Prevalence and determinants of obesity and its association with upper gastrointestinal diseases in people aged 40-69 years in Yangzhong, southeast China.

Several international epidemiological studies have established a link between obesity and upper gastrointestinal cancer (UGC), but Chinese evidence is limited. This study aimed to determine the prevalence of obesity, especially central obesity, while investigating its association with upper gastrointestinal diseases in the high-risk population of Yangzhong, a typical high-risk area for UGC in southeastern China. We conducted a cross-sectional study from November 2017 to June 2021 involving 6736 residents aged 40-69. Multivariate logistic regression was used to assess independent factors influencing overweight/obesity and central obesity. We also analyzed the relationship between obesity and upper gastrointestinal diseases using multinomial logistic regression. The prevalence of overweight, obesity, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)-central obesity were 40.6%, 12.0%, 49.9%, 79.4%, and 63.7%, respectively. Gender, age, smoking, tea consumption, sufficient vegetable, pickled food, spicy food, eating speed, physical activity, family history of cancer, and family history of common chronic disease were associated with overweight /obesity and central obesity. Besides, education and missing teeth were only associated with central obesity. General and central obesity were positively associated with UGC, while general obesity was negatively associated with UGC precancerous diseases. There were no significant associations between obesity and UGC precancerous lesions. Subgroup analyses showed that general and central obesity was positively associated with gastric cancer but not significantly associated with esophageal cancer. Obesity is negatively and positively associated with gastric and esophageal precancerous diseases, respectively. In conclusion, general and central obesity were at high levels in the target population in this study. Most included factors influenced overweight/obesity and central obesity simultaneously. Policymakers should urgently develop individualized measures to reduce local obesity levels according to obesity characteristics. Besides, obesity increases the risk of UGC but decreases the risk of UGC precancerous diseases, especially in the stomach. The effect of obesity on the precancerous diseases of the gastric and esophagus appears to be the opposite. No significant association between obesity and upper gastrointestinal precancerous lesions was found in the study. This finding still needs to be validated in cohort studies.

Comparison of obesity indicators for predicting cardiovascular risk factors and multimorbidity among the Chinese population based on ROC analysis.

To date, the best obesity-related indicators (ORIs) for predicting hypertension, dyslipidaemia, Type 2 diabetes mellitus (T2DM) and multimorbidity are still controversial. This study assessed the ability of 17 ORIs [body mass index (BMI), body fat percentage (BF%), c-index, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), a body shape index (ABSI), body adiposity index (BAI), waist circumference (WC), waist-hip ratio (WHR), waist-to-height ratio (WHtR), body roundness index (BRI), abdominal volume index (AVI), triglyceride glucose index (TYG), lipid accumulation product (LAP), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), waist triglyceride index (WTI) and cardiometabolic index (CMI)] to predict hypertension, dyslipidemia, T2DM, and multimorbidity in populations aged 40-69 years. From November 2017 to December 2022, 10,432 compliant residents participated in this study. Receiver operating characteristic curves were used to assess the ability of ORIs to predict target diseases across the whole population and genders. The DeLong test was used to analyse the heterogeneity of area under curves (AUCs). Multivariable logistic regression was used to analyse the association of ORIs with hypertension, dyslipidaemia, T2DM, and multimorbidity. The prevalence of hypertension, dyslipidaemia, T2DM, and multimorbidity was 67.46%, 39.36%, 12.54% and 63.58%, respectively. After excluding ORIs associated with the target disease components, in the whole population, CVAI (AUC = 0.656), BMI (AUC = 0.655, not significantly different from WC and AVI), CVAI (AUC = 0.645, not significantly different from LAP, CMI, WHR, and WTI), and TYG (AUC = 0.740) were the best predictor of hypertension, dyslipidemia, T2DM, and multimorbidity, respectively (all P < 0.05). In the male population, BF% (AUC = 0.677), BMI (AUC = 0.698), CMI (AUC = 0.648, not significantly different from LAP and CVAI), and TYG (AUC = 0.741) were the best predictors (all P < 0.05). In the female population, CVAI (AUC = 0.677), CUN-BAE (AUC = 0.623, not significantly different from BF%, WC, WHR, WHtR, BRI and BMI), CVAI (AUC = 0.657, not significantly different from WHR), TYG (AUC = 0.740) were the best predictors (all P < 0.05). After adjusting for all covariates, all ORIs were significantly associated with hypertension, dyslipidaemia, T2DM, and multimorbidity (all P < 0.05), except for ABSI and hypertension and BAI and T2DM, which were insignificant. Ultimately, after considering the heterogeneity of prediction of ORIs among different populations, for hypertension, BF% was the best indicator for men and CVAI for the rest of the population. The best predictors of dyslipidaemia, T2DM, and multimorbidity were BMI, CVAI and TYG, respectively. Screening for common chronic diseases in combination with these factors may help to improve the effectiveness.

Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study.

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.

Satisfaction in population-based cancer screening in a Chinese rural high-risk population: the Yangzhong early diagnosis and treatment of upper gastrointestinal cancer.

BACKGROUND: Screening for upper gastrointestinal cancer (UGC) effectively reduces morbidity and mortality in gastric and esophageal cancers. It is considered one of the effective measures for cancer control in China, but studies on its functional quality are lacking. Our study assessed the quality of screening service funded by Upper Gastrointestinal Cancer Early diagnosis and treatment (UGCEDAT) and its correlation in Yangzhong People's hospital, China. METHODS: A cross-sectional study was conducted among 516 screening users at a screening centre in Yanghzong People's hospital from April to July 2021. The service quality questionnaire (SERVQUAL) based on the service quality gap (SQG) model was adopted. We calculated the mean scores of perceptions and expectations and their gap. To determine the association between overall SQG and related features of participants, we used a multivariate logistic regression. RESULTS: The average scores of screening service users' perceptions and expectations were 4.05 and 4.55, respectively. The SQG of five dimensions (tangibles, reliability, responsiveness, assurance and empathy) were negative, and the overall SQG was -0.51. The responsiveness dimension had the largest gap, and tangibles had the smallest gap. Occupation status (AOR: 0.57; CI: 0.37-0.89), health self-assessment (AOR: 4.97; CI: 1.35-18.23), endoscopy experience (AOR: 0.55; CI: 0.38-0.81), distance from screening hospital (AOR: 1.85; CI: 1.25-2.73) and frequency of visit (AOR: 1.65; CI: 1.10-2.46) were associated with the overall SQG. CONCLUSIONS: We observed a negative gap between perceptions and expectations of the function quality of screening service, implying a high dissatisfaction across different dimensions. Service providers should take adequate measures to bridge the dimension with the largest quality gap. Meanwhile, attention should be paid to identifying the influencing factors of the overall SQG and the characteristics of dimensional expectations and perceptions to improve the effectiveness of the screening program.

The spatiotemporal control of KatG2 catalase-peroxidase contributes to the invasiveness of Fusarium graminearum in host plants.

Reactive oxygen species (ROS) are involved in the pathogen-host interactions, and play a Janus-faced role in the resistance and susceptibility of plants to biotrophic and necrotrophic pathogens. The ascomycete fungus Fusarium graminearum causes hazardous wheat Fusarium head blight worldwide. Deletion of the putative secreted catalase-peroxidase gene in F. graminearum, KatG2, reduced the virulence in wheat spike infection. However, it remains unclear when and where KatG2 scavenges ROS during the invasion of wheat. In this study, we delineate the change in ROS levels in the transition of the infection phase under microscopic observation. Correspondingly, the pathogen switches its strategy of infection with temporal and spatial regulation of KatG2 to counteract oxidative stress generated by host plant cells. With the native promoter-driven KatG2-mRFP strain, we show that KatG2-mRFP expression was induced in planta and accumulated in the infection front region at the early infection stage. In contrast to its ubiquitous cellular localization in runner hyphae, KatG2-mRFP is exclusively located on the cell wall of invading hyphal cells, especially at the pathogen-host cellular interface. Using posttranslational modification analysis, we found that asparagine residues at the 238 and 391 positions of KatG2 could be modified by N-glycosylation and that these two residues are required for KatG2 accumulation and cell wall localization in planta.

A cytoplasmic Cu-Zn superoxide dismutase SOD1 contributes to hyphal growth and virulence of Fusarium graminearum.

Superoxide dismutases (SODs) are scavengers of superoxide radicals, one of the main reactive oxygen species (ROS) in the cell. SOD-based ROS scavenging system constitutes the frontline defense against intra- and extracellular ROS, but the roles of SODs in the important cereal pathogen Fusarium graminearum are not very clear. There are five SOD genes in F. graminearum genome, encoding cytoplasmic Cu-Zn SOD1 and MnSOD3, mitochondrial MnSOD2 and FeSOD4, and extracellular CuSOD5. Previous studies reported that the expression of SOD1 increased during infection of wheat coleoptiles and florets. In this work we showed that the recombinant SOD1 protein had the superoxide dismutase activity in vitro, and that the SOD1-mRFP fusion protein localized in the cytoplasm of F. graminearum. The Δsod1 mutants had slightly reduced hyphal growth and markedly increased sensitivity to the intracellular ROS generator menadione. The conidial germination under extracellular oxidative stress was significantly delayed in the mutants. Wheat floret infection assay showed that the Δsod1 mutants had a reduced pathogenicity. Furthermore, the Δsod1 mutants had a significant reduction in production of deoxynivalenol mycotoxin. Our results indicate that the cytoplasmic Cu-Zn SOD1 affects fungal growth probably depending on detoxification of intracellular superoxide radicals, and that SOD1-mediated deoxynivalenol production contributes to the virulence of F. graminearum in wheat head infection.

[Clinical application of tacrolimus with low-dose prednisone in 21 children with steroid-resistant nephrotic syndrome].

OBJECTIVE: To analyze and evaluate the efficacy and safety of tacrolimus and low-dose steroids in the treatment of steroid-resistant nephrotic syndrome in children. METHOD: Twenty-one children with steroid-resistant nephrotic syndrome enrolled from October 2008 to July 2010 into this retrospective longitudinal study received oral tacrolimus treatment, 0.1 to 0.15 mg/kg per day and once every 12 hours, and prednisone 0.2 to 0.75 mg/kg per day simultaneously. During the treatment, the plasma concentration of tacrolimus, urine volume, urine, serum creatinine and liver function were regularly monitored. RESULT: After 1 to 3 months treatment, 14 cases showed complete remission and 7 cases had partial remission. Sixteen patients received renal biopsy, of whom 6 revealed minimal change nephropathy with complete remission in 3 cases, 3 cases had partial remission;4 cases revealed focal segmental glomerulosclerosis with 2 complete remission and 2 partial remission; other 5 children with IgM nephropathy and 1 mesangial proliferative glomerulonephritis achieved complete remission. Within treatment period, 6 patients presented transient adverse reactions, without altering the principle treatment strategy, but only taking the symptomatic treatment. During follow-up, 1 case was lost to follow-up and the remaining 20 cases were followed up from 2 months to 21 months. In 4 patients the disease relapsed within 1st-year follow-up, while at 2nd-year follow-up, 4 cases had (6 times) recurrence. CONCLUSION: Tacrolimus showed a reliable effect in children with steroid-resistant nephrotic syndrome. Less adverse reactions were seen, and most of them could be tolerated. Nevertheless, the patients had a higher relapse rate after 1 to 2 years treatment. Therefore, the long-term effects of tacrolimus for steroid-resistant nephrotic syndrome remains to be further evaluated.