Purine salvage-associated metabolites as biomarkers for early diagnosis of esophageal squamous cell carcinoma: a diagnostic model-based study.

Esophageal squamous cell carcinoma (ESCC) remains an important health concern in developing countries. Patients with advanced ESCC have a poor prognosis and survival rate, and achieving early diagnosis remains a challenge. Metabolic biomarkers are gradually gaining attention as early diagnostic biomarkers. Hence, this multicenter study comprehensively evaluated metabolism dysregulation in ESCC through an integrated research strategy to identify key metabolite biomarkers of ESCC. First, the metabolic profiles were examined in tissue and serum samples from the discovery cohort (n = 162; ESCC patients, n = 81; healthy volunteers, n = 81), and ESCC tissue-induced metabolite alterations were observed in the serum. Afterward, RNA sequencing of tissue samples (n = 46) was performed, followed by an integrated analysis of metabolomics and transcriptomics. The potential biomarkers for ESCC were further identified by censoring gene-metabolite regulatory networks. The diagnostic value of the identified biomarkers was validated in a validation cohort (n = 220), and the biological function was verified. A total of 457 dysregulated metabolites were identified in the serum, of which 36 were induced by tumor tissues. The integrated analyses revealed significant alterations in the purine salvage pathway, wherein the abundance of hypoxanthine/xanthine exhibited a positive correlation with HPRT1 expression and tumor size. A diagnostic model was developed using two purine salvage-associated metabolites. This model could accurately discriminate patients with ESCC from normal individuals, with an area under the curve (AUC) (95% confidence interval (CI): 0.680-0.843) of 0.765 in the external cohort. Hypoxanthine and HPRT1 exerted a synergistic effect in terms of promoting ESCC progression. These findings are anticipated to provide valuable support in developing novel diagnostic approaches for early ESCC and enhance our comprehension of the metabolic mechanisms underlying this disease.

In-Domain GAN Inversion for Faithful Reconstruction and Editability.

Generative Adversarial Networks (GANs) have significantly advanced image synthesis through mapping randomly sampled latent codes to high-fidelity synthesized images. However, applying well-trained GANs to real image editing remains challenging. A common solution is to find an approximate latent code that can adequately recover the input image to edit, which is also known as GAN inversion. To invert a GAN model, prior works typically focus on reconstructing the target image at the pixel level, yet few studies are conducted on whether the inverted result can well support manipulation at the semantic level. This work fills in this gap by proposing in-domain GAN inversion, which consists of a domain-guided encoder and a domain-regularized optimizer, to regularize the inverted code in the native latent space of the pre-trained GAN model. In this way, we manage to sufficiently reuse the knowledge learned by GANs for image reconstruction, facilitating a wide range of editing applications without any retraining. We further make comprehensive analyses on the effects of the encoder structure, the starting inversion point, as well as the inversion parameter space, and observe the trade-off between the reconstruction quality and the editing property. Such a trade-off sheds light on how a GAN model represents an image with various semantics encoded in the learned latent distribution.

Optimal starting age of endoscopic screening for esophageal cancer in China: A multicenter prospective cohort study.

BACKGROUND: Although endoscopic screening for esophageal cancer has been performed in high-risk areas in China for decades, there is limited and inconsistent evidence regarding the starting age for individuals participating in screening. The aim of this study is to investigate the optimal starting age of esophageal cancer screening. METHODS: This study is based on a multicenter prospective cohort consisting 338,017 permanent residents aged 40-69 years in six high-risk areas of esophageal cancer in China. The participation rate, detection rate, hazard ratios (HRs), cumulative incidence and mortality and number needed to screen (NNS) were calculated in each age group. Screening burden, benefit and risk were compared among screening strategies with different initiation ages to explore the optimal starting age for population-based screening in high-risk areas. RESULTS: Individuals aged 50-69 had a higher participation rate, a higher detection rate and improved screening effectiveness than those aged 40-49. The endoscopic screening had no significant effect on reducing the incidence of esophageal cancer in individuals under 55 and mortality in individuals under 45. Increasing the starting age to 50 years reduced the screening demand and NNS by 40% and 55%, and resulted in 12% of detectable positive cases, 16% of preventable incident cases, and 14% of preventable deaths being missed. CONCLUSIONS: Postponing the starting age of endoscopic screening to 50 years might yield a more-favorable balance between screening benefit and burden in high- risk areas with limited resources.

Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma.

Introduction: Altered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosylation and the carcinogenesis progression of ESCC, providing innovative biomarkers for the predictive identification and targeted prevention of ESCC. Methods: In total, 496 individuals of ESCC (n=114), precancerosis (n=187) and controls (n=195) from the discovery population (n=348) and validation population (n=148) were recruited in the study. IgG N-glycosylation profile was analyzed and an ESCC-related glycan score was composed by a stepwise ordinal logistic model in the discovery population. The receiver operating characteristic (ROC) curve with the bootstrapping procedure was used to assess the performance of the glycan score. Results: In the discovery population, the adjusted OR of GP20 (digalactosylated monosialylated biantennary with core and antennary fucose), IGP33 (the ratio of all fucosylated monosyalilated and disialylated structures), IGP44 (the proportion of high mannose glycan structures in total neutral IgG glycans), IGP58 (the percentage of all fucosylated structures in total neutral IgG glycans), IGP75 (the incidence of bisecting GlcNAc in all fucosylated digalactosylated structures in total neutral IgG glycans), and the glycan score are 4.03 (95% CI: 3.03-5.36, P<0.001), 0.69 (95% CI: 0.55-0.87, P<0.001), 0.56 (95% CI: 0.45-0.69, P<0.001), 0.52 (95% CI: 0.41-0.65, P<0.001), 7.17 (95% CI: 4.77-10.79, P<0.001), and 2.86 (95% CI: 2.33-3.53, P<0.001), respectively. Individuals in the highest tertile of the glycan score own an increased risk (OR: 11.41), compared with those in the lowest. The average multi-class AUC are 0.822 (95% CI: 0.786-0.849). Findings are verified in the validation population, with an average AUC of 0.807 (95% CI: 0.758-0.864). Discussion: Our study demonstrated that IgG N-glycans and the proposed glycan score appear to be promising predictive markers for ESCC, contributing to the early prevention of esophageal cancer. From the perspective of biological mechanism, IgG fucosylation and mannosylation might involve in the carcinogenesis progression of ESCC, and provide potential therapeutic targets for personalized interventions of cancer progression.

Development and Validation of Esophageal Squamous Cell Carcinoma Risk Prediction Models Based on an Endoscopic Screening Program.

Importance: Assessment tools are lacking for screening of esophageal squamous cell cancer (ESCC) in China, especially for the follow-up stage. Risk prediction to optimize the screening procedure is urgently needed. Objective: To develop and validate ESCC prediction models for identifying people at high risk for follow-up decision-making. Design, Setting, and Participants: This open, prospective multicenter diagnostic study has been performed since September 1, 2006, in Shandong Province, China. This study used baseline and follow-up data until December 31, 2021. The data were analyzed between April 6 and May 31, 2022. Eligibility criteria consisted of rural residents aged 40 to 69 years who had no contraindications for endoscopy. Among 161 212 eligible participants, those diagnosed with cancer or who had cancer at baseline, did not complete the questionnaire, were younger than 40 years or older than 69 years, or were detected with severe dysplasia or worse lesions were eliminated from the analysis. Exposures: Risk factors obtained by questionnaire and endoscopy. Main Outcomes and Measures: Pathological diagnosis of ESCC and confirmation by cancer registry data. Results: In this diagnostic study of 104 129 participants (56.39% women; mean [SD] age, 54.31 [7.64] years), 59 481 (mean [SD] age, 53.83 [7.64] years; 58.55% women) formed the derivation set while 44 648 (mean [SD] age, 54.95 [7.60] years; 53.51% women) formed the validation set. A total of 252 new cases of ESCC were diagnosed during 424 903.50 person-years of follow-up in the derivation cohort and 61 new cases from 177 094.10 person-years follow-up in the validation cohort. Model A included the covariates age, sex, and number of lesions; model B included age, sex, smoking status, alcohol use status, body mass index, annual household income, history of gastrointestinal tract diseases, consumption of pickled food, number of lesions, distinct lesions, and mild or moderate dysplasia. The Harrell C statistic of model A was 0.80 (95% CI, 0.77-0.83) in the derivation set and 0.90 (95% CI, 0.87-0.93) in the validation set; the Harrell C statistic of model B was 0.83 (95% CI, 0.81-0.86) and 0.91 (95% CI, 0.88-0.95), respectively. The models also had good calibration performance and clinical usefulness. Conclusions and Relevance: The findings of this diagnostic study suggest that the models developed are suitable for selecting high-risk populations for follow-up decision-making and optimizing the cancer screening process.

Progression of precancerous lesions of esophageal squamous cell carcinomas in a high-risk, rural Chinese population.

BACKGROUND AND AIMS: This study investigated the natural history of esophageal squamous cell carcinoma (ESCC) in rural Chinese. We sought to help provide more data to support ESCC screenings. METHODS: This study was based on an existing Screening Program in Feicheng, China. Esophageal precancerous lesions were identified in 1753 cases, diagnosed from esophageal cancer screenings from 2006 to 2016. We followed up with them through endoscopic screening until October 1, 2017. Pathology results from various grades of precancerous lesions were recorded and the annual transition probabilities and incidence density of ESCC were calculated. RESULTS: As of October 1, 2017, a total of 4055.8 person-years has been observed. The ESCC incidence density of mild, moderate, and severe dysplasia (SD) was 0.17, 0.79, and 1.77 per 100 person-years, respectively. The median follow-up time of mild, moderate, and SD was 3.5, 2.3, and 2.2 years, respectively. The annual transition probability of mild, moderate, and SD to the next pathological level was 0.025, 0.038, and 0.016, respectively. The ESCC incidence density of males was 2.6 times higher than females (0.58 vs. 0.22), and the older age group (56-69 age group) had a ESCC incidence density 1.2 times higher than the younger group (40-55 age group) (0.45 vs. 0.39). CONCLUSIONS: The higher the grade of precancerous lesions, the higher the incidence density of ESCC. Screening of esophageal cancer in males and the elderly should be strengthened. It is recommended to reinforce follow-up management for untreated patients with SD/carcinoma in situ. For patients with mild and moderate dysplasia in high-risk rural Chinese populations, endoscopic follow-up intervals can be appropriately adjusted to once every 2 years.

Dietary patterns and severity of symptom with the risk of esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional latent class analysis.

BACKGROUND: Dietary patterns and symptoms research among Chinese with esophageal squamous cell carcinoma (ESCC) and its precursor lesions is limited, especially as it relates to multiple food consumption and multiple co-occurring symptoms. The aim of our study was to identify the dietary patterns and severity of symptom classes with the risk of esophageal squamous cell carcinoma and its histological precursor lesions, and develop a risk prediction model for different stages of esophageal disease. METHODS: We analyzed data from a multicenter cross-sectional study carried out in ESCC high incidence areas between 2017 and 2018, which included 34,707 individuals aged 40-69 years. Dietary patterns and severity of symptom classes were derived by applying a latent class analysis (LCA). A multiple logistic regression model was used to derive the odds ratio (ORs) and corresponding 95% confidence intervals (CIs) for ESCC and the different stages of esophageal disease according to the dietary patterns and severity of symptom classes identified. We built the risk prediction model by using a nomogram. RESULTS: We identified five dietary patterns and three severity of symptom classes. The dietary patterns were classified as follows: "Healthy", "Western", "Lower consumers-combination", "Medium consumers-combination" and "Higher consumers-combination" patterns based on the intake of foods such as red meat, vegetables and fruits. The severity of symptoms was categorized into "Asymptomatic", "Mild symptoms" and "Overt symptoms" classes based on health-related symptoms reported by the participants. Compared to the "Healthy" pattern, the other four patterns were all associated with an increased risk of esophageal disease. Similarly, the other two symptom classes present different degrees of increased risk of esophageal disease compared to the "Asymptomatic". The nomograms reflect the good predictive ability of the model. CONCLUSION: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results supplied that subjects with diets rich in livestock and poultry meat and low in fruits and vegetables and subjects with typical symptoms were at increased ESCC risk. The findings highlight the importance of considering food and symptom combinations in cancer risk evaluation.

Cancer death and potential years of life lost in Feicheng City, China: Trends from 2013 to 2018.

ABSTRACT: This study aimed to evaluate the impact of cancer-related mortality on life expectancy in Feicheng City.We extracted the death records and population data of Feicheng City from 2013 to 2018 through the Feicheng Center for Disease Control and Prevention. The mortality, premature mortality, cause-eliminated life expectancy, potential years of life lost (PYLL), average potential years of life lost (APYLL), annual change percentage (APC), and other indicators of cancer were calculated. The age-standardized rates were calculated using the sixth national census (2010).From 2013 to 2018, the mortality rate of cancer in Feicheng City was 221.55/100,000, and the standardized mortality rate was 166.37/100,000. The standardized mortality rate increased from 2013 to 2014 and then decreased annually. The premature mortality of cancer was 8.98% and showed a downward trend (APC = -2.47%, t = -3.10, P = .04). From 2013 to 2018, the average life expectancy of residents in Feicheng City was 78.63 years. Eliminating the impact of cancer, life expectancy could increase by 3.72 years. The rate of life loss caused by cancer in men was higher than that in women. The total life loss caused by cancer deaths was 126,870.50 person-years, the potential life loss rate was 22.51‰, and the average potential life loss was 13.30 years. The standardized potential years of life lost rate showed a downward trend (APC = -2.96%, t = -3.72, P = .02), and APYLL decreased by 1.98% annually (t = -5.44, P = .01). The top 5 malignant tumors in APYLL were leukemia, breast cancer, brain tumor, liver cancer, and ovarian cancer.Lung cancer, esophageal cancer, female breast cancer, and childhood leukemia have a great impact on the life expectancy of residents in Feicheng City. Effective measures need to be taken to reduce the disease burden of malignant tumors.

Characterization of the Oral and Esophageal Microbiota in Esophageal Precancerous Lesions and Squamous Cell Carcinoma.

Important evidence indicates that the microbiota plays a key role in esophageal squamous cell carcinoma (ESCC). Here, paired saliva and brush specimens were obtained from 276 participants undergoing upper gastrointestinal endoscopic examination before or during screening for upper gastrointestinal (UGI) cancer. The esophageal microbiota was investigated by 16S rRNA gene profiling and next-generation sequencing. We observed that as the disease progressed, the α diversity in the saliva and cell brush samples decreased. Linear discriminant analysis effect size (LEfSe) results showed that in both the saliva and cell brush specimens, Granulicatella, Rothia, Streptococcus, Gemella, Leptotrichia and Schaalia were common biomarkers in patients with low-grade dysplasia, Lactobacillus was a common biomarker in patients with high-grade dysplasia, and Bosea, Solobacterium, Gemella, and Peptostreptococcus were common biomarkers in patients with esophageal cancer. The top 3 genera in the saliva and cell brush specimens had areas under the curve (AUCs) of 87.16 and 89.13%, respectively, to distinguish ESCC patients from normal people. The PICRUSt2 results identified in brush samples that patients with ESCC had decreased nitrate reductase functions. Our results suggest that future studies can focus on the function of the characteristic bacteria in ESCC.

Risk factors for esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional study.

BACKGROUND: Despite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions. METHODS: We performed an endoscopic examination of 44,857 individuals aged 40-69 years from five high incidence regions of China in 2017-2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors. RESULTS: We identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52-3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03-3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05-1.37) was essential risk factor of LGIN. CONCLUSIONS: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

The effects of smoking and drinking on the oral and esophageal microbiota of healthy people.

BACKGROUND: To explore the effects of smoking and drinking on the microbiota in the saliva and three segments of the esophagus (upper, middle, and lower) in healthy individuals. METHODS: Paired saliva and brush specimens were obtained from 76 participants who underwent upper gastrointestinal (UGI) endoscopic examination for UGI cancer screening. The esophageal microbiota was investigated by 16S rRNA gene profiling via next-generation sequencing. RESULTS: The saliva samples from non-smoking and non-drinking participants had a greater abundance of Neisseria, Prevotella, Porphyromonas, and Rothia, and lower levels of Streptococcus, Actinobacillus, and Haemophilus compared to the esophagus. There were no significant differences in the abundance of most bacterial genera in the upper, middle, and lower oesophagus. Similarly, in the saliva of patients who smoke and drink, there was a higher prevalence of Neisseria, Prevotella, Porphyromonas, Fusobacterium, and Rothia, and a lower prevalence of Streptococcus, Actinobacillus, and Haemophilus compared to the esophagus. There were no significant differences in the abundance of most genera in the upper, middle, and lower esophagus of patients with a history of drinking and smoking. There were slight differences in the microbiota between smoking and drinking individuals and non-smoking and non-drinking individuals. CONCLUSIONS: This pilot study demonstrated microbial diversity at different taxonomic levels in the oral cavity and esophagus of non-drinking and non-smoking individuals, as well as healthy people who drink and smoke . There was a slight difference in the microbiota between non-drinking and non-smoking people and individuals with a history of drinking and smoking. These results suggested that oral or esophageal cancer caused by smoking and drinking may not be mediated by mechanisms that affect surface microorganisms.

Development and Validation of an Esophageal Squamous Cell Carcinoma Risk Prediction Model for Rural Chinese: Multicenter Cohort Study.

BACKGROUND: There are rare prediction models for esophageal squamous cell carcinoma (ESCC) for rural Chinese population. We aimed to develop and validate a prediction model for ESCC based on a cohort study for the population. METHODS: Data of 115,686 participants were collected from esophageal cancer (EC) early diagnosis and treatment of cancer program as derivation cohort while data of 54,750 participants were collected as validation cohort. Risk factors considered included age, sex, smoking status, alcohol drinking status, body mass index (BMI), tea drinking status, marital status, annual household income, source of drinking water, education level, and diet habit. Cox proportional hazards model was used to develop ESCC prediction model at 5 years. Calibration ability, discrimination ability, and decision curve analysis were analyzed in both derivation and validation cohort. A score model was developed based on prediction model. RESULTS: One hundred eighty-six cases were diagnosed during 556,949.40 person-years follow-up in the derivation cohort while 120 cases from 277,302.70 in the validation cohort. Prediction model included the following variables: age, sex, alcohol drinking status, BMI, tea drinking status, and fresh fruit. The model had good discrimination and calibration performance: R 2, D statistic, and Harrell's C statistic of prediction model were 43.56%, 1.70, and 0.798 in derivation cohort and 45.19%, 1.62, and 0.787 in validation cohort. The calibration analysis showed good coherence between predicted probabilities and observed probabilities while decision curve analysis showed clinical usefulness. The score model was as follows: age (3 for 45-49 years old; 4 for 50-54 years old; 7 for 55-59 years old; 9 for 60-64 years; 10 for 65-69 years), sex (5 for men), BMI (1 for ≤25), alcohol drinking status (2 for alcohol drinkers), tea drinking status (2 for tea drinkers), and fresh fruit (2 for never) and showed good discrimination ability with area under the curve and its 95% confidence interval of 0.792 (0.761,0.822) in the deviation cohort and 0.773 (0.736,0.811) in the validation cohort. The calibration analysis showed great coherence between predicted probabilities and observed probabilities. CONCLUSIONS: We developed and validated an ESCC prediction model using cohort study with good discrimination and calibration capability which can be used for EC screening for rural Chinese population.

Serum metabolomics analysis for the progression of esophageal squamous cell carcinoma.

BACKGROUND: Previous metabolomics studies have found differences in metabolic characteristics between the healthy and ESCC patients. However, few of these studies concerned the whole process of the progression of ESCC. This study aims to explore serum metabolites associated with the progression of ESCC. METHODS: Serum samples from 653 participants (305 normal, 77 esophagitis, 228 LGD, and 43 HGD/ESCC) were examined by ultra-high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS). Principal component analysis (PCA) was first applied to obtain an overview of the clustering trend for the multidimensional data. Fuzzy c-means (FCM) clustering was then used to screen metabolites with a changing tendency in the progression of ESCC. Univariate ordinal logistic regression analysis and multiple ordinal logistic regression analysis were applied to evaluate the association of metabolites with the risk of ESCC progression, and adjusted for age, gender, BMI, tobacco smoking, and alcohol drinking status. RESULTS: After FCM clustering analysis, a total of 38 metabolites exhibiting changing tendency among normal, esophagitis, LGD, and HGD/ESCC patients. Final results showed 15 metabolites associated with the progression of ESCC. Ten metabolites (dopamine, L-histidine, 5-hydroxyindoleacetate, L-tryptophan, 2'-O-methylcytidine, PC (14:0/0:0), PC (O-16:1/0:0), PE (18:0/0:0), PC (16:1/0:0), PC (18:2/0:0)) were associated with decreased risk of developing ESCC. Five metabolites (hypoxanthine, inosine, carnitine (14:1), glycochenodeoxycholate, PC (P-18:0/18:3)) were associated with increased risk of developing ESCC. CONCLUSIONS: These results demonstrated that serum metabolites are associated with the progression of ESCC. These metabolites are capable of potential biomarkers for the risk prediction and early detection of ESCC.

The mediation effect of serum metabolites on the relationship between long-term smoking exposure and esophageal squamous cell carcinoma.

BACKGROUND: Long-term smoking exposure will increase the risk of esophageal squamous cell carcinoma (ESCC), whereas the mechanism is still unclear. We conducted a cross-sectional study to explore whether serum metabolites mediate the occurrence of ESCC caused by cigarette smoking. METHODS: Serum metabolic profiles and lifestyle information of 464 participants were analyzed. Multiple logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of smoking exposure to ESCC risk. High-dimensional mediation analysis and univariate mediation analysis were performed to screen potential intermediate metabolites of smoking exposure for ESCC. RESULTS: Ever smoking was associated with a 3.11-fold increase of ESCC risk (OR = 3.11, 95% CI 1.63-6.05), and for each cigarette-years increase in smoking index, ESCC risk increased by 56% (OR = 1.56, 95% CI 1.18-2.13). A total of 5 metabolites were screened as mediators by high-dimensional mediation analysis. In addition, glutamine, histidine, and cholic acid were further proved existing mediation effects according to univariate mediation analysis. And the proportions of mediation of histidine and glutamine were 40.47 and 30.00%, respectively. The mediation effect of cholic acid was 8.98% according to the analysis of smoking index. CONCLUSIONS: Our findings suggest that cigarette smoking contributed to incident ESCC, which may be mediated by glutamine, histidine and cholic acid.

CT assessment of the increased density of cerebral vessels in plateau region.

In this study, the relationship between the brain parenchymal density, the cerebral vessel density, the mean corpuscular hemoglobin (MCH) content, the mean corpuscular hemoglobin concentration (MCHC), and the morbidity associated with lacunar infarction of residents living in either the plains or the plateau regions were analyzed and compared for their potential clinical implications. Clinical data from the brain CT scans of individuals living in either the plain or plateau regions (129 each) were collected. Specifically, the CT values for basal ganglia, the middle cerebral artery, and the superior sagittal sinus, along with the number of patients with lacunar infarction, were collected. In addition, the MCH and MCHC values were measured in blood samples collected within 48 h following the CT scans. For statistical analysis, an independent sample t-test, Pearson's correlation test (permutation test), and Chi-squared test were employed. The inhabitants of the plateau had a significantly higher CT value of basal ganglia, the middle cerebral artery, and superior sagittal sinus and also higher levels of MCH and MCHC in the blood (ps < 0.001) than the inhabitants of the plains region. Further, there was a significant positive correlation between the three aforementioned CT values and the MCH and MCHC findings. However, no significant differences were found in the morbidity of lacunar infarction between these two regions (p > 0.05). The inhabitants in the plateau have a significantly higher brain parenchymal density, higher CT value for cerebral vessels density, and higher blood MCH and MCHC levels in comparison with individuals occupying the plains. Concurrently, the parenchymal density and the CT values are shown to be positively correlated with the MCH and MCHC content in the blood.

Effectiveness of one-time endoscopic screening programme in prevention of upper gastrointestinal cancer in China: a multicentre population-based cohort study.

OBJECTIVES: To estimate the effectiveness of endoscopic screening programme in reducing incidence and mortality of upper gastrointestinal cancer in high risks areas of China. DESIGN: This multicentre population-based cohort study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40 to 69 years were identified as target subjects. We refer to those who were invited for screening collectively as the invited group. Of these, we classify those who were invited and undertook endoscopic screening as the screened group and those who were invited but did not accept screening as the non-screened group. Target subjects who were not invited to the screening were assigned to the control group. The effectiveness of the endoscopic screening and screening programme were evaluated by comparing reductions in incidence and mortality from upper gastrointestinal cancer in the screened and invited group with control group. RESULTS: Our cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, upper gastrointestinal cancer incidence and mortality decreased by 23% (relative risk (RR)=0.77, 95% CI 0.74 to 0.81) and 57% (RR=0.43, 95% CI 0.40 to 0.47) in the screened group, respectively, and by 14% (RR=0.86, 95% CI 0.84 to 0.89) and 31% (RR=0.69, 95% CI 0.66 to 0.72) in the invited group, respectively. CONCLUSION: Among individuals aged 40 to 69 years in high risk areas of upper gastrointestinal cancer, one-time endoscopic screening programme was associated with a significant decrease in upper gastrointestinal cancer incidence and mortality.

Assessment of high sensitivity C-reactive protein and coronary plaque characteristics by computed tomography in patients with and without diabetes mellitus.

BACKGROUND: To evaluate the coronary plaque characteristics of coronary arteries using computed tomography angiography (CTA) in order to assess the risk of coronary artery disease and the relevance of high sensitivity C reactive protein (hs-CRP) in patients with Diabetes Mellitus (DM). METHODS: The clinical data of 400 DM patients and 400 non-DM patients from January 2017 to December 2019 were collected, including the results of coronaryCTA. The plasma hs-CRP level of the two groups were divided into three groups: CRP ≤ 1, 1 < CRP ≤ 2, CRP > 2. The correlation of the degree of stenosis, the number of plaques, the nature of plaques and hs-CRP value between the two groups was evaluated. RESULTS: Compared with non-DM patients, the incidence of coronary artery plaques and lumen stenosis in DM patients was more higher than that in non-DM patients. DM patients were more likely to have more diseased vessels, especially diffuse vascular disease (12.00% vs 1.75%; P < 0.001). Subjects with high hs-CRP levels were more likely to have any plaque compared with individuals showing normal hs-CRP levels (p<0.01). There was no statistical significance in non calcified plaque with high level of hs-CRP, but the occurrence of plaque types in DM group was statistically significant compared with other hs-CRP levels in non DM group. Subjects with high hs-CRP were observed to be at increased risk for the presence of calcified plaque and severe narrowing in the unadjusted values. CONCLUSIONS: Coronary CTA combined with hs-CRP can accurately detect the characteristics of coronary artery stenosis and plaque in DM patients, which has an important clinical value in the risk assessment of coronary heart disease in DM patients.

Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China.

INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.

Endoscopic resection techniques for squamous premalignant lesions and early carcinoma of the esophagus: ER-Cap, MBM, and ESD, how do we choose? A multicenter experience.

BACKGROUND: Endoscopic resection cap technique (ER-Cap), multiband mucosectomy (MBM), and endoscopic submucosal dissection (ESD) have been widely applied in the treatment of esophageal squamous neoplasia and cancer. However, little is known with regards to the comparison of these methods. This study aimed to compare the feasibility, safety, effectiveness, and costs of these three techniques. METHODS: A retrospective analysis of patients with squamous premalignant or early malignant lesions of the esophagus undergoing ER-Cap, MBM, or ESD from January 2009 to December 2015 in one of the centers in China was performed. The procedural data and follow-up data for all patients were recorded. RESULTS: A total of 672 patients with 733 lesions were included; 148 lesions (133 patients) were treated with ER-Cap, 427 lesions (388 patients) with MBM, and 158 lesions (151 patients) with ESD. The mean age was 61.59 years and the male-to-female ratio was 2.78:1. The operation time was significantly shorter for ER-Cap (29.26 ± 16.73 mins, p < 0.001) group, and the hospitalization costs were significantly lower in the MBM group (20,942.03 ± 8435.56ï¿¥, p = 0.003). The resection sample size of ESD was significantly larger (4.40 ± 1.20 cm, p < 0.001) and the en bloc resection rate of ESD was significantly higher (p < 0.001) than that of the other two groups. The frequencies of perforation, bleeding, and cicatricial stenosis were significantly lower in the MBM group (p < 0.001, p = 0.011, p = 0.009). Three local recurrences were observed in the ER-Cap group, while no recurrence was observed in MBM and ESD groups. There were three and two metastatic patients observed in the MBM and ESD groups, respectively. CONCLUSIONS: ER-Cap, MBM, and ESD are all minimally invasive, safe, and effective methods for treating early esophageal squamous cell carcinoma. MBM could be considered as a good alternative when performed by a less-experienced endoscopist in high-incidence areas with limited resources.