Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

Objective:To explore the value of a nomogram model based on the CT enterography (CTE) signs for prediction of intestinal penetrating lesions in patients with Crohn disease (CD).Methods:The clinical and CTE data of CD patients who underwent at least two CTE examinations from January 2010 to June 2020 in the First Affiliated Hospital of Sun Yat-sen University were retrospectively collected. A total of 112 patients were enrolled, and according to whether there was intestinal wall penetration in the last CTE observation were divided into non-penetration group (84 cases) and penetration group (28 cases). First, the clinical and CTE data for the first examination was analyzed by using univariate and multivariate Cox proportional hazards regression to screen out high-risk factors that could effectively predict intestinal wall penetrating lesions in CD patients and established a nomogram model. Then the change trend of CTE data (ΔCTE) between the first and last clinical and CTE signs was analyzed by using univariate and multivariate Cox proportional hazards regression, and built a nomogram model to sort out ΔCTE that may accompany the development of penetrating lesions in CD patients. The Harrell concordance index was used to evaluate the discriminative ability of the nomogram model.Results:In the first time clinical and CTE signs, multivariate Cox proportional hazards regression results showed that numbers of diseased bowel segments (HR=0.686, 95%CI 0.475-0.991, P=0.045) and the shortest diameter of the largest lymph node (HR=0.751, 95%CI 0.593-0.949, P=0.017) were independent protection factors for penetrating lesions, and rough bowel wall surface (HR=5.626, 95%CI 2.466-12.839, P<0.001) was an independent risk factor for penetrating lesions. The specificity and sensitivity of the nomogram model to predict non-penetration lesions were 82.1% and 59.5% respectively, and the Harrell concordance index was 0.810 (95%CI 0.732-0.888). In the ΔCTE signs, multivariate Cox proportional hazards regression showed that Δrough bowel wall surface (always rough bowel wall surface HR=12.344, 95%CI 2.042-74.625, P=0.006; slide bowel wall surface becomes rough bowel wall surface HR=28.720, 95%CI 4.580-180.112, P<0.001) and Δthe shortest diameter of the largest lymph node (HR=1.534, 95%CI 1.091-2.157, P=0.014) were independent risk factors for penetrating lesions. The specificity and sensitivity of the nomogram model were 89.3% and 79.2% respectively, and the Harrell concordance index was 0.876 (95%CI 0.818-0.934). Conclusion:The nomogram based on CTE signs of numbers of diseased bowel segments, the shortest diameter of the largest lymph node and rough bowel wall surface and ΔCTE can effectively predict the intestinal wall penetrating lesions of CD patients.

OBJECTIVE To explore the establishment of standardized training system for medication direction provided by pediatric pharmacists. METHODS Based on the questionnaire， the current needs of pediatric pharmacists and parents of children for medication direction were investigated， and the standardized training content of pediatric medication direction was constructed as a whole with reference to the survey results， instructions， databases and other literature. The basic knowledge of medication direction was integrated and summarized from the basic information of drugs such as drug name， usage and dosage， as well as the course of treatment， order of medication and special precautions， so as to form the general introduction of training content. In accordance with the principle of “integrated drug classification based on diseases”， a standardized framework of medication direction for various common diseases in children was constructed to form various theories of training content. Concomitantly， the pilot training of pharmacists in Qingdao Women and Children’s Hospital of Qingdao University was carried out， and the training effect was preliminarily evaluated. RESULTS After standardized training， the daily examination scores of pharmacists in this hospital were significantly higher than those before training， and the situation of ‘0’ times of receiving patients’ thank-you letters in the window service was broken through； the effective satisfaction rate of window service showed an increasing trend； after the pharmacist explained the medication to the patient， the times of patient returning to consult the doctor on how to use the medicine showed downward trend. CONCLUSIONS The establishment and implementation of a systematic standardized training system for pediatric-specialist pharmacists can help to further improve the professional skills and professionalism of pharmacists， strengthen the standardization of window medication direction and enhance patients’ sense of gain.

Objective:To develop a mesenteric creeping fat index (MCFI) based on CT enterography (CTE) to characterize the degree of creeping fat wrapping around the inflamed gut in Crohn disease (CD), and to assess the relationship between MCFI and the inflammatory intestinal stricture.Methods:From December 2018 to July 2019, the patients with CD who underwent surgery in the First Affiliated Hospital of Sun Yat-Sen University were prospectively collected. The extent of perienteric mesenteric vessels wrapping around the gut was reconstructed to develop MCFI based on CTE images. The intestinal stricture index was obtained by calculating the ratio of the maximal upstream luminal diameter divided by the minimum luminal diameter apparent within the stricturing region. Using region-by-region correlation between CTE and surgical specimen, creeping fat score in intestinal specimen was obtained by assessing the extent of creeping fat wrapping around the resected bowel segment, and HE staining was performed on the bowel specimen corresponding to creeping fat to obtain the pathological inflammatory score. The Spearman correlation analysis was used to evaluate the correlation between MCFI, creeping fat score in intestinal specimen, and inflammatory score, intestinal stricture index. The ROC curve analysis was used to assess the accuracy of MCFI in distinguishing moderate-severe and mild inflammatory bowel walls.Results:Totally 30 CD patients were enrolled. The creeping fat score in intestinal specimen positively correlated with pathological inflammatory score ( r s=0.403, P=0.027) and with intestinal stricture index ( r s=0.642, P<0.001). MCFI positively correlated with creeping fat score in intestinal specimen ( r s=0.840, P<0.001), with pathological inflammatory score ( r s=0.497, P=0.005), and with intestinal stricture index ( r s=0.599, P<0.001). ROC analysis showed that the area under the curve of MCFI for differentiating moderate-severely from mildly inflammatory bowel walls was 0.718 (95%CI 0.522-0.913). Using MCFI≥4 as a cutoff value, the sensitivity and specificity were 81.8% and 47.4%, respectively. Conclusions:There was a correlation between creeping fat and inflammatory intestinal strictures in CD. MCFI can non-invasively depict the degree of creeping fat wrapping around the gut and assess the inflammatory intestinal stricture.

OBJECTIVE: To establish a novel standardized magnetization transfer ratio (MTR) parameter which considers the element of the normal bowel wall and to compare the efficacy of the MTR, normalized MTR, and standardized MTR in evaluating intestinal fibrosis in Crohn's disease (CD).MATERIALS AND METHODS: Abdominal magnetization transfer imaging from 20 consecutive CD patients were analyzed before performing elective operations. MTR parameters were calculated by delineating regions of interest in specified segments on MTR maps. Specimens with pathologically confirmed bowel fibrosis were classified into one of four severity grades. The correlation between MTR parameters and fibrosis score was tested by Spearman's rank correlation. Differences in MTR, normalized MTR, and standardized MTR across diverse histologic fibrosis scores were analyzed using the independent sample t test or the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUC) was computed to test the efficacies of the MTR parameters in differentiating severe intestinal fibrosis from mild-to-moderate fibrosis.RESULTS: Normalized (r = 0.700; p < 0.001) and standardized MTR (r = 0.695; p < 0.001) showed a strong correlation with bowel fibrosis scores, followed by MTR (r = 0.590; p < 0.001). Significant differences in MTR (t = −4.470; p < 0.001), normalized MTR (Z = −5.003; p < 0.001), and standardized MTR (Z = −5.133; p < 0.001) were found between mild-to-moderate and severe bowel fibrosis. Standardized MTR (AUC = 0.895; p < 0.001) had the highest accuracy in differentiating severe bowel fibrosis from mild-to-moderate bowel wall fibrosis, followed by normalized MTR (AUC = 0.885; p < 0.001) and MTR (AUC = 0.798; p < 0.001).CONCLUSION: Standardized MTR is slightly superior to MTR and normalized MTR and therefore may be an optimal parameter for evaluating the severity of intestinal fibrosis in CD.
Crohn Disease ; Fibrosis ; Humans ; Magnetic Resonance Imaging ; ROC Curve

Objective:To explore the diagnostic efficacy of nomogram based on multi-parameter MRI for assessment of bowel fibrosis in patients with Crohn disease（CD).Methods:The clinical and imaging data of CD patients diagnosed by surgical histopathology in the First Affiliated Hospital of Sun Yat-sen University from June 2015 to March 2018 were prospectively collected. All the patients underwent conventional MRI and diffusion kurtosis imaging（DKI) within 2 weeks before surgery. Patients who underwent surgery between June 2015 and September 2017 were included in the model building group, and those who underwent surgery between October 2017 and March 2018 were included in the model validation group. We measured the apparent diffusion coefficient（ADC) from monoexponential model of diffusion-weighted imaging（DWI), apparent diffusional kurtosis（K app), and apparent diffusion for non-Gaussian distribution（D app) from non-Gaussian DKI model, and observed T 2WI signal intensity and enhancement pattern of the same segment. One to three intestinal specimens per patient were stained with Masson′s trichrome for the histological grading of fibrosis. Correlations between qualitative/quantitative MRI indexes and histological grades were evaluated using the Spearman rank test. Multivariate logistic regression analysis was performed to identify independent factors to be included into the nomogram for predicting the degree of bowel fibrosis and its diagnostic performance was assessed by internal and external validation. Results:A total of 40 CD patients were included, including 31 in the model construction group and 9 in the model verification group. A total of 81 intestinal specimens from 31 patients were graded as none-to-mild bowel fibrosis（ n=32) and moderate-to-severe bowel fibrosis（ n=49) according to a scoring system of fibrosis. In the training cohort, the K app value of moderate-to-severely fibrotic bowel walls was significantly higher than that of none-to-mildly fibrotic bowel walls, and the D appand ADC values of moderate-to-severely fibrotic bowel walls were significantly lower than those of none-to-mildly fibrotic bowel walls（ Z=-5.999, -4.521 and -3.893; P<0.001). There was no significant difference in T 2WI signal intensity or enhancement pattern between these two groups（χ2=1.571 and 0.103; P>0.05). Moderate and mild correlations of histological fibrosis grades with K appand D app( r=0.721 and -0.483; P<0.001), and a mild correlation with ADC（ r=-0.445, P<0.001) were found. Independent factors derived from multivariate logistic regression analysis to predict the degree of bowel fibrosis were K app and D app. Internal and external validation revealed good performance of the nomogram with concordance index of 0.901（95% confidence interval, 0.824-0.978) and 1.000, respectively, for differentiating none-to-mild from moderate-to-severe fibrosis. Conclusion:The DKI-based nomogram can be used to evaluate the bowel fibrosis in CD patients and provides a visual and simple prediction method for clinic.

Objective To determine the correlation between intravoxel incoherent motion (IVIM) parameters and both histologic inflammatory and fibrotic grades of Crohn disease (CD) in adults. Methods Prospectively, 17 patients (77 lesions) with a clinical and pathological diagnosis of CD in the first affiliated hospital of sun yat-sen university from July 2015 to June 2016 underwent MRE 15 days before surgery. All patients underwent T2WI, IVIM and enhanced MRI and calculated IVIM parameters include diffusion-related coefficient (D), perfusion-related coefficient (D*) and perfusion-related fraction (f). Histological intestinal inflammation and fibrosis was scored using the surgical histopathology as reference standard and further divided into mild-moderate (score 1 to 2) and severe (score 3 to 4) groups. Intestinal microvessel density (MVD) were also analyzed. Differences in IVIM parameters among different histological inflammation and fibrosis grades were assessed with the Kruskal-Wallis test. The Wilcoxon test was used for assessing differences in f between mild-moderate and severe fibrosis. The bivariate correlations between IVIM parameters and histological inflammation and fibrosis grades were analyzed using partial correlation . The bivariate correlations between IVIM parameters and MVD were analyzed using Spearman rank correlation. The areas under the receiver operating characteristics curves (AUROC) were analyzed to evaluate the efficacy for distinguishing severe from mild-moderate fibrosis. Results Of 77 surgical specimens, there were 41 mild-moderate and 36 severe inflammatory bowel segments, along with 22 mild-moderate and 55 severe fibrotic bowel segments. Positive correlation was shown between histologic inflammatory and fibrotic scores (r=0.592, P<0.01). MVD (42.7 ± 39.9)/HP presented weak positive correlation with histologic inflammatory scores (r=0.332, P=0.003) while no correlation with histologic fibrotic scores (r=0.129, P=0.262) was presented. Neither the D nor the D* values significantly correlated with histologic inflammation or fibrosis (P>0.05) while the f value significantly correlated with both histologic inflammation and fibrosis (P<0.05). Significant correlation was present between the f value and histologic inflammatory and fibrotic scores, respectively (r=-0.280, -0.520;P<0.05). There was significant difference in the f value between mild-moderate and severe fibrosis(Z=-5.255,P<0.01). The AUROC for the f value to distinguish between patients with mild-moderate fibrosis and severe fibrosis were 0.885. Using a threshold fractional perfusion of 0.33, the sensitivity and specificity values were 95.5％ and 81.8％, respectively. No correlation between f, D and D*value with histologic fibrotic scores (r=0.129, P=0.262) was presented. Conclusion The f value derived from IVIM could help to evaluate the severity of intestinal inflammation and fibrosis CD in adults.

Objective To assess the diagnostic value of magnetization transfer MRI (MTI) for bowel inflammation and fibrosis in humans with Crohn disease (CD). Methods From July 2014 through April 2017, 31 patients with a confirmed diagnosis of CD were prospectively recruited from the First Affiliated Hospital of Sun Yat Sen University. They were scheduled for elective surgery due to bowel obstruction and other complications, and underwent preoperative MR enterography (MRE) and MTI within 15 days of surgery. All cases had available intestinal specimens identified on MRE and resected bowel segments for region by region matching. All patients underwent breath hold conventional MRE and MTI examinations, and then the magnetization transfer ratios (MTRs) of pathological bowel segments were measured. Using region by region correlation between MTI and surgical specimen, the bowel segments were resected to stain with HE for evaluating bowel inflammation, Masson for bowel fibrosis, and typeⅠcollagen staining for the deposition of typeⅠcollagen within the bowel walls. The histologic sections from the most severe areas were scored as 0 (normal), 1 (mild), 2 (moderate) and 3 (severe). The correlations between MTR and histologic scores were analyzed by using Spearman rank correlation or partial correlation. The differences in MTR among different grades of bowel fibrosis were analyzed by one way ANOVA. The efficacy of MTR for predicting bowel fibrosis was evaluated by receiver operating characteristic curves analysis. The difference in MTRs between purely inflammatory bowel walls and mixed fibrotic and inflammatory bowel walls was analyzed by Student s t test. Results Sixty two resected bowel specimens from 31 patients including 9 purely inflammatory bowel walls and 53 mixed fibrotic and inflammatory bowel walls were obtained in this study. There were significant differences in MTR among non fibrotic [(21.45 ± 2.65)%], mildly [(30.88 ± 6.14)%], moderately [(35.14 ± 4.31)%] and severely [(35.14 ± 4.31)%] fibrotic walls (F=38.397,P<0.01). MTRs strongly correlated with fibrosis scores (r=0.681, P<0.01). High accuracy of MTRs was shown (curve under area=0.905, P<0.01) for differentiating moderately severely fibrotic from non fibrotic and mildly fibrotic bowel walls. Using MTR of 31.50% as a cutoff value, the sensitivity and specificity were 93.6% and 80.0%, respectively. The MTRs of purely inflammatory bowel walls [(21.45 ± 2.65)%] were significantly higher than that of mixed fibrotic and inflammatory [(36.28±5.21)%] bowel walls (t=-13.052,P<0.01). MTRs correlated with the scores of type Ⅰ collagen (r=0.325, P=0.044) but did not correlate with inflammation scores (r=-0.024, P=0.857). Conclusions MTI enables quantitative evaluation of bowel fibrosis in patients with CD and can be used to differentiate purely inflammatory CD from mixed fibrotic and inflammatory CD.

[Objective] To analyze the image findings of MR enterography (MRE) and diffusion weighted imaging (DWI) in Crohn disease (CD) and to discuss the diagnostic value of MRI for evaluating the activity of CD.[Methods] 26 patients proved by clinical,imaging and pathological data were enrolled in this study.The intra-/extra-intestinal image features of CD were retrospectively analyzed,and the intestinal lesions were evaluated by MRE+DWI scoring system.The differences in image features of active and inactive CD were compared.[Results] 26 bowel segments were evaluated and included active (n =20) and inactive CD (n =6).The intestinal performance of CD included wall thickening,T2WI hyperintensity and hyperenhancement.The pathological changes of active CD were more serious when comparing with that of inactive CD.DWI showed hyperintensity in the affected bowel wall.ADC of active C D [(0.9 ± 0.2) × 10-3 mm2/s] was significantly lower than that of inactive CD [(1.5 ± 0.4)× 10-3 mm2/s] (P ＜ 0.001).Extra-enteric performance of active CD included comb sign,lymphadenectasis of mesentery,mesenteric exudation,fistula and abdominal abscess.[Conclusion] MRE combined with DWI can accurately assess CD activity and diagnose extra-enteric complications.

[Objective]To explore the efficacy of T2* mapping for evaluating inflammatory activity in the patients with Crohn disease(CD).[Methods]A total of 98 CD patients underwent MR enterographywith T2*WI. T2* values were measured by put-ting regions of interest on the thickening bowel wall on T2*mapping. The activity of bowel segment was scored by magnetic resonance index of activity(MaRIA),to analyze the relationship between T2*values with CD activity.[Results]A total of 160 bowel segments were evaluated and includedinactive(MaRIA<7,n=26),mild(7≤MaRIA<11,n=23),and moderately-severe(MaRIA≥11, n = 111)active lesions. The differences in T2* values amongthese three groups were significant(all P < 0.05). T2* values of 160 bowel segments correlatedclosely withMaRIA(r=0.743,P<0.05). High accuracy of T2*values was shown for differentiating inac-tive from active CD(AUC=0.877)anddifferentiating inactive-mild from moderate-severe CD(AUC=0.848). The threshold T2*value of 20 ms allowed differentiation of mild from moderate-severe CD with74.5%sensitivity and 84%specificity.[Conclusions]T2*values, as thequantitative indexof T2*mapping,correlate well with CD activity and showsatisfiedefficacy for diagnosing inflammatoryactivity.