS: FLG knockdown induced impaired epidermal barrier function. Microarray, western blotting and fluorescence staining showed reduced expression of K10, ZO-1, E-cadherin, claudin-1 and occludin in FLG knockdown keratinocytes. Compared with cysteine protease activity in control cells, protease activity was dramatically enhanced in FLG knockdown keratinocytes. Furthermore, administration of cysteine protease inhibitors significantly recovered expression of K10 and tight junction proteins, and the barrier defect induced by FLG deficiency. CONCLUSIONS: This is the first observation of elevated endogenous cysteine protease activity in FLG-deficient keratinocytes, which may play an important role in impaired barrier function in AD skin. Modulation of cysteine protease activity might be a novel therapeutic approach for AD treatment.

Methylation of SOX1 and VIM promoters in serum as potential biomarkers for hepatocellular carcinoma.

Aberrant methylation of tumor-related genes has been identified as a promising biomarker for hepatocellular carcinoma (HCC). This study aimed to investigate the diagnostic value of SRY (sex determining region Y)-box 1 (SOX1) and Vimentin (VIM) promoter methylation for HCC. The study included 360 subjects, 240 patients with HCC, 29 with liver cirrhosis (LC), 66 with chronic hepatitis B (CHB) and 25 healthy controls (HCs). The methylation status of SOX1 and VIM promoters in the serum was detected by methylation-specific polymerase chain reaction (MSP). The methylation frequencies of SOX1 and VIM promoters in HCC patients were significantly higher than those in LC (p<0.001 and p<0.001), CHB (p<0.001 and p<0.001) and HC (p<0.001 and p<0.001) subjects. Furthermore, hypermethylation of SOX1 and VIM promoters were found in patients with advanced TNM stage (III-IV) and larger tumor size (≥5 cm) compared with early stage (I-II) (p<0.001 and p=0.004) patients with smaller tumor size (<3 cm) (p=0.018 and p=0.001). Moreover, the VIM promoter methylation frequency was higher in patients with portal vein tumor thrombosis (PVTT) (p=0.006) and vascular invasion (p=0.003). In addition, the combination of α-fetoprotein (≥20 ng/ml) with SOX1 and VIM promoter methylation significantly improved their diagnostic value. In conclusions, aberrant methylation of SOX1 and VIM promoters may be potential biomarkers for noninvasive detection of HCC and HCC metastasis.

Is vertebroplasty a risk factor for subsequent vertebral fracture, meta-analysis of published evidence?

UNLABELLED: In our paper, we systemically retrieved the eligible study evaluating whether increased incidence of subsequent vertebral fracture is associated with vertebroplasty. Main effect sizes were vertebral fracture rates reported in terms of hazard ratio (HR) for time-to-event data or relative risk (RR) for dichotomous outcome. Our results do not support the hypothesis that vertebroplasty contributes to increased risk of subsequent vertebral fracture, neither adjacent nor total vertebral fracture. INTRODUCTION: Vertebroplasty has been implicated in significant changes in vertebral strength, vertebral shape, and consequently increased risk for subsequent vertebral fracture, especially the adjacent level. Here, we further tested the hypothesis whether new-onset vertebral fracture is a natural result of osteoporosis or consequence of cement augmentation. METHODS: Relevant literatures were retrieved using PubMed, Web of Knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL), supplemented by a hand-search of the reference lists of selected articles. Eligible studies assessed whether increased morbidity of subsequent vertebral fracture is associated with vertebroplasty. Main effect sizes were vertebral fracture rates reported in terms of hazard ratio (HR) for time-to-event data or relative risk (RR) for dichotomous outcome. Random-effects model was used to account for clinical or methodological heterogeneity across studies. RESULTS: Thirteen studies with a number of 2,551 individuals (1,631 in vertebroplasty group and 920 in control group) were suitable for this meta-analysis. In trials that reported adjacent vertebral fracture as time-to-event data (two trials, n = 328), we found a similar incidence of vertebral fracture in percutaneous vertebroplasty (PVP) group compared to conservative therapy (HR 0.60, 95% confidence interval 0.29 to 1.26; P = 0.18). In trials that reported overall vertebral fracture as time-to-event data (three trials, n = 704), vertebroplasty was associated with a slightly increased but non-significant risk for vertebral fracture (HR 1.14, 95% confidence interval 0.65 to 2.00; P = 0.65). The outcome was further confirmed in the secondary meta-analysis of studies that reported vertebral fracture as dichotomous data. Subgroup analysis according to study design revealed no difference either. CONCLUSIONS: Our results do not support the hypothesis that vertebroplasty contributes to increased risk of subsequent vertebral fracture, neither adjacent nor total vertebral fracture. However, adequately designed randomized controlled trials are warranted to confirm the present findings.

Clinical value of electrophysiology in determining the diagnosis of visual dysfunction in neuro-ophthalmology patients.

PURPOSE: To assess clinical value of visual electrophysiology in identifying causes of visual dysfunction in patients referred from neuro-ophthalmology clinics. METHODS: A review of 410 subjects (aged 0.3-88 years) referred for visual electrophysiology from neuro-ophthalmologists between 2009 and 2013 was performed. Subjects were divided into those with unexplained poor vision, visual field defects, visual symptoms or other reasons (e.g. monitoring for drug toxicity or known conditions). Subjects underwent pattern, full-field and multifocal electroretinography (ERG) and pattern visual evoked potential (VEP) tests. Flash and multifocal VEP were included where indicated. RESULTS: Most subjects referred for poor vision (n = 158) had electrophysiology findings suggestive of retinopathy (37 %) or post-retinal pathology (34 %). Those with poorer vision (worse than 6/24) were more likely to have abnormal recordings (86 vs. 62 %, p = 0.002). Among subjects with unexplained visual field defects (n = 102), findings of retinopathy, post-retinal pathology and normal recordings were noted in 31, 24 and 28 %, respectively. Most subjects with other visual symptoms (n = 97) had normal findings (69 %). The multifocal ERG was most sensitive for detecting retinopathy (96 %) and maculopathy (95 %), while pattern VEP was most sensitive for post-retinal pathology (94 %). An indeterminate result was noted in 9 %. CONCLUSION: Electrophysiology was effective in differentiating between retinopathy, post-retinal pathology and normality in 91 % of subjects. Pre-testing provisional diagnoses of retinopathy and post-retinal pathology were revised in 30 and 42 %, respectively, after electrophysiology. Appreciation of characteristics of each test, correlation with the clinical picture and interpretation of results in totality are required to localize the site of pathology.

Conditions associated with extreme hyperferritinaemia (>3000 µg/L) in adults.

BACKGROUND: The clinical significance of extreme hyperferritinaemia has come under scrutiny with the increasing recognition of haemophagocytic lymphohistiocytosis (HLH) in adults. Most studies of hyperferritinaemia have focused on serum ferritin greater than 1000 µg/L, often in ambulatory patients. The conditions associated with more extreme hyperferritinaemia are poorly understood. AIMS: To examine conditions associated with extreme hyperferritinaemia greater than 3000 µg/L in acutely ill adults at a quaternary care hospital. METHODS: Patients with serum ferritin greater than 3000 µg/L at Vancouver General Hospital between 1 August 2011 and 1 August 2012 were identified. Those over 18 years of age and with clinical data available were included in the study. RESULTS: Eighty-three subjects were identified. Twenty-one cases (25%) were due to transfusional iron overload, 16 (19%) due to liver disease and 15 (18%) due to mixed factors. Haemophagocytic lymphohistiocytosis (HLH) was diagnosed in six of 83 patients (7%) with ferritin greater than 3000 µg/L, but six of eight patients (75%) with ferritin greater than 20 000 µg/L. CONCLUSIONS: Extreme hyperferritinaemia greater than 3000 µg/L is uncommon in adult patients. The highest serum ferritin values are seen in HLH, but the differential diagnosis for serum ferritin greater than 3000 µg/L remains broad with iron overload and liver disease being the most common causes.