High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma.

Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10-11) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10-8). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.

Body mass index and body shape before treatment and nasopharyngeal carcinoma prognosis: A population-based patient cohort study in southern China.

A concern of reverse causation exists about the association between nasopharyngeal carcinoma (NPC) prognosis and body mass index (BMI) at diagnosis, while the prognostic impact of BMI measured years before diagnosis is unknown. Therefore, we investigated associations of prediagnosis and pretreatment BMI and body shape on NPC mortality. From a population-based patient cohort in southern China between 2010 and 2013, we included 2526 incident NPC cases with prospective follow-up through 2018. We assessed the associations of BMI and body shape at age 20 years, 10 years before diagnosis, and at diagnosis with NPC mortality, combining strategies of stratification and statistical adjustment to minimize reverse causation. We observed 25% lower all-cause mortality (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.64-0.89) and 25% lower NPC-specific mortality (HR 0.75, 95% CI: 0.61-0.91) among overweight vs normal-weight NPC cases at diagnosis. Lean body shapes 1 and 2 at diagnosis were associated with 68% and 23% higher all-cause mortality, respectively, compared to normal body shape 3. No effect modification by cancer stage was detected for associations with all-cause or NPC-specific mortality. Associations with BMI and body shape 10 years before diagnosis were similar but attenuated, while body size and shape at age 20 were not associated with mortality. Being overweight at diagnosis decreased mortality, and thinner body shape increased mortality, compared to normal weight/body shape. These associations may be due to poorer nutrition and treatment intolerance, resulting in treatment discontinuation and worse survival outcomes.

Associations of Urinary Phthalate Metabolites with Thyroid Function and the Mediated Role of Cytokines: A Panel Study of Healthy Children.

Evidence on joint association of a phthalate mixture with thyroid function among children and its underlying mechanism is largely unknown. We aimed to explore the associations of 10 urinary phthalate metabolites (mPAEs), either as individuals or as a mixture, with thyroid function indicators [free thyroxine, free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH)] in 144 children aged 4-12 years with up to 3 repeated visits across 3 seasons. Significant and positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) with TSH, as well as monobenzyl phthalate (MBzP) with FT3 in dose-response manners. The relationship between MEHP and TSH remained robust in multiple-phthalate models. Bayesian kernel machine regression (BKMR) models revealed overall linear associations of the 10 mPAE mixture with higher TSH and FT3 levels, and MEHP and MBzP were major contributors. Meanwhile, MEHP, MiBP, and MnBP were linked to the elevation of multiple cytokines including CCL 27, CCL3, CXCL1, and IL-16. Among them, IL-16 mediated the relationships of MEHP and MiBP with TSH, and the mediated proportions were 24.16% and 24.27%, respectively. Our findings suggested that mPAEs dominated by MEHP were dose-responsively associated with elevated TSH among healthy children and mediated by IL-16.

Planktonic microbial community and biological metabolism in a subtropical drinking water river-reservoir system.

To understand the dynamics of planktonic microbial community and its metabolism processes in subtropical drinking water river-reservoir system with lower man-made pollution loading, this study selected Dongzhen river-reservoir system in Mulan Creek as object to investigate spatial-temporal characteristics of community profile and functional genes involved in biological metabolism, and to analyze the influence of environmental factors. The results indicated that Proteobacteria and Actinobacteria were the most diverse phyla with proportion ranges of 9%-80% in target system, and carbohydrate metabolism (5.76-7.12 × 10-2), amino acid metabolism (5.78-7.21 × 10-2) and energy metabolism (4.07-5.17 × 10-2) were found to be the dominant pathways of biological metabolism. Although there were variations in biological properties both spatially and temporally, seasonal variation had a greater influence on microbial community and biological metabolism, than locational differences. Regarding the role of environmental factors, this study revealed that microbial diversity could be affected by multiple abiotic factors, with total organic carbon, total phosphorus and temperature being more influential (absolute value of standardized regression weights >2.13). Stochastic processes dominated the microbial community assembly (R2 of neutral community model = 0.645), while niche-based processes differences represented by nutrients, temperature and pH level played secondary roles (R > 0.388, P < 0.01). Notably, the synergistic influences among the environmental factors accounted for the higher percentages of community variation (maximum proportion up to 17.6%). Additionally, pH level, temperature, and concentrations of dissolved oxygen, carbon and nitrogen were found to be the significant factors affecting carbon metabolism pathways (P < 0.05), yet only total organic carbon significantly affected on nitrogen transformation (P < 0.05). In summary, the microbial profile in reservoir is not completely dominated by that in feeding river, and planktonic microbial community and its metabolism in subtropical drinking water river-reservoir system are shaped by multiple abiotic and biotic factors with underlying interactions.

Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial.

Importance: Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). Objective: To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. Design, Setting, and Participants: This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. Interventions: Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]). Main Outcomes and Measures: The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). Results: Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. Conclusions and Relevance: Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02633202.

Association Between Lipid Profiles and Left Ventricular Hypertrophy: New Evidence from a Retrospective Study.

Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Coxmodel and Coxmodel with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95%CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95%CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95%CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95%CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95%CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95%CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95%CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Coxmodel with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.

Occupational exposures and risk of nasopharyngeal carcinoma in a high-risk area: A population-based case-control study.

BACKGROUND: The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. METHODS: The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. RESULTS: Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. CONCLUSIONS: Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. LAY SUMMARY: The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.

Chinese nonmedicinal herbal diet and risk of nasopharyngeal carcinoma: A population-based case-control study.

BACKGROUND: An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated. METHODS: This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake. RESULTS: Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79). CONCLUSIONS: Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.

Past and Recent Salted Fish and Preserved Food Intakes Are Weakly Associated with Nasopharyngeal Carcinoma Risk in Adults in Southern China.

BACKGROUND: Chinese-style salted fish intake in early life is considered an established risk factor for nasopharyngeal carcinoma (NPC). However, results for adult intakes of salted fish and preserved foods are inconsistent. OBJECTIVE: The aim of this study was to ascertain the relations of Chinese-style hard and soft salted fish and preserved food intakes with NPC risk. METHODS: We conducted a population-based case-control study in southern China with 2554 NPC cases identified through a rapid case ascertainment system and 2648 healthy controls, frequency-matched on age, sex, and area. Subjects (aged 20-74 y) were interviewed via a food-frequency questionnaire, including information on portion size. Data were also collected on alcohol consumption and potential confounders. Food intake was grouped into 3-5 energy-adjusted intake levels during adulthood (10 y prior) and adolescence (16-18 y). For childhood (at age 10 y), intake frequency of selected food items was collected. Multivariate-adjusted ORs with 95% CIs were estimated via logistic regression. RESULTS: We found no association between NPC and intake of hard Chinese-style salted fish during adulthood, and an increased risk at the highest level of intake during adolescence (OR: 1.19; 95% CI: 1.03, 1.39). In contrast, we found a decreased risk for the middle intake level of soft salted fish during adulthood (OR: 0.68; 95% CI: 0.57, 0.81) and adolescence (OR: 0.71; 95% CI: 0.59, 0.85). Preserved foods showed contrasting risk profiles, e.g., the highest adult intake level of salted egg (OR: 1.51; 95% CI: 1.22, 1.87) and fermented black beans (OR: 0.67; 95% CI: 0.56, 0.80). Associations with NPC were weaker than previously reported, e.g., for weekly childhood intake of salted fish (OR: 1.56; 95% CI: 1.24, 1.97). CONCLUSIONS: Hard and soft salted fish have different risk profiles. Salted fish and other preserved foods were at most weak risk factors for NPC in all periods and may play a smaller role in NPC occurrence than previously thought.

Preparation, characterization and performance of an electrospun carbon nanofiber mat applied in hexavalent chromium removal from aqueous solution.

Hexavalent chromium, Cr(VI), a highly toxic oxyanion known as a carcinogen and mutagen, is an issue of concern due to its adverse impact on human health. Therefore, development of effective technologies and/or materials for Cr(VI) removal from water has been of great interest for researchers. In this study, an electrospun carbon nanofiber (CNF) mat was prepared via electrospinning polyacrylonitrile (PAN), followed by thermal pre-oxidation and carbonization. Scanning electron microscopy (SEM) observation showed that the fiber diameter of the CNF with carbonization temperature of 950°C (CNF950) was about 266 nm. Potentiometric titration analysis demonstrated that the point of zero charge pH (pHpzc) of CNF950 was around 7.93. CNF950 demonstrated high adsorption capacity and fast adsorption kinetics for Cr(VI) at pH < 3. Langmuir isotherm calculations showed that the maximum adsorption capacity of Cr(VI) on CNF950 was 118.8 mg/g at pH 2. The adsorption isotherm of Cr(VI) on CNF950 was well described by the Redlich-Peterson model, revealing that Cr(VI) adsorption was the result of a combination of monolayer and multilayer adsorption, depending on the initial Cr(VI) concentration. Solution pH greatly affected Cr(VI) adsorption onto CNF950 due to the electrostatic interaction, and the adsorption capacity was relatively high when pH was below 3. X-ray photoelectron spectroscopy (XPS) analysis revealed that the removal of Cr(VI) might be the result of a combination of redox reaction and electrostatic adsorption. The adsorption-saturated CNF950 could be regenerated by NaOH solution. This study extends the potential applicability of electrospun CNF mats for Cr(VI)-contaminated water purification.

Medical History, Medication Use, and Risk of Nasopharyngeal Carcinoma.

Because persistent inflammation may render the nasopharyngeal mucosa susceptible to carcinogenesis, chronic ear-nose-throat (ENT) disease and its treatment might influence the risk of nasopharyngeal carcinoma (NPC). Existing evidence is, however, inconclusive and often based on methodologically suboptimal epidemiologic studies. In a population-based case-control study in southern China, we enrolled 2,532 persons with NPC and 2,597 controls, aged 20-74 years, from 2010 to 2014. Odds ratios were estimated for associations between NPC risk and history of ENT and related medications. Any history of chronic ENT disease was associated with a 34% increased risk of NPC. Similarly, use of nasal drops or aspirin was associated with approximately doubled risk of NPC. However, in secondary analyses restricted to chronic ENT diseases and related medication use at least 5 years prior to diagnosis/interview, most results were statistically nonsignificant, except a history of uncured ENT diseases, untreated nasal polyps, and earlier age at first diagnosis of ENT disease and first or most recent aspirin use. Overall, these findings suggest that ENT disease and related medication use are most likely early indications rather than causes of NPC, although the possibility of a modestly increased NPC risk associated with these diseases and related medications cannot be excluded.

Facile On-Site Aqueous Pollutant Monitoring Using a Flexible, Ultralight, and Robust Surface-Enhanced Raman Spectroscopy Substrate: Interface Self-Assembly of Au@Ag Nanocubes on a Polyvinyl Chloride Template.

Aquatic ecosystems and human health have been seriously threatened by illegal discharge of wastewater, while simple and effective monitoring methods are still sparse. Here, we propose a facile method for on-site pollutant monitoring by surface-enhanced Raman spectroscopy with a novel substrate. This substrate is fabricated by interface self-assembly of Au@Ag nanocubes (NCs) on a simultaneously formed polyvinyl chloride (PVC) template, followed by coating with a thin Au film. The Au@Ag@Au-NCs/PVC film is flexible, ultralight, and robust and could float on the surface of water and firmly contact with water even under harsh environmental conditions. Moreover, the Au@Ag@Au-NCs/PVC film is translucent, allowing penetration of laser beams and enhancement of Raman signals. When thiram was used as a model contaminant in aqueous solution, a good linear relationship ( R2 = 0.972) was obtained over the range of 0.1-50 ppb with a detection limit of 0.1 ppb. Raman signals of thiram can be instantly and consecutively detected with the enhancement of the film in the simulated experiments, suggesting its possible use in the long run. Furthermore, the film can be easily regenerated by NaBH4 solution washing, which could reduce the operating cost. In summary, the Au@Ag@Au-NCs/PVC film has great potential in on-site pollutant monitoring in aqueous environments with a portable Raman spectrometer.

Electrospun Chitosan Nanofiber Membrane for Adsorption of Cu(II) from Aqueous Solution: Fabrication, Characterization and Performance.

The preparation, characterization and application of chitosan (CS) based electrospun nanofiber membrane for the adsorptive removal of Cu(II) from water were systematically investigated. Homogeneous, porous polyvinyl alcohol (PVA)/CS nanofiber membrane with amorphous structure, and average fiber diameter of 49 nm was successfully fabricated. The adsorption of Cu(II) onto the positively charged PVA/CS nanofiber membrane (pH < 6) was due to chemisorption rather than electrostatic adherence, and was highly pH-dependent. The adsorption equilibrium of Cu(II) by the PVA/CS nanofiber was established within 120 min, which was much faster than that by CS beads, and the adsorption kinetics followed pseudo-second-order model well (r 2 > 0.995). The adsorption isotherm data were well fitted with Langmuir model, and the maximum Cu(II) adsorption capacity of PVA/CS nanofiber membrane was 90.3 mg·g-1, which was much higher than that of CS beads. The adsorbed Cu(II) formed strong inner-sphere complex with the adsorbent. Coexisting cations of iron, lead, cadmium, nickel, calcium, and magnesium have insignificant effect on the Cu(II) adsorption, indicating the adsorbent has good selectivity for Cu(II) adsorption. FTIR and XPS analysis reveal amine, hydroxyl and ether groups are responsible for the Cu(II) adsorption. This work demonstrates the electrospun PVA/CS nanofiber membrane is a promising adsorbent for heavy metal removals.

Active and Passive Smoking and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China.

The magnitude and patterns of associations between smoking and risk of nasopharyngeal carcinoma (NPC) in high-incidence regions remain uncertain. Associations with active and passive tobacco smoking were estimated using multivariate logistic regression in a population-based case-control study of 2,530 NPC cases and 2,595 controls in Guangdong and Guangxi, southern China, in 2010-2014. Among men, risk of NPC was significantly higher in current smokers compared with never smokers (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.14, 1.53) but not in former smokers (OR = 0.92, 95% CI: 0.73, 1.17). Risk increased with smoking intensity (per 10 cigarettes/day, OR = 1.09, 95% CI: 1.03, 1.16), smoking duration (per 10 years, OR = 1.11, 95% CI: 1.06, 1.16), and cumulative smoking (per 10 pack-years, OR = 1.08, 95% CI: 1.04, 1.12). Risk decreased with later age at smoking initiation (per year, OR = 0.97, 95% CI: 0.96, 0.98) but not greater time since smoking cessation. Exposures to passive smoking during childhood (OR = 1.24, 95% CI: 1.03, 1.48) and from a spouse during adulthood (OR = 1.30, 95% CI: 1.03, 1.63) were independently associated with increased NPC risk in never-smoking men and women, but exposure-response trends were not observed. In conclusion, active and passive tobacco smoking are associated with modestly increased risk of NPC in southern China; risk is highest among long-term smokers.

Quantification of familial risk of nasopharyngeal carcinoma in a high-incidence area.

BACKGROUND: To the authors' knowledge, no studies to date have explored familial risks of nasopharyngeal carcinoma (NPC) in detail and quantified its lifetime risk in high-incidence populations. METHODS: The authors conducted a population-based case-control study of 2499 NPC cases and 2576 controls randomly selected in southern China from 2010 through 2014. Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) associated with a family history of NPC. In addition, the authors compiled a reconstructed cohort comprising 40,781 first-degree relatives of cases and controls to calculate the lifetime cumulative risk of NPC. RESULTS: Individuals with a first-degree family history of NPC were found to be at a >4-fold risk of NPC (OR, 4.6; 95% CI, 3.5-6.1) compared with those without such a history, but had no excess risk of other malignancies. The excess risk was higher for a maternal than a paternal history and was slightly stronger for a sibling compared with a parental history, and for a sororal than a fraternal history. Among relatives of cases, the cumulative risk of NPC up to age 74 years was 3.7% (95% CI, 3.3%-4.2%), whereas that among relatives of controls was 0.9% (95% CI, 0.7%-1.2%). Cumulative risk was higher in siblings than in parents among relatives of cases, whereas no such difference was noted among relatives of controls. CONCLUSIONS: Individuals with a family history of NPC have a substantially higher risk of NPC. These relative and cumulative risk estimates can guide the development of strategies for early detection and clinical consultation in populations with a high incidence of NPC. Cancer 2017;123:2716-25. © 2017 American Cancer Society.

The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (P(HLA-A-aa-site-62) = 7.4 × 10(-29); P (HLA-B-aa-site-116) = 6.5 × 10(-19); P (HLA-C-aa-site-156) = 6.8 × 10(-8) respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China.

Removal of tetracycline from aqueous solution by a Fe3O4 incorporated PAN electrospun nanofiber mat.

Pollution of antibiotics, a type of emerging contaminant, has become an issue of concern, due to their overuse in human and veterinary application, persistence in environment and great potential risk to human and animal health even at trace level. In this work, a novel adsorbent, Fe3O4 incorporated polyacrylonitrile nanofiber mat (Fe-NFM), was successfully fabricated via electrospinning and solvothermal method, targeting to remove tetracycline (TC), a typical class of antibiotics, from aqueous solution. Field emission scanning electron microscopy and X-ray diffraction spectroscopy were used to characterize the surface morphology and crystal structure of the Fe-NFM, and demonstrated that Fe-NFM was composed of continuous, randomly distributed uniform nanofibers with surface coating of Fe3O4 nanoparticles. A series of adsorption experiments were carried out to evaluate the removal efficiency of TC by the Fe-NFM. The pseudo-second-order kinetics model fitted better with the experimental data. The highest adsorption capacity was observed at initial solution pH4 while relative high adsorption performance was obtained from initial solution pH4 to 10. The adsorption of TC on Fe-NFM was a combination effect of both electrostatic interaction and complexation between TC and Fe-NFM. Freundlich isotherm model could better describe the adsorption isotherm. The maximum adsorption capacity calculated from Langmuir isotherm model was 315.31 mg/g. Compared to conventional nanoparticle adsorbents which have difficulties in downstream separation, the novel nanofiber mat can be simply installed as a modular compartment and easily separated from the aqueous medium, promising its huge potential in drinking and wastewater treatment for micro-pollutant removal.

Self-assembly of Au nanoparticles on PMMA template as flexible, transparent, and highly active SERS substrates.

We report a simple and rapid method for fabricating a surface-enhanced Raman scattering (SERS) substrate, which offers good flexibility, excellent optical transparency, and high SERS activity. Specifically, the SERS substrate (AuNPs/PMMA film) was obtained through self-assembly of gold nanoparticles (AuNPs) on newborn poly(methyl methacrylate) (PMMA) template. The UV-vis spectroscopy analysis and scanning electron microscopy observation revealed that the gold nanoparticles were closely assembled on the flexible and transparent PMMA template. The fabricated AuNPs/PMMA film SERS substrate allowed detection of model molecule, malachite green isothiocyanate, at a concentration as low as 0.1 nM, and exhibited good reproducibility in the SERS measurement. The Raman enhancement factor (EF) of the AuNPs/PMMA film was found to be as high as (2.4 ± 0.3) × 10(7). In addition, measure of residual malachite green on fish surface was carried out, and the result indicated that the AuNPs/PMMA film had great potential in the in situ ultrasensitive detection of analyte on irregular objects.

Deletion of concurrent chemotherapy on the basis of sequential chemoradiotherapy for non-metastatic stage T4 nasopharyngeal carcinoma in IMRT era.

PURPOSE: Intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy is deemed as the mainstay treatment in locoregionally advanced nasopharyngeal carcinoma (NPC). Nevertheless, the tolerance of severe acute toxicity of concurrent chemotherapy was unsatisfied. In addition, T4 is the predicting factor of poor prognosis for NPC patients. In this retrospective analysis, the long-term outcomes IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy for T4 non-metastatic NPC were analyzed. MATERIALS AND METHODS: From January 2005 to November 2016, a total of 145 biopsy-proven non-metastatic T4 NPC was treated with IMRT combined by induction chemotherapy with or without adjuvant chemotherapy. The survival and side effects of the patients were analyzed. RESULTS: Median follow-up time was 74 months (ranges, 8-186 months). 10.0%, 61.3%, 27.3%, and 1.3% developed grade 1, 2, 3, and 4 mucositis during IMRT, respectively. 5.5% and 2.0% patients experienced grade 1 and 2 nausea and vomiting; no patients developed grade 3 or 4 nausea and vomiting. Of 145 patients enrolled, 5-year and 10-year overall survival(OS) rates were 73.7% and 53.9%, local progression-free survival(LPFS) rates were 86.1% and 71.6%, regional progression-free survival(RPFS) rates were 96.7% and 92.8%, distant metastasis-free survival (DMFS) rates were 86.7%, 78.2%, respectively. At the last follow-up, five patients developed cranial nerve injury, one patient developed mandibular bone necrosis, four patients developed temporal lobe injury, four patients developed nasopharyngeal massive hemorrhage (three cases after recurrence and one case without recurrence), and five patients developed second primary tumor. CONCLUSION: The survival outcomes of treating T4 NPC IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy are encouraging. Moreover, mucosal reaction, nausea, and vomiting reaction were reduced during IMRT.