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Mengfei Ji,1,* Xiaojing Qiu,2,* Lin Hou,1 Shengnan Huang,1 Yuanmin Li,1 Yang Liu,1 Shaofeng Duan,3,4 Yurong Hu1,5 1Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Henan Eye Institute, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3College of Pharmacy, Henan University, Kaifeng, People’s Republic of China; 4Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 5Key Laboratory of Key Technology of Drug Preparation, Ministry of Education, Institute of Drug Discovery & Development, Zhengzhou University, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Background: In order to achieve drug targeting and controlled release, we have successfully developed a novel drug release system DOX/AuNCs-PM-HA with gold nanocages (AuNCs) as photothermal cores, thermally responsive copolymer P(NIPAM-co-Am) (PM) as the near-infrared (NIR) stimuli gatekeeper and hyaluronic acid as a targeting ligand as well as a capping agent. Methods: Cell uptake and cell viability were investigated. In vivo photoacoustic tomography imaging in H22 tumor bearing mice was analyzed for the tumor targeting effect of the nanocomplexes. Antitumor efficacy and the tissue distribution in vivo were investigated.Results: In vitro results demonstrated that the DOX/AuNCs-PM-HA had significant anticancer activity against SMMC-7721 cells under NIR irradiation. Furthermore, in vivo photoacoustic tomography imaging of the nanocomplexes in H22 tumor bearing mice could indicate effective tumor targeting. Our studies on antitumor efficacy and the tissue distribution in vivo showed that many DOX/AuNCs-PM-HA nanocomplexes could efficiently accumulate at the tumor site so that they could inhibit the tumor growth effectively with limited side effects. The in vitro and in vivo results confirmed that the tumor-targeting and controlled-release drug system DOX/AuNCs-PM-HA with the combination of chemotherapy and photothermal therapy showed strong anti-tumor effect and would have great potential for future cancer therapy.Conclusion: This tumor targeting DOX/AuNCs-PM-HA nanocomplex responded not only to the external stimuli of NIR, but also the internal stimuli of hyaluronidase, providing the potential for pinpointed and multi-stimuli responsive intracellular drug release. Keywords: drug delivery, temperature-responsive polymers, hyaluronic acid, chemotherapy, photothermal therapy, photoacoustic imaging

Purpose: Screening for nasopharyngeal carcinoma (NPC) has shown an improvement in early detection and survival rates of NPC in endemic regions. It is critical to evaluate whether NPC screening can reduce NPC-specific mortality in the population., Methods: Sixteen towns in Sihui and Zhongshan cities, China, were selected; eight were randomly allocated to the screening group and eight to the control group. Residents age 30-69 years with no history of NPC were included from January 1, 2008, to December 31, 2015. Residents in the screening towns were invited to undergo serum Epstein-Barr virus (EBV) viral capsid antigen/nuclear antigen 1-immunoglobulin A antibody tests; others received no intervention. The population was followed until December 31, 2019. Nonparametric tests and Poisson regression models were used to estimate the screening effect on NPC mortality, accounting for the cluster-randomized design. The trial is registered with ClinicalTrials.gov (identifier: NCT00941538)., Results: A total of 174,943 residents in the screening group and 186,263 residents in the control group were included. NPC incidence and overall mortality were similar between the two groups. A total of 52,498 (30.0% of 174,943) residents participated in the serum EBV antibody test. The overall compliance rate for endoscopic examination and/or biopsies among baseline and ever-classified high-risk participants was 65.9% (1,110 of 1,685) and 67.6% (1,703 of 2,518), respectively. A significant 30% reduction in NPC mortality was observed in the screening group compared with the control group (standardized NPC-specific mortality rate of 8.2 NPC deaths per 1,000 person-years versus 12.5; adjusted rate ratio [RR], 0.70 [95% CI, 0.49 to 0.997]; P = .048). This benefit was most evident among individuals age 50 years and older (RR, 0.56 [95% CI, 0.37 to 0.85]; P = .007) compared with those younger than 50 years (RR, 0.96 [95% CI, 0.64 to 1.46]; P = .856)., Conclusion: In this 12-year trial, EBV antibody testing resulted in a significant reduction in NPC mortality.

Background: Early detection and screening of oesophageal squamous cell carcinoma rely on upper gastrointestinal endoscopy, which is not feasible for population-wide implementation. Tumour marker-based blood tests offer a potential alternative. However, the sensitivity of current clinical protein detection technologies is inadequate for identifying low-abundance circulating tumour biomarkers, leading to poor discrimination between individuals with and without cancer. We aimed to develop a highly sensitive blood test tool to improve detection of oesophageal squamous cell carcinoma., Methods: We designed a detection platform named SENSORS and validated its effectiveness by comparing its performance in detecting the selected serological biomarkers MMP13 and SCC against ELISA and electrochemiluminescence immunoassay (ECLIA). We then developed a SENSORS-based oesophageal squamous cell carcinoma adjunct diagnostic system (with potential applications in screening and triage under clinical supervision) to classify individuals with oesophageal squamous cell carcinoma and healthy controls in a retrospective study including participants (cohort I) from Sun Yat-sen University Cancer Center (SYSUCC; Guangzhou, China), Henan Cancer Hospital (HNCH; Zhengzhou, China), and Cancer Hospital of Shantou University Medical College (CHSUMC; Shantou, China). The inclusion criteria were age 18 years or older, pathologically confirmed primary oesophageal squamous cell carcinoma, and no cancer treatments before serum sample collection. Participants without oesophageal-related diseases were recruited from the health examination department as the control group. The SENSORS-based diagnostic system is based on a multivariable logistic regression model that uses the detection values of SENSORS as the input and outputs a risk score for the predicted likelihood of oesophageal squamous cell carcinoma. We further evaluated the clinical utility of the system in an independent prospective multicentre study with different participants selected from the same three institutions. Patients with newly diagnosed oesophageal-related diseases without previous cancer treatment were enrolled. The inclusion criteria for healthy controls were no obvious abnormalities in routine blood and tumour marker tests, no oesophageal-associated diseases, and no history of cancer. Finally, we assessed whether classification could be improved by integrating machine-learning algorithms with the system, which combined baseline clinical characteristics, epidemiological risk factors, and serological tumour marker concentrations. Retrospective SYSUCC cohort I (randomly assigned [7:3] to a training set and an internal validation set) and three prospective validation sets (SYSUCC cohort II [internal validation], HNCH cohort II [external validation], and CHSUMC cohort II [external validation]) were used in this step. Six machine-learning algorithms were compared (the least absolute shrinkage and selector operator regression, ridge regression, random forest, logistic regression, support vector machine, and neural network), and the best-performing algorithm was chosen as the final prediction model. Performance of SENSORS and the SENSORS-based diagnostic system was primarily assessed using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC)., Findings: Between Oct 1, 2017, and April 30, 2020, 1051 participants were included in the retrospective study. In the prospective diagnostic study, 924 participants were included from April 2, 2022, to Feb 2, 2023. Compared with ELISA (108·90 pg/mL) and ECLIA (41·79 pg/mL), SENSORS (243·03 fg/mL) showed 448 times and 172 times improvements, respectively. In the three retrospective validation sets, the SENSORS-based diagnostic system achieved AUCs of 0·95 (95% CI 0·90-0·99) in the SYSUCC internal validation set, 0·93 (0·89-0·97) in the HNCH external validation set, and 0·98 (0·97-1·00) in the CHSUMC external validation set, sensitivities of 87·1% (79·3-92·3), 98·6% (94·4-99·8), and 93·5% (88·1-96·7), and specificities of 88·9% (75·2-95·8), 74·6% (61·3-84·6), and 92·1% (81·7-97·0), respectively, successfully distinguishing between patients with oesophageal squamous cell carcinoma and healthy controls. Additionally, in three prospective validation cohorts, it yielded sensitivities of 90·9% (95% CI 86·1-94·2) for SYSUCC, 84·8% (76·1-90·8) for HNCH, and 95·2% (85·6-98·7) for CHSUMC. Of the six machine-learning algorithms compared, the random forest model showed the best performance. A feature selection step identified five features to have the highest performance to predictions (SCC, age, MMP13, CEA, and NSE) and a simplified random forest model using these five features further improved classification, achieving sensitivities of 98·2% (95% CI 93·2-99·7) in the internal validation set from retrospective SYSUCC cohort I, 94·1% (89·9-96·7) in SYSUCC prospective cohort II, 88·6% (80·5-93·7) in HNCH prospective cohort II, and 98·4% (90·2-99·9) in CHSUMC prospective cohort II., Interpretation: The SENSORS system facilitates highly sensitive detection of oesophageal squamous cell carcinoma tumour biomarkers, overcoming the limitations of detecting low-abundance circulating proteins, and could substantially improve oesophageal squamous cell carcinoma diagnostics. This method could act as a minimally invasive screening tool, potentially reducing the need for unnecessary endoscopies., Funding: The National Key R&D Program of China, the National Natural Science Foundation of China, and the Enterprises Joint Fund-Key Program of Guangdong Province., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Two open-framework zinc phosphates [C 3 N 2 H 12 ][Zn(HPO 4 ) 2 ] (1) and [C 6 N 4 H 22 ] 0.5 [Zn(HPO 4 ) 2 ] (2) were synthesized via hydrothermal reaction and characterized by powder X-ray diffraction, thermogravimetric analysis and scanning electron microscopy. Both compounds have a similar crystal structure and macroscopic morphology. However, the difference in equilibrium cations, in which the propylene diamine is for 1 and the triethylenetetramine is for 2, results in a significant distinction in the dense hydrogen grid. The diprotonated propylene diamine molecule in 1 is more favorable for forming a hydrogen-bond network in three dimensions than in 2, in which the twisted triethylenetetramine forms a hydrogen bond grid with the inorganic framework only in two dimensions owing to its large steric effect. This distinction further leads to a disparity in the proton conductivity of both compounds. The proton conductivity of 1 can reach 1.00 × 10 -3 S cm -1 under ambient conditions (303 K and 75% RH) and then increase to 1.11 × 10 -2 S cm -1 at 333 K and 99% RH, which is the highest value among the open-framework metal phosphate proton conductors operated in the same conduction. In contrast, the proton conductivity of 2 is four orders of magnitude smaller than 1 at 303 K and 75% RH and two orders smaller than 1 at 333 K and 99% RH., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To explore the mechanism by which the plant growth-promoting bacterium Brevibacillus sp. SR-9 improves sweet sorghum tolerance and enriches soil cadmium (Cd) under pot conditions, the effect of strain SR-9 inoculation on the microbial community of sorghum rhizosphere soil was analyzed by metagenomics. Gene expression in sweet sorghum roots was analyzed using transcriptomics. The results showed that strain SR-9 promoted the growth of sweet sorghum and improved the absorption and enrichment of Cd in the plants. Compared with the uninoculated treatment, the aboveground part and root dry weight in strain SR-9 inoculated with sorghum increased by 21.09% and 17.37%, respectively, and the accumulation of Cd increased by 135% and 53.41%, respectively. High-throughput sequencing showed that strain SR-9 inoculation altered the rhizosphere bacterial community, significantly increasing the relative abundance of Actinobacteria and Firmicutes. Metagenomic analysis showed that after inoculation with strain SR-9, the abundance of genes involved in amino acid transport metabolism, energy generation and conversion, and carbohydrate transport metabolism increased. KEGG functional classification showed that inoculation with strain SR-9 increased the abundance of genes involved in soil microbial metabolic pathways in the rhizosphere soil of sweet sorghum and the activity of soil bacteria. Transcriptome analysis identified 198 upregulated differentially expressed genes in sweet sorghum inoculated with strain SR-9, including those involved in genetic information processing, biological system, metabolism, environmental information processing, cellular process, and human disease. Most of the annotated differentially expressed genes were enriched in the metabolic category and were related to pathways such as signal transduction, carbohydrate metabolism, amino acid metabolism, and biosynthesis of other secondary metabolites. This study showed that plant growth-promoting bacteria can alter the rhizosphere bacterial community composition, increasing the activity of soil bacteria and upregulating gene expression in sweet sorghum roots. The findings enhance our understanding of the microbiological and botanical mechanisms by which plant growth-promoting bacterial inoculation improves the remediation of heavy metals by sorghum.

Heavy metal contamination affects microbial composition and diversity. The interaction between heavy metal contamination and soil microorganisms has been a hot topic in ecological research. Battery manufacturing has been going on for over six decades in Xinxiang City, resulting in severe soil heavy metal contamination due to battery wastewater runoff. Few studies have investigated the effect of heavy metal contamination due to long-term battery wastewater runoff on microbial diversity and metabolomics in Xinxiang City. In this study, we collected samples from three heavy metal contaminated sites in Xinxiang City and found that Cd and Pb exceeded the recommended thresholds by 34-66 fold and 1.5-2.32 fold, respectively. High-throughput sequencing showed that Bacillus, Arthrobacter, Sphingomonas , and Streptomyces were the dominant bacteria genera, while Olpidium, Plectosphaerella , and Gibellulopsis were the dominant fungi genera, indicating that heavy metal contaminated soil in Xinxiang City was rich in heavy metal tolerant bacteria and fungi due to the long-term heavy metal stress. Correlation analysis showed that total Cu, DTPA extract Cu, and water soluble Pb were significant factors in bacterial diversity, while total Cd, total Ni, total Pb, total Zn, DTPA extract Cu, and water soluble Pb were significant factors in fungal diversity. To better understand the effect of heavy metal contamination on the metabolism of soil microorganisms, we conducted non-targeted metabolomic profiling, which showed significant differences in metabolites across the samples. Pathway enrichment analysis showed that these differential metabolites were involved in pathways such as metabolism, environmental information processing, and genetic Information Processing, which may play a role in heavy metal stress mitigation and environmental adaptation.

As the water source for the Middle Route Project of the South-to-North Water Diversion Project (MR-SNWD) of China, the Danjiangkou Reservoir (DJR) is in the process of ecosystem reassembly, but the composition, function, and assembly mechanisms of bacterioplankton communities are not yet clear. In this study, the composition, distribution characteristics and influencing factors of bacterioplankton communities were analyzed by high-throughput sequencing (HTS); PICRUSt2 was used to predict community function; a molecular ecological network was used to analyze bacterioplankton interactions; and the assembly process of bacterioplankton communities was estimated with a neutral model. The results indicated that the communities, function and interaction of bacterioplankton in the DJR had significant annual and seasonal variations and that the seasonal differences were greater than that the annual differences. Excessive nitrogen (N) and phosphorus (P) nutrients in the DJR are the most important factors affecting water quality in the reservoir, N and P nutrients are the main factors affecting bacterial communities. Season is the most important factor affecting bacterioplankton N and P cycle functions. Ecological network analysis indicated that the average clustering coefficient and average connectivity of the spring samples were lower than those of the autumn samples, while the number of modules for the spring samples was higher than that for the autumn samples. The neutral model explained 66.3%, 63.0%, 63.0%, and 70.9% of the bacterioplankton community variations in samples in the spring of 2018, the autumn of 2018, the spring of 2019, and the autumn of 2019, respectively. Stochastic processes dominate bacterioplankton community assembly in the DJR. This study revealed the composition, function, interaction, and assembly of bacterioplankton communities in the DJR, providing a reference for the protection of water quality and the ecological functions of DJR bacterioplankton., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LY declared a shared affiliation with the authors Z-JC, Y-QL, Y-YL, L-AL, B-HZ, and M-FJ to the handling editor at the time of review., (Copyright © 2022 Chen, Liu, Li, Lin, Zheng, Ji, Li and Han.)

Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction., (© 2020 UICC.)

Metabolic reprogramming plays important roles in development and progression of nasopharyngeal carcinoma (NPC), but the underlying mechanism has not been completely defined. In this work, we found INSL5 was elevated in NPC tumor tissue and the plasma of NPC patients. Plasma INSL5 could serve as a novel diagnostic marker for NPC, especially for serum VCA-IgA-negative patients. Moreover, higher plasma INSL5 level was associated with poor disease outcome. Functionally, INSL5 overexpression increased, whereas knockdown of its receptor GPCR142 or inhibition of INSL5 reduced cell proliferation, colony formation, and cell invasion in vitro and tumorigenicity in vivo. Mechanistically, INSL5 enhanced phosphorylation and nuclear translocation of STAT5 and promoted glycolytic gene expression, leading to induced glycolysis in cancer cells. Pharmaceutical inhibition of glycolysis by 2-DG or blockade of INSL5 by a neutralizing antibody reversed INSL5-induced proliferation and invasion, indicating that INSL5 can be a potential therapeutic target in NPC. In conclusion, INSL5 enhances NPC progression by regulating cancer cell metabolic reprogramming and is a potential diagnostic and prognostic marker as well as a therapeutic target for NPC., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown., Patients and Methods: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City., Results: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49)., Conclusion: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis., Clinical Trial Number: NCT00941538., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Nephrolithiasis is a common disease of the urinary system, of which idiopathic calcium oxalate (CaOx) kidney stones, in particular, are one of the special types. In the initial stages of CaOx kidney stone formation, Randall's plaques (RPs) develop. Liver X receptors (LXRs) inhibit oxidative stress and inflammatory in other diseases; nevertheless, the role of LXRs in nephrolithiasis has yet to be elucidated. In this study, the role of LXRs in the progression of RP formation was investigated. Microarray analysis revealed that LXR/RXR levels were significantly greater in low-plaque tissues (<5%) than in high-plaque tissues (>5%), confirming the link between LXR activation and RP formation. Correspondingly, expression levels of two LXR target genes, LXRα and LXRβ, were lower in high-plaque tissues than in low-plaque tissues. In vitro, LXR agonist alleviated calcium oxalate monohydrate-induced cellular calcium deposits and apoptosis. LXR activation decreased reactive oxygen species production and gene expression of inflammatory mediators, including osteopontin that has recently been demonstrated to correlate with the development of RPs. Moreover, p38 MAPK and JNK signaling may mediate LXR-regulated expression in HK-2 cells. In an animal model, the deposition was reduced by activating LXR, and osteopontin expression was also inhibited. Our findings suggest a role for LXRs in the progression of idiopathic CaOx kidney stones; LXR agonists may have therapeutic potential for the treatment of nephrolithiasis., (© 2019 Wiley Periodicals, Inc.)

Objective: The aim of this study is to evaluate the level of plasma EBV DNA and nasal endoscopy in high risk population of nasopharyngeal carcinoma, and to explore the value of EBV DNA testing in nasal endoscopy. Method: The nasopharyngeal carcinoma was screened in High-incidence Area of Zhongshan City. EBV antibody was detected by ELISA, and 427 patients with high risk of nasopharyngeal carcinoma were identified. In the high risk population the plasma EBV-DNA was measured using Fluorescent quantitative PCR, and all patients were used nasal endoscopy in the first two years. The application value of EBV DNA and nasopharyngeal endoscopic biopsy were analyzed. Result: There were 427 NPC high risk population in first screening. The rates of nasopharyngeal biopsy in EBV DNA positive and EBV DNA negative population were 90.2% (55/61) and 13.9% (51/366), respectively. The rate of NPC nasopharyngeal biopsy in EBV DNA positive population was higher than that in EBV DNA negative population ( P <0.01). The rate of NPC detection in EBV DNA positive group (60.7%) was higher than that (3.3%) in EBV DNA negative population ( P <0.01). In first year follow up, there were 286 NPC high risk population. The rates of nasopharyngeal biopsy in EBV DNA positive and EBV DNA negative population were 91.2% (31/34) and 11.9% (30/252), respectively. The rate of NPC nasopharyngeal biopsy in EBV DNA positive population was higher than that in EBV DNA negative population ( P <0.01). The rate of NPC detection in EBV DNA positive group (17.6%) was higher than that (1.6%) in EBV DNA negative population ( P <0.01). The positive predicative value of serological risk assessment was 8.3% (59/713), but for NPC high risk group, adding quantitative analysis of plasma EBV DNA, the positive predicative value was 45.3% (43/95). The early diagnosis rates in EBV DNA positive and EBV DNA negative population were 79.1% (34/43) and 93.8% (15/16), respectively. There was no significant difference in early diagnosis rates in two groups ( P >0.05). Conclusion: The positive rate of plasma EBV DNA in high risk group of nasopharyngeal carcinoma may be helpful for nasal endoscopic nasopharyngeal biopsy, which can greatly improve the positive predictive value of high risk population of nasopharyngeal carcinoma. For NPC high risk population, Therefore, EBV DNA positive population are the focus for NPC screening., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

The members of the genus Picea form a dominant component in many alpine and boreal forests which are the major sink for atmospheric CO2. However, little is known about the growth response and acclimation of CO2 exchange characteristics to high temperature stress in Picea taxa from different altitudes. Gas exchange parameters and growth characteristics were recorded from four year old seedlings of two alpine (Picea likiangensis vars. rubescens and linzhiensis) and two lowland (P. koraiensis and P. meyeri) taxa. Seedlings were grown at moderate (25°C/15°C) and high (35°C/25°C) day/night temperatures, for four months. The approximated biomass increment (ΔD2H) for all taxa decreased under high temperature stress, associated with decreased photosynthesis and increased respiration. However, the two alpine taxa exhibited lower photosynthetic acclimation and higher respiratory acclimation than either lowland taxon. Moreover, higher leaf dry mass per unit area (LMA) and leaf nitrogen content per unit area (Narea), and a smaller change in the nitrogen use efficiency of photosynthesis (PNUE) for lowland taxa indicated that these maintained higher homeostasis of photosynthesis than alpine taxa. The higher respiration rates produced more energy for repair and maintenance biomass, especially for higher photosynthetic activity for lowland taxa, which causes lower respiratory acclimation. Thus, the changes of ΔD2H for alpine spruces were larger than that for lowland spruces. These results indicate that long term heat stress negatively impact on the growth of Picea seedlings, and alpine taxa are more affected than low altitude ones by high temperature stress. Hence the altitude ranges of Picea taxa should be taken into account when predicting changes to carbon fluxes in warmer conditions.

Nasopharyngeal carcinoma (NPC) is a cancer that occurs in high frequency in Southern China. A previous functional complementation approach and the subsequent cDNA microarray analysis have identified that serum amyloid A1 (SAA1) is an NPC candidate tumor suppressor gene. SAA1 belongs to a family of acute-phase proteins that are encoded by five polymorphic coding alleles. The SAA1 genotyping results showed that only three SAA1 isoforms (SAA1.1, 1.3 and 1.5) were observed in both Hong Kong NPC patients and healthy individuals. This study aims to determine the functional role of SAA1 polymorphisms in tumor progression and to investigate the relationship between SAA1 polymorphisms and NPC risk. Indeed, we have shown that restoration of SAA1.1 and 1.3 in the SAA1-deficient NPC cell lines could suppress tumor formation and angiogenesis in vitro and in vivo. The secreted SAA1.1 and SAA1.3 proteins can block cell adhesion and induce apoptosis in the vascular endothelial cells. In contrast, the SAA1.5 cannot induce apoptosis or inhibit angiogenesis because of its weaker binding affinity to αVβ3 integrin. This can explain why SAA1.5 has no tumor-suppressive effects. Furthermore, the NPC tumors with this particular SAA1.5/1.5 genotype showed higher levels of SAA1 gene expression, and SAA1.1 and 1.3 alleles were preferentially inactivated in tumor tissues that were examined. These findings further strengthen the conclusion for the defective function of SAA1.5 in suppression of tumor formation and angiogenesis. Interestingly, the frequency of the SAA1.5/1.5 genotype in NPC patients was ~2-fold higher than in the healthy individuals (P=0.00128, odds ratio=2.28), which indicates that this SAA1 genotype is significantly associated with a higher NPC risk. Collectively, this homozygous SAA1.5/1.5 genotype appears to be a recessive susceptibility gene, which has lost the antiangiogenic function, whereas SAA1.1 and SAA1.3 are the dominant alleles of the tumor suppressor phenotype.

To predict the ecological consequences of climate change for a widely distributed tree species, it is essential to develop a deep understanding of the ecophysiological responses of populations from contrasting climates to varied soil water availabilities. In the present study, we focused on Pinus tabuliformis, one of the most economically and ecologically important tree species in China. In a greenhouse experiment, we exposed trees from high-elevation (HP) and low-elevation (LP) populations to low (80 % of field capacity, FC), mild (60 % FC), moderate (40 % FC) and severe (20 % FC) water stresses. Leaf gas exchange, biomass production and allocation, as well as water-use efficiency, were measured during the experiment. Increasing soil water stress clearly decreased the relative growth rate (RGR), total dry mass (TDM), light-saturated photosynthetic rate (Asat), stomatal conductance (gs), total water use (TWU) and whole-plant water-use efficiency (WUEWP). In contrast, intrinsic water-use efficiency (WUEi) and carbon isotope composition (δ(13)C) both increased significantly with increasing soil water stress for both populations. Only in the LP did the root/shoot ratio (R/S ratio) significantly increase when the water stress increased. A strong positive correlation between Asat and gs coupled with a reduced intercellular CO2 concentration (Ci) probably suggested that stomatal limitations were the main cause of the decreased Asat. However, all the measured variables from the HP were affected less by drought compared with those of the LP, and most aspects of the HP were canalized against drought stress, which was reflected by the relatively higher RGR, TDM and WUEWP. Overall, the results suggest that the two populations responded differentially to drought stress with the HP showing higher drought tolerance than the LP, which was reflected by its faster seedling growth rate and more efficient water use under drought conditions., (Published by Oxford University Press on behalf of the Annals of Botany Company.)

Liver cancer is a common malignant tumor in China and a major health concern. We aimed to estimate the liver cancer incidence and mortality in China in 2010 using liver cancer data from some Chinese cancer registries and provide reference for liver cancer prevention and treatment. We collected and evaluated the incidence and mortality data of liver cancer in 2010 from 145 cancer registries, which were included in the 2013 Chinese Cancer Registry Annual Report, calculated crude, standardized, and truncated incidences and mortalities, and estimated new liver cancer cases and deaths from liver cancer throughout China and in different regions in 2010 from Chinese practical population. The estimates of new liver cancer cases and deaths were 358,840 and 312,432, respectively, in China in 2010. The crude incidence, age-standardized rate by Chinese standard population (ASR China), and age-standardized rate by world standard population (ASR world) were 27.29/100,000, 21.35/100,000, and 20.87/100,000, respectively; the crude, ASR China, and ASR world mortalities were 23.76/100,000, 18.43/100,000, and 18.04/100,000, respectively. The incidence and mortality were the highest in western regions, higher in rural areas than in urban areas, and higher in males than in females. The age-specific incidence and mortality of liver cancer showed a rapid increase from age 30 and peaked at age 80-84 or 85+. Our results indicated that the 2010 incidence and mortality of liver cancer in China, especially in undeveloped rural areas and western regions, were among high levels worldwide. The strategy for liver cancer prevention and treatment should be strengthened.

Background: The utility of circulating Epstein-Barr Virus (EBV) DNA as a tumor marker for nasopharyngeal carcinoma (NPC) detection suggests that it might improve the diagnostic performance of anti-EBV antibody markers in NPC screening. In this study, the authors evaluated whether circulating EBV DNA load is capable of distinguishing NPC patients from high-risk individuals who have positive anti-EBV antibodies., Methods: In a population-based NPC screening trial in Sihui City and Zhongshan City, Guangdong Province, China, the authors previously identified 862 high-risk participants with 2 screening markers, immunoglobulin A (IgA) antibodies to EBV capsid antigen (VCA/IgA) and nuclear antigen-1 (EBNA1/IgA). In the current study, real-time polymerase chain reaction was used to measure the baseline plasma EBV DNA load among 825 participants (97%). Follow-up was extended to the end of 2011 to evaluate the diagnostic and predictive values of plasma EBV DNA load., Results: By using 0 copies/mL as the cutoff value, plasma EBV DNA had a sensitivity of 86.8% (33 of 38 patients) for NPC detected within the first year of follow-up, yielding a positive predictive value of 30% (33 of 110 participants) and a negative predictive value of 99.3% (696 of 701 participants). The patients who had early stage NPC had lower sensitivity (81.5%; 22 of 27 patients) than those who had advanced NPC (100%; 11 of 11 patients). For the 14 patients who had NPC detected after 1 year of follow-up, only 50% (7 of 14 patients) tested positive for EBV DNA at baseline., Conclusions: The plasma EBV DNA load may improve the accuracy of diagnosing NPC in high-risk individuals, but it appears to have limited value in screening patients who have early stage NPC and predicting NPC development., (© 2013 American Cancer Society.)

A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.

Objective: To investigate the relationship between the expressions of p53 pathway genes and EZH2 in nasopharyngeal carcinoma (NPC)., Methods: The expression levels of p53, mdm2, p63 and EZH2 proteins were detected by immunohistochemistry in 47 cases of undifferentiated NPC and 12 cases of chronic nasopharyngitis, and their correlation to the clinical parameters and prognosis were analyzed., Results: The protein expressions of p53, mdm2, p63 and EZH2 in NPC were 31.9%, 85.1%, and 95.7%, respectively. mdm2 and EZH2 was not correlated to p53 protein expression (P>0.05); positive correlations was found between EZH2 and p63 expressions and between p53 and p63. The high expression of EZH2 and p63 proteins was correlated to advanced T stage and clinical stage of NPC (P<0.05). The five-year disease-free survival rate in patients with high EZH2 protein expression was significantly lower than that in patients with low EZH2 expression., Conclusion: mdm2 does not show an obvious correlation to p53 protein inactivation in NPC. p63 protein overexpression may be associated with p53 protein inactivation. The overexpression of EZH2 is correlated to NPC progression and poor prognosis.

In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody levels of the cohort fluctuated, the antibody levels of 93% of the patients with NPC were raised and maintained at high levels for up to 10 years prior to diagnosis. This suggests that the serologic window affords an opportunity to monitor tumor progression during the preclinical stage of NPC development, facilitating early NPC detection. We reviewed the clinical records of the 171 patients with NPC in the prospective study to assess the efficacy of early NPC detection by serologic screening and clinical examination. Of the 171 patients, 51 had Stage I tumor (44 were among the 73 patients detected by clinical examination and 7 were among the 98 patients presented to outpatient department). Initial serologic screening predicted 58 (95.1%) of the 61 patients detected within 2 years. The risk of the screened population (58/3093) raised 13 times relative to cohort (61/42 048) during this period. Clinical examination detected all the 58 predicted cases, and 35 (60.3%) of which were diagnosed with Stage I tumor. The serologic prediction rate fell to 33.6% (37/110) 2 to 16 years after screening. The proportion of cases detected by clinical examination fell to 40.5% (15/37). The proportion of Stage I tumors among the cases detected by clinical examination during both periods remained at about 60%. We concluded that early detection of NPC can be accomplished by repeated serologic screening to maintain high prediction rates and by promptly examining screened subjects to detect tumors before the symptoms develop.

Research papers and data concerning NPC epidemiology in China available worldwide were reviewed. It was found that although the results of three national all death-causes sampling surveys in China showed mortality rates in most sampling areas and all as overall to be declining continuously and remarkably, figures for 1987-2000 in some selected areas of China released by the World Health Organization were relatively stable, and the NPC incidence and mortality rates reported by Zhongshan and Sihui cities of Guangdong Province in China had shown ascending or stable trends, respectively. Differences with regard to change in NPC incidence and mortality rates over time may be caused by variation in the data quality from divergent sources, but the exact reasons clearly warrant further analysis.

Background and Objective: Nasopharyngeal carcinoma (NPC), with a remarkable geographic distribution, is consistently associated with Epstein-Barr virus (EBV) infection, and almost all NPC patients have sustained high levels of serum antibodies against EBV. This study was to compare the levels of six anti-EBV antibodies in healthy natives of Zhongshan (a high-incidence area of NPC) with those in provisional migrants from foreign provinces (low-incidence areas of NPC), and to illustrate the relationship between EBV infection and the geographic distribution of NPC., Methods: The serum levels of EBNA1-IgA, EBNA1-IgG, VCA-p18-IgA, VCA-p18-IgG, Zta-IgA and Zta-IgG in 303 healthy Zhongshan natives and 92 provisional migrants were tested using ELISA, and presented by values of adjusted relative absorbance (ArA). The serum levels and positive rates of the six antibodies were compared between the two groups., Results: The mean ArA values of both Zta-IgA and VCA-p18-IgA were significantly higher in Zhongshan natives than in provisional migrants (0.84+/-0.03 vs. 0.42+/-0.04, P <0.05; 0.96+/-0.05 vs. 0.40+/-0.05, P<0.05). In addition, the positive rates of Zta-IgA and VCA-p18-IgA in subjects aged of 30-49, or of 50 and above were significantly higher in Zhongshan natives than in provisional migrants (29.27% vs. 3.03% and 48.28% vs. 6.67% for Zta-IgA, P<0.05; 28.46% vs. 9.09% and 43.10% vs. 13.33% for VCA-p18-igA, P<0.05)., Conclusion: Zhongshan natives are likely to have an elevation of serum IgA antibodies against EBV lytic antigens (Zta and VCA-p18), which represents reactivation of EBV latency infection and implies that Zhongshan natives may have higher risk to develop NPC than provisional migrants.

The energetic equivalence rule, which is based on a combination of metabolic theory and the self-thinning rule, is one of the fundamental laws of nature. However, there is a progressively increasing body of evidence that scaling relationships of metabolic rate vs. body mass and population density vs. body mass are variable and deviate from their respective theoretical values of 3/4 and -3/4 or -2/3. These findings questioned the previous hypotheses of energetic equivalence rule in plants. Here we examined the allometric relationships between photosynthetic mass (M(p)) or leaf mass (M(L)) vs. body mass (beta); population density vs. body mass (delta); and leaf mass vs. population density, for desert shrubs, trees, and herbaceous plants, respectively. As expected, the allometric relationships for both photosynthetic mass (i.e. metabolic rate) and population density varied with the environmental conditions. However, the ratio between the two exponents was -1 (i.e. beta/delta = -1) and followed the trade-off principle when local resources were limited. Our results demonstrate for the first time that the energetic equivalence rule of plants is based on trade-offs between the variable metabolic rate and population density rather than their constant allometric exponents.

We have monitored Epstein-Barr virus (EBV) IgA antibody levels of 39 nasopharyngeal carcinoma (NPC) cases for up to 15 years before clinical onset of NPC, and assessed preclinical serologic status of another 68 cases. Our results identify a serologic window preceding diagnosis when antibody levels are raised and sustained. This window can persist for as long as 10 years, with a mean duration estimated to as 37+/-28 months. Ninety-seven of these 107 NPC cases exhibited such a window. Cases that did not may reflect individual antibody response to EBV. Serologic screening at enrollment identified those cases who had already entered the window and became clinically manifested earlier (median=28 months) than those who entered the window after enrollment (median=90 months). The former account for 19 of 21 cases diagnosed within 2 years of screening. Nasopharyngeal carcinoma risk levels among seropositive subjects were also highest during this period. Both prediction rates and risk levels declined thereafter; cases detected at later times were composed of increasing proportions of individuals who entered the serological window after screening. Our findings establish EBV antibody as an early marker of NPC and suggest that repeated screening to monitor cases as they enter this window has considerable predictive value, with practical consequences for cancer treatment.

Chromosomal abnormalities are associated with a variety of diseases. We have developed a new technique for detecting chromosomal abnormalities, and the technique combines conventional 4',6-diamidino-2-phenyl-indole staining (DAPI) with image analysis. The image analysis consists of two simple steps: deconvolution and three-dimensional reconstruction. The technique has been reported for analyzing plant chromosomes but has not been applied to analyze human chromosomes yet. To test the technique, we analyzed five translocations: 46,XX,t(3;21)(12;18), 46,XX,t(11;22), 46,XY,t(7;22), 46,XY,t(11;18), and 46,XY,t(3;7). The results showed that the karyotype of the 46,XX,t(3;21)(12;18) was 46,XX,t(3;21)(q11.1;p13),t(12;18) (q21.2;q23), and the karyotypes of the 46,XX,t(11;22), 46,XY,t(7;22), 46,XY,t(11;18), and 46,XY,t(3;7) were 46,XX,t(11;22)(q23;q12.1); 46,XY,t(7;22)(q32;q13.2); 46,XY,t(11;18)(q13.3;q23), and 46,XY,t(3;7)(q22.1;p13), respectively. The identity of derivative chromosomes involved in the translocations was verified by chromosome painting as well as FISH analyses with centromere probes. The new technique has two advantages: the procedure is simple and convenient, and the results are accurate. The technique has the potential to be used in cytogenetic studies and clinical diagnosis of human diseases in the future.

Objective: To investigate the effect of paclitaxel and 5-flurouracil (5-Fu) on growth inhibition and apoptosis of human hepatoma BEL-7402 cells., Methods: Growth inhibition of BEL-7402 cells treated with paclitaxel and 5-Fu, respectively, was measured by ATP-tumor chemosensitivity assay (ATP-TCA), and the cell cycle kinetics and apoptosis were analyzed by flow cytometry and microscopic examination., Results: BEL-7402 cells were highly sensitive to paclitaxel with growth inhibition observed in both dose- and time-dependent manners (IC(50)=5.58 x 10(-7) mol/L). Paclitaxel induced significantly higher rate of cell apoptosis than the control group (P<0.05) but significantly lower rate than that induced by 5-Fu (P<0.01). Necrosis was observed predominantly in paclitaxel-treated cells whereas 5-Fu caused mainly cell apoptosis (P<0.05). Levels of apoptosis increased in proportion to the decrement of paclitaxel concentration but directly proportional to increment of 5-Fu concentration., Conclusions: Paclitaxel and 5-Fu are effective in inducing growth inhibition and apoptosis of BEL-7402 cells. While 5-Fu causes mainly apoptosis in hepatoma cells, the anticancer mechanism of paclitaxel is predominantly through induction of necrosis.

Objective: To analyze the change of EB virus VCA/IgA and EA/IgA titer during the development of nasopharyngeal carcinoma (NPC), and the role in screening for NPC., Methods: VCA/IgA and EA/IgA were monitored in a period of 12 years by immunoenzymatic titration from the sera of 54 NPC patients after primary serological screening., Results: VCA/IgA and EA/IgA titer had shown gradual increment 1 - 7 years before NPC was pathologically diagnosed. The mean titer of VCA/IgA was 1:21.04, 7 - 4 years before diagnosis. VCA/IgA titer ascended quickly within 3 years before diagnosis. The geometric mean titer (GMT) of VCA/IgA and EA/IgA were 1:76.86 and 1:6.49 when NPC was diagnosed, which descended quickly after radiotherapy and, in 4 years, approached the average titer of VCA/IgA positive population., Conclusion: VCA/IgA titer rises uninterruptedly 3 years before NPC is diagnosed pathologically in most patients but their EA/IgA titer rises slowly. The detection of VCA/IgA titer can be used to find early NPC, whereas EA/IgA can not. The pre-clinical phase of NPC is 3 years according to this dynamic study.

Objective: To observe the character of Epstein-Barr(EB) virus serology, fibroscopy appearance and prognosis of asymptomatic nasopharyngeal carcinoma(NPC)., Methods: Viral capsid antigen's IgA (VCA/IgA) of EB virus and early antigen's IgA(EA/IgA) of EB virus were detected by immunoenzymatic method. The clinical examination was carried out, including indirect mirror examination and fibroscopy of the nasopharynx and multiple biopsies. All patients of NPC were followed up to the end of 1999., Results: 1. The geometric mean titer of VCA/IgA and EA/IgA are 1:100.79 and 1:10.76 respectively when asymptomatic NPC was diagnosed. There were no significant difference between VCA/IgA and EA/IgA antibody titres of asymptomatic patients and symptomatic cases (P > 0.05). The survival rates in these asymptomatic cases were higher than symptomatic patients (P < 0.05). 2. There was no correlation with the VCA/IgA or EA/IgA titer and the prognosis (P > 0.05) and the cervical lymph node metastasis (P > 0.05) when NPC was diagnosed., Conclusion: This is helpful to detect asymptomatic NPCs by EB serological screening periodically and nasopharyngeal fibroscopy and multiple biopsies.

Objective: To understand the distribution of Epstein-Barr virus (EBV) antibodies, namely EBNA 1/IgA, ZEBRA/IgA, EBNA 1/IgG in the populations of different ages or genders in Zhongshan City of Guangdong Province, China., Method: A total of 484 serum samples were obtained from the population of Zhongshan City including 16 patients with nasopharyngeal carcinoma (NPC) and were assayed with enzyme-linked immunosorbent assay (ELISA) for EBV antibodies., Results: The serum antibody level of EBNA1/IgA, represented by its relative optical density value abbreviated as D(lambda), was 0.726 +/- 0.541 in male and 0.563 +/- 0.340 in female subjects, showing significant difference (P<0.001). The level of ZEBRA/IgG in the male subjects was significantly lower than that of the female subjects (0.709 +/- 0.480 vs 0.829 +/- 0.480, P<0.01). EBNA1/IgG levels differed little between the male and the female subjects, being 0.781 +/- 0.285 and 0.784 +/- 0.302 respectively (P<0.05). The positivity rate of ZEBRA/IgG was obviously related to the subjects' ages with a correlation factor of 0.766 (P<0.05), and NPC patients had significantly higher levels of the 3 antibodies than did the healthy subjects (P<0.01)., Conclusions: The serum levels of these 3 antibodies fluctuate within a limited range in different age groups or between genders, significant increasing in NPC group and therefore may help the diagnosis of NPC. It can be imperative to set differently critical values of EBV antibody for different population groups to facilitate nasopharyngeal carcinoma (NPC) diagnosis and high-risk screening.

We have evaluated the performance of 3 new EBV ELISA for the diagnosis of nasopharyngeal carcinoma (NPC). The tests were specific for EBNA 1 IgA, EBNA 1 IgG and zta IgG, respectively. Their distinct antigenic specificity permits these assays to be used in concert in an approach that differentiates patients and apparently healthy subjects on the basis of their antibody spectrum. By so exploiting a distinguishing feature of NPC first described by Lloyd Olds and his group (Olds et al., Proc Nat Acad Sci 1966;56:1699-1704) [corrected] that the patients sustain high levels of a broad spectrum of serum EBV antibodies, this approach achieved a sensitivity of 92% and a specificity of 93%, surpassing the performance of each of these assays individually. The enhanced performance is especially useful in population screening. It was shown that relative risk of NPC sustained by apparently healthy subjects residing in a high incidence area for NPC in the Pearl River estuary in Southern China may vary according to EBV antibody spectrum. The risk of the cancer was markedly reduced with odds ratios of 0.009 for 59% of those who had low level of all 3 antibodies. The risk was increased as antibody spectrum broadens and the risk was the highest with an odds ratio of 138 for 0.4% of those who had high levels of all 3 antibodies. Thus, EBV antibody spectrum may serve to guide follow-up measures for early detection of the cancer and/or risk counseling according to level of the risk of the cancer sustained by the screened individuals., (Copyright 2001 Wiley-Liss, Inc.)