Anomalous staged hot-electron acceleration by two-plasmon decay instability in magnetized plasmas.

We present a staged hot-electron acceleration mechanism of the two-plasmon decay (TPD) instability in the transverse magnetic field under the parameters relevant to inertial confinement fusion experiments. After being accelerated by the forward electron plasma wave (FEPW) of TPD, the hot-electrons can be anomalously accelerated again by the backward electron plasma wave (BEPW) of TPD and then obtain higher energy. Moreover, the surfatron acceleration mechanism of TPD in the magnetic field is also confirmed, the electrons trapped by the TPD daughter EPWs are accelerated in the direction along the wave front. Interestingly, the velocity of electrons accelerated by surfing from the FEPW is quite easily close to the BEPW phase velocity, which markedly enhances the efficiency of the staged acceleration. The coexistence of these two acceleration mechanisms leads to a significant increase of energetic electrons generated by TPD in the magnetic field. Meanwhile the EPWs are dissipated, TPD instability is effectively suppressed, and the laser transmission increases.

Kinetic model and Vlasov simulation verification of two-ion decay instability.

A kinetic theory is developed to describe the longitudinal decay of two-ion decay (TID): The pump ion-acoustic wave (IAW) decays into two daughter IAWs with a longer wavelength. The instability growth rate and threshold are given by the theory. Both the simulations of full kinetic Vlasov and hybrid Vlasov (kinetic ions and Boltzmann electrons) are employed to verify the theory and have a high quantitative agreement with the theory for 8≤ZT_{e}/T_{i}≤15, where Z is the ion charge number and T_{i}(T_{e}) is the ion (electron) temperature. The kinetic model developed here solves a long-standing problem that the simple fluid theory underestimates growth rate by a factor of 2∼3. Also, a reasonable explanation is given to the typical characteristics of TID that the dependence curves of subharmonic growth rate γ and wave number k.

[Association study between haplotypes of WNT signaling pathway genes and nonsyndromic oral clefts among Chinese Han populations].

OBJECTIVE: To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios. METHODS: The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07). RESULTS: After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4). CONCLUSION: This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.

Polarization conversion in the caviton driven by linearly polarized lasers.

In one-dimensional particle-in-cell simulations of a plasma irradiated by linearly polarized lasers from both sides of boundaries, it is found that there is an appreciable growth of the electromagnetic field in cavitons in the transverse direction perpendicular to the direction of polarization, which indicates the polarization conversion of the electromagnetic field in cavitons. This paper demonstrates the mechanism of this phenomenon based on parametric resonance induced by ponderomotive force with twice the frequency of the electromagnetic radiation in the caviton. We develop a theoretical model and verify it with simulation results. This phenomenon contributes to the heating and acceleration of particles and traps more EM energy in cavitons.

RNAseq reveals extensive metabolic disruptions in the sensitive SF-295 cell line treated with schweinfurthins.

The schweinfurthin family of natural compounds exhibit a unique and potent differential cytotoxicity against a number of cancer cell lines and may reduce tumor growth in vivo. In some cell lines, such as SF-295 glioma cells, schweinfurthins elicit cytotoxicity at nanomolar concentrations. However, other cell lines, like A549 lung cancer cells, are resistant to schweinfurthin treatment up to micromolar concentrations. At this time, the precise mechanism of action and target for these compounds is unknown. Here, we employ RNA sequencing of cells treated with 50 nM schweinfurthin analog TTI-3066 for 6 and 24 h to elucidate potential mechanisms and pathways which may contribute to schweinfurthin sensitivity and resistance. The data was analyzed via an interaction model to observe differential behaviors between sensitive SF-295 and resistant A549 cell lines. We show that metabolic and stress-response pathways were differentially regulated in the sensitive SF-295 cell line as compared with the resistant A549 cell line. In contrast, A549 cell had significant alterations in response genes involved in translation and protein metabolism. Overall, there was a significant interaction effect for translational proteins, RNA metabolism, protein metabolism, and metabolic genes. Members of the Hedgehog pathway were differentially regulated in the resistant A549 cell line at both early and late time points, suggesting a potential mechanism of resistance. Indeed, when cotreated with the Smoothened inhibitor cyclopamine, A549 cells became more sensitive to schweinfurthin treatment. This study therefore identifies a key interplay with the Hedgehog pathway that modulates sensitivity to the schweinfurthin class of compounds.

Heavy metals as risk factors for human diseases - a Bayesian network approach.

Modern industrial agricultural processes expose human beings to multifactorial environmental pollution including heightened levels of heavy metals. The effects of acute heavy metal exposures at toxic levels are usually known; they are tested for and treated promptly. The effects of low/moderate-level chronic heavy metal exposures are less known as they may be subclinical, and pathogenic effects may only manifest clinically over time under the disguise of a diagnosable disease or miscellaneous symptoms attributed to aging. Consequently, the health impact of low-moderate heavy metal exposure is unlikely to be identified. Furthermore, established heavy metal safety levels often fail to recognize the potential toxic effects on humans. We report in this review what is known about the sub-chronic and chronic effects of exposure to heavy metals, particularly lead, mercury, cadmium, arsenic, and nickel, and we highlight their possible effects in the brain, cardiovascular and endocrine-metabolic systems, and on reproduction.

[Analysis on human papillomavirus infection in 2 110 patients with cervical cancer in Henan province].

Objective: To explore human papillomavirus (HPV) infection status in 2 110 patients with cervical cancer in Henan province and analyze the main infection subtypes. Methods: A total of 2 110 patients with cervical cancer were detected for HPV subtypes by flow-through hybridization after PCR. The results were analyzed. Results: Among 2 110 patients with cervical cancer, 1 856 were detected to be HPV positive and the infection rate was 87.96%(95%CI: 86.57%-89.35%). The top six genotypes were HPV16, 58, 18, 52, 35 and 33. Single infection was the main type of infection in HPV positive cervical cancer patients (77.48%), and double infection was the second type infection(16.76%). The infection rate of HPV16 was 60.19%, occupying a predominant position in single or multiple infections. Among HPV positive cervical cancer patients, 1 599 cases were detected to be infected with high-risk subtypes and covered by nine-valence HPV vaccine, and the coverage rate reached 86.15% (1 599/1 856). Cervical cancer patients were mainly distributed in age group 40- years. The main HPV subtypes of cervical cancer patients were different among different age groups, but HPV16 subtype was in a predominant position in any age group. Conclusions: The main subtypes of HPV infection were HPV16, 58, 18, 52, 35 and 33 in cervical cancer patients in this study. The main infection type was single infection. There were more cervical cancer patients in age group 40- years.

[Transepidermal water loss of scar skin in three types of scar patients and its correlation with scar severity].

Objective: To study the transepidermal water loss (TEWL) of scar skin in patients with superficial scars, hypertrophic scars, and atrophic scars, and to explore the correlation between TEWL and scar severity. Methods: A retrospective observational study was conducted. From February 2017 to February 2019, 120 scar patients who met the inclusion criteria were admitted to the General Hospital of Jilin Chemical Industry Group, including 78 males and 42 females, aged (35±14) years. According to the diagnosis on admission, there were 40 cases of superficial scar patients, 40 cases of hypertrophic scar patients, and 40 cases of atrophic scar patients. On admission, the Vancouver Scar Scale (VSS) was used to score the scar of each patient; the TEWL of scar skin and normal skin 1 cm from the edge of scar or the same site of the healthy side (hereinafter referred to as normal skin) of each patient was measured by water loss tester, and the difference value of TEWL between scar skin and normal skin (hereinafter referred to as the TEWL difference) was calculated. Data were statistically analyzed with chi-square test, Kruskal-Wallis rank sum test, paired sample t test, one-way analysis of variance, and Dunnett-t test for comparison, and the correlation between the difference value of TEWL and scar VSS score was analyzed with univariate linear regression analysis. Results: On admission, the scar VSS score of superficial scar patients was significantly lower than that of hypertrophic scar or atrophic scar patients (t=4.403, 4.768, P<0.01), and the scar VSS score of atrophic scar patients was significantly lower than that of hypertrophic scar patients (t=4.185, P<0.01). On admission, the TEWL of scar skin of superficial scar, hypertrophic scar, and atrophic scar patients were (18±4), (20±4), and (20±5) g·m-2·h-1 respectively, significantly higher than (12±3), (12±3), and (14±4) g·m-2·h-1 of normal skin (t=6.889, 10.221, 5.870, P<0.01). The difference values of TEWL of superficial scar, hypertrophic scar, and atrophic scar patients were (5.9±1.7), (8.1±1.7), and (6.4±2.1) g·m-2·h-1 respectively. In comparison among different types of scar patients, only the TEWL difference of hypertrophic scar patients was significantly higher than that of superficial scar patients (t=6.975, P<0.05). The TEWL difference and the scar VSS score in patients with superficial scars, hypertrophic scars, and atrophic scars were significantly positively correlated (r=0.805, 0.872, 0.826, P<0.01). Conclusions: The TEWL of scar skin in patients with superficial scars, hypertrophic scars, and atrophic scars is increased compared with normal skin, and the degree of increase was positively correlated with the severity of scars.

[Evaluating the effect of WNT pathway genes considering interactions on the risk of non-syndromic oral clefts among Chinese populations].

OBJECTIVE: In this study, we used genome-wide association study (GWAS) data to explore whether WNT pathway genes were associated with non-syndromic oral clefts (NSOC) considering gene-gene interaction and gene-environment interaction. METHODS: We conducted the analysis using 806 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios and 202 non-syndromic cleft palate (NSCP) case-parent trios among Chinese populations selected from an international consortium established for a GWAS of non-syndromic oral clefts. Genotype data and maternal environmental exposures were collected through DNA samples and questionnaires. Conditional Logistic regression models were adopted to explore gene-gene interaction and gene-environment in teraction using trio package in R software. The threshold of significance level was set as 3.47×10-4 using Bonferroni correction. RESULTS: A total of 144 single nucleotide polymorphisms (SNPs) in seven genes passed the quality control process in NSCL/P trios and NSCP trios, respectively. Totally six pairs of SNPs interactions showed statistically significant SNP-SNP interaction (P < 3.47×10-4) after Bonferroni correction, which were rs7618735 (WNT5A) and rs10848543 (WNT5B), rs631948 (WNT11) and rs556874 (WNT5A), and rs631948 (WNT11) and rs472631 (WNT5A) among NSCL/P trios; rs589149 (WNT11) and rs4765834 (WNT5B), rs1402704 (WNT11) and rs358792 (WNT5A), and rs1402704 (WNT11) and rs358793 (WNT5A) among NSCP trios, respectively. In addition, no significant result was found for gene-environment interaction analysis in both of the NSCL/P trios and NSCP trios. CONCLUSION: Though this study failed to detect significant association based on gene-environment interactions of seven WNT pathway genes and the risk of NSOC, WNT pathway genes may influence the risk of NSOC through potential gene-gene interaction.

Reconfigurable sensor and nanoantenna by graphene-tuned Fano resonance.

With the rapid developments in compact devices, the multi-function and reconfigurability of nanostructures are highly appreciated, while still very challenging. A majority of devices are usually mono-functional or hard to switch between different functions in one design. In this paper, we proposed graphene-wrapped core-shell nanowires to realize real-time reconfigurable sensors and nanoantenna by tuning the Fermi energies of graphene layers at the surfaces of core and shell, respectively. Owing to the electromagnetic coupling between the two graphene layer, two corresponding Fano resonances of scattering can arise in the Terahertz spectrum, which arises from the interference of bright modes and dark modes. Around the Fano resonances, the scattering can be considerably resonant (as an antenna) or suppressed (as a sensor). Interestingly, the field distributions are distinct at the suppressed scattering states for the two Fano resonances. The presented reconfigurable nanostructures may offer promising potentials for integrated and multi-functional electromagnetic control such as dynamic sensing and emission.

[Study regarding the parent-of-origin effect of WNT pathway genes on non-syndromic cleft lip with or without cleft palate among the Chinese population].

Objective: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with its genetic evidence widely explored. This study explored the potential the parent-of-origin (PoO) effect of WNT pathway on the risks of NSCL/P, using a case-parent trio design. Methods: Data on the single nucleotide polymorphism (SNP) of WNT genes were selected from a genome-wide association study (GWAS). A total of 806 Chinese non-syndromic cleft lip patients, with or without cleft palate (NSCL/P) case-parent trios, were gathered from an international consortium. PoO effect of WNT pathway genes and its haplotypes were explored by log-linear models. Additional Wald tests were performed to assess: a) the heterogeneity of PoO effect between different maternal exposures, b) the interaction between PoO effect, c) maternal exposure to environmental tobacco smoke (ETS), and d) multivitamin supplementation during pregnancy. The threshold for statistical significance was adjusted as 3.47×10(-4), according to Bonferroni correction. Results: After quality control, a total of 144 SNPs within seven genes were included for analyses, among which 8 SNPs were of potential PoO effect (P<0.05). However, none of them achieved the statistical significance after Bonferroni correction. The haplotype rs4074668-rs12725747 (T-A) on WNT9A showed significant PoO effect, based on the haplotype test for PoO (P=2.74×10(-4)). In addition, no statistically significant interaction was found in further exploration of this haplotype under environmental exposures as ETS or multivitamin supplementation. Conclusions: Genes in the WNT pathway may influence the NSCL/P risks through the potential PoO effect. Particularly, the haplotype rs4074668-rs12725747 (T-A) on WNT9A presented significant PoO effect on NSCL/P, statistically. From this current study, findings on WNT pathway related risks among the NSCL/P, need to be further validated by independent samples in the future.

LncRNA HOTAIR participates in the development and progression of adrenocortical carcinoma via regulating cell cycle.

OBJECTIVE: To explore the role of HOTAIR in the pathogenesis of adrenocortical carcinoma (ACC) and its underlying mechanism. PATIENTS AND METHODS: Differentially expressed lncRNA (HOTAIR) in ACC was screened out from the GEO database. The survival analysis and ROC curve were performed according to HOTAIR expressions in ACC patients. The correlation between HOTAIR expression and clinical information of ACC patients was analyzed by chi-square test. The univariate and multivariate COX regression analysis was carried out to analyze the relationship between HOTAIR expression, disease-free survival (DFS) and overall survival (OS) of ACC patients. We then detected HOTAIR expression in 77 ACC tissues and 30 normal tissues by qRT-PCR (quantitative Real-time polymerase chain reaction). ACC cell lines were further screened out for the following in vitro experiments. After altering HOTAIR expression in ACC cells by plasmid transfection, proliferation and cell cycle were detected by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Finally, Western blot was utilized to detect expressions of cell cycle-related genes in ACC cells. RESULTS: HOTAIR was overexpressed in ACC tissues than that of normal tissues. HOTAIR expression was remarkably increased in ACC with T3 and T4 stage than that of T1 and T2 stage. Moreover, HOTAIR expression was remarkably increased in ACC with stage III and IV than that of stage I and II. HOTAIR was an independent prognostic factor for DFS and OS of ACC patients. For in vitro experiments, inhibited proliferation and arrested cell cycle were observed in H295R cells transfected with si-HOTAIR. Opposite results were obtained after SW-13 cells were transfected with HOTAIR overexpression plasmid. Furthermore, expressions of cell cycle-related genes, including Cyclin D1, p-Rb and p-GSK3ß were remarkably decreased after HOTAIR knockdown. CONCLUSIONS: We demonstrated for the first time that HOTAIR is overexpressed in ACC and is a prognostic risk factor in ACC patients. HOTAIR participates in the development and progression of ACC via shortening cell cycle and promoting proliferation of ACC cells.

Variability of serum concentrations of cystatin C and urinary retinol-binding protein, neutrophil gelatinase-associated lipocalin, immunoglobulin G, and C-reactive protein in dogs.

BACKGROUND: Markers of kidney dysfunction and damage have potential to detect chronic kidney disease (CKD) in early stages. However, data on long-term variation of these markers in healthy dogs is lacking and is crucial for the interpretation of results. HYPOTHESIS/OBJECTIVES: To determine temporal variations of serum cystatin C (sCysC) and urinary retinol-binding protein (uRBP), neutrophil gelatinase-associated lipocalin (uNGAL), immunoglobulin G (uIgG), and C-reactive protein (uCRP) in healthy dogs. ANIMALS: Eight clinically healthy adult Beagles were evaluated. METHODS: Longitudinal observational study. Serum cystatin C was determined by particle-enhanced nephelometric immunoassay. Urinary retinol-binding protein, uNGAL, uIgG and uCRP were determined by ELISA and concentrations were indexed to urinary creatinine. Within- and between-dog variance components (VC) and within-dog coefficients of variation (CV) were determined from blood and urine collected at eight time points over 1.5 years. RESULTS: Urinary C-reactive protein (uCRP) concentrations were consistently below the detection limit (5.28 ng/mL). Mean ± within-dog standard deviation for sCysC, uRBP/c, uNGAL/c and uIgG/c was 0.15 ± 0.01 mg/L, 0.09 ± 0.03 mg/g, 2.32 ± 2.03 µg/g and 12.47 ± 10.98 mg/g, respectively. Within-dog CV for sCysC, uRBP/c, uNGAL/c and uIgG/c was 8.1%, 33.7%, 87.2% and 88.1%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum cystatin C, uRBP/c, uNGAL/c and uIgG/c exhibit a wide range of long-term within-dog variability. Researchers and veterinarians might need to take this into account when interpreting their results. To assess their diagnostic and predictive ability, future studies need to establish reference ranges for healthy dogs and dogs with CKD.

MiR-7 regulates the PI3K/AKT/VEGF pathway of retinal capillary endothelial cell and retinal pericytes in diabetic rat model through IRS-1 and inhibits cell proliferation.

OBJECTIVE: To investigate the role of miR-7 in diabetic retinopathy and the underlying mechanism. MATERIALS AND METHODS: The rat model of diabetic retinopathy (DR) was established. After that, the endothelial cell (EC) and retinal pericyte (RP) were isolated. QRT-PCR was used to detect the expression of miR-7 and insulin receptor substrate-1 (IRS-1) in ECs and RPs cells while the protein level of IRS1 was detected by Western blot. miR-7 mimic and miR-7 inhibitor were transfected to achieve miR-7 overexpression or knockdown. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay after miR-7 overexpression or knockdown. Besides, the expression levels of PI3K, AKT, and VEGF were detected by Western Blot. The luciferase reporter assay was performed to investigate whether miR-7 could be combined with IRS-1. Conversely, whether miR-7 could affect IRS-1 was also verified. RESULTS: miR-7 expression was significantly decreased in ECs and RPs of the experimental group compared with the control group, while the mRNA and protein levels of IRS-1 were increased. The CCK-8 assay showed that overexpression of miR-7 decreased the cell activity in ECs and RPs. In contrast, knock-down of miR-7 could increase the cell viability. Besides, Western blot showed that after overexpression of miR-7, the expressions of PI3K, AKT, and VEGF in ECs and RPs cells were down-regulated. Meanwhile, miR-7 knockdown upregulated the protein levels of PI3K, AKT, and VEGF. The luciferase reporter assay suggested that the 3'UTR region of IRS-1 could be combined with miR-7, which may be the downstream target gene for miR-7. Moreover, knockdown of IRS-1 could reverse the effect of the miR-7 inhibitor on cell proliferation in the diabetic model. CONCLUSIONS: MiR-7 was lowly expressed in ECs and RPs cells. Overexpression of miR-7 can down-regulate the expression levels of PI3K, AKT, and VEGF by down-regulating its downstream target gene IRS-1, and ultimately inhibit the proliferation of retinal cells.

[Progress in next-generation sequencing research of non-syndromic oral clefts].

Non-syndromic oral clefts (NSOC) are among the most common birth defects. The prevalence of NSOC is 1.13-1.30 per 1 000 live births in China, which is higher than those in other major ethnic groups. The etiology of NSOC is complex and heterogeneous, which involves both genetic and environmental risk factors. Although genome-wide association studies have identified a number of risk loci, these loci can only account for a small proportion of the heritability of NSOC. The next-generation sequencing research provides new ideas for further exploring the genetic risk factors of NSOC. This paper summaries the progress in the next-generation sequencing research of NSOC.

Low expression of miR-597 is correlated with tumor stage and poor outcome in breast cancer.

OBJECTIVE: MicroRNAs (miRNAs) have been reported to play important roles in the progression of breast cancer (BC). In the present study, we aimed to explore the association between miR-597 expression level and prognosis of BC. PATIENTS AND METHODS: The expression levels of miR-597 were measured using quantitative Real-time polymerase chain reaction (qRT-PCR) analysis. The association between miR-597 expression and clinicopathological factors was analyzed. Differences in BC patient survival were determined using the Kaplan-Meier method and log-rank test. The prognostic value of miR-597 was further verified using the Cox proportional hazards regression model. RESULTS: Our data indicated that miR-597 was lowly expressed in BC compared with adjacent non-malignant tissues (p<0.001). Low miR-597 expression was observed to be closely associated with positive lymph node metastasis (p=0.001), higher TNM stage (p = 0.003), and poorer pathological differentiation (p=0.006). Furthermore, patients with lower levels of miR-597 expression had a shorter overall survival time than patients with higher miR-597 expression levels (p=0.009). In addition, multivariate Cox proportional hazards model analysis confirmed that miR-597 was an independent prognostic indicator of overall survival (p=0.005; HR 2.273; CI 95%, 1.117-4.291). CONCLUSIONS: We showed, for the first time, that decreased miR-597 expression suggested unfavorable prognosis for BC patients.

Evidence of interaction between genes in the folate/homocysteine metabolic pathway in controlling risk of non-syndromic oral cleft.

OBJECTIVE: Little consistent evidence is available for the association between the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P) and any of the individual genes in the folate/homocysteine metabolic pathway. We investigated the genes in the folate pathway to further clarify its potential influence on the risk of NSCL/P considering gene-gene (G×G) interaction. SUBJECTS AND METHODS: We selected markers in 18 genes from the pathway and applied Cordell's method to test for G×G interaction using 1,908 NSCL/P case-parent trios ascertained in an international consortium where a genomewide association study (GWAS) of oral clefts was conducted. RESULTS: We found intriguing signals among Asian and European ancestry groups for G×G interaction between markers in betaine-homocysteine methyltransferase gene (BHMT/BHMT2) and dimethylglycine dehydrogenase gene (DMGDH) attaining genomewide significance. In the pooled data, the top significant interaction was found between rs13158309 (BHMT) and rs10514154 (DMGDH, p = 1.45 × 10-12 ). CONCLUSIONS: Our study illustrated the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P, and this study suggested both BHMT/BHMT2 and DMGDH should be considered as candidate genes for NSCL/P in future studies.

[The value of (18)F-FDG PET-CT imaging in predicting the malignant potential of GIST].

Objective: To evaluate the value of (18)F-FDG PET-CT in predicting the malignant potential of Gastrointestinal Stromal Tumors (GIST). Methods: The clinical and pathological features of 31 patients with GIST confirmed by surgery or biopsy were retrospectively analyzed. The malignant potential of GIST before treatment was assessed by (18)F-FDG PET-CT. The GIST risk classification was graded according to the Standard revised by the National Institutes of Health (NIH) in 2008. The relationship between the maximal standard uptake value (SUVmax) and GIST risk classification, tumor diameter, Ki-67 index, and mitotic count were analyzed respectively. The cut-off level of SUVmax for the diagnosis of malignant GIST was calculated from the Receiver Operating Characteristic (ROC) curve. Results: Among the 31 cases of GIST patients, 14 cases were gastric primary (stomach group) and 17 cases were nongastric primary (outside stomach group). The SUVmax, tumor diameter, Ki-67 index and mitotic count of the 31 patients were 8.21±4.68, (7.82±5.12)cm, (10.03±11.07)% and (12.29±10.55)/50 HPF, respectively. SUVmax was significantly correlated with GIST risk classification (r=0.727, P<0.01), but not with tumor diameter, Ki-67 index and mitotic count (r=0.348, r=0.284, r=0.290, P=0.055, P=0.121, P=0.114). The SUVmax, tumor diameter, Ki-67 index and mitotic count in the stomach group were 4.36±2.36, (6.08±4.31)cm, (3.43±3.03)% and (5.71±2.20)/50 HPF, respectively. SUVmax was significantly correlated with tumor diameter, GIST risk classification and Ki-67 index (r=0.682, r=0.868, r=0.732, P<0.01) but not with mitotic count (r=0.510, P=0.063). The SUVmax of the GIST in the gastric group and the outside gastric group were 4.36±2.36 and 10.68±5.50, respectively. The difference was statistically significant (P=0.001). The SUVmax in the malignant group of GIST (middle or high risk grade) was 8.90±4.89, which was significantly higher than 2.22±0.86 in the benign group (low or very low risk grade). The difference was statistically significant between the two group (P<0.01). ROC curve analysis showed that a SUVmax cut-off of 3.75 was the most sensitive for predicting malignant GIST. When the area under the curve of 0.969, the sensitivity was 84.6% and the specificity was 100%. Conclusions: The SUVmax was strongly correlated with the GIST risk category and also with the tumor diameter and Ki-67 index in the gastric primary GIST, so it can be used as an effective indicator in predicting malignant potential of GIST before treatment.

Melatonin regulates traumatic optic neuropathy via targeting autophagy.

OBJECTIVE: Traumatic optic neuropathy (TON) usually refers to the indirect damage to the optical nerve, which can cause partial or complete blindness. Melatonin (MT) is a kind of indole hormone, and the retina is one of its natural sites of secretion in the human body. This study aims to explore MT in the retina and optic nerve injuries due to TON. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were used for TON model in the study. After operation, rats were treated with MT or phosphate buffered saline (PBS) for 4, 7, 14, 21, and 28 days before sacrifice. The changes in retinal ganglion cells (RGCs) were observed via hematoxylin-eosin (HE) staining. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was applied to observe apoptosis. Immunofluorescence staining was applied to detect caspase-3 and Western blot was used to detect LC3, cleaved caspase-3 and glyceraldehyde phosphate dehydrogenase (GAPDH). RESULTS: The number of RGCs in MT group increased compared to the model group. After MT treatment, the increased number of TUNEL positive cells and the increased number of caspase-3 positive cells in the retina of MT group was alleviated. Moreover, Western blot analysis revealed that the LC3-II/LC3-I ratio in the retinal tissue of MT group was further increased, while the increased cleaved caspase-3 protein level in the retina of MT group was alleviated compared to the model group. CONCLUSIONS: The results of this study revealed that MT therapy affects the apoptosis level of RGCs after TON through alleviating the increased caspase-3 protein level. Its mechanism may be that it further up-regulates the autophagy level of RGCs after TON, ultimately inhibiting the apoptosis of RGCs after TON and playing a neuroprotective role.