Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis.

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg-1·d-1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1ß. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1ß, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

Individualized small bowel preparation for computed tomography enterography: A prospective randomized controlled trial.

BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2, 1500 mL for patients with 18.5 kg/m2 ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2, 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2, 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.

Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

A weighted cranial diffusion-weighted imaging scale for Wilson's disease.

Objectives: Cranial magnetic resonance imaging (MRI) could be a crucial tool for the assessment for neurological symptoms in patients with Wilson's disease (WD). Diffusion-weighted imaging (DWI) hyperintensity reflects the acute brain injuries, which mainly occur in specific brain regions. Therefore, this study aimed to develop a weighted cranial DWI scale for patients with WD, with special focus on specific brain regions. Materials and methods: In total, 123 patients with WD were enrolled, 118 of whom underwent 1.5 T-MRI on admission. The imaging score was calculated as described previously and depended on the following sequences: one point was acquired when abnormal intensity occurred in the T1, T2, and fluid-attenuation inversion recovery sequences, and two points were acquired when DWI hyperintensity were found. Consensus weighting was conducted based on the symptoms and response to treatment. Results: Intra-rater agreement were good (r = 0.855 [0.798-0.897], p < 0.0001). DWI hyperintensity in the putamen was a high-risk factor for deterioration during de-copper therapy (OR = 8.656, p < 0.05). The high-risk factors for readmission for intravenous de-copper therapies were DWI hyperintensity in the midbrain (OR = 3.818, p < 0.05) and the corpus callosum (OR = 2.654, p < 0.05). Both scoring systems had positive correlation with UWDRS scale (original semi-quantitative scoring system, r = 0.35, p < 0.001; consensus semi-quantitative scoring system, r = 0.351, p < 0.001.). Compared to the original scoring system, the consensus scoring system had higher correlations with the occurrence of deterioration (OR = 1.052, 95%CI [1.003, 1.0103], p < 0.05) and readmission for intravenous de-copper therapy (OR = 1.043, 95%CI [1.001, 1.086], p < 0.05). Conclusion: The predictive performance of the consensus semi-quantitative scoring system for cranial MRI was improved to guide medication, healthcare management, and prognosis prediction in patients with WD. For every point increase in the neuroimaging score, the risk of exacerbations during treatment increased by 5.2%, and the risk of readmission to the hospital within 6 months increased by 4.3%.

Comparison of Factors Associated with Myopia among Middle School Students in Urban and Rural Regions of Anhui, China.

SIGNIFICANCE: The prevention and control of myopia have become a major public health task throughout the world. The analysis of the modifiable factors associated with myopia will help in planning concrete strategies that can be widely implemented by schools and families. PURPOSE: This study assessed the modifiable factors associated with myopia and compared them between rural and urban regions. METHODS: Data were collected from December 2020 to March 2021. A multistage stratified cluster sampling method was used to select 6154 middle school students. All children underwent an eye examination, including visual acuity and cycloplegic refraction. Data on near work, sleep, and outdoor activities were collected in questionnaires. RESULTS: The myopia prevalence values in urban and rural regions were 68.1 and 63.7%, respectively ( χ2 = 15.57, P < .001). More than 3 hours of homework per day (odds ratio [OR] in urban and rural regions, 1.36 [95% confidence interval {CI}, 1.07 to 1.75] vs. 1.72 [95% CI, 1.43 to 2.07]), 36 to 40 core subjects per week (OR, 1.30 [95% CI, 1.04 to 1.57] vs. 1.42 [95% CI, 1.24 to 1.64]), and going to sleep before 10 o'clock (OR, 0.56 [95% CI, 0.32 to 0.93] vs. 0.50 [95% CI, 0.28 to 0.90]) were significantly associated with myopia in both regions. In contrast, taking breaks during near work was a significant factor in the rural region (<1 hour: OR, 0.57 [95% CI, 0.42 to 0.76]; 1 to 2 hours: OR, 0.63 [95% CI, 0.46 to 0.86]) but not in the urban region. More time outdoors per day was associated with a reduced prevalence of myopia only for urban children (2 to 3 hours: OR, 0.55 [95% CI, 0.31 to 0.97]; >3 hours: OR, 0.38 [95% CI, 0.19 to 0.75]). CONCLUSIONS: Homework loads and the time of going to sleep were associated with myopia for children in both urban and rural regions. However, time outdoors was only associated with myopia in urban regions, and taking breaks during near work was only associated with myopia in rural regions.

[Design and Verification of Human Metabolic Measurement System Based on STM32].

A high-precision human metabolic measurement system is designed. The system uses STM32F103 as the main control chip to acquire oxygen, carbon dioxide and flow signals to calculate four quantitative indicators: oxygen consumption(VO2), carbon dioxide production(VCO2), respiratory entropy(RQ) and resting energy metabolism(REE), and finally uses an upper computer to display the calculation results.In this paper, the signal acquisition circuit design was carried out for the oxygen sensor, carbon dioxide sensor and flow sensor, and the validity of the device was verified with the American machine MGCDiagnositcs using Bland-Altman analysis method, and the results showed that the four parameters of VO2,VCO2, RQ and REE of both devices fell in the agreement interval of more than 95%. The device thus provides accurate metabolic measurements and offers an effective tool for the field of general health and clinical nutrition support in China.

Retroflexed view for reexamination of the right colon after forward view examination: Systematic review and meta-analysis.

BACKGROUND: The effect of retroflexed view (RV) for the reexamination of the right colon after forward view (FV) examination has not been fully understood. METHODS: We searched multiple databases including PubMed, Embase, and the Cochrane Library for prospective studies exploring the role of RV for reexamination of the right colon. A meta-analysis was performed on outcomes including lesion detection rates, lesion miss rates, and withdrawal time. RESULTS: Four randomized controlled trials aimed to compare the impact of the second withdrawal from the right colon in RV vs. FV following a standard colonoscopy. Both the additional adenoma detection rate (AADR) and additional polyp detection rate (APDR) of the right colon were lower in the RV group compared with the FV group (risk ratio [RR] 0.73 for AADR; RR 0.76 for APDR); similar results were noted in comparisons of the adenoma miss rate and polyp miss rate. Six prospective cohort studies aimed to describe the effect of the RV examination of the right colon after one or two rounds of FV examination. Both the adenoma detection rate (ADR) and polyp detection rate (PDR) of the right colon were slightly higher in combined examinations with RV examination than single FV examination (RR 1.11 for ADR; RR 1.16 for PDR) or two FV examinations (RR 1.21 for ADR; RR 1.22 for PDR). CONCLUSIONS: FV may detect more adenomas and polyps than RV during the second withdrawal from the right colon. RV may detect additional adenomas and polyps in the right colon after two FV examinations.

Real-time artificial intelligence for endoscopic diagnosis of early esophageal squamous cell cancer (with video).

BACKGROUND AND AIMS: Endoscopic diagnosis of early esophageal squamous cell cancer (ESCC) is complicated and dependent on operators' experience. This study aimed to develop an artificial intelligence (AI) model for automatic diagnosis of early ESCC. METHODS: Non-magnifying and magnifying endoscopic images of normal/noncancerous lesions, early ESCC, and advanced esophageal cancer (AEC) were retrospectively obtained from Qilu Hospital of Shandong University. A total of 10,988 images from 5075 cases were chosen for training and validation. Another 2309 images from 1055 cases were collected for testing. One hundred and four real-time videos were also collected to evaluate the diagnostic performance of the AI model. The diagnostic performance of the AI model was compared with endoscopists by magnifying images and the assistant efficiency of the AI model for novices was evaluated. RESULTS: The AI diagnosis for non-magnifying images showed a per-patient accuracy, sensitivity, and specificity of 99.5%, 100%, 99.5% for white light imaging, and 97.0%, 97.2%, 96.4% for optical enhancement/iodine straining images. Regarding diagnosis for magnifying images, the per-patient accuracy, sensitivity, and specificity were 88.1%, 90.9%, and 85.0%. The diagnostic accuracy of the AI model was similar to experts (84.5%, P = 0.205) and superior to novices (68.5%, P = 0.005). The diagnostic performance of novices was significantly improved by AI assistance. When it comes to the diagnosis for real-time videos, the AI model showed acceptable performance as well. CONCLUSIONS: The AI model could accurately recognize early ESCC among noncancerous mucosa and AEC. It could be a potential assistant for endoscopists, especially for novices.

Cresyl violet as a new contrast agent in probe-based confocal laser endomicroscopy for in vivo diagnosis of gastric intestinal metaplasia.

BACKGROUND AND AIM: Cresyl violet (CV) is a topical dye that allows simultaneous chromoendoscopy and in vivo confocal laser endomicroscopy in identification of neoplastic changes of the lower gastrointestinal tract without intravenous injection of fluorescein, but as yet no investigation has reported its application in the diagnosis of gastric intestinal metaplasia (GIM). This study aims to assess the feasibility as well as diagnosis accuracy of topical CV for in vivo diagnosis of GIM by using probe-based confocal laser endomicroscopy (pCLE). METHODS: In this prospective, open-label, feasibility study, 129 confocal videos from 22 patients with known GIM were analyzed and compared with corresponding histological images to establish the CV staining characteristics. In addition, 47 patients with known or suspected GIM were prospectively enrolled to evaluate the accuracy of this topical CV endomicroscopic imaging. RESULTS: Probe-based confocal laser endomicroscopy with topical CV enabled clear visualization of the goblet cells, absorptive cells, and intestinal villi of GIM. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pCLE diagnosis of GIM on a per-location analysis was 93.01%, 91.95%, 93.51%, 86.96%, and 96.11%, respectively. The intraclass correlation coefficient for inter-observer agreement and mean kappa value for intra-observer agreement for the diagnosis of GIM was 0.82 and 0.87, respectively. CONCLUSIONS: Topical CV enables real-time chromoendoscopy in conjunction with pCLE examination of the stomach and warrants accurate diagnosis of GIM. It may be an acceptable and potentially alternative dye for confocal imaging in the future.

Evaluation of the performance of two neutral oral contrast agents in computed tomography enterography: A randomized controlled trial.

OBJECTIVE: To compare the performances, tolerability and acceptability of mannitol and polyethylene glycol (PEG) as oral contrast agents in patients undergoing computed tomography enterography (CTE). METHODS: Patients aged 18-75 years indicated for CTE were randomized to receive either mannitol or PEG as contrast agents. The coronal reconstructed images of each abdominal quadrant were assessed for maximum distention, proportion of distended bowel loops, presence of inhomogeneous contents and visibility of the small bowel wall. Overall subjective imaging quality assessment and patients' tolerability and acceptability were recorded. RESULTS: Seventy patients were enrolled and randomized into two groups. In the per-protocol analysis, no significant differences in imaging quality was found in bowel distention maximum diameter, wall visibility and intestinal homogeneity (all P > 0.05). The mean nausea score was lower in the mannitol group (0 [0-0] vs 1.0 [0-3.0], P < 0.001). Mannitol was superior to PEG in taste (9.0 [8.0-10.0] vs 7.0 [5.0-8.0], P < 0.001), patients' willingness to reuse the drug (9.0 [8.0-10.0] vs 8.0 [7.0-9.0], P = 0.036), satisfaction (9.0 [8.0-10.0] vs 8.0 [7.0-9.0], P = 0.022) and ease of completion (9.0 [8.0-9.3] vs 8.0 [6.5-9.0], P = 0.030). CONCLUSIONS: Both mannitol and PEG provided good bowel distention and visualization of the bowel wall. However, mannitol was significantly superior to PEG in patients' tolerability and acceptability.