TH1L involvement in colorectal cancer pathogenesis by regulation of CCL20 through the NF-κB signalling pathway.

TH1L (also known as NELF-C/D) is a member of the Negative Elongation Factor (NELF) complex, which is a metazoan-specific factor that regulates RNA Polymerase II (RNAPII) pausing and transcription elongation. However, the function and molecular mechanisms of TH1L in cancer progression are still largely unknown. In this study, we found that TH1L was highly expressed in colorectal cancer (CRC) tissues and the faeces of CRC patients. Overexpression of TH1L significantly enhanced the proliferation and migration of CRC cells, while its knockdown markedly suppressed these processes. In mechanism, RNA sequencing revealed that CCL20 was upregulated in TH1L-overexpressed CRC cells, leading to activation of the NF-κB signalling pathway. Rescue assays showed that knockdown of CCL20 could impair the tumour-promoting effects of THIL in CRC cells. Taken together, these results suggest that TH1L may play a vital role via the CCL20/NF-κB signalling pathway in CRC proliferation and migration and may serve as a potential target for diagnosis and therapy of CRC.

Effects of interaction of multiple large-scale atmospheric circulations on precipitation dynamics in China.

Different scenarios of precipitation, that lead to such phenomena as droughts and floods are influenced by concurrent multiple teleconnection factors. However, the multivariate relationship between precipitation indices and teleconnection factors, including large-scale atmospheric circulations and sea surface temperature signals in China, is rarely explored. Understanding this relationship is crucial for drought early warning systems and effective response strategies. In this study, we comprehensively investigated the combined effects of multiple large-scale atmospheric circulation patterns on precipitation changes in China. Specifically, Pearson correlation analysis and Partial Wavelet Coherence (PWC) were used to identify the primary teleconnection factors influencing precipitation dynamics. Furthermore, we used the cross-wavelet method to elucidate the temporal lag and periodic relationships between multiple teleconnection factors and their interactions. Finally, the multiple wavelet coherence analysis method was used to identify the dominant two-factor and three-factor combinations shaping precipitation dynamics. This analysis facilitated the quantification and determination of interaction types and influencing pathways of teleconnection factors on precipitation dynamics, respectively. The results showed that: (1) the Atlantic Multidecadal Oscillation (AMO), EI Niño-Southern Oscillation (ENSO), East Asia Summer Monsoon (EASM), and Indian Ocean Dipole (IOD) were dominant teleconnection factors influencing Standardized Precipitation Index (SPI) dynamics; (2) significant correlation and leading or lagging relationships at different timescales generally existed for various teleconnection factors, where AMO was mainly leading the other factors with positive correlation, while ENSO and Southern Oscillation (SO) were mainly lagging behind other factors with prolonged correlations; and (3) the interactions between teleconnection factors were quantified into three types: enhancing, independent and offsetting effects. Specifically, the enhancing effect of two-factor combinations was stronger than the offsetting effect, where AMO + NAO (North Atlantic Oscillation) and AMO + AO (Atlantic Oscillation) had a larger distribution area in southern China. Conversely, the offsetting effect of three-factor combinations was more significant than that of the two-factor combinations, which was mainly distributed in northeast and northwest regions of China. This study sheds new light on the mechanisms of modulation and pathways of influencing various large-scale factors on seasonal precipitation dynamics.

Computed tomography-based body composition parameters can predict short-term prognosis in ulcerative colitis patients.

OBJECTIVES: Emerging evidence suggests a potential relationship between body composition and short-term prognosis of ulcerative colitis (UC). Early and accurate assessment of rapid remission based on conventional therapy via abdominal computed tomography (CT) images has rarely been investigated. This study aimed to build a prediction model using CT-based body composition parameters for UC risk stratification. METHODS: In total, 138 patients with abdominal CT images were enrolled. Eleven quantitative parameters related to body composition involving skeletal muscle mass, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured and calculated using a semi-automated segmentation method. A prediction model was established with significant parameters using a multivariable logistic regression. The receiver operating characteristic (ROC) curve was plotted to evaluate prediction performance. Subgroup analyses were implemented to evaluate the diagnostic efficiency of the prediction model between different disease locations, centers, and CT scanners. The Delong test was used for statistical comparison of ROC curves. RESULTS: VAT density, SAT density, gender, and visceral obesity were significantly statistically different between remission and invalidation groups (all p < 0.05). The accuracy, sensitivity, specificity, and area under the ROC curve (AUC) of the prediction model were 82.61%, 95.45%, 69.89%, and 0.855 (0.792-0.917), respectively. The positive predictive value and negative predictive value were 70.79% and 93.88%, respectively. No significant differences in the AUC of the prediction model were found in different subgroups (all p > 0.05). CONCLUSIONS: The predicting model constructed with CT-based body composition parameters is a potential non-invasive approach for short-term prognosis identification and risk stratification. Additionally, VAT density was an independent predictor for escalating therapeutic regimens in UC cohorts. CRITICAL RELEVANCE STATEMENT: The CT images were used for evaluating body composition and risk stratification of ulcerative colitis patients, and a potential non-invasive prediction model was constructed to identify non-responders with conventional therapy for making therapeutic regimens timely and accurately. KEY POINTS: • CT-based prediction models help divide patients into invalidation and remission groups in UC. • Results of the subgroup analysis confirmed the stability of the prediction model with a high AUC (all > 0.820). • The visceral adipose tissue density was an independent predictor of bad short-term prognosis in UC.

Insights from CMIP6 SSP scenarios for future characteristics of propagation from meteorological drought to hydrological drought in the Pearl River Basin.

Drought is a common and widely distributed natural hazard. Analyzing and predicting drought characteristics and propagation are important for the early warning, prevention, and mitigation of drought disasters. This study used the precipitation and runoff outputs from General Circulation Models (GCMs) of Coupled Model Intercomparison Project Phase 6 (CMIP6) to evaluate the meteorological drought (MD) and hydrological drought (HD) characteristics in the Pearl River Basin (PRB) under two Shared Socioeconomic Pathways (SSPs) (i.e., SSP2-4.5 and SSP5-8.5). The propagation characteristics of external propagation (response between different type of drought) and internal propagation (drought development and recovery stages of a single type of drought) were also comprehensively investigated based on CMIP6. The results revealed that: 1) the percentage of grids within the dry range of MD and HD will decrease from the historical period to the future period under the two scenarios. The PRB is projected to exhibit wetter patterns; 2) Higher emission scenarios (SSP5-8.5) are more likely to weaken dryness conditions; 3) regarding the external propagation, the drought response time from MD to HD would be 2 months, and there would be no significant change under two scenarios; and 4) regarding the internal propagation, during three study periods (1971-2010, 2021-2060 and 2061-2100), the MD (HD) average recovery time changed from 3.90 (3.36) to 3.75 (3.41) and then to 3.95 (3.43) months under the SSP2-4.5 scenario, and changed from 3.93 (3.46) to 3 (3.51) and then to 3.7 (3.25) months under the SSP5-8.5 scenario. These results aid in understanding future drought characteristics and drought propagation under climate change.

Precipitation and vegetation transpiration variations dominate the dynamics of agricultural drought characteristics in China.

Agricultural drought posing a significant threat to agricultural production is subject to the complex influence of ocean, terrestrial and meteorological multi-factors. Nevertheless, which factor dominating the dynamics of agricultural drought characteristics and their dynamic impact remain equivocal. To address this knowledge gap, we used ERA5 soil moisture to calculate the standardized soil moisture index (SSI) to characterize agricultural drought. The extreme gradient boosting model was then adopted to fully examine the influence of ocean, terrestrial and meteorological multi-factors on agricultural drought characteristics and their dynamics in China. Meanwhile, the Shapley additive explanation values were introduced to quantify the contribution of multiple drivers to drought characteristics. Our analysis reveals that the drought frequency, severity and duration in China ranged from 5-70, 2.15-35.02 and 1.76-31.20, respectively. Drought duration is increasing and drought intensity is intensifying in southeast, north and northwest China. In addition, potential evapotranspiration is the most significant driver of drought characteristics at the basin scale. Regarding the dynamic evolution of drought characteristics, the percentages of raster points for drought duration and severity with evapotranspiration as the dominant factor are 30.7 % and 32.7 %, and the percentages with precipitation are 35.3 % and 35.0 %, respectively. Precipitation in northern regions has a positive effect on decreasing drought characteristics, while in southern regions, evapotranspiration dominates the dynamics in drought characteristics due to increasing vegetation transpiration. Moreover, the drought severity is exacerbated by the Atlantic Multidecadal Oscillation in the Yangtze and Pearl River basins, while the contribution of the North Atlantic Oscillation to the drought duration evolution is increasing in the Yangtze River basin. Generally, this study sheds new insights into agricultural drought evolution and driving mechanism, which are beneficial for agricultural drought early warning and mitigation.

Role of BMI in the relationship between dietary inflammatory index and non-alcoholic fatty liver disease: an intermediary analysis.

OBJECTIVE: Previous studies have indicated that a pro-inflammatory diet is associated with non-alcoholic fatty liver disease (NAFLD), but the role of BMI remains ambiguous. We aim to study the intermediary effect of BMI on the relationship between dietary inflammatory properties and NAFLD. METHODS: A total of 19536 adult participants from the National Health and Nutrition Examination Surveys (NHANES) were included. Dietary inflammatory index (DII) was used to evaluate the dietary inflammatory properties and NAFLD was diagnosed by non-invasive biomarkers. Weighted multivariable logistic regression models estimated ORs and 95% CIs between DII and incidence of NAFLD. Interaction effect between DII and BMI on NAFLD was tested and the mediation analysis of BMI was performed. RESULTS: Higher DII scores, representing higher inflammatory potential of diet, were positively associated with a higher risk of NAFLD. Compared with the first quartile of DII, people from the second quartile (OR: 1.23 [95% CI: 1.04, 1.46]) to the fourth quartile (OR: 1.59 [95% CI: 1.31, 1.94]) have a higher risk of NAFLD before adjustment for BMI. The overall association was completely mediated by BMI (89.19%). CONCLUSIONS: Our findings suggested that a higher pro-inflammatory potential diet was associated with a higher prevalence of NAFLD, and this association might be mediated by BMI.

The usefulness of fecal hemoglobin and calprotectin tests in diagnosing significant bowel diseases: a prospective study.

OBJECTIVES: Although colonoscopy remains the gold standard for determining bowel diseases, it's invasive and expensive. New non-invasive diagnostic methods are urgently needed as an initial screening modality. We aimed to investigate the value of fecal calprotectin (FC) and fecal immunochemical test (FIT) in differentiation of significant and non- significant bowel diseases. METHODS: In this prospective study, consecutive individuals were included if they underwent colonoscopy for symptoms of lower gastrointestinal (GI) tract, positive fecal occult blood test, surveillance for IBD or colorectal cancer (CRC) screening. Diagnostic value of FC and FIT in discriminating significant bowel diseases (advanced neoplasia, active inflammatory bowel diseases or bowel inflammation due to other causes) and non-significant bowel diseases (normal, asymptomatic diverticulum, non-adenomatous polyp, or non-advanced neoplasia) were evaluated. RESULTS: Among 201 individuals included, 107 patients had significant bowel diseases. FC and FIT had an area under the curve (AUC) of 0.722 (95% confidence interval [CI] 0.653-0.792) and 0.797 (95%CI 0.734-0.860), respectively, for determining significant bowel diseases. Combination of FC and FIT predicted significant bowel diseases with an AUC, sensitivity, specificity, and accuracy of 0.832 (95% CI 0.775-0.890), 77.6%, 74.5%, and 76.1%, respectively. Moreover, combination of FC and FIT was more sensitive among patients with lower GI symptoms than asymptomatic individuals (80.8% vs. 74.1%) to identify significant bowel diseases. CONCLUSIONS: A single measurement of FC or FIT is not sufficiently accurate to identify patients with significant bowel disease. However, combination of FC and FIT can help increase the sensitivity, especially in patients with lower GI symptoms.

Triglyceride glucose index and Atherogenic index of plasma for predicting colorectal neoplasms in patients without cardiovascular diseases.

Background and aims: Colorectal neoplasms (CRN) include colorectal cancer (CRC) and colorectal adenoma (CRA). The relationship between CRN and triglyceride-glucose (TyG) index or between CRN and atherogenic index of plasma (AIP) is unclear. This study aims to investigate the roles of TyG index and AIP in predicting CRN in people without cardiovascular disease (CVD). Methods: 2409 patients without CVD underwent colonoscopy were enrolled. Clinical information and relevant laboratory test results of these patients were collected and recorded. According to endoscopic and pathological results, all participants were divided into a neoplasms group and a non-neoplasms group. The TyG index was calculated as ln (TGs×FPG/2), while AIP was calculated as log (TGs/HDL-C). We used uni- and multivariate logistic regression and restricted cubic spline (RCS) to analyze the association between the TyG inedx, AIP and CRN, develop predictive models and construct the nomograms. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive value for CRN. Results: Participants in the neoplasms group were more likely to be older, have higher TyG index, higher AIP and higher rates of fecal occult blood test positivity, and were more likely to be male, smokers and those with the family history of CRC (P < 0.05). The higher TyG index was related to the higher risk of CRN [OR (95% CI): 1.23 (1.08 - 1.41), P = 0.003]. The higher AIP was related to the higher risk of CRN [OR (95% CI): 1.55 (1.16 - 2.06), P = 0.003]. These two indicators are better for predicting CRN in women than men. The combined use of the TyG index and other independent risk factors (age, sex, smoking status, family history and FOBT) to distinguish CRN was effective, with a sensitivity of 61.0%, a specificity of 65.1% and an AUC of 0.669 (95%CI, 0.639 - 0.698). Likewise, the combined use of the AIP and other independent risk factors to distinguish CRN was also effective, the model had an overall 56.3% sensitivity and 68.7% specificity with an AUC of 0.667 (95%CI, 0.638 - 0.697). Conclusion: This study showed that the TyG index and the AIP might be biomarkers that could be used to predict the risk of CRN in patients without CVD.

Predictors for malignant potential and deep submucosal invasion in colorectal laterally spreading tumors.

BACKGROUND: Colorectal laterally spreading tumors (LSTs) with malignant potential require en bloc resection by endoscopic submucosal dissection (ESD), but lesions with deep submucosal invasion (SMI) are endoscopically unresectable. AIM: To investigate the factors associated with high-grade dysplasia (HGD)/carcinoma and deep SMI in colorectal LSTs. METHODS: The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed. The characteristics of LST subtypes were compared. Risk factors for HGD/carcinoma and deep SMI (invasion depth ≥ 1000 µm) were determined using multivariate logistic regression. RESULTS: A total of 323 patients with 341 colorectal LSTs were enrolled. Among the four subtypes, non-granular pseudodepressed (NG-PD) LSTs (85.5%) had the highest rate of HGD/carcinoma, followed by the granular nodular mixed (G-NM) (77.0%), granular homogenous (29.5%), and non-granular flat elevated (24.2%) subtypes. Deep SMI occurred commonly in NG-PD LSTs (12.9%). In the adjusted multivariate analysis, NG-PD [odds ratio (OR) = 16.8, P < 0.001) and G-NM (OR = 7.8, P < 0.001) subtypes, size ≥ 2 cm (OR = 2.2, P = 0.005), and positive non-lifting sign (OR = 3.3, P = 0.024) were independently associated with HGD/carcinoma. The NG-PD subtype (OR = 13.3, P < 0.001) and rectosigmoid location (OR = 8.7, P = 0.007) were independent risk factors for deep SMI. CONCLUSION: Because of their increased risk for malignancy, it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD. Given their substantial risk for deep SMI, surgery needs to be considered for NG-PD LSTs located in the rectosigmoid, especially those with positive non-lifting signs.

Composition and diverse differences of intestinal microbiota in ulcerative colitis patients.

Objective: To explore the composition of the intestinal microbiota in ulcerative colitis (UC) patients and to identify differences in the microbiota between patients with active disease and those in remission. Methods: Between September 2020 and June 2021, we enrolled into our study, and collected stool samples from, patients with active UC or in remission and healthy control subjects. The diagnosis of UC was based on clinical, endoscopic, radiological, and histological findings. The composition of the intestinal microbiota was determined by sequencing of the 16S rRNA V3-V4 region and by bioinformatic methods. The functional composition of the intestinal microbiota was predicted using PICRUSt 2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) software. Results: We found that the intestinal flora was significantly less rich and diverse in UC patients than in healthy control subjects. Beta diversity analysis revealed notable differences in the intestinal flora compositions among the three groups, but there was no statistical difference in alpha diversity between UC patients with active disease and those in remission. At the phylum level, the relative abundances of Proteobacteria and Patescibacteria were significantly higher, and the relative abundances of Desulfobacterota and Verrucomicrobiota were lower, in UC patients with active disease than in the healthy control group. Higher levels of potential pathogens and lower levels of butyrate-producing bacteria were also detected in UC patients with active disease. Linear discriminant analysis Effect Size (LefSe) revealed that 71 bacterial taxa could serve as biomarkers, with 26 biomarkers at the genus level. In addition, network analysis showed that there was a positive correlation between Roseburia and Lachnospira. Functional predictions indicated that gene functions involving the metabolism of some substances, such as methane, lipopolysaccharide, geraniol, and ansamycins, were significantly different among the three groups. Conclusion: The richness and diversity of the intestinal microbiota differed significantly among the three groups. Richness describes the state of being rich in number of intestinal bacteria, whereas diversity is the number of different species of intestinal bacteria. Different bacterial taxa could be used as biomarkers, expanding our understanding of the relationship between the intestinal microbiota microenvironment and UC in the future.

Efficacy, safety and immunogenicity of hexavalent rotavirus vaccine in Chinese infants.

A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine (HRV) against rotavirus gastroenteritis (RVGE). A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV (n â€‹= â€‹3200) or placebo (n â€‹= â€‹3200) group. All the subjects received three oral doses of vaccine four weeks apart. The vaccine efficacy (VE) against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season. VE against severe RVGE, VE against RVGE hospitalization caused by serotypes contained in HRV, and VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated. All adverse events (AEs) were collected for 30 days after each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21% (95%CI: 53.31-79.69). VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36% (95%CI: 78.45-96.53) and 89.21% (95%CI: 64.51-96.72) respectively. VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88% (95%CI: 49.11-72.92), 85.51% (95%CI: 72.74-92.30) and 83.68% (95%CI: 61.34-93.11). Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable. There was no significant difference in incidences of SAEs in HRV and placebo groups. This study shows that this hexavalent reassortant rotavirus vaccine is an effective, well-tolerated, and safe vaccine for Chinese infants.

Prediction of clinical efficacy of subcutaneous immunotherapy for Artemisia sieversiana pollen allergic rhinitis by serum metabolomics.

BACKGROUND/PURPOSE: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. METHODS: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. RESULTS: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved. CONCLUSION: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.

Disposable versus reusable gastroscopes: a prospective randomized noninferiority trial.

BACKGROUND AND AIMS: Disposable gastroscopes have recently been developed to eliminate the risk of infection transmission from contaminated reusable gastroscopes. We compared the performance of disposable and reusable gastroscopes in patients undergoing gastroscopy. METHODS: Patients requiring gastroscopy were randomized to either the disposable or reusable digital gastroscope group. The primary endpoint was the success rate of photographing customary anatomic sites, with a noninferiority margin of -8%. Secondary endpoints were technical performance factors such as gastroscope imaging quality, maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, and safety. Data were analyzed using the Newcombe-Wilson score method and Fisher exact 2-tailed t test. RESULTS: Of 110 patients, 55 were treated using disposable gastroscopes and 55 using reusable gastroscopes. The success rate for capturing images of customary anatomic sites was 100% in both groups. The average imaging quality score was significantly lower (37.02 ± 3.09 vs 39.47 ± 1.92, P < .001) and the operating time significantly longer (P < .001) in the disposable gastroscope group. No significant differences in maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, or safety were found between the 2 groups. CONCLUSIONS: Given the overall safety profile and similar technical performance, disposable gastroscopes represent an alternative to reusable gastroscopes for routine examination, bedside first aid, and some certain circumstances.

Assessing the responses of vegetation to meteorological drought and its influencing factors with partial wavelet coherence analysis.

The increase in drought frequency in recent years is considered as an important factor affecting vegetation diversity. Understanding the responses of vegetation dynamics to drought is helpful to reveal the behavioral mechanisms of terrestrial ecosystems and propose effective drought control measures. In this study, long time series of Normalized Difference Vegetation Index (NDVI) and Solar-induced chlorophyll fluorescence (SIF) were used to analyze the vegetation dynamics in the Pearl River Basin (PRB). The relationship between vegetation and meteorological drought was evaluated, and the corresponding differences among different vegetation types were revealed. Based on an improved partial wavelet coherence (PWC) analysis, the influences of teleconnection factors (i.e., large-scale climate patterns and solar activity) on the response relationship between meteorological drought and vegetation were quantitatively analyzed to determine the roles of factors. The results indicate that (a) vegetation in the PRB showed an increasing trend from 2001 to 2019, and the SIF increased more than that of NDVI; (b) the vegetation response time (VRT) based on NDVI (VRTN) was typically 4-6 months, while the VRT based on SIF (VRTS) was typically 2-4 months. The VRT was shortest in the woody savannas and longest in the evergreen broadleaf forests. (c) The relationship between the SIF and meteorological drought was more significant than that between the NDVI and meteorological drought. (d) There was a significant positive correlation between meteorological drought and vegetation in the period of 8-20 years. The El Niño Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO) and sunspots were important driving factors affecting the response relationship between drought and vegetation. Specifically, the PDO had the greatest impacts among these factors.

Design and verification of individualized follow-up strategy of colonoscopy for postoperative patients with colorectal cancer.

BACKGROUND: Current guidelines do not establish an individual scheme for surveillance colonoscopy in postoperative colorectal cancer (CRC) patients. AIMS: The purpose of the study was to screen possible risk factors for the development of metachronous adenoma in postoperative CRC patients and to develop a risk prediction model and verify it. METHODS: Consecutive postoperative patients with CRC were enrolled from April 2007 to December 2013 as the derivation group. Baseline data of patients and clinicopathological features of the tumor were collected, logistic regression analysis was performed, and clinical model was established and was verified internally. The model was externally validated in an independent cohort (validation group) from January 2014 to October 2017 in the same hospital. RESULTS: A total of 734 patients were included, with average (64.6 ± 11.5) years old. The overall incidence of metachronous adenoma was 35.4%. There was no significant difference in the incidence of metachronous adenoma between the derivation group and validation group (P > 0.05). Age, diabetes mellitus, right colon cancer, moderately to poorly differentiated adenocarcinoma and synchronous adenoma were independent risk factors for metachronous adenoma. The C-index of the metachronous adenoma line chart model was 0.932, and the index decreased by 0.022 after internal verification. The C-index of external validation was 0.910. The Hosmer-Lemeshow test showed that the P value of metachronous adenoma risk prediction model was 0.247. CONCLUSIONS: Individual surveillance strategies should be designed for postoperative patients with CRC. For high-risk patients, it is appropriate to undergo more than two colonoscopies in 36 months after operation.

Construction of a novel predictive nomogram for difficult procedure of endoscopic submucosal dissection for colorectal neoplasms.

OBJECTIVES: To determine the predictors of difficult colorectal endoscopic submucosal dissection (ESD) and to develop a preoperative predictive model for difficult colorectal ESD procedures. METHODS: Colorectal neoplasms intended to be resected by ESD in our center between August 2013 and February 2019 were retrospectively enrolled. An ESD procedure which took more than 30 min, failed to remove the lesions en bloc or converted to surgery was defined as difficulty. Logistic regression analysis was conducted to find out the predictors of difficult ESD. A nomogram integrating independent predictors was developed and validated with respect to its discrimination, calibration and clinical application, using the receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA), respectively. RESULTS: A total of 368 colorectal neoplasms in 355 patients were included. The independent predictors for difficult colorectal ESD were size ≥2 cm (odds ratio [OR] = 6.102, p < .001), positive non-lifting sign (OR = 6.569, p = .005), lesions located in left colon (OR = 2.475, p = .036) or rectum (OR = 2.183, p = .048), laterally spreading tumors (LSTs) (OR = 2.501, p = .008) and less colorectal ESD experience (≤20 cases) (OR = 2.3091, p = .028). The nomogram model incorporating the above predictors performed well in both of the training and validation sets (area under the cure [AUC] = 0.786 and 0.784, respectively). DCA demonstrated the clinical benefit of the nomogram was superior to that of each independent predictor alone. CONCLUSIONS: The nomogram incorporating tumor size, location, morphology, non-lifting sign and ESD experience of operator can be conveniently used to facilitate the preoperative prediction of difficult colorectal ESD.

Prevalence and risk factors of allergic rhinitis and asthma in the southern edge of the plateau grassland region of northern China: A cross-sectional study.

BACKGROUND: The prevalence rates of allergic rhinitis (AR) and asthma in the border region of China may be different from those in the central region of plateau grasslands. A survey was performed to investigate the prevalence and risk factors for AR, asthma, and AR combined with asthma among adults (age ≥ 20 years) residing in the southern border of plateau grasslands in northern China. METHODS: From May to August 2018, a cross-sectional survey was completed by subjects that were selected using a cluster random sampling method. The subjects completed a questionnaire and were administered skin prick tests (SPTs). Risk factors for AR, asthma, and AR combined with asthma were examined by multivariate logistic regression analyses. RESULTS: A total of 1815 adult subjects in the selected region completed study. The prevalence rates of physician-diagnosed AR, asthma, and AR combined with asthma were 13.9% (253), 9.8% (177), and 2.9% (52), respectively. Among the patients with AR, 20.6% were found to have concurrent asthma; among the patients with asthma, 29.4% were found to have concurrent AR. Artemisia and Humulus pollen were the most common sensitizing pollen types. Approximately 70% of subjects with AR and <30% of asthma patients were sensitized to Artemisia and Humulus pollen. Symptoms of AR and asthma mainly appeared during August. A multivariable logistic regression analysis identified sensitization pollen as an independent risk factor for both AR and AR combined with asthma (AR: OR = 16.23, 95% CI: 10.15-25.96; AR combined with asthma: OR = 6.16, 95% CI: 1.28-29.66). An age >40 years old, family history of asthma, moderate-to-severe AR, adverse food reactions, and mold allergies were independent risk factors for AR combined with asthma. CONCLUSIONS: This study identified the prevalence rates of AR and asthma in the southern borders of the plateau grassland in northern China (>1500 m above sea level). Sensitization pollen is an independent risk factor for AR and AR combined with asthma.

Serum Uric Acid Is a Mediator of the Association Between Obesity and Incident Nonalcoholic Fatty Liver Disease: A Prospective Cohort Study.

Objective: Obesity has been demonstrated to show a consistent link with the increased possibility of nonalcoholic fatty liver disease (NAFLD). Since both serum uric acid (SUA) and obesity are essential components of metabolic syndrome (MetS), it is uncertain whether the incidence of NAFLD results from serum uric acid, obesity, or other potential factors based on previous studies. Patients and methods: This study enrolled 16,839 participants with no history of alcohol consumption and no fatty liver disease in 2010. All participants completed a survey which included health and lifestyle questionnaires, and underwent physical examination, ultrasonography, and laboratory examinations of blood samples. After the four-year follow up, 5,104 (30.31%) participants were diagnosed with NAFLD. The associations between SUA, BMI or obesity, and incident NAFLD were assessed by multivariate linear regression, logistic regression analysis, and mediation analysis, respectively. Results: By adjusting demographic and serum characteristics, linear correlation coefficients between obesity and SUA were 20.26 [95% confidence interval (CI)]: 15.74, 24.77), 13.31 (95% CI: 6.63, 19.99) and 22.21 (95% CI: 16.41, 28.02) in the total population, and in the female and male groups, respectively. The odds ratios were 2.49 (95% CI: 1.61, 3.87) in the total population, 5.71 (95% CI: 2.25, 14.45) in the female group and 1.99 (95% CI: 1.15, 3.45) in the male group for the correlation between obesity and incident NAFLD. The mediation analysis showed that SUA contributed to 10.03%, 0.58%, and 12.54% of obesity-related NAFLD development in the total population, females and males, respectively. Conclusion: The findings showed mediation linkages of both obesity and SUA with the incident NAFLD. The role of SUA as a mediator constitutes clinical significance that should be recognized and considered.

Aberrant expression of m6A mRNA methylation regulators in colorectal adenoma and adenocarcinoma.

BACKGROUND: As the most prevalent post-transcriptional mRNA modification in eukaryotes, N6-Methyladenosine (m6A) is closely linked to the occurrence and development of colorectal cancer (CRC). However, there is no systematic evaluation of the expression of m6A regulatory genes in CRC. METHODS: By analyzing the TCGA database, we identified METTL3, YTHDF1, IGF2BP1, IGF2BP3, EIF3B, HNRNPA2B1 as overexpressed m6A regulators in CRC. After verification by immunohistochemistry (IHC) in 10 CRC cases, YTHDF1, IGF2BP1, IGF2BP3, and EIF3B were identified as potential biomarkers in CRC. Further validation was done by IHC and qRT-PCR in two larger cohorts. RESULTS: We identified 6 up-regulated m6A regulatory genes in CRC in TCGA analysis, and verified that YTHDF1, IGF2BP1, IGF2BP3, and EIFB3 were all significantly differentially expressed between CRC and normal tissues by IHC (p < 0.0001). In another larger cohort, we further validated the overexpression of those genes in CRC as compared to both normal tissues (p < 0.0001) and adenoma tissues (p < 0.05). Detailed analysis suggested that detection of one of the three genes, YTHDF1, IGF2BP1 and IGF2BP3, and combined detection of EIF3B gene could be a good strategy for early diagnosis of both CRC and precancerous lesions. Furthermore, we found that the mRNA levels of YTHDF1, IGF2BP1, and IGF2BP3 were also significantly up-regulated in CRC but not adenoma as compared to normal tissues. CONCLUSION: We evaluted the abnormal expression of m6A regulatory genes during CRC carcinogenesis, and identified four m6A genes (YTHDF1, IGF2BP1, IGF2BP3, and EIF3B) as potential biomarkers of both CRC and adenoma.