Superoxide dismutases: marker in predicting reduced left ventricular ejection fraction in patients with type 2 diabetes and acute coronary syndrome.

AIM: To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). METHODS: The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. RESULTS: Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493-0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482-0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. CONCLUSIONS: Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Association of Plasma Pro-Brain-Derived Neurotrophic Factor (proBDNF)/Mature Brain-Derived Neurotrophic Factor (mBDNF) Levels with BDNF Gene Val66Met Polymorphism in Alcohol Dependence.

BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.

An Application of Fit Quality to Screen MDM2/p53 Protein-Protein Interaction Inhibitors.

: The judicious application of ligand or binding efficiency (LE) metrics, which quantify the molecular properties required to obtain binding affinity for a drug target, is gaining traction in the selection and optimization of fragments, hits and leads. Here we report for the first time the use of LE based metric, fit quality (FQ), in virtual screening (VS) of MDM2/p53 protein-protein interaction inhibitors (PPIIs). Firstly, a Receptor-Ligand pharmacophore model was constructed on multiple MDM2/ligand complex structures to screen the library. The enrichment factor (EF) for screening was calculated based on a decoy set to define the screening threshold. Finally, 1% of the library, 335 compounds, were screened and re-filtered with the FQ metric. According to the statistical results of FQ vs activity of 156 MDM2/p53 PPIIs extracted from literatures, the cut-off was defined as FQ = 0.8. After the second round of VS, six compounds with the FQ > 0.8 were picked out for assessing their antitumor activity. At the cellular level, the six hits exhibited a good selectivity (larger than 3) against HepG2 (wt-p53) vs Hep3B (p53 null) cell lines. On the further study, the six hits exhibited an acceptable affinity (range of Ki from 10² to 10³ nM) to MDM2 when comparing to Nutlin-3a. Based on our work, FQ based VS strategy could be applied to discover other PPIIs.

Comparison of Histological, Microbiological, and Molecular Methods in Diagnosis of Patients with TBLN Having Different Anti-TB Treatment Background.

OBJECTIVE: The influence of anti-tuberculosis (TB) treatment history on tuberculous lymphadenitis (TBLN) diagnosis is unclear. Therefore, this study aims to evaluate the diagnostic methods, including histology, microbiology, and molecular tests, used for TBLN. METHODS: In this study, suspected patients with TBLN and having different anti-TB treatment background were enrolled. All the samples were tested simultaneously by histology, Ziehl-Neelsen (ZN) staining, mycobacterial culture (culture), Xpert MTB/RIF (xpert), real-time PCR, and high-resolution melting curve PCR (HRM). Thereafter, the performance of these methods on samples with different anti-TB treatment background was assessed. RESULTS: In our study, 89 patients were prospectively included 82 patients with TBLN and 7 with other diseases. The overall sensitivities of Xpert, real-time PCR, histology, ZN staining, and culture were 86.6%, 69.5%, 58.5%, 43.9%, and 22.0%, respectively. The anti-TB treatment history revealed dramatic influences on the sensitivity of culture (P < 0.0001). In fact, the treatment that lasted over 3 months also influenced the sensitivity of Xpert (P < 0.05). However, the treatment history did not affect the performance of remaining tests (P > 0.05). For rifampicin drug susceptibility test (DST), the anti-TB treatment showed only significant influence on the success rate of culture DST (P = 0.001), but not on those of Xpert and HRM tests (P > 0.05). CONCLUSION: Other tests as well as culture should be considered for patients with TBLN having retreatment history or over 1-month treatment to avoid false negative results.

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients.

AIM: The eicosanoids derived from phospholipids play key roles in inflammation. However, the profiles of serum eicosanoids in subclinical hypothyroidism (SH) patients and the effects of thyroxine replacement therapy (TRT) on these eicosanoids remain unclear. Many studies show that TSH regulates lipid metabolism. As eicosanoids derived from phospholipids play key roles in oxidative stress and immune function and inflammatory process, it was necessary to explore the profiles of serum eicosanoids in SH patients and the effects of thyroxine replacement therapy (TRT) on the eicosanoids. METHODS: A total of 50 Chinese SH patients and 22 healthy volunteers were recruited. SH patients received TRT (L-T4, 25 and 50 mcg/d for patients with TSH≤10.0 mIU/L and TSH>10.0 mIU/L, respectively) for 3 months. Serum levels of major eicosanoids and cPLA2 were analyzed using LC-MS and clinical biochemical assays. RESULTS: The serum levels of cPLA2, eicosanoids (8-isoPGF2a, 11-dehydroTXB2 and 12-HETE) and 11-dehydroTXB2/6-Keto-PGF1a were significantly elevated in SH patients. The serum TSH levels were significantly correlated with the levels of cPLA2 (r=+0.65), 11-dehydroTXB2 (r=+0.32) and 11-dehydroTXB2/6-Keto-PGF1a (r=+0.37). After 3-month TRT, the serum levels of TSH, cPLA2 and the above-mentioned eicosanoids in SH patients were significantly decreased. CONCLUSION: The metabolism of eicosanoids is significantly altered in Chinese SH patients, and TRT can ameliorate the abnormalities of serum eicosanoid levels.

KILLER CELL IMMUNOGLOBULIN-LIKE RECEPTOR GENES AND THEIR HLA-C LIGANDS IN HASHIMOTO THYROIDITIS IN A CHINESE POPULATION.

OBJECTIVE: Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen-C (HLA-C) ligands. Alterations in NK cell activity have been associated with Hashimoto thyroiditis (HT). The aim of this study was to determine whether certain KIR/HLA-C genotype combinations play a role in HT pathogenesis. METHODS: The present study enrolled 107 unrelated HT patients and 108 random healthy individuals in a case-control study. Blood was collected for DNA extraction; typing of KIR genes and HLA-C alleles was performed by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by electrophoresis on agarose gels. RESULTS: Among a panel of KIR2D/HLA-C genotype combinations, the frequency of KIR2DS2/HLA-C1 was significantly increased in HT patients compared to controls (33.64% vs. 12.96%, P<.001). To further analyze the precise genotype, we investigated inhibitory or activating KIR/HLA-C gene pairs when their corresponding activating or inhibitory KIR genes were absent in the 2 groups. Only the frequency of KIR2DS2(-)2DL2/3(+)HLA-C1(+) was significantly decreased in HT patients compared to controls (48.60% vs. 70.37%, P = .001). CONCLUSION: Our data suggest that KIR2DS2/HLA-C1 may correlate with HT pathogenesis. On the contrary, the predominance of KIR2DL2/3/HLA-C1 in the absence of KIR2DS2 suggests a potential inhibitory role in HT pathogenesis. In conclusion, our findings may further elucidate the mechanisms underlying the pathogenesis of HT and other autoimmune diseases. ABBREVIATIONS: HLA-C = human leukocyte antigen-C HT = Hashimoto thyroiditis KIR = killer immunoglobulin-like receptor NK = natural killer PCR = polymerase chain reaction.

Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease.

AIM: To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS: Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were treated with Dio (20, 100 mg·kg(-1)·d(-1), ip) for 12 or 24 d. The serum levels of TT4 and TRAb were examined using radioimmunoassay and electrochemiluminescence. The size and morphology of thyroid glands were examined. Thyrocyte proliferation was determined using BrdU incorporation assay. The expression of proliferation-associated proteins IGF-1, NF-κB, cyclin D1, and PCNA in thyroids was analyzed using immunohistochemistry and real-time PCR. RESULTS: The GD mice showed significantly high serum levels of TRAb and TT4 compared to the normal mice. Treatment of the GD mice with Dio for 24 d dose-dependently reduced the TT4 level and thyroid size, but did not affect the abnormal level of TRAb. Furthermore, Dio treatment dose-dependently reversed the morphological changes and reduced excessive thyrocyte proliferation in thyroids of the GD mice. Dio treatment also dose-dependently reduced the mRNA and protein levels of IGF-1, NF-κB, cyclin D1, and PCNA in thyroids of the GD mice. CONCLUSION: Dio relieves goiter in a mouse model of GD through the inhibition of thyrocyte proliferation. The mechanisms involve the suppression of IGF-1, NF-κB, cyclin D1, and PCNA expression.

Overexpression of a novel chrysanthemum Cys2/His2-type zinc finger protein gene DgZFP3 confers drought tolerance in tobacco.

A drought stress-responsive Cys2/His2-type zinc finger protein gene DgZFP3 was previously isolated (Liu et al., Afr J Biotechnol 11:7781-7788, 2012b) from chrysanthemum. To assess roles of DgZFP3 in plant drought stress responses, we performed gain-of-function experiment. The DgZFP3-overexpression tobacco plants showed significant drought tolerance over the wild type (WT). The transgenic lines exhibited less accumulation of H2O2 under drought stress, more accumulation of proline and greater activities of peroxidase (POD) and superoxide dismutase than the WT under both control conditions and drought stress. In addition, there was greater up-regulation of the ROS-related enzyme genes (NtSOD and NtPOD) and stress-related genes (NtLEA5 and NtDREB) in transgenic lines under normal or drought conditons. Thus DgZFP3 probably plays a positive regulatory role in drought stress response and has the potential to be utilized in transgenic breeding to improve drought stress tolerance in plants.

[Value of detecting epidermal growth factor receptor mutations in non-small cell lung cancer tissue by TaqMan-amplification refractory mutation system].

OBJECTIVE: To explore the value of detecting mutations on epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) tissue by TaqMan-amplification refractory mutation system (TaqMan-ARMS). METHODS: TaqMan-ARMS and DNA sequencing were used to detect the EGFR exon 19 and 21 mutations in tumor tissues and the samples collected from 199 patients at 4 different 3A hospitals in Beijing from January 2008 to March 2011. RESULTS: The rate of mutations in EGFR exon 19 and 21 was 19.1% (38/199), according to their different pathological types. Based upon TaqMan-ARMS, the classification was as followed: adenocarcinoma (35.0% (36/103)), squamous carcinoma (2.2% (2/93)) and adenosquamous carcinoma (0). According to DNA sequencing, they were 19.6% (39/199), 35.9% (37/103), 2.2% (2/93) and 0 respectively. Thus, no statistically significant difference existed between two methods (McNemar Test, P = 1.000, κ = 0.984). The mutation rate of adenocarcinoma was higher than those of squamous and adenosquamous carcinoma. CONCLUSION: The detection of EGFR mutations is highly consistent in the NSCLC tissue by the methods of TaqMan-ARMS and DNA sequencing.

[Primary sinus histiocytosis of the trachea: a case report and review of literature].

OBJECTIVE: To study the clinicopathological features, diagnosis and prognosis of primary sinus histiocytosis (Rosai-Dorfman disease, RDD) of the trachea by case report and review of the literature. METHODS: A 63 year old man with a space-occupying lesion of the trachea firstly diagnosed as a malignant tumor was admitted to this hospital for further evaluation and treatment. The lesion was removed by surgery and the final diagnosis was primary RDD. The clinical data of the case was analyzed and the related literatures were reviewed. The literature review was carried out respectively with"Rosai-Dorfman disease" and "sinus histiocytosis"as the key words in Wanfang Med Online and with"Rosai-Dorfman disease","sinus histiocytosis","trachea or lung"as the key words in PubMed database by July 2012. RESULTS: The chest computerized tomography of the case showed that the mass was located at the right side of the trachea with heterogeneous density and contrast enhancement. Bronchoscopy revealed a neoplasma occluding the distal trachea. The lesion was excised by surgery. Microscopic histology showed that in the dark-staining area a large number of lymphocytes and plasma cells were noted while the light-staining area was formed by giant histiocytes. The pathological changes invaded the tracheal wall and eroded the cartilages. Intact lymphocytes and plasma cells were observed within the eosinophilic cytoplasm of the histiocytes. Immunohistochemistry showed that the giant histiocytes were strongly positive for S-100 protein and CD68 protein. Primary RDD of trachea was confirmed. The patient remained well without any other treatment or evidence of progression for 11 months. A total of 13 literatures and 26 cases were retrieved from Wanfang Med Online and Pubmed, including 21 cases of primary RDD of the upper respiratory tract and 4 cases of primary RDD of the lung. A total of 5 literatures and 5 cases of RDD affecting the trachea were retrieved from Wanfang Med Online and Pubmed. There was only one case of primary RDD of the trachea in Pubmed. A 39-year-old female patient with 1 month of dyspnea was misdiagnosed as having bronchial asthma and was unresponsive to empirical corticosteroid and bronchodilator therapy. The chest computerized tomography revealed an ill-defined irregular soft tissue in the trachea. A tracheal ring sleeve resection and reanastomosis was performed to prevent asphyxia. The mass was confirmed to be primary RDD of the trachea according to histopathology and immunohistochemistry. The patient was well without any treatment for 12 months. CONCLUSIONS: Primary RDD of the trachea is an extremely rare disease, with dyspnoea as a feature of the disease. When it is completely removed, the prognosis is good. Typical histopathology and immunohistochemistry are needed to make a definite diagnosis. The positive immunohistochemistry staining for S-100 and CD68 protein in giant histiocytes and lymphocyteemperipolesis are essential for the diagnosis. The differential diagnosis includes other benign or malignant space-occupying lesions of the trachea.

Chronic ethanol consumption increases the levels of chemerin in the serum and adipose tissue of humans and rats.

AIM: Chemerin is a new adipokine involved in adipogenesis and insulin resistance. Since ethanol affects the insulin sensitivity that is closely associated with adipokines. The aim of this study was to investigate the effects of ethanol on chemerin in humans and rats. METHODS: In the human study, 148 men who consumed alcohol for more than 3 years and 55 men who abstained from alcohol were included. Based on ethanol consumption per day, the drinkers were classified into 3 groups: low-dose (<15 g/d), middle-dose (15-47.9 g/d) and high-dose (≥48 g/d). Anthropometric measurements and serum parameters were collected. In the rat study, 27 male Wistar rats were randomly divided into 4 groups administered water or ethanol (0.5, 2.5, or 5 g·kg(-1)·d(-1)) for 22 weeks. The chemerin levels in the sera, visceral adipose tissue (VAT) and liver were measured using ELISA. RESULTS: In the high-dose group of humans and middle- and high-dose groups of rats, chronic ethanol consumption significantly increased the serum chemerin level. Both the middle- and high-dose ethanol significantly increased the chemerin level in the VAT of rats. In humans, triglyceride, fasting glucose, insulin and HOMA-IR were independently associated with chemerin. In rats, the serum chemerin level was positively correlated with chemerin in the VAT after adjustments for the liver chemerin (r=+0.768). High-dose ethanol significantly increased the body fat in humans and the VAT in rats. CONCLUSION: Chronic ethanol consumption dose-dependently increases the chemerin levels in the serum and VAT. The serum chemerin level is associated with metabolic parameters in humans. The increased serum chemerin level is mainly attributed to an elevation of chemerin in the VAT after the ethanol treatment.

Research progress of anti-γ-aminobutyric acid B receptor encephalitis and a case report of paraneoplastic associated encephalitis and treatment analysis.

Encephalitis is one of the common diseases in neurology. Early diagnosis and appropriate treatments are essential. Autoimmune encephalitis (AE) generally refers to a type of encephalitis mediated by autoimmune mechanisms. It is gradually considered to be an important cause of reversible encephalitis caused by noninfectious factors. It can occur in children, adolescents, and adults, and is clinically characterized by multifocal or diffuse brain damage such as personality changes, seizures, and cognitive impairment, with an overall good effect of immunotherapy. According to the clinical features of the patients, blood and cerebrospinal fluid tests, neuroelectrophysiology, cranial imaging, treatment and prognosis, AEs can be broadly divided into specific antigen (antibody)-related AEs and nonspecific antigen (or antibody) -related AEs. With the development of AEs research, more and more anti-neuron antibodies have been found, which provides an important reference for the diagnosis and treatment of AEs. Understanding the knowledge about AEs is important to discover new diseases and deepen the understanding of the immunopathological mechanisms of existing central nervous system diseases. Anti-γ-aminobutyric acid B (GABA-B) receptor encephalitis is a type of AE, but this disease is rare in AE, often develop to the clinical manifestations of marginal encephalitis, accompanied by obvious seizures or status epilepticus, Some patients had tumors, mainly small-cell carcinoma, prompt diagnosis, early immunotherapy and, if necessary, tumor treatment resulted in complete or partial neurological improvement in most patients.

An efficient strategy for digging protein-protein interactions for rational drug design - A case study with HIF-1α/VHL.

The ubiquitination of the hypoxia-inducible factor-1α (HIF-1α) is mediated by interacting with the von Hippel-Lindau protein (VHL), and is associated with cancer, chronic anemia, and ischemia. VHL, an E3 ligase, has been reported to degrade HIF-1 for decades, however, there are few successful inhibitors currently. Poor understanding of the binding pocket and a lack of in-depth exploration of the interactions between two proteins are the main reasons. Hence, we developed an effective strategy to identify and design new inhibitors for protein-protein interaction targets. The hydroxyproline (Hyp564) of HIF-1α contributed the key interaction between HIF-1α and VHL. In this study, detailed information of the binding pocket were explored by alanine scanning, site-directed mutagenesis and molecular dynamics simulations. Interestingly, we found the interaction(s) between Y565 and H110 played a key role in the binding of VHL/HIF-1α. Based on the interactions, 8 derivates of VH032, 16a-h, were synthesized by introducing various groups bounded to H110. Further assay on protein and cellular level exhibited that 16a-h accessed higher binding affinity to VHL and markable or modest improvement in stabilization of HIF-1α or HIF-1α-OH in HeLa cells. Our work provides a new orientation for the modification or design of VHL/HIF-1α protein-protein interaction inhibitors.

Overexpression of a novel chrysanthemum NAC transcription factor gene enhances salt tolerance in tobacco.

The plant-specific NAC (for NAM, ATAF1, 2 and CUC2) transcription factors (TFs) have been implicated in different cellular processes involved in stress responses such as cold, high salinity or drought as well as abscisic acid (ABA) signalling. However, the roles of the chrysanthemum NAC TF genes in plant stress responses are still unclear. A full-length cDNA designated DgNAC1, containing a highly conserved N-terminal DNA-binding NAC domain, has been isolated from chrysanthemum by RACE (rapid amplification of cDNA ends). It encodes a protein of 284 amino acids residues (=~32.9 kDa) and theoretical pI of 7.13. The transcript of DgNAC1 was enriched in roots and flowers than in stems and leaves of the adult chrysanthemum plants. The gene expression was strongly induced by ABA, NaCl, drought and cold treatment in the seedlings. Subcellular localization revealed that DgNAC1:GFP fusion protein was preferentially distributed to nucleus. To assess whether DgNAC1 is a practically useful target gene for improving the stress tolerance of chrysanthemum, we ectopically over-expressed the full-length DgNAC1 cDNA in tobacco and found that the 35S:DgNAC1 transgenic tobacco exhibited a markedly increased tolerance to salt. Despite this increased salt stress tolerance, the transgenic tobacco showed no detectable phenotype defects under normal growth conditions. These results proposed that DgNAC1 is appropriate for application in genetic engineering strategies aimed at improving salt stress tolerance in chrysanthemum.

Application value of molecular imaging technology in epilepsy.

Epilepsy is a common neurological disease with various seizure types, complicated etiologies, and unclear mechanisms. Its diagnosis mainly relies on clinical history, but an electroencephalogram is also a crucial auxiliary examination. Recently, brain imaging technology has gained increasing attention in the diagnosis of epilepsy, and conventional magnetic resonance imaging can detect epileptic foci in some patients with epilepsy. However, the results of brain magnetic resonance imaging are normal in some patients. New molecular imaging has gradually developed in recent years and has been applied in the diagnosis of epilepsy, leading to enhanced lesion detection rates. However, the application of these technologies in epilepsy patients with negative brain magnetic resonance must be clarified. Thus, we reviewed the relevant literature and summarized the information to improve the understanding of the molecular imaging application value of epilepsy.

Overexpression of nuclear transport factor 2 may protect against diabetic retinopathy.

PURPOSE: We performed human, animal, and in vitro studies to examine the potential role of nuclear transport factor 2 (NTF2) in conferring resistance to diabetic retinopathy (DR). METHODS: Blood NTF2 levels were assessed in two groups of patients with type 2 diabetes mellitus. Group P patients had a history of proliferative DR (PDR), while group N patients did not. The retinal vasculature was examined in diabetic rats three months after they received an intravitreal injection of a recombinant adeno-associated virus (rAAV) vector overexpressing NTF2 (rAAV2-NTF2). Control rats were treated with rAAV2 only. Rat retinal capillary endothelial cells (RRCECs) were infected with rAAV2-NTF2, or with a vector expressing siRNA targeted against NTF2, to assess the effects of overexpression and inhibition of NTF2 on vascular endothelial growth factor (VEGF) expression (mRNA and protein). RESULTS: There was a strong trend for patients with DR to have lower blood NTF2 levels compared to those who did not have DR (0.10+/-0.01 versus 0.20+/-0.08, p=0.079). There was significantly less retinal blood vessel leakage in diabetic rats infected with rAAV2-NTF2 compared to controls (16.5+/-2.9 versus 24.7+/-7.3, p=0.039). These rats exhibited normal retinal vasculature and blood-retinal barrier function. VEGF expression was inhibited by NTF2 overexpression and stimulated by NTF2 inhibition, (protein [0.41+/-0.05 versus 0.23+/-0.06] and mRNA [0.37+/-0.04 versus 0.23+/-0.06] p<0.01 for all). CONCLUSIONS: These finding suggest that NTF2 is a potential mediator of retinal vasculature integrity. NTF2 may act by altering VEGF expression, thereby influencing the development of DR in patients with diabetes mellitus.

Association Between Thyroid Nodules and Volume and Metabolic Syndrome in an Iodine-Adequate Area: A Large Community-Based Population Study.

Background: Given its high incidence, thyroid nodule (TN) warrants public attention. Thyroid volume (TV) has also been associated with multiple factors, such as iodine deficiency and supply and body mass index. It is well known that metabolic syndrome (MetS) comprises many metabolic disturbances, with insulin resistance being its major component. Materials and Methods: The aim of this study was to investigate the relationship between TN and TV and MetS and its components in an iodine-adequate area in Asia. All participants were asked to complete a questionnaire. After excluding 938 individuals based on the exclusion criteria, we reviewed data from 927 of 1865 participants. Adopting MetS diagnostic criteria, we found 437 subjects to be MetS positive [MetS(+)] and 490 subjects to be MetS negative [MetS(-)], respectively. Multivariate linear regression was used to assess the relationship between TNs and MetS. Moreover, univariate binary logistic regression analyses were used to calculate odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the associations between different variables and TNs. Results: A total of 232 females and 205 males were MetS(+), as diagnosed using the International Diabetes Federation criteria. However, there were 330 females and 160 males in the group of MetS(-) individuals. The prevalence of TNs was 38.29% in the MetS(+) group and 17.79% in the MetS(-) group. After adjusting for systolic blood pressure, diastolic blood pressure, and gender, only high-density lipoprotein, waist circumference (WC), and age were related to TNs (OR = 0.45, 95% CI 0.27-0.75, P = 0.0023; OR = 1.04, 95% CI 1.02-1.06, P = 0.0036). The TV of all participants was 13.98 (11.24, 17.01) mL; 13.26 (10.62, 16.17) mL for females and 14.96 (11.83, 18.01) mL for males. It was found that only WC was related to TV, after controlling for sex and age (P = 0.02). Conclusions: The morbidity among TN patients in the MetS(+) group was higher than that among the MetS(-) group. High-density lipoprotein cholesterol emerged as a protective factor, and WC was a risk factor for TN. Moreover, TV was related to MetS, and WC was an independent risk factor for TV.

[Relationship between vascular endothelial growth factor C expression level and lymph node metastasis in non small cell lung cancer].

OBJECTIVE: To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression level and lymph node metastasis in non small cell lung cancer (NSCLC). METHODS: Fifty-two NSCLC patients, 38 males and 14 females, aged (59+/-11) (29-77), were divided into 2 groups based on the pathological examination: lymph node metastasis positive group (n=25) and lymph node metastasis negative group (n=27). RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of VEGF-C in the tumor tissues and lymph nodes resected during operation. RESULTS: The VEGF-C mRNA expression level in the lung tumor tissue of the lymph node metastasis positive group was 0.273+/-0.179, significantly higher than that in the lymph node metastasis negative group (0.089+/-0.087, P<0.01). The VEGF-C mRNA expression level in the positive lymph node of the lymph node metastasis positive group was 0.207+/-0.174, significantly higher than that in the lymph node metastasis negative group (0.114+/-0.107, P<0.01), but not significantly different from that in the negative lymph nodes of the same group(0.196+/-0.186, P>0.05). The VEGF-C protein positive rate of the lung cancer tissues of the lymph node metastasis positive group was 93.3% (14/15), significantly higher than that of the lymph node metastasis negative group (6.7%, 1/15, P<0.01). The VEGF-C protein positive rate of the metastasis positive lymph noses was 80.4% (37/46), and all 52 metastasis negative lymph nodes were VEGF-C protein negative. CONCLUSION: VEGF-C mRNA and protein expression levels predict lymph node metastasis and can be useful predictors of lymph node metastasis in NSCLC.

Atherogenic Index of Plasma is Associated with Body Fat Level in Type 2 Diabetes Mellitus Patients.

OBJECTIVE: To investigate the characteristics of body fat distribution and the relationship between body fat index and Atherogenic Index of Plasma (AIP) in Type 2 Diabetes Mellitus (T2DM) patients. METHODS: A total of 316 participants were divided into a T2DM group and a non-diabetes group (controls). According to the Visceral Fat Area (VFA), all participants were further divided into VFA ≥100 cm2 and VFA <100 cm2 groups. To compare the differences of blood lipid, blood glucose, body fat index and AIP between the 2 groups, single factor correlation analysis was used to determine the correlation between the indexes and AIP, and multiple linear regression was used to analyse the correlation between the related factors and AIP. RESULTS: The body fat index (including body fat content, Percentage of Body Fat (PBF), Waist to Hip Fat Ratio (WHR) and VFA), Triglyceride (TG), Fasting Insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and AIP in T2DM group were significantly higher than in the control group, while High Density Lipoprotein Cholesterol (HDL-C) level was significantly higher in the control group. In the VFA≥100 cm2 group, TG, Low Density Lipoprotein Cholesterol (LDL-C), FINS, HOMAIR and AIP were all higher than that in the VFA <100 cm2 group. There was a positive correlation between AIP and VFA, body fat content, percentage of body fat, and WHR, respectively. There was also a negative correlation between AIP and HDL-C, which was not related to age, sex, Fasting Glucose (FPG), glycosylated haemoglobin (HbA1c), Total Cholesterol (TC), LDL-C and course of disease. Compared with the VFA <100 cm2 group, the VFA ≥100 cm2 group had higher blood Uric Acid (UA) levels and UA was positively correlated with VFA. After correcting the effect of UA on AIP, VFA was still an independent related factor of AIP, and VFA increased the risk of atherosclerosis by increased UA. CONCLUSION: T2DM patients have the abnormal distribution of body fat and a high VFA, which was associated with AIP.

[Expression of HDGF and its implication in stage I non-small cell lung cancer].

OBJECTIVE: To evaluate the expression of HDGF and its implication in patients who undergone radical resection for stage I non-small cell lung cancer. METHODS: Immunohistochemical technique was applied to detect the expression of HDGF in 118 lung cancer tissues and 30 normal lung tissues as control. At the same time, the expression of VEGF and Ki-67 labeling rate of the tumors was evaluated. RESULTS: HDGF expression was observed in all cases, and significantly higher than that in normal lung tissues (52.23 +/- 10.35 vs. 156.73 +/- 70.95, P < 0.01). Expresson of HDGF was closely related to histological classification, and the expression in adenocarcinoma was much stronger than that in squamous cell cancers (P = 0.001), but not related to other clinicopathological factors. VEGF expression was closely related to the expression of HDGF. HDGF expression in the VEGF high expression group was much higher than that in VEGF low expression group (171.77 +/- 81.07 vs. 142.81 +/- 59.84, P = 0.028). Ki-67 expression was also closely related to the expression of HDGF, the labeling rate of Ki-67 in high HDGF expression group was much higher than that in low HDGF expression group (30.49% +/- 7.88% vs. 17.80% +/- 5.63%, P = 0.001). Univariate analysis showed that the patients with high HDGF expression had a shorter overall survival than that with low HDGF expression (40.0% vs. 77.5%, P = 0.008), and multivariate Cox regression analysis showed that HDGF was a significantly independent predictive factors for patients with stage I NSCLC (RR = 1.011, P = 0.002). CONCLUSION: HDGF expression is upgraded in postoperative stage I non-small cell lung cancer patients. HDGF is a significantly independent predictive factor for patients with stage I NSCLC. HDGF may play an important role on carcinogenesis and development of stage I NSCLC through promoting cell proliferation and neoangiogenesis of the tumor.