Emerging concepts in alcohol, infection & immunity: A summary of the 2023 alcohol and immunology research interest group (AIRIG) meeting.

On December 8th 2023, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Anschutz Medical Campus in Aurora, Colorado. The 2023 meeting focused broadly on how acute and chronic alcohol exposure leads to immune dysregulation, and how this contributes to damage in multiple tissues and organs. These include impaired lung immunity, intestinal dysfunction, autoimmunity, the gut-Central Nervous System (CNS) axis, and end-organ damage. In addition, diverse areas of alcohol research covered multiple pathways behind alcohol-induced cellular dysfunction, including inflammasome activation, changes in miRNA expression, mitochondrial metabolism, gene regulation, and transcriptomics. Finally, the work presented at this meeting highlighted novel biomarkers and therapeutic interventions for patients suffering from alcohol-induced organ damage.

Effectiveness of Endoscopic Screening on Esophageal Cancer Incidence and Mortality: A 9-Year Report of the Endoscopic Screening for Esophageal Cancer in China (ESECC) Randomized Trial.

PURPOSE: To evaluate the effectiveness of endoscopic screening against incidence of and mortality from esophageal squamous cell carcinoma (ESCC). METHODS: From January 2012 to September 2016, we conducted a community-based cluster randomized controlled trial involving permanent residents age 45-69 years in a high-risk region for ESCC in northern China. A total of 668 targeted villages were randomly assigned in a 1:1 ratio to the screening group (offered Lugol's chromoendoscopy) or control group (no screening). Intention-to-treat and per-protocol analyses were performed to compare esophageal cancer (EC) incidence and mortality between the two groups. The per-protocol analysis adjusted for nonadherence to the screening procedure. RESULTS: A total of 33,847 participants were included in the analysis: 17,104 in the screening group, 15,165 (88.7%) of whom underwent screening, and 16,743 in the control group. During a maximum follow-up of 9 years, EC incidence in the screening and control groups were 60.9 and 72.5 per 100,000 person-years, respectively; mortality in the screening and control groups were 29.7 and 32.4 per 100,000 person-years, respectively. Compared with the control group, the incidence and mortality of the screening group reduced by 19% (adjusted hazard ratio [aHR], 0.81 [95% CI, 0.60 to 1.09]) and 18% (aHR, 0.82 [95% CI, 0.53 to 1.26]), respectively, in the intention-to-treat analysis; and by 22% (aHR, 0.78 [95% CI, 0.56 to 1.10]) and 21% (aHR, 0.79 [95% CI, 0.49 to 1.30]), respectively, in the per-protocol analysis. CONCLUSION: With a 9-year follow-up, our trial suggests that chromoendoscopic screening induces modest reductions in EC incidence and mortality. A more efficient strategy for EC screening and subsequent patient management should be established to guarantee the effectiveness of endoscopic screening.

Development and external validation of a quantitative diagnostic model for malignant gastric lesions in clinical opportunistic screening: A multicenter real-world study.

BACKGROUND: Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening. METHODS: We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial. RESULTS: This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750-0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570-0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios. CONCLUSION: This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

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.

The dynamic recruitment of LAB proteins senses meiotic chromosome axis differentiation in C. elegans.

During meiosis, cohesin and meiosis-specific proteins organize chromatin into an axis-loop architecture, coordinating homologous synapsis, recombination, and ordered chromosome segregation. However, how the meiotic chromosome axis is assembled and differentiated with meiotic progression remains elusive. Here, we explore the dynamic recruitment of two long arms of the bivalent proteins, LAB-1 and LAB-2, in Caenorhabditis elegans. LAB proteins directly interact with the axis core HORMA complexes and weak interactions contribute to their recruitment. LAB proteins phase separate in vitro, and this capacity is promoted by HORMA complexes. During early prophase, synapsis oppositely regulates the axis enrichment of LAB proteins. After the pachytene exit, LAB proteins switch from a reciprocal localization pattern to a colocalization pattern, and the normal dynamic pattern of LAB proteins is altered in meiotic mutants. We propose that LAB recruitment senses axis differentiation, and phase separation of meiotic structures helps subdomain establishment and accurate segregation of the chromosomes.

Integrating Surrounding Vehicle Information for Vehicle Trajectory Representation and Abnormal Lane-Change Behavior Detection.

The detection of abnormal lane-changing behavior in road vehicles has applications in traffic management and law enforcement. The primary approach to achieving this detection involves utilizing sensor data to characterize vehicle trajectories, extract distinctive parameters, and establish a detection model. Abnormal lane-changing behaviors can lead to unsafe interactions with surrounding vehicles, thereby increasing traffic risks. Therefore, solely focusing on individual vehicle perspectives and neglecting the influence of surrounding vehicles in abnormal lane-changing behavior detection has limitations. To address this, this study proposes a framework for abnormal lane-changing behavior detection. Initially, the study introduces a novel approach for representing vehicle trajectories that integrates information from surrounding vehicles. This facilitates the extraction of feature parameters considering the interactions between vehicles and distinguishing between different phases of lane-changing. The Light Gradient Boosting Machine (LGBM) algorithm is then employed to construct an abnormal lane-changing behavior detection model. The results indicate that this framework exhibits high detection accuracy, with the integration of surrounding vehicle information making a significant contribution to the detection outcomes.

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.

How should extra-large Lugol-unstained lesions of the esophagus be treated? Results from a population-based cohort study.

BACKGROUND: Current guidelines recommend only severe dysplasia and above (SDA) lesions of the esophageal squamous epithelium for clinical intervention. However, the histopathologic diagnosis derived from tissue biopsies may be subject to underestimation of severity. METHODS: 1073 participants from whom biopsies were taken at baseline chromoendoscopic examination in a population-based screening trial were enrolled in this study. The size of the Lugol-unstained lesions (LULs) was mainly analyzed. The outcome was defined as SDA lesions either identified at baseline screening, or during follow-up, collectively referred to as the cumulative risk of SDA. Multivariable logistic regression models were used to evaluate the cumulative risk of SDA. RESULTS: One hundred and forty-six SDA cases were identified in the study period. Participants with large LULs had a high cumulative incidence of SDA (cumulative incidence16-20mm : 55.88%; cumulative incidence>20mm : 76.92%) in the median of 7-year duration. LULs of large size were significantly associated with a higher cumulative risk of SDA, regardless of the pathologic diagnosis (adjusted OR16-20mmvs.≤5mm = 21.02, 95% CI: 7.56-58.47; adjusted OR>20mmvs.≤5mm = 33.62, 95% CI: 11.79-95.87). CONCLUSIONS: Results from this study suggest physician-patient shared decision-making regarding clinical treatment or intensive surveillance should be carried out for LULs >20 mm in the esophagus, regardless of the histologic diagnosis. For those with LULs of 16-20 mm, intensive surveillance would also best be considered.

Lugol-unstained lesions location in the esophagus affects the detection rate of malignancy: a population-based study.

INTRODUCTION: This study aimed to evaluate the impact of Lugol-unstained lesion (LUL) location on the detection yield, which may help the endoscopist select targets for biopsy. METHODS: We enrolled 1064 subjects who had LULs at the baseline screening of a population-based randomized controlled trial. There were 1166 LULs with recorded location and pathologic diagnosis, and these were used for analysis. The detection rate of severe dysplasia and above (SDA) was calculated as the number of LULs identified as SDA divided by the number of LULs biopsied. Logistic regression with a generalized estimating equation was applied to evaluate the association between the location of a given LUL and the risk of the LUL being SDA. RESULTS: The detection rate of SDA for LULs located in the lower, middle, and upper esophagus increased from 5.9% and 10.9% to 16.7%. LUL location was significantly associated with having SDA (adjusted odds ratio (OR)upper vs. lower  = 2.88, 95% confidential interval (CI) = 1.48-5.60; adjusted ORmiddle vs. lower  = 1.63, 95% CI = 0.96-2.76), and the association was stronger in subgroups with a family history of esophageal squamous cell carcinoma (ESCC) (adjusted ORupper vs. lower  = 9.72, 95% CI = 2.57-36.69; adjusted ORmiddle vs. lower  = 3.76, 95% CI = 0.93-15.21). CONCLUSIONS: Our results suggest that more attention should be paid by endoscopists to LULs in the upper and middle esophagus, particularly for individuals with a family history of ESCC.

[Effect of Kartogenin combined with adipose-derived stem cells on tendon-bone healing after anterior cruciate ligament reconstruction].

Objective: To investigate the effect of Kartogenin (KGN) combined with adipose-derived stem cells (ADSCs) on tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in rabbits. Methods: After the primary ADSCs were cultured by passaging, the 3rd generation cells were cultured with 10 µmol/L KGN solution for 72 hours. The supernatant of KGN-ADSCs was harvested and mixed with fibrin glue at a ratio of 1∶1; the 3rd generation ADSCs were mixed with fibrin glue as a control. Eighty adult New Zealand white rabbits were taken and randomly divided into 4 groups: saline group (group A), ADSCs group (group B), KGN-ADSCs group (group C), and sham-operated group (group D). After the ACL reconstruction model was prepared in groups A-C, the saline, the mixture of ADSCs and fibrin glue, and the mixture of supernatant of KGN-ADSCs and fibrin glue were injected into the tendon-bone interface and tendon gap, respectively. ACL was only exposed without other treatment in group D. The general conditions of the animals were observed after operation. At 6 and 12 weeks, the tendon-bone interface tissues and ACL specimens were taken and the tendon-bone healing was observed by HE staining, c-Jun N-terminal kinase (JNK) immunohistochemical staining, and TUNEL apoptosis assay. The fibroblasts were counted, and the positive expression rate of JNK protein and apoptosis index (AI) were measured. At the same time point, the tensile strength test was performed to measure the maximum load and the maximum tensile distance to observe the biomechanical properties. Results: Twenty-eight rabbits were excluded from the study due to incision infection or death, and finally 12, 12, 12, and 16 rabbits in groups A-D were included in the study, respectively. After operation, the tendon-bone interface of groups A and B healed poorly, while group C healed well. At 6 and 12 weeks, the number of fibroblasts and positive expression rate of JNK protein in group C were significantly higher than those of groups A, B, and D (P<0.05). Compared with 6 weeks, the number of fibroblasts gradually decreased and the positive expression rate of JNK protein and AI decreased in group C at 12 weeks after operation, with significant differences (P<0.05). Biomechanical tests showed that the maximum loads at 6 and 12 weeks after operation in group C were higher than in groups A and B, but lower than those in group D, while the maximum tensile distance results were opposite, but the differences between groups were significant (P<0.05). Conclusion: After ACL reconstruction, local injection of a mixture of KGN-ADSCs and fibrin glue can promote the tendon-bone healing and enhance the mechanical strength and tensile resistance of the tendon-bone interface.

Absence of Lugol staining indicates initiation of esophageal squamous cell carcinoma: A combined genomic and epidemiologic study.

The genomic characteristics during the carcinogenic process of esophageal squamous cell carcinoma (ESCC) remain largely unknown. We report here the genomic characteristics of 106 esophageal tissues of various stages from a population-based screening cohort in China ("Endoscopic Screening for Esophageal Cancer in China" trial) and 57 ESCC tissues from a local hospital. A significant increase in somatic mutation and copy number alterations is observed in the non-dysplastic Lugol unstaining lesions (ND-LULs). Extensive clonal expansion has emerged in the ND-LULs to an extent similar to that in higher-stage lesions. The burden of genomic alterations correlates with the size of LULs in the ND-LULs. 8-year follow-up shows that ND-LULs harbor an increased risk of progression to ESCC (adjusted IRR6-10 mm vs. none = 4.66, adjusted IRR>10 mm vs. none = 40.70), and the risk is correlated with LUL size for both non-dysplastic and dysplastic lesions. Lugol unstaining can be the initial stage in the carcinogenic process of ESCC.

Different internal fixation methods for Hoffa-like fractures of the tibial plateau: a finite element analysis.

Due to the low incidence of posteromedial tibial plateau fractures and limited clinical data available, the optimal treatment for this type of fracture remains to be established. This type of fracture, also known as Hoffa-like fracture of the tibial plateau, shares a similar mechanism of injury with the Hoffa fracture of the femoral condyle. In the field of orthopedics, finite element analysis is considered a valuable method to guide clinical decision-making. In this study, four methods used for internal fixation of Hoffa-like fractures of the tibial plateau were compared using computer simulation and applying a finite element method (FEM). The methods compared were lateral L-plate fixation alone (Model A); lateral L-plate combined with posterior anti-slip plate (reconstruction plate/T-plate) fixation (Model B); lateral L-plate combined with posterior hollow nail fixation of the fracture block (Model C); and lateral L-plate combined with anterior hollow nail fixation of the fracture (Model D). The maximum displacement of the model and the maximum stress of the internal fixation material were analyzed by applying an axial load of 2,500 N. The results showed that, in the normal bone model, the maximum displacement of the fracture in Model A was 0.60032 mm, with improved stability through the addition of posterior lateral plate fixation in Model B and reduction of the displacement to 0.38882 mm. The maximum displacement in Model C and Model D was comparable, amounting to 0.42345 mm and 0.42273 mm, respectively. Maximum stress was 1235.6 MPa for Model A, 84.724 MPa for Model B, 99.805 MPa for Model C, and 103.19 MPa for Model D. In the internal fixation analysis of the osteoporotic fracture model, we observed patterns similar to the results of the normal bone model. The results indicated that Model B yielded the overall best results in the treatment of Hoffa-like fractures of the tibial plateau. The orthopedic surgeon may wish to implement these insights into the perioperative algorithm, thereby refining and optimizing clinical patient care. In addition, our findings pave the way for future research efforts.

Association between time-restricted eating and non-alcoholic fatty liver disease in a nationwide cross-sectional study.

The association between time-restricted eating (TRE) and the risk of non-alcoholic fatty liver disease (NAFLD) is less studied. Moreover, whether the association is independent of physical exercise or diet quality or quantity is uncertain. In this nationwide cross-sectional study of 3813 participants, the timing of food intakes was recorded by 24-h recalls; NAFLD was defined through vibration-controlled transient elastography in the absence of other causes of chronic liver disease. OR and 95 % CI were estimated using logistic regression. Participants with daily eating window of ≤ 8 h had lower odds of NAFLD (OR = 0·70, 95 % CI: 0·52, 0·93), compared with those with ≥ 10 h window. Early (05.00-15.00) and late TRE (11.00-21.00) showed inverse associations with NAFLD prevalence without statistical heterogeneity (Pheterogeneity = 0·649) with OR of 0·73 (95 % CI: 0·36, 1·47) and 0·61 (95 % CI: 0·44, 0·84), respectively. Such inverse association seemed stronger in participants with lower energy intake (OR = 0·58, 95 % CI: 0·38, 0·89, Pinteraction = 0·020). There are no statistical differences in the TRE-NAFLD associations according to physical activity (Pinteraction = 0·390) or diet quality (Pinteraction = 0·110). TRE might be associated with lower likelihood of NAFLD. Such inverse association is independent of physical activity and diet quality and appears stronger in individuals consuming lower energy. Given the potential misclassification of TRE based on one- or two-day recall in the analysis, epidemiological studies with validated methods for measuring the habitual timing of dietary intake are warranted.

Germacrane Sesquiterpene Dilactones from Mikania micrantha and Their Antibacterial and Cytotoxic Activity.

Four new germacrane sesquiterpene dilactones, 2ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (1), 3ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (2), 1α,3ß-dihydroxy-4,9-germacradiene-12,8:15,6-diolide (3), and (11ß,13-dihydrodeoxymikanolide-13-yl)-adenine (4), together with five known ones (5-9) were isolated from the aerial parts of Mikania micrantha. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 4 is featured with an adenine moiety in the molecule, which is the first nitrogen-containing sesquiterpenoid so far isolated from this plant species. These compounds were evaluated for their in vitro antibacterial activity against four Gram-(+) bacteria of Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC) and Curtobacterium. flaccumfaciens (CF), and three Gram-(-) bacteria of Escherichia coli (EC), Salmonella. typhimurium (SA), and Pseudomonas Solanacearum (PS). Compounds 4 and 7-9 were found to show strong in vitro antibacterial activity toward all the tested bacteria with the MIC values ranging from 1.56 to 12.5 µg/mL. Notably, compounds 4 and 9 showed significant antibacterial activity against the drug-resistant bacterium of MRSA with MIC value 6.25 µg/mL, which was close to reference compound vancomycin (MIC 3.125 µg/mL). Compounds 4 and 7-9 were further revealed to show in vitro cytotoxic activity toward human tumor A549, HepG2, MCF-7, and HeLa cell lines, with IC50 values ranging from 8.97 to 27.39 µM. No antibacterial and cytotoxic activity were displayed for the other compounds. The present research provided new data to support that M. micrantha is rich in structurally diverse bioactive compounds worthy of further development for pharmaceutical applications and for crop protection in agricultural fields.

[Determination of organophosphate diesters in facility vegetable soils using ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry].

Organophosphate diesters (Di-OPEs) are biotic or abiotic degradation products of organophosphate esters (OPEs). Current analytical methods focus on detecting Di-OPEs in human urine. Human exposure to Di-OPEs in environmental matrices has not been systematically studied. Soil plays an important role in the environmental migration and transformation of organic pollutants. Previous studies found that OPEs are ubiquitous in soil. However, few studies reported OPEs metabolite pollution in soil, especially in facility vegetable soil. In this study, an ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry (UPHLC-Orbitrap HRMS) method was developed for the determination of five Di-OPEs (bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCP), di-n-butyl phosphate (DnBP), diphenyl phosphate (DPhP), and bis(2-ethylhexyl) phosphate (DEHP)) in the facility vegetable soil. The pretreatment process and chromatographic and mass spectrometric conditions were optimized in the present study. Comparative study of the purification effects of different solid-phase extraction columns showed that Oasis WAX cartridge had best purification efficiency for the five Di-OPEs. The cartridge was first activated using 3 mL methanol, 3 mL methanol containing 5% (v/v) ammonia, and 3 mL 0.1 mol/L sodium acetate-acetic acid buffer solution. Then, the cartridge was rinsed with 3 mL of 30% (v/v) methanol aqueous solution, and finally eluted using 8 mL methanol containing 5% (v/v) ammonia. The effects of mobile phase (with respect to solvent composition and flow rate) and column temperature on the shape and intensity of chromatographic peaks were studied. The optimized UHPLC conditions were as follows: chromatographic column, Thermo Accucore RP-MS; column temperature, 30 ℃; mobile phase, 0.2 mmol/L ammonium acetate aqueous solution and methanol; flow rate, 0.2 mL/min. In the UHPLC-Orbitrap HRMS experiment, the five Di-OPEs were analyzed in full MS mode with negative ionization. Instrumental parameters, such as sheath gas and auxiliary gas, were optimized to determine the MS conditions. The optimized Orbitrap HRMS conditions were as follows: heating electrospray ionization source (HESI), full MS mode with negative ionization; scan range, m/z 100-500; ion transfer tube temperature, 320 ℃; automatic gain control of target particle count, 1×106; sheath gas flow rate, 8.58 L/min; auxiliary gas flow rate, 17.40 L/min; spray voltage, 3.2 kV; and S-lens voltage, 50 V. The limits of detection and quantification were 0.001-0.047 ng/g and 0.004-0.156 ng/g, respectively. The correlation coefficients of the calibration curve were 0.9985-0.9999. At three spiked levels, 5.0, 25.0, and 50.0 ng/g, the recoveries of the five Di-OPEs ranged from 56.9% to 133.0% with relative standard deviations of 4.4%-18.9%. The established method was applied to the analysis of the five Di-OPEs in 16 facility vegetable soils. The detection frequencies of the five Di-OPEs exceeded 60% in all soil samples, indicating that the Di-OPEs were ubiquitous in the facility vegetable soil. The contents of the five Di-OPEs in the facility vegetable soil samples ranged from 2.53-6.94 ng/g. DnBP (1.37-3.20 ng/g) and DPhP (0.47-2.44 ng/g) were the predominant congeners in the facility vegetable soil samples, accounting for 23.4%-68.8% and 16.3%-35.9% of the five Di-OPEs, respectively. The developed method is simple, sensitive, and reproducible and can be used effectively for the determination of Di-OPEs in soil. The results of this study will be helpful for understanding the environmental behavior of Di-OPEs and their human exposure in facility vegetable soils.

A prospective cohort study of starchy and non-starchy vegetable intake and mortality risk.

Whether starchy and non-starchy vegetables have distinct impacts on health remains unknown. We prospectively investigated the intake of starchy and non-starchy vegetables in relation to mortality risk in a nationwide cohort. Diet was assessed using 24-h dietary recalls. Deaths were identified via the record linkage to the National Death Index. Hazard ratios (HR) and 95 % CI were calculated using Cox regression. During a median follow-up of 7·8 years, 4904 deaths were documented among 40 074 participants aged 18 years or older. Compared to those with no consumption, participants with daily consumption of ≥ 1 serving of non-starchy vegetables had a lower risk of mortality (HR = 0·76, 95 % CI 0·66, 0·88, Ptrend = 0·001). Dark-green and deep-yellow vegetables (HR = 0·79, 95 % CI 0·63, 0·99, Ptrend = 0·023) and other non-starchy vegetables (HR = 0·80, 95 % CI 0·70, 0·92, Ptrend = 0·004) showed similar results. Total starchy vegetable intake exhibited a marginally weak inverse association with mortality risk (HR = 0·89, 95 % CI 0·80, 1·00, Ptrend = 0·048), while potatoes showed a null association (HR = 0·93, 95 % CI 0·82, 1·06, Ptrend = 0·186). Restricted cubic spline analysis suggested a linear dose-response relationship between vegetable intake and death risk, with a plateau at over 300 and 200 g/d for total and non-starchy vegetables, respectively. Compared with starchy vegetables, non-starchy vegetables might be more beneficial to health, although both showed a protective association with mortality risk. The risk reduction in mortality plateaued at approximately 200 g/d for non-starchy vegetables and 300 g/d for total vegetables.

Multiple Lugol-unstained lesions predict higher cumulative risk of malignance in the esophagus.

BACKGROUND AND AIM: The impact of the presence of multiple Lugol-unstained lesions (LULs) in the esophagus on the risk of having severe dysplasia and above (SDA) lesions among asymptomatic individuals is unknown. METHODS: We collected demographic factors, behavioral variables, and features of LULs from 1073 participants who were biopsied at baseline endoscopic screening in a population-based screening trial, and these individuals were followed over a median time of 7 years. Outcome events were defined as SDA identified at screening, at reexamination, or during follow-up. "Multiple LULs" were defined as ≥ 2 LULs found in the entirety of the esophagus. Multivariable logistic regression models were fitted to assess the effect of "multiple LULs" on the cumulative risk of SDA. RESULTS: There were 147 SDA cases in the current study. After adjustment for potential risk factors and endoscopic features of LULs, the presence of "multiple LULs" slightly increased the cumulative risk of having SDA with no statistical significance (adjusted odds ratio [OR] = 1.26; 95% confidence interval [CI] [0.85, 1.88]). Further stratified analysis showed that this association was strong among subjects with small LULs (≤ 5 mm) (adjusted OR = 3.29; 95% CI [1.39, 7.79]). However, no such association was observed in subjects with larger LULs (adjusted OR = 0.99; 95% CI [0.63, 1.55], P interaction  = 0.022). CONCLUSIONS: The presence of "multiple small LULs (≤ 5 mm)" in chromoendoscopy indicates a higher cumulative risk of having SDA in the esophagus. We recommend biopsies be taken and surveillance be maintained at a more active level in individuals with relatively small but multiple LULs.

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.

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.

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.