Construction and validation of serum Metabolic Risk Score for early warning of malignancy in esophagus.

Using noninvasive biomarkers to identify high-risk individuals prior to endoscopic examination is crucial for optimization of screening strategies for esophageal squamous cell carcinoma (ESCC). We conducted a nested case-control study based on two community-based screening cohorts to evaluate the warning value of serum metabolites for esophageal malignancy. The serum samples were collected at enrollment when the cases had not been diagnosed. We identified 74 differential metabolites and two prominent perturbed metabolic pathways, and constructed Metabolic Risk Score (MRS) based on 22 selected metabolic predictors. The MRS generated an area under the receiver operating characteristics curve (AUC) of 0.815. The model performed well for the within-1-year interval (AUC: 0.868) and 1-to-5-year interval (AUC: 0.845) from blood draw to diagnosis, but showed limited ability in predicting long-term cases (>5 years). In summary, the MRS could serve as a potential early warning and risk stratification tool for establishing a precision strategy of ESCC screening.

Surgical quality determines the long-term survival superiority of right over left thoracic esophagectomy for localized esophageal squamous cell carcinoma patients: a real-world multicenter study.

OBJECTIVE: The objective was to compare the long-term overall survival (OS) of right versus left thoracic esophagectomy, and to evaluate whether surgical quality impacts comparison result. BACKGROUND: Controversy regarding the optimal thoracic esophagectomy approach persists for esophageal squamous cell carcinoma (ESCC). No study has assessed the effect of surgical quality in comparison between right and left approaches. METHODS: The authors consecutively recruited 5556 operable ESCC patients from two high-volume centers in China, of whom 2220 and 3336 received right and left thoracic esophagectomy, respectively. Cumulative sum was used to evaluate the learning curve for operation time of right approach, as the indicator of surgical proficiency. RESULTS: With a median follow-up of 83.1 months, right approach, harvesting more lymph nodes, tended to have a better OS than left approach (Mean: 23.8 vs. 16.7 nodes; adjusted hazard ratio (HR)=0.93, 95% CI: 0.85-1.02). Subset analysis by the extent of lymphadenectomy demonstrated that right approach with adequate lymphadenectomy (≥15 nodes) resulted in statistically significant OS benefit compared with left approach (adjusted HR=0.86, 95% CI: 0.77-0.95), but not with limited lymphadenectomy. Subset analysis by surgical proficiency showed that proficient right approach conferred a better OS than left approach (adjusted HR=0.75, 95% CI: 0.64-0.88), but improficient right approach did not have such survival advantage. CONCLUSIONS: Surgical quality plays a crucial role in survival comparison between surgical procedures. Right thoracic esophagectomy performed with adequate lymphadenectomy and surgical proficiency, conferring more favorable survival than left approach, should be recommended as the preferred surgical procedure for localized ESCC.

Postoperative serum squamous cell carcinoma antigen and carcinoembryonic antigen predict overall survival in surgical patients with esophageal squamous cell carcinoma.

Background: Tumor markers are routinely used in clinical practice. However, for resectable patients with esophageal squamous cell carcinoma (ESCC), they are applied infrequently as their prognostic significance is incompletely understood. Methods: This historical cohort study included 2769 patients with resected ESCC from 2011 to 2018 in a high-risk area in northern China. Their clinical data were extracted from the Electronic Medical Record. Survival analysis of eight common tumor markers was performed with multivariable Cox proportional hazards regressions. Results: With a median follow-up of 39.5 months, 901 deaths occurred. Among the eight target markers, elevated postoperative serum SCC (Squamous cell carcinoma antigen) and CEA (Carcinoembryonic antigen) predicted poor overall survival (SCC HRadjusted: 2.67, 95% CI: 1.70-4.17; CEA HRadjusted: 2.36, 95% CI: 1.14-4.86). In contrast, preoperative levels were not significantly associated with survival. Stratified analysis also demonstrated poorer survival in seropositive groups of postoperative SCC and CEA within each TNM stage. The above associations were generally robust using different quantiles of concentrations above the upper limit of the clinical normal range as alternative cutoffs. Regarding temporal trends of serum levels, SCC and CEA were similar. Their concentrations fell rapidly after surgery and thereafter remained relatively stable. Conclusion: Postoperative serum SCC and CEA levels predict the overall survival of ESCC surgical patients. More importance should be attached to the use of these markers in clinical applications.

Effects of combined physical and cognitive training on executive function of adolescent shooting athletes: A functional near-infrared spectroscopy study.

Individual executive function improvement through physical and cognitive training is a research hotspot in physical education and cognitive science. However, few studies have evaluated whether combined physical and cognitive training (CPCT) has greater benefits for executive function performance and cerebral oxygenation in adolescent athletes than cognitive training alone. This study randomly assigned 33 adolescent shooting athletes to a CPCT (n â€‹= â€‹17) or computerized cognitive training (CCT, n â€‹= â€‹16) group and compared their executive function after six weeks of training. All subjects were assessed using the 2-back, task-switching, and Stroop tests before and after training. The prefrontal cortex oxygenated hemoglobin (Oxy-Hb) activation level was monitored while executing the three tasks using functional near-infrared spectroscopy. Our results showed that the CPCT and CCT groups similarly improved their updating function as indicated by the 2-back task accuracy. The CPCT group significantly improved the switching function in the task-switching test accuracy, while the CCT group did not. However, both groups did not improve in behavioral performance as indicated by the inhibition function in the Stroop task. Cerebral oxygenation, indicated by the oxy-Hb activation level in the frontal pole area of the prefrontal lobe, significantly improved in the CPCT group during the three cognitive tasks, whereas the CCT group showed no change. These findings indicated that CPCT endowed greater advantages in task-switching in the behavioral performance of the executive function than CCT. Moreover, CPCT was superior to CCT in increasing task-efficient cerebral oxygenation during the activation of the prefrontal cortex in adolescent shooting athletes.

Proper use of light environments for mitigating the effects of COVID-19 and other prospective public health emergency lockdowns on sleep quality and fatigue in adolescents.

Coronavirus disease 2019 (COVID-19) remains a public health emergency of international concern, and some countries still implement strict regional lockdowns. Further, the upcoming 2023 Asian Games and World University Games will implement a closed-loop management system. Quarantine can harm mental and physical health, to which adolescents are more vulnerable compared with adults. Previous studies indicated that light can affect our psychology and physiology, and adolescents were exposed to the artificial light environment in the evening during the lockdown. Thus, this study aimed to establish and assess appropriate residential light environments to mitigate the effects of lockdowns on sleep quality and fatigue in adolescents. The participants were 66 adolescents (12.15 ± 2.45 years of age) in a closed-loop management environment, who participated in a 28-day (7-day baseline, 21-day light intervention) randomized controlled trial of a light-emitting diode (LED) light intervention. The adolescents were exposed to different correlated color temperature (CCT) LED light environments (2000 K or 8000 K) for 1 h each evening. The results for self-reported daily sleep quality indicated that the low CCT LED light environment significantly improved sleep quality (p < 0.05), and the blood test results for serum urea and hemoglobin indicated that this environment also significantly reduced fatigue (p < 0.05) and moderately increased performance, compared to the high CCT LED light environment. These findings can serve as a springboard for further research that aims to develop interventions to reduce the effects of public health emergency lockdowns on mental and physical health in adolescents, and provide a reference for participants in the upcoming Asian Games and World University Games.

Is Adjuvant Therapy a Better Option for Esophageal Squamous Cell Carcinoma Patients Treated With Esophagectomy? A Prognosis Prediction Model Based on Multicenter Real-World Data.

OBJECTIVE: To construct a prediction model for more precise evaluation of prognosis which will allow personalized treatment recommendations for adjuvant therapy in patients following resection of ESCC. BACKGROUND: Marked heterogeneity of patient prognosis and limited evidence regarding survival benefit of various adjuvant therapy regimens pose challenges in the clinical treatment of ESCC. METHODS: Based on comprehensive clinical data obtained from 4129 consecutive patients with resected ESCC in a high-risk region in China, we identified predictors for overall survival through a 2-phase selection based on Cox proportional hazard regression and minimization of Akaike information criterion. The model was internally validated using bootstrapping and externally validated in 1815 patients from a non-high-risk region in China. RESULTS: The final model incorporates 9 variables: age, sex, primary site, T stage, N stage, number of lymph nodes harvested, tumor size, adjuvant treatment, and hemoglobin level. A significant interaction was also observed between N stage and adjuvant treatment. N1+ stage patients were likely to benefit from addition of adjuvant therapy as opposed to surgery alone, but adjuvant therapy did not improve overall survival for N0 stage patients. The C -index of the model was 0.729 in the training cohort, 0.723 after bootstrapping, and 0.695 in the external validation cohort. This model outperformed the seventh edition American Joint Committee on Cancer staging system in prognostic prediction and risk stratification. CONCLUSIONS: The prediction model constructed in this study may facilitate precise prediction of survival and inform decision-making about adjuvant therapy according to N stage.

Minimally Invasive or Open Esophagectomy for Treatment of Resectable Esophageal Squamous Cell Carcinoma? Answer From a Real-world Multicenter Study.

OBJECTIVE: To evaluate the long-term and short-term outcomes of MIE compared with OE in localized ESCC patients in real-world settings. BACKGROUND: MIE is an alternative to OE, despite the limited evidence regarding its effect on long-term survival. METHODS: We recruited 5822 consecutive patients with resectable ESCC in 2 typical high-volume centers in southern and northern China, 1453 of whom underwent MIE. Propensity score-based overlap weighted regression adjusted for multifaceted confounding factors was used to compare outcomes in the MIE and OE groups. RESULTS: Five-year OS was 62.7% in the MIE group and 57.7% in the OE group. The overlap weighted Cox regression showed slightly better OS in the MIE group (hazard ratio 0.93, 95% confidence interval: 0.82-1.06). Although duration of surgery was longer and treatment cost higher in the MIE group than in the OE group, the number of lymph nodes harvested was larger, the proportion of intraoperative blood transfusions lower, and postoperative complications less in the MIE group. 30-day (risk ratio [RR] 0.77, 0.381.55) and 90-day (RR 0.79, 0.46-1.35) mortality were lower in the MIE group versus the OE group, although not statistically significant. These findings were consistent across different analytic approaches and subgroups, notably in the subset of ESCC patients with large tumors. CONCLUSIONS: MIE can be performed safely with OS comparable to OE for patients with localized ESCC, indicating MIE may be recommended as the primary surgical approach for resectable ESCC in health facilities with requisite technical capacity.

Dietary chitosan moderates the growth rate, antioxidant activity, immunity, intestinal morphology and resistance against Aeromonas hydrophila of juvenile hybrid sturgeon (Acipenser baerii♀ × Acipenser schrenckii♂).

This study investigated the effects of dietary chitosan on growth, antioxidant, immunity, intestinal morphology and resistance against Aeromonas hydrophila of hybrid sturgeon (Acipenser baerii♀ × Acipenser schrenckii♂). Sturgeons (18.18 ± 0.08 g) were randomly divided into four groups, fed with chitosan-supplemented diets for 8 weeks and then infected with A. hydrophila. The results showed significant differences of body weight gain, specific growth rate and feed conversion ratio in sturgeon fed chitosan and control diets. The oral administration of chitosan significantly increased the acid phosphatase, alkaline phosphatase, lysozyme, myeloperoxidase, superoxide dismutase, glutathione peroxidase and catalase activities, as well as the complement 3 and 4 contents and disease resistance against A. hydrophila. Moreover, enhancement of muscular thickness and goblet cells in mid intestine and increase of muscular thickness and villus height in spiral valve were observed in the chitosan supplemented groups. In addition, dietary chitosan-supplemented diets mitigated the changes of antioxidant and immune activity induced by A. hydrophila challenge, as well as prevented fish from bacterial invasion. The optimal dose was 3.00 g chitosan/kg diet for hybrid sturgeon.

Cost-effectiveness of precision screening for esophageal cancer based on individualized risk stratification in China: Real-world evidence from the ESECC trial.

Background: Conventional universal endoscopic screening with pathology-based endoscopic re-examination for esophageal squamous cell carcinoma is in need of reform in China. We established a "two-step" precision screening strategy using two risk prediction models and have evaluated the cost-effectiveness of this precision strategy compared with the traditional strategy based on a large population-level randomized controlled trial from a healthcare provider's perspective. Methods: Four precision screening strategies with different risk cutoffs at baseline screening and endoscopic surveillance were constructed, and then compared with traditional strategy through modeling using subjects from the screening cohort of the ESECC (Endoscopic Screening for Esophageal Cancer in China) trial. Total screening costs and the number of SDA (severe dysplasia and above in lesions of the esophagus) cases were obtained to calculate the average screening cost per SDA detected, the incremental cost-effectiveness ratio (ICER) and protection rates. Sensitivity analysis was conducted to evaluate uncertainties. Results: Compared to traditional strategy, all precision screening strategies have much lower average costs for detection of one SDA case ($7,148~$11,537 vs. $14,944). In addition, precision strategies 1&2 (strategies 1,2,3,4 described below) achieved higher effectiveness (143~150 vs. 136) and higher protection rates (87.7%~92.0% vs. 83.4%) at lower cost ($1,649,727~$1,672,221 vs. $2,032,386), generating negative ICERs (-$54,666/SDA~-$25,726/SDA) when compared to the traditional strategy. The optimal strategies within different willingness-to-pay (WTP) ranges were all precision screening strategies, and higher model sensitivities were adopted as WTP increased. Conclusions: Precision screening strategy for esophageal cancer based on risk stratification is more cost-effective than use of traditional screening strategy and has practical implications for esophageal cancer screening programs in China.

Co-infections of Aeromonas veronii and Nocardia seriolae in largemouth bass (Micropterus salmoides).

Largemouth bass (Micropterus salmoides) is an important commercial fish species that is widely cultured throughout China. With the application of high-density culture, M. salmoides is usually infected by different pathogens in water. Particularly, co-infection with multiple pathogens was common, which has considerably outweighed the impact caused by single infections. In this research, two bacteria strains were isolated from diseased fish by incubating on brain heart infusion agar. According to the results of 16S rRNA and gyrB sequence, as well as the analysis of morphological, physiological and biochemical features, the isolated bacterial strains were finally identified as Aeromonas veronii and Nocardia seriolae, respectively. In addition, eight virulence genes related to pathogenicity including enterotoxin, lipase, elastase, quorum sensing, hemolysin and adhesion were identified in A. veronii isolate and eight virulence genes encoding mammalian cell entry family proteins, glyceraldehyde-3-phosphate dehydrogenase, mycolyltransferase, nitrate reductase subunits, and putative cytotoxin/hemolysin were detected in N. seriolae isolate. Drug sensitivity testing indicated that both A. veronii and N. seriolae isolates were susceptible to kanamycin, streptomycin, gentamycin, neomycin, doxycycline, tetracycline, ciprofloxacin and levofloxacin, and resistant to amikacin, cefpimizole, ampicillin, piperacillin, carbenicillin, oxacillin, rifampicin, trimethoprim, vancomycin, meropenem, imipenem and sulfisoxazole. Moreover, serious histopathological changes, such as typical granulomas with necrotic center, cell degeneration and necrosis, hemorrhage and inflammatory cell infiltration, were found in the naturally diseased fish. The LD50 of A. veronii and N. seriolae isolates were 7.94 × 105 CFU/g and 3.16 × 106 CFU/g fish weight, respectively. In addition, the coinfection of A. veronii and N. seriolae induce quick and higher mortality in comparison with those challenged by single bacteria. These results revealed that both A. veronii and N. seriolae participated in the disease outbreaks of the M. salmoides, and concurrent of those two bacteria synergistically exacerbate the disease severity.

Comparative Transcriptome Analysis Provides Insights Into the Mechanism by Which 2,4-Dichlorophenoxyacetic Acid Improves Thermotolerance in Lentinula edodes.

As the widest cultivated edible mushroom worldwide, Lentinula edodes suffers serious yield and quality losses from heat stress during growth and development, and in our previous study, exogenous 2,4-Dichlorophenoxyacetic acid (2,4-D) was found to improve the thermotolerance of L. edodes strain YS3357, but the molecular mechanism remains unclear. Here, we explored the potential protective mechanism of exogenous 2,4-D against heat stress by transcriptome analysis. 2,4-D possible improve the thermotolerance of L. edodes through regulating antioxidant genes, transcription factors, energy-provision system, membrane fluidity, and cell wall remodeling. Furthermore, 2,4-D was also found to regulate the saturation levels of fatty acids and ATP content in L. edodes mycelium under heat stress. This study proposed a regulatory network of 2,4-D in regulating L. edodes response to heat stress, providing a theoretical basis for improving L. edodes thermotolerance, and facilitating the understanding of the molecular mechanism of exogenous hormones in alleviating abiotic stress damage to macrofungi.

Absence of NOTCH1 mutation and presence of CDKN2A deletion predict progression of esophageal lesions.

Currently, surveillance for esophageal squamous cell carcinoma (ESCC) runs a risk of underestimation of early lesions which show absence of iodine staining, with no or only mild histologic changes. The development of molecular markers that indicate risk of progression is thus warranted. We performed whole-exome sequencing on biopsies from two sequential endoscopies of a single esophageal lesion and matching blood samples. There were 27 pairs of age-, gender-, pathologic stage-, and sampling interval-matched progressors and non-progressors identified in a prospective community-based ESCC screening trial. Putative molecular progression markers for ESCC were first evaluated by comparing somatic mutation, copy number alteration (CNA), and mutational signature information among progressors and non-progressors. These markers were then validated with another 24 pairs of matched progressors and non-progressors from the same population using gene alteration status identified by target sequencing and quantitative PCR. Progressors had more somatic mutation and CNA burden, as well as apolipoprotein B mRNA editing catalytic polypeptide-like and age-related signature weights compared with non-progressors. A gene score consisting of somatic NOTCH1 mutation and CDKN2A deletion is predictive of risk of progression in lesions which show absence of iodine staining under endoscopy but have no or only mild dysplasia. This gene score was also validated in an external cohort of matched progressors and non-progressors. Absence of NOTCH1 mutation and presence of CDKN2A deletion are markers of progression in squamous lesions of the esophagus. This gene score would be an ideal indicator for assisting the pathologist in the identification of high-risk individuals who could be potentially 'missed' or subject to a risk underestimation by histologic analysis, and might improve the performance of ESCC surveillance. © 2022 The Pathological Society of Great Britain and Ireland.

Bacillus subtilis HG-15, a Halotolerant Rhizoplane Bacterium, Promotes Growth and Salinity Tolerance in Wheat (Triticum aestivum).

Certain plant growth-promoting bacteria (PGPB) reduce salt stress damage in plants. Bacillus subtilis HG-15 is a halotolerant bacterium (able to withstand NaCl concentrations as high as 30%) isolated from the wheat rhizoplane in the Yellow River delta. A qualitative and quantitative investigation of the plant growth-promoting characteristics of this strain confirmed nitrogen fixation, potassium dissolution, ammonia, plant hormone, ACC deaminase, and proline production abilities. B. subtilis HG-15 colonization of wheat roots, stems, and leaves was examined via scanning electron microscopy, rep-PCR, and double antibiotic screening. After inoculation with the B. subtilis HG-15 strain, the pH (1.08-2.69%), electrical conductivity (3.17-11.48%), and Na+ (12.98-15.55%) concentrations of rhizosphere soil significantly decreased (p < 0.05). Under no-salt stress (0.15% NaCl), low-salt stress (0.25% NaCl), and high-salt stress (0.35% NaCl) conditions, this strain also significantly increased (p < 0.05) the dry weight (17.76%, 24.46%, and 9.31%), fresh weight (12.80%, 20.48%, and 7.43%), plant height (7.79%, 5.86%, and 13.13%), and root length (10.28%, 17.87%, and 48.95%). Our results indicated that B. subtilis HG-15 can effectively improve the growth of wheat and elicit induced systemic tolerance in these plants, thus showing its potential as a microbial inoculant that can protect wheat under salt stress conditions.

Update and validation of a diagnostic model to identify prevalent malignant lesions in esophagus in general population.

Background: Previous risk prediction models taking esophageal malignant lesions detected during endoscopy as the primary outcome are not always sufficient to identify prevalent cases which are "overlooked" at screening. We aimed to update and externally validate our previous risk prediction model for malignant esophageal lesions by redefining the predicted outcome. Methods: 15,192 individuals from the Endoscopic Screening for Esophageal Cancer in China randomized controlled trial (ESECC trial, NCT01688908) were included as the training set, and 4576 participants from another population-based esophageal squamous cell carcinoma (ESCC) screening cohort (Anyang Esophageal Cancer Cohort Study, AECCS) served as the external validation set. Lesions with severe dysplasia or worse diagnosed at chromoendoscopy or identified via follow-up within 1 year after screening were defined as main outcome. Logistic regressions were applied to reconstruct the questionnaire-based prediction model using information collected before screening, with Akaike Information Criterion to determine the model structure. Findings: The final prediction model included age and its quadratic term, family history of ESCC, low body mass index (≤22 kg/m2), use of coal or wood as main fuel for cooking, eating rapidly, and ingestion of leftover food. The area under the curve was 0·77 (95% CI: 0·73-0·80) and 0·71 (95% CI: 0·65-0·78) in the training and validation set. When screening the top 50% or 10% of high-risk individuals within population, the detection rates can be increased in both cohorts, as compared to universal screening. Interpretation: The described tool may promote the efficiency of current national screening programs for ESCC and contribute to a precision screening strategy in high-risk regions in China. Funding: This work was supported by the National Natural Science Foundation of China (82073626, 81773501), the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Key R&D Program of China (2021YFC2500405), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204) and the Beijing Nova Program (Z201100006820093). Sponsors had no role in the study design, data collection, analysis, and interpretation of data.

Tumor-associated autoantibodies in ESCC screening: Detecting prevalent early-stage malignancy or predicting future cancer risk?

BACKGROUND: To assess potential roles for tumor-associated autoantibodies (TAAs) in esophageal squamous cell carcinoma (ESCC) screening: detecting early-stage malignancy, and predicting future cancer risk. METHOD: Thirteen candidate autoantibodies identified in previous literatures were measured using multiplex serological assays in sera from cases and matched controls nested in two population-level screening cohorts in China. To evaluate the role of TAAs in detecting prevalent esophageal malignant lesions, an identification set (150 cases vs. 560 controls) and an external validation set (34 cases vs. 121 controls) were established with pre-screening sera collected ≤ 12 months prior to screening-related diagnosis. To explore the role of TAAs in predicting future ESCC risk, an exploration set (105 cases vs. 416 controls) with pre-diagnostic sera collected > 12 months before clinical diagnosis was established. Two models, the questionnaire-based model and full model additionally incorporating TAA markers, were constructed. Area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to compare the performance of the two models. FINDINGS: In the identification set, NY-ESO-1 (OR=2·12, 95% CI=1·02-4·40) and STIP1 (OR=1·83, 95% CI=1·10-3·05) were positively associated with higher risk of esophageal malignancy. Elevated MMP-7 was associated with higher risk of malignancy in females (ORfemale=5·07, 95% CI=1·30-19·71). The estimates in validation set were consistent with these results, but were close to null in exploration set. Integration of selected TAAs improved the performance of questionnaire-based models in detecting prevalent esophageal malignancy (female: AUCfull model=0·745, 95% CI=0·675-0·814, AUCquestionnaire-based model=0·658, 95% CI=0·585-0·732, NRI=0·604, P<0·0001; male: AUCfull model=0·662, 95% CI=0·596-0·728, AUCquestionnaire-based model=0·619, 95% CI=0·548-0·690, NRI=0·357, P=0·0028). This improvement was also seen in validation set, but was not similarly effective in distinguishing long-term incident cases from healthy controls. INTERPRETATION: Serological autoantibodies against NY-ESO-1, STIP1, and MMP-7 perform well in detecting early-stage esophageal malignancy, but are less effective in predicting future ESCC risks. FUNDING: This work was supported by the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Natural Science Foundation of China (82073626), the National Key R&D Program of China (2016YFC0901404), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204), and the Natural Science Foundation of Beijing Municipality (7182033).

Enhanced Expression of Thaumatin-like Protein Gene (LeTLP1) Endows Resistance to Trichoderma atroviride in Lentinula edodes.

Lentinula edodes (shiitake mushrooms) is heavily affected by the infection of Trichoderma atroviride, causing yield loss and decreases quality in shiitake mushrooms. The selection and breeding of fungal-resistant L. edodes species are an important approach to protecting L. edodes from T. atroviride infection. Herein, a highly resistant L. edodes strain (Y3334) and a susceptible strain (Y55) were obtained by using a resistance evaluation test. Transcriptome analyses and qRT-PCR detection showed that the expression level of LeTLP1 (LE01Gene05009) was strongly induced in response to T. atroviride infection in the resistant Y3334. Then, LeTLP1-silenced and LeTLP1-overexpression transformants were obtained. Overexpression of LeTLP1 resulted in resistance to T. atroviride. Compared with the parent strain Y3334, LeTLP1-silenced transformants had reduced resistance relative to T. atroviride. Additionally, the LeTLP1 protein (Y3334) exhibited significant antifungal activity against T. atroviride. These findings suggest that overexpression of LeTLP1 is a major mechanism for the resistance of L. edodes to T. atroviride. The molecular basis provides a theoretical basis for the breeding of resistant L. edodes strains and can eventually contribute to the mushroom cultivation industry and human health.

Blood plasma resonance Raman spectroscopy combined with multivariate analysis for esophageal cancer detection.

We herein report a novel, reliable and inexpensive method for detecting esophageal cancer using blood plasma resonance Raman spectroscopy combined with multivariate analysis methods. The blood plasma samples were divided into late stage cancer group (n = 164), early stage cancer group (n = 35) and normal group (n = 135) based on clinical pathological diagnosis. Using a specially designed quartz capillary tube as sample holder, we obtained higher quality resonance Raman spectra of blood plasma than existing method. The study demonstrated that the carotenoids levels in blood plasma were reduced in esophageal cancer patients. The area under the receiver operating characteristic curve (and 95% confidence interval) calculated by wavenumber selection and principal component analysis combined with linear discriminant analysis (PC-LDA) algorithm were 0.894 (0.858-0.929), 0.901 (0.841-0.960) and 0.871 (0.799-0.942) for differentiating late cancer from normal, late cancer from early cancer, and early cancer from normal respectively. The contribution from the two carotenoids wavenumber regions of 1155 and 1515 cm-1 were more than 84.2%. The results show that the plasma carotenoids could be a potential biomarker for screening esophageal cancer using resonance Raman spectroscopy combined with wavenumber selection and PC-LDA algorithms.

Family history of esophageal cancer modifies the association of serum lipids and malignant esophageal lesions: a nested case-control study from the "Endoscopic Screening for Esophageal Cancer in China" trial.

BACKGROUND: The association of lipids and cancer has varied greatly among different cancer types, lipid components and study populations. This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium. METHODS: In the "Endoscopic Screening for Esophageal Cancer in China" (ESECC) trial, serum samples were collected and tested for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol at the time of subject enrollment. Cases were defined as malignant esophageal lesions identified by baseline endoscopic examination or by follow-up to May 31, 2018. Controls were randomly selected using incidence density sampling in the same cohort. Conditional logistic models were applied to identify the association of serum lipids and the risk of malignant esophageal lesions. Effect modification was evaluated by testing interaction terms of the factor under assessment and these serum lipid indicators. RESULTS: No consistent association between serum lipid levels and esophageal malignant lesions were found in a pooled analysis of 211 cases and 2101 controls. For individuals with a family history of esophageal cancer (EC), high TC, and LDL-C were associated with a significantly increased risk of having malignant lesions (odds ratio [OR]High vs. Low TC = 2.22, 95% confidence interval [CI]: 1.14-4.35; ORHigh vs. Low LDL-C = 1.93, 95% CI: 1.01-3.65). However, a negative association was observed in participants without an EC family history (ORHigh vs. Low TC = 0.69, 95% CI: 0.48-0.98, Pinteraction = 0.002; ORHigh vs. Low LDL-C = 0.50, 95% CI: 0.34-0.76, Pinteraction < 0.001). CONCLUSIONS: In this study, we found that the association of serum lipids and malignant esophageal lesions might be modified by EC family history. The stratified analysis would be crucial for population-based studies investigating the association of serum lipids and cancer. The mechanism by which a family history of EC modifies this association warrants further investigation.

Size of Lugol-unstained lesions as a predictor for risk of progression in premalignant lesions of the esophagus.

BACKGROUND AND AIMS: At present, the surveillance strategy for premalignant esophageal lesions in China is based solely on the pathologic diagnosis in Lugol's chromoendoscopy (LCE). In this study, we sought to determine the degree to which various unstained features under LCE may lead to improved ability to predict the risk of progression in esophageal lesions. METHODS: We re-examined and followed up on 1058 subjects who had Lugol-unstained lesions (LULs) together with a pathologic diagnosis that was lower than severe dysplasia at baseline screening based on a population-based randomized controlled trial over a median time of 5.8 years. We established a logistic regression model and calculated the adjusted cumulative incidence of severe dysplasia or malignancy. RESULTS: LUL size was predictive of progression to malignant lesions in individuals with a nondysplastic diagnosis (adjusted odd ratio6-10 mm vs ≤5 mm, 6.7; 95% confidence interval, 1.7-25.7; adjusted odds ratio>10 mm vs ≤5 mm, 27.9; 95% confidence interval, 7.3-105.7), and the corresponding adjusted cumulative incidence of malignant lesions was 3.6 and 13.2 per 100 persons. This is higher than that of small (≤5 mm) lesions, which showed mild dysplasia (2.7 per 100 persons), a condition for which surveillance every 3 years is recommended. Under the current approach, 65.3% of interval cancers missed at surveillance would be detected if individuals with medium (6-10 mm) and large (>10 mm) nondysplastic LULs were additionally monitored. CONCLUSIONS: We propose a modified surveillance strategy that combines findings under LCE examination and the pathologic analysis, where follow-up endoscopy is recommended for individuals with relatively large nondysplastic lesions.

An evaluation of EQ-5D-3L health utility scores using five country-specific tariffs in a rural population aged 45-69 years in Hua county, Henan province, China.

BACKGROUND: This study aims to compare the performance of the recently developed Chinese (city) tariff of the EQ-5D-3L against the UK, US, Japanese and Korean tariffs in a general rural population in China. METHODS: From November 2015 to September 2016, 12,085 permanent residents aged 45-69 from 257 villages randomly selected from Hua County, Henan Province, China, were interviewed using EQ-5D-3L, and a one-on-one questionnaire investigation was used to collect data on factors associated with HRQOL. The health utility scores were calculated using the UK, US, Japanese, Korean and Chinese (city) tariffs. The agreement, known-groups validity and sensitivity of these five tariffs were evaluated. Transition scores for pairs of observed EQ-5D-3L health states were calculated and compared. RESULTS: The Korean tariff yielded the highest mean health utility score (0.963), followed by the Chinese (city) (0.948), US (0.943), UK (0.930) and Japanese (0.921) tariffs, but the differences in the scores of any two tariffs did not exceed the MCID. The Chinese (city) tariff showed higher ICC values (ICCs> 0.89, 95% CI:0.755-0.964) and narrower limits of agreement (0.099-0.167) than the Korean tariff [(ICCs> 0.71, 95% CI:0.451-0.955); (0.146-0.253)]. The Chinese (city) tariff had a higher relative efficiency and effect size statistics in 10 out of 11 variables as compared to the UK, US and Japanese tariffs. The Chinese (city) tariff (0.215) was associated with moderate mean absolute transition scores compared with the UK (0.342), US (0.230), Japanese (0.149) and Korean (0.189) tariffs for 1485 observed pairs of the EQ-5D-3L health states. CONCLUSIONS: Health utility scores derived from the five tariffs differed. The Chinese (city) tariff was the most suitable of these tariffs and was without obvious weakness. We recommend adopting the Chinese (city) tariff when applying EQ-5D-3L to assess quality of life among the elderly in China's agricultural region with socio-economic status similar to Hua County. Results of this study had provided a crucial basis for health surveys, health promotion projects, health intervention trials, and health economic evaluation taking HRQOL as a target in rural areas of China.