Cross-Cultural Generalizability of the First Year Inventory for Early ASD Screening in China.

The First Year Inventory (FYI) is a parent report screening measure, aimed at identifying the risk of autism spectrum disorder (ASD) in 12-month-old infants. This study aimed to investigate the utility of FYI within the Chinese community and develop a short version, encompassing both a low-risk sample and a high-risk sample comprising infants with older siblings diagnosed with ASD. Parents of 53 high-risk (HR) infants and 519 low-risk (LR) infants, aged 11 to 13 months, were recruited. After comparing response distributions across Chinese and American samples, a new factorial structure was developed according to the factor analyses. The construct validity and internal consistency of the two FYI versions were examined. The implementation of FYI in the HR sample was also assessed. Noteworthy disparities in response distribution were observed between the Chinese and American samples. Both FYI 2.0 and the FYI short version demonstrated moderate construct validity and internal consistency, with the FYI short version exhibiting better predictive ability in the HR sample. Significant lower risk scores was observed in the HR sample compared to the LR sample. These findings substantiate the applicability and validity of the Chinese short version of FYI. Future research should include follow-up assessments with the Chinese sample to evaluate cutoff scores, considering the cutoff between sensitivity and specificity and the sample?s characteristics.

Longer serum phosphorus time in range associated with lower mortality risk among peritoneal dialysis patients: a multicenter retrospective cohort study.

BACKGROUND: Relationship between serum phosphorus time in range and mortality risk in peritoneal dialysis (PD) patients remains uncertain. We aimed to evaluate the association between serum phosphorus time in range and all-cause mortality in Chinese PD population. METHODS: This was a multicenter, retrospective, cohort study of 1,915 patients collected from January 2008 to October 2020 in 4 Chinese centers. Serum phosphorus time in range was estimated as the months during the first year that a patient's serum phosphorus level was within the target range (defined as 1.13-1.78 mmol/L). The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) mortality and PD withdrawal. Cox proportional hazards regression model with comprehensive adjustments was used to assess the association. RESULTS: The primary outcome occurred in 249 (13.0%) PD patients over a median follow-up of 28 months. Overall, the serum phosphorus time in range was negatively associated with all-cause mortality (per 3-month increments, adjusted HR [aHR], 0.83; 95%CI: 0.75-0.92), CV mortality (per 3-month increments, aHR, 0.87; 95%CI: 0.77-0.99), and PD withdrawal (per 3-month increments, aHR, 0.89; 95%CI: 0.83-0.95). Competing-risk model showed that the relationship of serum phosphorus time in range with all-cause mortality remained stable. None of the variables including demographics, history of diabetes and CV disease, as well as several PD-related and clinical indicators modified this association. CONCLUSIONS: PD patients with longer serum phosphorus time in range in the first year was negatively associated with all-cause mortality and CV mortality. Our findings highlight the importance of maintaining serum phosphorus levels within 1.13-1.78 mmol/L for PD patients.

Apparent Treatment-Resistant Hypertension in the First Year Associated With Cardiovascular Mortality in Peritoneal Dialysis Patients.

BACKGROUND: Few reports have focused on the association between apparent treatment-resistant hypertension (aTRH) and cardiovascular (CV) mortality in peritoneal dialysis (PD) population, thus we conducted this retrospective cohort to explore it. METHODS: This was a retrospective cohort study conducted from January 2011 to January 2020 with PD patients in 4 Chinese dialysis centers. aTRH was defined according to the American College of Cardiology and American Heart Association guidelines. aTRH duration was calculated as the total number of months when patients met the diagnostic criteria in the first PD year. The primary outcome was CV mortality, and the secondary outcomes were CV events, all-cause mortality, combined endpoint (all-cause mortality and transferred to hemodialysis [HD]), and PD withdrawal (all-cause mortality, transferred to HD, and kidney transplantation). Cox proportional hazards models were used to assess the association. RESULTS: A total of 1,422 patients were finally included in the analysis. During a median follow-up period of 26 months, 83 (5.8%) PD patients incurred CV mortality. The prevalence of aTRH was 24.1%, 19.9%, and 24.6% at 0, 3, and 12 months after PD initiation, respectively. Overall, aTRH duration in the first PD year positively associated with CV mortality (per 3 months increment, adjusted hazards ratio [HR], 1.29; 95% confidence interval 1.10, 1.53; P = 0.002). After categorized, those with aTRH duration more than 6 months presented the highest adjusted HR of 2.92. Similar results were found for secondary outcomes, except for the CV event. CONCLUSIONS: Longer aTRH duration in the first PD year is associated with higher CV mortality and worse long-term clinical outcomes. Larger studies are warranted to confirm these findings. CLINICAL TRIALS REGISTRATION: There is no clinical trial registration for this retrospective study.

High definition transcranial direct current stimulation of the Cz improves social dysfunction in children with autism spectrum disorder: A randomized, sham, controlled study.

The purpose of this study was to determine the effect of the Cz of high-definition 5-channel tDCS (HD-tDCS) on social function in 4-12 years-old children with autism spectrum disorder (ASD). This study was a randomized, double-blind, pseudo-controlled trial in which 45 ASD children were recruited and divided into three groups with sex, age, and rehabilitation treatment as control variables. Each group of 15 children with ASD was randomly administered active HD-tDCS with the Cz as the central anode, active HD-tDCS with the left dorsolateral prefrontal cortex (F3) as the central anode, and sham HD-tDCS with the Cz as the central anode with 14 daily sessions in 3 weeks. The Social Responsiveness Scale Chinese Version (SRS-Chinese Version) was compared 1 week after stimulation with values recorded 1 week prior to stimulation. At the end of treatment, both the anodal Cz and anodal left DLFPC tDCS decreased the measures of SRS-Chinese Version. The total score of SRS-Chinese Version decreased by 13.08%, social cognition decreased by 18.33%, and social communication decreased by 10.79%, which were significantly improved over the Cz central anode active stimulation group, especially in children with young age, and middle and low function. There was no significant change in the total score and subscale score of SRS-Chinese Version over the Cz central anode sham stimulation group. In the F3 central anode active stimulation group, the total score of SRS-Chinese Version decreased by 13%, autistic behavior decreased by 19.39%, and social communication decreased by 14.39%, which were all significantly improved. However, there was no significant difference in effect between the Cz and left DLPFC stimulation conditions. HD-tDCS of the Cz central anode may be an effective treatment for social dysfunction in children with ASD.

Zerovalent Iron/Cu Combined Degradation of Halogenated Disinfection Byproducts and Quantitative Structure-Activity Relationship Modeling.

Previous studies have reported that zerovalent iron (ZVI) can reduce several aliphatic groups of disinfection byproducts (DBPs) (e.g., haloacetic acids and haloacetamides) effectively, and the removal efficiency can be significantly improved by metallic copper. Information regarding ZVI/Cu combined degradation of different types of halogenated DBPs can help understand the fate of overall DBPs in drinking water distribution and storage systems consisting of unlined cast iron/copper pipes and related potential control strategies. In this study, we found that, besides aliphatic DBPs, many groups of new emerging aromatic DBPs formed in chlorinated and chloraminated drinking water can be effectively degraded by ZVI/Cu; meanwhile, total organic halogen and total ion intensity were reduced significantly after treatment. Moreover, a robust quantitative structure-activity relationship model was developed and validated based on the ZVI/Cu combined degradation rate constants of 14 typical aromatic DBPs; it can predict the degradation rate constants of other aromatic DBPs for screening and comparative purposes, and the optimized descriptors indicate that DBPs possessing a lower value of the lowest unoccupied molecular orbital energy and a higher value of dipole moment tend to present higher degradation rate constants. In addition, toxicity data of 47 DBPs (belonging to 18 groups) were predicted by two previously established toxicity models, demonstrating that, although most DBPs exhibit higher toxicity than their dehalogenated products, some DBPs show lower toxicity than their lowly halogenated analogs.

Social Brain Network of Children with Autism Spectrum Disorder: Characterization of Functional Connectivity and Potential Association with Stereotyped Behavior.

Objective: To identify patterns of social dysfunction in adolescents with autism spectrum disorder (ASD), study the potential linkage between social brain networks and stereotyped behavior, and further explore potential targets of non-invasive nerve stimulation to improve social disorders. Methods: Voxel-wise and ROI-wise analysis methods were adopted to explore abnormalities in the functional activity of social-related regions of the brain. Then, we analyzed the relationships between clinical variables and the statistical indicators of social-related brain regions. Results: Compared with the typically developing group, the functional connectivity strength of social-related brain regions with the precentral gyrus, postcentral gyrus, supplementary motor area, paracentral lobule, median cingulum, and paracingulum gyri was significantly weakened in the ASD group (all p < 0. 01). The functional connectivity was negatively correlated with communication, social interaction, communication + social interaction, and the total score of the ADOS scale (r = -0.38, -0.39, -0.40, and -0.3, respectively; all p < 0.01), with social awareness, social cognition, social communication, social motivation, autistic mannerisms, and the total score of the SRS scale (r = -0.32, -0.32, -0.40, -0.30, -0.28, and -0.27, respectively; all p < 0.01), and with the total score of SCQ (r = -0.27, p < 0.01). In addition, significant intergroup differences in clustering coefficients and betweenness centrality were seen across multiple brain regions in the ASD group. Conclusions: The functional connectivity between social-related brain regions and many other brain regions was significantly weakened compared to the typically developing group, and it was negatively correlated with social disorders. Social network dysfunction seems to be related to stereotyped behavior. Therefore, these social-related brain regions may be taken as potential stimulation targets of non-invasive nerve stimulation to improve social dysfunction in children with ASD in the future.

Molecular interactions between bovine serum albumin (BSA) and trihalophenol: Insights from spectroscopic, calorimetric and molecular modeling studies.

The issue of disinfection byproducts (DBPs) in the water has received critical attention due to the health effects on humans. In the water environment, interactions between bovine serum albumins (BSA), the most abundant water-soluble protein, and DBPs unavoidably occur. In this study, comparative binding interactions of two aromatic DBPs - 2,4,6-trichlorophenol (TCP) and 2,4,6-tribromophenol (TBP) with BSA were investigated systematically utilizing fluorescence spectrometry, UV absorption spectrometry, isothermal titration calorimetry and molecular docking approach. The fluorescence quenching results indicated that TCP/TBP could quench the endogenous fluorescence of BSA through static quenching mechanisms, and TBP showed a more substantial quenching effect. The binding constants were determined for TCP-BSA (3.638 × 105 L/mol, 303 K) and TBP-BSA (6.394 × 105 L/mol, 303 K) complexes, with TBP showing higher binding affinity than TCP. The thermodynamic study and docking analysis suggested that hydrogen bonding and van der Waals forces were the primary interaction forces. Both of TCP and TBP were located in the subdomain IIIA of BSA, and TBP could form more stable complex than TCP. The results of the present study contributed valuable information on the environmental behaviors of halophenols in water environment from perspectives of binding with BSA.

Investigation on detoxication effects of 2-hydroxypropyl-ß-cyclodextrin over two halogenated aromatic DBPs 2,4,6-trichlorophenol and 2,4,6-tribromophenol binding with human serum albumin.

The health effects of disinfection byproducts (DBPs) in drinking water drew great attention recently. Herein, by using in vitro (fluorescence quenching, UV absorbance, circular dichroism) and in silico (molecular docking) method, binding interactions of two halophenolic DBPs (2,4,6-trichlorophenol [TCP] and 2,4,6-tribromophenol [TBP]) with human serum albumin (HSA) and the influence of hydroxypropyl-beta-cyclodextrin (HPCD) on the interactions were investigated. TCP/TBP could form complexes with HSA mainly by hydrogen bonding, while changing its secondary structure, among which TBP showed more influential effect. Interestingly, the binding constants for halophenol-HSA complexes decreased obviously with the involvement of HPCD. Molecular docking results revealed that HPCD could include TCP/TBP into its cavity and change their original binding sites from subdomain IB to IIA, resulting in a more stable binding system. These findings are beneficial for understanding the toxicity of halophenols inside the human body and indicated that HPCD could be a promising detoxication agent for DBPs.

Evaluation of adjuvant therapy for T1-2N1miM0 breast cancer without further axillary lymph node dissection.

Background: For breast cancer (BC) with sentinel lymph node micrometastases (SLNMs), there are limited data to guide the selection of postoperative adjuvant therapy. This study aimed to identify target populations who might benefit most from adjuvant therapy and examine prognostic factors among patients with T1-2N1miM0 BC with one or two SLNMs who underwent sentinel lymph node biopsy (SLNB) alone. Methods: There were 7,423 patients diagnosed with T1-2N1miM0 BC between 2010 and 2015, and patients with one or two SLNMs were extracted from the Surveillance, Epidemiology, and End Results database. All the patients underwent SLNB alone without further axillary lymph node dissection, and they were stratified according to adjuvant therapy. The statistical significance of categorical variables was analyzed using the χ 2 test. Univariable and multivariable Cox analyses were used to analyze characteristics predictive of Breast-cancer-specific survival and overall survival (OS). Kaplan-Meier methods with the log-rank test was analyzed to compare survival difference between the different treatments. Results: Adjuvant chemotherapy and radiotherapy improved 5-year OS rates. Multivariate analysis revealed that age ≥70 years, high grade, T2 stage, triple-negative subtype, and absence of radiotherapy were poor prognostic factors for OS. Patients who received breast-conserving surgery (BCS), and those with invasive ductal carcinoma (IDC), luminal A, luminal B, or basal-like subtype, and T1c or T2 stage benefited from adjuvant radiotherapy. Patients who received BCS, and those with IDC, luminal A subtype, and T1b, T1c, or T2 stage benefited from adjuvant chemotherapy. Conclusion: Our findings provide a clinical evaluation of treatment choice after surgery, which may help clinicians make individualized clinical decisions.

Comparative Quantitative Toxicology and QSAR Modeling of the Haloacetonitriles: Forcing Agents of Water Disinfection Byproduct Toxicity.

The haloacetonitriles (HANs) is an emerging class of nitrogenous-disinfection byproducts (N-DBPs) present in disinfected drinking, recycled, processed wastewaters, and reuse waters. HANs were identified as primary forcing agents that accounted for DBP-associated toxicity. We evaluated the toxic characteristics of iodoacetonitrile (IAN), bromoacetonitrile (BAN), dibromoacetonitrile (DBAN), bromochloroacetonitrile (BCAN), tribromoacetonitrile (TBAN), chloroacetonitrile (CAN), dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN), bromodichloroacetonitrile (BDCAN), and chlorodibromoacetonitrile (CDBAN). This research generated the first quantitative, comparative analyses on the mammalian cell cytotoxicity, genotoxicity and thiol reactivity of these HANs. The descending rank order for HAN cytotoxicity was TBAN ≈ DBAN > BAN ≈ IAN > BCAN ≈ CDBAN > BDCAN > DCAN ≈ CAN ≈ TCAN. The rank order for genotoxicity was IAN ≈ TBAN ≈ DBAN > BAN > CDBAN ≈ BDCAN ≈ BCAN ≈ CAN ≈ TCAN ≈ DCAN. The rank order for thiol reactivity was TBAN > BDCAN ≈ CDBAN > DBAN > BCAN > BAN ≈ IAN > TCAN. These toxicity metrics were associated with membrane permeability and chemical reactivity. Based on their physiochemical parameters and toxicity metrics, we developed optimized, robust quantitative structure activity relationship (QSAR) models for cytotoxicity and for genotoxicity. These models can predict cytotoxicity and genotoxicity of novel HANs prior to analytical biological evaluation.

Comparative cytotoxicity of halogenated aromatic DBPs and implications of the corresponding developed QSAR model to toxicity mechanisms of those DBPs: Binding interactions between aromatic DBPs and catalase play an important role.

Halogenated aromatic disinfection byproducts (DBPs) are a new group of emerging DBPs identified recently. They have been detected in disinfected drinking water, wastewater effluents, recreational water and oil/gas produced water, at concentrations of ng/L to µg/L in general. Previously studies have demonstrated that most of them can induce developmental toxicity and growth inhibition in aquatic organisms based on in vivo bioassays. In this study, to further understand the adverse effects of aromatic DBPs to human health, the comparative cytotoxicity of 15 halogenated aromatic DBPs belonging to four subgroups (i.e., halophenols, halonitrophenols, halohydroxybenzaldehydes and halohydroxybenzoic acids) was evaluated with mammalian Chinese Hamster Ovary cells. The results indicated that the selected aromatic DBPs exhibited an in vitro toxicity rank order of halonitrophenols > halophenols > halohydroxybenzaldehydes > halohydroxybenzoic acids. The potential toxicity mechanisms involved with the antioxidant system were investigated by using molecular docking analysis between key antioxidant enzymes (i.e., catalase, superoxide dismutase, and glutathione S-transferase) and aromatic DBPs. Based on the observed cytotoxicity data and screening the candidate descriptors (including binding energies between the aromatic DBPs and key antioxidant enzymes as well as physical-chemical/quantum-chemical/topological descriptors), a QSAR model was developed as log (LC50) -1 = - 1.050ECAT + 0.300EHOMO - 0.238ELUMO- 0.164, indicating the importance of the interactions of aromatic DBPs towards catalase and the electrophilic/nucleophilic reactivity of aromatic DBPs in the toxicity mechanisms. In addition, the occurrence of the aromatic DBPs in tap water and finished water was studied in a mega city Shenzhen located in South China. Results showed that halogenated aromatic DBPs commonly existed in Shenzhen drinking water at ng/L levels, and three nitrogenous aromatic DBPs were detected in real drinking water for the first time. The major toxicity drivers among the target aromatic DBPs were identified through the integration of the measured concentrations and observed cytotoxicity; notably, DBPs with the highest concentrations may not contribute the highest proportions of overall toxicity.

Identification, Formation, and Predicted Toxicity of Halogenated DBPs Derived from Tannic Acid and Its Biodegradation Products.

Humic substances are commonly known disinfection byproduct (DBP) precursors. Tannic acid is one precursor of humic substances in organic degradation, and it occurs ubiquitously in both source water and wastewater. In this study, the biological degradation process was simulated under laboratory conditions, and the characteristics of DBP formation generated from the chlorination of tannic acid samples with different biodegradation times were explored. Twenty-six emerging halogenated DBPs were identified, and the formation pathways of the tannic acid-derived DBPs were tentatively proposed. Moreover, results demonstrated that the profile of the chlorinated DBP formation was significantly different from its brominated counterpart during biodegradation, and a general increasing trend of the ratio of TOBr/TOX or TIIPIS79/(TIIPIS79+TIIPIS35) as biodegradation time increasing was noticeable. The observed trend could be mainly ascribed to the reactive sites of tannic acid shifting from relatively fast to slow sites during biodegradation. In addition, the comparative toxicity of the detected DBPs derived from tannic acid was predicted by using two quantitative structure-activity relationship models established previously. On the basis of both the two toxicity metrics (involving developmental toxicity and growth inhibition potency), the predicted toxicity data indicated that the emerging DBP group trihalo-(di)hydroxycyclopentane-1,3-diones may possess extremely high toxic potencies.

Bioinformatic analysis of the prognostic value of the lncRNAs encoding snoRNAs in hepatocellular carcinoma.

Some lncRNAs can encode small nucleolar RNAs (snoRNAs), called small nucleolar RNA host genes (SNHGs), which exert diverse regulatory effects on cellular processes. In this study, using RNA-seq and survival data in the Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC), we examined the expression profile of some SNHG genes and explored their prognostic value in hepatocellular carcinoma (HCC). Level-3 RNA-sequencing data, the clinicopathological and survival data of patients with primary HCC were downloaded from the UCSC Xena browser (https://xenabrowser.net/), for a secondary analysis. Results showed that SNHG1, GAS5, SNHG3-7 and SNHG10-12 were significantly upregulated in HCC tissues (N = 49) compared with adjacent normal tissues (N = 49). After adjustment for confounding factors, the multivariate analysis confirmed that increased SNHG4 expression was independently associated with shorter OS (HR: 1.319, 95%CI: 1.131-1.537, P < 0.001), while increased GAS5 expression was an independent predictor of shorter RFS (HR: 1.287, 95% CI: 1.027-1.612, P = 0.028). Using the methylation data obtained from the Infinium HumanMethylation450 BeadChip, we found that SNHG4 expression was not likely to be modulated by methylation in HCC. In comparison, the methylation status of 5 CpG sites (cg07177756, cg17025683, cg16290996, cg03044573 and cg06644515) showed a moderately negative correlation (Pearson's r = -0.54, P < 0.001) with GAS5 expression. Based on these findings, we infer that SNHG4 and GAS5 might be valuable prognostic markers in HCC. DNA hypomethylation might play an important role in elevated GAS5 transcription in HCC. © 2018 BioFactors, 45(2):244-252, 2019.

Re-examining the self-contained quantum refrigerator in the strong-coupling regime.

We revisit the self-contained quantum refrigerator in the strong-internal-coupling regime by employing the quantum optical master equation. It is shown that strong internal coupling reduces the cooling ability of the refrigerator. In contrast to the weak-coupling case, strong internal coupling could lead to quite different and even converse thermodynamic behaviors.

The activation of protease-activated receptor 1 mediates proliferation and invasion of nasopharyngeal carcinoma cells.

Protease-activated receptor 1 (PAR-1) is a G-coupled membrane protein, which is involved in physiological and malignant invasion processes. It is activated by serine proteases such as thrombin through a unique form or by specific synthetic peptides. In this study, we determined the expression of PAR-1 in five nasopharyngeal carcinoma (NPC) cell lines with different characteristics of invasiveness and metastasis, and found that the levels of PAR-1 expression were higher in invasive or metastatic cell lines than those in low invasive or metastatic ones. Of the five NPC cell lines, CNE1-LMP1 cells had the highest expression levels of PAR-1, which was mainly distributed at the membrane and in the cytoplasm of tumor cells. Further study showed that the thrombin receptor synthetic activating peptide SFLLRN could stimulate the growth of CNE1-LMP1 cells in a dose-dependent manner. However, thrombin itself had a dual effect on the proliferation of NPC cells. Concentrations of thrombin in the range of 0.1-0.5 U/ml promoted cell growth, but concentrations higher than 0.5 U/ml impaired cell growth. Moreover, thrombin and SFLLRN also enhanced the invasive capabilities of CNE1-LMP1 cells in vitro, and this was partly due to enhancing the activities of MMP-2 and MMP-9. Our findings suggest that PAR-1 may contribute to the growth and invasive potential of NPC cells.

The Ku70 -1310C/G promoter polymorphism is associated with breast cancer susceptibility in Chinese Han population.

Ku70 plays an important role in the DSBR (DNA double-strand breaks repair) and maintenance of genomic integrity. Genetic variations within human Ku70 have been demonstrated to be associated with increased risk of several types of cancers. In this hospital-based case-control study, we aimed to investigate whether a single nucleotide polymorphism (SNP) in the promoter region (rs2267437) of Ku70 gene is associated with susceptibility to breast cancer in Chinese Han population. A total of 293 patients with breast cancer and 301 age-matched healthy controls were enrolled in this study. The Ku70 -1310C/G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A significant difference in genotype distribution and allele frequency was observed between patients and controls. The CG or GG carries were at higher risk of breast cancer compared with the CC homozygotes (OR=1.43, 95% CI=1.02-2.00, P=0.038 and OR=3.53, 95% CI=1.60-7.80, P=0.002, respectively). Further stratification analysis revealed that G allele was associated with an increased risk of breast cancer among premenopausal women (OR=1.68, 95% CI=1.21-2.33, P=0.002), but not in postmenopausal women (OR=1.33, 5% CI=0.85-2.10, P=0.216). Our study suggests that the Ku70 -1310C/G promoter polymorphism may be a susceptibility factor for breast cancer in Chinese Han population.

Acquired cisplatin resistance in human lung adenocarcinoma cells is associated with enhanced autophagy.

Activation of autophagy is a hallmark in tumor cells treated with chemotherapy, but the role of autophagy in acquired resistance of lung adenocarcinoma to cisplatin-based chemotherapy remains to be clarified. Our aim was to address that question by surveying the autophagic activity in parental lung adenocarcinoma cell line A549 and its 8-fold, more resistant subcell line, A549/DDP, which was obtained by treating cisplatin with increasing concentrations. A549/DDP and A549 cells were exposed to serum-free culture medium or ionizing radiation. To measure the stress-induced autophagy, LC3-II, as an autophagosome marker, was measured by immunofluorescence and Western blotting. To determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming acquired cisplatin resistance, the MTT assay and flow cytometry were performed. Western blotting analysis demonstrated that LC3-II was increased in A549/DDP cells, compared with those of parental A549 cells, under stress conditions. Meanwhile, immunofluorescence staining showed that LC3-II protein was located mainly in the cytoplasm of A549/DDP. We also found that 3-MA can enhance the growth inhibition and apoptotic effect of cisplatin in acquired resistant cells (A549/DDP). Collectively, our results provide evidence that the upregulation of autophagy plays a major role in cisplatin resistance of A549/DDP cells.

FAS-670A/G polymorphism: A biomarker for the metastasis of nasopharyngeal carcinoma in a Chinese population.

BACKGROUND: FAS-670 A/G single nucleotide polymorphism has been demonstrated to affect the expression of FAS gene by altering the transcriptional activity of FAS gene promoter. Downregulation of FAS with resultant resistance to death signals has been found in many cancers. We carried out a case-control study to investigate the biological significance of this polymorphism in nasopharyngeal carcinoma (NPC). METHODS: FAS-670 A/G polymorphism was examined in a Chinese population of 237 patients with NPC and 264 control subjects using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: There were no significant differences in the genotype or allele distribution of FAS-670 A/G polymorphism between cases and controls. FAS-670 (AG+GG) genotype and G allele showed significant associations with an increasing risk of lymph node metastasis (OR=2.08, P=0.01; OR=1.67, P=0.011, respectively) and distant metastasis (OR=3.87, P=0.015; OR=1.81, P=0.03, respectively) of NPC patients. In addition, FAS-670 (AG+GG) genotype showed an increasing incidence of advanced clinical stage, but this finding was not statistically significant (OR=1.79, P=0.066). CONCLUSION: The FAS-670 G allele could be used as a genetic risk marker for the metastasis of NPC patients.

Polymorphism of VEGF-2578C/A associated with the risk and aggressiveness of nasopharyngeal carcinoma in a Chinese population.

Polymorphism of vascular endothelial growth factor (VEGF) influences the VEGF responsiveness and is implicated in various types of diseases with a putative angiogenic basis, but its role in nasopharyngeal carcinoma (NPC) is not fully understood. In this report, we sought to investigate whether the VEGF-2578C/A polymorphism was associated with NPC in a Chinese population. We carried out polymerase chain reaction-restriction fragment length polymorphism in blood genomic DNA of 156 NPC patients and 161 control subjects. The VEGF-2578A allele carriers were significantly associated with an increased risk of NPC (odds ratio: 1.648; 95% confidence interval: 1.053-2.580; P = 0.029). In contrast, NPC patients with the -2578CC genotype were shown higher tumor aggressiveness of large tumor size, poor differentiation and advanced stage as compared to the -2578A allele carriers. No correlation was observed between the genotype or allele distribution and lymph node metastasis or family history of cancer. The VEGF-2578C/A polymorphism was shown to be inconsistent with the onset and aggressiveness of NPC. The precise mechanisms of the polymorphism on the differing status in NPC should be elucidated in further studies.